JP6765834B2 - Emulsified composition - Google Patents

Description

The present invention relates to an emulsified composition.

Conventionally, for skin diseases such as atopic dermatitis, rough skin, and eczema, an external preparation containing an anti-inflammatory agent such as a corticosteroid external preparation has been used. By further combining the external preparation with a local anesthetic such as lidocaine or an antihistamine such as diphenhydramine hydrochloride, it is possible to more effectively prevent or treat skin diseases.

Here, among the corticosteroid external preparations, ester-based steroids such as prednisolone valerate acetate acetic acid ester are extremely unstable components because they are hydrolyzed during storage. Therefore, external preparations are required to stabilize ester steroids.

For example, Patent Document 1 describes an external preparation containing prednisolone valerate ester acetate (topical corticosteroid for ester steroids) and lidocaine (local anesthetic), and the pH of the external preparation is 3 to 7 A technique for stabilizing prednisolone valerate acetate by adjusting to is disclosed. Further, Patent Document 2 describes an external preparation containing prednisolone valeric acid ester acetic acid ester and diphenhydramine hydrochloride (anti-histamine), which is a component in the external preparation by adding a stabilizer such as polyoxyethylene hydrogenated castor oil. Techniques for improving the separation stability of the ester are disclosed. However, simply adjusting the pH of the external preparation or adding a stabilizer such as polyoxyethylene hydrogenated castor oil to the external preparation will not only stabilize the prednisolone valerate acetate, but also in the emulsified composition. There was still room for improvement in improving the separation stability between the aqueous phase and the oil phase and not causing agglomerates of the contained components.

Therefore, with an external preparation containing prednisolone valerate acetate (particularly an emulsified composition), in addition to the stability of prednisolone valerate acetate, the separation stability in the external preparation can be improved and the components contained can be aggregated. It is very important not to give rise to things.

Japanese Unexamined Patent Publication No. 2001-72603 Japanese Unexamined Patent Publication No. 2006-28123

An object of the present invention is to provide an emulsified composition containing a prednisolone valeric acid ester acetic acid ester and having improved stability of the prednisolone valeric acid ester acetic acid ester.

An object of the present invention is to provide an emulsified composition in which the separation of an aqueous phase and an oil phase is suppressed.

An object of the present invention is to provide an emulsified composition that does not generate aggregates due to the contained components.

The present inventor has been diligently studying to solve the above-mentioned problems, and it is necessary to add a specific thickener (thickening agent) to improve the separation stability of the emulsified composition (emulsified preparation). I found it as one of the means to solve the problem.

Then, the present inventor added carmellose sodium (hereinafter, also referred to as “CMC-Na”) among the thickeners (thickeners) to the emulsified composition to improve the stability of the prednisolone valerate acetate acetate. In addition, it has been found that the aqueous phase and the oil phase do not separate in the emulsified composition and do not generate aggregates due to the contained components.

In the present invention, CMC-Na having a specific viscosity among CMC-Na further improves the stability of prednisolone valerate acetate, and separates the aqueous phase and the oil phase in the emulsified composition. It was also found that it suppresses more.

The present invention has been completed based on these findings, and has the following embodiments.

Item 1.
An emulsified composition comprising (a) prednisolone valerate acetate, (b) lidocaine, (c) diphenhydramine and / or hydrochloride thereof, and (d) sodium carmellose.

Item 2.
Item 2. The emulsified composition according to Item 1, wherein the (d) sodium carmellose is sodium carmellose having a viscosity of a 1 wt% aqueous solution of 500 mPa · s or more.

Item 3.
The emulsified composition according to Item 1 or 2, wherein the content of (d) sodium carmellose is 0.4% by weight or more.

Item 4.
(e) The emulsified composition according to any one of Items 1 to 3 above, which comprises a pH adjuster.

Item 5.
The emulsified composition according to any one of Items 1 to 4, which is an external preparation for skin.

