JPS58206753A - Production of anti-blood coagulable medical material - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to medical materials that come into direct contact with living organisms or biological components, and particularly relates to a method for producing medical materials with good anticoagulant properties and mechanical properties.

Polymer materials with excellent processability, elasticity, and flexibility have become widely used as medical materials in recent years. In the future, ice cubes will increasingly be used as disposable containers for syringes, blood bags, cardiac catheters, etc. In this case, the issue is safety, that is, whether various abnormal reactions occur in the living body and pose a danger to life support, and in the case of contact with blood, is there a condition that blood coagulation does not occur? required.

The anticoagulant polymer materials provided to date are (1)
3) polymeric material with heparin or its related compounds attached to the surface; (2) polymeric material with negative charge applied to the surface; (3) polymeric material with inactivated surface.
The materials that are phase-separated or provided in the present invention fall into category (1) above.

By the way, the method (1) (hereinafter referred to as surface heparinization method)
Further, (A) a blending method of polymer and heparin, (
B) A method of ionic bonding of heparin to a cationic group in a polymer; (C) A method of covalent bonding of a polymer and heparin. Over time, heparin is released and its effects are lost.

Even in method (B), when used in vivo for a long period of time, heparin is gradually desorbed and its effect is also lost. (
In the material obtained in C), heparin is covalently bonded, so it has the advantage of being easily desorbed, or it has the disadvantage that the covalent bond reduces the effect of heparin, that is, the anticoagulant effect.

In contrast, JP-A No. 50-139173 describes the general formula % formula % (!NL1 In the above general formula, R1+ Rt + R
4T R5 is an alkylene group having 2 to 4 carbon atoms, R3 is an alkyl group having 1 to 20 carbon atoms (m and n are integers of 1 to 30), and has a tertiary amino group and a polyether chain in the molecule. When "dihydric alcohol" is used as part or all of the diol component, the polyester or polyurethane is converted into a quaternary salt and "polyether-type polyester having a quaternary ammonium salt in the molecule." , if the values of m and n are too large, tertiary amino groups,
(As a result, the number of quaternized ammonium groups decreases, resulting in an insufficient amount of heparin coating and a decrease in blood coagulability.) On the other hand, when m and n are small, the mechanical properties In particular, the elasticity is reduced, making it unsuitable for use as an artificial organ.

From the above point of view, the inventors of the present invention in JP-A No. 56-128162 quaternized the tertiary amino group of high ether urethane by adding a tertiary amine group to the main chain, and then added heparin or its related compounds. We have proposed a method for producing anticoagulant medical materials characterized by imparting anticoagulant properties. In this case as well, there is a drawback that the anti-coagulant property is quite good, but when used in vivo for a long period of time, the release rate of heparin decreases, resulting in a slight decrease in the anti-coagulant property.

In order to obtain even better anticoagulant properties, the present inventors
A tertiary segmented polyether urethane in which a polyaminoether having a tertiary amino group in the hook, which is derived from an amino alcohol as shown in the following general formula (1), is used in part or all of the soft segment. Ami 7
We discovered that by quaternizing the group and adding heparin or its analogues, better anticoagulant properties could be obtained than when using a polyaminoether having 7 tertiary amine groups in the main chain. Achievement of the Invention An object of the present invention is to provide an anticoagulant medical material capable of increasing the amount of heparin coating without the above-mentioned disadvantages.

That is, the present invention has the following formula: 1 General formula (I) A different 1if1 ring may be formed.R3 is one or more tertiary amino alcohols selected from the group consisting of compounds represented by a hydrogen atom or carbon. An anti-acoagulant material characterized by quaternizing the tertiary amine 7 groups of a segmented fornoaminoether urethane using a polyaminoether reacted with a polyaminoether, and then adding heparin or an analogous compound thereof. It is a manufacturing method.

In the present invention, a segmented polyaminoether urethane using a polyaminoether resin obtained by reacting a tertiary amino alcohol represented by the general formula (+) with 50 mol% or more of the polyaminoether raw material in 11 reactions is used. Since the tertiary amino group is quaternized, the hydrophilic domain and the hydrophobic domain have a clear micro phase separation structure, and the thickness of the domain is also different from that of 0% amino alcohol or 0% amino alcohol, respectively. By choosing the molecular weight of the amino ether, you can use it freely.

