JP3480672B2 - Biocompatible polyolefin molded articles and biocompatible polymer materials - Google Patents

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a polyolefin molded article having excellent biocompatibility used for medical instruments, artificial organs, blood storage containers, pharmaceutical containers, and the like. More specifically, the present invention relates to a molded article having excellent biocompatibility, which is composed of a polyolefin having controlled adhesion work, which is a thermodynamic characteristic of the molded article surface, and heat of adsorption of water.

The present invention also relates to a biocompatible polymer material used for medical instruments, artificial organs, blood storage containers, pharmaceutical containers and the like. More specifically, the present invention relates to a polymeric material having excellent biocompatibility for medical use, which is composed of an oriented crystalline polymer.

[0003]

2. Description of the Related Art Medical devices such as artificial organs that come into contact with blood during use are desired to have highly reliable biocompatibility. As a polymeric material used in many medical devices such as blood bags and extracorporeal circulation circuits of blood for heart-lung machines, polyolefin-based materials, which have excellent mechanical strength and are easy to mold or process, are often used. Has been done.
Specifically, polymeric materials such as polypropylene are used in the manufacture of many medical devices such as syringes, blood bags, tubes, and some of the components of the extracorporeal circulation circuit of blood for heart-lung machines. .

However, since medical devices manufactured by using these polymeric materials are not biocompatible as they are, when blood comes into contact with these polymeric materials, blood coagulation starts. Therefore, it is essential to add an anticoagulant to blood when using these medical devices.

On the other hand, in order to avoid adverse effects on the human body and blood, the continuous use amount or continuous use time of the anticoagulant is naturally limited. Therefore, medical actions performed using these medical devices, such as extracorporeal blood circulation treatment, are subject to time constraints.

Therefore, it is an important subject to impart excellent biocompatibility to or improve the biocompatibility of a polymer material such as polyolefin which has been conventionally used for manufacturing medical devices.

[0007]

DISCLOSURE OF THE INVENTION The present inventors have conducted extensive studies in order to solve such conventional problems.
As a result, by controlling the molding conditions, etc. of the polyolefin, the adhesion work, which is the thermodynamic property of the surface of the molded product,
It was found that the heat of adsorption of water on the surface of the molded article is controlled, and thereby the surface of the molded article can be obtained which can suppress the adsorption of plasma proteins.

Further, when the crystalline polymer is oriented,
It has been found that a surface is obtained that suppresses the adsorption of plasma proteins.

The present invention has been completed based on the above findings.

As is clear from the above description, it is an object of the present invention to provide a polyolefin molded article having excellent biocompatibility and a crystalline polymer material having excellent biocompatibility.

[0011]

The above object can be achieved by the present invention described below. (First invention) (1) a polyolefin moldings state, and are bonded work 15 J / m ² or less of its surface, a medical in contact with blood
Biocompatible polyolefin moldings, characterized in be used in actual devices. [2] A polyolefin moldings state, and are heat of adsorption 7.7kJ / mol or more of water to the surface, the blood and contact
Biocompatible polyolefin moldings, characterized in be used in actual medical device to touch. [3] A biocompatible polyolefin molded article in which the polyolefin of [1] and [2] above is polypropylene. [4] A polyolefin moldings, is not less 15 J / m ² or less adhesion work of the surface, and state, and are heat of adsorption 7.7kJ / mol or more of water to the surface, the blood and contact
Biocompatible polyolefin moldings, characterized in be used in actual medical device to touch. [5] A biocompatible polyolefin molded article in which the polyolefin of [4] above is polypropylene. (2nd invention) [6] It consists of a crystalline polymer having a surface having at least an orientation, and the surface having the orientation suppresses adsorption of a plasma protein and contacts with blood.
A biocompatible polymer material, which is used for a medical device . [7] A biocompatible polymer material in which at least the degree of orientation of the crystalline polymer of [6] is 10% or more. [8] A biocompatible polymer material in which the crystalline polymer of [6] or [7] is a crystalline polyolefin

[9]
A biocompatible polymer material in which the crystalline polymer of [6] or [7] is polypropylene. [10] A biocompatible polymer material in which the crystalline polymer of [6] or [7] is polyethylene. [11] A biocompatible polymer material in which the crystalline polymer of [6] is a plate-like material having a surface provided with at least orientation by stretching. [12] A biocompatible polymer material in which the crystalline polymer of [6] is a fibrous material having a surface provided with at least orientation by stretching. [13] A biocompatible polymer material, wherein the crystalline polymer of [6] has a surface formed by at least imparting orientation to the surface layer by injection molding. [14] A biocompatible polymer material in the form of a hollow container having a surface obtained by imparting at least the orientation by crystalline molding of the crystalline polymer of [6]. [15] A biocompatible polymer material in which the degree of orientation of at least the surface of the crystalline polymer of [11] to [14] is 10% or more. [16] A biocompatible polymer material in which the crystalline polymer according to the above [11] to [14] is a crystalline polyolefin. [17] A biocompatible polymer material in which the crystalline polymer according to the above [11] to [14] is polypropylene. [18] A biocompatible polymer material in which the crystalline polymer of [11] to [14] above is polyethylene.

