External composition

Abstract

To provide an external composition which contains tocopherol and / or a derivative thereof, isopropyl myristate, and N-methyl-2-pyrrolidone, and which suppresses separation of the contained components.SOLUTION: An external composition contains: (A) tocopherol and / or a derivative thereof; (B) isopropyl myristate; (C) N-methyl-2-pyrrolidone; and (D) menthol.SELECTED DRAWING: None

Description

Technical Field

[0001] The present disclosure relates to an external composition containing tocopherol and / or its derivatives, isopropyl myristate, and N-methyl-2-pyrrolidone, in which the separation of the contained components is suppressed.

Background Art

[0002] Tocopherol and its derivatives have antioxidant, immunostimulatory, blood circulation promoting effects, etc., and are used as components of external compositions. Conventionally, various formulations have been developed for external compositions containing tocopherol and its derivatives from the viewpoints of drug efficacy and formulation stability. For example, Patent Document 1 reports that a topical skin composition containing tocopherol and / or its derivatives, diphenhydramine and / or its salt, and retinol and / or its derivatives exhibits an excellent antipruritic effect. Further, Patent Document 2 reports that an external emulsified composition containing tocopherol and / or its derivatives, ufenamate, and not containing allantoin can have excellent emulsion stability.

[0003] On the other hand, isopropyl myristate and N-methyl-2-pyrrolidone have an action of promoting the penetration of drugs into the skin and are used as percutaneous absorption promoters in the field of external compositions.

Prior Art Documents

Patent Documents

[0004]

Patent Document 1

Patent Document 2

Summary of the Invention

Problems to be Solved by the Invention

[0005] When isopropyl myristate and N-methyl-2-pyrrolidone are incorporated into a topical composition containing tocopherol and / or its derivatives, it can be expected to enhance the percutaneous absorbability of tocopherol and / or its derivatives. Therefore, the present inventor conducted studies to develop a topical composition containing tocopherol and / or its derivatives, isopropyl myristate, and N-methyl-2-pyrrolidone. However, in this topical composition, problems such as insolubilization of the contained components and separation occurred.

[0006] Therefore, an object of the present disclosure is to provide a topical composition containing tocopherol and / or its derivatives, isopropyl myristate, and N-methyl-2-pyrrolidone, in which separation of the contained components is suppressed.

Means for Solving the Problems

[0007] The present inventor conducted intensive studies to solve the above problems and found that by incorporating menthol into a topical composition containing tocopherol and / or its derivatives, isopropyl myristate, and N-methyl-2-pyrrolidone, insolubilization of the contained components is suppressed and separation is suppressed. The present disclosure was completed by further studies based on such findings.

[0008] That is, the present disclosure provides a topical composition in the following embodiments. Item 1. A topical composition containing (A) tocopherol and / or its derivatives, (B) isopropyl myristate, (C) N-methyl-2-pyrrolidone, and (D) menthol. Item 2. The topical composition according to Item 1, further containing (E) felbinac. Item 3. The topical composition according to Item 1 or 2, wherein the component (A) is tocopherol acetate. Item 4. The topical composition according to any one of Items 1 to 3, further containing (F) vanillyl amide of nonanoic acid. Item 5. The topical composition according to any one of Items 1 to 4, further containing (G) glycyrrhetinic acid and / or its derivatives. Item 6. Furthermore, a topical composition according to any one of Items 1 to 5, which contains (H) chlorpheniramine and / or a salt thereof. Item 7. Furthermore, a topical composition according to any one of Items 1 to 6, which contains (I) camphor. Item 8. Furthermore, a topical composition according to any one of Items 1 to 7, which contains (J) polyhydric alcohol. Item 9. Furthermore, a topical composition according to any one of Items 1 to 8, which contains (K) monohydric lower alcohol. Item 10. Furthermore, a topical composition according to any one of Items 1 to 9, which contains (L) water. [Advantages of the Invention]

[0009] According to the present disclosure, there is provided a formulation prescription capable of suppressing the separation of components in a topical composition containing tocopherol and / or its derivative, isopropyl myristate, and N-methyl-2-pyrrolidone. [Modes for Carrying Out the Invention]

[0010] The topical composition of the present disclosure is characterized by containing (A) tocopherol and / or its derivative, (B) isopropyl myristate, (C) N-methyl-2-pyrrolidone, and (D) menthol. Hereinafter, the topical 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.