Since the emulsified composition of the present invention contains CMC-Na, the stability of the prednisolone valeric acid ester acetic acid ester in the emulsified composition is more excellent.

By containing CMC-Na, the emulsified composition of the present invention can suppress the generation of aggregates due to components such as prednisolone valerate acetate, lidocaine, diphenhydramine and / or its hydrochloride.

By containing CMC-Na, the emulsified composition of the present invention can further suppress the separation between the aqueous phase and the oil phase.

By containing CMC-Na in the emulsified composition of the present invention, it is possible to suppress the generation of aggregates of each component even when a pH regulator is used in the emulsified composition.

The emulsified composition of the present invention contains CMC-Na showing a specific viscosity (viscosity of a 1 wt% aqueous solution) among the CMC-Nas, so that the stability of the prednisolone valerate acetic acid ester is more excellent. , The separation between the aqueous phase and the oil phase can be further suppressed.

These effects lead to improvement in the quality of the emulsified composition (external skin preparation).

(1) Emulsifying Composition The emulsifying composition of the present invention contains (a) prednisolone valerate acetate, (b) lidocaine, (c) diphenhydramine and / or its hydrochloride, and (d) carmellose sodium.

Hereinafter, the emulsified composition of the present invention will be described.

(a) Prednisolone valerate acetate ester Prednisolone valerate acetate ester (11β, 17α, 21-Trihydroxy- 1,4-pregnadiene-3,20-dione 21-acetate 17-valerate) (Prednisolone Valerate Acetate, also known as: Yoshi Prednisolone acetate) is an external corticosteroid, and has anti-inflammatory, anti-allergic, immunosuppressive, etc., pharmacological effects on eczema / dermatitis group, prurigo group, insect bites, psoriasis, palmoplantar pustulosis, etc. Has.

The content of the prednisolone valeric acid ester acetic acid ester in the emulsified composition of the present invention can be appropriately selected, and is preferably about 0.01 to 2% by weight, more preferably about 0.1 to 1% by weight.

(b) Lidocaine Lidocaine is a local anesthetic, and the one listed in the 16th revised Japanese Pharmacopoeia Manual (2011) can be used.

The content of lidocaine in the emulsified composition of the present invention can be appropriately selected, and is preferably about 0.1 to 5% by weight, more preferably about 1 to 4% by weight.

In the emulsified composition of the present invention, lidocaine may be contained in the form of lidocaine hydrochloride.

(c) Diphenhydramine and / or its hydrochloride Diphenhydramine and / or its hydrochloride (Diphenhydramine Hydrochloride) is an antihistamine (topical treatment for allergic diseases), and is the 16th revised Japanese Pharmacy Guide (2011). You can use the ones listed in.

The content of diphenhydramine and / or its hydrochloride in the emulsified composition of the present invention can be appropriately selected, and is preferably about 0.1 to 5% by weight, more preferably about 0.5 to 4% by weight.

(d) Carmellose Sodium The following is also referred to as "CMC-Na" (Carmellose Sodium, Carboxymethyl cellulose Sodium).

The emulsified composition of the present invention can improve the quality as an external preparation for skin by containing CMC-Na among thickeners (also referred to as thickeners).

The emulsified composition of the present invention contains CMC-Na as a thickener. CMC-Na dissolves in cold water or hot water to become a colorless and transparent viscous solution, which is usually added to increase the viscosity of a liquid in pharmaceuticals and cosmetics of emulsified compositions (creams, etc.). As CMC-Na, those listed in the 16th revised Japanese Pharmacopoeia Manual (2011) can be used.

As a substance name very similar to CMC-Na, there is "crystalline cellulose / CMC-Na". This component is mainly composed of crystalline cellulose and is not dissolved in water and becomes cloudy, and even if it is used, sufficient viscosity cannot be obtained. Therefore, crystalline cellulose / CMC-Na is a component different from CMC-Na in terms of its function and action.

