External components

Abstract

The object of this disclosure is to provide a topical composition containing ceramide 2 and glycyrrhetinic acid derivatives that can suppress creaming due to storage. [Solution] The topical composition containing (A) ceramide 2, (B) glycyrrhetinic acid derivatives, and (C) heparin-like substances has been found to suppress creaming during storage.

Description

Technical Field

[0001] The present disclosure relates to an external composition containing Ceramide 2 and glycyrrhetinic acids, which is capable of suppressing creaming.

Background Art

[0002] The stratum corneum is mainly composed of corneocytes and intercellular lipids forming a lamellar structure, and the lamellar structure of the intercellular lipids in the stratum corneum plays an important role in the barrier function and moisturizing function. It is known that about 50% of the intercellular lipids in the stratum corneum are composed of ceramides, and a decrease in the ceramide content in the stratum corneum leads to deterioration of the barrier function and moisturizing function.

[0003] Accordingly, conventionally, external compositions containing ceramide have been developed for the purpose of maintaining the function of the stratum corneum by replenishing ceramide 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 feeling upon use.

Prior Art Documents

Patent Documents

[0004]

Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0005] Ceramides are broadly classified into human-type ceramides, animal-derived ceramides, plant-derived ceramides, and pseudo-ceramides. Of these, human-type ceramides have the same structure as ceramides found in human skin and have excellent affinity with the skin. Among human-type ceramides, ceramide 2 is the most abundant in human skin and has a function that supports moisturizing, so it is mainly used in topical compositions dissolved in an oily base. On the other hand, glycyrrhetinic acid derivatives are functional ingredients with anti-inflammatory and anti-allergic effects, and are used in topical compositions dissolved in an oily base. The inventors of this invention proceeded with research to develop a topical composition containing ceramide 2 and glycyrrhetinic acid derivatives, but encountered the problem that creaming occurs during storage in topical compositions containing ceramide 2 and glycyrrhetinic acid derivatives.

[0006] Therefore, the object of this disclosure is to provide a topical composition containing ceramide 2 and glycyrrhetinic acid derivatives that can suppress creaming due to storage. [Means for solving the problem]

[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 a heparin-like substance in an external composition containing ceramide 2 and glycyrrhetinic acid derivatives. 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) ceramide 2, (B) glycyrrhetinic acid, its derivatives, and / or salts thereof, and (C) a heparin-like substance. Item 2. The external composition according to Item 1, wherein the content of component (B) per 1 part by weight of component (A) is 0.01 to 50 parts by weight. Item 3. The external composition according to item 1 or 2, wherein the content of component (C) per 1 part by weight of component (A) is 0.02 to 70 parts by weight. Item 4. The topical composition according to any one of items 1 to 3, wherein the content of component (A) 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 ceramide 2 and glycyrrhetinic acids, yet can suppress creaming during storage. Furthermore, in preferred embodiments, the topical compositions disclosed herein also exhibit improved glossiness when prepared as a cream. [Modes for carrying out the invention]

[0010] The topical composition of this disclosure is characterized by containing (A) ceramide 2 (hereinafter also referred to as "component (A)"), (B) glycyrrhetinic acid, its derivatives, and / or salts thereof (hereinafter also referred to as "component (B)" or "glycyrrhetinic acid derivatives"), and (C) heparinoid (hereinafter also referred to as "component (C)"). The topical composition of this disclosure has suppressed creaming due to storage. In this disclosure, creaming is a phenomenon in which the dispersed phase is partially concentrated due to the floating (if the dispersed phase is an oil phase) or sedimentation (if the dispersed phase is an oil phase) of the continuous phase and dispersed phase. The degree of suppression of creaming due to storage can be confirmed by diluting the topical composition 100 times with water to create harsh conditions, and by checking the presence or absence of a concentrated area of ​​the dispersed phase due to creaming, or the degree of its thickness. In a preferred embodiment, the topical composition of this disclosure further has improved gloss in appearance when prepared as a cream. The topical composition of this disclosure will be described in detail below. In this disclosure, the numerical range "X~Y" refers to the range between X and Y.

