JPH10251209A - (meth)acrylic serine ester, its production, copolymer and biocompatible material - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject new compound having compatibility specific to an organism component and useful as a raw material for biocompatible materials such as medical materials or biomaterials. SOLUTION: This compound is represented by formula I (R is H or methyl), e.g. O-methacryloyl-L-serine. The compound of formula I is obtained by reacting a compound of formula II with (meth)acrylic acid chloride at -30 deg.C to ambient temperature for 5-100hr by using dehydrochlorination agent to afford a compound of formula III, decomposing a protective group of the compound of formula III by using an acidic compound (e.g. trifluoroacetic acid), acidifying the compound to afford hydrochloride of (meth)acrylic acid serine ester and further, removing the hydrochloride by using a basic compound. A monomer mixture containing 0.5-10mol% component comprising the resultant (meth)acrylic acid serine ester is radically polymerized to provide a polymer of formula IV [R<1> is H, etc.; R<2> is a 1-4C alkyl; (m) is 1-3,000; (n) is 20-30,000].

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a serine (meth) acrylate, a method for producing the same, a polymer obtained by polymerizing the serine (meth) acrylate, and a biocompatible material using the polymer.

[0002]

2. Description of the Related Art In order to ensure biocompatibility with a polymer material, the chemical structure of the material surface is controlled to control the adsorption of a protein that triggers the formation of a thrombus, the adhesion of platelets, and the activation and aggregation of platelets. It is important to control. Therefore, control of the chemical structure of the material surface is an important issue in the development of biocompatible materials, and surface properties and biocompatibility of various medical polymers have been studied. As an effective method for imparting biocompatibility, there is known a method of introducing a main constituent component of a phospholipid bilayer membrane constituting a biological membrane to a material surface. For example, a polymer obtained by polymerizing a monomer of 2-methacryloyloxyethyl phosphorylcholine (abbreviated as MPC) in which the polar portion of a phospholipid is modified is known to control protein adsorption. Biomaterial, Vol. 9 (No. 5), pp. 243-249, (199)
1 year)｝. In addition, 2-glycol-containing glucose groups
(Glucosyloxy) ethyl methacrylate (GEMA
Is also known to control protein adsorption similarly. For example, Nakamae et al., The Society of Polymer Science, Proc. 17-0
9, (1990)｝. As described above, as an effective method for imparting biocompatibility to a general-purpose polymer material, a method of introducing a phosphorylcholine group of a phospholipid or a sugar of a glycolipid, which constitutes a biological membrane, onto a material surface has been performed. on the other hand,
Like a lipid, a material whose surface is modified with an amino acid constituting a biomembrane or protein is expected to have a favorable interaction with a biomaterial. For example, the interaction between alanine methacrylamide and methacryloyloxyethylalanine and proteins has been shown (for example, Sugiyama et al., The Society of Polymer Science, Proceedings, Vol. 44, p. 631 (19
95)｝. Heretofore, serine (meth) acrylate has not been known. Further, a polymer of the (meth) acrylic acid serine ester was not known. Furthermore, it has not been known that the polymer of the serine (meth) acrylate has excellent biocompatibility.

[0003]

SUMMARY OF THE INVENTION It is a first object of the present invention to provide a serine (meth) acrylate. A second object of the present invention is to provide a method for producing the serine (meth) acrylate. A third object of the present invention is to provide a polymer containing the serine (meth) acrylate as a constituent. Still another object of the present invention is to provide a biocompatible material using the polymer of serine (meth) acrylate.

