JPH0912652A - Thermally reversible hydrogel material and its production - Google Patents

Abstract

PURPOSE: To obtain a novel thermally reversible hydrogel which is excellent in uniformity in compsn.. stability of qualities such as sol-gel transition point, etc.. does not cause chemical cross-linking and well follows the movement of a living body or the deformation of a wound in the course of healing, is not broken and hence not taken into a tissue, is not dissolved in an exuding liq., and is useful as a biocompatible material, etc. CONSTITUTION: This material is a graft copolymer which is formed by grafting a water-sol. polymer onto the main chain comprising a polymer of which the aq. soln. has a cloud point. The copolymer has a mol.wt. of 100,000 or higher and is produced by copolymerizing a water-sol. polymer having one polymerizable functional group introduced thereinto and a monomer which gives a polymer of which the aq. soln. has a cloud point while satisfactorily controlling the physical properties and the insolubilization by cross-linking during production.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to a thermoreversible hydrogel material and a method for producing the same. More specifically, the present invention is a hydrogel material that retains a large amount of water in a gel, which is useful as a material separating material, medical devices, pharmaceuticals, agricultural chemicals, cosmetics, etc., and reversibly gels due to a change in temperature. The present invention relates to a thermoreversible hydrogel material and a method for producing the same.

[0002]

BACKGROUND OF THE INVENTION Among water-soluble polymers, it is known that an aqueous solution thereof forms a hydrogel in a reversible manner.
It is also used industrially in the field of cosmetics and the like. Typical examples are gelatin, which is a protein, and agar, which is a polysaccharide, and these aqueous solutions lose their fluidity upon cooling to become jelly-like hydrogels, which undergo a thermoreversible sol-gel transition that returns to the aqueous solution by heating. It is well known to show. On the contrary, as a material that becomes a hydrogel by heating, there is an aqueous solution of methylcellulose which is a polysaccharide derivative. However, as a problem common to these systems, since all of these water-soluble polymers are made of natural materials, it is difficult to secure quality stability and control of the sol-gel transition temperature is difficult. It is difficult, and it takes a long time to reach the gelation temperature and then to gel.

On the other hand, it is known that some nonionic surfactants form an aqueous solution thereof in a thermoreversible hydrogel. For example, a high-concentration aqueous solution of trade name Pronic F-127 (manufactured by Asahi Denka Kogyo Co., Ltd.) in which polyethylene oxide is bonded to both ends of polypropylene oxide becomes a hydrogel at about 20 ° C. or higher, and becomes an aqueous solution at a temperature lower than that. Are known (for example, International Journal of Pharmaceutics, 12 , 1
47-152 (1982)). However, in the case of this material, there is a problem that the hydrogel forms a hydrogel only at a high concentration of about 20 wt% or more, and the water content in the hydrogel is low. Further, even if the gelation temperature is maintained above the gelation temperature at a high concentration of about 20 wt% or more, there is a problem that the gel will be dissolved by further adding water. For example, when this gel is used as a wound dressing, the hydrogel is seriously dissolved by the exudate secreted from the wound surface. Since this material has a relatively low molecular weight, a high-concentration aqueous solution of about 20 wt% or more exhibits a very high osmotic pressure and easily permeates cell membranes, etc. In some cases, there is a problem in the use.

Furthermore, as a thermoreversible hydrogel material, a conjugate of poly-N-isopropylacrylamide and polyethylene oxide is known. In the manufacturing process, a plurality of reactive functional groups are introduced into both polymers. Therefore, there is a high risk of insolubilization due to chemical cross-linking during the binding reaction, which is not only difficult to manufacture, but it is also very difficult to control the physical properties of the resulting hydrogel.