By containing CMC-Na, the emulsified composition of the present invention can improve the stability of prednisolone valerate acetate acetate (component stability), and further, prednisolone valerate acetate acetate, lidocaine, diphenhydramine and / Or the generation of aggregates due to its hydrochloride or other additives can be suppressed (uniform dispersibility or component uniformity). By containing CMC-Na, the emulsified composition of the present invention can further suppress the separation between the aqueous phase and the oil phase (formulation stability or separation suppression).

Conventionally, there has been an invention in which a prednisolone valerate acetic acid ester is stabilized when an acid such as citric acid, phosphoric acid, malic acid, tartrate, or lactic acid is used for pH adjustment in an emulsified composition containing a prednisolone valerate acetic acid ester. However, by itself, it could not remain stable in the emulsified composition, and the aqueous phase and the oil phase tended to separate.

Since the emulsified composition of the present invention contains CMC-Na, even when an acid (pH regulator) such as citric acid or phosphoric acid is used to adjust the pH of the emulsified composition, each of them is contained in the emulsified composition. The generation of agglomerates due to the components is suppressed, the prednisolone valerate acetate remains stable, the aqueous phase and the oil phase do not separate, and the emulsified state (emulsion) is maintained stably for a long period of time. Is possible.

Viscosity of CMC-Na
As CMC-Na, it is preferable to use CMC-Na having a viscosity of about 500 mPa · s or more of the 1 wt% aqueous solution.

For the viscosity of a 1 wt% aqueous solution of CMC-Na, after uniformly dispersing and dissolving CMC-Na in water, place it in a constant temperature bath at 25 ° C ± 0.2 ° C for 30 minutes, and use an appropriate rotor of a BM type viscometer. Measure. Check the torque and adjust the rotation speed to 30 rpm to 60 rpm, which is an appropriate condition for the device.

Rotate the rotor, read the viscosity value after 3 minutes, and use this as the viscosity of the 1 wt% aqueous solution of CMC-Na.

The emulsified composition of the present invention can further stabilize the prednisolone valeric acid ester acetate by containing CMC-Na showing a specific viscosity among the CMC-Na, and can be combined with the aqueous phase of the emulsified composition. Separation from the oil phase can be further suppressed.

Degree of etherification (replacement) of CMC-Na
In CMC (or its sodium salt, CMC-Na), there are three primary or secondary alcoholic hydroxyl groups (OH groups) per anhydrous glucose unit of the cellulose constituting the CMC (or its sodium salt, CMC-Na). The carboxymethyl group in CMC (CMC-Na) is distributed in its hydroxyl group, and the number of hydroxyl groups etherified by this group per glucose unit is called the degree of etherification (or degree of substitution). In CMC-Na (CMC), the degree of etherification (substitution degree) can theoretically be up to 3.

The degree of etherification of CMC-Na is usually about 0.6 to 1.5. The degree of etherification of CMC-Na is that it has excellent solubility in the emulsified composition, improves the stability of prednisolone valerate acetic acid ester, suppresses the generation of aggregates due to the contained components, and emulsified composition. 0.6 to 1 is preferable for the reason of suppressing the separation of the aqueous phase and the oil phase of the ester.

Content of CMC-Na The content (lower limit) of CMC-Na in the emulsified composition of the present invention can be appropriately selected, and for the above reasons, it is preferably about 0.1% by weight or more, preferably about 0.4% by weight or more. Is more preferable, and about 0.6% by weight or more is further preferable. The content (upper limit) of CMC-Na in the emulsified composition of the present invention is preferably about 3% by weight or less, and more preferably about 1.5% by weight or less.

(e) pH regulator The emulsified composition of the present invention preferably contains a pH regulator.

As the pH adjuster, for example, those listed in the Pharmaceutical Additives Dictionary (2016) (Yakuji Nippo Co., Ltd.) can be used, and may contain organic acids and / or inorganic acids that can be usually added to pharmaceutical products. preferable.

