JPH11239612A - Blood conduit - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a blood conduit hardly generating a thrombus as compared with a conventional material and excellent in an adhesiveness with an endothelial cell. SOLUTION: This blood conduit is formed of a copolymer of urethane and a polyamino acid successively bonded with four pieces or more on average of an amino acid unit. This copolymer of a polyamino acid and urethane is a polyamino acid urethane resin obtained by reacting (a) α-amino acid-N- carboxylic acid anhydride with (b) a urethane prepolymer having an isocyanate group and (c) at least one kind selected from water, hydrazine and an organic amine.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a blood conduit having excellent antithrombotic properties and cytocompatibility. The blood conduit is a general term for an annular blood flow path used for an artificial blood vessel, a catheter, a dialysis artificial kidney, an artificial heart, a blood bypass tube, and the like.

[0002]

2. Description of the Related Art As materials for artificial blood vessels, which are one of blood conduits, polyester fibers such as Dacron and polytetrafluoroethylene are mainly used. It is used for the arterial part. Therefore, it is not suitable for a vein or a thin artery having a low blood flow velocity. Also other catheters,
Silicone rubber, polyurethane, tetrafluoroethylene, and the like are used in shunts, dialysis-type artificial kidneys, and the like, but these are not sufficient in both antithrombotic properties and biocompatibility (particularly, cell compatibility).

[0003] JP-A-61-13952 and JP-A-61-19552
13953 proposes a blood conduit having an amino acid polymer on its inner surface, which is suitable as a blood conduit because homopolymers of amino acids or polymers of amino acid mixtures containing leucine have the property of preventing cells from adhering. It is described. However, the amino acid homopolymer lacks flexibility as a blood conduit and has insufficient antithrombotic properties.

[0004] Further, there are many documents already known about blood conduits made of urethane resin having a high molecular weight, and depending on the structure or processing method, a blood vessel having excellent antithrombotic properties can be obtained. It has been put to practical use as a potting material for artificial kidneys. However, according to the study of the present inventors, as is apparent from the comparative examples described later, the artificial blood vessel made of urethane resin has poor adhesion and extensibility of endothelial cells, lacks self-organizing properties, and is biocompatible. In addition, the antithrombotic effect is insufficient for small-diameter artificial blood vessels.

JP-A-58-1715 discloses an antithrombotic material comprising polyurethane obtained by reacting a dimer of an α-amino acid having a hydroxyl group with an alkylene diol or its oligomer and diisocyanate. Similarly, Japanese Patent Application Laid-Open No. 60-92763 discloses that a linear dimer of an α-amino acid having a hydroxyl group is subjected to a polyaddition reaction with diisocyanate in the presence of polytetramethylene glycol to form a film from the obtained polyurethane. , This film is 130-25
There is disclosed a method for producing an antithrombotic membrane, wherein the method is heat-treated at a temperature of 0 ° C.

However, in these, since the amino acid dimer is used as a chain extender for urethane synthesis, the amino acid content is small, and a three-dimensional structure specific to polypeptides and proteins cannot be obtained. That is, the amino acid dimers specifically shown in these patents are:

[0007]

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Is a dipeptide diol having a molecular weight of 340, and the diisocyanate to be reacted therewith is
1,6-hexamethylene diisocyanate (HMDI,
Molecular weight 168) or 4,4'-diphenylmethane diisocyanate (MDI, molecular weight 250). The molecular weight of the urethane elastomer segment formed by this reaction is at least 508 per peptide bond (-NHCO-). However, an artificial blood vessel that can be actually used requires the addition of a polyol component in order to provide flexibility. The segment molecular weight per bond is further increased from 508. In addition, in this structure, the peptide bond does not take a unique α-helix or β structure compared to a normal polypeptide or protein having a continuous repeating unit, and is separated from the structure of a living cell,
Cell compatibility is considered poor. That is, in the case of poly-α-amino acids whose tertiary structure has been well studied, it is said that at least four amino acid units must be continuously linked in order to take at least an α-helical structure. Japanese Patent Application Laid-Open No. 7-48431 substantially discloses the following equations (1) and (2).

