JPS60208909A - Anti-inflammatory analgesic agent for external use - Google Patents

Abstract

PURPOSE:To provide the titled agent having excellent drug-releasing and transcutaneous absorption properties, and free from the skin irritation in application and the whitening of the skin after removing from the skin, by compounding an anti-inflammatory analgesic agent and an alcohol to a resin blend composed of an aliphatic polyamide resin and a maleic acid copolymer resin. CONSTITUTION:The objective agent can be prepared by compounding (A) 100pts. (wt.) of a resin composed of (i) 80-99.5pts. of an aliphatic polyamide resin, preferably a nylon resin soluble in lower alcohol and (ii) 0.5-20pts., preferably 1.0- 12pts. of a copolymer resin containing maleic acid (anhydride) and mono- and/or dialkyl maleate with (B) 0.1-600pts. of an anti-inflammatory analgesic agent, preferably an acidic anti-inflammatory analgesic agent such as methyl salicylate, ketoprofen, etc., (C) 0.1-600pts. of a polyhydric alcohol (derivative) and (D) 200-1,900pts. of a lower alcohol containing 0-50wt% water. Application of the agent to the skin gives a coating film having high adhesivity to endure the extension and abrasion, and releasable easily after use.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a topical anti-inflammatory analgesic agent that is applied several times or applied to the skin surface to form a film and allow medicinal ingredients to be absorbed transdermally. .

Traditionally, topical anti-inflammatory analgesics have been used as main anti-inflammatory analgesics such as methyl salicylate and glycol salicylate, as well as menthol,
Patch preparations include additives such as camphor, mixed with an adhesive base, and spread on cloth; ointments mixed with an ointment base;
Alternatively, a liquid preparation prepared by dissolving the main ingredient and additives in a suitable solvent, and an aerosol preparation prepared by adding an aerosol propellant to this liquid preparation are also used. However, if the adhesive patch is applied for a long time, it may inhibit physiological functions of the skin such as sweating and breathing, and may cause side effects such as dryness, and there are also problems such as hair pulling when removed. After application, the ointment remains sticky and unpleasant, and there is a risk of contaminating clothing, etc., and percutaneous absorption is not sufficient.

Furthermore, liquid agents, aerosol agents, and the like have the disadvantage that they cannot be expected to have a sustained effect because of volatilization of the drug.

On the other hand, several products are being used on the skin by applying the film-forming properties of polymeric compounds to protect affected areas, prevent contamination, and the like. For example, aerosol germicidal glass dressings are used as a substitute for pre- and post-surgical dressings. In this case, an acrylic acid ester resin was used as the polymer compound, and since it had strong adhesion to the skin, there was almost no peelability from the skin. recent years,
Attempts have been made to incorporate anti-inflammatory and analgesic drugs into a film-forming polymer base. For example, water-soluble polymer compounds such as polyvinylpyrrolidone and polyvinylpyrrolidone-polyvinyl acetate copolymer are blended with anti-inflammatory and analgesic agents (JP-A-54-46818, 54-46819).
or a combination of water-insoluble polymers such as soluble nylon, polyvinyl butyral, cellulose acetate butyrate, etc. with an anti-inflammatory analgesic agent (Japanese Patent Application Laid-open No. 14071-1989)
No. 3) etc. However, none of these are believed to be sufficient in terms of film-forming ability, film strength, skin safety, etc., and in particular, they are not satisfactory in terms of sustained drug release and transdermal absorption. The current situation is that an ideal topical anti-inflammatory analgesic has not yet appeared.

Therefore, the present inventors have determined that: 1) the drug has excellent drug release and longitudinal absorption, and has a sufficiently long-lasting effect; and 2) it is sufficiently safe and does not cause skin problems such as skin irritation or excessive whitening after application. As a result of extensive research into film-forming polymers that are easy to use, do not stain clothes, etc., and can withstand intense interlocking during application, we have developed an ideal film-forming polymer. They discovered an anti-inflammatory analgesic for external use and completed the present invention.

