JPH05148147A - Steroidal external agent - Google Patents

Abstract

PURPOSE:To provide the subject agent excellent in the percutaneous absorbability and the touch by adding a carboxyvinyl polymer and an organic amine to an aqueous alcohol solution containing borneol and/or eucalyptus oil and a steroidal antiinflammatory agent. CONSTITUTION:An aqueous alcohol solution containing 0.1-5wt.% of borneol and/or eucalyptus oil and 0.01-2wt.% of a steroidal antiinflammatory agent (e.g. dexamethasone acetate) is compounded with 0.5-3wt.% of a carboxyvinyl polymer and further with an organic amine (e.g. triethanolamine) to produce the water-soluble gel steroidal external agent having a pH of 3-8 and eliminated in the irritation. The agent was reduced in the tackiness at the time of coating on skins, gives an excellent refreshing feeling, gives a good touch and is excellent in the percutaneous absorbability of the steroid.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to an improved steroidal external preparation.

[0002]

2. Description of the Related Art Since steroidal anti-inflammatory drugs are poorly soluble in water, an oily base is used as a base for external preparations.
However, since the oily base is sticky, the feeling of use is poor,
This discomfort is especially noticeable in the summer. Although an external preparation for a water-soluble gel using carboxyvinyl polymer has been developed in order to improve this drawback, transdermal absorption of the main drug is not always sufficient.

[0003]

DISCLOSURE OF THE INVENTION In view of the above-mentioned drawbacks of conventional steroidal external preparations, the present invention provides a water-soluble steroidal steroidal gel having excellent transdermal absorbability and excellent refreshing feeling. It was made for the purpose of providing an external preparation.

[0004]

Means for Solving the Problems As a result of intensive studies, the present inventors have found that transdermal absorption of a steroidal anti-inflammatory drug is remarkable in an aqueous solution gel formulation using an aqueous alcohol solution of borneol and eucalyptus oil. The present invention has been completed, paying attention to the fact that it has the function of accelerating to, and is excellent in the feeling of use and has less irritation to the skin.

According to the invention, borneol and / or eucalyptus oil 0.1-5.0% by weight and steroidal anti-inflammatory 0.1% are used.
In an alcohol aqueous solution containing 01 to 2.0% by weight,
It is a steroidal external preparation containing 0.5 to 3.0% by weight of carboxyvinyl polymer and an organic amine necessary for adjusting the pH of the final composition within the range of 3.0 to 8.0.

The amount of borneol or eucalyptus oil used in the present invention can be appropriately selected within the range of 0.1 to 5.0% by weight of the total amount of the external preparation, but preferably 0.25 to 1.0% by weight. When the content is 10.0% by weight or more, the solubility of the steroidal anti-inflammatory drug in the base increases, the release from the base decreases, and the odor becomes too strong to be used. Borneol or eucalyptus oil can be used alone within the above-mentioned range of use, or can be used by mixing them at any ratio. As the alcohol aqueous solution, an aqueous solution of a lower alcohol such as ethanol, isopropanol or methanol is used. Ethanol is particularly preferred. The amount of alcohol is usually 5 to 50% by weight, preferably 10 to 30% by weight, and the amount of water is usually 5 to 95% by weight, preferably 30 to 50% by weight. The aqueous alcohol solution may be mixed with other water-miscible organic solvent such as glycols for the purpose of dissolving the drug and improving the feeling of use of the water-soluble gel. Preferred examples of glycols include 1,3-butanediol, propylene glycol, macrogol 300, and macrogol 40.
0, glycerin and the like.

Carboxyvinyl polymer is an acidic polymer compound mainly produced by polymerization of acrylic acid, and when quantified by drying, carboxy group is 58.0 to 63.0.
%including. When the carboxyvinyl polymer is dispersed in water, it becomes a highly viscous liquid, and when the triethanolamine solution is added while stirring, it becomes a strongly viscous liquid, a water-soluble gel.

