JPH01299217A - Plaster for external use - Google Patents

Abstract

PURPOSE:To provide a plaster for external use, compounded with an azulene derivative and effective in preventing rush without causing side-effect. CONSTITUTION:A plaster material composed of a drug for transcutaneous absorption and a pressure-sensitive tacky adhesive is compounded with a rush- preventive consisting of an azulene derivative known as an anti-inflammatory agent for oral cavity, e.g., 4-methyl-7-ethylazulene and the obtained mixture is spread on a flexible substrate to form the objective plaster for external use. The amount of the azulene derivative compounded to the plaster is 0.001-0.1mg/cm<2>, especially 0.002-0.2mg/cm<2>. The azulene derivative is not immediately absorbed in the blood after application of the plaster and is retained in the skin to exhibit rush-preventive effect.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to an external patch containing an azulene derivative as a protection agent.

[Conventional technology]

BACKGROUND ART As a means of administering transdermal drugs, formulations such as poultices, ointments, and tapes containing various drugs have been frequently used. However, these preparations often cause skin irritation due to excessive irritation of the drug or irritation of the base. In recent years, ODT therapy has also been used to swell the stratum corneum of the skin by sealing the skin surface with tape, etc.
Therapy is being implemented to achieve transdermal absorption by lowering the barrier function. However, since this also seals the skin for a long period of time, serious side effects such as redness, edema, and irritation occur due to stuffiness due to moisture, contact with the base, etc. Furthermore, in recent years, for the purpose of treating angina pectoris and hypertension,
Treatment and prevention have been attempted by transdermally absorbing systemic drugs. These techniques cover the skin with a tape, punch, etc. composed of a drug-impermeable membrane and a drug-containing adhesive layer to control the release of the drug and allow it to be absorbed transdermally.

However, since these drugs release and absorb the drug gradually and maintain effective blood concentration for a long period of time, the application time is inevitably long. Therefore, the base, adhesive, etc. cause more skin irritation than conventional external patches, and the occurrence of serious side effects such as redness, edema, and irritation cannot be avoided.

On the other hand, for the purpose of preventing these skin irritations, various skin irritation prevention agents have been mixed and used in external patches. For example, 0.01 to 1.0% by weight of diphenhydramine hydrochloride, chlorpheniramine maleate, diphenhydramine salicylate, ammonium glycyrrhizinate, glycyrrhetinic acid, etc. are used.

However, these anti-bleeding agents described above have poor stability in the base, and their effects are also insufficient. Therefore, attempts have been made to incorporate a large amount of the above-mentioned dry skin protection agent, but the drug itself has side effects, has an adverse effect on the skin, and even becomes a cause of dry skin irritation. In other words, the current situation is that the effects of conventional air-contamination prevention agents are insufficient.

Next, the conventional technology of azulene will be explained. Azulene is a general term for compounds having an azulene skeleton, such as chamaazulene (1,4-dimethyl-7-nityl azulene), which is a component of chamomile essential oil, and 1,4-dimethyl-7-iteropropylene obtained from eucalyptus oil. In addition, water-soluble azulene, which has a sulfone group introduced therein, is used as an anti-inflammatory agent for the oral cavity to treat pharyngitis and tonsillitis.

Widely used for stomatitis, acute gingivitis, glossitis 1 oral wounds.

However, there have been no examples of it being incorporated into external patches for the purpose of preventing exposure, and this is what the inventors of the present invention were able to do for the first time.

[Problem that the invention seeks to solve]

The inventors of the present application searched for the most appropriate exposure prevention agent for external patches, and after extensive research, they found that an outstanding effect could be obtained by incorporating the azulene derivative, which is known as an oral anti-inflammatory agent. They discovered that this could be done and completed the present invention.

That is, the problem to be solved by the present invention is to solve all the drawbacks of conventional air-prevention agents in external patches by using an azulene derivative.