Similarly, a conjugate of trifunctional polyethylene oxide and polypropylene oxide, or conversely, a trifunctional polypropylene oxide and polyethylene oxide has been proposed as a thermoreversible hydrogel, which is also manufactured. At times, chemical cross-linking occurred, and the same drawbacks as above were unavoidable. Furthermore, such chemical cross-linking is a state in which the cross-linked polymer has a sol-gel transition temperature or higher,
That is, in order to restrict the mobility between molecules in the gel state,
The ability to follow complicated movements of the living body or deformation of the wound during the healing process is significantly impaired, and at the same time, serious problems such as the incorporation of this gel fragment into the tissue due to brittle fracture due to chemical crosslinking are considered. .

Therefore, the present invention solves the problems of the conventional thermoreversible hydrogel materials as described above, and is excellent in stability of quality, controllability of sol-gel transition temperature and efficiency of gelation. Of course, it is possible to increase the water content, it has excellent compatibility with living organisms, and because it does not have chemical crosslinks, it is flexible and has excellent conformability to complex shapes and deformation. A stable new thermoreversible hydrogel material that can follow the movement of a solid body and deformability in wound healing process, at the same time is prevented from being taken up into tissues by brittle fracture, does not dissolve in exudate, and is stable To provide a manufacturing method.

[0007]

In order to solve the above-mentioned problems, the present invention is a graft copolymer in which a water-soluble polymer is bonded as a side chain to a main chain of a polymer whose aqueous solution has a cloud point. The graft copolymer provides a thermoreversible hydrogel material having a molecular weight of 100,000 or more. Furthermore, this invention introduces one polymerizable functional group into the water-soluble polymer chain of the graft copolymer constituting the thermoreversible hydrogel material,
Also provided is a method for producing a thermoreversible hydrogel material, which is obtained by copolymerizing the aqueous solution with a monomer constituting a polymer having a cloud point. More specifically, first, the graft copolymer as defined in the present invention is a polymer compound in which a linear polymer (main chain) serving as a trunk is bound with an arbitrary polymer branch (side chain). Means
The graft copolymer of the present invention is a polymer having a cloud point in its main chain and a water-soluble polymer in its side chain, and is essential.

The specific thermoreversible hydrogel material comprising the graft copolymer having such a structure is first provided by the present invention. The cloud point means a temperature at which a transparent polymer aqueous solution (concentration: 1 wt%) gradually becomes cloudy when gradually heated, and is not particularly limited in the present invention, The cloud point is preferably 0 ° C to 90 ° C, more preferably 0 ° C to 40 ° C. That is, a polymer whose aqueous solution has a cloud point dissolves in water at a temperature below the cloud point, but becomes insoluble in water at a temperature above the cloud point and precipitates from water. Examples of the polymer whose aqueous solution has a cloud point include poly-N-isopropylacrylamide, poly-Nn-propylacrylamide, poly-N-cyclopropylacrylamide, poly-
N, N-diethyl acrylamide, poly-N-acryloyl piperidine, poly-N-acryloyl pyrrolidine,
Poly-N-substituted acrylamide derivatives such as poly-N, N-ethylmethylacrylamide, poly-N-isopropylmethacrylamide, poly-N-substituted methacrylamide derivatives such as poly-N-cyclopropylmethacrylamide, polyvinyl methyl ether, polyvinyl alcohol partial vinegar And the like.

The cloud point of the above poly-N-substituted (meth) acrylamide derivative can be adjusted by a random copolymer with another monomer, and the cloud point is increased by the copolymerization with a hydrophilic monomer, and the hydrophobicity is increased. Copolymerization with the monomer lowers the cloud point. Here, examples of the hydrophilic monomer include N-vinylpyrrolidone, acrylamide, and acrylic acid, and examples of the hydrophobic monomer include n-butyl methacrylate, acrylonitrile, and styrene.

Examples of the water-soluble polymer in the present invention include polyalkylene oxides such as polyethylene oxide, poly N-vinylpyrrolidone, polyacrylamide, polyvinyl alcohol, methyl cellulose, dextran, polyvinyl pyridine, polymethacrylamide, poly Poly N-substituted acrylamide derivatives such as N-methyl acrylamide, polyhydroxymethyl acrylate, polyacrylic acid, polymethacrylic acid, polyvinyl sulfonic acid, polystyrene sulfonic acid and salts thereof, poly N, N-dimethylaminoethyl methacrylate, poly N, Examples thereof include N-diethylaminoethyl methacrylate, poly N, N-dimethylaminopropyl acrylamide and salts thereof.

It is also essential that the above-mentioned graft copolymer of the present invention has a molecular weight of 100,000 or more. Here, the graft copolymer having a molecular weight of 100,000 or more means an ultrafiltration membrane (YM1 manufactured by Amicon Co., Ltd.) having a molecular weight of 100,000, which is obtained by fractionating the aqueous solution thereof at a temperature below the cloud point of the main chain.
00) refers to those that are not filtered when ultrafiltered.

The average degree of polymerization of the water-soluble polymer side chain in the graft copolymer is preferably 10 or more. If the average degree of polymerization is less than 10, the steric hindrance effect (volume exclusion effect) of the water-soluble polymer hydrated in water becomes insufficient, and aggregation between the main chains at temperatures above the cloud point of the main chain occurs. Since it cannot be suppressed effectively, the entire system undergoes macroscopic phase separation (prominent gel syneresis), and it becomes difficult to obtain a stable hydrogel. On the other hand, when the average degree of polymerization of the side chains of the water-soluble polymer exceeds 1,000, the steric hindrance effect of the water-soluble polymer hydrated in water becomes excessive, resulting in aggregation between main chains at temperatures above the cloud point of the main chains. Since it inhibits, it becomes difficult to obtain a stable hydrogel. Therefore, the preferable range of the average degree of polymerization of the water-soluble polymer side chain is 10 to 1,000.

The proportion of side chains in the graft copolymer is preferably 10% by weight or more. If the amount is less than 10% by weight, the cohesive force between the main chains at a temperature above the cloud point of the main chain is too strong, so that a remarkable syneresis phenomenon of the gel occurs and a stable hydrogel cannot be obtained. When the chain proportion exceeds 90% by weight, the cohesive force between the main chains at a temperature above the cloud point of the main chains is insufficient, so that a hydrogel tends not to be formed. Therefore, the preferable proportion of side chains in the graft copolymer is from 10% by weight to 90% by weight.
% By weight.

Next, the production method of the present invention will be described. Generally, as a method for synthesizing a graft copolymer, 1) a method utilizing a chain transfer reaction of a polymer, 2) a free radical is split into a trunk polymer. Known methods include introducing a functional group to be obtained and initiating polymerization from the functional group, 3) initiating ionic polymerization from a trunk polymer. The graft copolymer of the present invention can also be obtained by these methods, but from the viewpoint of controlling the degree of polymerization of side chains, one polymerizable functional group is previously introduced into the water-soluble polymer chain, Obtaining the aqueous solution by copolymerizing with a monomer that constitutes a polymer having a cloud point in water provides good control of the physical properties of the obtained graft copolymer and control of cross-link formation during production. It is also an advantage.

Here, the number of the polymerizable functional groups introduced into the water-soluble polymer chain needs to be one, and when a plurality of polymerizable functional groups are introduced, the polymer having a cloud point after that is introduced. In the copolymerization with the monomer constituting the above, a chemically crosslinked gel insoluble in any solvent is produced, and a water-soluble graft copolymer to be a thermoreversible hydrogel material cannot be obtained. In order to introduce one polymerizable functional group into the water-soluble polymer chain, for example, a chain transfer agent is used when polymerizing a monomer that gives a water-soluble polymer, and the polymerizable functional group is directly or indirectly used. Can be introduced at one end of the polymer chain.

By carrying out a copolymerization reaction in water of a water-soluble polymer having one polymerizable functional group bonded in the molecule or at its terminal and a monomer of which the aqueous solution has a cloud point, It is possible to obtain a graft copolymer having a high degree of polymerization, which is essential to the invention. This is because the chain transfer coefficient of water is extremely small.

[0017]

As described above, the thermoreversible hydrogel material of the present invention is composed of a specific graft copolymer, and the thermoreversible hydrogel material is an aqueous solution which is fluid at low temperature and fluid at high temperature. It exhibits a thermoreversible sol-gel transition which loses its properties and becomes a hydrogel. The mechanism is presumed as follows. That is, at a temperature below the cloud point of the main chain of the graft copolymer, both the main chain and the side chains are water-soluble, so that they are completely dissolved in water. However, when the temperature of this aqueous solution is raised above the cloud point of the main chain, the main chain becomes water-insoluble and aggregates, resulting in intermolecular association. On the other hand, the side chains of the graft copolymer remain water-soluble even at the cloud point of the main chain or higher, so that aggregation between the main chains is prevented from leading to macroscopic phase separation, and a stable hydrogel is formed.

Since the thermoreversible hydrogel material of the present invention is a graft copolymer having the above-mentioned unique constitution, chemical crosslinking does not occur unlike conventional ones, and therefore, the manufacturing process thereof. It does not become insoluble in, and is flexible even in actual use and has excellent conformability to complex shapes and deformation. The thermoreversible hydrogel material of the present invention is particularly expected to be applied to medicine and medicine due to such excellent properties. In other words, when used as a wound dressing, for example, gels are formed only by physical crosslinks called hydrophobic bonds because conventional intramolecular chemical crosslinks do not occur, and the bond energy and life of the crosslinks are higher than those of chemical crosslinks. Small enough
The formation of the crosslinks can be controlled under physiological conditions. Therefore, the thermoreversible hydrogel material of the present invention has adaptability (adhesion) to a complicated living body shape, physical matching with a flexible living tissue, followability to movement of a living body and deformation of a wound surface, Without blocking the uptake into living tissue by brittle fracture and dissolving in exudate from the wound surface,
It is stable and excels in compatibility with living organisms such as discharging of diseased tissue.

[0019]

The present invention will be described below in more detail with reference to examples. Of course, the present invention is not limited to the following examples. Example 1 Polyethylene oxide having methacrylic acid ester at one end [NK ester M-900G (average degree of polymerization: 9
0), manufactured by Shin-Nakamura Chemical Co., Ltd.] 40 g and N-isopropylacrylamide 20 g are dissolved in 3000 ml of distilled water, and after nitrogen substitution, 1 g of ammonium persulfate and 5 ml of tetramethylethylenediamine are added, and the mixture is reacted overnight under a nitrogen atmosphere at room temperature. It was The reaction solution was purified by ultrafiltration using an ultrafiltration membrane with a molecular weight cutoff of 100,000 (YM100 manufactured by Amicon), and the non-filtered product was recovered and freeze-dried to give poly-N-isopropylacrylamide main chain with polyethylene. 55 g of a graft copolymer having an oxide side chain and having a molecular weight of 100,000 or more was obtained. From the analysis results of the nuclear magnetic resonance spectrum and the elemental analysis, the proportion of polyethylene oxide side chains in this graft copolymer was 66% by weight.

5 g of the above graft copolymer was added to distilled water 95
g to give a 5% by weight aqueous solution. This aqueous solution is 3
At 5 ° C or lower, the aqueous solution was completely transparent and had high fluidity, but at temperatures of 35 ° C or higher, it lost fluidity and became a slightly turbid, stable hydrogel with a water content of 95% by weight.
When the hydrogel was cooled, it returned to a clear aqueous solution at 35 ° C. This change was repeatedly observed reversibly. Further, this gel was put into a large amount of water at 40 ° C., but it did not dissolve. Example 2 Polyethylene oxide having methacrylic acid ester at one end [NK ester M-900G (average degree of polymerization: 9
0), manufactured by Shin-Nakamura Chemical Co., Ltd.] 20 g and N-n-
20 g of propylacrylamide was dissolved in 2000 ml of distilled water and, after purging with nitrogen, 1 g of ammonium persulfate and 5 ml of tetramethylethylenediamine were added and reacted overnight under a nitrogen atmosphere at room temperature. The reaction solution was purified by ultrafiltration using an ultrafiltration membrane with a molecular weight cutoff of 100,000 (YM100 manufactured by Amicon), and the unfiltered product was recovered and freeze-dried to obtain a poly-N-n-propylacrylamide main chain. 37 g of a graft copolymer having a molecular weight of 100,000 or more in which polyethylene oxide side chains were bound to was obtained. From the analysis results of the nuclear magnetic resonance spectrum and the elemental analysis, the proportion of polyethylene oxide side chains in this graft copolymer was 50% by weight.

5 g of the above graft copolymer was added to distilled water 95
g under ice-cooling to give a 5% by weight aqueous solution. This aqueous solution was a completely transparent and highly fluid aqueous solution at 25 ° C or lower, but lost the fluidity at a temperature of 25 ° C or higher, and became a slightly turbid and stable hydrogel with a water content of 95% by weight. When this hydrogel was cooled, it returned to its original clear aqueous solution at 25 ° C. This change was repeatedly observed reversibly. Example 3 Polyethylene oxide having methacrylic acid ester at one end [NK ester M-230G (average degree of polymerization: 2
3), manufactured by Shin-Nakamura Chemical Co., Ltd.] 40 g and N-n-
20 g of propylacrylamide was dissolved in 3000 ml of distilled water and, after purging with nitrogen, 1 g of ammonium persulfate and 5 ml of tetramethylethylenediamine were added, and the mixture was reacted overnight under a nitrogen atmosphere at room temperature. The reaction solution was purified by ultrafiltration using an ultrafiltration membrane with a molecular weight cutoff of 100,000 (YM100 manufactured by Amicon), and the unfiltered product was recovered and freeze-dried to obtain a poly-N-n-propylacrylamide main chain. 55 g of a graft copolymer having a molecular weight of 100,000 or more in which polyethylene oxide side chains are bound to was obtained. From the analysis results of the nuclear magnetic resonance spectrum and the elemental analysis, the proportion of polyethylene oxide side chains in this graft copolymer was 66% by weight.

5 g of the above graft copolymer was added to distilled water 95
g under ice-cooling to give a 5% by weight aqueous solution. This aqueous solution was completely transparent and highly fluid at 25 ° C. or lower, but lost its fluidity at temperatures of 25 ° C. or higher, and became a slightly turbid and stable hydrogel with a water content of 95% by weight. When this hydrogel was cooled, it returned to its original clear aqueous solution at 25 ° C. This change was repeatedly observed reversibly. Further, this gel was put into a large amount of water at 30 ° C., but it did not dissolve. Example 4 Polyethylene oxide (Blemmer PME-4000 (average degree of polymerization 9
8), manufactured by Nippon Oil & Fats Co., Ltd.), N-isopropylacrylamide 117 g, and n-butyl methacrylate 8 g were dissolved in benzene 1000 ml, and after nitrogen substitution, 2,
3 g of 2'-azobisisobutyronitrile was added, and the mixture was reacted at 60 ° C for 5 hours in a nitrogen atmosphere. The reaction solution was diluted with 1000 ml of chloroform, and the solution was added to 10 l of hexane to form a precipitate. The precipitate was dried and then dissolved in 4 l of distilled water. This aqueous solution was purified by ultrafiltration using an ultrafiltration membrane with a molecular weight cutoff of 100,000 (YM100 manufactured by Amicon). Those that were not filtered were collected and freeze-dried to obtain poly-N-isopropylacrylamide-n-butyl methacrylate. 170 g of a graft copolymer having a polyethylene oxide side chain bonded to the main chain and a molecular weight of 100,000 or more
I got From the analysis results of nuclear magnetic resonance spectrum and elemental analysis, the proportion of polyethylene oxide side chains in this graft copolymer was 66% by weight.