Furthermore, since the cylindrical molecule material of the present invention is appropriately desorbed from the I''tt heparin & layer and heparin in vivo, it has an extremely high anti-blood coagulation function and can be used as an anti-thrombotic material for a long period of time.

Furthermore, when a polymeric material is used in contact with blood, general interlayers include additives (
However, in the present invention, there is no need to add plasticizers, etc., and the segmented polymer can be There is no reason for this kind of inconvenience to occur because it is something that is formed.

In addition, polymeric materials are easily susceptible to complex effects such as oxidative decomposition and metabolism due to free radicals and enzymes in living organisms, or are chemically stable because they are based on segmented polyether urethane. It also rarely generates acceptable leachables.

The material of the present invention also includes a hydrophilic quaternary chlorinated polyaminoether segment, a hydrophobic polyether segment,
Because it is composed of crystalline urethane and urea bonds,
Upon fixation, phase separation occurs to form a one-microdomain structure, which is similar to the packing on the inner wall of a blood vessel.

Therefore, anticoagulant properties are expected from the structural aspect.

Next, each component constituting the polymer material of the present invention will be explained.

First, the tertiary amino alcohols represented by the caustic formula (I-) include 2-methyl-2-dimethylaminomethyl-1,3-propanediol, 2-methyl-2-diethylaminomethyl-1,3 -propanediol, 2-
Methyl-2-di-n-butylaminomethyl-1,3-propanediol, 2-methyl-2-di-n-propylaminomethyl-1,3-propanediol, 2-methyl-
2-di-1-provitaminomethyl-1,3-propanediol.

2-Methyl-2-di-1-butylaminomethyl-1,3
-Propanediol, 2-methyl-2-diphenylaminomethyl-1,3-propanediol.

2-methyl-2-dicyclohebansil 7minomethyl-1,
3-propanediol, 2-methyl-2-dibenzylaminomethyl-1,3-propanediol.

2-Methyl-2-sibizelidylaminomethyl-1゜3-
Propanediol, 2-ethyl-2-dimethylaminomethyl-1,3-propanediol, 2-ethyl-2-diethylaminomethyl-1,3-propanediol, 2-
Ethyl-2-di-n-pro and ruaminomethyl-1,3-
Propanediol, 2-ethyl-2-geniebutylaminomethyl-1,3-brobanediol, 2-ethyl-
2-diphenylaminomethyl-1,3-propanediol, 2-ethyl-2-dibenzylaminomethyl-1,3
-propanediol, 2,2-bis(dimethylaminomethyl)-1,3-propanediol, 2,2-bis(diethylaminomethyl)-1,3-pucopanediol,
2,2-bis(di-n-propylaminomethyl)-1,
3-propanediol, 2,2-bis(di-n-butylaminomethyl)-1,3-propanediol, 2.
2-bis(cypiperidylaminomethyl)-1,3-propanediol, 2,2-bis(diphenylaminomethyl)-1,3-propanediol.

2.2-bis(dibenzylaminomethyl)-1,3-propanediol, 2-dimethylaminomethyl-1,3-
Propanediol, 2-diethylamitumenal-1,3
-propanediol, 2-di-n-prodolua ζthumenal-1,3-propanediol.

2-di-n-butylaminomethyl-1,3-propanedi;? #12-di-1-propylaminomethyl-1,3-
Bucopanediol, 2-di-1-butyl-minomethyl, 3-propanediol, 2-dicyclohexyl)'
Minomethyl-e, 3-propanediol, 2-dibenzylaminomethyl-1,3-bubanol, 2-diphenylaminomethyl-1,3-propanodiol, etc.
sword) (07i shown as 9+1, these tertiary class Ami 7
The glycol raw material used to produce polyaminoether together with group-containing glycols has the general formula: % formula % () (Tenshi, R1 represents an alkylene group or arylene group having 2 to 20 carbon atoms -t-o) Krikhols represented by, also (=
There are glycols represented by the general formula;

Glycols represented by general formula (IV) include ethylene glycol, propylene glycol, tetramethylene glycol, hexamethylene glycol, neopentyl glycol, 2,2-di(4-denediphenol,
．． 4'-dihydroxydiphenyl, 4.4'-dihydroxydiphenylmethane.

4.4'-dihydroxydiphenylsulfone, 1.2-
Examples include dihydroxybenzene, 1,3-dihydroquinebenzene, and 1,4-dihydroxybenzenato.

