JPH0261262B2 - - Google Patents

Description

[Detailed description of the invention]

This invention relates to a method for producing a polyurethane membrane with excellent biological functionality. Polyurethane is a prepolymer synthesized by a polyaddition reaction between an oligomer diol and a diisocyanate, and then increased in molecular weight with a chain extender, and usually contains ether bonds, urethane bonds, and urea bonds. 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 bonds become proton acceptors, forming intermolecular hydrogen bonds between these bond groups,
Polyurethane has a spherulite structure and a microphase separation structure that is effective for antithrombotic properties. Linear or cyclic dimers of α-amino acids contain peptide bonds with strong hydrogen bonding ability.
The cyclic dimer of α-amino acid has a rigid molecular skeleton and therefore has good crystallinity. On the other hand, since linear dimers of α-amino acids have flexible molecular skeletons, their crystallinity is lower than that of cyclic dimers. Therefore α−
The linear or cyclic dimer of L-serine, which has a hydroxyl group in the amino acid side chain, can not only be used as a chain extender for polyurethane, but also contains peptide bonds with high hydrogen bonding capacity that were not contained in conventional polyurethane. Therefore, the development of a new form of phase structure is expected. Furthermore, by selectively using a cyclic dimer and a linear dimer, the crystallinity of polyurethane can be changed, making it possible to finely control the film function of a polyurethane film. The properties of the soft segment portion of the oligomer diol can be adjusted by changing its type and degree of polymerization. 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 this, the moisture content of the resulting polyurethane membrane increases, making it easier to separate urinary toxin-related substances. 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 urinary toxin-related substances and is biocompatible, and have completed the present invention. . That is, the gist of the present invention is to coexist polytetramethylene glycol and polyethylene glycol with a linear dimer 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. () Synthesis of polyurethane containing linear dipeptide as one component: This product synthesizes dipeptide diol by condensing an α-amino acid having a hydroxyl group in the side chain, and using this as a chain extender, polytetramethylene glycol and polyethylene glycol are added. It can be obtained by coexisting with diisocyanate and performing a polyaddition reaction with diisocyanate. (A) Synthesis of linear dipeptide diol: L-amino acid having a hydroxyl group in the side chain
An example using serine (hereinafter L-serine will be abbreviated as H-Ser-OH) will be described. H-Ser-
The linear dipeptide of OH activates the carboxyl terminal of Z-Ser-OH whose amino terminal is carbobenzyloxylated (hereinafter the carbobenzyloxy group is abbreviated as Z), and this is separately converted into H-Ser-OH.
The carboxyl group of H- is methyl esterified.
By condensation with Ser-OMe, a linear dipeptide of serine with both terminal groups protected, i.e., Z-
Ser−Ser−OMe is obtained. To specifically illustrate this, 20g of H-Ser-
The OH is suspended in methanol, kept at 0° C., and hydrogen chloride gas is bubbled through for about 6 hours. Next, methanol was distilled off, and the resulting solid was recrystallized from methanol to yield 17.7 g of H-Ser-OMe.HCl.
was obtained (yield 59%). The melting point of this thing is 162-165
℃, and it was confirmed by thin layer chromatography (hereinafter referred to as TLC) and infrared (hereinafter referred to as IR) spectrum that pure H-Ser-OMe.HCl was obtained. Add 8 g of H-Ser-OMe.HCl to a saturated aqueous solution of sodium bicarbonate, keep at about 20°C, and add 10 g of Z-Cl (1.1 of H-Ser-OMe.HCl) while stirring.
(double equivalent amount) was added dropwise and allowed to react for 4 hours. The separated oil layer was extracted with ethyl acetate, and the extract was diluted with 5%
After washing with hydrochloric acid and then water and drying over anhydrous sodium sulfate, ethyl acetate is distilled off. The obtained solid was recrystallized from a mixed solvent of pentane and ether to obtain 10.4 g of Z-Ser-OMe (yield: 80
%). The melting point of this product is 27-32℃, TLC,
Pure Z-Ser-OMe was determined by IR spectrum and high-performance liquid chromatography (hereinafter referred to as HPLC).
