JPS6077767A - Production of living body function membrane - 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] This invention is a polyurethane film soaked in biofunctionality.
This is completely different from the manufacturing method.

Polyurethane is obtained by e) synthesizing prepolymer 1 by polyaddition reaction between novomer diol and diisonoanate,
It is a polymer made by using a chain extender, and it contains ether bonds, urethane bonds, urea and other hexagonal groups. The N-H of this urethane bond and urea bond becomes a proton donor, and the ether oxygen of the ether bond, and the carbonyl oxygen of the urethane and urea bond become proton acceptors, and all intermolecular hydrogen bonds are formed between these bond groups. , polyurethane has a microphase content 1 that is effective for creating a spherulite structure and anti-blood framework.
lt1. It has a structure.

Linear or cyclic 2' of α-amino acids! The body contains peptide bonds with strong hydrogen bonding capacity. The cyclic uniter of α-amino acids has a rigid molecular skeleton and therefore has good crystallinity. On the other hand, linear and dimeric α-amino acids have flexible molecular skeletons, so the crystalline value is lower than that of cyclic and dimer forms.

Therefore, the leg-shaped, cyclic, or dimer of L-serine having a hydroxyl group in the side chain of α-amino acid can not only be used as a button VI lengthening agent for polyurethane, but also have hydrogen bonding ability not contained in conventional polyurethane. The development of a new form of phase structure is expected due to the delicious peptide bonding. It is possible to change the crystallinity of polyurethane by selectively using curled annular shapes, two-dimensional and linear shapes, and two-dimensional shapes, making it possible to delicately adjust the film function of polyurethane films.

By changing the type and degree of polymerization of oligomer diols, the properties of the soft segment portion can be completely controlled. When only polytetramethylene glycol is used as the oligomer diol, the moisture content of the membrane is small, but when hydrophilic polyethylene glycol is used together with it, the moisture content of the resulting polyurethane membrane increases, making it difficult to separate the substances related to the trial court. It is suitable for removal and can be used as a dialysis membrane for dialysis therapy.

Against this background, the present inventors have conducted extensive research with the aim of providing a membrane material that has excellent permeability to substances related to the original vehicle and is also biocompatible, and has successfully completed the present invention. It has arrived. That is, the gist of the present invention is to coexist polytetramethylene glycol and polyethylene glycol with a linear aggregate or cyclic dimer of an α-amino acid having a hydroxyl group, to cause a polyaddition reaction with a diisocyanate, and to process the resulting polyurethane. The present invention resides in a method for producing a biofunctional membrane, which is characterized by forming a membrane.

The present invention will be explained in detail below.

(1) Synthesis of polyurethane containing IWN-like dipeptide as one component: This product synthesizes dibebutide diol by condensing α-amino acid having a hydroxyl group in the side chain, and uses polytetramethylene glycol and polytetramethylene glycol as chain extenders. It is obtained by carrying out a polyaddition reaction with diincyanate in the presence of polyethylene glycol.

(A) Synthesis of thin dipeptide diol: An example in which L-serine (hereinafter abbreviated as L-serine fH-8θr-OH) is used as the α-amino acid having a hydroxyl group in the side chain will be described. The linear dipeptide of H-Ser-OH has the amine terminal carbopenzyloxylated (hereinafter, the 7 groups are abbreviated as Z) and fcZ-8er-○
A serine linear dipeptide in which both terminal groups are protected by activating the carboxyl terminal of H+4i k and condensing this with H-8θr-OMe, which is obtained by separately methyl esterifying the carboxyl group of H-8θr-OH, That is, Z
-Ser-Ser-OMe is obtained.

To give a concrete example of all this, 8! in -01 H-8or-OHf methanol! Let it become cloudy and keep at OC and bubble hydrogen chloride gas through it for about 6 hours. Then, by distilling off all the methanol and recrystallizing from the solid methanol obtained, H-8er-OMe jHC6/
7 ta @1 (yield: 59). The melting point of this product was 76.2 to 763C, and it was confirmed by thin layer chromatography (hereinafter referred to as TLC) and infrared (hereinafter referred to as IR) spectrum that pure H-8er-01+4e-HCl was obtained.

g2 of H-8er-OMe-HCtf was added to a saturated aqueous solution of sodium bicarbonate, maintained at about 20c, and added to Z-C6(H-6er-○+, (e-)(Ct
/, 7 times brighter) was added dropwise and allowed to react for 9 hours.

