Emulsified composition containing anti-inflammatory ingredients

Abstract

To provide an emulsified composition that contains glycyrrhetinic acid and is easy to spread and does not cause glycyrrhetinic acid precipitation, and also provided is an emulsified composition that contains glycyrrhetinic acid and other hydrophobic active ingredients and is easy to spread and does not cause glycyrrhetinic acid precipitation.SOLUTION: The inventors of the present invention have found that an emulsified composition, which does not cause precipitation while dissolving glycyrrhetinic acid when the pH of the emulsified composition is 7.9 or higher when 30 mL of water is added and suspended to 1 g of the emulsified composition, can be prepared and the above problems can be solved.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to an emulsified composition containing glycyrrhetinic acid as an anti-inflammatory component. The present invention also relates to an emulsified composition containing glycyrrhetinic acid as an anti-inflammatory component together with other anti-inflammatory components.

Background Art

[0002] Glycyrrhetinic acid is used as a skin drug as an anti-inflammatory component. However, since it is a poorly water-soluble component, it can be dissolved in polyhydric alcohols such as ethanol, butylene glycol (BG), dipropylene glycol (DPG), pentylene glycol, and propanediol, low molecular weight ester oils, and higher alcohols such as isostearyl alcohol, cetyl alcohol, and stearyl alcohol, and it is generally used by dissolving it in these solvents.

[0003] However, glycyrrhetinic acid does not have a high solubility in oil, and when the ratio of hydrocarbon oil components such as liquid paraffin and petrolatum or low-polarity oil components such as silicone oil is increased, it tends to be difficult to dissolve. Due to such characteristics, depending on the type of oil constituting the oil phase, it has the property of being likely to precipitate in the composition.

[0004] Conversely, by adding higher alcohols such as cetyl alcohol and stearyl alcohol to increase the polarity of the oil phase, glycyrrhetinic acid can dissolve in the oil phase. However, when trying to prepare an emulsified composition using these oily components, it is generally known that the viscosity of the emulsified composition increases depending on the addition amount and becomes a hard cream-like state. Due to such characteristics, higher alcohols are not suitable for use as a solvent for the production of emulsified compositions.

[0005] Furthermore, when preparing an emulsified composition containing glycyrrhetinic acid, an oily component and an aqueous component are mixed to create an emulsification. However, oily components such as low molecular weight ester oils inherently inhibit emulsification, and are generally used in small quantities when preparing the emulsified composition, making them insufficient for dissolving glycyrrhetinic acid. In addition, polyhydric alcohols such as ethanol, butylene glycol (BG), and dipropylene glycol (DPG) are known to precipitate glycyrrhetinic acid in the emulsified composition when mixed with water for emulsification, as they cannot keep the glycyrrhetinic acid dissolved.

[0006] Thus, even when attempting to prepare an emulsified composition containing glycyrrhetinic acid based on previous knowledge, there was a problem in that it was not possible to form an emulsified composition while keeping the glycyrrhetinic acid dissolved when using existing combinations of oil phase components.

[0007] Furthermore, when preparing skin medications, it is desirable to use not only glycyrrhetinic acid as an active ingredient, but also other hydrophobic active ingredients in combination. For example, ufenamate, one such hydrophobic active ingredient, is used in skin medications as an anti-inflammatory ingredient. However, it is a non-water-soluble component that is liquid at room temperature and is often used as an emulsified composition by mixing it with an oil phase. When used as a skin medication, ufenamate is generally included at a concentration of about 5% to obtain excellent anti-inflammatory effects. However, it requires a certain amount of oily component for emulsification, and this oily component reduces the solubility of glycyrrhetinic acid, making it prone to precipitation. As a result, it has not been possible to form an emulsified composition that can maintain a stable dissolved state.

[0008] Thus, while there is a need for emulsion compositions containing glycyrrhetinic acid as an active ingredient to be easily spreadable, such as for use in widespread dermatitis, the commercialization of emulsion compositions containing glycyrrhetinic acid has been difficult for the reasons mentioned above. [Prior art documents] [Non-patent literature]

[0009] [Non-Patent Document 1] The 18th Revised Japanese Pharmacopoeia [Overview of the Initiative] [Problems that the invention aims to solve]

[0010] The present invention aims to provide an easily spreadable emulsified composition containing glycyrrhetinic acid that does not cause glycyrrhetinic acid precipitation. The present invention also aims to provide an easily spreadable emulsified composition containing glycyrrhetinic acid and other hydrophobic active ingredients that does not cause glycyrrhetinic acid precipitation. [Means for solving the problem]

[0011] The inventors of the present invention have found that when 1 g of the emulsified composition is suspended in 30 mL of water and the pH is set to 7.9 or higher, it is possible to prepare an emulsified composition in which glycyrrhetinic acid remains dissolved without precipitation, thereby solving the above problem.

