JP2007151996A - Biocompatible material composed of polyurethane derivative - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a thermoplastic biocompatible material which is excellent in thermal molding of films or tubes and has reduced attachment of blood platelets and proteins in blood. <P>SOLUTION: The biocompatible material uses polyurethane including cyclic tetrasaccharide produced by the reaction of cyclic tetrasaccharide and diol compounds with diisocyanate compounds. In particular, the biocompatible material uses polyurethane including cyclic tetrasaccharide expressed by the general formula (1): -ä[CO-NH-R<SP>1</SP>-NH-CO]-[O-R<SP>2</SP>-O]}m-##-[[CO-NH-R<SP>1</SP>-NH-CO]-[O-CTS-O]]n- [1] ¾ (OH)<SB>10</SB>[where CTS is the framework of cyclic tetrasaccharide: cyclo ä→6)-α-D-glucopyranocyl-(1→3)-α-D-glucopyranocyl-(1→6)-α-D-glucopyranocyl-(1→3)-α-D-glucopyranocyl-(1→}]. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a biocompatible material characterized by using a polyurethane derivative containing a cyclic tetrasaccharide.

  Polyurethane is a polymer produced basically by addition polymerization of two main raw materials, polyol and diisocyanate. Applications include cushioning materials, heat insulating materials, sealing materials, waterproofing materials, flooring materials, paving materials, paints, adhesives, synthetic leather, elastic fibers, sporting goods members, bandages, gibbs, catheters, etc. It is used in a wide range of fields such as electrical products, civil engineering and construction, daily necessities, and medicine.

  Recently, in order to reduce the impact on the global environment by reducing the use of fossil resources as well as imparting water absorption and antithrombotic properties as a high-performance polyurethane, biomass materials such as monosaccharides, disaccharides, oligosaccharides, etc. A biodegradable polyurethane containing a saccharide such as a polysaccharide has been developed.

  For example, a polyurethane containing cyclodextrin as a polyurethane containing a cyclic oligosaccharide (for example, Patent Document 1 and Patent Document 3), a polyurethane containing starch and molasses or polysaccharide which is a modified product thereof (for example, Patent Document 2, Patent Document) 5) Polyurethanes containing monosaccharides, disaccharides, oligosaccharides and polysaccharides (for example, Patent Document 4), polyurethanes containing acylated monosaccharides, disaccharides, oligosaccharides and polysaccharides in the side chain, and deacylation thereof Polyurethanes (for example, Patent Document 6) are disclosed. Among these, the deacylated polyurethane of Patent Document 6 is shown to be biocompatible without platelet adhesion as compared with commercially available polyurethane.

  On the other hand, cyclo {→ 6) -α-D-glucopyranosyl- (1 → 3) -α-D-glucopyranosyl- (1 → 6) -α-D, which is a kind of cyclic tetrasaccharide which is the smallest cyclic oligosaccharide. Various derivatives of -glucopyranosyl- (1 → 3) -α-D-glucopyranosyl- (1 →} (see the following formula) are known (for example, Patent Document 7).

JP-A-5-86103 JP-A-5-186556 JP-A-7-53658 JP-A-9-12588 JP-A-9-104737 JP 11-71391 A JP 2003-160595 A

  For example, polyurethanes having monosaccharides, disaccharides, oligosaccharides and polysaccharides in the side chain disclosed in Patent Document 6 are shown to be non-adherent to platelets and biocompatible with commercially available polyurethanes. On the other hand, since these sugars are introduced into the side chain, there is a problem that the production is complicated and the production cost is increased.

  An object of the present invention is to provide a biocompatible material comprising a polyurethane derivative that is simpler to manufacture and less expensive to manufacture than the conventional products described above.

As a result of intensive studies in view of the above problems, the present inventors have found that a novel polyurethane derivative containing a cyclic tetrasaccharide obtained by the reaction of a cyclic tetrasaccharide, a polyol and a diisocyanate is excellent in a biocompatible material. It came to be completed. That is, the present invention provides the following general formula [1]:

^{- {[CO-NH-R} 1 -NH-CO] - [O-R 2 -O]} m- #



^{# - {[CO-NH-} R 1 -NH-CO] - [O-CTS-O]} n- [1]
｜
(OH) ₁₀

[Wherein, R ¹ represents a divalent aliphatic hydrocarbon group having 4 to 16 carbon atoms, a divalent aromatic hydrocarbon group having 6 to 16 carbon atoms, or a divalent aromatic group having 7 to 16 carbon atoms. Substituent-containing hydrocarbon group, R ² is the same or different, divalent organic group containing 1 to 100 units of oxyalkylene group having 2 to 12 carbon atoms and / or alkylene group having 2 to 6 carbon atoms, CTS Is a cyclic tetrasaccharide: cyclo {→ 6) -α-D-glucopyranosyl- (1 → 3) -α-D-glucopyranosyl- (1 → 6) -α-D-glucopyranosyl- (1 → 3) -α- D-glucopyranosyl- (1 →) represents a skeleton of the following formula (wherein, * represents a bonding position of a hydroxyl group).

m and n are the number of repeating units, m is 0 to 1000, n is an integer of 1 to 1000, and n / (m + n) is a number in the range of 0.01 to 1. When there are a plurality of R ¹ and R ² , they may be the same or different. ] The biocompatible material using the polyurethane containing the cyclic tetrasaccharide represented by this. Preferably, the biocompatible material is used in contact with blood, specifically, a blood tube, a blood bag, a catheter, or a blood separation filter.

  The polyurethane containing the cyclic tetrasaccharide of the present invention is thermoplastic and excellent in thermoformability to a film or a tube. Furthermore, they are useful as biomaterials because they are biocompatible and have no adhesion of proteins in platelets or blood.

  The biocompatible material of the present invention is a polyurethane containing a cyclic tetrasaccharide represented by the general formula [1].

In the general formula [1], R ¹ is a divalent aliphatic hydrocarbon group having 4 to 16 carbon atoms, a divalent aromatic hydrocarbon group having 6 to 16 carbon atoms, or 2 having 7 to 16 carbon atoms. It is a valent aromatic group-substituted hydrocarbon group. When these groups have a chain structure, they may be linear or branched. Specific examples of the R ¹ group include divalent groups such as a tetramethylene group, a pentamethylene group, a hexamethylene group, an octamethylene group, a hexadecamethylene group, a vinylene group, a propenylene group, a phenylene group, and a naphthylene group. Or a group obtained by removing one hydrogen atom bonded to an aromatic ring of a monovalent hydrocarbon group such as a methylphenyl group, an ethylphenyl group, a biphenyl group, a methylenebisphenyl group, or an ethylenebisphenyl group. Among these, a methylene bisphenyl group, a methylphenyl group, and a hexamethylene group are preferable.

In the above general formula [1], R ² is the same or different divalent organic group containing 1 to 100 units in total of oxyalkylene groups having 2 to 12 carbon atoms and / or alkylene groups having 2 to 6 carbon atoms. is there. As such, for example, a divalent organic group containing 1 to 100 units of the same or different oxyalkylene group having 2 to 12 carbon atoms, or a total of 1 to 1 identical or different alkylene groups having 2 to 6 carbon atoms. A divalent organic group containing 100 units, a divalent organic group containing a total of 1 to 100 units of the same or different oxyalkylene group having 2 to 12 carbon atoms and the same or different alkylene group having 2 to 6 carbon atoms, Good. Specifically, R ² is, for example, a (1)-(BO) _h-1 -B- group (where B represents an alkylene group having 2 to 12 carbon atoms, and h is an average addition of oxyalkylene groups. The number of moles represents a number of 1 to 100. When there are a plurality of B, they may be the same or different.), And these repeating unit groups BO may be linear or branched. Specific examples of such a repeating unit group BO include alkyleneoxy groups such as an ethyleneoxy group, a propyleneoxy group, a trimethyleneoxy group, a butyleneoxy group, and a tetramethyleneoxy group. R ² is, for example, (2) an alkylene ester group such as an ethylene adipate group, a propylene adipate group, a butylene adipate group, a hexamethylene adipate group, or a neopentyl adipate group, or an alkylene carbonate group such as a hexamethylene carbonate group, It may have a repeating unit such as a ring-opened caprolactone group (specifically, a divalent group obtained by removing OH at both ends from polyethylene adipate diol or the like). Further, R ² is, for example, a (3)-(E) _i -group (where E represents a divalent hydrocarbon group having 2 to 6 carbon atoms, and i is a number of 1 to 100 in terms of the average number of moles added). In the case where there are a plurality of E, they may be the same or different.), And the repeating unit group represented by E may be linear or branched, and may be a saturated group. It may be an unsaturated group, or a hydrogen atom may be substituted with another atom or substituent. Specific examples of such repeating unit groups include, for example, ethylene group, trimethylene group, tetramethylene group, hexamethylene group, nonamethylene group, —CH ₂ —CF ₂ —CF ₂ —CF ₂ —CF ₂ —CH. ₂ -groups, butadienylene groups, hydrogenated butadienylene groups, groups derived by removing one hydrogen atom from the carbon atoms at both chain ends of hydrogenated isoprene, polydimethylsiloxydimethylsilyl-n-propylbisethoxy group, etc. A bivalent group etc. are mentioned. Among these, R ² has an ethyleneoxy group, a propyleneoxy group, an ethylene adipate group, a propylene adipate group, a hexamethylene carbonate group, a ring-opening caprolactone group, a trimethylene group, a tetramethylene group, —CH _2. A group derived by removing one hydrogen atom from carbon atoms at both chain ends of a —CF ₂ —CF ₂ —CF ₂ —CF ₂ —CH ₂ — group, hydrogenated butadienylene group, hydrogenated isoprene, polydimethylsiloxy A dimethylsilyl-n-propylbisethoxy group is preferred. The groups represented by B and E in R ² are each repeated by the number of h or i. In this case, the same groups may be repeated or different combinations may be used. H represents an integer of 1 to 100.

