JPH01233213A - Plaster and production thereof - Google Patents

Abstract

PURPOSE:To obtain a plaster applicable to skin over a long period without causing rash and having extremely excellent transcutaneous absorbability of a drug, by covering one surface of a substrate with a tacky adhesive layer containing a drug and a lecithin and/or sorbitan fatty acid salt. CONSTITUTION:The objective plaster can be produced by mixing (A) an effective amount of a drug (0.5-40 pts.wt., especially 1-25 pts.wt., in the case of non- steroidal anti-inflammatory agent) and (B) 0.5-50 pts.wt., especially 1-20 pts.wt. of a lecithin and/or sorbitan fatty acid ester to (C) 100 pts.wt., of a tacky adhesive base preferably composed mainly of a copolymer of (i) an alkyl (meth) acrylate having 1-18C alkyl group and (ii) other polar monomers (e.g., vinylpyrrolidone), uniformly dissolving the above three components in a solvent, applying the solution to one surface of a substrate and drying the coating layer. The transcutaneous absorbability of the drug can be synergistically improved by adding an absorbefacient such as N-acyl-N-methylglycine to the tacky adhesive layer.

Description

[Detailed description of the invention] (Industrial application field) The present invention is a patch that can administer a drug transdermally.

In particular, the present invention relates to a patch with improved percutaneous absorption of the drug and a method for producing the same.

(Prior Art) In order to obtain systemic or local medicinal effects, drugs (physiologically active substances) are absorbed through the skin using patches, which are transdermal preparations. This transdermal administration method has many advantages over traditional oral administration methods. for example,
When a drug is orally administered, the drug is absorbed in the intestines and circulates to the liver where it undergoes metabolism, resulting in a significant amount of the drug being degraded before it exerts its medicinal effect. In contrast, with transdermal administration, the absorbed drug does not pass through the liver during its initial circulation in the body. Therefore, the medicinal efficacy is not significantly reduced due to metabolism in the liver. Particularly in the case of non-steroidal anti-inflammatory drugs, oral administration tends to cause gastrointestinal disorders, but transdermal administration has the advantage that such gastrointestinal disorders are less likely to occur. By controlling the absorption of drugs, it is possible to reduce side effects caused by large amounts of drugs being absorbed in a short period of time. If a constant blood concentration can be maintained over a long period of time, the frequency of drug administration can be reduced.

However, even if a drug is administered using a patch, it is often difficult for the drug to penetrate the skin, resulting in a low bioavailability. Therefore, attempts have been made to increase the absolute amount of drug present in the patch so that the required amount of drug can be absorbed transdermally.

For example, JP-A-60-185713 discloses a patch.

Transdermal absorption preparations have been disclosed in which a drug is contained in a base such as an ointment or a cream preparation in an amount exceeding the saturation solubility, and the drug is dispersed in the form of recrystallized fine particles. For example, when a patch is applied to the skin surface and the drug dissolved in the base is absorbed transdermally, the drug present in the form of fine particles in the base is sequentially dissolved and the dissolved drug is replenished. . Therefore, it is considered possible to administer a larger amount of the drug than in conventional formulations in which the amount of drug is less than the saturation solubility of the drug.

However, in reality, the drug, which is present in the form of particles, cannot be redissolved into the base material, so the absorption efficiency of the drug through the skin is not as high as expected.

Many patches containing absorption enhancers have also been prepared to enhance drug absorption. As absorption enhancers, a large number of compounds are generally used, such as salicylic acid, urea, dimethyl sulfoxide, propylene glycol, glycerin, and dimethyl sulfoxide. However, in all cases, transdermal absorption of the drug is not necessarily guaranteed. This is not a good result.When administering the above non-steroidal anti-inflammatory drug as a drug, phospholipids such as phosphatidylcholine are included in the adhesive to increase the retention of the non-steroidal anti-inflammatory drug under the skin. The method to increase the medicinal efficacy is
JP-A-58-150508 and JP-A-61-1
It is disclosed in Japanese Patent No. 72833. Although the anti-inflammatory effect is somewhat increased by adding phospholipids, the effect is not high enough to be therapeutically satisfactory. Thus, at present, a patch that can effectively absorb drugs has not yet been obtained.

(Problem to be solved by the invention) The present invention solves the above-mentioned conventional drawbacks.

