JP4731610B2 - W / O / W type composite emulsion - Google Patents

Description

  The present invention relates to a W / O / W type composite emulsion useful as a pharmaceutical or cosmetic preparation.

In order to produce a W / O / W type composite emulsion, it is necessary to prepare a W / O type emulsion as a dispersoid and then redisperse the W / O type emulsion in the outer aqueous phase.
However, part of the oil phase of the W / O emulsion is solubilized by the hydrophilic surfactant in the outer aqueous phase during the redispersion process, so the W / O emulsion is easily broken and consequently stable. It was difficult to obtain a W / O / W type composite emulsion excellent in properties at a high production rate. Conventionally, in order to prevent such phase inversion during the redispersion process (secondary emulsification), W / O emulsion (W ≦ O) in which the ratio of the oil phase to the inner aqueous phase is increased by primary emulsification. The preparation of was essential. However, when a W / O type emulsion having a higher ratio of the oil phase to the inner aqueous phase is used, there is a problem that a sticky feeling is generated and the original feeling of use of the W / O / W type is impaired.
Further, the W / O / W type composite emulsion is not only difficult to prepare at a high production rate, but also has a problem that the long-term stability, particularly freeze-recoverability, is remarkably inferior. Conventionally, several methods for stabilizing W / O / W type composite emulsions have been proposed. However, there has been no means for simultaneously solving good usability and long-term stability, particularly freeze-recoverability. That is, as a prior art example for producing a W / O / W type composite emulsion with a high production rate, as a method for preventing coalescence of composite particles (W / O particles), Patent Document 1 discloses a thickening in an external water phase. A method of using a water-soluble polysaccharide as an agent is described. However, this method cannot prevent coalescence of the inner aqueous phase, is insufficiently stabilized, and further increases the viscosity, impairing the feeling of use and is not practical. Patent Document 2 discloses a W / O type emulsion composition containing a sulfated polysaccharide. However, this method not only has insufficient long-term stability (maintenance of emulsion viscosity), but also has a sticky feeling because the outer phase is oil, and is not practical.
Further, Patent Document 3 discloses a W / O / W emulsified fragrance composition containing one or more selected from monosaccharides, disaccharides, polysaccharides and polyhydric alcohols in the inner aqueous phase. However, in this method, a large amount of the above components must be blended for stabilization, which is not practical.

JP 58-183611 A JP-A-7-118306 Japanese Patent Laid-Open No. 62-22712

  The present invention provides a W / O / W type composite emulsion that is excellent in long-term stability, in particular, freezing and restoring property and usability.

In the present invention, a stable high water content W / O emulsion that is difficult to be destroyed by secondary emulsification can be prepared by blending a polysaccharide having a sulfone group and / or a carboxyl group in the molecule with the inner aqueous phase. It has been found that by using the W / O emulsion as a dispersoid, a long-term stability, in particular, a W / O / W composite emulsion having excellent freezing and restoring properties can be obtained with a high production rate. .
That is, the present invention provides a W / O / W type composite emulsion characterized in that a polysaccharide having a sulfone group and / or a carboxyl group in the molecule is contained in the inner aqueous phase.

  Main monosaccharides constituting the polysaccharide of the present invention include D-glucosamine, D-galactosamine, D-glucuronic acid, L-iduronic acid, D-glucose, D-galactose, D-xylose and the like. The polysaccharide of the present invention is a polymer of one or more monosaccharides, and the sulfone group or carboxyl group is preferably contained in an average of 0.4 to 5 molecules per monosaccharide molecule, more preferably 0.5 to 3 molecules, Preferably 0.6 to 2 molecules are contained. The average molecular weight of the polysaccharide of the present invention is preferably 1,000 to 10,000,000, more preferably 3,000 to 1,000,000, and still more preferably 5,000 to 500,000.

Such polysaccharides include hyaluronic acid, chondroitin 4-sulfate, chondroitin 6-sulfate, dermatan sulfate, keratan sulfate, heparin, heparin-like substances (listed in the Japanese Pharmacopoeia Standards for Drugs), kappa, iota, or lambda. Acid mucopolysaccharides such as carrageenan and dabilia extract; and sulfated neutral mucopolysaccharides such as chitin. Of these, acidic mucopolysaccharides are preferable, and chondroitin 4-sulfate, heparin, heparin-like substances, iota-carrageenan, and hyaluronic acid are particularly preferable.
The polysaccharide of the present invention can be used regardless of natural products and synthetic products, and can be used alone or in combination of two or more.
The blending amount of the polysaccharide of the present invention is preferably 0.02 to 3%, more preferably 0.2 to 2%, still more preferably 0.7 to 1.5% with respect to the total mass of the inner aqueous phase. Preferably it is 0.01-2% with respect to the total mass of the W / O / W type | mold composite emulsion of this invention, More preferably, it is 0.03-1.5%, More preferably, it is 0.05-1%.