The separated oil layer is extracted with ethyl acetate, and the extract is washed with S polyhydrochloric acid and then with water, dried over an anhydrous sodium sulfate ram, and then the ethyl acetate is distilled off. The obtained solid was recrystallized from a mixed solvent of pentane and ether to give Z-8ar-
OMe / 0. 'lf was obtained (yield gθ%). The melting point of this product is 27-3.2C, TLC, IR7,
It was confirmed by high performance liquid chromatography (hereinafter referred to as HPLC) that pure Z-8er-OMe was obtained.

Dissolve Z-Sθr-OMθ of 7F in methanol, and prepare hydrazine hydrate S, RiS(Z-8er-OMe)3
2 equivalents) was added, and the mixture was reacted for about 1 OCT for 2 q hours. Then add ether and react for a further 6 hours under OC. F@ the precipitate H and recrystallize it from a mixed solvent of methanol and ether to obtain Z-8er-NHNH2 needle crystals 7,
g2 was obtained (yield: go%). The melting point of this substance is /gO~
7gIC, according to TLC and IR spectra! l
It was confirmed that pure Z-8er-NHNH2 was obtained.

Z-8er NHNH2' obtained as above)
, A; 9? is bathed in dimethylformamide, -5C
Do not stir with 3. ! ; / f isoamyl nitrite (
Add Z-8er-NHNH2 and equimolar amount). Although it is thought that Z-8er-N3 was produced in the solvent, this product was subjected to the following reaction without being isolated. That is, the above-synthesized H -Ser-
OM e・HC411,t, 7P (Z-ser
-NHNH, 1 equimolar amount) in dimethylformamide (containing a small amount of triethylamine) was added, and the mixture was reacted for λ days under OC. All volatile components were distilled off, the residue was extracted with ethyl acetate, and this extract was washed with aqueous rum solution, trivalent hydrochloric acid, and water, dried over anhydrous sodium sulfate, and extracted with iY￥. Ethyl acid was distilled off. The obtained solid was purified with a mixture of ethyl acetate and petroleum ether, and 3,32 needle-like dry crystals of Z-Ser-Ser-OMe were obtained (yield: 3 pieces, 3 pieces). ). The marking point of this product is /l/2~/GudaC, and the TLC1IR spectrum and elemental analysis show that it is pure Z-S e r
-Ser-OMe was obtained/this was confirmed. The methanol solution was 6 tatami-3.

The above reaction is expressed as follows.

H-S e r - OH le standing room H-S 8 r-.

Me-HCtm Z-8er-OMe -HCtn Z
-ser -NHNH2C5H1No ZSer-N3
H-8er-OMe-HClZ -S e r -S
e r -OM eAccording to this method, the specified reaction proceeds without modification or interference even if the side button group of serine is not retained.
It is possible to obtain Z-88r-8er-OMe with extremely high efficiency. be.

HO-CH2-CH-C-NH-CH-CH2-0H1
) 1 1 NHOC201 C=0 0 ((B) Synthesis of polyurethane containing all +91-type dipeptide diol: Polytetra of various degrees of polymerization is added to the linear dipeptide diol obtained as described in (A) above. Methylene glycol (hereinafter abbreviated as polytetramethylene glycol iPTMG) and polyethylene glycol (hereinafter abbreviated as polyethylene glycol '1PEG) are allowed to coexist, and a polyaddition reaction is performed with the total diisocyanate. PT
The ratio of MG and PEG to be used is usually selected from a molar ratio of about /v/.

In the above polyaddition reaction, an example will be described in which methylene bis(lI-diisocyanatobenzene) (hereinafter abbreviated as fMDT) is used as the diyne 7nate.

Example/PTllG with molecular weight/336 (hereinafter referred to as PTMG/336
It is abbreviated as In the description that follows, the numerical value appended after PTMGO represents the molecular weight thereof. ), molecular weight'
/ sq o PEG (hereinafter abbreviated as PEG lj da θ).

