External components

Abstract

The object of this disclosure is to provide a topical composition containing crotamiton that can suppress creaming. [Solution] The topical composition containing (A) crotamiton and (B) ceramide 2 has suppressed creaming.

Description

Technical Field

[0001] The present disclosure relates to an external composition that contains crotamiton and is capable of suppressing creaming.

Background Art

[0002] Crotamiton is used by being incorporated into anti-inflammatory analgesic external preparations as an antipruritic agent or a therapeutic agent for scabies. However, it is known that when crotamiton is incorporated into an emulsion composition, concerns arise regarding the formulation stability when the crotamiton content is, for example, 1 wt% or more.

[0003] Accordingly, it is known that the emulsion stability imparted by crotamiton can be enhanced by blending a specific thickener in a specific content together with an antifungal agent, an antihistamine agent, and crotamiton.

Prior Art Documents

Patent Document

[0004]

Patent Document 1

Summary of Invention

Problems to be Solved by the Invention

[0005] Since the formulation of Patent Document 1 has a limited variety of active ingredients, the treatment targets are limited. Accordingly, there is a demand for an external composition that contains crotamiton and has excellent formulation stability, with a formulation premised on application to a wider range of targets.

[0006] Accordingly, an object of the present disclosure is to provide an external composition that contains crotamiton and can suppress creaming during storage.

Means for Solving the Problems

[0007] The inventors of the present invention conducted diligent research to solve the aforementioned problems and found that creaming due to storage can be suppressed by including ceramide 2 in an external composition containing crotamiton. This disclosure was completed by further research based on this finding.

[0008] In other words, this disclosure provides external compositions in the following embodiments. Item 1. A topical composition containing (A) crotamiton and (B) ceramide 2. Item 2. The external composition according to Item 1, wherein the content of component (B) per 1 part by weight of component (A) is 0.0001 to 5 parts by weight. Item 3. The topical composition according to item 1 or 2, wherein the content of component (A) is 0.01 to 15% by weight. Item 4. The topical composition according to any one of items 1 to 3, wherein the content of component (B) is 0.001 to 10% by weight. Item 5. An emulsified composition, which is an external composition according to any one of items 1 to 4. Item 6. The topical composition described in Item 5, which is an oil-in-water type. [Effects of the Invention]

[0009] The topical compositions disclosed herein contain crotamiton, yet can suppress creaming due to storage. [Modes for carrying out the invention]

[0010] The topical composition disclosed herein is characterized by containing (A) crotamiton (hereinafter also referred to as "component (A)") and (B) ceramide 2 (hereinafter also referred to as "component (B)"). The topical composition disclosed herein is characterized by suppression of creaming due to storage. In this disclosure, creaming refers to the phenomenon in which the dispersed phase is partially concentrated due to the floating (if the dispersed phase is the oil phase) or sedimentation (if the dispersed phase is the oil phase) of the continuous phase and the dispersed phase. The topical composition disclosed herein is described in detail below. In this disclosure, the numerical range "X~Y" refers to the range from X to Y.

[0011] [(A) Crotamiton] The topical composition disclosed herein contains crotamiton as component (A). Conventionally, when crotamiton is incorporated into topical compositions, it causes creaming during storage, but the topical composition disclosed herein has suppressed creaming during storage.

[0012] Crotamiton, also known as N-ethyl-N-(2-methylphenyl)-2-butenamide, N-ethyl-No-tolyl-2-butenamide, etc., is a well-known ingredient used as an antipruritic and scabies treatment.

[0013] The content of component (A) in the topical composition of this disclosure is not particularly limited and can be set appropriately depending on the degree to which creaming suppression is required, the formulation form, etc., but for example, 0.01 to 15% by weight, preferably 0.01 to 12% by weight, more preferably 0.01 to 10% by weight, even more preferably 0.01 to 8% by weight, particularly preferably 0.01 to 6% by weight, or 0.01 to 5.5% by weight can be cited. Furthermore, since the topical composition of this disclosure has an excellent effect in suppressing creaming due to storage, creaming due to storage can be effectively suppressed even if the crotamiton content is relatively high. From this viewpoint, suitable content of component (A) can be 0.01 to 15% by weight, preferably 0.1 to 15% by weight, more preferably 1 to 15% by weight, even more preferably 3 to 15% by weight, particularly preferably 4 to 15% by weight, or 4.5 to 15% by weight can be cited.

