CN106232085A

CN106232085A - Microcapsule containing coloring agent

Info

Publication number: CN106232085A
Application number: CN201580021522.2A
Authority: CN
Inventors: 丹尼·戈尔茨坦; 奥尔加·普利伐洛伐; 利奥尔·本艾尔塔贝特; 雅尼夫·梅纳赫姆; 哈南·哈哲; 沙河·达奇
Original assignee: Tagra Biotechnologies Ltd
Current assignee: Tagra Biotechnologies Ltd
Priority date: 2014-03-04
Filing date: 2015-03-04
Publication date: 2016-12-14
Also published as: KR20160124902A; KR102329359B1; WO2015132791A1; CN113876599A

Abstract

The present invention discloses multiple Multi-layer microcapsule, including: a core, including one or above coloring agent；And two or above housing, including a wall formation macromolecular material, a light tight material and a soap, described housing is rupturable when rubbing or pressing on skin.The plurality of microcapsule is characterised by improving brightness value (L*) and/or the compatibility in multiple preparations of aqueous solution.The present invention also provides for including the multiple cosmetics of described microcapsule or medicine adornment preparation, such as, can be health skin care formulation or face protection preparation.

Description

Microcapsule containing coloring agent

Technical field

The present invention relates to encapsulated in certain embodiments, particularly but be not excluded for, relate to containing of novel designs Toner capsule, constituent and/or the preparation containing phase jljl, such as cosmetic formulations.

Background technology

The constituent applied for external (topical) includes that various coloring agent is well known in the art.Previously tasted Examination uses shielded coloring agent major part focus to be placed on the hydrophobic or decorative cosmetic of solid in dermal application, such as, make up Product, lipstick, rouge and powder-product.

U.S. Patent No. 5,320,835 " can activate " dormancy coloured particle or pigment with No. 5,382,433 announcements and comprise The cosmetic formulations of phase jljl, and further include a colored substrate phase and be dispersed in multiple coloring agent seizure base material of described substrate phase Granule.The coloring agent of described encapsulated it is said when applying mechanism is released to described substrate to described cosmetic formulations Xiang Zhong, and in the color of described substrate phase, produce a strong shade, and the plurality of coloring agent catches substrate particles and catches institute State the coloring agent of release and in the color of described substrate phase, produce a small shade.The pigment of described encapsulated is by one Prepared by coacervation.

U.S. Patent No. 5,380, No. 485 disclose color cosmetic constituents, including multiple granular fillers, be coated with The polymer of toner combination, and they are in the application of ornamental makeup.

The U.S. Patent application of publication number 2005/0031558 and 2005/0276774 discloses a kind of personal nursing or cosmetic Product constituent, containing multiple microparticles, is included in a shatter-resistant of the different colorant of micro encapsulation in a polymeric matrix and mixes Compound, even if the crosslinking preferably not allowing the coloring agent of any described seizure to be released under long-time use is poly- Polymer matrix.Described matrix polymer preferably printing opacity or semi-transparent, so that when applying described cosmetic composition, The mixture of described encapsulated coloring thing provides described cosmetics self and the dyeing of described skin.It is disclosed in the 2005/th The described microparticle of No. 0276774 is possibly together with multiple second granule (the most multiple hydrophobicitys being dispersed in whole described substrate Polymer, is different from multiple hydrophobic polymers of described matrix polymer).

U.S. Patent No. 4,756, No. 906 are disclosed decorative cosmetic product having constituent, micro-with multiple containing one first coloring agent Capsule, the plurality of microcapsule contains the second coloring agent of a solvation, is different from described first coloring agent.When described microcapsule When rupturing, make the described dyeing of described encapsulated pigment add in described constituent, thus change its color characteristic.

U.S. Patent Application Publication No. the 2008/81057th discloses multiple constituents, including at least one encapsulated and choosing From in multiple self-tanning agents (self-tanning agents) and at least one skin coloring agents of multiple melanogenesis activator. Owing to the plurality of self-tanning agent (self-tanning agents) or the described biological of the plurality of melanogenesis activator are made With, described constituent develops a slow and long color after being applied to described skin, and encapsulated provides institute simultaneously State the instant dyeing of skin.It is sightless by their encapsulation in described constituent that described pigment is purportedly, but works as By pressure applied during compositions is put on skin with destroy capsule and when putting on skin, easily from they Capsule discharges and becomes obvious.

Patent publication No. WO2004/045679 of World Intellectual Property Organization discloses rigidity and the most rupturable microcapsule, One mixture of constituent that is that contain at least two stains and that include them, it does not changes when being applied on described skin Their color.Owing to using crosslinked polymer matrix, it is many that it includes having the glass transformation temperature (Tg) higher than 80 DEG C Individual polymer, so the plurality of microcapsule is the most rupturable.

U.S. Patent No. 6,932, No. 984, this assignee the microcapsule disclosing a kind of monolayer and bilayer is used for one The method of microcapsule encapsulated substance, by using the solvent removal side of non-chlorinated solvent (non-chlorinated solvents) Method.Described method is based on physical process, and does not the most cause physics and/or chemical property, the biological work of original material Property and any change of safety.

U.S. Patent No. 7,838, is disclosed bilayer and/or three microcapsules by this assignee by No. 037, and design is by slightly Mechanism (such as on described skin wipe rub or press) and rupture, thus discharge the content of its encapsulation immediately.This is slightly Capsule is by using the described solvent minimizing technology of non-chlorinated solvent to prepare.The method provides for the plurality of microcapsule Physical stability, the ability of capture activating agent, protect the activating agent in described microcapsule and avoiding described micro encapsulation Activating agent be diffused into the aqueous phase in the described external world in an aqueous formulation (water-based preparation).

Patent publication No. WO2009/138978 of World Intellectual Property Organization, is disclosed by this assignee and is used in skin/external The cosmetic composition of application, including double-deck rupturable microcapsule, containing one or above microencapsulated colorants and many Individual active substance.When being applied to described skin, this constituent produces an instant color change effect to show described constituent Active substance contained by is transferred to skin.

Summary of the invention

In a cosmetic composition or preparation, highly desirable before administration described pigment or dyestuff are maintained at described In capsule, in order to maintain a long-term visual effect of cosmetic formulations.Also having demand is that the coloring agent protecting encapsulated avoids The potentially harmful impact caused by other materials, particularly merges preparation, it coloring agent including combining encapsulated one Active substance.

It is to depend on the composition that be set forth in microcapsule encapsulates by Single-layer microcapsules packaging protection or the described effectiveness sheltered Chemical constitution, molecular weight and physical property.For some pigment, the known method of Single-layer microcapsules encapsulation does not provides one enough Protect against leakage and/or a satisfied masking effect, and therefore use Single-layer microcapsules may cause described cosmetics group Become thing dyeing before it is applied to described skin.

Be currently known containing coloring agent microcapsule and not always provide enough protections in order to avoid leakage and/or satisfied Color masking effect, and explanation comprises their certain less desirable coloring degree of various preparations.It addition, this microcapsule Often in gel and other aqueous formulations, demonstrate poor stability and protect chromatic effect.It is not subject to and aqueous formulation finding In the microcapsule that incompatibility limits, and it will show substantial stability, and the color improved in aqueous formulation Masking effect and the release of encapsulation coloring agent within it, it is novel and light tight that inventor has designed and successfully implemented Multi-layer microcapsule.

A pattern according to some embodiments of the invention provides a kind of Multi-layer microcapsule, including: core microcapsule in；And extremely A few shell, is coated with described interior core microcapsule, and wherein said interior core microcapsule includes that a core, described core include a coloring Agent, described core is that the housing being included one first wall formation material is coated with, and described at least one shell includes one Two wall formation materials, a soap and a light tight material.

According to some in any embodiment described herein, at least one shell also includes a plasticizer.

According to some in any embodiment described herein, described plasticizer is selected from by triethyl citrate (triethyl citrate), triglyceride (tricaprylin), trilaurin (trilaurin), glyceryl tripalmitate (tripalmitin), glyceryl triacetate (triacetin), acetyl triethyl citrate (acetyltriethyl citrate), paraffin The group that oil (paraffin oil) and combination in any thereof are formed.

According to some in any embodiment described herein, described plasticizer is triethyl citrate.

According to some in any embodiment described herein, the scope of a quantity of described plasticizer is to be situated between by weight Between about 0.5% to about the 10% of the gross weight of described microcapsule or between about 0.5% to about 9.0% or about 1.0% to about Between 8.0% or between about 1.0% to about 7.0% or between about 1.5% to about 7.0% or about 1.5% to about 6.0% it Between or about 2.0% to about 6.0% between or about 2.5% to about 6.0% between or about 3.0% to about 6.0% between or about Between 3.5% to about 6.0% or between about 3.5% to about 5.5% or between about 3.5% to about 5.0% or be approximately 4.5%.

According to some in any embodiment described herein, described at least one outer layer further includes a dispersant, it is possible to Described coloring agent is disperseed when putting on skin.

According to some in any embodiment described herein, described dispersant is an esters of a fatty acid.

According to some in any embodiment described herein, the scope of a quantity of described dispersant is between described micro-glue Between about 0.5% to about the 10% of the gross weight of capsule or between about 0.5% to about 9.0% or between about 1.0% to about 8.0%, Or between about 1.0% to about 7.0% or between about 1.5% to about 7.0% or between about 1.5% to about 6.0% or about Between 2.0% to about 6.0% or between about 2.5% to about 6.0% or between about 3.0% to about 6.0% or about 3.5% to Between about 6.0% or between about 4% to about 6%.

According to some in any embodiment described herein, described light tight material is selected from by titanium dioxide, oxygen Change the group that zinc, aluminium oxide, boron nitride, Talcum, Kaolin, Muscovitum and any combination thereof are formed.

According to some in any embodiment described herein, the scope of a quantity of described light tight material is by weight It is between about 1% to about the 90% of the gross weight of described microcapsule or between about 30% to about 90% or about 30% to about Between 60%.

According to some in any embodiment described herein, described light tight material is titanium dioxide, and wherein dioxy Changing the scope of a quantity of titanium is between about 10% to about the 80% of the gross weight of described microcapsule or about 30% by weight Between about 80% or between about 30% to about 60%.

According to some in any embodiment described herein, described soap includes one or above fatty acyl Being selected from by stearic acid (stearic acid), arachidic acid of base, one or above fatty acyl group independence (arachidic acid), palmitoleic acid (palmitoleic acid), oleic acid (oleic acid), linoleic acid (linoleic Acid), linolenic acid (linolaidic acid), arachidonic acid (arachidonic acid), myristoleic acid The group that (myristoleic acid) and erucic acid (erucic acid) are formed.

According to some in any embodiment described herein, described soap selected from by magnesium stearate, magnesium oleate, The group that calcium stearate, calcium linoleate and sodium stearate are formed.

According to some in any embodiment described herein, described soap is magnesium stearate.

According to some in any embodiment described herein, the scope of a quantity of described soap is by weight Between about 0.05% to about the 5% of the gross weight of described microcapsule or between about 0.1% to about 3% or about 0.2% to about Between 3% or between about 0.5% to about 3% or between about 0.5% to about 2.0% or between about 1.0% to about 2.0%.

According to some in any embodiment described herein, described Multi-layer microcapsule includes: magnesium stearate is by weight It is in the range of the quantity between about the 1.0% to 2.0% of the gross weight of described microcapsule；Titanium dioxide is by weight It is in the range of the quantity between about the 30% to 75% of the gross weight of described microcapsule；And one dispersant be between In the range of a quantity between about the 4% to 6% of the gross weight of described microcapsule.

According to some in any embodiment described herein, the scope of a quantity of described interior core microcapsule is by weight It is between about 10% to about the 70% of the gross weight of described microcapsule or between about 10% to about 50%.

According to some in any embodiment described herein, described first wall formation material and the second wall formation material Expect each independent to include a polymer or copolymer, selected from by polyacrylate (polyacrylate), polymethylacrylic acid Ester (polymethacrylate), cellulose ether (cellulose ether), cellulose esters (cellulose ester) and The group that combination in any is formed.

According to some in any embodiment described herein, described polymer or copolymer selected from by polyacrylic acid Ester, polymethacrylates, acrylate/ammonio methacrylate copolymer (acrylate/ammonium methacrylate Copolymer), ammonio methacrylate copolymer Type B (ammonium methacrylate copolymer type B), low point Poly-(methyl methacrylate)-co-(methacrylic acid) (low molecular weight of son amount (about 15,000 dalton) (about 15,000Dalton) poly (methyl methacrylate)-co-(methacrylic acid)), poly-(propylene Acetoacetic ester)-co-(methyl methacrylate)-co-(trimethyl ammonium chloride-ethyl methacrylate chloride) (poly (ethyl acrylate)-co-(methyl methacrylate)-co-(trimethy lammmonium-ethyl methacrylate Chloride)), poly-(butyl methacrylate)-co-(methacrylic acid-2-dimethylamino ethyl ester)-co-(methacrylic acid Methyl ester) (poly (butyl methacrylate)-co-(2-dimethy laminoethyl methacrylate)-co- (methy1methacrylate)), poly-(styrene)-co-(maleic anhydride) (poly (styrene)-co-(maleic Anhydride)), the copolymer (copolymer of octylacrylamide) of octyl acrylamide, cellulose ether, fiber Element ester, PEG-black-poly-(propylene glycol)-black-PEG (poly (ethylene glycol)-black-poly (propylene glycol)-black-poly (ethylene glycol)), PLA (polylactic acid), PGA (polyglycolic acid) and The group that PLGA copolymer is formed.

According to some in any embodiment described herein, described second wall formation material includes a polymer or is total to Polymers, selected from the group being made up of acrylate/ammonio methacrylate copolymer, acetate fiber and combinations thereof.

According to some in any embodiment described herein, the scope of a quantity of described second wall formation material with Weight meter be between about 5% to about the 70% of the gross weight of described microcapsule or between about 5% to about 50% or about 5% to Between about 40% or between about 5% to about 30%.

According to some in any embodiment described herein, described Multi-layer microcapsule includes: described interior core microcapsule with Weight meter is in the range of the quantity between about the 10% to 50% of the gross weight of described microcapsule；Described second wall shape One-tenth polymer or copolymer are in the quantity between about the 5% to 30% of the gross weight of described microcapsule by weight In the range of；Magnesium stearate is the model in the quantity between about the 0.5% to 1% of the gross weight of described microcapsule by weight In enclosing；Titanium dioxide is the scope in the quantity between about the 25% to 50% of the gross weight of described microcapsule by weight In；And one dispersant be in the range of the quantity between about the 1% to 6% of the gross weight of described microcapsule.

According to some in any embodiment described herein, described Multi-layer microcapsule is a bilayered microcapsule.

According to some in any embodiment described herein, the brightness value (L*) of described Multi-layer microcapsule is between X- Rite measures in the range of on a brightness scale of system 60 to 100.

According to some in any embodiment described herein, described Multi-layer microcapsule in a gel preparation with 40 DEG C of trainings It is stable for supporting under reaching at least 3 months and stirring simultaneously.

A pattern according to some embodiments of the invention, it is provided that a kind of constituent including multiple Multi-layer microcapsule, at least The described Multi-layer microcapsule of a part includes multiple such as herein containing described in each embodiment any or its combination in any The microcapsule of toner.

According to some in any embodiment described herein, described many in the plurality of microcapsule containing coloring agent Microcapsule is identical or different.

According to some in any embodiment described herein, the plurality of Multi-layer microcapsule has an average-size, In the range of between about 50 microns to about 350 microns one.

A pattern according to some embodiments of the invention, it is provided that a kind of multilamellar of preparing contains the manufacture method of color microcapsule, institute State manufacture method and include step:

A () makes one first organic facies contact one first aqueous continuous phase, thus obtain and reassemble into emulsion, wherein one first more Described first organic facies include one second wall formation polymer or copolymer, a soap, a selective dispersant and One first water section misci-ble organic solvents, described first aqueous continuous phase is to utilize described organic solvent to form saturated and bag Include an emulsifying agent, described first organic facies or described first aqueous continuous phase and also include a light tight material and/or multiple monolayer Microcapsule, the plurality of Single-layer microcapsules respectively includes that a core, described core include that the one of a coloring agent or multiple coloring agent mixes Compound, and the wall being included one first wall formation material is coated with；

B () adds the water of a quantity in the emulsion of described formation, extract described organic molten from described emulsion with initiation Agent, thus obtain multiple bilayered microcapsule；And

(c) selectivity repeat step (a) and (b), use one second, third etc. organic facies and aqueous continuous phase, from And obtain multiple Multi-layer microcapsule.

According to some in any embodiment described herein, described manufacture method further includes and separates institute after step (b) State multiple microcapsule.

According to some in any embodiment described herein, described manufacture method further includes and is dried and sieves the plurality of Microcapsule, thus obtain a free flowing powder of the plurality of microcapsule.

According to some in any embodiment described herein, described wall formation polymer is acrylate/methyl-prop Olefin(e) acid ammonium copolymer, ammonio methacrylate copolymer Type B, cellulosic ether, Ethylcellulose or its combination in any.

According to some in any embodiment described herein, described organic solvent is selected from ethyl acetate, ethanol, first Acetoacetic ester or its combination in any.

According to some in any embodiment described herein, described plasticizer be selected from triglyceride, trilaurin, Glyceryl tripalmitate, glyceryl triacetate, triethyl citrate, acetyl triethyl citrate, paraffin oil or its combination in any.

According to some in any embodiment described herein, described light tight material is selected from titanium dioxide, oxidation Zinc, aluminium oxide, boron nitride, Talcum, Kaolin, Muscovitum and any combination thereof.

According to some in any embodiment described herein, described wall formation polymer is acrylate/methyl-prop Olefin(e) acid ammonium copolymer, ethyl cellulose or its combination in any；Described water section misci-ble organic solvents is ethyl acetate；Described point Powder is an esters of a fatty acid；Described fatty acid is magnesium stearate；And described light tight material includes titanium dioxide.

According to some in any embodiment described herein, the plurality of multilamellar microcapsule Han coloring agent is by such as existing Described manufacture method defined in any one in each embodiment and obtain.In other words, described manufacture method is for making Standby multiple microcapsules as described herein.

According to some in any embodiment described herein, the plurality of multilamellar microcapsule Han coloring agent described herein It is to be prepared according to manufacture method as described herein.

A pattern according to certain embodiments described herein, it is provided that a kind of cosmetics or medicine adornment preparation, including described group Becoming thing, described constituent includes described microcapsule as described herein.

According to some in any embodiment described herein, described preparation farther includes on cosmetics or on medicine adornment Acceptable carrier.

According to some in any embodiment described herein, described preparation is formulated into an O/w emulsion, Yi Youbao O/w emulsion, a water-in-oil emulsion, a water-in-oil-in-water compositions, an aqueous formulation, an anhydrous formulation, a silica-based preparation and Powder formulation.

According to some in any embodiment described herein, described preparation be with a gel, a powder, an emulsifiable paste, one Foam, an emulsion, an ointment, a spray, a grease, a pastel, a milk, a suspension, an aerosol or Presented in mousse.

