External components

Abstract

The object of this disclosure is to provide a topical composition containing ceramide 2 and glycyrrhetinic acid derivatives that can suppress separation during storage. [Solution] The topical composition containing (A) ceramide 2, (B) glycyrrhetinic acid derivatives, and (C) monoterpenes has been shown to suppress separation during storage.

Description

Technical Field

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

Background Art

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

[0003] Accordingly, conventionally, external compositions formulated with ceramide have been developed for the purpose of maintaining the function of the stratum corneum by supplementing ceramide in the stratum corneum. For example, Patent Document 1 reports that an emulsion 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 feel 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 separation 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 separation during storage. [Means for solving the problem]

[0007] The inventors of the present invention conducted diligent studies to solve the aforementioned problems and found that by including a monoterpene in an external composition containing ceramide 2 and glycyrrhetinic acid derivatives, separation due to storage can be suppressed. This disclosure was completed by further studies 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) monoterpenes. 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 0.05 to 200 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 are resistant to separation during storage. Furthermore, in preferred embodiments, the topical compositions disclosed herein also offer improved usability. [Modes for carrying out the invention]

[0010] The topical compositions of this disclosure are 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) monoterpene (hereinafter also referred to as "component (C)"). The topical compositions of this disclosure are resistant to separation during storage. In this disclosure, separation refers to the phenomenon in which the continuous phase of the topical composition contained in a container separates at the bottom of the container. In a preferred embodiment, the topical compositions of this disclosure also have improved feel (specifically, lightness). The topical compositions of this disclosure will be described in detail below. In this disclosure, the numerical range "X~Y" refers to a range of X or more and Y or less.

[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, separation occurs during storage. However, separation during storage is suppressed in the topical composition disclosed herein. Furthermore, conventionally, when ceramide 2 is incorporated into topical compositions, it tends to reduce the feel of the product, and this reduction in feel occurs when it is incorporated into topical compositions together with glycyrrhetinic acid derivatives. However, in a preferred embodiment of the topical composition disclosed herein, the feel of the product 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 separation suppression and / or improvement of usability, 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, separation occurs during storage, but separation during storage is suppressed in the topical compositions of the present disclosure. Furthermore, conventionally, when glycyrrhetinic acids are incorporated into topical compositions, they tend to reduce the feel of the product, and when incorporated into topical compositions together with ceramide 2, the feel of the product is reduced, but in preferred embodiments of the topical compositions of the present disclosure, the feel of the product 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 separation inhibition and / or improvement of usability.

[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 separation suppression and / or improvement of usability, 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 perspective of enhancing the effects of separation suppression and / or feeling improvement upon use, 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, still more preferably 0.1 to 20 parts by weight, or 0.1 to 10 parts by weight, even more preferably 0.2 to 5 parts by weight, or 0.3 to 4 parts by weight, and particularly preferably 0.5 to 3 parts by weight, or 0.5 to 2 parts by weight.

[0021] [(C) Monoterpene] The external composition of the present disclosure contains a monoterpene as component (C). Conventionally, external compositions containing ceramide 2 and glycyrrhetinic acids undergo separation during storage, but the external composition of the present disclosure can suppress separation during storage by using a monoterpene in combination with ceramide 2 and glycyrrhetinic acids. In addition, conventionally, external compositions containing ceramide 2 and glycyrrhetinic acids have a reduced feeling upon use, but in a preferred embodiment of the external composition of the present disclosure, the feeling upon use can also be improved by using a monoterpene in combination with ceramide 2 and glycyrrhetinic acids.

[0022] Monoterpenes are known components that commonly have a structure containing two isoprene units in the molecule and have a refreshing effect and the like.

[0023] The type of monoterpene used in the external composition of the present disclosure is not particularly limited as long as it is pharmaceutically or cosmetically acceptable, and examples thereof include alcohol-based monoterpenes such as menthol, thymol, geraniol, linalool, borneol, cineole, and terpineol; aldehyde-based monoterpenes such as citral, citronellal, perillaldehyde, and safranal; and ketone-based monoterpenes such as camphor, menthone, carbomenthone, and ionone. When optical isomers exist for these monoterpenes, any of the d-form, l-form, and dl-form may be used. These monoterpenes may be used singly or in combination of two or more types.

[0024] Furthermore, in the topical compositions of this disclosure, essential oils containing monoterpenes may be used as monoterpenes. Essential oils containing monoterpenes can be appropriately selected from known ones, but examples of essential oils containing menthol include peppermint oil and spearmint oil. In this specification, the descriptions of monoterpene content and ratios are values ​​converted to the amount of monoterpenes contained in the essential oil when an essential oil containing monoterpenes is used.

[0025] Among these monoterpenes, menthol is preferred, and l-menthol is even more preferred.

[0026] The content of component (C) in the topical composition of this disclosure is not particularly limited and may be set appropriately depending on the desired degree of separation inhibition and / or improvement of usability, the formulation, etc., but for example, 0.01 to 10% by weight is possible. From the viewpoint of enhancing the effect of separation inhibition and / or improvement of usability, a preferred content of component (C) is 0.01 to 10% by weight, more preferably 0.05 to 5% by weight, even more preferably 0.1 to 2% by weight, and even more preferably 0.5 to 1.5% by weight.

