Topical composition

Abstract

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.SELECTED DRAWING: None

Description

Technical Field

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

Background Art

[0002] Tocopherol and its derivatives have antioxidant, immunostimulating, and blood circulation promoting effects, and are used as components of external compositions. Tocopherol and its derivatives are easily soluble in ethanol but hardly soluble in water, so they have the drawback of being difficult to solubilize in an external composition of a mixed solvent system of ethanol and water.

[0003] Conventionally, pharmaceutical technologies for enhancing the solubility of tocopherol and its derivatives have been reported. For example, Patent Document 1 reports that a tocopherol preparation containing sucrose ester and alcohols does not cause turbidity even when added to water and can solubilize tocopherol. However, even if the technology of Patent Document 1 is adopted, tocopherol and its derivatives cannot be sufficiently solubilized in a mixed solvent system of ethanol and water, and further improvement is required.

Prior Art Documents

Patent Documents

[0004]

Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0005] An object of the present disclosure is to provide an external composition containing tocopherol and / or its derivatives, ethanol, and water, in which the tocopherol and / or its derivatives are solubilized.

Means for Solving the Problems

[0006] The present inventor has conducted intensive studies to solve the above problems and found that by formulating a topical composition containing tocopherol and / or its derivative, ethanol, and water with a nonionic surfactant having an HLB value of 11.0 to 15.0 and salicylic acids, tocopherol and / or its derivative can be solubilized. The present disclosure has been completed by further studies based on such findings.

[0007] That is, the present disclosure provides a topical composition in the following embodiments. Item 1. A topical composition containing (A) tocopherol and / or its derivative, (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 derivative, and their salts. Item 2. The topical composition according to Item 1, wherein the content of the component (B) is 22.84 to 25.0% by weight. Item 3. The topical composition according to Item 1 or 2, wherein the content of the component (B) is 22.84 to 25.0% by weight and the content of the component (C) is 50 to 65% by weight. Item 4. The topical composition according to any one of Items 1 to 3, wherein the component (A) is tocopherol acetate. Item 5. The topical composition according to any one of Items 1 to 4, 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. Item 6. The topical composition according to any one of Items 1 to 5, wherein the component (E) is salicylic acid and / or salicylic glycol.

Effect of the Invention

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

Mode for Carrying Out the Invention

[0009] The external composition of the present disclosure contains (A) tocopherol and / or its derivative, (B) ethanol, (C) water, (D) a nonionic surfactant with an HLB value of 11.0 to 15.0, and (E) at least one selected from the group consisting of salicylic acid, its derivative, and their salts. Hereinafter, the external composition of the present disclosure will be described in detail. In the present disclosure, the description of the numerical range "X to Y" refers to the range of X or more and Y or less.

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

[0011] Tocopherol is a known component known as vitamin E. The derivative of tocopherol is not particularly limited as long as it is pharmaceutically acceptable. For example, ester compounds with carboxylic acids such as acetic acid, nicotinic acid, and succinic acid, and diester compounds with phosphoric acid can be mentioned. In addition, the derivative of tocopherol may be any of the d-form, l-form, and dl-form, but preferably the dl-form. Furthermore, the derivative of tocopherol may be any of the α-form, β-form, γ-form, and δ-form, but preferably the α-form. In the external composition of the present disclosure, as component (A), one selected from tocopherol and its derivatives may be used alone, or two or more may be used in combination.

[0012] Among component (A), preferably a derivative of tocopherol, more preferably tocopherol acetate.

[0013] The content of component (A) in the external composition of the present disclosure may be appropriately set according to the dosage form and the like. For example, 0.01 to 10% by weight, preferably 0.01 to 5% by weight, more preferably 0.1 to 1% by weight can be mentioned.

[0014] [(B) Ethanol and (C) Water] The external composition of the present disclosure contains ethanol (which may also be referred to as component (B)) and water (which may also be referred to as component (C)).

[0015] Examples of the content of component (B) in the external composition of the present disclosure include 5 to 40% by weight, preferably 10 to 30% by weight, more preferably 20 to 25% by weight, still more preferably 22.84 to 25% by weight, and particularly preferably 22.84% by weight.

[0016] Examples of the content of component (C) in the external composition of the present disclosure include 40 to 80% by weight, preferably 45 to 70% by weight, and more preferably 50 to 65% by weight.

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

[0018] [(D) Nonionic surfactant with an HLB value of 11.0 to 15.0] In addition to the aforementioned components, the external composition of the present disclosure contains a nonionic surfactant with an HLB value of 11.0 to 15.0 (which may also be referred to as component (D)).

