JPS5867617A - Antiphlogistic and analgesic spreading plaster - Google Patents

Abstract

PURPOSE:The titled spreading plaster wherein an active ingredient is absorbed in the skin efficiently, not rubbed off by clothes, etc., and its proper amount is accurately controlled, obtained by adding etofenamate[2-(2-hydroxyethoxy) ethyl-N-(alpha,alpha,alpha-trifluoro-m-tolyl)anthranilate]to a specific acrylic pressure-sensitive adhesive layer bonded and formed on a substrate. CONSTITUTION:A pressure-sensitive adhesive comprising a copolymer consisting of an acrylic acid alkyl ester monomer having 5-12C of total carbon number of alkyl group and >=4C of carbon number of straight-chain carbon chain part, a functional monomer (e.g., acrylic acid, maleic anhydride) having a functional group copolymerizable with the monomer and/or vinyl acetate is blended with 10-300mg based on 1g polymer of etofenamate, and a pressure-sensitive adhesive polymer layer bonded to a substrate (e.g., paper, nonwoven cloth, film, etc.) is formed. The prepared plaster can be applied directly to the affected part by the use of the tack of the polymer layer.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention provides an anti-inflammatory and analgesic patch using etofenamate as an active ingredient.

Etofenamate is a viscous oily anti-inflammatory drug whose chemical name is 8-(tri-1-hydroxyethoxy)ethyl-N-(α,α,a-trifluoro-m-)lyl)anthranilate. It is used for diseases in the orthopedic field, such as knee osteoarthritis and spastic arthritis.

Anti-inflammatory agents and nonsteroidal anti-inflammatory supplements for the buttocks generally cause side effects such as gastric IIh disorders when administered under a tap, so they are formulated into ointments to penetrate the area. There are many.

However, in the case of ointments, it is difficult to precisely control the amount of the active ingredient, and if the ointment is simply applied to the body, it may rub off on clothing, etc. Not only is this accurate, but it also creates smudges that contaminate clothing. In order to prevent the ointment from being rubbed off, it is done to wrap the ointment around it, but this is a tedious process, and if the affected area is a joint, it is recommended to use a 4!11 band. Under these circumstances, which is a national crisis, the present inventors conducted extensive research with the aim of developing an anti-inflammatory formulation that does not cause gastrointestinal disorders or other drawbacks such as those found in ointments. However, even if ordinary non-steroidal anti-inflammatory agents are mixed into adhesives, they are not absorbed sufficiently through the skin, whereas Etofena, which is selected from among the many non-steroidal anti-inflammatory agents, It was discovered that etofenamate was absorbed into the skin at a 10,000% ratio when added to a specific acrylic thread adhesive.The present invention was completed based on this finding.
The purpose of this invention is to provide an external preparation that does not have the inaccuracy of injections found in ointments and has excellent moxibustion efficacy. In the present invention, etofenamate as an active ingredient is blended into a sticky polymeric material layer formed on a support, and the polymeric material layer is mixed with an acid alkyl ester monomer (however, The alkyl group has 5 to 12 carbon atoms, and the straight carbon chain has 4 carbon atoms.
above) and a functional monomer having a functional group capable of co-electrification with the monomer and/or a copolymer of vinyl acetate.
As described above, the present invention has a structure in which etofenamate is blended with a polymeric material made of a specific adhesive, and a streaked polymeric material layer is provided on a carrier. It can be applied directly to the affected area by utilizing the viscous force of the material layer.

By doing so, the active ingredient etofenamate is effectively absorbed into the skin I-, and the carrier prevents contact between the polymer material J- and clothing, etc., and the ointment It also avoids rubbing from clothing, which was a drawback of previous models.

As the carrier used in this invention, paper, woven fabric, nonwoven fabric, foam sheet, rubber sheet, plastic film, etc. are used. Among these materials, it is preferable to impart moisture permeability to materials with low moisture permeability by subjecting them to physicochemical processing. This is a good bottle to prevent rashes caused by too much moisture. Further, it is preferable that the carrier has the ability to expand and contract in at least one direction, and depending on the material, it may not have such an expansion and contraction function.
It is preferable to perform a process of applying extended radiation to the current. This is because having an elastic function allows it to follow the expansion and contraction of the HL chest surface when applied to the body.

