JPH0568266B2 - - Google Patents

Description

[Detailed description of the invention]

[Industrial Field of Application] The present invention relates to an external member that is applied directly to the skin for purposes such as patch tests, hemostasis, disinfection, and protection of diseased areas of the body, and drug administration locally or to the circulatory system. That is, it relates to so-called adhesive plasters for pharmaceutical or medical aid purposes, plasters, poultices, etc. for the purpose of analgesic and anti-inflammatory purposes. [Prior Art] Conventionally, such external members have been known to have a layer of polymer material that has pressure-sensitive adhesive properties at room temperature laminated on a support such as paper, nonwoven fabric, or thermoplastic resin. It is well known that dermatitis, a so-called bandage rash, can occur on the skin to which it is applied due to its adhesive strength and irritating properties, as it is applied directly to the skin for a long period of time. In order to improve this bandage rash, attempts have been made to research adhesive components such as resins and raw rubber, to find breathable supports that do not inhibit the physiological effects of the skin, and to examine methods of applying the adhesive to the supports. [Problems to be Solved by the Invention] However, these attempts have had little effect, and bandage rash remains one of the most well-known dermatitis types among adhesive dermatitis. In view of these circumstances, the inventors of the present invention have conducted extensive research in order to obtain an external member that suppresses skin irritation. As a result, the present inventors have developed a specific silicone compound, namely polyoxyalkylene-modified organopolysiloxane, which is a polymer that has pressure-sensitive adhesive properties at room temperature. It has been discovered that by incorporating it into the material layer, skin irritation can be reduced and bandage rash can be significantly reduced, and based on this knowledge, the present invention has been completed. [Means for Solving the Problems] That is, the present invention provides an external member comprising a sheet or tape-like support laminated with a polymer material layer having pressure-sensitive adhesive properties at room temperature. This is an externally used member containing polyoxyalkylene-modified organopolysiloxane. Hereinafter, the configuration of the present invention will be described in detail. Supports used in the present invention include papers such as Japanese paper and kraft paper, fabrics such as cotton cloth, stapler, and nonwoven fabrics, vinyl chloride, polypropylene, polyethylene, polyester, polycarbonate, copolymers thereof, cellophane, etc. Examples include plastic films, metal foils, and laminates of these various supports. Examples of polymeric substances having pressure-sensitive adhesive properties at room temperature used in the present invention include acrylic polymeric substances, such as (meth)acrylic acid n-butyl ester, (meth)acrylic acid n-hexyl ester, ( meth)acrylic acid-2-ethylbutyl ester, (meth)acrylic acid isooctyl ester,
(meth)acrylic acid-2-ethylhexyl ester, (meth)acrylic acid-n-decyl ester,
(meth)acrylic acid alkyl esters such as (meth)acrylic acid-n-dodecyl ester and (meth)acrylic acid tridecyl ester and/or (meth)acrylic acid copolymerizable with the above esters;
Itaconic acid, maleic acid, maleic anhydride, (meth)acrylic acid-2-hydroxyethyl ester, (meth)acrylic acid-2-hydroxypropyl ester, (meth)acrylamide, N,N-
Dimethyl (meth)acrylamide, (meth)acrylic acid dimethylaminoethyl ester, (meth)
Copolymers with functional group-containing monomers such as acrylic acid diethylaminoethyl ester and (meth)acrylic acid-2-methoxyethyl ester and/or vinyl monomers such as acrylonitrile, vinyl acetate, and vinyl propionate. Rubber-based polymer substances such as polyisoprene rubber, polyisobutylene rubber, polybutene rubber, butyl rubber, styrene-butadiene rubber, styrene-butadiene-styrene copolymer rubber, styrene-isoprene-styrene copolymer rubber, silicone rubber, etc. Examples include natural rubber and other vinyl-based polymer substances such as polyvinyl alcohol, polyvinyl ether, and polyvinyl acetate. In the present invention, these polymeric substances are used alone or in combination, taking into consideration adhesion, compatibility, etc. The polyoxyalkylene-modified organopolysiloxane used in the present invention is a compound represented by the following general formulas [A] to [D].

