CN104837479B

CN104837479B - Vesicle composition and the skin preparations for extenal use and cosmetics compounded with the vesicle composition

Info

Publication number: CN104837479B
Application number: CN201380057889.0A
Authority: CN
Inventors: 宫地树; 饭田亚美; 绀野義; 绀野義一
Original assignee: Kose Corp
Current assignee: Kose Corp
Priority date: 2012-11-05
Filing date: 2013-11-01
Publication date: 2018-01-09
Anticipated expiration: 2033-11-01
Also published as: WO2014069631A1; JPWO2014069631A1; TW201420124A; TWI622403B; CN104837479A; KR20150079710A; KR102100311B1; HK1207986A1; JP6185477B2

Abstract

There is provided long-time stability and percutaneous permeability is excellent and then pro-skin sense when in use is excellent vesicle composition and the skin preparations for extenal use and cosmetics compounded with the vesicle composition.A kind of vesicle composition and the skin preparations for extenal use and cosmetics compounded with the vesicle composition, the vesicle composition contain following compositions (A)~(D)：(A) one kind or two or more, the polypeptide that (C) cationic surfactant, (D) are using basic amino acid as main body of phosphatide, (B) in cholesterine and phytosterol.

Description

Vesicle composition and the skin preparations for extenal use and cosmetics compounded with the vesicle composition

Technical field

The present invention relates to containing composition (A) phosphatide, composition (B) a kind or 2 kinds in cholesterine and phytosterol with Upper, composition (C) cationic surfactant, composition (D) using basic amino acid as the vesicle composition of the polypeptide of main body and Compounded with the skin preparations for extenal use and cosmetics of the vesicle composition.

Background technology

In the past, as the method that water-insoluble active ingredient is compounded in skin preparations for extenal use, cosmetics, widely utilize The method for making water-insoluble active ingredient disperse in the form of vesicle particle in water solvent.

Generally, vesicle is to be carried out by the way that vesicle principal component and active ingredient are scattered in after water solvent at ultrasonic wave Reason, HIGH PRESSURE TREATMENT and manufacture what is obtained.In addition, vesicle principal component is made up of surfactant, the long-time stability of vesicle itself Dependent on molecular separating force possessed by surfactant.Therefore, because vesicle is easily influenceed and gathered by external environment Collection etc., long-time stability are bad, the vesicle excellent it is desirable to develop long-time stability.

Amphiphile as the composition vesicle of the long-time stability for improving vesicle, it is known that for example with the phosphorus of natural origin Fat as raw material, 2 acyl groups for the residue of unrighted acid phospholipid derivative (for example, referring to patent document 1).

In addition, the technology as the long-time stability for improving vesicle, it is known that：The use of phosphatidylcholine content is 90 weights It is used for cosmetic that the hydrogenated soya phosphatide and adjustment average grain diameter that amount more than %, iodine number are less than 0.1 are that 100~500nm is formed Vesicle (for example, referring to patent document 2)；In addition, one kind, which contains, is selected from phosphatide, sucrose fatty ester and acyl amino acid metal salt In vesicle film-forming material one kind or two or more and water soluble polymer vesicle composition, it is by utriculiform Into when water soluble polymer is existed and vesicle composition obtained from carrying out HIGH PRESSURE TREATMENT (for example, referring to patent document 3) Deng.

On the other hand, also there is the low material of percutaneous permeability, also it is desirable to it can be made efficiently to permeate in active ingredient Technology into skin.For example, in the presence of following technology：On a part at least its structure of the liposome formed by phosphatide promotes The material or its mixture of the intracellular penetration of active ingredient are stated, it by quaternary amine by comprising turning to formula R-N (R₁R₂R₃) type plant Thing protein (in formula, R be phytoprotein molecule symbol, R₁And R₂Stand alone as C1~C6 alkyl, R₃For carbon number 10~18 Alkyl) so as to improving intracellular penetration (for example, referring to patent document 4).

Prior art literature

Patent document

Patent document 1：Japanese Unexamined Patent Publication 2008-88133 publications

Patent document 2：Japanese Unexamined Patent Publication 2006-124378 publications

Patent document 3：Japanese Unexamined Patent Publication 2008-94808 publications

Patent document 4：No. 4950419 publication of patent

The content of the invention

Problems to be solved by the invention

The vesicle that the present invention will provide long-time stability and percutaneous permeability is excellent and then pro-skin sense when in use is excellent Composition and skin preparations for extenal use and cosmetics containing the vesicle composition.

The solution used to solve the problem

The present inventor etc. in depth study repeatedly, as a result, merely with specific described in patent document 2 Long-time stability are insufficient during phosphatide, in addition, the side that water soluble polymer is added when vesicle manufactures described in patent document 3 In method, water soluble polymer is felt sometimes so as to be restricted in terms of sense of touch.And then containing described in patent document 4 Have by the method for quaternary ammoniated phytoprotein, there is foul the long-time stability such as discoloration the problem of.

The present inventor etc. in depth study repeatedly, as a result found in view of such situation, by phosphatide and choosing From in the vesicle of the one kind or two or more formation in cholesterine and phytosterol, and then combine using basic amino acid and be used as main body Polypeptide, thus, the polypeptide promote the absorption of the vesicle of cuticula, make 1 containing phosphatide and in cholesterine and phytosterol Kind or during two or more and the vesicle that is formed effectively penetrate to the skin, and using when pro-skin sense become good.

