JP6148565B2 - Medical radiation sterilized vinyl chloride resin composition and medical device comprising the same - Google Patents

Description

The present invention relates to a vinyl chloride resin composition for radiation sterilization for medical use. More specifically, it has excellent discoloration resistance to a method of sterilization by irradiating with radiation such as gamma rays or electron beams (hereinafter abbreviated as radiation sterilization), and is an elution required for medical materials. The present invention relates to a vinyl chloride resin composition for radiation sterilization for medical use suitable for medical instruments such as medical tubes and medical bags.

Medical devices such as medical tubes such as catheters and medical bags such as blood bags, drug solution bags, and drain bags are used in terms of moldability, adhesiveness, processability, heat resistance, kink resistance, and low cost. Therefore, those made of soft vinyl chloride resin are widely used. Soft vinyl chloride resin should be melt kneaded by adding plasticizers to vinyl chloride resin to add properties such as flexibility, elasticity and cold resistance, and blending various additives such as stabilizers as necessary. Is obtained. As the plasticizer, phthalic acid esters such as di-2-ethylhexyl phthalate (hereinafter sometimes abbreviated as DEHP) have been used. (For example, Patent Document 1)

A medical tube is used by being inserted into a blood vessel, digestive tract, urethra, trachea, or the like. Blood and chemicals are sent to the body through the medical tube. The medical bag contains blood or a drug solution as contents, and these contents are transfused or infused from a blood vessel or the like into the body. Therefore, sterilization is indispensable for medical instruments such as medical tubes and medical bags. As a method of sterilization, γ-rays using cobalt 60 or the like as a radiation source are used because high sterilization is possible and sterilization after packing is possible, and sterilization can be speeded up and costs can be reduced. So-called radiation sterilization, such as a sterilization method (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, a medical device made of a soft vinyl chloride resin using DEHP as a plasticizer has a problem that it undergoes discoloration when subjected to radiation sterilization, and particularly discolors when subjected to γ-ray sterilization. In addition, it is indispensable that the medical device has no problem in the eluate test, and the amount of the eluate is required to be smaller.

Therefore, a soft vinyl chloride resin containing 2-ethylhexyl trimellitic acid (TOTM) or diisononylcyclohexane-1,2-dicarboxylate (DINCH) instead of DEHP as a plasticizer has been proposed (for example, Patent Documents 2 to 2). 5). However, even with these plasticizers, there still remains a problem of discoloration when subjected to radiation sterilization.

JP-A-63-218750 Japanese Patent Laid-Open No. 2005-230058 JP 2005-40397 A JP 2006-61226 A JP 2008-195898 A

The present invention has been made in view of the above circumstances, and its purpose is a medical vinyl chloride resin composition, which has excellent discoloration resistance against radiation sterilization, and is an elution required for medical materials. It is an object of the present invention to provide a vinyl chloride resin composition that can be used suitably for medical instruments such as medical tubes and medical bags.

As a result of intensive studies, the present inventor has found that the above object can be achieved by using an epoxy hexahydrophthalic acid ester as a plasticizer for a vinyl chloride resin.

That is, according to the first invention of the present invention,
Component (a) 100 parts by weight of vinyl chloride resin,
Component (b) 20 to 250 parts by mass of an epoxyhexahydrophthalate plasticizer,
The medical use vinyl chloride resin composition characterized by containing is provided.

According to the second invention, the component (b) is synthesized using a saturated or unsaturated aliphatic alcohol having 6 to 13 carbon atoms. A medical vinyl chloride resin composition is provided.

According to 3rd invention, 0.1-15 mass parts is further contained for component (c) silane compound with respect to 100 mass parts of said component (a), The 1st invention or 2nd invention characterized by the above-mentioned. The medical vinyl chloride resin composition described in the invention is provided.

According to 4th invention, it is a medical tube or a medical bag, Comprising: It consists of a medical vinyl chloride resin composition as described in any one of 3rd invention from 1st invention. A medical tube or medical bag is provided.

