JPH11255640A - Emulsified preparation for external use for skin - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject stable emulsified preparation with improved usability, namely, having nonsticky and refreshing feel when applied, by formulating a higher alcohol, a lipophilic nonionic surfactant and a silicone oil. SOLUTION: This emulsified preparation is obtained by including (A) as the principal medicament, one or more kinds selected from urea, sodium salicylate and pyrrolidonecarboxylic acid, (B) a water-soluble polymer (pref. a carboxyvinyl polymer, its amount to be formulated being >=0.15 wt.%), (C) a higher alcohol (pref. cetanol), (D) a lipophilic nonionic surfactant (pref. glycerol monofatty acid ester), and (E) a silicone oil (pref. <=50 mPa/s in viscosity at normal temperatures); wherein, it is preferable that, after emulsification process, such a process as to agitate and cool a mixture component containing at least component A from a temperature of >=50 deg.C is involved.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an emulsified preparation for external use on the skin, and more particularly, to an improvement in the usability of an emulsified preparation containing a high amount of a drug such as urea and a water-soluble polymer. It concerns a formulation.

[0002]

2. Description of the Related Art In general, a water-soluble polymer is generally incorporated into an emulsified preparation for external use on the skin in order to increase the viscosity and impart stability. Among the water-soluble polymers, carboxyvinyl polymer is a water-soluble polymer widely used in emulsion preparations. For example, such an external preparation for skin emulsification is disclosed in Japanese Patent Publication No. Hei 7-25674, Patent No. 26235.
No. 80, JP-A-7-291856, JP-A-9-2
No. 49555 and the like.

[0003]

However, when a water-soluble polymer such as a carboxyvinyl polymer is blended in order to ensure stability, there is a drawback that stickiness is observed in use. In particular, in a formulation containing urea and the like used for dry skin diseases such as keratosis and xerosis, in addition to the drug itself such as urea has a sticky, glycerin in order to enhance the moisturizing, A humectant such as propylene glycol or 1,3-butylene glycol is often used in combination, and therefore, the stickiness due to the water-soluble polymer becomes more remarkable. In order to reduce such sticky feeling, conventionally, lower alcohols such as ethanol have been blended as a solvent for dissolving a drug or the like, and the usability has been improved by imparting a refreshing feeling. It was insufficient from the viewpoint of reduction.

The present invention has been made in view of the above-mentioned conventional problems, and an object of the present invention is to improve the usability, that is, to provide a stable emulsion preparation for external use on the skin having a non-sticky and refreshing feeling. It is in.

[0005]

Means for Solving the Problems The present inventors have conducted intensive studies in order to solve the above problems, and have found that higher alcohols,
By blending a lipophilic nonionic surfactant and silicone oil, the external preparation for skin containing a drug such as urea and a water-soluble polymer has no stickiness and has a refreshing feel. I found it. Furthermore, it was found that the external preparation for external use of the skin of the present invention was excellent in stability over time, and further, it was found that there was no uncomfortable feeling upon use and there was no irritation.

[0006] That is, the present invention relates to a method comprising the steps of providing one or more of urea, sodium salicylate and pyrrolidone carboxylic acid as main agents, a water-soluble polymer, a higher alcohol, a lipophilic nonionic surfactant, and a silicone. It is an emulsified preparation for external use on the skin, characterized by being blended with oil. As the emulsion preparation for external use on the skin of the present invention, a preparation containing 0.15% by weight or more of a water-soluble polymer is most effective.

Hereinafter, the present invention will be described in detail. The main drug used in the emulsion preparation for external use on the skin according to the present invention is one or more selected from urea, sodium salicylate and pyrrolidone carboxylic acid, and the drug has a therapeutic effect on keratosis and xerosis. Is what it is. Among them, urea is also effective for senile xeroderma and dry skin diseases accompanied by itching, is the most frequently used drug, and is particularly suitable.

[0008] The compounding amount of the main agent used in the emulsified preparation for external use on the skin according to the present invention is preferably 3.0 to 25.0% by weight, more preferably 5.0 to 22.0% by weight, particularly preferably Preferably it is 10.0 to 20.0% by weight. If the compounding amount of the drug is small, it is difficult to obtain a desired healing effect. If the amount of the drug is too large, it is not preferable because the skin sticks to the skin.