The amount of the carboxyvinyl polymer used can be appropriately selected within the range of 0.5 to 3.0% by weight of the total amount of the external preparation, but 1 to 2% by weight is preferable. Examples of the steroidal anti-inflammatory drug include prednisolone, hydrocortisone, dexamethasone, triamcinolone, fluocinonide, betamethasone, and esters thereof, and dexamethasone acetate is particularly preferable. The amount used is the amount necessary for the onset of drug efficacy, and is usually 0.01 to 2.0 of the total amount of the external preparation.
% By weight, preferably 0.01 to 1.0% by weight. The pH of the external preparation is adjusted to 3.0 to 8.0 to eliminate irritation. The pH adjusting agent can be used without particular limitation as long as it is harmless and is not irritating, but organic amines such as triethanolamine and diisopropanolamine are preferable.

The steroidal external preparation of the present invention is prepared according to a conventional method. For example, a given amount of borneol and /
Alternatively, eucalyptus oil and a steroidal anti-inflammatory drug are dissolved in an aqueous alcohol solution, and a predetermined amount of carboxyvinyl polymer and an organic amine are added to the resulting solution and the mixture is stirred to obtain a water-soluble gel-like external steroidal preparation.

[0010]

Example Each steroidal external preparation having the following composition was prepared by the conventional method described above.

Example 1 Dexamethasone acetate 0.025 parts by weight Eucalyptus oil 0.5 parts by weight Carboxyvinyl polymer 1.5 parts by weight Triethanolamine 0.5 parts by weight 1,3-butanediol 30.0 parts by weight Absolute ethanol 20. 0 parts by weight Macrogol 400 10.0 parts by weight Purified water Residual amount 100 parts by weight

Example 2 Dexamethasone acetate 0.025 parts by weight Borneol 0.5 parts by weight Carboxyvinyl polymer 1.5 parts by weight Diisopropanolamine 0.4 parts by weight 1,3-butanediol 30.0 parts by weight Absolute ethanol 20.0 parts by weight Parts by weight Macrogol 400 10.0 parts by weight Purified water Residual amount 100 parts by weight

Example 3 Dexamethasone acetate 0.025 parts by weight Eucalyptus oil 0.5 parts by weight Carboxyvinyl polymer 1.5 parts by weight Triethanolamine 0.5 parts by weight Methanol-modified alcohol 20.0 parts by weight Polyoxyethylene hydrogenated castor oil 50 5.0 parts by weight Purified water Residual amount 100 parts by weight

Example 4 Dexamethasone acetate 0.025 parts by weight Dibucaine hydrochloride 0.3 parts by weight Diphenhydramine hydrochloride 1.0 parts by weight Glycyrrhetinic acid 0.3 parts by weight Isopropylmethylphenol 0.1 parts by weight 1,3-butanediol 30.0 Parts by weight absolute ethanol 20.0 parts by weight Macrogol 400 10.0 parts by weight carboxyvinyl polymer 1.5 parts by weight polyoxyl stearate 40 4.0 parts by weight diisopropanolamine 0.4 parts by weight eucalyptus oil 0.5 parts by weight purification Water balance 100 parts by weight

Example 5 Dexamethasone acetate 0.1 parts by weight Eucalyptus oil 3.0 parts by weight Carboxyvinyl polymer 2.5 parts by weight Triethanolamine 1.0 parts by weight Propylene glycol 20.0 parts by weight Isopropanol 30.0 parts by weight Glycerin 5 0.0 parts by weight Purified water Residual amount 100 parts by weight

Example 6 Prednisolone 0.2 parts by weight Borneol 2.0 parts by weight Carboxyvinyl polymer 1.0 parts by weight Triethanolamine 0.3 parts by weight Propylene glycol 30.0 parts by weight Methanol-modified alcohol 10.0 parts by weight Macrogol 300 30.0 parts by weight Purified water Residual amount 100 parts by weight

Comparative Example 1 A steroidal external preparation containing 0.025% by weight of a commercially available dexamethasone acetate and a carboxyvinyl polymer.