Namely, 1) aliphatic polyamide resin, 80 to 995 parts by weight, 11) copolymer resin containing (anhydrous) maleic acid, maleic acid monoalkyl ester, or/and maleic acid dialkyl ester (hereinafter referred to as maleic acid copolymer) a) Anti-inflammatory and analgesic agent 0.1-6 for a total of 100 parts by weight of a resin mixture consisting of 0.5-20 parts by weight of
00 parts by weight mouth) 0.1 to 600 parts by weight of a polyhydric alcohol and/or its derivative c) Lower alcohol containing 0 to 50% by weight of water, obtained by blending 200 to 1900 parts by weight, A topical anti-inflammatory analgesic with a film-forming ability can achieve ideal release properties and transdermal absorption, making it an excellent topical anti-inflammatory analgesic that has never existed before. As it turns out, the present invention has been completed.

Further, the external anti-inflammatory analgesic of the present invention essentially includes the above-mentioned composition, and may be a liquid preparation, a gel preparation, a stick preparation, or a liquid preparation.

When put into practical use as an aerosol and administered onto the skin,
A good film is formed in a short period of time, and release and transdermal absorption occur with ideal bioavailability depending on the drug contained.

The components of the present invention will be explained in detail below.1
) Alcohol-soluble nylon that forms a good film on the skin 11 is used as the aliphatic polyamide resin,
Especially lower alcohol-I soluble nylon, copolymerized nylon, and modified nylon.

Commercially available products include CM-4001, CM-8000, and B-A- manufactured by Toshisha Co., Ltd.
Ultraamide 1C manufactured by 8-F, Elbamide 8025, 8061, 8062 or 8066 manufactured by DuPont, etc. are used.

Next, the most characteristic feature of the present invention is a combination of a maleic acid copolymer resin and the alcohol-soluble nylon. The present inventors were able to discover that the release and transdermal absorption of the drug follow the most ideal nomiturn. In other words, it is thought that the reactivity of polyamides represented by nylon is based on the <100NH- of the folding unit and the -NH group at the terminal. It is said that this NH of -〇〇NH- easily reacts with the electronic reagent of the gods. Therefore, when a nylon resin alone is used in combination with an acidic anti-inflammatory drug having a carbonyl group, the drug is incorporated into the nylon resin.
There is concern that drug release may be suppressed. On the other hand, it is presumed that external anti-inflammatory analgesics prepared by adding a maleic acid copolymer can be expected to have increased drug release properties due to the repulsion between the maleic acid group and the acidic anti-inflammatory analgesic. Furthermore, as a result of a weight change test, it has been confirmed that the coating containing maleic acid copolymer has less drug dispersion into the outside air, and this is due to the presence of the maleic acid copolymer. This shows that the concentration is maintained well. Therefore, it is presumed that drug release is sustained over a long period of time.

Furthermore, it has been found that when a maleic acid copolymer resin is used, the lcj properties of the film are significantly improved due to interaction with alcohol-soluble nylon. In other words, a film with good skin adhesion that can withstand intense stretching movements and frictional peeling of clothing when applied to joints, etc., and has good skin releasability that can be easily removed when not in use is obtained. It was found that it would be an ideal topical anti-inflammatory and analgesic agent as it was fully satisfactory in terms of preventing irritation and skin whitening after peeling.

11) Maleic acid copolymer resin referred to in the present invention is one or a mixture of two or more of the resins listed below. That is, methyl vinyl ether/(anhydrous) maleic acid copolymer, such as Gantrez (Gan, manufactured by G, A, F)
trez)-A NM, methyl vinyl ether/maleic acid ethyl ester co-conjugate, e.g. G, A, F
Gantrez E 8-2 manufactured by
25. Methyl vinyl ether/maleic acid butyl ester co-polymer 1, e.g. Gantrez B5-425, B8-435 manufactured by G, A, F.
Methyl epinylether/maleic acid isoproyl ester copolymer, such as (Gantr) manufactured by G, A, F
ez) BS-555-I, styrene/(anhydrous)
Maleic acid copolymer 1 For example, 8MA10 manufactured by ARCO
DD, 2000.3000, styrene/maleic acid propyl ester copolymer 1, e.g. Oxirac 5H-101 manufactured by Nippon Shokubai Kagaku Co., Ltd., 8MAl 44 manufactured by ARCO Co., Ltd.
0.17352.2625, inbutylene/(anhydrous) maleic acid copolymers, such as Tamol 731 from Rohm & Haas, ethylene/(anhydrous) maleic acid copolymers, such as Mon5anl.

