JPH0366620A - Material for medical treatment and production thereof - Google Patents

Abstract

PURPOSE:To obtain a material for medical treatment of a polymer compound provided with bioavailability having stability for a long period of time by bonding a fatty acid macromer through a block copolymer to the polymer compound with covalent bond. CONSTITUTION:A functional group of a fatty acid macromer (e.g. one containing fatty acid at one end and amino group at the other) is linked by covalent bond to a functional group (e.g. carboxyl group) of a hydrophobic part of a block copolymer comprising a hydrophilic polymer part and a hydrophobic polymer part and then a functional group (e.g. epoxy group) of the hydrophilic part of the block copolymer is linked with covalent bond to a functional group of polymer compound to give a polymer compound having reduced blood clotting, suppressing activation of complement system and subduing platelet adhesion. A polymer shown by the formula [R<1> to R<4> are H or lower alkyl; R<5> is lower alkyl or hydroxyalkyl; X is fluorinated alkyl; m:n:o:p (weight ratio of raw material monomer)=(10-90):(0.01-60):(20-75):(0.1-20)] is preferable as the block copolymer.

Description

DETAILED DESCRIPTION OF THE INVENTION <Industrial Application Field> The present invention relates to medical materials, methods for producing the same, and medical instruments.

<Prior art> Medical devices such as artificial organs that have parts that come into contact with blood have been manufactured and used in the past, but when selecting the materials that make up these medical devices, biocompatibility must be considered. This is an important issue. The surface quality of the medical device used is an important factor in this biocompatibility. On the other hand, it goes without saying that physical properties as a medical device are also important.

Therefore, it is considered effective to select a material with appropriate physical properties for a medical device and modify its surface properties when applied as a medical material. fact,
From this point of view, various surface modification methods have been proposed. One of them is a lipid-soluble vitamin or fatty acid macromer having a reactive end, in which the reactive end is bonded to a base material (Japanese Patent Laid-Open No. 63-130069
Publication No., Terumo Corporation).

<Problem to be solved by the invention> This was revolutionary in that it fully demonstrated the physical properties of the base material as a medical material while imparting biocompatibility to its surface. It cannot be said that sufficient biocompatibility was obtained, and there was room for improvement in improving biocompatibility.

Therefore, an object of the present invention is to provide a new method for producing a medical material and a medical device that solve the above-mentioned problems.

Another object of the present invention is to provide a method for producing a medical material and a medical device that stably exhibits excellent biocompatibility over a long period of time.

<Means for Solving the Problems> In order to solve the above problems, the present invention comprises a polymer compound, a block copolymer consisting of a hydrophilic polymer part and a hydrophobic polymer part, a fatty acid macromer, Provided is a medical material characterized in that a block copolymer is covalently bonded to a polymer compound, and a fatty acid macromer is covalently bonded to the block copolymer.

The present invention also preferably includes a polymer compound in which a hydrophilic polymer portion of a block copolymer is bonded, and a fatty acid macromer is bonded to a hydrophobic portion of the block copolymer.

In the present invention, it is further preferable that the hydrophobic portion of the block copolymer has a fluorinated side chain.

The present invention also provides a first step of covalently bonding a functional group of a fatty acid macromer, a hydrophilic polymer portion, and a part of the functional group of a block copolymer having a hydrophilic polymer portion; Provided is a method for producing a medical material, characterized by comprising a second step of covalently bonding a part of the functional group of the union and a functional group of a polymer compound.

Further, in the present invention, some of the functional groups of the block copolymer in the first step are carboxyl groups, and some of the functional groups of the block copolymer in the second step are epoxy groups. It is preferable that

Furthermore, the present invention provides that the hydrophobic polymer portion of the block copolymer has a part of the functional group in the first step,
The hydrophilic polymer portion of the block copolymer preferably has a portion of the functional group in the second step.

