External composition for treating dermatitis

Abstract

To suppress viscosity change over time in an oil-in-water emulsion composition containing a medicinal ingredient used as a dermatitis treatment agent, a higher alcohol which is solid at normal temperature, and a polar oil which is liquid at normal temperature.SOLUTION: Provided is a method for suppressing viscosity change over time that occurs in an oil-in-water emulsion composition, which contains a component (A): a medicinal component used as a dermatitis treatment drug, a component (B): a higher alcohol that is solid at normal temperature, and a component (C): a polar oil that is liquid at normal temperature, by containing a component (D): N-Stearoyldihydrosphingosine. Also provided is a medicinal skin external application, which is an oil-in-water emulsion composition containing a component (A): a medicinal component used as a dermatitis treatment drug, a component (B): a higher alcohol that is solid at normal temperature, a component (C): a polar oil that is liquid at normal temperature, and a component (D): N-Stearoyldihydrosphingosine.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to an external application preparation containing a medicinal ingredient for use as a treatment for dermatitis, and in particular to a method for suppressing viscosity change over time. [Background technology]

[0002] Among the active ingredients used in dermatitis treatment drugs, those that do not dissolve in low-polarity oils such as hydrocarbons are often dissolved in polar oils such as higher alcohols or ester oils. Polar oils are also sometimes used to increase the transdermal absorption of drugs.

[0003] On the other hand, in oil-in-water emulsion compositions, higher alcohols are used as emulsifiers in addition to their function as solvents, and higher alcohols that are solid at room temperature increase the viscosity of the composition, so they are also used to adjust the viscosity of the composition. In contrast, ester oils that are liquid at room temperature increase the solubility of higher alcohols in the oil phase, which can cause a problem of delaying the time until the higher alcohol acts on the interface between the oil phase and the water phase to exert its viscosity adjustment function. That is, it is expected that the higher alcohol will act on the interface quickly during emulsification and cooling, but due to the presence of polar oils that are liquid at room temperature, the higher alcohol may actually act on the interface between the oil phase and the water phase over a period of several hours to several days, or even several weeks. As a result, when the emulsion composition is produced and stored, the viscosity increases after several days or weeks, which causes a problem of changing the feeling of use during the period of use. [Prior art documents] [Non-patent literature]

[0004] [Non-Patent Document 1] Masukawa, Y., et al., J. Lipid Res. 2008. 49: 1466-1476 [Non-Patent Document 2] Robson, KJ, et al., J. Lipid Res. 1994. 35: 2060-2068 Summary of the Invention [Problem to be solved by the invention]

[0005] An object of the present invention is to suppress the change in viscosity over time in an oil-in-water emulsion composition containing a medicinal ingredient used as a dermatitis treatment drug, a higher alcohol that is solid at room temperature, and a polar oil that is liquid at room temperature. [Means for solving the problem]

[0006] In the present invention, a method for suppressing viscosity change over time occurring in an oil-in-water emulsion composition containing the above-mentioned components (A), (B), and (C) can be provided by including component (D): N-stearoyldihydrosphingosine in an oil-in-water emulsion composition containing component (A): a medicinal ingredient used as a dermatitis treatment drug, component (B): a higher alcohol that is solid at room temperature, and component (C): a polar oil that is liquid at room temperature. The present invention can also provide a medicinal skin topical application agent that is an oil-in-water emulsion composition containing component (A): a medicinal ingredient used as a dermatitis treatment drug, component (B): a higher alcohol that is solid at room temperature, component (C): a polar oil that is liquid at room temperature, and component (D): N-stearoyldihydrosphingosine.

