JPH0377820A - Dermal ointment - Google Patents

Abstract

PURPOSE:To obtain a dermal ointment free from oiliness when used, good in adhesivity and absorbability, thus useful as a pharmaceutical, cosmetic, etc., by incorporating active ingredient(s) in a base component comprising a mixture of acrylic and methacrylic copolymers, a lower alcohol and water. CONSTITUTION:The objective dermal ointment can be obtained by incorporating (A) a base component comprising (1) a film-forming agent, a mixture of acrylic and methacrylic copolymers (e.g. copolymers from at least two kinds of monomers selected from methacrylic acid, methyl methacrylate, ethyl acrylate, etc.). (2) a lower alcohol such as ethanol or isopropanol, and (3) water, with (B) active ingredient(s) such as antifungal agent, anti-inflammatory agent and/or hair grower. The production process is as follows: the above-mentioned film- forming agent, when the final agent is a solution is dissolved in the lower alcohol, and the resultant solution is incorporated with the active ingredient(s) and water followed by filling in an application container. Or, said film-forming agent, when the final agent is in the form of aerosol, is put into a pressure vessel, into which a propellant is then pressed. The amount of the water to be used is pref., such as to be <=50wt.%, 5-50wt.% for solution; <=20wt.% for aerosol agent.

Description

DETAILED DESCRIPTION OF THE INVENTION 1) Industrial Application Field The present invention relates to an external skin preparation used in cosmetics, quasi-drugs, pharmaceuticals, and the like. More specifically, it contains an acrylic and methacrylic copolymer together with a film-forming agent, and forms a film by spraying or applying it onto the skin, thereby effectively applying the active ingredient to the skin. The present invention relates to a characteristic topical skin preparation. It is prescribed in the form of liquid, aerosol, etc., and is an anti-inflammatory agent and an anti-inflammatory agent. Can be applied to Norgy agent, hair growth agent, and insect repellent.

2) Prior Art Until now, preparations in which hydrophobic polymers are dissolved in acetin, ethyl acetate, etc. have been known as external preparation compositions that form a film (Japanese Unexamined Patent Publication No. 50-4914. Showa 50-
25725). However, these have problems in use, such as the film-forming agent becoming sticky when drying, and the removal from the skin causing discomfort. Furthermore, since it is dissolved in an organic solvent such as acetone or ethyl acetate, it poses problems such as being harmful to the body when applied. In addition, preparations using water-soluble polymers such as polyvinylbutyral and polyvinyl alcohol-soluble polyamide as film-forming agents are also known (JP-A-54-140714; JP-A-58-78).
633. JP 5947269, JP 57-1123
23), j, However, the transparency of these films is also poor and it takes time to form a film. It had drawbacks such as the coating being sticky and having a poor feel when used.

3) Problems to be Solved by the Invention The prior art of external preparations for skin containing film-forming agents have various problems as described above. Therefore, an object of the present invention is to obtain an external preparation for skin containing a film-forming agent having the following characteristics.

■Dries quickly and is not sticky.

■The film is strong and does not stain clothes.

■It must be a highly safe composition.

■Good skin adhesion and does not easily peel off.

4) Means for solving the problem In view of the above situation, the present inventors conducted intensive research and found that acrylic and methacrylic compounds, which have been conventionally used as film coating agents for oral preparations, have been developed. The present invention was completed based on the discovery that a formulation that fully satisfies the above objectives can be obtained by incorporating the polymer Eudragisoto as a film-forming agent.

That is, the present invention provides an active ingredient, Eudragisoto.

Liquid agent and active ingredient consisting of lower alcohol and water.

This is an external skin preparation containing a film-forming agent, characterized in that it is an aerosol consisting of Eudragift, a lower alcohol and/or a water propellant.

The present invention will be explained in more detail below.

The active ingredients included in the present invention include tolnaftate, clotrimazole, bifonazole, miconazole nitrate, econacyl nitrate, ketoconazole nitrate, omoconazole nitrate, oxiconazole nitrate, exalamide,
Torcyclate 5 Antibacterial agents such as siccanin, hydrocortisone, dexamethasone, clobetasol 17-propionate.

Dexamethasone 17-valerate, fluocinonide,
Steroid anti-inflammatory drugs such as haldinonide and amcinonide, indomethacin, and ketoprofen.

Flurbiprofen, Felbinac, Piroxicam, Ibuprofen Piconol, Benzadac.

Nonsteroidal anti-inflammatory agents such as butyl flufenamic acid and bufexamac, local irritants such as l-menthol, camphor, nonylic acid vanillylamide, kabsaicin, ketotifen, azelastine and their salts, chlorpheniramine maleate, oxatomide, Antiallergic agents such as tranilast, storium cromoglycolate, benzalkonium chloride, benzyl nicotinate, and estradiol.

