JP6219133B2 - Medical vinyl chloride resin composition and medical device comprising the same - Google Patents

Description

The present invention relates to a medical polyvinyl chloride resin composition that can be suitably used for medical infusion sets and medical joint tubes of medical blood circuits. More specifically, as a medical joint tube for connecting a medical tube made of a vinyl chloride resin composition containing a cyclohexanedicarboxylate-based plasticizer, since it is easy to insert and difficult to pull out, it can be suitably used. The present invention relates to a medical vinyl chloride resin composition that can be obtained.

A vinyl chloride resin composition in which a plasticizer is added to a vinyl chloride resin can be adjusted in a wide range of flexibility depending on the amount of the plasticizer, molding processability (extrusion moldability, injection moldability), adhesion The medical device such as a medical tube such as a catheter, a blood bag, a medical solution bag and a drain bag, medical blood, etc. It is widely used as a material for circuit joint members and medical containers.

Generally, a resin composition used for a medical instrument is required to pass a dissolution test. Further, in medical infusion sets and medical blood circuits, it is important to easily insert and remove tubes and joint tubes. Recently, di (2-ethylhexyl) phthalate (DOP), which is a general plasticizer for vinyl chloride resin compositions, has been used in a reduced amount due to the recent environmental problems. Carboxylate plasticizers are being studied. However, medical infusion sets and medical blood circuits made of a vinyl chloride resin composition containing a cyclohexanedicarboxylate plasticizer as a plasticizer are not sufficient for easy insertion and removal of tubes and joint tubes. (Patent Documents 1 and 2).

JP 2005-40397 A JP 2008-195898 A

This invention is made | formed in view of the said situation, The subject consists of a vinyl chloride resin composition containing the medical infusion set and the medical joint pipe | tube of a medical blood circuit, especially a cyclohexane dicarboxylate type plasticizer. As a medical joint tube for connecting a medical tube, it is easy to insert and difficult to remove, and since there is no problem in the elution test required for medical materials, it can be used preferably. It is providing the medical use vinyl chloride resin composition which can be obtained.

As a result of intensive studies, the present inventor has found that the above-mentioned problems can be achieved by using a specific amount of cyclohexanedicarboxylate plasticizer and a specific amount of epoxidized vegetable oil as a plasticizer for vinyl chloride resin.

That is, the first invention of the present invention is
Component (a) 100 parts by weight of vinyl chloride resin;
Component (b) 1-20 parts by mass of a cyclohexanedicarboxylate plasticizer;
Component (c) 1-9 parts by weight of epoxidized vegetable oil;
It is a medical vinyl chloride resin composition characterized by containing.

A second invention is the medical vinyl chloride resin composition according to the first invention, wherein the component (b) is diisononylcyclohexane-1,2-dicarboxylate.

The third invention further comprises 0.1 to 15 parts by mass of the component (d) silane compound with respect to 100 parts by mass of the component (a). The medical vinyl chloride resin composition described.

A fourth invention is the medical vinyl chloride resin composition according to any one of the first to third inventions, characterized in that it is used for medical infusion sets or blood circuit joint tubes.

5th invention is a joint pipe used for the connection of the medical tube which consists of a cyclohexane dicarboxylate type plasticizer containing vinyl chloride resin composition, It is any 1 of the invention of 1st-4th characterized by the above-mentioned. It is a medical vinyl chloride resin composition.

A sixth invention is a medical infusion set or a blood circuit joint tube comprising the medical vinyl chloride resin composition described in any one of the first to fifth inventions.

A seventh invention is the use of the joint pipe according to the sixth invention to connection of a medical tube made of a cyclohexanedicarboxylate-based plasticizer-containing vinyl chloride resin composition.

The medical joint pipe made of the medical vinyl chloride resin composition of the present invention can be easily inserted as a medical joint pipe for connecting a medical tube made of a vinyl chloride resin composition containing a cyclohexanedicarboxylate plasticizer. It can be suitably used because it is difficult to come out and there is no problem in the dissolution test required for medical materials.

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 / 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 number average polymerization degree of the vinyl chloride resin used as the component (a) of the present invention is preferably from 300 to 7,000, more preferably from 400 to 2,000.