Unless otherwise defined, the most all technology used herein and/or scientific terminology are logical with of the art What often technical staff was understood has identical meanings.Although can use with similar or identical method described herein or material In practice or test embodiments of the invention, but method that will be exemplary and/or material are described as follows.Situation in conflict Under, the definition comprised based on patent specification.In addition material, method and embodiment are only for explanation, and be not intended to must So property ground limits respective embodiment.

Accompanying drawing explanation

Some embodiments of the present invention describe the most in an exemplary fashion, with reference to accompanying drawing.Reference the most in detail Accompanying drawing, it is important that its shown details is by way of example, is only used for explanation and the enforcement of the present invention is discussed Example.In this, when explanation is combined accompanying drawing, how can go out embodiments of the invention and for skilled person be by concrete practice Obviously.

In the drawing:

Fig. 1 is show powder containing the commercial microcapsule including being packaged with redness, black or yellow colorants three Ware (ware of top), and containing including that some embodiments of the invention are packaged with identical redness, black or yellow colorants One image of three wares (ware of lower section) of the powder of Exemplary microcapsules, respectively as described by example 5,6 and 7.

Fig. 2 shows three images to bottle, contains a basic health cream at the described left bottle of every a pair, described It is exemplary containing color microcapsule (new red capsule, new black capsules that basic health cream includes according to some embodiments of the invention And yellow capsule), as described in example 8,9 and 10, and contain commercial microcapsule at the described right bottle of every a pair (red capsule 1, black capsules 1 and yellow capsule 1).

Fig. 3 is show powder containing the commercial microcapsule including being packaged with redness, black or yellow colorants three Ware (ware of lower section), and containing including that some embodiments of the invention are packaged with identical black, redness or yellow colorants One image of three wares (ware of top) of the powder of Exemplary microcapsules, respectively as described by example 8,9 and 10.

Fig. 4 shows three images to bottle, contains a basic body lotion, described base at the described right bottle of every a pair This health cream include according to some embodiments of the invention exemplary containing color microcapsule, (Jia Meilu is yellow, Jia Meilu is red and good U.S. Reveal black), as described in example 8,9 and 10, and contain commercial microcapsule (red glue at the described left bottle of every a pair Capsule 1, black capsules 1 and yellow capsule 1).

Fig. 5 A-5B shows for the exemplary microcapsule containing red stain according to some embodiments of the invention at X- Rite is compared to commercial microcapsule (red capsule 1) and obtains data (Jia Meilu is red, example 8) in measuring, and display exists The movement images (Fig. 5 A) shot under identical recording condition and the comparison of the reflectivity percentages showing the function as wavelength Figure (Fig. 5 B).

Fig. 6 A-6B shows for the exemplary microcapsule containing black colorant according to some embodiments of the invention at X- Rite is compared to commercial microcapsule (black capsules 1) and obtains data (Jia Meiluhei, example 9) in measuring, and display exists The movement images (Fig. 6 A) shot under identical recording condition and the comparison of the reflectivity percentages showing the function as wavelength Figure (Fig. 6 B).

Fig. 7 A-7B shows for the exemplary microcapsule containing yellow colorants according to some embodiments of the invention at X- Rite is compared to commercial microcapsule (yellow capsule 1) and obtains data (Jia Meilu is yellow, example 10) in measuring, and display exists The movement images (Fig. 7 A) shot under identical recording condition and the comparison of the reflectivity percentages showing the function as wavelength Figure (Fig. 7 B).

Detailed description of the invention

Before explaining in detail a present invention at least embodiment it should be appreciated that, the present invention need not be applied It is limited to details that is described below or that illustrated by embodiment.The present invention can have other embodiments, or with various Mode is put into practice or is carried out.

Seeking skin nursing, particularly cosmetics, comprising the product of encapsulated colorants, it provides the improvement of capsule Matter, the stability such as improved, the stability being included in aqueous formulation, and the color improved are sheltered and are discharged with color, this Case inventor has designed and has successfully implemented a kind of new microcapsule containing coloring agent.

Inventor has improved known in coloring agent is encapsulated in lighttight Multi-layer microcapsule molten Microencapsulation technology is removed in agent, on the one hand, when in industrially preparing process compound tense and when being maintained in aqueous environments aobvious Illustrate that beyond thought stability, significant enhancing are encapsulated in sheltering of coloring agent therein, and carry in cosmetic formulations Supply enough protections in order to avoid " bleeding (bleeding) " effect, and on the other hand, be only through applying mechanical pressure/cut Shear force (rubbing action to skin of such as one preparation) and be easily broken, thus discharge described packed color.

The solvent minimizing technology of described improvement is based on multiple physical processes, and it does not the most cause original The script physics of material and/or chemical property and any change of safety.This method provides the physically stable of described microcapsule Property, the protection of the described coloring agent captured in the ability of described coloring agent, described microcapsule and prevent microcapsule coloring agent The described external agency (before application) being diffused in oiliness and aqueous formulation.

Therefore, inventor has designed and has successfully implemented a kind of novel method, to obtain stable preparation, effectively Ground hides the color of the microencapsulated colorants wherein contained, and shows special long-term visual effect before administration, When using described microcapsule smooth and comfortable exhibition coffee and by only rubbing thirty years of age of described preparation on described skin I.e. discharge the coloring agent of described encapsulation.

Such as, inventor it has been proved that with by containing including prepared by foregoing solvent minimizing technology The corresponding preparations of the microcapsule of toner is compared, including the basic skin cream system containing color microcapsule using methods described herein to prepare The color of agent and pressed powder is substantially the brightest with brighter.Furthermore, inventor has turned out and provided herein is Containing color microcapsule when being maintained at 40 DEG C with continuous stirring, be stable upper reaching in most trimestral gel preparation.

The microcapsule that the present embodiment provides is to be constituted (the most generally spherical granule) with multiple granules, and it is typically envelope The structure closed, coloring agent containing packed (encapsulated) (encapsulating (enveloped), embedding (entrapped)) or The mixture of multiple coloring agent.The plurality of granule has one core-shell structure feature, and i.e. it includes at least two polymer Housing and by a core of these shell encapsulated, described core includes described coloring agent or can be made up of described coloring agent.More Concrete, the feature of described Multi-layer microcapsule include one in core microcapsule, including a core, it includes a coloring agent, by a shell Body is encapsulated, and described housing includes one first wall formation material and at least one extra shell, and including encapsulating, described inner core is micro- One second wall formation material of capsule (including described containing coloring agent core and a housing of one first wall formation material).

Each housing in described Multi-layer microcapsule typical and independent as a wall formation material (such as 1 One, second, third etc. wall formation material form the shell of described first, second, third, etc. etc. respectively), and be used as institute State a film of packed material.Owing to opaque material is included in it, described in being provided by the present embodiment, contain coloring agent In microcapsule one or above described shell are lighttight, and containing a soap.

Described shell is possibly together with a plasticizer, controlling its hardness；And/or a dispersant, promote that pigment is at described skin On described round and smooth extension, and described shell is designed to so that when described microcapsule rubs or presses on described skin being Rupturable.

The microcapsule of the present invention is except other purposes, it is adaptable to comprise the application of external, such as cosmetics, medicine adornment and medicine The application of (the most dermatologic).When being applied on skin, described microcapsule is such as wiped, when applying, the shearing force rubbed and press and is existed Can rupture time on skin, but they keep complete before the application in the preparation itself, and aqueous formulation and its Its preparation shows special stability.The hardness of described microcapsule is enough avoided the destruction of described shell and realizes in it Tolerant by separating, be dried, sieve technology manufacture processes such as (sieving).

The plurality of microcapsule:

A pattern according to some embodiments of the invention, is provided with a kind of Multi-layer microcapsule, including: core microcapsule bag in Including a core, described core includes that a coloring agent, described core are that the housing being included one first wall formation material is wrapped Cover；And at least one shell, including one second wall formation material, the described second wall formation material cladding micro-glue of described inner core Capsule.This Multi-layer microcapsule is also referred to as the microcapsule Han coloring agent.

One core of a kind of Multi-layer microcapsule as described herein includes one core-housing microcapsule, is claimed herein It is core microcapsule or one inner core-housing microcapsule in.Described interior core microcapsule includes a core, and it includes or by following group Become: a coloring agent or a mixture of multiple coloring agent；And it being coated with a housing of described inner core, it is referred to herein as one first Housing or one first shell.The described housing of described interior core microcapsule includes one first wall formation polymerization as described herein Thing, and optionally farther include a plasticizer as described herein.Described inner core-housing microcapsule is by one second Shell is coated with, and is optionally respectively coated with the housing before described by the shell of the three, the 4th etc..

In certain embodiments, a kind of Multi-layer microcapsule includes a shell, is coated with one inner core-housing micro- Capsule, thus form a kind of double-deck (or bilayer) microcapsule, maybe can include two shells, thus formed three layers (or three layers), Or three or above shell, it is referred to as multilamellar (or multilamellar) microcapsule.Bilayered microcapsule includes a shell, is coated with two institutes State interior core microcapsule, and three microcapsules include two continuous print shells, be coated with described interior core microcapsule.

In certain embodiments, the described Multi-layer microcapsule containing coloring agent as described herein be by one amendment molten Agent removing method and prepare, as described by example paragraph below.

In certain embodiments, an average-size of described microcapsule as described herein is to fall in a range, institute Scope of stating is between about 50 microns to about 350 microns or between about 50 microns to about 150 microns, it includes any son Scope and any intermediate value betwixt.

Some in any embodiment described herein, in addition to described wall formation material, one or above Shell also includes a soap and a light tight material, as described herein.

According to some in any embodiment of the present invention, described Multi-layer microcapsule is characterised by and previously described micro-glue A most shallow color compared by capsule, and it is with the difference of microcapsule provided herein: in its wall formation material not There is soap；And/or its preparation method.

According to some embodiments of the invention, a brightness of described microcapsule is to use described X-Rite measurement technology to survey Amount, and is the value with L*a*b*, or is represented by the comparison DL* value on described brightness scale, as with comprise phase With coloring agent but without soap, and the brightness that its similar microcapsule using aforesaid solvent minimizing technology to prepare is compared Difference.

According to some embodiments of the invention, a brightness of described microcapsule is to use described X-Rite measurement technology to survey Amount, is to represent with described brightness scale (L*), and is above 60, higher than 70, higher than 80 or higher than 90.In some embodiments In, described brightness is in the range of the 60 to 100 of described brightness scale L*.

In the exemplary embodiment, described micro-containing red, yellow or black colorant of some exemplary embodiments The brightness of capsule is to use described X-Rite measurements technology to measure, and as described below is observed, such as at the model of this paper Example 13, relative to comprise same colorant but do not contain soap and use prepared by different solvent minimizing technology exemplary The brightness of similar clause microcapsule, brightness value on described brightness scale (L*) is high 4-25 (being reflected by the DL*s value measured).

In further one exemplary embodiment, describe at example 13 and show with at Fig. 1-4, be prepared for comprising basis One vision of the colour brightness of the microcapsule of the exemplary embodiment of the present invention or the preparation of business microcapsule as herein described and Compare measurement qualitatively, and both contain identical coloring agent.Show and be packaged with identical black, redness or yellow with comprising The powder of the business microcapsule of coloring agent is compared with emulsion, comprises the powder of the microcapsule of the exemplary of the present invention Significant brighter and brighter of (Fig. 1 and 3) and basic body lotion (Fig. 2 and 4).

The microcapsule of these exemplary embodiments includes the titanium dioxide in the wall formation material outside them of the position, and And assume that titanium dioxide is coated with the polymeric shells (the first shell) of described interior core microcapsule uniformly, and not by any specific Theoretical constraint, this explanation color is shallower.

Without being bound to any particular theory, it is assumed that light tight material and optional outside are gathered to use a soap to illustrate The enhancing adhesiveness of the internal core microcapsule of compound housing, further illustrates the brighter color of microcapsule and stablizing of improvement Property.

According to some in any embodiment of the present invention, a kind of Multi-layer microcapsule described herein can when putting on skin Rupture and maybe can rupture, that is a microcapsule as described herein is in the described preparation comprise aqueous formulation and in industry manufacture During keep complete, but be easily broken when being pressed on skin friction.Described by monitoring (such as, using optical microscope) Microcapsule maintains the ability of its size and dimension in a basic emulsifiable paste or emulsion when carrying out low shear mixing, such as in room temperature Down and carry out 40-600 (or 80-100) rpm at 40 DEG C to reach 5-10 minute, evaluate microcapsule routinely and use it in external Front not disruptiveness.In capsule size, the change less than 10% represents can not the breaking of microcapsule during regular industrial Fragility.

Described Multi-layer microcapsule provided herein generally demonstrates special stability in aqueous formulation, particularly solidifying In glue preparation.

In multiple exemplary embodiments, such as, described by this paper example 14, test the exemplary enforcement in the present invention The Multi-layer microcapsule provided in example durability in gel preparation.It has been observed that will contain from about the present embodiment of 3 weight % Carbomer (carbomer) gel preparation of Exemplary microcapsules cultivate and reach at least 3 months 40 DEG C and continuous stirring, its Described in the Exemplary microcapsules of the present embodiment contain redness, yellow or black, and the color of described gel is not changed in, and does not i.e. have There is color to leak into described gel from described microcapsule, and the microcapsule of at least 90% is protected in whole long-time incubation Hold its shapes and sizes.

Described wall formation polymer:

Described wall formation material forms multiple housings of the Multi-layer microcapsule of the present embodiment, and as described encapsulation One film of material (such as coloring agent).According to multiple embodiments of the present invention, the described wall forming the plurality of housing forms use Each in material includes wall formation material or a copolymer.Some in any embodiment of the present invention, one or with On described shell farther include a light tight material and a soap, and alternative farther includes a plasticizer And/or a dispersant.

Its referred to herein as " wall formation of described term " wall formation polymer (wall-forming polymer) " With polymeric material (wall-forming polymer material) " refer to a kind of polymeric material (such as, polymer or Copolymer), or two kinds or the combination of above different polymeric material, as defined herein, it forms the exterior wall of microcapsule Or layer or a composition of housing.Described term " polymer " housing " refer to by including that described (multiple) wall is formed with the one of polymer Polymeric layer.

In certain embodiments, select described wall formation polymer to bear when microcapsule enters in industrial manufacturing process The shearing force being applied in during row synthesis, but only pipe so, but provides microcapsule when being applied in (such as wipe and rub or press) at skin Shearing force time upper is rupturable.

In certain embodiments, what each in wall formation polymeric material was independent includes the official containing a q.s Can base and the polymer of hydrogen bond can be formed.

In certain embodiments, formed described two or with in the described polymeric material of upper shell one or more, Or each include multiple hydrogen bond formed functional group, it is characterized by the total polymer weight of 4-40 percentage by weight.Hydrogen bond is formed to be used Functional group includes, but not limited to containing one or above electron donating property atom (electron-donating atom) many Individual functional group, such as oxygen, sulfur and/or nitrogen.

In certain embodiments, hydrogen bond formation functional group includes carboxylic acid (carboxylic acid), carboxylate (carboxylate), hydroxyl (hydroxy) or its combination in any.

In certain embodiments, formed described two or with in the described polymeric material of upper shell one or more, Or each include polyacrylate (polyacrylate), polymethacrylates (polymethacrylate), cellulose ether (cellulose ether) or esters or its combination in any.

Exemplary wall formation polymeric material including but not limited to, polyacrylate, polymethacrylates, low molecule Poly-(methyl methacrylate)-co-(methacrylic acid) (low molecular weight poly (methyl of amount Methacrylate)-co-(methacrylic acid)) (such as 1:0.16), poly-(ethyl acrylate)-co-(metering system Acid methyl ester)-co-(trimethyl ammonium chloride-ethyl methacrylate chloride) (poly (ethyl acrylate)-co- (methyl methacrylate)-co-(trimethylammmonium-ethyl methacrylate chloride)) (example Such as 1:2:0.1) (also referred to asRSPO), poly-(butyl methacrylate)-co-(methacrylic acid-2-dimethyl Amino ethyl ester)-co-(methyl methacrylate) (poly (butyl methacrylate)-co-(2- Dimethylaminoethyl methacrylate)-co-(methyl methacrylate)) (such as 1:2:1), poly-(benzene second Alkene)-co-(maleic anhydride) (poly (styrene)-co-(maleic anhydride)), octyl acrylamide (octylacrylamide) copolymer, cellulose ether, cellulose esters, PEG-black-poly-(propylene glycol)-black-poly-(second Glycol) (poly (ethylene glycol)-block-poly (propylene glycol)-block-poly (ethylene Glycol)), PLA (polylactic acid), PGA (polyglycolic acid), PLGA (PLA-co-poly-(Acetic acid, hydroxy-, bimol. cyclic ester) (poly (lactide)-co-poly (glycolide)) or its combination in any.

Any combination of polymer and copolymer is all considered for wall formation material, such as this paper institute as described herein State.

In some other embodiments, described polymeric material includes cellulose ether or esters, such as but not limited to, methyl Cellulose (methyl cellulose), ethyl cellulose (ethyl cellulose), hydroxypropyl methyl cellulose (hydroxypropyl methyl cellulose), hydroxypropyl cellulose (hydroxypropyl cellulose), cellulose Acetic acid (cellulose acetate), cellulosic phthalic acetate (cellulose acetate phthalate), Cellulose acetate butyrate (cellulose acetate butyrate) or hydroxypropyl methyl cellulose acetate phthalate Ester (hydroxypropyl methyl cellulose acetate phthalate).When cellulose ether or esters are used in polymerization During thing material, it preferably comprises multiple hydroxyls (hydroxyl groups) of the about 4-20% being freely formed multiple hydrogen bond (such as The hydroxyl not being partially alkylated or alkylated or be acylated).

Some in any embodiment described herein, the first shell of described interior core microcapsule includes as sent out in the U.S. A wall formation material described in bright patent the 6th, 932,984 patent No., it is incorporated herein by, as herein In illustrate completely.

Some in any embodiment described herein, the institute in the shell of or above second, third etc. State wall formation material and include acrylate/ammonio methacrylate copolymer (acrylate/ammonium methacrylate Copolymer), such asRSPO.The present invention describe other embodiments any in some, one or more than Second, third etc. shell in described wall formation material include a combination of polymer cited below, such as but Being not limited to, acrylate/ammonio methacrylate copolymer is (such asRSPO) with poly-(methyl methacrylate)- Co-(methacrylic acid) or the combination of cellulose acetate.

In certain embodiments, the described wall formation material bag in the shell of or above second, third etc. Include cellulose esters, such as cellulose acetate.Some in other embodiments any of the present invention, one or above second, Described wall formation material in the shell of the 3rd etc. includes cellulose acetate and acrylate/ammonio methacrylate copolymer (such asRSPO) combination or poly-(methyl methacrylate)-co-(methacrylic acid).

When two polymeric materials are taken as a wall formation material, the scope of the part by weight between it can be to be situated between In 10:1 to 1:1, the most such as, can be 5:1,4:1,3:1,2:1 or 3:2, be included in any intermediate value therebetween and subrange.

(the 1 of the most described internal microcapsule for wall formation material in each shell of microcapsule described herein One wall formation material, it is coated with one second wall formation material of one first shell of described internal microcapsule and selective One the 3rd wall formation material being coated with described second housing etc.) can be identical or different.

In certain embodiments, in bilayered microcapsule, the described wall formation material of first and second shell described is Different.In these embodiments some, described second wall formation material includes cellulose acetate, acrylate/methyl Ammonium acrylate copolymer is (such asOr a combination thereof RSPO).

