JPH0774144B2 - Skin composition containing urea - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION (Field of Industrial Application) The present invention relates to a novel dermatological composition characterized by containing urea in a stable manner.

More specifically, the present invention relates to a "urea-containing dermatological composition" which is useful as a base of a cream, or as a cream drug which can be applied to the treatment of various skin diseases even if the composition itself is used.

(Prior Art) As a prior art of a composition containing urea, JP-A-46-
11010, 51-48441, 52-105225, 55-5092
5, JP-A-55-122753, JP-B-56-30326, JP-A-58-16
7508 and 59-1347412 exist.

However, all of these prior arts incorporate various stabilizers in order to stabilize urea. However, the compounding of these stabilizers has a drawback that it is necessary to consider the reaction with the drug compounded in the cream, and thus the compounded drug is limited. In addition, there are examples of addition of inert water-soluble powders, but the amount of water is extremely small, leaving a problem in spreadability to the skin, stickiness, and transdermal absorbability of drugs, and adding a large amount of water. Of course, it cannot be applied to a composition containing urea.

In addition, it is a feature of the known art that a large amount of an electrically conductive substance that is greatly involved in the hydrolysis of urea is mixed.

Here, a composition containing urea and electrical conductivity will be briefly described.

It has been said that in a hydrophilic cream preparation containing a large amount of water, it is essential to mix an electrically conductive substance such as an electrolyte, an acidic substance or an alkaline substance in consideration of emulsion stability and feeling of use. However, the existence of a correlation between the electric conductivity and the hydrolysis rate of urea can be easily inferred from various literatures. Therefore, in the composition containing urea, the composition of the electrically conductive substance is Considering the stability of urea, it is completely unfavorable and must be judged as a contraindication.

Also, in the conventional hydrophilic cream, it has been attempted to neutralize organic acids such as stearic acid and carboxyvinyl polymer with an alkali to make soap for the purpose of improving the emulsion stability. When it is applied to a composition containing urea, even if the pH of the composition is adjusted using a pH adjusting agent or a buffering agent, the hydrolysis of urea is prevented. Have difficulty.

Similarly, in the conventional cream composition, there are many examples in which an ionic surfactant or an ester-based nonionic surfactant is blended, but when this is also applied to a composition containing urea, decomposition of urea occurs. And its use is not preferred.

(Problems to be Solved by the Invention) The present invention solves the drawbacks of the above-mentioned conventional techniques.
It is intended to obtain a "urea-containing skin composition".

More specifically, (1) no urea stabilizer is blended, (2) no highly electrically conductive substance is blended, (3) a large amount of water is blended, (4) emulsion stability, feeling of use, It is an object of the present invention to obtain a dermatological composition which satisfies conditions such as good transdermal absorbability of a drug and which can stabilize urea.

(Means for Solving Problems) The present inventor has earnestly studied for a skin composition such as a urea cream and a base for cream, in which urea is stably retained without blending a stabilizer. Although it has been repeated, focusing on the compounding recipe in which the electrical conductivity of the composition is the smallest, and further research has been made, the limited novel composition of the invention of the present application sufficiently satisfies the above-mentioned object and the conventional cream The present invention has been completed by finding that all the drawbacks of the composition are eliminated.

Now, the present invention relates to a skin composition comprising a hydrocarbon, a higher alcohol, an ether type surfactant, water and urea.

Hereinafter, each of the skin compositions will be described in detail.

As the hydrocarbon, white petrolatum, liquid paraffin, squalane, plastibase and the like may be used alone or in combination of 1 or more.
50% (weight% based on the composition of the present application, the same applies hereinafter), preferably 5 to 20% of white petrolatum and 0 to 10% of liquid paraffin or squalane, respectively.

As the higher alcohol, cetanol, stearyl alcohol, lauryl alcohol, 2-hexyldecanol, isostearyl alcohol, cetostearyl alcohol, oleyl alcohol, 2-octyldodecanol, behenyl alcohol, lanolin alcohol, cholesterol and the like can be used alone or in combination of 2 or more. 20%, preferably 5 to 15% of cetanol or stearyl alcohol, each alone or in a mixture of equal amounts.