Also in the subsequent descriptions, the numerical value appended after PEGO represents its molecular weight. ), MDI and the above (A)
[Hereinafter, this polyurethane will be referred to as PU (
PTMG/331. /P'F2G 7kQO, MDI,
Production of PT'lJG/336 of θ, 39 and o, tt!
A total of 0.0 g of an equal mixture of RY PEG/3'IO was dissolved in 0.0 g ml dimethylformamide. ．． 29P MD
The mixture was mixed with a solution of 2 mI (P T M G , P K G in moles twice) and 2 mi dissolved in formamide, and the mixture was replaced with nitrogen and reacted at 60°C for 7 hours. Then 0.209 2-8er-8er-OMe
(P T M G , equimolar to P 'B2 G),
! The solution soaked in ml of dimethylformamide was added and reacted for 50c'''C-9 hours.Then, the solvent dimethylformamide was distilled off and the viscous solution was poured into water, resulting in a viscous, slightly brown layer. A polymer was obtained. After washing with distilled water several times, it was exposed to light and dried on 1I phosphorus oxide for 2 q hours. This polyurethane was dissolved in dimethylformamide and its viscosity at 30C was measured. [η] = o, 3s and fco Under these conditions, the molecular weight calculated by applying the relationship between [η] and molecular weight reported for polymethyl methacrylate was approximately 1/10,000.

Molecular weight/100 P T ) if G (hereinafter P T
M G#//θO) and Molecular sumo wrestler/θOθ's P
E(] (hereinafter abbreviated as PEG /θ0θ) and PTM L3 (hereinafter referred to as PT
abbreviated as M0.2//7) and a molecular weight of 2000 PE.
Polyurethane was totally synthesized using a combination of G (hereinafter referred to as PEG 200θ and approximately 61) by an operation similar to I'o'1. Obtained PU (PT17G / 100/P
EG 100θ, MDI, Z-8er-8er-OMe
) is brown and [η:] = 0. ．． 3/, the converted numerator 1 was about J million. Also, P U (P T M
G, 2//7/PEG200θ, M
DI,Z-Ser-Ser-OMe
) is pale yellow, [η] is 20.3, and the equivalent molecular weight is approximately 31.
It was 10,000.

The solubility of these polyurethanes was that they were soluble in hexamethylphosphoamide, dimethylformamide, and dimethylformamide, and insoluble in water, acetonitrile, methanol, chloroform, benzene, and dioxane.

PU (PTMG 2//7/F#G, 2000゜M
FIG. 7 shows the rR spectrum of DI, Z-8et-8er-01/le) obtained by smearing method VC. In this IR spectrum, the absorption at /7.20σ-1 (location indicated by A in the figure) is based on urethane bonds and ester groups. /Otsu! θcm-' (in the figure, B
The absorption observed at the location shown in ) is Z −S er −
Sθr -OMθ is based on amide 1 of the amide group of the acid component. 75ri θcyn-' (location indicated by C in the figure) on the capital side is Z -Ser -Sθr-○
The absorption based on the amide ■ of the amide skin of the Me component and the phenyl group ÷ was 1211111, and it was confirmed that M DI was present in the polyurethane cloth. talented //
The absorption occurring on the side of θ0Crn-1 (both places indicated by D in the figure) is alkyl ether,! ;-CJT, -○-CH
, -.

Based on these facts, the above reaction is as follows, and the resulting polyurethane is thought to have the following structure.

-〆11111111'--ocNQco2-C>Nco aMF (1) Synthesis of polyurethane containing a cyclic dipeptide as one component: This product is produced by cyclization condensation of an α-amino acid having a hydroxyl group on its side axis. This can be obtained by synthesizing a cyclic dipeptide diol, and performing a polyaddition reaction with a diisocyanate in the coexistence of polytetramethylene glycol and polyethylene glycol as an elongating agent.

(A) Synthesis of cyclic dipeptide diol: An example of using L-serine as the α-amino acid having a hydroxyl group in the side chain will be described.

Z-8er-8e synthesized by method (A) of (1) above
r OMe /,! f f 'I Dissolve in Oml of methanol (kept saturated with HCl), add Pd black at θ, 32, and bubble in hydrogen for about S hours. The bath solution was filtered 1' and methanol was distilled off, and the resulting residue was washed several times with n-hexibun, and then diluted with H-8er-8er-OMe .HCl.
/, θta was obtained (yield q3.6). T.L.
Pure H-8er-8er by C and R spectra
It was confirmed that -OMe.HCl was obtained.

Thus obtained fc, H-8er-8θr-O
Dissolve H-8e in methanol (keep the NH3- saturated) in Me-HCl/, Of 'I/me.
The concentration of r-8er-OMe was 0.1 M), and the reaction was carried out at room temperature for 2 hours. After distilling off the volatile components and washing the residue with n-hexane, a dipeptide diol in which L-serine is cyclized and condensed [hereinafter abbreviated as -tc-(Ser)2] is obtained.
The needle-like crystals are Oj! ? (yield: 6.7 l). The melting point of this thing is 2! ~, 211gC, pure C-(ser) by elemental analysis and engineering R spectrum.
It was confirmed that 2 was obtained.