In this invention, the viscous agent constituting the polymeric material layer is a specific acrylic thread viscous agent, that is, acrylic 1≠-R, and the alkyl group has 5 to 12 carbon atoms, and its @
A copolymer with LNm vinyl and a functional monomer having a possible functional group 'Jk' with the monomer is used. Here, the alkyl part of the furkyl ester
, Tatooe is like an alkoxy group (an alkoxy group with 1 to 4 vertical strands)! Examples of the functional group in the zero-functional monomer which may have an IC substituent include a carboxyl group and a hydroxyl group.

Among the above-mentioned combinations, the combination of an acrylic alkyl ester and vinyl acetate is particularly preferred in terms of etofenamate release, safety against skin irritation, and cross-agent release. . A specific example of the above acrylic alkyl ester.

Examples include amyl acrylate, butyl acrylate,
Hexyl acrylate, heptyl acrylate, octyl acrylate, nonyl acrylate, 2-ethylhexyl acrylate, 2-methoxyethyl acrylate, etc.; Examples include acids, maleic anhydride, hydroxyethyl acrylate, hydroxypropyl acrylate, and the like.

In this invention, it! of etofenamate contained in the above acrylic thread adhesive! l [U, usually 10 to 300 sxN degrees for the adhesive acrylic thread polymer 11.

The preferred concentration varies depending on the purpose of use (symptoms), location of use, and thickness of the adhesive layer, but generally it is 50 to 150.
It is practical to set it to 111F. In addition, when incorporating etofenamate into the adhesive layer, it is usually done so that it is distributed uniformly over the whole pigeon, but if it is particularly desired, etofenamate is added to the outer surface of the adhesive layer (the side that comes into contact with the skin). You may try to make Isodo understand it in layman's terms.

In addition, if it is necessary to obtain a drug with a higher concentration than the above depending on the purpose of use, an absorption enhancer (for example, an externally active agent or oil that is less irritating to the skin) may be added as appropriate. However, from the point of view of puncture resistance, etc., the adhesive is 100%
It is preferable to limit the amount to 15.1 parts by weight.

The anti-inflammatory patch of the present invention is made by soaking the adhesive polymer material # containing etofenamate on the above-mentioned carrier. A method in which the pressure-sensitive adhesive composition is directly applied onto a carrier and dried;
Six methods can be employed, including a method of pasting the film onto a carrier and pressing it together.

Examples of this invention will be described below. In the following,
The terms "Zheng" and "%" shall mean 1 part and % by weight, respectively.

Example 1 93 parts of 2-ethylhexyl acrylate, 7/7 lylic acid
0.2s of benzoyl peroxide and 150% of ethyl acetate
sk, put into a reflux condenser and a stirrer and a reactor,
Polymerization was carried out at 6σC for 8 hours under a nitrogen gas atmosphere. Ethyl #acid was further added to the obtained copolymer solution to dilute it so that the solid content after drying was 20%.

This acrylic thread adhesive solution was mixed with 5 parts of etofenamate per 100 parts of its solid content, and this was applied and dried on a T-release liner to form a thickness of 40 parts containing etofenamate.
7 m of μ adhesive was formed. Next, the above-mentioned adhesive layer is laminated and pressure-bonded to the above-mentioned treatment 111 of the polyethylene film which has been subjected to the MTTS treatment, and the anti-inflammatory and analgesic patch with a release liner is completed. The adhesive layer of this patch contained 200 μf of etofenamate per square centimeter.
For #1 with 0 g, a patch containing etofenamate of 40 (Jpf) per square centimeter of adhesive layer was obtained by the same operation as in Example 1.

Example 3 In Example 1, except that the number of etofenamate compounded was changed to 15 parts, the same procedure as in Example 1 was carried out to prepare a patch containing 7) Etofenamate 1, in which the adhesive layer was applied to 9600 μy. get.

implementation? 114 60 parts of 2-ethylhexyl acrylate, 4 parts of vinyl acetate
01d5, 0.2 parts of azobisisobutyronitrile and 120 parts of ethyl acetate were charged into a reactor equipped with a draft-cooled MJ vessel and a stirring #iso, and 1iIi under a gas atmosphere, 6CrC
So I made a train connection at 8 o'clock. Ethyl acetate tIJEJ was further added to the obtained copolymerization bath solution so that the solid content after dry acupuncture was 20%.
It was diluted so that

Add 5 parts of etofenamate to 100 parts of the solid content in this acrylic thread thickening agent solution, apply this onto the release liner and dry it to give etofenamate a thickness of 40 mm.
A μ adhesive layer was formed. Thereafter, an anti-inflammatory and analgesic patch with a release liner was prepared in the same manner as in Example 1. The adhesive JgIIFi in this patch contained 200 μg of etofenamate per square centimeter, similar to Example 1.