[0014] [(B) Ceramide 2] The topical composition disclosed herein contains ceramide 2 as component (B). Conventionally, topical compositions containing crotamiton undergo creaming during storage, but in the topical composition disclosed herein, creaming during storage can be suppressed by using ceramide 2 in combination with crotamiton.

[0015] Ceramide 2 is N-stearoyldihydrosphingosine, a type of human-type ceramide.

[0016] The content of component (B) in the topical composition of this disclosure is not particularly limited and may be set appropriately depending on the desired degree of creaming suppression, the formulation form, etc., but for example, 0.001 to 10% by weight is possible. From the viewpoint of enhancing the creaming suppression effect, preferred content of component (B) is 0.01 to 10% by weight, more preferably 0.05 to 5% by weight, even more preferably 0.1 to 3% by weight, 0.15 to 2% by weight, or 0.2 to 1% by weight, and even more preferably 0.25 to 0.7% by weight, or 0.25 to 0.6% by weight.

[0017] In the topical composition disclosed herein, the ratio of component (A) to component (B) is determined according to the content of each component, but from the viewpoint of enhancing creaming suppression, the content of component (B) per 1 part by weight of component (A) is 0.0001 to 5 parts by weight, preferably 0.002 to 3 parts by weight, more preferably 0.02 to 2 parts by weight, even more preferably 0.05 to 0.13 parts by weight, 0.09 to 0.12 parts by weight, 0.05 to 0.1 parts by weight, or 0.06 to 0.1 parts by weight.

[0018] [water] The topical compositions of this disclosure contain water for preparation into a desired formulation. The water content in the topical compositions of this disclosure may be set appropriately depending on the formulation, etc., but examples include 20 to 97% by weight, preferably 30 to 95% by weight, more preferably 40 to 90% by weight, and even more preferably 50 to 85% by weight.

[0019] [Polyhydric alcohols] The external composition of the present disclosure may optionally contain a polyhydric alcohol as needed. The type of polyhydric alcohol is not particularly limited as long as it is pharmaceutically acceptable, and examples thereof include dihydric alcohols such as ethylene glycol, 1,3-butylene glycol, propylene glycol, isoprene glycol, diethylene glycol, dipropylene glycol, and polypropylene glycol; and trihydric alcohols such as glycerin. Among these polyhydric alcohols, 1,3-butylene glycol is preferred. These polyhydric alcohols may be used singly or in combination of two or more kinds.

[0020] When the external composition of the present disclosure contains a polyhydric alcohol, the content thereof is not particularly limited, and examples thereof include 1 to 20% by weight, preferably 4 to 15% by weight, and more preferably 6 to 10% by weight.

[0021] [Surfactant] The external composition of the present disclosure may contain a surfactant in order to be prepared into a desired dosage form. The surfactant may be any of a nonionic surfactant, an anionic surfactant, a cationic surfactant, or an amphoteric surfactant, and a nonionic surfactant is preferred.

[0022] The type of nonionic surfactant is not particularly limited as long as it is pharmaceutically acceptable, and examples thereof include polyoxyethylene sorbitan fatty acid esters, polyoxyethylene hydrogenated castor oil, glycerin fatty acid esters, polyglycerin fatty acid esters, polyoxyethylene glycerin fatty acid esters, sorbitan fatty acid esters, polyoxyethylene sorbitol fatty acid esters, polyoxyethylene alkyl ethers, polyethylene glycol fatty acid esters, lecithin derivatives, and the like.

[0023] Among these nonionic surfactants, polyoxyethylene sorbitan fatty acid esters and glycerin fatty acid esters are preferred, and self-emulsifying glyceryl monostearate (glyceryl stearate (SE)) and polyoxyethylene sorbitan monostearate (polysorbate 60) are preferred.