The medical vinyl chloride resin composition of the present invention is a method for sterilization by irradiating with radiation such as γ-rays or electron beams, and particularly has excellent discoloration resistance against γ-ray sterilization, and is required for medical materials. There is no problem in the dissolution test. Therefore, medical tubes such as tube feeding tubes, hemodialysis tubes, respiratory tubes, catheters, pressure monitor tubes and heparin tubes; medical bags such as blood bags, drug solution bags and drain bags It is suitably used for medical instruments such as; The medical vinyl chloride resin composition of the present invention is particularly suitable for medical tubes because of its extremely good extrusion moldability.

Each component constituting the medical vinyl chloride resin 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 / methyl (meth) acrylate copolymer, vinyl chloride / (meth) ethyl acrylate copolymer, vinyl chloride / maleic acid ester copolymer, vinyl chloride・ 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 Polymer, 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 preferably has a number average degree of polymerization of 300 or more and 7000 or less, more preferably 500 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) “Epoxyhexahydrophthalic ester plasticizer” ( essential component)
The epoxy hexahydrophthalic acid ester plasticizer used as component (b) of the present invention is an ester of epoxy hexahydrophthalic acid and an aliphatic alcohol.

As an aliphatic alcohol used for the synthesis | combination of the said component (b), a C6-C28 saturated or unsaturated aliphatic alcohol is preferable. When the number of carbon atoms is less than 6, or when the number of carbon atoms exceeds 28, discoloration easily occurs due to radiation sterilization. Moreover, the value of the hydrogen ion index (ΔpH) in the dissolution test is likely to deteriorate. More preferably, the aliphatic alcohol used for the synthesis of the component (b) is a saturated or unsaturated aliphatic alcohol having 6 to 13 carbon atoms. In this case, the resistance to discoloration due to radiation sterilization is particularly excellent.

Examples of the aliphatic alcohol used for the synthesis of the component (b) include heptanol, 2-ethylhexanol, n-octanol, isononanol, 3,5,5-trimethylhexanol, n-decanol, isodecanol, undecanol, dodecanol, tridecane. Decyl alcohol, Alfort 610 (manufactured by Vista Chemical Far East), Lineball 79, 911 (manufactured by Shell Chemical Co., Ltd.), Diadol 79, 911, 11 and 113 (manufactured by Mitsubishi Kasei), myristyl alcohol, Examples thereof include cetyl alcohol, stearyl alcohol, behenyl alcohol, oleyl alcohol, and dimerized alcohol obtained by the reaction of these alcohols.

The esterification reaction of epoxyhexahydrophthalic acid and an aliphatic alcohol can be performed using any method. The post-treatment after completion of the esterification reaction is not particularly limited. For example, excess alcohol is distilled off from the system, followed by neutralization and washing steps, and finally the component (b) is purified. Can be given. Moreover, it is also possible to use it as a component (b) only by distilling off excess alcohol out of a system, without refine | purifying.

The viscosity measured at 30 ° C. according to JIS K2283 of the epoxyhexahydrophthalate ester plasticizer used as component (b) of the present invention is 50 to 80 mPa · s. This is preferable.

The amount of the component (b) is such that the obtained medical vinyl chloride resin composition has excellent discoloration resistance against radiation sterilization and has no problem in the dissolution test required for medical materials. Therefore, it is 20-250 mass parts with respect to 100 mass parts of component (a). Preferably it is 20-150 mass parts. If it is less than 20 parts by mass, discoloration resistance against radiation sterilization is insufficient. If it exceeds 250 parts by mass, the ΔpH value of the dissolution test may deteriorate, or the component (b) may bleed out.

Component (c) “Silane Compound” (Optional Component)
The component (c) silane compound which is an optional component of 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), discoloration resistance against radiation sterilization can be improved. Further, the extrusion moldability can be made extremely stable. 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 Dialkoxysilanes such as ethoxysilane, methylaminoethoxypropyl dialkoxysilane, N- (βaminoethyl) -γ-aminopropylmethyldimethoxysilane, γ-glycidoxypropylmethyldimethoxysilane, γ-methacryloxypropylmethyldimethoxysilane Compound: methyltrimethoxysilane, methyltriethoxysilane, hexyltrimethoxysilane, phenyltrimethoxysilane, phenoxy Rutriethoxysilane, 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 Trialkoxysilane compounds such as beta-(3,4-epoxycyclohexyl) ethyltrimethoxysilane; 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.

