JPS61126143A - Production of anticoagulant material - Google Patents

Abstract

PURPOSE:To produce the title material which is flexible and has a smooth surface and excellent anticoagulating properties, by saponifying the surface of a specified polyurethane (urea) molding, neutralizing it and bonding it to heparin. CONSTITUTION:A compd. contg. two hydroxyl groups and one ester group per molecule (e.g. methyl dimethylkolpropionate) or a compd. contg. two amino groups andone ester group per molecule (e.g. methyl ester of L-lysine) and a diisocyanate (e.g. ethylene diisocyanate) are subjected to a polyaddition reaction in the presence or absence of a polyester diol having an MW of 200-800 to obtain a polyurethane (urea). The polyurethane (urea) is molded into a film or tube, which is them immersed in an alkaline soln. to saponify it. The saponified molding is immersed in an acidic soln. to neutralize it, and the neutralized molding is bonded to heparin.

Description

DETAILED DESCRIPTION OF THE INVENTION This invention provides a novel polyurethane/or polyurethane urea,
The present invention particularly relates to a method for producing polyurethane or polyurethaneurea having excellent anticoagulant properties.

Polyurethane/urea is obtained by polyaddition reaction between diol and diisocyanate, and polyurethaneurea is obtained by chain-extending a prepolymer obtained by polyaddition reaction between diol and diisocyanate with diamine. Due to the low compatibility of the chains of heterogeneous segments (ether segments and urethane segments or ether segments and urethane/and urea segments), a heterogeneous surface structure appears in the Poly2 membrane, and this heterogeneous surface structure is relatively Expresses high anticoagulant properties.

The present invention provides a polymer membrane with even better anticoagulant properties by using a polyurethane or polyurethaneurea having an ester group on the side, saponifying and neutralizing the ester group, and then coupling heparin. While maintaining the properties of polyurethane or polyurethane urea with excellent mechanical properties, the anticoagulant properties of the surface of the molded product are further enhanced through surface treatment.

In the present invention, it is also possible to adjust the properties of the soft segment by controlling the type, degree of polymerization, and content of the diol segment or diamine segment, and it is also possible to control the molecular weight of the entire polymer chain. This means that the amount of heparin adsorbed and the size of each hydrophilic and hydrophobic domain can be adjusted, and has the advantage that the material can be designed according to the purpose.

The present invention will be explained in detail below.

I. Synthesis of polyurethane having ester groups in the side chain: - Synthesis of a compound having 2 hydroxyl groups and 7 ester groups in the molecule, and coexistence of polyether or polyester diol as an extension agent. It can be obtained by carrying out a polyaddition reaction with an aliphatic or aromatic diisocyanate, with or without coexistence.

(A) Synthesis of diol having an ester group: An example in which methyl dimethylolpropionate is used as a diol having an ester group in the side chain will be described. This methyl ester is obtained by converting dimethylolpropionate into methyl ester.

To give a concrete example of this, 219 dimethylolpropionic acid was suspended in methanol, then it was
-) Add toluenesulfonic acid and reflux for approx. After cooling, Amberlite (anionic cross-resin manufactured by Rohm and Haas) is added to remove p-)luenesulfonic acid, and then methanol is distilled off. The resulting liquid is distilled under reduced pressure (
b, p, / / r °C/s may) and colorless transparent liquid methyl dimethylolpropionate, 6?
(0% yield) was obtained. Infrared (hereinafter referred to as R) spectroscopy and elemental analysis confirmed that pure methyl dimethylolpropionate was obtained. This compound has the following chemical structure, and polyurethane can be synthesized by polyaddition reaction with diisocyanate as a diol component.

OH3 HO-OH, -0-0)I, -OH 0-O-OH3 Diols having an ester group in the side chain include the above dimethylolpropio/acid esters,
Other ester groups such as ethyl and benzyl groups may also be used.

(B) Synthesis of polyurethane having an ester group: The diol having an ester group obtained in (A) above is mixed with a polyester diol or not, and is synthesized with various diisocyanates. Polyurethane is synthesized by carrying out an addition reaction.

As polyether diols, all diols conventionally used in the production of polyurethane can be used in the method of the present invention. Specifically, polyols with a molecular weight of 200 to rooo, such as polyoxyalkylene diols such as polyethylene glycol, polypropylene glycol, and polytetramethylene glycol; polyester diols include cepatic acid, succinic acid, oxalic acid, azelaic acid, terephthalic acid, and inphthalic acid. Examples include those synthesized from dicarboxylic acids such as acids and derivatives thereof, and those obtained by ring-opening polymerization of ε-caprolactone and the like.