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 dicarboxylate plasticizer” (essential component)
The cyclohexane dicarboxylate plasticizer used as component (b) of the present invention is an ester compound of cyclohexane-1,2-dicarboxylic acid and a linear or branched monohydric alcohol having 1 to 20 carbon atoms. is there.

Examples of the component (b) include dimethylcyclohexane-1,2-dicarboxylate, diethylcyclohexane-1,2-dicarboxylate, di-n-butylcyclohexane-1,2-dicarboxylate, di-2- Examples thereof include ethylhexylcyclohexane-1,2-dicarboxylate, diisononylcyclohexane-1,2-dicarboxylate, and diisodecylcyclohexane-1,2-dicarboxylate. As the component (b), one or a mixture of two or more of these can be used. Of these, diisononylcyclohexane-1,2-dicarboxylate is preferred. Easy to insert as a medical joint tube for connecting a medical tube made of a vinyl chloride resin composition containing a cyclohexanedicarboxylate-based plasticizer, difficult to remove, and has no problems in the dissolution test required for medical materials Can be obtained.

Examples of commercially available components (b) include “Hexamol (registered trademark) DINCH (trade name)” manufactured by BASF.

The compounding amount of the component (b) is a medical joint tube for connecting a medical tube made of a vinyl chloride resin composition containing a cyclohexanedicarboxylate-based plasticizer to 100 parts by mass of the component (a). In order to obtain a material that is easy to insert, difficult to remove, and has no problem in the dissolution test required for medical materials, the content is 1 part by mass or more. Preferably it is 3 parts by mass or more. Moreover, it is 20 mass parts or less from a viewpoint of hold | maintaining the rigidity calculated | required as a joint pipe | tube, such as a medical infusion set, and making it difficult to pull out the inserted tube. The amount is preferably 18 parts by mass or less.

Ingredient (c) "epoxidized vegetable oil" (essential ingredient)
The epoxidized vegetable oil used as component (c) of the present invention is produced by a known method of epoxidizing a naturally occurring vegetable oil with an organic peracid such as hydrogen peroxide or peracetic acid. And epoxidized linseed oil. As the component (c), one or a mixture of two or more of these can be used.

Examples of the epoxidized soybean oil include those having a viscosity of 100 to 800 mPa · s (25 ° C.). Further, those having an oxirane oxygen ratio of 6.0% to 7.0% are preferred. As a medical joint tube for connecting a medical tube made of a vinyl chloride resin composition containing a cyclohexanedicarboxylate-based plasticizer, an easy-to-insert and difficult-to-remove product is obtained. Particularly for connecting a medical tube made of a vinyl chloride resin composition containing a cyclohexanedicarboxylate-based plasticizer when the oxirane oxygen ratio is 6.0% to 6.6% and the iodine value is 6 or less. As a medical joint tube, it has a surprising effect on its ease of insertion and difficulty in removal.

The viscosity is a value measured using a B-type viscometer according to JIS K 7117-1: 1999. The oxirane oxygen ratio was measured by dissolving the sample in glacial acetic acid and titrating with glacial acetic acid solution of hydrobromic acid using crystal violet as an indicator based on the standard method for analysis of oils and fats (2013 version) of the Japan Oil Society. It is the value. Iodine value is JIS
K 0070: Measured according to 1992.

Examples of commercially available components (c) include epoxidized soybean oil “O-130P (trade name)” and epoxidized linseed oil “O-180A (trade name)” manufactured by ADEKA Corporation.

The compounding amount of the component (c) is a medical joint tube for connecting a medical tube made of a vinyl chloride resin composition containing a cyclohexanedicarboxylate-based plasticizer to 100 parts by mass of the component (a). In order to obtain a material that is easy to insert, difficult to remove, and has no problem in the dissolution test required for medical materials, the content is 1 part by mass or more. Preferably it is 2 parts by mass or more. Further, the amount is 9 parts by mass or less in order to obtain a medical joint tube that is easy to insert as a medical tube for connecting a medical tube made of a vinyl chloride resin composition containing a cyclohexanedicarboxylate-based plasticizer and is difficult to be removed. Preferably it is 8 mass parts or less.

