JPH093104A - Manufacturing method of medical adhesive - Google Patents

Abstract

(57) 【Abstract】 PROBLEM TO BE SOLVED: To effectively prevent the generation of gel during polymerization and the adhesion of gel to the wall surface of a reactor, which improves productivity and workability of cleaning the reactor after preparation. To obtain a method for producing a medical adhesive which is excellent and can shorten the reaction time. SOLUTION: A monomer composition containing a (meth) acrylic acid alkyl ester as a main component is added at a reaction temperature of 50 to 120 ° C.
Then, the solution is polymerized in a sealed state to produce a medical adhesive.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for producing a medical pressure-sensitive adhesive, and more specifically, an acrylic medical agent obtained by polymerizing a monomer composition containing (meth) acrylic acid alkyl ester as a main component. The present invention relates to a method for producing a pressure-sensitive adhesive.

[0002]

2. Description of the Related Art In recent years, percutaneous absorption preparations such as plasters and poultices have been widely used as a means for easily and transdermally administering drugs. In these transdermal preparations, the drug is contained in the adhesive, or the drug is placed on the back surface of the adhesive or in the area surrounded by the adhesive. By the way, as the above-mentioned pressure-sensitive adhesive, an acrylic pressure-sensitive adhesive or a rubber-based pressure-sensitive adhesive is used. Among them, it is easy to control physical properties such as pressure-sensitive adhesive force by combining various acrylic monomers, Adhesives are widely used.

The transdermal absorption preparation using the above-mentioned acrylic pressure-sensitive adhesive is generally produced by solution polymerization or emulsion polymerization of a base polymer such as an acrylic pressure-sensitive adhesive, and the obtained polymer solution is treated with a drug or an additive. Are mixed, then the solvent is dried and removed.

In the actual medical treatment, a transdermal preparation containing nitroglycerin is used as a therapeutic or preventive drug for heart diseases such as angina, myocardial infarction and heart failure. For example, JP-A-63-246325 discloses a nitroglycerin patch using a specific (meth) acrylic acid alkyl ester copolymer.

Further, among the above-mentioned acrylic adhesives,
A percutaneous absorption preparation using a medical adhesive consisting of a copolymer of (meth) acrylic acid alkyl ester and vinylpyrrolidone can exert its drug effect in a short time after application and exhibits long-term efficacy. It is known to obtain it (Japanese Patent Publication No. 3-70685).

On the other hand, in recent years, it has been strongly demanded to reduce skin irritation when using transdermal absorption preparations. As one of the methods for reducing skin irritation, a method is known in which a liquid component compatible with an adhesive is mixed with the adhesive to form an oily gel. However, in this case, although the stimulus-reducing effect is enhanced by the plasticizing action of the liquid component, the cohesive force of the pressure-sensitive adhesive is reduced, and problems such as adhesive residue and stringing during peeling occur.

Therefore, in JP-A-3-223212, a liquid component is blended and applied, and then a cross-linking treatment is applied.
By using an oily gel, it is possible to prevent a decrease in cohesive force, relieve and disperse the stress applied to the skin during peeling of the patch, and to improve the balance between skin adhesion and skin irritation. . However, if the crosslinking agent remains unreacted in the pressure-sensitive adhesive layer, there is a problem that it causes skin irritation.

Further, Japanese Patent Publication No. 28978/1990 discloses that
A method has been disclosed in which a pressure-sensitive adhesive is finely crosslinked with a polyfunctional monomer in advance.

[0009]

Medical adhesives used for percutaneous absorption preparations, etc., which are applied to the skin, are less likely to cause irritation to the skin and may cause less irritation, itchiness and erythema. Strongly demanded. However, in the medical adhesive using the above-mentioned conventional acrylic adhesive, it is necessary to reduce the residual monomer as much as possible in order to prevent skin irritation, rash, itching, erythema and the like. Therefore, in the conventional production of medical adhesives, the polymerization reaction had to be carried out for a long time, and the productivity was not sufficient. In addition, when the polymerization reaction is carried out for a long time, a gel insoluble in the solvent is likely to be generated, and the gel tends to adhere to the wall of the reactor. Therefore, there is a problem that a complicated work is forced to clean the reactor.

In particular, when the adhesive is finely crosslinked with a polyfunctional monomer, or when the copolymer is polymerized with a high-concentration monomer solution in order to obtain a high molecular weight, a large amount is added to the wall of the reactor. Gel will be attached. Therefore, the work such as cleaning of the reactor is extremely complicated, and the productivity and workability tend to be significantly reduced.

Further, when the above-mentioned gel is generated in the adhesive solution, there is a problem that the coatability of the adhesive is lowered and it becomes difficult to obtain a percutaneous absorption preparation of a preferable quality. The purpose of the present invention is to solve the various problems described above,
It is an object of the present invention to provide a method for producing an acrylic medical pressure-sensitive adhesive that can suppress the generation of gel during polymerization, is excellent in productivity and workability, and can shorten the reaction time.

