JPH09124467A - Medical tacky agent, medical transdermal patch and production of medical tacky agent - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a medical tacky agent little in age variation of the physical property of tackiness, stable for a long period in the property and hardly giving foreign feeling to the skin even after processed into a medical transdermal patch, and to prepare a medical transdermal patch. SOLUTION: This medical tacky agent is composed mainly of a copolymer prepared by the solution polymerization of a monomer composition mainly containing a (meth)acrylic acid alkyl ester in the presence of an initiator generating radicals, and the content of the remaining initiator is <=0.05wt.% of the total amount in terms of a solid component. The present invention also provides a medical transdermal patch in which a drug containing tacky agent layer composed of the medical tacky agent and a drug is formed on a soft supporting body.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a medical adhesive used for a medical patch known as a plaster or a poultice, a method for producing the medical patch and a medical adhesive, and particularly The present invention relates to a medical adhesive in which the content of residual monomers that may cause irritation to the human body is significantly reduced, a medical patch using the medical adhesive, and a method for producing a medical adhesive.

[0002]

2. Description of the Related Art Recently, medical patches such as plasters and poultices have been widely used as a simple means for transdermal administration of drugs. These medical patches have a structure in which a medical adhesive layer containing a drug is formed on a flexible support such as a sheet or tape.

As the above-mentioned medical adhesive, a general acrylic adhesive or rubber adhesive is used. Among them, the acrylic pressure-sensitive adhesive is widely used because the required physical properties such as adhesive strength can be easily controlled by adjusting the combination of various acrylic monomers. In general,
After polymerizing a monomer composition containing (meth) acrylic acid alkyl ester as a main component by solution polymerization or emulsion polymerization, and mixing drugs, additives, etc. in the obtained polymerization solution,
The above-mentioned medical patch is manufactured by drying and removing the solvent.

In the medical pressure-sensitive adhesive obtained by the above-mentioned production method, that is, the medical pressure-sensitive adhesive using a copolymer containing (meth) acrylic acid alkyl ester as a main component, irritation to human body, rash, itch, erythema, etc. In order to prevent the occurrence of the above, the residual monomer concentration is required to be as low as possible. Therefore, there has been proposed a medical pressure-sensitive adhesive in which the amount of residual monomers in the pressure-sensitive adhesive before compounding is 0.2% by weight or less based on the solid content (Japanese Patent Laid-Open No. 5-131022).

By the way, various methods have been adopted to reduce the residual monomer concentration when obtaining a copolymer, but generally, the amount of the polymerization initiator added is increased in the latter half of the polymerization reaction, A method of generating a large amount of free radicals by repeatedly adding a polymerization initiator is adopted.

[0006]

However, in the medical adhesive obtained by increasing the amount of the polymerization initiator added in the latter half of the polymerization reaction or repeatedly adding the polymerization initiator, the residual monomer content is Although it is lowered, the adhesive patch for medical use using the medical adhesive may have a large change in adhesive physical properties over time. In particular, among the adhesive physical properties, the holding power sometimes changed significantly over time.

Since the medical patch is to be applied to the human body, if the set adhesive property changes with time, it will greatly affect the usability of the product.
For example, when the adhesive strength increases over time, when the medical patch is peeled from the skin, the skin is damaged, or when the adhesive layer becomes hard over time, the skin may be damaged during use. Stress may be applied and skin irritation may increase. Also, if the adhesive strength decreases with time, the medical patch may peel from the skin during use,
Partial floating of the medical patch may occur.

An object of the present invention is to provide a medical pressure-sensitive adhesive which has little change with time in the adhesive physical properties even after being processed into a medical patch, and thus has stable adhesive physical properties for a long time, and such a medical adhesive. It is intended to provide a medical patch using the above and a method capable of producing the above medical adhesive.

[0009]

Means for Solving the Problems The inventors of the present invention have made extensive studies on the above-mentioned problems, and as a result, the change with time of the adhesive physical properties of the adhesive after obtaining the medical patch remained in the adhesive. Of the active and active polymerization initiator, it was found that the adhesive physical properties significantly change with time even if only a very small amount of this active polymerization initiator is present, and the present invention was accomplished based on this finding. It was

That is, the medical pressure-sensitive adhesive of the present invention is a copolymer obtained by solution polymerization of a monomer composition containing (meth) acrylic acid alkyl ester as a main component in the presence of an initiator that generates radicals. In a medical pressure-sensitive adhesive containing a polymer as a main component, the residual amount of the above-mentioned initiator is 0.05% based on the solid content.
It is a medical pressure-sensitive adhesive characterized by being extremely low at less than or equal to wt%.

