External components

Abstract

To provide external compositions containing cetylpyridinium chloride with enhanced adhesion to the skin.SOLUTION: We found that combining cetylpyridinium chloride with medium-chain fatty acid triglyceride or a liquid paraffin, a lipophilic nonionic surfactant, and water significantly increases the skin adhesion of formulations, and have completed the present invention. Preferably, it may be provided as a cream or emulsion. The external composition of the present invention is used, for example, for hemorrhoids, athlete's foot / ringworm, antipruritic and anti-inflammatory, nasal drops for rhinitis, sterilizing and disinfecting agents, deodorant agents, and the like, preferably it is used for hemorrhoids and sterilization and disinfection, and especially preferably it is used for hemorrhoids.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] The present invention relates to a topical composition containing cetylpyridinium chloride. [Background technology]

[0002] Cetylpyridinium chloride is incorporated into various over-the-counter drugs, including topical skin preparations, for the purposes of treating skin diseases caused by bacteria, disinfecting affected areas, and preventing infection. On the other hand, when a topical skin preparation or other liniment is applied to an affected area, the preparation is easily removed from the affected area due to external physical factors such as water, sweat, and friction with clothing, but for effective treatment, it is desirable to retain the preparation at the application site for a long period of time. Many inventions relating to methods for retaining preparations at the application site for a long period of time have been filed, and for example, a technology incorporating a methyl acrylate-2-ethylhexyl acrylate copolymer resin emulsion (Patent Document 1), a technology incorporating a carboxyvinyl polymer (Patent Document 2), and a composition incorporating a methyl acrylate-2-ethylhexyl acrylate copolymer resin emulsion, methylcellulose, and glycerin monostearate (Patent Document 3) have been reported. Therefore, there is a demand for external compositions containing cetylpyridinium chloride to be retained at the application site for a long period of time. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] Japanese Patent Application Publication No. 7-126164 [Patent Document 2] Japanese Patent Application Laid-Open No. 2006-104078 [Patent Document 3] Japanese Patent Application Publication No. 7-126191 Summary of the Invention [Problem to be solved by the invention]

[0004] An object of the present invention is to provide a topical composition containing cetylpyridinium chloride that has improved adhesion to the skin. [Means for solving the problem]

[0005] As a result of extensive investigations to solve the above-mentioned problems, the present inventors have found that the skin adhesion of a preparation can be significantly improved by combining cetylpyridinium chloride with a medium-chain fatty acid triglyceride or liquid paraffin, a lipophilic nonionic surfactant, and water, and have thus completed the present invention.

[0006] That is, the present invention provides: (1) A topical composition containing (a) cetylpyridinium chloride, (b) a medium-chain fatty acid triglyceride or liquid paraffin, (c) a lipophilic nonionic surfactant, and (d) water; (2) (c) The composition for external use according to (1), wherein the lipophilic nonionic surfactant is at least one selected from the group consisting of glycerin fatty acid esters and sorbitan fatty acid esters; (3) (d) The composition for external use according to (1) or (2), wherein the water content is 5 to 90% by mass. (4) The composition for external use according to any one of (1) to (3), which is a cream or emulsion. (5) The external composition according to any one of (1) to (4), which is for treating hemorrhoids. is. [Effects of the Invention]

[0007] According to the present invention, it is possible to provide a composition for external use containing cetylpyridinium chloride, which has high adhesion to the skin. [Brief explanation of the drawings]

[0008] [Figure 1] FIG. 1 is a photograph showing the topical composition of the present invention (Example 1) and the topical composition of Comparative Example 1 remaining on a slide glass when an adhesion test was conducted. [Figure 2]FIG. 2 is a photograph showing the topical compositions of the present invention (Examples 2 to 5) remaining on a slide glass when an adhesion test was conducted. [Figure 3] FIG. 3 is a photograph showing the topical compositions of the present invention (Examples 6 to 7) and the topical compositions of Comparative Examples 2 to 4 remaining on a slide glass when an adhesion test was carried out. DETAILED DESCRIPTION OF THE INVENTION

[0009] The topical composition of the present invention can be used as a drug, quasi-drug, or cosmetic. When the topical composition of the present invention is a drug, it can be used, for example, for hemorrhoids, athlete's foot / ringworm, antipruritic and anti-inflammatory, nasal drops for rhinitis, disinfectants, and deodorants, among which the use for hemorrhoids and disinfectants is preferred, and the use for hemorrhoids is particularly preferred.

