Topical composition

Abstract

To provide a topical composition which contains ceramide 2 and paraben and which can suppress separation.SOLUTION: Provided is a topical composition comprising: (A) ceramide 2; (B) paraben; and (C) a heparinoid.SELECTED DRAWING: None

Description

Technical Field

[0001] The present disclosure relates to an external composition containing ceramide 2 and parabens, which can suppress separation.

Background Art

[0002] The stratum corneum is mainly composed of corneocytes and intercellular lipids that form a lamellar structure. The lamellar structure of the intercellular lipids in the stratum corneum plays an important role in the barrier function and moisturizing function. Also, about 50% of the intercellular lipids in the stratum corneum are composed of ceramides, and it is known that when the ceramide content in the stratum corneum decreases, the barrier function and moisturizing function decrease.

[0003] Therefore, conventionally, external compositions containing ceramides have been developed for the purpose of maintaining the function of the stratum corneum by supplementing ceramides in the stratum corneum. For example, Patent Document 1 reports that an emulsified composition containing ceramide, a specific monoalkyl glyceryl ether or monoalkenyl glyceryl ether, a higher fatty acid, and a polyhydric alcohol has high stability and excellent usability.

Prior Art Documents

Patent Documents

[0004]

Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0005] Ceramides are roughly classified into human-type ceramides, animal-derived ceramides, plant-derived ceramides, and pseudo-ceramides. Among these, human-type ceramides have the same structure as the ceramides in human skin and are ceramides with excellent affinity for the skin. Also, among human-type ceramides, ceramide 2 is most abundantly contained in human skin and has the function of supporting the moisturizing function. On the other hand, parabens are used in topical compositions as relatively safe preservatives. The inventor conducted studies to develop a topical composition containing ceramide 2 and parabens, and faced the problem that separation occurred during storage in the topical composition containing ceramide 2 and parabens.

[0006] Therefore, an object of the present disclosure is to provide a topical composition containing ceramide 2 and parabens that can suppress separation.

Means for Solving the Problems

[0007] The inventor conducted intensive studies to solve the above problems and found that by containing a heparin-like substance in a topical composition containing ceramide 2 and parabens, separation during storage can be suppressed and excellent storage stability can be achieved. 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 aspects. Item 1. A topical composition containing (A) ceramide 2, (B) parabens, and (C) a heparin-like substance. Item 2. The topical composition according to Item 1, which is an emulsified preparation. Item 3. The topical composition according to Item 1 or 2, wherein the (B) parabens are methylparaben and / or propylparaben. Item 4. The topical composition according to Item 1 or 2, wherein the (B) parabens are methylparaben and the content of methylparaben is 0.15% by weight or more. Item 5. The topical composition according to Item 1 or 2, wherein the (B) parabens are propylparaben and the content of propylparaben is 0.01 to 0.08% by weight.

Effects of the Invention

[0009] According to the present disclosure, in an external composition containing ceramide 2 and parabens, a formulation prescription is provided that can suppress separation during storage and has excellent storage stability.

Mode for Carrying Out the Invention

[0010] The external composition of the present disclosure is characterized by containing (A) ceramide 2, (B) parabens, and (C) heparin-like substances. 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.

[0011] [(A) Ceramide 2] The external composition of the present disclosure contains ceramide 2. Ceramide 2 is N-stearoyl dihydrosphingosine and is one type of human ceramide.

[0012] The content of ceramide 2 in the external composition of the present disclosure may be appropriately set according to the dosage form and the like. For example, it may be 0.001 to 10% by weight, preferably 0.001 to 8% by weight, more preferably 0.005 to 5% by weight, still more preferably 0.01 to 3% by weight, even more preferably 0.1 to 3% by weight, particularly preferably 0.2 to 2.5% by weight, and particularly more preferably 0.5 to 2.5% by weight.