The above reaction is expressed as follows.

NH3/MelOH 8e　r　-01,-e-HCtC(Ser).

According to this method, Selin's 11! Even if the II M hydroxyl group (is not uniform, the specified reaction (H,,) proceeds without modification or hindrance, and it is possible to obtain < c-(ser)z with high efficiency.C-(Ser) It has the following chemical structure and can be totally synthesized as a polyurethane by subaddition reaction with diisocyanate as a diol component.

(B) Synthesis of polyurethane containing cyclic dipeptide diol: The cyclic dipeptide diol obtained as described in (A) above is mixed with PTMG and PEG of various degrees of polymerization, and subjected to polyaddition reaction with diisocyanate. have them do it. Mixture of PTMG and PEG
1 case may be generally the same as in case (1) above. An example in which all MDIs are used is shown below.

IJco PTMG /100/PPG /θ001M DI and C (Ser) 2 and min polyurethane [Hereinafter, this polyurethane i PU [: PTMG/100/
Production of PELJ 1000, MDI, C-(Ser)2]: θ, ? , 2 f's PTMG /100 and 0,2ri2
of PEG 1000 was bathed in g ml of dimethylformamide and 0. ．． 29f(D+iDr
CPTMG, equivalent to twice the molar amount of PEG) f J
The mixture was mixed with a solution dissolved in 7 ml of formamide, and after the atmosphere was replaced with nitrogen, the mixture was reacted in a tore for 7 hours. After that, O0
/2 C-(Ser).

(PTMG, PEG and equimolar) A solution dissolved in dimethylformamide of 'x 10 me was added and reacted at 5ore for 2q hours. After the reaction is complete, the solvent dimethylformamide is completely distilled off and concentrated, and the residue is poured into aqueous solution to precipitate polyurethane. When dried under reduced pressure on this "L'l" pentoxide, a light brown polyurethane was obtained. This material had a high water content, and showed a water content of 23%. As the alkylene diol, PTMG/3.) b/PF, G/!
;'70, Kept (Bow PTM G, 2//7
/ P E G , using 2000 combinations, 10''
Polyurethane was completely synthesized using the same procedure. The moisture content is P
U(:PTMG13.7b/pwo/sqo, MDI
, C-(Ser%) is 17.2, PU[PTMG co//7/PEG, 20θo, MDI, C-(Ser)
2′] was lI/%. In addition, these polyurethanes were dissolved in dimethylpolamide, and the viscosity at 30C was measured to determine [η]. Under these conditions, [η] and molecular weight lS reported for polymethyl methacrylate were determined.
When the molecular weight was calculated by applying the equation, it was found that PU [PTMG /100/PEG 1000. MDI,C
-(Se)2)], Lt [η] = o, 2q, molecular weight, 200,000, PU[PTMG/,? ab/pwa75riθ, MD I, C-(Ser)2:) Tl1Cη]
=0.3.2, molecular weight 2s, PTJ CPTMGj/
/7/PF2G, 200θ, MDI, C-(Set)
In 2), [η] = θ, 3q, and 20,000 in the numerator.

pu (PTMG 1loo/pFa 10oo.

The IR spectrum of MDI, C-(Ser), ) measured by the KBr method is shown in the figure. In this IR spectrum, 7
! , 20 boxes-1 (D in the figure) and / AA Ocm-'
The absorption observed at (B in the figure) is C~(Ser), based on the amide group of the component ('mo(7)theal./700
The absorption observed in ctn-' (A in the figure) is based on urethane bonds that occur as polyurethane is formed. /sqocm-' (several sets at C in the figure)] is based on the phenyl group of M D I. Based on these facts, it is believed that the polyurethane obtained in the above reaction has the following structure.

The production of segmented polyurethanes according to the invention is not limited to the above-mentioned cases, but also includes other cases.

For example, as the amino acid having a hydroxyl group as a component of the dipeptide diol used in the production of polyurethane ff, in addition to the above-mentioned lines, leonine and tyrosine can be used.

These α-amino acids have D# heptalytic forms, but any of them may be used. It is also possible to use a mixture of both, or a racema ξ form. , it is also possible to use a mixture of two or more different α-amino acids. In all these cases, both linear and concessional dipeptides can be synthesized and used as raw materials for polyurethane.