It is preferable to include phosphoric acid, hydrochloric acid (dilute hydrochloric acid) and the like as the inorganic acid. The organic acid preferably contains citric acid (or citric acid hydrate), succinic acid, DL-malic acid, tartaric acid, lactic acid, maleic acid (fumaric acid) and the like. As the pH adjuster, salt compounds such as sodium salt, potassium salt and calcium salt of the organic acid or inorganic acid can also be used.

The pH adjusting agent preferably contains at least one component selected from the group consisting of the organic acids and inorganic acids, and salt compounds thereof.

The content of the pH adjuster in the emulsified composition of the present invention can be appropriately selected in order to adjust the pH of the emulsified composition, and an appropriate amount may be added.

The emulsified composition of the present invention also contains CMC-Na as described above even when an acid such as citric acid or phosphoric acid is used for adjusting the pH of the emulsified composition in the emulsified composition. The prednisolone valerate acetate remains stable and can suppress the generation of aggregates by each component.

PH of emulsified composition
The pH of the emulsified composition of the present invention is not particularly limited and may be appropriately set according to the intended use. When the emulsified composition is applied to the skin as an external preparation, the pH is preferably in the range of weakly acidic to neutral. From the viewpoint of hypoallergenicity to the skin, it is preferable to adjust the emulsified composition to pH 4 to 7, and more preferably to pH 4 to 6.5.

Further, from the viewpoint of the stability of the prednisolone valeric acid ester acetic acid ester in the emulsified composition, it is preferable to adjust the emulsified composition to pH 4 to 6.

(2) Other Ingredients to be Blended in Emulsified Composition The emulsified composition of the present invention may contain a medicinal ingredient of another purpose in addition to the above-mentioned medicinal ingredients as long as the effects of the present invention are not impaired. It is possible. The medicinal properties are not particularly limited, but for example, steroids, local anesthetics other than lidocaine, anti-inflammatory agents other than prednisolone valerate acetate, bactericides, antipruritic agents, skin protectants, blood circulation promoting ingredients, etc. It is preferable to use vitamins and the like.

The external composition of the present invention includes, if necessary, a surfactant (glycerin monostearate, polyoxyethylene behenyl ether, etc.) and a thickener other than the above-mentioned CMC-Na, as long as the effects of the present invention are not impaired. , Stabilizers (sodium edetate, etc.), absorption promoters, adsorbents, fillers, antioxidants, preservatives (methyl paraoxybenzoate, propyl paraoxybenzoate, etc.), emulsifiers, solubilizers, bactericides, moisturizers , Perfume, deodorant, dispersant, pigment and the like may be contained.

As a component that does not belong to CMC-Na contained in the emulsified composition of the present invention, there are crystalline cellulose / CMC-Na, HPMC, CVP, xanthan gum, sodium alginate and the like as thickeners (thickeners). The emulsified composition of the present invention may further contain a thickener other than CMC-Na as necessary, as long as it does not interfere with the effects of the present invention.

(3) Method for preparing external composition The emulsified composition of the present invention comprises the above-mentioned (a) prednisolone valerate acetic acid ester, (b) lidocaine, (c) diphenhydramine and / or its hydrochloride, and (d) CMC-. Any acid containing Na, preferably using an acid such as citric acid or phosphate for pH adjustment, can be produced according to a usual method in the art.

The types, contents, blending ratios, etc. of the components used in the method for preparing the emulsified composition will be described in the same manner as described above.

In the preparation of the emulsified composition, first, the components that can be blended in the aqueous phase are mixed, heated to a temperature of about 70 to 90 ° C., and then using a mixer such as a homogenizer, a homomixer, or a stirrer. It is preferable to mix under predetermined conditions. This makes it possible to prepare an aqueous composition.

Separately, the components that can be blended in the oil phase are mixed, heated to a temperature of about 70 to 90 ° C., and then mixed under predetermined conditions using a mixer such as a homogenizer, a homomixer, or a stirrer. Is preferable. This makes it possible to prepare an oily composition.