[0013] [(B) Parabens] The external composition of the present disclosure further contains parabens. Parabens are paraoxybenzoic acid esters. In the external composition of the present disclosure, the types of parabens used are not particularly limited as long as they can be used in cosmetics or pharmaceuticals. Examples include methylparaben, ethylparaben, propylparaben, isopropylparaben, butylparaben, isobutylparaben, benzylparaben, and the like. Among these parabens, preferably, methylparaben, ethylparaben, propylparaben, isopropylparaben, butylparaben, and isobutylparaben are mentioned, and more preferably, methylparaben and propylparaben are mentioned. These parabens may be used alone or in combination of two or more.

[0014] Regarding the content of parabens in the external composition of the present disclosure, it may be appropriately set according to the type of parabens used, etc. For example, 0.001 to 2.6% by weight, preferably 0.001 to 0.5% by weight, more preferably 0.001 to 0.3% by weight can be mentioned. More specifically, in the case of using methylparaben, from the viewpoint of more effectively suppressing separation due to storage, as the content of methylparaben in the external composition, more preferably 0.15% by weight or more, even more preferably 0.15 to 0.25% by weight, and particularly preferably 0.18 to 0.22% by weight can be mentioned. Also, in the case of using propylparaben, from the viewpoint of more effectively suppressing separation due to storage, as the content of propylparaben in the external composition, more preferably 0.01 to 0.08% by weight, and particularly preferably 0.05 to 0.08% by weight can be mentioned.

[0015] [(C) Heparin-like substances] In the external composition of the present disclosure, in addition to the above components, it contains heparin-like substances. By including heparin-like substances in the external composition of the present disclosure, it becomes possible to suppress separation due to storage while containing ceramide 2 and parabens.

[0016] A heparin-like substance is a polysulfated mucopolysaccharide such as chondroitin polysulfate, which is a known component known to have a moisturizing effect and a blood circulation promoting effect. The origin of the heparin-like substance used in the present disclosure is not particularly limited, and examples thereof include those obtained by polysulfating mucopolysaccharides, those extracted from the tissues of edible animals (for example, lungs including bovine tracheal cartilage), and the like. In the external composition of the present disclosure, a heparin-like substance included in the Japanese Pharmaceutical Excipients Standard is preferably used as the heparin-like substance.

[0017] In the external composition of the present disclosure, as the ratio of ceramide 2 to the heparin-like substance, for example, per 100 parts by weight of ceramide 2, the heparin-like substance is 0.01 to 500 parts by weight, preferably 1 to 300 parts by weight, more preferably 5 to 200 parts by weight, still more preferably 10 to 150 parts by weight, even more preferably 10 to 70 parts by weight, and particularly preferably 10 to 60 parts by weight.

[0018] The content of the heparin-like substance in the external composition of the present disclosure is, for example, 0.01 to 10% by weight, preferably 0.01 to 1% by weight, more preferably 0.01 to 0.3% by weight, and still more preferably 0.1 to 0.3% by weight.

[0019] [Water] The external composition of the present disclosure contains water in order to be prepared into a desired dosage form. The content of water in the external composition of the present disclosure may be appropriately set according to the dosage form and the like, and examples thereof include 20 to 97% by weight, preferably 25 to 95% by weight, more preferably 30 to 90% by weight, and still more preferably 35 to 80% by weight.

[0020] [Polyhydric alcohol] The external composition of the present disclosure may optionally contain a polyhydric alcohol. 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, and polypropylene glycol; and trihydric alcohols such as glycerin can be mentioned. 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.

[0021] When the external composition of the present disclosure contains a polyhydric alcohol, its content is not particularly limited. For example, 1 to 15% by weight, preferably 1 to 10% by weight, more preferably 2 to 8% by weight can be mentioned.

[0022] [Surfactant] The external composition of the present disclosure may contain a surfactant in order to prepare a desired dosage form. The surfactant may be any of a nonionic surfactant, an anionic surfactant, a cationic surfactant, or an amphoteric surfactant, but preferably a nonionic surfactant.