It was confirmed that the results were obtained. Dissolve 9.7g of Z-Ser-OMe in methanol,
5.75 g of hydrazine hydrate (3 times the equivalent of Z-Ser-OMe) was added, and the mixture was reacted at about 20°C for 24 hours. Next, ether is added and the mixture is further reacted at 0° C. for 5 to 6 hours. The precipitate was collected and recrystallized from a mixed solvent of methanol and ether to obtain 7.8 g of needle-like crystals of Z-Ser-NHNH ₂ (yield: 80%). The melting point of this thing is
The temperature was 180-181°C, and it was confirmed by TLC and IR spectra that pure Z-Ser-NHNH ₂ was obtained. Z−Ser− obtained as above
7.59 g of NHNH ₂ is dissolved in dimethylformamide and 3.51 g of isoamyl nitrite (equimolar amount of Z-Ser-NHNH ₂ ) is added while stirring at -5°C.
Although it is thought that Z-Ser-N ₃ was generated in the solvent, this product was subjected to the following reaction without being isolated. That is, 4.67 g of H-Ser-OMe・HCl (Z-Ser-OMe・HCl synthesized above) was added to this reaction solution.
A dimethylformamide solution (containing a small amount of triethylamine) of _0.0
The reaction was carried out at ℃ for 2 days. The volatile components were distilled off, and the residue was extracted with ethyl acetate. This extract was washed with a 4% aqueous sodium bicarbonate solution, 3% hydrochloric acid, and water, dried over anhydrous sodium sulfate, and then the ethyl acetate was distilled off. did. The obtained solid was recrystallized from a mixture of ethyl acetate and petroleum ether to give Z-Ser-
3.3 g of needle-like crystals of Ser-OMe were obtained (yield 32.3%).
The melting point of this product is 142-144℃, TLC, IR
Pure Z-Ser by spectroscopy and elemental analysis
It was confirmed that -Ser-OMe was obtained. [α] ^24/D of the methanol solution was −3.1°. The above reaction is expressed as follows. H−Ser−OHMeOH／HCl ――――――――→ H−Ser −OMe・HCl2Cl ――――→ Z−Ser −OMe・HClNH ₂ NH ₂ ――――――――→ Z−Ser − NHNH ₂ C ₅ H ₁₁ NO ₂ ――――――――→ Z−Ser−N ₃ H−Ser−OMe・HCl ――――――――――→ Z−Ser−Sef−OMe According to this method, the desired reaction proceeds without modification or interference even if the side chain group of serine is not protected, and Z-Ser-Ser-OMe can be obtained extremely efficiently. Z-Ser-Ser-OMe has the following chemical structure, and polyurethane can be synthesized by polyaddition reaction with diisocyanate as a diol component. (B) Synthesis of polyurethane containing linear dipeptide diol: Polytetramethylene glycol with various degrees of polymerization (hereinafter, polytetramethylene glycol is abbreviated as PTMG) is added to the linear dipeptide diol obtained as described in (A) above. ) and polyethylene glycol (hereinafter referred to as polyethylene glycol) and polyethylene glycol (hereinafter referred to as PEG)