[0007] More specifically, in order to solve the above-mentioned problems, the present application provides the following aspects: [1]: A method for suppressing a change in viscosity of an oil-in-water emulsion composition, which contains component (A): a medicinal ingredient used as a dermatitis treatment drug, component (B): a higher alcohol which is solid at room temperature, and component (C): a polar oil which is liquid at room temperature, and which changes in viscosity over time, comprising adding component (D): N-stearoyldihydrosphingosine in addition to the above components (A), (B), and (C); [2]: The method for inhibiting a change in viscosity according to [1], wherein the component (A): active ingredient is one or more selected from the group consisting of betamethasone valerate, prednisolone valerate acetate, tocopherol acetate, heparinoids and panthenol; [3]: The method for suppressing a change in viscosity according to [1] or [2], wherein the component (B): higher alcohol that is solid at room temperature is one or more selected from the group consisting of cetanol, stearyl alcohol, cetostearyl alcohol, and behenyl alcohol; [4]: The method for suppressing a change in viscosity according to [1] or [2], wherein the component (C): polar oil that is liquid at room temperature is one or more selected from the group consisting of octyldodecanol, oleyl alcohol, hexyl laurate, isopropyl myristate, isopropyl palmitate, glyceryl tri-2-ethylhexanoate, and glyceryl tri(capryl / caprate); [5]: Component (A): The active ingredient is at least one selected from the group consisting of betamethasone valerate, prednisolone valerate acetate, tocopherol acetate, heparinoids and panthenol; Component (B): The higher alcohol that is solid at room temperature is at least one selected from the group consisting of cetanol, stearyl alcohol, cetostearyl alcohol, and behenyl alcohol, and Component (C): The room temperature liquid polar oil is at least one selected from the group consisting of octyldodecanol, oleyl alcohol, hexyl laurate, isopropyl myristate, isopropyl palmitate, glyceryl tri-2-ethylhexanoate, and caprylic / capric triglyceride; The method for suppressing a change in viscosity according to [1], [6]: The following components (A) to (D): Ingredient (A): An active ingredient used as a treatment for dermatitis Component (B): Higher alcohol that is solid at room temperature Component (C): Polar oil that is liquid at room temperature Ingredient (D): N-stearoyldihydrosphingosine a medicinal skin topical application agent, which is an oil-in-water emulsion composition comprising: [7]: Component (A): The pharmaceutical preparation for external application on the skin according to [6], wherein the active ingredient is one or more selected from the group consisting of betamethasone valerate, prednisolone valerate acetate, tocopherol acetate, heparinoids and panthenol; [8]: Component (B): the medicinal skin external application preparation according to [6] or [7], wherein the higher alcohol which is solid at room temperature is one or more selected from the group consisting of cetanol, stearyl alcohol, cetostearyl alcohol, and behenyl alcohol; [9]: Component (C): The pharmaceutical skin topical application preparation according to [6] or [7], wherein the polar oil which is liquid at room temperature is one or more selected from the group consisting of octyldodecanol, oleyl alcohol, hexyl laurate, isopropyl myristate, isopropyl palmitate, glyceryl tri-2-ethylhexanoate, and glyceryl tri(caprylate / caprate);

[10] : Component (A): The active ingredient is at least one selected from the group consisting of betamethasone valerate, prednisolone valerate acetate, tocopherol acetate, heparinoids and panthenol; Component (B): The higher alcohol that is solid at room temperature is at least one selected from the group consisting of cetanol, stearyl alcohol, cetostearyl alcohol, and behenyl alcohol; Component (C): The room temperature liquid polar oil is at least one selected from the group consisting of octyldodecanol, oleyl alcohol, hexyl laurate, isopropyl myristate, isopropyl palmitate, glyceryl tri-2-ethylhexanoate, and caprylic / capric triglyceride; The medicinal skin external application preparation according to [6],

[11] : The following components (B) to (D): Component (B): Higher alcohol that is solid at room temperature Component (C): Polar oil that is liquid at room temperature Ingredient (D): N-stearoyldihydrosphingosine Component (A): a base composition for producing an oil-in-water emulsion composition containing a medicinal ingredient used as a dermatitis treatment agent;

[12] : The base composition according to

[11] , wherein the component (B): higher alcohol which is solid at room temperature is one or more selected from the group consisting of cetanol, stearyl alcohol, cetostearyl alcohol, and behenyl alcohol;