[0023] The type of nonionic surfactant is not particularly limited as long as it is pharmaceutically acceptable. For example, 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 sorbit fatty acid esters, polyoxyethylene alkyl ethers, polyethylene glycol fatty acid esters, lecithin derivatives, etc. can be mentioned. Among these, examples of suitable nonionic surfactants include polyoxyethylene sorbitan fatty acid esters and polyoxyethylene hydrogenated castor oil. These nonionic surfactants may be used alone or in combination of two or more.

[0024] When a surfactant is contained in the external composition of the present disclosure, its content may be appropriately set according to the dosage form, the type of surfactant used, etc. For example, 0.1 to 20% by weight, preferably 0.5 to 10% by weight, more preferably 1 to 5% by weight can be mentioned.

[0025] [Thickener] The external composition of the present disclosure may contain a thickener as necessary for imparting viscosity or the like. The type of thickener is not particularly limited as long as it is pharmaceutically acceptable. For example, carboxyvinyl polymer, xanthan gum, guar gum, locust bean gum, carrageenan, dextran, methylcellulose, ethylcellulose, carboxymethylcellulose, hydroxyethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, 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, etc. can be mentioned. Among these thickeners, carboxyvinyl polymer is preferably mentioned. These thickeners may be used alone or in combination of two or more.

[0026] When the external composition of the present disclosure contains a thickener, its content is not particularly limited. For example, 0.05 to 5% by weight, preferably 0.1 to 3% by weight, more preferably 0.1 to 1% by weight can be mentioned.

[0027] [Oil component] The external composition of the present disclosure may contain an oil component in order to prepare it into a desired dosage form. The type of the oil component is not particularly limited as long as it is pharmaceutically acceptable. For example, it includes mineral oil, fatty acid alkyl ester, vegetable oil, animal oil, cholesterol, higher fatty acids having 12 to 34 carbon atoms, higher monohydric alcohols having 12 to 34 carbon atoms, silicone oil, and the like.

[0028] Among these oil components, as an example, mineral oil and fatty acid alkyl ester can be mentioned. Specifically, examples of the mineral oil include paraffin, hydrogenated polyisobutene, liquid paraffin, gelled hydrocarbon (such as plastibase), ceresin, microcrystalline wax, petrolatum, and the like. Examples of the fatty acid alkyl ester include esters of fatty acids having 6 to 30 carbon atoms and alcohols having 1 to 34 carbon atoms. Specifically, they include diisopropyl adipate, isopropyl myristate, isopropyl palmitate, cetyl palmitate, diethyl sebacate, ethyl oleate, and the like.

[0029] These oil components may be used alone or in combination of two or more.

[0030] When the external composition of the present disclosure contains an oil component, its content may be appropriately set according to the dosage form and the like. For example, it may be 1 to 80% by weight, preferably 5 to 70% by weight, more preferably 5 to 50% by weight, and still more preferably 10 to 40% by weight.

[0031] [Other Components] In addition to the aforementioned components, the external composition of the present disclosure may contain other commonly used additives as necessary. Examples of such additives include monohydric lower alcohols, pH adjusters, buffers, solubilizers, antioxidants, stabilizers, fragrances, colorants, and the like. When these additives are contained in the external composition of the present disclosure, their content may be appropriately set according to the type of the additives used and the like.

[0032] In addition to the aforementioned components, the topical composition of the present disclosure may also contain a pharmacological component. 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. Further, 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 pharmacological component used, the expected effect, and the like.

[0033] [Formulation form·Dosage form] The topical composition of the present disclosure may be an emulsified formulation such as an oil-in-water emulsion formulation or a water-in-oil emulsion formulation, or may be a non-emulsified formulation such as a solubilized formulation or an aqueous ointment. Originally, when ceramide 2 and parabens are contained in an emulsified formulation (especially an oil-in-water emulsion formulation), separation due to storage tends to be remarkable. However, in the topical composition of the present disclosure, even if it is an emulsified formulation, separation due to storage can be effectively suppressed. In view of such an effect, preferred examples of the topical composition of the present disclosure include an emulsified formulation, and more preferably an oil-in-water emulsion formulation.