Glycols represented by general formula (1) include alkylene glycols such as ethylene glycol, propylene glycol, tetramethylene glycol, 1,6-hexanediol, and neopentyl glycol, diethylene glycol, triethylene glycol, and molecular weights of 200 to 20.
00 polyethylene glycol, diethylene glycol) IJ 7' Robylene Glycol 9 Molecular weight 200~
1ooo polypropylene glycol, molecule λ200-
Examples include polyhexamethylene glycol No. 1000.

The polyaminoether according to the invention is one obtained by polymerizing IU of the same or different tertiary amino alcohol (1), using 30 mol% or more of the tertiary amino alcohol (1), and adding a diol to the polyamino ether. Examples include those obtained by copolymerizing group (U) and/or (1).

The polymerization reaction conditions for obtaining such a polyaminoether may not limit the present invention.Generally, a condensation catalyst such as phosphoric acid, phosphorous acid, or polyphosphoric acid is used at 150 to 2so℃,
The polyaminoether obtained here preferably has a molecular weight of 300 to 8000, and is reacted at 200 to 250°C, and the water produced and unreacted monomers and oligomers are distilled off under normal pressure or reduced pressure. 800-300
0. The segmented polyaminoether urethane according to the present invention is obtained by reacting the above-mentioned polyamide/ether with a polyisocyanate and, if necessary, a compound containing two or more active hydrogens capable of reacting with other isocyanate groups.

The method for producing the segmented polyaminoether urethane is not particularly limited, or, for example, the above-mentioned polyaminoether and a compound containing two or more active hydrogens that can react with other isocyanate groups are reacted together with a polyisocyanate, and a terminal inocyanate group-containing method is used. manufacture prepolymers,
2 active hydrogens that can react with low molecular weight isocyanate groups
There is a method in which segmented polyaminoether urethane is obtained by elongating the molecular chain with a compound containing more than 100% polyaminoether urethane.

In addition, polyaminoether is contained in the segmented polyaminoether urethane finally obtained in an amount of 1 to 90% by weight (
In addition to the above-mentioned polyaminoethers, active hydrogen-containing compounds forming soft segments in the production of segmented polyamide 7 ether urethane include general segmented polyaminoethers. Polyols (usually 200 to 8000 molecular types) used in the production of polyether urethanes are used. An example of such a polyol is polyethylene glycol.

Polyoxyalkylene diols such as polypropylene glycol and polytetramethylene glycol; ethylene glycol, propylene glycol.

Chitramethylene glycol, pentamethylene glycol, 2,2-dimethyltrimethylene glycol, hexamethylene glycol, decamethylene glycol, 1,4-
Dihydroxycyclohexane.

Diols (preferably having 2 to 15 carbon atoms) such as 1.4-dihydroyacymethylcyclo-\xane and dicarboxylic acids or ester-forming derivatives thereof (for example, sebanic acid,
Aliphatic dicarboxylic acids such as adipic acid, dodecanedicarboxylic acid, glutaric acid, succinic acid, ibh, azelaic acid,
Polyester diol obtained by reacting aromatic dicarboxylic acids such as terephthalic acid and isophthalic acid (halides, active esters, amides, etc.); ε-
Examples include polylactone diols obtained by ring-opening polymerization of caprolactone and the like.

As the polyisocyanate, all polyisocyanates conventionally used in the production of polyurethane as well as polyisocyanates that will be developed in the future can be used. Preferred are ethylene diisocyanate,
Trimethylene diisocyanate, tetramethylene diisocyanate.

Pentamethylene diisocyanate, octamethylene diisocyanate, undecamethylene diisocyanate, dodecamethylene diisocyanate, 3゜3'-diisocyanate propyl ether, cyclopentycine-1,3-
diisocyanate, cyclohexane-1,4-diisocyanate, 2,4-tolylene diisocyanate) +2+6
) lylene diisocyanate) +214-) Mixture of lylene diisocyanate and 2゜6-lylene diisocyanate, xylylene, 4-diisocyanate, xylylene-1,3-diisocyanate, 4.4'-diphenylmethane diisocyanate, 4.4'- Examples include diphenylpropane diisocyanate, m-phenylene diisocyanate, p-phenylene diisocyanate, 7talene-1,4-diincyanate, 7talene-1,5-diisocyanate, and the like.