[Means for solving problems]

The present invention relates to azulene derivatives (for example, 4-dimethyl-7-
Nithyl azulene, 4-dimethyl-7-ethyl azulene
Sodium 3-sulfonate, potassium 4-dimethyl-7-ethylazulene-3-sulfonate, 4-dimethyl-7
- Ituprobil azulene, sodium 4-dimethyl-7-isopropylazulene-3-sulfonate, potassium 4-dimethyl-7-itubropylazulene-3-sulfonate) are added as air exposure prevention agents. The present invention relates to a characteristic topical patch.

The first feature of the external patch of the present invention is that it contains an azulene derivative as a dry agent, and other components include a transdermally absorbable drug and a pressure-sensitive adhesive. A plaster consisting of these structures is spread on a flexible support to form a patch for external use. The effective amount to be blended is 0.1 to 0.001 μ/d, preferably 0.1 to 0.001 μ/d, depending on the paste used and the azulene derivative. By blending O1 to O, QO1 /cd, more preferably 0.02 to 0.002 /d, the characteristics of the present invention as a gentle external patch can be fully exhibited.

Next, the percutaneously absorbable drug to be incorporated into the topical patch of the present application may be any drug that exerts the desired pharmacological effect through transdermal absorption.Specifically, salicylic acid, methyl salicylate, etc. , glycol salicylate, l-menthol, camphor, peppermint oil, thymol, nicotinic acid benzyl ester, capsicum extract, kabsaicin, pentazocine, eptazocin, zenazole, mepirizole, piroxicam, benzydamine, thiaramide, bufexamac, acetaminophen, and ibuprofen. , alclofenac, acemethacin, indomethacin, ketoprofen, nabroxeno, sulindac,
benoxaprofen, indobufen, mefenamic acid,
Tolmetin, methiazine acid, protidic acid, pranoprofen, sintal, fuenbufuene, fentiazazac, diflunisal, zomepirac, bimeprofen,
Skin irritants and analgesic anti-inflammatory agents such as pendazac, miloprofen, amfenafuku, suprofen, and their ester derivatives, central nervous system acting agents such as fluphenazine, thioridazine, diazepam, chlorpromazine, nitrazepam, hydrothiazide, pendroflunathiazide,
Antihypertensive diuretics such as reserpine, antihypertensive agents such as clonidine and pindolol, nitroglycerin, nitroglycol, isosorbitinitrate, papaverine hydrochloride, dipyridamole, nifedipine, coronary vasodilators such as diltiazem hydrochloride, 6MfJl salbutamol, turopterol hydrochloride, fumar Antitussive and expectorant agents such as acid ketotifen, procaterol hydrochloride, and ephedrine hydrochloride, vitamin preparations such as vitamin A, vitamin D, vitamin E1, and other vitamins, antispasmodics such as scopolamine, prostaglandin, antiallergic agents, antiulcer agents, and diabetes treatment. and the like, and these are used by appropriately blending one or more medicinal ingredients.

As the pressure-sensitive adhesive, commonly used adhesives such as natural, synthetic, oil-based, or water-based adhesives that are safe to the skin can be used as appropriate. Among these, natural rubber, IR (synthetic polyisoprene rubber), SIS system (styrene-isoprene-styrene copolymer), SBS system (styrene-butadiene-styrene copolymer), silicone system, acrylic resin, gelatin/polymer Sodium acrylate, methyl vinyl ether, and the like are preferably used.

Examples of the support include those that act as a protective agent for adhesion of the topical patch to the skin, such as polyethylene, polypropylene, polybutadiene,
Films or sheets of ethylene vinyl acetate copolymer, polyvinyl chloride, polyester, nylon, polyurethane, etc., or porous bodies, foams, paper, cloth,
Selected from nonwoven fabrics, etc.

Specific formulation forms of the patch of the present invention having the above structure include plasters, poultices, tape formulations, etc., and these formulations may be prepared as appropriate.

[Effect]

In the topical patch of the present invention, azulene, which is blended as a dry agent, is not immediately absorbed into the blood, but remains on the skin and exhibits a dry protection effect.

This will be explained in more detail using the following Examples and Test Examples.

Note that "middle of the text" refers to parts by weight.