Examples of ether type nonionic surfactants include polyoxyethylene alkyl ethers [eg, polyoxyethylene (20) cetyl ether, polyoxyethylene (23) cetyl ether, polyoxyethylene (25) cetyl ether, polyoxyethylene (20 ) Oleyl ether, polyoxyethylene (20) phytostyrene, polyoxyethylene (9) lauryl ether, etc.], polyoxyethylene polyoxypropylene alkyl ether, for example, polyoxyethylene (20) polyoxypropylene (8) cetyl ether, Polyoxyethylene (20) polyoxypropylene (4) cetyl ether, etc.], polyoxyethylene alkylphenyl ether [eg, polyoctyethylene (15) nonylphenyl ether, etc.] or a mixture of 0.5 to 10 % Together they are preferably polyoxyethylene (20) cetyl ether, or polyoxyethylene (23) cetyl ether are blended 1-5%. The ether type nonionic surfactant to be blended in the present invention preferably has an HLB value of 10 to 20.

Next, the blending amount of water is 50 to 80%.

The amount of urea compounded in the composition of the present invention is 1 to 30%.

A novel skin composition containing the urea of the present invention is obtained by blending the above-mentioned composition in the described amount, and the composition is unpublished and can be easily thought of. Not considered an invention.

When the present invention is used as a cream base, the agents to be added to it are dissolved in a dissolving agent such as crotamiton, benzyl alcohol, peppermint oil, salicylic acid glycol ester, isopropyl adipate, diisopropyl sebacate, and diethyl sebacate. You may use it.

Further, the composition of the present invention contains a preservative such as methylparaben, ethylparaben, propylparaben, butylparaben, isopropylmethylphenol, and chlorobutanol.
Also, dibutylhydroxytoluene, dl-α-tocopherol, propylic gallate and the like may be used together as antioxidants.

When the composition of the present invention is used as a base for creams, the drug that can be added to it is not particularly limited, and any drug can be applied.

Incidentally, as an example, lidocaine, procaine, mepivacaine, dibucaine, local anesthetics such as tetracaine,
Steroid anti-inflammatory agents such as prednisolone, dexamethasone, triamnocylonone, flumethasone, fluocinonide, betamethasone valerate, fluocinolone acetolide, hydrocortisone acetate, clobetasol propionate, methyl salicylate, salicylate glycol ester, ibuprofen, indomethacin, flurubi. Non-steroidal anti-inflammatory agents such as profen, naproxen, piroxicam, tolnaftate, antimicrobial agents such as clotrimazole, miconazole, isoconazole, econazole, trifonazole, erythromycin, penicillin, tetracycline, chloramphenicol and other antibiotics, etc. , And these can be freely blended without any conditions. Drugs that are particularly susceptible to hydrolysis, such as betamethasone valerate, fluocinolone acetonide, fluocinonide, clobetasol propionate,
When a drug having an ester bond, such as indomethacin, methyl salicylate, glycol salicylate, and clotrimazole, is compounded, unprecedented good results and usefulness can be expected.

Next, a method for producing the skin composition of the present invention will be described.

In the production of the dermatological composition of the present invention, the oil phase component and the water phase component, which are the conventional methods for producing a cream, are 60 to 60 times, respectively.
The method of heating to 90 ° C. and emulsifying causes hydrolysis of urea, which is not preferable at all.

Therefore, in the present invention, first, the oil phase is heated to 60 to 90 ° C. to be uniformly dissolved, and the water phase heated to 60 to 90 ° C. is added to this while stirring to emulsify. Then, after emulsification, the mixture is heated to 50 ° C.
When the following temperature is reached, urea in which water is dissolved is added separately and mixed by stirring to obtain the composition of the present invention.

Incidentally, in the above method, of course, a method of adding an oil phase to the water phase may be used. Further, when the composition of the present invention is used as a base for creams, the method of incorporating a drug into the composition may be mixing in the oil phase, and when urea is added, it may be incorporated simultaneously or separately. You may.

(Action, Effect) The “urea-containing skin composition” of the present invention is: 1. As a medicinal product of a cream containing urea as an active ingredient,
In addition, 2. Each is industrially useful as a base for creams, and the details of its action and effect are as follows.

(1) Effective in treating skin diseases such as atopic eczema, keratosis, ichthyosis, psoriasis.

(2) The blended urea has good stability (particularly thermal stability), and therefore has an effect that a long-term storage is possible and a useful drug or base is obtained.

(3) Since a large amount of water is blended, vanishing is quick as in the case of a usual hydrophilic cream, and there is no stickiness or stickiness, and the feeling of use is good.

(4) When used as a base for creams, it has the effect of enhancing the stability and transdermal absorbability of the drug to be blended.

To further explain the above effects, the test results for the dermatological composition of the present invention are shown.

Test Example 1 Test Method 5 g of the composition obtained in Example 1 and commercially available urea creams A and B were filled in a tube and stored at 40 ° C., and the residual amount of urea and the appearance change of the tube were changed with time. I observed.

The results are shown in Table 1.

As is clear from Table 1, the dermatological composition of the present invention is more stable than commercially available urea creams.

Test Example 2 Test Method The cream of Example 3 in which the dermatological composition of the present invention was used as a base for a cream was tested for stability of urea and a drug over time under storage conditions at 40 ° C.

The results are shown in Table 2.

From Table 2, it is clear that the cream using the dermatological composition of the present invention as a base enhances not only the stability of urea but also the stability of drugs susceptible to hydrolysis.

(Examples) In order to describe the present invention in more detail, examples will be shown below. In addition, Examples 1 and 2 are examples in which the composition of the present invention is compounded and formulated as a medicine for a cream, and Examples 3 to 7 use the composition of the present invention as a base for a cream, and a drug is added thereto. The examples are shown below.

Example 1 White petrolatum (15 g), cetostearyl alcohol (10 g), liquid paraffin (5 g), polyoxyethylene (23) cetyl ether (3 g) and methylparaben (0.2 g) were heated to 80 ° C. and uniformly dissolved. To this, 52.8 g of purified water heated to 80 ° C is added and emulsified with a homogenizer. After completion of the emulsification, 5 g of urea dissolved in 10 g of purified water at 45 ° C. was added and further stirred to obtain a composition of the present invention.

Example 2 White petrolatum 15 g, cetanol 4.5 g, stearyl alcohol 4.5 g, squalane 3 g, polyoxyethylene (23) cetyl ether 2 g, and methyl paraben 0.2 g were heated to 80 ° C.,
Dissolve uniformly. To this, 56.8 g of purified water heated to 80 ° C is added, and the mixture is emulsified with a homogenizer. Urea at 45 ℃ after emulsification
What added 5g dissolved in 10g of purified water was added, and further stirred,
A composition of the invention was obtained.

Example 3 (Blending ratio: wt%) White petrolatum 15 Cetanol 5 Stearyl alcohol 5 Polyoxyethylene (23) cetyl ether 2 Liquid paraffin 2 Urea 5 Purified water 62.95 Crotamiton 3 Fluocinonide 0.05 Fluocinonide is dissolved in crotamiton by heating. Next, another oil phase is added and heated to 80 ° C to dissolve. Separately purified water 80
The mixture is heated to 0 ° C., added to the above oil phase with stirring, and then emulsified with a homogenizer. After completion of the emulsification, the mixture was cooled with stirring, urea dissolved in purified water was added at 45 to 50 ° C., and the mixture was further stirred to obtain an anti-flame cream.

Example 4 (Compounding ratio: wt%) Plastibase 14 Cetostearyl alcohol 10 Squalane 1 Polyoxyethylene (23) cetyl ether 3 Urea 10 Purified water 55.8 Indomethacin 1 Crotamiton 5 Methylparaben 0.2 Digestive analgesic cream according to the production method of Example 1. I got an agent.

Example 5 (blending ratio: wt%) White petrolatum 15 Cetostearyl alcohol 9 Liquid paraffin 3 Polyoxyethylene (23) cetyl ether 3 Urea 5 Purified water 62 Clotrimazole 1 Benzyl alcohol 2 According to the production method of Example 1. An antibacterial cream was obtained.

Example 6 (blending ratio: wt%) White petrolatum 15 Cetanol 4.5 Stearyl alcohol 4.5 Polyoxyethylene (23) cetyl ether 2 Urea 5 Purified water 62.9 Tetracycline 1 Crotamiton 5 Methylparaben 0.1 Antibacterial cream according to the production method of Example 1 Got

Example 7 (blending ratio: wt%) White petrolatum 15 Cetostearyl alcohol 10 Polyoxyethylene (23) cetyl ether 2 Liquid paraffin 5 Urea 5 Purified water 62.75 Clobetasol propionate 0.05 Methylparaben 0.2 The oil phase was heated to 80 ° C. Dissolve evenly. Next, after heating purified water to 80 ° C and adding to the above oil phase with stirring,
Emulsify with a homogenizer. After the emulsification is completed, the mixture is cooled with stirring, and clobetasol propionate suspended in a small amount of purified water is added at 50 ° C and the mixture is stirred. Next, urea dissolved in purified water was added and stirred to obtain an anti-inflammatory cream.

Claims (1)

[Claims] 1. A hydrocarbon content of 1 to 50% by weight, a higher alcohol of 2 to 20% by weight, an ether type nonionic surfactant of 0.5 to 10% by weight, water of 50 to 80% by weight, and urea of 1-3
A dermatological composition containing 0% by weight.