JPH0366903B2 - - Google Patents

Description

Detailed Description of the Invention (Industrial Field of Application) The present invention relates to an infusion storage bag, a blood storage container,
This invention relates to improvements in processing members made of vinyl chloride resin for storing or transporting blood and transfusions, such as tubes for blood circuits in artificial kidneys.

(Prior Art) Vinyl chloride resins are used as medical devices such as blood transfusion sets or artificial organs, such as heart-lung machines, blood circuits for artificial kidneys, blood bag catheters, etc., and medical devices such as infusion sets, such as infusion bags, infusion circuits, etc. However, blood bags, infusion bags, etc. need to be flexible, do not deteriorate, and keep the contents intact even if they come into contact with blood or infusion for a long time. It is said that it must not transfer foreign or harmful substances into the infusion, or absorb certain components in the blood or infusion.

Conventionally, as a forming material for blood and infusion bags, etc., a large amount of dioctyl phthalate was added to vinyl chloride resin, and non-toxic metal soaps such as calcium stearate and zinc stearate were used as stabilizers, and epoxidized as stabilizing aids. A composition supplemented with soybean oil was used. 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 fact that they absorb ethylene oxide is also considered a drawback. In addition, infusion bags are sometimes exposed to steam at 121°C for sterilization, but in such cases, dioctyl phthalate is eluted into the liquid inside the bag, increasing the number of particulates specified in the testing method for plastics for infusions. , this was also considered a drawback.

Many proposals have been made with the aim of eliminating the above-mentioned drawbacks of vinyl chloride resin compositions that use dioctyl phthalate as a plasticizer. It has been shown that a composition containing -carbon monoxide-vinyl acetate copolymer can be used as a material for infusion bags and the like. Generally, due to its structure, vinyl chloride resin decomposes due to heat and generates hydrochloric acid, so non-toxic metal soaps such as calcium stearate and zinc stearate are used as stabilizers in medical resin compositions. Yes, but
If used in large quantities, it may impede the transparency of molded products,
The amount of ignition residue specified in the Test Method for Plastic Containers for Infusions increases, and if the amount of metal soap used is reduced, the heat aging resistance of the molded product will be poor and it will become discolored. In order to avoid such inconveniences, it has been found that epoxidized soybean oil can be used in combination with the above-mentioned non-toxic metal soap, and a stabilizer based on the combination of epoxidized soybean oil has been commonly used. Also in the composition disclosed in the above-mentioned publication, since the composition does not contain a plasticizer such as dioctyl phthalate, it has few eluted components and is suitable as a resin composition for medical equipment without hemolysis and cytotoxicity. However, due to the above-mentioned circumstances, since epoxidized soybean oil was used in combination, it was difficult to reach a sufficiently good level in the particulate test specified in the Test Method for Plastic Containers for Infusions.

(Problems to be Solved by the Invention) The present invention solves the above-mentioned conventional drawbacks, and aims to provide excellent thermal stability and moldability, as well as to reduce the hemolytic and cellular properties of substances such as dioctyl phthalate. An object of the present invention is to provide a blood or infusion treatment member made of a resin composition that does not contain a toxic plasticizer. Another object of the present invention is to provide a plastic container for use in artificial kidneys that significantly reduces particulates as measured by the plastic container test method for infusions, has no problems with hemolysis or cytotoxicity, and has no adverse effects on blood or infusions. It is an object of the present invention to provide blood or infusion processing members that can be safely used in various medical applications such as blood circuits, catheter infusion bags, and infusion circuits.

(Means for Solving the Problems) The blood or infusion processing member of the present invention is a copolymer of vinyl chloride resin (A), glycidyl (meth)acrylate, and (meth)acrylic acid ester or styrene. at least 5% by weight of glycidyl (meth)acrylate as a copolymerization component;
Contains at least 10% by weight of (meth)acrylic acid ester or styrene, and has a weight average molecular weight of 5000~
50000, a copolymer with a glass transition point of 60-120℃
(B), a stabilizer (C) with a melting point of 60°C or higher, and other additives (D) with a melting point of 60°C or higher added as necessary;
It consists of a resin composition containing 0.5 to 20% by weight of the copolymer (B) based on the total amount of the vinyl chloride resin (A) and the copolymer (B), thereby achieving the above purpose. achieved.

