JPH09208462A - Autoadhesive cataplasm - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain an autoadhesive cataplasm high in absorbability along with sufficient tack force by formulating both polybutene and gelatin in a cataplasm base prescription based on water and a fatty acid dialkylolamide to stably incorporating diclofenac sodium in the base. SOLUTION: This cataplasm is obtained by formulating a cataplasm base with (A) pref. about 0.1-5.0wt.% diclofenac sodium, (B) pref. about 10-70wt.% water and (C) pref. 0.01-10wt.% a fatty acid dialkylolamide followed by both (D) pref. 0.5-5wt.% polybutene with a molecular weight of pref. about 400-6,000 and (E) pref. 0.5-5wt.% gelatin.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a self-adhesive poultice containing sodium diclofenac, and more particularly to a self-adhesive poultice having good absorbability of diclofenac sodium from the skin and having sufficient adhesive strength. .

[0002]

Diclofenac sodium is one of the most commonly used non-steroidal anti-inflammatory antipyretic and analgesic drugs at present, and oral agents and suppositories are clinically used. However, oral administration of diclofenac sodium has side effects such as gastrointestinal disorders and its use is limited.

In recent years, in order to solve the problems of oral administration of diclofenac sodium, various transdermal absorption preparations such as ointments and poultices containing this as an active ingredient have been studied and developed. The current situation is that a transdermal drug preparation of diclofenac sodium with sufficient effect and ease of use has not been obtained yet.

That is, for example, when sodium polyacrylate or sodium carboxymethyl cellulose, which is widely known as an adhesive base for poultices, is used as a base for poultices containing diclofenac sodium, the compatibility of these with diclofenac sodium. Since it was bad, it was easily crystallized, and sufficient transdermal absorption was not obtained.

Therefore, the present inventors conducted a search for a compound capable of dissolving diclofenac sodium and having excellent compatibility with the above water-soluble polymer base, and as a result, coconut oil fatty acid diethanolamide. And other fatty acid dialkyl amides have been found. However, although the compounding of diclofenac prevents the crystallization of diclofenac sodium in a poultice, diclofenac sodium inhibits the tackiness of the adhesive base, and the initial tack and persistent tackiness of the poultice base are impaired. Therefore, it was difficult to say that a practically satisfying poultice was obtained.

[0006]

SUMMARY OF THE INVENTION Therefore, a base which stably dissolves diclofenac sodium and has a persistently sufficient adhesive force was found, and development of a highly practical self-adhesive poultice has been demanded. .

[0007]

SUMMARY OF THE INVENTION In view of the above problems, the present inventors have proposed a PAP base that stably dissolves diclofenac sodium and has good initial tack and long lasting tackiness.
As a result of diligent research, if polybutene and gelatin were added to a Pap base formulation based on water and fatty acid dialkylolamide, stable dissolution of diclofenac sodium and sustained and high tackiness were achieved at the same time. The present invention has been completed by finding out that

That is, the present invention is a self-adhesive poultice which is characterized in that a poultice base is mixed with diclofenac sodium, water and oil fatty acid dialkylolamide, and polybutene and gelatin are further added. is there.

[0009]

BEST MODE FOR CARRYING OUT THE INVENTION The self-adhesive poultice of the present invention comprises:
It is prepared by further blending polybutene and gelatin into a Pap base blended with diclofenac sodium, water and fatty acid dialkyrolamide.

It is necessary to mix both polybutene and gelatin in the base, and in either case, sufficient tackiness cannot be obtained. The amount of polybutene is 0.5 to 5% by weight based on the poultice base.
(Hereinafter, simply indicated by "%"), and gelatin is 0.5% to 5%. When polybutene and gelatin are both 0.5% or less, sufficient tackiness cannot be obtained, and when they are 5% or more, the plaster, which is a PAP base, becomes too hard to mix and spread, Also, the absorbability of diclofenac sodium is reduced.

The above polybutene is a liquid polymer mainly composed of isobutylene and partly reacted with n-butene, and a polymer having a molecular weight of about 400 to 6000 can be preferably used. As for gelatin, those which are generally used can be used, and for example, those having a molecular weight of 20,000 to 1,000,000 (average 150,000)
0-200,000), jelly strength is 80-350
Some g can be used.

