JPH1087702A - Cellulose derivative, its production, grated cellulose and its application - Google Patents

Abstract

PROBLEM TO BE SOLVED: To produce a cellulose derivative useful as a biocompatible material by reacting an intermediate of a reaction between an azo compound and cellulose with an alcohol. SOLUTION: The object derivative is expressed by formula I [R<1> is a 1-20C divalent hydrocarbon; R<2> and R<3> are each a 1-20C monovalent hydrocarbon; (m) is a molar fraction and a real number of 0.001-1]. Further, in order to produce the derivative, (A) an azo compound having a carboxylic acid chloride group, expressed by formula II, is made to react with (C) a cellulose in the presence of a basic catalyst (e.g. pyridine) to obtain an intermediate expressed by formula III, and the obtained intermediate is allowed to react with (D) an alcohol (e.g. methyl alcohol) e.g. at a reaction temperature of 0-100 deg.C for a reaction time of about 1min to 10hr.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a novel and useful cellulose derivative, a method for producing the same, a grafted cellulose using the cellulose derivative as a radical initiation source, and a biocompatible material comprising the grafted cellulose.

[0002]

2. Description of the Related Art Until now, cellulose having an azo group introduced is not known. By the way, the following (1) to (4) are known as methods for grafting cellulose. (1) Hydroperoxidation of cellulose by ozone oxidation and grafting of methacrylate and acrylate monomers by this decomposition [J. Polym. Sci.
C, 251 (1972)], (2) Impregnating cellulose fibers with an initiator such as persulfate, periodate, or permanganate, and grafting with a series of monomers such as styrene or vinyl acetate. Kagaku [Textile Magazine, Vol. 19, p. 217, 2
21 (1963)], (3) Grafting by a combination of hydrogen peroxide-metal salt (Fe ²⁺ ) which is a typical redox initiator [J. Chem. Soc. Volume 15,
(1949); Soc. Dyer. Color,
67, p. 338 (1951)], (4) a method in which cellulose is reacted with ethylene sulfide or the like to introduce a mercapto group, and a radical generated from a radical initiator is chain-transferred and grafted [J. Appl. P
olym. Sci. , 5, vol. 558 (1961)
Year)〕.

[0003] However, in the above methods (1) to (3), since a peroxide is used, an oxidization reaction occurs from the cellulose main chain, and an unnecessary dehydrogenation reaction accompanies the method. In the method (4), since the graft polymerization is carried out by radical chain transfer to the sulfur compound, the method is not suitable for polymerization into a monomer having low reactivity, and there is a problem that usable monomers are limited.

Further, the following is known as a method for introducing a radical into cellulose to cause a reaction. For example, it is known that a cerium salt easily forms a complex with cellulose, and this complex is disproportionated to generate a cellulose radical, which becomes an active site, thereby enabling graft polymerization of a monomer [J. Polym.
Sci. 31 242 (1958)].

[0005] However, the above method has to be carried out under the condition that oxygen is not present at the time of polymerization. In addition, when the grafted cellulose obtained by the above method is used as a biocompatible material, it is necessary to remove cerium ions after polymerization, and the operation must be complicated.

As a method for imparting biocompatibility to cellulose, a method of heparinizing the membrane surface has been proposed (JP-A-51-194). However, sufficient effects have not been obtained. Also, a method of graft-polymerizing 2-methacryloyloxyethyl phosphorylcholine onto a cellulose membrane [Bio Industry Vol. 8 (6), vol.
12-420 (1991)]. However, this method uses cerium in the same manner as described above, and is not suitable for use as it is as a biocompatible material because of the use of metal. In addition, there is a problem that the operation of removing the metal becomes complicated and not preferable.

[0007]

SUMMARY OF THE INVENTION A first object of the present invention is to provide a novel and useful cellulose derivative containing an azo group and a method for producing the same. A second object of the present invention is to provide an intermediate of the azo group-containing cellulose derivative and a method for producing the same. A third object of the present invention is to provide a novel grafted cellulose obtained by graft-polymerizing a radically polymerizable monomer to the above azo group-containing cellulose, which is useful as a biocompatible material. . A fourth object of the present invention is to provide a biocompatible material comprising the above grafted cellulose and having little protein adsorption and denaturation.