But by phosphatide and one kind or two or more formed vesicle in cholesterine and phytosterol, with When basic amino acid is combined as the polypeptide of main body, in cosmetics or skin preparations for extenal use etc. occur long-time stability it is poor, Because of the aggregation caused by it the problems such as.

Therefore, the present inventor etc. is further inquired into, and is as a result found, in phosphatide, in cholesterine and phytosterol It is one kind or two or more and using basic amino acid as the polypeptide of main body in, and with cationic surfactant, thus, sun from Sub- property surfactant makes one kind or two or more and polypeptide containing phosphatide, in cholesterine and phytosterol and formed The dispersiveness of vesicle becomes good, not only improves long-time stability, and when also improving percutaneous permeability and the use of the vesicle Pro-skin sense, so far complete the present invention.

That is, the present invention provides a kind of vesicle composition, and it contains following compositions (A)~(D)：

(A) phosphatide,

(B) in cholesterine and phytosterol it is one kind or two or more,

(C) cationic surfactant,

(D) polypeptide of main body is used as using basic amino acid.

In addition, the present invention provides above-mentioned vesicle composition, wherein, mentioned component (C) for the sun with amino acid residue from Sub- property surfactant.

In addition, the present invention provides above-mentioned vesicle composition, wherein, mentioned component (C) is single-N- long acyl basic amine groups Sour lower alkyl esters salt.

In addition, the present invention provides above-mentioned vesicle composition, wherein, the number-average molecular weight of mentioned component (D) for 1500~ 10000。

In addition, the present invention provides above-mentioned vesicle composition, wherein, the basic amino acid of mentioned component (D) is selected from smart ammonia It is one kind or two or more in acid, lysine and histidine.

In addition, the present invention provides above-mentioned vesicle composition, wherein, the ratio of the basic amino acid of mentioned component (D) is More than 60% mole.

In addition, the present invention provides above-mentioned vesicle composition, wherein, mentioned component (C) is N- cocoyls-L-arginine second Ester pyrrolidone carboxylic acid salt.

In addition, the present invention provides above-mentioned vesicle composition, wherein, mentioned component (D) is poly-D-lysine.

In addition, the present invention provides above-mentioned vesicle composition, in the range of its 25 DEG C pH is 3.0~6.5.

In addition, the present invention provides above-mentioned vesicle composition, its 25 DEG C zeta potential is 5~100.

Additionally, it is provided a kind of skin preparations for extenal use and cosmetics, it includes above-mentioned vesicle composition.

The effect of invention

According to the present invention, by by phosphatide, one kind or two or more, cationic table in cholesterine and phytosterol Face activating agent, the polypeptide using basic amino acid as main body are combined, using the teaching of the invention it is possible to provide long-time stability and percutaneous permeability are excellent The excellent vesicle composition of pro-skin sense different and then when in use and the skin preparations for extenal use comprising the vesicle composition and change Cosmetic.

Brief description of the drawings

Fig. 1 is the figure of the confocal laser microscope observation result of the three-dimensional cutaneous model for the vesicle composition for showing this technology Piece replacement photo.

Fig. 2 is the figure of the confocal laser microscope observation result of the three-dimensional cutaneous model for the vesicle composition for showing comparative example Piece replacement photo.

Embodiment

This technology be containing composition (A) phosphatide, composition (B) in cholesterine and phytosterol it is one kind or two or more, Vesicle composition using basic amino acid as the polypeptide of main body of composition (C) cationic surfactant, composition (D), He Bao Skin preparations for extenal use and cosmetics containing the vesicle composition.

Hereinafter, it is described in detail for this technology (present invention).It should be noted that "~" means in this specification Include the scope of the numerical value before and after it.

The phosphatide of workable composition (A) is can be as the phosphorus that vesicle constituent uses in this technology in this technology Fat, as long as can be in common cosmetics, skin preparations for extenal use etc. using being just not particularly limited.As preferable specific Example, can include phosphatidyl choline, phosphatidyl-ethanolamine, phosphatidylserine, phosphatidyl glycerol, phosphatidylinositols, sphingomyelins Deng being selected among them one kind or two or more.

Further, can be the composition containing one kind or two or more phosphatide as described above as composition (A). Contain the composition of phosphatide as this, can also include such as soybean lecithin (also referred to as " soybean lecithin "), egg yolk lecithin (also referred to as " yolk phospholipid ") and their hydride, by them as obtained from ferment treatment haemolysis lysolecithin Deng.Wherein, preferably hydrogenated phospholipid, more preferably hydrogenated soya phosphatide.

Among them, a kind or appropriate two or more use of selection combination can be used as needed.

As specific commodity, can include provided by YMC Co., Ltd.s HSL-70, by Nikko Chemicals Co., Nikkol Lecinol S-10E of Ltd. offers, the Basis LS- provided by Nisshin OilliO Group, Ltd. 60HR, by Kewpie Corporation yolk lysolecithin LPC-1 provided etc..

The content of composition (A) in this technology is not particularly limited, in vesicle composition, from long-time stability, parent From the viewpoint of skin sense, preferably 0.01~5 mass %, from the viewpoint of long-time stability, more preferably 0.05~4 matter Measure %, and then preferably 0.1~2 mass %.