The reaction conditions for producing the segmented polyaminoether urethane do not limit the present invention, but in terms of -V, the incyanate group/hydroxyl group (molar ratio) is 1.1 to 5.0 (
The prepolymer is produced by reacting each raw material so that the molecular weight is preferably 1.5 to 3.0).

This prepolymer has incyanate groups at both ends, and the molecular chain is extended by reacting with an active hydrogen-containing compound that reacts with the incyanate groups, such as a low molecular weight diol, diamine, or amino alcohol. and a segmented polyaminoether urethane is obtained.

The molecular chain extenders used here include low molecular weight diols, diamines and amino alcohols, both known and new, which can be applied to the present invention. Particularly preferred diols include ethylene glyfur, propylene glycol, tetramethylene glycol, 1,5-bentanediol, 1,6-hexanediol, 1°10-tecanediol, 1,4-diol, and Examples include droxycyclohexane, 1,4-dihydroxymethylcyclohexane, diethylene glycol, triethylene glycol, etc. Examples of the diamine include ethylene diamine, prohylene diamine, butylene dirmine, hexamethylene diamine, xylitine diamine, phenylene diamine, 4. Examples include 4'-diaminodiphenylmethane, and further examples of amino alcohols include methanolamine, 2-amine ethanol, 3-aminopropanol,
Examples include 4-amino/butanol.

The segmented polyaminoether urethane thus chain-extended is then subjected to a quaternary chlorination reaction. Quaternary chlorination does not occur before or after the molding of segmented polyaminoether urethane, but it can be applied to halogenated hydrocarbons (for example, in a solvent such as dimethylformamide before molding, or as it is after molding). Butyl chloride, aryl chloride.

It is generally carried out by reacting benzyl chloride, butyl bromide, methyl iodide, etc.) at room temperature or below the boiling point of the yarn.

In this case, it is desirable to convert all tertiary amino groups into quaternary salts; if any tertiary amino groups remain, it is difficult to maintain anticoagulant properties over a long period of time even if heparin is reacted. However, in general, 7 parts or more of quaternary chloride can be sufficiently used depending on the purpose, and the more preferable lower limit of the '' class chloride is 80%.

Finally, heparin is added, and this reaction does not matter after the formation or shaping of the polymeric material. However, preferably
This is carried out by immersing the molded article in a solution of heparins as described below. The solution usually contains 0.1 to 10%
A degree A, preferably 0.5 to 5% mW is used. Does the reaction proceed even at room temperature?
It is also preferable to carry out heating to .degree. Heparin m used here Toha, heparin, heparin, gold^i+,
Not only derivatives such as 4-heparin metal salts, but also heparinoids such as chondroitin sulfate and dextran sulfate, etc.
1: Also includes heparin analogs such as PVA@ethyl acid.

In the present invention, as described above, a polymeric material with a large amount of heparin attached can be obtained, so that a good anticoagulant property can be obtained during extracorporeal circulation of blood without the need for concomitant use of henomarin. In addition, it has good mechanical properties such as elasticity, and there are few harmful eluates when it comes into contact with body fluids such as blood.

By taking advantage of these advantages, it can be widely applied to medical instruments and equipment in each building. To give specific examples, it can be used as a sheet, tube, or hollow fiber for hemodialysis of patients with renal failure.
It can also be used as a coating agent for adsorbing wastes in blood. In addition to such pre-artificial materials, membrane materials for artificial lungs (
It is also used as a sheet material for sheet lungs in heart-lung machine and heart-lung machines. Its small aortic balloon, artificial blood, blood bag, catheter, cannula.

Used in a wide range of fields such as shunts and blood circuits.

Next, non-inventive examples will be described, and "parts" in the examples mean parts by weight. In addition, the basic nitrogen content was measured by dissolving the sample in phenol/ethanol (5:l S wood), and bromophenol blue was determined using the fingertips. scientific method (T,
Biomed-Mater, Res, 6. l
65 (1972)).

Example-L 2-Methyl-2-dimethylaminomethyl-1,3-propanediol (147m) and phosphorous acid (O, S parts) are placed in an autoclave and distilled out at 230°C for 15 hours under a nitrogen stream. The reaction was carried out while removing. It was then evaporated to 0°3wH9 over 90 minutes to reduce the basic nitrogen content to 10%.
5% polyaminoether was obtained.