In the case of a linear dipeptide, it is necessary to protect the amine group and the carboxyl group.

As the protecting group for 7mi/4, in addition to carbobenzyloxy7 group, t-butyloxycarbonyl group and formyl group can be used.

In addition to methyl ester, benzyl ester and amide can be used as the anchoring group for the truncated carboxyl group.

When a mixture of PTMG and PEG is used according to the method of the present invention, the resulting polyurethane has a higher water content and potash than when PTMG is used alone, and its utility value as a dialysis membrane is reduced.

In addition to the above-mentioned M D , diisonanates that can be used in the production of polyurethane include aromatic diisonanates such as hexamethylene diisocyanate, toluene diisocyanate, phenyle//ino/anate, and quinolyl diisoneanate. , also methylene bis(4
Aliphatic diisocyanates such as I-isocyanatocyclohexane), l-carbomethoxy-/I6-diisocyanatohexane and the like can be mentioned.

(+10.Method for forming a polyurethane film containing 1M-shaped or lateral dipeptide diol: To obtain a film from polyurethane formed as described in (1) and (It) above, conventionally known formation methods are used. It can be carried out according to the membrane method.

The method is illustrated below.

Example 3 Method for forming a polyurethane film under irradiation with an infrared lamp: 0.0 sP polyurethane is dissolved in z ml of dimethylformamide and stirred day and night to form a uniform G solution. This was cast onto a clean horizontal glass plate, and a 25θW infrared drying lamp was placed at the 3θ position above the glass plate.
A stand was set up, a transparent dustproof case was placed over the lamp, and the lamp was turned on for 2 seconds while air was fed into the transparent case to remove evaporated dimethylformamide. The obtained polyurethane film easily peels off from the glass plate when immersed in distilled water. This was dried over phosphorus pentoxide for 2 days. The obtained polyurethane film is a transparent homogeneous film,
The iQ thickness was approximately -04 m. AT of this membrane, R-4
The R spectrum was measured and there was no difference between both sides of the film.

In order to investigate the cross-sectional structure of this shredded film, it was placed in liquid nitrogen (−
79! rc) and examined with a scanning electron microscope. As a result, a large number of micropores were observed on the air-side surface of the film during film formation, which is thought to be caused by rapid evaporation of dimethylformamide due to irradiation with an infrared lamp.

Example: Polyurethane film forming method at room temperature and atmospheric pressure: 0.0! Polyurethane k of 9, dissolved in dimethylformamide of 2 m: - stirred day and night to form a homogeneous solution. This was cast onto a clean horizontal glass plate, and approximately 2
The sample was allowed to stand for λ days at a room temperature of 5C and atmospheric pressure to gradually scatter dimethylformamide, and then dried under vacuum for 3 days.

When the resulting polyurethane 1 dust was placed in distilled water, it easily peeled off from the glass plate. This was vacuum dried over phosphorous pentoxide for an additional 2 days. The obtained film was a transparent homogeneous film similar to the film obtained by irradiation with an infrared lamp, and the film thickness was about -0 μm. When the ATR-IR spectrum of this film was measured, there was no difference between both sides of the film.

In addition, in order to investigate the cross-sectional structure of this membrane, the membrane was fractured with a liquid phoneme and examined with a scanning electron microscope. I couldn't.

As the film forming method, methods other than those exemplified above can be used. When dimethylformamide is used as a solvent, the temperature is suitably in the range of room temperature to about 1001::. There are 14 pressure ranges from /atmosphere to 0raaHf. In addition to dimethylformamide, hexamethylphosphoamide, dimethylsulfoxide, and the like can be used as the film-forming solvent.

Next, the biofunctionality of the polyurethane film obtained by the method of the present invention will be explained.

(IV) Urine blue h'1-related substance permeability test: A membrane containing amino acid components such as the one obtained by the method of the present invention can be expected to selectively interact with solutes. Permeability was measured using creatinine, urea, and uric acid solutes.

The samples used in this test are as follows.