Example 5 Using the adhesive shielding agent of Example 4, the number of copies of etofenamate distributed'! The amount of 1 to 10 parts was 400 μf per square centimeter of the adhesive layer by the same operation as in Example 1.
A moisturizing agent containing etofenamate is obtained.

Example 6! J Example 40 Using a viscous agent, the number of parts of etofenamate to be mixed was determined by the same operation as in Example 1. obtain a patch.

Example 7 80 parts of butyl acrylate, 18 parts of vinyl acetate, 2 parts of acrylic acid, 0.2 parts of benzoyl peroxide and 150 parts of ethyl acetate were charged into a reactor containing a reflux condenser and a stirrer, and the mixture was heated under a nitrogen gas atmosphere. , 6σC for 8 hours.

Ethyl acetate was further added to the obtained copolymer solution to dilute it so that the solid content after drying was 20%.

5 parts of etofenamate was added to this acrylic thread adhesive solution based on 100 parts of its solid content, and this was applied onto the mold release 2 inner and dried to give a thickness of 40 μm containing etofenamate.
Form an adhesive layer. Thereafter, an anti-inflammatory and analgesic patch with a -m liner was prepared in exactly the same manner as in Example 1. The adhesive layer of this patch contained etofenamate at 200 μf per square centimeter as in Example 1.

Example 8 Using the adhesive of Example 7 and changing the number of etofenamate to 10 parts, the same procedure as in Example 1 was carried out to apply 400 μf of etofena per 1 square 7 cm of the adhesive layer. Obtain a patch containing mate.

implementation? 19 Using the adhesive of Example 7 and adding 15 parts of etofenamate, the adhesive layer was removed by 1 square centimeter in the same manner as in Example 1.1) Containing 600 pf of etofenamate obtain a patch.

Example 10 95 parts of ethylhexyl acrylate, 2 parts of doroxyethyl acrylate, 3 parts of methacrylic acid, 0.2 s of azobisin butyronitrile and 15 l of ethyl acetate were combined with a reflux condenser and a stirrer. The solution was put into a reactor with a nitrogen gas atmosphere and allowed to combine for 8 hours at 6σC. Ethyl acetate was further added to the resulting combined solution to dilute it so that the solid content after drying was 20 years.

5 parts of etofenamate was added to this acrylic adhesive solution per 100 parts of its solid content, and this was dried evenly on a release liner to form a thickness of 40 μm containing etofenamate.
An adhesive layer was formed. Thereafter, in the same manner as in Example 1, a releasable 2-iner anti-inflammatory analgesic patch was obtained. The adhesive layer of this patch, as in Example 1, contained etofenamate at 15F and 200μF per 7cm.

Example 11 Using the adhesive of Example 10, etofenamate was added at 400 μV per square centimeter of the adhesive layer in the same manner as in Example 1, except that the number of etofenamate was 1 to 10 parts. Obtain a patch containing:

Example 12 The same procedure as in Example 1 was carried out, except that the adhesive of Example 10 was used and the number of etofenamate was 15 parts.
A patch containing 600 μV of etofenamate per square centimeter of adhesive layer is obtained.

Example 13 2-Ethylhexyl acrylate) 5 (25 parts of 1,2-methoxyethyl acrylate, 25 parts of vinyl acetate, 0.2 part of azobisin butyronitrile and 150 parts of ethyl acetate)
into a reactor equipped with a reflux condenser and a stirrer,
The mixture was combined for 8 hours at 6σC in a nitrogen gas atmosphere. Ethyl acetate was further added to the obtained 1 vol. of the copolymer to dilute it so that the solid content after drying was 20%.

5 parts of etofenamate was added to this acrylic adhesive solution based on 100 parts of its solid content, and this was applied and dried on the adhesive liner to form an etofenamate-containing adhesive layer. Thereafter, in the same manner as in Example 1, a releasable 2-inner anti-inflammatory and analgesic patch was prepared. As in Example 1, the adhesive layer of this patch contained 200 μf of etofenamate per square centimeter.