Component (d) “Silane compound” (optional component)
The silane compound used as 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 (d) with respect to 100 parts by weight of the component (a), 0.1 to 15 parts by weight are used, thereby including a cyclohexanedicarboxylate-based plasticizer. As a medical joint tube for connecting a medical tube made of a vinyl chloride resin composition, it is possible to obtain a tube with further improved ease of insertion and removal. More preferably, it is 1-15 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.

The organosilane compound is a group other than the alkoxysilane compound, the acetoxysilane compound, and the chlorosilane compound, and a group such as an alkyl group, a vinyl group, a (meth) acryl group, an allyl group, or a methyl acetate group directly on the silicon atom. This indicates a bonded silane compound, and examples thereof include triisopropylsilane, triisopropylsilyl acrylate, allyltrimethylsilane, and methyl trimethylsilylacetate.

Among these silane compounds, monoalkoxysilane is used for obtaining a medical joint tube that is easy to insert as a medical joint tube for connecting a medical tube made of a vinyl chloride resin composition containing a cyclohexanedicarboxylate-based plasticizer and is difficult to be removed. One or more alkoxysilane compounds selected from the group consisting of compounds, dialkoxysilane compounds, trialkoxysilane compounds and tetraalkoxysilane compounds are preferred, trialkoxysilane compounds and tetraalkoxysilane compounds are more preferred, and 3-methacryloxy More preferred is propyltriethoxysilane.

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, you may mix | blend the stabilizer normally used for the hard vinyl chloride resin for medical uses as an arbitrary component with the medical vinyl chloride resin composition of this invention. Examples of the stabilizer include organotin compounds, barium-zinc and calcium-zinc stabilizers. From the viewpoint of the effect of the invention, a preferred stabilizer is an organotin compound. As for the compounding quantity of a stabilizer, 0.1-10 mass parts is preferable with respect to 100 mass parts of component (a). Further, for example, polyethylene wax can be added as a lubricant.

The medical vinyl chloride resin composition of the present invention comprises component (a) vinyl chloride resin, component (b) cyclohexanedicarboxylate plasticizer, component (c) epoxidized vegetable oil, and optional components used as desired. It can be obtained by melt kneading using a single screw extruder, a twin screw extruder, a roll, a mixer or various kneaders. Preferably, it can be obtained by melt kneading at a resin temperature of 150 to 180 ° C. using a twin screw extruder.

The medical joint pipe of the present invention can be obtained by injection molding or extrusion molding using the medical vinyl chloride resin composition of the present invention. Preferably it is obtained by injection molding. The joint pipe is also called a connector or a tube adapter, and its shape is substantially cylindrical or T-shaped, and some have a branch cock function.

EXAMPLES Hereinafter, although an Example demonstrates this invention, this invention is not limited to this.

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

Component (b) Cyclohexanedicarboxylate-based plasticizer component (b-1):
Manufacturer: BASF Japan Ltd. Product Name: Hexamol ^R DINCH
Type: Diisononylcyclohexane-1,2-dicarboxylate (DINCH)

Component (c) Epoxidized vegetable oil component (c-1): Epoxidized soybean oil Manufacturer: ADEKA Corporation
Product name: O-130P
Viscosity: 280 mPa · s (25 ° C)
Oxirane oxygen ratio: 6.7%
Iodine number: 2

Component (c-2) Epoxidized soybean oil viscosity: 280 mPa · s (25 ° C.)
Oxirane oxygen ratio: 6.3%
Iodine number: 2

Component (c-3) Epoxidized linseed oil manufacturing company: ADEKA Corporation
Product name: O-180A
Viscosity: 650 mPa · s (25 ° C)
Oxirane oxygen ratio: 9.1%
Iodine number: 5

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

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

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

Component (e) Other optional component 1 (stabilizer)
Ingredient (e): Dioctyltin dimercapto stabilizer Manufacturing company: ADEKA Corporation
Product Name: ADK STAB 465
Type: Dioctyltin dimercapto

Component (f) Other optional component 2 (lubricant)
Ingredient (f): Polyethylene wax-based lubricant manufacturer: Mitsui Chemicals, Inc. Product name: High Wax 4202E
Type: Polyethylene wax

Measuring method 1. Medical aptitude test The following test was conducted in accordance with the “Japanese Pharmacopoeia Plastic Drug Container Testing Method”.