The invention according to claim 2 is a medical patch comprising a medical adhesive, wherein the content of the residual initiator is 0.05% by weight or less based on the solid content. ,
It is characterized in that a layer containing the medical adhesive according to the invention of claim 1 and a drug is provided on a flexible support.

Further, the invention described in claim 3 is the first invention.
A method for producing a medical pressure-sensitive adhesive according to the invention described in 1, wherein a monomer composition containing (meth) acrylic acid alkyl ester as a main component is solution polymerized in the presence of an initiator that generates radicals. In producing a medical pressure-sensitive adhesive containing a copolymer obtained as a main component, at least in the latter half of the polymerization, the reaction temperature is set to a temperature above the boiling point of the polymerization solution in a sealed state, and the start of remaining in the pressure-sensitive adhesive. The method for producing a medical pressure-sensitive adhesive is characterized in that the copolymer is prepared so that the content of the agent is 0.05% by weight or less based on the total solid content.

The term "second half of polymerization" in the sealed state at least in the latter half of polymerization means a state in which the polymerization rate has progressed by 95% or more. Hereinafter, the details of the present invention will be described.

Monomer Composition Examples of the alkyl residue of the (meth) acrylic acid alkyl ester used as the main component in the present invention include a methyl group, an ethyl group, a propyl group, an isopropyl group, an n-butyl group, Isobutyl group, n-hexyl group, isohexyl group, 2-ethylhexyl group, n-octyl group, isooctyl group, nonyl group, decyl group, lauryl group, stearyl group and the like, and one or more of them may be mentioned. Used.

As the (meth) acrylic acid alkyl ester used in the present invention, any appropriate one can be used as long as it has one or two or more of the above alkyl residues. ) Ethyl acrylate, 2-ethylhexyl (meth) acrylate, octyl (meth) acrylate, dodecyl (meth) acrylate and the like can be mentioned.

Further, in the present invention, a medical pressure-sensitive adhesive whose main component is a copolymer obtained by solution polymerization of the monomer composition whose main component is the (meth) acrylic acid alkyl ester is constituted. Is contained in the monomer composition,
The monomer to be copolymerized with the (meth) acrylic acid alkyl ester may be (meth) during preparation of an acrylic pressure-sensitive adhesive.
As a monomer to be copolymerized with the acrylic acid alkyl ester, an appropriate monomer conventionally used can be used depending on the adhesive physical properties required. Examples of the monomer copolymerized with the (meth) acrylic acid alkyl ester include vinyl acetate, vinylpyrrolidone, diacetone acrylamide, acrylonitrile, dimethyl acrylamide, ethylene glycol mono (meth) acrylic acid ester, and styrene. Is mentioned. These monomers can be used to the extent that they do not affect the tackiness or cohesiveness of the pressure-sensitive adhesive. The maximum amount of these monomers used is
Usually, it is 40 mol% of the entire monomer composition.

Further, in obtaining the medical pressure-sensitive adhesive of the present invention, a monomer composition containing the (meth) acrylic acid alkyl ester and a monomer copolymerized with the (meth) acrylic acid alkyl ester. Further, a polyfunctional monomer may be added to the product, whereby a copolymer having a higher degree of polymerization can be obtained, and thus an adhesive having excellent cohesiveness can be obtained. As such a polyfunctional monomer, one having two or more radically polymerizable functional groups such as vinyl group and allyl group in one molecule can be used, and examples thereof include divinylbenzene, methylenebisacrylamide, Ethylene glycol di (meth) acrylate, propylene glycol di (meth) acrylate,
Examples thereof include butylene glycol di (meth) acrylate, hexylene glycol di (meth) acrylate, polyethylene glycol di (meth) acrylate, polypropylene glycol di (meth) acrylate, and trimethylolpropane tri (meth) acrylate. The amount of these polyfunctional monomers added is usually 0.1% by weight or less based on the total amount of the monomer composition. When the amount of the polyfunctional monomer added is more than 0.1% by weight, it becomes difficult to adjust the degree of polymerization during the reaction, the reaction solution easily gels, and it becomes difficult to uniformly mix the drugs in the subsequent steps.