The total amount (w/w) of (multiple) wall formation material of the plurality of shell (getting rid of internal capsule) accounts for described Total microcapsule weight can be within the scope of one, and described scope is by weight selected between about 5% to 70%, Jie Yuyue Between 5% to 50%, between about 5% to 40% or between about 5% to 30% or between about 8% to 21% it Between, comprise anyon scope and any intermediate value betwixt.

In described wall formation material includes multiple embodiments of cellulose acetate, the plurality of shell (is got rid of internal Capsule) a quantity of (multiple) wall formation polymeric material account for described total microcapsule weight can be within the scope of one, institute Scope of stating is by weight between 5% to 20% or between 5% to 20%.

One light tight material:

Multiple housings of the plurality of microcapsule can be independent be light tight, half light tight or non-opaque (transparent ).Provided herein containing in color microcapsule, shell described at least, such as, described outmost shell is lighttight.

In some embodiments of the invention, the opacity (opacity) of the shell of described Multi-layer microcapsule is to pass through One light tight material and obtain.

As used herein one " light tight material " is a kind of nontransparent and stops at least 70% light passed through The material of line.

Therefore, light tight shell stops the described light of 70% to 100%.Half light tight shell stops the institute reaching 50% State light.Non-light tight or transparent outer cover stops less than 30% light passed through.

Described term " light obscuration " and " light tight " are referring herein to ultraviolet-visible light (UV-vis light), such as Daylight.

Exemplary light tight material including but not limited to, titanium dioxide, zinc oxide, aluminium oxide, boron nitride, Talcum, kaolinite Soil, Muscovitum and any combination thereof.

The described total amount of described light tight material is in a range, and described scope is between described microcapsule by weight Gross weight about 1% to about 90% between or about 30% to about 90% between about 30% to about 80% between or about 30% Between about 60%, comprise anyon scope and any intermediate value betwixt.

Some in any embodiment described herein, described light tight material is or includes titanium dioxide, and one In a little embodiments, a quantity of titanium dioxide is in a range, and described scope is total between described microcapsule by weight Between about 10% to about the 85% of weight, between 30% to about 80%, between 30% to about 75%, between 30% to about 60%, bag Containing anyon scope and any intermediate value betwixt.

Some in any embodiment described herein, described light tight material includes the knot of titanium dioxide and boron nitride Close.

One soap:

One technical characteristic of the Multi-layer microcapsule of the present embodiment, it is assumed to maintain light obscuration and in aqueous environments Keep stable ability, be one or above described shell comprises soap.

Some in any embodiment described herein, are included in embodiment the most out of the ordinary The described outer soap further included in embodiment the most out of the ordinary of light tight material.

Soap includes long hydrophobicity hydrocarbon chain (having 4 to 30 carbon atoms in such as length) carboxylate anion (fat Acyl group) and cation, it is shown below:

(R-C (=O)-O^-)_nM⁽ⁿ⁺⁾

Wherein, R is the substituted or unsubstituted straight or branched hydrocarbon chain with 4 to 30 carbon atoms；M+ is cation, excellent Choosing is metal cation, and n is the integer of number representing the fatty acyl group interacted with cation, and also represent sun from The charge number (such as, 1,2,3 etc.) of son.

Use the soap of some in any embodiment of the present invention can contain 1 to 3 fatty acyl chain, Mei Gelian Independent in length comprise 4 to 30 or 8 to 24 carbon atoms (C8-C24).Therefore, soap can be monovalence, bivalence or The salt of trivalent metal ion or the salt of organic cation.

Monovalent metallic ion is it may be that such as sodium ion, potassium ion, cesium ion, lithium ion；Bivalent metal ion is selected from magnesium Ion, calcium ion, iron ion (II), cobalt ion, nickel ion, copper ion, manganese ion, cadmium ion, strontium ion or zinc ion.Trivalent Metal ion can be such as iron ion (III), lanthanum ion, europium ion or gadolinium ion: organic cation can be such as ammonium, Sulfonium or arsenic.

Described fatty acyl group can derived from fatty acid, such as but not limited to, stearic acid (stearic acid), arachidic acid (arachidic acid), palmitoleic acid (palmitoleic acid), oleic acid (oleic acid), linoleic acid (linoleic Acid), linolenic acid (linolaidic acid), arachidonic acid (arachidonic acid), myristoleic acid (myristoleic acid) and erucic acid (erucic acid).Have also contemplated that other fatty acid.

Inventionwithout being bound to any specific theory, it is assumed that hydrocarbon chain makes to minimize with contacting of aqueous environments, cation head Ionic interaction is formed with hydrone and anionic species.Therefore, preparation the present invention Multi-layer microcapsule method one In a little embodiments, when making salt and the wall formation polymer contact of interior core microcapsule and opaque material and fatty acid, institute State the long hydrophobic chain of fatty acid carboxylate salt around the hydrophobic enclosure of kernel microcapsule spontaneous parcel they, simultaneously by them Ion head point to aqueous environments, thus by hydrone solvation, or most frequently, be to attract anionic compound or have The compound of partial negative charge.Therefore, the cation most probable of soap attracts the opaque materials being dispersed in water-based emulsion The free carboxy of the granule of matter and optionally wall formation polymer and/or hydroxyl, cause light tight material and polymeric material Preferably gluing is to the outer layer of interior core microcapsule, and therefore provides effectively sheltering of coloring agent in interior core microcapsule, produces simultaneously Multi-layer microcapsule, final result is as herein defined with microcapsule that relatively light light tone is characterized.

Soap can be used for preparing Single-layer microcapsules, simultaneously encapsulating material and wall formation polymer and have invariably Transparency material joins in organic facies together.Connect with the aqueous phase containing light tight material such as titanium dioxide making organic facies When touching, spontaneous parcel cake is looped around encapsulated substance by aliphatic chain, and the head of their polarity/ion will electricity contrary with band The light tight material of lotus and the group with oppositely charged on polymer react, thus strengthen around comprising encapsulation material The formation of the light tight polymer encapsulated of the core of material.

Exemplary fatty hydrochlorate include but not limited to magnesium stearate, magnesium oleate, calcium stearate, calcium linoleate, sodium stearate, Arachidonic acid magnesium (magnesium arachidonate), magnesium palmitate (magnesium palmitate), magnesium linoleate, Arachidonic acid calcium (calcium myristoleate), calcium myristate (calcium myristoleate), linoleic acid sodium, Calcium linoleate, sodium stearate, potassium stearate, sodium laurate (sodium laurate), Sodium myristate (sodium Myristate), sodium palmitate (sodium palmitate), potassium laurate (potassium laurate), potassium myristate (potassium myristate), potassium palmitate (potassium palmitate), calcium laurate (calcium Laurate), calcium myristate (calcium myristate), calcium palmitate (calcium palmitate), Dodecanoic acid, zinc salt (zinc laurate), Grillocin P 176 (zinc myristate), Hexadecanoic acid, zinc salt (zinc palmitate), zinc stearate (zinc stearate), Magnesium dilaurate (magnesium laurate) and magnesium myristate (magnesium myristate).

In certain embodiments, described soap is magnesium stearate.

Described soap is generally in a quantitative range, and described scope is the gross weight between described microcapsule by weight About 0.05% to about 5% between or about 0.1% to about 45% between about 0.2% to about 4% between or about 0.5% to Between about 4% or between about 0.5% to about 3.0% or between about 0.75% to about 3% or about 1.0% to about 3.0% it Between or about 1.0% to about 2.0% between or about 1.0% or about 2.0%, comprise anyon scope and any centre betwixt Value.

One dispersant and/or plasticizer:

In certain embodiments, one of described Multi-layer microcapsule or above shell include a dispersant, preferably One low alkyl group fatty acid ester, different such as but not limited to isopropyl myristate (isopropyl myristate), myristic acid Propyl group butyl ester (isopropyl butyryl myristate), propylene glycol stearate (propylene glycol Stearate), coconut oil butanediol ester (butylene glycol cocoate), hydrolecithin (hydrogenated And Jojoba oil (jojoba oil) lecithin).

In certain embodiments, described dispersant is isopropyl myristate (IPM), propylene glycol stearate or its group Close.It has been observed that when the shell of bilayered microcapsule comprises a dispersant such as IPM or propylene glycol stearate, it is thus achieved that more soft Soft and be easier to the microcapsule sprawled.Assuming that when the micro capsules are broken, the coloring agent of encapsulation is released and is coated with oiliness and divides Powder, thereby results in more smooth on skin of coloring agent and uniformly sprawls.The agent of such fat is considered as increasing Mould agent and dispersant and work.

The most in a range, described scope is the pact of the gross weight between described microcapsule to the quantity of dispersant by weight Between 0.5% to about 10% or between about 0.5% to about 9% or between about 1.0% to about 8.0% or about 1.0% to about Between 7.0% or between about 1.5% to about 7.0% or between about 1.5% to about 6.0% or about 2.0% to about 6.0% it Between or about 2.5% to about 6.0% between or about 3.0% to about 6.0% between or about 4.0% to about 6.0% between, comprise Anyon scope and any intermediate value betwixt.

In some embodiments of any embodiment of the present invention, at one or above shell (such as at bilayered microcapsule In one first and/or second housing) farther include a plasticizer.

Herein and in the art, one " plasticizer " describes a kind of plasticity improving constituent or the material of mobility.? In the context of the embodiment of the present invention, plasticizer is joined in wall formation material to control the physical property of microcapsule shell And spring level.

Exemplary plasticizers including but not limited to, triethyl citrate (triethyl citrate), triglyceride (tricaprylin), trilaurin (trilaurin), glyceryl tripalmitate (tripalmitin), glyceryl triacetate (triacetin), second Acyl triethyl citrate (acetyltriethyl citrate), paraffin oil (paraffin oil) and combination in any thereof.Showing In example embodiment, described plasticizer is triethyl citrate.

The quantity of described plasticizer can in a range, and described scope is the gross weight between described microcapsule by weight Between about 0.5% to about 10% or between about 0.5% to about 9% or between about 1.0% to about 8.0% or about 1.0% to about Between 7.0% or between about 1.5% to about 7.0% or between about 1.5% to about 6.0% or about 2.0% to about 6.0% it Between or about 2.5% to about 6.0% between or about 3.0% to about 6.0% between or about 3.5% to about 6.0% between or about Between 3.5% to about 5.5% or between about 3.5% to about 5.0% or about 4.5%, comprise anyon scope and betwixt Any intermediate value.

Coloring agent:

It is interchangeable in term used herein " coloring agent ", " color agent " and " pigment " and refers to organic pigment, such as Synthesis or natural dye, inorganic pigment such as metal-oxide or color lake (lakes) selected from any known FD&C or D&C dyestuff And any combination (mixture).In some exemplary embodiments, coloring agent is inorganic pigment, such as metal-oxide.

Described coloring agent can be oil-soluble or be dispersible in oil or have limited dissolubility in water. Generally, include but not limited to have according to the suitable coloring agent for micro encapsulation of some in any embodiment of the present invention Machine and inorganic pigment, color lake, natural and synthetic dyestuffs and any combination thereof.

In certain embodiments, described color agent is inorganic pigment, such as but not limited to metal-oxide such as ferrum oxide, two Titanium oxide (TiO₂), titanium suboxide, aluminium oxide, zirconium oxide, cobalt oxide, cerium oxide, nickel oxide, chromium oxide (chrome green), oxidation Zinc and synthesis of metal oxide；Metal hydroxides such as calcium hydroxide, hydrated ferric oxide., aluminium hydroxide, chromic oxide gel, magnesium hydroxide With synthesis metal hydroxides；Other coloring agent such as ferric ferrocyanide ammonium (ferric ammonium ferrocyanide), general Shandong scholar blue (Prussian blue), iron sulfide (iron sulfides), manganese violet (manganese violet), white carbon black (carbon black), Muscovitum (mica), Kaolin (kaolin) and any combination thereof.

Some in any embodiment, described inorganic pigment is selected from ferrum oxide, titanium dioxide, zinc oxide, chromium oxide/hydrogen Oxide and mixture thereof.In further preferred embodiment, coloring agent is any in three primary colors-redness, yellow or black A kind of ferrum oxide, or most preferably its mixture.Optionally, in order to provide any required final color or color to compositions The purpose adjusted, described coloring agent also can comprise titanium dioxide in addition to the mixture of ferrum oxide.Preferably, when be encapsulated in described in Time in core microcapsule, titanium dioxide uses, such as but not limited to anatase (anatase), plate with its any mineral forms Titanium ore (brookite) or rutile (rutile) or its any combination.

In some other embodiments, described coloring agent is by with metallic salts such as aluminum, calcium or barium salt precipitation is natural or The color lake organic pigment that synthetic dyestuffs produce.This coloring agent typically oil-dispersing property and be widely used in cosmetics.Color The example of shallow lake pigment includes but not limited to but is not limited to indigo color lake (Indigo Lakes), carmine lake (Carmine Lakes), color lake series FD&C and the D&C series dye of name, the red 21 aluminum color lakes of such as D&C (D&C Red 21Aluminum Lake), the red 7 calcium color lakes of D&C (D&C Red 7Calcium Lake).

As described herein, during described coloring agent is comprised in a core of described interior core microcapsule.In some embodiments In, the described interior core microcapsule comprising described coloring agent, described wall formation agent and other additives is as in U.S. patent US6, described in 932,984, comprises any embodiment described in it and combinations thereof.

The quantity of the interior core microcapsule containing described coloring agent generally the most in a range, described scope be by weight between Between about 10% to about 80% or between about 10% to about 70% or between about 10% to about 60% or between about Between 10% to about 50% or between about 10% to about 40%, comprise anyon scope and any intermediate value betwixt. The amount that it would be recognized by those skilled in the art that the coloring agent of the gross weight of Multi-layer microcapsule is by weight percentage.

Some in any embodiment described herein, described microcapsule contain only a type of pigment or two kinds or The mixture of above pigment, can the most packed and/or one or more the mixture of coloring agent can be encapsulated in In the core of bilayer or Multi-layer microcapsule.Skilled artisan would know how that the combination selecting pigment and pigment is with described A desired color effects is produced on skin.

Constituent containing coloring agent:

One side according to some embodiments of the present invention, it is provided that a kind of constituent, including multiple microcapsules, at least one Part multiple microcapsules be Multi-layer microcapsule, Multi-layer microcapsule include one in core microcapsule, described interior core microcapsule includes: extremely A few coloring agent and one first housing, described first housing includes: one first wall formation polymeric material, encapsulates described core Portion；And one or above shell, encapsulate described interior core microcapsule, as described by any embodiment in described herein. Such constituent is herein also referred to as containing coloring agent constituent or color constituent.

In certain embodiments, in constituent at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, at least 98% or at least 99% or complete Multiple microcapsules in portion are the microcapsules containing coloring agent, described by any one of embodiment as described herein.

" constituent " used herein refers to multiple microcapsule, and it can be same or different, when difference, and can To have multiple feature or various features.According to the multiple embodiment of the present invention, multiple microcapsules represent this at least partially The all technical characteristic of bright microcapsule, any one of embodiment, such as there are at least two shells, encapsulate a coloring Agent, include a soap, include a dispersant, skin is rupturable and is lighttight during friction.

Term " at least partially " refers at least 20%, at least 50%, at least 70%, at least 60%, at least 80%, at least 90%, at least 95%, at least 98%, at least 99% or all of microcapsule is multilamellar and the microcapsule containing color, as appointed herein Described in meaning embodiment.

In certain embodiments, described herein as described in constituent as described in can be identical containing coloring agent microcapsule Or can be differently configured from packed coloring agent within it and/or by including the wall formation polymeric material of described housing Quantity or the another one of kind.

In an at least some of or part for multiple microcapsules of constituent provided herein, described toner can be phase With or different, and/or described microcapsule can be encapsulated in the mixture of coloring agent of its core.

In relating to some embodiments of constituent of the present invention, particularly relate to multiple microcapsules in constituent Part, it represents the combination of multiple technical characteristics of Multi-layer microcapsule of the present invention.Each microcapsule can containing a coloring agent or One mixture of two or more coloring agent.In some other embodiments, the microcapsule containing a coloring agent can with contain The capsule of one mixture of other coloring agent or multiple coloring agent mixes in described color constituent.

Every kind of microcapsule as herein described can in any combination, and with as described herein for containing phase jljl Each embodiment of preparation/compositions be used together.

In some exemplary embodiments of the present invention, one second wall formation material includes: quantity is being situated between by weight Magnesium stearate in the range of the 1.0% to 2.0% of the gross weight of described microcapsule；Quantity is by weight between described micro-glue Titanium dioxide in the range of the 30.5% to 75% of the gross weight of capsule；And quantity is by weight in the gross weight between described microcapsule 4% to 6% in the range of dispersant (such as, the isopropyl myristate of propylene glycol stearate).

In some exemplary embodiments, Multi-layer microcapsule as described herein is packaged with a coloring agent, described coloring agent For ferrum oxide, iron sesquioxide and/or ferroso-ferric oxide, and include a wall formation material, its individually include acrylate/ Ammonio methacrylate copolymer or the combination of the cellulose esters with such as cellulose acetate.

In some example embodiment, Multi-layer microcapsule as described herein includes: quantity is by weight between about 30% A coloring agent to 50% or include the multiple internal microcapsule of a coloring agent；Quantity is by weight between about 10% to 30% One wall formation polymer or copolymer；Quantity by weight between 0.5% to 1% magnesium stearate；Quantity is situated between by weight In the titanium dioxide of 25% to 50%；And quantity by weight between 1% to 6% isopropyl myristate.

In some exemplary embodiments, including constituent of the present invention microcapsule be double-deck micro-glue at least partially Capsule, it includes the titanium dioxide as light tight material, and quantity is by weight between about 30% to 45%, and described wall is formed Include with material: acrylate/ammonio methacrylate copolymer is (such asRSPO), total amount is about by weight 10% to 30% and quantity be the magnesium stearate of 1%, and internal microcapsule includes a metal-oxide coloring agent, is selected from Ferroso-ferric oxide (black), ferrum oxide (yellow) and iron sesquioxide (red), its quantity is total capsule weight by weight 36% to 45%.Example 1 describes and includes the exemplary containing red constituent of these constituents.

In some exemplary embodiments, at least some of microcapsule being included in constituent of the present invention is double-deck micro-glue Capsule, comprising: acrylate/ammonio methacrylate copolymer, quantity is about 14.5% by weight；Titanium dioxide, quantity with Weight is calculated as about 41%；Iron sesquioxide, quantity is about 36% by weight, and farther includes described plasticizer: citric acid Triethyl (triethyl citrate), quantity is 4.5% by weight.Example 3 and 4 is respectively described containing yellow and containing black group Become thing.

In some exemplary embodiments, at least some of microcapsule being included in constituent of the present invention is red, yellow Color and black containing color constituent, it includes that bilayered microcapsule, described bilayered microcapsule include described dispersant: myristic acid is different Propyl ester, quantity is 3.0% by weight.

