JPH02209150A - Blood or transfusion treating member - Google Patents

Abstract

PURPOSE:To obtain the blood or transfusion treating member having excellent thermal stability and moldability by compounding a specific copolymer (C) at a specific ratio of the total weight of a vinyl chloride resin (A) and an ethylene/carbon monoxide/alkyl (meth)acrylate copolymer (B). CONSTITUTION:The blood or transfusion treating member consists of the resin compsn. which contains the vinyl chloride resin (A), the ethylene/carbon monoxide/alkyl (meth)acrylate copolymer (B), and the copolymer (C) which is the copolymer of glycidyl (meth)acrylate and (meth)acrylate or styrene, contains at least 10wt.% glycidyl (meth)acrylate as a copolymer component and has 5000 to 50000 weight average mol.wt. and 60 to 120 deg.C glass transition point. This resin copsn. is compounded with the copolymer (C) at 0.5 to 10 pts.wt. per 100 pts.wt. total weight of the vinyl chloride resin (A) and the copolymer (B). The blood or transfusion treating member which has less elution components, has no hemolytic property and cytotoxic effect and has excellent transparency and resistance to thermal aging is accordingly provided.

Description

Detailed Description of the Invention (Field of Industrial Application) The present invention relates to polyvinyl chloride for storing or transporting blood or infusions, such as infusion storage bags, blood storage containers, and tubes for blood circuits of artificial hearts. This invention relates to improvements in processing members made of resin.

(Prior Art) Vinyl chloride resins are used as medical devices such as blood transfusion sets and artificial organs, such as heart-lung machines, blood circuits for artificial kidneys, blood bags, catheters, etc., and medical devices such as infusion sets, such as infusion bags, They are used as infusion circuits, etc., but blood bags, infusion bags, etc. are flexible and do not deteriorate.
It must be able to maintain the content of the fluid in its original state even if it comes into contact with blood or transfusion for a long time, and it must also be able to keep the contents intact even if it comes into contact with blood or transfusion for a long time. It is said that it must not be something that can be absorbed.

Conventional materials for forming blood and infusion bags are made by adding a large amount of dioctyl phthalate as a plasticizer to vinyl chloride resin, and adding non-toxic metal soaps such as calcium stearate and zinc stearate as stabilizers. A composition was used with the addition of epoxidized soybean oil as an auxiliary agent. This composition was excellent in terms of flexibility, transparency, etc., but a drawback was that a small amount of dioctyl phthalate was eluted. In addition, blood bags are sometimes brought into contact with ethylene oxide gas for sterilization, and the absorption of ethylene oxide in such cases has also been considered a drawback. In addition, the infusion bag should be sterilized for 12 hours.
Steam at 1°C may be brought into contact with this, but in such cases, dioctyl phthalate will be eluted into the bag contents.
The number of fine particles specified in the testing method for plastics for infusions increased, and this point was also considered a drawback.

Many proposals have been made for the purpose of eliminating the above-mentioned drawbacks of vinyl chloride resin compositions using dioctyl phthalate as a plasticizer, for example, Japanese Patent Application Laid-Open No. 57-17
Publication No. 7042 discloses the use of a composition containing a vinyl chloride resin and an ethylene-carbon oxide-vinyl acetate copolymer as a material for infusion bags and the like. in general,
Due to its structure, vinyl chloride resin decomposes due to heat and generates hydrochloric acid, so metal soaps such as the above-mentioned calcium stearate and zinc stearate are used as stabilizers in medical resin compositions. If a large amount of these metal soaps is used, the transparency of the molded product will be impaired, and the ignition residue required by the Infusion Plastic Container Test Method will increase. Conversely, if the amount of metal soap used is small, the molding The product has the disadvantage of poor heat aging resistance and discoloration.

In order to avoid such inconveniences, it has been found that epoxidized soybean oil can be used in combination with the non-toxic metal soap, and when metal soap is used, epoxidized soybean oil is usually used in combination.