Comparative Example 2 Carboxyvinyl polymer 1.5 parts by weight Diisopropanolamine 0.4 parts by weight 1,3-butanediol 30.0 parts by weight Absolute ethanol 20.0 parts by weight Macrogol 400 10.0 parts by weight Purified water Balance 100 parts by weight

Comparative Example 3 Dexamethasone acetate 0.025 parts by weight Eucalyptus oil 10.0 parts by weight Carboxyvinyl polymer 1.5 parts by weight Triethanolamine 0.5 parts by weight 1,3-butanediol 30.0 parts by weight Absolute ethanol 20 .0 parts by weight Macrogol 400 10.0 parts by weight Purified water Residual amount 100 parts by weight

Test Example 1 (Usability test) Four kinds of sensory sensations, namely, a refreshing feeling when the external preparations of Example 1 and Comparative Example 1 were applied to the skin using 20 volunteers, a feeling of application, stickiness, and comprehensive judgment The test was conducted. The test was carried out by applying 0.1 g of each reagent so that the upper arms, which had been washed with water and dried well, did not overlap each other, and the feeling during use was preferred (+2), somewhat preferred (+1), normal (0), slightly Unfavorable (-1), unfavorable (-
It was determined by 2) and scored.
The results are shown in Figure 1. As is clear from FIG. 1, Example 1 exceeded the feeling of use of the external preparation of Comparative Example 1 for all the items. The other pharmaceutical preparations according to the present invention also showed similar excellent effects.

Test Example 2 (Absorption Test) The transdermal absorption reagents of the external preparations of Examples 1 and 2 and Comparative Examples 1 and 2 were carried out by a Mackenzie test using 4 volunteers. In the test, 0.1 g of each sample was closed-patched on the inside of the left forearm of each test subject using a patch test adhesive bandage (small size), peeled after 20 hours of patching, and 1, 4 and 8 hours after peeling. Regarding the vasoconstriction reaction, no reaction was scored as 0, light pallor was recognized as 1, and clear pallor was recognized as 2.
It was done by scoring. The results are shown in Table 2.
In FIG. 2, the horizontal axis represents the elapsed time after peeling and the vertical axis represents the total score. As is clear from FIG. 2, in comparison with the external preparations of Comparative Example 1 and Comparative Example 1, in Example 1 and Example 2, the drug effect continues even 8 hours after peeling, and good transdermal absorbability is exhibited. Indicated. In particular, the external preparation of Example 2 was significantly effective. The other pharmaceutical preparations according to the present invention also showed similar excellent effects.

Test Example 3 (Release Test) The release properties of steroids from each of the external preparations of Example 1 and Comparative Example 3 were compared with each other by using a release tester having a translucent cellulose acetate film. did. Results are shown in FIG. Figure 3
As is apparent from the above, Example 1 is superior to the external preparation of Comparative Example 3 in that
It was found that the release was excellent. The other pharmaceutical preparations according to the present invention also showed similar excellent effects.

Industrial Applicability As described above, the external preparation of the steroid of the present invention has less stickiness when applied to the skin, has a good feeling in use, and has excellent transdermal absorption of steroid.

[Brief description of drawings]

FIG. 1 is a graph showing the results of the usability test of the external preparations of Example 1 and Comparative Example 1.

FIG. 2 is a graph showing the results of percutaneous absorption of the external preparations of Examples 1 and 2 and Comparative Examples 1 and 2.

FIG. 3 is a graph showing the release results of the external preparations of Example 1 and Comparative Example 3.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁵ Identification number Office reference number FI technical display location A61K 47/32 E 7329-4C F 7329-4C

Claims (1)

[Claims] 1. Borneol and / or eucalyptus oil 0.1-5.0% by weight and steroidal anti-inflammatory drug 0.01-
An aqueous alcohol solution containing 2.0% by weight of an organic solvent necessary to adjust the pH of the carboxyvinyl polymer to 0.5 to 3.0% by weight and the final composition within the range of 3.0 to 8.0. A steroidal external preparation containing an amine.