[ka]

[ka]

[ka]

[Formula, R is an alkyl group having 1 to 3 carbon atoms or a phenyl group, R' is hydrogen or an alkyl group having 1 to 12 carbon atoms, p is an integer of 1 to 5, and q is 2 or 3 , m is an integer of 5 to 100, and n and x are integers of 1 to 50.) The polyoxyalkylene-modified organopolysiloxane used in the present invention preferably has an average molecular weight of 3000 or more, more preferably 5000 or more. be. Further, it is preferable that the polyoxyalkylene-modified organopolysiloxane molecule contains 2 to 80% by weight of polyoxyalkylene groups, and more preferably 11 to 50% by weight from the viewpoint of effect expression. The amount of polyoxyalkylene-modified organopolysiloxane blended is 0.1 to 90% by weight, preferably 0.1 to 50% by weight in the polymer material layer. If it is blended in a large amount, it tends to impair the adhesion of the external member to the skin, which is not preferable. In the present invention, in addition to the above-mentioned essential components, various additives such as drugs, dissolution/diffusion improvers, water retention agents, keratin softeners, transdermal absorption enhancers, etc. can be incorporated into the polymeric material layer. . Specific examples of these drugs include: a. Analgesic and anti-inflammatory agents: for example, salicylic acid, methyl salicylate, glycol salicylate, 1-menthol, camphor, nonylic acid vanillylamide, tocopherol, pepper oil, thymol, capsicum extract, capsicum Tocopherol acetate, dl-camphor, acetaminophen, mefenamic acid, flufenamic acid, indomethacin,
Diclofenatuk, alcroenatuk, oxyphenbutazone, phenylbutazone, ibuprofen, flurbuprofen, etc.b Antibacterial substances: For example, nitrofurazone, nystatin, acetosulfamine, clotrimazole, pentamycin, amphotericin B, pyrrolnitrin, etc. c Antibiotics: e.g. β-lactan antibiotics (penicillins, cephalosporins), oxytetracycline, fradiomycin sulfate, erythromycin, chloramphenicol, etc. d Vitamins: e.g. vitamin A, ergocalciferol, cholecalciferol , octothiamine, riboflavin butyrate, etc.e Coronary vasodilators: e.g. nitroglycerin, nifemipine, dipyridamole, isosorbide dinitrate, erythritose tetranitrate, pentaerytose tetranitrate, etc. f Antihistamines: e.g. diphenhydramine hydrochloride , chlorpheniramine, diphenylimidazole, etc.g Corticosteroids: For example, hydrocortisone, prezonisolone, paramethasone, beclomethasone propionate, flumethasone, betamethasone, beclomethasone propionate,
Dexamethasone, triamcinolone, triamcinolone acetonide, fluocinolone, fluocinolone acetonide, fluocinolone acetonide acetate, clobexol propionate, etc.H Hypnotic analgesics: For example, barbitals such as phenobarbital, amobarbital, cyclobarbitalI Tranquilizers : For example, fluphenazine, thioridazine, benzodiazepines (for example, diazepam, lorazeban, flunitrazeban), chlorpromazine, etc. Antihypertensive agents: For example, clonidine, kallikrein, etc. Antihypertensive diuretics: For example, hydrothiazide,
Bendroflumethiazide, etc. Anesthetics: e.g. lidocaine, benzocaine,
Ethyl aminobenzoate, etc. Antiepileptic drugs: Examples include nitrazepam and meprobamate. Transdermal absorption enhancers include dimethyl sulfoxide, dodecyl sulfoxide, methyl octyl sulfoxide, dimethyl decyl phosphooxide,
Mono- or diethylacetamide, N-hydroxyethyl lactamide, dimethylacetamide, N,N
-dimethyldodecamide, dimethylformamide,
Toluic acid diethylamide, tetrahydrofurfuryl alcohol, tetrahydrofuran, sorbitol, dodecylpyrrolidone, methylpyrrolidone,
Urea, diethyl adipate, squalene, squalane, acetylated lanolin, cetyl lactate,
Dioctyl sebacate, ethoxylated stearyl alcohol, lanolin acid lanolin alcohol, higher fatty acid alcohol, salicylic acid, styliisooctanoate, liquid paraffin, squalane, petrolatum, amino acid, protease, ethyl nicotinate, 1-menthol, salpurul, high grade Examples include fatty acid triglyceride, polyoxyalkylene glycol, fatty acid mono(or di)ethanolamide, ethylene glycol monoethyl ether, polyoxypropylene alkyl ether, polyglycerin alkyl ester, and higher alkyl sulfone. In addition, solubilizers and water retention agents include lanolin, olive oil, glycerin, benzyl alcohol, butyl benzoate, isopropyl silistate, octanol, 1,3-butylene glycol, (poly)
Examples include ethylene glycol. Other optional components include fillers, adhesion aids, softeners, etc. for maintaining the shape retention of the polymer layer. Fillers include silica, titanium oxide, calcium carbonate, kaolin, mica, zinc white, aluminum hydroxide, barium sulfate, starch, talc, clay, etc. Adhesive aids include ethyl acetate, butyl acetate,