Further, the present invention provides a method in which at least the part that comes into contact with blood is composed of a polymer compound, a block copolymer consisting of a hydrophilic polymer part and a hydrophobic polymer part, and a fatty acid macromer, and the block copolymer is added to the polymer compound. To provide a medical device characterized in that it is formed from a medical material in which a block copolymer is covalently bonded and a fatty acid macromer is covalently bonded to a block copolymer.

The present invention will be explained in more detail below.

The medical material of the present invention consists of a polymer compound, a block copolymer consisting of a hydrophilic polymer part and a hydrophobic polymer part, and a fatty acid macromer, and the block copolymer is covalently bonded to the polymer compound. In addition, it is characterized in that a fatty acid macromer is covalently bonded to the block copolymer.

In this way, in the medical material of the present invention, the fatty acid macromer is covalently bonded to the polymer compound via the block copolymer, so a large number of fatty acids are fixed to one bonding point of the polymer compound. , more excellent biocompatibility is obtained, there is no release of fatty acids, and stable biocompatibility is exhibited over a long period of time. In addition, the presence of the molecular chain (part of the spacer) between the fatty acid and the block copolymer is expected to suppress platelet adhesion, which provides higher biocompatibility and allows for easier control of the molecular chain length.
Stable mobility can be expected.

Furthermore, since the block copolymer is composed of a hydrophilic polymer portion and a hydrophobic polymer portion, it has a good balance of hydrophilic and hydrophobic properties, thereby providing excellent reactivity with polymer compounds and surface orientation.

In addition, if the block copolymer is one in which the hydrophilic polymer portion is bonded to a high molecular compound and the hydrophobic polymer portion is bonded to a fatty acid macromer, the fatty acid macromer acts more effectively, resulting in a higher Biocompatibility is achieved.

As a raw material monomer for the hydrophilic polymer portion, as a compound having an epoxy group, (meth)acrylic acid-based glycidyl ester is preferable, and in order to synthesize a polymer of any composition, and from its copolymerizability, (Meth)acrylic acid or (meth)acrylic acid-based ester is suitably used as the comonomer.

Further, as the raw material monomer for the hydrophobic polymer portion having a reactive functional group, it is preferable that the functional group is a carboxyl group, and specific examples thereof include (meth)acrylic acid and the like.

Furthermore, the hydrophobic polymer portion has a fluorinated side chain (
The use of meth)acrylic acid ester is preferable because activation of the immune system is suppressed when the hydrophobic polymer portion comes into contact with blood.

A preferred copolymer having both hydrophilic and hydrophobic membranes is represented by the following formula.

In the above formula, R' 2 R3 and R4 represent a hydrogen atom or a lower alkyl group, and may be the same or different, and R5 represents a lower alkyl group or a hydroxyalkyl group. X represents a fluorinated alkyl group, m,
n, o, p indicate the weight ratio [%] of the raw material mass, m: n
:o:pw10~90:0.01~60:20~7
5:0.1-20.

In particular, the above RI R2R3 and R4 are preferably hydrogen or a methyl group, R5 is preferably a methyl group, ethyl group, propyl group, butyl group, hydroxyethyl group, or hydroxypropyl group, X is of the formula -CFs -
CLCFs, -CHF-tl:F3, -CF2CF3,
-Clh (Ch) 28. -CH(CFs)2, -C
A group having H2(CFz) 4H1-CHzC)I2CaF+y, etc. is preferable. The weight ratio [%] of the raw material polymer of the above copolymer is preferably m:n:o:p=20~
The ratio is 50:0.1 to 50:1 to 50:1 to 10.

A particularly preferred copolymer is represented by the following formula.

Preferred weight ratio of m%n%O%P%Q and r [% is 10-30:10-30:0-10:1-10:30
~50:1-10.

In the copolymer of the present invention, the hydrophilic polymer portion and the hydrophobic polymer portion are contained in a weight ratio [about 70% to %] of the raw material monomers.
50:30-50 is desirable.

The block copolymer used in the present invention can be obtained by a commonly used industrial method, such as aqueous suspension polymerization, emulsion polymerization, or solution polymerization.

