JP2023090338A - emulsion composition - Google Patents

Abstract

To provide a pharmaceutical formulation containing prednisolones and lidocaine which improves the solubility of an oil phase during preparation and suppresses foam entrapment.SOLUTION: There is provided an emulsion composition comprising prednisolones and lidocaine in which the solubility of an oil phase during preparation is improved and foaming is suppressed by blending tocopherols, menthol and allantoin.SELECTED DRAWING: None

Description

TECHNICAL FIELD The present invention relates to an emulsified composition containing prednisolones and lidocaine and having excellent dispensability.

External preparations containing prednisolone or its derivatives are known as preparations intended for treating skin diseases accompanied by skin pain, itching, hot flashes, and the like. Prednisolone and its derivatives, such as prednisolone valerate acetate, are known as external corticosteroids, and are used in combination with external creams for the purpose of antipruritic and eczema treatment.

Lidocaine and its salts are the most widely used local anesthetics in the world, and are well-known drugs that are used for various sites because of their fast onset of action. For the purpose of local anesthesia, creams and tapes containing lidocaine and its salts are known.

External preparations containing such prednisolone and its derivatives and lidocaine are known. For example, Patent Document 1 discloses an external preparation containing a basic local anesthetic such as prednisolone acetate valerate and lidocaine. External preparations containing prednisolone or a derivative thereof and lidocaine are formulated as emulsifying creams and the like, and Patent Document 2 discloses that diphenhydramine is blended to improve the feeling of use of such emulsifying creams to achieve a predetermined range of light transmission. Formulations are disclosed that are prepared to have a rate of increase in modulus.

JP-A-2001-72603 JP 2018-108992 A

So far, formulations of emulsified compositions containing prednisolones and lidocaine have been studied, but sufficient studies have not been made on improving the solubility of the components during preparation and suppressing air bubbles. In particular, prednisolones themselves have poor solubility in oily bases, which affects formulation efficiency. In addition, air bubbles generated during emulsification when the emulsified composition contains a surfactant (hereinafter also referred to as "foam bubbles") not only reduce the dispensing efficiency, but also allow the emulsified composition to come into contact with air. Since it increases the surface area, it also affects the quality of the emulsified composition.

Accordingly, an object of the present invention is to provide a pharmaceutical formulation that contains prednisolones and lidocaine, has improved solubility in the oil phase during preparation, and suppresses foaming.

As a result of intensive studies in order to solve the above-mentioned problems, the present inventors found that by blending tocopherols, menthol, and allantoin in an emulsified composition containing prednisolones and lidocaine, the solubility of the oil phase at the time of preparation was found to be improved and foam entrapment was suppressed. The present invention has been completed through further studies based on these findings.

That is, the present invention provides inventions in the following aspects.
Section 1. (A) prednisolone and/or a pharmaceutically acceptable derivative thereof, (B) lidocaine, (C) tocopherol and/or a pharmaceutically acceptable derivative thereof, (D) menthol, and (E) allantoin and an emulsified composition.
Section 2. Item 1. The emulsified composition according to Item 1, further comprising (F) a higher alcohol.
Item 3. Item 3. The emulsion composition according to item 1 or 2, wherein the content of component (C) is 3 to 20 parts by weight per 1 part by weight of component (A).
Section 4. Item 4. The emulsion composition according to any one of Items 1 to 3, wherein the content of component (D) is 1 to 30 parts by weight per 1 part by weight of component (A).
Item 5. Item 5. The emulsion composition according to any one of Items 1 to 4, wherein the content of the component (E) is 0.05 to 2% by weight.
Item 6. Item 6. The emulsion composition according to any one of Items 1 to 5, wherein the content of component (E) is 0.007 to 0.3 parts by weight per 1 part by weight of the surfactant.
Item 7. Item 7. The emulsion composition according to any one of items 2 to 6, wherein the content of component (E) is 0.005 to 0.05 parts by weight per 1 part by weight of component (F).
Item 8. Item 8. The emulsion composition according to any one of Items 1 to 7, which does not contain crotamiton.
Item 9. Item 9. The emulsion composition according to any one of Items 1 to 8, which is a cream.