Examples of the softening agent include triethyl citrate and butyl alcohol, various plasticizers, polybutene, polyisobutylene low polymers, and the like. To manufacture the external member according to the present invention, any known method used for manufacturing pressure-sensitive adhesive sheets or tapes can be used. For example, a polyoxyalkylene-modified organopolysiloxane is added to a solution of a polymeric substance dissolved in a solvent or an emulsion in which a polymeric substance is dispersed in an aqueous medium, and the polyoxyalkylene-modified organopolysiloxane is dispersed therein. A method of applying a solution or emulsion and drying it to form a material for external use, or forming a polymer layer on a sheet or tape-shaped support without adding polyoxyalkylene-modified organopolysiloxane using the same method as above. Thereafter, the polyoxyalkylene-modified organopolysiloxane may be blended by coating or spraying. To form a polymer material layer (pressure-sensitive adhesive layer) on a sheet or tape-shaped support, the polymer material solution or emulsion is coated with a spray coating method, a roll coating method, a gravure coating method, or a reverse coating method. Known coating methods such as dip coating, screen printing, and flexographic printing can be used. The coating film may be dried under conditions such that the liquid component of the aqueous medium, the solvent in the polymer solution, etc. are scattered. For this purpose, heating may be performed at about 90 to 180° C. for about 1 to 10 minutes by a hot air drying method, a drying method using infrared irradiation, a drying method using far infrared irradiation, or the like. The thickness of the polymer material layer with pressure-sensitive adhesive properties varies depending on the type of externally used member, but in general, the thickness after drying is preferably 0.5 mm or less for adhesive plasters, and 0.5 mm or more for plasters, poultices, etc. . [Examples] The present invention will be described in detail with reference to Examples below, but the present invention is not limited to these examples, and various modifications can be made without departing from the technical idea of the present invention. It should be noted that all references to "Example Middle" represent parts by weight. In addition, skin irritation, holding power, and adhesive residue were measured using the following methods. Skin irritation A test piece with a width of 4 cm and a length of 7 cm was prepared from each external use member, and this was applied to the forearm of a test subject who is relatively prone to rashes as a bandage for 24 hours, and then removed. , 24-hour skin irritation values were evaluated. Evaluation of irritation was performed based on the following criteria. No reaction such as erythema ...-- Faint erythema ...± Erythema ...+ Strong erythema ... Strong erythema and edema ... Retention power 4 cm width and 7 cm length from each external component A test piece was created and attached to the subject's forearm for 24 hours.
It was determined whether the test piece would peel off from the skin. Adhesive Residue For each external member, it was determined whether adhesive remained on the release sheet when the release sheet was peeled off from the pressure-sensitive adhesive layer during use. In addition, when the external member was applied to the human forearm and removed after 24 hours, it was determined whether there was any adhesive residue on the applied skin surface. Example 1, Comparative Example 1 80 parts of adhesive was prepared using a set of a commercially available acrylic adhesive containing acrylic acid ester as the main component and a curing agent containing ethyl acetate as the main solvent (Cybinol AT-301, manufactured by Seiden Chemical Co., Ltd.). and 20 parts of a curing agent, and further mixed with 4 parts of polyoxyethylene-modified organopolysiloxane having the structure of general formula (A), containing 20% by weight of polyoxyethylene groups, and having an average molecular weight of 6000. . This was applied uniformly onto a vinyl chloride film and dried at room temperature to obtain a member for external use, which was designated as Example 1. In addition, a component for external use containing no polyoxyethylene-modified organopolysiloxane was obtained in the same manner, and this was designated as Comparative Example 1. Table 1 shows the skin irritation evaluation results of Example 1 and Comparative Example 1.

