JPH10130172A - Percutaneously absorbable pharmaceutical preparation - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain an excellent percutaneously absorbable pharmaceutical preparation having light stability while securing absorbability and applicability of medicines contained in the pharmaceutical preparation as well as storage stability of the preparation. SOLUTION: This percutaneously absorbable pharmaceutical preparation, the base of which contains an absorbefacient having an amide bond, comprises a gel or lotion base which contains a gelling agent composed of polycarboxylic acids, an absrobefacient composed of a fatty acid alkanolamide or a polyoxyethylene fatty acid alkanolamide in a quantity of 0.1-10wt.%, and an ultraviolet light absorbed in a quantity of 0.01-10wt.% based on the whole weight of the pharmaceutical preparation.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a transdermal preparation having excellent drug absorbability, utility, and stability, and also having excellent light stability.

[0002]

2. Description of the Related Art It is generally well known that a drug is transdermally absorbed in the form of a gel or lotion. In such transdermal absorption preparations, to express high drug absorption,
Transdermal absorption enhancers are widely added. For example, Japanese Patent Publication No. 7-59519 discloses a method in which an anionic surfactant and a surfactant having a nitrogen atom in a molecule are mixed at a fixed ratio. A skin absorption enhancer and an external preparation for skin containing the same are disclosed.

[0003] In general, gels and lotions as transdermal preparations have the advantage that they are easier to apply than ointments and the like, but they have good fluidity, so that it is difficult to accurately measure them. Since a drug is generally required to be administered in a precise dose, such a drawback as a transdermal preparation has been a very important problem. To solve this problem, single-use tubes have been proposed for gels and lotions. However, such a single-use tube is uneconomical because waste is generated depending on the number of uses, and the tube itself has environmental problems and, as a result, the container with the drug attached thereto is discarded. Therefore, in the case of a drug that exhibits an effect even in a small amount, there is a problem of environmental destruction and the like.

[0004] In recent years, a pump-type container that allows convenient collection of a used container and can be handled at the time of quantification of a drug has attracted attention. However, when a gel or a lotion containing a fatty acid or a polyoxyethylene fatty acid alkanolamide is used for a polycarboxylic acid base such as polyacrylic acid, the preparation may be discolored to yellow by light. . Therefore, such a preparation must always be preserved from light and cannot be stored in a transparent container, and thus there is a problem that the remaining amount of the drug cannot be confirmed. Since the remaining amount of the medicine provides important information such as the use state of the medicine and the timing of going to the hospital,
The problem in terms of convenience of use was significant.

[0005]

SUMMARY OF THE INVENTION In view of the above, an object of the present invention is to provide an excellent percutaneously absorbable preparation having photostability while ensuring the absorption, utilization and stability of the preparation. With the goal.

[0006]

The present invention relates to a transdermal preparation containing a drug and an absorption promoter having an amide bond in the molecule in a base, wherein the base is a polyvalent carboxylic acid. A gel base or a lotion base containing a gelling agent consisting of: a fatty acid alkanolamide or a polyoxyethylene fatty acid alkanolamide; and 0% of the whole percutaneous absorption preparation. .1
A percutaneous absorption preparation which contains 0.01 to 10% by weight of an ultraviolet absorber and 0.01 to 10% by weight of the whole percutaneous absorption preparation. Hereinafter, the present invention will be described in detail.

The percutaneous absorption preparation of the present invention contains a drug in a base and an absorption promoter having an amide bond in the molecule.
In the present invention, the base is a gel base or a lotion base containing a gelling agent composed of a polyvalent carboxylic acid. The polyvalent carboxylic acid is not particularly limited as long as it is within a pharmaceutically acceptable range, and includes, for example, polyacrylic acid, carboxymethyl cellulose, carboxymethyl starch, and the like. The content of the polycarboxylic acid in the gel base or lotion base is preferably 0.1 to 5% by weight. If it is less than 0.1% by weight, gelling will not occur, and if it exceeds 5% by weight, the spreadability of the gel will be poor, and the feeling of use will be significantly impaired.

Preferably, a neutralizing agent is added to the above base. The neutralizing agent is not particularly limited as long as it can gel the polycarboxylic acid, and examples thereof include inorganic bases and amines. Examples of the neutralizing agent include sodium hydroxide, diethanolamine, diisopropanolamine, and polyvinylpyrrolidone. Is preferably used. It is preferable to add the neutralizing agent in such an amount that the pH of the base becomes 4 to 8. p
When H is less than 4 or more than 8, irritation to skin becomes strong. If necessary, an inorganic filler such as silicic acid, zinc oxide, or titanium oxide, a humectant such as sorbitol, a viscosity modifier, or the like may be added to the base.