INDUSTRIAL APPLICABILITY According to the present invention, there is provided a pharmaceutical formulation that contains prednisolones and lidocaine, improves the solubility of the oil phase during preparation, and suppresses foaming.

The emulsified composition of the present invention comprises (A) prednisolone and/or a pharmaceutically acceptable derivative thereof (hereinafter also referred to as "component (A)" or "prednisolones") and (B) lidocaine ( Hereinafter, also referred to as "component (B)"), and (C) tocopherol and/or a pharmaceutically acceptable derivative thereof (hereinafter also referred to as "component (C)" or "tocopherols". ), (D) menthol (hereinafter also referred to as “(D) component”), and (E) allantoin (hereinafter also referred to as “(E) component”). and In addition, the emulsified composition of the present invention can further contain (F) a higher alcohol (hereinafter also referred to as "component (F)"). The emulsified composition of the present invention is described in detail below.

(A) Prednisolones The emulsified composition of the present invention contains prednisolone and/or a pharmaceutically acceptable derivative thereof as component (A).

Prednisolone is a known drug as a fat-soluble topical corticosteroid. Derivatives of prednisolone are not particularly limited as long as they are fat-soluble and pharmaceutically acceptable. or esters with dicarboxylic acids (2-7 carbon atoms); methylprednisolone; are mentioned.

In the emulsified composition of the present invention, as the component (A), one compound may be selected from prednisolone and/or derivatives thereof and used alone, or two or more compounds may be used in combination. may be used.

Among the components (A) in the emulsified composition of the present invention, prednisolone derivatives are preferred, and esters of prednisolone and mono- or dicarboxylic acids (having 2 to 7 carbon atoms) are more preferred. includes esters of prednisolone and mono- or dicarboxylic acids (having 2 to 7 carbon atoms), particularly preferably prednisolone valerate acetate.

The content of component (A) in the emulsified composition of the present invention is not particularly limited, and may be appropriately set depending on the efficacy to be exhibited, for example 0.01 to 5% by weight, preferably 0.05. ~1 wt%, more preferably 0.1 to 0.3 wt%.

(B) Lidocaine The emulsified composition of the present invention contains lidocaine as component (B). Lidocaine is known to have local anesthetic effects and is a known fat-soluble drug, also called xylocaine.

The content of component (B) in the emulsified composition of the present invention may be appropriately set according to the efficacy to be exhibited, and is, for example, 0.2 to 5% by weight, preferably 1 to 3% by weight. be done.

In the emulsified composition of the present invention, the content ratio of components (A) and (B) is determined according to the above content of each component. , preferably 5 to 20 parts by weight, more preferably 10 to 20 parts by weight.

(C) Tocopherols The emulsified composition of the present invention contains tocopherol and/or a pharmaceutically acceptable derivative thereof as component (C). Component (C) improves the solubility of the oil phase at the time of formulation by blending with other components in the emulsified composition of the present invention.

Tocopherol, also known as vitamin E, is a well-known ingredient. The tocopherol used in the present invention may be either d-form or dl-form, and may have any of α, β, γ, and δ structures.

Derivatives of tocopherol are not particularly limited as long as they are pharmaceutically acceptable, and examples thereof include esters of tocopherol and organic acids. Specific examples of esters of tocopherol and organic acids include tocopherol acetate, tocopherol nicotinate, tocopherol succinate, and tocopherol linolenate.

In the emulsified composition of the present invention, one of tocopherols and/or derivatives thereof may be selected and used, or two or more thereof may be used in combination.

In the emulsified composition of the present invention, the (C) component is preferably a tocopherol derivative, more preferably a tocopherol acetate.

The content of component (C) in the emulsified composition of the present invention is not particularly limited, and may be appropriately set according to the effect of improving the solubility of the oil phase at the time of preparation to be imparted. 2.5% by weight. From the viewpoint of further improving the solubility of the oil phase during preparation, the content of component (C) in the emulsified composition of the present invention is preferably 1 to 2.5% by weight, more preferably 1.8 to 1.8% by weight. 2.5% by weight.