In the invention described in any one of claims 1 to 3, the monomer composition contains the above-mentioned (meth) acrylic acid alkyl ester as a main component, and is further copolymerized with the above-mentioned (meth) acrylic acid alkyl ester. A monomer, and optionally the polyfunctional monomer as described above. Preferred examples of such a monomer composition include (meth) acrylic acid alkyl ester 40 to 99 mol% and vinyl. A composition composed of 1 to 60 mol% of pyrrolidone and a polyfunctional monomer which is contained in an amount of 0.001 to 0.1 mol of the polyfunctional monomer with respect to 100 mol of all the monomers. Monomer composition, 2-ethylhexyl methacrylate 40-90
In a composition containing a (meth) acrylic acid alkyl ester having 6% or more carbon atoms in the alkyl group contained in wt% as a main component, the polyfunctional monomer is added to 0.0 per 100 mol of all monomers.
Examples thereof include a monomer composition prepared by blending a polyfunctional monomer so as to contain 01 to 0.1 mol.

Solvent In the present invention, when the above-mentioned monomer composition is solution-polymerized, an appropriate solvent which is commonly used in the solution-polymerization of an acrylic copolymer is used, if necessary. Examples of such a solvent include ester solvents such as ethyl acetate, propyl acetate and butyl acetate; ketone solvents such as methyl ethyl ketone and cyclohexanone; aromatic solvents such as benzene and toluene; methyl cellosolve;
A cellosolve solvent such as ethyl cellosolve can be used alone or in combination of two or more kinds.

Polymerization Initiator As the polymerization initiator for generating a radical used in the present invention, a general thermal radical initiator such as peroxycarbonate, ketone peroxide, peroxyketal, hydroperoxide, dialkyl peroxide ( Laurolyl peroxide, benzoyl peroxide, etc.), diacyl peroxide, peroxy ester, and other organic peroxides; 2,2′-azobis (2,2
4-dimethylvaleronitrile), azo compounds such as dimethyl 2,2′-azobisisobutyrate.

These radical initiators are selected according to the polymerization temperature and may be used alone or in combination of two or more kinds. In addition, when the above-mentioned polymerization initiator is added to the system, the polymerization initiator may be added at once, or may be divided and added.

The amount of the polymerization initiator used is 1 for the monomer composition.
When it is set to 00% by weight, it is preferably 0.0001 to 5% by weight, but in order to reduce the residual monomer amount,
Usually, 0.1% by weight or more is necessary.

Residual initiator content In the invention described in claims 1 to 3, the residual amount of the polymerization initiator in the medical pressure-sensitive adhesive, that is, the residual initiator content is 0.05% based on the solid content. It is set to be not more than wt%, and thereby, changes in the adhesive physical properties of the adhesive with time are suppressed.

That is, the remaining polymerization initiator, after being processed into a medical patch, decomposes over time to generate radicals, a crosslinking reaction due to hydrogen abstraction of the acrylic pressure-sensitive adhesive, a drug to be added or an additive. It is considered to cause an addition reaction to an active group such as an agent. Therefore,
It is preferable that the residual amount of the above-mentioned polymerization initiator is as small as possible, and as will be apparent from the examples described below, the present inventors have said that if the solid content ratio in the adhesive is 0.05% by weight or less, It has been found that such problems can be effectively suppressed.

The content of the residual initiator is 0.0% of the total solid content in the medical adhesive of the present invention as described above.
It is necessary to be 5% by weight or less, but it is preferably 0.01% by weight or less, whereby it is possible to further prevent changes in the adhesive physical properties of the adhesive with time. When the content of the residual initiator exceeds 0.05% by weight in terms of solid content, the change in the adhesive properties with time becomes remarkable.

The method for reducing the content of the residual initiator in the pressure-sensitive adhesive is not particularly limited, but for example, the temperature is raised in the latter half of the polymerization, and the temperature is kept at the elevated temperature for a necessary time or longer. There is a method. Considering the time required for the polymerization, the method of raising the temperature in the latter half of the polymerization is a preferable method because the residual initiator content can be reduced in a short time.
In this case, more specifically, a method in which the reaction solution is boiled under reflux or a pressure-closed system is used to maintain the temperature at the boiling point or higher can be adopted.