[0011] [(A) Ceramide 2] The topical composition disclosed herein contains ceramide 2 as component (A). Conventionally, when ceramide 2 is incorporated into topical compositions together with glycyrrhetinic acid derivatives, creaming occurs during storage. However, the topical composition disclosed herein suppresses creaming during storage. Furthermore, conventionally, when ceramide 2 is incorporated into topical compositions together with glycyrrhetinic acid derivatives, the glossiness of the cream when prepared is reduced. However, in a preferred embodiment of the topical composition disclosed herein, the glossiness of the cream when prepared can also be improved.

[0012] Ceramide 2 is N-stearoyldihydrosphingosine, a type of human-type ceramide.

[0013] The content of component (A) in the topical composition of this disclosure is not particularly limited and can be appropriately set according to the desired degree of creaming suppression and / or gloss improvement when prepared as a cream, the formulation form, etc., but examples include 0.001 to 10% by weight, or 0.002 to 8% by weight, preferably 0.01 to 5% by weight, more preferably 0.01 to 3% by weight, even more preferably 0.1 to 3% by weight, even more preferably 0.2 to 1.5% by weight, 0.3 to 1% by weight, 0.4 to 0.8% by weight, or 0.45 to 0.6% by weight.

[0014] [(B) Glycyrrhetinic acid derivatives] The topical compositions of the present disclosure contain glycyrrhetinic acid, its derivatives, and / or salts thereof as component (B). Conventionally, when glycyrrhetinic acids are incorporated into topical compositions together with ceramide 2, creaming occurs during storage, but the topical compositions of the present disclosure suppress creaming during storage. Furthermore, conventionally, when glycyrrhetinic acids are incorporated into topical compositions together with ceramide 2, the glossiness of the appearance when prepared as a cream decreases, but in preferred embodiments of the topical compositions of the present disclosure, the glossiness of the appearance when prepared as a cream can also be improved.

[0015] Glycyrrhetinic acid is a well-known component that is known to have anti-inflammatory and anti-allergic effects.

[0016] Derivatives of glycyrrhetinic acid are not particularly limited as long as they are pharmaceutically or cosmetically acceptable, but specific examples include pyridoxine glycyrrhetinate, stearyl glycyrrhetinate, glyceryl glycyrrhetinate, and monoglucuronide glycyrrhetinate. These derivatives of glycyrrhetinic acid may be used individually or in combination of two or more.

[0017] The salts of glycyrrhetinic acid and / or its derivatives are not particularly limited as long as they are pharmaceutically or cosmetically acceptable, but specifically, examples include alkali metal salts such as sodium salts and potassium salts; and ammonium salts. These salts may be used individually or in combination of two or more.

[0018] In the topical compositions of this disclosure, one of glycyrrhetinic acid, its derivatives, and salts thereof may be selected as component (B), or two or more may be used in combination. Among the components of (B), glycyrrhetinic acid is preferred from the viewpoint of further enhancing the effect of inhibiting creaming and / or improving gloss when prepared as a cream.

[0019] The content of component (B) in the topical composition of this disclosure is not particularly limited and can be set appropriately depending on the desired degree of creaming suppression and / or gloss improvement when prepared as a cream, the formulation form, etc., but examples include 0.001 to 5% by weight, preferably 0.005 to 1% by weight, 0.08 to 0.8% by weight, or 0.1 to 0.6% by weight, more preferably 0.15 to 0.5% by weight, and even more preferably 0.2 to 0.4% by weight.

[0020] In the external composition of the present disclosure, the ratio of component (A) to component (B) is determined according to the content of each of the above components, but from the viewpoint of enhancing the effect of suppressing creaming and / or improving gloss when prepared as a cream, the content of component (B) per 1 part by weight of component (A) is preferably 0.01 to 50 parts by weight, 0.01 to 40 parts by weight, more preferably 0.05 to 30 parts by weight, even more preferably 0.1 to 20 parts by weight, or 0.1 to 10 parts by weight, still more preferably 0.2 to 5 parts by weight, and particularly preferably 0.3 to 3 parts by weight.

[0021] [(C) Heparinoid] The external composition of the present disclosure contains a heparinoid as component (C). Conventionally, external compositions containing ceramide 2 and glycyrrhetinic acids undergo creaming during storage, but the external composition of the present disclosure can suppress creaming during storage by using the heparinoid in combination with ceramide 2 and glycyrrhetinic acids. In addition, conventionally, external compositions containing ceramide 2 and glycyrrhetinic acids have reduced appearance gloss when prepared as a cream, but in a preferred embodiment of the external composition of the present disclosure, the appearance gloss when prepared as a cream can also be improved by using the heparinoid in combination with ceramide 2 and glycyrrhetinic acids.