1-1. Preparation of test solution 15.00 g of a 1 mm thick test piece obtained by press-molding the vinyl chloride resin composition obtained below was washed with water and dried at room temperature. This test piece was put into an Erlenmeyer flask having an internal volume of 500 ml, added with 300 ml of distilled water, sealed with a silicone rubber stopper, and heated at 121 ° C. for 60 minutes using a high-pressure steam sterilizer. After decompression, the Erlenmeyer flask containing the test piece was taken out from the autoclave and left to reach room temperature. The test piece was transferred to a 300 ml volumetric flask together with distilled water, and distilled water was added to make exactly 300 ml, which was used as a test solution. Moreover, the test liquid which does not contain a test piece as a blank test liquid was prepared by said method. The following tests (i) to (iv) were performed on the test solution and the blank test solution.

(I) pH test Measurement was performed using a pH meter “Seven Easy AG8603 (trade name)” manufactured by METTER TOLEDO. After calibration with a pH standard solution, 1 ml of a potassium chloride aqueous solution having a concentration of 1.0 g of potassium chloride in 1000 ml of distilled water was added to 20 ml of the test solution, and the pH after stirring for 30 seconds was measured. Similarly, the pH of the blank test solution was measured. The absolute value of the difference between the pH of the test solution and the pH of the blank test solution was calculated as ΔpH.

(Ii) 10 ml of a potassium permanganate reducing substance test test solution is collected, put into a 100 ml Erlenmeyer flask, 20 ml of 0.01N potassium permanganate (KMnO ₄ ) aqueous solution, diluted sulfuric acid (manufactured by Wako Pure Chemical Industries, Ltd.) After adding 5.7 ml of concentrated sulfuric acid for precision analysis (concentration 96% by volumetric analysis) to 10 ml of distilled water, cooling, and adding distilled water to 100 ml.) After adding 1 ml and boiling for 3 minutes, Cooled to room temperature. After adding 0.1 g of potassium iodide and allowing to stand for 8 minutes, 15 ml of 0.01 N sodium thiosulfate aqueous solution was added dropwise. After leaving for 10 minutes, a starch test solution was added as an indicator, stirred, and titrated with 0.01N aqueous sodium thiosulfate solution, and the end point at which the solution became transparent was measured. Similarly, measurement was performed on the blank test solution. The potassium permanganate consumption was calculated by the following formula. It means that the larger the ΔKMnO ₄ , the greater the amount of potassium permanganate reducing substance (mainly organic matter) eluted.
KMnO ₄ consumption (ΔKMnO ₄ ) = (KMnO ₄ consumption of blank test liquid) − (KMnO ₄ consumption of test liquid)

(Iii) Evaporation residue test 20 ml of the test solution was evaporated and solidified on a water bath, the residue was dried at 105 ° C. for 1 hour, and its mass (mg) was measured.

(Iv) Ultraviolet absorption spectrum test The ultraviolet absorption spectrophotometer "U-3010 (trade name)" manufactured by Hitachi, Ltd. was used. Take the blank test solution prepared above in a quartz cell with a thickness of 10 mm and correct the photometer, then put the test solution prepared above in the same manner in the quartz cell and measure the maximum absorbance at a wavelength of 220 to 350 nm. did.

2. Ease of insertion test (1) Using a vinyl chloride resin composition obtained below, an approximately cylindrical joint pipe having an inner diameter of 6 mm, a wall thickness of 2 mm (outer diameter of 10 mm), and a length of 50 mm was obtained using an injection molding machine. Created.
(2) Next, a vinyl chloride resin composition (100 parts by mass of polyvinyl chloride having an average degree of polymerization of 1300, 50 parts by mass of diisononylcyclohexane-1,2-dicarboxylate, and 1 part by mass of a calcium-zinc stabilizer) Prepared by melting and kneading.) One tube with an outer diameter of 6 mm, a wall thickness of 1 mm, and a length of 1 m was prepared, and 10 mm was inserted into the joint part of the joint pipe obtained above and inserted. Ease was evaluated by the ratio of the number of the 10 testers who answered that it was easy to insert.
◎: Very easy to insert 10 out of 10 people ○: Easy to insert 5 out of 7 people out of 10 people △: Slightly difficult to insert 2 out of 4 people out of 10 people ×: Difficult to insert out of 0 out of 10 people

