JPS61233077A - Patch - Google Patents

Abstract

PURPOSE:A patch having improved adhesiveness to the skin, suitable fro feeding a drug to the skin or the subcutaneous deep part, obtained by forming a base comprising rubber-like block copolymers having different types, an adhesiveness imparting resin and a drug on the surface of a flexible substrate. CONSTITUTION:A base comprising (A) a block copolymer [e.g., styrene (S)- isoprene (I)-styrene block copolymer, having 14 wt.% S content, etc.] of a type shown by the formula I (S1 and S2 are monovinyl aromatic block polymer; I1 is conjugated diene block polymer; total content of S1 and S2 is at least 5 wt.%; n is 1-5 integer), (B) a block copolymer (e.g., S-I block copolymer having 23 wt.% S content, etc.) of a type shown by the formula II (S3 is monovinyl aromatic block polymer; I2 is conjugated diene block polymer; content of S3 is at least 15 wt.%), (C) an adhesiveness imparting resin and (D) a rug is formed on the surface of a flexible substrate (e.g., nonwoven fabric, etc.) to give the aimed patch. A weight ratio of the component A:B is preferably 70-99:30-1.

Description

DETAILED DESCRIPTION OF THE INVENTION <Industrial Field of Application> The present invention relates to a drug-containing patch with appropriate adhesiveness that is designed to be applied directly to the skin surface.

<Prior art and its problems> Conventionally, patches have been made using an adhesive base made of a thermoplastic rubber-like substance such as natural rubber, isoprene rubber, or neoprene rubber mixed with an adhesion-imparting resin such as rosin or ester gum. Plates in which medicinal ingredients such as methyl salicylate, monoglycol salicylate, and anti-inflammatory analgesics such as menthol are mixed and the mixture is spread on a carrier such as cloth are widely used.

Although these patches have good adhesiveness and skin adhesion, the compatibility of the medicinal ingredients with the base is not necessarily sufficient, so the medicinal ingredients gradually become sticky while the patches are stored for a long period of time. It begins to separate in the adhesive base and migrates into the release liner or carrier that protects the surface of the base, 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, the surface to which it is applied is covered with a liquid substance, in other words, the medicinal ingredient blooms, resulting in poor sweat-resistant adhesion. Furthermore, even when adhered, the adhesive has an unfavorable effect on the cohesive force of the adhesive base, resulting in adhesive residue on the skin surface when peeled off. In addition, these patches have poor diffusion and mobility of medicinal ingredients, so in order to improve this, oily substances such as lanolin and liquid paraffin are added, but this results in a significant decrease in cohesive force, making it difficult to store. In some cases, undesirable results such as sagging phenomenon and adhesive residue upon peeling may occur.

<Problems to be Solved by the Invention> In recent years, styrene-isoprene-styrene block copolymer rubber represented by the general formula 5-I-8 has been used as one of the synthetic rubbers constituting the base of adhesive patches. There is.

Since these block copolymer rubbers have a special structure of 5-I-8, they have good compatibility with medicinal ingredients and are less prone to blooming problems. That is, when the above-mentioned block copolymer comb is blended with a liquid medicinal ingredient such as methyl salicylate or monoglycol salicylate, the medicinal ingredient is absorbed into the styrene block polymer, that is, the hard polymer domain, which has a similar solubility index. The compatibility of each component is good even when stored for a long time, so there is no deterioration in performance due to separation as described above. Furthermore, the hard polymer domains have the function of somewhat improving the reduction in cohesive force upon addition of oily substances.

Civic styrene-isoprene-styrene block copolymer rubber has sufficient adhesive properties to be used alone as an adhesive base, and it tends to agglomerate if an attempt is made to improve it by adding a large amount of oily substance. It had a negative impact on power. Therefore, it has been proposed to blend natural rubber or isobrene rubber into the base material to impart flexibility and improve skin adhesion. This has the disadvantage that the above-mentioned excellent properties inherently possessed by the block copolymer cannot be fully utilized because of the reduction in the properties of the block copolymer.