[0004]

Means for Solving the Problems The present inventors have conducted intensive studies in view of the above problems, and as a result, protected the amino group of serine and reacted with (meth) acrylic chloride with the hydroxyl group of serine to form (meth) ) That it is possible to synthesize serine acrylate and that the polymer of serine (meth) acrylate has excellent biocompatibility,
The present invention has been completed. That is, the present invention includes the following (1) to (5). (1) The following general formula [1]

Embedded image (Wherein, R represents a hydrogen atom or a methyl group)
A (meth) acrylic acid serine ester represented by the formula: (2) The method for producing serine (meth) acrylate according to claim 1, comprising the following step (1) and step (2). Step (1); the following formula [2]

Embedded image Is reacted with (meth) acrylic acid chloride using a dehydrochlorinating agent to give the following formula [3]

Embedded image The step of synthesizing Step (2): The above-mentioned product is decomposed with an acidic compound to decompose the protecting group, and then acidified to obtain a hydrochloride of serine (meth) acrylate. Removal process. (3) A polymer containing 0.5 mol% to 10 mol% of a component based on serine (meth) acrylate obtained by radical polymerization. (4) The polymer has the following general formula [4]

Embedded image (Wherein R and R ¹ represent a hydrogen atom or a methyl group,
R ² is an alkyl group having 1 to 4 carbon atoms;
Means serine (meth) acrylate and (meth)
In the addition mole number of the alkyl acrylate,
m = 1 to 3000, n = 20 to 30,000.
Further, when 2 ≦ m and 20 ≦ n, [] may be added in a block shape or a random shape. ) (Meta)
Weight average molecular weight of serine acrylate 2,000
~ 5,000,000 polymers. (5) A biocompatible material characterized by using a polymer containing 0.5 mol% to 10 mol% of the constituent component based on the serine (meth) acrylate obtained by radical polymerization.

[0005]

BEST MODE FOR CARRYING OUT THE INVENTION In the general formula [1], R represents a hydrogen atom or a methyl group.

The serine (meth) acrylate represented by the general formula [1] can be easily produced by the following method. That is, it is a method for producing serine (meth) acrylate comprising the following step (1) and step (2). Step (1); the following formula [2]

Embedded image Is reacted with (meth) acrylic acid chloride using a dehydrochlorinating agent to give the following formula [3]

Embedded image The step of synthesizing

Step (2): The above product is decomposed with an acidic compound to decompose the protecting group, and then acidified to obtain a hydrochloride of serine (meth) acrylate. Removing the hydrochloride.

In the step (1), Nt-butoxycarbonyl-OL represented by the general formula [1] of the raw material is used.
-Serine includes, for example, commercially available products (manufactured by Aldrich, Aldrich, Tokyo Kasei, Sigma, etc.). Alternatively, it may be synthesized from L-serine according to a standard method. For example, Reference book, published by Maruzen Co., Ltd., Izumiya et al., "Peptide synthesis" 1975
Year)}. In addition, as (meth) acrylic acid chloride,
A commercially available product can be used as it is or after purification. For example, commercially available products include acrylic acid chloride and methacrylic acid chloride manufactured by Aldrich, Tokyo Chemical Industry Co., Ltd., and Wako Pure Chemical Industries, Ltd. In the reaction in the above step (1), the reaction solvent may be any solvent that dissolves the reactant and the product, or a solvent that dissolves the reactant and the product and precipitates a hydrogen chloride salt that is produced. Examples of such solvents include chloroform, dichloromethane, tetrahydrofuran (TH
F) and ethers. Preferably, it is THF. Examples of the dehydrochlorinating agent include trialkylamines such as trimethylamine, triethylamine and tripropylamine; aromatic tertiary amines such as dimethylaniline; and cyclic tertiary amines such as pyridine and dimethylaminopyridine. Triethylamine and the like are preferably mentioned from the viewpoint of handling and availability. In addition, the general formula [1] of the raw material:
The reaction is preferably carried out at a molar ratio of (meth) acrylic acid chloride to dehydrochlorinating agent of 1: 0.8 to 1.5: 1 to 2. Further, the reaction temperature is from -30C to room temperature, preferably from -20C to 0C. The reaction time is 5 to 100 hours, preferably 15 to 30 hours. The reaction is preferably performed in an atmosphere of a dry inert gas stream such as nitrogen gas or a dry air stream. The salt thus formed is separated by filtration, and after distilling off the solvent, the compound of the above formula [3] in which the amino group is blocked (protected) can be obtained by distillation under reduced pressure. After the reaction, hexane, petroleum ether,
It can be purified by recrystallization using diethyl ether or the like.