[0012]

The present invention has been made to achieve the above object, and the invention as set forth in claim 1 is a monomer containing (meth) acrylic acid alkyl ester as a main component. A method for producing a medical pressure-sensitive adhesive, which comprises subjecting a body composition to solution polymerization at a reaction temperature of 50 to 120 ° C in a sealed state.

That is, the method for producing a medical pressure-sensitive adhesive according to the first aspect of the present invention is characterized in that a monomer composition containing a (meth) acrylic acid alkyl ester as a main component is treated under the above specific temperature conditions. Further, it is characterized in that the solution polymerization is carried out in a sealed state.

If the reaction temperature during the above-mentioned polymerization is too low, the reactivity becomes low and the polymerization takes a long time, resulting in a decrease in productivity. On the other hand, when the reaction temperature becomes high, the initial reactivity becomes high, and it becomes difficult to control the polymerization reaction. Therefore, as mentioned above, the reaction temperature is in the range of 50 to 120 ° C, preferably 60 to 100 ° C. The reaction may be carried out at a constant temperature as long as the temperature is in the range of 50 to 120 ° C., or the temperature may be changed at appropriate intervals for the reaction.

The solvent used for the solution polymerization is
For example, 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; cellosolve solvents such as methyl cellosolve and ethyl cellosolve. The solvent may be used alone, or two or more kinds of solvents may be used in combination.

In the present invention, the monomer composition containing the (meth) acrylic acid alkyl ester as a main component is solution polymerized in the sealed state at the above reaction temperature. To carry out solution polymerization in this closed state, solution polymerization may be carried out using a closed polymerization reactor. For example, nitrogen gas is purged in the polymerization reactor, air remaining in the reactor is discharged, and nitrogen gas is further discharged by a vacuum pump to maintain the inside of the reactor in a vacuum state (10 to 200 mmHg). . The polymerization reactor is not particularly limited as long as it has a pressure resistant structure, and for example, reactors of various shapes such as a tank type, a tower shape, and a tank shape can be used.

Next, a monomer composition containing a (meth) acrylic acid alkyl ester, which will be described later, as a main component is fed into the reactor. In this case, each of the monomers constituting the monomer composition may be supplied in a predetermined amount all at once, or may be divided and supplied at an appropriate ratio. Further, a polymerization initiator described below is added to allow the polymerization reaction to proceed. At this time, as for the polymerization initiator, a predetermined amount may be collectively supplied into the reactor or may be dividedly supplied.

In the present invention, the polymerization reaction is carried out in the sealed state as described above. Therefore, the reaction temperature can be higher than the boiling point of the solvent used under normal pressure. When the polymerization temperature is higher than the boiling point of the solvent used, the equilibrium state between the liquid phase part and the gas phase part is established in the reactor, and conversely, when the temperature is lower than the boiling point, The part becomes steam.

Further, in the reactor, a pressure corresponding to the vapor pressure of the solvent at a predetermined temperature is generated, but since the gas component is removed in the initial stage, the pressure increase is small and it does not pose a problem.

Mainly composed of (meth) acrylic acid alkyl ester
In the present invention, a monomer composition containing a (meth) acrylic acid alkyl ester as a main component as described above is used, and solution polymerization is carried out at the specific reaction temperature and in a sealed state. To do. The (meth) acrylic acid alkyl ester used in this case is not particularly limited, and examples thereof include methyl (meth) acrylate, ethyl (meth) acrylate, propyl (meth) acrylate, isopropyl (meth) acrylate, ( N-butyl (meth) acrylate, isobutyl (meth) acrylate, n-hexyl (meth) acrylate, isohexyl (meth) acrylate, n-octyl (meth) acrylate, isooctyl (meth) acrylate, (meth) 2-ethylhexyl acrylate, nonyl (meth) acrylate,
1 to 1 carbon atoms such as decyl (meth) acrylate, lauryl (meth) acrylate, and stearyl (meth) acrylate
(Meth) acrylic acid ester composed of 8 alkyl groups can be used, and at least one of them is used.