The objective is to provide a patch that allows the drug it contains to be effectively absorbed through the skin. Another object of the present invention is to provide a patch containing an absorption aid that enhances the transdermal absorption of the drug contained therein, is non-irritating to the skin, and is safe for living organisms. Still another object of the present invention is to provide a patch that can maintain local and systemic efficacy, for example, for non-steroidal anti-inflammatory drugs.

Still another object of the present invention is to provide a patch that reduces the number of drug administrations per day, is easy to use, and can obtain patient compliance.

(Means for Solving the Problems) The patch of the present invention is a patch having an adhesive layer provided on one side of a support, and the adhesive layer is a drug.

and lecithin and/or sorbitan fatty acid ester, and the drug is uniformly dispersed in the adhesive layer, thereby achieving the above object.

The method for producing the patch of the present invention includes a drug, lecithin and/or
or a step of uniformly dissolving the sorbitan fatty acid ester and the adhesive base in a solvent; and a step of applying the obtained solution to one side of the support and drying; or a step of applying the obtained solution to the surface of a release paper and drying. , a step of bringing a support into close contact with the surface of the formed adhesive layer, thereby achieving the above object.

The lecithin used in the patch of the present invention refers to glycerinated phospholipids that are widely distributed in nature, including phosphatidylcholine (lecithin in the narrow sense). In addition to the above phosphatidylcholine, lecithin also contains phosphatidylethanolamine.

phosphatidylserine, phosphatidylinositol,
Examples include phosphatidic acid. Easily available lecithin-containing products containing one or more of these include:
Soy lecithin, egg yolk lecithin.

Hydrogenated lecithin, etc.

The above-mentioned sorbitan fatty acid ester has a carbon number of 10 to 26,
Preferably, it is an esterified product of 4 to 22 fatty acids (which may be saturated fatty acids or unsaturated fatty acids) and sorbitol. For that.

Sorbitan monolaurate Examples include sorbitan monopalmitate, sorbitan monooleate, sorbitan sesquioleate, and sorbitan trioleate.

The lecithin and/or sorbitan fatty acid ester increases the solubility of the drug in the base.

As a result, it has the effect of increasing the drug utilization rate.

These compounds are usually included in the adhesive base described below.

They are contained within a range that does not exceed their respective saturation solubility. The concentration varies depending on the composition of the adhesive base, etc.9 Usually,
The amount is in the range of 0.5 to 50 parts by weight, preferably 1 to 20 parts by weight, based on 100 parts by weight of the adhesive base.

If the amount is too small, the solubility of the drug in the adhesive base will not improve, and as will be described later, it will not be possible to contain a large amount of the drug in a substantially amorphous state. Even if the amount is excessive, not only the effect of promoting transdermal absorption of the drug in proportion to the amount cannot be obtained, but also the adhesive strength of the adhesive decreases. The amount of lecithin and/or sorbitan fatty acid ester is preferably a high concentration close to the saturation concentration for the base, within a range that does not reduce the adhesive force of the adhesive base or the diffusion rate of the drug in the base.

The drug (physiologically active substance) to be used is not particularly limited, as long as it permeates the skin through transdermal administration and exerts a medicinal effect locally or systemically. For example, nonsteroidal anti-inflammatory drugs, steroids, antihypertensive drugs, anesthetics,
These include antifungals, antiepileptics, coronary vasodilators, hormonal agents and antihistamines.

Non-steroidal anti-inflammatory drugs include piroxicam, phenylbutacin, acetylsalicylic acid, flufenamic acid,
mefenamic acid, ibuprofen.

These include ketoprofen, flurbiprofen, sulindac, indomethacin, diclofenac, alclofenac, fenbuene, tinoridine, and emorfazone. As steroids.

Corticosteroids include prednisolone and clobetasol propionate. Antihypertensive agents include clonidine, nifedipine, and propranolol.

Lidocaine is an anesthetic.

Examples include pensicaine. Antifungal agents include clotrimazole and pentamycin. Antiepileptic drugs include nitrazebam and mebrobamate. Coronary vasodilators include nitroglycerin and isosorbide dinitrate. Examples of hormonal agents include estradiol. Examples of antihistamines include diphenhydramine hydrochloride and diphenylimidazole.