[0022] The heparinoid is a polysulfated mucopolysaccharide such as chondroitin polysulfate, and is a known component known to have a moisturizing effect, a blood circulation promoting effect, and the like. The origin of the heparinoid used in the present disclosure is not particularly limited, and examples thereof include those obtained by polysulfating mucopolysaccharides, those extracted from edible animal tissues (for example, lungs including bovine tracheal cartilage), and the like. In the external composition of the present disclosure, the heparinoid listed in the Japanese Non-Pharmacopoeial Drug Standards is suitably used as the heparinoid.

[0023] The content of component (C) in the topical composition of this disclosure is not particularly limited and can be set appropriately depending on the desired degree of creaming suppression and / or gloss improvement when prepared as a cream, the formulation form, etc., but for example, 0.01 to 10% by weight is possible. From the viewpoint of enhancing the effect of creaming suppression and / or improvement of usability, a preferred content of component (C) is 0.01 to 1% by weight, more preferably 0.01 to 0.4% by weight, even more preferably 0.1 to 0.35% by weight, and even more preferably 0.2 to 0.3% by weight.

[0024] In the topical composition of the present disclosure, the ratio of component (A) to component (C) is determined according to the content of each component, but from the viewpoint of enhancing the effect of suppressing creaming and / or improving gloss when prepared as a cream, the content of component (C) per 1 part by weight of component (A) is preferably 0.02 to 70 parts by weight, 0.02 to 50 parts by weight, more preferably 0.05 to 30 parts by weight, 0.1 to 20 parts by weight, 0.2 to 10 parts by weight, even more preferably 0.28 to 5 parts by weight, 0.3 to 4 parts by weight, 0.3 to 3 parts by weight, 0.3 to 2 parts by weight, or 0.3 to 1 part by weight, and even more preferably 0.45 to 0.75 parts by weight, or 0.5 to 0.7 parts by weight.

[0025] In the topical composition of this disclosure, the ratio of component (B) to component (C) is determined according to the content of each component, but from the viewpoint of enhancing the effect of suppressing creaming and / or improving gloss when prepared as a cream, the content of component (C) per 1 part by weight of component (B) is preferably 0.05 to 30 parts by weight, more preferably 0.1 to 10 parts by weight, even more preferably 0.3 to 5 parts by weight, even more preferably 0.5 to 3 parts by weight, and particularly preferably 1 to 2 parts by weight.

[0026] [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.

[0027] [Oily base] The topical compositions disclosed herein include an oily base (oil) for preparation 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] The content of the oily base in the topical composition of this disclosure may be set appropriately depending on the formulation form, etc., but for example, the total amount of the oily base may be 1 to 80% by weight, preferably 3 to 60% by weight, more preferably 5 to 40% by weight, even more preferably 10 to 20% by weight, and particularly preferably 10 to 15% by weight.

[0032] [Polyhydric alcohols] The topical compositions disclosed herein may optionally contain polyhydric alcohols. The type of polyhydric alcohol is not particularly limited, as long as it is pharmaceutically acceptable, but examples 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 individually or in combination of two or more.

[0033] When a polyhydric alcohol is included in the topical composition of this disclosure, the amount is not particularly limited, but for example, it may be 1 to 20% by weight, preferably 4 to 15% by weight, and more preferably 6 to 10% by weight.

[0034] [Surfactants] The topical compositions disclosed herein may contain surfactants for preparation into desired formulations. The surfactant may be a nonionic surfactant, anionic surfactant, cationic surfactant, or amphoteric surfactant, but a nonionic surfactant is preferred.

[0035] The types of nonionic surfactants are not particularly limited, as long as they are pharmaceutically acceptable, but examples 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 sorbitan fatty acid esters, polyoxyethylene alkyl ethers, polyethylene glycol fatty acid esters, lecithin derivatives, etc.

[0036] 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.

[0037] These nonionic surfactants may be used individually or in combination of two or more.

[0038] 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.

[0039] 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, even more preferably 2 to 7% by weight, and particularly preferably 3 to 5% by weight.

