Topical composition

Abstract

[Problem] The problem to be addressed by the present disclosure is to provide a topical composition which contains tocopherol and / or a derivative thereof, ethanol, and water, wherein the tocopherol and / or the derivative thereof is solubilized. [Solution] This topical composition contains (A) tocopherol and / or a derivative thereof, (B) ethanol, (C) water, (D) a nonionic surfactant having an HLB value of 11.0-15.0, and (E) at least one component selected from the group consisting of salicylic acid and derivatives thereof, and salts of salicylic acid and the derivatives.

Description

External composition

[0001] The present disclosure relates to a topical composition comprising tocopherol and / or its derivatives, ethanol, and water, in which the tocopherol and / or its derivatives are solubilized.

[0002] Tocopherol and its derivatives have antioxidant, immunostimulatory, and blood circulation promoting effects, and are used as components of topical compositions. While tocopherol and its derivatives are readily soluble in ethanol, they are practically insoluble in water, and therefore have the drawback of being difficult to solubilize in topical compositions based on a mixed solvent of ethanol and water.

[0003] Formulation techniques for increasing the solubility of tocopherol and its derivatives have been reported. For example, Patent Document 1 reports that a tocopherol formulation containing a sucrose ester and an alcohol can solubilize tocopherol without causing turbidity when added to water. However, even when the technique of Patent Document 1 is applied, tocopherol and its derivatives cannot be sufficiently solubilized in a mixed solvent system of ethanol and water, and further improvement is required.

[0004] Japanese Unexamined Patent Publication No. 62-226975

[0005] An object of the present disclosure is to provide a composition for external use that contains tocopherol and / or a derivative thereof, ethanol, and water, in which the tocopherol and / or a derivative thereof is solubilized.

[0006] The present inventors have conducted extensive research to solve the above-mentioned problems and have found that tocopherol and / or its derivatives can be solubilized by adding a nonionic surfactant with an HLB value of 11.0 to 15.0 and salicylic acids to a topical composition containing tocopherol and / or its derivatives, ethanol, and water. The present disclosure was completed based on this finding and through further research.

[0007] That is, the present disclosure provides topical compositions of the following aspects: Item 1. A topical composition containing (A) tocopherol and / or a derivative thereof, (B) ethanol, (C) water, (D) a nonionic surfactant having an HLB value of 11.0 to 15.0, and (E) at least one selected from the group consisting of salicylic acid, its derivatives, and salts thereof. Item 2. The topical composition according to Item 1, wherein the content of component (B) is 22.84 to 25.0 wt. Item 3. The topical composition according to Item 1 or 2, wherein the content of component (B) is 22.84 to 25.0 wt. % and the content of component (C) is 50 to 65 wt. Item 4. The topical composition according to any one of Items 1 to 3, wherein component (A) is tocopherol acetate. Item 5. Item 6. The topical composition for topical use according to any one of Items 1 to 4, wherein component (D) is at least one selected from the group consisting of polyoxyethylene hydrogenated castor oil, polyoxyethylene sorbitan fatty acid ester, and polyoxyethylene polyoxypropylene alkyl ether. Item 7. The topical composition for topical use according to any one of Items 1 to 5, wherein component (E) is salicylic acid and / or glycol salicylate.

[0008] According to the present disclosure, a pharmaceutical formulation capable of solubilizing tocopherol and / or its derivatives in a topical composition comprising ethanol and water is provided.

[0009] The topical composition of the present disclosure is characterized by containing (A) tocopherol and / or a derivative thereof, (B) ethanol, (C) water, (D) a nonionic surfactant having an HLB value of 11.0 to 15.0, and (E) at least one selected from the group consisting of salicylic acid, its derivatives, and salts thereof. The topical composition of the present disclosure is described in detail below. Note that in this disclosure, the term "X to Y" referring to a numerical range refers to a range from X to Y.

[0010] [(A) Tocopherol and / or its derivative] The topical composition of the present disclosure contains tocopherol and / or its derivative (sometimes referred to as component (A)).

