External components

Abstract

The object of this disclosure is to provide a topical composition comprising ceramide 2 and tocopherol and / or its derivatives that can suppress creaming. [Solution] A topical composition containing (A) ceramide 2, (B) tocopherol and / or its derivatives, and (C) heparin-like substance has suppressed creaming.

Description

Technical Field

[0001] The present disclosure relates to an external composition containing ceramide 2 and tocopherol and / or its derivatives, which can suppress creaming.

Background Art

[0002] The stratum corneum is mainly composed of stratum corneum cells and intercellular lipids that form a lamellar structure. The lamellar structure of intercellular lipids in the stratum corneum plays an important role in the barrier function and moisturizing function. In addition, 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 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 plays a role in supporting moisturizing function. On the other hand, tocopherol and / or its derivatives have antioxidant and anti-inflammatory effects and are used in topical compositions to prevent skin aging and improve rough skin. The inventors of this invention proceeded with research to develop a topical composition containing ceramide 2 and tocopherol and / or its derivatives, but encountered the problem that creaming occurs during storage in topical compositions containing ceramide 2 and tocopherol and / or its derivatives.

[0006] Therefore, the object of this disclosure is to provide a topical composition comprising ceramide 2 and tocopherol and / or its derivatives that can suppress creaming. [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 tocopherol and / or its 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) tocopherol and / or its derivatives, and (C) a heparin-like substance. Item 2. The topical composition according to Item 1, wherein the content of component (A) is 0.001 to 10% by weight. Item 3. The external composition according to item 1 or 2, wherein the content of component (B) per 1 part by weight of component (A) is 0.01 to 100 parts by weight. Item 4. The external composition according to any one of items 1 to 3, wherein the content of component (C) per 1 part by weight of component (A) is 0.001 to 50 parts 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 tocopherol and / or derivatives thereof, yet can suppress creaming due to storage. Furthermore, in preferred embodiments, the topical compositions disclosed herein have an excellent feel, as they do not feel sticky during use and provide a noticeable coverage to the skin after application. [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) tocopherol and / or its derivatives (hereinafter also referred to as "component (B)" or "tocopherols"), and (C) heparinoid (hereinafter also referred to as "component (C)"). The topical compositions of this disclosure have 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 the oil phase) or sedimentation (if the dispersed phase is the oil phase) of the continuous phase and dispersed phase. In a preferred embodiment, the topical compositions of this disclosure further have improved non-greasy and / or covering properties (hereinafter also referred to as "feel"). 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 either tocopherols or heparin-like substances, creaming occurs during storage. However, the topical composition disclosed herein suppresses creaming during storage. Furthermore, while conventional topical compositions containing tocopherols and heparin-like substances tend to cream during storage, the topical composition disclosed herein suppresses creaming during storage by using ceramide 2 in combination with tocopherols and heparin-like substances. Moreover, in a preferred embodiment of the topical composition disclosed herein, the feel of use can also be improved by using ceramide 2 in combination with tocopherols and heparin-like substances.

[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 set appropriately depending on the desired degree of creaming suppression and / or improvement of usability, the formulation, etc., but for example, 0.001 to 10% by weight is possible. From the viewpoint of enhancing the effect of creaming suppression and / or improvement of usability, preferred content of component (A) is 0.01 to 10% by weight, more preferably 0.1 to 10% by weight, even more preferably 0.3 to 10% by weight, even more preferably 0.4 to 10% by weight, particularly preferably 0.45 to 10% by weight, 0.45 to 5% by weight, 0.45 to 3% by weight, or 0.45 to 2% by weight.

[0014] [(B) Tocopherols] The topical compositions of this disclosure contain tocopherol and / or its derivatives as component (B). Conventionally, when tocopherols are incorporated into topical compositions together with either ceramide 2 or heparin-like substances, creaming occurs during storage. However, the topical compositions of this disclosure suppress creaming during storage. Furthermore, conventional topical compositions containing ceramide 2 and heparin-like substances experience creaming during storage. However, in the topical compositions of this disclosure, creaming during storage can be suppressed by using tocopherols in combination with ceramide 2 and heparin-like substances. Moreover, in a preferred embodiment of the topical compositions of this disclosure, the feel of use can be improved by using tocopherols 2 in combination with ceramide 2 and heparin-like substances.