3. Detachability test (1) Using a vinyl chloride resin composition obtained below, an approximately cylindrical joint pipe having an inner diameter of 6 mm, a wall thickness of 2 mm (outer diameter of 10 mm), and a length of 50 mm was obtained using an injection molding machine. Created.
(2) Next, a vinyl chloride resin composition (100 parts by mass of polyvinyl chloride having an average degree of polymerization of 1300, 50 parts by mass of diisononylcyclohexane-1,2-dicarboxylate, and 1 part by mass of a calcium-zinc stabilizer) Obtained by melt kneading.) Prepare one tube of outer diameter 6mm, wall thickness 1mm, length 1m, and insert it 10mm into the joint part of the joint pipe obtained above, then connect it to JIS
K 7100: In accordance with 1999, put a joint pipe with a tube connected to a constant temperature and humidity chamber “SE-47CIA (trade name) manufactured by Kato Corporation” adjusted to a temperature of 80 ± 2 ° C. and a humidity of 70 ± 5%, It was allowed to stand for 72 hours, and after being left in a constant temperature and humidity chamber (temperature 23 ± 2 ° C., humidity 50 ± 5%) for 24 hours, Evaluation was based on the percentage of people who answered that it was difficult to escape.
◎: Very difficult to remove 10 out of 10 people ○: Difficult to remove 5 out of 7/10 people △: Slightly out of 2-4 people out of 10 people ×: Easy out of 0 out of 10 people

Examples 1-15, Comparative Examples 1-6
A vinyl chloride resin composition was produced by melt-kneading the components (parts by mass) shown in any one of Tables 1 to 3 at 150 to 180 ° C. using a twin screw extruder. The above tests 1 to 3 were performed. The results are shown in any one of Tables 1-3.

As shown in any one of Tables 1-3, the composition of the present invention is a medical joint tube for connecting a medical tube made of a vinyl chloride resin composition containing a cyclohexanedicarboxylate-based plasticizer. It is easy to insert and difficult to remove, and there is no problem in the dissolution test required for medical materials. On the other hand, Comparative Example 1 in which the blending amount of component (b) is less than specified is inferior to Tests 2 and 3. Comparative Example 2 in which the blending amount of component (b) is larger than specified is inferior to Test 3. Comparative Example 3 in which the amount of component (c) is less than specified is inferior to Tests 2 and 3. Comparative Example 4 in which the blending amount of component (c) is larger than specified is inferior to Test 3. The comparative examples 5 and 6 which do not use the component (c) are inferior to the tests 2 and 3.

Claims (7)

Component (a) 100 parts by weight of vinyl chloride resin;
Component (b) 1-20 parts by mass of a cyclohexanedicarboxylate plasticizer;
Component (c) 1-9 parts by weight of epoxidized vegetable oil;
A medical vinyl chloride resin composition comprising:
The medical vinyl chloride resin composition according to claim 1, wherein the component (b) is diisononylcyclohexane-1,2-dicarboxylate.
Furthermore, 0.1-15 mass parts of component (d) silane compounds are contained with respect to 100 mass parts of said component (a), The medical vinyl chloride resin composition of Claim 1 or 2 characterized by the above-mentioned.
The medical vinyl chloride resin composition according to any one of claims 1 to 3, which is used for a medical infusion set or a joint pipe of a blood circuit.
The medical vinyl chloride resin composition according to any one of claims 1 to 4, wherein the medical vinyl chloride resin composition is used for a joint pipe used for connection of a medical tube made of a cyclohexanedicarboxylate-based plasticizer-containing vinyl chloride resin composition. object.
A medical infusion set or a blood circuit joint tube comprising the medical vinyl chloride resin composition according to any one of claims 1 to 5.
Use of the joint pipe according to claim 6 to connection of a medical tube made of a cyclohexanedicarboxylate plasticizer-containing vinyl chloride resin composition.