The composition disclosed in the above-mentioned publication does not contain a plasticizer such as dioctyl phthalate, so it has few eluted components and is suitable as a resin composition for medical equipment without hemolysis or cytotoxicity. Due to circumstances, epoxidized soybean oil was used in combination, so it was difficult to reach a sufficiently good level in the particulate test specified in the Test Method for Plastic Containers for Infusions.

A vinyl chloride resin composition containing ethylene-carbon oxide-vinyl acetate copolymer instead of dioctyl phthalate has excellent transparency and flexibility, and meets the basic requirements for resin compositions for medical devices. The physical properties are satisfied. However, when this composition is heated during molding and processing, the plasticizer, ethylene-carbon oxide-vinyl acetate copolymer, partially decomposes and acetic acid is released, and this acetic acid is eluted into contents such as blood. However, there was a problem in that it gave unfavorable results in ΔpH and hemolysis in the dissolution test specified in the Japanese Pharmacopoeia and the notification of the Ministry of Health and Welfare. Therefore, for example, Japanese Patent Application Laid-open No. 56-41240 discloses that in order to eliminate the adverse effects caused by the elimination of acetic acid, a vinyl chloride resin composition using an ethylene-carbon oxide-vinyl acetate copolymer as a plasticizer is proposed. A method of adding magnesium oxide or calcium oxide as a scavenger for acetic acid has been proposed. However, although this composition can capture the acetic acid generated by thermal decomposition from the plasticizer, the amount of acetic acid released from the plasticizer increases or the thermal history during molding becomes longer. If the amount increases, it is necessary to increase the amount of scavenger mixed, and as a result, the transparency of the resulting vinyl chloride resin composition may decrease, or the ignition residue may increase, exceeding the Japanese Pharmacopoeia's regulation value. There was a problem that the

(The topic to be solved by the invention) The present invention solves the above-mentioned conventional drawbacks, and its purpose is to eliminate plasticizers that are hemolytic and cytotoxic, such as dioctyl phthalate, and that cause fine particles. An object of the present invention is to provide a blood or infusion treatment member formed from a resin composition that does not contain epoxidized soybean oil and has excellent thermal stability and moldability.

Another object of the present invention is to provide artificial kidney blood circuits, catheters, transfusion bags, etc. that significantly reduce the pH measured by the plastic test method for infusions, have no hemolytic problems, and have no adverse effects on blood and transfusions. It is an object of the present invention to provide a blood or infusion processing member that can be safely used for various medical purposes.

(Means for Solving the Problems) The blood or infusion processing member of the present invention comprises vinyl chloride resin (A), ethylene/carbon oxide/(meth)acrylic acid alkyl ester copolymer (B), glycidyl (meth) ) A copolymer of acrylate and (meth)acrylic acid ester or styrene, containing at least 10% by weight of glycidyl (meth)acrylate as a copolymerization component and having a weight average molecular weight of 5.000 to 50.000, A copolymer (C) having a glass transition point of 60 to 120°C, and based on 100 parts by weight of the total amount of the vinyl chloride resin (^) and the copolymer (B), It is characterized by comprising a resin composition containing 0.5 to 10 parts by weight of coalesce (C), thereby achieving the above object.

Further, the resin composition further contains a stabilizer (D) having a melting point of 60° C. or higher, and the content of the stabilizer (D) is the total amount of the vinyl chloride resin (A) and the copolymer (B). The amount may be 0.01 to 1 part by weight per 100 parts by weight, and the resin composition further contains an additive (E) other than the stabilizer (D) having a melting point of 60°C or higher, and the additive (E) has a melting point of 60°C or higher. The content of E) may be 0.01 to 5 parts by weight based on 100 parts by weight of the total amount of vinyl chloride resin (A) and copolymer (B).

Examples of the vinyl chloride resin (A) in the present invention include the following.