[0009]

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[0010] A polyurethane urea polymer for medical use having excellent antithrombotic properties, which is represented by a structure in which (wherein, n is 0 to 20 and m is 0 to 10) is alternately connected. In the above formula, R ¹ is a mixture of a polyether having both terminal alkylene groups and a polysiloxane having both terminal alkylene groups selected from polyethers, polyesters and polycarbonates having both terminal alkylene groups, and R ² is a divalent compound having a molecular weight of 500 or less. A hydrocarbon group, R ³ represents a divalent hydrocarbon group obtained by removing two amino groups from an amino acid having two amino groups or an amine.

Here, R ³ is substantially the same as an amino acid having two amino groups except for the amino group. Specific examples of the amino acid used include amino acids such as ortinine, kynurenine, cystathionine, cystine, lysine and cystamine. Amino acids having two groups are mentioned. Further, it is described that (formula 1) and (formula 2) are alternately linked. In an embodiment for producing the same, a polyol of polycarbonate diol or polytetramethylene diol is added to a polyol of polydimethylsiloxane propylene. Diisocyanate is reacted with a diol (number average molecular weight, 194) or a low molecular weight diol of propylene glycol to form an isocyanate-terminated prepolymer,
This is obtained by extending the chain with the amino acid having two amino groups. Therefore, since it has no peptide bond and the amount of amino acids occupying the whole is very small, it is considered that compatibility with a living cell based on a protein composed of the peptide bond is inferior.

On the other hand, JP-A-59-140217 discloses α
-Amino acid-N-carboxylic acid anhydride and urethane prepolymer are added to water, hydrazine or an amine having active hydrogen and reacted to obtain a polyamino acid urethane resin, which is used for treating artificial skin and hermetically sealed bandages having high gas permeability. It describes that it can be applied to medical products such as films. Japanese Unexamined Patent Publication (Kokai) No. 1-12464 proposes an adhesion preventing film formed by mixing a drug with a polyamino acid urethane resin to form a film. However, none of them mentions the possibility of application to blood vessels.

[0013]

DISCLOSURE OF THE INVENTION The present invention has been made in view of the above circumstances, and has as its object that, firstly, thrombus is less likely to be formed and secondly, endothelial cells are less likely to be formed than conventional materials. Is to provide a blood conduit with good adhesion.

[0014]

Means for Solving the Problems The inventors of the present invention have conducted intensive studies for the above purpose, and as a result, a polyamino acid has been copolymerized with a conventional material of polyurethane which has excellent antithrombotic properties, so that it can be used as an artificial blood vessel. Excellent antithrombotic properties when
In addition, the inventors have found that an artificial blood vessel having significantly higher endothelial cell adhesion than polyurethane can be obtained, and arrived at the present invention. That is, the gist of the present invention resides in a blood conduit formed of a copolymer of a polyamino acid and polyurethane in which an average of 4 or more amino acid units are continuously bonded.

[0015]

DESCRIPTION OF THE PREFERRED EMBODIMENTS The present invention will be described below in detail. In the present invention, a polyamino acid in which four or more amino acid units are continuously linked on average means a structure in which four or more amino acids of the same or different kind are continuously linked on average. In this case, the amino acid may be any of a racemic form, an optically active form, and a mixture thereof. There are roughly two methods for synthesizing such a copolymer of polyamino acid and urethane.

The first method is a method in which a polyamino acid and a polyurethane are separately synthesized and then copolymerized. This method is a method of reacting urethane with a polyamino acid obtained by polymerizing an active monomer as a polyamino acid synthesized by sequentially linking amino acids or as a precursor of the polyamino acid.
With this method, it is difficult to increase the molecular weight of the polyamino acid or copolymer.

The second method is a method in which an active monomer (polymerizable monomer) as a precursor of a polyamino acid is copolymerized with urethane. In this method, when an α-amino acid-N-carboxylic anhydride is used as a precursor of the polyamino acid, it is easy to increase the molecular weight of both the polyamino acid chain and the copolymer in the resulting copolymer. is there. Accordingly, the blood conduit of the present invention may be used in this second method, namely: (a) α-amino acid-N-carboxylic anhydride;
It is preferably formed of (b) a urethane prepolymer having an isocyanate group and (c) a polyamino acid urethane resin obtained by reacting at least one selected from water, hydrazine and an organic amine.

The amino acids used are neutral amino acids having 2 to 12 carbon atoms such as glycine, alanine, leucine, isoleucine, valine, α-aminoheptanoic acid, and β.
-Benzyl aspartic acid, γ-methyl-L-glutamate, γ-methyl-D-glutamate, γ-benzyl-
Monoesterified acidic amino acids such as L-glutamate,
α-ω in which an ω-amino group such as ε-acyl lysine, δ-acyl ortinine is protected by an appropriate masking group
Α-amino acid derivatives such as -diaminocarboxylic acid derivatives and O-acetylthreonine are used. Α−
As the amino acid, any of a racemic form and an optically active form can be used.

When α-amino acid-N-carboxylic anhydride (hereinafter, N-carboxylic anhydride is abbreviated as NCA) is used as the precursor of the polyamino acid, all of the above α-amino acids are used.
-Amino acid-NCA can be used. Representative examples are glycine-NCA, alanine-NCA, leucine-NCA, γ-methyl-L-glutamate-NC.
A and the like.

The urethane prepolymer having a terminal isocyanate group can be obtained by reacting a polyisocyanate compound with a polyol under an equivalent ratio of NCO / OH> 1. As the polyisocyanate component, usually, an aromatic diisocyanate, an aliphatic diisocyanate and an alicyclic diisocyanate alone or a mixture thereof are used. For example, toluene-2,4-diisocyanate, 4,
4'-diphenylmethane diisocyanate, metaphenylene diisocyanate, 3,3'-dimethyl-4,4 '
-Biphenyl diisocyanate, meta-xylene diisocyanate, para-xylene diisocyanate, 1,6-hexane diisocyanate, 1,10-decamethylene diisocyanate, 1,4-cyclohexane diisocyanate, dicyclohexylmethane-4,4'-diisocyanate, 3-isocyanatomethyl-3 , 5,5-trimethylcyclohexyl isocyanate (isophorone diisocyanate) and the like.

Examples of the polyol component include a polyether polyol and a polyester polyol alone or a mixture thereof. Examples of polyether polyols are polypropylene ether glycol, polyethylene polypropylene ether glycol, polytetramethylene ether glycol, polypentamethylene ether glycol, polyethylene polytetramethylene ether random copolymer, polyethylene polytetramethylene ether block copolymer alone or Examples of such a mixture include glycols having an aromatic ring obtained by adding propylene oxide or ethylene oxide to bisphenol A, and the like.

Representative examples of polyester polyols include polycaprolactone polyol or ethylene glycol,
Diols such as 1,4-butanediol and adipic acid,
Those obtained by reaction with a dibasic acid such as sebacic acid are used. Special polyols such as polyols obtained by adding caprolactone to polytetramethylene ether polyol or polypropylene ether polyol, and polysiloxane polyols can also be used. Furthermore, a polycarbonate polyol obtained by adding a molar ratio excess of 1,6-hexanediol or 3-methylpentanediol to diethylene carbonate and removing the ethanol is used.

The polyether polyol, polyester polyol and special polyol preferably have a number average molecular weight of 200 or more. The water used in the present invention means ordinary water, and may be any of tap water, non-demineralized water, or demineralized water. Hydrazine may be either anhydrous hydrazine or hydrous hydrazine, and industrially hydrous hydrazine is more advantageous in terms of safety.