[0019] The HLB (Hydrophile-Lipophile Balance) value indicates the affinity of a non-ionic surfactant for water and oil. In the present disclosure, the HLB value of the non-ionic surfactant is a value determined by a measurement method based on the actual measurement of the HLB value by the emulsification method described on pages 854 - 855 of the "Handbook - Cosmetics and Formulation Raw Materials - Revised Edition", published by Nikko Chemicals Co., Ltd. on February 1, 1977. Specifically, a non-ionic surfactant to be measured for the HLB value is combined with polyoxyethylene sorbitan monostearate (NIKKOL TS-10, HLB 14.9) as a standard substance. The total amount of these two emulsifiers is made constant, and only the ratio is changed to emulsify liquid paraffin (HLB 10.1), which is the emulsion target. After leaving it for a whole day and night, the optimal ratio of the surfactant with stability is determined from the amount of creaming, turbidity, and water separation in the lower layer, and the HLB value x of the surfactant is calculated by the following formula (1). y = (x × usage amount (mass%) + z × usage amount (mass%)) / 100 ··· Formula (1) In the above formula (1), x represents the HLB value of the non-ionic 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 the same manner by combining sorbitan monostearate (NIKKOL SS-10, HLB 4.7) and polyoxyethylene sorbitan monostearate (NIKKOL TS-10, HLB 14.9).

[0020] The HLB value of the non-ionic surfactant used in the present disclosure is not particularly limited as long as it is within the range of 11.0 to 15.0, but preferably 12.0 to 15.0, more preferably 12.2 to 15.0, and still more preferably 12.5 to 15.0.

[0021] The types of nonionic surfactants used in the present disclosure are not particularly limited as long as the HLB value is within the range of 11.0 to 15.0. Examples include polyoxyethylene hydrogenated castor oil, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene polyoxypropylene alkyl ether, polyoxyethylene alkyl ether, polyglycerol fatty acid ester, polyoxyethylene glycerol fatty acid ester, glycerol fatty acid ester, polyoxyethylene sorbit fatty acid ester, sorbitan fatty acid ester, polyoxyethylene alkyl ether, polyethylene glycol fatty acid ester, and the like. Among these, polyoxyethylene hydrogenated castor oil, polyoxyethylene sorbitan fatty acid ester, and polyoxyethylene polyoxypropylene alkyl ether are preferably used.

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

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

[0024] Among the components (D), from the viewpoint of more effectively solubilizing tocopherol and / or its derivatives, preferably, POE hydrogenated castor oil, POE sorbitan fatty acid ester, and POEPOE alkyl ether; more preferably, 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 may be mentioned.

[0025] In the topical composition of the present disclosure, as the ratio of the component (A) to the component (D), for example, per 1 part by weight of the component (A), the component (D) is 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 still more preferably 1 to 10 parts by weight.

[0026] Regarding the content of the component (D) in the topical composition of the present disclosure, it may be appropriately set according to the dosage form and the like. For example, 0.1 to 10% by weight, preferably 0.5 to 8% by weight, more preferably 1 to 8% by weight, and particularly preferably 3 to 5% by weight may be mentioned.

[0027] [(E) Salicylic acids] In addition to the aforementioned components, the external composition of the present disclosure contains at least one selected from the group consisting of salicylic acid, its derivatives, and their salts (which may also be referred to as component (E) or salicylic acids). In an external composition containing tocopherol and / or its derivative, ethanol, and water, by combining a nonionic surfactant and salicylic acids, it becomes possible to solubilize tocopherol and / or its derivative.

[0028] Salicylic acid is a known component with anti-inflammatory, analgesic, and keratolytic effects. The derivatives of salicylic acid are not particularly limited as long as they are pharmaceutically acceptable. Examples include salicylic acid esters such as salicylic acid glycol, acetylsalicylic acid (aspirin), salicylamide (ethenzamide), sulfosalicylic acid, methyl salicylate, ethyl salicylate, ethylene glycol salicylate, dipropylene glycol salicylate, titanium salicylate, 2-ethylhexyl salicylate, homomenthyl salicylate, phenyl salicylate, etc. Examples of the salts of salicylic acid and its derivatives include alkali metal salts such as sodium and potassium; alkaline earth metal salts such as magnesium.

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

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

[0031] In the external 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] Regarding the content of the component (E) in the external composition of the present disclosure, it may be appropriately set according to the dosage form and the like. For example, it may be 0.01 to 10% by weight, preferably 0.01 to 5% by weight, and more preferably 0.1 to 1% by weight.