Most preferably, as the monomer composition containing (meth) acrylic acid alkyl ester as a main component, 40 weight parts of 2-ethylhexyl (meth) acrylate is used as in the invention of claim 2. % To 90% by weight, a monomer composition containing a (meth) acrylic acid alkyl ester having a carbon number of 6 or more as the main component is used. In this case, when the content of 2-ethylhexyl (meth) acrylate increases, the pressure-sensitive adhesive layer becomes hard when formulated using the obtained pressure-sensitive adhesive, and the adhesive strength decreases,
Easy to peel off. On the other hand, if the content of 2-ethylhexyl (meth) acrylate is too low, when a drug such as nitroglycerin is blended at a high concentration, the cohesive force of the pressure-sensitive adhesive decreases, and the pressure-sensitive adhesive layer becomes too soft, Adhesive residue occurs during peeling. Therefore, the above-mentioned (meth) acrylic acid 2-
Ethylhexyl is preferably 40 to 40% in the monomer composition.
The content is 90% by weight, more preferably 60 to 80% by weight.

When the number of carbon atoms in the alkyl group of the above-mentioned (meth) acrylic acid alkyl ester is small, the saturated solubility of a drug such as nitroglycerin is high, and when it is made into a copolymer, the affinity for the drug is high. , The distribution rate to the skin is reduced, and the transdermal absorbability is reduced. Therefore, claim 2
In the invention described in (1) above, an alkyl (meth) acrylate whose acrylic group has 6 or more carbon atoms is used as described above.

Examples of the (meth) acrylic acid alkyl ester having an alkyl group having 6 or more carbon atoms include n-hexyl (meth) acrylic acid, isohexyl (meth) acrylic acid, heptyl (meth) acrylic acid, and (meth) acrylic acid. N-octyl acrylate, isooctyl (meth) acrylate, 2-ethylhexyl (meth) acrylate, (meth)
Examples thereof include nonyl acrylate, decyl (meth) acrylate, dodecyl (meth) acrylate, lauryl (meth) acrylate, and stearyl (meth) acrylate.

Further, in the invention described in claim 2, the (meth) acrylic acid 2 contained in the monomer composition is
As the monomer other than ethylhexyl, one or more kinds of (meth) acrylic acid alkyl esters are preferably selected from those in which the resulting copolymer has a ball tack value of 2 or less.

In the invention described in claim 3, the above-mentioned monomer composition is (meth) acrylic acid alkyl ester 40 to 9
9 mol% and 1 to 60 mol% vinylpyrrolidone.
In the invention according to claim 3, among the (meth) acrylic acid alkyl esters used in the present invention described above, an appropriate (meth) acrylic acid alkyl ester is used depending on the copolymerization ratio with vinylpyrrolidone and the required physical properties. To be

In the invention described in claim 3, as described above, 40 to 99 mol% of (meth) acrylic acid alkyl ester and 1 to 60 mol% of vinylpyrrolidone, preferably 50 (meth) acrylic acid alkyl ester. .About.97 mol% and vinylpyrrolidone 3 to 50 mol%. This is because when the amount of the (meth) acrylic acid alkyl ester is low, the adhesiveness is low, and when the amount of the (meth) acrylic acid alkyl ester is too high, the initial sustained release property of the percutaneous absorption preparation is low.

The invention according to claim 4 is the same as the invention according to any one of claims 1 to 3, wherein the monomer composition is polymerized with an alkyl (meth) acrylate in one molecule. A polyfunctional monomer having two or more functional double bonds,
It is characterized by comprising a composition containing 0.001 to 0.1 mol per 100 mol of the (meth) acrylic acid alkyl ester. As the (meth) acrylic acid alkyl ester used in the invention of claim 4, the (meth) acrylic acid alkyl ester having an alkyl group having 1 to 18 carbon atoms used in the present invention can be used. In the invention according to claim 4, the polyfunctional monomer has two or more polymerizable double bonds in one molecule.

Examples of the polyfunctional monomer include divinylbenzene, methylenebisacrylamide, ethylene glycol-di- (meth) acrylic acid ester, propylene glycol di (meth) acrylic acid ester, butylene glycol di (meth). Acrylic ester, hexylene glycol di (meth) acrylic ester, 1,6
-Hexanediol di (meth) acrylic acid ester, polyethylene glycol di (meth) acrylic acid ester,
Examples thereof include polypropylene glycol di (meth) acrylic acid ester and trimethylolpropane tri (meth) acrylic acid ester.

In the invention described in claim 4, when the content of the polyfunctional monomer is small, the aggregation effect is insufficient, and when the content is large, it becomes difficult to adjust the polymerization degree during the reaction, and the reaction solution becomes It becomes easy to gel, and it becomes difficult to keep the solution in a stable state for a long time even when a copolymer solution can be obtained without gelation. Therefore, the amount of the polyfunctional monomer is 0.001 to 0.1 mol, and preferably 0.001 per 100 mol of the (meth) acrylic acid alkyl ester.
It is contained in the range of 3 to 0.07 mol.

By adding the polyfunctional monomer as described above, the polymer to be formed is partially cross-linked and is in a so-called "slightly cross-linked" state. By this micro-crosslinking,
Appropriate cohesiveness is imparted to the pressure-sensitive adhesive, the adhesiveness is improved, and adhesive residue during peeling can be suppressed. In addition, the stability of the obtained pressure-sensitive adhesive solution is also enhanced.