【table】

[Table] As is clear from Table 1, while skin irritation was observed in the comparative example containing no polyoxyethylene-modified organopolysiloxane, the product of the present invention was found to have less skin irritation in all test subjects. It can be seen that even in subjects who showed a slight irritability value, the irritability disappeared in a short period of time. Further, in Comparative Example 1, adhesive residue was observed on the release sheet and on the skin surface to which it was applied, whereas this was not observed in Example 1, and the adhesive had good retention on the skin. Example 2, Comparative Example 2 120 g/m ² of the polyoxyethylene-modified organopolysiloxane used in Example 1 was applied to a commercially available patch test bandage (manufactured by Torii Pharmaceutical) to obtain an external member, which was used as Example 2. . In addition, Comparative Example 2 was a commercially available patch test adhesive itself. The skin irritation evaluation results for Example 2 and Comparative Example 2 are shown in Table 2. As is clear from Table 2, skin irritation was observed in Comparative Example 2, whereas Example 2 had no skin irritation and was found to be excellent in safety. Furthermore, the product of the present invention had no adhesive residue and had good holding power, but the commercially available product had adhesive residue.

【table】

[Table] Example 3 4 parts of the polyoxyethylene-modified organopolysiloxane in Example 1 had the structure of general formula (B),
An external member was obtained using the same formulation and method as in Example 1, except that 45 parts of polyoxyethylene-modified organopolysiloxane containing 75% by weight of polyoxyethylene groups and having an average molecular weight of 30,000 was used. Example 4 4 parts of the polyoxyethylene-modified organopolysiloxane in Example 1 was replaced with a polyoxyethylene-modified one having the structure of general formula (C), containing 7% by weight of polyoxyethylene groups, and having an average molecular weight of 3000. Example 1 except that 0.5 part of organopolysiloxane was substituted.
A member for external use was obtained in the same manner as above. Example 5 4 parts of the polyoxyethylene-modified organopolysiloxane in Example 1 was replaced with a polyoxyethylene-modified one having the structure of general formula (A), containing 50% by weight of polyoxyethylene groups, and having an average molecular weight of 20,000. Example 1 except that the substitution was made with 20 parts of organopolysiloxane.
A member for external use was obtained in the same manner as above. Table 3 shows the skin irritation evaluation results for Examples 3 to 5 2 hours after peeling. As is clear from Table 3, the external use members of Examples 3 to 5 have little skin irritation and are excellent in safety. The external members of Examples 3 to 5 had good holding power, and no adhesive residue was observed.

【table】

[Table] Example 6 6 parts of the same polyoxyethylene-modified organopolysiloxane used in Example 1 was mixed with 100 parts of a commercially available vinyl adhesive containing polyvinyl alcohol as the main component, and then applied onto a polyethylene film. It was applied uniformly and dried to obtain a member for external use. Comparative Example 3 In the same manner as in Example 6, an external member containing no polyoxyethylene-modified organopolysiloxane was obtained. Table 4 shows the skin irritation evaluation results of Example 6 and Comparative Example 3 2 hours after peeling. As is clear from Table 4, skin irritation was observed in Comparative Example 3, whereas Example 6 showed less skin irritation and was superior in safety. Further, in Comparative Example 3, adhesive residue was observed on the release sheet and on the skin surface to which it was applied, whereas this was not observed in Example 6, and the adhesive had good retention on the skin.

