KR102584365B1 - Foaming external composition - Google Patents

Abstract

Provided is an external composition that forms foam upon use, comprising a polymer surfactant as a foam-generating component. The external composition of the present application is provided by filling, for example, a pump former container or a squeeze former container.

Description

Foaming external composition

The present invention relates to a composition for external use that forms a foam upon use.

Conventionally, ointments, creams, lotions, etc. have been used as external medicines for use on the skin (including the scalp), but in recent years, they can be easily applied without dripping and can be spread smoothly, making them excellent in usability. An aerosol-type formulation that ejects in a foamy form using a foaming liquid and a propellant has been developed. However, since this aerosol formulation uses liquefied gas such as liquefied propane as a propellant, it is subject to regulations regarding volatile organic compounds, and there are environmental problems such as the inability to repeatedly use used cans. Recently, a non-gas type formulation that takes on a foamy appearance when discharged using a pump former container or a squeeze former container has also been developed.

In general, surfactants are known as ingredients that form foam. Anionic surfactants have high foaming power but are considered to be irritating, while nonionic surfactants have low irritating properties but are considered to have low foaming power. Therefore, no satisfactory foaming power and safety have been obtained with a single type of surfactant. . It has been reported that safe and good foam can be formed by combining polyoxyethylene alkyl ether and/or polyoxyethylene alkenyl ether with polyoxyethylene fatty acid ester and/or polyoxyethylene hydrogenated castor oil as a nonionic surfactant. (Patent Document 1).

Japanese Patent Publication No. 2017-214407

However, in order to lessen the burden on the skin, it is preferable to use fewer additives, and with fewer additives, new foaming properties can be achieved, such as better foam quality, moderate foam retention without dripping, and foam with a good feeling of use. There is a strong desire to develop compositions for external use.

The object of the present invention is to provide a foaming composition for external use that can produce foam with better foam quality, moderate foam retention without dripping, and a good feeling of use.

The present inventors conducted extensive research in consideration of this situation and discovered that the desired purpose can be achieved by using a polymer surfactant as a foaming agent. That is, the present invention relates to an external composition that forms foam when used, and which contains a polymer surfactant as a foam-generating component.

As is clear from the results of the examples described below, by using the formulation of the present invention, a new external composition can be obtained with better foam quality, moderate foam retention without dripping, and good feeling of use, and in particular, a pump that does not require a gas. By using a foamer container or a squeeze foamer container, a composition suitable for the treatment of skin diseases such as atopic dermatitis was obtained, which can be used as a non-gas type preparation that exhibits a foamy form when discharged.

Figure 1 is a photograph showing the results (foam formation) of Example 1.
Figure 2 is a photograph showing the results of Example 2 (foam sustainability (evaluated with polyurethane)).
Figure 3 is a photograph showing the results of Example 2 (foam sustainability (evaluated with Kim Towel)).
Figure 4 is a photograph showing the results of Example 2 (dripping of foam).

The external composition of the present invention can be used as a spray or a base for spraying the solution onto the skin by foaming the solution at the time of use. Additionally, the stock solution refers to a liquid composition capable of generating foam. The external composition of the present invention can be used using a foam discharge container that sprays the stock solution in the container with a pump without using a propellant. The foam discharge container is not particularly limited as long as it can be discharged in a foamed state by mixing the composition of the present invention with air. For example, a pump spray (pump former) container discharged from a pressure pump, or a foam discharge container by pressing the body portion of a soft container. A squeeze former container that discharges is suitably used.

The polymer surfactant of the present invention includes ethylcellulose, methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose (hypromellose), carboxymethylcellulose, carboxymethylcellulose sodium, carboxymethylethylcellulose, etc. It is at least one type selected from cellulose derivatives, polyvinyl alcohol, polyvinylpyrrolidone, polyethylene glycol, and polyacrylic acid. Preferably, at least one selected from cellulose derivatives, polyvinyl alcohol, polyvinylpyrrolidone, polyethylene glycol, and polyacrylic acid, more preferably hydroxypropylmethylcellulose, hydroxyethylcellulose, methylcellulose, and polyvinyl At least one selected from alcohol, polyvinylpyrrolidone, polyethylene glycol, and polyacrylic acid, especially hydroxypropylmethylcellulose (hypromellose), is preferred. As hypromellose, one with a degree of substitution type of 2906 or 2910 specified in the Japanese Pharmacopoeia is suitably used. The polymer surfactant is present in an amount of 0.01 to 10% by weight, preferably 0.1 to 5% by weight, more preferably 0.2 to 3% by weight, especially about 0.5% by weight, about 0.75% by weight, or about 1% by weight, based on the total weight of the composition. Containing is exemplified. In addition, in this specification and claims, when a numerical value is referred to as "about", it shall include values up to ±20%, ±10%, or 5% of the indicated numerical value. According to the present invention, the desired effect can be achieved with only one type of polymer surfactant.