The invention described in claim 4 is the same as claim 1.
To 3), the polyfunctional monomer is also contained in the monomer composition in the inventions described in claims 2 and 3 in the specific ratio. Can
The above-mentioned effects are exhibited.

In the invention described in claim 5, the monomer composition is at least selected from the group consisting of (meth) acrylic acid alkyl ester and a carboxyl group, a hydroxyl group, an amide group, an epoxy group or an amino group. It contains from 1 to 10% by weight of monomers with one group. Examples of the (meth) acrylic acid alkyl ester include the (meth) acrylic acid alkyl ester having an alkyl group having 1 to 18 carbon atoms, which is used in the present invention, and the (meth) acrylic acid alkyl ester. The type of ester is appropriately selected depending on the copolymerization ratio with a monomer having a reactive functional group described below and required physical properties.

The monomer having at least one reactive functional group used in the invention according to claim 5 is at least selected from the group consisting of a carboxyl group, a hydroxyl group, an amide group, an epoxy group or an amino group. It is a monomer having one functional group.

Examples of the monomer having a carboxyl group include (meth) acrylic acid, crotonic acid, itaconic acid, fumaric acid and maleic acid. Examples of the hydroxyl group-containing monomer include hydroxyethyl (meth) acrylate, hydroxypropyl (meth) acrylate, mono (hydroxyethyl) maleate, and propylene glycol mono (meth) acrylate. it can.

Examples of the amide group-containing monomer include (meth) acrylamide. Examples of the monomer having an epoxy group include, for example,
Examples thereof include glycidyl (meth) acrylate.

Examples of the above-mentioned monomer having an amino group include dimethylaminoethyl (meth) acrylate and t-butylaminoethyl (meth) acrylate.

When the content of the above-mentioned monomer having a reactive functional group is small, the crosslinking becomes insufficient, and when it is large, the tackiness of the obtained copolymer is lowered and the skin adhesiveness is lowered. Therefore, the monomer having a reactive functional group is contained in the monomer composition in an amount of 1 to 10% by weight, preferably 2 to 8% by weight.

The monomer having at least one functional group selected from the group consisting of the carboxyl group, the hydroxyl group, the amide group, the epoxy group and the amino group is preferably the monomer of the invention according to claim 6. like,
(Meth) acrylic acid is used, and (meth) acrylic acid is contained in the monomer composition in an amount of 1 to 10% by weight, preferably 2 to 8% by weight. This is because when the content of (meth) acrylic acid increases, when the obtained pressure-sensitive adhesive is formulated, the pressure-sensitive adhesive layer becomes harder, the adhesive strength decreases, and it becomes easy to peel off. This is because you cannot get

In the invention described in claims 1 to 6, in the polymerization reaction, in addition to the above-mentioned monomer and solvent, if necessary, other monomers, a polymerization initiator and the like are usually used in the polymerization reaction. Appropriate additives used may be added.

Examples of the other monomer include vinyl acetate, vinylpyrrolidone, diacetone acrylamide,
Examples thereof include acrylonitrile, dimethyl acrylamide, ethylene glycol mono (meth) acrylic acid ester, styrene and the like. In addition, in the invention described in claim 3, since vinylpyrrolidone is contained in the monomer composition in the above-mentioned specific ratio, a monomer other than vinylpyrrolidone is used as the other monomer. To be

The above-mentioned other monomers can be added within a range that does not affect the tackiness and cohesiveness of the pressure-sensitive adhesive, and usually 0.01 to 30% by weight in the monomer composition. Is compounded in.

In the invention described in claims 5 and 6, as the other monomer, a polyfunctional compound having two or more polymerizable double bonds in one molecule used in the invention described in claim 4 is used. A polymerizable monomer may be used, whereby a copolymer having a higher degree of polymerization can be obtained, the cohesive force of the pressure-sensitive adhesive layer can be increased, and the generation of adhesive residue can be effectively suppressed. In this case, if the content of the polyfunctional monomer having two or more polymerizable double bonds in one molecule, which is used as another monomer, is small, the aggregation effect is insufficient, and if it is large, gelation occurs during polymerization. Occurs, and a uniform copolymer solution cannot be obtained. Therefore, it is usually blended in an amount of 0.001 to 0.1 mol per 100 mol of (meth) acrylic acid alkyl ester.