[0011] [(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)).

[0012] Tocopherol is a known component known as vitamin E. As derivatives of tocopherol, there are no particular restrictions as long as they are pharmaceutically acceptable. Examples include ester compounds with carboxylic acids such as acetic acid, nicotinic acid, and succinic acid, and diester compounds with phosphoric acid. Further, 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 the component (A), one kind may be selected from tocopherol and its derivatives and used alone, or two or more kinds may be used in combination.

[0013] Among the component (A), preferably a derivative of tocopherol, more preferably tocopherol acetate, may be mentioned.

[0014] The content of the 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 2% by weight, more preferably 0.05 to 1% by weight, and still more preferably 0.05 to 0.5% by weight may be mentioned.

[0015] [(B) Isopropyl myristate] The external pharmaceutical composition of the present invention contains isopropyl myristate (which may also be referred to as component (B)). Isopropyl myristate is a fatty acid alkyl ester in which myristic acid and isopropyl alcohol are ester-bonded.

[0016] In the external composition of the present disclosure, as the ratio of the component (A) to the component (B), for example, per 1 part by weight of the component (A), the component (B) is 0.1 to 500 parts by weight, preferably 1 to 100 parts by weight, more preferably 10 to 50 parts by weight.

[0017] As the content of component (B) in the external composition of the present disclosure, for example, 0.1 to 45% by weight, preferably 0.1 to 10% by weight, more preferably 0.5 to 8% by weight, still more preferably 1 to 5% by weight can be mentioned.

[0018] [(C) N-Methyl-2-pyrrolidone] The external pharmaceutical composition of the present invention contains N-methyl-2-pyrrolidone (which may also be referred to as component (C)). N-Methyl-2-pyrrolidone is a compound in which a methyl group is substituted for the nitrogen atom of 2-pyrrolidone.

[0019] In the external composition of the present disclosure, as the ratio of component (A) to component (C), for example, per 1 part by weight of component (A), component (C) is 0.1 to 500 parts by weight, preferably 1 to 100 parts by weight, more preferably 10 to 40 parts by weight.

[0020] As the content of component (C) in the external composition of the present disclosure, for example, 0.1 to 4% by weight, preferably 0.5 to 4% by weight, more preferably 1 to 4% by weight, still more preferably 2 to 4% by weight can be mentioned.

[0021] [(D) Menthol] The external composition of the present disclosure contains, in addition to the aforementioned components, menthol (which may also be referred to as component (D)). By blending menthol into an external composition containing tocopherol and / or its derivative, isopropyl myristate, and N-methyl-2-pyrrolidone, it becomes possible to suppress the insolubilization of the contained components and suppress the separation of the contained components.

[0022] Menthol is a type of monoterpene and is a well-known component known as a cooling component and the like. The menthol used in the present disclosure may be any of the l-form, d-form, and dl-form, but preferably the l-form. Further, as menthol, essential oils containing menthol may be used. Examples of essential oils containing terpenes include, for example, essential oils containing menthol such as peppermint oil, peppermint oil, and spearmint oil. In the present disclosure, the description regarding the ratio and content of menthol is a value converted to menthol contained in the essential oil when using an essential oil containing menthol.

[0023] In the external 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 0.1 to 500 parts by weight, preferably 1 to 250 parts by weight, more preferably 10 to 100 parts by weight, and still more preferably 40 to 80 parts by weight.

[0024] The content of the component (D) in the external composition of the present disclosure is, for example, 0.001 to 18% by weight, preferably 0.001 to 10% by weight, more preferably 0.1 to 10% by weight, still more preferably 1 to 10% by weight, and still more preferably 4 to 8% by weight.

[0025] [(E) Felbinac] The external composition of the present disclosure may optionally contain felbinac (which may also be referred to as component (E)). Felbinac is a phenylacetic acid-based non-steroidal anti-inflammatory drug. When the component (E) is contained in the external composition of the present invention, the content thereof may be appropriately set according to the medicinal effects to be provided, etc., and examples include 0.01 to 5% by weight, preferably 0.01 to 3% by weight, and more preferably 1 to 3% by weight.