Then, the aqueous composition (aqueous phase) and the oily composition (oil phase) are mixed and emulsified to prepare an emulsified composition.

(4) Method for Stabilizing Predonizolone Valeric Acid Ester Acetic Acid in Emulsifying Composition The method for stabilizing prednisolone valerate acetate in the emulsifying composition of the present invention is a method for stabilizing prednisolone valeric acid ester in an emulsifying composition containing prednisolone valeric acid ester. , CMC-Na coexist.

The types, contents, blending ratios, etc. of the components in the emulsified composition will be described in the same manner as described above.

The method for stabilizing the prednisolone valeric acid ester acetic acid ester in the emulsified composition can be carried out according to the method for preparing the emulsified composition described above.

According to the stabilization method of the present invention, as shown in Examples described later, by adding CMC-Na as a thickener (thickener) to the emulsified composition, prednisolone oxalate ester acetate can be obtained. Stability can be improved, that is, its residual rate can be increased.

This is because, as described above, even when an acid (pH regulator) such as citric acid or phosphoric acid is used to adjust the pH of the emulsified composition, the prednisolone valeric acid ester is contained by containing CMC-Na. This leads to improved stability of the acetic acid ester.

Further, according to the dispersion stabilization method of the present invention, the aqueous phase and the oil phase are not separated in the emulsified composition, and agglomerates of prednisolone valerate acetate acetic acid ester, lidocaine, diphenhydramine hydrochloride and the like in the aqueous phase. It is possible to suppress the occurrence of.

Therefore, according to the present invention, the bias of the contained components in the emulsified composition can be reduced, and the variation in the effect can be effectively eliminated. As a result, the appearance of the emulsified composition is also good. The emulsified composition of the present invention can stably maintain an emulsified state (emulsion) for a long period of time.

According to the present invention, the quality of an emulsified composition containing a component such as prednisolone valeric acid ester acetic acid ester can be improved.

(5) Applicable target of emulsified composition The applicable target of the external composition of the present invention is not limited, but the prednisolone valerate ester acetate, which is an external corticosteroid, has anti-inflammatory, anti-allergic, immunosuppressive, etc. Any aspect may be used as long as it exhibits the pharmacological action of.

The application target is preferably skin (including scalp), for example. When the emulsified composition is intended to be applied to the skin, for example, as long as it is applied to the skin of cosmetics, quasi-drugs for external use of skin, pharmaceuticals for external use of skin, etc. Not limited. For example, it is preferable that the form is suitable for various desired external preparations such as ointment, cream, paste, mousse, gel, jelly, suspension, milky lotion, and liquid. As the emulsifying composition, a creamy external preparation is suitable.

When the emulsified composition of the present invention is used, for example, by applying it to human skin, the amount and number of times the external composition is applied to the skin are not particularly limited. For example, once a day to several times depending on the type and concentration of bioactive substances such as prednisolone valerate acetate contained, age, sex, degree of symptoms, application form, expected degree, etc. of the user. It is preferable to apply an appropriate amount to the skin (particularly the site where the symptoms occur) at a frequency of each time.

By containing CMC-Na in the emulsified composition of the present invention, the prednisolone valeric acid ester acetic acid ester remains more stably, and the generation of aggregates due to the contained components can be further suppressed. By containing CMC-Na, the emulsified composition of the present invention can further suppress the separation between the aqueous phase and the oil phase. These effects lead to improvement in the quality of the emulsified composition (external skin preparation).

The present invention will be specifically described based on examples, but the present invention is not limited thereto.

(1) Details of CMC-Na A cellogen manufactured by Dai-ichi Kogyo Seiyaku Co., Ltd. was used.

CMC-Na (1): The viscosity is 1000 mPa · s or more, and the degree of etherification of the carboxymethyl group is 0.6 to 0.8.