[0034] The dosage form of the topical composition of the present disclosure is not particularly limited as long as it can be applied transdermally, and it may be in any form such as liquid, semi-solid (cream, gel, ointment, paste), solid, etc., but preferably liquid or semi-solid.

[0035] In addition, the topical composition of the present disclosure is used as a topical skin pharmaceutical (including quasi-drugs). Specific examples of the formulation form of the topical composition 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 preferably mentioned.

[0036] [Manufacturing method] The external composition of the present disclosure can be manufactured according to known formulation techniques according to its dosage form. For example, when the external composition of the present disclosure is an emulsion formulation, the components to be included are divided into water-soluble components and oil components, an aqueous phase containing the water-soluble components and an oil phase containing the oil components are prepared, and these are emulsified according to known techniques to prepare the composition.

Examples

[0037] Examples are shown below to more specifically explain the present disclosure, but the present disclosure is not limited thereto.

[0038] Test Example External compositions (emulsion-type water-in-oil emulsified formulations) having the compositions shown in Tables 1 and 2 were prepared. Specifically, ceramide 2 (N-stearoyl dihydrosphingosine), pseudo-ceramide, propyl paraben, isopropyl myristate, white petrolatum, liquid paraffin, polyoxyethylene hydrogenated castor oil 50, and polysorbate 60 were mixed in predetermined amounts and heated and dissolved at 75 to 85°C to prepare an oil-phase composition. Separately, a heparin-like substance, methyl paraben, 1,3-butylene glycol, carboxyvinyl polymer, and purified water were mixed in predetermined amounts to prepare an aqueous-phase composition. Next, the aqueous-phase composition heated to 80°C was gradually added to the oil-phase composition heated to 80°C and mixed to perform an emulsification operation to obtain an external composition (emulsion-type water-in-oil emulsified formulation). The external compositions immediately after production were all in an emulsified state without separation.

[0039] 6 g of each external composition immediately after preparation was filled into a 10-ml glass bottle and stored for 15 days under light-shielded conditions at 60°C. The appearance of each external composition after storage was visually observed, and the stability was evaluated according to the following criteria. <Stability Criteria> AA: Not separated (Separation cannot be visually confirmed in either the upright or tilted state of the glass bottle, and the same state as immediately after preparation is maintained). A: Slightly separated (separation is not visible when the glass bottle is upright, but slight separation can be seen when the glass bottle is tilted). B: Somewhat separated (separation can be seen in both the upright and tilted states of the glass bottle, but the degree of separation is slight and within the acceptable range). C: Separated (Obvious separation is observed, and the separated state can be clearly seen without tilting the glass bottle). D: Significantly separated (Obvious separation that is noticeable at a glance is observed).

[0040] The results are shown in Tables 1 and 2. When neither ceramide 2 nor parabens (methylparaben or propylparaben) were included, and when only one of ceramide 2 or parabens was included, no separation occurred after storage, and excellent storage stability was exhibited (Reference Examples 1 to 3). Also, in the external composition containing pseudo-ceramide and parabens, no separation occurred after storage, and excellent storage stability was exhibited (Reference Example 4). On the other hand, when ceramide 2 and parabens were included, separation was observed after storage (Comparative Examples 1 to 5). In contrast, in the external composition containing a heparin-like substance together with ceramide 2 and parabens, separation after storage could be suppressed (Examples 1 to 8).

[0041]

Table 1

[0042]

Table 2

Claims

Claim 1 An external composition containing (A) ceramide 2, (B) parabens, and (C) heparin analogs. Claim 2 The external composition according to claim 1, which is an emulsion preparation. Claim 3 The external composition according to claim 1 or 2, wherein the (B) parabens are methylparaben and / or propylparaben. Claim 4 The external composition according to claim 1 or 2, wherein the (B) parabens are methylparaben and the content of methylparaben is 0.15% by weight or more. Claim 5 The external composition according to claim 1 or 2, wherein the (B) parabens are propylparaben and the content of propylparaben is 0.01 - 0.08% by weight.

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