JPS60203664A - Patching agent - Google Patents

Abstract

PURPOSE:To obtain a patching agent of high skin adhesivity, sweat-resistant adhesivity and pharmacological effectiveness, along with good storage stability, by incorporating a specific block copolymer with aromatic hydrocarbon solvent, tackifying component and pharmacologically active ingredient. CONSTITUTION:The objective patching agent can be obtained by incorporating (A) 100pts.wt. of an A-B-A type thermoplastic block copolymer constituted by (1) rigid polymer A with a glass transition temperature Tg >=70 deg.C and weight- average molecular weight Mw 1,000-50,000 (e.g. polystyrene) and (2) flexible polymer B with a Tg -100-30 deg.C and Mw 4,500-1,000,000 (e.g. polybutadiene) with (B) 5-150pts.wt. of an aromatic hydrocarbon with a boiling point 150- 400 deg.C and viscosity 5-500cps, (C) 10-400pts.wt. of a tackifying component (e.g. resin), and (D) pref. 0.1-30wt%, based on the adhesive base made up of the components (A), (B) plus (C), of a pharmacologically active ingredient. This patching agent in then provided on a substrate.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention provides a patch that has good adhesion to the skin surface and has excellent storage stability by suppressing decomposition reactions of medicinal ingredients and separation from the adhesive base during storage. It is related to.

Conventionally, adhesive bases are prepared by blending thermoplastic materials such as natural rubber or block copolymer rubber with viscosity 1=J resins and liquid paraffin or higher fatty acids in patches, and methyl salicylate, monosalicylic acid, etc. A medicinal ingredient such as an anti-inflammatory analgesic agent such as glycol is mixed and spread on a carrier such as cloth.1. These patches are commercially available.Although these patches have excellent adhesiveness and skin adhesion, during long-term storage, the medicinal ingredients and oil components such as liquid rose wine separate from the adhesive base, resulting in loss of pharmacological effects. In some cases, this may cause a decrease in skin adhesion and a decrease in skin adhesion. That is, in order to improve the diffusion and mobility of medicinal ingredients, 1. Since the liquid paraffin produced in the liquid paraffin is not always compatible with the above-mentioned thermoplastic substance, it gradually begins to separate in the adhesive base along with the medicinal ingredients during long-term storage of the patch. It migrates into the release liner that protects the base surface and into the carrier, resulting in a decrease in the anchoring force with the carrier and a decrease in adhesiveness. In addition, when a patch that causes this phenomenon is applied to the skin IM surface, the surface of the patch becomes covered with an oily substance, resulting in poor sweat-resistant adhesion, and even if the adhesive is Favorable for cohesive force of adhesive base, etc. 1. <No influence 1. As a result, there were drawbacks such as a residual Ka phenomenon occurring during peeling.

In view of the above-mentioned problems, the present inventors have conducted intensive research and found that an aromatic hydrocarbon solvent and a T3-improving component/medicinal component are added to A-B- and A-type thermoplastic block copolymers. The patch obtained by this method has good compatibility of each component during long-term storage, and therefore has excellent skin adhesion, sweat-resistant adhesion, and pharmacological effects. This is the finding 17 that led to the present invention.

That is, the present invention involves adding a medicinal ingredient to a sticky base consisting of an A-B-Alv thermal o7q block co-merging component, an aromatic hydrocarbon solvent, and an adhesive (=I acid-donating component).
The present invention provides a patch comprising an adhesive base containing a medicinal component on a carrier.

The A-B-Ax thermoplastic used in the present invention (hereinafter referred to as "block co-combination") is a block having the structure A-B-A9 consisting of a hard four-wheel combination A and a soft polymer B. It is a copolymer, and the A block is a hard electropolymer made of a vinyl compound such as styrene 1. methylstyrene, whose glass transition temperature is 70°C or higher, and has a glass transition temperature ranging from about 10% to 50,000%. A polymer having an average molecular weight is effective.The B block is a soft polymer made of a conjugated diene compound such as butadiene or isobunne, and its glass transition temperature is -
1 (approximately 45011 N1000 at 10-30℃)
Polymers having an average molecular weight of M in the range of 0 (10) are effective. The terminal A block of the Uami block copolymer is comprised of about 5 to 65 overweight of the copolymer.