[0012] More specifically, this application provides the following embodiments to solve the aforementioned problems: [1]: An emulsified composition containing glycyrrhetinic acid, characterized in that the pH of the emulsified composition when suspended in 30 mL of water at a concentration of 1 g is 7.9 or higher; [2]: The emulsified composition according to [1], further comprising a hydrophobic active ingredient other than glycyrrhetinic acid as an active ingredient; [3]: The emulsified composition according to [1] or [2], wherein the pH of the emulsified composition when suspended in 30 mL of water by adding diisopropanolamine, a component of the oil phase component, or by adding diisopropanolamine, a component of the oil phase component, and a hydrophobic active ingredient other than glycyrrhetinic acid, is pH 7.9 or higher; [4]: The emulsified composition according to [2] or [3], wherein the hydrophobic active ingredient other than glycyrrhetinic acid is one or more active ingredients selected from the group consisting of ufenamate, tocopherol acetate, isopropylmethylphenol, diphenhydramine, lidocaine, benzethonium chloride and l-menthol; [5]: The emulsified composition according to any one of [2] to [4], comprising ufenamate as a hydrophobic active ingredient other than glycyrrhetinic acid; [6]: The emulsified composition according to any one of [2] to [5], comprising one or more active ingredients selected from the group consisting of diphenhydramine and lidocaine as hydrophobic active ingredients other than glycyrrhetinic acid; [7]: The emulsified composition according to any one of [1] to [6], wherein the amount of glycyrrhetinic acid contained in the emulsified composition is 0.3% of the emulsified composition, and the amount of oil phase components is 22.0% or more of the emulsified composition; [8]: The emulsified composition according to any one of [1] to [7], further containing a carboxyvinyl polymer and lactic acid; [9]: An emulsion composition according to any one of [1] to [8], which is in the form of a milky liquid. [Effects of the Invention]

[0013] The emulsified composition of the present invention can be provided in which glycyrrhetinic acid as an active ingredient remains dissolved and does not precipitate, making it easy to spread. The emulsified composition of the present invention can also be provided in which glycyrrhetinic acid and other hydrophobic active ingredients remain dissolved and do not precipitate, making it easy to spread. This makes it possible to realize diversity in emulsified compositions containing glycyrrhetinic acid. [Brief explanation of the drawing]

[0014] [Figure 1] Figure 1 shows images obtained by microscopic observation of the presence or absence of precipitated glycyrrhetinic acid crystals in the emulsion compositions of each composition of Example 1 (Comparative Examples 2-4, Production Examples 1-3) the day after the emulsion compositions were prepared. [Figure 2] Figure 2 shows images obtained by observing, using a microscope, the presence or absence of precipitated glycyrrhetinic acid crystals in the emulsion compositions of various compositions from Example 2 (Comparative Examples 5-8, Production Examples 4-5) the day after the emulsion compositions were prepared. [Figure 3] Figure 3 shows images obtained by microscopic observation of the presence or absence of precipitated glycyrrhetinic acid crystals in the emulsion compositions of each composition (production examples 6-8) of Example 3, the day after the emulsion compositions were prepared. [Modes for carrying out the invention]

[0015] As a result of diligent research, the inventors of the present invention have shown that when 1 g of the emulsifying composition is suspended in 30 mL of water and the pH is set to 7.9 or higher, it is possible to prepare an emulsifying composition in which glycyrrhetinic acid remains dissolved without precipitation. In other words, the present invention can provide an emulsifying composition containing glycyrrhetinic acid, characterized in that when 1 g of the emulsifying composition is suspended in 30 mL of water and the pH is set to 7.9 or higher.

[0016] In the present invention, the term "emulsified composition" refers to a form of "lotion" classified as "external liquid preparation" among "preparations applied to the skin, etc." in the Japanese Pharmacopoeia. A "lotion" is defined as a dosage form in which an active ingredient is dissolved, emulsified, or finely dispersed in an aqueous solution. The emulsified compositions that can be provided in the present invention are classified as "emulsified lotions" (so-called emulsions, hereinafter simply referred to as "emulsions") containing oily components, and can be in a fluid, emulsion-like state. Like creams, emulsions are characterized by their good spreadability, non-greasy feel, and ability to be washed off with water, compared to ointments.