Polytetramethylene glycol (molecular weight 1300: 1
．． 300 parts) 4.4'-Diphenylmethane diisocyanate) 1-ooo Juku) was incubated at 60°C under a nitrogen stream for 30 minutes, and then dimethylformamide (hereinafter abbreviated as DMF: 2300 parts) was added and homogenized. Dissolve 1 ice cold in 30
Do this for minutes. Here, 50% D' of the above polyaminoether
Add MF solution (3060 parts) and react for 30 minutes under water cooling. After the reaction was completed, DM'F (4047 parts) was further added, and a 10% DMIF solution (14 oas) of 1,2-propylenediamine was added dropwise over 60 minutes, and further n-
129 ml of 20% DMF solution was added and reacted for 30 minutes.

A 20% DMF solution of acetic anhydride (50 kg) was then added,
React for 60 minutes to make the solution 30% viscous IJ-120
DM of segmented polyaminoether urethane with 0 voids (25°C)? I got the solution. This solution was diluted with DMF to make a 10% solution, poured onto a horizontal glass plate, and heated at 70°C for 4 hours at 2 hours under a gentle nitrogen stream.
MF was evaporated. After further drying at 40° C. under vacuum for 10 hours to form a segmented polyamide/ether film with a monobasic nitrogen content of 4.02%, the film was taken out, washed with methanol, and air-dried. The field-based nitrogen content of this film was 0. ,
It was immersed in a 2% aqueous heparin sodium solution containing 100% quaternary chloride at 70° C. for 24 hours. This film was taken out, rinsed with distilled water 110 times for 15 minutes, and then dipped in an aqueous toluidine blue solution, which turned reddish-purple, proving that heparin was fixed.

In addition, 3C: A film cut into a square was attached to the surface of a watch glass with a slotted stopper, and blood was collected from a dog.
Blood (250 μl) was placed thereon, and a 001M calcium chloride aqueous solution (25 μl) was added to initiate the coagulation reaction.

After 12 minutes of contact at 37°C, water was added to stop the coagulation reaction and the resulting blood clot was fixed with formalin. After removing moisture using P#, the weight is measured using a chemical balance. A similar operation is performed only with a glass watch glass, and the resulting clot cap is set as 100, and the subcoagulability is determined by the relative vehicle (coagulation rate) to this.

Table 1 shows uninvented heparinized polymers, segmented polyether urethanes containing no polyaminoether,
The results of measurements on silicon and glass for stalling are shown.

From the results shown in Table 1, it is clear that the heparinized polymer of the present invention has excellent anticoagulant properties.

Gallery Example-2 2-Methyl-2-dimethylaminomethyl-1,3-propanediol (147%), 1,6-hexanediol (59.1 parts) and phosphorous acid (1.2 parts) were autoclaved. 1 and reacted in the same manner as in Example 1 to obtain a molecular weight of 1370. A polyaminoether containing 7.83% of basic nitrogen was obtained. Polytetramethylene glycono V (molecular weight 130071300 parts) and 4,4'-diphenylmethane diisocyanate (1000 parts) were mixed at 60°C with 3
After reacting for 0 minutes, 1 DMF (2300 parts) was added and dissolved uniformly, and the mixture was cooled with water for 30 minutes. Add 50% DMF bath H (2740jds) of the above polyamino ether and react for 30 minutes under water cooling.After the reaction is complete, add DMF
4934N'/ was added, and a 10% DMF solution (1408 parts) of 1,2-propylenediamine Y was added dropwise for 60 minutes using a power bow.Furthermore, the termination reaction was carried out in the same manner as in Example 2-1, and the solution a degree 30%8
A DMF solution of segmented polyamine ether urethane with 90 voids (25°a) was obtained. Example of this solution
A film was formed under the same conditions as in Example 1 to obtain a 50 μm thick film of segmented polyether urethane with a radical nitrogen content of 2°80%. This film was subjected to quaternary salt treatment in the same manner as in Example-1, and the tertiary amino groups were converted to 100%, 75% and iJ:
The quaternary chloride was divided into three stages of 50%, and each was divided into Example 1.
Heparinization was performed under the same conditions as . In addition, a 100% quaternized heparinized film was immersed in physiological saline and stored in a beaker for 3 months while occasionally replacing the saline. When a sample film was dyed with toluidine blue aqueous solution, it turned reddish-purple. It was confirmed that heparin was stably attached.