Sample (I) PU (PTi, 40/100/PBG
1000゜+V+D I, Z ser Ser C1
+, (e) Sample (21PU(PTW, G /y3b/
pEo/sg0, MDI, Z-8er-8er-
OMe) Trial wood 031 PU (Pl, τGλ//7/P
EG, 2000, MDI, Z-Ser-
S e r -OM e )ii,! Department (4i P U
[PTM() / /θo7pEaioθO1MDI
, C-(Ser)2] Sample (5ri PU['PTMG /3.36/P, EG
/! ;IIθ,MDI,C-(Ser),] Sample+6) PU[PTMG 2//P E o
Sample (7) Cellulose acetate The above samples (1) to (7) were formed into films using a dimethylformamide solution using an underground lamp irradiation method. Sample (7
) has been used as a dialysis membrane material for artificial kidneys, and is included here for comparison.

The test was conducted as follows. 0.7g5c of sample M
It is sandwiched between a piece of silicone rubber with a circular hole of size NL, and immobilized on both sides with two dialysis cells made of methacrylic resin. (In order to improve the adhesion between silicone rubber and sample membrane,
Silicone grease was used on the parts other than the holes. ) A bath solution with a known concentration on one side of the dialysis cell, and 70% distilled gold on the other side.
0 ml of the solution was added and stirred with a stirrer, and the change over time in the concentration of the solute that permeated was investigated. Further, in this test, the dialysis cell was placed in a 2&fi constant temperature bath. The time-dependent change in solute concentration during permeation is due to the increase in solute concentration on the distilled water side over time.
mb was collected and its concentration determined. Then, based on the theoretical transmission formula, ln□ and time t'ipC"-, 2C
1; By making lots, the permeability coefficient P for each membrane was determined from the slope.

P: Permeability coefficient CCTdl''-'IA: Permeation membrane area (m) δ: Membrane thickness (1) V: Permeation cell volume fj't (m) C''2 Initial vA degree on the feed liquid side (mole/crd )C
t: Solute concentration (mole /
crd) The film thickness was measured using a simple film thickness tester.

The deviation measurement of each melt 15 is as follows.

For N a Ct, C by IJ Oh 1- method
It was determined by titration of t-, using chromium potassium as an indicator. When θ, θ/H silver nitrate d is dropped, p
, yct scuttling occurs, and when it passes the end point, A92Cr04
It produces red sedimentation.

Urea was quantified using varadimethelaminopenzaldehyde, which was derived from Nuch's base as shown below. θjml of PDAB-H + bath solution was added to the sample/ml, and after standing for 70 minutes, the absorbance of Gugu Onm was measured using UV light.

On the other hand, a calibration curve was created using a urea standard solution of known concentration. This calibration curve was determined by the JS square method. Therefore,
The concentration of urea can be determined from the absorbance. Also PDA
B-H+solution HPDAB! ? Dissolve it in special grade ethanol, make /θOml and take it into a volumetric flask (100ml), gently add concentrated sulfuric acid Sme, add PDAB solution and make 100ml PDAB・H.
''Solution V1.'' was prepared.

Calibration curves were prepared for creatinine and uric acid, and the maximum extinction coefficient 'max was calculated from the slope of the calibration curves. And this ε
The solute tQ degree of the sample was determined using maX. Next, in uric acid, since water has 9++i Rr properties, pP
+9. /g of borate buffer was used. The measurement results are shown in the table below.

The value of the transmission coefficient includes an error of about IO. It can be seen from this table that as the molecular weight of PTMG/PEG increases, the water content increases and the permeability coefficient also increases. It can also be seen that the permeability coefficient decreases as the molecular weight of the solute increases (N a CL, urea, creatinine, uric acid). Cellulose (sample 7) has a low water content, so solutes hardly pass through it.

It was confirmed that the membrane produced by the method of the present invention exhibits the above-mentioned unique physical properties and also has good antithrombotic properties. Therefore, the obtained membrane is expected to have excellent effects as a dialysis material for artificial kidneys.

What has been described above is related to typical examples to help understand the present invention, and the present invention is not limited to these examples, and other modifications can be made within the gist of the invention.

[Brief explanation of the drawing]

Figure / is obtained by example / in the text, fCPU (PTMG
, 2//7/PEG, 2000, MDI, Z-Her
-8er-OMe).
, G 1000. IR of MDI, C-(Ssr)2')
A spectrum diagram is shown. In the figures / and -, the vertical axis is the transmittance (channel), and the horizontal axis is the wave number (cm'').

Claims (1)

[Claims] Linear dimer or cyclic u of α-amino acid with hydroxyl sound
1. A method for producing a biofunctional membrane, characterized in that the iit isomer, polytetramethylene glycol, and polyethylene glycol all coexist and undergo a polyaddition reaction with diisonoanate, and the resulting polyurethane is formed into a film.