[0017] When preparing an emulsion composition in the present invention, it can be prepared by emulsifying 10% to 60% of an oil-phase component with respect to the total amount of the emulsion composition in 90% to 40% of an aqueous-phase component. The amount of the oil-phase component can be changed according to the form of the emulsion composition to be prepared. When preparing an emulsion composition with a low viscosity and a smooth feel, the proportion of the oil-phase component in the emulsion composition can be relatively reduced (for example, the proportion of the oil-phase component is set to 30% or less), and when preparing an emulsion composition with a high viscosity and a relatively greasy and heavy feel, the proportion of the oil-phase component in the emulsion composition can be relatively increased (for example, the proportion of the oil-phase component is set to 30% or more), so as to obtain the target emulsion composition.

[0018] The amount of the oil-phase component in the emulsion composition can also be changed according to the amount of glycyrrhetinic acid contained in the emulsion composition to be prepared. The more the amount of glycyrrhetinic acid contained in the emulsion composition, the more necessary it is to set a larger minimum amount of the oil-phase component. For example, · When the amount of glycyrrhetinic acid contained in the emulsion composition is 0.2%, the amount of the oil-phase component in the emulsion composition is 14.7% or more, · When the amount of glycyrrhetinic acid contained in the emulsion composition is 0.3%, the amount of the oil-phase component in the emulsion composition is 22.0% or more, · When the amount of glycyrrhetinic acid contained in the emulsion composition is 0.5%, the amount of the oil-phase component in the emulsion composition is 36.7% or more, · When the amount of glycyrrhetinic acid contained in the emulsion composition is 0.8%, the amount of the oil-phase component in the emulsion composition is 58.7% or more can be achieved.

[0019] The emulsifying composition of the present invention can be provided as an oil-in-water type emulsifying composition. All oil phase components, including glycyrrhetinic acid, which is the active ingredient of the emulsifying composition of the present invention, and other hydrophobic active ingredients, are mixed together, heated as necessary, and stirred to dissolve the active ingredients in the oil phase components. On the other hand, all components of the aqueous phase are mixed together, heated as necessary, and stirred to prepare an aqueous solution consisting of the aqueous phase components. The oil phase components are gradually added to this aqueous solution consisting of the aqueous phase components while stirring, and the mixture is emulsified to obtain the emulsifying composition. To stabilize the emulsification of the emulsifying composition, a hydrophilic thickener may be added as an aqueous phase component.

[0020] In the present invention, the glycyrrhetinic acid used as the active ingredient in the emulsified composition is a substance obtained by hydrolysis of glycyrrhizic acid derived from the herbal medicine licorice. Glycyrrhetinic acid has anti-inflammatory, anti-allergic, and bacterial growth inhibitory effects (against Staphylococcus aureus, diphtheriae, Salmonella, etc.), and is particularly effective against acute and chronic dermatitis, and is therefore used as a topical medicine to suppress inflammation and rashes.

[0021] Furthermore, glycyrrhetinic acid is widely used in cosmetics (basic skincare products, makeup products, toothpaste, etc.) because it has almost no side effects even with continuous use and is easily soluble in higher alcohols. When using glycyrrhetinic acid in cosmetics, there are limits on the amount that can be added: 0.8% for cosmetic soaps, shampoos, conditioners, and facial cleansers, and 0.2% for other cosmetics.

[0022] In the present invention, the emulsified composition may further contain other hydrophobic active ingredients in addition to glycyrrhetinic acid. Other hydrophobic active ingredients that can be used as active ingredients in the emulsified composition of the present invention may be any hydrophobic active ingredient (i.e., a non-water-soluble active ingredient) commonly used in compositions for skin application, and are not limited to any specific one. Examples of such other hydrophobic active ingredients include ufenamate, tocopherol acetate, isopropylmethylphenol, diphenhydramine, lidocaine, benzethonium chloride, and l-menthol.

[0023] In the present invention, ufenamate, which can be used as an active ingredient in the emulsified composition, is an anthranilic acid-based nonsteroidal anti-inflammatory agent that is miscible with methanol, acetone, and diethyl ether, readily soluble in ethanol, and practically insoluble in water. Ufenamate acts directly on the site of inflammation, suppressing the production of inflammatory substances and reducing inflammation and pain in the affected area.

[0024] In the present invention, tocopherol acetate, which can be used as an active ingredient in the emulsified composition, is a vitamin E agent that is miscible with ethanol (99.5%), acetone, chloroform, diethyl ether, hexane, or vegetable oil, is readily soluble in ethanol (95%), and is practically insoluble in water. Tocopherol acetate has antioxidant properties (prevents peroxidation reactions of polyunsaturated fatty acids present in biological membranes by scavenging free radicals, is involved in maintaining membrane structure and permeability, and also prevents oxidation of -SH compounds and vitamin A, etc.) and microcirculation improving properties (increases capillary resistance and skin blood flow to promote skin temperature increase and skin temperature recovery after cold exposure, and also improves circulatory dynamics through anticoagulant and fibrinolysis promoting effects).