[0026] [(F) Vanillylamide of nonanoic acid] The external composition of the present disclosure may optionally contain vanillylamide nonanoate (which may also be referred to as the (F) component). Vanillylamide nonanoate is a type of capsinoid and is a known component known as a blood circulation promoting component and the like. When the (E) component is contained in the external composition of the present invention, the content thereof may be appropriately set according to the medicinal effects to be provided, etc. For example, 0.0001 to 0.5% by weight, preferably 0.0001 to 0.2% by weight, more preferably 0.001 to 0.1% by weight can be mentioned.

[0027] [(G) Glycyrrhetinic acid and / or its derivatives] The external composition of the present disclosure may optionally contain glycyrrhetinic acid and / or its derivatives (which may also be referred to as the (G) component). Glycyrrhetinic acid is a type of β-amyrin-based pentacyclic terpenoid derivative and is a known component known as an anti-inflammatory component, an anti-allergic component, and the like.

[0028] The derivatives of glycyrrhetinic acid are not particularly limited as long as they are pharmaceutically acceptable. For example, pyridoxine glycyrrhetinate, stearyl glycyrrhetinate, glyceryl glycyrrhetinate, monoglucuronide glycyrrhetinate, etc. can be mentioned.

[0029] In the external composition of the present disclosure, as the (G) component, one kind may be selected from glycyrrhetinic acid and its derivatives and used alone, or two or more kinds may be used in combination. Among the (G) components, preferably glycyrrhetinic acid can be mentioned.

[0030] When the (G) component is contained in the external composition of the present invention, the content thereof may be appropriately set according to the medicinal effects to be provided, etc. For example, 0.01 to 5% by weight, preferably 0.01 to 1% by weight, more preferably 0.05 to 0.5% by weight can be mentioned.

[0031] [(H) Chlorpheniramine and / or its salt] The external composition of the present disclosure may optionally contain chlorpheniramine and / or its salt (sometimes referred to as the (H) component). Chlorpheniramine is a known component known as an antihistamine drug.

[0032] The salt of chlorpheniramine is not particularly limited as long as it is pharmaceutically acceptable. Examples include organic acid salts such as maleate and fumarate; inorganic acid salts such as hydrochloride and sulfate. Among these salts of chlorpheniramine, maleate is preferably mentioned.

[0033] In the external composition of the present disclosure, as the (H) component, one kind may be selected from chlorpheniramine and its salts and used alone, or two or more kinds may be used in combination. Among the (H) components, preferably a salt of chlorpheniramine, more preferably chlorpheniramine maleate, is mentioned.

[0034] When the external composition of the present invention contains the (H) component, its content may be appropriately set according to the required medicinal effects and the like. For example, 0.01 to 5% by weight, preferably 0.01 to 1% by weight, more preferably 0.05 to 0.5% by weight may be mentioned.

[0035] [(I) Camphor] The external composition of the present disclosure may optionally contain camphor (sometimes referred to as the (I) component). Camphor is a kind of bicyclic monoterpene ketone and is a known component known as an analgesic component, an anti-inflammatory component, an astringent component, etc. The camphor used in the present disclosure may be any of the d-form, l-form, and dl-form, but preferably the dl-form and d-form are mentioned.

[0036] When the external composition of the present invention contains the (I) component, its content may be appropriately set according to the required medicinal effects and the like. For example, 0.01 to 5% by weight, preferably 0.05 to 3% by weight, more preferably 0.1 to 1% by weight may be mentioned.

[0037] [(J) Polyhydric Alcohol] The external composition of the present disclosure may contain a polyhydric alcohol (sometimes referred to as component (J)) 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, polypropylene glycol, etc.; trihydric alcohols such as glycerin, etc. Among these polyhydric alcohols, dihydric alcohols are preferred, and propylene glycol is more preferred. These polyhydric alcohols may be used alone or in combination of two or more.

[0038] When the external composition of the present invention contains component (J), its content is not particularly limited. For example, 0.1 to 20% by weight, preferably 1 to 10% by weight, more preferably 3 to 8% by weight can be mentioned.