CMC-Na (2): The viscosity is 500 to 800 mPa · s, and the degree of etherification of the carboxymethyl group is 0.6 to 0.8.

CMC-Na (3): The viscosity is 350 to 500 mPa · s, and the degree of etherification of the carboxymethyl group is 0.6 to 0.7.

<Explanation of CMC-Na viscosity (mPa · s)>
A 1% by mass aqueous solution in which carmellose sodium (CMC-Na) is uniformly dispersed and dissolved in water is placed in a constant temperature bath at 25 ° C ± 0.2 ° C for 30 minutes and measured with an appropriate rotor of a BM type viscometer. did. The number of revolutions was adjusted to 30 rpm to 60 rpm, which is an appropriate condition for the device, after confirming the torque. The rotor was rotated, the numerical value of the viscosity after 3 minutes was read, and this was adopted as the viscosity (mPa · s) of CMC-Na.

In Table 1, crystalline cellulose / CMC-Na is used in Comparative Example 1. This crystalline cellulose / CMC-Na is a component mainly composed of crystalline cellulose, which is not dissolved in water and becomes cloudy, and sufficient viscosity cannot be obtained. Crystalline cellulose CMC-Na is a component different from CMC-Na used in the emulsified composition of the present invention.

(2) Preparation of emulsified composition An emulsified composition was prepared according to the formulation shown in Table 1.

<Explanation of words in Table 1>
1,3-BG: 1,3-butylene glycol crystalline cellulose / CMC-Na: crystalline cellulose / sodium carmellose
HPMC: Hydroxypropyl Methyl Cellulose
CVP: Carboxyvinyl Polymer Nicotinamide: Vitamin B ₃
Tocopherol acetate: Vitamin E
IPMP: Isopropylmethylphenol (bactericidal and antibacterial ingredient)
POE Hardened Castor Oil: Polyoxyethylene Hardened Castor Oil

<Preparation>
Aqueous phase: First, each of the ingredients listed in the table (1,3-BG, CMC-Na, etc.) is weighed, heated in water at 80 ° C. to mix, and uniformly dissolved to prepare an aqueous composition. Prepared.

Oil phase: Next, each of the ingredients listed in the table (prednisolone valeric acid ester acetic acid ester, lidocaine, etc.) was weighed, heated at 80 ° C. and mixed, and uniformly dissolved to prepare an oily composition. ..

The aqueous composition and the oily composition were mixed, and diphenhydramine hydrochloride, citric acid, phosphoric acid or malic acid was added during stirring and cooling to adjust the pH of the emulsified composition to 4-6.

The final temperature was cooled to 40 ° C. or lower to prepare an emulsified composition.

The emulsified composition was creamy.

(3) Evaluation of formulation stability The presence or absence of separation of the formulation (separation stability) was confirmed in the emulsified composition.

The evaluation criteria are as follows.
Evaluation 3: The emulsified composition was stable for 2 months or more under 50 ° C. acceleration conditions.
Evaluation 2: The emulsified composition was stable for 1 month or longer under 50 ° C. acceleration conditions.
Evaluation 1: The emulsified composition was stable for 2 weeks or more under 50 ° C. acceleration conditions.
Evaluation 0: The emulsified composition was separated within 2 weeks under 50 ° C. accelerated conditions.

Evaluation 1 or higher is an acceptable mode, and evaluation 2 or higher is a preferable mode.

(4) Evaluation of uniform dispersibility It was confirmed whether or not the emulsified composition was uniformly dispersed (presence or absence of agglomerates).

The evaluation criteria are as follows.
Evaluation 3: Uniformly dissolved, no aggregates were confirmed. The final emulsified composition is uniform.
Evaluation 2: Aggregates were present at the time of preparation, but they were uniformly dissolved, and no aggregates were finally confirmed. The final emulsified composition is uniform.
Evaluation 1: Aggregates were confirmed under a microscope.
Evaluation 0: Aggregates were visually confirmed or did not dissolve uniformly.