Examples of the above-mentioned polymerization initiator include peroxycarbonate, ketone peroxide, peroxyketal, hydroperoxide, dialkyl peroxide, diacyl peroxide, peroxy ester (laurolyl peroxide, benzoyl peroxide, etc.). Such as organic peroxides, 2,2′-azobisisobutyronitrile, 2,2′-azobis (2-methylbutyronitrile), 2,2′-azobis (2,4-dimethylvaleronitrile), Examples thereof include azo compounds such as dimethyl 2,2′-azobisisobutyrate, and these polymerization initiators may be used alone or in combination of two or more kinds. The polymerization initiator used can be appropriately selected according to the reaction temperature, and the amount of the polymerization initiator used is preferably in the range of 0.0001 to 5 parts by weight with respect to 100 parts by weight of the monomer composition.

Application of Medical Adhesive of the Present Invention The medical adhesive of the present invention according to any one of claims 1 to 6 obtained as described above is, for example, in the form of a film prepared by adding and mixing a drug or the like as necessary. It can be made into a patch by molding into a sheet and attaching a support. In addition, a drug layer may be formed on the back surface of the medical pressure-sensitive adhesive of the present invention, and a support may be attached from the back surface side to form a patch.

[0045] In the invention described in the action claims 1-6, as described above (meth)
A monomer composition containing an acrylic acid alkyl ester as a main component, in the above-mentioned specific temperature range, and since solution polymerization is performed in a sealed state, the endothermic reaction is suppressed by preventing the reflux of the solvent, It is difficult for the reaction to occur due to the local concentration increase near the gas-liquid interface. Therefore, it is considered that the generation of gel is effectively suppressed. Further, it is considered that local heating is unlikely to occur in the vicinity of the vessel wall that is in contact with the heating medium, so that a non-uniform reaction is also prevented in the vicinity of the vessel wall, whereby gel is unlikely to adhere to the vessel wall.

Further, since it is a closed system, the polymerization can be carried out under pressure, and therefore, the liquid temperature at the time of the polymerization can be kept above the boiling point under normal pressure, so that the polymerization time can be shortened. .

[0047]

The present invention will be clarified below by describing non-limiting examples of the present invention.

[Embodiments of the Invention According to Claims 1 and 2] Example 1 A pressure-resistant closed polymerization reactor having a stirrer, a temperature controller, a nitrogen gas introducing pipe, a heating and cooling jacket was used.
First, the polymerization reactor was purged with nitrogen gas, the air remaining in the reactor was discharged, and the vacuum (about 60 mmHg) was maintained. Ethyl acrylate 1 bubbled with nitrogen gas in advance
000 g, 800 g of octyl acrylate, 200 g of methyl methacrylate and 2000 g of ethyl acetate were suction-supplied. Next, while stirring at a speed of 30 rpm, the inside of the reactor was maintained at a temperature of 80 ° C., and a 1.0 wt% ethyl acetate solution of lauroyl peroxide was successively added every 2 hours for 10 times to carry out polymerization. It was During the polymerization, heat is generated,
By lowering the jacket temperature (heat medium temperature), the temperature inside the polymerization vessel was controlled to be maintained at 80 ° C. 24
Polymerization is carried out for a period of time, and after cooling, ethyl acetate is added and mixed so that the polymer concentration becomes 30% by weight.
An adhesive solution was obtained and the adhesive solution was withdrawn from the reactor.

Example 2 Polymerization was carried out in the same manner as in Example 1 except that the reaction temperature during the polymerization was changed from 80 ° C to 60 ° C.

Example 3 Benzoylperoxide was used in place of lauroyl peroxide, and the reaction temperature was from 80 ° C to 110 ° C.
Polymerization was conducted in the same manner as in Example 1 except that
An adhesive solution was obtained.

Example 4 As a monomer composition, a mixture of 1600 g of 2-ethylhexyl methacrylate, 200 g of 2-ethylhexyl acrylate and 200 g of dodecyl methacrylate and 2000 g of ethyl acetate as a solvent was used.
Further, polymerization was carried out in the same manner as in Example 1 except that the reaction temperature was 60 ° C. to obtain a pressure-sensitive adhesive solution.

Example 5 Polymerization was carried out in the same manner as in Example 4 except that the reaction temperature was changed from 60 ° C to 80 ° C to obtain an adhesive solution.

Example 6 A pressure sensitive adhesive solution was obtained in the same manner as in Example 4 except that benzoyl peroxide was used as a catalyst instead of lauroyl peroxide and the reaction temperature was 110 ° C.

Example 7 2-Ethylhexyl Methacrylate 8 as a Monomer Composition
00 g, 500 g of 2-ethylhexyl acrylate and 700 g of dodecyl methacrylate, and 2000 g of ethyl acetate as a solvent were used, and the reaction temperature was 8
Polymerization was carried out in the same manner as in Example 4 except that the temperature was 0 ° C. to obtain an adhesive solution.

Example 8 2-Ethylhexyl methacrylate 1 as a monomer composition
800 g and 200 g of 2-ethylhexyl acrylate were used, and a mixture of 2000 g of ethyl acetate as a solvent was used, except that the reaction temperature was 80 ° C.
Polymerization was performed in the same manner as in Example 4 to obtain a pressure sensitive adhesive solution.

Comparative Example 1 A reflux cooling pipe was provided in one of the introduction pipes of the polymerization reactor used in Example 1, and the upper portion was opened. The same monomer composition and solvent as in Example 1 were charged into the polymerization reactor, and the inside of the polymerization reactor was replaced with nitrogen. Next, while stirring at 30 rpm, nitrogen is added to
The mixture was heated to reflux while flowing at 0 ml / min. The temperature of the jacket was maintained at 3 ° C. higher than that in the reactor, and a 1 wt% ethyl acetate solution of lauroyl peroxide as a polymerization initiator was added and polymerized in the same manner as in Example 1. Since the temperature in the reactor decreases with the progress of polymerization, the temperature of the jacket was controlled so as to maintain a temperature higher by 3 ° C. than in the reactor. After polymerization for 24 hours and cooling, ethyl acetate was added to the reactor so that the polymer concentration was 30% by weight and mixed to obtain an adhesive solution.

Comparative Example 2 A reflux cooling tube was attached to one of the introduction tubes of the polymerization reactor used in Example 4, and the upper portion was opened. Into this polymerization reactor, the same monomer composition as used in Example 1 was charged and the atmosphere was replaced with nitrogen. Then flush with nitrogen at 30 ml / min,
The mixture was heated at reflux with stirring at 30 rpm and refluxed. The reaction was initially carried out at 90 ° C., and was adjusted to 80 ° C. after about 10 hours, and a 1 wt% ethyl acetate solution of lauroyl peroxide as a polymerization initiator was successively added every 2 hours for 10 times to carry out polymerization. It was Since the temperature in the polymerization reactor decreases as the polymerization progresses, the jacket temperature (heat medium temperature) was kept at 3 ° C. higher than the temperature in the polymerization reactor. After polymerization for 24 hours and cooling, ethyl acetate was added and mixed so that the polymer concentration would be 30% by weight.
An adhesive solution was obtained.

Comparative Example 3 An adhesive solution was prepared in the same manner as Comparative Example 2 except that the monomer composition used in Example 7 was used as the monomer composition.

Comparative Example 4 A pressure-sensitive adhesive solution was prepared in the same manner as in Comparative Example 2 except that the monomer composition used in Example 8 was used as the monomer composition.

The compositions, solvents, polymerization initiators and reaction temperatures of the monomer compositions in Examples 1 to 8 and Comparative Examples 1 to 4 are shown in Tables 1 and 2 below. In Tables 1 and 2, "EA" is ethyl acrylate, "OA" is octyl acrylate, "MMA" is methyl methacrylate, "EHM" is 2-ethylhexyl methacrylate,
"EHA" means 2-ethylhexyl acrylate, "D
“M” represents dodecyl methacrylate, and “EtAc” represents ethyl acetate. Further, "LPO" of the polymerization initiator represents lauroyl peroxide, and "BPO" represents benzoyl peroxide.

[0061]

[Table 1]

[0062]

[Table 2]

[Embodiment of Invention of Claim 3] Next, Embodiments 9 to 18 of the invention of Claim 3 are described.
Will be described together with Comparative Examples 5 to 10.

Examples 9 to 18 A predetermined amount of the alkyl acrylate, vinylpyrrolidone and ethyl acetate shown in Table 3 below were mixed and fed to the polymerization reactor, and the polymerization initiator shown in Table 3 below was used. Polymerization was performed in the same manner as in Example 1 except that the pressure-sensitive adhesive solution was used and the reaction temperatures shown in Table 3 below were used to obtain a pressure-sensitive adhesive solution.

Comparative Examples 5 to 10 Polymerization was carried out in the same manner as in Comparative Example 1 except that a predetermined amount of alkyl acrylate, vinylpyrrolidone and ethyl acetate shown in Table 3 below were used in combination. And the adhesive solution was obtained.

The symbols in Table 3 below are the same as those in Table 1,
The same symbols as those shown in 2 indicate the same contents, and "V
"P" indicates vinylpyrrolidone. In the VP column, the upper numerical value is the weight (g) and the lower numerical value is the ratio (m) in the monomer composition.
ol%).

[0067]

[Table 3]

[Embodiment of Invention of Claim 4] Next, Embodiments 19 to 3 of the invention of Claim 4
2 and Comparative Examples 11 to 16 for comparison.

Examples 19 to 23 Those containing the (meth) acrylic acid alkyl ester shown in Table 4 below, the polyfunctional monomer, and ethyl acetate in the proportions shown in Table 4 below were used. Polymerization was performed in the same manner as in Example 1 except that the polymerization initiator and the reaction temperature were set as shown in Table 4 below to obtain a pressure-sensitive adhesive solution.

Comparative Examples 11 to 13 A monomer composition containing the (meth) acrylic acid alkyl ester shown in Table 4 below and a polyfunctional monomer in the proportions shown in Table 4 below was used. Polymerization was performed in the same manner as in Comparative Example 1 except that a pressure-sensitive adhesive solution was obtained.

Examples 24 to 29 (Meth) acrylic acid alkyl ester shown in Table 5 below, vinylpyrrolidone (VP), and a polyfunctional monomer,
Polymerization was carried out in the same manner as in Example 1 except that the one containing ethyl acetate in the ratio shown in Table 5 below was used, and the polymerization initiator and the reaction temperature were as described in Table 5 below. , An adhesive solution was obtained.

Comparative Examples 14 and 15 A monomer composition containing (meth) acrylic acid alkyl ester shown in Table 5 below, vinylpyrrolidone, and a polyfunctional monomer in the proportions shown in Table 5 below. Polymerization was performed in the same manner as in Comparative Example 1 except that the above was used to obtain an adhesive solution.

Examples 30 to 32 Those containing the (meth) acrylic acid alkyl ester shown in Table 6 below, the polyfunctional monomer, and ethyl acetate in the proportions shown in Table 6 below were used. Polymerization was performed in the same manner as in Example 1 except that the polymerization initiator and the reaction temperature were set as shown in Table 6 below to obtain a pressure-sensitive adhesive solution.

Comparative Example 16 Except that a monomer composition containing the (meth) acrylic acid alkyl ester shown in Table 6 below and a polyfunctional monomer in the proportion shown in Table 6 below was used. Polymerization was carried out in the same manner as in Comparative Example 1 to obtain an adhesive solution.

The twenty-fourth to twenty-ninth embodiments are claimed in claim 4.
It is an embodiment of the invention described in claim 3, and
It is an example using a monomer composition containing vinylpyrrolidone in a specific ratio as in the invention described in 1.

Further, the above-mentioned Embodiments 30 to 32 are defined by Claim 4.
The (meth) acrylic acid alkyl ester is an example according to the invention described in (1) above, and is constituted by the specific (meth) acrylic acid alkyl ester of the invention described in claim 2.

In Tables 4, 5 and 6, for the symbols indicating the respective monomers, the same symbols as those shown in Tables 1 to 3 have the same meanings, and "BA" means butyl acrylate. , "BM" is butyl methacrylate, "HDA" is 1,
6-hexanediol-diacrylic ester, "PG
"DM" indicates polyethylene glycol-dimethacrylic acid ester.

[0078]

[Table 4]

[0079]

[Table 5]

[0080]

[Table 6]

[Examples According to the Invention of Claim 5] Next, Examples 33 to 39 according to the invention of Claim 5 and Comparative Examples 17 to 19 for comparison will be described.

Examples 33 to 39 Monomers containing (meth) acrylic acid alkyl ester shown in Table 7 below, a monomer having a reactive functional group, and ethyl acetate as a solvent in the proportions shown in Table 7 below. Example 1 was repeated except that the monomer composition was used, the polymerization initiator shown in Table 7 below was used as the polymerization initiator, and the reaction temperature was set to the value shown in Table 7 below. Polymerization
An adhesive solution was obtained.

Comparative Examples 17 to 19 The (meth) acrylic acid alkyl ester shown in Table 7 below, the monomer having a reactive functional group and ethyl acetate were used in the proportions shown in Table 7 below, and Table 7 below. Polymerization was carried out in the same manner as in Comparative Example 1 except that the polymerization temperature was changed to the temperature shown in Table 7 below to obtain a pressure-sensitive adhesive solution.

In Table 7 below, among the symbols indicating the monomer and the polymerization initiator, the same symbols as those shown in Tables 1 to 6 have the same meanings, and “AAc” means acryl. Acid, “HEMA” is hydroxyethyl methacrylate, “AAm” is acrylamide, “GMA” is glycidyl methacrylate, and “DAEA” is dimethylaminoethyl acrylate.

[0085]

[Table 7]

[Embodiment of Invention of Claim 6] Next,
Examples 40 to 44 according to the invention described in claim 6 and comparative examples 20 to 22 for comparison will be described.

Examples 40 to 44 The following Table 8 shows alkyl (meth) acrylic acid alkyl esters.
And a monomer composition containing acrylic acid and ethyl acetate in the proportions shown in Table 8 below, and the one shown in Table 8 below as a polymerization initiator,
Further, polymerization was carried out in the same manner as in Example 1 except that the polymerization temperature was set to the values shown in Table 8 below to obtain a pressure-sensitive adhesive solution.