These drugs are contained in the base in an amount that exceeds the saturation solubility of the drug. Preferably, the amount of the drug to be added is at least the usual daily dose of the drug. The amount to be blended varies depending on the type of drug, the composition of the adhesive base, the purpose of use of the resulting patch, etc.1 For example, when blending a non-steroidal anti-inflammatory drug as the drug, 100% by weight of the adhesive base described below. 0.5-40 per part! i parts, preferably 1 to 25 parts by weight. If the amount of drug is too small, sufficient medicinal efficacy and sustained medicinal efficacy cannot be obtained. If it is in excess, the drug will precipitate from the adhesive layer,
Adhesive strength decreases.

The adhesive base for the patch of the present invention is not particularly limited as long as it has enough adhesive strength to fix the patch to the skin for a long time at room temperature. For example, acrylic.

Adhesives such as rubber-based and silicone resin-based may be used.
Usually, acrylic and rubber adhesives are used.

Regarding acrylic adhesives, their adhesive properties, etc.

In particular, polymers and/or copolymers containing (meth)acrylic acid alkyl esters having an alkyl group of 1 to 18 carbon atoms (including copolymers containing other polar monomers as copolymerization components) are preferably used. It will be done. The above (meth)acrylic acid alkyl esters include methyl (meth)acrylate, ethyl (meth)acrylate, and butyl (meth)acrylate.
Acrylate 2-ethylhexyl (meth)acrylate.

Examples include dodecyl (meth)acrylate. The other polar monomer mentioned above is (meth)acrylic acid.

Vinylpyrrolidone, diacetone acrylamide.

(Poly)ethylene glycol (meth)acrylate (poly)propylene glycol (meth)acrylate, 2-
There are monomers with hydrophilic groups such as hydroxyethyl (meth)acrylate.

When the content of the polar monomer in the copolymer is high, the solubility of the drug in the copolymer increases, making it possible to obtain a patch containing a high content of the drug. Among acrylic adhesives, copolymers of (meth)acrylic acid alkyl esters and vinylpyrrolidone and/or diacetone acrylamide are particularly preferably used. The (meth)acrylic acid alkyl ester used in such a copolymer is particularly butyl (meth)acrylate.

2-Ethylhexyl (meth)acrylate, dodecyl (
Preferred are meth)acrylates and the like. Vinylpyrrolidone and/or diacetone acrylamide is generally present in the above copolymer in an amount of 5 to 50% by weight, preferably 1% by weight.
It is contained in a range of 0 to 40% by weight. If it exceeds 50% by weight, the copolymer becomes hard and its tackiness decreases slightly.

As the rubber adhesive, styrene-isoprene-styrene block copolymer, styrene-butadiene copolymer,
Examples include polybutene, polyisoprene, butyl rubber, and natural rubber. As a silicone resin adhesive,
Silicone rubber such as polyorganosiloxane is used.

The adhesive patch of the present invention further contains an absorption enhancer and other additives as necessary. As an absorption enhancer, N
At least one of -acyl-N-methylglycine (N-acylsarcosine), fatty acid jetanolamide, and polyoxyethylene-added fatty acid jetanolamide (POE-added fatty acid jetanolamide) is preferred. Among the above absorption enhancers, N-acyl-N-methylglycine includes lauroylsarcosine, myristoylsarcosine, valmitoylsarcosine, oleoylsarcosine, and the like. Examples of fatty acid jetanolamide include lauroyl jetanolamide, caproyl jetanolamide, myristoyl jetanolamide, and coconut oil fatty acid jetanolamide. P.O.B.
Examples of the added fatty acid jetanolamide include polyoxyethylene lauroyl jetanolamide and polyoxyethylene coconut oil fatty acid jetanolamide.

The absorption enhancer is preferably contained in the adhesive base at a concentration close to its saturated solubility. Its concentration varies depending on the composition of the adhesive base and the amount of lecithin, etc.9 Usually,
It is contained in a proportion of 0.2 to 30 parts by weight, preferably 0.5 to 15 parts by weight, based on 100 parts by weight of the base. If the amount is too low, the effect of promoting transdermal absorption of the drug cannot be obtained. If it is in excess, the adhesive properties of the adhesive base will deteriorate, making it easier for the patch applied to the skin surface to peel off due to sweating, for example.

Other additives include softeners, fillers, anti-aging agents, and the like. Examples of the softening agent include fatty acid esters such as isopropyl myristate and medium-chain fatty acid triglyceride; and higher alcohols such as triacetin, triethyl citrate, and octyldodecanol.