In the emulsified composition of the present invention, the content ratio of components (A) and (C) is determined according to the above-mentioned content of each component, but the content of component (C) with respect to 1 part by weight of component (A) As, for example, 3 to 20 parts by weight, preferably 6 to 20 parts by weight, more preferably 10 to 20 parts by weight, still more preferably 13 to 20 parts by weight, from the viewpoint of further improving the solubility of the oil phase during preparation 20 parts by weight or 13 to 15 parts by weight.

(D) Menthol The emulsified composition of the present invention contains menthol as component (D). Component (D) is blended with other components in the emulsified composition of the present invention to improve the solubility of the oil phase at the time of preparation, and in some cases, in addition to improving the solubility at the time of preparation, foaming suppress

Menthol may be any of d-, l-, and dl-forms, preferably l-form. Moreover, you may use the essential oil containing menthol as menthol.

The content of component (D) in the emulsified composition of the present invention is not particularly limited, and is appropriately set according to the effect of improving the solubility of the oil phase during preparation to be imparted, or the effect and the effect of suppressing foam formation. For example, 0.1 to 5% by weight can be mentioned. From the viewpoint of further improving the solubility of the oil phase during preparation, or from the viewpoint of further suppressing foam formation in addition to the above viewpoint, the content of the component (D) in the emulsified composition of the present invention is preferably 0.5 to 5% by weight, more preferably 2 to 5% by weight, still more preferably 3 to 5% by weight or 3 to 4% by weight.

In the emulsified composition of the present invention, the content ratio of components (A) and (D) is determined according to the above content of each component. As, for example, 1 to 30 parts by weight, preferably 3 to 30 parts by weight from the viewpoint of further improving the solubility of the oil phase at the time of dispensing, or from the viewpoint of further suppressing foaming in addition to this viewpoint. , more preferably 10 to 30 parts by weight, more preferably 20 to 30 parts by weight or 20 to 25 parts by weight. In addition, content of the (D) component shown here is the value converted into the amount of menthol, when using the essential oil containing menthol as (D) component.

(E) Allantoin The emulsified composition of the present invention contains allantoin as component (E). Component (E) is incorporated in the emulsified composition of the present invention together with other components to suppress foam build-up during formulation. Improves solubility.

Allantoin, also called 5-ureidohydantoin, is a water-soluble compound, and is a known drug known to have anti-inflammatory, cell-activating, hemostatic, bactericidal, and anti-ulcer effects.

The content of the component (E) in the emulsified composition of the present invention is not particularly limited, and is appropriately set according to the effect of suppressing foam formation during preparation to be imparted, or the effect and the effect of improving the solubility of the oil phase. For example, 0.05 to 2% by weight can be mentioned. From the viewpoint of further improving the foam tightness at the time of dispensing, or from the viewpoint of further improving the solubility of the oil phase in addition to this viewpoint, the content of the component (E) in the emulsified composition of the present invention is preferably 0.1 to 2 wt%, more preferably 0.14 to 2 wt%, more preferably 0.19 to 2 wt%, 0.19 to 1 wt%, 0.19 to 0.3 wt%, or 0 .19 to 0.25% by weight.

In the emulsified composition of the present invention, the content ratio of the surfactant and the component (E) is determined according to the content of each component. 0.007 to 0.3 parts by weight, preferably 0.01 to 0.01 from the viewpoint of further improving the foaming at the time of dispensing, or from the viewpoint of further improving the solubility of the oil phase in addition to this viewpoint 0.3 parts by weight, more preferably 0.02 to 0.3 parts by weight, more preferably 0.025 to 0.1 parts by weight or 0.025 to 0.03 parts by weight.

When the emulsion composition of the present invention contains component (F), the content ratio of component (F) and component (E) is determined according to the content of each component, but relative to 1 part by weight of component (F) ( The content of component E) is, for example, 0.005 to 0.05 parts by weight. From the viewpoint of further improving foaming during dispensing, it is preferably 0.01 to 0.05 parts by weight, more preferably 0.02 to 0.05 parts by weight, still more preferably 0.025 to 0.05 parts by weight. parts, 0.025 to 0.04 parts by weight, or 0.025 to 0.03 parts by weight.

(F) Higher Alcohol The emulsified composition of the present invention may contain a higher alcohol as the component (F). Component (F) further improves the solubility of the oil phase during formulation when blended with other components in the emulsified composition of the present invention. In addition, when a higher alcohol is added to an emulsified composition, foaming tends to occur. It is possible to effectively suppress foam entrapment.