(hereinafter abbreviated as )) are allowed to coexist, and this is subjected to a polyaddition reaction with diisocyanate. The ratio of PTMG to PEG to be used is usually selected from a molar ratio of approximately 1:1. An example will be described in which methylene bis(4-diisocyanatobenzene) (hereinafter abbreviated as MDI) is used as the diisocyanate in the above polyaddition reaction. Example 1 PTMG with a molecular weight of 1336 (hereinafter abbreviated as PTMG1336. Also in the subsequent descriptions, the number after PTMG represents the molecular weight of itself), PEG with a molecular weight of 1540 (hereinafter abbreviated as PEG1540. In the subsequent descriptions) The number added after PEG indicates its molecular weight), MDI and polyurethane containing Z-Ser-Ser-OMe obtained by (A) above [hereinafter, this polyurethane will be referred to as PU
(PTMG1336/PEG1540, MDI, Z-Ser-Ser
-OMe)]: Dissolve an equal mixture of 0.39 g of PTMG1336 and 0.45 g of PEG1540 in 8 ml of dimethylformamide, and add 0.29 g of MDI (corresponding to twice the mole of PTMG, PEG) to 2 ml. The mixture was mixed with a solution dissolved in formamide, and the atmosphere was replaced with nitrogen, followed by reaction at 60°C for 1 hour. Then 0.20 g of Z−Ser−Ser−OMe
A solution prepared by dissolving PTMG (equal moles of PEG) in 2 ml of dimethylformamide was added, and the mixture was reacted at 50°C for 24 hours. Thereafter, the solvent dimethylformamide was distilled off, and the viscous solution was poured into water, yielding a viscous slightly brown colored polymer. This was washed twice with distilled water and then dried over phosphorus pentoxide for 24 hours in the absence of light. When this polyurethane was dissolved in dimethylformamide and its viscosity at 30°C was measured, it was found that [η]=0.35. Under these conditions, the molecular weight calculated by applying the relationship between [η] and molecular weight reported for polymethyl methacrylate was approximately 310,000. A combination of PTMG with a molecular weight of 1100 (hereinafter abbreviated as PTGM1100) and PEG with a molecular weight of 1000 (hereinafter abbreviated as PEG100), and PTMG with a molecular weight of 2117 (hereinafter abbreviated as PTMG2117) and PEG with a molecular weight of 2000
(hereinafter abbreviated as PEG2000), polyurethane was synthesized in the same manner.
Obtained PU (PTMG1100/PEG1000, MDI, Z
-Ser-Ser-OMe) was brown in color, [η] = 0.31, and the equivalent molecular weight was approximately 230,000. Also PU
(PTMG2117/PEG2000, MDI, Z-Ser-Ser
-OMe) was pale yellow, [η] = 0.36, and the equivalent molecular weight was approximately 340,000. The solubility of these polyurethanes was that they were soluble in hexamethylphosphoamide, dimethylsulfoxide, and dimethylformamide, and insoluble in water, acetonitrile, methanol, chloroform, benzene, and dioxane. PU (PTMG2117/PEG2000, MDI, Z-Ser
-Ser-OMe) obtained by the staining method is shown in Figure 1. 1720 in this IR spectrum
The absorption observed at cm ^-1 (location indicated by A in the figure) is based on urethane bonds and ester groups.
The absorption observed at 1650 cm ^-1 (location indicated by B in the figure) is based on the amide of the amide group of the Z-Ser-Ser-OMe component. The absorption observed at 1540cm ^-1 (point C in the figure) is Z-Ser-Ser-
Amide and phenyl group of amide group of OMe component

Absorption based on the formula was observed, and it was confirmed that MDI was present in the polyurethane chain.