As the support for the patch, a support commonly used for patches is used. Such supports include polyethylene, polyester, polyamide.

Films made of polyethylene-vinyl acetate copolymer, polyvinylidene chloride, polyurethane, aluminum, etc.;
These laminate films include nonwoven fabrics and the like.

A drug-containing (adhesive) N containing a drug and an absorption aid (lecithin and/or sorbitan fatty acid ester) is formed on the surface of the support to obtain a patch. Various coating methods such as a solvent coating method and a hot melt coating method are used to form the adhesive layer. Among these, the solvent coating method is suitable.

For example, 1 to form an adhesive layer using a solvent coating method.

The adhesive base is diluted with a suitable solvent, and the drug, lecithin and/or sorbitan fatty acid ester, and, if necessary, the above-mentioned absorption enhancers and additives are added and uniformly mixed and dissolved. Apply the solution to the support surface.
dry. Instead of applying the solution directly to the surface of the support, it may be applied onto a release paper coated with silicone resin or the like, and after drying, the solution may be brought into close contact with the support. As the above solvent,
Preferably, it is capable of dissolving adhesive bases, drugs, etc. and has a low boiling point. The type of solvent is appropriately selected depending on the adhesive base and the type of drug. For example, ethyl acetate, cyclohexane, toluene, tetrahydrofuran, methylene chloride, methanol, ethanol, etc. are used. As the release paper, a polyester film, a polyethylene-coated high-quality paper, a polyolefin-coated glassine paper, a polypropylene film, etc., which has been subjected to a silicone release treatment on one side, is used. Such release paper is used to protect the surface of the adhesive layer of the patch until use. In the hot melt coating method, instead of using the solvent used in the above-mentioned solvent coating method, the adhesive base, drug, etc. are uniformly dissolved by heating, and coating is performed on the support or release paper. The thickness of the adhesive layer also varies depending on the purpose of use, but is usually about 30
uI11 to about 2rtm. If it is less than 30 μm, it will not be possible to contain the necessary amount of drug and the adhesiveness will be insufficient.

Above 2M, it becomes difficult to remove the solvent, especially in the case of solvent coating. Drug release is also reduced.

(Function) Immediately after preparation, the adhesive layer of the patch obtained according to the present invention is transparent, with the drug, lecithin, etc. being uniformly dissolved therein. When this patch is stored at room temperature, the drug gradually precipitates out. The drug precipitates uniformly throughout the adhesive base, and the precipitate is substantially amorphous. In other words, rather than recrystallized drug particles as described in the prior art,
It exists in an amorphous state or as ultrafine particles that are difficult to observe. The condition of such drugs is
This is achieved due to the presence of lecithin and/or sorbitan fatty acid ester in the adhesive base. The substantially amorphous drug diffuses into the adhesive base more easily at lower temperatures and is absorbed through the skin than the drug that exists as recrystallized particles. Therefore, the efficiency of drug utilization increases. Due to the presence of lecithin and/or sorbitan fatty acid ester, the solubility of the drug in the base is also high, making it possible to contain the drug at a high concentration in the adhesive base.

Therefore, a patch that can exhibit medicinal efficacy over a long period of time can be obtained. Since lecithin and sorbitan fatty M ester do not impair the tackiness of the adhesive base, they can be used as a single patch (adhesive on the support) without separately preparing the adhesive layer and drug-retaining layer. It can be easily prepared in the form of a layered patch). In other words, the adhesive layer functions both as a drug reservoir and as an adhesive. For example, when a nonsteroidal anti-inflammatory drug is used as the drug, anti-inflammatory effects can be exerted not only locally but also systemically over a long period of time.

Since it is not administered orally, it does not cause gastrointestinal disorders.

When a drug absorption enhancer is further contained in the adhesive layer, even higher transdermal absorption of the drug can be obtained due to the synergistic effect with the above-mentioned lecithin and the like.

In this way,9 by using the patch of the present invention, it is possible to increase the amount of drug administered at a time, and since the drug is released continuously, it is possible to reduce the number of administrations per day. Yes, patient compliance is obtained.

(Example) The invention will be explained below with reference to examples.