The aromatic hydrocarbon solvent used together with the above block copolymer evaporates during the heating process during production and during long-term storage, which will be described later, resulting in losses of 1. It is preferable that there is no, and the boiling point is 150 ~
400°C and a viscosity of 5 to 500 centivoise (at
High boiling point solvents having a temperature of 37° C.) are preferably used. These aromatic hydrocarbon solvents are solvents that are compatible with the A block having a ψ-like structure such as an aromatic ring,
Examples include Evahis (α-methylbenzylxylene), 1-xylyl-1-(3-methylbenzyl)ethane, l-xylyl (3-diphenylbutane), and these solvents are used alone or in combination. The amount added is the block copolymer 10() weight at
A range of 5 to 150 parts by weight per part is effective, and the amount of these additions depends on the type and amount of 1 part of tackification described below.
It is determined as appropriate based on the relationship between the final product and the flexibility of the patch obtained in step 1.

The tackifier components used in the present invention include rosin, modified rosin, petroleum resin, coumaron indene 11
Effect, methylindene resin, polyterpene tree 11 effect, polystyrene camellia' IIW, hydroabiechi! Examples include real alcohol, polybutene, and liquid polyisobutylene, and it is desirable to use these in a proportion of usually 111 to 400 parts by weight per 1 part by weight of the block copolymer 10.

The adhesive patch of the present invention can be prepared by thoroughly kneading a mixture of the above-mentioned 1-block copolymer component, aromatic hydrocarbon M agent, and tackifying component at a predetermined ratio under heating conditions to maintain fluidity. 1. It can be obtained by preparing an oily gel-like adhesive base that has high viscosity and no fluidity at room temperature, and spreading this on a carrier.

1. Prepared in advance in a predetermined ratio to this oily gel-like adhesive base. The medicinal ingredient (or its solution) is added and mixed, but it is desirable to carry out this step at the lowest possible temperature to prevent the medicinal ingredient from volatilization or loss due to thermal decomposition reaction.

The medicinal effect used in this process is not particularly limited as long as it shows a pharmacological effect after being released from the patch to the shoulder surface opposite to the applied patch, and the medicinal effect is exerted near the skin surface of the patch. Even if a local medicinal ingredient is used, a systemic medicinal ingredient that exerts its effect after being absorbed into the blood may be used. Examples of these medicinal ingredients and 1- include the following.

b) Corticosteroids: For example, Hi-F locortisone, prednisolone, beclomethasone propionate, flumethacin, triamcinolone, doriamcinolone acetonide, fluocinolone, fluocinolone acetonide,
Fluocinolone acetonide acetate, clobetasol propionate, etc.; b) Analgesic anti-inflammatory agents: e.g. acetaminophen, mefenamic acid, flufenamic acid, indomethacin, diclofenac, diclofenac sodium, alclofenac, oxyphenbutacin, phenylbutacin. Sin, ibuprofen, flurbiprofen, salicylic acid, methyl salicylate, ■-menthol, camphor, sulindac, tolmetin sodium, naproxen, 7-embbuen, etc. /') 4m Parvicool, Lorazepa I\, Haloperidol, etc. 2) Tranquilizers: e.g. flu7enazine, theoridazine, diazepam, flunitrazepam, chlorpromazine, etc. e) Antihypertensive agents 0 e.g. clonidine, clonidine hydrochloride, etc.
pindolol, propranolol, propranolol hydrochloride, bufranol, indenolol, bucumolol, nifedipine, etc. f) Antihypertensive diuretics: e.g. hydrothiazide, hentroflunathiazide, cyclopenthiazide, g) Antibiotics: e.g. penicillin, tetracycline,
Oxytetracycline, 7-radiomycin sulfate, erythromycin, chloramphenicol, etc. Anesthetics: e.g. lidocaine, pensicaine, aminobenzene ethyl, etc. B) Antibacterial properties Toughness: e.g. pendelkonium chloride, nitro-7 lazone, Nyscutin, acetosulfamine, clotrimazole tx, nu) Antibiotics, such as pentamycin, amphotericin B1, pyrrolnidrine, clotrimazole, etc., l) Vitamin preparations: such as vitamin A1, ergocalciferol, cholecalcin Ferrol, octothiamine, riboflavin acetic acid ester fx, wo) Pile! M51III
Agents: For example, nitrazepam, mebrobamate, clonazebam, etc. (b) Coronary blood alpha dilators, such as nitroglycerin, nitroglycol, insorbidodinitrate, erythritol tetranitrate, pentaerythritol tetranitrate, propyl nitrate, etc. (1) Antihistamines: For example, diphenhydramine, chlorpheniramine, diphenylimitasol, etc. (2) Antitussives: For example, dextromethorphan, tilbutamine, ephedrine, ephedrine hydrochloride, etc. (3) Anti-inflammatory drugs: For example, progesterone, estradiol, etc. , B) Anti-aging agents, such as doxepinat, N) Others, such as 5-fluorouracil, dihydroergotamine, 7-entanyl, tesmobrecin, digoxin, dioquitoxin, metoclobraside, domperid,
Examples include scopolamine, scopolamine with low hydrogen bromide, prostaglandins, etc., and combinations of two or more of these 1
．． 0.1 to 3" in adhesive base.
It is effective to add the drug in a wide range of 100 s to exert a pharmacological effect.