[0011] Tocopherol is a well-known component known as vitamin E. Tocopherol derivatives are not particularly limited as long as they are pharmaceutically acceptable, and examples include esters with carboxylic acids such as acetic acid, nicotinic acid, and succinic acid, and diesters with phosphoric acid. The tocopherol derivative may be in the d-, l-, or dl-form, with the dl-form being preferred. The tocopherol derivative may be in the α-, β-, γ-, or δ-form, with the α-form being preferred. In the topical composition of the present disclosure, one of tocopherol and its derivatives may be selected and used alone as component (A), or two or more may be used in combination.

[0012] Of the components (A), tocopherol derivatives are preferred, and tocopherol acetate is more preferred.

[0013] The content of component (A) in the topical composition of the present disclosure may be set appropriately depending on the formulation, etc., but may be, for example, 0.01 to 10 wt %, preferably 0.01 to 5 wt %, and more preferably 0.1 to 1 wt %.

[0014] [(B) Ethanol and (C) Water] The topical composition of the present disclosure contains ethanol (sometimes referred to as component (B)) and water (sometimes referred to as component (C)).

[0015] The content of component (B) in the topical composition of the present disclosure is, for example, 5 to 40% by weight, preferably 10 to 30% by weight, more preferably 20 to 25% by weight, even more preferably 22.84 to 25% by weight, and particularly preferably 22.84% by weight.

[0016] The content of component (C) in the topical composition of the present disclosure is, for example, 40 to 80% by weight, preferably 45 to 70% by weight, and more preferably 50 to 65% by weight.

[0017] In particular, when the content of component (B) in the topical composition of the present disclosure is 22.84% by weight and the content of component (C) is 50 to 65% by weight, the tocopherol and / or its derivatives can be solubilized more effectively, resulting in an appearance with high clarity.

[0018] [(D) Nonionic surfactant with an HLB value of 11.0 to 15.0] In addition to the components described above, the topical composition of the present disclosure contains a nonionic surfactant with an HLB value of 11.0 to 15.0 (sometimes referred to as component (D)).

[0019] The HLB (hydrophile-lipophile balance) value is a value that indicates the affinity of a nonionic surfactant for water and oil. In the present disclosure, the HLB value of a nonionic surfactant is a value determined by a measurement method based on the actual measurement of HLB values ​​by the emulsification method described in "Handbook - Cosmetics and Pharmaceutical Ingredients - Revised Edition," published by Nikko Chemicals Co., Ltd. on February 1, 1977, pages 854-855. Specifically, a nonionic surfactant whose HLB value is to be measured is combined with polyoxyethylene sorbitan monostearate (NIKKOL TS-10, HLB 14.9) as a standard substance, and liquid paraffin (HLB 10.1) is emulsified by varying only the ratio of these two emulsifiers while keeping the total amounts of these two emulsifiers constant. After leaving the mixture overnight, the optimal surfactant ratio for stability is determined based on the amount of creaming, turbidity, and water separation from the lower layer, and the HLB value x of the surfactant is calculated using the following formula (1): y = (x × amount used (mass %) + z × amount used (mass %)) / 100... Formula (1) In formula (1), x represents the HLB value of the nonionic surfactant (measurement target), y represents the HLB value of liquid paraffin, and z represents the HLB value of polyoxyethylene sorbitan monostearate (standard substance). The HLB value of the liquid paraffin can be determined in a similar manner using a combination of sorbitan monostearate (NIKKOL SS-10, HLB 4.7) and polyoxyethylene sorbitan monostearate (NIKKOL TS-10, HLB 14.9).

[0020] The HLB value of the nonionic surfactant used in the present disclosure is not particularly limited, but is limited to 11.0 to 15.0, preferably 12.0 to 15.0, more preferably 12.2 to 15.0, and even more preferably 12.5 to 15.0.