In the step (2), the target compound can be obtained by removing the amino group-protected group of serine using a solution of the intermediate of the formula [3] and an acidic compound. Examples of the acidic compound include trifluoroacetic acid; an acetic acid solution of hydrogen bromide, an acetic acid solution of hydrogen chloride; and a reaction solvent solution of hydrochloric acid or formic acid. Preferably, it is trifluoroacetic acid. It is desirable to use a dehydrated product as the solvent. Examples of the type of the solvent used include chloroform and methylene chloride. Preferably, methylene chloride is used. The molar ratio of the compound of the formula [3] to the acidic compound is from 1: 1 to 10. As the reaction temperature,
The temperature is from -30C to 50C, preferably from 0C to room temperature. The reaction time is 0.1 to 10 hours, preferably 0.5 to 3 hours. The reaction is preferably performed in an atmosphere of a dry inert gas stream such as nitrogen gas or a dry air stream. After removing the protective group for the amino group of serine from the compound of the formula [3] with an acidic compound, excess hydrochloric acid is added under ice cooling and dissolved in a solvent such as methanol to obtain a hydrochloride form of the product. In this case, the hydrochloric acid is preferably an ethyl acetate solution. Then, after distilling off the solvent, diethyl ether, T
After washing with a solvent such as HF, the hydrochloride form of the product is obtained with high purity. Then, the hydrochloride form of this product is dispersed in a solvent such as acetonitrile, and under ice-cooling, an equimolar or more basic compound such as triethylamine is added and dehydrochlorinated to obtain the desired compound of the formula [1] (Meth) acrylic acid serine ester can be obtained. Examples of the basic compound include, in addition to triethylamine, the compounds of the above-described dehydrochlorinating agent.

The method for producing a polymer of serine (meth) acrylate can be easily obtained by the following method. That is, a polymer is obtained by radically polymerizing the above-mentioned serine (meth) acrylate and a copolymerizable monomer in a random or block manner. The polymer is a polymer containing 0.5 mol% to 10 mol% of a constituent unit based on serine (meth) acrylate. If the content of the component based on the (meth) acrylic acid serine ester is less than 0.5 mol%, the amount of the (meth) acrylic acid serine ester as a component is reduced, and the effect such as biocompatibility is not exhibited. . When the content of the component based on the (meth) acrylic acid serine ester is more than 10 mol%, the content of the component based on the other copolymerizable monomer decreases, and there is no suitable solvent, and the strength and adhesion are high. This is not preferable because effects of physical properties such as properties are not exhibited. The polymerization method is a commonly used polymerization method and includes, for example, solution polymerization, bulk polymerization, emulsion polymerization, suspension polymerization and the like.
Monomers copolymerizable with (meth) acrylic acid serine ester include methyl (meth) acrylate, ethyl (meth) acrylate, propyl (meth) acrylate, and (meth) acrylate.
Alkyl (meth) acrylates such as butyl acrylate, hexyl (meth) acrylate, lauryl (meth) acrylate, stearyl (meth) acrylate; (meth)
Acrylic acid methylamide, (meth) acrylic acid ethylamide, (meth) acrylic acid propylamide, (meth) acrylic acid butylamide, (meth) acrylic acid hexylamide, (meth) acrylic acid laurylamide, (meth) acrylic acid stearylamide, etc. (Meth) acrylic acid alkylamides; styrene and the like. Preferably, an alkyl (meth) acrylate having 1 to 4 carbon atoms is used. As the solvent used for the polymerization, the monomer may be dissolved or dispersed, and specifically, water, methanol,
Examples include ethanol, propanol, t-butanol, benzene, toluene, dimethylformamide, tetrahydrofuran, and the like, and mixtures thereof. As the polymerization conditions, polymerization can be carried out under the conditions usually used. The reaction temperature is, for example, 40 ° C to 100 ° C, and the reaction time is 1 hour to 50 hours. As the radical polymerization initiator, any ordinary radical polymerization initiator may be used. Specifically, 2,2′-azobisisobutyronitrile (AIBN), azobisvaleronitrile,
Aliphatic azo compounds such as 2,2′-azobis [2- (2-imidazolin-2-yl) propane] dihydrochloride; organic peroxides such as benzoyl peroxide and lauroyl peroxide; ammonium persulfate; potassium peroxide And the like. Although the molecular weight of the obtained polymer is not particularly limited, it is preferably 2,000 to 5,000,000, and more preferably 5,000 to 1,000,000.
0. If the molecular weight of the polymer is less than 2,000, it is easy to peel off by coating or the like, and if the molecular weight of the polymer is more than 5,000,000, the viscosity becomes high and it becomes difficult to handle, which is not desirable. The above general formula [4]
In the formula, m = 1 to 2,000 and n = 20 to 3
It is 0000.

The obtained polymer may be purified by a solvent commonly used, or may be directly used as particles by emulsion polymerization or suspension polymerization.

The serine (meth) acrylate of the present invention has a (meth) acrylic polymerizable group and can be polymerized. Serine (meth) acrylate has biocompatibility and can be polymerized to impart biocompatibility. The copolymer using the (meth) acrylic acid serine ester has specific compatibility with a biological component, and the polymer can be used as it is in the form of particles, or can be processed. Also, cast from an organic solvent and used as a film, or a polymer,
It can be used by irradiating energy such as plasma, gamma ray, ultraviolet ray or the like onto the surface of a polymer of another material or the like. Specifically, housing materials for medical devices such as catheters, cannulas, and hollow fibers, or medical devices such as hollow fibers, medical supplies such as medical materials, eye care supplies such as contact lenses, cosmetic materials, and toiletry supplies It is expected that it can be used as a biocompatible material.

[0013]

Industrial Applicability The present invention is a novel serine (meth) acrylate, which can be polymerized to give biocompatibility. ADVANTAGE OF THE INVENTION The manufacturing method of this invention protects an amino group, has high reactivity of esterification, and can produce this (meth) acrylic acid serine ester with high purity and high yield. The copolymer using the (meth) acrylic acid serine ester has specific compatibility with a biological component, and is expected to be used as a biocompatible material such as a medical material and a medical material.

[0014]

Next, the present invention will be described based on embodiments. Example 1 Synthesis 1-1: Synthesis of Nt-butoxycarbonyl-O-methacryloyl-L-serine (Boc-serMA) A 500 ml equipped with a stirrer, a cooling tube with a ball, a nitrogen inlet tube, and a dropping funnel. 25.0 g of Nt-butoxycarbonyl-L-serine was added to the necked flask (0.132 mol).
l) and 20.03 g of triethylamine (0.198 mol)
l) and 300 ml of dehydrated tetrahydrofuran (T
HF). 20.70 g of methacrylic acid chloride (0.198 g) was stirred at −20 ° C. under a nitrogen stream.
mol) was added dropwise over 1 hour. After dropping, -20
The reaction was carried out at 10 ° C for 10 hours and further at -5 ° C for 5 hours. Next, in order to induce unreacted methacrylic acid chloride into methacrylic acid, 50 g of water was added and stirred. After the reaction,
Diethyl ether was added, and the precipitated triethylamine hydrochloride was filtered off and dried over anhydrous sodium sulfate overnight. The anhydrous sodium sulfate was filtered off and concentrated by a rotary evaporator to obtain a viscous solid. Recrystallization from hexane gave 19.38 g of white crystals. This compound is abbreviated as Boc-serMA. The yield of Boc-serMA was 53.8%. Also, this Boc-serMA
Had a melting point of 95 to 98 ° C.

The results of ¹ H-NMR, IR analysis and elemental analysis of Boc-serMA are shown below. 1. ^{1 H-NMR (δ (ppm} ): TMS / DMSO) 1.28-1.48 (m, 9H); -C (C H 3) 3 1.87 (d, 3H); -C H 3 4. 08 (m, 1H); - CH - 4.22 (m, 1H); - CH 2 - 4.33 (m, 1H); - CH 2 - 5.69 (m, 2H); -C = C H ₂ 2. IR (NaCl plate) νcm ⁻¹ 2960 cm ⁻¹ ; -CH ₃ 2930; = CH ₂ 1760; -COOH 1720; -CO-O- 1680; -CO-NH- 3. Elemental analysis value C ₁₂ H ₁₉ O ₆ N = 273.286 Calculated value: C: H: N = 52.74%: 7.01%: 5.
13% Found: C: H: N = 52.57%: 6.61%: 4.
From 81% or more, Boc-serMA (Nt-butoxycarbonyl-O-methacryloyl-L-serine) was identified as having the following formula.

Embedded image

Synthesis 1-2: Synthesis of O-methacryloyl-L-serine (= serine methacrylate; serMA) In a 200 ml four-necked flask equipped with a stirrer, a condenser tube with a ball, a nitrogen inlet tube, and a dropping funnel. Synthesis 1-1
16.44 g (0.060 g) of Boc-serMA obtained in
mol) and 40.0 g of trifluoroacetic acid (0.358 m
ol) and 100 ml of dehydrated methylene chloride, and the reaction was continued for 1 hour while stirring at room temperature. After completion of the reaction, methylene chloride as a solvent was distilled off using a rotary evaporator, and 50 ml of diethyl ether was added. After stirring, the supernatant was decanted to extract unreacted trifluoroacetic acid. Dissolve the residue in 400 ml of dehydrated methanol, stir under ice-cooling, and add 4H
-HCl in ethyl acetate was added to make it acidic. After distilling off methanol with a rotary evaporator and vacuum-drying at room temperature, the obtained viscous solid was repeatedly washed with 50 ml of diethyl ether until white crystals were obtained,
The hydrochloride salt of serMA was obtained. Further, the hydrochloride of serMA was dispersed in 200 ml of acetonitrile, and triethylamine (6.06 g) in an equimolar amount to the hydrochloride of serMA was added under ice cooling, followed by stirring. The mixture was filtered through a glass filter (17G-4) and repeatedly washed with chloroform to obtain 5.02 g of white crystals of serMA. serM
The yield of A was 48.2%. Also, this serMA
Has a decomposition point of 114 to 119 ° C. and an isoelectric point of 5.0.
It was 8.

The results of ¹ H-NMR, IR analysis and elemental analysis of the obtained serMA are shown below. 1. ^{1 H-NMR (δ (ppm} ): TMS / DMSO) 1.86 (s, 3H); -C H 3 4.07 (m, 1H); - CH - 4.53 (m, 2H); - CH _{2 - 5.70-6.11 (m, 2H)} ; -C = C H 2 - 2. IR (NaCl plate) ν cm ^-1 2100 cm ^-1 ; -NH ₃ ⁺ 1720; -CO-O-1620; -NH ₃ ⁺ 1520; -NH ₃ ⁺ 1470; -COO ^- 3. Elemental analysis value: C ₇ H ₁₁ O ₄ N = 173.169. Calculated value: C: H: N = 48.55%: 6.40%: 8.
09% found: C: H: N = 48.50%: 6.32%: 8.
19% or more, serMA (O-methacryloyl-L
-Serine) was identified as

