JPS593966B2 - patch - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a patch that has good adhesive properties and causes less pain and skin irritation when removed.

Conventional anti-inflammatory and analgesic patches use an adhesive base made of rubber such as natural rubber or synthetic rubber with rosin, ester gum, etc. added as a tackifying resin, and anti-inflammatory agents such as methyl salicylate, menthol, camphor, and thymol. Analgesics are mixed and the mixture is spread on a carrier such as cloth to form a patch.

In manufacturing these patches, methods are used, such as melting the adhesive base with heat, mixing and spreading it, or dissolving it in an organic solvent, applying it to cloth, etc., and then evaporating the organic solvent. However, since heat is applied during the manufacturing process, the chemical volatilizes to a large extent, and there is a drawback that it is necessary to calculate the amount of volatilization in advance and mix a larger amount of the chemical.

In addition, in order to reduce these drug losses as much as possible,
For example, when manufacturing patches using the hot-melt method, the adhesive base production process, drug mixing process, and spreading process are separated, and consideration is given to lowering the operating temperature in the spreading process as much as possible. As long as a small thermoplastic elastomer such as natural rubber or synthetic rubber used from
heating temperature is required, and there is a problem of a considerable amount of chemical volatilization.

On the other hand, as another method to solve these chemical volatilization problems, we have proposed a method in which only an adhesive base is applied to a base material such as cloth in advance, and then a chemical mixed with lanolin etc. is applied on top of this in a separate process. has been done.

However, although this type of method can certainly reduce the amount of drug volatilization, it has the disadvantage that if stored for a long period of time, the drug will plasticize the adhesive base, leaving a plaster on the skin during use and poor adhesiveness.

Furthermore, because the general pain-relieving and anti-inflammatory patches currently on the market place too much emphasis on adhesive properties, many of them have the disadvantage of being painful when removed, as evidenced by the fact that they also remove body hair when removed. Furthermore, those that do not cause pain when peeled off lack adhesiveness, and currently there is no one that has a good balance between the two.

In addition, when these patches are applied to the skin, contact dermatitis often occurs due to contact with the plaster, which is foreign to the skin (although analgesic and anti-inflammatory effects can be expected, after the patch is removed,
It was necessary to treat the contact dermatitis, so-called rash.

As a result of intensive research in order to solve the drawbacks of the prior art, the present inventors have developed a general configuration A-B-A type plotter block copolymer having thermoplasticity as a base component, and adding an oil component and a tackifying component to this copolymer. By adding an anti-inflammatory agent that prevents contact dermatitis, the ability to adjust peel resistance to the skin and the drug efficacy enhancement function to increase absorption of drugs from the skin is improved, and furthermore, contact dermatitis caused by patching can be improved. This discovery led to the present invention.

That is, the present invention provides a support for a paste mixture containing, as essential components, a thermoplastic elastomer having a general configuration A-B-A type, an oil component, a tackifying component, an anti-inflammatory analgesic agent, and an anti-inflammatory agent for preventing contact dermatitis. The present invention provides a patch that is spread on the skin.

The general configuration A-B-A type thermoplastic nidistomer (hereinafter referred to as elastomer) used in the present invention is an elastomer with an A-B-A type structure consisting of a hard polymer A and a soft polymer B, and the A block is, for example, Hard polymers of vinyl compounds such as styrene and methylstyrene, which have a glass transition temperature of 70° C. or higher and have an average molecular weight in the range of about 1,000 to 500,000, are effective.

In addition, the B block is, for example, butadiene 1. A soft polymer of conjugated diene compounds such as isoprene with a glass transition temperature of 1100 to 30°C, approximately 4500 to 1000°C.
Polymers having an average molecular weight in the range of 0.000 are useful.

The terminal A block of the elastomer consists of 15 to 65% by weight of the elastomer.

The oil component to be used with the above elastomer includes an oily substance that is liquid at room temperature and is compatible with the B block of the Nidistomer and incompatible with the A block, such as machine oil, cylinder oil, transformer oil, rosin oil, etc. Various liquid paraffin oils are preferably used, but mixtures of these oily substances with addition of substances that become oily when heated, such as paraffin wax with a melting point of 120° C. or less and low molecular weight polyethylene, are also useful as the oil component of the present invention. .