[0008]

DISCLOSURE OF THE INVENTION The present invention provides a novel and useful cellulose derivative, a method for producing the same, a grafted cellulose using the cellulose derivative as a radical initiation source, and a biocompatible material comprising the grafted cellulose. It is. (1) General formula (1)

Embedded image (Wherein, R ¹ is a divalent hydrocarbon group having 1 to 20 carbon atoms, R ²
And R ³ represent a monovalent hydrocarbon group having 1 to 20 carbon atoms. m represents a mole fraction and is a real number of 0.001 to 1. An azo group-containing cellulose derivative represented by the formula: (2) General formula (2)

Embedded image (Wherein, R ¹ is a divalent hydrocarbon group having 1 to 20 carbon atoms, R ²
Is a monovalent hydrocarbon group having 1 to 20 carbon atoms. An azo compound having a carboxylic acid chloride group represented by the formula (a):
Is reacted with cellulose (b) in the presence of a basic compound to give a compound of the general formula (3)

Embedded image (Wherein, R ¹ is a divalent hydrocarbon group having 1 to 20 carbon atoms, R ²
And R ³ represent a monovalent hydrocarbon group having 1 to 20 carbon atoms. m represents a mole fraction and is a real number of 0.001 to 1. The method for producing an azo group-containing cellulose derivative according to the above (1), wherein an intermediate represented by the formula (1) is obtained, and the intermediate is reacted with an alcohol (c). (3) General formula (3)

Embedded image (Wherein, R ¹ is a divalent hydrocarbon group having 1 to 20 carbon atoms, R ²
And R ³ represent a monovalent hydrocarbon group having 1 to 20 carbon atoms. m represents a mole fraction and is a real number of 0.001 to 1. An azo group-containing cellulose derivative represented by the formula: (4) General formula (2)

Embedded image (Wherein, R ¹ is a divalent hydrocarbon group having 1 to 20 carbon atoms, R ²
Represents a monovalent hydrocarbon group having 1 to 20 carbon atoms. An azo compound having a carboxylic acid chloride group represented by the formula (a):
And (c) reacting the cellulose (b) in the presence of a basic compound. (5) Grafted cellulose obtained by graft-polymerizing one or more radically polymerizable monomers (d) to the azo group-containing cellulose derivative according to (1). (6) The radical polymerizable monomer (d) is 2- (meth)
The grafted cellulose according to the above (5), which is acryloyloxyethyl phosphorylcholine. (7) A biocompatible material comprising the grafted cellulose according to (5) or (6).

In the present invention, “(meth) acryl” means “methacryl” and / or “acryl”.

The azo group-containing cellulose derivative represented by the general formula (1) of the present invention (hereinafter sometimes referred to simply as a cellulose derivative) is a compound having a structure in which an azo group is bonded by an ester bond. R ^{1 in the} general formula (1) is a divalent hydrocarbon group having 1 to 20, preferably 1 to 6, carbon atoms. Specific examples thereof include methylene, ethylene, trimethylene, propylene, and isopropylene. Group, tetramethylene group, butylene group, isobutylene group, heptamethylene group, amylene group, hexamethylene group, hexylene group, octamethylene group, decamethylene group, octadecamethylene group, etc. And the like. R ¹ in the general formula (1) may be the same or different.

R ^{2 in the} general formula (1) is a hydrocarbon group having 1 to 20 carbon atoms, preferably 1 to 6 carbon atoms, and specific examples thereof include methyl, ethyl, n-propyl, isopropyl, and n. -Butyl group, sec-butyl group, tert-butyl group, pentyl group, hexyl group, heptyl group, octyl group, nonyl group, decyl group, undecyl group, dodecyl group,
Examples thereof include an alkyl group having 1 to 20 carbon atoms, preferably 1 to 6 carbon atoms, such as a tridecyl group, a tetradecyl group, a pentadecyl group, a hexadecyl group, a heptadecyl group, an octadecyl group, a nonadecyl group and an escioil group. R ² in the general formula (1) may be the same or different.

R ^{3 in the} general formula (1) is a hydrocarbon group having 1 to 20, preferably 1 to 6 carbon atoms, and specific examples thereof include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, -Butyl group, sec-butyl group, tert-butyl group, pentyl group, hexyl group, heptyl group, octyl group, nonyl group, decyl group, undecyl group, dodecyl group,
Examples thereof include an alkyl group having 1 to 20 carbon atoms, preferably 1 to 6 carbon atoms, such as a tridecyl group, a tetradecyl group, a pentadecyl group, a hexadecyl group, a heptadecyl group, an octadecyl group, a nonadecyl group and an escioil group. R ² and R ³ in the general formula (1) may be the same or different.