[0025] In the present invention, isopropylmethylphenol (IPMP), which can be used as an active ingredient in the emulsified composition, is an isomer of "thymol," the main component of the volatile oil of the Lapisopteraceae family of plants, and is readily soluble in ethanol, benzene, and acetic acid, and sparingly soluble in water. Isopropylmethylphenol has broad-spectrum bactericidal properties and is effective against bacteria, yeast, and mold. For example, it is used in acne care products to suppress acne-causing bacteria, in antiperspirants to suppress the growth of odor-causing bacteria, and as a bactericidal ingredient in medicated hand soaps. When isopropylmethylphenol is used in cosmetics, there are limits on the amount that can be added. For "non-rinse cosmetics that are not used on mucous membranes" and "cosmetics that may be used on mucous membranes," the limit is 0.10g per 100g.

[0026] In the present invention, diphenhydramine, which can be used as an active ingredient in the emulsified composition, is one of the compounds belonging to the first-generation antihistamines among histamine nerve receptor (H1 receptor) antagonists. It is very soluble in methanol or acetic acid (100), readily soluble in water or ethanol (95), slightly soluble in anhydrous acetic acid, and practically insoluble in diethyl ether. Diphenhydramine is an antagonist of histamine H1 receptors and is used as a topical agent for urticaria, eczema, infantile pruritus, pruritus, and insect bites.

[0027] In the present invention, lidocaine, which can be used as an active ingredient in the emulsified composition, is a component with local anesthetic properties, is very soluble in methanol, ethanol, and chloroform, readily soluble in acetic acid or diethyl ether, and insoluble in water. Lidocaine has the effect of suppressing the action of histamine and relieving itching, pain, and hypersensitivity.

[0028] As one embodiment of the emulsifying composition of the present invention, An emulsified composition characterized by containing glycyrrhetinic acid and ufenamate as active ingredients, and having a pH of 7.9 or higher when 1 g of the emulsified composition is suspended in 30 mL of water; An emulsified composition containing glycyrrhetinic acid, diphenhydramine, and lidocaine as active ingredients, characterized in that the pH of the emulsified composition when suspended in 30 mL of water at a concentration of 1 g is 7.9 or higher; An emulsified composition containing glycyrrhetinic acid, ufenamate, diphenhydramine, and lidocaine as active ingredients, characterized in that the pH of the emulsified composition when suspended in 30 mL of water at a concentration of 1 g is 7.9 or higher; An emulsified composition containing glycyrrhetinic acid, ufenamate, tocopherol acetate, isopropylmethylphenol, diphenhydramine, and lidocaine as active ingredients, characterized in that the pH of the emulsified composition when suspended in 30 mL of water at a concentration of 1 g is 7.9 or higher; These can be provided. All of these emulsified compositions can be provided in which glycyrrhetinic acid remains dissolved without precipitation.

[0029] In the present invention, the pH of the emulsified composition is expressed as the pH measured when 1 g of the emulsified composition is suspended in 30 mL of water. The inventors of the present invention have revealed that when the pH of the emulsified composition of the present invention, as shown by this method, is 7.9 or higher, the glycyrrhetinic acid contained in the emulsified composition can remain dissolved and not precipitate out.

[0030] In the present invention, the pH of the emulsified composition can be adjusted by methods such as adding an oil phase component that has the effect of raising the pH of the emulsified composition, adding an aqueous phase component that has the effect of raising the pH of the emulsified composition, or adding an active ingredient that has the effect of raising the pH of the emulsified composition. The pH can be adjusted by any one of these methods, or by a combination of these methods.

[0031] In the present invention, the pH of the emulsified composition is determined by the following components that can be used to adjust the pH when 1 g of the emulsified composition is suspended in 30 mL of water: Diisopropanolamine can be cited as a component of the oil phase. Examples of aqueous phase components include water-soluble alkaline components such as triethanolamine and sodium hydroxide. Examples of active ingredients include diphenhydramine and lidocaine.

[0032] In the present invention, when adjusting the pH of the emulsified composition by adding an oil phase component that has the effect of raising the pH of the emulsified composition, the pH of the emulsified composition when 1 g of the emulsified composition is suspended in 30 mL of water can be adjusted to pH 7.9 or higher by adding diisopropanolamine, which is one of the oil phase components.

