JPH0380762B2 - - Google Patents

Description

BACKGROUND TECHNICAL FIELD OF THE INVENTION The present invention relates to a novel base composition for external use, and more particularly to a base composition for external use that hardens itself to form a film when applied to the skin. This invention relates to the base composition used. Prior art and its problems Conventionally, as a base composition for external use that forms a film on the skin, a water-insoluble film-forming polymer and a 2.0 to 50%
Aqueous emulsions with % by weight of water-soluble film-forming polymers (JP 50-25725), topical preparations consisting of crotamiton, propylene glycol, water and carboxyvinyl polymers (JP 51-73115) and hydrophilic A coating material (Japanese Unexamined Patent Publication No. 55-28918) comprising a water-insoluble polymer, a high-boiling plasticizer of the polymer and/or an organic solvent, and an aqueous liquid is known. These base compositions are suitable for topical use on the skin,
Since it forms a continuous film on the skin, it has the advantage that the medicine applied like an ointment will not contaminate clothes or be rubbed off by them. However, conventional film-forming bases do not necessarily have sufficient affinity for the skin and are poor in flexibility, so there has been a desire for an external base composition with improved adhesion. OBJECTS OF THE INVENTION The first object of the present invention is to provide an external base composition that forms a highly flexible film on the skin that spreads well. Even when such a coating is formed on the joints of hands and feet, it does not peel off or cause a feeling of resistance or discomfort during bending and stretching movements. A second object of the present invention is to provide an external base composition that forms a film on the skin that has excellent release properties of medicinal ingredients and is highly percutaneously absorbed into the human body. A third object of the present invention is to provide an external base composition that forms a film on the skin with excellent adhesion to the skin. A fourth object of the present invention is to provide an external base composition that forms a moisture permeable film on the skin. Other objects of the invention will become apparent from the detailed description below. DETAILED DESCRIPTION OF THE INVENTION In order to achieve the above objects, the present invention has the configurations described in the following sections. (1) A water-soluble vinyl polymer having film-forming properties,
It consists of a plasticizer for the water-soluble vinyl polymer, an aqueous phase formed by an aqueous liquid, an oil phase formed by a fatty acid ester, and a nonionic surfactant that emulsifies the fatty acid ester in the aqueous liquid. . A base composition for external use, characterized in that the oil phase is present in an emulsified state in the aqueous phase. (2) In the composition of the present invention, the water-soluble vinyl polymer is one selected from the group consisting of fully saponified or incompletely saponified polyvinyl alcohol, polyvinylpyrrolidone, and vinylpyrrolidone-vinyl acetate copolymer, or It is a polymer of two or more types. (3) The composition of the present invention comprises the vinylpyrrolidone-
In the vinyl acetate copolymer, the monomer ratio of vinyl acetate to vinylpyrrolidone does not exceed 1. (4) The composition of the present invention is characterized in that the fatty acid ester is an aliphatic alcohol having 2 to 20 carbon atoms and an aliphatic alcohol having 3 carbon atoms.
It is an ester with 1 to 16 fatty acids. (5) In the composition of the present invention, the plasticizer is a polyhydric alcohol having 2 or 3 carbon atoms or sorbitol. (6) In the composition of the present invention, the water-soluble liquid is water or an aqueous ethanol solution. (7) In the composition of the present invention, the nonionic surfactant is one or two selected from the group consisting of polyhydric alcohol esters, polyoxyethylene derivatives, and polyoxyethylene-polyoxypropylene block copolymers. It is more than one nonionic surfactant. (8) In the composition of the present invention, the proportion of the water-soluble vinyl polymer in the composition is 10 to 40% by weight. (9) In the composition of the present invention, the proportion of the fatty acid ester in the composition is 1 to 20% by weight. (10) The composition of the present invention has a ratio of the plasticizer to the water-soluble vinyl polymer of 5:1 to 1:2.