As for the diisocyanate, all the diisocyanates conventionally used in the production of urethane can also be used in the method of the present invention. Examples of preferred diisocyanates are ethylene diisocyanate, propylene diisocyanate, tetramethylene diisocyanate, pentamethylene diisocyanate, octamethylene diinucanate, undecamethylene diisocyanate, dodecamethylene diisocyanate, j , J'-diisonanatoglobyl ether, cyclopentelene/, J-diisocyanate, cyclohexene/, 4t-diiso7anate, -2
≠-tolylene diisocyanate, λ, butylene diisocyanate, 2,4t-) mixture of lylene diisonanate and 11-tolylene diisocyanate, xylylene-/, ≠-diisocyanate, yasilylene -/, J
-diisocyanate, ≠, μ'-diphenylmethane diisocyanate (MDI), ≠, ≠'-diphenylpropane diisocyanate, p-incyanatobenzyl isocyanate, m-phenylene isocyanate, p-phenylene isocyanate, Naphthalene/, Hiro-diiso 7
Anate, naphthalene-7,j-diisocyanate, and the like.

Production example/Methyl dimethylolpropionate, polytetramethylene glycol (hereinafter referred to as PTMG), and ≠,
Production of polyurethane containing diphenylmethane diisocyanate (hereinafter referred to as MDI): 3.? ? 7) Dissolve PTMG (molecular weight/2 PI) in 3-dimethylformamide, i, sr MD
I: (corresponding to twice the mole of PTMG) was mixed with a solution of 2yJ of dimethylformamide, and after the atmosphere was replaced with nitrogen, a reaction reaction was carried out at 60° C. for 3 hours. Thereafter, a solution of methyl dimethylolpropionate (equal mole to PTMG) dissolved in sml of dimethylformamide was added, and the mixture was reacted at 50° C. for a period of time.

Thereafter, o,o6-n-hexylamine (corresponding to 1O mol of the initially used MDI) was added to convert the inquanate group present at the end of the reaction product into a substituted urea and stabilize it. Pour the resulting polyurethane solution into distilled water,
It was purified by precipitation. Upon drying, a white polyurethane was obtained. When this polyurethane was dissolved in dimethylformamide and the viscosity at 30°C was measured, it was found that [η
] = O0 Hiroko Q.

The R spectrum of the polyurethane obtained by this method is shown in Figure/Ic. The absorption observed at i73ocm (A in the figure) is based on the ester group of methyl dimethylolpropionate, and it is thought that this is combined with the absorption of the urethane bonds generated as polyurethane is formed. The absorption at /100 Rho 1 (B in the figure) is based on the alkyl ether group -OH, -0-OH, -, which indicates the presence of PTMG. Based on these facts, it is thought that the polyurethane obtained by the above reaction has the following structure.

l Synthesis of polyurethaneurea having an ester group in the side chain: - Synthesize a compound having two 7-mino groups and one ester group in the molecule, and use this as a #1 extender to form a polyether diol. Alternatively, it can be obtained by carrying out a polyaddition reaction with an aliphatic or aromatic diisocyanate, with or without a polyester diol.

(N Synthesis of diamine having an ester group: As a diamine having an ester group in the side chain, p IJ syn (hereinafter referred to as
methyl ester (abbreviated as L-Lys) (hereinafter,
An example using L-Lys-OMe (abbreviated as L-Lys-OMe) will be described.

To give a specific example, L-Lys.coHO1 of jf is added to 200 ml of methanol saturated with dry hydrogen chloride, left to stand for one hour, and then refluxed. .

After distilling off methanol, vacuum drying is performed. The white solid produced is purified by recrystallization from ethyl acetate and methanol. In this way, °, 7rit's b -Lys-OM
s@2HCL was obtained. It was confirmed that pure I+-Lys-OMa-2HC2 was obtained by the engineering R spectrum and elemental analysis.

Next ≠, L of 7ri f -Dye -OMe @λHCj
Dissolve t in distilled water to make a saturated aqueous solution, which is K jjc
jt sodium bicarbonate (L -4+ya-OMe
-corresponding to twice the mole of HOl) was added, and after stirring for 7 hours.

Freeze dry. Add methanol, filter the soluble portion, and distill off the methanol. Furthermore, add the solvent (liqroform-methanol<2:/) and perform the same operation,
Finally, a colorless and transparent liquid with high viscosity (/j7 f's L-]
] IJ78-OMe) was obtained (yield 60%). It was confirmed that it was pure L-Lye-0M6 by R spectrum and elemental analysis. This compound has the following chemical structure, and polyurethaneurea can be synthesized by polyaddition reaction with diisocyanate as a diamine component.