In the organosilane compound, a group such as an alkyl group, a vinyl group, a (meth) acryl group, an allyl group, or a methyl acetate group is directly bonded to a silicon atom other than the alkoxysilane compound, acetoxysilane compound, or chlorosilane compound. Examples thereof include triisopropylsilane, triisopropylsilyl acrylate, allyltrimethylsilane, and trimethylsilylmethyl acetate.

Among these silane compounds, one or more alkoxysilanes selected from the group consisting of monoalkoxysilane compounds, dialkoxysilane compounds, trialkoxysilane compounds, and tetraalkoxysilane compounds from the viewpoint of radiation resistance and extrusion moldability. Compounds are preferred, trialkoxysilane compounds and tetraalkoxysilanes are more preferred, and 3-methacryloxypropyltriethoxysilane is even more preferred.

Moreover, in this invention, it is also possible to use 2 or more types of these silane compounds together, and it does not specifically limit.

Moreover, the medical vinyl chloride resin composition of this invention may mix | blend the stabilizer normally used for the vinyl chloride resin for medical uses, and its resin composition as an arbitrary component. Examples of the stabilizer include organotin compounds, barium-zinc and calcium-zinc stabilizers. As for the addition amount of a stabilizer, 0.1-10 mass parts is preferable with respect to 100 mass parts of component (a).

The medical vinyl chloride resin composition of the present invention comprises a component (a) a vinyl chloride resin, a component (b) an epoxytetrahydrophthalic acid diester plasticizer, and an optional component that is used as desired. It can be obtained by melt-kneading using an extruder, a roll, a mixer or various kneaders. Preferably, it can be obtained by melt kneading at a resin temperature of 120 to 160 ° C. for 5 to 10 minutes using a pressure kneader.

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

Raw materials used Component (a) Vinyl chloride resin component (a-1):
Manufacturer: Kaneka Corporation Type: Polyvinyl chloride Average degree of polymerization: 700

Component (a-2):
Manufacturer: Shin Daiichi PVC Co., Ltd. Type: Polyvinyl chloride Average degree of polymerization: 1300

Ingredient (b): Epoxy hexahydrophthalic acid ester plasticizer Manufacturing company: Shin Nippon Rika Co., Ltd. Product name: Sanso Sizer ^R E-PS
Type: Epoxy hexahydrophthalate di-2-ethylhexyl Viscosity: 65 mPa · s (measured at 30 ° C. according to JIS K2283)
CAS No. 10138-36-0

Component (b ') Plasticizer other than epoxy hexahydrophthalate plasticizer (Comparative component)
Comparative component (b′-1):
Manufacturer: J Plus Co., Ltd. Product name: DOP
Type: Di (2-ethylhexyl) phthalate (DEHP)

Comparative component (b′-2):
Manufacturer: Kao Corporation Product Name: TOTM
Type: trimellitic acid 2-ethylhexyl (TOTM)

Comparative component (b′-3):
Manufacturer: J Plus Co., Ltd. Product name: DOA
Type: Di (2-ethylhexyl) adipate (DEHA)

Comparative component (b′-4):
Manufacturer: BASF Japan Ltd. Product Name: Hexamol ^R DINCH
Type: Diisononylcyclohexane-1,2-dicarboxylate (DINCH)

Component (c) Silane Compound Component (c-1): Trialkoxysilane Compound Manufacturing Company: Toray Dow Corning Silicon Co., Ltd. Product Name: Z-6036
Type: 3-methacryloxypropyltrimethoxysilane

Component (c-2): Trialkoxysilane compound manufacturer: Toray Dow Corning Silicon Co., Ltd. Product name: Z-6519
Type: Vinyltriethoxysilane

Component (c-3): Tetraalkoxysilane compound manufacturer: Toray Dow Corning Silicon Co., Ltd. Product name: Z-6697
Type: Tetraethoxysilane

Component (d) Other optional component 1 (stabilizer)
Ingredient (d-1): Dioctyltin dimercapto stabilizer Manufacturing company: ADEKA Corporation
Type: Dioctyltin dimercapto

Ingredient (d-2): Calcium zinc composite stabilizer Manufacturer: ADEKA Corporation
Type: calcium zinc

Ingredient (e) Other optional ingredient 2 (lubricant)
Ingredient (e-1): Polyethylene wax-based lubricant manufacturer: Mitsui Chemicals Co., Ltd. Type: Polyethylene wax