■Vinyl chloride polymer ■Copolymer of vinyl chloride and a monomer that can be copolymerized with it ■Graft polymer obtained by polymerizing vinyl chloride to a copolymer of ethylene and vinyl acetate, or chloride Graft polymer obtained by graft polymerization of vinyl and a monomer that can be copolymerized with vinyl; Blends of the polymers listed in ■ to ■ above; and blends containing these polymers as the main component and other polymers. Examples of monomers copolymerizable with vinyl chloride include ethylene, propylene, vinyl acetate, vinyl ether, acrylic ester, methacrylic ester, and the like.

Other polymers that can be blended with the vinyl chloride copolymer include ethylene/vinyl acetate copolymer, ethylene/vinyl acetate/carbon oxide terpolymer, styrene/acrylonitrile copolymer, styrene/vinyl acetate copolymer, and styrene/vinyl acetate copolymer. Examples include methyl methacrylate copolymer, methyl methacrylate/butyl methacrylate copolymer, and methyl methacrylate/butyl methacrylate/styrene copolymer.

In the ethylene/carbon oxide/(meth)acrylic acid alkyl ester copolymer (B) used in the present invention, ethylene is present in an amount of 40 to 80% by weight, preferably 60 to 70% by weight, and carbon oxide is present in an amount of 5% by weight. ~30% by weight, preferably 5
In an amount of ~15% by weight, the (meth)acrylic acid alkyl ester is 15-60% by weight, preferably 20-35% by weight.
It is desirable that the monomer is contained in an amount of 1, and it is also possible to further copolymerize other monomers as necessary. this(
The alkyl group in the meth)acrylic acid alkyl ester is linear or branched, and has 1 to 1 carbon atoms.
8 is preferable, and specific examples thereof include methyl group, ethyl group, n-propyl group, isopropyl group, hexyl group, octyl group, etc. Among these, those having 2 to 6 carbon atoms are more preferable.

In order to produce such an ethylene/carbon oxide/alkyl (meth)acrylate copolymer, the monomers ethylene, carbon oxide, and alkyl (meth)acrylate are each used as a catalyst. t-Butylperoxydeutroxybutyrate or azodiisobutyronitrile, etc. were fed into a high-speed stirring reaction vessel at a predetermined ratio and mixed, and the mixture was heated at a high temperature (160 to 230°C) under high pressure (24.0°C).
This ethylene-carbon oxide-(meth)acrylic acid alkyl ester copolymer can be produced by copolymerizing the monomers by stirring at high speed (0t)-27,000psi), and the melt flow rate (MFR) is 1~500g/
10 minutes, preferably 5 to 100 g/10 minutes.

Next, the copolymer (C) used in the present invention is a copolymer of glycidyl acrylate or methacrylate and acrylic acid or methacrylic acid ester or styrene, and glycidyl (meth)acrylate as a copolymerization component. at least 5% by weight, at least 10% by weight of one or more of (meth)acrylic acid ester or styrene, and has a weight average molecular weight of 5.000 to 50.0%.
000, the glass transition point is 60 to 120°C. This copolymer (for example, solution polymerization, suspension polymerization,
It can be obtained by techniques such as emulsion polymerization.

Examples of the acrylic ester which is a copolymerization component of the copolymer (C) include ethyl acrylate, butyl acrylate, propyl acrylate, 2-ethylhexyl acrylate, lauryl acrylate, stearyl acrylate, behenyl acrylate, etc. Examples of acid esters include methyl methacrylate, butyl methacrylate, ethyl methacrylate, butyl methacrylate, n-octyl methacrylate, 2-ethylhexyl methacrylate, lauryl methacrylate, cetyl methacrylate, stearyl methacrylate, behenyl methacrylate, and the like.