On the other hand, the base used in the preparation of the self-adhesive poultice of the present invention is a mixture of a usual poultice base with diclofenac sodium, water and fatty acid dialkyrolamide. The preferred amounts of these components in the poultice base are 0.1-5.0% diclofenac sodium and 10-70% water, respectively.
The fatty acid dialkylol amide is about 0.01 to 10%.

The fatty acid dialkylol amide to be added to the PAP base is a compound obtained by condensing a fatty acid and dialkylol amine, and the fatty acid portion thereof is coconut oil fatty acid, palm kernel oil fatty acid, palmitin. acid,
Examples include myristic acid, stearic acid, lauric acid, oleic acid, linoleic acid, isostearic acid, capric acid, and caprylic acid, and examples of the dialkylamine to be condensed include dilower alkanolamines such as diethanolamine and diisopropanolamine. To be

Preferred fatty acid dialkyrolamides include coconut oil fatty acid diethanolamide, palm kernel oil fatty acid diethanolamide, stearic acid diethanolamide, lauric acid diethanolamide, oleic acid diethanolamide, linoleic acid diethanolamide and isostearic acid diethanolamide. Can be mentioned. Among these, coconut oil fatty acid diethanolamide, lauric acid diethanolamide, and stearic acid diethanolamide are particularly preferable.

The above-mentioned poultice base includes, in addition to the above-mentioned components, well-known absorption promoters, inorganic fillers, pH regulators, polyhydric alcohols, water-soluble polymers, base additives, and stabilizers. Agents, emulsifiers, preservatives, solubilizers and the like can be included.

Examples of these additives include, for example, the following. Absorption enhancers: lauryl alcohol, oleyl alcohol, octyldodecanol, isopropyl myristate, diisopropyl adipate, diethyl sebacate, diisopropyl sebacate, propylene glycol caprate, medium chain fatty acid triglycerides, squalane, etc.

Organic filler: Kaolin, light anhydrous silicic acid, hydrous silicon dioxide, silicic acid anhydride, magnesium aluminometasilicate, aluminum hydroxide, aluminum glycinate, talc, titanium oxide, magnesium hydroxide, synthetic silicic acid Aluminum, bentonite, calcium carbonate, zinc oxide, etc.

PH regulator: tartaric acid, citric acid, malic acid, lactic acid, hydrochloric acid, phosphoric acid, acetic acid, fumaric acid, maleic acid, sodium hydroxide, ammonia, urea, ethylenediamine, diisopropanolamine, diethanolamine, triisopropanol Amines, triethanolamine, etc.

Polyhydric alcohols: propylene glycol, 1,3-butylene glycol, polyethylene glycol, sorbitol, glycerin, mannitol and the like.

Water-soluble high molecular weight: carboxymethylcellulose or salts thereof, polyacrylic acid or salts thereof, carboxyvinyl polymer or salts thereof, alginic acid or salts thereof, propylene glycol alginate ester, chitosan, hydroxypropylcellulose, hydroxypropylmethylcellulose, Hydroxyethyl cellulose, ethyl cellulose, methyl cellulose, polyvinyl alcohol, polyvinyl pyrrolidone, N-vinyl acetamide polymer, polyvinyl methacrylate, polyethylene glycol, pluronic, gelatin, methyl vinyl ether maleic anhydride copolymer, soluble starch, pullulan, methyl acrylate, acrylic acid- 2-
Ethylhexyl copolymer and the like.

Stabilizer: sodium edetate, citric acid, sodium citrate, oxybenzone, ascorbic acid, tocopherol, dibutylhydroxytoluene, butylhydroxyanisole, propyl gallate,
Sodium bisulfite and the like.

Interface activator: lecithin, lecithin derivative, propylene glycol fatty acid ester, glycerin fatty acid ester, sorbitan fatty acid ester, polyoxyethylene sorbitan fatty acid ester, polyethylene glycol fatty acid ester, polyoxyethylene hydrogenated castor oil, polyoxyethylene alkyl ether , Pluronic etc.

Preservatives: parabens such as methylparaben, ethylparaben, propylparaben, benzyl alcohol, benzalkonium chloride, benzethonium chloride,
Chlorobutanol, etc.

Dissolution aid: Lower alcohols such as ethanol and isopropyl alcohol.

In the self-adhesive type poultice of the present invention, polybutene and gelatin are added to the above-mentioned poultice base and sufficiently mixed, and this is applied to a support, and a release paper or the like is further attached to the surface of the plaster. It is prepared by

The support for the poultice is not particularly limited, and examples thereof include films or sheets of polyolefin, polyester, polyvinylidene chloride, polyurethane, polyvinyl alcohol, polyamide, etc., non-woven fabric, cotton cloth or laminated films or sheets thereof. Is mentioned.

The self-adhesive poultice of the present invention thus obtained has the active ingredient diclofenac dissolved in the plaster and has good absorption from the skin, and may be appropriately applied to the affected area. .

[0028]

EXAMPLES The present invention will be described below with reference to examples, but the present invention is not limited to these examples.

Example 1 Production of poultices: Inventive and comparative poultices were prepared with the compositions shown below. In the composition, Table 1 shows an invention product and Table 2 shows a comparative product.

(Invention Product 1) In a beaker, diclofenac sodium, coconut oil fatty acid diethanolamide and purified water in the amounts according to the compounding ratio shown in Table 1 were put and mixed to obtain a diclofenac sodium solution (solution A). In another beaker, gelatin in an amount according to the compounding ratio in Table 1 was dissolved in warm water or hot water to obtain a seratin solution (solution B).

In another beaker, sodium polyacrylate, sodium carboxymethyl cellulose, tartaric acid, aluminum hydroxide gel, polybutene, and oleyl alcohol were dispersed in propylene glycol in the amounts according to the compounding ratio shown in Table 1 to obtain a mixed solution ( Liquid C). Solution A, solution B, D-sorbitol solution and light anhydrous silicic acid were mixed with a spatula while stirring, and solution C was gradually added to obtain 1 kg of a uniform plaster. The obtained paste was spread on a non-woven fabric and covered with a plastic film to obtain a poultice.

(Invention product 2) In the production of the invention product 1,
It was prepared in the same manner except that lauric acid diethanolamide was used instead of coconut oil fatty acid diethanol. (Invention Products 3 to 5) In the production of Invention Product 1, sodium polyacrylate was reduced to 3.0% by weight, and polyvinyl alcohol, hydroxypropyl methylcellulose,
Alternatively, it was prepared by the same operation except that 1.0% by weight of N-vinylacetamide polymer was used.

(Comparative product 1) In the production of the invention product 1,
It was prepared by the same operation except that polybutene was not used and the amount thereof was adjusted with purified water. (Comparative product 2) In the manufacture of the invention product 1, the same procedure was used except that gelatin was not used and the amount was adjusted with purified water.

(Comparative products 3 to 11) In the production of the invention product 1, instead of gelatin and polybutene, a polymer generally known as an adhesive base (in Table 2, Nicazole T) was used.
S-620-casein sodium) was used, but the same procedure was used.

(Method)

[Table 1]

[0036]

[Table 2]

Example 2 Adhesiveness test of poultices: Inventive products 1 to 5 obtained in Example 1
And for the poultices of Comparative Products 1-11, tackiness was evaluated by examining their initial tack and persistent tackiness. Regarding the initial tack, the sticking and the functionality during sticking were examined. Table 3 shows the results.

(1) Evaluation of initial tack Adhesion test: A 10 × 14 cm poultice was applied to the arm, and when the poultice was dropped upside down, x was given, and the pasted one was ◯.
And Sensory test: A finger was pressed onto the plaster of the poultice and the tackiness when released was evaluated according to the following criteria.

(2) Evaluation of continuous tackiness A 10 × 14 cm poultice was vertically attached to a human knee, and the one that was applied for 8 hours or more was marked with ◯, and the one that was peeled off in the middle was marked with x.

(3) Result

Example 3 Efficacy test of poultice: Using rat carrageenin footpad edema model, anti-inflammatory effect of diclofenac sodium poultice of the present invention (Invention 1) and a commercial indomethacin preparation (Product name: Catrep Sumitomo Pharma) Were compared. The application area of each preparation was 3 × 3.9 cm, and the anti-inflammatory effect was shown by the edema suppression rate (%) 3 hours after the administration of carrageenin. The control used was one to which no poultice was applied. The results are shown in the table below.

[0042]

As is clear from the above results, the self-adhesive poultice of the present invention had an excellent anti-inflammatory action as compared with the indomethacin preparation already on the market (comparative product).

Example 4 A poultice of the composition shown in Table 5 was prepared, in which the ratio of polybutene and gelatin was changed. Each of the obtained poultices had excellent self-adhesiveness and transdermal absorbability.

(Composition)

Example 5 A poultice of Table 6 was obtained in which oleyl alcohol was replaced with another compound as the absorption enhancer. Each of the obtained poultices had excellent self-adhesiveness and transdermal absorbability.

(Composition)

Practical Example 6 Patching agent: A patching agent was prepared with the following composition and production method. (Composition) Amount (%) A Diclofenac sodium 2.0 Coconut oil fatty acid diethanolamide 2.0 Purified water 33.65 B Gelatin 3.0 Purified water 12.0 C D-sorbitol 30.0 Light anhydrous silicic acid 2.0 D oleyl alcohol 1.0 Propylene glycol 7.0 Sodium polyacrylate 5.0 Sodium carboxymethyl cellulose 1.0 Polybutene 1.0 Tartaric acid 0.15 Aluminum hydroxide 0.2

(Production method) A was mixed to obtain a transparent aqueous solution of diclofenac sodium. Next, B in another container
Was heated to obtain a gelatin solution. A, B and C were mixed, and the mixed solution of D was added with stirring to obtain a uniform gel.
This gel was spread on a non-woven fabric to obtain a poultice.

Practical Example 7 Pap agent: A poultice was prepared by the following composition and production method. (Composition) Amount (%) A Diclofenac sodium 1.5 Coconut oil fatty acid diethanolamide 1.5 Purified water 34.65 B Gelatin 3.0 Purified water 12.0 CD D-sorbitol 30.0 Light anhydrous silicic acid 2.0 D oleyl alcohol 1.0 1,3-butylene glycol 7.0 sodium polyacrylate 5.0 sodium carboxymethyl cellulose 1.0 polybutene 1.0 tartaric acid 0.15 aluminum hydroxide 0.2

(Production method) A was mixed to obtain a transparent aqueous solution of diclofenac sodium. Next, B in another container
Was heated to obtain a gelatin solution. A, B and C were mixed, and the mixed solution of D was added with stirring to obtain a uniform gel.
This gel was spread on a non-woven fabric to obtain a poultice.

Practical Example 8 Pap agent: A poultice was prepared by the following composition and production method. (Composition) Amount (%) A Diclofenac sodium 1.0 Coconut oil fatty acid diethanolamide 1.5 Purified water 32.15 B Gelatin 3.0 Purified water 12.0 CD D-sorbitol 30.0 Light anhydrous silicic acid 2.0 D oleyl alcohol 1.0 1,3-butylene glycol 10.0 sodium polyacrylate 5.0 sodium carboxymethyl cellulose 1.0 polybutene 1.0 tartaric acid 0.15 aluminum hydroxide 0.2

(Production method) A was mixed to obtain a transparent aqueous solution of diclofenac sodium. Next, B in another container
Was heated to obtain a gelatin solution. A, B and C were mixed, and the mixed solution of D was added with stirring to obtain a uniform gel.
This gel was spread on a non-woven fabric to obtain a poultice.

[0054]

The self-adhesive poultice of the present invention has a good absorption of diclofenac sodium and has an adhesive strength such that it does not peel off from the skin without using other fixing means. Therefore, it can be extremely advantageously used as a percutaneous absorption preparation of diclofenac sodium. that's all

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification code Office reference number FI Technical display location A61K 9/70 369 A61K 9/70 369 47/16 47/16 G 47/32 47/32 Z 47 / 42 47/42 Z (72) Inventor Kazuyuki Ishikawa 3586 Yoshiwara, Ami-cho, Inashiki-gun, Ibaraki Tsumura Co., Ltd. (72) Inventor Takaaki Matsumoto 3586 Yoshihara, Ami-cho, Inashiki-gun, Ibaraki Tsumura Co., Ltd.

Claims (1)

[Claims] 1. A self-adhesive poultice, characterized in that, in the poultice base, diclofenac sodium, water and fatty acid dialkylolamide are blended, polybutene and gelatin are further added.