Ingredient (e-2): Montanic acid-based lubricant manufacturer: Clariant Japan Co., Ltd. Type: Montanic acid partially saponified ester

Evaluation method 1. Radiation-resistant discoloration (ΔYI value)
(1) A sheet was prepared from the vinyl chloride resin composition obtained below using a test roll, and this was further molded into a 2 mm-thick press sheet using a press device to obtain a test sample. Two test samples were prepared.
(2) About the test sample obtained above, the yellowness (YI value) before irradiation is measured according to JIS.
In accordance with K7105, measurement was performed using a computer color matching system (manufactured by Sumika Color Co., Ltd.).
(3) Next, one of the test samples was irradiated with 20 KGy of γ rays using cobalt 60 as a radiation source, and the other was irradiated with 40 KGy. After irradiation, the sample was allowed to stand for 3 days under constant temperature and humidity conditions (23 ° C., 50% relative humidity). This is because the colored yellowing of the test sample gradually proceeds for a while after irradiation, so that the color is stabilized.
(4) Thereafter, the YI value of the post-irradiation sample was measured by the same method as described above, and each post-irradiation YI value was obtained. As an evaluation index for the degree of discoloration, the degree of yellowing (ΔYI value) defined by the following equation was calculated.
ΔYI value = (YI value after irradiation) − (YI value before irradiation)

2. Radiation resistance (1) Test sample What was created by the same method as the measurement of radiation-proof discoloration (ΔYI value) was used.
(2) The polyvinyl chloride resin compound I standard of the medical plastics test standard established by the Japan Medical Equipment Association for the test sample before irradiation with γ-ray and the test sample after irradiation with 40KGy of γ-ray with cobalt 60 as the radiation source In accordance with the above, ΔpH and ultraviolet absorption spectrum were measured.
(3) That is, the test sample was cut into 3 mm squares, 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.
(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.
(5) Further, 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, and the difference (ΔUV) Was calculated.
(6) As described above, 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 obtained. (7) About ΔpH, before irradiation and after irradiation. In any case, 1.5 or less was judged to be acceptable.
(8) For ΔUV, 0.1 or less was determined to be acceptable before and after irradiation.

3. Extrudability 40mm single-screw extruder and flat plate mold are used, and extrusion sheet molding is performed under the conditions of a mold outlet resin temperature of 180 ° C and a screw rotation speed of 40rpm. Were observed and evaluated according to the following criteria.
(Double-circle): There is no problem about the drawdown property and the surface appearance and shape of the extruded sheet.
○: Although the surface of the extruded sheet is slightly rough, there is no problem with the drawdown property and the shape of the extruded sheet.
Δ: There is rough skin on the surface of the extruded sheet and the shape of the end portion is disturbed, but there is no problem with the drawdown property.
X: Remarkable rough skin on the surface of the extruded sheet, large irregularities in the shape of the end, and poor drawdown.

Examples 1-14, Comparative Examples 1-6
The components (parts by mass) shown in any one of Tables 1 to 3 were melt-kneaded at about 160 ° C. using a pressure kneader to obtain a vinyl chloride resin composition. The above tests 1 to 3 were performed. The results are shown in any one of Tables 1-3.

As shown in Table 1 and Table 2, the medical vinyl chloride resin compositions of the present invention of the examples have excellent discoloration resistance against radiation sterilization, and are problematic in dissolution tests required for medical materials. No extrudability and excellent extrudability. On the other hand, in the comparative example, at least any one of discoloration resistance against radiation sterilization, dissolution test required for medical materials, and extrusion moldability was inferior.

Claims (2)

Component (a) 100 parts by weight of vinyl chloride resin;
Component (b) 20-250 parts by weight of an epoxy hexahydrophthalate plasticizer; and
Component (c) 0.1-15 parts by mass of a silane compound;
Contains, wherein said component (b) is a saturated or medical radiation sterilization corresponding vinyl chloride resin composition, characterized in that is synthesized using an aliphatic alcohol unsaturated having 6 to 13 carbon atoms object.
A medical tube or a medical bag, comprising the polyvinyl chloride resin composition for medical radiation sterilization according to claim 1 .