5 g of the above graft copolymer was added to 95 g of distilled water.
Was dissolved under ice-cooling into a 5% by weight aqueous solution. This aqueous solution was completely transparent and highly fluid at 20 ° C. or lower, but lost its fluidity at temperatures of 20 ° C. or higher, and became a slightly turbid and stable hydrogel with a water content of 95% by weight. When this hydrogel was cooled, it returned to a clear aqueous solution at 20 ° C. This change was repeatedly observed reversibly. Further, this gel was put into a large amount of water at 25 ° C., but it did not dissolve. Example 5 22.6 g of N-vinylpyrrolidone and 800 ml of benzene
Dissolved in 6.2 g of 2-mercaptoethylamine, 2,
1.6 g of 2'-azobisisobutyronitrile was added, and 6
The reaction was carried out at 0 ° C for 8 hours. The solvent was distilled off under reduced pressure to 100 m
The mixture was concentrated to 1 and added to 2000 ml of diethyl ether to precipitate. The precipitate was dried under vacuum and distilled water 200
It is dissolved in ml and ultrafiltered using an ultrafiltration membrane with a molecular weight cutoff of 3000 (YM3 manufactured by Amicon), and then the filtrate is an ultrafiltration membrane with a molecular weight cutoff of 1000 (YM1 manufactured by Amicon).
Was purified by ultrafiltration, and what was not filtered was collected and freeze-dried to give poly-N-vinylpyrrolidone 1 having a molecular weight of 1000 to 3000 and having a primary amino group at one end.
0 g was obtained. 1 using trinitrobenzene sulfonic acid
When the number average degree of polymerization was determined by quantifying the primary amine,
It was about 20.

This poly- having a primary amino group at one end
10 g of N-vinylpyrrolidone was dissolved in 50 ml of carbon tetrachloride, and acrylic acid chloride (manufactured by Kokusan Kagaku Co., Ltd.)
46 g and triethylamine 0.69 ml were added, and the mixture was reacted overnight at room temperature. After filtration, the solvent was distilled off under reduced pressure to obtain poly-N-vinylpyrrolidone monoacrylamide having a polymerizable functional group introduced at one end.

20 g of this mono-acrylamide of poly-N-vinylpyrrolidone and 10 g of Nn-propyl acrylamide were dissolved in 1500 ml of distilled water under ice cooling, and after nitrogen substitution, 0.3 g of ammonium persulfate and 200 μl of tetramethylethylenediamine were added. In addition, the mixture was reacted overnight under an ice-cold nitrogen atmosphere. The reaction solution is purified by ultrafiltration using an ultrafiltration membrane having a molecular weight cut off of 100,000 (YM100 manufactured by Amicon), and the unfiltered product is recovered and freeze-dried.
Poly-N-n-propylacrylamide Main chain of poly-N
-27 g of a graft copolymer having a side chain of vinylpyrrolidone and a molecular weight of 100,000 or more was obtained. From the analysis results of the nuclear magnetic resonance spectrum and the elemental analysis, the ratio of the poly-N-vinylpyrrolidone side chain in this graft copolymer was 66% by weight.