In addition, the absorption observed at 1100 cm ^-1 (location indicated by D in the figure) is due to the alkyl ether group -CH ₂ -O-CH ₂ -
It is based on Based on these facts, the above reaction is as follows, and the resulting polyurethane is considered to have the following structure. () Synthesis of polyurethane containing a linear dipeptide as one component: This product synthesizes a cyclic dipeptide diol by cyclocondensation of an α-amino acid having a hydroxyl group in its side chain, and uses this as a chain extender with polytetramethylene glycol and It can be obtained by carrying out a polyaddition reaction with diisocyanate in the presence of polyethylene glycol. (A) Synthesis of cyclic dipeptide diol: L-amino acid having a hydroxyl group in the side chain
An example using serine will be described. Z-Ser- synthesized by method (A) in () above
Dissolve 1.5 g of Ser-OMe in 40 ml of methanol (saturated with HCl), add 0.3 g of Pd black, and bubble in hydrogen for about 5 hours. The solution was filtered and methanol was distilled off, and the resulting residue was washed several times with n-hexane to obtain 1.0 g of Z-Ser-Ser-OMe.HCl (yield 93.6%). TLC and IR spectra confirmed that pure Z-Ser-Ser-OMe.HCl was obtained. H-Ser-Ser- thus obtained
Dissolve 1.0 g of OMe・HCl in 41 ml of methanol (saturated with _NH3 ) (H-Ser-Ser-
(The concentration of OMe was 0.1M) and the reaction was carried out at room temperature for 24 hours. The volatile components were distilled off, and the residue was washed with n-hexane to obtain 0.55 g of needle-shaped crystals of dipeptide diol (hereinafter abbreviated as C-(Ser) ₂ ) in which L-serine was cyclized and condensed. (Yield 76.7%). The melting point of this product is 245-248℃, and elemental analysis and IR
The spectrum confirmed that pure C-(Ser) ₂ was obtained. The above reaction is expressed as follows. Z−Ser−Ser−OMeH ₂ /Pd ――――――――――→ HCl/MeOHH −Ser−Ser−OMe・HClNH ₃ /MeOH ――――――――――→ C(Ser) ₂ According to this method, even if the side chain hydroxyl group of serine is not protected, the specified reaction proceeds without interference with the modification, and C-(Ser) ₂ can be obtained extremely efficiently. C-(Ser) ₂ has the following chemical structure, and polyurethane can be synthesized by polyaddition 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 polyaddition reaction is performed with diisocyanate. let The mixing ratio of PTMG and PEG may generally be the same as in the case () above. An example of using MDI as the diisocyanate is shown below. Example 2 PTMG1100/PEG1000, MDI and C-(Ser) ₂
[Hereinafter, this polyurethane will be referred to as PU [PTMG1100/PEG1000, MDI, C-
(Ser) ₂ ] Production: Dissolve an equal mixture of 0.32 g of PTMG1100 and 0.29 g of PEG1000 in 8 ml of dimethylformamide, and add 0.29 g of MDI (corresponding to twice the mole of PTMG, PEG). was mixed with a solution dissolved in 2 ml of formamide, the atmosphere was replaced with nitrogen, and the mixture was reacted at 60°C for 1 hour. Then, 0.1 g of C-(Ser) ₂ (PTMG, PEG
A solution of 10 ml of dimethylformamide was added, and the mixture was reacted at 50°C for 24 hours. After the reaction is completed, the solvent dimethylformamide is distilled off and concentrated, and the residue is poured into water to precipitate polyurethane. This was dried under reduced pressure over phosphorus pentoxide to obtain a light brown polyurethane. This material had a high moisture content, showing a moisture content of 23%. PTMG1336/PEG1540 as alkylene diol, or
Polyurethane was synthesized using the PTMG2117/PEG2000 combination in a similar manner. The moisture content is
PU [PTMG1336/PEG1540, MDI, C-(Ser) ₂ ]
42%, PU [PTMG2117/PEG2000, MDI,
C-(Ser) ₂ ], it was 41%. In addition, these polyurethanes are dissolved in dimethylformamide,
The viscosity at 30°C was measured to determine [η], and the molecular weight was determined by applying the relationship between [η] and molecular weight reported for polymethyl methacrylate under these conditions. PEG1000,
MDI, C-(Ser) ₂ ], [η] = 0.29, molecular weight 20
10,000, PU [PTMG1336/PEG1540, MDI, C-
(Ser) ₂ ], [η] = 0.32, molecular weight 250,000, PU
[PTMG2117/PEG2000, MDI, C-(Ser) ₂ ] had [η]=0.34 and a molecular weight of 290,000. PU [PTMG1100/PEG1000, MDI, C-
Figure 2 shows the IR spectrum of (Ser) ₂ ] obtained by the KBr method. In this IR spectrum, 1520cm ^-1
The absorptions observed at (D in the figure) and 1660 cm ^-1 (B in the figure) are based on the amide group of the C-(Ser) ₂ component. The absorption observed at 1700 cm ^-1 (A in the figure) is based on urethane bonds that occur as polyurethane is produced. The absorption observed at 1590 cm ^-1 (C in the figure) is based on the phenyl group of MDI. Based on these facts, the polyurethane obtained in the above reaction is considered to have 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 an amino acid having a hydroxyl group as a component of dipeptide diol used in the production of polyurethane, not only serine mentioned above but also threonine and tyrosine can be used. These α-amino acids exist in D-form and L-form, and either of them may be used. It is also possible to use a mixture or racemate of both. It is also possible to use a mixture of two or more different α-amino acids. In all these cases, both linear and cyclic dipeptides can be synthesized and used as raw materials for polyurethane. In the case of linear dipeptides, the amino and carboxyl groups must be protected. In addition to carbobenzyloxy group, as a protecting group for amino group,