The time required for holding at the high temperature is the time until the content of the residual initiator becomes less than 0.05% by weight of the total solid content, and the following formula of the initiator concentration reduction rate k ( It can be calculated by substituting the characteristic values (frequency factor, activation energy) of the initiator used, the concentration of the initiator, and the treatment temperature into 1) and (2).

[0028]

(Equation 1)

Where [I] is the initiator concentration, [I] ₀ is the initial (t = 0) initiator concentration, t is the time, A is the frequency factor, Ea is the activation energy, R is the gas constant, and T is the gas constant. Is the temperature.

Medical patch The medical patch according to the invention described in claim 2 is a drug-containing adhesive comprising the medical adhesive according to claim 1 and a drug obtained as described above. An agent layer is provided on a flexible support.

The drug contained in the adhesive is not particularly limited, and anti-inflammatory and analgesic agents, anti-inflammatory agents, coronary vasodilators, tranquilizers, antihypertensive agents, antibiotics, anesthetics, antibacterial agents, antihistamines. , Sex hormones, cerebral circulation improving agents, anti-ulcer agents and the like. The content of the drug varies depending on the kind of the drug, but usually 0.1 to 30% by weight in the adhesive.
Range.

Further, if necessary, the pressure-sensitive adhesive layer may appropriately contain an absorption promoter, a drug dissolving agent, a tackifier, a crosslinking agent, a filler, an antioxidant and the like. The material of the flexible support includes polyethylene, polypropylene, polybutadiene, ethylene-vinyl acetate copolymer, ethylene-
Propylene copolymers, ethylene-alkyl (meth) acrylate copolymers, olefins such as polybutene; styrene / isoprene / styrene copolymers, styrene / butadiene / styrene copolymers and polystyrenes such as water additives thereof; Polyvinylidene chloride, vinylidene chloride
Vinylidene chloride type such as styrene copolymer; polyvinyl chloride type such as polyvinyl chloride, vinyl chloride-ethylene copolymer, vinyl chloride-alkyl acrylate copolymer; silicone resin; polyfluorinated ethylene, polyethylene terephthalate, polybutylene Examples include polyesters such as terephthalate, polyurethane, polyamide and the like.

The flexible support is not limited to the one made of the resin material as described above, and may be a laminate of these resin films and cotton cloth or non-woven cloth. further,
The flexible support may have any shape such as a film shape, a sheet shape, or a tape shape.

The flexibility of the flexible support is not particularly limited, but since it is applied to the skin, it is preferably flexible enough to follow the movement of the human body. Is configured to have. The thickness of the support varies depending on the material used, but in the case of a film-like support, it is 500 μm or less, preferably 40 to 20.
0 μm.

The adhesive layer supporting surface of the film-like support may be subjected to undercoating treatment, corona discharge treatment, chemical oxidation treatment, ozone treatment or the like, if necessary, in order to enhance the adhesiveness with the adhesive layer. Processing is performed.

A medical pressure-sensitive adhesive layer containing the above-mentioned drug may be provided on the flexible support to provide a medical adhesive layer.
Although the medical patch according to the invention described in 1) is obtained, generally, in the medical patch, the drug-containing pressure-sensitive adhesive layer is shielded from the outside air, and the pressure-sensitive adhesive layer can be attached to other parts before use. In order to prevent this, release paper is attached to the surface of the drug-containing pressure-sensitive adhesive layer. Also in the medical patch of the invention described in claim 2, it is preferable that such a release paper is stuck on the surface of the drug-containing medical adhesive layer,
As the release paper, one made of polyethylene film, polypropylene film, polyethylene terephthalate film or the like can be used. The thickness of the release paper is usually 3
The thickness is set to 00 μm or less, preferably 10 to 200 μm.

Method for producing medical patch The method for producing the medical patch according to the invention described in claim 2 can be appropriately selected from the conventionally used methods. That is, a usual adhesive coating method such as bar coater or gravure coating can be used. The thickness of the pressure-sensitive adhesive layer is not particularly limited, but is usually 20 to 1000 μm.
m. If this thickness is 20 μm or less, it may be difficult to contain the required amount of drug, or the adhesiveness may be insufficient. If the thickness is 1000 μm or more, the drug contained in the pressure-sensitive adhesive layer near the support may not sufficiently diffuse, and the drug utilization rate may decrease.