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

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

[0035] [Thickener] The external composition of the present disclosure may contain a thickener as necessary for imparting viscosity or the like. The type of the thickener is not particularly limited as long as it is pharmaceutically acceptable. For example, carboxyvinyl polymer, hydroxypropyl methylcellulose, xanthan gum, guar gum, locust bean gum, carrageenan, dextran, methylcellulose, ethylcellulose, carboxymethylcellulose, hydroxyethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, sodium alginate, propylene glycol alginate ester, polyvinyl alcohol, polyvinylpyrrolidone, polyvinyl methyl ether, acrylic acid methacrylic acid alkyl copolymer, sodium polyacrylate bentonite, dextrin fatty acid ester, pectin and the like can be mentioned. Among these thickeners, carboxyvinyl polymer and hydroxypropyl methylcellulose are preferably mentioned. These thickeners may be used alone or in combination of two or more.

[0036] When the external composition of the present disclosure contains a thickener, the content thereof is not particularly limited. For example, 0.01 to 10% by weight, preferably 0.1 to 5% by weight, more preferably 0.5 to 2.5% by weight can be mentioned.

[0037] [Other components] In addition to the components described above, the external composition of the present disclosure may contain other commonly used additives as necessary. Examples of such additives include pH adjusters, buffers, solubilizers, preservatives, preservatives, antioxidants, stabilizers, fragrances, colorants and the like. When these additives are contained in the external composition of the present disclosure, the content thereof may be appropriately set according to the type of the additive used and the like.

[0038] In addition to the components described above, the topical composition of the present disclosure may also contain a pharmacological component. Examples of such pharmacological components include antihistamines, local anesthetics, humectants, bactericides, antibacterial agents, antipruritics, skin protectants, blood circulation promoting components, vitamins, and the like. These pharmacological components may be used alone or in combination of two or more. In the topical composition of the present disclosure, when these pharmacological components are contained, the concentration thereof may be appropriately set according to the type of the pharmacological component used, the expected effect, and the like.

[0039] [Formulation form·Dosage form] The topical composition of the present disclosure may be either a topical pharmaceutical or a cosmetic. Further, the dosage form of the topical composition of the present disclosure is not particularly limited as long as it is applicable for transdermal application, and may be any of liquid, semi-solid, solid, etc., but preferably liquid or semi-solid.

[0040] The formulation form of the topical composition of the present disclosure is not particularly limited as long as it is applicable for transdermal application, and examples thereof include solutions (including lotions, sprays, aerosols, and emulsions), foams, ointments, creams, gels, patches, and the like. Among these, a gel is mentioned as a preferred example.

[0041] In the topical composition of the present disclosure, tocopherol and / or its derivative is solubilized, and turbidity caused by tocopherol and / or its derivative can be suppressed. Therefore, in a preferred embodiment, it is a topical composition having a clear appearance (including a slightly white and clear appearance).

[0042] [Manufacturing method] The topical composition of the present disclosure can be manufactured according to a known formulation technique corresponding to its formulation form.

Examples

[0043] Examples are shown below to more specifically explain the present disclosure, but the present disclosure is not limited thereto.

[0044] Test Example An external composition (gel) was prepared by mixing the components shown in Table 1 in predetermined amounts. After placing 15 mL of the external composition immediately after preparation in a 20 mL transparent glass bottle and allowing it to stand for 1 day, the appearance was observed and the degree of solubilization was evaluated according to the following criteria. <Evaluation Criteria for Degree of Solubilization> AA: Slightly white, clear or almost clear appearance A: Translucent, slightly see-through appearance B: Translucent, hardly see-through appearance C: Cloudy, non-see-through appearance

[0045] The results obtained are shown in Tables 1 and 2. When tocopherol acetate was blended in an external composition containing ethanol and water, tocopherol acetate could not be solubilized and became cloudy (Comparative Examples 1 to 4). Also, when only one of a nonionic surfactant (HLB value in the range of 11.0 to 15.0) or salicylic acid was blended together with tocopherol acetate in an external composition containing ethanol and water, tocopherol acetate could not be solubilized and became cloudy (Comparative Examples 5 to 11). Further, when a combination of a nonionic surfactant with an HLB value less than 11.0 or greater than 15.0 and salicylic acid was blended together with tocopherol acetate in an external composition containing ethanol and water, tocopherol acetate could not be solubilized and became cloudy (Comparative Examples 12 to 15). In contrast, when a combination of a nonionic surfactant with an HLB value of 11.0 to 15.0 and salicylic acids (salicylic acid or salicylic acid glycol) was blended together with tocopherol acetate in an external composition containing ethanol and water, tocopherol acetate was solubilized and cloudiness was suppressed (Examples 1 to 11).

[0046]

Table 1

[0047]

Table 2

Claims

1. (A) Tocopherol and / or its derivatives, (B) ethanol, (C) water, (D) a nonionic surfactant with 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 their salts. An external composition containing these components.

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

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

4. The external composition according to Claim 1 or 2, wherein component (A) is tocopherol acetate.

5. The external composition according to Claim 1 or 2, 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.

6. The external composition according to Claim 1 or 2, wherein component (E) is salicylic acid and / or salicylic glycol.

Images