In addition to the polymer surfactant, the composition of the present invention may contain other surfactants that can be used in the pharmaceutical and cosmetic fields, such as anionic surfactants, cationic surfactants, amphoteric surfactants, and nonionic surfactants, depending on the purpose. You can do it. Anionic surfactants include, for example, N-acyl-N-methylglycine salt, sodium alkylsulfonate, sodium alkyl sulfate, polyoxyethylene alkyl ether carboxylate, sodium lauryl sulfate, etc. Cationic surfactants include, for example, Examples of benzalkonium chloride, benzethonium chloride, aliphatic amine salts, aliphatic quaternary ammonium salts, and amphoteric surfactants include, for example, lauryldimethylaminoacetic acid betaine, stearyldimethylaminoacetic acid betaine, and 2-alkyl-N-carboxylic acid. Nonionic surfactants such as methyl-N-hydroxyethylimidazolium betaine, lauryl dimethylamine oxide, amidopropyl betaine laurate, cocamidopropyl betaine, and lauryl hydroxysulfobetaine, For example, polyoxyethylene alkyl ether, polyoxyethylene alkenyl ether, polyoxyethylene hydrogenated castor oil, polyoxyethylene fatty acid ester, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene fatty acid glyceryl, polyoxypropylene polyoxyethylene. Examples include alkyl ether and polyoxypropylene polyoxyethylene alkenyl ether.

The composition of the present invention may contain alcohol. Alcohols include monohydric alcohols such as ethanol and isopropyl alcohol, polyethylene glycol, glycerin, 1,3-butylene glycol, erythritol, sorbitol, xylitol, maltitol, propylene glycol, dipropylene glycol, diglycerol, and isoprene glycol. , 1,2-pentanediol, 2,4-hexanediol, 1,2-hexanediol, 1,2-octanediol, and other polyhydric alcohols are exemplified, and may include one or two or more types. In particular, glycerin, propylene glycol, polyethylene glycol, and 1,3-butylene glycol are suitable examples. The total content of the alcohol is 5 to 60% by weight, preferably 10 to 50% by weight, and more preferably 15 to 40% by weight.

The composition of the present invention preferably has a pH value in the range of 3 to 12. A more preferable pH value is 4 to 10. Examples of pH adjusters for adjusting the composition to a pH value in the above range include potassium dihydrogen phosphate, citric acid, etc., which are used to adjust the composition to a low pH range, and those used to adjust the composition to a high pH range include hydroxide. Examples include sodium, potassium hydroxide, sodium lactate, sodium citrate, L-arginine, and diisopropanolamine. Particularly preferred pH adjusters include potassium dihydrogen phosphate, potassium hydroxide, sodium citrate, citric acid, diisopropanolamine, and sodium edetate.

In addition to the above components, the liquid composition according to the present invention may contain additives commonly used in external preparations for skin, such as preservatives (preservatives), antioxidants, humectants, stabilizers, and ultraviolet absorbers.

Examples of the preservative include paraoxybenzoic acid esters (parabens) such as methyl paraoxybenzoate, ethyl paraoxybenzoate, and propyl paraoxybenzoate, sodium benzoate, and phenoxyethanol. As for the said preservative, only one type may be used, or multiple types may be used together. The content of the preservative in the composition is preferably in the range of 0.01 to 1% by weight, and more preferably in the range of 0.1 to 0.5% by weight.

The composition of the present invention may be provided as a base for producing pharmaceuticals or cosmetics by mixing active pharmaceutical ingredients or ingredients effective as cosmetics, and the composition of the present invention may also contain an active pharmaceutical ingredient. A composition containing an active pharmaceutical ingredient is also one of the aspects of the present invention.

The composition of the present invention is an external preparation provided by application to the skin, and is used to treat skin inflammation, eczema, atopic dermatitis, psoriasis, acne, scars, bedsores, acne, etc. (cure, improve symptoms, prevent worsening, treat symptoms) It is suitable for application to skin diseases such as prevention (including prevention, etc.), and is also suitable for application to hair parts such as the scalp as well as the skin.

The active ingredients to be mixed in the composition of the present invention are not particularly limited as long as they are applied to the skin, and include steroids, non-steroidal anti-inflammatory agents, bactericides, antibacterial agents, antifungal agents, vitamins, immunosuppressants, mucopolysaccharides, cAMP derivatives, and fibroblasts. Growth factors, naphthoic acid derivatives, benzoyl peroxide, etc. are exemplified. There is no particular limitation as to the steroids as long as they have a steroid skeleton, but examples of the non-steroidal anti-inflammatory drugs include cortisone, hydrocortisone, fludrocortisone acetate, prednisolone, methylprednisolone, dexamethasone, betamethasone, clobetasol and derivatives thereof, etc. Methacin, suprofen, ketotifen, allantoin, dipotassium glycyrrhizinate, etc., the disinfectants include chlorhexidine gluconate, benzalkonium chloride, etc., and the antibacterial agents include tetracycline hydrochloride, chloramphenicol, pradiomycin sulfate, and nadifloc. Sacin, clindamycin phosphate ester, oxenoxacin, oxytetracycline hydrochloride, polymyxin B sulfate, etc., gentamicin sulfate, sodium fusidate, etc., the above antifungal agents include terbinafine, butenafine, bifonazole, ketoconazole, etc., the above vitamins. Examples of vitamin A or its derivatives (e.g. vitamin A oil, etc.), vitamin B or its derivatives (e.g. panthenol, etc.), vitamin C or its derivatives, vitamin D or its derivatives (e.g. active vitamin D3) etc.), vitamin E or its derivatives (e.g., tocopherol acetate, etc.), vitamin K or its derivatives, etc., the immunosuppressants include tacrolimus, cyclophosphamide, etc., and the mucopolysaccharides include heparin-like substances or hyaluronic acid. Examples of ronic acid and its salts and cAMP derivatives include bucladesine sodium, fibroblast growth factors such as trafermine, and naphthoic acid derivatives include adapalene. Their content is 0.001 to 10% by weight, preferably 0.01 to 10% by weight, and more preferably 0.01 to 5% by weight. In particular, external compositions containing heparin-like substances or mucopolysaccharides such as hyaluronic acid and its salts are suitable examples.