As the vinyl chloride resin (A) in the present invention,
Vinyl chloride polymer, copolymer of vinyl chloride and a monomer copolymerizable with it, ethylene and vinyl acetate copolymer with vinyl chloride or vinyl chloride and a monomer copolymerizable with it The main component is a graft polymer obtained by graft polymerization, a blend of these vinyl chloride polymers, or these polymers. Blends of this and other polymers are used. Monomers copolymerizable with vinyl chloride include ethylene, propylene, vinyl acetate, vinyl ether, acrylic ester,
Examples include methacrylic acid esters.

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

Next, the copolymer (B) used in the present invention is
A copolymer of glycidyl acrylate or methacrylate and acrylic or methacrylic acid ester or styrene, which contains at least 50% glycidyl (meth)acrylate as a copolymerization component.
% by weight, contains at least 10% by weight of one or more of (meth)acrylic acid ester or styrene, has a weight average molecular weight of 5,000 to 50,000, and has a glass transition point of 60 to 120°C.
However, this copolymer can be obtained by, for example, solution polymerization, suspension polymerization, emulsion polymerization, or the like. Examples of acrylic esters used for this include ethyl acrylate, butyl acrylate, propyl acrylate, 2-ethylhexyl acrylate, lauryl acrylate, stearyl acrylate, phenyl acrylate, etc., and examples of methacrylic esters include:
Methyl methacrylate, ethyl methacrylate,
Examples include butyl methacrylate, n-octyl methacrylate, 2-ethylhexyl methacrylate, lauryl methacrylate, cetyl methacrylate, stearyl methacrylate, and behenyl methacrylate.

As mentioned above, the copolymer (B) needs to contain at least 5% by weight of glycidyl (meth)acrylate; however, if it is less than 5% by weight, the heat aging resistance of the resin composition will deteriorate. Therefore, it is more preferable that the content is 20% by weight or more. Moreover, in the copolymer (B),
It is necessary that at least 10% by weight of one or more of (meth)acrylic acid ester or styrene is contained, but the reason is that if the content is less than 10% by weight, it is considered to be a vinyl chloride resin (A). This is because the compatibility of 20 to 80% by weight of
It is more preferable that

Preferred combinations of copolymerized components of the copolymer (B) 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 combinations.

Furthermore, if the weight average molecular weight of the copolymer (B) is too low, the number of fine particles eluted when the infusion bag etc. produced according to the present invention is steam sterilized will tend to increase; If the molecular weight is too high, it tends to reduce the transparency of the composition.
Those in the range of 5000 to 50000 are used,
Also, the glass transition point of the copolymer (B) is 60
If it is lower than 120°C, it tends to be eluted during steam sterilization, which is undesirable, and if it is lower than 120°C, there is a tendency to increase the buildup in the composition, so a temperature in the range of 60°C to 120°C is used. .

The stabilizer (C) used in the present invention needs 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 in combination with zinc stearate and calcium stearate. preferable.

The amount of stabilizer (C) used is based on 100 parts by weight of the total amount of vinyl chloride resin (A) and copolymer (B).
It is common to use 0.01-1 parts by weight. When the stabilizer is zinc stearate, 0.01 to 0.5 parts by weight, especially 0.02 parts by weight per 100 parts by weight of the resin component.
It is preferable to use ~0.2 parts by weight, and when using a combination system of calcium stearate/zinc stearate, 0.02 parts by weight per 100 parts by weight of the resin component.
0.01~0.4/0.1 parts by weight, especially 0.04/0.02~0.2/0.05
Preferably, parts by weight are used.

In addition, in the present invention, stabilizing aids,
Additives (D) other than the stabilizer (C) such as processing aids can be added, but if the melting point of the additive (D) is lower than 60°C, the above-mentioned Since the number of fine particles increases, the additive (D) is required to have a melting point of 60°C or higher.

Examples of the additive (D) include polyethylene wax with a melting point of 60°C or higher, oxidized polyethylene wax,
Partially saponified montanic acid ester waxes, glycerin ester waxes, etc. can be used, and polymeric processing aids containing methyl methacrylate as a main component can also be used.