These include EMA-91 manufactured by Co., Ltd., ethylene/butyl maleic acid ester copolymer, divinyl ether/(anhydrous) maleic acid copolymer, and the like. The blending amount of this maleic acid copolymer resin is also as described above in the present invention.

The key point for obtaining ideal drug release and film properties is that the blending amount of the maleic acid copolymer resin in the resin mixture of (1) and (11) mentioned above is 0. It is 5 to 20 weight % (preferably 1.0 to 15 weight %, more preferably 1.0 to 12 weight %). If the amount of maleic acid copolymer resin is less than 0.5%, the skin adhesion of the film will be poor, and if it is more than 20%, it will show excessive skin adhesion and have problems in peelability. . Furthermore, even if they have good skin density, many of them have low compatibility and transparency with alcohol-soluble nylons, such as polyvinylpyrrolidone, polyvinyl alcohol, hydroxypropyl cellulose, and polyvinyl acetate. However, it has been a national challenge to find one that exhibits satisfactory compatibility and transparency. On the other hand, the maleic acid copolymer resin of the present invention showed excellent compatibility, making it possible to form a transparent polymer blend with alcohol-soluble nylon, thereby achieving the object of the present invention. .

Next, on the combination of alcohol-soluble nylon and maleic acid copolymer resin of the present invention, the most effective specific acidic anti-inflammatory analgesics include methyl salicylate, glycol salicylate, :) clofenac sodium salt, ketoprofen, and nazoloxene. , indomethacin, flurbizolofen, acemethacin, clidanac, piroxicam, roquinpro-7ene, ibuprofen, pranoprofen, and ester derivatives thereof. The blending amount of the anti-inflammatory analgesic agent is 10 in total of the resin mixture of the above and (11).
0 parts by weight, 0.1 to 600 parts by weight (preferably 0.5 to 400 parts by weight, more preferably 1 part by weight)
~500 Juryūbu). Of course, these drugs
It may be blended alone into the base component. It may also be used dissolved or suspended in a polyhydric alcohol and/or its derivatives.

The above-mentioned polyhydric alcohol and or its derivative means polyhydric alcohols, polyhydric alcohol alkyl ethers, polyhydric alcohol alkyl esters, and the like. These are solubilizers and release aids for the above-mentioned anti-inflammatory and analgesic agents, and maintain the flexibility and moisturizing effect of the film. Examples of polyhydric alcohols include ethylene glycol, diethylene glycol, triethylene glycol, (poly)ethylene glycols such as PEG-200 and PEG-400, flopylene glycol, and polyethylene glycol-polyzolobylene glycol block copolymers. Combine, glycerin, toilet.

Examples include shield alcohols such as erythritol and arabite.

Examples of polyhydric alcohol alkyl ethers include seronlubs such as ethyl cellosolve and butyl cellosolve, polyoxyethylene such as polyoxyethylene diuryl ether, polyoxyethylene cetyl ether, polyoxyethylene stearyl ether, and polyoxyethylene oleyl ether. Examples include alkyl ethers, polyoxyethylene alkylphenol ethers such as polyoxy7ethylene octylphenol ether, and polyoxyethylene nonylphenyl ether. Examples of polyhydric alcohol alkyl esters include glycerin stearate, glycerin oleate, glycerin fatty acid esters, sorbitan fatty acid esters such as luhitan monolaurate, sorbitan monostearate, and sorbitan tristearate, and polyoxyethylene sorbitan. Polyoxyethylene sorbitan fatty acid esters such as monolaurate and polyoxyethylene sorbitan monostearate, polyoxyethylene fatty acid esters such as polyoxyethylene monolaurate and polyoxyethylene monostearate, etc. One or more of these can be used. The blending amount of the polyhydric alcohol and/or its derivative is 0.1 to 600 parts (preferably 0.5 to 2 parts) per 100 parts of the resin mixture.
00 parts by weight, more preferably 1.0 to 50 parts by weight.

The above-mentioned lower alcohol means ethyl alcohol, isopropyl alcohol, etc., and is used as a solubilizer for the alcohol-soluble nylon and maleic acid copolymer resin mixture. If the water content is more than 50 cm, the soluble nylon will be difficult to dissolve, resulting in an uneven solution, poor skin adhesion and peeling properties, and a decrease in drying properties. A range of % is preferred. The amount of water-containing or anhydrous alcohol to be blended is preferably 200 to 1.9 parts by weight per 100 parts by weight of the resin mixture.