In particular, the foam-generating composition containing a heparin-like substance is because the heparin-like substance has an effect of inhibiting blood coagulation, increasing blood flow, promoting hematoma disappearance or expulsion, enhancing keratin moisture retention, and inhibiting fibroblast proliferation. , dry skin disease, sebum deficiency, progressive keratoderma, chilblains, hypertrophic scar keloid, pain and inflammatory diseases based on blood flow disorders (induration and pain after injection), thrombophlebitis (including hemorrhoids), trauma ( It is also suitable as a composition for treating swelling, hematoma, tenosynovitis, muscle pain, arthritis, myogenic torticollis, etc. after bruises, sprains, and strains.

Below, the present application will be described in more detail through experimental examples and the effects of the present application will be revealed, but these are mere examples and the scope of the present application is not limited thereto.

[Example]

Example 1

According to the following prescription, the prepared sample was filled into a pump former container, and the presence or absence of foam formation when discharged from the container was evaluated (Table 1, Figure 1).

Additionally, from sample A, I and N are polymer surfactants.

The source of each sample used in this example is shown below.

It was found that each of the polymer surfactants blended in the foam-generating external composition of the present invention is effective as a foam generator on its own.

Example 2

According to the following prescription, the prepared sample was filled into a pump former container, and the presence or absence of foam formation, foam quality, foam retention time, and presence or absence of dripping were measured (Tables 3 and 4). In condition A, a mat made of polyurethane was used as a material close to the skin of a healthy person, and in condition B, a Kimtowel (キムタオル) assuming relatively severe dry skin was used and discharged on it (Figures 2 and 3) ). In addition, after discharging onto a polyurethane mat, it was tilted at about 45°C to observe whether it was dripping (Figure 4).

Hypromellose formed a high-quality, stable foam as a single substance, which was maintained even after 5 minutes and did not drip even after 3 minutes. This effect was further improved by combining polyhydric alcohols. On the other hand, polyoxyethylene hydrogenated castor oil 60 combined with polyoxyethylene cetyl ether or polyoxyethylene lauryl ether does not form foam, or even if foam is formed, it has low elasticity, short holding time, dripping, and polyoxyethylene foam. Even when combined with alcohol, elasticity and holding time were inferior compared to preparations using hypromellose.

Example 3

Hypromellose with different viscosities was used to evaluate the presence or absence of foam formation depending on concentration. Additionally, the foam quality evaluation criteria were the same as in Example 1.

Regardless of the viscosity of hypromellose, foam was formed at a concentration of 0.2% or higher.

Example 4

Two types of compositions containing a heparin-like substance at a concentration of 0.1 or 0.3% were prepared according to the prescription shown in Raw Material Name 2 in Table 2 of Example 2, and filled into a pump former container to determine the presence or absence of foam formation and foam retention time. And the presence or absence of dripping was measured (Table 5).

As shown in Table 5, using the composition of the present invention, a pharmaceutical composition containing a heparin-like substance was obtained, which had good foam quality in both texture and elasticity, and maintained an appropriate foam without dripping.

Claims (13)

A composition containing 0.2 to 3% by weight of hydroxypropylmethylcellulose as a foaming component and 15 to 40% by weight of 1,3-butylene glycol based on the total amount of the composition is filled in a pump former container or a squeeze former container. An external product that forms foam upon use, characterized in that it does not contain a propellant in the container. The product according to claim 1, containing 0.8 to 1.2% by weight of hydroxypropylmethylcellulose based on the total weight of the composition. The product according to claim 1, comprising at least one pharmaceutically active ingredient. The product according to claim 3, wherein the medicinally active ingredient is mucopolysaccharide. The product according to claim 3, wherein the content of the pharmaceutically active ingredient is 0.01 to 5% by weight based on the total weight of the composition. The product according to claim 5, comprising as a medicinal active ingredient at least one selected from heparin-like substances, hyaluronic acid and salts thereof. The product according to any one of claims 3 to 6 for the treatment of skin diseases.
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