In some exemplary embodiments, Multi-layer microcapsule as described herein includes: quantity is by weight between described One coloring agent of about the 10% to 30% of the gross weight of constituent or include the multiple internal microcapsule of a coloring agent；Quantity is with weight Count between described constituent gross weight about 5% to 15% wall formation polymer or a copolymer；Quantity is situated between by weight In described constituent gross weight 1% to 2% magnesium stearate；Quantity by weight between described constituent gross weight 30% To the titanium dioxide of 75%；And quantity by weight between described constituent gross weight 4% to 6% propylene glycol stearic acid Ester.

In some exemplary embodiments, the microcapsule being included in constituent of the present invention is double-deck micro-at least partially Capsule, it includes the titanium dioxide as light tight material, and quantity is by weight between about 30% to 75%, and described wall shape One-tenth material includes: acrylate/ammonio methacrylate copolymer is (such asRSPO) with the group of ethyl cellulose Close, quantity be about by weight 5% to 15% and quantity be the magnesium stearate of 2%, and internal microcapsule includes a metal oxygen Compound coloring agent, selected from ferroso-ferric oxide (black), ferrum oxide (yellow) and iron sesquioxide (red), its quantity is with weight It is calculated as the 10% to 30% of total capsule weight.Example 8-10 and 12 describe include these constituents one exemplary containing colour cell become Thing.

In some exemplary embodiments, the microcapsule being included in constituent of the present invention is double-deck micro-at least partially Capsule, it includes the titanium dioxide as light tight material, and quantity is by weight between about 70% to 75%, and described wall shape One-tenth material includes ethyl cellulose, quantity be about by weight 5% to 10% and quantity be the magnesium stearate of 2%, and interior Portion's microcapsule includes a blue colorant, and its quantity is the 10% to 15% of total capsule weight by weight.Example 11 describes bag Include the exemplary containing color constituent of these constituents.

In some exemplary embodiments, the microcapsule being included in constituent of the present invention be at least partially include double Microcapsule containing redness, yellow, blueness, green and/or the constituent of black, wherein said second wall formation material bag Including or be made up of cellulose acetate, and comprising dispersant: propylene glycol stearate, its quantity is microcapsule gross weight by weight The 4% to 6% of amount.

Manufacture method:

It is according to U.S. Patent number US6,932,984 for preparing the preparation method of present invention microcapsule as described herein Seal with the described microcapsule disclosed by patent publication No. WO2012/156965 of US7,838,037 and World Intellectual Property Organization Dress solvent minimizing technology (microencapsulation solvent removal method), is incorporated to by way of reference, As illustrated the most completely.According to this technology, active component is present in the core of microcapsule.This technology is by each micro-cladding (micro-capped) composition seals to avoid chemistry and cross-linking reaction (cross-link), degraded, variable color or was producing Loss in efficiency in journey, for the storage time extended.Described solvent minimizing technology is based on following four key step, as Lower described:

I () prepares a homogenizing organic solution, including described encapsulants, a wall formation polymeric material, a light tight thing Matter, a plasticizer and a water section misci-ble organic solvents；

(ii) emulsion of the preparation aqueous continuous phase containing emulsifying agent, and described aqueous continuous phase is that use is described organic molten The identical organic solvent of liquid and formed saturated；

(iii) described homogenizing organic solution is mixed mutually with described water-based emulsion, under high shear is stirred, thus form one Plant many constituents emulsion；And

(iv) by the water of a quantity is joined in the emulsion formed in step (iii), to cause from described emulsion Extract described organic solvent, thus obtain microcapsule.

As at U.S. Patent number US7,838,037 are taught, by first adjusting the list formed according to step (i)-(iv) The surface of microcapsule, is then dispersed in organic solution together with wall formation material when kernel microcapsule, makes surface modification Interior core microcapsule experience one or the circulation of above step (i)-(iv), to form double-deck and three microcapsules.

But, in some embodiments of the method after described adjustment provided herein, described interior core microcapsule is with described Light tight material, such as titanium dioxide, is dissolved or dispersed in continuous water-based emulsion.It addition, by soap such as magnesium stearate Join in organic solution.By being transferred in aqueous phase by titanium dioxide, and in organic solution, add magnesium stearate, to obtain Bilayer and three microcapsules, wherein titanium dioxide is evenly coated with outer polymer shell, thus provides for interior core microcapsule and cover Cover layer.Therefore, in certain embodiments, can be carried out by the solvent removal method after adjusting according to the Multi-layer microcapsule of the present invention Preparation, comprises the following steps:

A () makes one first organic facies contact one first aqueous continuous phase, thus obtain and reassemble into emulsion, wherein one first more Described first organic facies include one second wall formation polymer or copolymer, a soap, a selective dispersant and One first water section misci-ble organic solvents, described first aqueous continuous phase is to utilize described organic solvent to form saturated and bag Including an emulsifying agent, a light tight material and/or multiple Single-layer microcapsules, the plurality of Single-layer microcapsules respectively includes: a coloring agent Or a mixture of multiple coloring agent；And one first wall formation agent, thus obtain constituent emulsion more than one first；

In further step, after step (b), separate the plurality of microcapsule, and be dried and sieve the plurality of micro- Capsule, thus obtain a free flowing powder of the plurality of microcapsule.

These steps are further described below:

In step (a) homogeneous solution of preparation be achieved in that miscible with water section and can dissolve or point Dissipate in the organic solvent of described wall formation polymer, preparation any one described wall formation polymeric material as described herein The organic solution of material or dispersion.In the exemplary embodiment, described organic solvent is a kind of to be can be used for topical applications by core Organic solvent, such as but not limited to ethyl acetate, ethanol, Ethyl formate or its any combination.In some embodiments, organic Solvent is ethyl acetate.

Described by any one in described soap each embodiment as described herein.One optional dispersant is such as this Described by any one in each embodiment described in literary composition.

When using a plasticizer, be generally selected from triglyceride (tricaprylin), trilaurin (trilaurin), three Tripalmitin (tripalmitin), glyceryl triacetate (triacetin), triethyl citrate (triethyl citrate), acetyl Fructus Citri Limoniae Triethylenetetraminehexaacetic acid ester (acetyltriethyl citrate), paraffin oil (paraffin oil) or its combination in any.

Until a homogenizing, the solution of selectivity printing opacity obtains the constituent of organic solution described in ability mixed/stirred.

The organic solvent that described first aqueous continuous phase forms organic solution is formed saturated, and generally comprises emulsifying Agent, described light tight material and Single-layer microcapsules contain: a coloring agent or the mixture of multiple coloring agent；And one first wall formed With material (interior core microcapsule, as described herein).Arbitrary in described light tight material as described herein each embodiment Individual described.In the preferred embodiment, light tight material is titanium dioxide.The most described internal single portion microcapsule can pass through Known solvent minimizing technology obtains, such as at U.S. Patent number US6, described in 932,984.

Organic solution and the first aqueous continuous phase are mixed under low sheraing stirs, thus forms many constituents emulsion.

In step (b), adding a certain amount of water in step (a) in many constituents emulsion of preparation, thus extraction has Machine solvent also makes bilayered microcapsule be formed.

If needing three layers or the microcapsule of other multilamellars, use one second, third etc. organic facies and aqueous continuous Repeating step (a) and (b) mutually, wherein said organic solvent can be identical or different, described wall formation material, institute It can be same or different for stating plasticizer with described light tight material, described soap and described dispersant.

In the context of the embodiment of the present invention, term " low sheraing stirring (low sheer stirring) " refers to 100-800 the most per minute turns mixing under (rpm), preferably turns (rpm) at 200-600 the most per minute.

The composition used in some exemplary embodiments, described manufacture method includes acrylate/ammonium methacrylate The wall of copolymer formed with polymer, the water section misci-ble organic solvents of ethyl acetate, the dispersant of isopropyl myristate, The soap of magnesium stearate and the light tight material of titanium dioxide.

In other embodiments of some of method after adjustment provided herein, described interior core microcapsule and light tight thing Matter such as titanium dioxide is dissolved or dispersed in described organic facies, and is also added to organic molten by soap such as magnesium stearate In liquid.These embodiments preferably relate to being included in one or above shell (such as second and/or outmost housing) The microcapsule of cellulose acetate.Inventor it has been proved that by use cellulose acetate as wall formation polymer One of material, when comprising light tight material such as titanium dioxide in organic facies, it is thus achieved that the opaqueness of improvement so that is being obtained In the bilayer obtained and three-decker, titanium dioxide is coated with outer polymer shell equably, thus inwardly core microcapsule offer is covered Cover layer.Therefore, in certain embodiments, can be prepared by modified solvent minimizing technology according to the Multi-layer microcapsule of the present invention, Said method comprising the steps of:

A () makes one first organic facies contact one first aqueous solution, thus obtain and reassemble into emulsion, Qi Zhongsuo more one first State the first organic facies and include one second wall formation polymer or copolymer, a soap, a light tight material and containing having The Single-layer microcapsules of one mixture of toner or multiple coloring agent, a selective dispersant and a plasticizer and one first water Partial miscibility organic solvent, described first aqueous solution is to utilize described organic solvent formed saturated and be typically include one Emulsifying agent；

These steps are further described below:

In step (a) homogeneous solution of preparation be achieved in that miscible with water section and can dissolve or point In the organic solvent of scattered described second wall formation polymer, preparation one second wall of any one as described herein is formed to use and gathers The organic solution of laminate material or dispersion.In the exemplary embodiment, described organic solvent is that one be can be used for external by core The organic solvent of application, such as but not limited to ethyl acetate, ethanol, Ethyl formate or its any combination.In some embodiments In, organic solvent is ethyl acetate.

Described light tight material is as described in this article described by any one in each embodiment.At preferred embodiment In, described light tight material is titanium dioxide, optionally combines boron nitride.Described internal single portion microcapsule can be by The solvent minimizing technology known obtains, such as at U.S. Patent number US6, described in 932,984.

The organic solvent that described first aqueous continuous phase forms organic solution is formed saturated, and generally comprises emulsifying Agent.Organic solution and the first aqueous continuous phase are mixed under low sheraing stirs, thus forms many constituents emulsion.

The further step of these embodiments is described above.

Exemplary microcapsules and constituent:

In some exemplary embodiments, Multi-layer microcapsule as described herein encapsulates and includes a wall formation material, It individually includes acrylate/ammonio methacrylate copolymer, or the combination of the cellulose esters with such as cellulose acetate.One In a little example embodiment, Multi-layer microcapsule as described herein includes multiple internal microcapsule, and quantity is by weight between about The multiple internal microcapsule including an activating agent of 30% to 50%；Quantity by weight between about 10% to 30% a wall shape One-tenth polymer or copolymer；Quantity by weight between 0.5% to 1% magnesium stearate；Quantity is by weight between 25% To the titanium dioxide of 50%；And quantity by weight between 1% to 6% isopropyl myristate.

In some exemplary embodiments, including constituent of the present invention microcapsule be double-deck micro-glue at least partially Capsule, it includes the titanium dioxide as light tight material, and quantity is by weight between about 30% to 45%, and described wall is formed Include with material: acrylate/ammonio methacrylate copolymer is (such asRSPO), total amount is about by weight 10% to 30%, quantity be 1% magnesium stearate and internal microcapsule include an activating agent, its quantity is total glue by weight The 36% to 45% of capsule weight.

In some exemplary embodiments, at least some of microcapsule being included in constituent of the present invention is to include bilayer The constituent of microcapsule, described bilayered microcapsule includes described dispersant: isopropyl myristate, quantity is by weight 3.0%.

In some exemplary embodiments, Multi-layer microcapsule as described herein includes: quantity is by weight between described One activating agent of about the 10% to 30% of the gross weight of constituent；Quantity by weight between described constituent gross weight about 5% To wall formation polymer or a copolymer of 15%；Quantity by weight between described constituent gross weight 1% to 2% Magnesium stearate；Quantity by weight between described constituent gross weight 30% to 75% titanium dioxide；And quantity is with weight Count between described constituent gross weight 4% to 6% propylene glycol stearate.

In some exemplary embodiments, the microcapsule being included in constituent of the present invention is double-deck micro-at least partially Capsule, it includes the titanium dioxide as light tight material, and quantity is by weight between about 30% to 75%, and described wall shape One-tenth material includes: acrylate/ammonio methacrylate copolymer is (such asRSPO) with the group of ethyl cellulose Close, total amount be about by weight 5% to 15% and quantity be the magnesium stearate of 2%, and internal microcapsule, its quantity is with weight Amount is calculated as the 10% to 30% of total capsule weight.

In some exemplary embodiments, the microcapsule being included in constituent of the present invention is double-deck micro-at least partially Capsule, it includes the titanium dioxide as light tight material, and quantity is by weight between about 70% to 75%, and described wall shape One-tenth material includes ethyl cellulose, total amount be about by weight 5% to 10% and quantity be the magnesium stearate of 2%, and interior Portion's microcapsule, its quantity is the 10% to 15% of total capsule weight by weight.

In some exemplary embodiments, the microcapsule being included in constituent of the present invention be at least partially include double Microcapsule containing color constituent, wherein said second wall formation material includes or is made up of cellulose acetate, and comprising Dispersant: propylene glycol stearate, its quantity is the 4% to 6% of microcapsule gross weight by weight.

Manufacture method:

A () makes one first organic facies contact one first aqueous continuous phase, thus obtain and reassemble into emulsion, wherein one first more Described first organic facies include one second wall formation polymer or copolymer, a soap, a selective dispersant and One first water section misci-ble organic solvents, described first aqueous continuous phase is to utilize described organic solvent to form saturated and bag Including an emulsifying agent, a light tight material and/or multiple Single-layer microcapsules, the plurality of Single-layer microcapsules respectively includes: one or with On color agent；And one first wall formation agent, thus obtain constituent emulsion more than one first；

These steps are further described below:

The organic solvent that described first aqueous continuous phase forms organic solution is formed saturated, and generally comprises emulsifying Agent, described light tight material and Single-layer microcapsules contain: a coloring agent or the mixture of multiple coloring agent；And one first wall formed With material (interior core microcapsule, as described herein).

Described by any one in described light tight material each embodiment as described herein.In preferred embodiment In, light tight material is titanium dioxide.

The most described internal single portion microcapsule can be obtained by known solvent minimizing technology, such as in United States Patent (USP) Described in number US6,932,984.

A () makes one first organic facies contact one first aqueous solution, thus obtain and reassemble into emulsion, Qi Zhongsuo more one first State the first organic facies include one second wall formation polymer or copolymer, a soap, a light tight material and contain one The Single-layer microcapsules of individual or above color agent, a selective dispersant and a plasticizer and one first water section compatibility Organic solvent, described first aqueous solution is to utilize described organic solvent formed saturated and be typically include an emulsifying agent；

These steps are further described below:

Described light tight material is as described in this article described by any one in each embodiment.At preferred embodiment In, described light tight material is titanium dioxide, optionally combines boron nitride.

Described internal single portion microcapsule can be obtained by known solvent minimizing technology, such as at U.S. Patent number Described in US6,932,984.

The further step of these embodiments is described above.

External preparation (topical formulation):

In certain embodiments, constituent provided herein is for cosmetics, medicine adornment or pharmaceutical preparation, such as skin care formulation (skin care formulations), cosmetics (make-up) or dermatologic (dermatological) or other outside With pharmaceutical preparation (topical pharmaceutical formulations), comprise microcapsule as described herein (such as originally Color constituent described in literary composition).Described preparation is selectable and preferably farther includes a carrier, and optional includes volume Outer activating agent and/or additive.

As used herein " preparation (formulation) " refers to the forms such as Emulsion, emulsion, cream, gel, powder Carrier, comprises the microcapsule Han coloring agent as described herein, has physiologically acceptable carrier (carriers) and figuration Agent (excipients), constituent (compositions) and selectivity other chemical compositions (chemical Components), that such as make up, medicine adornment or the agent (such as medicine) of medicine.

" physiologically acceptable " refers to be ratified by federal or administrative organization of state government as the term is employed herein Or it is listed in American Pharmacopeia (Pharmacopeia) or other pharmacopeia that It is generally accepted, on animal, and particularly It is for the mankind.

Phrase " carrier being physiologically suitable for " refers to approved carrier or a diluent herein, will not be to organism Cause significant stimulation and biological activity and the character of possible activating agent will not be eliminated.

Here " excipient (excipient) " refers to the inert substance joining in pharmaceutical compositions, to promote further Enter the manufacture method of active component and use.

In some embodiments of the invention, cosmetics or medicine adornment preparation are formulated into a form, are suitable to using of external On region.

By selecting suitable carrier and other compositions selectable, it can be included in described constituent, as below Middle detailed description, the constituent of the present embodiment can be commonly used to external use to be configured to any form.

Described preparation can be aqueous (water-based), (oil-based) of oiliness or silicon matrix (silicon-based)。

Preparation e.g. skin-protection product, cosmetic product (can include eye shadow, cosmetics, lipstick, lip honey as described herein (lacquer) etc., or any other products as herein described).

In certain embodiments, the form that described preparation is is cream (cream), ointment (ointment), paste (paste), gel (gel), emulsion (lotion), breast (milk), oil (oil), suspension (suspension), solution (solution), aerosol (aerosol), spraying (spray), foam (foam), powder (such as, pressed powder or loose powder End) or mousse (mousse).

Ointment (ointments) is semi-solid prepared product, it is common that based on mineral fat (petrolatum) or oil spread out Biological.The optimal delivery of the active substance of the particular formulations that concrete ointment base is used to provide for, and it is preferably provided Its desired characteristic (such as skin moistening effect).When using with other carriers or medium, ointment base should be inert, stable , nonirritant and without sensitization.As at Remington: the science of pharmacy and put into practice (The Science and Practice of Pharmacy), the 19th edition, Easton, Pa., Mack publishing company (Mack Publishing Co), 1995 Year, explained for page 1399 to page 1404: ointment base can be divided into four classes: oleaginous base (oleaginous bases), Emulsible substrate (emulsifiable bases), emulsion matrix (emulsion bases) and water-soluble base (water- soluble bases).For example, oil-containing ointment base includes vegetable oil, the fat that obtains from animal, obtains from oil Semisolid and hydrocarbon.Emulsible ointment base is also referred to as the ointment base of absorbability, containing a small amount of or the most aqueous, and wraps Include, such as sulphuric acid hydroxy stearate (hydroxystearin sulfate), anhydrous lanolin (anhydrous lanolin) and parent Aqueous mineral fat (hydrophilic petrolatum).Emulsion ointment base is oil-in-water (water-in-oil, W/O) emulsion Or Water-In-Oil (oil-in-water, O/W) emulsion, and such as include spermol (cetyl alcohol), glycerol monostearate Ester (glyceryl monostearate), lanoline (lanolin) and stearic acid (stearic acid).Preferably water solublity Ointment base is to be prepared by the Polyethylene Glycol (polyethylene glycols) of different molecular weight.

Emulsion (lotion) is the prepared product being applied to skin surface and reducing friction.Emulsion (lotion) is typically liquid Body or semi-liquid preparations, wherein solid particle (including the microcapsule containing sunscreen) is present in water or alcohol substrate.Due to easily In applying more fluidised form constituent, emulsion (lotion) is typically to be preferably used in and covers/protect vast body region.Emulsion It is typically the suspension of solid, and often comprises water-in-oil type (oil-in-water) liquid oil emulsion.By emulsion (lotion) insoluble substance in carries out in small, broken bits being commonly necessary.Emulsion (lotion) usually contains suspending agent to produce more Good dispersion (dispersion) effect, and for activating agent being fixed and keeping and contact skin, such as methylcellulose (methylcellulose), the useful compound such as sodium carboxymethyl cellulose (carboxymethyl-cellulose).