000H3)! , N OH, OH, C) i, OH, OH compounds having one ester group and two amino groups in the molecule include L-ornithine ester ( For example, methyl ester), L-α,
r-diaminobutyric acid ester (e.g. methyl ester),
b-α, β-diaminopropionic acid esters (for example, methyl esters), or nine or racemic forms of these compounds can also be used.

(B) Synthesis of polyurethaneurea having an ester group: A polyurethaneurea is produced by polyaddition reaction with various diisocyanates, with or without mixing a diamine having an ester group with a polyether diol or a polyester diol. are synthesized.

As the polyether diol, polyester diol, and diisocyanate, those mentioned in ICB) above can be used.

Production Example 1 Production of polyurethaneurea containing Ia-Ly@-OMe %PTMG and MDI in a molar ratio of /:/:, 2: PTM () (molecular weight t4θ) of J-
Dissolve in dimethylformamide /,j f MDI
(equivalent to twice the mole of PTMG) was mixed with a solution of 2-dimethylformamide, and the mixture was replaced with nitrogen.
Let it react at 0℃ for 1 hour. After that, O1 Hirort's I, -
Lya -OMe' (equimolar to P T M G)
Add a solution dissolved in cc of dimethylformamide,
The reaction was allowed to proceed at room temperature for 3 hours. Thereafter, o,o tat n-hexylamine (equivalent to 10 mol of MDI initially used) was added to convert the incyanato groups present at the ends of the reaction product into substituted hydrogen and stabilize it. The obtained polycretane urea solution was poured into distilled water and purified by precipitation.

Upon drying, a white polyurethaneurea was obtained. When this was dissolved in dimethylformamide and the viscosity at 70°C was measured, it was 0,! ≠! I failed.

Polyurethane urea was synthesized in the same manner using FTMG with a molecular weight of 12 oq 100. The former is [:v]
= 0.4 here, the latter is [η] = 0.6 / j and nine.

FIG. 2 shows the engineering R spectrum obtained by the polyurethaneurea spreading method when using PTMG with the molecule @rto. l
The absorptions observed at y3ocm (A in the figure) and /100G (B in the figure) are the same as in Figure 1, but in Figure 2, /F! Near θα (in the figure,
Absorption based on urea bonds was observed in C), indicating the presence of urea bonds in the polymer. Based on these facts, the polyurethane obtained in the above reaction is considered to have the following structure.

(n-x: x=/:/) Production example-L-Lye-OMe, PTM G, MD
Production of polyurethaneurea containing I in a molar ratio of 3:l:
Dissolved in l dimethylformamide, J, Of MDI
(equivalent to ≠ times the mole of PTMG) was mixed with a solution of 31 dissolved in dimethylformamide, and after purging with nitrogen, 6
The reaction was carried out at 0°C for 1 hour. 44pt L-X to the rear
Jys-OMe (equivalent to 3 times the mole of PTMG)! d
A solution of 100% dissolved in dimethylformamide was added, and the mixture was reacted at room temperature for 3 hours. After that, o, ixwtt n-hexylamine (corresponding to iomolti used initially and qMD engineering)
was added to stabilize the reaction product by converting it into an incyanate-based substituted urea present at the end. The obtained polyurethaneurea solution was poured into distilled water and purified by precipitation. Upon drying, a white polyurethaneurea was obtained. When this was dissolved in dimethylformamide and the viscosity was measured at 30°C, [η] = 0. It was J/7.

Cypolyurethaneurea was synthesized in the same manner using PTMG with a molecular weight of 12 and 100, respectively. The former is [η] = 0.3≠-1, the latter is [η] = 0
．． 4170 and b nine. L-IJ75! -0MI
A polyurethaneurea containing S, PTMG, MDI″lr:j: /:6% lr ratio was synthesized in the same manner.When the molecular weight of FTMG is rto, /290.λioo, the viscosity of the synthesized polyurethaneurea was measured. Then, (1] = 0.210.0.1AIrOyobig, z2
I got h with r.

Using PTMG with a molecular weight of 0! , -LA8-OM
FIG. 3 shows an IR spectrum obtained by the polyurethaneurea spreading method when the molar ratio of e, PTMG, and MD was 3:l:≠. 1730cm-” (h in the figure), iioc
The absorption assignment of m (B in the figure) is the same as in Figure 2.