<Means for solving the problem> In view of the above-mentioned problems, the present inventors have conducted extensive research on the rubber components used in patches, and have developed (S, -1,)
n-I1) n-S2 type butry copolymer and 5s-1
, a type block copolymer and a medicinal ingredient added to the formulation have high compatibility with oily/liquid substances, have the function of adjusting skin adhesion and shape retention, and have the ability to diffuse and transfer medicinal ingredients. It has been discovered that the release property due to the increase in the number of particles is improved, leading to the present invention.

That is, the present invention provides general formula (S, -1,)n -I1)n
- S2 type block copolymer (wherein 81 and Ss are monovinyl aromatic block polymers, 1. is a conjugated diene block polymer, and the total content of Sl and Sl is at least 5% by weight; n is 1 ~5 integer) and general formula 8. - type I2 block copolymer (wherein %Sm is a monovinyl aromatic block polymer, L is a conjugated diene block polymer and the content of %Sm is at least 15% by weight) and an adhesion-imparting resin. The present invention provides a patch in which a base consisting of a compound containing a drug and a drug is formed on a flexible carrier surface.

The general formula (S, -1,) used in the present invention is
n-I1) As n-S2 type block copolymers (hereinafter referred to as block copolymers), SR and Sl are represented by styrene, α-methylstyrene, tertiary-butylstyrene, methyl methacrylate, vinylsilene, etc. A monovinyl aromatic block polymer having a glass transition temperature of at least 20°C and a weight average molecular weight of about 1,000 to 1,250,000;
It has a weight average molecule i of 500 to 2,500,000. and the total content of block polymers S1 and Sl is at least 5% by weight, preferably from 10 to 80% by weight
It must be within the range of .

In addition, the S, -1, type block copolymer (hereinafter referred to as B block copolymer) is a block polymer in which Sm is a monovinyl aromatic group, has a glass transition temperature of at least 70°C, and has a weight average of about 10,000 or more. has a molecular weight,
L is a block polymer of conjugated diene and has a glass transition temperature of -15°C or lower.

Those with a weight average molecular weight of about 30,000 are mentioned,
The Ss content is at least 15! amount%, preferably 20
~50% by weight.

The adhesive patch of the present invention is a mixture of a compound containing the A block copolymer, B block copolymer, and adhesion-imparting resin, and a drug, and has excellent skin adhesion and cohesive properties, and has excellent skin adhesion and cohesive properties. It provides an adhesive base that leaves no adhesive residue and continuously supplies drugs to the skin surface or deep subcutaneously,
The blending ratio of the A block copolymer and the 1111--B block copolymer is preferably adjusted so that one does not exceed 50% by weight;
:B=70-99:30-1 (weight ratio) is preferable.

Therefore, the human block copolymer and the B block copolymer include rosin and modified rosin, petroleum resin, coumaron-indene resin, methylindene resin, Resins such as polyterpene resins and polystyrene resins (preferably those with a softening point of about 55
~150° C.) or liquid materials such as hydroxyabiethyl alcohol, polybutene, and liquid polyisobutylene.

In addition, oil components such as liquid paraffin, machine oil, cylinder oil, transformer oil, resin oil, waxes with a melting point of 120°C or less, low molecular weight polyethylene, and attack polypropylene are added to 100 parts by weight of the formulation. The oil component may be added in an amount of 20 to 300 parts by weight, preferably 50 to 200 parts by weight, and in addition to the above, the oil component may include animal waxes such as natural products such as lanolin,
Synthetic higher fatty acid varnish synthesized from higher fatty acid esters such as vegetable waxes such as carnauba wax, or fatty acids having 6 to 22 carbon atoms such as diisopropyl adipate and ethyl laurate, and alcohols having 1 to 17 carbon atoms. is thoroughly mixed under heating and heating conditions to the extent that the system has fluidity,
By cooling the gel base prepared by mixing a drug or a drug solution therein, an oily gel-like and sticky base having high viscosity and shape retention at room temperature can be obtained.