Cream (cream) is viscous liquid or semisolid emulsion (emulsions), for oil-in-water (water-in-oil；W/ Or Water-In-Oil (oil-in-water O)；O/W).Cream (cream) substrate typically can be washed with water, and containing oil phase (oil Phase), emulsifying agent (emulsifier) and aqueous phase (aqueous phase).Oil phase is also referred to as " internal " phase, typically by ore deposit Thing fat (petrolatum) and/or fatty alcohol (fatty alcohol), such as spermol (cetyl alcohol) or stearyl alcohol (stearyl alcohol).Aqueous phase generally (although non-must) exceedes the volume of oil phase, and usually contains wetting agent (humectant).Emulsifying agent in cream formulation is typically nonionic (nonionic), anionic (anionic), sun Ion (cationic) type or amphoteric surfactant (amphoteric surfactant).It is referred to Remington: medicine Learn science and put into practice (The Science and Practice of Pharmacy) to obtain more information.

Paste (paste) is semisolid dosage form, during wherein bioactivator is suspended in suitable matrix.Depend on the spy of substrate Property, paste is divided into fat paste (fatty paste) or by single phase aqueous gel (single-phase aqueous Gels) paste made by.The substrate of fat paste is typically mineral fat (petrolatum), hydrophilic mineral fat (hydrophilic petrolatum) etc..From the paste that single phase aqueous gel (single-phase aqueous gels) is prepared Agent is routinely incorporated into carboxymethyl cellulose (carboxymethylcellulose) or the like as its substrate.Additionally can join Examine the science of Remington: pharmacy and to put into practice (The Science and Practice of Pharmacy) more to obtain Information.

Gel (gel) preparation is semisolid suspension-type systems.Single-phase gels contains organic macromolecule (organicmacromolecules) it is uniformly distributed in whole carrier liquid (typically aqueous matrix), and preferably contains There are alcohols and optional oils.Preferably organic macromolecule (i.e. gellant) is the acrylate copolymer of crosslinking, thus as card The family of ripple nurse polymer (carbomer polymers), the poly-alkylene of such as carboxyl (carboxypolyalkylenes), it can With at trade mark Carbopol^TMUnder buied by commercial sources.The most other type of preferred polymers is hydrophilic Polymer.Such as polyethylene oxide (polyethylene oxides), Pluronic F68 (polyoxyethylene-polyoxypropylene copolymer) and polyvinyl alcohol (polyvinylalcohol)；Fiber Element polymer (cellulosic polymer), such as hydroxypropyl cellulose (hydroxypropyl cellulose), ethoxy Cellulose (hydroxyethyl cellulose), hydroxypropyl methyl cellulose (hydroxypropyl Methylcellulose), hydroxypropylmethyl cellulose phthalate (hydroxypropyl methylcellulose And methylcellulose (methyl cellulose) phthalate)；Resin such as tragakanta (tragacanth) and xanthan gum (xanthan gum), sodium alginate (sodium alginate) and gelatin (gelatin).In order to prepare uniform gel, permissible Add dispersant (dispersing agents) such as alcohols or glycerol, or gellant (gelling agents) can pass through Grind, mechanical mixture or stirring or a combination thereof and disperseed.

Spray (sprays) generally provides activating agent in aqueous and/or alcohol solution, is delivered to being atomized shape Skin.Spray includes that those preparations to provide the activator solution of concentration to site of administration after delivery, such as, are sprayed easily Can be made up of alcohols or other similar volatile liquids, active substance is dissolvable in water wherein.When being delivered on skin, carrier steams Send out and stay the activating agent of concentration in site of administration.

Foam component (foam compositions) is general with single-phase or multi-phase fluid form, and is contained in a conjunction In suitable container, selectively with a kind of propellant (propellant) to promote constituent to discharge from container, thus executing Added-time converts it into foam.Other formation of foam technology includes, such as " bucket inner bag (bag-in-a-can) " preparation technique.Cause This constituent being configured usually contains a lower boiling hydrocarbons (hydrocarbon), such as isopropyl alkane (isopropane).At body The using and stir and cause the evaporation of isopropyl alkane to produce foam of described constituent under temperature, its mode is similar to pressurized aerosol foam system System (pressurized aerosol foaming system).Foam can be water-based or water alcohol, but is typically formulated There is high alcohol content, evaporate rapidly time on the skin being applied to a user, driven to therapentic part by upper skin layer Dynamic active component.

The prepared product of described preparation can be homogenized all the components by mixing, except described containing coloring agent microcapsule, The microcapsule Han coloring agent, subsequently mixture described in low shear mixing is added at the end of.

The Multi-layer microcapsule of the present invention can be used on provides external to use in pharmaceutical compositions, it such as includes pharmaceutically active agents Dermatology (dermatological) or percutaneous (transdermal) application.

Any preparation described herein, it may include extra reagent and/or additive.These reagent and/or add Add agent and can be packaged or unpackaged.

In certain embodiments, one or many person of these reagent and/or additive is packed.

In some these embodiments, microcapsule is utilized to encapsulate these reagent and/or additive, such as U.S. Patent number US6, 932,984 and US7,838,037 with patent publication No. WO2009/138978 of World Intellectual Property Organization any one described in.

Some unrestricted representative example of additive (additives) and/or reagent (agents) include wetting agent (humectants), deodorizer (deodorants), antiperspirant (antiperspirants), Sunless tanning agent (sunless Tanning agents), hair conditioner (hair conditioning agents), pH value regulator (pH adjusting Agents), chelating agen (chelating agents), preservative (preservatives), emulsifying agent (emulsifiers), close Suppository (occlusive agents), emollient (emollients), thickening agent (thickeners), solubilizing agent (solubilizing agents), penetration enhancers (penetration enhancers), counter-stimulus (anti- Irritants), coloring agent (colorants), propellant (propellants) and surfactant (surfactants).

The representative example of wetting agent (humectants) includes, but is not limited to guanidine (guanidine), glycolic (glycolic acid) and glycollate (glycolate salts, such as ammonium salt ammonium salt and season alkylammonium salt Alkyl ammonium salt), with various any type of Aloes (aloe vera, such as Aloe gel aloe vera Gel), allantoin (allantoin), urazole (urazole), polyhydroxy-alcohol (polyhydroxy alcohols) are such as Sorbitol (sorbitol), glycerol (glycerol), hexanetriol (hexanetriol), propylene glycol (propyleneglycol), butanediol (butylene glycol), hexanediol (hexylene glycol) etc., Polyethylene Glycol (polyethylene glycols), sugar With starch, sugar and starch derivant (such as alkoxylated glucose alkoxylated glucose), hyaluronic acid (hyaluronic acid), lactamide monoethanolamine (lactamide monoethanolamine), acetamide monoethanolamine (acetamide monoethanolamine) and combination in any thereof.

Suitably pH value regulator (pH adjusting agents) such as includes the adipic acid (adipic of one or many person Acids), glycine (glycines), citric acid (citric acids), calcium hydroxide (calcium hydroxides), magnesium Aluminum metasilicate (magnesium aluminometasilicates), buffer agent (buffers) or its any combination.

The representative example of deodorizer (deodorants) includes, but is not limited to quaternary ammonium (quaternary ammonium) Compound, such as cetyl trimethylammonium bromide (cetyl-trimethylammonium bromide), cetyl chloride pyrrole Pyridine (cetyl pyridinium chloride), rope oronain (benzethonium chloride), diisobutyl benzene oxygen Base oxethyl ethyl dimethyl ammonium chloride (diisobutyl phenoxy ethoxy ethyl dimethyl benzyl Ammonium chloride), N-sodium lauryl sarcosinate (sodium N-lauryl sarcosine), N-bis-palmityl flesh ammonia Acid (sodium N-palmItyl sarcosine), Hamposyl L (lauroyl sarcosine), the sweet ammonia of N-Semen Myristicae Acid (N-myristoyl glycine), potassium N-cocoyl sarcosine (potassium N-lauryl sarcosine), stearyl (stearyl), trimethyl ammonium chloride (trimethyl ammonium chloride), sodium aluminate chlorine hydroxylactic acid (sodium Aluminum chlorohydroxy lactate), three-cetylmethylammonium chloride (tricetylmethyl ammonium Chloride), 2,4,4'-tri-chloro-2'-hydroxy diphenyl ether (2,4,4'-trichloro-2'-hydroxy diphenyl Ether), diaminourea amide (diaminoalkyl amides), such as 1B hexadecyl amide (L-lysine Hexadecyl amide), citrate (heavy metal salts of citrate), salicylate (salicylate) With heavy metallic salt and the acid thereof of Octopirox (piroctose), especially its zinc salt, the heavy metal of pyrrole sulfur (pyrithione) Salt, especially Zinc Pyrithione (zinc pyrithione) and phenol zinc sulfate (zinc phenol sulfate).Other removes Smelly dose includes, but is not limited to odor absorbing material, such as carbonate and bicarbonate, such as alkali carbonate and carbonic acid Hydrogen salt, ammonium and tetra-allkylammonium carbonate and bicarbonate (ammonium and tetraalkylammonium carbonates And bicarbonates), especially sodium salt and potassium salt or above-mentioned combination in any.

Antiperspirant (antiperspirant agents) can mix in the constituent of the present invention, either with dissolve or Particle form, such as and include astringent salts (astringent salts) or the complex of aluminum or zirconium (zirconium) (complex)。

The representative example of Sunless tanning agent (sunless tanning agents) includes and nonrestrictive, dihydroxy Acetone (dihydroxyacetone), glyceraldehyde (glyceraldehyde), indole (indoles) and its derivant.Exempt to shine U.S. Black dose can use with sunscreen composition.

Described chelating agen (chelating agents) is optionally added preparation, to increase keeping quality or preservation system.Excellent The chelating agen of choosing is gentle reagent, such as ethylenediaminetetraacetic acid (EDTA), EDTA derivant (EDTA derivatives) or Its combination in any.

Suitably preservative (preservatives) include, but is not limited to one or more alkanol (alkanols), EDETATE SODIUM (disodium EDTA, ethylenediaminetetraacetic acid ethylenediamine tetraacetate), edta salt (EDTA Salts), EDTA fatty acid conjugate (EDTA fatty acid conjugates), oxazoline ketone (isothiazolinone), P-Hydroxybenzoate (parabens), such as methyl parahydroxybenzoate (methylparaben) and P-hydroxybenzoic acid third Ester (propylparaben), propyleneglycoles (propyleneglycols), sorbate (sorbates), carbamide (urea) Derivant, such as pyrazolidinyl carbamide (diazolindinyl urea) or its combination in any.

Suitably emulsifying agent (emulsifiers) such as includes one or more anhydro sorbitol (sorbitans), alkoxyl Change fatty alcohol (alkoxylated fatty alcohols), alkyl polyglycoside (alkylpolyglycosides), soaps (soaps), alkyl sulfate (alkyl sulfates), monoalkyl and Acidic phosphates salt (monoalkyl and dialkyl Phosphates), alkylsulfonate (alkyl sulphonates), acyl group different sulfur generation (acyl isothionates) or its Combination in any.

Suitably occlusive agent (occlusive agents) such as includes mineral fat (petrolatum), mineral oil (mineral oil), Cera Flava (beeswax), silicone oil (silicone oil), lanoline and oil-soluble lanolin derivative (lanolin and oil-soluble lanolin derivatives), saturated and unsaturated fatty alcohol (saturated And unsaturated fatty alcohols), such as behenyl alcohol (behenyl alcohol), hydro carbons (hydrocarbons), Such as squalane (squalane) and various animal and plant oil, such as almond oil (almond oil), Oleum Arachidis hypogaeae semen (peanut oil), wheat germ oil (wheat germ oil), Semen Lini oil (linseed oil), simmondsia oil (jojoba Oil), Fructus Pruni pit (oil of apricot pits), Semen Juglandis (walnuts), palm nut (palm nuts), pistachio fruit (pistachio nuts), til seed (sesame seeds), the oil (rapeseed) of Semen Brassicae campestris, cade oil (cade oil), Semen Maydis oil (corn oil), Semen Persicae oil (peach pit oil), seed of Papaver somniferum L. powder (poppyseed oil), Oleum Pini (pine Oil), Oleum Ricini oil (castor oil), soybean oil (soybean oil), Avocado Oil (avocado oil), safflower oil (safflower oil), Oleum Cocois (coconut oil), hazelnut oil (hazelnut oil), olive oil (olive oil), Portugal Grape seed oil (grape seed oil) and sunflower seed oil (sunflower seed oil).

Suitably emollient (emollients) such as includes dodecane (dodecane), squalane (squalane), gallbladder Sterin (cholesterol), 2-Methylpentadecane (isohexadecane), isononyl isononanoate (isononyl Isononanoate), PPG ether (PPG Ethers), mineral fat (petrolatum), lanoline (lanolin), safflower oil (safflower oil), Oleum Ricini (castor oil), Oleum Cocois (coconut oil), Oleum Gossypii semen (cottonseed Oil), palm-kernel oil (palm kernel oil), Petiolus Trachycarpi oil (palm oil), Oleum Arachidis hypogaeae semen (peanut oil), soybean oil (soybean oil), polyol carboxylate (polyol carboxylic acid esters) mix with its derivant and its Thing.

Suitably thickening agent (thickeners) such as includes non-ionic water-soluble polymer (non-ionic water- Soluble polymers), such as hydroxyethyl cellulose (hydroxyethylcellulose, commercial commercially available trade (brand) name For Natrosol.RTM.250 or 350), cationic water-soluble polymer (cationic water-soluble polymers), Such as polyquaternary ammonium salt 37 (Polyquat 37, commercial commercially available trade (brand) nameCN), fatty alcohol (fatty Alcohols), fatty acid (fatty acids) and its alkali metal salt and its mixture.

The representative embodiment of the solubilizing agent (solubilizing agents) that can be used on the present invention includes (but not limiting In), the solubilizing agent (complex-forming solubilizing agents) that complex is formed, such as citric acid (citric acid), ethylenediaminetetraacetic acid (ethylenediamine-tetraacetate), Polymeric sodium metaphosphate. (sodium Meta-phosphate), succinic acid (succinic acid), carbamide (urea), cyclodextrin (cyclodextrin), polyethylene Ketopyrrolidine (polyvinylpyrrolidone), diethyl-o-benzoic acid methyl ester (diethylammonium-ortho- And micelle formation solubilizing agent (micelle-forming solubilizers), such as TWEENS and span benzoate) (spans), such as TWEEN 80.Can be used on the generation of other solubilizing agents (solubilizing agents) of the constituent of the present invention Table embodiment, e.g. polyoxyethylene sorbitan fatty acid ester (polyoxyethylene sorbitan fatty Acid ester), polyoxyethylene alkyl ether (polyoxyethylene n-alkyl ethers), alkyl amine n-oxide (n-alkyl amine n-oxides), poloxamer (poloxamers), organic solvent, phospholipid and cyclodextrin (cyclodextrines)。

Suitably penetration enhancers (penetration enhancers) includes, but is not limited to dimethyl sulfoxide (dimethylsulfoxide, DMSO), dimethylformamide (dimethyl formamide, DMF), allantoin (allantoin), urazole (urazole), N,N-dimethylacetamide (N, N-dimethylacetamide, DMA), methyl in the last of the ten Heavenly stems Sulfoxide (decylmethylsulfoxide, C10MSO), polyethylene glycol monolaurate (polyethylene glycol Monolaurate, PEGML), propylene glycol (propyleneglycol, PG), PGML (propyleneglycol monolaurate, PGML), glyceryl monolaurate (glycerol monolaurate, GML), Lecithin (lecithin), 1-substituted azacycloheptan-2-one (1-substituted azacycloheptan-2- Ones), particularly 1-n-dodecane basic ring azacycloheptan-2-one (1-n-dodecylcyclazacycloheptan-2- One, can be from the Virginia Richmond Hui Te trade mark than research company Whitby Research Incorporated Azone^RTMBuy), alcohols and analog.Penetration enhancer is alternatively vegetable oil.This oil such as includes safflower oil (safflower oil), Oleum Gossypii semen (cottonseed oil) and Semen Maydis oil (corn oil).

Suitably counter-stimulus (anti-irritants) such as includes steroidal and non-steroidal anti-inflammatory agent or other material, example Such as Aloe (aloe vera), Flos Chrysanthemi (chamomile), α-bisabolol (alpha-bisabolol), the extraction of cola Fargesia Thing (cola nitida extract), Green tea extract (green tea extract), tea tree oil (tea tree oil), sweet Grass extract (licorice extract), allantoin (allantoin), caffeine (caffeine) or other xanthine (xanthines), glycyrrhizic acid (glycyrrhizic acid) and its derivant.

The most exemplary additional active agent includes, but is not limited to antibiotic agent (antibiotic agent), antibacterial (antimicrobial agent), anti-acne agents (anti-acne agent), anti-ageing Agent (anti-aging agent), wrinkle reducing agent (wrinkle-reducing agent), skin whitening agent (skin Whitening agent), sebum reduce agent (sebum reducing agent), steroidal anti-inflammatory agents (steroidal anti- Inflammatory agent), antibacterial (antibacterial agent), antifungal (antifungal agent), anti- Viral agent (antiviral agent), non-steroidal anti-inflammatory agent (non-steroidal anti-inflammatory), anesthetis (anesthetic agent), antieczematic (antipruriginous agent), antiprotozoan agent (antiprotozoal Agent), antioxidant (anti-oxidant), antitumor agent (antineoplastic agent), immunomodulator (immunomodulator), interferon (interferon), antidepressant (antidepressant), antihistamine (anti Histamine), vitamin, hormone (hormone) and one or many person of dandruff removing agent (anti-dandruff agent), or Combination in any.

These embodiment include alpha-hydroxy acid and ester (alpha-hydroxy acids and esters), beta-hydroxy acid and Ester (beta-hydroxy acids and ester), polyhydroxy acid and ester (polyhydroxy acids and esters), Kojic acid and ester (kojic acid and esters), ferulic acid and Resina Ferulae derivant (ferulic acid and ferulate Derivatives), vanillic acid and ester (vanillic acid and esters), diacid (dioic acids, such as He in the last of the ten Heavenly stems two Azoles acid sebacid and azoleic acids) and ester (esters), retinol (retinol), retinal (retinal), regard Yellow base ester (retinyl esters), hydroquinone (hydroquinone), tertiary butylated hydroquinone (t-butyl hydroquinone), Mulberry Tree extract (mulberry extract), Radix Glycyrrhizae extract (licorice extract) and resorcinol derivatives (resorcinol derivatives)。

Suitable anti-acne agents (anti-acne agents) for the present invention includes, but is not limited to keratolysis Agent, as salicylic acid (salicylic acid), sulfur (sulfur), hydroxyl (glycolic), acetone acid (pyruvic acid), Benzodiazepines (resorcinol) and NAC (N-acetylcysteine) and retinoid (retinoids), Such as tretinoin and derivant (retinoic acid and its derivatives, the such as ester of cis and trans) thereof.