[0013] The molecular weight of the cellulose derivative represented by the general formula (1) is determined by the cellulose used in the production. When natural cellulose is used, the molecular weight is usually several thousand to one hundred thousand hundred thousand.

The cellulose derivative represented by the general formula (1) can be produced by the following method. First, cellulose (b) is subjected to a dehydrochlorination reaction with the carboxylic acid chloride represented by the general formula (2) and the azo compound (a) having an azo group in the presence of a basic compound, and the intermediate represented by the general formula (3) ) To obtain an azo group-containing cellulose derivative (hereinafter sometimes referred to as an intermediate). Since no peroxide is used in this reaction, oxidation reaction may occur,
Unnecessary dehydrogenation does not occur due to radicals generated by decomposition, and therefore, the main chain of cellulose is not chemically modified by a side reaction.

[0015] R ¹ and R ² in the general formula (2) is the same as R ¹ and R ² in the general formula (1). Wherein R ¹ of R ^1, R ² and m are of the general formula (3) (1),
It is the same as R ² and m. Specific examples of the azo compound (a) represented by the general formula (2) include 4,4 ′
-Azobis (4-cyanovaleric chloride) and the like. The azo compound (a) is a known method in which an azo compound having a corresponding carboxylic acid is reacted with a chlorinating agent such as phosphorus pentachloride, phosphorus trichloride, or thionyl chloride in a suitable organic medium such as benzene or toluene. Can be obtained by

As the cellulose (b) to be reacted with the azo compound (a), for example, ordinary natural cellulose, hydrated cellulose, etherified cellulose, esterified cellulose having a molecular weight of several thousands to hundreds of hundreds of thousands, and a part of these are used. Modified ones and the like can be used, and commercial products can also be used.

Examples of the basic compound include tertiary amines such as pyridine, triethylamine, tripropylamine, N, N-dimethylaniline and 4-dimethylaminopyridine. These can be used alone or in combination of two or more. It is preferable to use anhydrides or dehydrated or dried ones.

As a reaction medium, pyridine, methylene chloride, chloroform and a mixture thereof can be used. The reaction is carried out at a reaction temperature of -30 to + 50 ° C, preferably -2.
0 ° C. to room temperature, reaction time 1 to 120 hours, preferably 2
It is desirable to carry out under the condition of 100 hours.

Preferred reactions between the azo compound (a) and the cellulose (b) include the following methods. That is, after impregnating the cellulose (b) with an anhydrous tertiary amine such as anhydrous pyridine, the temperature is preferably -30 to 50 ° C, preferably-
The azo compound (a) dissolved in a halogen-based medium such as dehydrated methylene chloride and dehydrated chloroform is dropped and stirred at a temperature of 20 to 0 ° C. After the completion of the dropping, the reaction is further stirred at room temperature for 2 to 100 hours.

Next, the general formula (3) obtained as described above
The alcohol (c) represented by R ³ —OH (where R ³ is the same as above) is added to the intermediate represented by the formula (1), and the remaining azo compound (a) and one of the two are reacted and left. The resulting chloride is subjected to a dehydrochlorination reaction to obtain a cellulose derivative represented by the general formula (1).

As the alcohol (c), methyl alcohol, ethyl alcohol, n-propyl alcohol, isopropyl alcohol, n-butyl alcohol,
sec-butyl alcohol, tert-butyl alcohol, pentyl alcohol, hexyl alcohol, heptyl alcohol, octyl alcohol, nonyl alcohol, decyl alcohol, undecyl alcohol, dodecyl alcohol, tridecyl alcohol, tetradecyl alcohol, pentadecyl alcohol, hexadecyl alcohol , Heptadecyl alcohol, octadecyl alcohol, nonadecyl alcohol, eicosyl alcohol and the like having 1 to 20 carbon atoms. Among them, alcohols having 1 to 6 carbon atoms are preferable.

The reaction can be carried out at a reaction temperature of 0 to 100 ° C., preferably at room temperature to 50 ° C., for a reaction time of 1 minute to 10 hours. The intermediate represented by the general formula (3) is collected by filtration. The reaction proceeds sufficiently only by washing with alcohol (c). After completion of the reaction, the reaction solution is filtered to obtain a cellulose derivative represented by the general formula (1).