Embedded image

Example 2-1; serMA-co-MMA
Synthesis of copolymer (f = 1) 0.413 g (2.4 m) of serMA synthesized in Example 1
mol) and 24.0 g of methyl methacrylate (MMA)
(240 mmol) as a radical polymerization initiator,
2'-azobis [2- (2-imidazolin-2-yl) propane] dihydrochloride {VA-044, Wako Pure Chemical Industries, Ltd.
0.077 g (0.24 mmol) manufactured by the Company and 150 g of ion-exchanged water are placed in a 500 ml four-necked flask equipped with a thermometer, a nitrogen blowing tube, a cooling tube, and a stirrer. stirring speed of .m., 6
Emulsion polymerization was performed under the condition of time. The polymerized polymer particles were purified using an ion exchange resin (manufactured by Mitsubishi Kasei, Diaion, anion resin: cationic resin = 1: 1).
21.85 g of polymer was obtained. The polymer yield was 89.5%
Met. Using the obtained polymer particles, the particle size, X-ray photoelectron spectrometer (= XPS), water content, and zeta potential (= ζ-potential) were measured by the test methods described below. The results are shown in Table 1.

The results of ¹ H-NMR and IR analyzes of the obtained polymer are shown below. 1. ^{1 H-NMR (δ (ppm} ): TMS / CDCl 3) 1.8 -2.1; -C H 3, - CH 2 - ( backbone) 3.35-3.45; - CH - (serine portion ) 3.45-3.50; - CH ₂ - (serine unit) 3.50-3.65; -COO CH ₃ 2. IR (NaCl plate) ν cm ^-1 2100 cm ^-1 ; -NH ₃ ⁺ 1720; -CO-O- 1620; -NH ₃ ⁺ 1520; -NH ₃ ⁺ 1470; -COO ^{-From the} above, the relationship between serMA and MMA The copolymer was identified as having the following formula.

[0020]

Embedded image

Example 2-2: serMA-co-MMA
Synthesis of copolymer (f = 3) 0.413 g of serMA used in Example 2-1
(2.4 mmol) in 1.246 g of serMA (7.2
The polymerization was carried out in the same manner as in Example 2-1 except that the polymerization was performed in the same manner as in Example 2-1. 18.05 g of polymer was obtained. The polymer yield was 71.5%. ¹ H-N of the obtained polymer
As a result of MR and IR analysis, the peak position was the same as that of Example 2-1. The obtained polymer was similarly tested. The results are also shown in Table 1.

Comparative Example 2-1: Polymerization of PMMA 0.413 g of serMA used in Example 2-1
(2.4 mmol) without using 24.0 g (24 mmol) of MMA.
Polymerization was carried out in exactly the same manner as in Example 2-1 except that only 0 mol) was used. 21.65 g of a polymer were obtained. The polymer yield was 90.2%. The results are shown in Table 1.

[0023]

[Table 1] The molecular weight was measured by gel permeation chromatography (GPC) in terms of solvent THF and standard PMMA conversion.

The conditions of the test method used are as follows. <Measurement of particle size>: Standard polystyrene latex (Dow
Chemical Company, Uniform Latex Part
ices φ = 474 nm Lot. No. 1 × 9
The particle size was determined in comparison with the SEM photograph of 4). Further, the particle size distribution was determined by Pacific Scientific N
It was determined by a light scattering method using ICOMP-370. <XPS analysis>; X-ray photoelectron spectrometer (XPS) Shimadzu ESCA-750 was used for the polymer particle surface. The polymer particles are placed on a stainless steel holder, and 5 × 10 ⁻⁷ Torr or less, MgKα (12
53.6 eV). <Measurement of water content (%)>: A polymer sample was dissolved in a solvent, and the film obtained by the solvent developing method was dissolved in a phosphate buffer solution at 25%.
It was immersed at 24 ° C. for 24 hours and calculated from the weight increase before and after immersion. <Measurement of ζ-potential> The transfer time of polymer particles that migrate 50 μm when a DC electric field having a potential difference of 50 V was applied was measured at room temperature using a microelectrophoresis device manufactured by Mitamura Riken Co., Ltd.

Comparative Example 2-3: Synthesis of poly (MPC) MPC 2.0 g (6.77 mmol) AI as initiator
BN 0.054 g (0.068 mmol) ethanol /
10 ml of a mixed solvent of THF (= 90/10 V / V%) was placed in a glass polymerization tube and sealed under reduced pressure. Reaction temperature 60
After polymerizing under polymerization conditions of shaking at 12 ° C. for 12 hours, the content was poured into a large amount of diethyl ether to precipitate poly-MPC, thereby obtaining a polymer. The obtained polymer was similarly used as a sample of Comparative Example 3-2 described later.

Example 3-1: Protein adsorption test Example 3-1-1 is the polymer of Example 2-1 and Example 3-
1-2 uses the polymer synthesized in Example 2-2 and uses albumin (Alb) and globulin (Gl
Using o), a protein adsorption test was performed under the following test conditions. The amount of protein adsorbed was calculated by the Lowry method. <Protein adsorption test> In the case of albumin; initial albumin concentration 50 mg / liter, pH = 5.6, ionic strength 0.01, temperature 25
After immersing the polymer at 2 ° C. for 2 hours, the polymer particles were removed by filtration, and the amount of adsorbed albumin was calculated from the measurement of albumin concentration in the solution. In the case of globulin; initial globulin concentration 50 mg / liter, pH = 6.2, ionic strength 0.01, temperature 25
After immersing the polymer at 2 ° C. for 2 hours, the polymer particles were removed by filtration, and the amount of adsorbed globulin was calculated from the measurement of the globulin concentration in the solution. The results are shown in FIG.

Comparative Example 3-1-1 to 3-5-1-5;
In the same manner as -1, Comparative Example 3-1-1 uses PMMA (polymethyl methacrylate) polymerized in Comparative Example 2-1. Comparative Examples 3-1-2 to 3-1-5 are: The Society of Polymer Science, Proceedings, 44, 631 (1995)
AlaMAm (alanine methacrylamide) according to
AlaEMA (methacryloyloxyethylalanine)
An albumin and globulin adsorption test was performed using a copolymer of MPC and MMA. Fig. 1 shows the results.
It was shown to.

From the above results, it can be seen that the polymer containing 1 and 3 mol% of the constituent component based on serMA is specific in the type and amount of adsorption of albumin and globulin.

[0029]

[Brief description of the drawings]

FIG. 1. Results of protein adsorption test by polymer

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁶ Identification code FI // (C08F 220/14 220: 36)

Claims (5)

[Claims] 1. A compound represented by the following general formula [1] (Wherein, R represents a hydrogen atom or a methyl group)
A (meth) acrylic acid serine ester represented by the formula: 2. A method for producing serine (meth) acrylate, comprising the following step (1) and step (2). Step (1): The following formula [2] Nt-butoxycarbonyl-OL-serine represented by the following formula is reacted with (meth) acrylic acid chloride using a dehydrochlorinating agent to give the following formula [3] The step of synthesizing Step (2): The above-mentioned product is decomposed with an acidic compound to decompose the protecting group, and then acidified to obtain a hydrochloride of serine (meth) acrylate. Removal process. 3. A polymer containing from 0.5 mol% to 10 mol% of a component based on serine (meth) acrylate obtained by radical polymerization. 4. The polymer according to claim 3, wherein the polymer is represented by the following general formula [4]: (Wherein R and R ¹ represent a hydrogen atom or a methyl group,
R ² is an alkyl group having 1 to 4 carbon atoms;
Means serine (meth) acrylate and (meth)
In the addition mole number of the alkyl acrylate,
m = 1 to 3000, n = 20 to 30,000.
In the case of 2 ≦ m and 20 ≦ n, [] may be added in a block shape or a random shape. ) Represented by (meth) acrylic acid serine ester has a weight average molecular weight of 2,000 to 5,
1,000,000 polymers. 5. The (meth) according to claim 3, which is subjected to radical polymerization.
A biocompatible material comprising a polymer containing 0.5 mol% to 10 mol% of a constituent component based on serine acrylate.