[13] : The base composition according to

[11] or

[12] , wherein the component (C): polar oil which is liquid at room temperature is one or more selected from the group consisting of octyldodecanol, oleyl alcohol, hexyl laurate, isopropyl myristate, isopropyl palmitate, glyceryl tri-2-ethylhexanoate, and glyceryl tri(caprylate / caprate);

[14] : Component (A): The base composition according to

[11] or

[12] , wherein the active ingredient is one or more selected from the group consisting of betamethasone valerate, prednisolone valerate acetate, tocopherol acetate, heparinoids and panthenol;

[15] : Component (A): The active ingredient is one or more selected from the group consisting of betamethasone valerate, prednisolone valerate acetate, tocopherol acetate, heparinoids, and panthenol; Component (B): The higher alcohol that is solid at room temperature is at least one selected from the group consisting of cetanol, stearyl alcohol, cetostearyl alcohol, and behenyl alcohol, and Component (C): The room temperature liquid polar oil is at least one selected from the group consisting of octyldodecanol, oleyl alcohol, hexyl laurate, isopropyl myristate, isopropyl palmitate, glyceryl tri-2-ethylhexanoate, and caprylic / capric triglyceride; The base composition according to

[11] ,

[16] : Component (D): an agent for suppressing viscosity change in an oil-in-water emulsion composition containing N-stearoyldihydrosphingosine, component (B): a higher alcohol that is solid at room temperature, and component (C): a polar oil that is liquid at room temperature;

[17] : Component (B): The viscosity change inhibitor according to

[16] , wherein the higher alcohol that is solid at room temperature is one or more selected from the group consisting of cetanol, stearyl alcohol, cetostearyl alcohol, and behenyl alcohol;

[18] : Component (C): The viscosity change inhibitor according to

[16] or

[17] , wherein the polar oil that is liquid at room temperature is one or more selected from the group consisting of octyldodecanol, oleyl alcohol, hexyl laurate, isopropyl myristate, isopropyl palmitate, glyceryl tri-2-ethylhexanoate, and glyceryl tri(capryl / caprate);

[19] : The viscosity change inhibitor according to

[16] or

[17] , wherein the oil-in-water emulsion composition contains, as an active ingredient, component (A): a medicinal ingredient used as a dermatitis treatment drug;

[20] : Component (A): A viscosity change inhibitor as described in

[19] , wherein the active ingredient is one or more selected from the group consisting of betamethasone valerate, prednisolone valerate acetate, tocopherol acetate, heparinoids and panthenol. Effect of the Invention

[0008] In the present invention, a method for suppressing the viscosity change over time that occurs in an oil-in-water emulsion composition containing the above-mentioned components (A), (B), and (C) can be provided by adding component (D): N-stearoyldihydrosphingosine to an oil-in-water emulsion composition containing the above-mentioned components (A), (B), and (C). The present invention can also provide a medicinal skin topical application agent that is an oil-in-water emulsion composition containing component (A): a medicinal ingredient used as a dermatitis treatment drug, component (B): a higher alcohol that is solid at room temperature, component (C): a polar oil that is liquid at room temperature, and component (D): N-stearoyldihydrosphingosine. [Brief description of the drawings]

[0009] [Figure 1] FIG. 1 is a graph showing the rate of change in viscosity of each emulsion composition after a two-week temperature cycle test from the viscosity at the time of production. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0010] As described above, some oil-in-water emulsion compositions containing a medicinal ingredient and used as a dermatitis treatment drug contain polar oils such as higher alcohols and ester oils. However, in such oil-in-water emulsion compositions, due to the chemical relationship between the higher alcohols and polar oils such as ester oils, when the emulsion composition is produced and stored, the viscosity increases after several days or weeks, causing a problem that the feeling of use changes during the period of use.

[0011] Means for Solving the Problem The inventors of the present invention have conducted extensive research in order to solve the above-mentioned problem of suppressing the change in viscosity over time that occurs in an oil-in-water emulsion composition containing component (A): an active ingredient used as a dermatitis treatment drug, component (B): a higher alcohol that is solid at room temperature, and component (C): a polar oil that is liquid at room temperature. As a result, they have found that when producing an oil-in-water emulsion composition containing components (A), (B), and (C), it is possible to suppress the change in viscosity over time by adding additional component (D): N-stearoyldihydrosphingosine, and have thus completed the present invention.