The drug contained in the base is not particularly limited as long as it is a drug that acts by being taken into the blood or a drug that acts locally at the site of administration.
Hypnotics and sedatives such as sodium thiopental and sodium pentobarbital; antiepileptics; analgesics such as morphine, codeine, acetanilide, aminopyrine, aspirin; anti-inflammatory analgesics such as indomethacin, diclofenac sodium, ketoprofen, piroxicam; hydrocortisone, prednisolone, dexamethasone Steroidal anti-inflammatory drugs such as methamphetamine;
Stimulants; antipsychotics such as chlorpromazine, thioridazine, meprobamate, reserpine, chlordiazeboxide; muscle relaxants such as suxamethonium hydrochloride and eperisone hydrochloride; antispasmodics such as methylatropine bromide and scopolamine;
Antiparkinson agents such as chlorzoxazone and levodopa; antifungal agents such as naphthemate and clotrimazole; antibiotics such as penicillin, cephalosporin, erythromycin, streptomycin; antihistamines such as difendamine hydrochloride and chlorferamine maleate; Cardiotonic drugs such as dichitocin and digoxin; antiarrhythmic drugs such as procainamide hydrochloride, lidocaine hydrochloride, propranolol hydrochloride, metoprolol tartrate, and atenolol; diuretics such as hydroflumethiazide and furosemide; Antihypertensive drugs, vasoconstrictors such as phenylephrine hydrochloride; vasodilators such as diltiazem hydrochloride, isosorbide dinitrate, nicorandil, nitroglycerin, and trazoline hydrochloride; anti-atherosclerotic drugs; Lumpur, isoproterenol hydrochloride, antitussive 啖薬 such ketotifen fumarate; glycopyrronium bromide, cimetidine, anti-peptic ulcer drugs such Supizofuron;
Hormones such as progesten, stanozolol, estriol, and distosterone; hemorrhoids; wound protectants; antipruritics; emollients; vitamins such as vitamin A, vitamin B, and vitamin C; Anti-diabetic agents such as tributamide, chlorpropamide, sodium glidisin, and insulin; anti-neoplastic agents such as 5-fluorouracil, cyclophosphamide, actinomycin; cytokines Substances and the like.

The concentration of the above-mentioned drug in the above-mentioned percutaneous absorption preparation is as follows:
Depending on the type of drug used, it is usually 0.0
1-10% by weight is preferred. If the amount is less than 0.01% by weight, sufficient drug absorbability cannot be obtained. Extremely damaging. More preferably, it is 0.05 to 5% by weight.

In the present invention, an absorption promoter having an amide bond in the molecule is used. The absorption promoter is not particularly limited, and examples thereof include fatty acid alkanolamides and polyoxyethylene fatty acid alkanolamides, among which fatty acid diethanolamide is preferred. The above-mentioned absorption enhancer contains 0.1% of the whole percutaneous absorption preparation.
It is contained in an amount of 1 to 10% by weight. If it is less than 0.1% by weight, a sufficient accelerating effect cannot be obtained, and if it exceeds 10% by weight, the pH becomes too high and gelation becomes difficult, so the content is limited to the above range. More preferably, it is 0.5 to 7% by weight.

The percutaneous absorption preparation of the present invention contains an ultraviolet absorber. The ultraviolet absorber is not particularly limited as long as it is pharmaceutically acceptable. For example, compounds that chemically absorb in the UV region, for example, benzophenone-based compounds,
Examples thereof include p-aminobenzoic acid, cinnamic acid, salicylic acid, and urocanic acid.

Examples of the above-mentioned benzophenone-based ultraviolet absorber include 2-hydroxy-4-methoxybenzophenone and 2-hydroxy-4-methoxybenzophenone.
5-sulfonic acid, sodium 2-hydroxy-4-methoxybenzophenone-5-sulfonate, 2,2'-dihydroxy-4,4'-dimethoxybenzophenone,
Sodium 2'-dihydroxy-4,4'-dimethoxybenzophenone-5-sulfonate, 2,4-dihydroxybenzophenone, 2,2 ', 4,4'-tetrahydroxybenzophenone and the like can be mentioned. Examples of the cinnamic acid-based ultraviolet absorber include methoxycinnamic acid-2-
Ethylhexyl, 2-ethoxyethyl 4-methoxycinnamate and the like. Examples of the salicylic acid-based ultraviolet absorber include 2-ethylhexyl salicylate,
Examples thereof include phenyl salicylate and homomenthyl salicylate.