The additive (D) can be used within a range that does not show abnormalities in the hemolytic test and cytotoxicity test of the resin composition, and is usually used in an amount of 100 parts by weight of the resin component.
It is used in an amount of 5 parts by weight or less, preferably 4 parts by weight or less.

The treated member of the present invention is made of a resin composition in which predetermined amounts of the vinyl chloride resin (A), copolymer (B), stabilizer (C), and optional additive (D) are added. However, in order to make a resin composition by adding each component, a conventional method may be adopted. For example, the above-mentioned components may be added and mixed in a mixer to make a composition. Often, a previously prepared copolymer (B) is present in the polymerization system for producing the vinyl chloride resin (A), and the copolymer (B)
The vinyl chloride resin may be polymerized in the presence of , and then components such as the stabilizer (C) may be added to form a composition.

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

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

The hemolytic test, fine particle test, and dissolution test of the molded product obtained below were conducted in accordance with the test method for plastic containers for infusions in the "General test methods" of the Japanese Pharmacopoeia Law. Also, "parts" means parts by weight.

Example 1 Weight average molecular weight is 9000, glass transition temperature is 69℃
The melt index was 22 g/10 min of ethylene containing 27% by weight glycidyl methacrylate, 53% by weight methyl methacrylate, 10% by weight styrene, 10% by weight ethyl acrylate, and 40% by weight vinyl acetate. - 100 parts of a graft polymer obtained by graft polymerizing 47 parts of vinyl acetate copolymer, 46 parts of vinyl chloride, and 7 parts of 2-ethylhexyl acrylate, 0.01 part of calcium stearate, 0.02 part of zinc stearate, and polyethylene oxide One part of wax (Hiwax 4202E, manufactured by Mitsui Petrochemicals, melting point 105°C or higher) was mixed, formed into pellets, and extruded into a 0.4 mm thick sheet.

This sheet has a light transmittance of 80% at a wavelength of 700mm,
In addition, it was flexible with a Shore hardness of 80A at 20°C, and the results of the hemolysis test and cytotoxicity test were equivalent to the control solution.

Next, the sheets were stacked and high-frequency welded to create a 500 c.c. bag. Inside this bag
Wash it with distilled water through a 0.1μ filter, put 300c.c. of the above distilled water and 50c.c. of air passed through a 0.1μ filter into the bag, and seal the injection port.
Sterilization was performed at 121°C for 25 minutes using an autoclave.
After that, the bag was taken out at a liquid temperature of 80℃, shaken for 5 minutes, left to cool, and left to stand at room temperature for 24 hours.Then, the liquid in the container was passed through the needle of a clean infusion set into a measuring container.
The number of particles larger than 2μ was measured using a light beam automatic particle measurement device, and the result was 20 particles/ml.

In addition, 0.4 mm sheets were stacked and heated and pressed at 170℃ for 3 minutes to make a 1 mm thick plate, and the yellowing degree was measured using a color difference meter (Z-1001DP manufactured by Nippon Denshoku Kogyo), and the result was 9.0, indicating good heat aging resistance. It was something.

Example 2 5 parts of the glycidyl methacrylate copolymer used in Example 1, 100 parts of vinyl chloride-ethylene copolymer with an apparent average degree of polymerization of 1350 (measured according to JISK-6721) containing 4% by weight of ethylene, 60 parts of ethylene-vinyl acetate-carbon monoxide copolymer (DuPont Elvaloy-741), 0.01 part of calcium stearate, 0.02 part of zinc stearate, 1 part of polyethylene oxide wax (Hiwax 4202E, manufactured by Mitsui Petrochemicals), and acrylic processing. Mix 1 part of auxiliary agent (Metablen P-700 manufactured by Mitsubishi Rayon),
The pellets were made into pellets and then extruded into sheets with a thickness of 0.4 mm.

This sheet had a light transmittance of 86%, a Shore hardness of 88A at 20°C, and 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.

Next, a bag of 500c.c. was made in the same manner as in Example 1, and the number of particles of 2μ or more was measured.
It was hot at K/ml.

Further, the yellowing degree of the 1 mm thick plate was 7.0, and the heat aging resistance was good.

Example 3 A glycidyl methacrylate copolymer with a weight average molecular weight of 10,000 and a glass transition temperature of
At 74 °C, glycidyl methacrylate 46% by weight,
The procedure of Example 2 was repeated except that 5 parts of a copolymer containing 54% by weight of methyl methacrylate was used.

The light transmittance of the 0.4mm thick sheet is 88% and 20%.
The Shore hardness in °C was 89A.

In addition, the results of the hemolytic test and cytotoxicity test were equivalent to the control solution.

Next, a 500c.c. bag was created in the same manner as in Example 1, and the number of particles of 2μ or more was similarly measured.
It was 25 pieces/ml.

Further, the yellowing degree of the 1 mm thick plate was 5.0, and the heat aging resistance was good.

Comparative Example 1 5 parts of epoxidized soybean oil, 40% by weight of vinyl acetate
Contains 47 parts of ethylene-vinyl acetate copolymer with a melt index of 2 gr/10 minutes and 46 parts of vinyl chloride.
100 parts of a graft copolymer obtained by graft polymerizing 7 parts of 2-ethylhexyl acrylate,
0.01 part of calcium stearate, 0.02 part of zinc stearate, and 1 part of oxidized polyethylene wax (HIWAX 4202E, manufactured by Mitsui Petrochemicals) were mixed, formed into pellets, and then extruded into a 0.4 mm thick sheet.

This sheet has a light transmittance of 82% at a wavelength of 700mm,
In addition, it was flexible with a Shore hardness of 79A at 20°C, and the results of the hemolytic test and cytotoxicity test were equivalent to the target solution.

Next, a 500 c.c. bag was prepared in the same manner as in Example 1, and the number of fine particles of 2 μ or more was measured in the same manner, and the result was 5900 particles/ml. Further, the yellowing degree of the 1 mm thick plate was 10.

Comparative Example 2 The same procedure as in Example 2 was carried out except that 5 parts of epoxidized soybean oil was used instead of the glycidyl methacrylate copolymer.

The light transmittance of the obtained 0.4 mm thick sheet was 88%.
Moreover, the Shore hardness at 20°C was 88A, and the results of the hemolysis test and cytotoxicity test were equivalent to the control solution.

Next, a bag of 500 c.c. was made in the same manner as in Example 1, and the number of fine particles of 2 μ or more was measured in the same manner. The result was 1200 particles/ml, and the yellowing degree of a 1 mm thick plate was 14. It was hot.

Comparative Example 3 The same procedure as Comparative Example 2 was carried out except that 10 parts of epoxidized soybean oil was used. The light transmittance of the 0.4 mm thick sheet was 90%, and the Shore hardness at 20°C was 88 A, and the results of the hemolysis test and cytotoxicity test were equivalent to the control solution.

Next, a bag of 500 c.c. was made in the same manner as in Example 1, and the number of fine particles of 2 μ or more was measured in the same manner. The result was 1690 particles/ml, and the yellowing degree of the 1 mm thick plate was 8. Ta.

(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 results in the particulate test specified in the Infusion Plastic Container Test Method. We can provide a blood or infusion processing member that can be safely used in applications such as catheters, tubes for artificial kidneys and other artificial organ circuits, infusion or blood transfusion tubes, blood bags, and infusion bags. It is possible.

Claims (1)

[Scope of Claims] 1. A copolymer of vinyl chloride resin (A), glycidyl (meth)acrylate, and (meth)acrylic acid ester or styrene, with a small amount of glycidyl (meth)acrylate as a copolymerization component. Tomo 5
% by weight, contains at least 10% by weight of (meth)acrylic acid ester or styrene, and has a weight average molecular weight of
5000 to 50000, a copolymer (B) with a glass transition point of 60 to 120°C, a stabilizer (C) with a melting point of 60°C or higher, and other additives with a melting point of 60°C or higher added as necessary (D). Blood or Infusion processing parts. 2 The amount of stabilizer (C) added is 0.01 to 1 part by weight per 100 parts by weight of the total amount of vinyl chloride resin (A) and copolymer (B).
The blood or infusion processing member according to claim 1, which is in parts by weight. 3 The amount of other additives (D)
The blood or infusion treatment member according to claim 1, wherein the amount is 5 parts by weight or less based on 100 parts by weight of the total amount of (A) and copolymer (B).