  In the general formula [1], CTS is a cyclic tetrasaccharide: cyclo {→ 6) -α-D-glucopyranosyl- (1 → 3) -α-D-glucopyranosyl- (1 → 6) -α-D-glucopyranosyl- ( 1 → 3) -α-D-glucopyranosyl- (1 →} represents a skeleton, and * part represents a bonding position of a hydroxyl group.

  In the above general formula [1], m and n are the number of repeating units, m is 0 to 1000, preferably 10 to 1000 from the viewpoint of polymer strength and polymer moldability, and n is 1 to 1000, blood compatible From the viewpoint of properties, preferably represents an integer of 10 to 1000, and n / (m + n) is 0.01 to 1, and preferably 0.02 to 0 from the viewpoint of the balance of blood compatibility, polymer strength, and polymer moldability. A number in the range of .80. Note that the arrangement of the repeating units in the general formula [1] may be regular or irregular.

The polyurethane containing a cyclic tetrasaccharide, which is the biocompatible material of the present invention, can be produced, for example, as follows.
General formula [2]:

HO-CTS-OH
｜
(OH) ₁₀

[Where CTS is the same as above]

And a cyclic tetrasaccharide represented by the general formula [3]:

HO-R ² -OH

[Wherein R ² is the same as defined above]

A diol represented by general formula [4]:

O = C = N-R ¹ -N = C = O

[Wherein R ¹ is as defined above]

It is made to react with the diisocyanate represented by these. Alternatively, the cyclic tetrasaccharide represented by the general formula [2] is reacted with the diisocyanate represented by the general formula [4]. At this time, a mixture of the acylated cyclic tetrasaccharide represented by the general formula [2] and the diol represented by the general formula [3] may be reacted with the diisocyanate represented by the general formula [4] ( One-shot method), or first, a diol represented by the general formula [3] and a diisocyanate represented by the general formula [4] are reacted to form a prepolymer, and then a cyclic tetrasaccharide represented by the general formula [2] (The prepolymer method 1), or first, the cyclic tetrasaccharide represented by the general formula [2] and the diisocyanate represented by the general formula [4] are reacted to form a prepolymer, A diol represented by the formula [3] may be reacted (prepolymer method 2). In this case, the diol represented by the general formula [3] may be reacted with one or more different diols. Even when no diol is used, it can be carried out according to the above.

  The diisocyanate of the general formula [4] used in the present invention is, for example, diphenylmethane diisocyanate, paraphenylene diisocyanate, xylylene diisocyanate, tetramethylxylylene diisocyanate, tolylene diisocyanate, hexamethylene diisocyanate, isophorone diisocyanate, dicyclohexylmethane diisocyanate, or Examples include prepolymers having isocyanate groups at both ends. These can use 1 type (s) or 2 or more types.