As mentioned above, this copolymer (C) needs to contain at least 5% by weight of glycidyl (meth)acrylate, but if it is less than 5% by weight, the heat aging resistance of the resin composition will deteriorate. This is because it causes problems in
It is more preferable that the content is 20% by weight or more,
Furthermore, it is necessary that the copolymer (C) contains at least 10% by weight of one or more of (meth)acrylic acid ester or styrene; the reason is that the content is less than 10% by weight. This is because if the content is less than 20%, the compatibility with the vinyl chloride resin (A) will be poor and cause fish eyes.
More preferably, it is 80% by weight.

Preferred combinations of copolymerized components of the copolymer (C) include a combination of glycidyl methacrylate and methyl methacrylate, a combination of glycidyl methacrylate, methyl methacrylate, and styrene, and a combination of glycidyl methacrylate, methyl methacrylate, styrene, and ethyl acrylate. Examples include.

In addition, if the weight average molecular weight of the copolymer (C) is too low, the number of fine particles eluted will tend to increase when an infusion bag etc. produced according to the method described below is steam sterilized, and the molecular weight If the molecular weight is too high, it tends to reduce the transparency of the composition.
If the glass transition point of the copolymer (C) is lower than 60°C, it tends to be eluted during steam sterilization, which is undesirable, and if it is higher than 120°C, If the glass transition point is 60°C to 1°C, fish eyes tend to increase in the composition.
A temperature range of 20°C is used.

Further, the resin composition may contain a stabilizer (D) as needed.
) is required to have a melting point of 60°C or higher, since the number of fine particles increases if the melting point is lower than 60°C. Suitable examples of the stabilizer include calcium stearate, zinc stearate, barium stearate, cerium stearate, etc. In particular, it is preferable to use zinc stearate alone or a combination system of zinc stearate and calcium stearate. preferable.

The amount of the stabilizer (D) used is vinyl chloride resin (
0 per 100 parts by weight of the total amount of A) and copolymer (B)
．． It is common to use 0.01 to 1 part by weight. When the stabilizer is zinc stearate, 0.01 to 0.5 parts by weight, particularly 0.02 parts by weight, per 100 parts by weight of the resin components of the vinyl chloride resin (A) and copolymer (B). ~0.2
It is preferable to use parts by weight, and when using a combination system of calcium stearate/zinc stearate as a stabilizer, 0.02 parts per 100 parts by weight of the above resin component is used.
0.01 to 0.410.1 parts by weight, especially 0.04/
It is preferable to use 0.02 to 0.2/0.05 parts by weight.

In addition, the resin composition may contain additives (E) other than the stabilizer (D), such as stabilizing aids and processing aids, if necessary, but the melting point of the additive (E) is If the temperature is lower than 60°C, the number of fine particles increases as in the case of the stabilizer (D), so the additive (E) is required to have a melting point of 60°C or higher.

Examples of the additive (E) include polyethylene wax with a melting point of 60° C. or higher, oxidized polyethylene wax, partially saponified montanic acid ester wax, glycerin ester wax, etc., and polymers containing methyl methacrylate as the main component. Processing aids may also be used. The additive (
E) can be used within the range that does not show any abnormality in the hemolytic test and cytotoxicity test of the resin composition of the present invention,
It is usually used in an amount of 5 parts by weight or less, preferably 4 parts by weight or less, per 100 parts by weight of the resin component.

Vinyl chloride resin (A) according to the present invention and ethylene-
The carbon oxide/(meth)acrylic acid copolymer (B) can be mixed in any amount. However, in order to use it as a blood or transfusion processing member, which is the object of the present invention, it is necessary to have flexibility and transparency that can be used in practice. To maintain flexibility, vinyl chloride resin (A) and ethylene/carbon oxide/(meth)acrylic acid alkyl ester copolymer (B) are used.
) It is preferable that the copolymer (B) accounts for at least 25% by weight or more based on the total amount of the copolymer (B).
Increasing the amount added improves the flexibility of the resulting treated member, but since fish eyes and surface blocking occur, the amount is preferably 70% by weight or less.

The processing member of the present invention comprises the vinyl chloride resin (A), copolymers (B) and (C), and optionally a stabilizer (D),
It is molded from a resin composition obtained by adding predetermined amounts of each of the additives (D), but conventional methods are used to add each component to obtain the resin composition. For example, the above-mentioned components may be added and mixed in a mixer to form a resin composition, and a pre-prepared copolymer (C) may be added to the polymerization system for producing vinyl chloride resin (A>). (and/or copolymerization # (B))
is present, the vinyl chloride resin is polymerized in the presence of the copolymer (C), and then the copolymer (B) (and/or copolymer (C)), stabilizer (D) A composition may be prepared by adding other components.

In order to manufacture the processing member of the present invention from the above resin composition,
Various molding machines such as an extruder, an injection molding machine, a calendar roll, and a press may be used. Examples of blood or infusion processing members in the present invention include catheters, tubes for artificial kidney circuits, infusions or blood transfusions, blood bag,
Examples include components that have parts that come into direct contact with blood and transfusions, such as blood transfusion bags.

(Example) Examples of the present invention are listed below.

The test was conducted in accordance with the Infusion Solution Plastic Container Test Method in the Pharmacopoeia "General Test Methods." Also, "1 part" means parts by weight.

The weight average molecular weight is 9.000 and the glass transition temperature is 69℃.
The average degree of polymerization was 1.320 (JIS
100 parts of vinyl chloride/ethylene copolymer (measured by K 6721), ethylene/carbon oxide/n-butyl acrylate copolymer (n-butyl acrylate content 30% by weight, -carbon oxide content 10% by weight, melt flow rate (MFR) 10 parts g/min) 100 parts by weight, zinc stearate @ 0.04 parts, 1 part of oxidized polyethylene wax (Mitsui Petrochemicals, Hiwax 4202E), and acrylic processing aid (fl Fuchi Chemical, Kane Ace) PA-10
0) After mixing 0.5 parts and making a pellet, 0.4+
It was extruded into a sheet with a thickness of nm.

This sheet had a light transmittance of 82% at a wavelength of 700 nm and a Shore hardness of 73 at 20° C., was flexible, and the results of the hemolytic test and cytotoxicity test were as good as the control solution. In addition, pt+ in the eluate test is 0
．． It was 8.

Next, the sheets were stacked and high-frequency welded to create a bag with a capacity of 5 oocc. The inside of this bag is 0.
Wash with distilled water that has passed through a 1μ filter, put 400cc of the above distilled water and 50cc of air that has passed through a 0.1μ filter into the bag, seal the injection port, and then use an autoclave to sterilize. Sterilized at 121°C for 25 minutes. After that, the bag was taken out at a liquid temperature of 80°C, placed in a container for 5 minutes, and the number of particles larger than 2μ was measured using a closed light path automatic particle measuring device. It was 0 pieces/ml.

5 parts of the glycidyl methacrylate copolymer used in Example 1, average degree of polymerization 1.3 containing 4% by weight of ethylene
50 (measured according to JIS K 6721) 100 parts of vinyl chloride/ethylene copolymer, 60 parts of the ethylene/carbon oxide/n-butyl acrylate copolymer used in Example 1, 0.01 part of calcium stearate, stearic acid 0.02 parts of zinc, 1 part of oxidized polyethylene wax (High Wax 4202K manufactured by Mitsui Petrochemicals) and acrylic processing aid (Kane Ace PA-100 manufactured by Kanebuchi Chemical)
One part was mixed, formed into a pellet, and then extruded into a 0.4 mm thick sheet.

The light transmittance of this sheet was 80%, the Shore A hardness at 20° C. was 82, it was flexible, and the results of the hemolytic test and cytotoxicity test were the same as those of the control solution, and there were no abnormalities.

Further, the pH was 0.5, which was good.

Next, in the same manner as in Example 1, a 500CC bag was made, and the number of particles of 2 μ or more was measured, and the result was 15 particles/
+al, the number of fine particles of 5 μ or more was 1.5 particles/ml.