[0010] The dosage form of the topical composition of the present invention is not particularly limited, but examples thereof include creams, emulsions, gels, etc., with creams and emulsions being preferred.

[0011] The cetylpyridinium chloride used in the present invention may be in the form of a hydrate. The content of cetylpyridinium chloride used in the present invention in the topical composition of the present invention is 0.04 to 1.25% by mass, preferably 0.04 to 0.3% by mass, and more preferably 0.04 to 0.2% by mass.

[0012] The medium-chain fatty acid triglyceride or liquid paraffin used in the present invention is listed in the Pharmaceutical Additives Encyclopedia 2021 and is readily available. The content of the medium-chain fatty acid triglyceride or liquid paraffin in the topical composition of the present invention is 0.5 to 30% by mass, preferably 3 to 30% by mass.

[0013] Examples of lipophilic nonionic surfactants used in the present invention include glycerin fatty acid esters (e.g., glycerin monostearate) and sorbitan fatty acid esters (e.g., sorbitan monostearate), which are listed in the Pharmaceutical Additives Encyclopedia 2021 and are readily available. The content of the lipophilic nonionic surfactant (total amount when two or more types are included) in the topical composition of the present invention is 4 to 20% by mass. The water content of the topical composition of the present invention is 5 to 90% by mass, preferably 10 to 90% by mass, more preferably 20 to 85% by mass, even more preferably 30 to 80% by mass, and particularly preferably 30 to 70% by mass. The water content in the topical composition can be measured, for example, by the Karl Fischer method.

[0014] The topical composition of the present invention may further contain a polyhydric alcohol to improve the feel during use. Examples of such polyhydric alcohols include 1,3-butylene glycol, dipropylene glycol, glycerin, and propylene glycol, and two or more types may be contained. From the standpoint of feel during use, the content of the polyhydric alcohol in the topical composition of the present invention is preferably 5 to 30% by mass, more preferably 10 to 30% by mass.

[0015] The pH of the topical composition of the present invention is preferably adjusted to a range of 2-9, more preferably 3-8, and even more preferably 4-7.

[0016] The pH adjuster is not particularly limited, and acids and basic compounds commonly used in pharmaceuticals and cosmetics can be used. Examples of basic compounds include sodium hydroxide, potassium hydroxide, sodium citrate, disodium hydrogen phosphate, diisopropanolamine, and triethanolamine. Examples of acids include hydrochloric acid, phosphoric acid, lactic acid, citric acid, tartaric acid, acetic acid, and boric acid. When adjusting the pH, these pH adjusters can be used alone or in combination of two or more.

[0017] The topical composition of the present invention may contain optional ingredients used in topical compositions, as long as they do not impair the effects of the present invention. Examples of such optional ingredients include solubilizers such as lower alcohols, hydrocarbons, wax components, surfactants, antioxidants, emulsion stabilizers, gelling agents, adhesives, extracts from various plants and animals, preservatives, chelating agents, fragrances, colorants, and liquefied gases. The topical composition of the present invention may also contain medicinal ingredients, such as analgesics, antihistamines, anti-inflammatory agents, tissue repair agents, antipruritics, moisturizers, vasoconstrictors, antiallergic agents, cooling agents, oxygen scavengers, vitamins, ultraviolet absorbers, and ultraviolet scattering agents, as long as they do not impair the effects of the present invention.

[0018] The topical composition of the present invention is preferably an emulsion type, and may be either an O / W type or a W / O type.

[0019] EXAMPLES The present invention will be described in detail below with reference to Examples, Comparative Examples and Test Examples, but the scope of the present invention is not limited to these.