The present invention will be described in detail below.

[0013]

BEST MODE FOR CARRYING OUT THE INVENTION (First Invention) A polyolefin molded article excellent in biocompatibility according to the present invention has a bonding work which is a thermodynamic property of the surface of the polyolefin and a heat of adsorption of water on the surface. By controlling the value within a predetermined range, adsorption of plasma proteins is suppressed.

The polyolefin used in the molded article of the present invention is
A polyolefin alone or at least one type of polyolefin is contained. That is, the polyolefin may be either a single polyolefin, a mixture of two or more kinds, or a mixture containing at least one kind of polyolefin.

For example, the polyolefin may be an olefin homopolymer or copolymer, a mixture of two or more olefin homopolymers, a mixture of two or more olefin copolymers, or an olefin homocopolymer. It may be either a blend or a mixture of olefin copolymers. Further, the polyolefin may be polypropylene.

Specific examples of preferable homopolymers of polyolefin include propylene homopolymer and ethylene homopolymer. Specific examples of preferred copolymers of polyolefin include ethylene-propylene copolymer, ethylene-propylene-butene-1 copolymer,
Propylene-butene-1 copolymer, propylene-hexene-1 copolymer, propylene-octene-1 copolymer,
Ethylene-butene-1 copolymer, ethylene-hexene-
1 copolymer, ethylene-octene-1 copolymer. Of these polyolefins, a propylene homopolymer, an ethylene homopolymer, an ethylene-propylene copolymer, and an ethylene-propylene-butene-1 copolymer are particularly preferable.

A rubber-like polymer can be mixed with the above-mentioned polyolefin. Examples of the rubber-like polymer include ethylene-propylene rubber, ethylene-propylene-diene rubber, styrene-ethylene-butylene-
Examples thereof include styrene rubber.

The method for producing the above polyolefin is
Although not particularly limited, it can be produced by various methods well known to those skilled in the art. For example, a method of polymerizing a predetermined monomer in the presence of a polymerization catalyst comprising a combination of a transition metal compound catalyst such as titanium trichloride and titanium tetrachloride and an organometallic compound cocatalyst such as an organoaluminum compound may be mentioned. it can.

Further, for example, the polyolefin is present in the presence of a polymerization catalyst comprising a combination of a metallocene compound and an organometallic compound such as methylaluminoxane.
The method of polymerizing a predetermined monomer can be mentioned.

In the present invention, the surface of the molded article is controlled so that the work of adhesion, which is a thermodynamic property of the surface of the polyolefin, and the heat of adsorption of water on the surface are within a predetermined range. Plasma protein adsorption was suppressed,
It is possible to obtain the polyolefin molded article of the present invention having excellent biocompatibility.

The value of the work of adhesion, which is a thermodynamic property of the surface, and the heat of adsorption of water on the surface can be controlled by, for example, controlling the crystallinity of polyolefin or the degree of orientation of polymer chains. Can be done by.

As a method of controlling the crystallinity, for example, a method of lowering the melting point of polyolefin by copolymerization, changing a cooling temperature or a cooling rate at the time of molding, adding a nucleating agent, or adding a rubber-like polymer is known. The method of can be mentioned.

As a method for controlling the degree of orientation of the polymer chains, for example, a known stretching apparatus well known to those skilled in the art is used, and an extruded product obtained by a known extrusion molding method is stretched by a known stretching method. The method can be illustrated. Known stretching methods include, for example, a uniaxial stretching method, a simultaneous biaxial stretching method, a sequential biaxial stretching method, and the like. Furthermore, the degree of orientation can be controlled by an injection molding method known to those skilled in the art. That is, by selecting the injection conditions, the orientation layer called a skin layer formed on the surface of the injection-molded article or the surface layer including the surface at the time of injection molding is controlled, and thereby the degree of orientation is controlled. .

The work of adhesion polyolefin surface is preferably 15 J / m ² or less, in particular 12 J / m ² or less is preferred,
The closer the adhesion work is to 0 J / m ² , the more preferable.

The heat of adsorption of water on the surface of the polyolefin is preferably 7.7 kJ / mol or more, and particularly 8.0 kJ / m.
It is more than or equal to ol, and the higher the higher the more preferable.

The polyolefin used in the present invention contains various additives (antioxidants, antioxidants) usually used in thermoplastic resins.
Nucleating agent) and the like can be added. (Second invention) The biocompatible polymer material of the present invention is characterized by having a surface on which adsorption of plasma proteins is suppressed by imparting an orientation to the crystalline polymer. It is an excellent polymer material.

The crystalline polymer used in the present invention contains at least one crystalline polymer.
That is, the crystalline polymer may be a single polymer having crystallinity, a mixture of two or more kinds, or a mixture containing at least one polymer having crystallinity. For example, the crystalline polymer is a crystalline polymer homopolymer or copolymer, a mixture of two or more homopolymers, a mixture of two or more copolymers, or a homopolymer or It may be any mixture of copolymers. Further, the crystalline polymer further,
For example, crystalline polyolefin may be used.