[0024] These nonionic surfactants may be used individually or in combination of two or more.

[0025] A preferred example of a surfactant used in the topical composition of this disclosure is a combination of polyoxyethylene sorbitan fatty acid ester and glycerin fatty acid ester. When using polyoxyethylene sorbitan fatty acid ester and glycerin fatty acid ester in combination, the ratio is not particularly limited, but for example, per 100 parts by weight of glycerin fatty acid ester, the amount of polyoxyethylene sorbitan fatty acid ester can be 1 to 1000 parts by weight, preferably 10 to 500 parts by weight, more preferably 20 to 200 parts by weight, even more preferably 30 to 100 parts by weight, even more preferably 40 to 80 parts by weight, and particularly preferably 50 to 70 parts by weight.

[0026] When a surfactant is included in the topical composition of this disclosure, the amount can be appropriately set depending on the formulation form, the type of surfactant used, etc., but for example, the total amount of surfactant can be 0.1 to 20% by weight, preferably 0.5 to 15% by weight, more preferably 1 to 10% by weight, and even more preferably 2 to 7% by weight.

[0027] [Oily base] The topical compositions disclosed herein may contain an oily base (oil) to prepare them into a desired formulation. The type of oily base is not particularly limited as long as it is pharmaceutically acceptable, but examples include mineral oil, higher monohydric alcohol, fatty acid alkyl ester, vegetable oil, animal oil, cholesterol, higher fatty acids having 12 to 34 carbon atoms, silicone oil, etc.

[0028] Among these oily bases, mineral oils and higher monohydric alcohols are good examples. Specific examples of mineral oils include paraffin, hydrogenated polyisobutene, liquid paraffin, gelling hydrocarbons (such as Plastibase), ceresin, microcrystalline wax, and petrolatum. Higher monohydric alcohols are monohydric alcohols with 6 to 34 carbon atoms. Preferably, higher monohydric alcohols have 10 to 18 carbon atoms, and specific examples include octyl alcohol, decyl alcohol, lauryl alcohol, myristyl alcohol, cetanol, stearyl alcohol, oleyl alcohol, and eicosanol.

[0029] These oily bases may be used individually or in combination of two or more.

[0030] A preferred example of an oily base used in the external compositions of this disclosure is a combination of mineral oil and a higher monohydric alcohol. When mineral oil and a higher monohydric alcohol are used in combination, the ratio is not particularly limited, but for example, per 100 parts by weight of mineral oil, the higher monohydric alcohol may be 0.1 to 1000 parts by weight, preferably 0.1 to 500 parts by weight, more preferably 1 to 200 parts by weight, even more preferably 5 to 100 parts by weight, even more preferably 10 to 50 parts by weight, and particularly preferably 20 to 40 parts by weight.

[0031] When an oily base is included in the topical composition of this disclosure, the amount can be appropriately set depending on the formulation form, etc., but for example, the total amount of the oily base can be 1 to 80% by weight, preferably 3 to 60% by weight, more preferably 5 to 40% by weight, and even more preferably 10 to 20% by weight.

[0032] [Other ingredients] In addition to the components described above, the topical compositions of this disclosure may contain other commonly used additives as needed. Examples of such additives include monohydric lower alcohols, pH adjusters, buffers, thickeners, solubilizers, antioxidants, stabilizers, fragrances, colorants, and the like. When these additives are included in the topical compositions of this disclosure, their content may be appropriately determined depending on the type of additive used.

[0033] Furthermore, the topical compositions disclosed herein 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 steroids (strong steroids (such as beclomethasone propionate, fluocinolone acetonide, betamethasone valerate, prednisolone acetate valerate, clobetazone butyrate, triamcinolone acetonide, and hydrocortisone propionate butyrate), and weak steroids (such as dexamethasone acetate, dexamethasone, hydrocortisone acetate, hydrocortisone, and prednisolone). These pharmacological components may be used individually or in combination of two or more. When these pharmacological components are included in the topical compositions disclosed herein, their concentrations may be appropriately set according to the type of pharmacological component used, the expected effect, etc. Because the topical compositions of this disclosure can be applied to a wide range of subjects, in preferred embodiments they do not contain steroids, preferably combinations of two or more steroids, more preferably combinations of two or more steroids of different strengths, and even more preferably combinations of the strong steroid and the weak steroid.