2-ethylhexyl methacrylate 2-ethylhexyl acrylate and dodecyl acrylate (molar ratio 8
:1:1) was polymerized in ethyl acetate using lauroyl peroxide to obtain a copolymer (S[lK) solution with a solid content of 50% and a weight average molecular weight of 1,090,000. 100 parts by weight of the copolymer (adhesive base) obtained by drying this solution, 7 parts by weight of piroxicam, 5 parts by weight of soybean lecithin, and 15 parts by weight of isopropyl myristate (IPM) were added to 330 parts by weight of methylene chloride, and then It was dissolved in This solution was spread on polylaminated glassine release paper, and
Dry at °C.

An adhesive layer with a thickness of 80 μm was formed. In this adhesive layer,
A polyethylene terephthalate film was adhered as a support to obtain a patch having release paper.

(B) Evaluation of patch The following items were tested. The results are shown in the table below. The results of Examples 2 to 9 and Comparative Examples 1 to 3, which will be described later, are also shown in the table below.

(2) Appearance of adhesive layer: After storing the patch at room temperature for 7 days, the adhesive layer was visually observed and, if necessary, observed using a polarizing microscope.

■Drug skin permeability evaluation: 1nvit by the following method
Drug permeability testing was performed using an ro diffusion cell.

The drug permeability (%) after 24 hours is shown in the table below. This drug permeability rate is a measure of the amount of drug absorbed transdermally when the patch is applied for 24 hours. The index of the amount of drug absorption is expressed as the amount of administered drug x drug permeability.

Drug permeability measurement method using an in vitro diffusion cell: A Franz-shaped diffusion cell with an aperture diameter of 25 cm is prepared.

A phosphate buffer solution adjusted to pi (7.2) is placed in a part of the receptor of a Franz-type diffusion cell, and the outer wall is heated at 37°C.
The temperature of a part of the receptor is kept constant by circulating hot water.

A patch test piece is applied to the excised epidermis (approximately 3 cd) from the back of a nude mouse, and the epidermis is attached to a cell. Fill the receptor fluid, being careful not to introduce air bubbles between the skin and the receptor fluid level. After 24 hours, the receptor fluid is sampled, the drug concentration is measured by high performance liquid chromatography, and the drug permeability is calculated from the following formula.

(2) Pole tack value: The pole tack value was measured using , yt, s Z 0237 (adhesive tape/adhesive sheet testing method).

The procedure was the same as in Example 1 except that no soybean lecithin was added.

Same as Example 1 except that 5 parts by weight of lauroylsarcosine was further added to the base solution.

Regarding this patch, drug absorption was further evaluated using the following 9 methods. First, apply this patch to 2.5 ci x 2.
It was cut into 5 cm pieces and applied to the upper arms of five panelists for 24 hours. The drug was extracted from the patch after application with methanol, and its concentration was measured by liver LC to determine the amount of drug present in the patch. The amount of drug in the patch used was measured in advance, and the drug absorption rate (%) was calculated using the following formula.

Drug absorption rate (%) As a result, the drug absorption rate was 12.8%. When this patch 100CIIT is applied to the skin surface, per -day,
.

It can be seen that a therapeutically effective amount of approximately 5.4 μm of piroxicam can be absorbed transdermally.

The procedure was the same as in Example 1 except that 2 parts by weight of lauroylsarcosine was further added to the main base solution.

The procedure was the same as in Example 1 except that 2 parts by weight of lauroyl sarcosine was further added to the sharpening base solution and the amount of soybean lecithin was adjusted to 20 parts by weight.

The procedure was the same as in Example 1 except that 10 parts by weight of lauroyl sarcosine was further added to the base solution.

Copolymer (SDK) solution obtained in Example 1 (solid content 5
0%), 8 parts by weight of indomethacin, 5 parts by weight of soybean lecithin, and 15 parts by weight of isopropyl myristate (IPM) are added and mixed with respect to 100 parts by weight of solid content,
A homogeneous solution was obtained. This was spread on polyester release paper and dried at 60°C to form an adhesive layer with a thickness of 50 μm. A polyethylene film was adhered to this adhesive layer as a support to obtain a patch having release paper.

Example 6 Same as Example 6 except that sorbitan trioleate was used instead of soybean lecithin.

Upper comparison cell 1 Same as Example 1 except that soybean lecithin was not added.