Specific examples of preferable homopolymers of the crystalline polyolefin include propylene homopolymers and ethylene homopolymers. In addition, specific examples of preferable copolymers of crystalline polyolefin include ethylene-propylene copolymer, ethylene-propylene-butene-1 copolymer, propylene-butene-1 copolymer, propylene-hexene-1 copolymer. Combined, ethylene-butene-1
Examples thereof include copolymers and ethylene-hexene-1 copolymers. Among these crystalline polyolefins, ethylene homopolymer, propylene homopolymer, ethylene-propylene copolymer, and ethylene-propylene-butene-1 copolymer are particularly preferable.

An amorphous polymer can be mixed with the crystalline polyolefin. Examples of the amorphous polymer include ethylene-propylene rubber and ethylene-propylene-diene rubber.

The method for producing the crystalline polyolefin is not particularly limited, but the crystalline polyolefin can be produced by any suitable method well known to those skilled in the art. For example, it is synthesized by polymerizing a predetermined monomer in the presence of a polymerization catalyst composed of a combination of a transition metal compound catalyst such as titanium trichloride and titanium tetrachloride and an organometallic compound promoter such as an organoaluminum compound. be able to. Further, for example, the crystalline polyolefin can be synthesized by polymerizing a predetermined monomer in the presence of a polymerization catalyst composed of a combination of a metallocene compound and an organometallic compound such as methylaluminoxane.

In the present invention, the biocompatible polymer material of the present invention having a surface in which the adsorption of plasma proteins is suppressed can be obtained by imparting orientation to the crystalline polymer.

The orientation can be imparted by using a known stretching device well known to those skilled in the art and stretching by a known stretching method. Known stretching methods include, for example, a uniaxial stretching method, a simultaneous biaxial stretching method, a sequential biaxial stretching method, and the like. Further, the stretching may be continuous stretching of the sheet or film melt-extrusion cooled and solidified, and further, the sheet or film is wound once,
You may stretch | stretch after the manufacturing process of the sheet or film.

Further, in the injection molding known to those skilled in the art, the orientation is imparted by controlling the orientation layer called a skin layer formed on the surface of the injection-molded article or the surface layer including the surface by the injection molding conditions. can do.

Similarly, in the process of manufacturing a fibrous material, which is a technique known to those skilled in the art, orientation can be imparted by stretching or the like. For example, a specific example is gel spinning.

Further, orientation can be imparted by stretching or the like in the manufacturing process of blow molding known to those skilled in the art.

The degree of orientation of the crystalline polymer is preferably 10
% Or more, more preferably 15% or more, and particularly preferably 20% or more, and the closer the orientation degree is to 100%, the more preferable. Here, the degree of orientation refers to the degree of plane orientation of a plate-shaped molded product or a hollow molded product when these products are used. Further, in the case of an injection molded product, it means the degree of plane orientation of the skin layer. further,
In the case of a fibrous molded product, it means the degree of orientation in the fiber axis direction.

The crystalline polymer used in the present invention can be blended with additives (antioxidants, nucleating agents, etc.) usually used in thermoplastic resins. The addition method and amount of these additives may be in accordance with known methods.

The medical device formed by the biocompatible polymeric material of the present invention is to contact the blood or the like, adsorption of plasma protein is inhibited, activation of platelets is suppressed, or prevented as a result . Therefore, various blood
It is useful as a material for manufacturing medical devices that come into contact with . Examples of the medical device include artificial organs, blood storage containers or blood bags, catheters, other tubes, and blood extracorporeal circulation circuit components.

[0039]

EXAMPLES The present invention will be described in more detail below with reference to examples. (First Invention) The polyolefin used in this example is abbreviated as follows.

P1: Crystal melting point by differential scanning calorimeter is 1
62 ° C, recrystallization temperature 116 ° C, weight average molecular weight 2
10000 propylene homopolymer.

P2: Crystal melting point by differential scanning calorimeter is 1
38 ° C, recrystallization temperature 102 ° C, weight average molecular weight 3
00000, ethylene-propylene copolymer having an ethylene content of 3.3% by weight.

P3: Crystal melting point by differential scanning calorimeter is 1
29 ° C, recrystallization temperature 92 ° C, weight average molecular weight 23
0000, ethylene content 3.3% by weight, butene-1
An ethylene-propylene-butene-1 copolymer having a content of 2.8% by weight.

The amount of plasma protein adsorbed on the surface of the biocompatible polyolefin molded article was measured by the following method. That is, the biocompatible polyolefin molded product is dipped in a plasma protein solution, the plasma protein adsorbed to the biocompatible polyolefin molded product is peeled and collected with a surfactant, and the collected plasma protein is colored with an indicator, and then its absorbance is measured. The amount of plasma protein adsorbed was measured and calculated. This adsorbed plasma protein quantification method is described in `` H. Tanaka, H. Mori, K. Nitta, M.
Terano, N. Yui, J. Biomater. Sci. PolymerEdn., Vo
l.8, No. 3, p211-224 (1996) ”.

The method of measuring the work of adhesion on the surface of the biocompatible polyolefin molded article is as follows. That is, using Adcoat AD-308 manufactured by Toyo Morton Co., Ltd. as an adhesive, and a polypropylene biaxially stretched film (FOR-No. 25 manufactured by Nimura Chemical Co., Ltd.) as an object to be bonded, pressurizing at 1 MPa for 25 seconds at room temperature for molding A polypropylene biaxially stretched film was adhered to the product surface. Then 1 at 40 ℃
It was dried for 2 hours and then dried at room temperature for 48 hours. The polypropylene biaxially stretched film thus adhered was subjected to a peel test. The peeling test was carried out by using a tensile tester (Autograph AGS-5kND) manufactured by Shimadzu Corporation under the condition of a peeling angle of 180 degrees at a pulling speed of 300 mm / sec. From the obtained peel strength, RS Rivin, Paint
The work of adhesion was calculated according to the method described in Technology, 9 , 215 (1944).

The structure of water adsorbed on or adsorbed on the biocompatible polyolefin molded article was analyzed by FT-manufactured by JASCO.
It was performed by using IR to determine the contraction vibration wave number of water on the surface of the molded product. Structural analysis method and calculation method of sorption or heat of adsorption are described in H. Kusanagi, Koubunshi-High Pol
It carried out according to the method described in ymers, Japan, 42 , 314 (1993).

(Example 1) 100 Polyolefin P1
Parts by weight, pentaerythylyl-tetrakis [3- (3,3
0.05 parts by weight of 5-di-t-butyl-4-hydroxyphenyl) propionate was added and mixed, and the mixture was uniformly mixed with a Henschel mixer. The obtained mixture was put into an extruder and melt-kneaded (melting temperature: 200 ° C.) to obtain a pelletized composition. Using a molding machine equipped with a T-die, this composition was molded into a plate-shaped product at a die temperature of 185 ° C., a take-up speed of 2 m / min, and a cooling roll surface temperature of 50 ° C. The obtained plate-shaped molded product was stretched 3 times in the longitudinal direction at a stretching temperature of 148 ° C. to obtain a plate-shaped biocompatible polyolefin molded product having a thickness of 240 μm.

(Comparative Example 1) Polyolefin P1 is 100
Parts by weight, pentaerythylyl-tetrakis [3- (3,3
0.05 parts by weight of 5-di-t-butyl-4-hydroxyphenyl) propionate was added and mixed, and the mixture was uniformly mixed with a Henschel mixer. The obtained mixture was put into an extruder and melt-kneaded (melting temperature: 200 ° C.) to obtain a pelletized composition. Mold this composition with a molding machine,
A plate-shaped material having a thickness of 600 μm was obtained. Die temperature is 18
5 ° C., take-off speed 2 m / min, chill roll surface temperature 5
It was 0 ° C.

(Example 2) Polyolefin P1 100
Parts by weight, pentaerythylyl-tetrakis [3- (3,3
0.05 parts by weight of 5-di-t-butyl-4-hydroxyphenyl) propionate was added and mixed, and the mixture was uniformly mixed with a Henschel mixer. The obtained mixture was put into an extruder and melt-kneaded (melting temperature: 200 ° C.) to obtain a pelletized composition. This composition was molded using a molding machine with a T-die at a die temperature of 185 ° C., a take-up speed of 2 m / min, and a cooling roll surface temperature of 50 ° C. to obtain a plate-shaped molded product.
The obtained plate-shaped molded product was stretched in the longitudinal direction at a temperature of 148 ° C. for 5 minutes.
The film was double-stretched to obtain a plate-shaped biocompatible polyolefin molded product having a thickness of 130 μm.

(Example 3) 100 Polyolefin P1
Parts by weight, pentaerythylyl-tetrakis [3- (3,3
0.05 parts by weight of 5-di-t-butyl-4-hydroxyphenyl) propionate was added and mixed, and the mixture was uniformly mixed with a Henschel mixer. The obtained mixture was put into an extruder and melt-kneaded (melting temperature 200 ° C.), and then a pelletized composition was produced. Using a molding machine equipped with a T-die, this composition was subjected to a die temperature of 185 ° C., a take-up speed of 2 m / min,
Molding was performed at a surface temperature of the cooling roll of 50 ° C. to form a plate-shaped molded product. The obtained plate-shaped molded product is stretched in the longitudinal direction at a temperature of 1
It was stretched 7 times at 48 ° C. to obtain a plate-shaped biocompatible polyolefin molded product having a thickness of 240 μm.

Example 4 Polyolefin P2 was added to 100
Parts by weight, pentaerythylyl-tetrakis [3- (3,3
0.05 parts by weight of 5-di-t-butyl-4-hydroxyphenyl) propionate was added and mixed, and the mixture was uniformly mixed with a Henschel mixer. The obtained mixture was put into an extruder and melt-kneaded (melting temperature 200 ° C.), and then a pelletized composition was produced. Using a molding machine equipped with a T-die, this composition was subjected to a die temperature of 185 ° C., a take-up speed of 2 m / min,
Molding was performed at a surface temperature of the cooling roll of 50 ° C. to obtain a plate-shaped molded product. The obtained plate-shaped molded product was stretched in the longitudinal direction at a temperature of 128.
It was stretched 3 times at 0 ° C. to obtain a plate-shaped biocompatible polyolefin molded product having a thickness of 240 μm.

(Example 5) Polyolefin P2 100
Parts by weight, pentaerythylyl-tetrakis [3- (3,3
0.05 parts by weight of 5-di-t-butyl-4-hydroxyphenyl) propionate was added and mixed, and the mixture was uniformly mixed with a Henschel mixer. The obtained mixture was put into an extruder and melt-kneaded (melting temperature 200 ° C.), and then a pelletized composition was produced. Using a molding machine equipped with a T-die, this composition was subjected to a die temperature of 185 ° C., a take-up speed of 2 m / min,
Molding was performed at a surface temperature of the cooling roll of 50 ° C. to obtain a plate-shaped molded product. The obtained plate-shaped molded product was stretched in the longitudinal direction at a temperature of 128.
The film was stretched 5 times at 0 ° C. to obtain a plate-shaped biocompatible polyolefin molded product having a thickness of 240 μm.

(Comparative Example 2) Polyolefin P2 is 100
Parts by weight, pentaerythylyl-tetrakis [3- (3,3
0.05 parts by weight of 5-di-t-butyl-4-hydroxyphenyl) propionate was added and mixed, and the mixture was uniformly mixed with a Henschel mixer. The obtained mixture was put into an extruder and melt-kneaded (melting temperature 200 ° C.), and then a pelletized composition was produced. Using a molding machine equipped with a T-die, this composition was subjected to a die temperature of 185 ° C., a take-up speed of 2 m / min,
Molded at a chill roll surface temperature of 50 ℃, thickness 130μ
m plate-like material was obtained.

Example 6 Polyolefin P3 is 100
Parts by weight, pentaerythylyl-tetrakis [3- (3,3
0.05 parts by weight of 5-di-t-butyl-4-hydroxyphenyl) propionate was added and mixed, and the mixture was uniformly mixed with a Henschel mixer. The obtained mixture was put into an extruder and melt-kneaded (melting temperature 200 ° C.), and then a pelletized composition was produced. Using a molding machine equipped with a T-die, this composition was subjected to a die temperature of 185 ° C., a take-up speed of 2 m / min,
Molding was performed at a surface temperature of the cooling roll of 50 ° C. to obtain a plate-shaped molded product. This plate-shaped molded product was stretched 3 times in the longitudinal direction at a stretching temperature of 110 ° C. to obtain a plate-shaped biocompatible polyolefin having a thickness of 240 μm.

Comparative Example 3 Polyolefin P3 was added to 100
Parts by weight, pentaerythylyl-tetrakis [3- (3,3
0.05 parts by weight of 5-di-t-butyl-4-hydroxyphenyl) propionate was added and mixed, and the mixture was uniformly mixed with a Henschel mixer. The obtained mixture was put into an extruder and melt-kneaded (melting temperature 200 ° C.), and then a pelletized composition was produced. Using a molding machine equipped with a T-die, this composition was subjected to a die temperature of 185 ° C., a take-up speed of 2 m / min,
Molded at a cooling roll surface temperature of 50 ° C, thickness 235μ
m plate-like material was obtained.

Example 7 Polyolefin P2 was added to 100
Parts by weight, pentaerythylyl-tetrakis [3- (3,3
0.05 parts by weight of 5-di-t-butyl-4-hydroxyphenyl) propionate was added and mixed, and the mixture was uniformly mixed with a Henschel mixer. The obtained mixture was put into an extruder and melt-kneaded (melting temperature 200 ° C.), and then a pelletized composition was produced. This composition was injection molded using an injection molding machine to obtain a plate-shaped biocompatible polyolefin molded product. The surface temperature of the mold was 50 ° C.

Example 8 Polyolefin P2 was added to 100
Parts by weight, pentaerythylyl-tetrakis [3- (3,3
0.05 parts by weight of 5-di-t-butyl-4-hydroxyphenyl) propionate was added and mixed, and the mixture was uniformly mixed with a Henschel mixer. The obtained mixture was put into an extruder and melt-kneaded (melting temperature 200 ° C.), and then a pelletized composition was produced. This composition was subjected to an injection stretch blow molding machine to obtain a hollow biocompatible polyolefin molded product.

Example 9 Polyolefin P2 was added to 100
Parts by weight, pentaerythylyl-tetrakis [3- (3,3
0.05 parts by weight of 5-di-t-butyl-4-hydroxyphenyl) propionate was added and mixed, and the mixture was uniformly mixed with a Henschel mixer. The obtained mixture was put into an extruder and melt-kneaded (melting temperature 200 ° C.), and then a pelletized composition was produced. This composition was heated and melted at a temperature of 200 ° C. and a pressure of 10 MPa for 3 minutes using a press molding machine, and then cooled at a temperature of 50 ° C. and a pressure of 10 MPa to obtain a plate-shaped biocompatible polyolefin molded product. Thickness is 4
It was 40 μm.

Example 10 Polyolefin P1 was used as 10
0 parts by weight and pentaerythylyl-tetrakis [3-
(3,5-di-t-butyl-4-hydroxyphenyl)
0.05 parts by weight of propionate was blended and added, and uniformly mixed with a Henschel mixer. After the obtained mixture is put into an extruder and melt-kneaded (melting temperature 200 ° C.),
A pelletized composition was produced. This composition was heated and melted at a temperature of 200 ° C. and a pressure of 10 MPa for 3 minutes using a press molding machine, and then cooled at a temperature of 50 ° C. and a pressure of 10 MPa to obtain a plate-shaped biocompatible polyolefin molded product. The thickness was 440 μm.

With respect to the biocompatible polyolefin molded articles of Examples 1 to 10 and the materials of Comparative Examples 1 to 3, the work of adhesion, the heat of sorption or heat of adsorption, and the amount of fibrinogen adsorbed were measured. The measurement results are shown in Tables 1 to 3.

[0060]

[Table 1]

[0061]

[Table 2]

[0062]

[Table 3] (Second invention) The polymer used in this example is abbreviated as follows.

P1: Crystal melting point by differential scanning calorimeter is 1
62 ° C, recrystallization temperature 116 ° C, weight average molecular weight 2
10000, a propylene homopolymer.

P2: Crystal melting point by differential scanning calorimeter is 1
38 ° C, recrystallization temperature 102 ° C, weight average molecular weight 3
00000, ethylene-propylene copolymer having an ethylene content of 3.3% by weight.

P3: Crystal melting point by differential scanning calorimeter is 1
29 ° C, recrystallization temperature 92 ° C, weight average molecular weight 23
0000, ethylene content 3.3% by weight, butene-1
An ethylene-propylene-butene-1 copolymer with a content of 2.8% by weight.

The degree of orientation was determined by a known method by measuring the birefringence with an Abbe refractometer. See IM Ward, Structure and Properties for details on measurement and calculation.
ofOriented Polymers, Applied Science Publishers L
td., London, Chapter 3, Section 3.1, p.57-69 ”.

Regarding the amount of the plasma protein adsorbed on the surface of the biocompatible polymer material, the biocompatible polymer material was immersed in a plasma protein solution, and the adsorbed plasma protein was peeled and recovered with a surfactant, and then recovered. The obtained plasma protein was colored with an indicator and determined from its absorbance. The method for quantifying plasma proteins adsorbed on the material surface used in the examples is described in “H. Tanaka, H. Mori, K. Nitta, M. Terano,
N. Yui, J. Biomater.Sci. Polymer Edn., Vol.8, No.
3, p211-224 (1996) ”.

Example 11 100 parts by weight of the polymer P1 and 0.05 part by weight of pentaerythylyl-tetrakis [3- (3,5-di-t-butyl-4-hydroxyphenyl) propionate are added. Then, it was mixed uniformly using a Henschel mixer. The obtained mixture was put into an extruder and melt-kneaded (melting temperature: 200 ° C.) to obtain a pelletized composition. Using a molding machine with a T-die, a plate-shaped molded product was produced from this composition at a die temperature of 185 ° C., a take-up speed of 2 m / min, and a cooling roll surface temperature of 50 ° C.
The obtained plate-shaped molded product was stretched in the longitudinal direction at a temperature of 148 ° C. for 3
The film was double-stretched to obtain a plate-shaped biocompatible polymer material having a thickness of 240 μm.

COMPARATIVE EXAMPLE 4 100 parts by weight of the polymer P1 and 0.05 part by weight of pentaerythylyl-tetrakis [3- (3,5-di-t-butyl-4-hydroxyphenyl) propionate were added. Then, it was mixed uniformly using a Henschel mixer. The obtained mixture was put into an extruder and melt-kneaded (melting temperature: 200 ° C.) to obtain a pelletized composition. Using a molding machine, die temperature 18
5 ° C, take-up speed 2m / min, chill roll surface temperature 50 ° C
In the above, a plate-shaped material having a thickness of 600 μm was manufactured with this composition. (Example 12) 100 parts by weight of the polymer P1 and 0.05 parts of pentaerythylyl-tetrakis [3- (3,5-di-t-butyl-4-hydroxyphenyl) propionate.
And parts by weight were added and mixed uniformly using a Henschel mixer. The obtained mixture was put into an extruder and melt-kneaded (melting temperature: 200 ° C.) to obtain a pelletized composition. Using the molding machine with T-die, die temperature 185
At this temperature, the take-up speed was 2 m / min, and the surface temperature of the cooling roll was 50 ° C. A plate-shaped molded product was produced from this composition. The obtained plate-shaped molded product was stretched 5 times in the longitudinal direction at a stretching temperature of 148 ° C. to obtain a plate-shaped biocompatible polymer material having a thickness of 130 μm.

Example 13 100 parts by weight of the polymer P1 and 0.05 parts by weight of pentaerythylyl-tetrakis [3- (3,5-di-t-butyl-4-hydroxyphenyl) propionate were added in combination. Then, it was mixed uniformly using a Henschel mixer. The obtained mixture was put into an extruder and melt-kneaded (melting temperature: 200 ° C.) to obtain a pelletized composition. Using a molding machine with a T-die, a plate-shaped molded product was formed into a film with this composition at a die temperature of 185 ° C., a take-up speed of 2 m / min, and a cooling roll surface temperature of 50 ° C.
The obtained plate-shaped molded product was stretched in the longitudinal direction at a temperature of 148 ° C for 7
The film was double-stretched to obtain a plate-shaped biocompatible polymer material having a thickness of 240 μm.

Example 14 100 parts by weight of the polymer P2 and 0.05 parts by weight of pentaerythylyl-tetrakis [3- (3,5-di-t-butyl-4-hydroxyphenyl) propionate are added. Then, it was mixed uniformly using a Henschel mixer. The obtained mixture was put into an extruder and melt-kneaded (melting temperature: 200 ° C.) to obtain a pelletized composition. Using a molding machine with a T-die, a plate-shaped molded product was produced from this composition at a die temperature of 185 ° C., a take-up speed of 2 m / min, and a cooling roll surface temperature of 50 ° C.
The obtained plate-shaped molded product was stretched in the longitudinal direction at a temperature of 128 ° C for 3
The film was double-stretched to obtain a plate-shaped biocompatible polymer material having a thickness of 240 μm.

(Example 15) 100 parts by weight of the polymer P2 and 0.05 part by weight of pentaerythylyl-tetrakis [3- (3,5-di-t-butyl-4-hydroxyphenyl) propionate are added. Then, it was mixed uniformly using a Henschel mixer. The obtained mixture was put into an extruder and melt-kneaded (melting temperature: 200 ° C.) to obtain a pelletized composition. Using a molding machine with a T-die, a plate-shaped molded product was produced from this composition at a die temperature of 185 ° C., a take-up speed of 2 m / min, and a cooling roll surface temperature of 50 ° C.
The obtained plate-shaped molded product was stretched in the longitudinal direction at a temperature of 128 ° C for 5
The film was double-stretched to obtain a plate-shaped biocompatible polymer material having a thickness of 240 μm.

(Comparative Example 5) 100 parts by weight of the polymer P2 and 0.05 part by weight of pentaerythylyl-tetrakis [3- (3,5-di-t-butyl-4-hydroxyphenyl) propionate were added. Then, they were mixed uniformly using a Henschel mixer. The obtained mixture was put into an extruder and melt-kneaded (melting temperature: 200 ° C.) to obtain a pelletized composition. Using a molding machine with a T-die, a die-shaped material having a thickness of 130 μm was produced from this composition at a die temperature of 185 ° C., a take-up speed of 2 m / min, and a cooling roll surface temperature of 50 ° C.

Example 16 100 parts by weight of the polymer P3 and 0.05 part by weight of pentaerythylyl-tetrakis [3- (3,5-di-t-butyl-4-hydroxyphenyl) propionate were added. Then, they were mixed uniformly using a Henschel mixer. The obtained mixture was put into an extruder and melt-kneaded (melting temperature: 200 ° C.) to obtain a pelletized composition. Using a molding machine with a T-die, a plate-shaped molded product was produced from this composition at a die temperature of 185 ° C., a take-up speed of 2 m / min, and a cooling roll surface temperature of 50 ° C. The obtained plate-shaped molded product was stretched 3 times in the longitudinal direction at a stretching temperature of 110 ° C. to obtain a plate-shaped biocompatible polymer material having a thickness of 240 μm.

Comparative Example 6 100 parts by weight of the polymer P3 and 0.05 part by weight of pentaerythylyl-tetrakis [3- (3,5-di-t-butyl-4-hydroxyphenyl) propionate are added. Then, it was mixed uniformly using a Henschel mixer. The obtained mixture was put into an extruder and melt-kneaded (melting temperature: 200 ° C.) to obtain a pelletized composition. Using a molding machine equipped with a T-die, a plate-shaped material having a thickness of 235 μm was produced from this composition at a die temperature of 185 ° C., a take-up speed of 2 m / min, and a cooling roll surface temperature of 50 ° C.

Example 17 100 parts by weight of the polymer P2 and 0.05 part by weight of pentaerythylyl-tetrakis [3- (3,5-di-t-butyl-4-hydroxyphenyl) propionate were added. Then, it was mixed uniformly using a Henschel mixer. The obtained mixture was put into an extruder and melt-kneaded (melting temperature: 200 ° C.) to obtain a pelletized composition. Using an injection molding machine, a plate-shaped molded product was produced from this composition at a mold surface temperature of 50 ° C.

Example 18 100 parts by weight of the polymer P2 and 0.05 part by weight of pentaerythylyl-tetrakis [3- (3,5-di-t-butyl-4-hydroxyphenyl) propionate were added. Then, it was mixed uniformly using a Henschel mixer. The obtained mixture was put into an extruder and melt-kneaded (melting temperature 200 ° C.) to obtain a pelletized composition. Using injection stretch blow molding machine,
A hollow molded article was produced from this composition.

The degree of orientation and the amount of fibrinogen adsorbed on the biocompatible polymer materials of Examples 11 to 18 and the materials of Comparative Examples 4 to 7 were measured. The measurement results are shown in Table 4. In Examples 11 to 16 and Comparative Examples 4 to 6, the degree of orientation was the degree of plane orientation. Further, in Example 17, the degree of plane orientation was measured for the skin layer sliced from the surface to a thickness of about 200 μm. In Example 18, the degree of plane orientation of the plate-shaped piece cut out from the hollow molded product was measured.

[0079]

[Table 4]

[0080]

INDUSTRIAL APPLICABILITY In the biocompatible polyolefin molded product of the present invention, the polyolefin is simply molded and the work of adhesion, which is the thermodynamic property of the surface, and the heat of adsorption of water are controlled to a predetermined value. As a result, biocompatibility can be imparted. That is, the present biocompatible polyolefin molded product can be easily manufactured by simply molding without any chemical treatment or surface treatment. The biocompatible polyolefin molded article produced in this manner has an action of suppressing the adsorption of plasma proteins, and when contacted with blood or the like, the adsorption of plasma proteins is suppressed, resulting in the activity of platelets. Suppression is suppressed or avoided. Therefore, the biocompatible polyolefin molded article is useful as a material for manufacturing various medical devices such as artificial organs, blood storage containers or blood bags, catheters, other tubes, blood extracorporeal circuit components, etc. is there.

Since the biocompatible polymer material of the present invention has a structure in which at least the surface of the crystalline polymer is oriented, plasma protein adsorption can be suppressed. The method of giving orientation to the crystalline polymer is also extremely simple, for example, simply stretching. Furthermore, since the biocompatible material of the present invention suppresses adsorption of plasma proteins by itself, when a medical device manufactured using this is used, it is possible to reduce the use of an anticoagulant, etc. A compatible medical device can be obtained.

─────────────────────────────────────────────────── ─── Continuation of front page (72) Inventor Nobuhiko Yui 1-50 Asahidai, Tatsunokuchi-cho, Nomi-gun, Ishikawa A-11 (72) Inventor Naofumi Kawamoto 8890 Goi, Ichihara-shi, Chiba Chisso Kawagishi Apartment C Building 332 (72) Inventor Yasuhiro Shiraishi 1-13-4 Izumidai, Ichihara-shi, Chiba (56) Reference JP-A-3-28246 (JP, A) JP-A-8-168520 (JP, A) JP-A-4- 255737 (JP, A) JP 9-99055 (JP, A) JP 6-218 (JP, A) JP 60-92765 (JP, A) JP 60-92341 (JP, A) JP-A-60-45360 (JP, A) JP-A-6-7427 (JP, A) JP-A-8-260225 (JP, A) JP-A-2-271865 (JP, A) JP-A-7-255831 (JP, A) JP-A-10-99426 (JP, A) (58) Fields investigated (Int. Cl. ⁷⁾ , DB name) A61L 13/00 A61L 33/00 C08L 23/00

Claims (18)

(57) [Claims] 1. A polyolefin molded article state, and are bonded work 15 J / m ² or less of the surface, to contact with the blood
Biocompatible polyolefin moldings, characterized in be used in actual medical device that. 2. A polyolefin moldings state, and are heat of adsorption 7.7kJ / mol or more of water to the surface, the blood
Biocompatible polyolefin moldings, characterized in be used in actual medical device in contact with liquid. 3. The biocompatible molded article according to claim 1, wherein the polyolefin is polypropylene. A wherein the polyolefin molded articles, the work of adhesion of the surface is at 15 J / m ² or less, and state, and are heat of adsorption 7.7kJ / mol or more of water to the surface, the blood
Biocompatible polyolefin moldings, characterized in be used in actual medical device in contact with liquid. 5. The biocompatible molded article according to claim 4, wherein the polyolefin is polypropylene. 6. A crystalline polymer having a surface having at least an orientation, wherein the surface having the orientation suppresses adsorption of plasma proteins , and
A biocompatible polymer material, which is used for a medical device that comes into contact . 7. The biocompatible polymer material according to claim 6, wherein the orientation degree of at least the surface of the crystalline polymer is 10% or more. 8. The biocompatible polymer material according to claim 6 or 7, wherein the crystalline polymer is a crystalline polyolefin. 9. The biocompatible polymer material according to claim 6, wherein the crystalline polymer is polypropylene. 10. The biocompatible polymer material according to claim 6, wherein the crystalline polymer is polyethylene. 11. The biocompatible polymer material according to claim 6, wherein the crystalline polymer is a plate-like material having a surface having at least orientation imparted by stretching. 12. The biocompatible polymer material according to claim 6, wherein the crystalline polymer is a fibrous material having a surface provided with at least orientation by stretching. 13. The biocompatible polymer material according to claim 6, wherein the crystalline polymer has a surface in which at least orientation is imparted to the surface layer by injection molding. 14. The biocompatible polymer material according to claim 6, wherein the crystalline polymer is in the form of a hollow container having a surface formed by imparting at least orientation by hollow molding. 15. The biocompatible polymer material according to claim 11, wherein the crystalline polymer has a degree of orientation of at least 10% or more on its surface. 16. The biocompatible polymer material according to claim 11, wherein the crystalline polymer is a crystalline polyolefin. 17. The biocompatible polymer material according to claim 11, wherein the crystalline polymer is polypropylene. 18. The biocompatible polymer material according to claim 11, wherein the crystalline polymer is polyethylene.