JP2002193793A - Non-steroidal antiinflammatory analgesic plaster - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a plaster containing at least one kind of non-steroidal antiinflammatory analgesic agents belonging to phenylpropionic acid and selected from among ibuprofen, ketoprofen, suprofen, loxoprofen sodium, fenoprofen and flurbiprofen or diclofenac sodium or piroxicam and having excellent storage stability of the drug component. SOLUTION: At least one kind of non-steroidal antiinflammatory analgesic agents belonging to phenylpropionic acid and selected from among ibuprofen, ketoprofen, suprofen, loxoprofen sodium, fenoprofen and flurbiprofen or diclofenac sodium or piroxicam is dissolved in polyethylene glycol and homogeneously dispersed in a tacky substrate to obtain a plaster having excellent storage stability of the non-steroidal antiinflammatory analgesic agent included in the tacky substrate.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a water-soluble patch having excellent storage stability of a nonsteroidal anti-inflammatory analgesic (excluding indomethacin) incorporated in a water-soluble patch and a method for producing the same.

[0002]

2. Description of the Related Art At present, various anti-inflammatory analgesics are used as remedies for pain associated with stiff shoulders and muscle fatigue, bruises, sprains and the like. Among them, non-steroidal anti-inflammatory analgesics are widely used not only as oral drugs but also as transdermal patches because of their excellent prostaglandin synthesis inhibitory activity, and their usefulness is highly evaluated. ing. However, these patches have a problem in storage stability. In other words, these patches are prepared by dissolving a non-steroidal anti-inflammatory drug in a lipophilic dissolving agent such as crotamiton or peppermint oil in order to improve the percutaneous absorption of the non-steroidal anti-inflammatory drug, and then dissolving the adhesive base. Contained in
This was considered to be one of the causes of the decrease in the content of the drug in the patch over time.

[0003]

DISCLOSURE OF THE INVENTION The present invention solves the above-mentioned problems, and is a preparation wherein a nonsteroidal anti-inflammatory drug is stably retained in a water-soluble patch for a long time without impairing transdermal absorbability. The purpose is to provide.

[0004]

Means for Solving the Problems The present inventors have made intensive studies to solve the above-mentioned problems, and as a result, have dissolved or dispersed a nonsteroidal anti-inflammatory drug in glycol having 3 to 30 carbon atoms. After that, the non-steroidal anti-inflammatory analgesic is stabilized by dispersing in a gel containing glycerin, and a patch having good storage stability can be obtained without impairing the transdermal absorbability of the non-steroidal anti-inflammatory analgesic. Thus, the present invention has been completed. That is, the present invention dissolves or disperses a non-steroidal anti-inflammatory analgesic in glycol having 3 to 30 carbon atoms and uniformly disperses the same in a gel containing glycerin to stably blend the non-steroidal anti-inflammatory analgesic. And a method for producing the same.

[0005]

BEST MODE FOR CARRYING OUT THE INVENTION The non-steroidal anti-inflammatory analgesic used in the present invention (excluding indomethacin) is a non-steroidal anti-inflammatory analgesic belonging to the phenylpropionic acid group. Specifically, ibuprofen, ketoprofen, suprofen, loxoprofen sodium , Fenoprofen and flurbiprofen, and diclofenac sodium and piroxicam as other non-steroidal anti-inflammatory analgesics.

The non-steroidal anti-inflammatory analgesic according to the present invention has 3 to 3 carbon atoms for dissolving or dispersing.
Examples of the glycol 30 include propylene glycol, dipropylene glycol, butylene glycol, polyethylene glycol and the like, and in particular, polyethylene glycol 200, polyethylene glycol 300, polyethylene glycol 400, polyethylene glycol 600, propylene glycol, and 1,3 butylene glycol. preferable.

The amount of the glycol having 3 to 30 carbon atoms in the gel is 2 to 20% by weight, preferably 2.5 to 1% by weight.
5% by weight. That is, when the amount of the glycol having 3 to 30 carbon atoms blended in the gel is less than 2% by weight, the carbon
Non-steroidal anti-inflammatory analgesics are insufficiently dissolved in glycols of up to 30 and it is difficult to disperse the non-steroidal anti-inflammatory analgesics uniformly in the adhesive base. Cannot be incorporated into the patch. Conversely, if the amount of the glycol having 3 to 30 carbon atoms contained in the gel exceeds 20% by weight, a phenomenon of deterioration in shape retention due to a decrease in gel viscosity is observed, making it impossible to mold as a patch. . The amount of glycerin in the gel is 10 to 40% by weight, preferably 15 to 40% by weight.
30% by weight. That is, if the blending amount of glycerin in the gel is less than 10% by weight, the water-soluble polymer cannot be sufficiently dispersed, and the gel is left in the gel. Further, when the amount of glycerin in the gel is more than 40% by weight, glycerin which cannot be held on the surface of the gel causes an embossing phenomenon, which causes a problem that stickiness occurs during application. By using these glycols having 3 to 30 carbon atoms and glycerin particularly in the above-mentioned amounts, the gel fluidity is increased, the spreadability is excellent, and the initial tackiness is good. A water-soluble patch can be prepared.