In FIG. 3, from the diagram λ/is j 0cIR-”
It can be seen that the absorption based on the urea bond (C in the figure) is increasing. This shows that the urea bond content in the polymer is higher than that in Production Example. The result obtained here is thought to have the following structure.

(2) Synthesis of a heparinized polyurethane or polyurethaneurea having an ester group in the side chain: This product is the aforementioned polyurethane or polyurethaneurea [hereinafter, both will be referred to as polyurethane (urea) when referred to collectively. 〕of,
Obtained by saponification, neutralization, and coupling with heparin.

Saponification treatment is performed after molding the polyurethane (urea). Molding here refers to polymer.

Refers to the processing of - into glue-like or tube-like shapes for various uses. A polyurethane (urea) molded product is immersed in alkaline melting to saponify it. This treatment changes the side chain from an ester group to a carboxylade group.

Neutralization treatment is performed by immersing the material in an acidic solution after sacrificing. This treatment converts the carboxylade group into a carboxyl group.

Heparinization treatment is performed after neutralization treatment.

A polyurethane (urea) molded product is neutralized and the side chains that have become carboxyl groups are reacted with water-soluble carbodiimide. Heparin is added here to camp the 7-mino group in the hebari/molecule and the carboxyl group in the molded product, thereby covalently bonding the heparin. In the method of the present invention,
Heparin, heparin, heparin, heparin, heparin,
metal salts can be used.

Examples Polyurethane urea (L-Lea-OMe, PT
M Gr60. MDI=/ :/ :J)'lji/chi#
After dissolving 10% by weight in formamide and casting it on a glass plate, it was heated with an infrared lamp to distill off the dimethylformamide, and was further vacuum dried to completely remove the dimethylformamide, forming a membrane. did.

This membrane is immersed in a solution of 4CN sodium hydroxide aqueous solution and methanol in a volume ratio of /:3 at room temperature for 3 hours. After this, wash thoroughly with distilled water.

Next, this membrane is immersed in a solution of 10% citric acid aqueous solution and methanol in a volume ratio of /:3 for 3 hours at room temperature, and then thoroughly washed with distilled water.

The thus treated membrane was further treated with IQ%l-ethyl-j
-(j-dimethylaminepropyl)carbodiimide aqueous solution (pH 41,73Kp4 in 0,/MMKday (JMES(N-solfluorino)ethanesulfonic acid) buffer)
Soak for 3 minutes at room temperature. After washing thoroughly with distilled water! Immerse in a chronic heparin aqueous solution (adjusted to pH≠7j with O,/MMK8 buffer) at room temperature for 72 hours. Finally, thoroughly wash with distilled water to obtain heparinized polyurethane urea.

The ATR spectra of the saponified polyurethaneurea membrane, the neutralized polyurethaneurea after saponification, and the heparinized polyurethaneurea membrane are shown in Figures a, b, and c of the figure. In Figure ≠ a, by saponification treatment / t & Jan
-' (A in the figure), absorption based on the carboxyl group was observed, and in figure μb, the peak disappeared by citric acid treatment, and the absorption of the carboxyl group overlapped with the absorption of the urethane bond /7J0crn.

In Figure PC, after heparinization treatment, 1oji,
/0/6an, absorption based on the ether bond of the sugar moiety of heparin (B in the figure) was observed.

(2) Anticoagulant test The heparin-bound polyurethane (urea) obtained by the method of the present invention has excellent anticoagulant properties, and the test results are shown below together with comparative examples.

The samples used in this test are as follows.