Representative examples of organic amines include trimethylamine, triethylamine and tripropyldiamine.
Primary amine, secondary diamine such as piperazine, ethylenediamine, 1,3-propanediamine, primary diamine such as 1,4-butanediamine, 1,2-propanediamine,
Both primary and secondary amines such as 1,3-butanediamine and dihydrazides having a hydantoin ring, for example, 1,3
-Bis (hydrazidecarboethyl) -5-isopropylhydantoin is suitable.

The α-amino acid used to obtain the polyamino acid urethane resin
The weight ratio of the amino acid NCA to the urethane prepolymer is
90:10 to 10:90, more preferably 80:
20:20:80. This weight ratio is determined according to the physical properties of the target blood conduit. The amount of hydrazine and the organic amine having a primary or secondary active hydrogen to be used is preferably 1/2 equivalent or more, more preferably 2/3 equivalent or more, as the amino group with respect to the isocyanate group of the urethane prepolymer. The use amount of the tertiary amine is preferably 1/1000 mol or more of the α-amino acid NCA.

Since water reacts with isocyanate groups to form amino groups, it can be used as an alternative to amines. The polyamino acid urethane resin in the present method is obtained by reacting an α-amino acid-N-carboxylic anhydride, a urethane prepolymer having an isocyanate group at a terminal, and water, hydrazine or an organic amine in an organic solvent.

Examples of the organic solvent used herein include chlorinated aliphatic hydrocarbons such as dichloromethane, 1,2-dichloroethane, 1,1,2-trichloroethane, chloroform, 1,1,2,2-tetrachloroethane, and the like. Benzene, toluene, aromatic hydrocarbons such as xylene, chlorobenzene, chlorinated aromatic hydrocarbons such as dichlorobenzene, ethyl acetate, acetate such as butyl acetate, acetone,
Does not contain active hydrogens such as ketones such as methyl ethyl ketone, methyl isobutyl ketone and cyclohexanone, dimethylformamide, diethylformamide, dimethylacetamide, N-methylpyrrolidone, ethylene carbonate, dimethylsulfoxide, dioxane, tetrahydrofuran and hexamethylphosphoramide. Examples thereof include a water-soluble organic solvent, and a mixture of two or more thereof.

The amount of the organic solvent used is such that the resin concentration of the final product in the polyamino acid urethane resin solution is usually in the range of 3 to 50% by weight, preferably 10 to 30% by weight in terms of the produced resin solution. It is good to be in the range of. If the concentration is too high, the viscosity becomes extremely high and the mixture becomes a gel. When processed into a blood conduit, it may be diluted with a solvent and used, but handling is difficult. If the concentration is too low, high viscosity (1
(More than 000 cps) is difficult to obtain, and versatility is poor.

When the optically active α-amino acid NCA is used in the present method, the reaction temperature for producing a polyamino acid urethane resin solution is a temperature at which a high molecular weight polyamino acid single polymer can be synthesized from the α-amino acid NCA. Preferably, the range of 10 to 60 ° C is good. If the temperature is higher than 60 ° C., it is difficult for the amino acid chain to take an α-helix structure during copolymerization, so that the degree of polymerization of the amino acid chain does not increase, and a high molecular weight one may not be obtained. Further, when the reaction is performed at a high temperature, the urea bond generated by the reaction between the isocyanate group and the amino group may cause a Buret reaction of the isocyanate group to cause gelation.

The polyamino acid urethane resin solution obtained as described above has a low content of α-amino acid NCA, for example, when the weight ratio of α-amino acid NCA to urethane prepolymer is in the range of 5:95 to 15:85. The solution becomes relatively less turbid, and as the ratio of α-amino acid NCA increases, the turbidity increases and the viscosity becomes 10 cps to 1,000,000 c.
Any viscosity can be obtained within the range of ps / 25 ° C.
Further, structurally, when an optically active α-amino acid NCA is used as an amino acid component, when the amino acid content is low, the α-helix content is low and the β structure content is high, and when the amino acid content is high, the α-helix is high. The content tends to increase and the β structure tends to decrease.

As a preferred method for obtaining a polyamino acid urethane resin, (a) a method in which a urethane prepolymer and an α-amino acid NCA are mixed in the above-mentioned organic solvent, and then a tertiary amine is added and reacted. (B) A method in which an α-amino acid NCA and a urethane prepolymer are mixed in the organic solvent, and then reacted by adding water, hydrazine or an organic amine having active hydrogen. (C) A method in which the urethane prepolymer and the α-amino acid NCA are mixed in the organic solvent, and water, hydrazine, or an organic amine having active hydrogen is added and reacted, and then a tertiary amine is added and reacted. (D) in the organic solvent, a urethane prepolymer;
A method comprising reacting water, hydrazine or an organic amine having active hydrogen, and then adding and reacting an α-amino acid NCA. (E) A method in which an α-amino acid NCA and a urethane prepolymer are mixed in the organic solvent, and then water, hydrazine or an organic amine having active hydrogen is added and reacted, and further, a urethane prepolymer is added. (F) After reacting the urethane prepolymer with water, hydrazine, or an amine having active hydrogen in the organic solvent, α-amino acid-N-carboxylic anhydride is added and mixed, and then water is added. , Hydrazine or an amine having active hydrogen. And the like.

In the present invention, a polyamino acid or a polyurethane resin can be mixed with the polyamino acid urethane resin obtained by the above-mentioned method. The blood conduit of the present invention is obtained by molding the polyamino acid urethane resin obtained by the above method into a non-porous or porous tube, or after previously molding into a ring with another polymer material,
It can be obtained by coating on the inner surface, outer surface or both surfaces.

In particular, an artificial blood vessel made by processing a polyamino acid urethane resin alone or a tube mainly using the same as a main component, and a fiber formed from the above-described one, processed into a woven or non-woven fabric, In the case of using an artificial blood vessel made in this manner, when the amino acid content exceeds a certain amount, the polyamino acid urethane resin is absorbed into the living body with the lapse of time after being embedded as an artificial blood vessel. On the other hand, a living blood vessel is formed in the artificial blood vessel. Therefore, there is a possibility that only a living blood vessel is finally regenerated by using an amino acid having an appropriate amino acid content (regeneration of only a living blood vessel may solve all the problems of the conventional artificial blood vessel) There is).

In this case, if the amino acid content in the polyamino acid urethane resin is too large, the artificial blood vessel is absorbed before the living blood vessel is regenerated in the artificial blood vessel. If the amino acid content is too small, the artificial blood vessel will not be absorbed into the living body,
Or, it takes too long to be absorbed and the new blood vessel wall formed in the artificial blood vessel has the same problem (arteriosclerotic change, ulceration or shedding) as a conventional artificial blood vessel (for example, a polyester fiber artificial blood vessel). To form a thrombus there). As described above, in the case of a polyamino acid urethane resin using α-amino acid NCA as an amino acid,
The weight ratio of A to the urethane prepolymer is 90:10 to 1
0:90, but as an amino acid α-amino acid NCA
When amino acids other than the above are used, those conforming to this range are preferable.

In the case where the polyamino acid urethane resin is directly formed into a tube without forming a fibrous form as described above, it is preferable that the tube wall is made porous. As a method, the polyamino acid urethane resin solution is formed into a tube and the tube is formed. It can be made by pouring into a liquid in which the resin is insoluble and the solvent is soluble and wet-solidified. For example, in the case of using a polyamino acid urethane resin solution using dimethylformamide as a solvent in the embodiment of the present invention, a porous tube can be made by forming the solution into a tube in a mold and placing it in water.