Specific examples of the cellulose derivative represented by the general formula (1) include those represented by the following formula (4).

Embedded image

The grafted cellulose of the present invention is obtained by adding a radical polymerizable monomer (d) to the cellulose derivative represented by the general formula (1) obtained as described above, using the azo group of the cellulose derivative as a radical initiation source. And a compound represented by the following general formula (5).

Embedded image (In the formula, R ¹ , R ² and m are the same as those in the general formula (1). X represents a polymerized group of the radical polymerizable monomer (d).)

Specific examples of the radical polymerizable monomer (d) include 2-methacryloyloxyethyl phosphorylcholine (hereinafter sometimes abbreviated as MPC), 2-acryloyloxyethyl phosphorylcholine, methyl methacrylate (Hereinafter sometimes abbreviated as MMA), methyl acrylate, ethyl (meth) acrylate, propyl (meth) acrylate, butyl (meth) acrylate, hexyl (meth) acrylate, lauryl (meth) acrylate, (Meth) acrylic acid stearyl, (meth) acrylic acid methylamide, (meth) acrylic acid ethylamide, (meth) acrylic acid propylamide, (meth) acrylic acid butylamide, (meth) acrylic acid hexylamide, (meth) acrylic acid lauryl Amide, stearyl (meth) acrylate Bromide, styrene, Glico -
2-hydroxyethyl monomethacrylate (GEM
A), oligoethylene glycol methacrylate, polyethylene glycol monomethacrylate, and mixtures thereof.

The properties of the cellulose can be improved by selecting the radically polymerizable monomer (d) to be grafted on the cellulose. For example, MPC or MP
Grafted cellulose obtained by grafting C and MMA has little protein adsorption and denaturation, and is particularly suitable for a biocompatible material.

When the compound represented by the general formula (4) is used as the cellulose derivative represented by the general formula (1) and MPC is used as the radical polymerizable monomer (d), the following general formula (6- 1) When using MMA, the following general formula (6)
-2) When a mixture of MPC and MMA is used, a grafted cellulose represented by the following general formula (6-3) is obtained. In the formula, PMPC is a group obtained by polymerizing MPC, PMMC
Is a group in which MMA is polymerized, and P (MPC / MMA) is MPC
And a group in which MMA is polymerized.

Embedded image

The grafted cellulose of the present invention can be produced by the following production method. That is, the cellulose derivative represented by the general formula (1) is charged into a polymerization vessel together with the radically polymerizable monomer (d) in a reaction medium, and deaerated or charged with an inert gas or under an inert gas flow. The reaction is carried out at a temperature of 40 to 100 ° C, preferably 50 to 80 ° C, with stirring for 0.5 to 50 hours, preferably 3 to 20 hours.

Examples of the reaction medium include alcohols such as methanol, ethanol and propanol; ethers such as diethyl ether, tetrahydrofuran (THF) and dioxane; ketones such as acetone and methyl ethyl ketone; and mixtures thereof. It is preferable to use anhydrides or dehydrated or dried ones.

After completion of the reaction, the product can be obtained as a grafted cellulose by injecting into a medium such as methanol and precipitating. Further, the reaction product is subjected to Soxhlet extraction with a medium such as ethanol or benzene,
It can be purified by a known method such as removal of a homopolymer of the radical polymerizable monomer (d).

[0031] The grafted cellulose thus obtained can be used as a biocompatible material. In particular, cellulose grafted with MPC is particularly excellent in biocompatibility and is useful as a medical material.

The grafted cellulose of the present invention may be used as it is, or may be used together with additives such as an oxidation stabilizer, an ultraviolet absorber, a coloring agent and a plasticizer by a melt molding method or a solvent casting method. It can also be formed into a desired shape such as a sheet, a film, a fibrous shape, or a tube by a method and used. In particular, biocompatible materials include, for example, medical devices such as catheters, dialysis membranes, artificial organs, blood circuits, and dialyzers for artificial dialysis.

[0033]

The azo group-containing cellulose derivative of the present invention represented by the general formula (1) is a novel compound and is useful as a raw material for grafted cellulose suitable as a biocompatible material. The method for producing an azo group-containing cellulose derivative represented by the general formula (1) of the present invention can easily produce the above-mentioned cellulose derivative.

The azo group-containing cellulose derivative represented by the general formula (3) of the present invention is a novel compound and is useful as an intermediate of the above cellulose derivative. The method for producing an intermediate according to the present invention can easily produce the intermediate.