[0039] [(K) Monohydric Lower Alcohol] The external composition of the present disclosure may contain a monohydric lower alcohol (sometimes referred to as component (K)) as one of the bases. The type of monohydric lower alcohol is not particularly limited as long as it is pharmaceutically acceptable. For example, monohydric alcohols having 2 to 5 carbon atoms, specifically, ethanol, propanol, isopropanol, butanol, etc. Among these monohydric lower alcohols, ethanol is preferred. These monohydric lower alcohols may be used alone or in combination of two or more.

[0040] When the external composition of the present invention contains component (K), its content is not particularly limited. For example, 30 to 80% by weight, preferably 60 to 80% by weight, more preferably 65 to 75% by weight can be mentioned.

[0041] [(L) Water] The external composition of the present disclosure may contain water (which may also be referred to as component (L)) as one of the bases. When the external composition of the present invention contains component (L), the content thereof is not particularly limited, and examples thereof include 1 to 30% by weight, preferably 2 to 20% by weight, and more preferably 5 to 15% by weight.

[0042] [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, surfactants, buffers, solubilizers, preservatives, preservatives, antioxidants, stabilizers, fragrances, colorants, and the like. In the external composition of the present disclosure, when these additives are contained, the content thereof may be appropriately set according to the type of additive used and the like.

[0043] In addition, the external composition of the present disclosure may contain pharmacological components in addition to the components described above. Examples of such pharmacological components include antihistamines, local anesthetics, moisturizers, 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 external composition of the present disclosure, when these pharmacological components are contained, the concentration thereof may be appropriately set according to the type of pharmacological component used, the expected effect, and the like.

[0044] [Formulation form · Dosage form] The external composition of the present disclosure may be either a skin-external pharmaceutical or a cosmetic, but is preferably a skin-external pharmaceutical. In addition, the dosage form of the external composition of the present disclosure is not particularly limited as long as it can be applied transdermally, and may be any of liquid, semi-solid, solid, etc., but preferably liquid or semi-solid.

[0045] Regarding the dosage form of the external composition of the present disclosure, there is no particular limitation as long as it can be applied transdermally. For example, liquid preparations (including lotions, sprays, aerosols, and emulsions), creams, gels, foams, ointments, patches, etc. may be mentioned. Among these, liquid preparations, gels, and creams are preferably mentioned.

[0046] In the external composition of the present disclosure, insolubilization of the contained components is suppressed, and sedimentation of the contained components and turbidity of the external composition can be suppressed. Therefore, in a preferred embodiment, the external composition has a transparent appearance.

[0047] [Manufacturing method] The external composition of the present disclosure can be manufactured according to known formulation techniques according to its dosage form.

Examples

[0048] Examples are shown below to more specifically explain the present disclosure, but the present disclosure is not limited thereto.

[0049] Test Example An external composition (liquid preparation) was prepared by mixing the components shown in Table 1 in predetermined amounts. The external composition immediately after preparation was allowed to stand on a flat surface, and its appearance was observed, and the degree of separation of the contained components was evaluated according to the following criteria. <Evaluation criteria for the degree of separation of the contained components> AA: No sedimentation of the contained components and no turbidity of the external composition are observed, and it has a transparent appearance. A: Slight sedimentation of the contained components or slight turbidity of the external composition is observed, but there are almost no problems in appearance. B: Sedimentation of the contained components or turbidity of the external composition is clearly observed. C: Sedimentation of the contained components or turbidity of the external composition is remarkably observed.

[0050] The obtained results are shown in Table 1. When isopropyl myristate and N-methyl-2-pyrrolidone were not formulated in the external composition containing tocopherol acetate, insolubilization of the contained components could be almost suppressed, and almost no separation was observed (Reference Example 1). On the other hand, when isopropyl myristate and N-methyl-2-pyrrolidone were not formulated in the external composition containing tocopherol acetate, significant insolubilization of the contained components occurred, and remarkable separation was observed (Comparative Example 1). In contrast, when menthol was formulated together with isopropyl myristate and N-methyl-2-pyrrolidone in the external composition containing tocopherol acetate, insolubilization of the contained components could be sufficiently suppressed, and no separation was observed at all (Example 1).

[0051]

Table 1

Claims

1. An external composition containing (A) tocopherol and / or its derivative, (B) isopropyl myristate, (C) N-methyl-2-pyrrolidone, and (D) menthol.

2. The external composition according to Claim 1, further containing (E) felbinac.

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

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