[0033] In the present invention, when adjusting the pH of an emulsified composition by adding an active ingredient that has the effect of raising the pH of the emulsified composition, the pH of the emulsified composition when 1 g of the emulsified composition is suspended in 30 mL of water can be adjusted to pH 7.9 or higher by adding one or more active ingredients selected from the group consisting of diphenhydramine and lidocaine as the hydrophobic active ingredient that has the effect of raising the pH.

[0034] In the emulsified composition of the present invention, additives commonly used in emulsified compositions for external use may be added. Compared to semi-solid cream formulations, low-viscosity emulsified compositions have a higher risk of separation of the oil phase and the aqueous phase; therefore, it is common practice to maintain emulsification stability by adding a polymeric thickener. In the emulsified composition of the present invention, a polymeric thickener may also be added, and a carboxyvinyl polymer can be used as such a polymeric thickener.

[0035] The emulsifying composition of the present invention may further contain lactic acid as a commonly used additive for the purpose of maintaining quality and adjusting pH.

[0036] The emulsified composition of the present invention can be provided as a fluid, milky emulsion filled into a plastic container or the like. The form of the plastic container is not particularly limited.

[0037] The present invention will be specifically illustrated below with reference to examples. The examples shown below do not limit the present invention in any way. [Examples]

[0038] Example 1: Example of preparation of an emulsified composition containing glycyrrhetinic acid and ufenamate In this example, the component composition for producing an emulsified composition containing glycyrrhetinic acid and ufenamate was investigated.

[0039] As shown in Table 1, 0.3 g of carboxyvinyl polymer (AQUPEC HV-801EG (Sumitomo Seika Co., Ltd.)) was dispersed in 5.0 g of 1,3-butylene glycol, and then purified water (the total amount indicated in the column for each composition) was added and stirred to dissolve. Subsequently, 0.2 g of lactic acid was added and stirred, and this was heated in a water bath to a liquid temperature of 70°C to 80°C.

[0040] On the other hand, the active ingredients (0.3 g of glycyrrhetinic acid and 5.0 g of ufenamate) were mixed with the oil phase components shown in Table 1, namely 2.0 g of polyoxyethylene behenyl ether (beheneth-20), 1.0 g of glyceryl monostearate, 3.0 g of cetyl palmitate, 2.0 g of cetostearyl alcohol, 2.0 g of α-olefin oligomer, 6.0 g of isopropyl myristate, and 0.0 g, 0.2 g, 0.4 g, 0.6 g, 0.7 g, 0.8 g, or 1.6 g of diisopropanolamine. The mixture was heated in a water bath to a liquid temperature of 70°C to 80°C to melt the contents, and then stirred and mixed.

[0041] The aqueous and oil phases prepared as described above were mixed while emulsifying by gradually adding the oil phase to the aqueous phase while stirring, and then cooled while stirring to obtain an emulsified composition.

[0042] <Dissolution of glycyrrhetinic acid> During heating in the oil phase preparation, the dissolution of glycyrrhetinic acid in the oil phase was visually observed. The dissolution of glycyrrhetinic acid was evaluated as follows, based on whether it dissolved or not: ○: Glycyrrhetinic acid dissolved, and a clear oil phase was obtained; ×: Glycyrrhetinic acid did not dissolve.

[0043] As a result, when diisopropanolamine was mixed into the oil phase (0.2 g, 0.4 g, 0.6 g, 0.7 g, 0.8 g, or 1.6 g), glycyrrhetinic acid dissolved in the oil phase, resulting in a clear oil phase. However, when diisopropanolamine was not mixed (0.0 g), glycyrrhetinic acid did not dissolve in the oil phase. The condition in which glycyrrhetinic acid did not dissolve in the oil phase (when diisopropanolamine was not mixed (0.0 g)) was not used as a control for subsequent studies on the properties of the emulsified composition and was therefore not evaluated.

[0044] <Presence or absence of precipitation> Next, the day after the emulsion composition was prepared, the presence or absence of precipitated glycyrrhetinic acid crystals in the emulsion composition was observed using a microscope. The images observed under the microscope are shown in Figure 1. Based on the results of the microscopic observation, the dissolution of glycyrrhetinic acid was evaluated as follows, based on whether or not it dissolved: ○: No precipitated crystals were observed; ×: Precipitated crystals were observed; -: No rating.

[0045] As a result, when 0.2 g, 0.4 g, or 0.6 g of diisopropanolamine was mixed, glycyrrhetinic acid precipitate crystals formed in the emulsion composition the day after it was prepared. However, when 0.7 g, 0.8 g, or 1.6 g of diisopropanolamine was mixed, no glycyrrhetinic acid precipitate crystals formed in the emulsion composition even the day after it was prepared.

[0046] <Liquidity> 50 g of the emulsified composition was placed in a 100 mL beaker, and the beaker was tilted on its side. The fluidity was evaluated as follows based on whether or not the emulsified composition flowed out: ○: Fluid (flows out of the beaker); ×: No fluidity (does not flow out of the beaker).

[0047] As a result, when diisopropanolamine was mixed in (0.2 g, 0.4 g, 0.6 g, 0.7 g, 0.8 g, or 1.6 g), all of the emulsified compositions had fluidity suitable for use as emulsified compositions.

[0048] <ph> One g of the emulsified composition was weighed into a 50 mL centrifuge tube, 30 mL of water was added, and the mixture was shaken by hand until no semi-solid material was visible. The pH of the resulting solution was then measured using a pH meter. The pH values ​​of each emulsified composition are summarized in Table 1.

[0049] As a result, it became clear that the pH value increased as the amount of diisopropanolamine mixed increased from 0.2 g, 0.4 g, 0.6 g, 0.7 g, 0.8 g, to 1.6 g.

[0050] [Table 1]

[0051] In summary, these results show that when the amount of diisopropanolamine mixed was 0.7 g, 0.8 g, or 1.6 g, no precipitate crystals of glycyrrhetinic acid formed in the emulsion composition even the day after preparation, and the fluidity of the emulsion composition was maintained. From these results, it became clear that when the emulsion composition contains 0.7 g or more (0.7% or more of the total emulsion composition) of diisopropanolamine, or when the pH value is 7.91 or higher, glycyrrhetinic acid precipitation does not occur in the emulsion composition, and a desirable emulsion composition can be provided.

[0052] Example 2: Example of production of an emulsified composition containing glycyrrhetinic acid In this example, the component composition for producing an emulsified composition containing glycyrrhetinic acid was investigated.

[0053] As shown in Table 2, 0.3 g of carboxyvinyl polymer (AQUPEC HV-801EG (Sumitomo Seika Co., Ltd.)) was dispersed in 5.0 g of 1,3-butylene glycol, and then purified water (the total amount indicated in the column for each composition) was added and stirred to dissolve. Subsequently, 0.2 g of lactic acid was added and stirred, and this was heated in a water bath to a liquid temperature of 70°C to 80°C.

[0054] On the other hand, the active ingredient (0.3 g of glycyrrhetinic acid) was mixed with the oil phase components shown in Table 2, namely 2.0 g of polyoxyethylene behenyl ether (beheneth-20), 1.0 g of glyceryl monostearate, 3.0 g of cetyl palmitate, 2.0 g of cetostearyl alcohol, 2.0 g or 7.0 g of α-olefin oligomer, 6.0 g or 11.0 g of isopropyl myristate, and 0.7 g or 0.8 g of diisopropanolamine. The mixture was heated in a water bath to a liquid temperature of 70°C to 80°C to melt the contents, and then stirred and mixed.

[0055] The aqueous and oil phases prepared as described above were mixed while emulsifying by gradually adding the oil phase to the aqueous phase while stirring, and then cooled while stirring to obtain an emulsified composition.

[0056] <Dissolution of glycyrrhetinic acid> During heating in the oil phase preparation, the dissolution of glycyrrhetinic acid in the oil phase was visually observed. The dissolution of glycyrrhetinic acid was evaluated as follows, based on whether it dissolved or not: ○: Glycyrrhetinic acid dissolved, and a clear oil phase was obtained; ×: Glycyrrhetinic acid did not dissolve; △: Glycyrrhetinic acid dissolved, but immediately afterward the solution became cloudy.

[0057] As a result, when diisopropanolamine was mixed into the oil phase (0.7 g or 0.8 g), glycyrrhetinic acid dissolved in the oil phase and a clear oil phase was obtained. However, in Comparative Example 7, where the amount of oil phase components was adjusted by increasing the amount of α-olefin oligomer, glycyrrhetinic acid dissolved, but immediately afterward the solution became cloudy.

[0058] <Presence or absence of precipitation> Next, the day after the emulsion composition was prepared, the presence or absence of precipitated glycyrrhetinic acid crystals in the emulsion composition was observed using a microscope. The images observed under the microscope are shown in Figure 2. Based on the results of the microscopic observation, the dissolution of glycyrrhetinic acid was evaluated as follows, based on whether or not it dissolved: ○: No precipitated crystals were observed; ×: Precipitated crystals were observed; -: No rating.

[0059] As a result, in Comparative Examples 5 and 8, where the amount of oil phase components was approximately 17% of the amount of emulsion composition, mixing 0.7 g or 0.8 g of diisopropanolamine was insufficient to prevent the precipitation of glycyrrhetinic acid, which was present in the oil phase component of 0.3 g. The day after the emulsion composition was prepared, precipitated crystals of glycyrrhetinic acid formed in the emulsion composition.

[0060] On the other hand, when the amount of oil phase components was 22% or more of the amount of the emulsified composition (Comparative Example 6, Comparative Example 7, Production Example 4, Production Example 5), and the pH value was below 7.91 (in this example, when 0.7 g of diisopropanolamine was mixed) (Comparative Example 6, Comparative Example 7), precipitated crystals of glycyrrhetinic acid formed in the emulsified composition the day after the emulsified composition was prepared. However, when the pH value was 7.91 or higher (in this example, when 0.8 g of diisopropanolamine was mixed) (Production Example 4, Production Example 5), precipitated crystals of glycyrrhetinic acid did not form in the emulsified composition even the day after the emulsified composition was prepared.

[0061] <Liquidity> 50 g of the emulsified composition was placed in a 100 mL beaker, and the beaker was tilted on its side. The fluidity was evaluated as follows based on whether or not the emulsified composition flowed out: ○: Fluid (flows out of the beaker); ×: No fluidity (does not flow out of the beaker).

[0062] As a result, when diisopropanolamine was added (0.7 g or 0.8 g), both emulsion compositions exhibited fluidity suitable for use as an emulsion.

[0063] <ph> One g of the emulsified composition was weighed into a 50 mL centrifuge tube, 30 mL of water was added, and the mixture was shaken by hand until no semi-solid material was visible. The pH of the resulting solution was then measured using a pH meter. The pH values ​​of each emulsified composition are summarized in Table 2.

[0064] [Table 2]

[0065] In summary, these results show that when the amount of oil phase components was approximately 17% of the amount of the emulsified composition, it was insufficient to prevent the precipitation of 0.3 g of glycyrrhetinic acid. On the other hand, when the amount of oil phase components was sufficient at 22% or more of the amount of the emulsified composition, and the pH value was 7.91 or higher (in this example, when 0.8 g of diisopropanolamine was mixed), no precipitated crystals of glycyrrhetinic acid formed in the emulsified composition even the day after preparation, and the fluidity of the emulsified composition was maintained. From these results, it became clear that in order to include glycyrrhetinic acid in an emulsified composition without precipitation, the emulsified composition must contain an amount of oil phase components commensurate with the concentration of glycyrrhetinic acid, and that when the pH value is 7.91 or higher, glycyrrhetinic acid precipitation in the emulsified composition does not occur, and a desirable emulsified composition can be provided.

[0066] Example 3: Production example of an emulsified composition containing glycyrrhetinic acid and ufenamate, as well as other active ingredients. In this example, we investigated the component composition for producing a chemical composition containing glycyrrhetinic acid and ufenamate, as well as other active ingredients.

[0067] As shown in Table 3, 0.3 g of carboxyvinyl polymer (AQUPEC HV-801EG (Sumitomo Seika Co., Ltd.)) was dispersed in 5.0 g of 1,3-butylene glycol, and then purified water (the total amount indicated in the column for each composition) was added and stirred to dissolve. Subsequently, 0.2 g of lactic acid was added and stirred, and this was heated in a water bath to a liquid temperature of 70°C to 80°C.

[0068] On the other hand, the active ingredients (glycyrrhetinic acid, ufenamate, tocopherol acetate, isopropylmethylphenol, diphenhydramine, and lidocaine in the amounts specified for each composition in Table 3) were mixed with the oil phase components shown in Table 3, namely 2.0 g of polyoxyethylene behenyl ether (beheneth-20), 1.0 g of glyceryl monostearate, 3.0 g of cetyl palmitate, 2.0 g of cetostearyl alcohol, 2.0 g of α-olefin oligomer, 6.0 g of isopropyl myristate, and 0.4 g or 0.8 g of diisopropanolamine. The mixture was heated in a water bath to a liquid temperature of 70°C to 80°C to melt the contents, and then stirred and mixed.

[0069] The aqueous and oil phases prepared as described above were mixed while emulsifying by gradually adding the oil phase to the aqueous phase while stirring, and then cooled while stirring to obtain an emulsified composition.

[0070] <Dissolution of glycyrrhetinic acid> During heating in the oil phase preparation, the dissolution of glycyrrhetinic acid in the oil phase was visually observed. The dissolution of glycyrrhetinic acid was evaluated as follows, based on whether it dissolved or not: ○: Glycyrrhetinic acid dissolved, and a clear oil phase was obtained; ×: Glycyrrhetinic acid did not dissolve.