The water-soluble polymers used in the emulsified preparation for external use on the skin according to the present invention include polyacrylic acid (salt), carboxymethylcellulose (salt), alginic acid (salt), polyvinyl alcohol, polyvinylpyrrolidone, hydroxypropylcellulose, and gum arabic. , Gum karaya, gum tragacanth, gum xanthan, gum locust bean, guar gum, carrageenan, galactomannan, gelatin, agar, pullulan, pectin, starch, cellulose derivatives, sodium hyaluronate, carboxyvinyl polymer and the like. These can be used alone or in combination of two or more. Among these, a particularly preferred water-soluble polymer is a carboxyvinyl polymer, and when a carboxyvinyl polymer is used, the effect of improving the usability is most remarkable.

The carboxyvinyl polymer is a water-soluble vinyl polymer having a carboxyl group in the molecule. For example, Hibiswako 103 and 104 manufactured by Wako Pure Chemical Industries, Ltd.
And 105, and Carbopol 934, 940 and 941 manufactured by Goodrich Chemical Co., Ltd.

The amount of the water-soluble polymer used in the present invention is preferably 0.15 to 3.0% by weight, more preferably 0.2 to 2.0% by weight, and particularly preferably 0.25 to 2.0% by weight. 1.
0% by weight. If the amount of the water-soluble polymer is less than 0.15% by weight, it may be difficult to obtain a thickening effect and a stabilizing effect of the system. Further, since the whole system is not very sticky, the effect of reducing stickiness, which is a feature of the present invention, is not sufficiently exhibited. 3.0% by weight of water-soluble polymer
Exceeding the viscosity is not preferred because the viscosity of the system becomes too high.

The higher alcohol used in the present invention includes cetanol, stearyl alcohol, myristyl alcohol, behenyl alcohol, cetostearyl alcohol,
One or more selected from lauryl alcohol, oleyl alcohol, octyldodecanol, hexadecyl alcohol, hexadecyl isostearate, cholesterol and the like. Of these, particularly preferred are cetanol, stearyl alcohol, myristyl alcohol, behenyl alcohol and cetostearyl alcohol.

The amount of the higher alcohol used in the present invention is preferably 0.3 to 6.0% by weight, preferably 0.4 to 4.0% by weight, and particularly preferably 0.5 to 3.0% by weight. 0
% By weight. 0.3% by weight of higher alcohol
If the amount is less than 6, the system stabilizing effect cannot be sufficiently obtained, and the stickiness reducing effect is inferior. Therefore, if it is more than 6.0% by weight, the viscosity and hardness of the system become too high.

The lipophilic nonionic surfactant used in the present invention has an HLB value of 6.5 or less.
Glycerin monofatty acid ester such as glycerin monostearate, glycerin monooleate, glycerin monopalmitate, glycerin distearate, glycerin dioleate, glycerin difatty acid ester such as glycerin dipalmitate, sorbitan fatty acid ester And polyethylene glycol fatty acid esters. Here, the fatty acid is preferably a straight-chain or branched-chain fatty acid having 12 to 18 carbon atoms. These are used alone or in combination of two or more. Of these, glycerin monofatty acid ester is particularly preferred.

The amount of the lipophilic nonionic surfactant used in the present invention is preferably from 0.5 to 5.0% by weight,
Preferably it is 1.0 to 4.0% by weight, particularly preferably 1.
2 to 3.0% by weight. If the compounding amount of the lipophilic nonionic surfactant is less than 0.5% by weight, the effect of stabilizing the system cannot be sufficiently obtained, and the effect of reducing stickiness is inferior. It is not preferable because the viscosity and hardness of the system become too high.

The silicone oil used in the present invention preferably has a viscosity at room temperature of 50 mPa · s or less.
Such silicone oils include, for example, chain polysiloxanes such as dimethylpolysiloxane, methylphenylpolysiloxane and methylhydrogenpolysiloxane, cyclic polysiloxanes such as decamethylpolysiloxane, dodecamethylpolysiloxane and tetramethyltetrahydrogenpolysiloxane. Siloxane. Commercially available products include, for example, Silicon KF-9 manufactured by Shin-Etsu Chemical Co., Ltd.
6A-2, Silicon KF-96A-6, Execol D
-4 and Execol D-5.

The amount of the silicone oil used in the present invention is preferably 0.5 to 5.0% by weight, more preferably 1.0 to 4.0% by weight, and particularly preferably 2.0 to 3.0% by weight. 0
% By weight. If the amount of the silicone oil is less than 0.5% by weight, the effect of suppressing stickiness cannot be sufficiently obtained, and if the amount is more than 5.0% by weight, it is not preferable because the usability is liable to slip.