[0015] Tocopherol is a known component known as vitamin E. Derivatives of tocopherol are not particularly limited to those that are pharmaceutically acceptable, but examples include esters with carboxylic acids such as acetic acid, nicotinic acid, and succinic acid, and diesters with phosphoric acid. Furthermore, the tocopherol derivative may be the d-isomer, l-isomer, or dl-isomer, but the dl-isomer is preferred. Additionally, the tocopherol derivative may be the α-isomer, β-isomer, γ-isomer, or δ-isomer, but the α-isomer is preferred. In the topical compositions of this disclosure, one tocopherol and its derivatives may be selected and used alone, or two or more may be used in combination.

[0016] Among these tocopherols and their derivatives, tocopherol derivatives are preferred, and tocopherol acetate is preferred, from the viewpoint of enhancing the effect of suppressing creaming and / or improving the feel of use.

[0017] 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 improvement of usability, the formulation form, etc., but for example, 0.01 to 12% by weight is possible. From the viewpoint of enhancing the effect of creaming suppression and / or improvement of usability, a preferred content of component (B) is 0.1 to 8% by weight, more preferably 0.5 to 4% by weight, and even more preferably 1 to 3% by weight.

[0018] In the topical composition of this disclosure, the ratio of component (A) to component (B) is determined according to the content of each component, but from the viewpoint of enhancing the effect of suppressing creaming and / or improving the feel of use, the content of component (B) per 1 part by weight of component (A) is preferably 0.01 to 100 parts by weight, more preferably 0.1 to 50 parts by weight, even more preferably 0.5 to 20 parts by weight, even more preferably 1 to 10 parts by weight, and particularly preferably 2 to 5 parts by weight.

[0019] [(C) Heparinoid] The topical composition disclosed herein contains a heparin-like substance as component (C). Conventionally, topical compositions containing ceramide 2 and tocopherols undergo creaming upon storage, but in the topical composition disclosed herein, creaming upon storage can be suppressed by using a heparin-like substance in combination with ceramide 2 and tocopherols. Furthermore, conventionally, when a heparin-like substance is incorporated into a topical composition together with either ceramide 2 or tocopherols, creaming upon storage occurs, but creaming upon storage is suppressed in the topical composition disclosed herein. Moreover, in a preferred embodiment of the topical composition disclosed herein, the feel of use can also be improved by using a heparin-like substance in combination with ceramide 2 and tocopherols.

[0020] A heparin-like substance is a polysulfated mucopolysaccharide such as chondroitin polysulfate, and is a known component known to have a moisturizing effect and a blood circulation promoting effect, etc. Regarding the origin of the heparin-like substance used in the present disclosure, it is not particularly limited, and examples thereof include those obtained by polysulfating mucopolysaccharides, those extracted from tissues of edible animals (for example, lungs including bovine tracheal cartilage), etc. In the external composition of the present disclosure, as the heparin-like substance, a heparin-like substance listed in the specifications of drugs outside the Japanese Pharmacopoeia is preferably used.

[0021] The content of the component (C) in the external composition of the present disclosure is not particularly limited, and may be appropriately set according to the degree required for suppressing creaming and / or improving the feeling of use, the dosage form, etc. For example, 0.01 to 10% by weight can be mentioned. From the viewpoint of enhancing the effect of suppressing creaming and / or improving the feeling of use, the preferable content of the component (C) is 0.01 to 1% by weight, more preferably 0.01 to 0.4% by weight, still more preferably 0.1 to 0.3% by weight, still more preferably 0.2 to 0.3% by weight.

[0022] In the external composition of the present disclosure, the ratio of the component (A) to the component (C) is determined according to the content of each of the above components. From the viewpoint of enhancing the effect of suppressing creaming and / or improving the feeling of use, in terms of the content of the component (C) per 1 part by weight of the component (A), preferably 0.001 to 50 parts by weight, more preferably 0.01 to 20 parts by weight, still more preferably 0.03 to 10 parts by weight, still more preferably 0.06 to 5 parts by weight, still more preferably 0.1 to 3 parts by weight or 0.1 to 1 part by weight, particularly preferably 0.3 to 0.7 parts by weight can be mentioned.

[0023] In the topical composition disclosed herein, 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 the feel of use, the content of component (C) per 1 part by weight of component (B) is preferably 0.001 to 50 parts by weight, more preferably 0.01 to 10 parts by weight, even more preferably 0.03 to 1 part by weight, even more preferably 0.06 to 0.7 parts by weight, and particularly preferably 0.1 to 0.5 parts by weight.

[0024] [water] The topical compositions disclosed herein contain water for preparation into a desired formulation. The water content in the topical compositions disclosed herein 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 80% by weight.

[0025] [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.

[0026] 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.

[0027] [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.

[0028] 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.

[0029] 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.

[0030] These nonionic surfactants may be used individually or in combination of two or more.