Symptomitis ■ 2-ethylhexyl acrylate and vinylpyrrolidone (molar ratio 65:35) were polymerized in ethyl acetate using lauroyl peroxide as a catalyst, resulting in a solid content of 35%9.
A copolymer solution having a weight average molecular weight of 720,000 was obtained. 100 parts by weight of a copolymer (adhesive base) obtained by drying this solution,
20 parts by weight of piroxicam, 5 parts by weight of soybean lecithin and 5 parts by weight of lauroyl sarcosine were added to 330 parts by weight of methylene chloride and uniformly dissolved. Using this solution, a patch was prepared according to Example 1.

Northern comparison m Same as Example 8 except that soybean lecithin and lauroyl sarcosine were not used.

Example 1 Same as Example 2 except that lauroyl jetanolamide was used instead of elauroyl sarcosine and the amount of IPH was 10 parts by weight.

(The following is a blank space) A comparison between Example 1 and Comparative Example 1 shows that the patch of the present invention containing lecithin in the base has excellent transdermal absorbability and good adhesiveness. The patch (Example 2) further contains an absorption enhancer.

Drug permeability is further improved. Although the patch containing a large amount of lecithin (Example 4) improves drug permeability, the effect is not proportional to the amount of lecithin. Adhesiveness also decreases slightly. The patch (Example 5) contains a large amount of absorption enhancer.

Although the drug permeability is further improved, the adhesive's tackiness is reduced, making it easier to peel off due to sweating or the like. Comparative Example 2 not containing lecithin and sorbitan fatty acid ester
For the patch, the drug crystallizes and precipitates from the adhesive base, but for the patches of Examples 6 and 7 containing lecithin or sorbitan fatty acid ester, the precipitated drug does not crystallize. Therefore, it has excellent drug permeability.

Adhesive strength also does not decrease. A patch using an adhesive base containing vinylpyrrolidone and containing lecithin (Example 8)
), it is particularly possible to incorporate a large amount of the drug into the adhesive base.

(Effects of the Invention) According to the present invention, as described above, lecithin and/or sorbitan fatty acid ester and a drug in a substantially amorphous state exceeding the saturation solubility are contained in an adhesive base, and the drug is transdermally administered. A patch with extremely excellent absorbency can be obtained. Because of the excellent absorption of the drug, it is possible to increase the single dose of the drug. Since drug release is sustained, the number of administrations per day can be reduced. Since the lecithin and sorbitan fatty acid ester used are not irritating to the skin, they do not cause rashes or exhibit any side effects even if applied for a long time. Furthermore, these factors do not cause the drug to change in quality, and the drug does not precipitate or deteriorate in adhesive properties. In such a patch, various drugs can be absorbed transdermally, and the therapeutic effect when using the patch is also high. Therefore, it can be used for various medical purposes depending on the type of drug contained.

Claims (1)

[Scope of Claims] 1. A patch having an adhesive layer provided on one side of a support, the adhesive layer containing a drug, and lecithin and/or sorbitan fatty acid ester; A patch uniformly dispersed in the adhesive layer. 2. The adhesive layer further includes an absorption enhancer for the drug, and the absorption enhancer is at least one selected from N-acyl-N-methylglycine, fatty acid diethanolamide, and polyoxyethylene-added fatty acid diethanolamide. The adhesive patch according to claim 1. 3. The adhesive patch according to claim 1, wherein the adhesive base of the adhesive layer is mainly composed of a copolymer of an alkyl (meth)acrylic acid ester and another polar monomer. 4. A step of uniformly dissolving the drug, lecithin and/or sorbitan fatty acid ester, and adhesive base in a solvent, and a step of applying the obtained solution to one side of the support and drying it;
Alternatively, a method for producing a patch comprising the steps of applying the obtained solution to the surface of a release paper, drying it, and then bringing a support into close contact with the surface of the formed adhesive layer. 5. A step of dissolving an absorption enhancer of the drug in the solvent together with the drug, lecithin and/or sorbitan fatty acid ester, and the adhesive base, wherein the absorption enhancer is N-acyl-N-methylglycine. , fatty acid diethanolamide, and polyoxyethylene-added fatty acid diethanolamide, the method according to claim 4. 6. The method according to claim 4, wherein the adhesive base of the adhesive layer is mainly composed of a copolymer of an alkyl (meth)acrylic acid ester and another polar monomer.