Example 14 Using the adhesive of Example 13 and adding 10 seconds of etofenamate, L1 was prepared in the same manner as in Example 1.
A patch containing 400 μV of etofenamate per square centimeter of adhesive layer is obtained.

Example 15 Using the adhesive of Example fI113, the same procedure as in Example 1 was carried out except that the number of etofenamate blended was t-15 parts.
A patch containing etofenamate is obtained.

Comparative Example 1 Styrene-isoprene-styrene block copolymer 70
Etofenamate is added in an amount of 5 parts to 105 parts of the solid content after coating and drying to an adhesive solution consisting of 130 parts of liquid buff in Apply it on the liner and let it dry.
A fake anti-inflammatory patch with a mold liner was obtained in the same manner as in Example 1. The adhesive layer of this patch was Example 1 and pf
Comparative Example 2 Using the adhesive of Comparative Example 1, formulation 5I of etofenamate was prepared using the adhesive of Comparative Example 1.
A patch containing 400 micrometers of etofenamate per 1 square centimeter of the adhesive layer was obtained by Hakasha Co., Ltd., as described in Example 1 and P1.

Comparative Example 3 Using the adhesive of Comparative Example 1, the number of etofenamate blended was adjusted to 600 μf per square centimeter of the adhesive layer using the procedures of Hakahiro and Example 1 and Oka. The adhesive patches of Examples 1 to 15 and Comparative Examples 1 to 3 were subjected to the following characteristic tests.

(1) Absorption rate test 111 $ The hair on the back skin of five guinea pigs was shaved, and after - days had passed, each patch of Examples 1 to 15 and Comparative Examples 1 to 3 was applied to the skin surface in an area of 4 square centimeters. It was attached for 8 hours with the size of . Thereafter, the patch was peeled off, the etofenamate content t remaining in the adhesive layer was examined, and the etofenamate absorption rate (11) was calculated from the comparison with the initial content.

The above test results were as shown in Table 1.

(Leaving space below) (2) Carrageenin intradermal edema suppression test A group of 6 Wistar male rats weighing approximately 25 of each rat was shaved off the hair on the back of each rat, and after 15 hours, the A test piece and a control piece were pasted on two places on the left and right sides of the test piece. Here, the test piece is 1! r The patches of Example 1-15 and Comparative Examples 1 to 3 were cut into pieces of 4 square centimeters in size, and the control pieces were those of Example 17-5 above except that etofenamate was not added. A patch prepared in the same manner as in Comparative Example 1 was used, and the patch was adjusted to a size of 4 square centimeters.

Two hours after application 1, the patch was removed, and 0.05 ml of 0.5 ml of 0.5 strength lagenin saline was intradermally injected into both peeling marks. After 4 hours, the rats were sacrificed, and the skin at the injection site was peeled off and punched out to a diameter of 12111 around the edematous area. The weight of the punched skin was measured, and the difference in weight between the area where the test piece was applied and the area where the control piece was applied was taken as the amount of floating area charge, and the inhibition rate of carrageenan intradermal floating was calculated using the following formula.

VC-Va Carrageenin intradermal edema suppression rate (9) - x 100 (E) c (However, in the formula, yC and Vsd, respectively, the control piece and the test piece attached indicate one child with intradermal edema in the group) The above test results are ,
It was as shown in Table 2.

(Leaving space below) Procedural amendment (voluntary) December 18, 1981 Commissioner of the Japan Patent Office l Case description 1982 Patent Application No. 166172 2 Title of the invention Anti-inflammatory and analgesic patch 3. Case of the person making the amendment Relationship between Patent Applicant (396) Representative 3rd Department 4, Agent 〒541 6 Number of inventions increased by amendment No. 1) On page 6 of the specification, line 4, next to “acrylate”
, methoxyethyl methacrylate, ethoxyethyl acrylate, ethoxyethyl methacrylate, butoxyethyl acrylate, butoxyethyl methacrylate” are fully inserted.

Claims (1)

[Claims] Etofenamate as an active ingredient causes at+vf on the body
! fst, and one molecular material layer thereof is an acrylic alkyl ester monomer (however, the alkyl group has 5 to 1 carbon atoms).
2, and the number of carbon atoms in the linear carbon chain portion thereof is 4 or more) and a functional seven-mer and/or vinyl acetate having a functional group copolymerizable with the upper polymer. An anti-inflammatory analgesic patch characterized by: