JPS6135210B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a novel block copolymer, and more specifically, to a polymer compound in which hydrophilic chains and hydrophobic chains are supported in one molecule in a controlled manner. Conventionally, polyhydroxy acrylate and polyhydroxy methacrylate have an affinity for water because they have hydroxyl groups in their side chains, but their affinity for water has been limited due to the high hydrophobicity of their backbones. Poly 2-hydroxyethyl methacrylate, a typical polymer compound, is known as hydron and has a hydrophobic α-methyl group and a hydrophilic hydroxyl group located away from the backbone and main chain in one molecule. Therefore, it has both hydrophobic and hydrophilic properties as a medical polymer material. Due to this property, the above-mentioned polymer has biocompatibility and is attracting attention as a promising material particularly in the field of medical polymer materials. However, due to the presence of irreversibly produced diesters, i.e., monomers with two double bonds, this monomer causes a three-dimensional reaction during polymerization and tends to gel, making it extremely difficult to obtain a chain polymer. Katta. This was extremely undesirable from the viewpoint of polymer design with controlled molecular chain length. In other words, conventional manufacturing methods are
Since it is difficult to control the molecular structure and molecular chain length, its application and the scope of use of the obtained polymer have been limited. This three-dimensional polymer has water content, so it is used in medical fields such as contact lenses and catheters.
Although various uses are being developed, the mechanical strength is weak, and the adhesion between polymers and water absorption are insufficient, so that only some of them have been put into practical use. From the above, although this three-dimensional polymer has a hydrophilic hydroxyl group in its side chain, its affinity with water is limited because the α-methyl group in its side chain and the back bone in its main chain are hydrophobic. However, they have the disadvantage of limited biocompatibility, such as the inability to produce polymers that have hydrophilic and hydrophobic chains in one molecule, and the fact that they do not constitute hydrophilic and hydrophobic regions at the molecular assembly level. was. In order to improve such drawbacks, a method of obtaining a material having hydrophilic and hydrophobic properties using two types of molecular chains, one hydrophilic and one hydrophobic, is a method of blending or random copolymerization of the different types of molecular chains. There is. However, these methods merely bring out properties that are correlated to the composition ratio of two types of polymers or hydrophilic and hydrophobic chain units. On the other hand, block copolymers in which different types of chains are combined into one molecule form microdomains at the aggregate level of molecules, in other words, they are given new functions to form microphase-separated structures. It is possible to do so. Thus, regulation at the molecular level has been an important issue in order to obtain a new material that is both hydrophilic and hydrophobic, and also has biocompatibility. Regarding block copolymers, with the recent development of living anionic polymerization methods, it has become possible to synthesize block copolymers having various structures with high monodispersity. According to this method, a monomer such as styrene is polymerized in anhydrous tetrahydrofuran using a sodium-naphthalene complex as a polymerization initiator, and the active species is retained at the polymerization terminal at the end of polymerization, resulting in chain transfer and no termination reaction. A living polymer is obtained, and by adding other monomers to this living polymer, a block copolymer is obtained. However, in this method, when hydroxymethacrylate in which a polar group such as a hydroxyl group is present in the system is used instead of styrene, a transfer reaction occurs, the living anion activity is deactivated, and the growth of the molecule is stopped. Therefore, with this living anionic polymerization method, it is extremely difficult to synthesize a block copolymer using hydroxyalkyl acrylate or hydroxyalkyl methacrylate having a hydroxyl group. Furthermore, no conventional method for synthesizing block copolymers using hydroxyacrylate or hydroxymethacrylate has been found. As mentioned above, there are limits to the biocompatibility of polymers that have both hydrophilic and hydrophobic properties at the molecular level. However, biological membranes are thought to have hydrophilic and hydrophobic regions (domains) at the level of molecular assembly, and this structure is extremely important for biocompatibility. The purpose of the present invention is to provide a novel block copolymer in which hydrophilic and hydrophobic heterogeneous chains are combined, which can form hydrophilic and hydrophobic regions in solution at the molecular level, which is different from the molecular level. It's about doing. The present invention is based on the general formula HX ₁ -SR ₁ NR ₂ CONHR ₃ NHCOO-X ₂ - CONH-R ₃ NHCONR ₂ R ₁ S-X ₁ H {wherein, X ₁ is the general formula (In the formula, R ₄ is a hydrogen atom or a carbon atom number of 1 to
R ₅ is an alkylene group having 2 to 10 carbon atoms when m is 1 or 2 to 3 carbon atoms when m is 2 to 10, and n is 10 to 3.
500 integers), X ₂ is a general formula (In the formula, R ₆ is a hydrogen atom or a carbon atom number of 1 to
an alkyl group having 4 atoms, R ₇ has 1 to 1 carbon atoms;
(l represents an integer from 10 to 1100), R ₁ is a hydrocarbon residue of a mercaptan having an amino group, and R ₂ is a mercaptan residue of the mercaptan.
This is a novel block copolymer represented by the hydrogen atom or methyl group of the residue, and R ₃ is a hydrocarbon residue of a diisocyanate. The acrylic acid derivative polymer having a hydroxyl group used as the acrylic acid derivative chain for producing the novel block copolymer of the present invention is treated in the presence of a mercaptan having one amino group in the molecule as a chain transfer agent. is synthesized by reacting an acrylic acid derivative having a hydroxyl group in a solvent at a predetermined functional group concentration, molar ratio, and temperature. The acrylic acid derivative having a hydroxyl group used in the present invention has the general formula (In the formula, R ₄ is a hydrogen atom or a carbon atom number of 1 to
When m is 1, R ₅ represents an alkylene group having 2 to 10 carbon atoms, or when m is 2 to 10, it represents an alkylene group having 2 to 3 carbon atoms. Representative examples include 2-hydroxyethyl acrylate, 2-hydroxypropyl acrylate, 3-hydroxypropyl acrylate, 2-hydroxybutyl acrylate, 3-hydroxypropyl acrylate,
Hydroxybutyl acrylate, 4-hydroxybutyl acrylate, 5-hydroxypentyl acrylate, 6-hydroxyhexyl acrylate, 2-hydroxyethyl methacrylate, 2-
Hydroxypropyl methacrylate, 3-hydroxypropyl methacrylate, 2-hydroxybutyl methacrylate, 3-hydroxybutyl methacrylate, 4-hydroxybutyl methacrylate, 5-hydroxypentyl methacrylate, 6
-Hydroxyhexyl methacrylate, etc. Examples of chain transfer agents for mercaptans having at least one amino group in the molecule include 1-aminomethanethiol, 1-aminoethanethiol, and 2-aminoethanethiol.
-Aminoethanethiol, 1-aminopropanethiol, 2-aminopropanethiol, 3-aminopropanethiol, 1-aminobutanethiol, 2-aminobutanethiol, 3-aminobutanethiol, 4-aminobutanethiol, 1-methyl -2-Aminoethanethiol, 1-methyl-
1-aminoethanethiol, 3-aminocyclopentadiene-1-thiol, 1-aminobenzenethiol, 2-aminobenzenethiol, 3-aminobenzenethiol, 1-aminomethylbenzenethiol, 2-aminomethylbenzenethiol, 3- Examples include aminomethylbenzenethiol, 1-aminoethylbenzenethiol, 2-aminoethylbenzenethiol, and 3-aminoethylbenzenethiol. The amount of these chain transfer agents used is 1 to 100 parts by weight, preferably 1.5 to 80 parts by weight, based on 100 parts by weight of the hydroxyl group-containing acrylic acid derivative monomer. The molecular weight of the polymer depends on the amount of chain transfer agent used,
That is, it can be adjusted by changing the molar ratio to the monomer. Examples of organic solvents include methanol, ethanol,
n-propanol, isopropanol, n-butanol, isobutanol, sec-butanol, ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, ethylene glycol monobutyl ether, dimethylformamide, dimethyl sulfoxide, hexaalkylphosphoramide, acetonitrile, pro- Examples include pionitrile and benzonitrile. These organic solvents are used in an amount of 100 to 1000 parts by weight, preferably 150 to 500 parts by weight, per 100 parts by weight of the monomer of the acrylic acid derivative having a hydroxyl group. As a polymerization initiator, tert-butyl peroctoate, benzoyl peroxide, isopropyl percarbonate, 2,4-dichlorobenzoyl peroxide, methyl ethyl ketone peroxide, cumene hydroperoxide, dicumyl peroxide, azobisisobutyronitrile and so on. These polymerization initiators are used in an amount of 0.01 to 30 parts by weight, preferably 0.05 to 20 parts by weight, per 100 parts by weight of the acrylic acid derivative monomer having a hydroxyl group. The polymerization reaction of an acrylic acid derivative having a hydroxyl group is carried out by adding a monomer, a chain transfer agent, and a polymerization initiator to the above-mentioned organic solvent, and heating the acrylic acid derivative at 50 to 200°C, preferably.
10 minutes to 30 hours at a temperature of 55-150℃, preferably 0.5
It will be held for ~25 hours. To recover the polymer from the reaction mixture polymerized in this way, the reaction mixture must be concentrated.
Alternatively, the polymer may be taken out from the reactor as it is or diluted with an organic solvent, dropped into a poor solvent such as ethyl ether of 10 to 50 times the volume to precipitate the polymer, separated, and then dried. You can take the following method. The obtained polymer having an amino group at one end can be obtained by vapor pressure osmosis.
The number average molecular weight measured by Osmometry Method is about 1,000 to about 40,000 (the following number average molecular weights are based on the same measurement method). The polyalkylene oxide having isocyanate groups at both ends, which is used as a polyalkylene oxide chain for producing the novel block copolymer of the present invention, can be used as a polyalkylene oxide chain while retaining one functional group of diisocyanates. It is synthesized by selectively reacting one functional group with polyoxyalkylene glycol in an organic solvent at a predetermined functional group concentration, functional group ratio, and temperature. The polyoxyalkylene glycol having hydroxyl groups at both ends used in the present invention has the following general formula: (In the formula, R ₆ is a hydrogen atom or a carbon atom number of 1 to
an alkyl group having 4 atoms, R ₇ has 1 to 1 carbon atoms;
(1 represents an integer from 10 to 1100). Typical examples include polyethylene glycol, polypropylene glycol, polybutylene glycol, polypentylene glycol, and polyhexylene glycol. By using reprecipitation or fractional precipitation of these polymers, any highly monodisperse fractional component having a molecular weight in the range of 500 to 40,000 can be obtained. Diisocyanates include aliphatic or aromatic diisocyanates, such as m-phenylene diisocyanate, p-phenylene diisocyanate, 1-chloro-2,4-phenylene diisocyanate, 2,4 -Tolylene diisocyanate,
2,6-tolylene diisocyanate, 3,3'-dimethyl-4,4'-biphenylene diisocyanate, 3,3'-dimethoxy-4,4'-biphenylene diisocyanate, 2,2', 5,5'-tetramethyl-4,4'-biphenylene diisocyanate,
Examples include 4,4'-methylenebis(phenyl isocyanate), 4,4'-methylenebis(2-methylphenylisocyanate), and 4,4'-sulfonylbis(phenyl isocyanate). The addition reaction of diisocyanates to the polymer is carried out in an organic solvent at a functional group ratio of about 2:1 between isocyanate groups and hydroxyl groups, and at a functional group concentration of 0.002 to 0.20 M/cm.
The temperature is adjusted to 60 to 120°C, preferably 80 to 90°C for 20 to 75 hours, preferably 30 to 50 hours. Examples of organic solvents include chlorobenzene, toluene, xylene, and benzene. In the reaction mixture obtained in this way, unreacted diisocyanates almost disappear after a predetermined period of time, so further purification is required to avoid deactivation of isocyanate groups that occurs during reprecipitation purification. It can be used as is for the next reaction. The polymer reaction between the obtained acrylic acid derivative polymer having an amino group at one end and a polyalkylene oxide having an isocyanate group at both ends is performed by reacting the acrylic acid derivative polymer with N,N-dimethylformamide, benzene, acetone,
In a solvent without active hydrogen such as THF, the reaction mixture of the polyalkylene oxide is mixed with the functional group ratio of isocyanate groups to amino groups of 1:1, and the functional group concentration is 0.002 to 0.2. Adjust, −10
20-75 hours at a temperature of ~15℃, preferably 0-10℃,
It is preferably carried out for 30 to 50 hours. In order to recover the reaction mixture from the polymer-reacted reaction mixture in this way, the reaction mixture is diluted with an organic solvent and taken out from the reactor, and then poured into 10 to 50 times the volume of a poor solvent such as ethyl ether. Any method can be used, such as dropping the reaction mixture dropwise to precipitate it, separating it, and then drying it. The obtained block copolymer can be purified using a fractional precipitation method or a reprecipitation method. In this case, the fractional precipitation method takes advantage of the difference in temperature dependence of solubility between the two prepolymers and the block copolymer, and the reprecipitation method uses the difference in temperature dependence of the solubility of the two prepolymers and the block copolymer. This is a method in which reprecipitation is repeated in a solvent in which the block copolymer is insoluble. 〓〓〓〓
The block copolymer thus obtained is
General formula HX ₁ −SR ₁ NR ₂ CONHR ₃ NHCOO―X ₂ ― CONH―R ₃ NHCONR ₂ R ₁ S―X ₁ H {In the formula, X ₁ is the general formula (In the formula, R ₄ is a hydrogen atom or a carbon atom number of 1 to
R ₅ is an alkylene group having 2 to 10 carbon atoms when m is 1 or 2 to 3 carbon atoms when m is 2 to 10, and n is 10 to 3.
500 integers), X ₂ is a general formula (In the formula, R ₆ is a hydrogen atom or a carbon atom number of 1 to
an alkyl group having 4 atoms, R ₇ has 1 to 1 carbon atoms;
(l represents an integer from 10 to 1100), R ₁ is a hydrocarbon residue of a mercaptan having an amino group, R ₂ is a hydrogen atom or a methyl group of a residue of the mercaptan, R ₃ is a hydrocarbon residue of a diisocyanate. Among these, X ₁ has a hydrophobic main chain and a side chain.
When R ₄ is an alkyl group, it is hydrophobic, and the other side chain hydroxyl groups are hydrophilic. The main chain of X ₂ having an ether bond is hydrophilic, and when R ₆ of the side chain is an alkyl group, it is hydrophobic. Therefore,
The degree of hydrophilicity and hydrophobicity of X ₁ and X ₂ varies greatly depending on the type of side chain. For example, among hydroxyalkyl acrylates and hydroxyalkyl methacrylates, polyhydroxyethyl acrylate is water-soluble, but polyhydroxyethyl methacrylate having an α-methyl group in its side chain is insoluble in water. On the other hand, in polyalkylene oxide,
Polyethylene oxide is soluble in water, whereas polypropylene oxide having an α-methyl group in its side chain is soluble in water. A water-soluble or water-combinable block copolymer can be obtained by arbitrarily selecting the above-mentioned X ₁ and X ₂ . In addition, regarding water-soluble block copolymers, X ₁ of the water-insoluble chain shrinks to avoid contact with water, making the molecular shape compact, and X ₂ of the water-soluble chain has a high affinity for water, so the molecule becomes compact. The form expands. This block copolymer assumes the opposite structural form in a suitable hydrophobic solvent. In general, the molecular morphology of these block copolymers in solution varies greatly depending on the properties of the solvent used, and the state of assembly of the chains can be controlled by changing the affinity of the solvent for each chain. is possible. Therefore, when producing a film by dissolving these block copolymers in a solvent and casting them,
By selecting an appropriate solvent, a microphase-separated structure having arbitrary hydrophilicity and hydrophobicity can be realized even in block copolymers having the same molecular structure. Furthermore, by using block copolymers with various molecular structures, the microphase separation structure can be controlled over a wide range. Control of this microphase-separated structure having hydrophilicity and hydrophobicity cannot be achieved using a blender. Furthermore, a surface having such a microphase-separated structure exhibits good biocompatibility that homopolymers or random copolymers do not have. Especially, 200
This effect was remarkable in hydrophilic and hydrophobic lamellar structures around ~5000 Å and in sea-island structures with hydrophilic seas. This block copolymer is transparent and can be dissolved in a solvent and cast or cast into any shape such as a film, plate, or tube, and then molded after removing the solvent, making it suitable for use as artificial skin. . The microphase separation structure of a molded product can be determined by the type of solvent used during molding, that is, which molecular chain makes a good solvent. Furthermore, the water-soluble block copolymer is nonionic and can be used as a biocompatible material such as a hemolysis inhibitor, a plasma substitute, and a fractionating agent for plasma components when blood is circulated outside the body using a heart-lung machine. Furthermore, water-soluble block copolymers with highly hydrophobic chains are
As nonionic polymer surfactants, synthetic resins,
It can be used for emulsion polymerization, paints, pigments, etc.
It can also be applied to fields such as medicine, fragrance, and cosmetics industries. In the method for producing the novel block copolymer of the present invention, hydrophilic regions and hydrophobic regions can be freely designed to ensure biocompatibility.
In other words, the chain length of an acrylic acid derivative having a hydroxyl group is determined by the molar ratio of the monomer and the chain transfer agent, and the chain length of a polyalkylene oxide having an isocyanate group at both ends is determined by regenerating polyoxyalkylene glycol. It is determined by screening the molecular weight by a precipitation method or a fractional precipitation method. These operations are easy and convenient. Furthermore, the bonding between the hydrophobic chain and the hydrophilic chain occurs through a quantitative reaction between the amino group at one end of the acrylic acid derivative polymer and the isocyanate groups at both ends of the polyalkylene oxide.
This reaction between the functional groups produces a block copolymer having hydrophobic chains and hydrophilic chains, so that a block copolymer with a clear molecular structure and desired properties can be produced. According to this manufacturing method, the molecular weight, molecular chain, and molecular chain length ratio as designed can be obtained. Therefore, the block copolymer of the present invention can form hydrophilic and hydrophobic regions at the molecular assembly level compared to conventional polymers that have hydrophilicity and hydrophobicity, thereby improving biocompatibility. Can be used as a material. First, a method for producing a polyalkylene oxide having isocyanate groups at both ends will be described in detail. Polymer A Polyethylene glycol with number average molecular weight 7110
100g and 2,4-toluene diisocyanate 4.899
g was dissolved in 1556 g of chlorobenzene, and the reaction was carried out at a temperature of 80° C. for 48 hours. The mixed solution before the reaction has a functional group ratio of isocyanate groups to hydroxyl groups of approximately 2:1, and a functional group concentration of approximately
Adjusted to 0.02M/. After the reaction was completed, analysis revealed that the number average molecular weight was 7460, with an average of 1.96 isocyanate groups per molecule.
of polymer is obtained. The reaction rate was 98%. Polymer B Polyethylene glycol 100 with number average molecular weight 500
g and 2,4-toluene diisocyanate 69.660 g
Polymer A was dissolved in 2214 g of chlorobenzene.
The reaction was carried out in the same manner. The functional group ratio of the pre-reaction mixed solution was adjusted to be the same as that of Polymer A, and the functional group concentration was adjusted to 0.2M/. A polymer having a number of isocyanate groups per molecule of 1.98 and a number average molecular weight of 850 was obtained with a reaction rate of 99%. Polymer C Polyethylene glycol with a number average molecular weight of 50,000
100g and 2,4-toluene diisocyanate 0.697
g was dissolved in 2214 g of chlorobenzene, and the reaction was carried out in the same manner as Polymer A. The functional group ratio before the reaction was adjusted to be the same as that of Polymer A, and the functional group concentration was adjusted to 0.002M/. A polymer having 2 isocyanate groups per molecule and a number average molecular weight of 50,400 was obtained with a reaction rate of 100%. Polymer D Polyethylene glycol with a number average molecular weight of 20,000
100g and 2,4-toluene diisocyanate 1.742
g was dissolved in 2214 g of chlorobenzene, and the reaction was carried out in the same manner as Polymer A. The functional group ratio before the reaction was adjusted to be the same as that of Polymer A, and the functional group concentration was adjusted to 0.005M/. A polymer having 1.96 isocyanate groups per molecule and a number average molecular weight of 20,250 was obtained with a reaction rate of 98%. Next, a method for producing an acrylic acid derivative polymer having an amino group at one end will be described in detail. Polymer E: Add 100 g of 2-hydroxyethyl methacrylate and α,α′-azobisisobutyronitrile to the polymerization tube.
0.252 g, 2-aminoethanethiol, 41.50 g, and 290.3 g of N,N-dimethylformamide were charged, sealed in a vacuum tube, and reacted for 8.5 hours while shaking in a constant temperature bath maintained at a temperature of 60°C. Ta. After the reaction was completed, the reaction mixture was diluted with acetone and taken out from the polymerization tube, and then dropped into 20 times the volume of ethyl ether to precipitate the polymer. After separation and vacuum drying, the number of amino groups per molecule was 1. 〓〓〓〓
A polymer with a number average molecular weight of 2640 was obtained in a yield of 21.50%. Polymer F Reaction and purification were carried out under the same conditions as Polymer E except for using 26.68 g of 2-aminoethanethiol and 5 hours of reaction time. 19.20% polymer with number average molecular weight 5200
was obtained in a yield of . Polymer G 2-aminoethanethiol 20.75g, reaction time
Reaction and purification were carried out under the same conditions as Polymer E except for 3.5 hours. 24.33% polymer with number average molecular weight 11270
was obtained in a yield of . Polymer H 2-aminoethanethiol 5.04g, reaction time
Reaction and purification were carried out under the same conditions as Polymer E except for 1.5 hours. 18.30% polymer with number average molecular weight 37900
was obtained in a yield of . Polymer I 100 g of 2-hydroxyethyl acrylate instead of 2-hydroxyethyl methacrylate, 2-
The reaction was carried out under the same conditions as Polymer E except for 13.40 g of aminoethanethiol, 0.285 g of α,α'-azobisisobutyronitrile, 328.1 g of N,N-dimethylformamide, and 10.5 hours of reaction time. Further, the polymer was purified in the same manner as Polymer E using N,N-dimethylformaminide as the diluent and 20 times the volume of acetone as the reprecipitation solvent. A polymer with a number average molecular weight of 1920 was obtained with a yield of 21.8%. Polymer J 2-aminoethanethiol 5.36g, reaction time 8
The reaction and purification were carried out under the same conditions as Polymer I except for the time. A polymer with a number average molecular weight of 4780 was obtained with a yield of 15.6%. Polymer K 2-aminoethanethiol 4.02g, reaction time
Reaction and purification were carried out under the same conditions as Polymer I except for 5.5 hours. 25.93% polymer with number average molecular weight 6400
was obtained in a yield of . Polymer L 2-aminoethanethiol 1.01g, reaction time
Reaction and purification were carried out under the same conditions as Polymer I except for 1.5 hours. 18.16% polymer with number average molecular weight 25600
was obtained in a yield of . Next, a method for producing a block copolymer using a polyalkylene oxide having isocyanate groups at both ends and an acrylic acid derivative polymer having an amino group at one end will be described in detail. Block copolymer A: 100 g of a chlorobenzene solution containing polymer E at a concentration of 7.1 wt% and 74.3 g of N,N-dimethylformamide containing polymer A at a concentration of 7.1 wt% were mixed and heated at a temperature of 0°C for 48 hours. Performed molecular reactions. The functional group ratio before the reaction was adjusted to be approximately 1:1 of isocyanate groups to amino groups, and the concentration of functional groups was 0.02M/. After the completion of the reaction, the reaction solution was diluted with methanol, taken out from the reactor, and added dropwise to 20 times the volume of ethyl ether to precipitate the reaction mixture, separated and dried.