[0012] In one specific aspect, the present invention can provide a method for suppressing a change in viscosity of an oil-in-water emulsion composition, which contains component (A): an active ingredient used as a dermatitis treatment drug, component (B): a higher alcohol that is solid at room temperature, and component (C): a polar oil that is liquid at room temperature, and which changes in viscosity over time, comprising adding component (D): N-stearoyldihydrosphingosine in addition to the above components (A), (B), and (C).

[0013] The present invention is characterized in that, in producing an oil-in-water emulsion composition containing component (A), component (D): N-stearoyldihydrosphingosine is contained in addition to components (A), (B), and (C). By including this component (D) in the oil-in-water emulsion composition, it is possible to suppress an increase in viscosity during storage after production of the oil-in-water emulsion composition, and to prevent a change in the feel during use.

[0014] Here, N-stearoyldihydrosphingosine, component (D), is a component classified as ceramide NDS (ceramide 10) (formerly known as ceramide NG and ceramide 2). Originally, N-stearoyldihydrosphingosine is a substance that has been shown to improve the barrier and enhance water retention by reinforcing ceramide when applied to a rough skin model caused by surfactant treatment on the inside of the forearm.

[0015] In the present invention, by including component (D): N-stearoyldihydrosphingosine, it is possible to exhibit the effect of suppressing an increase in viscosity after production, which is different from the above-mentioned effect of the oil-in-water emulsion composition containing components (A), (B), and (C).

[0016] In the present invention, component (D) may be contained in an amount of 0.1 to 100 mg (0.01 to 10%), more preferably 1.0 to 50.0 mg (0.1 to 5.0%), even more preferably 5.0 to 10.0 mg (0.5 to 1.0%), and most preferably 10.0 mg (1.0%), per 1 g of the oil-in-water emulsion composition.

[0017] In the present invention, the component (A) that can be contained in the target oil-in-water emulsion composition may be any medicinal ingredient used as a dermatitis treatment drug, so long as it is insoluble or poorly soluble in low-polarity oils such as hydrocarbons. Examples of medicinal ingredients that can be used in the present invention include, but are not limited to, betamethasone valerate, prednisolone valerate acetate, tocopherol acetate, heparinoids, panthenol, etc.

[0018] In the present invention, component (A) to be contained in the target oil-in-water emulsion composition may be contained in an amount that is acceptable for inclusion in the oil-in-water emulsion composition of the desired component.

[0019] When betamethasone valerate, a fat-soluble component, is selected as component (A), it can be contained in an amount of 0.1 to 15 mg (0.01 to 1.5%), more preferably 0.5 to 3 mg (0.05 to 0.3%), even more preferably 1.0 to 1.5 mg (0.10 to 0.15%), and most preferably 1.2 mg (0.12%), per gram of the oil-in-water emulsion composition.

[0020] When the fat-soluble component prednisolone valerate acetate is selected as component (A), it can be contained in an amount of 0.1 to 15 mg (0.01 to 1.5%), more preferably 0.5 to 3 mg (0.05 to 0.3%), even more preferably 1.0 to 2.0 mg (0.10 to 0.20%), and most preferably 1.5 mg (0.15%) per gram of the oil-in-water emulsion composition.

[0021] When tocopherol acetate, a fat-soluble component, is selected as component (A), it can be contained in an amount of 1 to 100 mg (0.1 to 10%), more preferably 5 to 50 mg (0.5 to 5%), even more preferably 15.0 to 25.0 mg (1.5 to 2.5%), and most preferably 20 mg (2.0%), per gram of the oil-in-water emulsion composition.

[0022] When a water-soluble heparinoid is selected as component (A), it can be contained in an amount of 0.1 to 50 mg (0.01 to 5%), more preferably 0.5 to 10 mg (0.05 to 1%), even more preferably 1.0 to 5.0 mg (0.1 to 0.5%), and most preferably 3.0 mg (0.3%) per gram of the oil-in-water emulsion composition.