[0008] There is no particular limitation on the composition constituting the gel, and a commonly used composition such as a water-soluble polymer,
Excipients, humectants, stabilizers, crosslinking agents and the like can be added.

Examples of the water-soluble polymer include gelatin,
Hydrolyzed gelatin, polyacrylic acid, polyacrylate, partially neutralized polyacrylic acid, starch polyacrylate, polyvinyl alcohol, polyvinylpyrrolidone, hydroxypropylcellulose, hydroxypropylmethylcellulose, methylcellulose, carmellose sodium, carboxyvinyl polymer, A methoxyethylene maleic anhydride copolymer, an N-vinylacetamide copolymer or the like can be used alone or in combination of two or more. The compounding amount is 3 to 20% by weight, preferably 5 to 15% by weight.

As an excipient, for example, kaolin, titanium oxide, light anhydrous silicic acid, zinc oxide, bentonite and the like can be used alone or in combination of two or more. The compounding amount is 0.5 to 10% by weight.

Examples of humectants include D-sorbitol solution, propylene glycol, dipropylene glycol,
Butylene glycol, pyrrolidone carboxylate and the like can be used alone or in combination of two or more. The compounding amount is 5 to 30% by weight, preferably 10 to 20%.
% By weight. The amount of water in the gel is 30-60% by weight
And preferably 35 to 50% by weight.

As the stabilizer, for example, edetate, p-hydroxybenzoate, tartaric acid and the like can be used alone or in combination of two or more.

As the crosslinking agent, for example, aluminum hydroxide, aluminum glycinate, dihydroxyaluminum aminoacetate, synthetic hydrotalcite, polyvalent metal compounds such as metal aluminate metasilicate, synthetic aluminum silicate, etc., alone or in combination of two or more. It can be used in combination of the above.

If necessary, an absorption enhancer, a preservative,
Antioxidants, plasticizers, emulsifiers, surfactants and the like can be added.

As a support for the patch, polyethylene,
Porous materials such as polypropylene, polyvinyl chloride, polyester, nylon, and polyurethane, foamed materials, woven fabrics, nonwoven fabrics, and laminates of a film or sheet with porous materials, foamed materials, woven fabrics, and nonwoven fabrics can be used. .

As the plastic film for covering the surface of the adhesive base, polyethylene, polypropylene, polyester or those obtained by releasing these with silicone can be used.

A patch can be formed by spreading the pressure-sensitive adhesive composition formed as described above on a support and covering the surface of the pressure-sensitive adhesive material with a plastic film. Hereinafter, the present invention will be specifically described with reference to Examples and Test Examples, but the present invention is not limited to the following Examples.

[0018]

EXAMPLES Example 1 2.75 g of polyvinyl alcohol, 1.2 g of tartaric acid,
20 g of 70% D-sorbitol solution, 3 g of kaolin, 20 g of concentrated glycerin, 3 g of carmellose sodium, 5 g of partially neutralized polyacrylic acid, 0.07 g of dihydroxyaluminum aminoacetate, 0.1 g of sodium edetate, 0.3 g of polysorbate 80, purified water
An appropriate amount was uniformly mixed to prepare a hydrogel. Next, to 4.5 g of polyethylene glycol 200, 0.33 g of flurbiprofen and 0.15 of p-hydroxybenzoate were added.
After dissolving g, the mixture was uniformly dispersed in the previously prepared hydrogel to obtain an adhesive base. The adhesive base was spread on a stretchable nonwoven fabric, and the surface of the adhesive base was covered with a polypropylene film to form a patch.

Examples 2-3 and Comparative Examples 1-3 Each patch described in Table 1 was molded into a patch in the same manner as in Example 1.

[Table 1]

Test Example 1 Each of the patches of Examples 1 to 3 and Comparative Examples 1 to 3 was sealed in an aluminum bag as five bags, and then stored at 40 ° C. and 50 ° C. for one month. The content of nonsteroidal anti-inflammatory analgesic in each patch was measured by high performance liquid chromatography. Table 2 shows the results.