The grafted cellulose of the present invention is a novel compound and is useful as a biocompatible material. The biocompatible material of the present invention has excellent biocompatibility, such as little protein and denaturation.

[0036]

DESCRIPTION OF THE PREFERRED EMBODIMENTS Next, the present invention will be described based on embodiments. Synthesis Example 1 << Synthesis of 4,4'-azobis (4-cyanovaleric acid chloride) >> In a 500 mL flask equipped with a stirrer and a Dimroth connected to a liquefied calcium tube, 4,4'-azobis (4
14.0 g (0.05 mol) of cyanovaleric acid) and 200 mL of benzene were added, and 31.2 g (0.15 mol) of phosphorus pentachloride was added little by little while stirring under cooling. Thereafter, the temperature was returned to room temperature, and the mixture was further stirred for 7 hours. After completion of the reaction, the reaction solution was concentrated to about 50 mL under reduced pressure at about 30 ° C., and then concentrated to n-hexane / diethyl ether (= 3
/ 1, V / V) to precipitate crystals. The obtained crystals were dissolved in methylene chloride, and then purified by repeating twice the operation of injecting into n-hexane to cause reprecipitation.
12.10 g of pale yellowish white crystals of 4'-azobis (4-cyanovaleric chloride) were obtained. The yield was 74.1%. The results of infrared absorption spectrum (IR) analysis are shown below.

IR (KBr Tablet, [ν cm ^-1 ]) 2260 -CN 1800 -COCl

Example 1 << Synthesis of 4,4'-azobis (4-cyanovaleric acid) -cellulose (V-501-Cell) >> 50 g of dry cellulose was placed in a 500 mL flask equipped with a stirrer and a Dimroth. A mixture of 300 mL of pyridine and 100 mL of water was added, soaked overnight, and stirred to activate. The pyridine was removed by filtration through a 17G-4 glass filter, and the cellulose was immersed in anhydrous pyridine for 2 to 3 hours. This operation was repeated three times.

Next, 50.0 g of the pyridine-treated cellulose was placed in a 200 mL flask equipped with a stirrer, a Dim funnel equipped with a calcium chloride tube, and a dropping funnel.
(0.3 mol) and 400 mL of dry pyridine were added and stirred under ice-cooling. Then dry methylene chloride 50
After 14.7 g (46.2 mmol) of 4,4'-azobis (4-cyanovaleric acid chloride) dissolved in mL was added dropwise over 0.5 hours, the mixture was further stirred at room temperature for 72 hours. After completion of the reaction, the reaction solution was filtered with a glass filter,
The obtained powder was sufficiently washed with methanol and methylene chloride to obtain 52.6 g of a white powder of 4,4'-azobis (4-cyanovaleric acid) -cellulose (hereinafter abbreviated as V-501-Cell). . The yield was 81.2%.
The results of the infrared absorption spectrum analysis are shown below and in FIG.

IR (KBr Tablet, [ν cm ^-1 ]) 3350 -OH 2260 -CN 1830 -COO- 1750 -COO-

The results of the elemental analysis are shown below. Elemental analysis value: C: H: N = 43.73%: 5.91%: 1.13% Azo group introduction rate (%) = 8.82% The calculation formula is as follows. Azo group introduction rate (%) = (N% of elemental analysis) /12.81

Example 2 << Synthesis of PMPC-grafted Cellulose (PMPC-g-Cell) >> 1.00 g of V-501-Cell synthesized in Example 1
And 5.90 g (19.2 mmol) of PMC were mixed with 10 mL of a mixed medium of anhydrous ethanol / anhydrous THF (= 9/1, V / V) and poured into a glass polymerization tube. The polymerization tube was repeatedly frozen, degassed, and replaced with nitrogen gas in a liquid nitrogen bath, and then sealed under vacuum. The polymerization tube was polymerized with shaking at 50 ° C. for 12 hours. Thereafter, the contents of the sealed tube are opened and the contents of the sealed tube are taken out, poured into a large amount of methanol, then washed with methanol, dried in vacuum until the temperature becomes constant, and PMPC-grafted cellulose (hereinafter abbreviated as PMPC-g-Cell) is obtained. Obtained. Thereafter, Soxhlet extraction was performed with ethanol for 20 hours to remove the MPC homopolymer. The results are shown below.