Except for using 5 parts of a copolymer of 46% by weight of glycidyl methacrylate and 54% by weight of methyl methacrylate with a weight average molecular weight of 10.000 and a glass transition temperature of 74° C. , 0.4mmmm-t was obtained in the same manner as in Example 2.

This sheet had a light transmittance of 80% and a Shore A hardness of 80 at 20°C. Furthermore, the results of the hemolysis test and cytotoxicity test were the same as the control solution, and the pH was 0.5, which was good.

Next, a 500 cc bag was prepared in the same manner as in Example 1, and the number of particles with a size of 2μ or more was measured in the same manner.The number of particles with a size of 2μ or more was 25/ml, and the number of particles with a size of 5μ or more was 3/ml.

A sheet with a thickness of 0.4 mm was obtained in the same manner as in Example 2, except that 5 parts of epoxidized soybean oil was used instead of the single-stripe yuglycidyl methacrylate copolymer.

The light transmittance of this sheet was 85%, the Shore A hardness at 20° C. was 78, and the results of the hemolysis test and cytotoxicity test were the same as the control solution, and p[( was 0.6).

Next, a 500cc bag was made in the same manner as in Example 1, and the number of particles of 2μ or more was measured in the same manner.
,200 pieces/m! and 40 cases/+wl of 5μ or more.

L Comparison 1: Using 10 parts of epoxidized soybean oil and using ethylene/carbon oxide/vinyl acetate copolymer instead of ethylene/carbon oxide/n-butyl acrylate copolymer, the ethylene content was 66.
Weight %, - Carbon oxide content 10 weight %, MFR 35 parts g/
win) 0.4mmmm-t was obtained in the same manner as Comparative Example 2 except that the amount was 100 parts by weight.

The test results were similar to the control solution. Also, pi(is 1
．． 50, which was the standard of the Japanese Pharmacopoeia.

Next, a 500cc bag was made in the same manner as in Example 1, and the number of particles of 2μ or more was measured in the same manner.
020 particles/ml, and the number of fine particles of 0.5μ or more is 70 particles/ml.
It was ml.

(Effects of the Invention) According to the present invention, there are few eluted components, no hemolysis or cytotoxicity, excellent transparency and heat aging resistance, and good performance in the fine particle test and pH test stipulated in the Infusion Plastic Container Test Method. It is possible to provide a blood or infusion processing member that exhibits excellent results. This processing member can be safely used in applications such as catheters, artificial kidney and other artificial organ circuit tubes, infusion or blood transfusion tubes, blood bags, and infusion bags.

Claims (1)

[Claims] 1. Vinyl chloride resin (A), ethylene/carbon monoxide/(meth)acrylic acid alkyl ester copolymer (B), glycidyl (meth)acrylate and (meth)acrylic ester or A copolymer with styrene, containing at least 10% by weight of glycidyl (meth)acrylate as a copolymerization component, and having a weight average molecular weight of 5,000 to 5,000.
50,000 and a copolymer (C) having a glass transition point of 60 to 120°C, based on 100 parts by weight of the total amount of the vinyl chloride resin (A) and the copolymer (B). , the copolymer (C) is from 0.5 to
A blood or infusion treatment member comprising a resin composition containing 10 parts by weight. 2. The resin composition further contains a stabilizer (D) having a melting point of 60°C or higher, and the content of the stabilizer (D) is equal to the total amount of the vinyl chloride resin (A) and the copolymer (B). The blood or infusion processing member according to claim 1, wherein the amount is 0.01 to 1 part by weight per 100 parts by weight. 3. The resin composition further contains an additive (E) other than the stabilizer (D) with a melting point of 60°C or higher, and the content of the additive (E) is such that the content of the additive (E) is copolymerized with the vinyl chloride resin (A). The blood or infusion processing member according to claim 1 or 2, wherein the amount is 0.01 to 5 parts by weight based on 100 parts by weight of the total amount of the blood or infusion processing member with the combined substance (B).