  The diol represented by the general formula [3] is not particularly limited as long as it is a diol having a primary hydroxyl group. Specifically, for example, ethylene glycol, 1,3-propanediol, 1,4-butanediol, 1,6-hexanediol, 1,9-nonanediol, 2,2,3,3,4,4, Low molecular weight diols such as 5,5-octafluoro-1,6-hexanediol; polyethylene glycol, polytetramethylene ether glycol, polypropylene glycol, ethylene oxide-propylene oxide copolymer, tetrahydrofuran-ethylene oxide copolymer, tetrahydrofuran-propylene Polyether diols such as oxide copolymers, polyethylene adipate glycol, polydiethylene adipate glycol, polypropylene adipate glycol, polybutylene adipate glycol, polyhexamethylene adipate glycol Polyester glycol such as polyneopentyl adipate glycol and polycaprolactone glycol, polycarbonate diol such as polyhexamethylene carbonate glycol, polyolefin glycol such as polybutadiene glycol, hydrogenated polybutadiene glycol, hydrogenated polyisoprene glycol, bis (hydroxy High molecular weight diols such as silicone diols such as ethoxy-n-propyldimethylsilyl) polydimethylsiloxane. These can use 1 type (s) or 2 or more types.

  The solvent for producing the polyurethane may be any solvent that can dissolve the reaction product and the polyurethane to be produced. Specifically, for example, organic solvents such as dimethyl sulfoxide (DMSO), N-methyl-2-pyrrolidone (NMP), N, N-dimethylformamide (DMF), N, N-dimethylacetamide (DMAc) alone or the like The mixed solvent is mentioned.

  In the production of polyurethane, the cyclic tetrasaccharide of the general formula [2] and, if applicable, the general formula [3] in a solution of the diisocyanate of the general formula [4] through a dry inert gas such as nitrogen. ] Diol is added. The charged molar ratio of the compound of the general formula [4]: the compound of the general formula [3]: the compound of the general formula [2] is preferably 3: 0 to 2.99: 0.01 to 3, more preferably 3: 0.2-2.5: 0.5-2.8. The reaction temperature is preferably 10 to 150 ° C, more preferably 20 to 120 ° C, and the reaction time is preferably 1 to 10 hours, more preferably 2 to 6 hours.

  After completion of the reaction, the reaction solution is put into an organic solvent such as methanol and acetone, and the solid content obtained by repeating filtration, washing, and reprecipitation purification as necessary is dried under reduced pressure at room temperature to 100 ° C for about 1 to 24 hours. Thus, the polyurethane of the present invention represented by the general formula [1] can be obtained.

  The polyurethane containing the cyclic tetrasaccharide represented by the general formula [1] obtained in this way is excellent in biocompatibility and can be used as a biocompatible material. Preferably, since it has the characteristic that platelets and proteins in blood are difficult to adhere, it is suitable for applications where blood comes into contact, such as blood tubes, blood bags, catheters, or blood separation filters.

  EXAMPLES Next, although this invention is demonstrated further in detail based on an Example, this invention is not limited to these.

  The monomer compound used for polymerization is abbreviated as follows.

CTS = cyclic tetrasaccharide MDI = methane diphenyl diisocyanate PPG = polypropylene glycol PTMG = polytetramethylene glycol PSiG = bis (hydroxyethoxy-n-propyldimethylsilyl) polydimethylsiloxane

(Synthesis Example 1)
Synthesis of CTS-PPG-MDI (molar ratio 1/2/3) polyurethane (prepolymer method 1)
Put a polypropylene glycol (average molecular weight 700, 6.48 g), dimethylacetamide (60 ml), methanediphenyl diisocyanate (3.64 g) into a 4-neck flask equipped with a mechanical stirrer (with nitrogen gas replacement) and stir from room temperature. The temperature was gradually raised to 90 ° C. and reacted for 1 hour. Next, after cooling this reaction liquid to room temperature, cyclic tetrasaccharide (3.00 g) was added and reacted at this temperature for 4 hours. The reaction solution was poured into methanol to precipitate the product, filtered, washed with methanol, and then vacuum dried to obtain the product (yield 77%).

  It was confirmed by proton NMR that it was the desired product.

Proton NMR proton (solvent: heavy dimethyl sulfoxide)
1.05, 1.20; CH ₃ −
_{3.20-3.60; -O-CH-CH 2} -O-
_3.60-5.40; -CH 2 -, - CH-
3.76; —CH ₂ —
7.05,7.32; _-C 6 _{H 4}
8.52; -NH-CO-

(Synthesis Example 2)
Synthesis of CTS-PPG-MDI (molar ratio 0.5 / 2.5 / 3) polyurethane (prepolymer method 1)
The target polyurethane was prepared in the same manner as in Synthesis Example 1 using polypropylene glycol (average molecular weight 700, 8.10 g), dimethylacetamide (65 ml), methanediphenyl diisocyanate (4.25 g), and cyclic tetrasaccharide (3.00 g). Obtained (yield 90%).