4.75 g MPC homopolymer; 0.15 g Graft efficiency; 95.43%

## EQU1 ## Grafting efficiency (%) = ｛(total polymer weight) −
(Extracted polymer weight)｝ × 100 / (total polymer weight)

Next, the results of elemental analysis of the obtained graft polymer are shown. The Figure 2 The infrared absorption spectrum, ¹³
The CCP / MAS solid state NMR spectrum is shown in FIG.
The DSC thermogram of No. 2 is shown in FIG. Elemental analysis: C: H: N = 41.73%: 7.46%: 3.40%

Example 3-1 << Synthesis of PMMA-grafted cellulose (PMMA-g-Cell) >> 1.00 g of V-501-Cell synthesized in Example 1
Then, 2.00 g (0.02 mol) of MMA and 10 mL of a mixed medium of anhydrous ethanol / anhydrous THF (= 9/1, V / V) were mixed and poured into a glass polymerization tube. The polymerization tube was repeatedly frozen, degassed, and replaced with nitrogen gas in a liquid nitrogen bath, and then sealed under vacuum. The polymerization tube was polymerized with shaking at 50 ° C. for 12 hours. Thereafter, the contents of the sealed tube are opened and the contents of the sealed tube are taken out, poured into a large amount of methanol, then washed with methanol, dried in vacuum until the temperature becomes constant, and PMMA-grafted cellulose (hereinafter abbreviated as PMMA-g-Cell) is obtained. Obtained. Thereafter, Soxhlet extraction was performed with benzene for 20 hours to remove the MMA homopolymer. The results are shown below. FIG. 2 shows the infrared absorption spectrum.

Graft polymer: 0.52 g MMA homopolymer; 0.37 g Graft efficiency: 57.82% Elemental analysis; C: H: N = 48.89%: 6.80%: 0%

Example 3-2 << P (MPC / MMA) Grafted Cellulose (P (MPC / MMA) -g-Cel)
Synthesis of l) >> V-501-Cell 1.00 synthesized in Example 1
g, MPC 1.48 g (4.8 mmol) and MM
A 1.50 g (0.15 mol) of absolute ethanol /
It was mixed with 10 mL of a mixed medium of anhydrous THF (= 9/1, V / V) and poured into a glass polymerization tube. The polymerization tube was repeatedly frozen, degassed, and replaced with nitrogen gas in a liquid nitrogen bath, and then sealed under vacuum. The polymerization tube was polymerized with shaking at 50 ° C. for 12 hours. Thereafter, the contents of the sealed tube are taken out by opening the container, poured into a large amount of methanol, then washed with methanol, dried in vacuum until the temperature becomes constant, and grafted with P (MPC / MMA) -grafted cellulose [P (MPC / MMA) -G-Ce
11). Thereafter, Soxhlet extraction was performed with ethanol and then with benzene for 20 hours to remove other polymers such as a polymer of MPC and MMA. The results are shown below. FIG. 2 shows the infrared absorption spectrum.

Graft polymer: 1.22 g Other polymer: 0.46 g Graft efficiency: 72.63% Elemental analysis; C: H: N = 48.16%: 7.16%: 1.47%

Example 4 << Protein Adsorption Test >> 10 mL of a 50 mg / L protein (albumin; Alb, globulin; Glo) solution and the PMPC- of Example 3-1 in which the diameter was adjusted to about 112.5 μm by sieving.
g-Cell or P of Example 3-2 (MPC / MM
A) 0.3 g of -g-Cell powder was placed in a test tube.
The test tube was placed in a thermostat at 25 ° C., and the time to reach the adsorption equilibrium was 2 hours. 10 mL of the mixed solution was collected, centrifuged (12,500 rpm) for 15 minutes, and 2 mL of the supernatant was collected to determine the protein concentration in the supernatant. That is, 2 mL of the supernatant was collected with 2 mL of supernatant.
mL was added and left to stand for 10 minutes. Add Reagent B and add another 30
After leaving still for a minute, it was subjected to UV measurement. The protein concentration in the supernatant was determined using a calibration curve from the absorption intensity at 750 nm. The amount of protein adsorbed on the polymer powder was determined from the difference between the amount of protein charged and the amount of protein in the supernatant.