Suitable antibiotic (antibiotics) for the present invention includes, but is not limited to benzoyl peroxide (benzoyl peroxide), Octopirox (octopirox), erythromycin (erythromycin), zinc (zinc), tetracycline (tetracyclin), triclosan (triclosan), Azelaic Acid (azelaic acid) and derivant, phenoxyethanol (phenoxy ethanol) and benzene oxygen propanol (phenoxy proponol), ethyl acetate (ethylacetate), chlorine Lincoln are mould Element (clindamycin) and meclocycline (meclocycline)；Uncommon Sándor Posta (sebostats), such as flavonoid (flavinoids), α and beta hydroxy acid (alpha and beta hydroxy acids) and bile salts (bile salts), example Such as scymnol sulfate (scymnol sulfate) and derivant, dexycholate (deoxycholate) and cholate (cholate)。

Suitable non-steroidal anti-inflammatory agent (non-steroidal anti-inflammatory for the present invention Agents) representative embodiment include, but is not limited to former times health class (oxicams), such as piroxicam (piroxicam), she Rope former times health (isoxicam), tenoxicam (tenoxicam), sudoxicam (sudoxicam) and CP-14304, salicylate (salicylates), such as aspirin (aspirin), salsalate (disalcid), benorylate (benorylate), three willows Acid magnesium choline (trilisate), the general woods of sofa (safapryn), Suo Pulin (solprin), diflunisal (diflunisal), With fendosal (fendosal), acetogenin (acetic acid derivatives), such as diclofenac (diclofenac), fenclofenac (fenclofenac), indomethacin (indomethacin), sulindac (sulindac), Tuo Mei Fourth (tolmetin), Isoxepac (isoxepac), furofenac (furofenac), tiopinac (tiopinac), zidometacin (zidometacin), acemetacin (acematacin), sweet smell are for (fentiazac), zomepirac (zomepirac), clidanac (clindanac) heptan, is disliked because of (oxepinac), felbinac (felbinac) and ketorolac (ketorolac), that acids of sweet smell (fenamates), such as first is gone out (mefenamic), first chlorine fragrant (meclofenamic), fluorine fragrant (flufenamic), nitrogen fluorine go out And tolfenamic acid (tolfenamic acids), propanoic derivatives (propionic acid (niflumic) Derivatives), such as ibuprofen (ibuprofen), naproxen (naproxen), Benoxaprofen (benoxaprofen), fluorine Than ibuprofen (flurbiprofen), ketoprofen (ketoprofen), fenoprofen (fenoprofen), fenbufen (fenbufen), indoprofen (indopropfen), pirprofen (pirprofen), carprofen (carprofen), oxaprozin (oxaprozin), pranoprofen (pranoprofen), miroprofen (), benzene dislike sulfur propanoic acid (tioxaprofen), suprofen (suprofen), alminoprofen (alminoprofen), thiophene ibuprofen (tiaprofenic), and pyrazoles (pyrazoles), such as Phenylbutazone (phenylbutazone), oxyphenbutazone (oxyphenbutazone), feprazone (feprazone), azapropazone And trimetazone (trimethazone) (azapropazone).These non-steroidal anti-inflammatory agents (non-steroidal anti- Inflammatory agents) mixture and Dermatology on the ester of acceptable salt and these reagent be used as.Such as The derivant (flufenamic acid derivative) of etofenamate (etofenamate), fluorine sweet smell acid is in application external Time particularly useful.

The representative example of steroidal anti-inflammatory medicine (steroidal anti-inflammatory agents) includes (but not limiting In) corticosteroid (corticosteroids), as hydrogenation can body pine (hydrocortisone), hydroxyl triamcinolone acetonide can body Pine (hydroxyltriamcinolone), Alpha-Methyl dexamethasone (alpha-methyl dexamethasone), fill in rice Pine-phosphate (dexamethasone-phosphate), beclomethasone dipropionate (beclomethasone Dipropionates), valeric acid clobetasol (clobetasol valerate), desonide (desonide), deoxidation Sai meter Song (desoxymethasone), desoxycortone acetas (desoxycorticosterone acetate), dexamethasone (dexamethasone), dichlorisone (dichlorisone), diflorasone diacetate (diflorasone diacetate), Valerate nerisona (diflucortolone valerate), flurandrenolide (fluadrenolone), flucloronide (fluclorolone acetonide), fluorine hydrogen can body pine (fludrocortisone), flumetasone Pivalates (flumethasone pivalate), Flucinoloni Acetonid (fluosinolone acetonide), fluocinonide (fluocinonide), the pungent butyl ester of fluorine body (flucortine butylesters), fluocortolone (fluocortolone), fluorine sprinkle Buddhist nun determines acetic acid (fluprednidene (fluprednylidene) acetate), fluorine hydrogen hydroxyl dragon (flurandrenolone), breathes out Xi Naide (halcinonide), hydrocortisone acetate (hydrocortisone acetate), hydrocortisone butyrate (hydrocortisone butyrate), methylprednisolone (methylprednisolone), triamcinolone acetonide (triamcinolone Acetonide), can body pine (cortisone), can the many pines of head (cortodoxone), fluorine the west how (flucetonide), fluorine hydrogen Can body pine (fludrocortisone), difluoro Luo Song bis-acetic acid (difluorosone diacetate), fluorine hydrogen hydroxyl dragon (fluradrenolone), fluorine hydrogen can body pine (fludrocortisone), difluoro Luo Song bis-acetic acid (diflurosone Diacetate), fluorine hydrogen hydroxyl Long Annaide (fluradrenolone acetonide), medrysone (medrysone), Anxi are received Expense (amcinafel), Anxi are received all (amcinafide), betamethasone and its ester (betamethasone and the Balance of its esters), chlorine strong body pine (chloroprednisone), chlorine strong body pine acetic acid (chlorprednisone acetate), clocortolone (clocortelone), can beautiful pungent nandrolone (clescinolone), double Chlorine pine (dichlorisone), double fluorine join how (diflurprednate), fluorine chloronaphthalene (flucloronide), flunisolide (flunisolide), fluorometholone (fluoromethalone), fluprednisolone (fluperolone), fluprednisolone (fluprednisolone), hydrogenation can body pine valerate (hydrocortisone valerate), hydrogenation can body DNA releaxed circular DNA penta the third How (hydrocortisone cyclopentylpropionate) but, his beautiful (hydrocortamate), methyl strong body pine of water (meprednisone), Pa Sai meter Song (paramethasone), prednisolone (prednisolone), prednisone (prednisone), beclomethasone dipropionate (beclomethasone dipropionate), triamcinolone , and its mixture (triamcinolone).

Be suitable for pruritus (antipruritic agents) include, but is not limited to methdilazine (methdilazine) and The pharmaceutically acceptable salt of alimemazine (trimeprazine).

The limiting examples of the anesthetis (anesthetic drugs) be applicable to the context of the invention includes benefit Caine (lidocaine), bupivacaine (bupivacaine), chloroprocaine (chlorprocaine), cinchocaine (dibucaine), etidocaine (etidocaine), first croak caine (mepivacaine), tetracaine (tetracaine), reach Cronin (dyclonine), hexylcaine (hexylcaine), procaine (procaine), cocaine (cocaine), chlorine Amine ketone (ketamine), pramoxine (pramoxine) and the pharmaceutically acceptable salt of phenol (phenol).

Be suitable for antimicrobial (antimicrobial agents), including antibacterium, antifungal, protozoacide and Antiviral agent, is included, but is not limited to beta-lactam medicine (beta-lactam by use in the context of the present invention Drugs), quinolone medicine (quinolone drugs), ciprofloxacin (ciprofloxacin), norfloxacin (norfloxacin), tetracycline (tetracycline), erythromycin (erythromycin), amikacin (amikacin), triclosan (triclosan), doxycycline (doxycycline), capreomycin (capreomycin), chlorhexidine (chlorhexidine), chlortetracycline (chlortetracycline), oxytetracycline (oxytetracycline), clindamycin (clindamycin), ethambutol (ethambutol), metronidazole (metronidazole), pentylenetetrazol (pentamidine), gentamycin (gentamicin), kanamycin (kanamycin), Lincomycin (lineomycin), methylene (methacycline), hexamethylenamine (methenamine), minocycline (minocycline), neomycin (neomycin), netilmicin (netilmicin), streptomycin (streptomycin), appropriate cloth Mycin (tobramycin) and miconazole (miconazole).Additionally include quadracycline (tetracycline Hydrochloride), farnesol (farnesol), erythromycin estolate (erythromycin estolate), stearic acid are red Mycin (salt) (erythromycin stearate (salt)), amikacin sulfate (amikacin sulfate), hydrochloric acid strength Mycin (doxycycline hydrochloride), chlorhexidine gluconate (chlorhexidine gluconate), chlorine are own Determine hydrochlorate (chlorhexidine hydrochloride), chlortetracycline hydrochloride (chlortetracycline Hydrochloride), tetramycin hydrochloride (oxytetracycline hydrochloride), Clindamycin Hydrochloride (clindamycin hydrochloride), ebutol (ethambutol hydrochloride), metronidazole hydrochloric acid Salt (metronidazole hydrochloride), hydrochloric acid pentamidine hydrochlorate (pentamidine hydrochloride), Gentamycin sulfate (gentamicin sulfate), kanamycin sulfate (kanamycin sulfate), lincomycin hydrochloride (lineomycin hydrochloride), hydrochloric acid methylene hydrochlorate (methacycline hydrochloride), Wu Luotuo Product hippurate (methenamine hippurate), methenamine mandelate (methenamine mandelate), salt Acid minocycline (minocycline hydrochloride), polygynax (neomycin sulfate), netilmicin (netilmicin sulfate), paromomycin sulfate (paromomycin sulfate), streptomycin sulfate (streptomycin sulfate), tobramycin sulfate (tobramycin sulfate), hydrochloric acid miconazole (miconazole Hydrochloride), his fourth (amanfadine hydrochloride) of hydrochloric acid Oman, his fourth (amanfadine of sulphuric acid Oman Sulfate), triclosan (triclosan), Octopirox (octopirox), parachlorometaxylenol (parachlorometa xylenol), nystatin (nystatin), tolnaftate (tolnaftate) and clotrimazole And mixture (clotrimazole).

The limiting examples of the most useful antioxidant (anti-oxidants) includes Vitamin C Acid (vitamin C, ascorbic acid (vitamin C)) and salt, acid ascorbyl ester (the ascorbyl esters of fatty acid Of fatty acids), ascorbic acid derivates (ascorbic acid derivatives, such as magnesium L-ascorbyl-2-phosphate Salt magnesium ascorbyl phosphate, NAP salt sodium ascorbyl phosphate, anti- Bad hematic acid sorbate ascorbyl sorbate), tocopherol (tocopherol, vitamin E vitamin E), tocopherol mountain Pears acid esters (tocopherol sorbate), tocopheryl acetate (tocopherol acetate), other esters of tocopherol (other esters of tocopherol), butylated hydroxy benzoic acids (butylated hydroxy benzoic Acids) and salt, trolox (6-hydroxy-2,5,7,8- Tetramethylchroma n-2-carboxylic acid, can be with trade name Trolox^RBuy) (commercially available under the trade name Trolox^R)), gallic acid and Arrcostab (gallic acid and thereof Its alkyl esters), especially propylgallate (propyl gallate), carbamide (uric acid) and salt thereof and Arrcostab (alkyl esters), sorbic acid (sorbic acid) and salt thereof, thioctic acid (lipoic acid), amine (amines, Such as N, N-diethyl hydroxylamine N, N-diethylhydroxylamine, amino-guanidine amino-guanidine), sulfhydryl compound (sulfhydryl compounds), such as glutathion (glutathione), the second light industry bureau Fumaric acid (dihydroxy Fumaric acid) and salt, glycine pidolic acid ester (lycine pidolate), glycine pidolic acid ester (glycine pidolate), arginine (arginine pilolate), nordihydroguaiaretic acid (nordihydroguaiaretic acid), bioflavonoids (bioflavonoids), Rhizoma Curcumae Longae (curcumin), lysine (lysine), methionine (methionine), proline (proline), superoxide dismutase (superoxide Dismutase), silymarin (silymarin), tea extraction thing, Pericarpium Vitis viniferae/seed extracts, melanin (melanin) and fan The most fragrant extract (rosemary extracts).

The limiting examples of the most useful " antitumor agent (antineoplastic agents) " Including daunorubicin (daunorubicin), doxorubicin (doxorubicin), idarubicin (idarubicin), the soft ratio of ammonia Star (amrubicin), pirarubicin (pirarubicin), epirubicin (epirubicin), mitoxantrone (mitoxantrone), etoposide (etoposide), teniposide (teniposide), vinblastine (vinblastine), Vincristine (vincristine), ametycin (mitomycin C), 5-FU, paclitaxel (paclitaxel), Taxotere Alcohol (docetaxe), actinomycin D (actinomycin D), colchicine (colchicin), hycamtin (topotecane), irinotecan (irinotecan), gemcitabine cyclosporin (gemcitabine cyclosporin), Verapamil (verapamil), valspodar (valspodor), probenecid (probenecid), MK571, GF120918, LY335979, biricodar (biricodar), terfenadine (terfenadine), quinidine (quinidine), pubescence Folium Cocoe Cry out A (pervilleine A) and XR9576.

The limiting examples of the antidepressant (antidepressants) being usable in the context of the present invention includes NRI (norepinephrine-reuptake inhibitors, NRIs), selectivity serum The suppression of element reuptake inhibitor (selective-serotonin-reuptake inhibitors, SSRIs), monoamine oxidase, MAO Agent (monoamine-oxidase inhibitors, MAOIs), serotonin-and-NRI (serotonin-and-noradrenaline-reuptake inhibitors, SNFIs), thyroliberin discharge The factor (corticotropin-releasing factor, CRF) antagonist (antagonists), adrenoceptor antagonism Agent (α-adrenoreceptor antagonists), NK1-receptor antagonist (NK1-receptor antagonists), 5- HT1A receptor stimulating agent (5-HT 1A-receptor agonist), antagonist and part accelerator and atypia antidepressant Medicine (partial agonists and atypical antidepressants), and norepinephrine reuptake suppression Agent (norepinephrine-reuptake inhibitors, NRIs), such as but not limited to: amitriptyline (amitriptyline), demethyl amitriptyline (desmethylamitriptyline), clomipramine (clomipramine), doxepin (doxepin), imipramine (imipramine), imipramine oxide (imipramine- Oxide), trimeprimine (trimipramine), A Dingnazhi blue (adinazolam), A meter Er are for woods oxide (amiltriptylinoxide), amoxapine (amoxapine), desipramine (desipramine), maprotiline (maprotiline), nortriptyline (nortriptyline), protriptyline (protriptyline), peace miaow how fourth (amineptine), butriptyline (butriptyline), Di Meixi put down for woods (demexiptiline), double benzene breath (dibenzepin), double first Ya Kelin (dimetacrine), many Xi Erping (dothiepin), fluorine Jassy are pungent (fluacizine), Ai Pingduo (iprindole), lofepramine (lofepramine), melitracen (melitracen), U.S. Ta Pamin (metapramine), promise Raleigh handkerchief quick (norclolipramine), that seat can criticize handkerchief for woods (noxiptilin), Europe Rub (opipramol), (perlapine), the replaced woods of skin (pizotyline), ripple skin Xiping (propizepine), Kui are equalled in pula Niu Paming (quinupramine), reboxetine (reboxetine), tianeptine (tianeptine) and serotonin reuptake Inhibitor (serotonin-reuptake inhibitors), such as but do not limit and send general than Nei Dalin (binedaline), m-chloro Pungent (m-chloropiperzine), citalopram (citalopram), duloxetine (duloxetine), Ai Duopairui ketone (etoperidone), femoxetine (femoxetine), fluoxetine (fluoxetine), fluvoxamine (fluvoxamine), Indalpine (indalpine), indeloxazine (indeloxazine), midalcipran (milnacipran), nefazodone (nefazodone), Ou Safula ketone (oxaflazone), paroxetine (paroxetine), Pu Lintan (prolintane), Ritanserin (ritanserin), Sertraline (sertraline), tandospirone (tandospirone), venlafaxine And zimeldine (zimeldine) (venlafaxine).

The exemplary anti-dandruff composition (anti-dandruff agents) that can be used for present invention includes but not limited to, Vancide ZP (zinc pyrithione), leaf rock oil (shale oil) and its derivant, the most sulfonated leaf rock oil (sulfonated shale oil), selenium sulfide (selenium sulfide), sulfur (sulfur)；Salicylic acid (salicylic acid), coal tar (coal tar), povidone iodine (povidone-iodine), imidazoles (imidazoles) Such as ketoconazole (ketoconazole), Dichlorobenzene base are according to the blue (dichlorophenyl of rice big Zuro Dai Oushan Imidazolodioxalan), clotrimazole (clotrimazole), itraconazole (itraconazole), miconazole (miconazole), climbazole (climbazole), tioconazole (tioconazole), sulconazole (sulconazole), cloth Health azoles (butoconazole), fluconazol (fluconazole), miconazole nitrite (miconazolenitrite) and its Any possible stereoisomer and derivant such as anthraline (anthralin), piroctone olamine (piroctone Olamine, Octopirox Octopirox), selenium sulfide (selenium sulfide) and ciclopirox olamine (ciclopirox And its mixture olamine),.

The limiting examples of the most useful vitamin includes vitamin A and the like and derives Thing: retinol (retinol), retinal (retinal), retinyl palmitate (retinyl palmitate), tretinoin (retinoic acid), tretinoin (tretinoin), ((iso-tretinoin) is all known which are retinoid to isotretinoin (retinoids)), vitamin E (tocopherol (tocopherol) and derivant thereof), vitamin C (L-AA (L- Ascorbic acid) and ester and other derivant), vitamin B3 (nicotiamide (niacinamide) and derivant thereof), α hydroxyl Acid (alpha hydroxy acids) is (such as glycolic (glycolic acid), lactic acid (lactic acid), tartaric acid (tartaric acid), malic acid (malic acid), citric acid (citric acid) etc.) and β hydroxy acid (beta hydroxy Acids) (such as salicylic acid (salicylic acid) etc.).

The most useful dermatological active composition (dematologcial active Ingredients) limiting examples includes jojoba oil (jojoba oil) and aromatic oil (aromatic Oils) such as methyl salicylate (methyl salicylate), Ilicis Purpureae (wintergreen), Oleum menthae (peppermint Oil), laurel fat (bay oil), case tree oil (eucalyptus oil) and tangerine oil (citrus oils) and ammonium phenol sulphur Acid (ammonium phenolsulfonate), bismuth alkali formula gallic acid (bismuth subgallate), zinc phenol (zinc And zinc salicylate (zinc salicylate) phenolsulfonate).The limiting examples of antifungal includes miconazole (miconazole), clotrimazole (clotrimazole), butoconazole (butoconazole), fenticonazole (fenticonasole), tioconazole (tioconazole), terconazole (triaconazole) (terconazole), sulconazole (sulconazole), Fluconazol (fluconazole), haloprogin (haloprogin) but, gram more than that frustrates (ketonazole), ketoconazole (ketoconazole), oxiconazole (oxinazole), econazole (econazole), itraconazole (itraconazole), Terbinafine (terbinafine), nystatin (nystatin) and griseofulvin (griseofulvin).

The limiting examples of the most useful hydryllin (antihistamines) includes chlorobenzene That quick (chlorpheniramine), brompheniramine (brompheniramine), dexchlorpheniramine (dexchlorpheniramine), triprolidine (tripolidine), clemastine (clemastine), diphenhydramine (diphenhydramine), promethazine (promethazine), croak piperazine class (piperazines), croak pyridine class (piperidines), astemizole (astemizole), loratadine (loratadine) and terfenadine (terfenadine)。

Anticipated present patent application during the life that maturation is a patent, many relevant coloring agent, wall formation material And development is completed by light tight material, term " coloring agent ", " wall formation polymer " and the scope of " light tight material " are the most pre- Phase can include all this new techniques in advance.

Term " includes (comprises) ", " including (comprising) ", " including (includes) ", " comprise (including) ", " there is (having) " and morphological change refers to " including but not limited to ".

Term " by ... composition (consisting of) " mean " include and be limited to ".

Term " substantially by ... composition (consisting essentially of) " refer to constituent, method Or structure can include extra composition, step and/or some, but only when extra composition, step and/or some not Substantially change the basic of composition required for protection, method or structure and novel characteristics.

Singulative used herein " one (a) ", " one (an) " and " described (the) " include plural reference, unless on The most otherwise expressly specified.Such as, term " compound " or " at least one compound " can include multiple compound, including Its mixture.

In whole the application, various embodiments of the present invention can be presented in a scope.Should be appreciated that with The description of one range format, only because facilitate and succinct, should not be construed as the rigid restriction to the scope of the invention.Therefore, should When think described scope describe specifically disclose all possible subrange and described in the range of single numerical value.Example As, it should think from 1 to 6 scope describe subrange is the most specifically disclosed, such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6 etc., and the single numeral in the range of institute's number, such as 1,2,3,4,5 and 6, scope tube is not the most all for this It is suitable for.

Whenever pointing out numerical range in this article, refer to any numeral (mark or whole quoted in the range of indication Number).Term, the first designation number and the second designation number " between scope " and the first designation number " arrive " the second indicated number Word " scope " is the most interchangeable, refers to include first and second designation number, and all marks therebetween and integer.

Term " percentage by weight (weight percents) " or " being by weight ... % (%by weight) " or " weight Amount % (%wt) " the most interchangeable use.

As the term is employed herein " method (method) " refer to the mode (manner) for completing a particular task, Means (means), technology (technique) and program (procedures), include but not limited to, those modes, means, technology And program, it is known, or from known mode, means, technology or program easily by chemistry, pharmacology, biology, life Change and medical domain practitioner is developed.

As used herein, term " treatment (treating) " includes eliminating, substantially suppressing, slow down or reverse entering of disease Exhibition, substantially improves clinic or the aesthetical symptoms of disease or is essentially prevented from the clinic of disease or the appearance of aesthetical symptoms.

The special characteristic being appreciated that in the present invention, for clarity sake, described in the interior literary composition of separate embodiment, also Can provide in the combination of single embodiment.On the contrary, in the present invention, for brevity, in the interior literary composition of single embodiment Described various features, it is also possible to dividually or with any suitable sub-portfolio or be applicable to any of the present invention Other embodiments described provide.Special characteristic described in the interior literary composition of various embodiments, is not qualified as those The essential feature of embodiment, unless described embodiment does not has those elements the most inoperative.

Various embodiments of the invention mentioned above and that asked with claim item parts and aspect, can be following Embodiment find experiment support.

Multiple examples

Now along with above description with reference to following example, some embodiments of the present invention are described in a non-limiting manner.

Example 1

The preparation bilayered microcapsule containing red stain

Preparation organic facies/masterbatch (Master Batch；MB):

By the most gradually the wall formation polymer of 10 grams: acrylate/ammonio methacrylate copolymer (RSPO) add in the ethyl acetate (ethyl acetate) of 117.4 grams, and stir the mixed of described acquisition Compound is until obtaining a homogenizing and the mixture (about 10 points) of printing opacity, to prepare an organic facies (interchangeably referred to herein as " masterbatch " (MB)).Afterwards the magnesium stearate of a gram it is added in described solution and under agitation reaches about 2 minutes, finally 3 grams Boron nitride add and carry out the stirring of extra 2 minutes.The constituent of described MB is listed in table 1.

Table 1: masterbatch forms part

The preparation of emulsion:

By mixing to prepare an aqueous by the solution (4% polyvinyl alcohol (PVA) of 36.7 grams) of water (550 grams) with 4% Solution, to cause the ultimate density of the PVA in described aqueous phase to be 0.25% by weight.Afterwards, under agitation (450rpm) Add described light tight material: titanium dioxide (TiO₂；41 grams), be first 5 minutes stirring and be extra 8 points of ends afterwards Homogenizing (2500rpm).Ethyl acetate is joined in described aqueous phase, be stirred for up to 2 minutes with 450rpm simultaneously.Afterwards, containing one Red stain (titanium dioxide two ferrum；45 grams) Single-layer microcapsules, referred to herein as " red inner bag (Red Inners) ", it is as existed Prepare (in the case of with or without a plasticizer) described in U.S. patent Nos the 6th, 932,984, gradually joined Described aqueous phase the persistently stirring of 2 minutes.By under the stirring of 450rpm gradually above-mentioned containing described dissolving or scattered The MB (131.4 grams) of polymer joins described ethyl acetate/aqueous emulsion, and is stirred for up to further extra 2 minutes, and this is slightly Capsule is covered by the one of wall formation material further layer or is coated with.The ratio of MB: emulsion (w/w) is 1:3.Described The component of emulsion is shown in Table 2.

Table 2: emulsion (emulsion) composition part

The extraction of organic solvent:

Described spe medium is to put in place in the water of 3796 grams of 10 liters of buckets by above-mentioned emulsion (869.6 grams) being gradually added into Formed, and use a manual pump to be stirred with 150rpm.Described extraction phase stirs further and reaches extra 15 points.Gained Mixture at room temperature settles and reaches about 5 hours.The constituent of described spe medium is as shown in table 3.

Table 3: spe medium forms part

The washing of microcapsule, dried and screened:

The microcapsule that step 1.3 is obtained is to pass through isolated by vacuum filtration.Pouring out supernatant liquid from described bucket, shake is surplus Remaining suspension, and filter afterwards, and rinse precipitate on the filter with the water of 400 milliliters.Described suspension is turned Move on in a drying receptacle, and microcapsule is stored at 4 DEG C.At described drying stage, by microcapsule lyophilization (lyophilizing) Reach 48 hours.

Sieve (sifting) stage described, used automatically cribellum " Ari j-Levy Sifter MIC.300 " to sieve The microcapsule being dried.Microcapsule after sieving is stored in refrigerator in appropriate containers.

Example 2

Preparation contains bilayer and the microcapsule of plasticizer-containing of red stain

Preparation includes interior core microcapsule containing red stain and includes the shell of plasticizer (triethyl citrate) Bilayered microcapsule, it is as described in example 1 above but except the use of plasticizer.

Therefore, by the most gradually wall formation polymer: acrylate/ammonio methacrylate copolymer (RSPO；14.5 grams) add in the ethyl acetate (ethyl acetate) of 117.4 grams, stir simultaneously Until described mixture is homogenizing and printing opacity (about 10 points), to prepare described masterbatch (MB).Then, under agitation by plasticising Agent: triethyl citrate (4.5 grams) joins in described mixture.Afterwards the magnesium stearate of a gram is added in described solution also Under agitation reach about 2 minutes, and finally the boron nitride of 3 grams added and carry out the stirring of extra 2 minutes.

As described in example 1, by the poly-vinyl alcohol solution (PVA 4% by water (550 grams) Yu 4%；36.7 grams), Being the polyvinyl alcohol of 0.25% to reach ultimate density, the most under agitation (450rpm) adds titanium dioxide (41 grams), first Continue stirring in 5 minutes, and the homogenizing (2500rpm) continuing extra 8 minutes afterwards.Add ethyl acetate (65.2 grams afterwards；? Be stirred for up to 2 minutes under 450rpm), and gradually red inner bag (containing described red stain: the micro-glue of monolayer of iron sesquioxide Capsule；36 grams) add.By gradually the MB of described forming step being added under the stirring of 450rpm, and it is stirred for up to further Extra 2 minutes, these microcapsules were covered by the one of wall formation material further layer or are coated with.Described than MB: emulsion (weight Amount/weight) it is 1:3.

The extraction of ethyl acetate and the formation of bilayered microcapsule is carried out as described in example 1, then microcapsule is washed, Dried and screened.The key component of gained microcapsule is shown in Table 4.

Table 4

Example 3

Preparation contains bilayer and the microcapsule of plasticizer-containing of yellow colorants

Bilayered microcapsule is by using yellow iron oxide capsule (yellow inner bag) to carry out as described in top example 1 and 2 Preparation, described bilayered microcapsule includes the interior core microcapsule containing a yellow colorants (ferrum oxide) and a shell, described shell Including a plasticizer (triethyl citrate), described yellow iron oxide capsule is as U.S. patent Nos the 6th, 932,984 Described in be prepared (with or without using under plasticizer) rather than use described red inner bag.Gained microcapsule main Component is shown in Table 5.

Table 5

Example 4

Preparation contains bilayer and the microcapsule of plasticizer-containing of black colorant

Bilayered microcapsule is to be prepared as described in top example 1 and 2, and described bilayered microcapsule includes containing a black Toner (ferroso-ferric oxide) and the interior core microcapsule of a shell, described shell includes a plasticizer (triethyl citrate), simultaneously Using black inner bag, it is as being prepared described in U.S. patent Nos the 6th, 932,984 (with or without using plasticizer Under) rather than use described red inner bag.The key component of gained microcapsule is shown in Table 6.

Table 6

Example 5

Preparation includes the bilayered microcapsule of Semen Myristicae isopropyl propionate and red stain

The inventors have discovered that by comprising Semen Myristicae isopropyl propionate in the wall formation material of bilayered microcapsule (isopropyl myristate；IPM), it is thus achieved that the more soft and microcapsule that is more easily extensible.When putting on skin, contain The microcapsules rupture of IPM easier its inclusions of release.In Exemplary microcapsules, IPM is with about 5 weights of microcapsule gross weight The quantity of amount percentage ratio uses.When described microcapsules rupture, the coloring agent of described cladding is released and uses oiliness IPM to coat, Thus cause more smooth on skin of coloring agent and be uniformly distributed.Therefore Semen Myristicae isopropyl propionate is considered as plasticizer Work with dispersant.

According to example package manufacture method provided herein, being joined by IPM in described masterbatch (MB), cost is by two Titanium oxide is added in described emulsion.

Therefore, in order to prepare containing coloring agent and the microcapsule containing IPM, by the most gradually wall formation being polymerized Thing: acrylate/ammonio methacrylate copolymer (RSPO；14.5 grams) join in ethyl acetate, with In time, stir until described mixture is homogenizing and printing opacity (about 10 points), to prepare described masterbatch.Under agitation by plasticising Agent: triethyl citrate (4.5 grams) adds.Afterwards, the magnesium stearate of a gram it is added in described solution and under agitation reaches About 2 minutes, and finally the boron nitride of 3 grams added and carry out the stirring of extra 2 minutes.

As carried out with described in 2 at example 1, mix the extraction of described emulsion formulations, described MB and the most described organic solvent Take thing.Carry out as described in example 1, carry out the washing of described microcapsule, dried and screened.The key component of gained microcapsule is shown In table 7.

Table 7

Example 6

Preparation includes the bilayered microcapsule of Semen Myristicae isopropyl propionate and yellow colorants

Preparation as described in example 5 up comprises the bilayered microcapsule of interior core microcapsule, and described interior core microcapsule contains: one Yellow colorants (ferrum oxide), as described in example 3；IPM；And a shell, including a plasticizer (triethyl citrate).Gained is micro- The key component of capsule is shown in Table 8.

Table 8

Example 7

Preparation includes the bilayered microcapsule of Semen Myristicae isopropyl propionate and black colorant

Preparation as described in example 5 up comprises the bilayered microcapsule of interior core microcapsule, and described interior core microcapsule contains: one Black colorant (ferroso-ferric oxide), as described in example 4；IPM；And a shell, including a plasticizer.Gained microcapsule main Component is shown in Table 9.

Table 9

Example 8

Preparation includes the micro-glue of double-deck cellulose acetate of red iron oxide (Jia Meilu red (Cameleon Red) microcapsule) Capsule

Preparation organic facies/masterbatch (MB):

By the most gradually the wall formation polymer of 10 grams: cellulose acetate (RSPO) And the most under agitation acrylate/ammonio methacrylate copolymer added in ethyl acetate, and stir the mixed of described acquisition Compound is until mixture is homogenizing and printing opacity.The most under agitation add to act on described herein as IPM in solution and be point The propylene glycol stearate of powder/plasticizer, stir about 5 minutes, it is subsequently adding magnesium stearate (Magnesium Stearate； And stir about 5 minutes MgSt).Then, in mixture, titanium dioxide (TiO is under agitation added₂) about 5 minutes, gained is mixed Compound carries out homogenizing about 8 minutes.Afterwards red inner capsule (Red Inner capsules) (as described in example 1) is existed Stirring is lower to add the most about five minutes.

The constituent of described MB composition is as shown in table 10 below with each quantity.

Table 10: masterbatch forms part

The preparation of emulsion:

It is stirred by adding polyvinyl alcohol (PVA) aqueous solution of 4% in water simultaneously, is subsequently adding the spermaceti of 4% (polyoxyethylene ether (polyoxyethylene ether), as emulsifying for stereth 25 (Ceteareth 25) aqueous solution Agent), it is subsequently adding described aqueous phase: ethyl acetate, stir about 1-2 minute.After above-mentioned MB under the stirring of about 400RPM by Gradually join described emulsion and last up to 2 minutes.It is 1:3 between described masterbatch ratio (w/w) between described emulsion. Described constituent is as shown in table 11 with each quantity of described emulsion.

Table 11: emulsion forms part

Material	Weight (gram)
		Water	808
Polyvinyl alcohol	90
		Ceteareth 25	2.25
Ethyl acetate	100
		MB	333.3

The extraction of organic solvent:

Described spe medium is that (the such as PVA ultimate density in described extract is with 4%PVA aqueous solution by water The PVA of 0.2%) composition.Above-mentioned emulsion is gradually added into the extract put in place at 15 liters of buckets, uses a manual pump to enter with 150rpm Row stirs, and the mixture of gained is stirred reaching extra 15 points.The mixture of gained settles at 25 DEG C and reaches about 24 hours. The constituent of described spe medium is as shown in table 12 with quantity.

Table 12: spe medium forms part

Material	Weight (gram)
		Emulsion	1333.3
Water	4180
		4%PVA solution	144

The washing of microcapsule, dried and screened:

Filter to separate at the microcapsule obtained by centrifugal or vacuum.In centrifugal process, upper phase is in bucket Pouring out (decant), vibration remaining suspension liquid also loads drying receptacle.In filter process, upper strata phase liquid pours out from bucket (decant), the remaining suspension that vibrates then filters, and with the water of 400 milliliters, precipitate is rinsed (rinse) on the filter. Suspension is transferred in drying receptacle.At drying stage, microcapsule carries out lyophilization (lyophilizing) in 48 hours.

In (sifting) stage of sieving, automatic sieving machine " Ari j-Levy Sifter MIC.100 " is used to sieve dry Microcapsule.In microcapsule storage after sieving appropriate containers at room temperature.

Mainly comprising shown in table 13 of the microcapsule of gained.

Table 13

Example 9

Preparation includes that the double-deck cellulose acetate of black iron oxide (Jia Meiluhei (Cameleon Black) microcapsule) is micro- Capsule

By using capsule as internal in the black as shown in example 4 to prepare such as the MB described in example 9.Afterwards, An emulsion, spe medium and manufacture process as described at this paper example 8 is used to include that the bilayer of black inner core is micro-with preparation Capsule.The microcapsule obtained to mainly comprise part as shown in table 14.

Table 14

Example 10

Preparation includes that the double-deck cellulose acetate of yellow iron oxide (yellow (Cameleon Yellow) microcapsule of Jia Meilu) is micro- Capsule

By using capsule as internal in the yellow as shown in example 3 to prepare such as the MB described in example 8.Afterwards, An emulsion, spe medium and manufacture process as described at this paper example 8 is used to include that the bilayer of black inner core is micro-with preparation Capsule.

The microcapsule obtained to mainly comprise part as shown in Table 15.

Table 15

Example 11

Containing ferric ferrocyanide (Ferric Ammonium Ferrocyanide) (barba hispanica), (Jia Meilu is blue in preparation (Cameleon Blue) microcapsule) double-deck cellulose acetate microcapsule

Preparation organic facies/masterbatch (MB) stage:

By the most gradually cellulose acetate add and carry out uniform stirring until described mixture be homogenizing and Printing opacity, to prepare an organic facies (interchangeably referred to herein as " masterbatch " (MB)).Afterwards, under agitation add in solution Enter magnesium stearate (Magnesium Stearate；MgSt) reach about 5 minutes, add boron nitride (Boron Nitrite afterwards； BN) about 5 minutes are reached.Afterwards, titanium dioxide is joined described solution and reaches about 5 minutes, and the mixture obtained is carried out Homogenize and reach about 8 minutes.As prepared at (under with or without plasticizer) described by U.S. patent Nos the 6,932,984th Barba hispanica inner bag (Iron blue inners), is under agitation added to described mixture and reaches about 5 minutes.The composition of described MB composition Thing is as shown in table 16 with each quantity.

Table 16: masterbatch forms part

The preparation of emulsion:

It is stirred by adding polyvinyl alcohol (PVA) aqueous solution of 4% in water simultaneously, is subsequently adding the spermaceti of 4% (polyoxyethylene ether (polyoxyethylene ether), as emulsifying for stereth 25 (Ceteareth 25) aqueous solution Agent), it is subsequently adding described aqueous phase: ethyl acetate, stir about 1-2 minute.After above-mentioned MB under the stirring of about 400RPM by Gradually join described emulsion and last up to 2 minutes.It is 1:3 between described masterbatch ratio (w/w) between described emulsion. Described constituent is as shown in table 17 with each quantity of described emulsion.

Table 17: emulsion forms part

Material	Weight (gram)
		Water	910
Polyvinyl alcohol	90
		Ethyl acetate	100
MB	333.3

The extraction of organic solvent:

Described spe medium is that (the such as PVA ultimate density in described extract is with 4%PVA aqueous solution by water The PVA of 0.2%) composition.Above-mentioned emulsion is gradually added into the extract put in place at 15 liters of buckets, uses a manual pump to enter with 150rpm Row stirs, and the mixture of gained is stirred reaching extra 15 points.The mixture of gained settles at 25 DEG C and reaches about 24 hours. The constituent of described spe medium is as shown in table 18 with quantity.

Table 18: spe medium forms part

Material	Weight (gram)
		Emulsion	1333.3
Water	4178
		4%PVA solution	144

The washing of microcapsule, dried and screened are carried out as described at example 8.

Mainly comprising of the microcapsule obtained is as shown in Table 19.

Table 19

	Material	In terms of gross weight 100 grams
			1	Cellulose acetate	6
2	Magnesium stearate	2
			3	Boron nitride	8.8
4	Titanium dioxide	72
			5	The internal capsule of barba hispanica	11.2

Example 12

The preparation micro-glue of double-deck cellulose acetate containing chrome oxide green (Jia Meilu green (Cameleon Greeen) microcapsule) Capsule

By using the green internal capsule containing chrome oxide green to be prepared, described green as described in example 8 Internal capsule be as described by U.S. patent Nos the 6,932,984th (under with or without plasticizer) and be prepared.Afterwards, An emulsion, spe medium and manufacture process as described at this paper example 8 is used to include that the bilayer of green inner core is micro-with preparation Capsule.

The microcapsule obtained to mainly comprise part as shown in table 20.

Table 20

Example 13

Color detection result (X-Rite)

The microcapsule of the present embodiment is encapsulated red, black or yellow colorants (is called new red capsule herein (RedCap New), new black capsules (Black Cap New) and new yellow capsule (YellowCap New)), and encapsulation institute State identical coloring agent (herein referred as red capsule 1 (RedCap 1), black capsules 1 (Black Cap 1) and yellow capsule 1 (YellowCap 1)) the color of business microcapsule measure and specify, but described business microcapsule is different from the present invention's The method prepared for it described herein of microcapsule, and there is not soap.

Preparation containing microcapsule in accordance with an exemplary embodiment of the invention or business microcapsule as herein described The vision of colour brightness, qualitative compare measurement, all comprise identical coloring agent, as Figure 1-4.

Fig. 1 is show powder containing the commercial microcapsule including being packaged with black, redness or yellow colorants three Ware (ware of top), is referred to as " Ta Gela capsule 1 (TagraCap1) " (black capsules 1 (BlackCap1), red capsule 1 (RedCap1) and yellow capsule 1 (Yellow Cap 1)), and containing include the present invention be packaged with identical black, redness or Three wares (ware of lower section) of the powder of the microcapsule of yellow colorants, respectively as described by example 5,6 and 7.

Fig. 2 shows three to bottle, left containing a basic health cream, described basic health cream includes according to this Brighter embodiments exemplary containing color microcapsule (new yellow capsule (YellowCap New), new red capsule (RedCap New), new black capsules (Black Cap New)), as described in example 5,6 and 7, and in right containing retouching herein The commercial microcapsule (red capsule 1, black capsules 1 and yellow capsule 1) stated.

As clearly visible, containing the powder formulation of the Exemplary microcapsules of with good grounds some embodiments of the present invention in Fig. 1 and 2 Than the preparation containing business microcapsule, particularly comprise red and black colorant preparation the brightest and brighter.

Fig. 3 shows three wares of the powder containing the commercial microcapsule including being packaged with black, redness or yellow colorants (ware of top), is referred to as " Ta Gela capsule 1 (TagraCap1) " (red capsule 1 (RedCap1), black capsules 1 (BlackCap1) and yellow capsule 1 (Yellow Cap 1)), and containing including that the present invention is packaged with identical redness, black Or three wares (ware of lower section) of the powder of the microcapsule of yellow colorants, it is referred to as " good U.S. holiday capsule (CameleonCaps) ", Respectively as described by example 8,9 and 10.

Fig. 4 shows three to bottle, left containing a basic body lotion, described basic health cream includes according to this Brighter embodiments exemplary containing color microcapsule (Jia Meilu red, Jia Meiluhei and Jia Meilu yellow), as in example 8,9 and 10 Described, and right containing commercial microcapsule (red capsule 1, black capsules 1 and yellow capsule 1) described herein.

Fig. 3 and 4 further demonstrates that, the powder formulation ratio of the Exemplary microcapsules containing with good grounds some embodiments of the present invention Containing the preparation of business microcapsule, particularly comprise red and black colorant preparation the brightest and brighter.

Quantitative color is measured, by using CIE color system to use described X-Rite to measure (based on CIE L*a* B* color scale, wherein L* defines brightness, and a* represents red/green value, b* yellow/blue valve).Standard for color measuring Light source is daylight.

By value/data that the three of color visual elements are measured be integrated obtain quantitative color value: tone (hue) (that is, the color-redness of our how perceptive object, orange, green, blue etc.), colourity (chroma) (color fresh Gorgeous or dim, i.e. color and Lycoperdon polymorphum Vitt or the degree of closeness of pure hue) and brightness (lightness) (that is, classification color is light color Or it is dark-coloured).By using these three attribute description color, can accurately identify particular color and by itself and any other face Zone is separately.

For brightness value quantitative shown in the Exemplary microcapsules of the present embodiment and the table 21 and 22 of business microcapsule , and point out this microcapsule brightness relative to commercially available microcapsule intensity deviation (DL*) on brightness scale L* (L*).Table 21 With 22 in the positive DL* value that presents represent, compared with commercially available microcapsule, the microcapsule of the present invention on brightness scale the most more Light, more bright color direction on displacement.

Table 21

Table 22

The data that Fig. 5-7 display obtains in X-rite measures.

Fig. 5 A, 6A and 7A show according to some embodiments of the present invention, obtain containing same colorant from X-rite device Different powder similar photo under the conditions of the visual of shooting, and show powder brighter and brighter containing microcapsule Visual.

Fig. 5 B, 6B and 7B show the reflectivity percentages (R%) shown at different wavelengths and prove according to this The microcapsule containing powder of some bright embodiments obtains the comparison diagram of higher color masking effect.

Example 14

The stability test of gel preparation

In order to evaluate the stability containing color microcapsule of some exemplary embodiments of the present invention, by by carbomer (carbomer) mix with water (carbomer of by weight 1 to 1.5%), and by respectively as described in embodiment 5,6 and 7 Microcapsule (the 3% of total weight of formulation) containing red, yellow or black colorant joins in carbomer gel and mixed, To prepare gel preparation.Preparation is cultivated at least 3 months at 40 DEG C, is stirred with 2500rpm simultaneously.Supervise in the training period Survey the color of gel, and take out gel sample and observe under an optical microscope.Find so observe at least 90% micro- Capsule even still keeps its shape after the cultivation of 3 months, and does not observe the color leakage from microcapsule to gel.

Although the present invention combines its specific embodiment and is described, it is obvious that it is right that many substitutes, revises and changes Will be apparent from those skilled in the art.Therefore, it is intended to include falling into the scope of the appended claims In all replacements, revise and change.

All announcements, patent and the patent application mentioned in this manual is passed through to quote into this theory at this with its entirety In bright book, its degree as each single announcement, patent or patent application specifically and individually indicated and by quote into Herein.Additionally, any list of references that is cited or that point out is not necessarily to be construed as recognizing that these lists of references can be as this The prior art of invention.In the application, title division is used for making this specification easy to understand in this article, and is not necessarily to be construed as Necessary restriction.

Claims

1. a Multi-layer microcapsule, it is characterised in that: described Multi-layer microcapsule includes: core microcapsule in；And at least one shell, Being coated with described interior core microcapsule, wherein said interior core microcapsule includes that a core, described core include a coloring agent, described core It is that the housing being included one first wall formation material is coated with, and described at least one shell includes one second wall formation material Material, a soap and a light tight material.

2. Multi-layer microcapsule as claimed in claim 1, it is characterised in that: described at least one shell also includes a plasticizer.

3. Multi-layer microcapsule as claimed in claim 2, it is characterised in that: described plasticizer is selected from by Fructus Citri Limoniae triethylenetetraminehexaacetic acid Ester, triglyceride, trilaurin, glyceryl tripalmitate, glyceryl triacetate, acetyl triethyl citrate, paraffin oil and combination in any institute group thereof The group become.

4. Multi-layer microcapsule as claimed in claim 2, it is characterised in that: described plasticizer is triethyl citrate.

5. the Multi-layer microcapsule as described in any one of claim 2 to 4, it is characterised in that: the model of a quantity of described plasticizer Enclose be by weight between about 0.5% to about the 10% of the gross weight of described microcapsule or between about 0.5% to about 9.0%, Or between about 1.0% to about 8.0% or between about 1.0% to about 7.0% or between about 1.5% to about 7.0% or about Between 1.5% to about 6.0% or between about 2.0% to about 6.0% or between about 2.5% to about 6.0% or about 3.0% to Between about 6.0% or between about 3.5% to about 6.0% or between about 3.5% to about 5.5% or about 3.5% to about 5.0% Between or be approximately 4.5%.

6. the Multi-layer microcapsule as described in any one of claim 1 to 5, it is characterised in that: described at least one outer layer further includes one Dispersant, it is possible to disperse described coloring agent when putting on skin.

7. Multi-layer microcapsule as claimed in claim 6, it is characterised in that: described dispersant is an esters of a fatty acid.

8. Multi-layer microcapsule as claimed in claim 6, it is characterised in that: the scope of a quantity of described dispersant is between described Between about 0.5% to about the 10% of the gross weight of microcapsule or between about 0.5% to about 9.0% or about 1.0% to about 8.0% it Between or about 1.0% to about 7.0% between or about 1.5% to about 7.0% between or about 1.5% to about 6.0% between or about Between 2.0% to about 6.0% or between about 2.5% to about 6.0% or between about 3.0% to about 6.0% or about 3.5% to Between about 6.0% or between about 4% to about 6%.

9. the Multi-layer microcapsule as described in any one of claim 1 to 8, it is characterised in that: described light tight material is selected from The group being made up of titanium dioxide, zinc oxide, aluminium oxide, boron nitride, Talcum, Kaolin, Muscovitum and any combination thereof.

10. the Multi-layer microcapsule as described in any one of claim 1 to 9, it is characterised in that: a quantity of described light tight material Scope be by weight between about 1% to about the 90% of the gross weight of described microcapsule or between about 30% to about 90%, Or between about 30% to about 60%.

11. Multi-layer microcapsule as claimed in claim 10, it is characterised in that: described light tight material is titanium dioxide, and The scope of one quantity of middle titanium dioxide be by weight between about 10% to about the 80% of the gross weight of described microcapsule or Between about 30% to about 80% or between about 30% to about 60%.

12. Multi-layer microcapsule as described in any one of claim 1 to 11, it is characterised in that: described soap includes one Being selected from by stearic acid, arachidic acid, Petiolus Trachycarpi oil of fatty acyl group more than or, one or above fatty acyl group independence The group that acid, oleic acid, linoleic acid, linolenic acid, arachidonic acid, myristoleic acid and erucic acid are formed.

13. Multi-layer microcapsule as claimed in claim 12, it is characterised in that: described soap selected from by magnesium stearate, The group that magnesium oleate, calcium stearate, calcium linoleate and sodium stearate are formed.

14. Multi-layer microcapsule as claimed in claim 13, it is characterised in that: described soap is magnesium stearate.

15. Multi-layer microcapsule as described in any one of claim 12 to 14, it is characterised in that: a quantity of described soap Scope be by weight between about 0.05% to about the 5% of the gross weight of described microcapsule or about 0.1% to about 3% it Between or about 0.2% to about 3% between or about 0.5% to about 3% between or about 0.5% to about 2.0% between or about 1.0% Between about 2.0%.

16. Multi-layer microcapsule as described in any one of claim 1 to 15, it is characterised in that: including: magnesium stearate is by weight It is in the range of the quantity between about the 1.0% to 2.0% of the gross weight of described microcapsule；Titanium dioxide is by weight It is in the range of the quantity between about the 30% to 75% of the gross weight of described microcapsule；And one dispersant be between In the range of a quantity between about the 4% to 6% of the gross weight of described microcapsule.

17. Multi-layer microcapsule as described in any one of claim 1 to 16, it is characterised in that: a number of described interior core microcapsule Amount scope be by weight between about 10% to about the 70% of the gross weight of described microcapsule or about 10% to about 50% it Between.

18. Multi-layer microcapsule as described in any one of claim 1 to 17, it is characterised in that: described first wall formation material Each with the second wall formation material independent include a polymer or copolymer, selected from by polyacrylate, polymethyl The group that acid esters, cellulose ether, cellulose esters and combination in any thereof are formed.

19. Multi-layer microcapsule as claimed in claim 18, it is characterised in that: described polymer or copolymer are selected from by poly-third Olefin(e) acid ester, polymethacrylates, acrylate/ammonio methacrylate copolymer, ammonio methacrylate copolymer Type B, low point Son amount poly-(methyl methacrylate)-co-(methacrylic acid) of (about 15,000 dalton), poly-(ethyl acrylate)-co- (methyl methacrylate)-co-(trimethyl ammonium chloride-ethyl methacrylate chloride), poly-(butyl methacrylate)- Co-(methacrylic acid-2-dimethylamino ethyl ester)-co-(methyl methacrylate), poly-(styrene)-co-(maleic acid Acid anhydride), the copolymer of octyl acrylamide, cellulose ether, cellulose esters, PEG-black-poly-(propylene glycol)-black-poly-(second Glycol), the group that formed of PLA (polylactic acid), PGA (polyglycolic acid) and PLGA copolymer.

20. Multi-layer microcapsule as claimed in claim 18, it is characterised in that: described second wall formation material includes a polymerization Thing or copolymer, selected from the family being made up of acrylate/ammonio methacrylate copolymer, acetate fiber and combinations thereof Group.

21. Multi-layer microcapsule as described in any one of claim 18 to 20, it is characterised in that: described second wall formation material The scope of a quantity be by weight between about 5% to about the 70% of the gross weight of described microcapsule or about 5% to about Between 50% or between about 5% to about 40% or between about 5% to about 30%.

22. Multi-layer microcapsule as described in any one of claim 1 to 21, it is characterised in that: including: described interior core microcapsule with Weight meter is in the range of the quantity between about the 10% to 50% of the gross weight of described microcapsule；Described second wall shape One-tenth polymer or copolymer are in the quantity between about the 5% to 30% of the gross weight of described microcapsule by weight In the range of；Magnesium stearate is the model in the quantity between about the 0.5% to 1% of the gross weight of described microcapsule by weight In enclosing；Titanium dioxide is the scope in the quantity between about the 25% to 50% of the gross weight of described microcapsule by weight In；And one dispersant be in the range of the quantity between about the 1% to 6% of the gross weight of described microcapsule.

23. Multi-layer microcapsule as described in any one of claim 1 to 22, it is characterised in that: described Multi-layer microcapsule is one Bilayered microcapsule.

24. Multi-layer microcapsule as described in any one of claim 1 to 23, it is characterised in that: the brightness of described Multi-layer microcapsule Value (L*) is in the range of on the brightness scale that X-Rite measures system 60 to 100.

25. Multi-layer microcapsule as described in any one of claim 1 to 24, it is characterised in that: described Multi-layer microcapsule is coagulated one It is stable under glue preparation reaching at least 3 months with 40 DEG C of cultivations and stirring simultaneously.

26. 1 kinds of constituents including multiple Multi-layer microcapsule, it is characterised in that: at least one of described Multi-layer microcapsule bag Include multiple microcapsule containing coloring agent as described in any one of claim 1 to 25.

27. constituents as claimed in claim 26, it is characterised in that: described in the plurality of microcapsule containing coloring agent Multi-layer microcapsule is identical or different.

28. constituents as described in claim 26 or 27, it is characterised in that: the plurality of Multi-layer microcapsule has an average chi Very little, in the range of between about 50 microns to about 350 microns.

Prepare multilamellar containing the manufacture method of color microcapsule for 29. 1 kinds, it is characterised in that: described manufacture method includes step:

A () makes one first organic facies contact one first aqueous continuous phase, thus obtain and reassemble into emulsion one first more, wherein said First organic facies includes one second wall formation polymer or copolymer, a soap, a selective dispersant and 1 One water section misci-ble organic solvents, described first aqueous continuous phase is to utilize described organic solvent formed saturated and include one Emulsifying agent, described first organic facies or described first aqueous continuous phase also include a light tight material and/or the micro-glue of multiple monolayer Capsule, the plurality of Single-layer microcapsules respectively includes that a core, described core include a mixture of a coloring agent or multiple coloring agent, And the wall being included one first wall formation material is coated with；

B () adds the water of a quantity in the emulsion of described formation, extract described organic solvent to cause from described emulsion, from And obtain multiple bilayered microcapsule；And

C () selectivity repeats step (a) and (b), use one second, third etc. organic facies and aqueous continuous phase, thus obtain Obtain multiple Multi-layer microcapsule.

30. manufacture methods as claimed in claim 29, it is characterised in that: further include separate after step (b) the plurality of micro- Capsule.

31. manufacture methods as claimed in claim 30, it is characterised in that: further include and be dried and the plurality of microcapsule that sieves, Thus obtain a free flowing powder of the plurality of microcapsule.

32. manufacture methods as described in any one of claim 29 to 31, it is characterised in that: described wall formation polymer is third Olefin(e) acid ester/ammonio methacrylate copolymer, ammonio methacrylate copolymer Type B, cellulosic ether, Ethylcellulose or it is any Combination.

33. manufacture methods as described in any one of claim 29 to 32, it is characterised in that: described organic solvent is selected from second Acetoacetic ester, ethanol, Ethyl formate or its combination in any.

34. manufacture methods as described in any one of claim 29 to 33, it is characterised in that: described plasticizer is selected from glycerol Three esters, trilaurin, glyceryl tripalmitate, glyceryl triacetate, triethyl citrate, acetyl triethyl citrate, paraffin oil or its any group Close.

35. manufacture methods as described in any one of claim 29 to 34, it is characterised in that: described light tight material is selected from Titanium dioxide, zinc oxide, aluminium oxide, boron nitride, Talcum, Kaolin, Muscovitum and any combination thereof.

36. manufacture methods as described in any one of claim 29 to 35, it is characterised in that: described wall formation polymer is third Olefin(e) acid ester/ammonio methacrylate copolymer, ethyl cellulose or its combination in any；Described water section misci-ble organic solvents is second Acetoacetic ester；Described dispersant is an esters of a fatty acid；Described fatty acid is magnesium stearate；And described light tight material includes Titanium dioxide.

37. manufacture methods as described in any one of claim 29 to 36, it is characterised in that: the plurality of multilamellar is micro-containing coloring agent Capsule is as defined in any one of claim 1 to 25.

38. constituents as described in any one of claim 27 to 29, it is characterised in that: the plurality of multilamellar micro-glue Han coloring agent Capsule is prepared with the manufacture method as described in any one of claim 29 to 36.

39. 1 kinds of cosmetics or medicine adornment preparation, it is characterised in that: include claim 26 to 28 with 38 any one as described in Constituent.

40. cosmetics as claimed in claim 39 or medicine adornment preparations, it is characterised in that: described cosmetics or medicine adornment preparation enter one Walk and include on cosmetics or acceptable carrier on medicine adornment.

41. cosmetics as described in claim 39 or 40 or medicine adornment preparation, it is characterised in that: described cosmetics or medicine adornment preparation It is formulated into an O/w emulsion, an oil in water in oil emulsion, a water-in-oil emulsion, a water-in-oil-in-water compositions, an aqueous system Agent, an anhydrous formulation, a silica-based preparation and a powder formulation.

42. cosmetics as described in any one of claim 39 to 41 or medicine adornment preparation, it is characterised in that: described cosmetics or medicine Adornment preparation is with a gel, a powder, an emulsifiable paste, a foam, an emulsion, an ointment, a spray, a grease, a pasty state Presented in thing, a milk, a suspension, an aerosol or a mousse.