Comparative Examples 20 to 22 Using a monomer composition containing the alkyl (meth) acrylate shown in Table 8 below, acrylic acid and ethyl acetate in the proportions shown in Table 8 below, lauryl was used as a polymerization initiator. Polymerization was carried out in the same manner as in Comparative Example 1 using peroxide,
An adhesive solution was obtained.

The meaning of each symbol in Table 8 is as follows.
The same symbols as shown in Table 7 represent the same meaning contents.

[0090]

[Table 8]

After the pressure sensitive adhesive solutions obtained in Examples 1 to 44 and Comparative Examples 1 to 22 were extracted, the state of gel adhesion on the wall surface of the polymerization reactor was observed. Further, in order to dissolve the gel adhering to the vessel wall, ethyl acetate was put into the polymerization reactor, heated for 3 hours, refluxed and washed, and after extracting ethyl acetate, the state of residual gel adhering was observed. .

As a result, in all of Examples 1 to 44, no gel adhesion was observed on the wall surface of the reactor when the pressure-sensitive adhesive solution was extracted. On the other hand, Comparative Example 1
In Nos. 22 to 22, gel adhesion was observed in all cases at the time when the pressure-sensitive adhesive solution was extracted, and residual gel was observed in all cases even after washing as described above.

[0093]

As described above, in the method for producing a medical pressure-sensitive adhesive of the present invention, the monomer composition containing the above-mentioned (meth) acrylic acid alkyl ester as a main component is used at a reaction temperature of 50 to 12
The solution polymerization reaction is carried out at 0 ° C. in a sealed state.
Therefore, since the solvent is prevented from refluxing, the adhesion of the gel to the wall of the reactor is significantly reduced. Therefore, the workability of the step of washing the reactor after preparing the pressure-sensitive adhesive solution can be significantly improved, and the productivity of the pressure-sensitive adhesive can be increased.

Further, even in the obtained pressure-sensitive adhesive, since the gel does not remain, it can be suitably used as a medical pressure-sensitive adhesive,
A preferred formulation can be obtained. Furthermore, since the polymerization reaction can be carried out at a temperature not lower than the boiling point of the solvent, the reaction time can be shortened, which also makes it possible to enhance the productivity of the medical adhesive.

 ─────────────────────────────────────────────────── ─── Continuation of the front page (31) Priority claim number Japanese Patent Application No. 7-96905 (32) Priority date Hei 7 (1995) April 21 (33) Country of priority claim Japan (JP) (31) Priority Claim number Japanese patent application No. 7-96906 (32) Priority date Hei 7 (1995) April 21, (33) Priority claiming country Japan (JP) (72) Inventor Ken Nakachi 4560 Kaisei-cho, Shinnanyo-shi, Yamaguchi Prefecture Tokuyama Sekisui Kogyo Co., Ltd. (72) Inventor Mitsue Shiga 4560 Kaisei-cho, Shinnanyo-shi, Yamaguchi Prefecture Tokuyama Sekisui Kogyo Co., Ltd.

Claims (6)

[Claims] 1. A monomer composition containing a (meth) acrylic acid alkyl ester as a main component at a reaction temperature of 50 to 120 ° C.
The method for producing a medical pressure-sensitive adhesive, characterized in that the solution polymerization is carried out in a sealed state. 2. The (meth) acrylic acid alkyl ester contains 2-ethylhexyl (meth) acrylic acid in an amount of 40 to 40%.
The method for producing a medical pressure-sensitive adhesive according to claim 1, which is a (meth) acrylic acid alkyl ester containing 90% by weight and having an alkyl group having 6 or more carbon atoms. 3. The method for producing a medical pressure-sensitive adhesive according to claim 1, wherein the monomer composition contains (meth) acrylic acid alkyl ester 40 to 99 mol% and vinylpyrrolidone 1 to 60 mol%. 4. The monomer composition comprises an alkyl (meth) acrylate and a polymerizable double bond in one molecule.
The polyfunctional monomer having the above is added in an amount of 0.001 to 0.1 per 100 mol of the (meth) acrylic acid alkyl ester.
The method for producing a medical pressure-sensitive adhesive according to any one of claims 1 to 3, which is a composition containing a mole. 5. The monomer composition comprising a (meth) acrylic acid alkyl ester and at least one functional group selected from the group consisting of a carboxyl group, a hydroxyl group, an amide group, an epoxy group or an amino group. Quantities 1 to
The method for producing a medical pressure-sensitive adhesive according to claim 1, which is a monomer composition containing 10% by weight. 6. The carboxyl group, the hydroxyl group,
The method for producing a medical pressure-sensitive adhesive according to claim 5, wherein the monomer having at least one functional group selected from the group consisting of an amide group, an epoxy group, or an amino group is (meth) acrylic acid.