(Synthesis Example 3)
Synthesis of CTS-PPG-MDI (molar ratio 0.25 / 2.75 / 3) polyurethane (prepolymer method 1)
The target polyurethane was prepared in the same manner as in Synthesis Example 1 using polypropylene glycol (average molecular weight 700, 8.91 g), dimethyl sulfoxide (60 ml), methanediphenyl diisocyanate (4.55 g), and cyclic tetrasaccharide (3.00 g). Obtained (yield 92%).

(Synthesis Example 4)
Synthesis of CTS-PPG-MDI (molar ratio 0.1 / 2.9 / 3) polyurethane (prepolymer method 1)
The target polyurethane was prepared in the same manner as in Synthesis Example 1 using polypropylene glycol (average molecular weight 700, 9.40 g), dimethylacetamide (65 ml), methanediphenyl diisocyanate (4.73 g), and cyclic tetrasaccharide (3.00 g). Obtained (yield 90%).

(Synthesis Example 5)
Synthesis of CTS-PTMG-MDI (molar ratio 1/2/3) polyurethane (prepolymer method 1)
Using polytetramethylene glycol (average molecular weight 1000, 9.26 g), dimethyl sulfoxide (65 ml), methanediphenyl diisocyanate (3.64 g), and cyclic tetrasaccharide (3.00 g) in the same manner as in Synthesis Example 1, A polyurethane was obtained (yield 93%).

(Synthesis Example 6)
Synthesis of CTS-PTMG-MDI (molar ratio 0.5 / 2.5 / 3) polyurethane (prepolymer method 1)
In the same manner as in Synthesis Example 1 using polytetramethylene glycol (average molecular weight 1000, 11.57 g), dimethylacetamide (65 ml), methanediphenyl diisocyanate (4.25 g), and cyclic tetrasaccharide (3.00 g), A polyurethane was obtained (yield 92%).

(Synthesis Example 7)
Synthesis of CTS-PSiG-PPG-MDI (molar ratio 1 / 0.1 / 1.9 / 3) polyurethane (prepolymer method 1)
Synthesis example using polypropylene glycol (average molecular weight 700, 6.16 g), dimethyl sulfoxide (65 ml), methanediphenyl diisocyanate (3.64 g), cyclic tetrasaccharide (3.00 g) SiG (average molecular weight 1000, 0.46 g) 1 was obtained in the same manner as in Example 1 (yield 91%).

(Synthesis Example 8)
Synthesis of CTS-PSiG-PPG-MDI (molar ratio 0.5 / 0.2 / 2.3 / 3) polyurethane (prepolymer method 1)
Synthesis using polypropylene glycol (average molecular weight 700, 7.45 g), dimethyl sulfoxide (65 ml), methanediphenyl diisocyanate (4.25 g), cyclic tetrasaccharide (3.00 g), PSiG (average molecular weight 1000, 0.93 g) In the same manner as in Example 1, the desired polyurethane was obtained (yield 91%).

(Synthesis Example 9)
Synthesis of PPG-MDI (molar ratio 1/1) polyurethane Synthetic mechanical stirrer equipped with 4-neck flask (nitrogen gas substituted), polypropylene glycol (average molecular weight 700, 14.70 g), dimethylacetamide (100 ml), methanediphenyl diisocyanate (5.50 g) was added, and while stirring, the temperature was gradually raised from room temperature to 120 ° C. and reacted at this temperature for 4 hours. The reaction solution was poured into methanol to precipitate the product, filtered, washed with methanol, and then vacuum dried to obtain the product (yield 90%).

  It was confirmed by proton NMR that it was the desired product.

Proton NMR proton (solvent: heavy dimethyl sulfoxide)
1.05, 1.20; CH ₃ −
_{3.20-3.60; -O-CH-CH 2} -O-
3.76; —CH ₂ —
7.05,7.32; _-C 6 _{H 4}
8.52; -NH-CO-

(Examples 1-8, Comparative Examples 1-4)
<Production of press film>
A press film was prepared with a pressure molding machine using the various polyurethanes obtained in Synthesis Examples 1-9. The temperature of the production conditions was 150 to 160 ° C., the pressure was 3 MPa, and the time was 2 minutes.