[0020] Example 1 0.2 g of cetylpyridinium chloride hydrate was added to 66.8 g of purified water and heated to approximately 70°C to form an aqueous phase. Separately, a mixture of 8 g of medium-chain fatty acid triglyceride, 15 g of glycerol monostearate, and 10 g of 1,3-butylene glycol was heated to approximately 70°C to form an oil phase. The aqueous phase was added to the oil phase and stirred until uniform, and then cooled to room temperature while stirring to obtain an emulsion-type topical composition.

[0021] Example 2 0.2 g of cetylpyridinium chloride hydrate was added to 44.8 g of purified water and heated to approximately 70°C to prepare an aqueous phase. Separately, a mixture of 30 g of medium-chain fatty acid triglyceride, 15 g of glycerol monostearate, and 10 g of 1,3-butylene glycol was heated to approximately 70°C to prepare an oil phase. The aqueous phase was added to the oil phase and stirred until uniform, and then cooled to room temperature while stirring to obtain an emulsion-type topical composition.

[0022] Example 3 0.2 g of cetylpyridinium chloride hydrate was added to 71.8 g of purified water and heated to approximately 70°C to form an aqueous phase. Separately, a mixture of 3 g of medium-chain fatty acid triglyceride, 15 g of glycerol monostearate, and 10 g of 1,3-butylene glycol was heated to approximately 70°C to form an oil phase. The aqueous phase was added to the oil phase and stirred until uniform, and then cooled to room temperature while stirring to obtain an emulsion-type topical composition.

[0023] Example 4 0.2 g of cetylpyridinium chloride hydrate was added to 77.8 g of purified water and heated to approximately 70°C to form an aqueous phase. Separately, a mixture of 8 g of medium-chain fatty acid triglyceride, 4 g of glycerol monostearate, and 10 g of 1,3-butylene glycol was heated to approximately 70°C to form an oil phase. The aqueous phase was added to the oil phase and stirred until uniform, and then cooled to room temperature while stirring to obtain an emulsion-type topical composition.

[0024] Example 5 0.2 g of cetylpyridinium chloride hydrate was added to 30 g of purified water and heated to approximately 70°C to form an aqueous phase. Separately, a mixture of 30 g of medium-chain fatty acid triglyceride, 20 g of glycerol monostearate, and 19.8 g of 1,3-butylene glycol was heated to approximately 70°C to form an oil phase. The aqueous phase was added to the oil phase and stirred until uniform, and then cooled to room temperature while stirring to obtain an emulsion-type topical composition.

[0025] Example 6 0.2 g of cetylpyridinium chloride hydrate was added to 66.8 g of purified water and heated to approximately 70°C to form an aqueous phase. Separately, a mixture of 8 g of liquid paraffin, 15 g of glycerol monostearate, and 10 g of 1,3-butylene glycol was heated to approximately 70°C to form an oily phase. The aqueous phase was added to the oily phase and stirred until homogenous, and then cooled to room temperature while stirring to obtain an emulsion-type topical composition.

[0026] Example 7 0.2 g of cetylpyridinium chloride hydrate was added to 66.8 g of purified water and heated to approximately 70°C to form an aqueous phase. Separately, a mixture of 8 g of medium-chain fatty acid triglyceride, 15 g of sorbitan monostearate, and 10 g of 1,3-butylene glycol was heated to approximately 70°C to form an oil phase. The aqueous phase was added to the oil phase and stirred until uniform, and then cooled to room temperature while stirring to obtain an emulsion-type topical composition.

[0027] (Comparative Example 1) 0.2 g of cetylpyridinium chloride hydrate was added to 66.8 g of purified water and heated to approximately 70°C to form an aqueous phase. Separately, a mixture of 8 g of isostearic acid, 15 g of glycerol monostearate, and 10 g of 1,3-butylene glycol was heated to approximately 70°C to form an oil phase. The aqueous phase was added to the oil phase and stirred until homogenous, and then cooled to room temperature while stirring to obtain an emulsion-type topical composition.