One kind or two or more in cholesterine and phytosterol of workable composition (B) helps to steep in this technology Capsule formed in bimolecular film structure stability, can be by improving long-time stability containing it.Cholesteric and can also be used Alcohol and phytosterol.

Cholesterine is generally refined and obtained by natural goods, can also be utilized in this technology as obtained by arbitrary natural goods is refined Cholesterine.

As long as the material can that phytosterol is typically categorized into phytosterol (plant sterols) uses, as structure Into composition, the material containing campesterol, sitosterol, stigmastanol etc. is preferably exemplified.The composition can be by cereal Plumule etc. obtained from organic solvent is extracted and removes water-soluble portion, but commercially available commodity can also be bought Utilized.

The content of composition (B) in this technology is not particularly limited, in vesicle composition, from long-time stability, parent From the viewpoint of skin sense, preferably 0.01~5 mass %, from the viewpoint of pro-skin sense, more preferably 0.05~3 mass %, And then preferably 0.05~1 mass %.

In addition, the ratio between content ratio of composition (A) and composition (B) is preferably set to 1：0.01~1：1.

The cationic surfactant of workable composition (C), which has, in this technology makes the dispersiveness of vesicle become good The effect of pro-skin sense when percutaneous permeability being provided well and then also and being used.

As composition in this technology (C) cationic surfactant, as long as in common cosmetics, external preparation for skin The material used in agent etc. is just not particularly limited, and can also use any one.

As composition (C), such as CTAB, cetyltrimethylammonium bromide, stearyl can be exemplified Trimethyl ammonium chloride, stearyl trimethyl ammonium bromide, Shan Yu base trimethyl ammonium chloride, Shan Yu base trimethylammonium bromide, Shan Yu bases Trimethylammoniumethyl sulfate, VARISOFT TA100, two oleyl dimethyl ammonium bromides, cetyl Shan Yu base diformazans Base ammonium methyl sulphate, stearalkonium chloride, two paimcarboxyethyl hydroxyethyl ammonium Methylsulfates, two cocounut oil acyls The quaternary ammonium salts such as ethyl-hydroxyethyl ammonium methyl sulphate, distearyl ethyl-hydroxyethyl ammonium methyl sulphate；Stearoyl lysine fourth Ester hydrochloride, N- coco-nut oil fatty acids acyl group-L-arginine ethyl ester DL- pyrrolidone carboxylic acid salts, lauroyl-ornithine Single-N- long acyl basic amino acid lower alkyl esters salt such as propyl ester acetate；Decyl guanidine acetate, 2- guanidine Ethyl Lauroyl bases Guanidine derivatives such as amide hydrochloride, 2- guanidine butyl stearmide DL- pyrrolidone carboxylic acid salts etc., can be selected among them It is one kind or two or more.In addition, as their salt, such as halogen, Methylsulfate, sulfovinate and inclined phosphorus can be included Hydrochlorate etc..

Wherein, in this technology, preferably quaternary ammonium salt and singly-N- long acyl basic amino acid lower alkyl esters salt.And then In quaternary ammonium salt, preferably two long acyl alkylhydroxyalkyl ammonium salts are (for example, two paimcarboxyethyl hydroxyethyl ammonium Methylsulfates, two Cocounut oil acyl ethyl-hydroxyethyl ammonium methyl sulphate and distearyl ethyl-hydroxyethyl ammonium methyl sulphate etc.).

In " two long acyl alkylhydroxyalkyl ammonium salts " and " single-N- long acyl basic amino acid lower alkyl esters salt " The carbon number of above-mentioned " long acyl " is preferably 10~30, and more preferably 8~22.In addition, " long acyl " can be department of botany The material in fatty acid mixed (for example, laurate system grease of coco-nut oil fatty acid and palm kernel fatty acid etc. etc.) source is dynamic The material in fatty acid mixed (for example, tallow acid etc.) source of thing system.As the aliphatic acid as " long acyl ", can arrange Enumerate such as laurate, myristic acid, palmitic acid, linoleic acid, oleic acid, leukotrienes and stearic acid, can be selected among them Select one kind or two or more use.In addition, in the case of " two long acyls ", they can be with identical or different.

In addition, above-mentioned " alkyl ", " hydroxyalkyl " and the carbon number of " low alkyl group " be preferably 1~7, more preferably 1~5, make To be above-mentioned " alkyl " and " low alkyl group ", it can include such as methyl, ethyl, propyl group and butyl.

In addition, as above-mentioned " basic amino acid ", can include such as lysine, arginine, histidine, ornithine, And their derivative.

Further, in above-mentioned cationic surfactant, it is also preferred that the cationic surface with amino acid residue Activating agent.As long as the material with cationic in vesicle composition of the surfactant used in this technology is Can.As the cationic surfactant with amino acid residue, the preferably amino acid residue is that basic amino acid is residual Base.As the cationic surfactant with amino acid residue, surfactant preferably with L-arginine residue ( Referred to as " surfactant of L-arginine system ").In the case of the surfactant of L-arginine system, as long as in vesicle group In compound it is in the material of cationic, even if also having no relations for amphoteric surfactant.