[0021] The type of nonionic surfactant used in the present disclosure is not particularly limited, as long as the HLB value is 11.0 to 15.0, and examples thereof include polyoxyethylene hydrogenated castor oil, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene polyoxypropylene alkyl ethers, polyoxyethylene alkyl ethers, polyglycerin fatty acid esters, polyoxyethylene glycerin fatty acid esters, glycerin fatty acid esters, polyoxyethylene sorbit fatty acid esters, sorbitan fatty acid esters, polyoxyethylene alkyl ethers, polyethylene glycol fatty acid esters, etc. Among these, polyoxyethylene hydrogenated castor oil, polyoxyethylene sorbitan fatty acid esters, and polyoxyethylene polyoxypropylene alkyl ethers are preferred.

[0022] Specific examples of nonionic surfactants having an HLB value of 11.0 to 15.0 include POE hydrogenated castor oils such as POE hydrogenated castor oil 30, POE hydrogenated castor oil 40, POE hydrogenated castor oil 50, and POE hydrogenated castor oil 60; POE sorbitan fatty acid esters such as POE (20) sorbitan tristearate, POE (20) sorbitan trioleate, POE (20) sorbitan monooleate, and POE (20) sorbitan monoisostearate; POE (20) POP (8) cetyl ether, POE (30) POP (6) decyl tetradecyl ether, and POE (20) POP (6) decyl Examples of such POE alkyl ethers include POEPOE alkyl ethers such as tetradecyl ether; POE alkyl ethers such as POE(9) lauryl ether, POE(10) cetyl ether, and POE(10) oleyl ether; polyglycerol fatty acid esters such as hexaglyceryl monolaurate and decaglyceryl monomyristate; POE glycerol fatty acid esters such as POE(15) glyceryl monooleate; and POE sorbitol fatty acid esters such as POE(60) sorbitol tetrastearate, POE(40) sorbitol tetraoleate, and POE(60) sorbitol tetraoleate. Here, "POE" is an abbreviation for polyoxyethylene, and "POP" is an abbreviation for polyoxypropylene, and the number in parentheses following POE or POP is the average number of moles added.

[0023] In the topical composition of the present disclosure, as component (D), one type of nonionic surfactant having an HLB value of 11.0 to 15.0 may be selected and used alone, or two or more types may be used in combination.

[0024] Among the (D) components, from the viewpoint of more effectively solubilizing tocopherol and / or its derivatives, preferred are POE hydrogenated castor oil, POE sorbitan fatty acid esters, and POEPOE alkyl ethers; more preferred are POE hydrogenated castor oil 30, POE hydrogenated castor oil 40, POE hydrogenated castor oil 50, POE hydrogenated castor oil 60, POE (20) sorbitan monooleate (polysorbate 80), POE (20) POP (8) cetyl ether, POE (30) POP (6) decyltetradecyl ether, and POE (20) POP (6) decyltetradecyl ether.

[0025] In the topical composition of the present disclosure, the ratio of component (A) to component (D) is, for example, 0.01 to 500 parts by weight, preferably 0.05 to 100 parts by weight, more preferably 0.1 to 50 parts by weight, and even more preferably 1 to 10 parts by weight of component (D) per 1 part by weight of component (A).

[0026] The content of component (D) in the topical composition of the present disclosure may be set appropriately depending on the formulation, etc., but may be, for example, 0.1 to 10 wt %, preferably 0.5 to 8 wt %, more preferably 1 to 8 wt %, and particularly preferably 3 to 5 wt %.

[0027] [(E) Salicylic Acids] In addition to the components described above, the topical composition of the present disclosure contains at least one member selected from the group consisting of salicylic acid, its derivatives, and salts thereof (sometimes referred to as component (E) or salicylic acids). In a topical composition containing tocopherol and / or its derivatives, ethanol, and water, the inclusion of a nonionic surfactant in combination with a salicylic acid enables the tocopherol and / or its derivatives to be solubilized.