[0031] 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 a combination of polyoxyethylene sorbitan fatty acid ester and glycerin fatty acid ester, the ratio is not particularly limited, but for example, per 100 parts by weight of polyoxyethylene sorbitan fatty acid ester, the amount of glycerin 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.

[0032] 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.

[0033] [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.

[0034] 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.

[0035] These oily bases may be used individually or in combination of two or more.

[0036] 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.

[0037] 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.

[0038] [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.

[0039] 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 the like. 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 desired effect, etc.

[0040] [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 tocopherol and / or derivatives thereof are included in emulsified formulations (particularly oil-in-water emulsions), creaming due to storage tends to be significant. In contrast, the topical compositions disclosed herein can effectively suppress creaming due to storage, even when they are emulsified formulations. In view of these effects, emulsified formulations, and more preferably oil-in-water emulsions, are preferred as topical compositions of the disclosure.

[0041] 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.

[0042] [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]

[0043] The present disclosure will be explained in more detail below with reference to examples, but the present disclosure is not limited to these examples.

[0044] Test example The topical compositions (oil-in-water emulsion compositions, creams) shown in Table 2 were prepared. Specifically, the topical compositions were prepared by dissolving and mixing an oil phase composition consisting of component [1] and an aqueous phase composition consisting of components [2] and [3] at 80°C, stirring, and cooling to room temperature.

[0045] <Evaluation of creaming suppression> The prepared topical compositions were filled into vials and stored at 60°C for 7 days. The degree of creaming was evaluated based on the appearance after storage, on a 10-point scale, with a score of "1" indicating no creaming and a score of "10" 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). Table 1 shows representative examples of the appearance when the degree of creaming is a score of 1, 6, or 10. In Table 1, the arrows indicate the position of the lower end of the region where the dispersed phase (oil phase) is concentrated due to creaming; the lower the relative position, the greater the degree of creaming. The results are shown in Table 2.

[0046] [Table 1]

[0047] <Evaluation of user experience> Ten expert panelists evaluated the feel of the topical composition immediately after preparation. Specifically, they evaluated the degree of stickiness and coverage (the feeling that the skin is covered by a layer of the topical composition) on the inner forearm after applying the composition to the inner side of the forearm on a three-point scale: satisfied (high degree), neither satisfied nor dissatisfied (low degree). The percentage of people who answered "satisfied" was then calculated. The results are shown in Table 2.

[0048] [Table 2]

[0049] As shown in Table 2, no creaming occurred in the topical composition that did not contain components (A) to (C) (Reference Example), but significant creaming occurred in the topical composition containing components (A) and (B) (Comparative Example 1). Furthermore, considerable creaming occurred in the topical composition containing components (B) and (C) (Comparative Example 2), and in the topical composition containing components (A) and (C) (Comparative Example 3). In contrast, creaming was suppressed and storage stability improved in the topical compositions containing all of components (A) to (C) (Examples 1 to 3). In particular, creaming was suppressed to such an extent that it was not observed in the topical composition with the composition of Example 1, and storage stability was significantly improved.

[0050] Furthermore, topical compositions that did not contain components (A) to (C) did not exhibit much stickiness (Reference Example), but topical compositions containing components (A) and (B) (Comparative Example 1), topical compositions containing components (B) and (C) (Comparative Example 2), and topical compositions containing components (A) and (C) (Comparative Example 3) exhibited significant stickiness. In contrast, topical compositions containing all of components (A) to (C) (Examples 1 to 3) showed improved non-stickiness. In particular, the topical compositions of Examples 1 and 2 showed improved non-stickiness to a level equal to or greater than that of the Reference Example, and the topical composition of Example 1 showed superior non-stickiness that surpassed the Reference Example, resulting in high satisfaction.

[0051] Furthermore, no coverage was observed in topical compositions that did not contain components (A) to (C) (Reference Example), while improved coverage was observed in topical compositions containing components (A) and (B) (Comparative Example 1), topical compositions containing components (B) and (C) (Comparative Example 2), and topical compositions containing components (A) and (C) (Comparative Example 3). Improved coverage was also observed in topical compositions containing all components (A) to (C) (Examples 1 to 3), with the compositions of Examples 1 and 2 showing even greater improvement in coverage. In particular, the composition of Example 1 showed a remarkable improvement in coverage, resulting in high satisfaction.

Claims

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

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

3. The external composition according to claim 1 or 2, wherein the content of component (B) per 1 part by weight of component (A) is 0.01 to 100 parts by weight.

4. The external composition according to claim 1 or 2, wherein the content of component (C) per 1 part by weight of component (A) is 0.001 to 50 parts 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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