Sample (1) Glass sample (2) Polyurethaneurea (L-Lye-OMe
:PTMG2100 :MD Engineering==/:/:j) Sample (3) Polyurethaneurea (L-Lys-OMe:
PTMG 160:MD Engineering=/:/L) Sample (Ly8-Ly8-OMs: PTMG/Cog0: MD)
PTMG / Jri 0: MD engineering = j: /: 4ri sample (6)
Polyurethaneurea (LLysOMe:PT
MG/JRIO:MDI=j:/l) Sample (7) Surface saponified polyurethaneurea (L-Lye-OMe:
PTMG 2/00 :MD engineering=/:/:J) Sample 0>Surface saponified polyurethane urea (L-L
ys -OMe: PTMG r A O: MD Engineering: /:/:Co) Sample ('P) Surface saponified polyurethaneurea (L
-Lys-OMe: PTMG/2ri0:MD Engineering=
=/:/:ko) Sample (surface of /, 9 polyurethane urea (L-L
ye-OMe: PTM G/2riO:MD
= 3:/ :4c) Sample (lr) surface saponified polyurethane urea (T,
-Lye -OMe: PTMG/2
TaO:MnI=j:/:A) Sample (lλ) surface neutralized polyurethane urea (L-Ly
s-OMe: PTM02100:MD Engineering=/:/
:J) Sample (/3) - surface neutralized polyurethaneurea (b -
4+ys -OMe: PTMG I 60: MD
I:/:/:J) Sample (/ly surface neutralized polyurethaneurea (p-Ly
s -OMe: P T M G /λ θ:MD engineering=l:l:λ) Sample (/j) surface neutralized polyurethane urea (I, -L
ye-OMe: PTM G/2riO:MD
= j:/:4') Sample (16) Surface neutralized polyurethaneurea (r, -L
y+-OMe: PTMG/2riO:MD Engineering=r:
/:/i) Sample (17) Heparinized polyurethaneurea (L-
Lys-OMe: PTMG 2/00: MD engineering=l:l:λ) Sample (it) Heparinized polyurethaneurea (I+-
Lye-OMe: PTMG 140:MDI:/
:/ :ko) Sample (1) Heparinized polyurethane urea (L-L
ys-OMe: PTMG /2riO:MD engineering==
/ : / :λ) Sample (-11ff) Heparinized polyurethaneurea (
L-Lye-OMe: FTMG/JRIO:MD Engineering=3:l:≠) Sample (-Z/) Heparinized polyurethaneurea (r,
-Lye -OMe: PTMG/290:
MD engineering=j:/:6) Sample (22) Polyurethane (dimethylolpro[methyl pionate: 1'TMG/Jri0: MD engineering=l
:l:λ) Sample (-27) Saponified nine polyurethane (methyl dimethylolpropionate: PTMG#RI0:MD Engineering=/:/:λ) Sample (coli-neutralized polyurethane (methyl dimethylolpropionate:
PTMG /290:MDI=/ :/ :2) The above samples (2) to (λ) were made into a dimethylformamide solution, placed on a watch glass made of the same glass as the above sample (1), and the solvent was evaporated with an infrared lamp. The test sample was prepared by distilling it off and drying it under reduced pressure for one night.Saponification, neutralization, and heparinization were then carried out.For comparison, a watch glass without any treatment was used as a sample (1 ).

The test was conducted as follows. Take 30ml of blood from the femoral artery of a female, add 1ml of AOD solution (a solution consisting of citric acid, sodium citrate, and glucose), and pour 2ml of this into a watch glass as described above. Pour into each sample prepared above and add 0. /M aqueous calcium chloride solution is added to initiate clotting. Distilled water is added every time a set period of time elapses to stop blood clotting, and the resulting frame is fixed with formalin and replaced with distilled water.

Remove the wet clot with a spatula, sandwich it between tissue paper to absorb excess water, and weigh. The results of the thrombus formation test are shown in Table 1.

Table 1 Sample number (1) (ko) (3) Weight Chi Weight Chi Weight Chi After 10 minutes ss, ≠ 100 /λ, j λko, 131. !
4≠, l/! Z! ! , 4L 100
2, / 3, t ≠0.1 73.7
J□＃! ! , u 100 /I, /J
J7 4c6. J IrJj sample number (≠)
(j) (4) Heavy t
% Weight Large Weight After IO minutes 2
13! 2,0 2r,j! /,j J/J
! 7. J/Jr I 441. J r/, l
r30. Ta jr, r 34c, a
ti, it 20 y 36,3 49. A JJ',
70,2 J/, Ojl, ri2jzzfl
Tarr, 2 37. OAt, r 2ri,
a rx, r・sample number (7)
(1) (ri) Weight
Weight Width Weight - After 70 minutes Core, /
Hiro 1. Ta /7. j Jl, 1. Jl, j ri, Hiroshi/II Kohe J Jl, j ko l, 63reta core, Hiroshi ≠2. jkoQgJ9,1
42. Ko 2! , l dub, 6 λ Otsu!
≠2. Buco j z 4L/, 0 7J, j
Jl, Ta 6/, Ko λri, J
jJ, 7 sample number (10) (/
/) (/ko) Weight Ch Weight
Weight After io minutes /7. j Jl,A
23. Ta 4c3. / Jl, 0 6J, /
/zg /&, J λri, 2 32.0
! 7.1 4C2,j 74,4c KOI l ri, I Jl, 7 kot, l
4c7. J Jo, i zu, 7ko1120, 23bu,, r 21. J Il,/
Kot, i μ7.7 sample number (jJ)
(/ri (lri weight)
Weight Chi Weight Chi 10 minutes later JJ, 7
60. Ta /! ,j 21.0 /rij
Jl, Jlj y j/, $ r6.
A 3, j! r, J λ7.
t 4c, octopus 0 # IAO,! 7
J, / 223 4c/, J Jtj
70. /Ko! z 4! ! , J Il, J /j
, OJ7. / 4A7,0 111,0 Sample number
(/A) (/7)
(tr) Weight Chi Weight Chi Weight
10 minutes later Koj, 7 6. Hiro 00
00/jlJri, 2 70,7 θ 0
0020 z 4L4c, 4A 10.
λ/, 2. JJ, 2. / 0 02
1g! 0. j tao, ir io
, Ta lji, 700 sample number (
(Jl) (Jl) Weight Chi Weight Chi Weight After 10 minutes
O, Ta /,! 7. lr/4, /
0 0/! z /, 7 J, 0 0
0 σ 0λ01 /λ, 12
λ/8ta oo o.