[0036]

EXAMPLES Hereinafter, the present invention will be described more specifically with reference to examples and comparative examples, but the present invention is not limited to the following examples unless it exceeds the gist of the invention. In addition, the test method of the evaluation as a blood conduit in the following examples is as follows. <Blood compatibility> Platelet adhesion test a) A polymer solution to be evaluated was coated on the surface of glass beads, and this was filled into a platelet adhesion measurement column using physiological saline to prepare a sample column. b) Blood Blood was collected from a rabbit carotid artery, and a 3.8% aqueous solution of sodium citrate was added thereto at 10 vol% (v / v), dispersed, and then centrifuged for 20 minutes to obtain upper platelet-rich plasma. (PRP) was used without dilution. c) Experimental method Immediately before flowing PRP through the sample column, 4 to 6 Ca ²⁺ was added.
mmol / L was added. Immediately, a syringe pump was attached, and the sample column was connected to the syringe. PRP is flowed at a flow rate of 0.2 to 0.3 ml / min and flows out.
Was collected in an amount of 1 ml (7.7 mmol /
100 μl of L EDTA solution is added). The platelet count in the obtained PRP was measured using a platelet counter, and the adhesion ratio was calculated by comparing the platelet count with the platelet count before passing through the column.

2. Antithrombotic test a) The tube having an inner diameter of 1 mm produced in the example was cut as shown in FIG. 1 and soaked in an antiseptic solution (Hibiten). As shown in FIG. 2, a rat (Wistar II) was laparotomized under bent parbital anesthesia, the aorta was exposed, blood flow was stopped by clipping two places, a part of the blood vessel between the clips was cut, and the test was performed. The tube is placed in a blood vessel, and both ends of the tube are tied and fixed with a thread from above the blood vessel, and then the clip is removed to resume blood flow. B) The wound is sutured, and the rats are raised as usual. C) After breeding for a certain period of time, the rat was anesthetized with bent parbital, the vena cava was incised, a 2% glutaraldehyde solution of physiological saline was refluxed from the heart, the blood was washed out, and the tube embedded in the blood vessel was taken out. The presence or absence of thrombus formation was examined.

<Adhesion to vascular endothelial cells> Adhesion to cast film a) Sample A cast prepared by applying the polymer to be evaluated on a glass plate
Prepare a film. b) Cells Endothelial cells collected from bovine carotid artery c) Method Flexipalm (Heraeu) on cast film
s company, Germany, diameter 16 mm) was set up to make a well, and cells (5 × 10 ⁴ cells / ml in 10% FCS-
MEM) is added at 1 ml / well. After culturing in a CO ₂ incubator at 37 ° C. for 3 hours, the plate is washed twice with a phosphate buffered saline (PBS). Then 0.25
% Glutaraldehyde, the number of cells was measured under an inverted microscope, and the average value was determined.

As a control, the cell adhesion rate was 24 w
Adhesion to the cell plate was confirmed by microscopy. A 24-well pl for culture was tested in parallel with the average value of the number of 1-well-1 HPF of the sample divided by the average value of the number of 8-well 1-HPF.
ate, 8 wells, and 1% of the average value of the adhesion ratio.

Example 1 a) Preparation of polymer Polytetramethylene ether glycol (OH value: 57.
25) 980 g and tolylene diisocyanate (2,4
174 g of a mixture of tolylene diisocyanate and 2,6-tolylene diisocyanate, 2,4-tolylene diisocyanate (80% by weight) is reacted at 70 ° C. for 5 hours, and a urethane prepolymer having an isocyanate group at a terminal (NCO equivalent) , 1164). 58.2 g of the urethane prepolymer and γ-methyl-L-glutamate N
58.2 g of CA and dimethylformamide (DMF) 3
94.3 g of hydrazine hydrate.
A solution in which 375 g was dissolved in 20 g of DMF was dropped and reacted to obtain a polyamino acid urethane resin solution (a) having a viscosity of 18000 cp / 25 ° C.

The average degree of polymerization of the amino acid chains in the solution was determined by the reactivity between primary amine and isocyanate and the mechanism of polymerization of NCA by primary amine (Murray G).
goodman and John Hutchiso
n. J. Am. Chem. Soc. , 88,3627
(1966)), it was about 62.
The ratio of the α-helical structure to the β-structure in the film of the copolymer was determined by IR-spectrum 1655.
cm ^-1 (α-helix C = O expansion and contraction) and 1625 cm ^-1
(Β-Structure C = O stretching) 95 /
5 and mostly α-helical structure.