The emulsified preparation for external use on the skin of the present invention comprises 50 parts of a mixed component containing at least a water-soluble polymer after the emulsification step.
It is preferably manufactured by a manufacturing method including a step of stirring and cooling from a temperature of not less than ° C. The stirring and cooling step in producing the emulsified preparation for external use on the skin according to the present invention relates to a step that is performed following the emulsification step that has been performed in a usual manner in advance. That is, a step of stirring and cooling a mixed component containing at least a water-soluble polymer having a temperature of 50 ° C. or more is required when producing the external preparation for skin according to the present invention. The cooling method may be rapid cooling or slow cooling, but it is characterized by a stirring step. As a stirring method, for example, turbine stirring, paddle stirring,
Anchor stirring, homomixer stirring, homodisper stirring, homogenizer stirring and the like are mentioned, but homomixer stirring is preferred. By producing by the above method, it is possible to obtain an emulsified preparation for external use on the skin that is less sticky and has a refreshing feeling. Although the reason for this is not clearly understood, it is considered that the main drug and the water-soluble polymer which cause the stickiness are present in a form coated with a higher alcohol or the like, not in the original form. .

The external preparation for skin according to the present invention may contain a polyhydric alcohol for promoting the effects of the above-mentioned drugs. Examples of the polyhydric alcohol used here include, for example, propylene glycol, dipropylene glycol, 1,3-butylene glycol, glycerin, diglycerin, polyglycerin, polyethylene glycol, maltose, fructose, xylitol, inositol, pentaerythritol, sorbitol, Maltitol, sorbitol, mavit, maltotriose, sucrose, glucose, etc., and one or more of these are used.

The external preparation for skin according to the present invention may further contain, if necessary, a drug other than the above components, a pH adjuster, a cooling agent, an antioxidant, a chelating agent, an absorption enhancer, an oil, an inorganic powder, Surfactants, preservatives, fragrances, coloring agents, and the like can be added as long as the effects of the present invention are not impaired.

[0021]

EXAMPLES Next, the present invention will be described in more detail with reference to Examples, Comparative Examples and Test Examples of the emulsified preparation for external use on the skin of the present invention, but these do not limit the present invention at all.
In the following examples, “%” indicates “% by weight” unless otherwise specified, and numerical values in the composition table also indicate “% by weight”.

Example 1, Comparative Example 1 An emulsion preparation for external use on the skin was prepared according to the formulation shown in the following Table 1 and the method described later, and its usability and stability were evaluated by the methods described later. Table 2 shows the results.

(1) Production method Production method of Example 1 Urea, concentrated glycerin, 1,3-butylene glycol, carboxyvinyl polymer, and sodium hydroxide were sequentially added to purified water, and heated and dissolved at 70 ° C. to prepare an aqueous phase. . Also, diphenhydramine, lidocaine, L-menthol, glycyrrhetinic acid, tocopherol acetate, cetanol, glycerin monofatty acid ester, POE monostearate (40), hardened oil, squalane, glycerin triisooctanoate (TIO: a product of Nisshin Seimitsu Oil Co., Ltd.) Name),
Methylpolysiloxane (silicon KF-96A-6: trade name, manufactured by Shin-Etsu Chemical Co., Ltd.) was sequentially added and dissolved by heating at 75 ° C. to prepare an oil phase. The oil phase was added to the aqueous phase and emulsified with a homomixer to prepare an oil-in-water emulsion. Subsequently, a homomixer treatment (7,000
While stirring and cooling at (rpm), an external preparation for skin application of the present invention was obtained.

Urea, concentrated glycerin, carboxyvinyl polymer, sodium hydroxide and ethanol were sequentially added to purified water at 70 ° C.
To prepare an aqueous phase. Diphenhydramine, lidocaine, L-menthol, glycyrrhetinic acid, tocopherol acetate, POE monooleate (20)
Add sorbitan, white petrolatum, and squalane sequentially and add 7
An oil phase was prepared by heating and dissolving at 0 ° C. The oil phase was added to the aqueous phase and emulsified with a homomixer to prepare an oil-in-water emulsion. Subsequently, the mixture was stirred and cooled from 70 ° C. while being subjected to a homomixer treatment (7,000 rpm) to obtain a skin external emulsion preparation of Comparative Example 1.

(2) Evaluation Method Evaluation of Usability Usability was evaluated for stickiness, discomfort and irritation during use. In the method, 0.5 g of a sample was applied to the inner part of the forearm of 10 healthy subjects, and stickiness, discomfort and irritation when extended by hand were evaluated according to the following criteria based on sensory characteristics. (Evaluation criteria for stickiness) ：: 0 out of 10 people answered that they were sticky. Δ: One or more and less than 5 out of 10 respondents answered that they were sticky. ×: 5 or more out of 10 persons who answered that they were sticky. (Evaluation criteria for discomfort and irritation) ：: No discomfort and irritation. Δ: Almost no discomfort or irritation. X: There is discomfort and irritation.

Evaluation of stability Regarding stability, 50 ° C., one month and 40 ° C.
Evaluation was performed at 75% humidity and 3 months according to the following criteria. (Evaluation criteria for stability) ：: No separation or precipitation was observed in any case. Δ: Slight separation and precipitation were observed in any of them. ×: Separation and precipitation are observed in any of them.

[0027]

[Table 1] Compounding ingredients Example 1 Comparative Example 1尿素 Urea 10.0 10.0 Difehydramine 1.0 1.0 Lidocaine 2.0 2.0 L-Menthol 0.5 0.5 Glycyrrhetinic acid 0.3 0.3 Tocopherol acetate 0.1 0.1 Cetanol 0.7-Glycerin monostearate 1.6-POE monostearate (40) 1.0-Sorbitan monooleate-1.0 Hardened oil 2.0-White petrolatum-2.0 Squalane 8.0 2.0 Glycerin triisooctanoate (TIO) 5.0 -Methylpolysiloxane (6cs) 2.0-(Silicon KF-96A-6) Condensed glycerin 15.0 5.0 1,3-butylene glycol 3.0-Carboxyvinyl polymer 0.3 0.3 Suitable for sodium hydroxide Amount Appropriate amount Ethanol − 10.0 Purified water Residue Residue ──────────────────────────────────

[0028]

[Table 2]

As can be seen from the results in Table 2, it was confirmed that the external preparation for skin according to the present invention was clearly usable compared to Comparative Example 1 with less stickiness and had good stability.

Examples 2, Comparative Examples 2 to 4 Preparations having the compositions shown in Table 3 were prepared, and tested for their usability and stability. Note that the evaluation method is the same as in Example 1. Table 4 shows the test results. Each preparation was prepared according to the method of Example 1.

[0031]

[Table 3] 配合 Ingredients Example 2 Comparative Example 2 Comparative Example 3 Comparative Example 4 Urea 10.0 10.0 10.0 10.0 Diphenhydramine 1.0 1.0 1.0 1.0 Lidocaine 2.0 2.0 2.0 2.0 L-menthol 0.3 0.3 0.3 0.3 Dipotassium glycyrrhizinate 0.5 0.5 0.5 0.5 Tocopherol acetate 0.1 0.1 0.1 0.1 Cetanol 1.0-1.0 1.0 Glycerin monostearate 1.5 1.5-1.5 POE monostearate (40) 1.0 1.0 1.0 1.0 Hardened oil 1.8 1.8 1.8 1.8 Liquid paraffin 8.0 8.0 8.0 8.0 Tetra-2-ethylhexanoic acid Pentaerythlit 5.0 5.0 5.0 5.0 Methylpolysiloxane (6cs) 2.5 2.5 2.5-Concentrated glycerin 15.0 15.0 15.0 15.0 1,3-butylene glycol 3.5 3.5 3.5 3.5 Carboxy Nyl polymer 0.5 0.5 0.5 0.5 Sodium edetate Appropriate amount Appropriate amount Appropriate amount Appropriate amount of sodium hydroxide Appropriate amount Appropriate amount Appropriate amount Purified water Residual Residual Residual ───────────────────────── ──────────

[0032]

[Table 4] Example 2 Comparative Example 2 Comparative Example 3 Comparative Example 4 ────────────────────────────────── Stickiness (sensory evaluation) ○ × × × Discomfort, irritation (sensory evaluation) ) ○ ○ ○ 製 剤 Formulation stability (test evaluation) △ × ○ ───────────────────────────────── ─

As can be seen from Table 4, the emulsion preparation for external use on the skin of the present invention can be expected even if any one of the constituents, such as higher alcohol, lipophilic nonionic surfactant and silicone oil, is missing. It was recognized that usability and stability could not be obtained.