[0040] [Other ingredients] The topical compositions of this disclosure may or may not contain, in addition to the components described above, other commonly used additives as needed. Examples of such optional additives include one or more monohydric lower alcohols, pH adjusters, buffers, thickeners, solubilizers, antioxidants, stabilizers, fragrances, colorants, and metal oxide powders (oxides of elements such as Al, Mg, Sn, Zn, Co, Fe, Zr, Ti, Ce, etc.). When other additives are included in the topical compositions of this disclosure, their content may be appropriately determined depending on the type of additive used. In a preferred form of the topical composition of this disclosure, metal oxide powders are not included.

[0041] Furthermore, the topical compositions disclosed herein may contain other pharmacological components in addition to the components described above. Examples of such other pharmacological components, whether present or absent, include one or more of the following: antihistamines, local anesthetics, moisturizers, bactericides, antibacterial agents, antipruritics, skin protectants, blood circulation promoters, vitamins, etc. When other 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.

[0042] [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 glycyrrhetinic acid derivatives 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, and more preferably an oil-in-water emulsion.

[0043] 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.

[0044] [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]

[0045] The present disclosure will be explained in more detail below with reference to examples, but the present disclosure is not limited to these examples.

[0046] Test example Topical compositions (oil-in-water emulsion compositions, creams) shown in Tables 1 and 2 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 oil-phase and aqueous-phase compositions were mixed at 80°C, stirred, and cooled to room temperature to prepare the topical compositions.

[0047] <Evaluation of creaming suppression> Naturally, the more uniform and small the emulsion particles are, the higher the stability of the emulsion. Conversely, if the emulsion particles are non-uniform or large, the emulsion state deteriorates, leading to creaming. It is well known from Stokes' sedimentation equation that creaming is more likely to occur when the viscosity of the continuous phase is low. In this test example, in order to evaluate the degree of creaming of the topical composition, the emulsion was subjected to harsh conditions by forcibly lowering the viscosity of the continuous phase through dilution, thereby allowing for a more nuanced evaluation of the difference in emulsion stability of the topical composition before dilution. Specifically, the prepared topical composition was diluted 100 times with water, placed in a vial, and mixed by inversion. The degree of creaming was evaluated from the appearance after 3 minutes.

[0048] The diluted topical composition 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) (the length from the lower end of the concentrated region to the upper surface of the topical composition) to the height of the diluted topical composition in the vial. A larger ratio of this thickness (i.e., a higher score) indicates a greater degree of creaming when the topical composition was stored before dilution. The results are shown in Tables 1 and 2.

[0049] <Evaluation of the cream's appearance> The appearance of the topical composition (cream) immediately after preparation was evaluated by expert panelists on a three-point scale: "1" for excellent gloss, "2" for slight gloss, and "3" for no gloss. The results are shown in Tables 1 and 2.

[0050] [Table 1]

[0051] [Table 2]

[0052] As shown in Table 1, no creaming occurred in topical compositions that did not contain components (A) to (C) (Reference Example 1), and no significant creaming was observed in topical compositions containing either component (A) or component (B) (Reference Examples 2 and 3). However, creaming did occur in topical compositions containing both components (A) and (B) (Comparative Example 1). In contrast, as shown in Table 2, creaming was suppressed and storage stability improved in topical compositions containing all of components (A) to (C) (Examples 1 to 5). In particular, creaming was sufficiently suppressed in the topical compositions of Examples 1 to 4, and storage stability was further improved. Especially in the topical composition of Example 1, creaming was significantly suppressed to the same extent as in Reference Example 1, and storage stability was significantly improved.

[0053] Furthermore, as shown in Table 1, gloss was observed in the external composition (cream) that did not contain components (A) to (C), and in the external composition that contained component (A) or component (B) (Reference Examples 1 to 3), but gloss was lost in the external composition (cream) that contained both component (A) and component (B) (Comparative Example 1). In contrast, as shown in Table 2, the gloss of the external composition (cream) that contained all of components (A) to (C) improved to the same level as Reference Examples 1 to 3 (Examples 1 to 5).

Claims

1. A topical composition containing (A) ceramide 2, (B) glycyrrhetinic acid, its derivatives, and / or salts thereof, and (C) a heparin-like substance.

2. The topical composition according to claim 1, wherein the content of component (B) per 1 part by weight of component (A) is 0.01 to 50 parts by weight.

3. The external composition according to claim 1 or 2, wherein the content of component (C) per 1 part by weight of component (A) is 0.02 to 70 parts by weight.

4. The topical composition according to claim 1 or 2, wherein the content of component (A) 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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