In addition, among the above medicinal ingredients, d44 anti-inflammatory agents, which are usually used in poultices, such as methyl salicylate, monoglycol salicylate, etc. - Menthol, canker, horse chestnut extract, mustard oil, funnel extract, etc. are preferred in terms of diffusion mobility in the adhesive base, compatibility, and pharmacological effect.

Like this 1. The adhesive base material containing the medicinal properties obtained is placed on a flammable carrier and then cooled to room temperature (1) to form a gel, thereby retaining the medicinal properties (1);
A patch consisting of the following is obtained.

As the carrier used in the present invention, leather is used! J[lI
In order to improve sound tightness to J, it is desirable to use a material that has iiJ scorching properties, and the material used has traditionally been the same as that of the carrier in poultices. Fabrics such as flannel, thick non-woven fabrics, or foamed eye 2 rem can all be used, but in addition to these, synthetic resin films, paper, metal W, or laminated films of these can also be used. is also possible.

In addition, various commonly used additives such as anti-dust agents such as thymol and boric acid can be added to the patch of the present invention at any step in the above-mentioned manufacturing method, if necessary. It is not prohibited to add oil components such as paraffin oil, higher fatty acids or esters thereof, lanolin, etc. to an extent that does not adversely affect the compatibility of each component.

Furthermore, for the purpose of imparting cold S to the patch of the present invention and improving the diffusion and mobility of medicinal ingredients, water in the range of about 5 to 70% by weight is added to the patch during the manufacturing process. It can also be a W2O type hydrogel emulsion patch.

As mentioned above, since the adhesive patch of the present invention is made from an adhesive base consisting of specific essential ingredients, each ingredient and medicinal ingredient have excellent compatibility, and each patch is suitable for long-term storage. There is no separation of components, and there is no loss of medicinal ingredients due to decomposition reactions or volatilization, and it has appropriate skin rot adhesion and sweat resistance.

In addition, since it contains an aromatic hydrocarbon solvent during use, the diffusion and mobility of the medicinal ingredient in the adhesive base is improved, transdermal absorption rate and amount are increased, and sufficient pharmacological effects are obtained. It has the advantage that it can be obtained.

Examples of the present invention are shown below.1. , will be explained more specifically, but the present invention is not limited thereto. In the text, ``bu'' means ``M''.

Examples 1 and 2 Samples 71i1 and A2 were prepared by adding the mixed medicinal ingredients shown in Table 2 to the 6 ingredients of Formulation Examples I & R shown in Table 1 (1-).

Comparison 1 Yield: The mixed medicinal ingredients shown in Table 2 were added to each component of the comparative example shown in Table 1. Ta.