The reagent A was a 2% Na ₂ CO ₃ solution (0.1%).
2N-NaOH aqueous solution) is a mixed solution of 20 mL, 1% CuSO ₄ aqueous solution 0.4 mL and 2% potassium tartrate 0.4 mL, and the reagent B is Fol diluted twice with water.
in-Ciocalteu's reagent [Folin Ciocalteu test (sodium tungstate 100 g, sodium molybdate 25 g, 85% phosphoric acid 50 mL, concentrated hydrochloric acid 10)
ml of water dissolved in 700 ml of water, which is a reagent for quantifying alkaline phosphatase in blood]. FIG. 5 shows the protein adsorption amount of each polymer.

As can be seen from the results shown in FIG. 5, untreated cellulose and PMPC-g were compared to PMMA-g-Cell.
-Cell, P (MMA / MPC) -g-Cell greatly suppressed albumin (Alb) adsorption. A decrease in the amount of adsorbed globulin (Glo) was observed as compared with untreated cellulose.

Reference Example 1 << Measurement of Water Content >> The equilibrium water contents of various polymers shown in Table 1 were determined. The results are shown in Table 1. The equilibrium water content was determined by immersing various polymers in distilled water at 25 ° C. for 24 hours, measuring the weight increase of the polymer before and after immersion with an ultra-microbalance, and using the following formula. Equilibrium water content (%) = [(Ws−Wd) / Ws] × 100 where Wd is the weight of the polymer before immersion in water, and Ws is the weight of the polymer after immersion in water.

[0053]

[Table 1]

[Brief description of the drawings]

FIG. 1 is an infrared absorption spectrum of the azo group-containing cellulose derivative and cellulose obtained in Example 1.

FIG. 2 is an infrared absorption spectrum of the grafted cellulose obtained in Example 2, Example 3-1 and Example 3-2.

FIG. 3 is a ¹³ C CP / MAS solid-state NMR spectrum of the grafted cellulose and cellulose obtained in Example 2.

FIG. 4 is a Run 2 DSC thermogram of the grafted cellulose, cellulose and MPC polymer obtained in Example 2.

FIG. 5 is a graph showing the results of a protein adsorption test of Example 4.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁶ Identification code FI // (C08F 251/02 230: 02)

Claims (7)

[Claims] 1. A compound of the general formula (1) (Wherein, R ¹ is a divalent hydrocarbon group having 1 to 20 carbon atoms, R ²
And R ³ represent a monovalent hydrocarbon group having 1 to 20 carbon atoms. m represents a mole fraction and is a real number of 0.001 to 1. An azo group-containing cellulose derivative represented by the formula: 2. A compound of the general formula (2) (Wherein, R ¹ is a divalent hydrocarbon group having 1 to 20 carbon atoms, R ²
Is a monovalent hydrocarbon group having 1 to 20 carbon atoms. An azo compound having a carboxylic acid chloride group represented by the formula (a):
Is reacted with cellulose (b) in the presence of a basic compound to give a compound of the general formula (3) (Wherein, R ¹ is a divalent hydrocarbon group having 1 to 20 carbon atoms, R ²
And R ³ represent a monovalent hydrocarbon group having 1 to 20 carbon atoms. m represents a mole fraction and is a real number of 0.001 to 1. The method for producing an azo group-containing cellulose derivative according to claim 1, wherein an intermediate represented by the formula (1) is obtained, and the intermediate is reacted with an alcohol (c). 3. General formula (3) (Wherein, R ¹ is a divalent hydrocarbon group having 1 to 20 carbon atoms, R ²
And R ³ represent a monovalent hydrocarbon group having 1 to 20 carbon atoms. m represents a mole fraction and is a real number of 0.001 to 1. An azo group-containing cellulose derivative represented by the formula: 4. A compound of the general formula (2) (Wherein, R ¹ is a divalent hydrocarbon group having 1 to 20 carbon atoms, R ²
Represents a monovalent hydrocarbon group having 1 to 20 carbon atoms. An azo compound having a carboxylic acid chloride group represented by the formula (a):
4. The method for producing an azo group-containing cellulose derivative according to claim 3, wherein cellulose (b) is reacted in the presence of a basic compound. 5. A grafted cellulose obtained by graft-polymerizing one or more radically polymerizable monomers (d) to the azo group-containing cellulose derivative according to claim 1. 6. The method according to claim 1, wherein the radically polymerizable monomer (d) is 2-
The grafted cellulose according to claim 5, which is (meth) acryloyloxyethyl phosphorylcholine. 7. A biocompatible material comprising the grafted cellulose according to claim 5 or 6.