B) Production of blood conduit (tube) The polyamino acid urethane resin solution (a) obtained in a) is coated on a stainless wire having a diameter of 1 nm.
Dry at 80 ° C for 5 minutes. Immerse in water at 50 ° C for 10 minutes. 80
C. x 5 minutes drying. Steps (1) to (4) were repeated to prepare a stainless wire coating having a resin thickness of 1 mm and a length of 20 cm. This stainless wire coating was immersed in water at 50 ° C. for 3 hours, allowed to stand at room temperature for one week, and then the stainless wire was pulled out.
A tube (blood conduit) 〜0.6 mm long 20 cm was obtained. Using the polyamino acid urethane resin and tube obtained in the above examples, an evaluation test was performed by the above-described evaluation method. The results are shown in Tables 1, 2 and 3.

Comparative Example 1 1.25 g of hydrazine hydrate was dissolved in 80.5 g of DMF, and 52.8 g of the same urethane prepolymer used in Example 1 was added to 58.2 DMF in a nitrogen atmosphere.
g, and the solution was dropped and reacted to obtain a viscosity of 17,000.
A cp / 25 ° C. urethane resin solution (b) was obtained. Using this resin solution, a tube was manufactured in the same manner as in Example 1. Using the urethane resin and the tube obtained in Comparative Example 1, evaluation was performed in the same manner as in Example 1, and the results were shown in Tables 1 and 2.
2, shown in Table-3.

[0044]

[Table 1] Sample: Blood collected from two rabbits (individuals a and b)

[0045]

[Table 2] ；: Little blood clots are observed. Δ: Thrombus is observed in part of the tube.

[0046]

[Table 3]

^* 1 Average value (calculation formula) m; Arithmetic mean SD; Standard deviation ^* 2 Cell adhesion rate (Calculation formula) 24 well plate (PLATE) for culture 1
average adhesion of well-1HPF; 99%

From the above test results, the resin obtained in Example 1 had lower platelet adhesion than the urethane resin of Comparative Example 1 in which no amino acid was incorporated (Table 1).
1), the formation of thrombus is slow (Table 2), and in the endothelial cell adhesion test, it is clear that the number of adhered cells is remarkably large and the cell compatibility is large (Table 3). That is, the resin of Example 1 was prepared in vitro and in vivo.
It is clear that in each of the tests, excellent results were obtained as compared with the resin of Comparative Example 1.

[0049]

The blood conduit made of the polyamino acid urethane resin of the present invention has better antithrombotic properties and much better cell compatibility as compared with urethane resin blood conduits which have been studied conventionally. It has excellent performance as a medical material.

[Brief description of the drawings]

FIG. 1 is a schematic view of a tube used for an antithrombotic test.

FIG. 2 is a diagram showing a step of implanting a tube into a rat aorta in order to perform an antithrombotic test.

 ──────────────────────────────────────────────────の Continuing on the front page (72) Inventor Koichi Tamura 1 Tohocho, Yokkaichi-shi, Mie Mitsubishi Chemical Corporation Yokkaichi Office (72) Inventor Osamu Kishiro 1000 Kamoshidacho, Aoba-ku, Yokohama-shi, Kanagawa Prefecture Mitsubishi Chemical Yokohama Research Institute, Inc.

Claims (2)

[Claims] 1. A blood conduit formed of a copolymer of a polyamino acid and urethane having an average of four or more amino acid units connected continuously. 2. A copolymer of a polyamino acid and urethane, comprising: (a) α-amino acid-N-carboxylic anhydride;
2. A polyamino acid urethane resin obtained by reacting (b) a urethane prepolymer having an isocyanate group, and (c) at least one selected from water, hydrazine and an organic amine. Blood conduit.