Next, in order to explain the emulsified preparation for external use on the skin of the present invention more concretely, examples of preparation will be shown. About these manufacturing methods, it followed Example 1. That is, each of the compositions was prepared by emulsifying and then stirring and cooling from 70 ° C. with homomixer stirring (7,000 rpm).

Example 3 (Cream formulation) (Prescription) Compounding amount (% by weight) Urea 10.0 Difehydramine 1.0 Lidocaine 2.0 L-Menthol 0.5 Glycyrrhetinic acid 0.3 Tocopherol acetate 0.1 Cetanol 3. 0 Glycerin mono fatty acid ester 2.5 POE monostearate (40) 1.0 Hardened oil 2.0 Squalane 8.0 Glycerin triisooctanoate (TIO) 5.0 Decamethylcyclopentasiloxane 3.0 (Execol D-5 ) Concentrated glycerin 15.0 1,3-butylene glycol 3.0 Carboxyvinyl polymer 0.3 Citric acid qs Sodium citrate qs Sodium edetate qs Purified water residue

Example 4 (Emulsion formulation) (Formulation) Amount (% by weight) Urea 20.0 Difehydramine 1.0 Lidocaine 2.0 L-Menthol 0.5 Dipotassium glycyrrhizinate 0.3 Tocopherol acetate 0.1 Behenyl alcohol 0 0.2 Cetanol 0.5 Glycerin mono fatty acid ester 1.8 Hardened castor oil POE (60) 1.0 White petrolatum 2.0 Liquid paraffin 10.0 Isopropyl myristate 3.0 Methylpolysiloxane (2cs) 1.5 (Silicon KF-96A-2) Concentrated glycerin 13.0 Dipropylene glycol 2.0 Carboxyvinyl polymer 0.25 Sodium hyaluronate 0.005 Potassium hydroxide Appropriate amount Lactic acid Appropriate amount Sodium edetate Appropriate amount Ethyl paraben Appropriate amount Purified water Residue

Example 5 (Cream formulation) (Prescription) Compounding amount (% by weight) Sodium salicylate 10.0 L-menthol 0.5 Tocopherol acetate 0.1 Behenyl alcohol 2.5 Glycerin monofatty acid ester 3.5 Monostearate POE (40) 1.5 Hardened oil 2.0 Liquid paraffin 4.0 Squalane 3.0 Methylpolysiloxane (6cs) 2.5 (Silicon KF-96A-6) Triisooctanoate glycerin (TIO) 2.0 Concentrated glycerin 6 0.0 Propylene glycol 3.0 Carboxyvinyl polymer 0.45 Sodium hydroxide qs Tartaric acid qs Dibutylhydroxytoluene qs Purified water residue

[0038]

As described above, the emulsion preparation for external use of the skin of the present invention has less stickiness of the water-soluble polymer than the conventional preparation, and is excellent in stability over time, and has a feeling of discomfort and irritation during use. Without.

──────────────────────────────────────────────────続 き Continued on front page (51) Int.Cl. ⁶ Identification code FI A61K 7/48 A61K 7/48 31/40 31/40 31/60 31/60

Claims (8)

[Claims] 1. A composition comprising one or more selected from the group consisting of urea, sodium salicylate and pyrrolidone carboxylic acid, a water-soluble polymer, a higher alcohol, a lipophilic nonionic surfactant, and a silicone oil. An external preparation for skin characterized by being blended. 2. The content of the water-soluble polymer is 0.15% by weight.
The emulsion preparation for external use on the skin according to claim 1, which is the above. 3. The emulsion preparation for external use on the skin according to claim 1, wherein the water-soluble polymer is a carboxyvinyl polymer. 4. The emulsion preparation for external use on the skin according to claim 1, wherein the higher alcohol is one or more selected from the group consisting of cetanol, stearyl alcohol, myristyl alcohol, behenyl alcohol, and cetostearyl alcohol. 5. The emulsified preparation for external use on the skin according to claim 1, wherein the lipophilic nonionic surfactant is glycerin monofatty acid ester. 6. The silicone oil has a viscosity of 50 mPa at room temperature.
The emulsion preparation for external use on the skin according to claim 1 or 2, which is not more than s. 7. The method for producing an external preparation for skin according to claim 1, comprising, after the emulsifying step, a step of stirring and cooling at least a mixed component containing a water-soluble polymer from a temperature of 50 ° C. or higher. A method for producing an emulsion preparation for external use on the skin, characterized by comprising: 8. The method according to claim 7, wherein the stirring method in the stirring and cooling step is homomixer stirring.