[0028] (Comparative Example 2) 0.2 g of isopropylmethylphenol was added to 66.8 g of purified water and heated to approximately 70°C to prepare an aqueous phase. Separately, a mixture of 8 g of medium-chain fatty acid triglyceride, 15 g of glycerol monostearate, and 10 g of 1,3-butylene glycol was heated to approximately 70°C to prepare an oil phase. The aqueous phase was added to the oil phase and stirred until uniform, and then cooled to room temperature while stirring to obtain an emulsion-type topical composition.

[0029] (Comparative Example 3) 0.2 g of dequalinium chloride was added to 66.8 g of purified water and heated to approximately 70°C to form an aqueous phase. Separately, a mixture of 8 g of medium-chain triglyceride, 15 g of glycerol monostearate, and 10 g of 1,3-butylene glycol was heated to approximately 70°C to form an oil phase. The aqueous phase was added to the oil phase and stirred until uniform, and then cooled to room temperature while stirring to obtain an emulsion-type topical composition.

[0030] Comparative Example 4 0.2 g of cetylpyridinium chloride hydrate was added to 66.8 g of purified water and heated to approximately 70°C to form an aqueous phase. Separately, a mixture of 8 g of medium-chain fatty acid triglyceride, 15 g of polyoxyethylene stearyl ether, and 10 g of 1,3-butylene glycol was heated to approximately 70°C to form an oil phase. The aqueous phase was added to the oil phase and stirred until uniform, and then cooled to room temperature while stirring to obtain an emulsion-type topical composition.

[0031] (Adhesion test) To evaluate the adhesiveness of the compositions, a test was conducted using a dissolution tester according to the paddle method described in the Japanese Pharmacopoeia. Approximately 0.15 g of each of the topical compositions of Examples 1 to 7 and Comparative Examples 1 to 4 was applied to a 2 cm x 2.5 cm area on a glass slide, and after leaving it for 1 hour, a test was conducted using a dissolution tester (NTR-6100A / Toyama Sangyo Co., Ltd.) under the following conditions: Test liquid: water (900 mL), temperature: 25°C, paddle rotation speed: 150 rpm, stirring time: 15 minutes After stirring, the presence or absence of the formulation remaining on the slide glass was visually evaluated. (Evaluation criteria) The evaluation results were quantified according to the following criteria, and the results are shown in Tables 1 and 2. 3: Most of the formulation remains. 2: About half of the formulation remains. 1: Almost no formulation remaining. 0: No formulation left.

[0032] The formulations of Example 1 and Comparative Example 1 and the evaluation results are shown in Table 1.

[0033] [Table 1]

[0034] As shown in Table 1, almost no preparation remained in Comparative Example 1. On the other hand, most of the preparation remained in Example 1, and the adhesion of the preparation was significantly improved by combining cetylpyridinium chloride with medium-chain fatty acid triglyceride, glycerin monostearate, and water.

[0035] Table 2 shows the formulations and evaluation results of Examples 2 to 7 and Comparative Examples 2 to 4.

[0036] [Table 2]

[0037] As shown in Table 2, most of the formulation remained in Examples 2 to 7, and the adhesion of the formulation was significantly improved by combining cetylpyridinium chloride with a medium-chain fatty acid triglyceride or liquid paraffin, glycerin monostearate or sorbitan monostearate, and water. On the other hand, almost no formulation remained in Comparative Examples 2 and 3, which contained other disinfectants, and Comparative Example 4, which contained a hydrophilic nonionic surfactant. [Industrial Applicability]

[0038] The present invention provides a topical composition containing cetylpyridinium chloride with improved skin adhesion. This is expected to contribute to the development of the pharmaceutical industry and other industries through the commercialization of skin preparations with higher commercial value.

Claims

1. An external composition for hemorrhoids containing (a) cetylpyridinium chloride, (b) a medium-chain fatty acid triglyceride or liquid paraffin, (c) at least one lipophilic nonionic surfactant selected from the group consisting of glycerin fatty acid esters and sorbitan fatty acid esters, and (d) water.

2. The topical composition according to claim 1, wherein the content of (d) water is 5 to 90% by mass.

3. The composition for external use according to claim 1 or 2, which is a cream or emulsion.

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