5 g of the above graft copolymer was added to distilled water 95
g under ice-cooling to give a 5% by weight aqueous solution. This aqueous solution was completely transparent and highly fluid at 25 ° C. or lower, but lost its fluidity at temperatures of 25 ° C. or higher, and became a slightly turbid and stable hydrogel with a water content of 95% by weight. When this hydrogel was cooled, it returned to its original clear aqueous solution at 25 ° C. This change was repeatedly observed reversibly. Further, this gel was put into a large amount of water at 30 ° C., but it did not dissolve. Comparative Example 1 40 g of polyethylene oxide [NK ester 23G (average degree of polymerization 23), manufactured by Shin-Nakamura Chemical Co., Ltd.] having methacrylic acid ester at both ends and 20 g of Nn-propyl acrylamide were dissolved in 3000 ml of distilled water. After substituting with nitrogen, 1 g of ammonium persulfate and 5 ml of tetramethylethylenediamine were added and reacted at room temperature under a nitrogen atmosphere. As a result, a chemically crosslinked gel insoluble in any solvent was formed in about 1 hour. Comparative Example 2 Polyethylene oxide having methacrylic acid ester at one end [NK ester M-900G (average degree of polymerization: 9
0), manufactured by Shin-Nakamura Chemical Co., Ltd.] 40 g and N-isopropylacrylamide 20 g are added to chloroform 3000.
After dissolving in ml and substituting with nitrogen, 0.3 g of 2,2'-azobisisobutyronitrile was added, and the mixture was subjected to boiling point reflux reaction overnight under a nitrogen atmosphere. After distilling off the solvent under reduced pressure, distilled water 1000 m
dissolved in 1 and subjected to ultrafiltration using an ultrafiltration membrane having a molecular weight cutoff of 100,000 (YM100 manufactured by Amicon), and then the filtrate was subjected to an ultrafiltration membrane having a molecular weight cutoff of 3000 (YM3 manufactured by Amicon).
Was purified by ultrafiltration using, and the unfiltered product was recovered and freeze-dried to obtain 50 g of a graft copolymer having a molecular weight of 3000 to 100,000 in which a polyethylene oxide side chain was bonded to a poly-N-isopropylacrylamide main chain. Obtained. From the analysis results of the nuclear magnetic resonance spectrum and the elemental analysis, the proportion of polyethylene oxide side chains in this graft copolymer was 66% by weight.

5 g of the above graft copolymer was added to distilled water 95
g to give a 5% by weight aqueous solution. This aqueous solution is 5
Even when the temperature was raised to 0 ° C. or higher, the aqueous solution had high fluidity and did not become a hydrogel.

[0028]

As described above in detail, the aqueous solution of the thermoreversible hydrogel material of the present invention becomes an aqueous solution at a specific temperature or lower, and becomes a hydrogel at a specific temperature or higher. Since this gelling temperature depends on the cloud point of the aqueous polymer solution which becomes the side chain in the graft copolymer, it can be arbitrarily controlled by adjusting this cloud point. The thermoreversible hydrogel material of this invention is
As it is a synthetic material, it does not contain the unknown impurities found in natural materials, it can easily guarantee the uniformity of composition and stability of performance, and it is a polymer with a large molecular weight, so there is no worry of toxicity, and it can be used in cells and organisms. Also, it can be used without any problem in applications for living organisms. Further, the hydrogel from the thermoreversible hydrogel material of the present invention, if kept above the gelling temperature,
Since there is no problem that the gel dissolves even if water is further added, the gel can be used in a state of being dispersed in water. Since the aqueous solution of the thermoreversible hydrogel material of the present invention gels even at a low concentration of 10 wt% or less, the water content of the hydrogel is high, and the hydrogel material is effectively used for separation of substances, pharmaceuticals, agricultural chemicals, cosmetics and the like. In addition, since no intramolecular chemical cross-linking occurs, it is flexible and has excellent conformability to complex shapes and deformation, and is extremely useful as a biocompatible material or the like.

Furthermore, in the method for producing the thermoreversible hydrogel material of the present invention, the aqueous solution thereof contains a single polymerizable functional group in the polymer chain having a cloud point to give a water-soluble polymer. Since a graft copolymer is synthesized by copolymerizing with a monomer mainly in water, there is no fear of forming a chemically crosslinked gel in the process of synthesis, it is easy to control the physical properties, and a large amount of organic solvent is used. Since it is not necessary, it is very advantageous for industrial production.

Claims (2)

[Claims] 1. A graft copolymer in which an aqueous solution is bound to a main chain of a polymer having a cloud point with a water-soluble polymer as a side chain, and the graft copolymer has a molecular weight of 10
Thermoreversible hydrogel material characterized by more than 10,000. 2. The method of producing the thermoreversible hydrogel material according to claim 1, wherein the graft copolymer constituting the thermoreversible hydrogel material is an aqueous solution of a water-soluble polymer having one polymerizable functional group introduced therein. A method for producing a thermoreversible hydrogel material, which comprises controlling the physical properties and insolubilization due to cross-link formation during production by copolymerizing with a monomer that gives a polymer having a cloud point.