The higher alcohol used in the present invention may be any pharmaceutically or cosmetically acceptable monohydric alcohol having 6 or more carbon atoms, such as monohydric alcohol having 10 to 24 carbon atoms (eg, caprin alcohol, lauryl alcohol, myristyl alcohol, cetanol, stearyl alcohol, oleyl alcohol, linoleyl alcohol, arachidyl alcohol, behenyl alcohol, linoglyceryl alcohol, etc.), preferably monohydric alcohols having 14 to 22 carbon atoms, more preferably 16 carbon atoms -18 monohydric alcohols. Further, the carbon chain of the higher alcohol used in the present invention may be either linear or branched, preferably linear. The carbon chain of the higher alcohol used in the present invention may be either saturated or unsaturated, preferably saturated.

In the emulsified composition of the present invention, the component (F) preferably includes saturated linear higher alcohols having 10 to 24 carbon atoms, preferably 14 to 22 carbon atoms, more preferably cetanol, stearyl alcohol, and behenyl alcohol. and particularly preferably a mixture of cetanol and stearyl alcohol (cetostearyl alcohol).

When the emulsified composition of the present invention contains component (F), the content of component (F) is not particularly limited, and may be appropriately set according to the effect of improving the solubility of the oil phase during preparation to be imparted. is, for example, 1 to 10% by weight. From the viewpoint of further improving the solubility of the oil phase during formulation, the content of component (F) in the emulsified composition of the present invention is preferably 3 to 10% by weight, more preferably 5 to 10% by weight, More preferably 6 to 10% by weight, 6 to 9% by weight, or 6 to 8% by weight.

When the emulsified composition of the present invention contains component (F), the content ratio of component (A) and component (F) is determined according to the above content of each component, but component (A) is 1 part by weight. For example, the content of component (F) is 10 to 70 parts by weight, and from the viewpoint of further improving the solubility of the oil phase during preparation, preferably 30 to 70 parts by weight, more preferably 40 to 70 parts by weight. parts by weight, more preferably 45 to 60 parts by weight or 45 to 50 parts by weight.

Oily Base The emulsified composition of the present invention contains an oil phase base component. The oleaginous base is not particularly limited as long as it is pharmaceutically or cosmetically acceptable. Rapeseed oil, sunflower oil, cottonseed oil, peanut oil, lard, squalane, fish oil, etc.), mineral oil (liquid paraffin, paraffin, gelling hydrocarbon, vaseline, etc.), waxes or waxes (beeswax, carnauba wax, candelilla wax, ceresin , rice wax, microcrystalline wax, etc.), ester oil (cetyl isooctanoate, isopropyl myristate, isopropyl adipate, diethyl sebacate, isopropyl sebacate, isopropyl palmitate, cetyl palmitate, ethyl oleate, etc.), fatty acid alkyl ester , higher fatty acids (stearic acid, oleic acid, palmitic acid, behenic acid, linoleic acid, lanolin, etc.), higher fatty acid esters (cetyl palmitate, isopropyl palmitate, ethyl linoleate, etc.), higher alcohols (stearyl alcohol, cetanol, behenyl alcohol) , myristyl alcohol, oleyl alcohol, hexadecyl alcohol, lanolin alcohol, etc.), cholesterol, glyceryl tri-2-ethylhexanoate, cetyl 2-ethylhexanoate, silicone oil (dimethylpolysiloxane, cyclic silicone, etc.).

These oils may be used singly or in combination of two or more.

Among these oleaginous bases, mineral oils are preferred, and liquid paraffin and petrolatum are more preferred.

The content (total amount) of the oily base in the emulsified composition of the present invention is, for example, 1 to 20% by weight, preferably 5 to 15% by weight, more preferably 8 to 12% by weight.

Water The emulsified composition of the present invention contains water as a base component of the aqueous phase. The content of water in the emulsified composition of the present invention is also not particularly limited, but is, for example, 55 to 85% by weight, preferably 60 to 80% by weight, more preferably 65 to 75% by weight, still more preferably 65 to 70% by weight. %.

Surfactant The emulsion composition of the present invention contains a surfactant for emulsifying the oil phase and the water phase. Surfactants are not particularly limited as long as they are pharmaceutically or cosmetically acceptable. Examples include nonionic surfactants, anionic surfactants, cationic surfactants, and amphoteric surfactants. etc. Among these other surfactants, nonionic surfactants are exemplified from the viewpoint of improving emulsion stability.

Specific examples of nonionic surfactants include polyoxyethylene hydrogenated castor oil; sorbitan fatty acid esters (e.g., sorbitan monooleate, sorbitan monoisostearate, sorbitan monolaurate, sorbitan monopalmitate, sorbitan mono Stearate (sorbitan monostearate), sorbitan sesquioleate, sorbitan trioleate, diglycerol sorbitan penta-2-ethylhexylate, diglycerol sorbitan tetra-2-ethylhexylate, etc.); glycerin fatty acid esters (for example, monocottonseed fatty acid) glyceryl, glyceryl monoerucate, glyceryl sesquioleate, glyceryl monostearate (glyceryl stearate), α,α'-pyroglutamate glyceryl oleate, glyceryl monostearate malic acid, etc.); propylene glycol fatty acid esters (e.g., mono propylene glycol stearate, etc.); glycerin alkyl ether; steareth-2; ; polyoxyethylene sorbitol fatty acid esters (e.g., polyoxyethylene sorbitol monolaurate, polyoxyethylene sorbitol monooleate, polyoxyethylene sorbitol pentaoleate, polyoxyethylene sorbitol monostearate, etc.); polyoxyethylene glycerin fatty acid esters (e.g., polyoxyethylene glycerin monostearate, polyoxyethylene glycerin monoisostearate, polyoxyethylene glycerin triisostearate, etc.); polyoxyethylene fatty acid esters (e.g., polyoxyethylene monooleate, poly oxyethylene monostearate (polyoxyl stearate), polyoxyethylene distearate, polyoxyethylene monodioleate, ethylene glycol distearate, etc.); polyoxyethylene alkyl or aralkyl ethers (e.g., polyoxyethylene lauryl ether, polyoxyethylene oleyl ether, polyoxyethylene stearyl ether, polyoxyethylene cetyl ether, polyoxyethylene behenyl ether, polyoxyethylene 2-octyldodecyl ether, polyoxyethylene aralkyl ether, polyoxyethylene cholestanol ether, etc.) and these Phosphoric acid or phosphate (polyoxyethylene cetyl ether sodium phosphate, etc.); Pluronic (registered trademark) types (e.g., Pluronic (registered trademark), etc.); Oxyethylene/polyoxypropylene-cetyl ether, Polyoxyethylene/polyoxypropylene-2-decyltetradecyl ether, Polyoxyethylene/polyoxypropylene monobutyl ether, Polyoxyethylene/polyoxypropylene hydrogenated lanolin, Polyoxyethylene/ polyoxypropylene glycerin ether, etc.);

These surfactants may be used singly or in combination of two or more.

Among these nonionic surfactants, from the viewpoint of further improving emulsion stability,
Polyoxyethylene hydrogenated castor oil and sorbitan fatty acid esters (preferably sorbitan monostearate (sorbitan monostearate)) can be mentioned.

The content of the surfactant in the emulsified composition of the present invention may be appropriately set according to the type of the surfactant to be used. 6 to 8% by weight is more preferable.

Other Ingredients The emulsified composition of the present invention may optionally contain other commonly used additives in addition to the aforementioned ingredients. Such additives include, for example, polyhydric alcohols, thickeners, pH adjusters, buffers, solubilizers, chelating agents, preservatives, preservatives, antioxidants, stabilizers, perfumes, colorants. etc.

Examples of thickeners include cellulose-based thickeners (eg, carmellose sodium, hydropropylcellulose, hydroxyethylmethylcellulose, methylcellulose, carboxymethylcellulose, etc.), xanthan gum, carboxyvinyl polymer, and the like. These thickeners may be used singly or in combination of two or more. Among these thickeners, cellulose-based thickeners are preferred, and carmellose sodium is more preferred. When the emulsified composition of the present invention contains a thickening agent, the content of the thickening agent is not particularly limited. 8 to 1.2% by weight.

Furthermore, the emulsified composition of the present invention may contain, if necessary, a medicinal component capable of exhibiting a physiological function in terms of medicine or cosmetics, in addition to the components described above. Examples of such medicinal ingredients include steroids, antihistamines, local anesthetics, anti-inflammatory agents, bactericidal agents, antipruritic agents, moisturizers, blood circulation-promoting ingredients, vitamins, mucopolysaccharides, and the like. These medicinal ingredients may be used singly or in combination of two or more. When these medicinal ingredients are contained in the emulsified composition of the present invention, the content may be appropriately set according to the type of medicinal ingredient to be used, the expected effect, and the like.

Among the above-mentioned active ingredients, crotamiton is known as an antipruritic agent, and emulsified compositions containing crotamiton generally have particularly excellent solubility in the oil phase at the time of preparation. The solubility of the oil phase of is markedly reduced. On the other hand, since the emulsified composition of the present invention has excellent solubility in the oil phase at the time of preparation, it is possible to effectively improve the solubility of the oil phase at the time of preparation without containing crotamiton. From this point of view, the preferred embodiment of the present invention does not contain crotamiton.

Form of formulation The emulsified state of the emulsified composition of the present invention may be either oil-in-water type or water-in-oil type. Since the emulsified composition of the present invention has excellent solubility in the oil phase at the time of preparation, it is possible to effectively improve the solubility of the oil phase even in the case of an oil-in-water composition that inherently contains a small amount of oily base. From such a point of view, the preferred emulsified state of the emulsified composition of the present invention is an oil-in-water type.

The formulation form of the emulsified composition of the present invention is not particularly limited, and examples thereof include emulsions, creams, creams, lotions and the like. Since the emulsified composition of the present invention is excellent in the effect of suppressing foam formation during preparation, it is particularly useful for creams that are highly viscous and difficult to defoam when foam is generated. From this point of view, the formulation form of the emulsified composition of the present invention is preferably a cream.

Specific examples of the emulsified composition of the present invention include pharmaceuticals, quasi-drugs, cosmetics and the like. Among these dosage forms, pharmaceuticals and quasi-drugs are preferred.

The emulsified composition of the present invention is preferably an external preparation, more preferably an external preparation for skin.

Manufacturing Method The emulsified composition of the present invention can be manufactured according to a known emulsified composition manufacturing method. Examples of the method for producing the emulsified composition of the present invention include the method shown below. First, components (A), (B), (C), (D), an oleaginous base, and optionally added (F) and other lipophilic components are mixed to obtain an oil. A phase composition is prepared. Separately, the component (E), water, and other water-soluble components added as necessary are mixed to prepare a composition for an aqueous phase. The surfactant may be added to and mixed with either or both of the oil phase composition and the aqueous phase composition, but is preferably added to the oil phase composition. Next, the obtained oil phase composition and aqueous phase composition are mixed and emulsified by an emulsification technique such as a homomixer to produce the emulsified composition of the present invention.

EXAMPLES The present invention will be described in more detail below with reference to Examples, but the present invention is not limited to these Examples.

Creamy oil-in-water emulsified compositions having compositions shown in Test Examples Tables 3 and 4 were produced. Specifically, among the components shown in Tables 3 and 4, predetermined amounts of the oil phase component and the surfactant were weighed, heated to 80° C. and mixed to prepare an oil phase composition. The prepared oil phase was subjected to evaluation of <1> below. Separately, a predetermined amount of an aqueous phase component was weighed out to prepare an aqueous phase composition. After heating the composition for the aqueous phase to 60°C, the composition for the oil phase at 80°C was added little by little, and the mixture was stirred and mixed at 200 rpm. did The obtained emulsified composition was subjected to evaluation of <2> below.

<1> Solubility evaluation of oil phase at the time of preparation Based on the following criteria, 8-grade evaluation was performed according to the degree of solubility of the oil phase. A score of 4 or more indicates that the desired effect of improving solubility was obtained. Table 1 shows the specific appearance of the oil phase corresponding to points 8 and 1. Tables 3 and 4 show the results.
8 points: Uniform solution with no undissolved white grains.
4 points: Uniform solution with only a few undissolved white grains.
1 point: Many white undissolved raw materials remain in the solution.