[0028] Salicylic acid is a known ingredient known for its anti-inflammatory and analgesic effects and keratin softening effects. Salicylic acid derivatives are not particularly limited as long as they are pharmaceutically acceptable, and examples thereof include salicylic acid esters such as glycol salicylate, acetylsalicylic acid (aspirin), salicylamide (ethenzamide), sulfosalicylic acid, methyl salicylate, ethyl salicylate, ethylene glycol salicylate, dipropylene glycol salicylate, titanium salicylate, 2-ethylhexyl salicylate, homomenthyl salicylate, and phenyl salicylate. Salts of salicylic acid and its derivatives include, for example, alkali metal salts such as sodium and potassium salts; and alkaline earth metal salts such as magnesium salts.

[0029] In the topical composition of the present disclosure, as component (E), one of salicylic acid, its derivatives, and salts thereof may be selected and used alone, or two or more of them may be used in combination.

[0030] Of the components (E), from the viewpoint of more effectively solubilizing tocopherol and / or its derivatives, preferred are salicylic acid and its derivatives, more preferred are salicylic acid and glycol salicylate, and even more preferred is salicylic acid.

[0031] In the topical composition of the present disclosure, the ratio of component (A) to component (E) is, for example, 0.01 to 100 parts by weight, preferably 0.1 to 10 parts by weight, more preferably 1 to 5 parts by weight, and even more preferably 0.5 to 2 parts by weight of component (E) per 1 part by weight of component (A).

[0032] The content of component (E) in the topical composition of the present disclosure may be set appropriately depending on the formulation, etc., but may be, for example, 0.01 to 10 wt %, preferably 0.01 to 5 wt %, and more preferably 0.1 to 1 wt %.

[0033] [Polyhydric Alcohol] The topical composition of the present disclosure may contain a polyhydric alcohol, if necessary. The type of polyhydric alcohol is not particularly limited, as long as it is pharmaceutically acceptable. Examples include dihydric alcohols such as ethylene glycol, 1,3-butylene glycol, propylene glycol, isoprene glycol, diethylene glycol, dipropylene glycol, polyethylene glycol (polyethylene glycol 200, polyethylene glycol 300, polyethylene glycol 400, polyethylene glycol 600, etc.), and polypropylene glycol; and trihydric alcohols such as glycerin. Of these polyhydric alcohols, 1,3-butylene glycol is preferred. These polyhydric alcohols may be used alone or in combination of two or more.

[0034] When the topical composition of the present disclosure contains a polyhydric alcohol, the content thereof is not particularly limited, but may be, for example, 1 to 40% by weight, preferably 1 to 30% by weight, and more preferably 5 to 20% by weight.

[0035] [Thickener] The topical composition of the present disclosure may contain a thickener as needed to impart viscosity, etc. The type of thickener is not particularly limited as long as it is pharmaceutically acceptable, but examples include carboxyvinyl polymer, hydroxypropylmethylcellulose, xanthan gum, guar gum, locust bean gum, carrageenan, dextran, methylcellulose, ethylcellulose, carboxymethylcellulose, hydroxyethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, sodium alginate, propylene glycol alginate, polyvinyl alcohol, polyvinylpyrrolidone, polyvinyl methyl ether, acrylic acid alkyl methacrylate copolymer, sodium polyacrylate bentonite, dextrin fatty acid ester, pectin, etc. Among these thickeners, carboxyvinyl polymer and hydroxypropylmethylcellulose are preferred. These thickeners may be used alone or in combination of two or more.

[0036] When a thickener is contained in the topical composition of the present disclosure, the content thereof is not particularly limited, but may be, for example, 0.01 to 10 wt %, preferably 0.1 to 5 wt %, and more preferably 0.5 to 2.5 wt %.

[0037] [Other components] In addition to the above-mentioned components, the topical composition of the present disclosure may contain other commonly used additives as needed.Such additives include pH adjusters, buffers, solubilizers, antiseptics, preservatives, antioxidants, stabilizers, fragrances, colorants, etc.When these additives are contained in the topical composition of the present disclosure, their content can be appropriately set according to the type of additives used, etc.