[Table 2]

From the results shown in Table 2, at least one selected from the group consisting of ibuprofen, ketoprofen, suprofen, loxoprofen sodium, fenoprofen and flurbiprofen, which are nonsteroidal anti-inflammatory analgesics belonging to the phenylpropionic acid series, is represented by polyethylene glycol. The patches of Examples 1 to 3 of the present invention, which were uniformly dispersed in an adhesive base after being dissolved in the adhesive base, were compared with Comparative Examples 1 to 3 even under the above-mentioned conditions. It was confirmed that the decrease in the content of the preparation over time was suppressed, and that the non-steroidal anti-inflammatory analgesic compound contained in the patch had good storage stability.

Formulation Example Formulation Example 1 5.4 g of polyacrylic acid, 1.5 g of castor oil, 70%
D-sorbitol solution 10 g, sodium polyacrylate 2.5 g, carmellose sodium 4.0 g, concentrated glycerin 16.0 g, polyvinyl alcohol 3.0 g,
3.0 g of kaolin, 0.5 g of titanium oxide, 0.12 g of synthetic hydrotalcite, 0.05 of sodium edetate
g and purified water were uniformly mixed to prepare a hydrogel. Next, after dissolving and dispersing 0.5 g of ketoprofen in 3.0 g of polyethylene glycol 300 and 0.2 g of twin 20, it was uniformly dispersed in the previously prepared hydrogel to obtain an adhesive base. This adhesive base was spread on a stretchable nonwoven fabric, and the surface of the adhesive base was coated with polyethylene terephthalate to prepare a patch.

Formulation Example 2 0.5 g of gelatin and 0.2 g of polyvinyl alcohol were dissolved in 2.5 g of purified water heated to 50 ° C. 5.0 g of this solution and partially neutralized polyacrylic acid, 3.5 g of carmellose sodium, 25 g of concentrated glycerin, 0.55 g of dried aluminum hydroxide gel, 20 g of 70% D-sorbitol solution, 6.5 g of kaolin, edetate 0.08 g of sodium, 1.8 g of tartaric acid, and an appropriate amount of purified water were uniformly mixed to prepare a hydrogel. Next, 8.0 g of polyethylene glycol 400, 1.0 g of castor oil,
0.5 g of flurbiprofen was dissolved and dispersed in 0.5 g of sorbitan monooleate, and then dispersed uniformly in the previously prepared hydrogel to obtain an adhesive base. This adhesive base was spread on a woven fabric, and the surface of the adhesive base was coated with polyethylene terephthalate to prepare a patch.

Formulation Example 3 0.5 g of hydrolyzed gelatin was dissolved in 2.5 g of purified water. This solution and partially neutralized polyacrylic acid 3.0
g, starch polyacrylate 1.0 g, concentrated glycerin
12.5 g, dihydroxyaluminum aminoacetate 0.05 g, hydroxypropylcellulose 0.5
g, sodium edetate 0.05 g, tartaric acid 1.2 g
An appropriate amount of purified water was uniformly mixed to prepare a hydrogel. Next, 4.5 g of polyethylene glycol 600, l
-After dissolving and dispersing 0.35 g of ibuprofen in 0.5 g of menthol and 200.3 g of twin, it was dispersed uniformly in the previously prepared hydrogel to obtain an adhesive base. This adhesive base was spread on a woven fabric, and the surface of the adhesive base was coated with polyethylene terephthalate to prepare a patch.

Formulation Example 4 Polyvinyl alcohol 2.25 g, tartaric acid 1.2 g,
Concentrated glycerin 20g, carmellose sodium 3.0
g, partially neutralized polyacrylic acid 5.0 g, 70% D-
Sorbitol solution 20 g, kaolin 3.0 g, sodium edetate 0.1 g, synthetic aluminum silicate 0.0
8 g and an appropriate amount of purified water were uniformly mixed to prepare a hydrogel. Next, after dissolving and dispersing 0.35 g of ketoprofen in 4.5 g of polyethylene glycol 600, the dispersion was uniformly dispersed in the previously prepared hydrogel to obtain an adhesive base. This adhesive base was spread on a woven cloth, and the surface of the adhesive base was coated with silicon-treated polyethylene terephthalate to prepare a patch.

Formulation Example 5 1.0 g of gelatin and 0.4 g of polyvinyl alcohol were added to 6
It was dissolved in 5.6 g of purified water heated to 0 ° C. This solution and a preliminarily prepared solution A (3.5 g of sodium polyacrylate, 2.0 g of carmellose sodium,
15 g of concentrated glycerin, 0.5 g of dihydroxyaluminum aminoacetate, 1.7 of carboxyvinyl polymer
g, tartaric acid 0.2 g, urea 1.5 g) and Preparation B (7
20 g of a 0% D-sorbitol solution, 0.2 g of sodium edetate, 0.1 g of ethyl paraben, and an appropriate amount of purified water) were uniformly mixed to prepare a hydrogel. Next, purified water 1.5
g, 1.5 g of diisopropanolamine and 0.05 g of sodium sulfite were dissolved and dispersed in 3.0 g of diclofenac sodium, and then dispersed uniformly in the previously prepared hydrogel to obtain an adhesive base. The adhesive base was spread on a polyurethane foam, and the surface of the adhesive base was covered with a polypropylene film to prepare a patch.

Formulation Example 6 3.0 g of polyvinyl alcohol was dissolved in 17 g of purified water heated to 60 ° C. This solution and concentrated glycerin 25
g, partially neutralized polyacrylic acid 5.0 g, carmellose sodium 3.0 g, hydroxypropyl cellulose 0.5 g, kaolin 3.0 g, metal metasilicate aluminate 0.25 g, tartaric acid 1.5 g and purified water Were mixed uniformly to prepare a hydrogel. Next, piroxicam 0.25 g and methyl paraben 0.15 g in 13 g of polyethylene glycol 600 and 0.3 g of polysorbate 80
Was dissolved and dispersed, and then uniformly dispersed in the previously prepared hydrogel to obtain an adhesive base. This adhesive base was spread on a woven fabric, and the surface of the adhesive base was covered with a polyethylene film to prepare a patch.

[0028]

According to the present invention, a non-steroidal anti-inflammatory drug is dissolved or dispersed in a glycol having 3 to 30 carbon atoms and uniformly dispersed in a glycerin-containing gel by dissolving or dispersing the non-steroidal anti-inflammatory drug (excluding indomethacin). An analgesic can be stably compounded, and it has become possible to provide a water-soluble patch having significantly improved storage stability of a nonsteroidal anti-inflammatory analgesic as compared with a conventional dissolving cataplasm. Further, by combining a glycol having 3 to 30 carbon atoms with glycerin, a gel flowability is increased, and a water-soluble patch having excellent initial spread and excellent initial adhesive strength can be produced.

──────────────────────────────────────────────────の Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI theme coat ゛ (reference) A61K 45/00 A61K 45/00 47/10 47/10 A61P 29/00 A61P 29/00 F-term (reference) 4C076 AA74 BB31 CC05 DD38A DD38E FF15 4C084 AA01 AA17 MA32 MA63 NA03 ZA081 ZA891 ZB111 4C086 AA01 BB02 MA02 MA05 MA09 MA32 MA63 NA03 ZA08 ZA89 ZB11 4C206 AA01 DA22 DA23 DA24 DA25 FA52 MA02 MA05

Claims (8)

[Claims] 1. A glycerin-containing gel having 3 to 3 carbon atoms.
A patch comprising a non-steroidal anti-inflammatory analgesic (excluding indomethacin) dissolved or dispersed in glycol 0. 2. The patch according to claim 1, wherein the amount of the glycol having 3 to 30 carbon atoms in the gel is 2 to 20% by weight. 3. The patch according to claim 1, wherein the amount of glycerin in the gel is 10 to 40% by weight. 4. The patch according to claim 1, wherein the amount of the glycol having 3 to 30 carbon atoms in the gel is 2 to 20% by weight, and the amount of glycerin is 10 to 40% by weight. 5. A water-soluble patch, comprising dissolving or dispersing a non-steroidal anti-inflammatory analgesic (excluding indomethacin) in a glycol having 3 to 30 carbon atoms and then dispersing in a glycerin-containing gel. Manufacturing method 6. The patch according to claim 1, wherein the non-steroidal anti-inflammatory analgesic is a non-steroidal anti-inflammatory analgesic belonging to the phenylpropionic acid type. 7. The method according to claim 1, wherein the phenylpropionic acid-based anti-inflammatory analgesic is at least one selected from ibuprofen, ketoprofen, suprofen, loxoprofen sodium, fenoprofen and flurbiprofen.
The patch according to the above. 8. The patch according to claim 1, wherein the nonsteroidal anti-inflammatory drug is at least one selected from diclofenac sodium and piroxicam.