<Blood compatibility evaluation>
(1) Evaluation of blood cell adhesion Blood: Human blood was collected, and heparin was added to 3 IU / ml.

Sample 1) Examples 1-8, Comparative Example 3: Polyurethane press film of Synthesis Examples 1-9 2) Comparative Example 1: Commercially available vinyl chloride (PVC) blood bag
T-020 (Telflex)
3) Comparative Example 2: of commercially available polyurethane (Nippon Polyurethane Milactolan E385)
Press film
4) Control example: only blood without film (control)
Ten pieces of the above samples 1) to 3) cut into 5 mm squares were put in polypropylene test tubes, 5 ml of blood (added with 3 IU / ml of heparin) was added, and contacted at 37 ° C. for 1 hour ( n = 2). Only blood was collected into another test tube, and the platelet count, red blood cell count, and white blood cell count were measured with a particle counter. The adhesion rate (%) of red blood cells, white blood cells, and platelets was calculated by the following formula.

Adhesion rate (%) = [(number of blood cells in control) − (number of blood cells in test sample)] ÷ (number of blood cells in control) × 100

(2) Evaluation of blood activation and protein adhesion The blood sample contacted by the above method is collected in a separate test tube, and plasma is collected from this, and platelet activity, blood coagulation activity, leukocyte activity and protein adhesion are collected by the following methods. It was measured.

  βTG, TAT, PMN-E: An antigen or an antibody labeled with a labeling substance with an enzyme was added to a sample plasma, an antigen-antibody reaction was performed, and a chromogenic substrate was added to measure enzyme activity.

  Total protein: A pyrogallol red-molybdate complex was added to the sample plasma under acidic conditions, bound to the protein, and the absorbance near 600 nm was measured to quantify the total protein in the sample.

  Albumin: A turbid material caused by an antigen-antibody reaction was irradiated with light, and the light scattering intensity was measured by a nephrometry method.

  FDP: Latex particles that bind antigen or antibody to the sample plasma, perform antigen-antibody reaction, and measure the turbidity of aggregation due to antigen-antibody reaction by irradiating near infrared light and measuring transmittance It measured by the immunoturbidimetric method.

  Fibrinogen: Thrombin was added to the sample plasma and measured by the thrombin clotting time method for measuring the clotting time.

  The measurement was performed by an immunoturbidimetric method in which the turbidity resulting from the IgG: antigen-antibody reaction was irradiated with light and the transmittance was measured.

  The results of (1) and (2) are shown in Tables 1 and 2.

  From the above results, as shown in Examples 1 to 8, the polyurethane of the present invention has less platelet adhesion in the blood compared to the polymers in Comparative Examples 1 to 3, and protein adhesion is a commercially available PVC blood bag (Comparative Example). It was shown to have excellent biocompatibility because it is equivalent to 1) and has low platelet activity, blood coagulation activity, and leukocyte activity.

Claims (3)

The following general formula [1]:

^{- {[CO-NH-R} 1 -NH-CO] - [O-R 2 -O]} m- #



^{# - {[CO-NH-} R 1 -NH-CO] - [O-CTS-O]} n- [1]
｜
(OH) ₁₀

[Wherein, R ¹ represents a divalent aliphatic hydrocarbon group having 4 to 16 carbon atoms, a divalent aromatic hydrocarbon group having 6 to 16 carbon atoms, or a divalent aromatic group having 7 to 16 carbon atoms. Substituent-containing hydrocarbon group, R ² is the same or different, divalent organic group containing 1 to 100 units of oxyalkylene group having 2 to 12 carbon atoms and / or alkylene group having 2 to 6 carbon atoms, CTS Is the following formula:

(Wherein, * represents a bonding position of a hydroxyl group): Cyclic tetrasaccharide represented by: cyclo {→ 6) -α-D-glucopyranosyl- (1 → 3) -α-D-glucopyranosyl- (1 → 6 ) -Α-D-glucopyranosyl- (1 → 3) -α-D-glucopyranosyl- (1 →}
m and n are the number of repeating units, m is 0 to 1000, n is an integer of 1 to 1000, and n / (m + n) is a number in the range of 0.01 to 1. When there are a plurality of R ¹ and R ² , they may be the same or different. ] The biocompatible material characterized by using the polyurethane containing the cyclic tetrasaccharide represented by these.   The biocompatible material according to claim 1, which is used for an application in contact with blood.   The biocompatible material according to claim 1, which is used for a blood tube, a blood bag, a catheter, or a blood separation filter.