The reaction mixture was collected. Add this reaction mixture to ethyl cellosolve and add 50
After heating and dissolving at a temperature of 0.degree. C., the mixture was cooled to a temperature of 0.degree. C. to precipitate insoluble polymer A and the block copolymer at a low temperature. Thereafter, the mixture was gradually heated to 25° C. to dissolve the block copolymer, and in order to remove the precipitated unreacted polymer A, the mixture was separated using a centrifuge at a rotational speed of 5000 rpm. The supernatant liquid after centrifugation was gradually cooled to a temperature of 0°C again to precipitate the block copolymer, and then centrifuged at a rotation speed of 5000 rpm to remove unreacted polymer E dissolved at this temperature. It was separated and the precipitate was collected. The above separation operation was repeated twice, and the finally obtained precipitate was diluted with methanol and taken out, dropped into 20 times the volume of ethyl ether to precipitate the block copolymer, separated and dried in vacuum. number average molecular weight
A block copolymer of 12700 was obtained with a yield of 76%. This block copolymer was soluble in water at 10% by weight or more, and no cloud point was observed up to a temperature of 50 to 60°C. 〓〓〓〓
This block copolymer also had good biocompatibility. Block copolymers B to F Reactions and purification were carried out under the same conditions as for block copolymer A except as shown in Table 1. As a result, a block copolymer having the properties and number average molecular weight shown in Table 2 was obtained.

【table】

[Table] In addition, these block copolymers have been tested for heavy metals, leachables, acute toxicity, intradermal reaction, pyrogenic substance, hemolytic, I passed all the transplant tests. As mentioned above, these block copolymers have localized hydrophilic regions and hydrophobic regions. Among these, the water-soluble block copolymer can be mixed with other plasma preparations or used alone as an aqueous solution as a plasma expander, hemolysis inhibitor, plasma component fractionating agent, etc. Highly water-containing block copolymers are produced by casting or pouring, because by using solvents with different solubility for each molecular chain, the molecular chains of the block copolymer with lower solubility in the solvent take an aggregated form. When molded after spreading and removing the solvent, the molded product retains the same domain structure as in the solvent and is biocompatible. A tube with this domain structure can be used as an artificial blood vessel, and a film can be used as an artificial skin. 〓〓〓〓

Claims (1)

[Claims] 1 General formula HX ₁ -SR ₁ NR ₂ CONHR ₃ NHCOO-X ₂ - CONH-R ₃ NHCONR ₂ R ₁ S-X ₁ H {In the formula, X ₁ is the general formula (In the formula, R ₄ is a hydrogen atom or a carbon atom number of 1 to
R ₅ is an alkylene group having 2 to 10 carbon atoms when m is 1 or 2 to 3 carbon atoms when m is 2 to 10, and n is 10 to 3.
500 integers), X ₂ is a general formula (In the formula, R ₆ is a hydrogen atom or a carbon atom number of 1 to
an alkyl group having 4 atoms, R ₇ has 1 to 1 carbon atoms;
(l represents an integer from 10 to 1100), R ₁ is a hydrocarbon residue of a mercaptan having an amino group, R ₂ is a hydrogen atom or a methyl group of a residue of the mercaptan, R ₃ is a hydrocarbon residue of a diisocyanate.