A t-butyloxycarbonyl group or a formyl group can be used. Furthermore, as a protecting group for a carboxyl group, benzyl ester or amide can be used in addition to methyl ester. When PTMG and PEG are used in combination according to the method of the present invention, the moisture content of the resulting polyurethane is higher than when PTMG is used alone, and its utility as a dialysis membrane is increased. In addition to the above-mentioned MDI, examples of diisocyanates that can be used in producing polyurethane include aromatic diisocyanates such as hexamethylene diisocyanate, toluene diisocyanate, phenylene diisocyanate, and xylylene diisocyanate; Also, methylenebis(4-isocyanatocyclohexane), 1-carbomethoxy-1,6
- Diisocyanates Mention may be made of aliphatic diisocyanates such as hexane. () Method for forming a polyurethane film containing linear or cyclic dipeptide diol: To obtain a film from the polyurethane obtained as explained in () and () above, a conventional film forming method is followed. It can be done with The method is illustrated below. Example 3 Method for forming a polyurethane film under irradiation with an infrared lamp: Dissolve 0.05 g of polyurethane in 2 ml of dimethylformamide and stir overnight to form a homogeneous solution. This was cast onto a clean horizontal glass plate, a 250W infrared drying lamp was installed 30cm above the glass plate, and a transparent dust-proof case was placed to remove the evaporated dimethylformamide. The lamp was turned on for 5 hours while blowing air into the transparent case. 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 film thickness was approximately 20 μm. The ATR-IR spectrum of this film was measured, and there was no difference between the two sides of the film.
In addition, to investigate the cross-sectional structure of this film, the film was ruptured in liquid nitrogen (-195°C) and examined using 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 4 Method for forming a polyurethane film at room temperature and atmospheric pressure: Dissolve 0.05 g of polyurethane in 2 ml of dimethylformamide and stir overnight to form a homogeneous solution. This was poured onto a clean horizontal glass plate, and approximately 25
The sample was left standing at room temperature (°C) under atmospheric pressure for 2 days to gradually scatter dimethylformamide, and then vacuum-dried for 3 days. The obtained polyurethane film was easily peeled off from the glass plate when immersed in distilled water. 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 20 μm. The ATR-IR spectrum of this film was measured, but there was no difference between the two sides of the film. In addition, in order to investigate the cross-sectional structure of this film, the film was ruptured with liquid nitrogen and examined using a scanning electron microscope. I couldn't help it. As the film forming method, methods other than those exemplified above can be used. When dimethylformamide is used as a solvent, a suitable temperature range is from room temperature to about 100°C. The pressure can be adjusted in the range of 1 atm to 0 mmHg. 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. () Urine toxicity-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 a solute of uric acid. The samples used in this test are as follows. Sample (1) PU (PTMG1100/PEG1000, MDI, Z
-Ser-Ser-OMe) Sample (2) PU (PTMG1336/PEG1540, MDI, Z
-Ser-Ser-OMe) Sample (3) PU (PTMG2117/PEG2000, MDI, Z
-Ser-Ser-OMe) Sample (4) PU [PTMG1100/PEG1000, MDI, C
-(Ser) ₂ ] Sample (5) PU [PTMG1336/PEG1540, MDI, C
-(Ser) ₂ ] Sample (6) PU [PTMG2117/PEG2000, MDI, C
−(Ser) ₂ ] Sample (7) Cellulose acetate The above samples (1) to (7) were formed into a dimethylformamide solution and formed into films by an infrared lamp irradiation method. Sample (7), cellulose acetate, is conventionally used as a dialysis membrane material for artificial kidneys, and is included for comparison. The test was conducted as follows. sample membrane
It is sandwiched between two sheets of silicone rubber with a circular hole of 0.785 cm ² and immobilized with two dialysis cells made of methacrylic resin from both sides. (In order to improve the adhesion between the silicone rubber and the sample membrane, silicone grease was used on the parts other than the holes.) Pour 100ml of a solution of known concentration into one side of the dialysis cell and distilled water into the other side, and stir with a stirrer. The changes over time in the concentration of solutes that permeated through the tube were investigated. Furthermore, in this test, the dialysis cell was placed in a constant temperature bath at 25°C. The time-dependent change in the concentration of solutes passing through the solution 1 on the distilled water side changes over time.