Production Examples Examples 1 and 2 and comparative samples were prepared by heating the block copolymer (S-1-3) at 90 to 120°C in a pressurized Ni-Goo for 10 minutes. After masticating for a minute, an aromatic hydrocarbon solvent, liquid paraffin, polybutene or abiethyl alcohol is added and mixed uniformly under an inert gas atmosphere L1, and a petroleum resin is added and mixed.

After lowering the temperature of the resulting mixture to about 70° C., the mixed medicinal ingredients are added to obtain a uniform sticky base. Then, put this on a nonwoven fabric of about 60 to 65 tons! Each sample and a comparative sample were obtained by spreading with a calendar roll at a temperature of

Table 1 The abbreviations used in Table 1 and their properties are as follows.

S-1-8: Styrene-isobrene-styrene block copolymer, average molecular weight 12.5011 (tostyrene/rubber ratio 14/86, melt index (G conditions) 101/, JI!It, melt viscosity (25°C, 25 (in toluene solution) l 6 , (ill (l CpS aromatic hydrocarbon solvent: xylene thread solvent, product name Hysol SA S-296 Nippon Petrochemical Co., Ltd. liquid paraffin: specific gravity (15,/4°C) 11.83・
Viscosity (37.8°C) 9.5 cst Hollybutene: Average molecular weight 126°・Excitation/JE (210”F) 32i1(+ (s
(・Ratio i (15/4℃) +1.895 Petroleum resin: Alicyclic saturated hydrocarbon resin・Average molecular weight
630 - Softening point: 9 ()°C Table 2 Table 3 shows the general characteristics and practical test results of the patch samples and comparatively soft samples of the present invention.

Table 3 Test method in Table 3 [Adhesive strength] A test piece was placed in a width of 12 mm and a length of 250 mm.
First, wash the surface of the phenolic resin test plate with clean ethanol, dry it thoroughly, wipe it with a well-dried clean cloth, and leave it at room temperature for 30 minutes. 85119 rubber roller is passed over the test piece twice at a speed of 3017 MIX for 1 minute. Looking at the Schoppa complete pendulum type tensile tester, 31)
(Measurement of the load when peeling 180 degrees with beer at a speed of 1 penalty/minute is 1-. (Average value of 4 times at 20 degree intervals) [Steel ball tack] On a slope with a 30 degree angle Place it with the dry side facing up,
Cover the upper part 1 om and the lower part 15 with appropriate paper and place it in the middle 5.
Leaves a sticky surface. A series of steel balls with diameters of 3.2.1 to 2.0 mm and 5 mm were rolled from the upper end of the slope and stopped on the adhesive surface to measure the maximum ball diameter.

Table 4 shows the patch samples of the present invention and the comparison sample at 50°C.
The results of measuring the residual rate of each medicinal ingredient after 3 months of storage in 1i111a are shown.

In addition, the initial amount of 4-T is calculated using l D 0% and 1-.
is.

In Table 4, monoglycol salicylate was determined by liquid chromatography, and other medicinal ingredients were determined by gas chromatography.

Table 5 t Uninvented patch sample and 4″6 sample of ratio 1 trial edition
The adhesive base surface was protected with a polyethylene 111Il: mold liner, and polyethylene V-aluminum? 'tS
i';i I So Film Sealing Packaging Device - Later, 51
1° shows the results of measuring the transfer of medicinal ingredients for the release liner and packaging material after 3 months of storage at 1°C under constant humidity and film. In addition, each migration rate (%) was calculated based on the initial content of 100% and 1-, and the quantitative method was in accordance with the method shown in Table 4.

@ 5 Table As is clear from the test results in the above examples, the patch of the present invention exhibits excellent efficacy such as moderate skin adhesion, sweat resistance #6, and long duration of drug effect. Therefore, there is very little loss of medicinal ingredients due to migration or number of species.

Patent issuer Nitto Electric Industry Co., Ltd. Representative Doriki Sanbe

Claims (1)

[Claims] 1) Adding a medicinal ingredient to an adhesive base consisting of an A-B-A type plastic block copolymer rubber, an aromatic hydrocarbon solvent, and a tackifier.1. A patch comprising an adhesive base containing a medicinal ingredient on a carrier.