<2> Evaluation of suppression of bubble formation at the time of dispensing 0.5 g of the obtained emulsified composition was inserted with two slide glasses, and evaluated in 6 grades according to the degree of bubble formation based on the following criteria. did With a score of 3 or more, it can be evaluated that the desired effect of suppressing bubble entrapment was obtained. Table 2 shows specific appearances of the emulsified compositions corresponding to 6 points and 1 point. Tables 3 and 4 show the results.
6 points: Almost no large bubbles are observed in the cream.
3 points: Only a few large bubbles are observed in the cream.
1 point: Numerous large bubbles were generated in the cream.

As shown in Comparative Example 1, many undissolved raw materials remained in the oil phase composition containing the components (A) and (B), and many bubbles were observed even after emulsification. As shown in Comparative Example 2 in comparison with Comparative Example 1, even if the component (C) was further added, the oil phase solubility was only slightly improved, but was not sufficient. As shown in Comparative Example 3 in contrast to Comparative Example 2, even if component (D) was further added, the oil phase solubility was improved, but a large number of foams were still observed after emulsification. As shown in Comparative Example 4 in contrast to Comparative Example 2, when the component (E) was further added, foam formation after emulsification was improved, but oil phase solubility was not improved. As shown in Comparative Example 5 in contrast to Comparative Example 2, when the component (F) was further added, the oil phase solubility was improved, but the foaminess after emulsification was significantly worsened.

As shown in Example 1 in contrast to Comparative Example 3, by further adding component (E) to components (A) to (D), both oil phase solubility and foam retention are improved. The improvement effect of foaming was remarkable. Furthermore, as shown in Example 3 in contrast to Example 1, when the amount of component (E) was increased, the effect of improving foam build-up was significantly improved. A similar tendency was also observed in other examples.

As shown in Example 1 in contrast to Comparative Example 4, by further adding component (D) to components (A) to (C) and component (E), both oil phase solubility and foam retention were improved. In particular, the effect of improving oil phase solubility was remarkable. Further, as shown in Example 6 compared with Example 4, when the amount of component (D) was increased, the oil phase solubility was further improved, and the same tendency was observed in Example 7 compared with Example 5. rice field.

As shown in Example 2 compared with Example 1, when the amount of component (C) was increased, the oil phase solubility was further improved, and the same tendency was observed in Example 4 compared with Example 3.

As shown in Example 5 in contrast to Example 4, when the component (F) was further added, the oil phase solubility was improved, and foam formation as seen in Comparative Example 5 in contrast to Comparative Example 2 was observed. No significant deterioration of the foaming was observed, and foaming was effectively suppressed. A similar tendency was observed in Example 7 as compared with Example 6. Further, even when cetostearyl alcohol as the component (F) in Examples 5 and 7 was replaced with stearyl alcohol, cetanol, or behenyl alcohol, respectively, the oil phase solubility was improved to the same extent as in Examples 5 and 7. and foaming was effectively suppressed.

Claims (9)

(A) prednisolone and/or a pharmaceutically acceptable derivative thereof, (B) lidocaine, (C) tocopherol and/or a pharmaceutically acceptable derivative thereof, (D) menthol, and (E) allantoin and an emulsified composition. The emulsified composition according to claim 1, further comprising (F) a higher alcohol. 3. The emulsified composition according to claim 1, wherein the content of component (C) per 1 part by weight of component (A) is 3 to 20 parts by weight. The emulsion composition according to any one of claims 1 to 3, wherein the content of component (D) per 1 part by weight of component (A) is 1 to 30 parts by weight. The emulsion composition according to any one of claims 1 to 4, wherein the content of component (E) is 0.05 to 2% by weight. The emulsion composition according to any one of claims 1 to 5, wherein the content of component (E) per 1 part by weight of the surfactant is 0.007 to 0.3 parts by weight. The emulsion composition according to any one of claims 2 to 6, wherein the content of component (E) per 1 part by weight of component (F) is 0.005 to 0.05 parts by weight. The emulsion composition according to any one of claims 1 to 7, which does not contain crotamiton. The emulsion composition according to any one of claims 1 to 8, which is a cream.