ml was taken and the concentration was determined. Then, by plotting lnC''/C''- _2Ct and time t based on the theoretical permeation formula, the permeability coefficient P for each membrane was determined from the slope thereof. lnC″/C″−2C _t = 2PA/δVt P: Permeability coefficient (cm ² /min) A: Permeation membrane area (cm ² ) δ: Film thickness (cm) V: Volume of permeation cell (cm ³ ) C″ : Initial concentration on the feed liquid side (mole/cm ³ ) C _t : Concentration of the solute that permeated after t time (mole/cm ³ ) Film thickness was measured using a simple film thickness meter. The measurement of the concentration of each solute is shown below. As for NaCl, in the determination of Cl ^- by the Mohr method,
The amount was determined using potassium chromate as an indicator.
When 0.01N silver nitrate solution is added dropwise, AgCl
A white precipitate of Ag ₂ CrO ₄ forms after the end point. Urea was quantified using paradimethylaminobenzaldehyde, which was derived from Schiff's base as shown below. 0.5 ml of PDAB·H ⁺ solution was added to 1 ml of the sample, and after being left for 10 minutes, the absorbance at 440 nm 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 least squares method. Therefore, the concentration of urea can be determined from the absorbance. In addition, PDAB・H ⁺ solution is prepared by dissolving 5g of PDAB in special grade ethanol and adding 100%
ml and take about 50ml into a volumetric flask (100ml).
Gently add 5 ml of concentrated sulfuric acid, then add the PDAB solution.
PDAB·H ⁺ solution was prepared as 100 ml. A calibration curve was created for creatinine and uric acid, and the maximum extinction coefficient max was determined from the slope of the curve.
Then, the solute concentration of the sample was determined using this max. Next, since uric acid is poorly soluble in water,
A borate buffer with a pH of 9.18 was used. The measurement results are shown in the table below.

[Table] Transmission coefficient values include an error of approximately 10%. 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 as the molecular weight of the solute increases (NaCl, urea, creatinine, uric acid), the permeability coefficient decreases. Cellulose (sample 7)
Since the water content is low, solutes hardly pass through. 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 the understanding of 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 1 shows the PU obtained in Example 1 in the main text.
(PTMG2117/PEG2000, MDI, Z-Ser-Ser
-OMe), Figure 2 is shown in the text, obtained by Example 2 [PTMG1100/PEG1000,
MDI, C-(Ser) ₂ ] is shown. In FIGS. 1 and 2, the vertical axis is transmittance (%) and the horizontal axis is wave number (cm ^-1 ).

Claims (1)

[Claims] 1. A linear dimer or a cyclic dimer of an α-amino acid having a hydroxyl group is allowed to coexist with polytetramethylene glycol and polyethylene glycol, and a polyaddition reaction is performed with a diisocyanate, and the resulting polyurethane is formed into a film. Characteristic method for producing biofunctional membranes.