Evaluation 1 or higher is an acceptable mode, and evaluation 2 or higher is a preferable mode.

(5) Evaluation of component stability The stability of prednisolone valerate acetate was confirmed in the emulsified composition.

The evaluation criteria are as follows.
Evaluation 3: In the emulsified composition, the residual rate of prednisolone valeric acid ester acetic acid ester was 95% or more after 1 month of acceleration at 50 ° C.
Evaluation 2: In the emulsified composition, the residual rate of prednisolone valeric acid ester acetic acid ester was 90% or more after 1 month of acceleration at 50 ° C.
Evaluation 1: In the emulsified composition, the residual rate of prednisolone valerate acetate was 85% or more after 1 month of acceleration at 50 ° C.
Evaluation 0: In the emulsified composition, the residual rate of prednisolone valerate acetate was 85% or less after 1 month of acceleration at 50 ° C.

Evaluation 1 or higher is an acceptable mode, and evaluation 2 or higher is a preferable mode.

(6) Comprehensive evaluation of emulsified composition A comprehensive evaluation is shown in consideration of formulation stability, uniform dispersibility and component stability of the above emulsified composition.
⊚: In the emulsified composition, all scores are 3.
◯: In the emulsified composition, all scores are 1 or more.
X: In the emulsified composition, there is even one score of 0.

The Examples and the Comparative Examples are compared.

As shown in the comparative example, no thickener (viscosity agent) is added to the emulsified composition containing prednisolone valerate acetate, lidocaine and diphenhydramine hydrochloride, or as a thickener (viscosity agent). , Crystalline cellulose ・ By adding CMC-Na, HPMC, CVP, xanthan gum or sodium alginate, the aqueous phase and oil phase are separated, aggregates due to the contained components are formed in the emulsified composition, and prednisolone valerate is used. The result was that the ester acetate was unstable.

On the other hand, as shown in the examples of the present invention, by adding CMC-Na as a thickener (viscosity agent) to an emulsified composition containing prednisolone valerate acetic acid ester, lidocaine and diphenhydramine hydrochloride. , The aqueous phase and the oil phase were not separated (formulation stability), no agglomerates of the contained components were confirmed in the emulsified composition (uniform dispersibility), and the prednisolone valerate acetate acetic acid ester remained stable (components). Stability).

As shown in the examples, even if citric acid or phosphoric acid acid is used to adjust the pH of the emulsified composition, the prednisolone valerate acetic acid ester remains stable by containing CMC-Na as a thickener. , Aggregates of each component were not confirmed, and the aqueous phase and the oil phase were not separated.

As shown in Examples 2 to 9, the emulsified composition contained 0.4% by weight or more of CMC-Na, so that the formulation stability and the component stability were further improved.

As shown in Examples 3, 4, 6 to 9, as CMC-Na to be added to the emulsified composition, CMC-Na having a viscosity of about 500 mPa · s or more in a 1 wt% aqueous solution is used. Formulation stability and ingredient stability were further improved.

The effects exerted by these emulsified compositions of the present invention lead to improvement in quality as an external preparation for skin.

Claims (6)

Containing (a) prednisolone valerate acetate, (b) lidocaine, (c) diphenhydramine and / or its hydrochloride, and (d) sodium carmellose (excluding crystalline cellulose and CMC-Na) . A characteristic emulsified composition. The emulsified composition according to claim 1, wherein the (d) sodium carmellose is sodium carmellose having a viscosity of a 1 wt% aqueous solution of 500 mPa · s or more. The emulsified composition according to claim 1 or 2, wherein the (d) sodium carmellose is sodium carmellose having a degree of etherification of 0.6 to 1.5. The emulsified composition according to any one of claims 1 to 3, wherein the content of (d) sodium carmellose is 0.4% by weight or more. (e) The emulsified composition according to any one of claims 1 to 4 , which comprises a pH adjuster. The emulsified composition according to any one of claims 1 to 5 , which is an external preparation for skin.