Example 1 3 parts of indomethacin was blended with 97 parts of a pressure-sensitive adhesive made of 2-ethylhexyl acrylate/vinyl acetate copolymer, and then azulene was added at a ratio of 0.05 μ/-, and then ethylene-acetic acid was added. 1100 on vinyl copolymer sheet
The patch of the present invention was prepared by spreading it to a thickness of p.

Example 2 Styrene-isoprene-styrene block copolymer 30
part, 35 parts of rosin modified resin, 22 parts of liquid paraffin, and 6.5 parts of glycol salicylate. - After blending 6.5 parts of menthol and then adding azulene to 0.035 μ/ctJ, 150-
The patch of the present invention was prepared by rolling it out to a thickness of .

Example 3 6 parts of methyl salicylate, 4 parts of N-menthol, and 2 parts of glycol salicylate were blended with 30 parts of natural rubber, 18 parts of rosin resin, 12 parts of polybutene, and 18 parts of zinc oxide, and then 0.08 μ/d of azulene was added. After adding the mixture to a thickness of 200 ps, it was spread on a nonwoven fabric to a thickness of 200 ps to obtain a patch of the present invention.

Example 4 Styrene-isoprene-styrene block copolymer 25
1 part, 37 parts of alicyclic petroleum resin, and 30 parts of liquid paraffin were blended with 8 parts of clonidine, and then 0.0 parts of azulene was added. O1■
/d, then add 10 to the polyester film.
The patch of the present invention was prepared by spreading it to a thickness of 100 mL.

Example 5 10 parts of isosorbite cinitrate was blended with 90 parts of a pressure-sensitive adhesive made of 2-ethylbutyl acrylate, and then azulene was added to give o, oos■/d, and then aluminum was vapor-deposited. The patch was spread on a polyvinyl chloride sheet so as to have a thickness of 60p to obtain a patch according to the present invention.

Example 6 Styrene-isoprene-styrene block copolymer 30
1.0 parts, 44 parts of alicyclic petroleum resin, 22 parts of liquid paraffin, 2 parts of ketoprofen, and 6 parts of peppermint oil were blended, and then azulene was added at a concentration of 0.003 μ/d. The adhesive patch of the present invention was prepared by spreading it to a thickness of -.

Test Example 1 Human Skin Irritation Test Using the patch obtained in Example 1.2, a 48-hour patch test was conducted on the inside of the human upper arm, and the degree of skin change was observed 1 hour and 24 hours after removal. The degree of skin irritation was determined. Note that Reference Examples 1a and 2a in Table 1 are Example 1. Comparative Examples 1 and 2 correspond to Example 2, excluding azulene, respectively, and Comparative Examples 1 and 2 correspond to Example 1.2, respectively.
In 1, diphenhydramine hydrochloride was added, and in 2, glycyrrhetinic acid was added at 1.0%.

In addition, the criteria for determining skin irritation are as follows.

No change; slight redness, indicated as -; clear redness, indicated as +; severe feeling, indicated as +; Table 1, indicated as ``Table 1'' As is clear from the results of Table 1, the patch of the present invention showed a higher effect of preventing exposure to air than those containing no azulene or those containing a known anti-aging agent.

〔Effect of the invention〕

As is clear from the above test examples, the topical patch of the present invention has the following properties:
It has a remarkable effect of preventing exposure, and is very useful medically.

Procedural amendment 0. Eh, 1. Indication of the case 1988 Patent Order No. 131038 2 Title of the invention Topical patch 3 Person making the amendment 4 Date of the amendment order 5 In the specification to be amended, "3. Detailed description of the invention" Column fl) In the specification, in the column ``3. Detailed Description of the Invention,'' in the second line from the first line, ``Feelings'' is corrected to ``Feelings''.

Claims (1)

[Claims] 1. An external patch containing an azulene derivative. 2. External patch containing an azulene derivative as a protection agent. 3. An external patch consisting of a transdermal absorbable drug, a pressure-sensitive adhesive, and an azulene derivative as an anti-contamination agent. 4. 0.1 to 0.001 mg/cm^ of azulene derivative
4. The external patch according to claim 1, 2 or 3, comprising: