JP2016044296A - Medical vinyl chloride-based resin composition and medical device containing the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a medical vinyl chloride resin composition excellent in crack resistance and color fastness to radiation sterilization, especially γ ray sterilization, good in injection moldability, having no problem in a leachability test required for medical materials and therefore capable of being used for medical devices such as a medical infusion set, a joint member of a medical blood circuit and a medical hard container.SOLUTION: There is provided a medical vinyl chloride-based resin composition containing 100 pts.mass of (a) vinyl chloride-based resin and 1 pts.mass or more and less than 15 pts.mass of (b) cyclohexane-1,2-dicarboxylic acid di(isononyl)ester with a cis isomer of 90 to 100 mol% and a trans isomer of 10 to 0 mol%, obtained by hydrogenation of diisononyl phthalate ester of cas No.28553-12-0.SELECTED DRAWING: None

Description

The present invention relates to a medical vinyl chloride resin composition. More specifically, it has excellent crack resistance with respect to a method of sterilization by irradiation with radiation such as γ-rays or electron beams (hereinafter sometimes abbreviated as radiation sterilization), and is excellent in injection moldability. The present invention relates to a medical radiation sterilization-compatible vinyl chloride resin composition that can be suitably used for medical infusion sets, medical blood circuit joint members, medical containers, and the like.

Medical parts must be (1) not harmful to the human body due to elution of heavy metals, etc. (2) easy to use in the medical field, (3) sterility is maintained until use, (4) It is necessary to be able to confirm the state of the internal liquid.

In recent years, sterilization of medical parts can be performed at a high level and can be sterilized after packing, which can speed up sterilization and reduce costs. So-called radiation sterilization, such as a sterilization method using a wire (hereinafter sometimes abbreviated as γ-ray sterilization) and a sterilization method using an electron beam, has become widespread. In particular, γ-ray sterilization is widespread because γ-ray permeability is large and sterilization can be performed uniformly and without lot fluctuation. However, γ-ray sterilization has a problem in that it tends to cause color change and cracks in irradiated medical parts.

Currently, soft vinyl chloride resin compositions are widely used in soft medical parts such as dialysis circuit tubes, catheters, blood bags, and infusion bags, and various types used in connection with medical parts such as dialysis circuit tubes. It is desirable to use the same material, that is, a hard vinyl chloride resin composition, for hard medical parts such as syringes, tube connecting members, branch valves, and speed control parts. For this reason, various efforts have been made to solve the problem that hard vinyl chloride resin compositions are susceptible to color change and cracking due to radiation sterilization (for example, Patent Document 1), but this is not sufficient.

JP 2007-2138 A

The present invention has been made in view of the above circumstances, and its purpose is a vinyl chloride resin composition for medical use, which is excellent in resistance to cracking and discoloration against radiation sterilization, particularly γ-ray sterilization, and injection molding. It is suitable for medical instruments such as medical infusion sets, medical blood circuit joint members, and medical rigid containers. It is to provide a medical vinyl chloride resin composition that can be used.

As a result of intensive studies, the present inventors have found that the above object can be achieved by a vinyl chloride resin composition containing a specific amount of a specific plasticizer.

That is, the present invention relates to (a) 100 parts by mass of a vinyl chloride resin; and (b) casNo. 1 mass of cyclohexane-1,2-dicarboxylic acid di (isononyl) ester having a cis isomer of 90 to 100 mol% and a trans isomer of 10 to 0 mol% obtained by hydrogenating 28553-12-0 phthalic acid diisononyl ester A vinyl chloride resin composition for medical use, comprising at least 15 parts by mass and less than 15 parts by mass.

2nd invention contains 0.1-15 mass parts of (c) silane compounds with respect to 100 mass parts of said components (a) further, The medical vinyl chloride as described in 1st invention characterized by the above-mentioned. System resin composition.

A third invention is a medical infusion set or a blood circuit joint member or a medical container, characterized by comprising the medical vinyl chloride resin composition described in the first invention or the second invention.

The vinyl chloride resin composition of the present invention has excellent crack resistance and discoloration resistance against radiation sterilization, especially γ-ray sterilization, has good injection moldability, and has a problem in the dissolution test required for medical materials. Absent. Therefore, it can use suitably for medical instruments, such as a medical infusion set, a joint member of a medical blood circuit, and a medical hard container.

Each component constituting the composition of the present invention will be described.

Component (a) "Vinyl chloride resin" (essential component)
The vinyl chloride resin used as component (a) of the present invention refers to all polymers having a group represented by —CH ₂ —CHCl—, a vinyl chloride homopolymer; a vinyl chloride / vinyl acetate copolymer. , Vinyl chloride / (meth) acrylic acid copolymer, vinyl chloride / (meth) methyl acrylate copolymer, vinyl chloride / (meth) ethyl acrylate copolymer, vinyl chloride / maleic acid ester copolymer, chloride Vinyl / ethylene copolymer, vinyl chloride / propylene copolymer, vinyl chloride / styrene copolymer, vinyl chloride / isobutylene copolymer, vinyl chloride / vinylidene chloride copolymer, vinyl chloride / styrene / maleic anhydride ternary Copolymer, vinyl chloride / styrene / acrylonitrile terpolymer, vinyl chloride / butadiene copolymer, vinyl chloride / isoprene copolymer Copolymerized with vinyl chloride and vinyl chloride, such as vinyl chloride / chlorinated propylene copolymer, vinyl chloride / vinylidene chloride / vinyl acetate terpolymer, vinyl chloride / acrylonitrile copolymer, vinyl chloride / various vinyl ether copolymers, etc. Copolymers with other possible monomers; Post-chlorinated vinyl copolymers and other vinyl chloride homopolymers and modified vinyl chloride copolymers; and structurally vinyl chloride resins such as chlorinated polyethylene And similar chlorinated polyolefins.

The vinyl chloride resin has a number average degree of polymerization of preferably 300 or more and 7000 or less, more preferably 400 or more and 2000 or less.

As the component (a) of the present invention, one or a mixture of two or more of these vinyl chloride resins can be used.

Component (b) “cyclohexane-1,2-dicarboxylic acid having 90 to 100 mol% of cis isomer and 10 to 0 mol% of trans isomer obtained by hydrogenation of diisononyl phthalate of cas No. 28553-12-0 Di (isononyl) ester "(essential component)
The vinyl chloride resin composition of the present invention comprises component (b) casNo. 28553-12-0 phthalic acid diisononyl ester (hereinafter sometimes abbreviated as DINP) obtained by hydrogenation of 90 to 100 mol% of cis isomer, 10 to 0 mol% of cyclohexane-1, 2-dicarboxylic acid di (isononyl) ester. Since the component (b) is obtained by hydrogenating DINP, the resin composition of the present invention has excellent crack resistance and discoloration resistance against radiation sterilization, particularly γ-ray sterilization, and has injection moldability. It will be satisfactory and will have no problem in the dissolution test required for medical materials.

The DINP is not particularly limited, and DINP synthesized by a known method can be used.

The component (b) is a mixture of 90 to 100 mol% of cis isomer and 10 to 0 mol% of trans isomer. Therefore, a resin composition having particularly excellent moldability, sticking resistance, and kink resistance can be obtained. A mixture of 95 to 100 mol% of cis isomer and 5 to 0 mol% of trans isomer is preferable. Here, the sum of the cis isomer and the trans isomer is 100 mol%.

The mixture of the cis isomer and the trans isomer can be obtained by hydrogenating DINP by a known method (for example, a technique described in JP 2013-513477 A).

The ratio of the cis isomer to the trans isomer of the component (b) can be determined from a nuclear magnetic resonance spectrum of proton (hereinafter sometimes abbreviated as ¹ H-NMR). The methine proton of dialkyl hexahydrophthalate shows a signal at 2.5-3.0 ppm, of which 2.7-3.0 ppm is in the cis isomer and 2.5-2.7 ppm is in the trans isomer. Be attributed. Thus, the cis isomer ratio is 2.7-3.0 ppm integrated area to 2.5-3.0 ppm integrated area, and the trans isomer ratio is 2.5-3.0 ppm integrated area 2. It can be determined as an integrated area of 5 to 2.7 ppm. The measurement of ¹ H-NMR can be performed with reference to, for example, JP-T-2005-504119. It can also be done by requesting measurements from Mitsui Chemical Analysis Center.

The amount of the component (b) is 1 part by mass or more with respect to 100 parts by mass of the vinyl chloride resin from the viewpoint of crack resistance, discoloration resistance, injection moldability, and elution resistance against γ-ray sterilization. is there. Preferably it is 3 parts by mass or more. On the other hand, the rigidity required as a joint member or a medical hard container of a medical infusion set is maintained, and for example, less than 15 parts by mass from the viewpoint of making it difficult for the infusion tube to come out of the joint member or to easily open the container. It is. Preferably it is 14 mass parts or less.

Component (c) “Silane compound” (optional component)
The silane compound that can be used in the present invention is one or more silane compounds selected from the group consisting of alkoxysilane compounds, chlorosilane compounds, acetoxysilane compounds, and organosilane compounds.

By using 0.1 to 15 parts by weight of the component (c) with respect to 100 parts by weight of the component (a), crack resistance and injection moldability against γ-ray sterilization can be improved. More preferably, it is 1-10 mass parts.

Examples of the alkoxysilane compound include monoalkoxysilane compounds such as trimethylmethoxysilane, trimethylethoxysilane, triethylmethoxysilane, and triethylethoxysilane; dimethyldimethoxysilane, diethyldimethoxysilane, dimethyldiethoxysilane, diphenyldimethoxysilane, diphenyldi Dialkoxy such as ethoxysilane, methylaminoethoxypropyl dialkoxysilane, N- (βaminoethyl) -γ-aminopropylmethyldimethoxysilane, γ-glycidoxypropylmethyldimethoxysilane, and γ-methacryloxypropylmethyldimethoxysilane Silane compounds; methyltrimethoxysilane, methyltriethoxysilane, hexyltrimethoxysilane, phenyltrimethoxysilane, Phenyltriethoxysilane, vinyltrimethoxysilane, vinyltriethoxysilane, γ-chloropropyltrimethoxysilane, γ-aminopropyltriethoxysilane, N- (β-aminoethyl) -γ-aminopropyltrimethoxysilane, N- (Phenyl) -γ-aminopropyltrimethoxysilane, γ-glycidoxypropyltrimethoxysilane, 3-methacryloxypropyltrimethoxysilane, 3-methacryloxypropyltriethoxysilane, γ-mercaptopropyltrimethoxysilane, γ- (Polyethyleneamino) propyltrimethoxysilane, γ-ureidopropyltriethoxysilane, heptadecafluorodecyltrimethoxysilane, tridecafluorooctyltrimethoxysilane, vinyltris (β-methoxyethoxy) silane Emissions, and beta-(3,4-epoxycyclohexyl) ethyl trialkoxysilane compounds such as trimethoxysilane; and can include tetramethoxysilane, tetra-alkoxysilane compounds such as tetraethoxysilane and the like.

Examples of the acetoxysilane compound include vinyltriacetoxysilane.

Examples of the chlorosilane compound include trimethylchlorosilane, dimethyldichlorosilane, methyltrichlorosilane, vinyltrichlorosilane, and γ-chloropropylmethyldichlorosilane.

The organosilane compound is a group in which an alkyl group, vinyl group, (meth) acryl group, allyl group, methyl acetate group or the like is directly bonded to a silicon atom other than the alkoxysilane compound, acetoxysilane compound, and chlorosilane compound. For example, triisopropylsilane, triisopropylsilyl acrylate, allyltrimethylsilane, and methyl trimethylsilylacetate can be used.

Among these silane compounds, from the group consisting of monoalkoxysilane compounds, dialkoxysilane compounds, trialkoxysilane compounds and tetraalkoxysilane compounds from the balance between discoloration resistance and crack resistance against γ-ray sterilization and other properties. One or more selected alkoxysilane compounds are preferred, trialkoxysilane compounds and tetraalkoxysilanes are more preferred, and 3-methacryloxypropyltriethoxysilane is still more preferred.

As said component (c), these 1 type, or 2 or more types of mixtures can be used.

Moreover, the stabilizer normally used for the hard vinyl chloride resin for medical uses can be mix | blended with the medical vinyl chloride-type resin composition of this invention as an arbitrary component. Examples of the stabilizer include organotin compounds, barium-zinc-based, and calcium-zinc-based stabilizers. From the viewpoint of the effect of the invention, a preferred stabilizer is an organotin compound. As a stabilizer, these 1 type, or 2 or more types of mixtures can be used. As for the compounding quantity of a stabilizer, 0.1-10 mass parts is preferable with respect to 100 mass parts of component (a).

In the resin composition of the present invention, the vinyl chloride resin and various additives usually used in the resin composition (for example, heat stabilizer, filler, lubricant, Foaming agents, pigments, ultraviolet absorbers, etc.) and various fillers (for example, calcium carbonate, clay, talc, etc.) can be further included.

Furthermore, the resin composition of the present invention may contain a small amount of a plasticizer other than the component (b) as long as the object of the present invention is not adversely affected.

In the resin composition of the present invention, the above component (a), the above component (b), and an optional component used as desired can be mixed with any melt kneader (for example, a single screw extruder, a twin screw extruder, a roll, It can be obtained by melt-kneading using a mixer and various kneaders. Preferably, it can be obtained by melt kneading at a resin temperature of 150 to 180 ° C. using a twin screw extruder.

Examples The present invention will be described in more detail with reference to examples. However, the present invention is not limited to these examples.

Examples 1-13, Comparative Examples 1-6
The components (parts by mass) shown in any one of Tables 1 to 3 were melt-kneaded at 160 ° C. using a twin screw extruder to obtain a vinyl chloride resin composition. The following tests (1) to (5) were performed. The results are shown in any one of Tables 1-3.

Raw materials used Component (a):
(A-1) Polyvinyl chloride having a number average polymerization degree of 700 of Kaneka Corporation.

Component (b):
(B-1) A diisononylcyclohexane-1,2-dicarboxylate plasticizer having 92 mol% of cis isomer and 8 mol% of trans isomer obtained by hydrogenating DINP.
(B-2) A diisononylcyclohexane-1,2-dicarboxylate plasticizer having 100 mol% of cis isomer and 0 mol% of trans isomer obtained by hydrogenating DINP.

Comparative component (b ′):
(B′-1) A diisononylcyclohexane-1,2-dicarboxylate plasticizer having 85 mol% of cis isomer and 15 mol% of trans isomer obtained by hydrogenating DINP.
(B′-2) casNo. A diisononylcyclohexane-1,2-dicarboxylate plasticizer containing 95 mol% of cis isomer and 5 mol% of trans isomer obtained by hydrogenating 68515-48-0 phthalic acid diisononyl ester.

Component (c):
(C-1): Toray Dow Corning Silicon Co., Ltd. trialkoxysilane compound (3-methacryloxypropyltrimethoxysilane) “Z-6036 (trade name)”.
(C-2): A trialkoxysilane compound (vinyltriethoxysilane) “Z-6519 (trade name)” manufactured by Toray Dow Corning Silicon Co., Ltd.
(C-3): Tetraalkoxysilane compound (tetraethoxysilane) “Z-6697 (trade name)” manufactured by Toray Dow Corning Silicon Co., Ltd.

Component (d) Other optional component 1 (stabilizer):
(D-1) Dioctyltin dimercapto stabilizer “ADEKA STAB 465 (trade name)” of ADEKA Corporation.

Component (e) Other optional component 2 (lubricant):
(E-1) Polyethylene wax lubricant “High Wax 4202E (trade name)” manufactured by Mitsui Chemicals, Inc.
(E-2) Montanic acid partially saponified ester lubricant “Licowax OP (trade name)” manufactured by Clariant Japan Co., Ltd.

Evaluation method (1) Injection moldability:
Using an injection molding machine with a mold clamping pressure of 120 tons, a test piece having a width of 10 mm, a length of 80 mm, and a thickness of 2 mm was molded at a molding temperature of 180 ° C., a mold temperature of 40 ° C., an injection speed of 50 mm / sec, and an injection pressure of 1400 kg / cm ^2. , holding pressure 400~1400Kg / cm ^2, injection time 10 seconds, and were molded at a molding condition of the cooling time 45 seconds.
(1-1) Molding appearance:
About the molded article obtained above, the presence or absence of sink marks, flow marks, and weld marks was visually observed and evaluated according to the following criteria.
A: Sink marks, flow marks and weld marks are not recognized.
○: Slight sink marks, flow marks or weld marks are observed.
Δ: Sink marks, flow marks and weld marks are observed.
X: Severe sink marks, flow marks and weld marks are recognized.
(1-2) Releasability:
Evaluation was made according to the following criteria.
○: The mold opens and the ejector protrudes, so that the molded product falls spontaneously immediately.
(Triangle | delta): It takes time until a molded article falls spontaneously after an ejector protrudes.
X: Even if the ejector protrudes, the molded product does not fall naturally but remains on the fixed side of the mold.

(2) Radiation crack resistance:
A test piece having a width of 10 mm, a length of 80 mm, and a thickness of 2 mm prepared in the same manner as the injection moldability was visually observed for the presence or absence of cracks after irradiating 40 kgy of γ rays using cobalt 60 as a radiation source.

(3) Radiation resistance:
(3-1) Using the obtained vinyl chloride resin composition, a sheet was prepared using a test roll, and this was further formed into a 2 mm-thick press sheet using a press device to obtain a test sample.
(3-2) A polyvinyl chloride resin compound of the medical plastic test standard established by the Japan Medical Equipment Association for test samples before irradiation with gamma rays and test samples after irradiation with 40 gamma rays of cobalt 60 as a radiation source In accordance with the I standard, ΔpH and ultraviolet absorption spectrum were measured.
(3-3) That is, a test sample was cut into a 3 mm square, precisely weighed in a predetermined amount, put into a hard glass container, and extracted by heating at 121 ° C. for 1 hour. A predetermined amount of the extract was precisely weighed to prepare a test solution. A blank was prepared by performing the same operation as above except that no test sample was added.
(3-4) The hydrogen ion exponent (pH) of the test solution obtained above and the hydrogen ion exponent (pH) of the blank were measured, and the difference (ΔpH) was calculated.
(3-5) In addition, the maximum value of the absorbance of the ultraviolet absorption spectrum at a wavelength of 220 to 350 nm of the test solution obtained above and the maximum value of the absorbance of the ultraviolet absorption spectrum at a wavelength of 220 to 350 nm of the blank are measured. ΔUV) was calculated.
(3-6) ΔpH and ΔUV of the test sample before γ-ray irradiation and ΔpH and ΔUV of the test sample after 40 KGy irradiation of γ-ray were determined as described above (3-7) Before and after irradiation, 1.5 or less was judged as acceptable (shown as “◯” in the table).
(3-8) For ΔUV, it was determined that 0.1 or less was acceptable (shown as “◯” in the table) before and after irradiation.

(4) Hand test:
The touch of the molded body obtained in the test (1) was evaluated according to the following criteria.
○: It is smooth and has no stickiness.
Δ: Slightly caught by hand, but not sticky.
X: There is a feeling of being caught in a hand and there is also a sticky feeling.

As shown in Tables 1 to 3, the compositions of the present invention in the examples show excellent crack resistance of members against γ-ray sterilization, have excellent injection moldability, and are required for medical materials. No problem in dissolution test. On the other hand, Comparative Examples 1-3 were inferior in at least any one of the crack resistance of the member with respect to γ-ray sterilization, injection moldability, and the dissolution test required for medical materials.

Reference example 1
All were performed in the same manner as in Example 1 except that the amount of component (b) was 20 parts by mass. The results are shown in Table 3. Although the results of the above tests (1) to (4) are good, since the blending amount of the plasticizer is large, the instantaneous value of the D type durometer hardness measured according to JIS K6253-3 is 80. Is judged to have insufficient hardness (rigidity).

Claims (3)

(A) 100 parts by mass of a vinyl chloride resin; and (b) casNo. 1 mass of cyclohexane-1,2-dicarboxylic acid di (isononyl) ester having a cis isomer of 90 to 100 mol% and a trans isomer of 10 to 0 mol% obtained by hydrogenating 28553-12-0 phthalic acid diisononyl ester More than 15 parts by weight;
A medical vinyl chloride resin composition comprising:
Furthermore, 0.1-15 mass parts of (c) silane compounds are included with respect to 100 mass parts of said component (a), The medical vinyl chloride-type resin composition of Claim 1 characterized by the above-mentioned.
A medical infusion set or a blood circuit joint member or a medical container comprising the medical vinyl chloride resin composition according to claim 1 or 2.