[0038] In addition, the topical composition of the present disclosure may contain pharmacological ingredients in addition to the above-mentioned ingredients. Examples of such pharmacological ingredients include antihistamines, local anesthetics, moisturizers, disinfectants, antibacterial agents, antipruritics, skin protectants, blood circulation promoters, vitamins, etc. These pharmacological ingredients may be used alone or in combination of two or more. Furthermore, when these pharmacological ingredients are contained in the topical composition of the present disclosure, their concentrations may be appropriately determined depending on the type of pharmacological ingredient used, the desired effect, etc.

[0039] [Form of preparation / dosage form] The topical composition of the present disclosure may be either a pharmaceutical or cosmetic for topical application to the skin. The dosage form of the topical composition of the present disclosure is not particularly limited as long as it is applicable transdermally, and may be any of liquid, semi-solid, solid, etc., but is preferably liquid or semi-solid.

[0040] The formulation of the topical composition of the present disclosure is not particularly limited as long as it is applicable transdermally, and examples thereof include liquids (including lotions, sprays, aerosols, and emulsions), foams, ointments, creams, gels, patches, etc. Among these, gels are a preferred example.

[0041] In the topical composition of the present disclosure, tocopherol and / or its derivatives are solubilized, and the cloudiness caused by tocopherol and / or its derivatives can be suppressed. Therefore, in a preferred embodiment, the topical composition has a clear appearance (including a pale white, clear appearance).

[0042] [Manufacturing Method] The topical composition of the present disclosure can be manufactured according to known formulation methods appropriate for the formulation form.

[0043] The present disclosure will be explained in more detail below by showing examples, but the present disclosure is not limited to these examples.

[0044] Test Example A topical composition (gel) was prepared by mixing the components shown in Table 1 in the specified amounts. 15 mL of the topical composition immediately after preparation was placed in a 20 mL transparent glass bottle and left to stand for one day, after which the appearance was observed and the degree of solubilization was evaluated according to the following criteria. <Evaluation criteria for the degree of solubilization> AA: Faint white, clear or almost clear appearance A: Translucent, slightly see-through appearance B: Translucent, almost opaque appearance C: Cloudy, opaque appearance

[0045] The results are shown in Tables 1 and 2. When tocopherol acetate was blended into a topical composition containing ethanol and water, the tocopherol acetate was not solubilized, resulting in a cloudy appearance (Comparative Examples 1 to 4). Furthermore, when either a nonionic surfactant (with an HLB value of 11.0 to 15.0) or salicylic acid was blended into a topical composition containing ethanol and water, the tocopherol acetate was not solubilized, resulting in a cloudy appearance (Comparative Examples 5 to 11). Furthermore, when a topical composition containing ethanol and water was blended with a combination of salicylic acid and a nonionic surfactant with an HLB value of less than 11.0 or more than 15.0, the tocopherol acetate was not solubilized, resulting in a cloudy appearance (Comparative Examples 12 to 15). In contrast, when a topical composition containing ethanol and water was formulated with tocopherol acetate in combination with a nonionic surfactant having an HLB value of 11.0 to 15.0 and a salicylic acid (salicylic acid or glycol salicylate), the tocopherol acetate was solubilized, and cloudiness was suppressed (Examples 1 to 11).

[0046]

[0047]

Claims

1. A composition for external use comprising (A) tocopherol and / or a derivative thereof, (B) ethanol, (C) water, (D) a nonionic surfactant having an HLB value of 11.0 to 15.0, and (E) at least one member selected from the group consisting of salicylic acid, its derivatives, and salts thereof.

2. The topical composition according to claim 1, wherein the content of component (B) is 22.84 to 25% by weight.

3. The topical composition according to claim 1 or 2, wherein the content of the (B) component is 22.84 to 25% by weight, and the content of the (C) component is 50 to 65% by weight.

4. The topical composition according to claim 1 or 2, wherein the component (A) is tocopherol acetate.

5. The topical composition according to claim 1 or 2, wherein the component (D) is at least one selected from the group consisting of polyoxyethylene hydrogenated castor oil, polyoxyethylene sorbitan fatty acid ester, and polyoxyethylene polyoxypropylene alkyl ether.

6. The topical composition according to claim 1 or 2, wherein the component (E) is salicylic acid and / or glycol salicylate.

Images