In the medical adhesive according to the first aspect of the present invention, as described above, the content of the residual initiator is 0.05% by weight or less of the total amount of the medical adhesive, based on the solid content, and the residual initiator is contained. The amount is very low. Therefore, when the pressure-sensitive adhesive layer of a medical patch is constituted by using the medical pressure-sensitive adhesive according to the invention of claim 1, various reactions based on the generation of radicals caused by the polymerization initiator after the patch is processed. For example, it is possible to suppress the addition reaction or the hydrogen abstraction reaction in the double bond, and thus it is possible to effectively suppress the change in the adhesive property over time.

Since the medical patch of the invention described in claim 2 is constituted by using the medical adhesive of the invention described in claim 1, the above-mentioned various kinds of residual initiators caused by the residual initiator are used. Since the reaction is suppressed, it is possible to provide a medical patch, in which the adhesive physical properties of the adhesive layer are less likely to change with time.

Further, in the invention described in claim 3, in carrying out solution polymerization of a monomer composition containing (meth) acrylic acid alkyl ester as a main component in the presence of an initiator for generating radicals, In the latter half, in order to raise the reaction temperature to a temperature equal to or higher than the boiling point of the polymerization solution in a sealed state, the content of the residual initiator according to the invention of claim 1 is 0.05% by weight or less based on the total solid content. It is possible to easily and surely obtain the adhesive.

[0041]

EXAMPLES The present invention will be clarified by giving Examples and Comparative Examples below. Examples 1 to 9 A five-necked flask equipped with a stirring rod, a thermometer, a reflux condenser, a nitrogen introducing tube and a dropping funnel was used. A predetermined amount of the monomer shown in Table 1 below and ethyl acetate were put into the flask, and the inside of the flask was replaced with nitrogen. While carrying out the nitrogen replacement, stirring was carried out at 30 rpm to start the temperature rise.
Then, the mixture was refluxed at a boiling point for about 30 minutes to discharge excess oxygen, and then cooled to a polymerization temperature shown in Table 2 below.

A polymerization initiator solution was prepared by dissolving 1.0 g of laurolyl peroxide in ethyl acetate so that the total amount was 30 ml. The above initiator solution was added dropwise to the monomer solution set to the above polymerization temperature in the pattern shown in Table 2 below to carry out polymerization. After completion of the polymerization, ethyl acetate was added to the system and mixed so that the solid content concentration became 30% by weight, to prepare an adhesive solution.

Comparative Examples 1 to 6 The same apparatus as in Examples 1 to 9 was used, except that predetermined amounts of the monomers and ethyl acetate shown in Table 1 below were added, and the same procedure as in Examples 1 to 9 was performed. However, the polymerization was carried out under the conditions shown in Table 2 below. After completion of the polymerization, as in the case of Examples 1 to 9, ethyl acetate was added and mixed so that the solid content concentration was 30% by weight, to prepare an adhesive solution.

Examples 10 to 18 A closed polymerization reactor having a pressure resistant structure having a stirrer, a temperature controller, a nitrogen gas introducing pipe, a reflux cooling pipe, a heating jacket and a cooling jacket was used.

First, the inside of the polymerization reactor was purged with nitrogen gas, the air remaining in the reactor was discharged, and the nitrogen gas was further discharged with a vacuum pump to obtain about 60 mmHg in the polymerization reactor.
The vacuum degree was maintained at. A predetermined amount of a monomer bubbling with nitrogen gas and ethyl acetate were sucked in at a ratio shown in Table 3 below and supplied into the polymerization reactor.

Next, the monomer solution in the polymerization reactor was washed with 30
The inside of the polymerization reactor was maintained at a predetermined polymerization temperature shown in Table 4 below while stirring at rpm. In addition, in Examples 10, 11,
In 13, 14, 16 and 17, the above-mentioned closed state was maintained, in Examples 12, 15 and 18, the upper part of the reflux cooling pipe was opened, and in Examples 1 to 18, the following operations were carried out, respectively. .

The initiator solution prepared in Example 1 was prepared as the initiator solution, and the initiator solution was added dropwise to the monomer solution set to the above polymerization temperature in the pattern shown in Table 4 below.
Polymerization was performed. However, in Examples 12, 15, and 18, after the final initiator solution was charged, the polymerization reactor was closed and the polymerization was carried out.