21 # /lr, OJJ, J j
, 4Cta, 700 sample number (2
2) (JJ) (Stiff weight Chi Weight Chi Weight Chi 10 minutes later aYj z3,4c 21.2 31
F, 3 tri, u Jl, 0/II
ko r, 7 jJJ ko sen, j ≠4L, 2
λJ, r 4! J, j λσ t JP, /
jJ, ko Jl, r #/,, 2 23
．． 9 143. IJj y 21.0!
0. / λμ, 3 ≠ 3. t 2ri,
/jJ, jtable/%C, the weight is the cape, and the magnification value is the weight of the clot when using glass (sample 1).
0096, and shows the relative responsibility for this.

According to this table, blood completely coagulates within 70 minutes on glass (sample 1).

The untreated polyurethaneurea of samples (2) to (6) was saponified (sample (7) to <ii>), neutralized (sample (l)
~(#)) K tends to improve anticoagulability. This is thought to be because the polymer surface becomes hydrophilic through saponification and neutralization.

Furthermore, when samples (17) to (U/) were heparinized, very excellent anticoagulability was obtained.

In particular, no thrombus formation was observed in samples (Il) and (Col), which have a high ester group content and a large amount of heparin bound.

Polyurethane membranes are flexible and have smooth surfaces, and they also exhibit excellent antithrombotic properties based on their microphase-separated structure. The present invention has shown that the antithrombotic properties of heparin can be further improved by supporting it on a polyurethane (urea) membrane.

Based on the excellent mechanical properties of polyurethane (urea),
The polyurethane material obtained by the present invention can be used in various medical materials that require antithrombotic properties, such as vascular catheters, cannulae, shunts, extracorporeal blood transport circuits, blood pumps for artificial hearts, etc., and in parts that come into contact with blood vessels. All can be used. In addition, by changing the type and composition of the constituent components of the microphase-separated structure of polyurethane (urea), the interaction with blood components such as blood proteins and platelets can be adjusted, so it can be used as a biocleaner, bioseparator, bioactivator, etc. It can also be used.

What has been explained above and shown in the specific examples of implementation is related to typical illustrations to aid understanding of the present invention.
The present invention is not limited to these examples, but is bound only by the scope of the claims, and may include other modifications and variations within that scope.
Modifications can be made.

[Brief explanation of drawings]

Figure 7 is the engineering R spectrum of the polyurethane manufactured by the smearing method of 13IJ Preparation Example 1 of I] Figure 3 shows the H term B
Figure ≠ shows the ATR spectrum of the polyurethane urea produced by the coating method produced in Production Example 2. Rarely in the R spectrum are a and b in the figure.
, c are ATR spectra of surface-saponified polyurethaneurea, surface-neutralized polyurethaneurea, and heparinized polyurethaneurea, respectively. In FIG. 1-≠, the vertical axis is absorption and the horizontal axis is wave number (α). Placement attenuation Accommodation cm-1 2 Wave number cm''''1 Figure 3 Wataku cm'

Claims (1)

[Claims] Polyurethane obtained by polyaddition reaction of a diisocyanate with a compound having two hydroxyl groups and one ester group in the same molecule, or a compound having two amino groups and one ester group in the same molecule Or after molding polyurethaneurea, saponifying the surface of the molded product, and further neutralizing it,
Method for producing an anticoagulant material characterized by binding heparin