As these oil components, those having low volatility and a boiling point higher than the melting point of the gel component described below are preferably used.

The effective amount of the oil component to be used is 100 parts by weight per 5 to 120 parts by weight of the elastomer. Determined by degree relationship.

Examples of the tackifying component used in this invention include rosin and modified rosin, petroleum-based resins, coumaron intene resins, methyl indene resins, polyterpene resins, polystyrene resins, hydroabiethyl alcohol, polybutene, liquid polyisobutylene, etc. These may be used in an amount of usually 50 to 400 parts by weight per 100 parts by weight of the elastomer.

In this production example, a mixture of elastomer, tackifying component, and oil component in predetermined proportions is heated to about 80-170° C. and dissolved.

This melting system has a temperature of 10 to 70%
It is a fluid with a viscosity in the 0 poise range, and its viscosity increases rapidly as the temperature decreases, becoming an oily gel with no fluidity in the 50° C. to room temperature range.

The step of adding and mixing an anti-inflammatory analgesic and an anti-inflammatory drug for preventing contact dermatitis, which have been mixed in advance at a predetermined ratio, to this oily gel is carried out at about 60°C.

Commonly used anti-inflammatory agents such as methyl salicylate, monoglycol salicylate, menthol, camphor, capsicum extract, mustard oil, and lotus extract can be used.As an anti-inflammatory agent to prevent contact dermatitis, hydrochloric acid can be used. Schiff-reinhydramine, chlorpheniramine maleate, ammonium clycyrrhizate, dexamethacin, betamethacin, fluocinolone acetonide, etc. can be used.

The amount of the anti-inflammatory agent to be added may be any amount that is normally used for the prevention of contact dermatitis.

The thus obtained drug-containing paste mixture is spread on a flexible carrier and then rapidly cooled to room temperature to form a gel. And a patch containing an anti-inflammatory agent for preventing contact dermatitis is obtained.

As flexible carriers, cloths such as flannel, which have been conventionally used as carriers for poultices, and thick non-woven foamed films can be used, but in addition to these, synthetic resin films can also be used. It is possible.

In addition, various commonly used additives such as preservatives and fungicides such as thymol and boric acid can be added to this patch at any step in the above-mentioned manufacturing method, if necessary.

The patch of this invention has excellent compatibility with anti-inflammatory analgesic agents such as methyl salicylate, monoglycol salicylate, menthol, and camphor, so the volatilization of the anti-inflammatory analgesic agent over time is small; In addition to the above-mentioned liquid paraffin, the oil component used in the present invention has the advantage of increasing transdermal absorption rate and absorption amount due to the action of the oil component, obtaining a sufficient drug effect, and having appropriate adhesive properties. There are higher fatty acid esters such as animal waxes such as lanolin and vegetable waxes such as carnauba wax as natural products, and fatty acids of 06 to C2□ and C1 to C1□ such as diisopropyl adipate and ethyl laurate.
Synthetic higher fatty acid esters synthesized from alcohols can also be used.

Next, the present invention will be explained in more detail with reference to Examples, but the present invention is not limited to these Examples.

In addition, parts and parts below refer to weight. means 1 part.

Example Mixtures shown in Table 2 (a) were added to the formulation examples ■ to ■ shown in Table 1 to give Samples A1 to 3, and Comparative Examples I and ■ shown in Table 1 were added with the mixed drugs shown in Table 2 (b). ) to prepare comparative samples A1 and 2.

The test results are shown in Tables 3-5.

Samples A1 to A3 and Comparative Sample Haruka 2 were prepared by melting and mixing the elastomer (S-I-8), liquid paraffin, polybutene, and anti-aging agent using a sealed stirring and dissolving mixing pot under an inert gas flow ( 90-120℃), then petroleum resin and lanolin (formulation example ■) diisopropyl laurate (
Formulation example (2) is added and mixed uniformly, the temperature of the pot is lowered, and when the temperature of the mixture reaches 70°C, the mixed drug is added to obtain a uniform paste mixture.

Then, this is spread on a nonwoven fabric using a calendar roll at a temperature of about 60 to 65°C, and then rapidly cooled to obtain a sample.