It is. (11) In the composition of the present invention, the proportion of the water-soluble liquid in the composition is 40 to 80% by weight. (12) In the composition of the present invention, the proportion of the nonionic surfactant in the composition is 1 to 15% by weight. (13) In the composition of the present invention, the water-soluble vinyl polymer is a mixture of polyvinyl alcohol and polyvinylprolidone. (14) In the composition of the present invention, the aqueous phase contains an acrylic resin alkanolamine solution or dextran. In the composition of the present invention, the water-soluble vinyl polymer (component A) is a component that forms a continuous film on the skin or wound surface, and is a water-soluble vinyl polymer that is not toxic or irritating to the skin. is used,
Preferred examples of such polymers include fully saponified and/or incompletely saponified polyvinyl alcohol, polyvinylpyrrolidone, and vinylpyrrolidone-vinyl acetate copolymer. Here, completely saponified polyvinyl alcohol refers to polyvinyl acetate obtained by polymerizing vinyl acetate monomer, which has been completely saponified to polyvinyl alcohol, and which has substantially no acetyl groups in the polymer. means. In addition, incompletely saponified polyvinyl alcohol refers to polyvinyl acetate that is not completely saponified and some acetyl groups remain in the polymer. Polyvinyl acetate in which 50% or more of the acetyl groups are saponified, ie, a saponification degree of 50 or more, preferably 70 or more, is used. The degree of polymerization is preferably about 300 to 2000. The average molecular weight of polyvinylpyrrolidone is
Approximately 1,500 to 700,000 is desirable. The vinylpyrrolidone-vinyl acetate copolymer has a monomer ratio of vinyl acetate to vinylpyrrolidone that does not exceed 1;
That is, a copolymer in which the vinyl acetate component is not more than the vinyl pyrrolidone component is preferably used. If the above ratio exceeds 1, it becomes difficult to dissolve in water, which is not desirable. The average molecular weight of the above copolymer is desirably about 100,000 to 100,000. The above-mentioned water-soluble vinyl polymers can be used alone or in combination of two or more kinds of polymers. In the present invention, fatty acid ester (component B)
provides skin compatibility and flexibility to the coating, and also makes the composition non-sticky and refreshing. Furthermore, it has the effect of facilitating the penetration of the drug contained in the composition of the present invention into the skin. The fatty acid ester of the present invention is preferably an ester of an aliphatic alcohol having 2 to 20 carbon atoms and an aliphatic alcohol having 3 to 16 carbon atoms. Preferred examples include isopropyl myristate, myristyl lactate, cetyl lactate, and lauric acid. Examples include hexyl ester, sebacic acid diethyl ester, adipic acid diisopropyl ester, and the like. The plasticizer (component C) of the present invention can form a uniform aqueous solution together with the water-soluble vinyl polymer, and imparts plasticity to the formed film. However, this plasticizer alone cannot create a film that adheres to the skin for a long time, and the presence of the aforementioned fatty acid ester is required. Such plasticizers have 2 or 3 carbon atoms.
polyhydric alcohols (e.g. ethylene glycol,
Propylene glycol or glycerin) or sorbitol are preferably used. The aqueous liquid (component D) of the present invention is used as a solvent, and is essentially water (preferably distilled water), but it can shorten film formation time, dissolve medicinal ingredients, and disperse polymers. Ethanol can be added for purposes such as improving the quality. In that case,
The appropriate concentration of ethanol is 5 to 20% (V/V). The nonionic surfactant (component F) of the present invention is used to emulsify the fatty acid ester in an aqueous liquid, and any general surfactant can be used without particular limitation as long as it does not have ionicity. Typical examples include polyhydric alcohol esters (e.g., monoglyceryl stearate, sorbitan monooleate, sorbitan sesquioleate, etc.), polyoxyethylene derivatives (e.g., polyoxyethylene lauryl ether, polyoxyethylene sorbitan monooleate, etc.) , polyoxyethylene monooleate, polyoxyethylene hydrogenated castor oil, etc.) and polyoxyethylene-polyoxypropylene block copolymers. In the composition of the present invention, the ratio of each component is not critical, but a film is formed within a short time after application to the skin, and the film has appropriate adhesion and flexibility and is free of drug components. In order to have good release properties,
In the whole composition, component A is 10 to 40% (W/W%, the same applies hereinafter), preferably 15 to 30%, component B is 1 to 20%,
Preferably 2-10%, C component 1-30%, preferably 5-20%, D component 40-80%, E component 1-30%.
It is 15%. In the above composition, the amount of component C (plasticizer) depends on the amount of component A (water-soluble vinyl polymer) used, and is in a ratio of 5:1 to 1:2, preferably 3:1 to component A. Used in a ratio of ~1:1. In the composition of the present invention, an acrylic resin alkanolamine solution or dextrin (component F) can be added as a tackifying component to further improve the adhesion of the film to the skin.
What is acrylic resin alkanolamine liquid here?
It refers to a solution obtained by subjecting acrylic acid, an acrylic ester, and a methacrylic ester to solution polymerization in ethanol, and adding an alkanolamine solution to the resulting polymerization solution. The amount of component F used is not critical, but it is in the entire composition.
It is within 20%, preferably 5 to 15%. If the amount of F component used exceeds 20%, the formed film will become sticky, which is not preferable. The composition of the present invention can contain various medicinal ingredients conventionally used as external medicines. For example, antibiotics such as oxytetracycline, chlortetracycline, and neomycin sulfate, antihistamines such as diphenhydramine, anesthetics such as benzocaine and lidocaine, and antibacterial agents such as iodine, nitrofurazone, benzalkonium chloride, tolnaftate, and clotrimazole. , corticosteroids such as hydrocortisone and triamcinolone acetonide, and non-steroidal anti-inflammatory agents such as indomethacin, flubiprofen and bufuexamac. These drugs are included in the compositions of the invention at pharmaceutically effective concentrations. The concentration range is not particularly limited, but is usually 0.01 to 20% by weight of the total composition. When the composition of the present invention is applied to the skin or wound surface, the medicinal ingredient is
It is absorbed into the human body through the formed film. The composition of the present invention is prepared according to conventional methods. For example, a vinyl polymer is dispersed in distilled water, heated and dissolved while stirring, and a plasticizer and, if desired, an acrylic resin alkanolamine solution or dextrin are added and dissolved to form an aqueous phase. Separately, a mixture of a fatty acid ester and a nonionic surfactant is heated and dissolved (oil phase), and added to the aqueous phase with vigorous stirring to emulsify. When cooled to room temperature while stirring, the topical base composition of the present invention is obtained as a uniform semi-solid. In order to include a medicinal ingredient in the composition of the present invention,
Depending on the nature of the medicinal ingredient, it is dissolved in the aqueous or oil phase. The composition of the present invention is a semi-solid with appropriate hardness, is stored in a sealed container such as a tube, and is applied to the skin or wound surface in the same manner as conventional ointments and creams. It dries in 2 to 5 minutes after application, forming a flexible film. The film adheres to the skin for 12 to 24 hours, causing no discomfort or discomfort, and does not interfere with daily life. After use, the coating can be easily removed by peeling off with fingers or washing with water. Next, the present invention will be explained in more detail by giving Examples and Comparative Examples. Example 1

【table】

[Table] (Production method) In Example (1), polyvinyl alcohol is dispersed in distilled water, heated to 90°C to dissolve it, then concentrated glycerin is added and cooled to 75°C to form an aqueous phase. Separately, isopropyl myristate and sorbitan monooleate are heated to 75°C and dissolved, added to the aqueous phase while stirring vigorously to emulsify, and then slowly cooled to room temperature to produce it. In Comparative Example a, in the same manner as in Example 1, only the aqueous phase was prepared and cooled to room temperature. In Comparative Example b, a commercially available cosmetic pack was used as it was. The composition thus obtained was applied to a polyester film plate (Lumirror, manufactured by Toray Industries, Inc.) to a thickness of 200 μm, and the elongation response curve of the film obtained by drying is shown in FIG. It was found that Example (1) according to the present invention had lower initial stress and greater flexibility than Comparative Example (a) and Comparative Example (b), and was excellent as an external base composition. Example 2

【table】

[Table] (Production method) In Example (2), fluocinolone acetonide is added to propylene glycol and dissolved by heating to 60°C. Separately, disperse polyvinyl alcohol in water and
The mixture is heated to ℃ and dissolved, and propylene glycol in which polyvinylpyrrolidone and fluocinolone acetonide are dissolved is added, and the mixture is cooled to 75℃ to form an aqueous phase. Separately, diisopropyl adipate and polyoxyethylene monostearate are heated to 75°C, dissolved, added to the aqueous phase while stirring vigorously, emulsified, and cooled to room temperature to produce. Comparative example (c) was prepared by dissolving cetanol, white petrolatum and liquid paraffin by heating them to 75°C on a water bath.
The well-stirred mixture is added to a mixture of fluocinolone acetonide dissolved in propylene glycol and other chemicals dissolved in purified water and heated to 75°C, and the mixture is cooled to room temperature. In order to confirm the release of fluocinolone acetonide, a medicinal ingredient, from the external composition obtained in this way, the amount of fluocinolone acetonide released into 100 ml of absorption liquid using a Sartorius ointment release simulator. was measured over time. As a control, Comparative Example (c) was used as a cream formulation currently used in dermatology. The results are shown in Figure 2. From the above tests, it is clear that the composition according to the invention has excellent drug release properties. Example 3 (Formulation) Ingredients Composition (wt%) Polyvinyl alcohol (manufactured by Shin-Etsu Chemical Co., Ltd., PA-05)
15 Isopropyl myristate (Nikko Chemicals Co., Ltd.)
10 Concentrated glycerin 10 (Asahi Denka Co., Ltd.: Glycerin G) Acrylic resin alkanolamine liquid (Gouoi Kagaku Co., Ltd.)
Manufacturer: Plus Size L-53P) 15 Sorbitan sesquioleate (Nikko Chemicals Co., Ltd.)
Manufactured by: SO-15) 5 Distilled water 45 (Manufacturing method) Polyvinyl alcohol is separated into distilled water, heated to 90°C while stirring to dissolve it, cooled to 75°C, and then mixed with acrylic resin alkanolamine solution and concentrated glycerin. to form an aqueous phase. Separately, isopropyl myristate and sorbitan sesquioleate are heated to 75°C, dissolved, and added to the aqueous phase with vigorous stirring to emulsify. Next, cool to room temperature while stirring slowly to obtain a homogeneous semi-solid material. The external base composition thus obtained has a suitable semi-solidity like an ointment and can be easily spread on the skin. When this external base composition was evaluated on the flexor side of the human forearm, the time it took to dry to the touch (time until the stickiness disappeared) on the skin was about 3 minutes, and it remained fixed for 24 hours, and it did not stick to clothes. No falling off due to friction was observed. Effects of the Invention According to the present invention, there is provided an external base composition that forms a film on the skin or wound surface with excellent adhesion to the skin and excellent drug release properties. That is, as shown in the elongation test of Example 2, the composition of the present invention provides a coating with low initial stress and high flexibility. The small initial stress means that
It means that the coating is stretched by a slight force,
Even if the coating is formed on the joints of the hands and feet, the coating will not peel off during bending and stretching movements, and will not cause a feeling of resistance or discomfort. As shown in the release test of Example 2, the composition of the present invention has excellent release properties of the drug contained therein. Therefore, when the composition of the present invention contains medicinal ingredients and is applied to the skin or wound surface, the drug is well absorbed into the human body and a high therapeutic effect can be expected. In particular, in the external base composition of the present invention, the oil phase formed by the fatty acid ester is combined with a nonionic surfactant to form a film-forming water-soluble vinyl polymer and a plasticizer for the water-soluble vinyl polymer. and an aqueous liquid in an emulsified state, so when the base composition of the present invention is applied to the skin and the aqueous liquid evaporates, it is dispersed in the aqueous liquid. The oil droplets of the fatty acid ester that had been mixed partially aggregate on the coating surface, and the fatty acid ester is scattered in the formed coating, and the scattered fatty acid ester improves the adhesiveness of the coating. In addition, if a drug is contained in this fatty acid ester, when it is applied, the drug that was present within the thickness of the composition and did not come into contact with the skin surface will be removed by the volatilization of the aqueous liquid. aggregation of fatty acid esters,
Its migration to the skin surface can reduce the drug that comes into contact with the skin and never comes into contact with the skin surface, which is permanently trapped in the base composition, reducing the release of the medicinal ingredient and improving the ability of the human body to Excellent transdermal absorption. Similarly, when the drug is water-soluble, it forms a thin film due to the volatilization of the aqueous liquid that is its own solvent, and since it does not contain any other film-forming components, the composition does not thicken when applied. Since the drug that is present within the skin and has not come into contact with the skin surface also moves to the skin surface, it is also excellent in release of medicinal ingredients and percutaneous absorption into the human body. The composition of the present invention also forms a film on the skin with excellent adhesion to the skin. The water-soluble vinyl polymer itself has excellent adhesiveness, but by incorporating acrylic resin alkanolamine or dextrin into this composition, the adhesiveness is further improved, which, together with the above-mentioned good spreadability, improves the adhesion to the skin. Provides an extremely good coating. The composition of the present invention forms a moisture permeable film. Since the film has moisture permeability, the moisture from sweat is released into the outside air, so that it does not cause stuffiness or rash even after long-term use. Furthermore, it does not cause any discomfort or discomfort to the skin. Furthermore, the composition of the present invention has no toxicity to the skin.
Forms a non-irritating film. As described above, the present invention provides an external base that is pleasant to use and forms a coating with high therapeutic effects.

[Brief explanation of drawings]

FIG. 1 shows the stress curve of the coating, and FIG.
Figure 2 shows the release curve of fluocinolone acetonide. In FIG. 1, 1 is the coating of the present invention obtained in Example 1,
A shows the stress curve of the coating film obtained in Comparative Example a, and b shows the stress curve of a commercially available cosmetic pack having the composition of Comparative Example b. In FIG. 2, 2 shows the drug release curve of the coating of the present invention obtained in Example 2, and c shows the drug release curve of a commercially available cream formulation having the composition of Comparative Example C.

Claims (1)

[Claims] 1. A water-soluble vinyl polymer having film-forming properties;
an aqueous phase formed by the plasticizer of the water-soluble vinyl polymer and an aqueous liquid; an oil phase formed by an ester of an aliphatic alcohol having 2 to 20 carbon atoms and a fatty acid having 3 to 16 carbon atoms; An external base composition comprising a nonionic surfactant that emulsifies the fatty acid ester in the aqueous liquid, and wherein the oil phase is present in an emulsified state in the aqueous phase. 2. The water-soluble vinyl polymer is one or more polymers selected from the group consisting of fully saponified or incompletely saponified polyvinyl alcohol, polyvinylpyrrolidone, and vinylpyrrolidone-vinyl acetate copolymer. An external base composition according to claim 1. 3. The external base composition according to claim 2, wherein in the vinylpyrrolidone-vinyl acetate copolymer, the monomer ratio of vinyl acetate to vinylpyrrolidone does not exceed 1. 4. The external base composition according to claim 1, wherein the plasticizer is a polyhydric alcohol having 2 or 3 carbon atoms or sorbitol. 5. The external base composition according to claim 1, wherein the aqueous liquid is water or an ethanol aqueous solution. 6. The nonionic surfactant is one or two selected from the group consisting of polyhydric alcohol esters, polyoxyethylene derivatives, and polyoxyethylene-polyoxypropylene block copolymers.
The external base composition according to claim 1, which is one or more nonionic surfactants. 7. The external base composition according to any one of claims 1 to 3, wherein the proportion of the water-soluble vinyl polymer in the composition is 10 to 40% by weight. 8 The proportion of fatty acid ester in the composition is 1 to 1.
Claim 1 or 7 which is 20% by weight
The external base composition described in 1. 9 Claim 1, wherein the ratio of plasticizer to water-soluble vinyl polymer is from 5:1 to 1:2.
The external base composition according to item 1, 4, 7 or 8. 10. The external base composition according to any one of claims 1, 5, or 7 to 9, wherein the proportion of the aqueous liquid in the composition is 40 to 80% by weight. 11 Claim 1, wherein the proportion of nonionic surfactant in the composition is 1 to 15% by weight
The external base composition according to item 1 or any one of items 6 to 10. 12. The external base composition according to claim 1, wherein the water-soluble vinyl polymer is a mixture of polyvinyl alcohol and polyvinylpyrrolidone. 13. The external base composition according to claim 1, wherein the aqueous phase contains an acrylic resin alkanolamine liquid or dextran.