[0034] [Formulation form / dosage type] The topical composition disclosed herein may be an emulsified formulation such as an oil-in-water emulsion or a water-in-oil emulsion, or it may be a non-emulsified formulation such as a solubilized formulation or an aqueous ointment. In the prior art, when ceramide 2 and isopropyl myristate are included in an emulsified formulation (particularly an oil-in-water emulsion), creaming due to storage tends to be significant. In contrast, the topical composition disclosed herein can effectively suppress creaming due to storage, even if it is an emulsified formulation. In view of these effects, the topical composition disclosed herein is preferably an emulsified formulation, more preferably an oil-in-water emulsion.

[0035] Furthermore, the topical compositions of this disclosure are used as topical dermatological pharmaceuticals or quasi-drugs, and are preferably used as topical dermatological pharmaceuticals. Specific formulations of the topical compositions of the present invention include creams, lotions, gels, emulsions, liquids, poultices, patches, liniments, aerosols, aqueous ointments, packs, and the like. Among these, creams and emulsions are preferred, and creams are more preferred.

[0036] [Manufacturing method] The topical compositions disclosed herein can be manufactured according to known formulation methods corresponding to their formulation form. For example, if the topical composition disclosed herein is an emulsified formulation, it can be prepared by separating the components to be contained into water-soluble components and oily components, preparing an aqueous phase containing the water-soluble components and an oil phase containing the oily components, and emulsifying these according to known methods. [Examples]

[0037] The present disclosure will be explained in more detail below with reference to examples, but the present disclosure is not limited to these examples.

[0038] Test example The topical compositions (oil-in-water emulsion compositions, creams) shown in Table 1 were prepared. Specifically, an oil-phase composition consisting of components [1] and [2] and an aqueous-phase composition consisting of component [3] were dissolved at 75-86°C. Both the oil-phase and aqueous-phase compositions were in a dissolved state. The topical compositions were prepared by mixing the oil-phase and aqueous-phase compositions at 80°C, stirring, and cooling to room temperature.

[0039] <Evaluation of creaming suppression> The prepared topical compositions were filled into vials and stored at 50°C for one day. The appearance after storage was evaluated on a 5-point scale, with a score of "1" indicating no creaming and a score of "5" indicating significant creaming. More specifically, the degree of creaming was evaluated according to the ratio of the thickness of the creaming phase (the region where the dispersed phase (oil phase) is concentrated due to creaming) to the height of the topical composition in the vial (the length from the lower end of the concentrated region to the upper surface of the topical composition). The results are shown in Table 1.

[0040] [Table 1]

[0041] As shown in Table 1, no creaming occurred in the topical composition without component (A) (Reference Example), but significant creaming occurred in the topical composition containing component (A) (Comparative Example 1). In contrast, creaming was suppressed and storage stability improved in the topical compositions containing components (A) and (B) (Examples 1-4). In particular, the topical compositions of Examples 2 and 3 showed significantly suppressed creaming to the same extent as the Reference Example, and significantly improved storage stability.

Claims

1. A topical composition containing (A) crotamiton and (B) ceramide 2.

2. The topical composition according to claim 1, wherein the content of component (B) per 1 part by weight of component (A) is 0.0001 to 5 parts by weight.

3. The topical composition according to claim 1 or 2, wherein the content of component (A) is 0.01 to 15% by weight.

4. The topical composition according to claim 1 or 2, wherein the content of component (B) is 0.001 to 10% by weight.

5. The external composition according to claim 1 or 2, which is an emulsified composition.

6. The topical composition according to claim 5, wherein it is an oil-in-water type.

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