In addition, Table 2 shows the results of the anticoagulant test conducted in the same manner as in Example-1.

These results indicate that the anticoagulant properties of the heparinized polymer of the present invention (
It is especially preferable that it is extremely excellent, and that it is effective for a long period of time even under physiological conditions (m%), and that all the tertiary amino groups contained are quaternized and heparinized. 0 Example - & 2-Methylh-2-diethylaminomethyl-1,3-propanediol (175 parts) and phosphorous acid (0.8 parts) were placed in an autoclave and reacted in the same manner as in Example 1. Let me...
A basic nitrogen goldfish 8°60%9 polyaminoether with a molecular weight of 1□670 was obtained. This polyaminoether (167
0%3), polytetramethylene glycol (molecular weight 15
DM? The mixture was added dropwise over 60 minutes. The termination reaction was carried out in the same manner as in Example 1, and heparinization was performed on Segume et al. having a solution viscosity of 850 voids. The results of blood coagulability tests performed in the same manner as in Example 1 are shown in the third column.

Comparative Example 1 Polyethylene glycol (molecular weight 19'008100 parts), ethylene glycol (10 parts), general formula: % formula %) (21) Amine-modified polyether diol (log
)l diphenylmethane-4,4'-diisocyanate (80 h) r DMF (600 parts) was mixed and polymerized at 80°C. The viscous solution was formed into a film and heparinized in the same manner as in Example 1, and the anticoagulant properties were tested. Table 4 shows the results.

Example 1 The 100% quaternized polyamide/ether urethane film obtained in Example 1 was immersed in physiological saline and stored in a beaker for 3 months while occasionally replacing the saline. Cut out a 31 square piece and attach it to the surface of a watch glass with a slot stopper.
Place 0μ on this and mark ○. IMm aqueous solution (
The clotting reaction was started by adding 25 μl. Table 5 shows the results of measuring the coagulation rate in the same manner as in Example 1 by changing the coagulation reaction time at 37°C.Comparative Example 2 3-n-propyl-3-aza-1,5- Bentanediol (147 parts) and phosphorous acid (0.8 parts) were placed in an autoclave and heated at 210 to 220°C for 3 hours under a nitrogen stream.
The reaction was carried out without removing the distilled water.

Next, the pressure was reduced to 0.3 mHa over 90 minutes, and the reaction was continued for 2 hours to obtain a molecular weight of 1700. Basic element content 1d
11.3% polyaminoether was obtained. Polytetramethylene glycol (molecular weight 1300: 1300g)
4.4/-diphenylmethane diisocyanate) (1
000 evil) for 30 minutes at 60'Q under nitrogen flow, DM? (4000 parts) was added and uniformly dissolved. Cool on ice and add a 30% DMF solution of the above polyaminoether (5
667) and reacted for 30 minutes under water cooling. after that,
1. 20% DMF solution of diamine (33
3 parts) over 2 hours, and then 20% DMFiJ? of n-butylamine. ff (36.5 parts) was added and reacted for 30 minutes. Next, a 20% DMF solution of stirrup water acetic acid (5%
DMF of segmented polyaminoether urethane with a solution viscosity of 500 voids for 60 minutes.
A solution was obtained. This DMF solution was prepared in the same manner as in Example 1, and the coagulation rate was measured. The results are shown in Table 5.

Table 5 From the results shown in Table 5, it is clear that the present invention has more durable anticoagulant properties.

Patent applicant: Toyobo Co., Ltd.

Claims (1)

[Claims] 3 (In the formula, Ro and R2 each have between - or different carbon numbers of 1
~15 alkyl groups, aryl groups, or aralkyl groups, and R1 and R2 may form a heterocyclic ring. R3 is a hydrogen atom, an alkyl group having 1 to 9 carbon atoms, or -C
Indicates H2NR1 group. Segmented polyamino ether using a polyaminoether prepared by reacting one or more tertiary amino alcohols selected from the group consisting of compounds represented by 'R2) in a proportion of 30 mol% or more of the polyaminoether raw material. 1. A method for producing an anti-blood coagulant medical material, which comprises quaternizing the tertiary amino group of ether urethane and then adding heparin or an analogous compound thereof.