[Table] Next, external members containing drugs will be described in detail by giving examples. The following method was used to measure drug release properties and drug solubility. Drug release properties: Create a 4cm x 7cm test piece from each external component.
The release of the drug from the adhesive was determined by applying this tape to the skin of a healthy person for a predetermined period of time and quantifying the amount of drug remaining in the tape after peeling off. Drug Solubility After each external use member was stored at room temperature for one month, the polymer material layer was observed under a microscope to determine the presence or absence of precipitation of drug crystals. Example 7 To 80 parts of the same adhesive and 20 parts of curing agent used in Example 1, 6.9 parts of l-menthol, 4.9 parts of glycol salicylate, and 0.018 parts of vanillylamide nonylate were added.
After adding and mixing 5 parts of polyoxyethylene-modified organopolysiloxane having the structure of general formula (A), containing 20% by weight of polyoxyethylene groups, and having an average molecular weight of 6000, a polyolefin nonwoven fabric is prepared. The mixture was coated uniformly and dried to obtain a member for external use. Comparative Example 4 A member for external use was obtained using the same formulation and method as in Example 7, except that 5 parts of polyoxyethylene-modified organopolysiloxane were removed. As shown in the results in Table 5, the skin irritation of the obtained external use member was found in Comparative Example 4, whereas the product of Example 7, which is a product of the present invention, showed no skin irritation in any of the test subjects. It can be seen that the irritation level disappears after a short period of time even in the subjects who showed a slight irritation value.
In addition, the obtained external member had good retention on the skin, and no adhesive residue was observed on the release sheet or the skin surface to which it was applied. Furthermore, drug release properties were good, drug solubility was also good, and no crystal precipitation was observed.

【table】

[Table] Example 8, Comparative Example 5 A commercially available anti-inflammatory and analgesic plaster was used as Comparative Example 5, and 120 g/m ² of the same polyoxyethylene-modified organopolysiloxane as that used in Example 7 was applied to it to prepare an external member. This was designated as Example 8. Table 6 shows the skin irritation evaluation results. As is clear from Table 6, the commercially available anti-inflammatory analgesic plaster of Comparative Example 5 has skin irritation, whereas the product of the present invention, Example 8, has less skin irritation and is superior in safety. Recognize.

[Table] Example 9 80 parts of the same adhesive used in Example 7 and 20 parts of curing agent, 9.5 parts of l-menthol, 6.8 parts of glycol salicylate, 0.024 parts of vanillylamide nonylate,
and 45 parts of a polyoxyethylene-modified organopolysiloxane having the structure of general formula (B), containing 75% by weight of polyoxyethylene groups, and having an average molecular weight of 30,000, and then mixing. A component for external use was obtained by the method described above. Example 10 80 parts of the same adhesive and 20 parts of curing agent used in Example 7, 6.6 parts of l-menthol, 4.7 parts of glycol salicylate, 0.017 parts of vanillylamide nonylate,
and polyoxyethylene-modified organopolysiloxane having the structure of general formula (C), containing 11% by weight of polyoxyethylene groups, and having an average molecular weight of 3000.
After adding and mixing 0.5 part, an external member was obtained in the same manner as in Example 7. Example 11 80 parts of the same adhesive and 20 parts of curing agent used in Example 7, 13.1 parts of l-menthol, 9.3 parts of glycol salicylate, 0.033 parts of vanillylamide nonylate,
and 100 parts of polyoxyethylene-modified organopolysiloxane having the structure of general formula (A), containing 50% by weight of polyoxyethylene groups, and having an average molecular weight of 20,000. A component for external use was obtained by the method described above. Table 7 shows the skin irritation results (2 hours after peeling) of the external use members of Examples 9 to 11. As is clear from Table 7, all of the externally used members have little skin irritation and are excellent in safety. In addition, all of the external members had good holding power, no adhesive residue was observed, and drug release and drug solubility were also good.