Further, in the cationic surfactant with amino acid residue in this technique, as L-arginine The surfactant of system, it can include for example：As アミセー OffLMA-60 (trade mark, Ajinomoto Co., Inc. system) N- [3- alkyl (the C sold₁₂And C₁₄) oxo -2- hydroxypropyls alcohol]-the aqueous solution of L-arginine hydrochloride 2%, as CAE (trade mark, Ajinomoto Co., Inc. system) N- cocoyls-L-arginine ethylester pyrrole alkanone carboxylate for having sold etc., preferably N- cocounut oil Acyl group-L-arginine ethylester pyrrole alkanone carboxylate.Using be selected from they among it is one kind or two or more when, not only improve length Phase stability, and further turn into the excellent vesicle composition of percutaneous permeability, therefore be preferable.

The content of composition (C) in this technology is not particularly limited, in vesicle composition, from long-time stability and skin From the viewpoint of skin permeability, preferably 0.001~1.0 mass %, more preferably 0.02~0.5 mass %, from Cutaneous permeation From the viewpoint of property, more preferably 0.005~0.5 mass %.

The polypeptide using basic amino acid as main body of workable composition (D), which has, in this technology oozes the skin of vesicle The effect that pro-skin sense when permeability and use improves.Basic amino acid refers to such as arginine, lysine, histidine and bird ammonia Acid waits (usually using L-type), when using the polypeptide using one kind or two or more in basic amino acid as main body, into For the vesicle composition that pro-skin sense is excellent, therefore it is preferable.Polypeptide using basic amino acid as main body refers to basic amine group Ratio of the acid in polypeptide is more than 60% mole, preferably more than 70% mole, more preferably more than 80% mole, Jin Eryou Elect more than 90% mole as.

It should be noted that the number-average molecular weight of the polypeptide of composition (D) is different according to amino acid, preferably 1500~ 10000.In addition, the number-average molecular weight of the polypeptide of composition (D) can be calculated by the chart of high performance liquid chromatography (HPLC).

Further, it is above-mentioned using basic amino acid as the polypeptide of main body in, preferably poly-D-lysine, polyhistidyl etc.. During using one kind or two or more among them, the excellent vesicle of pro-skin sense when turning into percutaneous permeability and using combines Thing, therefore be preferable.

As the commercially available product of the polypeptide, it can use and pass through INCI names (International Nomenclature Cosmetic Ingredient labeling names) poly-D-lysine 10 that is expressed as Polyepsilon-Lysine (contains Have the aqueous solution (ICHIMARU PHARCOS Co., Ltd. system) of 10% poly-D-lysine) etc..

The content of composition (D) in this technology is not particularly limited, in vesicle composition, from percutaneous permeability and length From the viewpoint of phase stability, preferably 0.001~5.0 mass %, from the viewpoint of long-time stability, more preferably 0.005~1.0 mass %, and then preferably 0.025~0.1 mass %.

In addition, the vesicle composition of this technology also contains water in addition to mentioned component (A)~(D).Water can be used as above-mentioned The decentralized medium of composition and use, be neccessary composition as vesicle composition.The content of water in this technology passes through this area skill Art personnel suitably determine according to composition (A)~(D) content, in vesicle composition, preferably approximately 60~95 mass %. As such water, Purified Water, thermal water, rose water or lavender liquid etc. can be used to be derived from the steam distillation water of plant Deng.It can be used among them one kind or two or more.

In addition, it is necessary to maintain mentioned component (A)~(D) (especially compositions (A) well during vesicle is formed (B)) dispersiveness, for the purpose of improving the dispersiveness of each composition, can add in media as well propane diols, 1,3-BDO, The polyalcohols such as DPG, 1,2- pentanediols, glycerine, two glycerine, D-sorbite.It is polynary in this technology in vesicle composition The content of alcohol is preferably 1~20 mass %.

In addition, in the range of the effect of this technology is not damaged, the vesicle composition of this technology can also add various except upper State the alcohol beyond composition, finish, surfactant, thickener, powder, chelating agent, pH regulators, ultra-violet absorber, be derived from Various medicaments, the spices such as plant, the extract of microorganism, NMF, anti-inflammatory agent, cell activator etc..In addition, various additions Agent can be added when vesicle manufactures, and can also be added after vesicle manufacture.Furthermore it is possible to be allowed to be encapsulated in vesicle, can also Without encapsulating.

In addition, in the vesicle composition of this technology, due to increasing zeta potential, therefore long-time stability, percutaneous permeability carry Height, therefore be preferable.Zeta potential is not particularly limited, for 5~100 (more preferably more than 7 and less than 80 and then preferably For more than 10 and less than 50) when, long-time stability are more excellent, therefore are preferable.It should be noted that zeta potential is to use Otsuka Electronics Co., Ltd. electrophoretic light scattering photometer LEZ-600 are at 25 DEG C of temperature obtained by measure Value.

In addition, the pH of the vesicle composition of this technology is not particularly limited, make steady in a long-term due to increasing zeta potential Property, percutaneous permeability improves, it is therefore preferred in the range of 25 DEG C of pH is 3.0~6.5 (are preferably 3.5~5.0).

The manufacture method of the vesicle composition of this technology is not particularly limited, can be manufactured by usual way. Such as it can manufacture by the following method：Eddy-current method (vortexing method) [A.D.Bangham, J.Mol.Biol., 13,238 (1965)], Ultrasonic treatment [C.Huang, Biochem., 8,344 (1969)], pre- vesicle method (prevesicle Method) [H.Trauble, Neurosci.Res.Prog.Bull., 9,273 (1971)], alcohol injection [S.Batzri, Biochem.Biophys.Acta., 298,1015 (1973)], French press extrusion molding [Y.Barenholz, FEBS Lett., 99,210 (1979)], cholic acid remove method [Y.Kagawa, J.Biol.Chem., 246,5477 (1971)], TritonX- 100 batch processes [W.J.Gerritsen, Eur.J.Biochem., 85,255 (1978)], Ca²⁺Fusion method [D.Papahadojopoulos, Biochem.Biophys.Acta., 394,483 (1975)], ether injection method [D.Deazer, Biochem.Biophys.Acta., 443,629 (1976)], heat treating process (annealing) [R.Lawaczeck, Biochem.Biophys.Acta., 443,313 (1976)], freeze thawing fusion method [M.Kasahara, J.Biol.Chem., 252, 7384 (1977)], W/O/W emulsion methods [S.Matsumoto, J.Colloid Interface Sci., 62,149 (1977)), it is inverse Phase evaporation [F.Szoka, Proc.Natl.Acad.Sci.USA, 75,4194 (1978)], polyol process [Japanese Unexamined Patent Application 60- No. 7932 publications] etc..

As the autofrettage of the vesicle composition of this technology, such as following method can be included：Using mentioned component (A) and Main membrane constituent of the mentioned component (B) as vesicle particle, by these compositions (A) and (B), composition (C) and composition (D), And appropriate other any conditions are compounded, are cooled down after heating mixing, thus obtain vesicle composition.When carrying out heating mixing Temperature conditionss be preferably 60~100 DEG C.

In addition, [composition (A)+composition (B)]：The content ratio of composition (C) is preferably 1：0.001~1, more preferably 1： 0.01~0.4.

In addition, [composition (A)+composition (B)]：The content ratio of composition (D) is preferably 1：0.001~1, more preferably 1： 0.01~0.8, and then preferably 0.02~0.08.

In addition, composition (D)：The content ratio of composition (C) is preferably 1：0.01~10, more preferably 0.1~5, Jin Eryou Elect 1 as：1~4.

As one example, composition (A) and composition (B) are disperseed at 80 DEG C, are dissolved in the water systems such as Purified Water, polyalcohol In solvent, the material after composition (C) is added in Purified Water and is dissolved by heating at 80 DEG C is added thereto and is mixed, And then add the material after composition (D) is added into Purified Water and dissolved by heating at 80 DEG C and mixed, then, slowly Untill being cooled to 40 DEG C, obtain therefrom.

In addition, the confirmation method that vesicle is formed can be carried out by the following method：Confirmed using polarization microscope orthogonal The presence or absence of Maltese cross image under Nicol prism；Use high brightness small angle X ray scattering device SAXS (Anton Paar Company system) confirm based on spectrometric peak of small angle X ray scattering etc..The confirmation that the vesicle of the vesicle composition of this technology is formed It is that sample is observed under Nicol crossed by using polarization microscope (Olympus Corporation systems), confirms The presence or absence of Maltese cross image and carry out.

The purposes of the vesicle composition of this technology is not particularly limited.The vesicle composition of this technology can be outside skin It is each with agent (for example, skin preparations for extenal use of pharmaceuticals and quasi- medicine), cosmetics, pharmaceuticals (oral, injection etc.), food etc. Used in the manufacture of the composition of kind purposes.The heat resistance of the vesicle composition of this technology is also excellent, even if it is manufactured at them When be compounded, can also play the effect that this technology is expected.These compositions may finally be liquid, semi liquid state (including gel Shape and pasty state), the arbitrary form such as solid.

The vesicle composition of this technology has this excellent feature of percutaneous permeability, from this viewpoint, preferably its conduct Skin preparations for extenal use or cosmetics are used or used when manufacturing them.

The vesicle composition of this technology can use directly as skin preparations for extenal use, cosmetics, alternatively, it is also possible to contain it There are other compositions and be used as skin preparations for extenal use, cosmetics to use.Skin preparations for extenal use or cosmetics are being made containing other compositions In the case of, the content of the vesicle composition of this technology in these products is not particularly limited, preferably 1.0~90 matter Measure %, more preferably 3.0~50 mass %.

Institute is for example descended using the one of skin preparations for extenal use obtained by the vesicle composition of this technology or the manufacture method of cosmetics State.It is to include manufacturing the vesicle composition of above-mentioned this technology and carry out above-mentioned vesicle composition and active ingredient etc. The skin preparations for extenal use of mixing etc. or the manufacture method of cosmetics.

25 DEG C of pH of manufactured skin preparations for extenal use or cosmetics is not particularly limited, preferably above-mentioned vesicle composition The small person of difference of pH and the skin preparations for extenal use or the pH of cosmetics that finally produce during manufacture, specifically, its difference for 1.0 with When lower, in skin preparations for extenal use or cosmetics, the shape of vesicle is also maintained, and can maintain dispersiveness and long-term point well Dissipate property.

The formulation of skin preparations for extenal use or cosmetics to this technology is not particularly limited.Can be liquid, semi liquid state, solid-state Deng any one.As its example, can include：Emulsion, creams, toner, Essence (serum), facial mask, cleaning agent, color make-up The various skin preparations for extenal use such as cosmetics, ointment or cosmetics.In addition, in the skin preparations for extenal use or cosmetics of this technology, except this skill Beyond the vesicle composition of art, in the range of the effect of this technology is not damaged, can be properly joined into skin preparations for extenal use or Usually used various composition in cosmetics, i.e. alcohol, finish, surfactant, thickener, powder, chelating agent, pH regulators, Ultra-violet absorber, from various medicaments, perfume (or spice) such as plant, the extract of microorganism, NMF, anti-inflammatory agent, cell activators Material etc..

The function of vesicle in the skin preparations for extenal use or cosmetics of this technology is not particularly limited.It is to be formed by phosphatide Vesicle, there is this excellent feature of percutaneous permeability.Furthermore it is possible to active ingredient is encapsulated in vesicle, in this mode, It is not only able to obtain above-mentioned function, and also obtains the effect that the slow release based on active ingredient is brought.

This technology can also use following scheme.

[1] a kind of vesicle composition, it contains following compositions (A)~(D)：

(A) phosphatide,

(B) in cholesterine and phytosterol it is one kind or two or more,

(C) cationic surfactant,

(D) polypeptide of main body is used as using basic amino acid.

[2] vesicle composition according to above-mentioned [1], wherein, mentioned component (C) for amino acid residue sun from Sub- property surfactant.

[3] vesicle composition according to above-mentioned [1] or [2], wherein, mentioned component (C) is single-N- long acyl alkali Acidic amino acid lower alkyl esters salt.

[4] vesicle composition according to any one of above-mentioned [1]~[3], wherein, the number of mentioned component (D) is equal Molecular weight is 1500~10000.

[5] vesicle composition according to any one of above-mentioned [1]~[4], wherein, the alkalescence of mentioned component (D) Amino acid is one kind or two or more in arginine, lysine and histidine.

[6] vesicle composition according to any one of above-mentioned [1]~[5], wherein, the alkalescence of mentioned component (D) The ratio of amino acid is more than 60% mole.

[7] vesicle composition according to any one of above-mentioned [1]~[6], wherein, mentioned component (C) is N- coconut palms Oleoyl-L-arginine ethylester pyrrole alkanone carboxylate.

[8] vesicle composition according to any one of above-mentioned [1]~[7], wherein, mentioned component (D) is poly Lysine.

[9] vesicle composition according to any one of above-mentioned [1]~[8], its 25 DEG C pH are 3.0~6.5 In the range of.

[10] vesicle composition according to any one of above-mentioned [1]~[9], its 25 DEG C zeta potential are 5~100.

[11] vesicle composition according to any one of above-mentioned [1]~[10], wherein, the content of above-mentioned (A) is 0.01~5 mass %.

[12] vesicle composition according to any one of above-mentioned [1]~[11], wherein, the content of above-mentioned (B) is 0.01~5 mass %.

[13] vesicle composition according to any one of above-mentioned [1]~[12], wherein, the content of above-mentioned (C) is 0.001~1 mass %.

[14] vesicle composition according to any one of above-mentioned [1]~[13], wherein, the content of above-mentioned (D) is 0.001~5.0 mass %.

[15] vesicle composition according to any one of above-mentioned [1]~[14], wherein, [mentioned component (A)+on State composition (B)]：The content ratio of mentioned component (C) is 1：0.001~1.

[16] vesicle composition according to any one of above-mentioned [1]~[15], [mentioned component (A)+mentioned component (B)]：The content ratio of mentioned component (D) is 1：0.001~1.

[17] vesicle composition according to any one of above-mentioned [1]~[16], mentioned component (D)：Composition (C) Content ratio is 1：0.01~10.

[18] vesicle composition according to any one of above-mentioned [1]~[17], its by heat mixing it is above-mentioned into Divide (A)~(D) and cooled down and obtained.

[19] vesicle composition according to any one of above-mentioned [1]~[18], it in water solvent by adding Hot mixing mentioned component (A) and mentioned component (B), the water after heating mixing dissolves by heating mentioned component (C) and (D) thereto Series solvent and obtain.During heating mixing, pharmacologically permissible additive (being preferably effective component) is preferably compounded.

[20] a kind of skin preparations for extenal use or cosmetics, it includes the vesicle group described in any one of above-mentioned [1]~[19] Compound.

[21] a kind of skin preparations for extenal use or cosmetics, it includes the vesicle group described in any one of above-mentioned [1]~[19] Compound and pharmacologically permissible additive.The content of the vesicle composition is preferably 1~90%.

Embodiment

Hereinafter, embodiment and test example are included in order to illustrate this technology (present invention), but this technology (this hair It is bright) it is not limited to these embodiments etc..

Embodiment 1~11 and comparative example 1~3：Vesicle composition

The vesicle composition formed shown in Tables 1 and 2 is manufactured by following manufacture methods, on the " long-term steady of each sample It is qualitative ", " percutaneous permeability ", " pro-skin sense ", evaluated and judged by method described below, result is shown in Tables 1 and 2 in the lump In.

[table 1]

(%)

[table 2]

(%)

Note 1：HSL-70 (YMC Co., Ltd. system)

Note 2：Nissui Marine cholesterol (Nippon Suisan Kaisha, Ltd. system)

Note 3：25-NBD Chloresterol (Avanti Polar Lipids company systems)

Note 4：Phytosterol (Eisai Food＆Chemical Co., Ltd. system)

Note 5：DEHYQUART AU-56/G (Cognis company systems)

Note 6：(ICHIMARU PHARCOS Co., Ltd.s system, 5000) molecular weight is about to poly-D-lysine 10

Note 7：CAE (Ajinomoto Co., Inc. system)

(manufacture method)

A：Composition 1~6 is heated to 80 DEG C, forms solution.

B：Adding ingredient 7~9 and composition 10~11 are distinguished in A resulting solutions when being maintained at 75 DEG C, is mixed using scattered Conjunction machine obtains dispersion liquid.

C：Dispersion liquid obtained by B is slowly cooled to 40 DEG C, obtains vesicle composition.

[pH measure]

The pH of each sample is measured using the pH meter (HORIBA company systems) of glass electrode at 25 DEG C.

[zeta potential measure]

The zeta current potentials of each sample use Otsuka Electronics Co., the electrophoretic light scattering photometer of Ltd. manufactures LEZ-600 is measured at 25 DEG C.Measure has been carried out 3 times, is as a result represented with its average value.

[validation test of vesicle]

Observed under Nicol crossed using polarization microscope (Olympus Corporation systems) and just produced Each sample come, confirm the presence or absence of Maltese cross image.

[long-time stability]

On long-time stability, for the long-time stability of vesicle, polarized light microscope observing Maltese cross figure is used Picture, evaluated.Specifically, using the state just manufactured of each sample as benchmark, observe and stand 1 month at 50 DEG C State afterwards, judge the quantity of confirmed Maltese cross image using following (i) 4 grades of judgment standards.

(i) 4 grades of judgment standards

(judgement)：(evaluation)

◎：The quantity for confirming Maltese cross image is more than 80%

○：The quantity for confirming Maltese cross image is 60% less than 80%

△：The quantity for confirming Maltese cross image is 30% less than 60%

×：The quantity for confirming Maltese cross image is less than 30%

[percutaneous permeability]

By Toyobo Co., the three-dimensional cutaneous model (TESTSKIN LSE) of Ltd. manufactures is soaked to true with PBS (pH7.4) The mode of skin side is placed in aluminium dish, is respectively coated by fluorescence cholesterine (25-NBD Chloresterol, Avanti Polar Lipids company systems) above-described embodiment 1~11 and comparative example 1~3 for making marks, it is 5 μ g/cm², stand 4 hours.So Afterwards, three-dimensional cutaneous model is taken out, thin layer section is made after freezing, passes through confocal laser microscope (FV-1000, Olympus Corporation systems) taken pictures.Penetration degree of the fluorescent material to cuticula, and 4 grades of use following (ii) are calculated from following formula Judgment standard is judged.It should be noted that calculating 10 local penetration degrees, their average value is calculated.In addition, bubble Capsule composition is all prepared into average grain diameter about 200nm using miniature extruder (Avanti Polar Lipids company systems).

Thickness × 100 of thickness/cuticula entirety after penetration degree (%)=fluorescence cholesterine infiltration

Fig. 1 shows the confocal laser of the three-dimensional cutaneous model of the vesicle composition of the embodiment 1 of this technology (present invention) The result of micro- sem observation, the front end of white arrow represent the orlop of cuticula.Fig. 1 left side is the photo of thin layer section, The white portion of the photo on right side is cholesteric with the fluorescence of the thin layer at the photo in left side same position section to represent to penetrate into Photo.

Fig. 2 shows the result of the confocal laser microscope observation of the three-dimensional cutaneous model of the vesicle composition of comparative example 1, The front end of white arrow represents the orlop of cuticula.The photo that Fig. 2 left side is cut into slices for thin layer, the white portion of the photo on right side It is divided into and represents to penetrate into the cholesteric photo of fluorescence with the section of the thin layer at the photo in left side same position.

From Fig. 1 and Fig. 2, compared with comparative example, fluorescence cholesterine exists the vesicle composition of this technology (present invention) Infiltration in cuticula entirety is excellent.

In addition, the heat endurance of the vesicle composition of this technology is also excellent, even the system of embodiment 13~16 is being manufactured Heating process be present during product (being specially cosmetics or skin preparations for extenal use etc.), also can play this technology well to resulting product Vesicle composition function.

(ii) 4 grades of judgment standards

(judgement)：(evaluation)

◎：Penetration degree is more than 50%

○：Penetration degree is 40% less than 50%

△：Penetration degree is 30% less than 40%

×：Penetration degree is less than 30%

[pro-skin sense]

For each sample, cosmetic evaluation is specially judged the people of group 20 and will applied according to following absolute evaluations in wrist inside portion The pro-skin sense felt during cloth is evaluated as 6 grades, gives and scores, for always calculating it by all scorings of judge group per each sample Average value, judged by following 4 grades of judgment standards.