[0023] When panthenol is selected as component (A), it can be contained in an amount of 1 to 200 mg (0.1 to 20%), more preferably 5 to 150 mg (0.5 to 15%), even more preferably 10 to 100 mg (1 to 10%), and most preferably 50 mg (5%), per gram of the oil-in-water emulsion composition.

[0024] In the present invention, the component (B) that can be contained in the target oil-in-water emulsion composition is a higher alcohol (monohydric alcohol having 6 or more carbon atoms (C6)) that is approved for addition to pharmaceuticals and cosmetics, and any alcohol that is solid at room temperature can be used. Such higher alcohols that are solid at room temperature are used as emulsion stabilizers, emulsification aids, etc., and for adjusting the spreadability and hardness of creams. Examples of higher alcohols that can be used in the present invention include, but are not limited to, cetanol, stearyl alcohol, cetostearyl alcohol, behenyl alcohol, etc.

[0025] In the present invention, component (B) to be contained in the target oil-in-water emulsion composition can be contained in an amount capable of emulsifying component (A) contained in the oil-in-water emulsion composition. Since the ease of emulsification in the oil-in-water emulsion composition varies depending on the type of medicinal ingredient of component (A), the content of component (B) may vary depending on the medicinal ingredient selected as component (A).

[0026] For example, when cetostearyl alcohol is selected as component (B), it may be contained in an amount of 5.0 to 200.0 mg (0.5 to 20.0%), more preferably 10.0 to 100.0 mg (1.0 to 10.0%), even more preferably 30.0 to 70.0 mg (3.0 to 7.0%), and most preferably 50.0 mg (5.0%), per gram of the oil-in-water emulsion composition.

[0027] In the present invention, the component (C) that can be contained in the target oil-in-water emulsion composition can be any polar oil that is liquid at room temperature and is approved for addition to pharmaceuticals and cosmetics. Such polar oils that are liquid at room temperature are used to increase the solubility of the higher alcohol of component (B) in the oil phase, and examples of such polar oils include higher alcohols, ester oils, and fatty acid triglycerides that are liquid at room temperature. Specific examples of polar oils that are liquid at room temperature that can be used in the present invention include, but are not limited to, higher alcohols that are liquid at room temperature such as octyldodecanol and oleyl alcohol, ester oils such as hexyl laurate, isopropyl myristate, and isopropyl palmitate, and fatty acid triglycerides such as glyceryl tri-2-ethylhexanoate and tri(capryl-caprate).

[0028] In the present invention, the component (C) to be contained in the target oil-in-water emulsion composition can be contained in an amount that can increase the solubility of the component (B) contained in the oil-in-water emulsion composition in the oil phase. Since the solubility in the oil phase varies depending on the type of the medicinal ingredient of the component (B), the content of the component (C) may vary depending on the medicinal ingredient selected as the component (B).

[0029] For example, when hexyl laurate is selected as component (C), it can be contained in an amount of 5.0 to 200.0 mg (0.5 to 20.0%), more preferably 10.0 to 100.0 mg (1.0 to 10.0%), even more preferably 30.0 to 70.0 mg (3.0 to 7.0%), and most preferably 50.0 mg (5.0%), per gram of the oil-in-water emulsion composition.

[0030] As another specific embodiment, the present invention relates to the following components (A) to (D): Ingredient (A): An active ingredient used as a treatment for dermatitis Component (B): Higher alcohol that is solid at room temperature Component (C): Polar oil that is liquid at room temperature Ingredient (D): N-stearoyldihydrosphingosine It is possible to provide a medicinal skin external application agent which is an oil-in-water emulsion composition containing the above.

[0031] This medicinal skin topical application can be provided as an oil-in-water emulsion composition in which the change in viscosity over time is suppressed by adding an additional component (D) when producing an oil-in-water emulsion composition containing components (A), (B), and (C).

[0032] As mentioned above, among oil-in-water emulsion compositions containing medicinal ingredients used as dermatitis treatment drugs, there is a problem that the viscosity of the oil-in-water emulsion composition increases after several days or weeks when it is stored after production due to the inclusion of polar oils such as higher alcohols and ester oils, and the feeling of use changes during the period of use. The present invention is based on the novel finding that the viscosity increase of the oil-in-water emulsion composition can be suppressed by adding component (D) to such an oil-in-water emulsion composition containing components (B) and (C).

[0033] Therefore, in another specific embodiment, the present invention provides the following components (B) to (D): Component (B): Higher alcohol that is solid at room temperature Component (C): Polar oil that is liquid at room temperature Ingredient (D): N-stearoyldihydrosphingosine It is possible to provide a base composition for producing an oil-in-water emulsion composition containing component (A): a medicinal ingredient used as a dermatitis treatment agent, comprising the above formula:

[0034] This medicinal skin topical application agent shows the effect that when the oil-in-water emulsion composition containing component (A) is produced, and the oil phase is added with component (B) and component (C) for emulsification of component (A), the base composition further contains component (D) to suppress the viscosity change over time of the oil-in-water emulsion composition containing component (A). Therefore, the present invention can be a base composition containing component (B), component (C), and component (D) for producing the oil-in-water emulsion composition containing component (A).

[0035] The present invention can also provide a viscosity change inhibitor for an oil-in-water emulsion composition containing component (D): N-stearoyldihydrosphingosine, and containing component (B): a higher alcohol that is solid at room temperature, and component (C): a polar oil that is liquid at room temperature. This viscosity change inhibitor for an oil-in-water emulsion composition is characterized by being effective when the oil-in-water emulsion composition contains component (B) and component (C). In addition, this oil-in-water emulsion composition can be designed as a composition for containing component (A): a medicinal ingredient used as a dermatitis treatment drug, and when the oil-in-water emulsion composition contains components (B) and (C) as components necessary for emulsification, the viscosity change inhibitor containing component (D) of the present invention becomes useful.

[0036] The present invention will be described in more detail below with reference to examples, but the following examples are not intended to limit the present invention in any way. EXAMPLES

[0037] Example 1: Preparation of test formulations In this example, a test formulation was prepared for use in the present invention.

[0038] For each of the preparation examples and comparative examples shown in Tables 1 and 2, the components were weighed out, and the oil phase and water phase containing the compositions shown were heated to 75 to 85°C, stirred, and visually confirmed to be clearly dissolved.

[0039] After confirming dissolution, the water phase was gradually added while stirring the oil phase, and emulsified by stirring to obtain each preparation. Thereafter, these were cooled to room temperature while stirring to obtain an emulsion composition.

[0040] [Table 1]

[0041] [Table 2]

[0042] Example 2: Measurement of viscosity change rate In this example, the change in viscosity over time of the various oil-in-water emulsion compositions produced in Example 1 was measured.

[0043] The viscosity of each emulsion composition obtained in Example 1 during production was measured using a rheometer (HAAKE VISCOTESTER iQ, manufactured by Thermo Fisher Scientific). A "C60 2° / Ti" (Thermo Fisher Scientific) was used as the measurement rotor, and the temperature of each emulsion composition during measurement was kept constant at 25°C.

[0044] Using this apparatus, the shear rate (1 / s) was increased linearly from 0 to 50 over a period of 60 seconds, and the viscosity (Pa·s) was obtained when the shear rate (1 / s) reached 50.

[0045] Next, each of the emulsion compositions obtained in Example 1 was filled into an aluminum tube and subjected to the following temperature cycle test conditions: After 11 hours at 5°C, increase to 40°C over 1 hour, maintain at 40°C for 11 hours, return to 5°C over 1 hour, maintain at 5°C for 11 hours, and repeat this 24-hour cycle continuously; It was stored for 2 weeks.

[0046] By repeating the above temperature change, the change in viscosity of the emulsion composition can be accelerated and detected in a short period of time. After storage for two weeks, the viscosity of each emulsion composition was measured under the same test conditions as those used during production.

[0047] The formula below: Viscosity change rate = (viscosity measurement result after temperature cycle test) / (viscosity measurement result at the time of manufacture) x 100 The viscosity change rate was calculated based on the above.

[0048] The results of the viscosity change rate are shown in FIG. 1. In Comparative Example 1 to Comparative Example 5, the viscosity change rate was high, and it was found that the viscosity increased during storage. On the other hand, in Preparation Examples 1 to 6, which are emulsion compositions produced by adding N-stearoyldihydrosphingosine, the viscosity change rate was about 100%, and it was found that almost no viscosity change occurred. These results show that by including N-stearoyldihydrosphingosine as a component during the production of an oil-in-water emulsion composition, it is possible to suppress the increase in viscosity over time. [Industrial Applicability]

[0049] In the present invention, a method for suppressing the viscosity change over time that occurs in an oil-in-water emulsion composition containing the above-mentioned components (A), (B), and (C) can be provided by adding component (D): N-stearoyldihydrosphingosine to an oil-in-water emulsion composition containing the above-mentioned components (A), (B), and (C). The present invention can also provide a medicinal skin topical application agent that is an oil-in-water emulsion composition containing component (A): a medicinal ingredient used as a dermatitis treatment drug, component (B): a higher alcohol that is solid at room temperature, component (C): a polar oil that is liquid at room temperature, and component (D): N-stearoyldihydrosphingosine.

Claims

1. A method for suppressing a change in viscosity of an oil-in-water emulsion composition, which contains component (A): an active ingredient used as a dermatitis treatment drug, component (B): a higher alcohol that is solid at room temperature, and component (C): a polar oil that is liquid at room temperature, and which changes in viscosity over time, comprising adding component (D): N-stearoyldihydrosphingosine in addition to the above components (A), (B), and (C).

2. Component (A): The method for inhibiting viscosity change according to claim 1, wherein the active ingredient is one or more selected from the group consisting of betamethasone valerate, prednisolone valerate acetate, tocopherol acetate, heparinoids and panthenol.

3. 3. The method for inhibiting viscosity change according to claim 1 or 2, wherein component (B): a higher alcohol that is solid at room temperature is one or more selected from the group consisting of cetanol, stearyl alcohol, cetostearyl alcohol, and behenyl alcohol.

4. 3. The method for inhibiting viscosity change according to claim 1 or 2, wherein component (C): polar oil that is liquid at room temperature is one or more selected from the group consisting of octyldodecanol, oleyl alcohol, hexyl laurate, isopropyl myristate, isopropyl palmitate, glyceryl tri-2-ethylhexanoate, and glyceryl tri(caprylate / caprate).

5. Component (A): The active ingredient is at least one selected from the group consisting of betamethasone valerate, prednisolone valerate acetate, tocopherol acetate, heparinoids and panthenol; Component (B): The higher alcohol that is solid at room temperature is at least one selected from the group consisting of cetanol, stearyl alcohol, cetostearyl alcohol, and behenyl alcohol, and Component (C): The polar oil that is liquid at room temperature is at least one selected from the group consisting of octyldodecanol, oleyl alcohol, hexyl laurate, isopropyl myristate, isopropyl palmitate, glyceryl tri-2-ethylhexanoate, and caprylic / capric triglyceride; 2. The method for suppressing a change in viscosity according to claim 1,

6. The following components (A) to (D): Ingredient (A): An active ingredient used as a treatment for dermatitis Component (B): Higher alcohol that is solid at room temperature Component (C): Polar oil that is liquid at room temperature Ingredient (D): N-stearoyldihydrosphingosine A medicinal skin topical application agent which is an oil-in-water emulsion composition comprising:

7. 7. The pharmaceutical skin topical application preparation according to claim 6, wherein the component (A) is one or more medicinal ingredients selected from the group consisting of betamethasone valerate, prednisolone valerate acetate, tocopherol acetate, heparinoids and panthenol.

8. 8. The pharmaceutical skin topical application preparation according to claim 6 or 7, wherein the component (B): higher alcohol that is solid at room temperature is one or more selected from the group consisting of cetanol, stearyl alcohol, cetostearyl alcohol, and behenyl alcohol.

9. 8. The medicinal skin topical application preparation according to claim 6 or 7, wherein component (C): the polar oil that is liquid at room temperature is one or more selected from the group consisting of octyldodecanol, oleyl alcohol, hexyl laurate, isopropyl myristate, isopropyl palmitate, glyceryl tri-2-ethylhexanoate, and glyceryl tri(caprylate / caprate).

10. Component (A): The active ingredient is at least one selected from the group consisting of betamethasone valerate, prednisolone valerate acetate, tocopherol acetate, heparinoids and panthenol; Component (B): The higher alcohol that is solid at room temperature is at least one selected from the group consisting of cetanol, stearyl alcohol, cetostearyl alcohol, and behenyl alcohol; Component (C): The polar oil that is liquid at room temperature is at least one selected from the group consisting of octyldodecanol, oleyl alcohol, hexyl laurate, isopropyl myristate, isopropyl palmitate, glyceryl tri-2-ethylhexanoate, and caprylic / capric triglyceride; 7. The pharmaceutical skin external application preparation according to claim 6,

11. The following components (B) to (D): Component (B): Higher alcohol that is solid at room temperature Component (C): Polar oil that is liquid at room temperature Ingredient (D): N-stearoyldihydrosphingosine Component (A): A base composition for producing an oil-in-water emulsion composition containing a medicinal ingredient used as a dermatitis treatment agent.

12. 12. The base composition according to claim 11, wherein the component (B): higher alcohol that is solid at room temperature is one or more selected from the group consisting of cetanol, stearyl alcohol, cetostearyl alcohol, and behenyl alcohol.

13. Component (C): The base composition according to claim 11 or 12, wherein the polar oil that is liquid at room temperature is one or more selected from the group consisting of octyldodecanol, oleyl alcohol, hexyl laurate, isopropyl myristate, isopropyl palmitate, glyceryl tri-2-ethylhexanoate, and caprylic / capric triglyceride.

14. Component (A): The base composition according to claim 11 or 12, wherein the active ingredient is one or more selected from the group consisting of betamethasone valerate, prednisolone valerate acetate, tocopherol acetate, heparinoids and panthenol.

15. Component (A): The active ingredient is at least one selected from the group consisting of betamethasone valerate, prednisolone valerate acetate, tocopherol acetate, heparinoids and panthenol; Component (B): The higher alcohol that is solid at room temperature is at least one selected from the group consisting of cetanol, stearyl alcohol, cetostearyl alcohol, and behenyl alcohol, and Component (C): The polar oil that is liquid at room temperature is at least one selected from the group consisting of octyldodecanol, oleyl alcohol, hexyl laurate, isopropyl myristate, isopropyl palmitate, glyceryl tri-2-ethylhexanoate, and caprylic / capric triglyceride; 12. The base composition of claim 11, wherein

16. A viscosity change inhibitor for an oil-in-water emulsion composition containing component (D): N-stearoyldihydrosphingosine, component (B): a higher alcohol that is solid at room temperature, and component (C): a polar oil that is liquid at room temperature.

17. Component (B): A viscosity change inhibitor as described in claim 16, wherein the higher alcohol that is solid at room temperature is one or more selected from the group consisting of cetanol, stearyl alcohol, cetostearyl alcohol, and behenyl alcohol.

18. Component (C): A viscosity change inhibitor as described in claim 16 or 17, wherein the polar oil that is liquid at room temperature is one or more selected from the group consisting of octyldodecanol, oleyl alcohol, hexyl laurate, isopropyl myristate, isopropyl palmitate, glyceryl tri-2-ethylhexanoate, and glyceryl tri(caprylate / caprate).

19. 18. The viscosity change inhibitor according to claim 16 or 17, wherein the oil-in-water emulsion composition comprises, as an active ingredient, component (A): a medicinal ingredient used as a dermatitis treatment drug.

20. Component (A): A viscosity change inhibitor as described in claim 19, wherein the active ingredient is one or more selected from the group consisting of betamethasone valerate, prednisolone valerate acetate, tocopherol acetate, heparinoids and panthenol.

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