A general method for forming a base on a carrier is to cast the gel base on the carrier surface and cool it. A method such as casting on a treated polyester film and transferring it onto a carrier may also be used. Examples of the carrier include flexible materials such as flannelette, woven fabric, nonwoven fabric, felt, foam, plastic film, metal foil, and other single or composite materials.

The drug used in the present invention is not particularly limited as long as it exhibits a pharmacological effect after being released from the patch onto the applied skin surface. However, systemic medicinal ingredients that exert their pharmacological effects after being absorbed into the blood may also be used. Examples of these medicinal ingredients include the following:

b) Corticosteroids: e.g. hydrocortiscin, punto 1 nizolone, beclomethasone probionate,
flumethacin, triamcinolone, triamcinolone acetonide, fluocinolone, fluocinolone acetonide, fluocinolone acetonide acetate, clobetasol propionate, etc.) Analgesic anti-inflammatory agents: e.g. acetaminophen, mefenamic acid, indomethacin, diclofenac, lurbibrofen, salicylic acid, Methyl salicylate, camphor, sulindac, tolmetin sodium, naproxen, fenbufen, etc., sedatives: such as phenoparbital, amoparbital, cyclovalpital, lorazepam, heloberidol, etc., 2) tranquilizers : For example, fluphenazine, theoridazine, diazepam, flunitrazebam, chlorpromazine, etc. →Antihypertensive agents: For example, clonidine, clonidine hydrochloride, pindolol, flopranolol, propranolol hydrochloride, vubranol, indenolol, bukumolol, nifedipine, etc. To) Antihypertensive diuretics: For example Hydrothiazide, bendroflunathiazide, cyclopenthiazide, etc. g) Antibiotics: For example, penicillin, tetracycline,
oxytetracycline, fradiomycin sulfate, erythromycin, chloramphenicol, etc. 1) Anesthetics: e.g. lidocaine, pensicaine, ethyl aminobenzoate, etc. 3) Antibacterial substances: e.g. benzalkonium chloride, nitrofurazone, nyscutin, acetosulfamine, Clotrimazole, etc. n) Antifungal substances: For example, pentamycin 1 amphotericin B1 pyrrolenidrine, clotrimazole, etc.

0 Vitamin preparations: e.g. vitamin A1 ergocalciferol, cholecalciferol, octothiamine, riboflavin butyrate, etc., w) Antiepileptics: e.g. Nitraze/fum, Mebro/4:mate, clonazepam, etc., w) Coronary blood vessels. Extending agents: e.g. nitroglycerin, nitroglycol, insorbide dinitrate, erythritol tetranitrate, pentaerythritol tetranitrate, propyl nitrate, etc.) Antihistamines: e.g. diphenhydramine hydrochloride,
Chlorpheniramine, diphenylrayondazole, etc., 2) Antitussives: e.g. dextromethorphan, tilbutamine, ephedrine, ephedrine hydrochloride, etc., li) Sex hormones: e.g. progesterone, estradiol, etc., c) Antibiotics, e.g. doxepin, etc. ) Others: Examples include 5-fluorouracil, dihydroergotamine, fentanyl, desmobrecin, digoxin, diquitoxin, metoclobraside, dosiperid, scopolamine, scopolamine hydrobromide, prostaglandins, etc., and two or more of these can be used in combination. It is effective to add it in an amount of 0.1 to 30% by weight in the adhesive base in order to exhibit pharmacological effects.

Also, among the above medicinal ingredients, analgesic and anti-inflammatory agents that are commonly used in poultices, such as methyl salicylate and monoglycol salicylate! - Menthol, camphor, capsicum extract, mustard oil, funnel extract, etc. are preferable in terms of diffusion mobility in the adhesive base, compatibility, and pharmacological effect.