[0071] As a result, in all compositions of this example in which diisopropanolamine was mixed with the oil phase, glycyrrhetinic acid dissolved in the oil phase, and a clear oil phase was obtained.

[0072] <Presence or absence of precipitation> Next, the day after the emulsion composition was prepared, the presence or absence of precipitated glycyrrhetinic acid crystals in the emulsion composition was observed using a microscope. The images observed under the microscope are shown in Figure 2. Based on the results of the microscopic observation, the dissolution of glycyrrhetinic acid was evaluated as follows, based on whether or not it dissolved: ○: No precipitated crystals were observed; ×: Precipitated crystals were observed; -: No rating.

[0073] As a result, in all of the compositions in this example in which diisopropanolamine was mixed with the oil phase, no precipitated crystals of glycyrrhetinic acid were formed in the emulsion composition even the day after the emulsion composition was prepared.

[0074] <Liquidity> 50 g of the emulsified composition was placed in a 100 mL beaker, and the beaker was tilted on its side. The fluidity was evaluated as follows based on whether or not the emulsified composition flowed out: ○: Fluid (flows out of the beaker); ×: No fluidity (does not flow out of the beaker).

[0075] As a result, all of the emulsified compositions in this example, in which diisopropanolamine was mixed with the oil phase, had fluidity suitable for use as an emulsified composition.

[0076] <ph> One g of the emulsified composition was weighed into a 50 mL centrifuge tube, 30 mL of water was added, and the mixture was shaken by hand until no semi-solid material was visible. The pH of the resulting solution was then measured using a pH meter. The pH values ​​of each emulsified composition are summarized in Table 3.

[0077] As a result, it was found that the pH was 8 or higher in all compositions of this example, regardless of the amount of diisopropanolamine mixed into the oil phase.

[0078] [Table 3]

[0079] In summary, these results indicate that in Production Examples 7 and 8, even when the amount of diisopropanolamine mixed was 0.4 g, which was lower than the boundary value of 0.8 g (Production Example 1), no precipitate crystals of glycyrrhetinic acid formed in the emulsion composition the day after preparation, and the fluidity of the emulsion composition was maintained.

[0080] These results revealed that the amount (percentage) of diisopropanolamine added is not the only decisive factor. On the other hand, it was found that when the pH value is 7.91 or higher with the addition of various components including diisopropanolamine, glycyrrhetinic acid precipitation does not occur in the emulsified composition, and a desirable emulsified composition can be provided. [Industrial applicability]

[0081] The emulsified composition of the present invention can be provided in which glycyrrhetinic acid as an active ingredient remains dissolved and does not precipitate, making it easy to spread. The emulsified composition of the present invention can also be provided in which glycyrrhetinic acid and other hydrophobic active ingredients remain dissolved and do not precipitate, making it easy to spread. This makes it possible to realize diversity in emulsified compositions containing glycyrrhetinic acid.< / ph> < / ph> < / ph>

Claims

1. An emulsified composition containing glycyrrhetinic acid, characterized in that diisopropanolamine, a component of the oil phase, is added, and the pH of the emulsified composition when suspended in 30 mL of water at a concentration of 1 g is set to pH 7.9 or higher.

2. The emulsified composition according to claim 1, further comprising a hydrophobic active ingredient other than glycyrrhetinic acid as an active ingredient.

3. The emulsified composition according to claim 2, wherein the hydrophobic active ingredient other than glycyrrhetinic acid consists of one or more active ingredients selected from the group consisting of ufenamate, tocopherol acetate, isopropylmethylphenol, diphenhydramine, lidocaine, benzethonium chloride, and l-menthol.

4. The emulsified composition according to claim 2 or 3, comprising ufenamate as a hydrophobic active ingredient other than glycyrrhetinic acid.

5. The emulsified composition according to any one of claims 2 to 4, comprising one or more active ingredients selected from the group consisting of diphenhydramine and lidocaine as hydrophobic active ingredients other than glycyrrhetinic acid.

6. The emulsified composition according to any one of claims 1 to 5, wherein when the amount of glycyrrhetinic acid contained in the emulsified composition is 0.3% of the emulsified composition, the amount of oil phase components is 22.0% or more of the emulsified composition.

7. The emulsifying composition according to any one of claims 1 to 6, further containing a carboxyvinyl polymer and lactic acid.

8. An emulsion composition according to any one of claims 1 to 7, which is in the form of a milky liquid.

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