Absolute evaluation benchmark

(scoring)：(evaluation)

6 points：Fully feel pro-skin sense

5 points：Feel pro-skin sense

4 points：Slightly feel pro-skin sense

3 points：Common impression

2 points：Do not feel very much pro-skin sense

1 point：Pro-skin sense is not felt

4 grades of judgment standards

(judgement)：(average mark of scoring)

◎：More than 5 points

○：More than 3.5 points and less than 5 points

△：More than 2 points and less than 3.5 points

×：Less than 2 points

Can be clear and definite by the result of Tables 1 and 2, the vesicle composition of the embodiment 1~11 of this technology (present invention) it is long-term Stability, percutaneous permeability, pro-skin sense are all excellent.On the other hand, not containing N- cocoyls-L-arginine ethylester pyrrole alkane The percutaneous permeability of the comparative example 1 of keto carboxylic acid salt and poly-D-lysine and pro-skin sense are insufficient.Do not contain N- cocoyls-L- The long-time stability of the vesicle of the comparative example 2 of arginine ethyl ester pyrrolidone carboxylic acid salt are particularly poor, assemble, in pro-skin sense side Face also fails to be met.Comparative example 3 not containing poly-D-lysine especially fails to be met in terms of percutaneous permeability.

Embodiment 12：Vesicle composition

Note 8：STEARYL GLYCYRRHETINATE (Maruzen Pharmaceuticals Co., Ltd. system)

(manufacture method)

A：Composition 1~4 is heated to 80 DEG C, forms solution.

B：Adding ingredient 5~7 and composition 8~9 are distinguished in A resulting solutions when being maintained at 75 DEG C, utilizes dispersion mixing Machine obtains dispersion liquid.

The long-time stability of the vesicle composition of embodiment 12, percutaneous permeability, pro-skin sense are all excellent.

Embodiment 13：Essence

(note 9) METOLOSE 65SH4000 (Shin-Etsu Chemical Co., Ltd. system)

(manufacture method)

A：Composition 1~5 is heated to 70 DEG C, equably dissolving mixing.

B：Composition 6~10 is equably mixed at 70 DEG C.

C：B is added into A, is emulsified at 70 DEG C.

D：C is cooled to 40 DEG C, adding ingredient 11~13 equably mixes, and obtains Essence.

The Essence of embodiment 13 is that the long-time stability of percutaneous permeability and vesicle are excellent and pro-skin sense, moistening effect Excellent Essence.

Embodiment 14：Oil-in-water type eye cream

(manufacture method)

A：Composition 1~8 is heated to 70 DEG C, dissolved by heating.

B：After composition 9~13 is dissolved by heating at 70 DEG C, it is added in A and is emulsified.

C：After B is cooled into room temperature, adding ingredient 14~15, oil-in-water type eye cream is obtained.

The oil-in-water type eye cream of embodiment 14 is the excellent long-time stability of percutaneous permeability and vesicle and pro-skin sense, protected The oil-in-water type eye cream of wet excellent effect.

Embodiment 15：Toner

(manufacture method)

A：By the mixed dissolution of composition 5~8.

B：By composition 1~4,10~11 mixed dissolutions.

C：A is added in B and mixed, further adding ingredient 9 is mixed, and obtains toner.

The toner of embodiment 15 is that the long-time stability of percutaneous permeability and vesicle are excellent and pro-skin sense, moistening effect Excellent toner.

Embodiment 16：Emulsion oil-in-water

Note 10：Pemulen TR-2 (Noveon, Inc system)

(manufacture method)

A：Composition 1~6 is dissolved by heating at 70 DEG C.

B：After composition 7~11 is heated at 70 DEG C, it is added in A and is emulsified.

C：B is cooled to room temperature.

D：Composition 13~16 is added in C, obtains emulsion oil-in-water.

The emulsion oil-in-water of embodiment 16 is the excellent long-time stability of percutaneous permeability and vesicle and pro-skin sense, protected The emulsion of wet excellent effect.

Claims

1. a kind of vesicle composition, it contains following compositions (A)~(D)：

0.01~5 mass % (A) phosphatide,

0.01~5 mass % (B) in cholesterine and phytosterol it is one kind or two or more,

0.001~1.0 mass % (C) cationic surfactant,

Ratio of 0.001~5.0 mass % (D) basic amino acid in polypeptide is more than 60% mole of polypeptide,

Composition (D)：The content ratio of composition (C) is 1：0.01~10,

Wherein composition (C) is the one or two selected from quaternary ammonium salt and single-N- long acyl basic amino acid lower alkyl esters salt, The carbon number of the long acyl is 10~30, and the carbon number of the low alkyl group is 1~7.

2. vesicle composition according to claim 1, wherein, the number-average molecular weight of the composition (D) for 1500~ 10000。

3. vesicle composition according to claim 1, wherein, the basic amino acid of the composition (D) be selected from arginine, It is one kind or two or more in lysine and histidine.

4. the vesicle composition according to any one of claims 1 to 3, wherein, the composition (C) is two palmityl second Base hydroxyethyl ammonium Methylsulfate or N- cocoyls-L-arginine ethylester pyrrole alkanone carboxylate.

5. the vesicle composition according to any one of claims 1 to 3, wherein, the composition (D) is that poly relies ammonia Acid.

6. the vesicle composition according to any one of claims 1 to 3, its 25 DEG C pH is 3.0~6.5 scope It is interior.

7. the vesicle composition according to any one of claims 1 to 3, its 25 DEG C zeta potential is 5~100.

8. a kind of skin preparations for extenal use, it includes the vesicle composition described in any one of claim 1~7.

9. a kind of cosmetics, it includes the vesicle composition described in any one of claim 1~7.