[Table] Example 12 To 100 parts of a commercially available vinyl adhesive whose main component is polyvinyl alcohol, 11.7 parts of l-menthol,
Added 12.4 parts of methyl salicylate, 0.5 parts of peppermint oil, 2.0 parts of dl-camphor, 0.5 parts of thymol, 0.3 parts of tocopheryl acetate, 3.4 parts of glycol salicylate, and 6 parts of the same polyoxyethylene-modified organopolysiloxane used in Example 7. This was then uniformly applied to a polyolefin nonwoven fabric and dried to obtain an external member. Comparative Example 6 A member for external use was obtained in the same manner as in Example 12, except that 6 parts of the polyoxyethylene-modified organopolysiloxane was removed, and this was designated as Comparative Example 6. As shown in the results in Table 8, the skin irritation of the obtained external member (2 hours after peeling) shows that Comparative Example 6 showed skin irritation, whereas Example 12, which is a product of the present invention, showed skin irritation. There was little sex. Also Example 12
The external use member had good retention, no adhesive residue was observed, drug release and drug solubility were also good, and no crystal precipitation was observed.

[Table] Example 13 To 100 parts of the same commercially available vinyl adhesive mainly composed of polyvinyl alcohol as in Example 12, 11.7 parts of l-menthol, 12.4 parts of methyl salicylate, 0.5 parts of pepper oil, 2.0 parts of dl-camphor, Thymol 0.5 parts, tocopherol acetate 0.3 parts, glycol salicylate
3.4 parts and 3 parts of the same polyoxyethylene modified organopolysiloxane used in Example 7,
Three parts of the same polyoxyethylene-modified organopolysiloxane as used in Example 9 were added and mixed, and then this was uniformly applied to a polyolefin nonwoven fabric and dried to obtain an external member. Comparative Example 7 A member for external use was obtained in the same manner as in Example 13, except that a total of 6 parts of polyoxyethylene-modified organopolysiloxane was removed, and this was designated as Comparative Example 7. As shown in the results in Table 9, the skin irritation of the obtained external member (2 hours after peeling) shows that Comparative Example 7 had skin irritation, whereas Example 13, which is a product of the present invention, showed skin irritation. There were few. In addition, the external member of Example 13 had good holding power, no adhesive residue was observed, and drug release and drug solubility were also good, with no crystal precipitation observed.

[Table] [Effects of the Invention] The external member of the present invention has low skin irritation, extremely high safety to the human body, and excellent adhesiveness, adhesive residue, drug solubility, and drug release properties.

Claims (1)

[Scope of Claims] 1. A member for external use comprising a sheet or tape-like support laminated with a polymer layer having pressure-sensitive adhesive properties at room temperature, wherein the polymer layer is coated with a polyoxyalkylene-modified organopolysiloxane. An external component characterized by being mixed. 2. The external member according to claim 1, wherein the polyoxyalkylene-modified organopolysiloxane is selected from compounds represented by the following general formulas [A] to [D]. 3. The external member according to claim 1 or 2, wherein the polyoxyalkylene-modified organopolysiloxane has an average molecular weight of 3000 or more. 4. The external member according to any one of claims 1 to 3, wherein the polyoxyalkylene-modified organopolysiloxane has an alkylene oxide content of 11 to 50% by weight. [C] [C] [C] [C] [C] (In the formula, R is an alkyl group having 1 to 3 carbon atoms or a phenyl group, R' is hydrogen or an alkyl group having 1 to 12 carbon atoms, and p is 1 to 12) (q is an integer of 5, q is 2 or 3, m is an integer of 5 to 100, n and x are integers of 1 to 50.)