If it is less than 200 parts by weight, a non-uniform solution will be obtained due to the relationship with the solubility of the resin mixture, resulting in poor skin release properties and extremely low solution stability. Also 1
If the amount is greater than 900 parts by weight, the polymer concentration will be diluted, resulting in poor drying properties, and a sagging phenomenon will occur during application, resulting in uneven film thickness and poor peelability.

The above is the basic composition of the external anti-inflammatory analgesic of the present invention, but in addition, conventionally known percutaneous absorption enhancers, stabilizers, anti-aging agents, -
Additives such as fragrances, mineral oils, antioxidants, reinforcing fillers, ultraviolet absorbers, bulking inorganic fillers, and adhesives, as well as skin irritants, keratin emollients, antihistamines, and vitamins, such as dl-camphor, l- Menthol, thymol, nonylic acid vanillylamide, nicotinic acid benzyl ester, capnizone, ethyl ξ2-aminobenzoate, 2-hydroxy-4-methoxybenz9phenone, 2-ethoxyethyl 4-methoxycinnamate, diphenhydramine hydrochloride, queniramine , Diphenhydramine, Tori Renamine,'
) Phenylimitasol, tondialumine, chlorpheniramine maleate, vitamin E, etc. may be added as necessary.

Next, the method for producing the external anti-inflammatory analgesic of the present invention will be described.

Alcohol-soluble nylon and maleic acid copolymer resin are added to water-containing or non-water-containing lower alcohols at 60℃~
After heating to 80° C. to uniformly dissolve, cool to room temperature, add an active ingredient such as an anti-inflammatory analgesic, and thoroughly mix and dissolve or disperse to obtain the external anti-inflammatory analgesic of the present invention. Furthermore, it goes without saying that it can be molded into liniments, aerosols, sticks, gels, etc. using conventionally known techniques.

As mentioned above, the topical anti-inflammatory analgesic of the present invention was created for the first time by the present inventor, and is made of alcohol-soluble nylon,
The combination of the present invention has the characteristics of a maleic acid copolymer resin and a specific acidic anti-inflammatory analgesic, and has excellent drug release and transdermal absorption, as well as a long-lasting effect. It does not cause skin problems such as dryness or excessive whitening, and can be applied evenly to curved areas, etc. After application, it quickly forms into a single film, has good skin adhesion, and can be peeled off. It is an ideal topical anti-inflammatory analgesic that can be easily removed when desired.

Next, the external anti-inflammatory analgesic agent of the present invention will be explained in more detail with reference to Test Examples and Examples. Note that the present invention is not limited to this.

Trial and Complaint Example 1 Transdermal Absorption Test Prepare the external anti-inflammatory M2R agent of Example 1, and add 100 μl of it.
The dorsal skin of a rat that has been shaved (circle with a diameter of 6.5 mm)
Blood was collected 1, 2, 4.6 and 8 hours after the application was applied uniformly to the skin, and the concentration of salicylic acid in the serum was measured. or,
For comparison, the liquid formulation of Reference Example 1 was prepared and the same test was conducted.

The results are shown in Figure 1. Here, 1 indicates the external anti-inflammatory analgesic solution of Example 1, and 2 indicates the external anti-inflammatory analgesic solution of Reference Example 1.

As is clear from the results shown in FIG. 1, the external anti-inflammatory analgesic solution of Example 1 of the present invention showed better transdermal absorption and superior sustained effects compared to the solution of Reference Example 1. found.

Test Example 2 Skin irritation test Example 3, Example 4, Reference Example 2, commercially available anti-inflammatory analgesic patch (
4@, which is made of natural rubber and contains methyl salicylate, was applied to the upper backs of 25 healthy men for 48 hours. After peeling 3
The degree of skin irritation was evaluated at 0 minutes and 24 hours later. (The skin used as a criterion for evaluation. The degree of rash is as follows.) The results are shown in Table 1.

As is clear from the above results, Examples 6 and 4 of the present invention were found to cause significantly less skin irritation than Reference Example 2 and commercially available anti-inflammatory analgesics. The agent was found to be of excellent quality.

Test Example 6 Usage Comparison Test 20 subjects were given Examples 6 and 4 of the present invention, Reference Examples 2 and 6 as comparative examples, and commercially available Linimen) [100% each].
It was applied to the surface of the forearm in an area of 2×2 cIIL using a dab.

The results are shown in Table 2, and it was found that Examples 6 and 4 of the present invention were significantly superior to commercially available liniment preparations, Reference Examples 2 and 6, which supports the usefulness of the present invention. Ta.

Test item a) Fast-acting (time to start feeling irritation) within 2 minutes...
0 Within 2-5 minutes...△ More than 5 minutes...× Mouth) Persistence (time until irritation disappears) More than 6 hours
・ 0 1 to 3 hours ・・ C Within 1 hour × C) Drying property (@Time until blood removal and stickiness disappears) Within 2 minutes ・ ・ 0 2 to 5 minutes ・・・・−△ 5 minutes or more X 2 ) Sting (strength of the sheet is very strong ・ 0 Strong Mu weak × E) Skin adhesion (time for the formed film to peel off from the surrounding area) 4 hours or more 0 1 to 4 hours To less than 1 hour Skin releasability (Can the formed film be peeled off as a single film?) Can it be peeled off as a single film? ・0 Breaks in the middle and cannot be peeled off ・-／＼ The adhesion is too strong and it cannot be peeled off... X Table 2 Actual drawing example 1 Soluble nylon 15.0% (Ultraamide IC, manufactured by BASF) Methyl vinyl ether/maleic acid ethyl ester copolymer 2.0 (Gantrez ES-225, manufactured by GAF) Glycerin 1.5 Ethanol/water (80/20 W/W) 62.5 Methyl salicylate 7.6 1-menthol 5,8 dl-camphor 4.9 Thymol 1.0 100.0 nylon (Ultraamide IC) soluble in aqueous ethanol
) and methyl vinyl ether/maleic acid ethyl ester copolymer (Gantrez ES-225),
- After soaking day and night to swell, heat to 60°C to 80°C to uniformly dissolve. This was cooled to room temperature, methyl salicylate, l-menthol, dll-camphor, thymol and hyclycerin were added to it and thoroughly mixed and dissolved to obtain an external anti-inflammatory analgesic solution of the present invention. This product has excellent drug release and transdermal absorption, and after application, it quickly becomes a film, acts on the affected area immediately, and has an immediate effect, but the effect remains good for several hours or more. It lasted for. Furthermore, during and after application, it does not cause skin irritation such as skin irritation or whitening, and has good skin adhesion and can be used even on curved areas.Furthermore, this film is highly flexible, so There was no feeling of stiffness during use, and even when it was peeled off after use, it was painless and could be easily removed as a single film.

Example 2 Soluble nylon 15.0 t (Ultraamide IC, made by BASF) Methyl vinyl ether/maleic anhydride copolymer 2.0 (made by Gantrez A N, G AF) Glycerin 2.0 Ethanol/zk (80 /20 w/w) 77.5 pheniramine 05 ketoprofen 3.0 ioo, o* One bottle of external anti-inflammatory analgesic liquid was prepared according to the manufacturing method of Example 1.

Similar to Example 1, this product showed good characteristics.

Example 3 Soluble nylon 1 [LOchi (CM-8000, manufactured by Toshi Co., Ltd.) Methyl vinyl ether/maleic acid butyl ester co-M combination 2.0 ((1antrez gs-425, manufactured by GAF) Ethylene glycol 2.6 Ethanol/ Water (8o/20 w/w) 65.5iM acid diphenhydramine 0.2 Methyl nalycylate 8.0 β-menthol 7.0 dl-camphor 4.18 Nonyl-valinylamide 0.02 Thymol 08 100.0 yen Example 1 The present topical anti-inflammatory analgesic solution was prepared according to the manufacturing method.

Similar to Example 1, this product showed good characteristics.

Example 4 Soluble nylon 16.0% (Elpamide-8023, manufactured by DuPont) Methyl vinyl ether/maleic acid ethyl ester copolymer 1.5 (Gantrez ES-225, manufactured by GAF) Propylene glycol 1.1 Ethanol/water ( 85/15 W/W) 59.0 Diphenhydramine 0.4 Methyl salicylate 12, O l-menthol 7.0 dl-camphor 4.47 Nonylic acid valiinylamide 0.03 Thymol 0.5 Vitamin E1.0 ioo, According to the manufacturing method of Example 1, the present external anti-inflammatory analgesic liquid was prepared.

Similar to Example 1, the crystal exhibited good characteristics.

Example 5 Soluble nylon 60.0 t (Ultraamide I C, BASF) Inbutylene/(anhydrous) maleic acid copolymer 1.0 (Tamo+ 731 + Rohm & Haas lining) Polyoxyethylene lauryl ether 0. 5 Ethanol/Water (90/10 W/W) 65.5 4-Methoxycinnamate-2-ethoxyethyl 0.5 Torirenamine 0.5 Naproxen 2.0 100.0 Ch According to the manufacturing method of Example 1 We prepared this topical anti-inflammatory analgesic solution.

Similar to Example 1, the crystal exhibited good characteristics.

Example 6 Soluble nylon 25.0 cm (CM-4001, manufactured by Toshi Co., Ltd.) Styrene/(anhydrous) maleic acid copolymer 4.0 (BM
A-2000, ARCO) Diethylene glycol 2.5 Ethanol/Water (80/20 W/W) 62.0.4 Ethyl aminobenzoate 1.0 Diphenylimidazole 0.5 Ketoprofen 5.0 100.0 The present topical anti-inflammatory analgesic solution was prepared according to the manufacturing method.

Similar to Example 1, the crystal exhibited good characteristics.

Example 7 Soluble nylon 20.0cm (CM-4001, manufactured by Komeshi Co., Ltd.) Ethylene/(anhydrous) maleic acid copolymer 4.0cm (BM
A-91+ Mon5anto) polyoxyethylene nonylphenyl ether 1.0 ethanol/water (
90/10 W/W) 70.02-hydroxy-4-
Methoxybenzophenone 0.5 tons Dialmine 0.
5 Diclofenac sodium salt 4.0 ioo, os The present topical anti-inflammatory analgesic solution was prepared by FA according to the manufacturing method of Example 1.
I arranged it.

Similar to Example 1, the crystal exhibited good characteristics.

Example 8.

Soluble nylon 5.0chi (Elbamide-8062, manufactured by DuPont) Sunare //
Flovyle maleate copolymer 0.5 (Oxirac 8H-101, Nippon Shokubai Kagaku M) Triethylene glycol 4.5 Ethanol/water (9515W/W) 59.0 Chlorpheniramine maleate 1.0 Methyl salicylate 12
．． O 4-menthol 12.9 dl-camphor 6.05 Nonylic acid valinylamide 0.05 Thymol 1.0 ioo, o% 50 parts of the liquid formulation of the above formulation and 12 chlorofluorocarbons were prepared by a known method.
50 parts were mixed to prepare one bottle of external anti-inflammatory analgesic aerosol.

Similar to Example 1, the crystal exhibited good characteristics.

Example 9 Soluble nylon 15.0% (Ultraamide IC, manufactured by BASF) Methyl vinyl ether/maleic acid isopropyl ester copolymer 2.0% (Gantre
z ES-335-I, manufactured by GAF) PEG-200
8.0 Ethanol/Water (92/8 W/W) 58.5 Dibenzylidene sorbitol 3.5 Diphenhydramine 1.0 Methyl salicylate 5.0! -Menthol 5,0 dl-Camphor 1.0 Thymol 1.0 100, On The present external anti-inflammatory analgesic solid stick having the above formulation was prepared by a known method.

Similar to Example 1, this product showed good characteristics.

Example 10 Of-soluble nylon 13.0% (CM-8000, Toshisha Co., Ltd.) Methyl vinyl ether/maleic ethyl ester copolymer 0.9 (Gantrez MS-225, GAF Co., Ltd. #) Styrene/furovir maleate Ester copolymer 0.6 (Oxirac 8H-101, manufactured by Nippon Shokubai Kagaku Co., Ltd.) Butyl cellosolve 0.7 Ethanol/water (70/30 W/W) 62.3 Carboxy vinyl polymer 1.6 (Carboball 940) (manufactured by Goodrich) Triethanolamine 1.9 Methyl salicylate 3.0 Glycol salicylate 10.

l-Menthol 4.0 Thymol 20 ioo, oq6 The present external anti-inflammatory camphor gel with the above formulation was prepared by a known method.

Similar to Example 1, this product showed good characteristics.

Reference example 1 Soluble nylon 15.0% (Ultraamide IC, manufactured by BAaF) Glycerin
1.5 Ethanol/water (80/20 W/W) 64.5 Methyl salicylate 73 1-menthol 5.8 dl-camphor 4.9 Thymol 1.0 ioo, o according to the manufacturing method of Example 1, This topical anti-inflammatory analgesic solution was prepared.

Reference example 2 Soluble nylon 10.0% (CM-8000, manufactured by Toshi Co., Ltd.) Ethylene glycol 1.6 Ethanol/Water (80/20 W/W) 68.5 Diphene hydrochloride/Hydramine 0.2% Rittel's methyl 8. O e-menthol 7.0 dji' -/J y full 4.18 Nonylic acid valinylamide 0.02 Thymol 0.8 ioo, os According to the manufacturing method of Example 1, the present external anti-inflammatory analgesic liquid was prepared.

Reference Example 3 Soluble nylon 16.0% (Elbamide-8025, manufactured by DuPont) Propylene glycol 1.1 Ethanol/Water (85/15 W/W) 60.5 Diphenyl chloride 10.4 Methyl salicylate 12.0! -Menthol ZO dl-Camphor 4.47 Nonylic acid valinylamide 0.05 Thymol 0.5 Vitamin E1.0 100.0% According to the manufacturing method of Example 1, this topical anti-inflammatory M &+ ft
'l.

The agent was adjusted.

[Brief explanation of drawings]

FIG. 1 is a graph showing that the external anti-inflammatory analgesics obtained in Example 1 and Reference Example 1 of the present invention were applied to the skin of each rat separately. 1 - Topical anti-inflammatory analgesic agent of Example 1 2- Topical anti-inflammatory analgesic agent of Reference Example 1 Patent attorney Door 1) Parent Male Figure 1

Claims (1)

[Claims] tlHI) Aliphatic polyamide resin, 80 to 995 parts by weight; (II (1M water) maleic acid, copolymer resin containing maleic acid monoalkyl ester or/and maleic acid dialkyl ester, 20 ~0.5 heavy lid parts; For a total of 100 heavy lid parts, a resin mixture consisting of: (ii) anti-inflammatory analgesic agent, 0.1 to 600 parts by weight; (b) polyhydric alcohol and/or its derivative, 0.1・～60
0 heavy electric part; ei Lower alcohol containing 0 to 50 times of water, 2
00 to 1900 parts; An external anti-inflammatory analgesic agent. (2) External anti-inflammatory analgesic agent according to claim 11, wherein the aliphatic polyamide resin is alcohol-soluble nylon. (3) (Anhydrous) maleic acid, maleic acid monoalkyl ester or/and maleic acid dialkyl ester The copolymer resin containing methyl vinyl ether/
(Anhydrous) Maleic acid copolymer, methyl vinyl ether/
Maleic acid monoalkyl ester and/or maleic acid dialkyl ester copolymer, styrene/(anhydrous)
Maleic acid copolymer, styrene/maleic acid monoalkyl ester and/or maleic acid dialkyl Nisder copolymer, isobutylene/(anhydrous) maleic acid copolymer, imbutylene/maleic acid monoalkyl ester and/or maleic acid copolymer acid dialkyl ester copolymer,
A copolymer consisting of one or more of ethylene/(anhydrous) maleic acid copolymer, ethylene/maleic acid monoalkyl ester and/or maleic acid dialkyl ester copolymer, or divinyl ether/(anhydrous) maleic acid copolymer. The external anti-inflammatory analgesic agent according to claim 11 or (2), which is a polymer resin. (4) The anti-inflammatory analgesic agent is methyl salicylate, glycol salicylate, diclofenac sodium salt, ketoprofen, nazoloxene, intomethane, furur. biprofen, hiroxicam, acemethacin, loxoprofen,
The external anti-inflammatory analgesic agent according to claim (1), (2), or (3), which is selected from Klidanac, ibuprofen, pranoprofen, and these Nisdels.