Flooding agents such as capsicum tincture 2 photosensitizer, insect repellents such as diethyl toluamide, turpentine oil 3 camphor, etc. are blended. These active ingredients are blended in a range of 0.0001 to 5% by weight depending on the effective amount of each active ingredient.

Eudragit, which is blended as a film forming agent, contains methacrylic acid, methyl methacrylate, ethyl methacrylate, butyl methacrylate,
2 such as trimethylammonium chloride, edyl acrylate, dimethylaminoethyl methacrylate, etc.
Eudragit E100 (methyl methacrylate, butyl methacrylate, dimethylaminoethyl methacrylate copolymer), Eudragit L30D-55, Eudragit L100-55 (methacrylic acid Eudragit (ethyl acrylate copolymer), Eudragit) Lloo (methacrylic acid/methyl acrylate copolymer), Eudragit 5100 (methacrylic acid/methyl methacrylate copolymer), Eudragit R3IOOL
, Eudragit R5PML, Eudragit R330
DL, Eudragit R3100, Eudragit R3
Use products such as PM, Eudragit i-RS 30D (ethyl acrylate, methyl methacrylate, trimethylammonium ethyl methacrylate chloride copolymer), Eudragit NE30D (methyl methacrylate, ethyl acrylate copolymer), etc. be able to.

The blending amount of these Eudragits is 0.05□5% by weight, preferably 0.1 to 2% by weight, either alone or in combination of two or more. Lower alcohols such as ethanol and isopropanol are blended as a solvent for dissolving Eudragit. Ethanol is most preferred as the lower alcohol.

The amount of lower alcohol blended is sufficient to dissolve Eudragit, that is, 5 = 80% by weight. The liquid formulation is 10 to 80% by weight, preferably 40 to 70% by weight,
For aerosols, 5 to 60% by weight, preferably 1
O-=50% by weight is blended. Further, water is blended in an amount of 50% by weight or less. In the case of a liquid agent, 5 to 50% by weight, preferably 10 to 40% by weight, and in the case of an aerosol agent, 20% by weight.
It is blended in an amount of not more than 10% by weight, preferably not more than 10% by weight.

In the case of making an aerosol, a film-forming aerosol can be produced by adding a propellant used in ordinary aerosols. Examples of the propellant include liquefied petroleum gas, dimethyl ether, carbon dioxide gas, or chlorofluorocarbons. Freon 113. Freon i i 4
Propellants such as can be used. These propellants also range in weight from 10=50 to
It is press-fitted so that the angle is 8°0 pupil/(2). Among the above propellants, a combination of liquefied petroleum gas and dimethyl ether is most preferred from the viewpoint of Eudragit solubility and film drying properties. Further, the blending ratio of liquefied petroleum gas and dimethyl ether is preferably 50:50 = 80820% by volume in terms of flammability and solubility of the film forming agent.

In addition to the above essential ingredients, in order to dissolve the above active ingredients,
Crotamiton, benzyl alcohol, fatty acid ester,
It is also possible to incorporate a solubilizing agent such as glycol, and powders such as talc, nylon powder silicon powder, and polystyrene powder for the purpose of improving the feeling of use.

Next, the manufacturing method of the present invention will be described. To produce the formulation of the present invention, first dissolve the film-forming agent Eudragisoto in a lower alcohol, add the active ingredient, other additives, and/or purified water, and use a coating container or sprayer. Just fill it into a container. To make an aerosol, Eudragift is dissolved in lower alcohol, the active ingredient, other additives and/or purified water are added to it, the mixture is placed in a pressure-resistant container, and a valve is attached.
It can be produced by press-fitting a propellant.

EXAMPLES The present invention will be explained in more detail with reference to Examples below.

Example 1 60 g of ethanol was added to 1 g of clotrimazole and dissolved by stirring. Add Eudragift L100 1 to this solution.
g was added and dissolved. Next, a solution of 1 g of diisopropanol dissolved in 37 g of purified water was added and stirred until homogeneous to obtain a solution containing an antibacterial agent.

Example 2 60 g of ethanol was added to 2 g of ketoprofen and dissolved by stirring. Add 1g of Eudragit E100 to this solution.
was added and dissolved. Next, a solution of 1 g of diisopropanol dissolved in 36 g of purified water was added and stirred until homogeneous to obtain a liquid preparation containing an anti-inflammatory agent.

Example 3 40 g of ethanol was added to 1 g of clotrimazole and dissolved by stirring. Add Eudragit l-5ioo to this solution.
Ig was added and stirred to dissolve. Next, this was placed in a pressure-resistant container, and after opening the valve, 29.4 g of liquefied petroleum gas/dimethyl ether (65/35% by weight) was press-fitted to obtain an aerosol formulation containing an antibacterial agent.

Example 4 35 g of ethanol was added to 2 g of ρ-menthol and 0.5 g of glycol salicylate, and the mixture was stirred and dissolved.

Add Eudragi) RSPML Ig to this solution,
Stir to dissolve. Next, 5 g of purified water was added to this solution and stirred, then placed in a pressure-resistant container and fitted with a valve.
729.4 g was injected under pressure to obtain an aerosol formulation containing an anti-inflammatory agent.

Example 5 40 g of ethanol was added to 1 g of ketoprofen and dissolved by stirring. Add Eudragit R5PM I to this solution.
g and stirred to dissolve. Next, this was placed in a pressure-resistant container, and after a valve was attached, 29.4 g of liquefied petroleum gas/dimethyl ether (65/35% by weight) was press-fitted to obtain an aerosol formulation containing an anti-inflammatory agent.

Example 6 40 g of ethanol and 1 g of crotamiton were added to 1 g of clotrimazole and dissolved by stirring. Eudragift L30D-551g was added to this solution and dissolved by stirring. Next, put this in a pressure-resistant container and attach a valve, then liquefied petroleum gas/dimethyl ether (65/35% by weight) 2
7.4 g was press-injected to obtain an aerosol preparation containing an antibacterial agent.6 Example 7 40 g of ethanol and 2 g of diethyl sebacate were added to 1 g of ketoprofen and dissolved by stirring.

1 g of Eudragit L100 was added to this solution and dissolved by stirring. Next, put this in a pressure-resistant container and attach a valve, then liquefied petroleum gas/dimethyl ether (65/35
% by weight) was press-injected to obtain an aerosol formulation containing an anti-inflammatory agent.

Example 8 40 g of ethanol and 1 g of isobutyl myristate were added to 0.0004 g of ethinyl estradiol and 0.01 g of benzyl nicotinate, and dissolved with stirring.

Eudragift L100 Ig was added to this solution, stirred and dissolved. Next, this was placed in a pressure-resistant container and a valve was attached, followed by liquefied petroleum gas/dimethyl ether (65/3
5% by weight) was injected under pressure to obtain an aerosol formulation containing a hair growth agent.

Example 9 085 g of ketotiphen, 40 g of ethanol, and 1 g of isopropyl myristate were added and dissolved with stirring. Eudragi Nol-31001g was added to this solution and dissolved by stirring. Next, put this in a pressure-resistant container and attach a valve, then liquefied petroleum gas/dimethyl ether (65/35
% by weight) was press-injected to obtain an aerosol formulation containing an anti-allergic agent.

Example 10 Add diethylamide Ig, 0.5 g of 7-camphor, 40 g of ethanol and isopropyl myristate,
Stir to dissolve. Add Eudragift 5100 to this solution.
Add 1g and stir to dissolve.

Next, put this in a pressure-resistant container, and after attaching a valve, liquefied petroleum gas/dimethyl ether (65/35% by weight) 27,
4 g was injected under pressure to obtain an aerosol formulation containing an insect repellent.

Reference Example 1 Clotrimazole Ig and 5 g of soluble nylon (CM-9000) were added and dissolved in 70 g of ethanol, placed in a pressure-resistant container, and fitted with a valve, followed by 11.30 g of Freon.
Then, 1245 g of Freon was compressed to obtain an aerosol formulation containing an antibacterial agent.

Test Example 1 The aerosol formulation of Example 1 of the present invention and the aerosol formulation of Reference Example 1 were sprayed onto the forearm of a healthy adult male and tested for dryness and feeling of use. The results are shown in Table 1.

Table 1 Spray m test of film-forming aerosol formulation It is also superior to other film-forming agents in terms of safety.

From the above, the skin external preparation of the present invention containing antibacterial agents, anti-inflammatory agents, anti-allergy agents, hair growth agents, and insect repellents as active ingredients is very useful industrially as cosmetics, pharmaceutical parts, and pharmaceuticals. It is.

As can be seen from Table 1, the film-forming agent-containing aerosol formulation of the present invention was superior to the aerosol formulation of the reference example in terms of drying properties of the film and feeling of use.

5) Effect of invention

Claims (1)

[Scope of Claims] 1. An external skin preparation comprising an active ingredient blended into a base component consisting of a mixture of acrylic and methacrylic copolymers, a lower alcohol, and water. 2. An external skin preparation comprising an active ingredient blended into a base consisting of a mixture of acrylic and methacrylic copolymers, a lower alcohol and/or water, and a propellant. 3. Acrylic and methacrylic copolymers 0.05~
2. The skin external preparation according to claim 1, which is a liquid preparation containing an active ingredient in a base component consisting of a mixture of 5% by weight, 10 to 80% by weight of lower alcohol, and 5 to 50% by weight of water. 4. Acrylic and methacrylic copolymers 0.05~
Claim 2, which is an aerosol agent containing an active ingredient in a base component consisting of a mixture of 5% by weight, 5 to 60% by weight of lower alcohol and/or 20% by weight or less of water, and 10 to 50% by weight of a propellant. External skin preparation.