The epoxy groups of the hydrophilic polymer moiety can be polymerized using glycidyl acrylate or glycidyl methacrylate with other monomers, or glycidyl acrylate or glycidyl methacrylate can be reacted with the hydrophilic polymer moiety in the presence of a polymerization initiator. It can be introduced into the block copolymer by

The molecular weight of the block copolymer is 500 to soo, ooo
If the molecular weight is less than 500, it is difficult to efficiently cover the entire material surface, and if the molecular weight is higher than 500,000, it becomes difficult to use due to the decrease in solubility of the polymer and reactivity with the material surface. .

The weight ratio of monomers having epoxy groups in the block copolymer is 0.01 to 0.01 as the amount of glycidyl methacrylate.
The amount is preferably 60% by weight, more preferably 1 to 10% by weight. If this monomer weight ratio exceeds 60% by weight, the polymer tends to gel during synthesis, and 0.01
If it is less than % by weight, the reactivity decreases, which is not preferable.

In the present invention, the fatty acids that bind to the hydrophobic polymer moiety as a ligand include unsaturated fatty acids such as elaidic acid,
These include oleic acid, linoleic acid, lylunic acid, arachidonic acid, and eicosapentaenoic acid, or the saturated fatty acids lauric acid, mainly listic acid, pentacylic acid, palmitic acid, and stearic acid, among which linoleic acid has particularly good compatibility with blood. Acids are preferred. Further, in the present invention, each fatty acid may be used alone or as a mixture.

These fatty acids have the function of improving blood compatibility, so by binding a ligand to the surface of a polymer compound, it is possible to improve blood compatibility with the polymer compound. ri coagulability can be weakened or eliminated.

The fatty acids are bound together as a fatty acid macromer via a spacer, preferably a hydrophilic spacer.

In the present invention, the fatty acid macromer has, for example, a fatty acid at one end and an amino group at the other end, and this amine group and the functionality of the hydrophobic polymer portion of the block copolymer described above By bonding groups, especially carboxyl groups, it is possible to obtain polymer derivatives in which fatty acids are present on the surface.

The term "macromer" refers to a polymer having a polymerizable functional group at the end, but in this specification, it is used in a broader sense to mean a polymer having a reactive functional group at the end. should be interpreted as

Specific examples of the spacer include alkylene glycols having highly reactive functional groups at both ends, with polyethylene glycol diamine, polypropylene glycol diamine, and polytetramethylene glycol diamine being preferred, and polyethylene glycol diamine being particularly preferred.

For example, when the spacer has an alkylene glycol skeleton, the degree of polymerization varies depending on the type of alkylene, but is preferably about 1 to 100. In particular, the alkylene glycol includes polyethylene glycol and polypropylene. Glycols are preferred, and polyethylene glycols with a degree of polymerization of 20 to 90 and polypropylene glycols with a degree of polymerization of 10 to 50 are particularly preferred.

The reaction for synthesizing the polymer derivative can be carried out using a conventional method.

On the other hand, as the polymer compound, cellulose having a hydroxyl group and its derivatives are most preferably used, and in addition, polyvinyl alcohol, partially saponified polyvinyl acetate, ethylene vinyl alcohol copolymer, ethylene vinyl acetate copolymer, etc. Partially saponified products, polyacrylic acid or polymethacrylic acid and copolymers thereof, polyhydroxyethyl methacrylate, chitin, chitosan, collagen, polyacrylic acid, and the like can be used.

The reaction between the block copolymer or polymer derivative and the polymer compound is carried out by dissolving the polymer derivative in a suitable organic solvent such as acetone, methyl ethyl ketone, dioxane, tetrahydrofuran, etc., and adding a Lewis acid catalyst and This is carried out by adding a basic catalyst and a polymer compound. Examples of the Lewis acid catalyst in the present invention include carbon tetrachloride, boron trifluoride, tin tetrachloride, and zinc chloride, with boron trifluoride being preferred from the viewpoint of reactivity.

In addition, as basic catalysts, among alkaline earth metals, hydroxides such as calcium, strontium, barium, radium, lithium hydroxide, sodium hydroxide, potassium hydroxide, rubidium hydroxide, cesium hydroxide, hydroxide, etc. Hydroxides of alkali metals such as francium are used, and among these, sodium hydroxide is most preferred in terms of solubility and reactivity.

The polymer compound referred to in the present invention includes various molded bodies, such as membranes,
Hollow fibers, fibers, etc. can be used, and in that case, the reaction is carried out by immersing the molded body in a solution of the polymer derivative and catalyst.

The reaction product thus obtained is biocompatible. In addition, when using a molded polymer compound,
Biocompatibility with a molded polymer compound can be obtained by simply changing the surface properties of the molded polymer without impairing its physical properties. In other words, the properties of the polymer compound that cause blood coagulation, activation of the immune system, deformation of platelets, etc. are reduced or eliminated, so it is particularly useful for artificial organs and medical equipment that come into contact with blood, such as dialysis machines, blood It is suitable as a material for filter A devices, plasma separation M devices, intravascular catheters, etc.

<Example> Hereinafter, the present invention will be specifically explained based on Examples.

(Example 1) Synthesis of linoleic acid macromer Linoleic acid 2
Dissolve 0.0 g in 70 mft of dry benzene, put it in flask C, and add 14.8 g of phosphorus pentachloride to it under a nitrogen stream.
Added in batches. After stirring at room temperature for 12 hours, rapid flow was continued for an additional 2 hours. Next, phosphoryl trichloride, a by-product of the reaction with benzene, and hydrogen chloride were distilled off, and 14.0 g of linoleic acid chloride was obtained by distillation under reduced pressure (boiling point 15
5°C/1.5mmHg, yield 76%).

In a flask, 50.4 g of polyethylene glycol cyanide (PGD-40 manufactured by Toshi ■, molecular weight 4114), 1.48 g of triethylamine, and 120 g of dichloromethane were added.
mft, and add 3.66 g of linoleic acid chloride to this under nitrogen flow and water cooling (0°C).
The solution was slowly added dropwise over 30 minutes. Thereafter, the mixture was stirred for 2 hours while gradually returning to room temperature. After the reaction is complete,
Triethylamine hydrochloride, a reaction by-product, was filtered off, triethylamine and dichloromethane were distilled off under reduced pressure, and the residue was dissolved in 100 mJl of chloroform and 100 mJl of water.
Washed gently. The organic layer was separated, dried over anhydrous sodium sulfate, and then concentrated. This was transferred to a flash chromatograph containing Fucogel C-300 (decomposition eluent:
When purification was carried out using chloroform/methanol (9/1 volume ratio), 13.7 g of purified product was obtained (yield 26
%).

This is performed using infrared spectroscopy (rR method), proton nuclear magnetic resonance method (
The structure was confirmed by 'H-NMR method), and the absence of linoleic acid and PGD-40 was confirmed by overnight body chromatography (GPC mode, eluent THF). The results of the above characteristic values are shown below.

IR method: 1B50cm-'Ayodo carbonyl stretching vibration 1540cl'Ayodo NH bending vibration 1100cm-'Ether CO stretching vibration') I-IJ
MR method: 60.9ppm linoleic acid -CH361,3pp
m Linoleic acid -CH263,7ppm Polyethylene glycol-〇 C) (2CH20- δ5.3ppm Linoleic acid olefin -CH=CH- GPC method: Retention capacity Purified product 11.4mfLPGD-
4012,6mJL Linoleic acid 15.1m square (Example 2) Synthesis of block copolymer Next, copolymers A (Table 1) and B having the following compositions
(Table 2) was synthesized.

Table 1 Copolymer A This was dissolved in a mixed solvent of MEK (methyl ethyl ketone)/MIBK (methyl isobutyl ketone) 4o/ao (volume ratio) at 30 (W/V)% and stored.

200 mJ2 of methanol was added to the obtained crude product, and the mixture was stirred at room temperature for about 30 minutes until there were no lumps, followed by centrifugation, and the supernatant was removed by decantation. After performing the same operation twice more, vacuum drying was performed, and 13.21 g of white solid polymer derivative B was obtained.

(Example 5) Graft copolymerization of polymer derivatives onto regenerated cellulose membrane The polymer derivatives A and B obtained in Example 3.4 were graft copolymerized onto the surface of the regenerated cellulose membrane in the following manner. .

First, sodium hydroxide 0.5 (W/V)% aqueous solution 1
00m1, each regenerated cellulose membrane (film thickness 0.2
mm) 0.3g was immersed for 30 minutes. Next, the polymer derivatives A and B obtained in Example 3.4 were added at 0.5 (W/
Each of the cellulose membranes was immersed in an acetone solution containing V)% and allowed to react at room temperature for 24 hours.

After the reaction was completed, the cellulose membrane was taken out and thoroughly washed in the order of acetone, ethanol, and distilled water, and these were used as medical materials A and B, respectively, as samples for the following examples.

(Example 6 and Comparative Example 1) Using the medical material A%B obtained in Example 5, the following evaluation tests 1 and 2 were conducted, and the results are shown in Tables 3 and 4.
Each is shown in the table.

Evaluation test 1 Platelet diastolic ability test 3.8% sodium citrate (1/10 of the amount of blood collected)
Venous blood from a healthy individual was collected using a polypropylene syringe containing 800 r, p, m.
, centrifuged for 5 minutes, and the supernatant platelet-rich plasma (PRP
) was collected and diluted with a 3.8% sodium citrate diluent (1/10 volume relative to Ringer's lactate) to prepare a platelet suspension. The number of platelets in this platelet suspension is 6600.
It was 0 pieces/mm2.

0.2 ml of this platelet suspension was used as an example of the present invention, medical materials A and B obtained in Example 5 were used as a polymer derivative-treated regenerated cellulose membrane sample IXI (Cm), and an untreated regenerated cellulose membrane sample as Comparative Example 1. Cellulose membrane sample 1xl (c
m) individually to a thickness of 2 mm and at room temperature for 30 minutes.
The contact was made for a minute. After the specified time, each sample was reduced to 3.8%.
Wash lightly with diluted sodium citrate solution, then 2.5
% geltaraldehyde/Lactated Ringer's solution, the sample was stored in a cool place overnight for suspension. After further washing with a 3.8% diluted sodium citrate solution, step dehydration was carried out in an ethanol series to 50%, 60%, 70%, 80%, and 90%.
, 95%, and 100% in ethanol solution, respectively.
Process for one minute at a time. ), air-dried, scanning electron microscope
(JSM-840 manufactured by JEOL). The evaluation method was to look at the number of platelets attached to 0.07 mm' and changes in their morphology. Morphological changes were classified into the following three types.

■Type: From the normal platelet shape of a disc to a spherical shape, 3~
It has four pseudopods and is thought to have relatively weak adhesion to the material surface.

Type II: Those with several or more pseudopods extended and the cytoplasm extending to half of the pseudopods, which appear to have strongly adhered to the material surface.

■Type: One with a thin cell expanded to more than half the length of the pseudopod; the cell has expanded almost completely, exhibiting a circular shape, and appears to have completely adhered to the material surface.

The test results are shown in Table 3.

No. 3 table The consumption rate was calculated by measuring the change in

It is shown in Table 4.

Table 4 Evaluation of Results Test 2 Measurement of Change in Complement Value Regarding the medical materials A and B of the present invention obtained in Example 5, changes in complement value were measured by Mayer's original method shown below.

Each sample is pre-soaked in physiological saline to bring it into a state of sorption equilibrium. Gently remove moisture from the surface of each sample, 1 sample 2
0 cm" small piece, place it in a plastic test tube, and add 1 ml of adult dog serum. After activating it by keeping it at 37°C for 3 hours, the complement value CH50 (complement value by 50% hemolysis method) From Table 4, it is clear that the cellulose sheet of the present invention shows a very small decrease in serum complement (i[[1cH50) compared to the untreated cellulose sheet.

(Example 7 and Comparative Example 2) Copper ammonia regenerated cellulose hollow fibers were placed in a glass tube,
Connect one end to an aspirator and the other end to NaOH0,5
(W/V)% aqueous solution. Furthermore, the hollow fibers were filled with NaOH* solution using the suction force of an aspirator. After filling, the container was left at room temperature for 30 minutes. Then, after discharging the NaOH* solution in the hollow fiber, Example 3
and 0.5 (W
/V)%-containing musioxane solution was filled into a dialyzer in the same manner as described above, and left at room temperature for 24 hours. Thereafter, the solution was discharged, and then washed with dioxane, thoroughly washed with acid and distilled water, and dried with air at a temperature of 25°C. Furthermore, in order to ensure complete drying, it was left in an oven at 60° C. overnight.

FIG. 1 shows a module for extracorporeal circulation experiments of a dialyzer, and will be specifically explained.

That is, the dialyzer (artificial kidney III) 1 forms a hollow fiber bundle 2 using 341 copper ammonia regenerated cellulose hollow fibers with an inner diameter of about 200 μm, an outer diameter of about 224 μm, and an effective length of 14 cm, and is inserted into a cylindrical body 3. The dialyzer (artificial kidney) 1 was prepared by inserting it and fixing both ends with a polyurethane botting agent 4.5, and then attaching headers 6.7 to both ends and fixing them with caps 8.9. The inner membrane area of this product was 300 cm'. In the dialyzer shown in FIG. 1, an inlet pipe 10 and an outlet pipe 11 for dialysing fluid are provided near both ends of the cylindrical main body 3. After that, fill it with distilled water, put the dialyzer in this state into an autoclave, and keep it at a temperature of 115℃ for 3 hours.
Sterilization was performed for 0 minutes. Using this dialyzer, the following evaluation tests were conducted.

Evaluation test 3 Extracorporeal circulation test The rabbit was fixed in the dorsal position on a Kitajima fixation table.

Next, the hair in the surgical field was trimmed with electric clippers and wiped with alcohol cotton. Make an incision along the midline from the bottom to the clavicle with a hacksaw, roughly open the fascia, and dissect the right (left) common carotid artery, being careful not to damage the nerves, branch vessels, and surrounding tissues. did. The left (right) facial vein was then carefully and deeply dissected in the same way, and Saniflo (registered trademark of Terumo Corporation) was placed by Terumo Corporation with a rubber cap for mixed injection filled with IIU/mu of heparinized saline. A catheter was inserted and ligated and fixed. Similarly, a catheter was also inserted into the artery and ligated and fixed.

Rabbit 2o prepared in this way was tested using a dialyzer using the polymer derivatives A and B and a non-IA cuprammonium regenerated cellulose hollow fiber membrane dialyzer (Comparative Example 2) having the same membrane area as a comparison control. An experimental circuit was prepared. That is, as shown in FIG. 2, a catheter 21 connected to an artery of a rabbit 20 is connected to a pump 22, and a chamber 23 and a rabbit 2o are roughly connected.
The catheter 25 was connected to the vein of the patient. The pump 22 and the dialyzer 1 are connected through a tube 26, and the tube 26 communicates with the inlet 27 side of the manometer. Furthermore, the dialyzer 1 and a chamber 23 communicating with the out 24 side of the manometer were communicated through a tube 28.

On the other hand, the dialysate inlet and outlet of dialyzer 1 is tube 2.
9, a pump 3o was installed in the tube 29, and the tube 29 was immersed in a water bath 31 at 37°C. The circuit thus constructed was cleaned by blanching with IIIJ/mfL of heparinized saline (100 mfl).

Extracorporeal circulation increases blood flow to 10mj! /minute. No anticoagulant was used in the experimental conditions. Immediately after the start of circulation, 5 minutes, 10 minutes, 15 minutes, 20 minutes, 3
After 0 minutes, 45 minutes, 60 minutes, and 120 minutes, 1 ml of blood was collected, and the collected blood was anticoagulated with 1.5% EDTA-2Na physiological saline.
The number of blood cells was calculated using a method (manufactured by ment).

The resulting white blood cell count (WBC), platelet count (P
LT) and hematocrit value () IcT) in Table 5~
Table 7 shows data from an experimental circuit using a treated cuprammonium regenerated cellulose hollow fiber membrane dialyzer obtained using polymer derivatives A and B, respectively. are data from an experimental circuit using an untreated cuprammonium regenerated cellulose hollow fiber membrane dialyzer (Comparative Example 2) as a control. In addition, the white blood cell count and platelet count are corrected for Ht value using the following formula,
I(I) immediately before the start of circulation is expressed as a value.

Blind-2-Shadow Cx: Correction value CO: Actual measurement calculation value) 1tx: Correction standard) Ht value - first) It value Hto
: Ht value when the Co value was obtained.Furthermore, the fluctuations in the number of white blood cells based on these data are shown in a graph in FIG.

PIC stands for Percent of In1tia.
l Count (% of initial value) is shown.

Explanation of Toko-Kei code 1... Dialyzer 3... Cylindrical body, 2... Hollow fiber bundle, 4.5... Botting material, 6.7... Header 8.9. ...Cap, 10...Inlet tube, 11...Outlet tube, 20...Rabbit, 21...Catheter 22...Pump, 23...Chamber 24...Manometer out, 25... - Catheter, 26... Tube, 27... Manometer inn, 28... Tube, 29... Tube, 30... Pump <Effects of the Invention> The medical material of the present invention has a fatty acid macromer. Because it is covalently bonded to a polymer compound via a block copolymer,
Since the blood coagulability of the polymer compound is reduced, activation of the complement system is suppressed, and platelet adhesion is suppressed, stable biocompatibility is imparted to the polymer compound over a long period of time.

Moreover, according to the method for manufacturing medical materials of the present invention, the above-mentioned medical materials can be manufactured extremely efficiently.

[Brief explanation of drawings]

FIG. 1 is a partially cutaway perspective view of an extracorporeal circulation experiment module of a dialyzer applied to an embodiment of the present invention. FIG. 2 shows an experimental circuit used in an example of the present invention. FIG. 3 is a graph showing the results of temporal changes in white blood cells conducted in an example of the present invention. 1...Water bath

Claims (7)

[Claims] (1) Consisting of a polymer compound, a block copolymer consisting of a hydrophilic polymer part and a hydrophobic polymer part, and a fatty acid macromer, the block copolymer is covalently bonded to the polymer compound, and the block copolymer is A medical material characterized by a fatty acid macromer covalently bonded to a polymer. (2) The medical material according to claim 1, wherein the hydrophilic polymer portion of the block copolymer is bonded to the polymer compound, and the fatty acid macromer is bonded to the hydrophobic polymer portion of the block copolymer. (3) The medical material according to claim 1 or 2, wherein the hydrophobic polymer portion of the block copolymer has a fluorinated side chain. (4) In producing the medical material according to claim 1, a functional group of a fatty acid macromer and a part of a functional group of a block copolymer consisting of a hydrophilic polymer part and a hydrophobic polymer part are combined. Production of a medical material characterized by having a first step of covalently bonding, and a second step of covalently bonding a part of the functional group of the block copolymer and a functional group of a polymer compound. Method. (5) A part of the functional groups of the block copolymer in the first step are carboxyl groups, and a part of the functional groups of the block copolymer in the second step are epoxy groups. 4. The method for producing a medical material according to 4. (6) The hydrophobic polymer portion of the block copolymer has a part of the functional group in the first step, and the hydrophilic polymer portion of the block copolymer has a part of the functional group in the second step. The method for producing a medical material according to claim 4 or 5, which comprises a part of. (7) A medical device characterized in that at least a portion that comes into contact with blood is formed from the medical material according to any one of claims 1 to 3.