[0027] In the topical composition of this 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 separation and / or improving the feel of use, the content of component (C) per 1 part by weight of component (A) is preferably 0.02 to 70 parts by weight, or 0.1 to 50 parts by weight, more preferably 0.5 to 30 parts by weight, 1 to 20 parts by weight, and even more preferably 1.8 to 15 parts by weight, 1.8 to 12 parts by weight, 1.8 to 8 parts by weight, or 1.8 to 6 parts by weight.

[0028] 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 separation and / or improving the feel of use, 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 0.5 to 8 parts by weight, 1 to 5 parts by weight, or 2 to 4 parts by weight.

[0029] [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.

[0030] [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.

[0031] 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.

[0032] These oily bases may be used individually or in combination of two or more.

[0033] 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.

[0034] 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.

[0035] [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.

[0036] 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.

[0037] [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.

[0038] 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.

[0039] 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.

[0040] These nonionic surfactants may be used individually or in combination of two or more.

[0041] 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.

[0042] 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.

[0043] [Other ingredients] The topical compositions disclosed herein may or may not contain other commonly used additives in addition to the components described above, as needed. Examples of such optional additives include one or more monohydric lower alcohols, pH adjusters, buffers, thickeners, solubilizers, antioxidants, stabilizers, fragrances, colorants, etc. When other additives are included in the topical compositions disclosed herein, their content may be appropriately determined depending on the type of additive used.

[0044] Furthermore, the topical compositions of this disclosure 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 promoting components, and vitamins (vitamin A, vitamin B1, vitamin B2, vitamin B5, vitamin B6, vitamin B12, folic acid, panthenol (pantothenyl alcohol), vitamin C, vitamin D, vitamin E, vitamin K, vitamin H, etc.). When other pharmacological components are included in the topical compositions of this disclosure, their concentrations may be appropriately set according to the type of pharmacological component used, the expected effect, etc. In a preferred embodiment of the topical composition of this disclosure, panthenol (pantothenyl alcohol) is not included.

[0045] [Formulation form / dosage type] The topical compositions disclosed herein may be emulsified formulations such as oil-in-water emulsions and water-in-oil emulsions, or non-emulsified formulations such as solubilized formulations and aqueous ointments. In the prior art, when ceramide 2 and glycyrrhetinic acids are included in emulsified formulations (especially oil-in-water emulsions), separation during storage tends to be significant. In contrast, the topical compositions disclosed herein can effectively suppress separation during storage, even in emulsified formulations. In view of these effects, emulsified formulations, and more preferably oil-in-water emulsions, are preferred as topical compositions of the disclosure.

[0046] 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.

[0047] [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]

[0048] The present disclosure will be explained in more detail below with reference to examples, but the present disclosure is not limited to these examples.

[0049] Test example Topical compositions (oil-in-water emulsion compositions, creams) shown in Tables 2 and 3 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.

[0050] <Evaluation of separation and control> The prepared topical compositions were placed in vials and stored at 60°C for one day. The degree of separation at the bottom was evaluated based on the appearance after storage. A score of "1" was used to indicate no separation of the topical composition after storage, and a score of "5" indicated significant separation. Table 1 shows representative examples of the appearance when the degree of separation was a score of 1, 2, or 5. Tables 2 and 3 show the evaluation results for separation inhibition.

[0051] [Table 1]

[0052] <Evaluation of user experience> Regarding the feel of the topical composition immediately after preparation, expert panelists evaluated the weight of the texture of the topical composition when spread on the skin on a 5-point scale: heavy = "5", slightly heavy = "4", neither heavy nor light = "3", slightly light = "2", and light = "1". The results are shown in Tables 2 and 3.

[0053] [Table 2]

[0054] [Table 3]

[0055] As shown in Table 2, no separation occurred in topical compositions that did not contain components (A) to (C), and in topical compositions containing either component (A) or component (B) (Reference Examples 1 to 3). However, significant separation occurred in a topical composition containing both components (A) and (B) (Comparative Example 1). In contrast, as shown in Table 3, separation was suppressed and storage stability improved in topical compositions containing all of components (A) to (C) (Examples 1 to 4). In particular, the topical compositions in Examples 1 to 3 showed even greater suppression of separation and even greater storage stability.

[0056] Furthermore, as shown in Table 2, topical compositions that did not contain components (A) to (C) had a light feel and were not problematic (Reference Example 1), but topical compositions containing component (A) or component (B) tended to have a heavier feel (Reference Examples 2 and 3), and the topical composition containing both component (A) and component (B) (Comparative Example 1) had a heavier feel (Comparative Example 1). In contrast, as shown in Table 3, topical compositions containing all of components (A) to (C) (Examples 1 to 4) had a lighter feel to the same extent as Reference Example 1 (Examples 1 to 4).

Claims

1. A topical composition comprising (A) ceramide 2, (B) glycyrrhetinic acid, its derivatives, and / or salts thereof, and (C) monoterpenes.

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 0.05 to 200 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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