Examples of the oil phase of the present invention include hydrocarbons such as liquid paraffin, petrolatum, microcrystalline wax, squalane, vegetable oils such as olive oil, safflower oil, soybean oil, almond oil, castor oil, beeswax, whale wax, lanolin and the like. Animal solid wax, isopropyl myristate, isopropyl palmitate, octyldodecyl myristate, fatty acid ester such as tri (caprylic / capric) glycerin, and the like are particularly limited as long as they are used in general external preparations and cosmetics. Can be used without
The W / O / W type composite emulsion of the present invention can be preferably produced by the following method.
(1) Primary emulsification An inner aqueous phase component solution (preferably containing an active ingredient) containing a polysaccharide having a sulfone group and / or a carboxyl group in the molecule and an oil phase component solution (preferably a lipophilic surfactant) Is heated to 65 to 85 ° C., particularly preferably 70 to 80 ° C., and each is uniformly dissolved. After dissolution, stirring the oil phase component with a homomixer or the like under the same temperature condition, the inner aqueous phase / oil phase = 50/50 to 90/10, preferably 60/40 to 85/15, more preferably 65 / The inner aqueous phase is slowly added so as to obtain a mass ratio of 35 to 80/20 to prepare a W / O type emulsion. The stirring conditions are appropriately selected depending on the size of the stirring blade and the emulsified composition, but it is preferable to emulsify for 5 to 20 minutes at a rotational speed of about 3000 to 6000 rpm. The formation of a W / O emulsion is confirmed by the fact that the electrical conductivity of the emulsion is almost zero (the outer phase is oil).

(2) Secondary emulsification While stirring an external aqueous phase solution (preferably containing a hydrophilic surfactant) with a homomixer under a temperature condition of 45 to 70 ° C., particularly preferably 50 to 65 ° C. (1 The W / O emulsion obtained in (1) is a W / O emulsion / outer aqueous phase = 30/70 to 80/20, preferably 40/60 to 70/30, more preferably 45/55 to 60/40. The W / O / W type composite emulsion is prepared by adding to the outer aqueous phase so that the mass ratio is as follows. The emulsification conditions are preferably selected as appropriate so that the composite particles once generated are not destroyed, but it is preferable to emulsify for 20 to 90 minutes at a rotational speed of approximately 500 to 3000 rpm.
With the configuration of the present invention, it is possible to increase the water content of the inner aqueous phase. The mixing mass ratio of the inner aqueous phase and the oil phase of the W / O type emulsion as the dispersoid is: inner aqueous phase / oil phase = preferably 50/50 to 90/10, more preferably 60/40 to 85/15, More preferably, 70/30 to 80/20 is desirable. Within this range, a preferable feeling of use of the preparation can be obtained, which is preferable.
The mass ratio of the W / O emulsion to the outer aqueous phase as a dispersion medium is W / O emulsion / outer aqueous phase = preferably 30/70 to 80/20, more preferably 40/60 to 70/30, More preferably, 45/55 to 60/40 is desirable. Within this range, the production rate and stability of the emulsion of the present invention are good, which is preferable. The proportion of the inner aqueous phase is preferably 15 to 75%, more preferably 25 to 60%, and still more preferably 30 to 50% with respect to the entire W / O / W composite emulsion of the present invention. The total amount of the inner aqueous phase and the outer aqueous phase is preferably 70 to 95%, more preferably 75 to 93%, and still more preferably 80 to 90%. Within this range, emulsification is good, which is preferable.
Unless otherwise specified in the present specification, “%” represents mass%.

In addition to the above, the W / O / W emulsion of the present invention preferably contains the following components that are usually used in W / O / W type composite emulsions.
Preferred as the lipophilic surfactant (emulsifier used in the primary emulsification) is a lipophilic surfactant having an HLB by Griffin of 10 or less, more preferably 7 or less, and even more preferably 6 or less. Lipophilic surfactants that are blended in general external preparations and cosmetics to form W / O type emulsions can be used. Examples include sorbitan fatty acid ester, glycerin fatty acid ester, propylene glycol fatty acid ester, lipophilic polyglycerin fatty acid ester, lipophilic polyoxyethylene castor oil, lipophilic polyoxyethylene hydrogenated castor oil, lipophilic sucrose fatty acid ester, and the like. However, it is not particularly limited to these. Of these, sorbitan fatty acid esters and lipophilic polyoxyethylene hydrogenated castor oil are preferred. These lipophilic surfactants may be used alone or in combination of two or more. The blending amount of the lipophilic surfactant varies depending on the type and oil phase component, but is preferably 3 to 50%, more preferably 5 to 40%, and the entire W / O / W type composite emulsion with respect to the oil phase. On the other hand, it is preferably 1 to 10%, more preferably 2 to 8%.

  As a hydrophilic surfactant (emulsifier used in secondary emulsification), a hydrophilic surfactant that is blended in general external preparations and cosmetics to form an O / W type emulsion can be used. For example, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene glycerin fatty acid ester, hydrophilic polyglycerin fatty acid ester, polyoxyethylene sorbit fatty acid ester, hydrophilic polyoxyethylene castor oil, hydrophilic polyoxyethylene hydrogenated castor oil, polyoxyethylene Sterol, hydrophilic polyethylene glycol fatty acid ester, hydrophilic polyoxyethylene alkyl ether, polyoxyethylene alkyl phenyl ether, polyoxyethylene polyoxypropylene alkyl ether, polyoxyethylene polyoxypropylene polymer, hydrophilic sucrose fatty acid ester, etc. However, it is not limited to these. Of these, hydrophilic polyethylene glycol fatty acid esters and hydrophilic polyoxyethylene alkyl ethers are preferred. These hydrophilic surfactants may be used alone or in combination of two or more. The blending amount of the hydrophilic surfactant varies depending on the type and blending amount of the oil phase component and the lipophilic surfactant, but is preferably 0.3 to 10%, more preferably 0.5 to 8% with respect to the outer water phase, More preferably, it is 1 to 6%, and preferably 0.3 to 5%, more preferably 0.5 to 3% with respect to the whole W / O / W type composite emulsion. At this time, a blending amount within a range not solubilizing the lipophilic surfactant used to produce the W / O type emulsion is necessary, and the blending ratio of both is lipophilic surfactant / hydrophilic surfactant = 0.5. / 1 to 20/1, preferably 0.8 / 1 to 15/1, more preferably 1/1 to 10/1.

The present invention can be used for pharmaceutical preparations and cosmetics by containing an active ingredient in an aqueous phase component. As water-soluble active ingredients, moisturizing ingredients such as urea and glycerin, vitamins such as ascorbic acid and pantothenic acid, local anesthetics such as dibucaine hydrochloride and lidocaine hydrochloride, antihistamines such as diphenhydramine hydrochloride and homosulfamine, and anti-histamines such as guaiazulene Mention may be made of inflammatory components. Different water-soluble components can be blended in the inner aqueous phase and the outer aqueous phase, respectively. The kind of active ingredient is not limited to the above, but is appropriately selected.
Moreover, the base component normally mix | blended with an external preparation can be mix | blended suitably as needed in the range which does not impair the effect of this invention. For example, antiseptics such as parabens, benzoic acids, benzalkonium chloride, benzethonium chloride, cetylpyridinium chloride, alkyltrimethylammonium chloride, chlorobutanol, phenoxyethanol, anticoagulants such as tocopherol, erythorbic acid, propyl gallate, BHT, BHA, NDGA, etc. An oxidizing agent and a fragrance | flavor can be mentioned.

W / O / W type composite emulsions were prepared with the compositions of Examples and Comparative Examples shown in Tables 1 to 4 below, the production rate and storage stability in each temperature range, and the obtained W / O / W The feeling of use of the mold composite emulsion was evaluated.
(Preparation method)
An inner aqueous phase, an oil phase, and an outer aqueous phase were separately prepared, and each was heated and stirred at 70 ° C. to 80 ° C. to be uniformly dissolved. While stirring the oil phase at 4000 rpm to 5000 rpm using a homomixer at a temperature of 70 ° C. to 80 ° C., slowly add the inner aqueous phase and emulsify for 5 to 10 minutes. Obtained. Subsequently, while stirring the outer aqueous phase at 500 to 1000 rpm, the W / O emulsion was slowly added and emulsified for 30 to 60 minutes to obtain a W / O / W composite emulsion.
(Production rate)
The W / O / W production rate (%) was obtained by preparing an emulsion by mixing potassium chloride as a marker substance in the inner aqueous phase, and then measuring the chloride ion concentration present in the outer aqueous phase by dialysis with an ion meter. A production rate of 100% means that all marker substances are enclosed in the inner aqueous phase, and a production rate of 0% means that all marker substances have moved to the outer aqueous phase and have undergone O / W phase inversion. is there.
The production rate was evaluated according to the following 5 levels, and ◎ ○ Δ was judged as a high production rate.
(Production rate (%): 85% or more: ◎, 70 to 85%: ○, 60 to 70%: △, 50 to 60%: ▲, less than 50%: ×, emulsification not possible:-)

(Stability)
Storage stability was evaluated by putting the prepared emulsion in a sample tube with a screw cap and storing it under a predetermined condition, and then observing the state.
The stability was evaluated according to the following 5 grades, and ◎ ○ △ was judged to be a stable level.
(Storage stability: no change: ◎, slightly reduced viscosity: ◯, reduced viscosity: △, slightly exuded on the surface: ▲, phase separation: ×)
The evaluation of freeze-restoration was evaluated by storing the emulsion at −20 ° C. for 1 day and freezing it, then allowing it to stand at room temperature for 3 days, and observing the state.
(Usage feeling)
Using the W / O / W type composite emulsions of the following examples and comparative examples, a use test was conducted on 20 panelists.
The method is to rest for 15 minutes under constant temperature and humidity of 20 ° C./50% RH, and then apply a predetermined amount (0.5 mL) of the sample to the inner side of the forearm. The five items of goodness, freshness after application, no stickiness, and overall evaluation were rated on a five-point scale, and the total score of 20 people was evaluated.
(Evaluation criteria for each item: very good: 5 points, good: 4 points, normal: 3 points, bad 2 points, very bad: 1 point)
The feeling of use was evaluated according to the following five grades, and ◎ ○ △ was judged as a good feeling of use.
(Score evaluation: 85 points or more: ◎, 70-85 points: ○, 60-70 points: △, 50-60 points: ▲, less than 50 points: ×)

Claims (6)

Containing chondroitin 4-sulfate, heparin, heparin-like substance (listed in the Japanese Pharmacopoeia Standards), iota-carrageenan or hyaluronic acid in the inner aqueous phase as a polysaccharide having a sulfone group and / or a carboxyl group in the molecule W / O / W type composite emulsion characterized by 2. The W / O / W type composite emulsion according to claim 1, wherein the polysaccharide is chondroitin 4-sulfate, heparin, heparin-like substance (listed in the Japanese Pharmacopoeia Standards for Drugs) or hyaluronic acid . The W / O / W type composite emulsion according to claim 1 or 2, wherein the inner water phase / oil phase containing the polysaccharide is 50/50 to 90/10 (mass ratio). The W / O type emulsion comprising the inner aqueous phase and the oil phase containing the polysaccharide / the outer aqueous phase = 30/70 to 80/20 (mass ratio). W / O / W type composite emulsion according to item. As an emulsifier for primary emulsification, a sorbitan fatty acid ester, glycerin fatty acid ester, propylene glycol fatty acid ester, lipophilic polyglycerin fatty acid ester, lipophilic polyoxyethylene castor oil, lipophilic polyoxyethylene castor oil, and lipophilic polyoxyethylene hydrogenated castor oil having an HLB by Griffin of 10 or less The W / O / W type composite emulsion according to any one of claims 1 to 4, further comprising a surfactant selected from the group consisting of lipophilic sucrose fatty acid esters . As emulsifier for secondary emulsification, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene glycerin fatty acid ester, hydrophilic polyglycerin fatty acid ester, polyoxyethylene sorbit fatty acid ester, hydrophilic polyoxyethylene castor oil, hydrophilic polyoxyethylene hardened castor Oil, polyoxyethylene sterol, hydrophilic polyethylene glycol fatty acid ester, hydrophilic polyoxyethylene alkyl ether, polyoxyethylene alkyl phenyl ether, polyoxyethylene polyoxypropylene alkyl ether, polyoxyethylene polyoxypropylene polymer and hydrophilic W / O / W type multiple emulsion of any one of claims 1 to 5, characterized in that it comprises a surfactant selected from the group consisting of sugar fatty acid esters