Comparative sample boiled 1 was prepared by first masticating natural rubber and anti-aging agent in a pressure kneader for 8 minutes at 170°C), then mixing gum rosin, polybutene and lanolin, and raising the temperature of the uniformly mixed mixture to 150°C. and add the mixed drug to obtain a paste mixture.

This is spread on a nonwoven fabric using a calendar roll at a temperature of 140°C, and then rapidly cooled to obtain a sample.

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

5-I-8: Styrene-isoprene-styrene teleblock elastomer・Average molecular weight 125000・Styrene/rubber top 14/6・Melt index (G condition) 10? /mi
n・Solution viscosity (25°C, 25wt%, toluene solution)
1600 cps Natural rubber: Pale crepe Petroleum resin: Alicyclic saturated hydrocarbon resin, average molecular weight 630 ・Softening point -90 ・Acid value 0 Gum rosin: Chinese gum rosin, Softening point 95-105℃ Polybutene: Average molecular weight 1260 ・Kinematic viscosity (210'F) 3200cst.

・Specific gravity (15/4℃) 0.895 Liquid paraffin: Specific gravity (15/4℃) 0.83・Viscosity (
37°C8°C') 9.5 cst.

Anti-aging agent: alkylated bisphenol Table 3 shows the general characteristics and practical test evaluation test results of the patch samples of the present invention and comparative samples.

Test method in Table 3 [Adhesive strength] Prepare a sample piece with a width of 12 mm and a length of 2501 m, wash the surface of the phenol resin test plate with clean ethanol in advance, dry it thoroughly, and then dry it with a well-dried clean cloth. After wiping with water, the sample piece was left at room temperature for 30 minutes, and then a rubber roller of 850 rpm was immediately passed over the sample piece twice at a speed of 300 mm per minute.

Using a Schottspa pendulum type tensile tester, the load at 180 degrees beer peeling was measured at a speed of 300 mm/min.

It was expressed as the average value of four measurements at 20 mm intervals.

[Steel ball tack]

Place it on a slope with an angle of 30 degrees with the adhesive side facing upward, and cover the upper part 10CrfL and the lower part 15CrIL with a suitable paper, leaving an adhesive side of 5crrL in the center.

A series of steel balls with a diameter of 3.2 mm to 15.9 mm are rolled from the upper end of the slope, and the maximum ball diameter that can be stopped by the adhesive surface at the center is measured.

[Incidence of contact dermatitis]

Each sample was applied for 6 hours, and after removal there was a slight erythema (
e) The percentage of expression of the above is shown.

Table 4 shows the measured (quantified) content of each drug in the plaster mixture of the patch samples of the present invention and comparative samples.

Assay method in Table 4 Plasma 101 is dissolved in 25ml of 1C ethyl acetate containing an internal standard substance.

Next, an excess of meth)L alcohol is added to cause precipitation, the supernatant is filtered, and the remaining precipitate is subjected to the same procedure to obtain a supernatant.

The supernatant liquid obtained in the above two operations was concentrated using a low-volume evaporator, and the sample liquid was diluted to 50 ml with a methyl alcohol knife and quantified using a high performance liquid chromatograph.

The numbers in Table 4 are based on the theoretical value of 100.

Table 5 shows the content of the anti-inflammatory and analgesic agent in the paste mixture after it was applied to the human body for 6 hours.

The quantitative method in Table 5 is based on Table 4.

The numbers in Table 5 are based on the numbers in Table 4 as 100.

As is clear from the above examples, the patch of the present invention has both appropriate adhesion and peelability, prevents contact dermatitis, and has little transpiration loss or decomposition of each drug during manufacturing (Table 4). (see).

Furthermore, it is remarkable that the anti-inflammatory and analgesic agent contained in the paste mixture is well released into the skin, and the amount of the used patch remaining in the paste mixture is small (see Table 5).

Claims (1)

[Scope of Claims] 1. A plaster containing as essential components an A-B-A type thermoplastic elastomer component having a general configuration, an oil component, a tackifier component, an anti-inflammatory analgesic agent, and an anti-inflammatory agent for preventing dermatitis. A patch made by spreading a mixture on a carrier. 2. The patch according to claim 1, wherein the oil component is one or more selected from the group of paraffin oils and/or higher fatty acid esters. 3,