Also in Examples 10 to 18, as in Examples 1 to 9, after completion of the polymerization, ethyl acetate was added and mixed so that the solid content concentration was 30% by weight,
An adhesive solution was prepared.

Comparative Examples 7 to 12 The same apparatus as in Examples 10 to 18 was used, except that the monomers and ethyl acetate in the predetermined amounts shown in Table 3 below were added,
Open the reflux condenser upper part from the beginning to the end of the polymerization reaction,
Polymerization was performed in a nitrogen stream under the conditions shown in Table 4 below.

After completion of the polymerization, ethyl acetate was added so that the solid content concentration would be 30% by weight and mixed to prepare an adhesive solution. In addition, the content of the symbol which shows the monomer in the following Table 1 and Table 2 is as follows.

EHA ... 2-ethylhexyl acrylate,
EA ... ethyl acrylate, OA ... octyl acrylate,
VP ... N-vinylpyrrolidone, EHMA ... 2-ethylhexyl methacrylate, DM ... Dodecyl methacrylate

[0052]

[Table 1]

[0053]

[Table 2]

[0054]

[Table 3]

[0055]

[Table 4]

The polymerization temperature marked with * in Table 2 means that the temperature was raised to boiling reflux (liquid temperature = 77 ° C.) 20 hours after the initiation of the polymerization. Further, the description of the polymerization temperature in Examples 10 to 18 in Table 4 means (temperature 20 hours before the start of polymerization) / (temperature 20 hours after the start of polymerization). For example, 70/10 of Example 10
0 means that the temperature 20 hours before the initiation of polymerization is 70 ° C. and the temperature 20 hours after the initiation of polymerization is 100 ° C.

In Comparative Examples 9 and 10, boiling reflux (liquid temperature = 77 ° C.) was carried out 20 hours after the initiation of polymerization. Evaluation of Examples and Comparative Examples The concentration of the polymerization initiator remaining in the pressure-sensitive adhesive was determined by an iodometric titration method using an iodine compound (potassium iodide), which is one of the methods for analyzing active oxygen in peroxide (1 / The concentration was determined by titration with a 10N sodium thiosulfate solution), and the weight% concentration relative to the solid content of the adhesive is shown in Tables 5 and 6 below.

(2) The holding power after processing the medical adhesive tape
Evaluation Examples 1-5, 10-14 and Comparative Examples 1-4, 7-10
For the pressure-sensitive adhesive solution obtained in step 1, the pressure-sensitive adhesive solution was dried using a knife coater so that the thickness after drying was 50 μm.
The surface was coated on a polyethylene-treated polyethylene terephthalate film and dried. Furthermore, it was laminated with a support made of a polyethylene terephthalate-vinyl acetate copolymer film.

Regarding the pressure-sensitive adhesive solutions obtained in Examples 6 and 15, isosorbide dinitrate was mixed with the pressure-sensitive adhesive solution so that the concentration of isosorbide dinitrate was 10% by weight based on the total solid content, and then a knife coater was used. It was applied to a polyethylene terephthalate film whose surface was treated with silicon so that the thickness after drying was 50 μm, and dried.
Furthermore, it was laminated with a support made of a polyethylene terephthalate-vinyl acetate copolymer film.

Examples 7-9, 16-18 and Comparative Example 5,
Regarding Nos. 6, 11, and 12, nitroglycerin was mixed in the adhesive solution so that the concentration was 10% by weight based on the total solid content ratio, and the thickness after drying was 5 using a knife coater.
The surface was coated on a polyethylene terephthalate film whose surface had been treated with silicon so that the thickness was 0 μm, and the film was dried.
Furthermore, it was laminated with a support made of a polyethylene terephthalate-vinyl acetate copolymer film.

In any case, the pressure-sensitive adhesive tape was dried at 60 ° C. for 30 minutes after the pressure-sensitive adhesive was applied. Further, a part of the obtained adhesive tape is cut, and the cut adhesive tape is sealed with an aluminum packaging material, and the temperature is 60 ° C.
It was stored for 2 weeks in the constant temperature bath (acceleration test).

In evaluating the change with time of the adhesive physical properties,
With respect to the pressure-sensitive adhesive tape 3 days after the pressure-sensitive adhesive was applied as described above and the pressure-sensitive adhesive tape after the acceleration test, the holding power was measured in the following manner.