The content of the ultraviolet absorbent is 0.01 to
10% by weight. If it is less than 0.01% by weight, a sufficient ultraviolet absorbing effect cannot be obtained, and if it exceeds 10% by weight,
The precipitation is limited to the above range because precipitation of crystals or the like occurs and gives a problem to the usability. More preferably, it is 0.02 to 5% by weight.

[0015] The addition of the ultraviolet absorber suppresses yellowing of the transdermal absorption preparation due to light, and makes it possible to use a transparent pump-type container as a container for the transdermal absorption preparation. The percutaneous absorption preparation stored in such a transparent container is extremely convenient because the user can clearly determine the remaining amount of the drug.

[0016]

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

Example 1 40 g of ethanol, 30 g of propylene glycol, and 1 g of carboxyvinyl polymer (Hibiswako 104, manufactured by Wako Pure Chemical Industries) were rotated for 150 minutes using a homomixer (manufactured by Tokushu Kika Kogyo Co., Ltd.). And stirred. Thereafter, 0.5 g of norethisterone acetate, 1 g of lauric acid diethanolamide (STAFATE DL, Nippon Oil & Fat), 2-g
0.02 g of hydroxy-4-methoxybenzophenone was charged into the solution, and the mixture was further stirred for 60 minutes. Finally, 27.48 g of water in which 0.2 g of sodium edetate was dissolved was added, and the mixture was rotated and stirred for 150 minutes to prepare an ointment. The coloring property of the obtained transdermal absorption preparation was evaluated by the following method, and the results are shown in Table 1.

Evaluation of coloring properties About 50 g of the obtained transdermal absorption preparation was sealed in a transparent pump container (manufactured by Hanshin Containers Co., Ltd.), and a mercury lamp (300, 360, 4
00 and 440 nm emission line spectra) with an illuminance of 6
It stored at 25 degreeC under 0000 lx irradiation. As an initial sample, one protected from light with an aluminum packaging material was stored at 4 ° C. After 14 days, the sample was taken out and the degree of coloring of the initial sample was evaluated. The samples that were more colored than the initial samples were represented by 10, and those that did not change were represented by 1.

Example 2 1 g of 2-hydroxy-4-methoxybenzophenone
Then, a percutaneous absorption preparation was prepared and evaluated in the same manner as in Example 1 except that the amount of distilled water was changed to 26.5 g. The results are shown in Table 1.

Example 3 5 g of 2-hydroxy-4-methoxybenzophenone
Example 1 except that distilled water was changed to 22.5 g.
A percutaneous absorption preparation was prepared and evaluated in the same manner as described above. The results are shown in Table 1.

Example 4 A transdermal preparation was prepared in the same manner as in Example 2 except that norethisterone acetate was changed to desestosterone.
evaluated. The results are shown in Table 1.

Example 5 A transdermal preparation was prepared and evaluated in the same manner as in Example 2 except that norethisterone acetate was changed to procaterol hydrochloride. The results are shown in Table 1.

Example 6 A transdermal preparation was prepared and evaluated in the same manner as in Example 1, except that lidethine was used instead of norethisterone acetate. The results are shown in Table 1.

Comparative Example 1 2-hydroxy-4-methoxybenzophenone was added in an amount of 0.00
5g and distilled water was changed to 27.5g,
A percutaneous absorption preparation was prepared and evaluated in the same manner as in Example 1. The results are shown in Table 1.

Comparative Example 2 15 g of 2-hydroxy-4-methoxybenzophenone
A percutaneous absorption preparation was prepared and evaluated in the same manner as in Example 1 except that distilled water was changed to 12.5 g. In the obtained transdermal absorption preparation, the ultraviolet absorber could not completely dissolve,
Ultraviolet absorber crystals were floating in the gel. The results are shown in Table 1.

[0026]

[Table 1]

[0027]

EFFECT OF THE INVENTION Since the transdermal preparation of the present invention has the above-mentioned constitution, it also has photostability while ensuring the absorption, utilization and stability of the drug, and is particularly transparent. Since it can be stored in a simple container, the convenience is extremely high.

Claims (2)

[Claims] 1. A percutaneous absorption preparation containing a drug and an absorption promoter having an amide bond in a molecule in a base, wherein the base contains a gelling agent composed of a polyvalent carboxylic acid. A gel base or a lotion base, wherein the absorption enhancer comprises a fatty acid alkanolamide or a polyoxyethylene fatty acid alkanolamide, and
0.1 to 10% by weight of the whole percutaneous absorption preparation, and the ultraviolet absorbent is contained in 0.0% by weight of the whole percutaneous absorption preparation.
A percutaneous absorption preparation characterized by containing 1 to 10% by weight. 2. A transdermally absorbable preparation according to claim 1, which is contained in a transparent container.