In addition, various commonly used additives such as preservatives and antifungal 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.

Furthermore, in order to impart a cooling sensation to the patch of the present invention and to improve the diffusion and mobility of the medicinal ingredients, water in the range of about 5 to 70% by weight is added to the patch during the manufacturing process. As mentioned above, the patch of the present invention uses both the A block copolymer and the B block copolymer. To,
It has the characteristics of high compatibility between each component, excellent skin adhesion and cohesion, good shape retention, no sagging, and excellent release properties due to increased diffusion and movement of medicinal ingredients. have

<Examples> Examples of the present invention will be shown below and will be explained more specifically, but the present invention is not limited thereto. In the text, parts mean parts by weight.

Example 1 Styrene-isoprene-styrene block copolymer (weight average molecular weight of initial polystyrene block = 1100
0 Weight average molecular weight of polyisoprene block = 13
8000 Weight average molecular weight of the last polystyrene block = 11000 Total content of styrene in the polymer (14% by weight) 180 parts, styrene-isoprene block copolymer (weight average molecular weight of polystyrene block =
21000 Weight average molecular weight of polyisoprene = 6
9000 Styrene content in polymer 23% by weight)
60 parts, liquid paraffin 60 parts, polybutene (HV-3
00) Prepare a tar base consisting of 50 parts, 190 parts of petroleum resin (softening point 90°C), and 60 parts of the following mixed drug, and spread it on a nonwoven fabric with a 200 μ-thick groove to a thickness of 800 μ. The mixture was then allowed to stand at room temperature for a period of time to obtain a patch having an oily gel-like adhesive base.

Drug combination> Methyl salicylate 10 parts - mesitol, 10 parts di-camphor
6 parts Examples 2 to 3 and Comparative Example A patch was obtained in the same manner as in Example 1 using the compounding ratios shown in Table 1. The same 〇 as in Example 1 was used as the styrene-isoprene-styrene block copolymer and the styrene-isoprene block copolymer.

Table 1 (Unit part) Tables 2 and 3 show the evaluation results of Examples 1 to 3 and Comparative Examples. Table 2 shows the practical test evaluation results, and Table 3 shows the pharmacological effect test evaluation.

Table 2 Evaluation method in Table 2 The practical test was conducted by 10 panelists.
The patches of Examples 1 to 3 and Comparative Example were applied to the test tube. Skin adhesion was evaluated on a three-grade scale of good, fair, and poor, based on whether there was any natural peeling when applied, whether there was any adhesive residue or pain when removed, etc.Skin sweat resistance adhesion time was evaluated based on whether there was any natural peeling when applied, whether there was any adhesive residue or pain when removed, etc. The test was conducted indoors at 35° C. under humidified conditions, and the evaluation was based on the time it took until 50% or more of the area of the patch applied to the center of the back was found to be lifted. The onset and duration of the medicinal effect were determined by the subject's experience.

Table 3 In Table 3, the amount of drug before application to the human body is taken as 100%, and the amount of drug in the base after application for 6 hours is quantified.

Claims (1)

[Claims] 1) A block copolymer of the general formula (S_1-I_1)_n-S_2 type (wherein S_1 and S_2 are monovinyl aromatic block polymers, I_1 is a conjugated gene block polymer, S_1 and S_2 (n is an integer from 1 to 5) and the general formula S
_2-I_2 type block copolymer (wherein S_2 is a monovinyl aromatic block polymer, I_2 is a conjugated gene block polymer, and the content of S_2 is at least 15% by weight) and an adhesion-imparting resin. A patch in which a base consisting of a compound containing a drug and a drug is formed on a flexible carrier. 2) Claims in which the blending ratio of the general formula (S_1-I_1)_n-S_2 type block copolymer and the general formula S_2-I_2 type block copolymer is 70 to 99:30 to 1 (weight ratio) The patch according to item 1.