Measurement of holding power: width 25 mm, length 150 m
A sample of m was prepared and attached to a stainless steel plate so as to contact with an area of 25 × 25 mm, and the non-attached portion was folded over with the inner surface, that is, the adhesive layer surface inside. Using a 2 kg roller, the test piece was reciprocated once at a crimping speed of about 300 mm / min for crimping. 4 samples with the above test piece adhered to a stainless steel plate
After holding in a constant temperature bath of 0 ° C. for 20 minutes or more, one end of the test piece is fixed with a stopper, and the test piece hangs vertically, and 1 is attached to the end of the unfolded folded portion.
A weight of kg was attached, and the time until the weight fell (holding time) was measured. The results are shown in Tables 5 and 6 below.

[0064]

[Table 5]

[0065]

[Table 6]

In the adhesives of Examples 1 to 18, Tables 5 and 6 are used.
As is clear from the above, the residual initiator content was 0.
Since it is less than 05% by weight, it can be seen that the holding time does not change so much between after coating and after the acceleration test.

On the other hand, in Comparative Examples 1 to 12, the residual initiator content was as high as 0.05% by weight or more, so that the holding power of the sample after the acceleration test was significantly higher than that after coating. You can see that it is being done. That is, Comparative Examples 1 to 1
When the pressure-sensitive adhesive tape of No. 2 is used, the holding power is remarkably increased as described above when it is applied to the skin surface, and it is considered that a great discomfort can be given during use.

In Comparative Example 4, the temperature was raised to boil and reflux in the latter half of the polymerization, but the residual initiator content did not decrease sufficiently, probably because the treatment time was short. Therefore, the acceleration test was performed as described above. The holding power afterwards was significantly higher. Similarly, in Comparative Examples 9 and 10, in the latter half of the polymerization, the boiling reflux state, which is the highest polymerization reaction temperature, was carried out in the conventional open system polymerization equipment. Fell to 0.073% by weight and 0.052% by weight. Therefore, as is clear from Table 6, the holding power after the acceleration test was considerably higher than the holding power after coating.

[0069]

As described above, according to the invention described in claim 1, the residual initiator content is 0.05% of the total solid content ratio.
Since the content is less than or equal to wt%, changes in the adhesive physical properties of the medical adhesive, particularly the holding power, with time are effectively suppressed. Therefore, when the medical patch according to claim 2 using the medical adhesive according to claim 1 is processed, the pressure-sensitive adhesive property of the adhesive layer in the medical patch changes with time. Since it is difficult to change, it is possible to reduce the discomfort felt by the user. That is, it is possible to reduce stress and skin irritation on the skin. In addition, since the adhesive strength is less likely to decrease with time, the medical patch is less likely to be peeled off from the skin during use, and the medical patch is less likely to be partially lifted.

Further, according to the invention of claim 3,
To obtain a copolymer, which is the main component of the medical adhesive, by solution polymerization of the monomer composition containing the (meth) acrylic acid alkyl ester as the main component in the presence of an initiator that generates radicals, In the latter half of the polymerization reaction, since the reaction temperature is set to a temperature not lower than the boiling point of the polymerization solution in a closed state to carry out the polymerization, the medical adhesive according to the invention according to claim 1, that is, the residual initiator content. It is possible to reliably and efficiently obtain a medical pressure-sensitive adhesive having a solid content ratio of 0.05% by weight or less of the whole in a short time.

Claims (3)

[Claims] 1. A medical pressure-sensitive adhesive containing as a main component a copolymer obtained by solution polymerization of a monomer composition containing (meth) acrylic acid alkyl ester as a main component in the presence of an initiator capable of generating radicals. In the medical adhesive, the residual initiator content is 0.05% by weight or less of the total solid content. 2. A medical patch, comprising a drug-containing pressure-sensitive adhesive layer comprising the medical pressure-sensitive adhesive according to claim 1 and a drug on a flexible support. 3. A medical adhesive containing as a main component a copolymer obtained by solution polymerization of a monomer composition containing (meth) acrylic acid alkyl ester as a main component in the presence of an initiator for generating radicals. In producing the agent, the reaction temperature is set at a temperature equal to or higher than the boiling point of the polymerization solution in a sealed state at least in the latter half of the polymerization reaction so that the residual initiator content in the medical pressure-sensitive adhesive is 0% of the total solid content. 0.05% by weight
A method for producing a medical pressure-sensitive adhesive, which comprises preparing a copolymer as described below.