JPH02305834A - Radiation-resistant polybutadiene composition - Google Patents

Abstract

PURPOSE:To obtain a composition useful for the production of a medical appliance which does not adsorb a chemical such as nitroglycerol and is sufficiently flexible and suitable for radiation sterilization by mixing polybutadiene with a hindered amine as a stabilizer. CONSTITUTION:A polybutadiene composition prepared by mixing 100 pts.wt. polybytadiene with 0.01-2 pts.wt. hindered amine. It is desirable that the above composition further contains a lubricant. A product which accomplishes the above purpose is a medical appliance comprising the above composition. This medical applicane may be one which contains a liquid in its inside. As the polybutadiene, a syndiotactic 1,2-polybutadiene which has at least 90% 1,2 bonds is desirable because it has both flexibility and strength.

Description

[Detailed description of the invention] [Industrial application field] The present invention relates to radiation-resistant polybutadiene compositions.

More specifically, the present invention relates to a radiation-resistant polybutadiene composition in which adsorption of drugs such as nitroglycerin is suppressed.

[Prior art and problems to be solved by the invention] Conventionally, connecting tubes for infusion circuits, such as infusion sets, are required to be flexible, so those made of soft polyvinyl chloride resin have been widely used. . However, since soft polyvinyl chloride adsorbs fat-soluble drug components such as nitroglycerin, isosorbite nitrate, and diazepam, there are problems in actual administration. Regarding nitroglycerin, polyethylene, polypropylene, fluororesin, etc. are known as non-adsorbent resins, but these resins are all hard materials and lack flexibility, so they cannot be used for infusion tubes. I can't.

The inner layer is made of low-density polyethylene (LDPE), which does not adsorb nitroglycerin, and the outer layer is made of ethylene-vinyl acetate copolymer (EVA), which adsorbs nitroglycerin but is flexible and has good adhesion to low-density polyethylene.
Layered tubes have been put into practical use. However, these two
In layered tubes, in order to maintain the strength of the inner layer, LD
The flexibility of the tube cannot be said to be satisfactory because the wall thickness of PE must be greater than a certain level. In addition, a tube made of a blended resin of low-density polyethylene and thermoplastic polystyrene elastomer has been proposed, but even this tube does not have sufficient flexibility and is insufficient in terms of suppressing drug adsorption. Met.

The present invention solves the above problems, and aims to provide a medical material that does not adsorb drugs such as nitroglycerin, is highly flexible, and is suitable for sterilization by radiation irradiation.

[Means for Solving the Problems] The present invention that achieves the above objects is based on polybutadiene 100
It is composed of a radiation-resistant polybutadiene composition containing o, oi to 2 parts by weight of a hindered amine.

Preferably, the radiation-resistant polybutadiene composition further contains a lubricant.

The molecular weight of the hindered amine is 700 to 10,000.
It is preferable that

The lubricant is preferably a saturated hydrocarbon type or an amide type lubricant.

Further achieving the above object is a medical device comprising the radiation-resistant polybutadiene composition.

The medical device may contain a liquid containing a drug therein.

Specifically, the medical device has a portion that comes into contact with a liquid containing a drug.

The polybutadiene used in the present invention has the general formula (C)
It is a polymer of butadiene represented by z--CH=CHCHz)n, and the three-dimensional structure is divided into cis-1,4, trans-1,4, and 1.2 structures depending on the bonding mode of the monomers. The latter also has isotactic and syndiotactic stereoisomerism.

Since butadiene does not have any polar groups, it has the effect of being difficult to adsorb fat-soluble drug components such as nitroglycerin. Therefore, it can be suitably used as a material for a tube for administering a liquid containing a drug into the body, a bag containing a liquid containing a drug, and the like. Furthermore, since it has sufficient flexibility, it can be particularly suitably used as a material for things that require deformation in shape, such as tubes, but is not limited thereto. Here, as the polybutadiene, syndiotactic 1.2 polybutadiene containing 90% or more of 1.2 bonds is preferable because it has both flexibility and strength.

Further, the degree of crystallinity is preferably 15 to 30%. Within this range, it has a suitable melting point and has excellent processability.

The hindered amine used as a stabilizer has a structure in which all hydrogens on the carbons at the 2- and 6-positions of piperidine are substituted with hydrocarbon groups, mainly methyl groups. As the hindered amine, known ones are used, but the molecular weight is 70
0 or more and contains amine (piperidine nitrogen ratio)
It is preferable that the value is relatively large. If the molecular weight is less than 700, the hindered amine may elute and cause toxicity. Furthermore, those with a relatively high amine content have sufficient effects with a small amount, so there is little risk of toxicity. Examples of suitable hindered amines include tetrakis(2,2,6,6-tetramethyl-4-piperidyl)-
1,2,3,4-butanetetracarboxylate or poly((6-(1,1,3,3-tetramethylbutyl)imino-1,3,5-)riazine-2,4-diylene) ( Examples include 2,2,6,6-tetramethyl-4-piperidyl)imino)hexamethylene ((2,2,6,6-tetramethyl-4-piperidyl)imino).

The blending ratio of each of these components is preferably 0.01 to 2 parts of hindered amine per 100 parts by weight of polybutadiene. If the amount is less than 0.01 part by weight, the effect will not be sufficiently exhibited, and if it exceeds 2 parts by weight, no further effect can be expected and toxicity may occur, which is not practical.

Other additional ingredients can be added to the compositions of the invention. Additional components include commonly used antioxidants, clarifying agents, nucleating agents, ultraviolet absorbers, lubricants, antistatic agents, R additives, peroxides, dispersants such as metal soaps, and neutralizing agents. can be mentioned.

Examples of antioxidants include 3,5-di-t-butyl-4
-hydroxy-toluene, tetrakis [methylene-3-
(3,5-di-t-butyl-4-hydroxyphenyl)
propionate] methane, etc., but since these cause yellowing during T-ray irradiation, it is desirable to add a small amount.

Also, distearyl-pentaerythritol-di-phosphite, di-(di-(di-nonylphenyl) mono-
(p-nonylphenyl) phosphite and the like have an antioxidant effect and also have a yellowing improvement effect.

Examples of clarifying agents and nucleating agents include 1,3,2,4-dibenzylideisorbitol, which is a condensation product of sorbitol and benzaldehyde, and methyl, ethyl, n-butyl, and butyl in the benzene ring of this compound. There are those substituted with alkyl groups such as, or alkoxy groups such as methoxy, ethoxy, propoxy, etc. Further, there are aluminum-pt-butyl-benzoate, aromatic acidic phosphate ester derivatives, and the like.

As ultraviolet absorbers, 2-hydroxy-4-n-octoxy-benzophenone, 2-(2'-hydroxy-3
°.

Examples include 5'-di[-butyl-phenyl)5-chlorobenzotriazole.

Examples of peroxides include benzoylperoxy), 1
．． Examples include 34''-s(L-butylperoxyisopropyl)benzene, 2,5-dimethyl-2,5-di(L-butylperoxyfuhexane), and the like.

As dispersants and neutralizing agents, calcium stearate,
Examples include salts such as magnesium and sodium.

The lubricant bleeds onto the tube surface and has the function of preventing blocking of the tube. Examples of lubricants include:
Polyethylene-based waxes or amide-based waxes are preferably used because they do not affect drug adsorption and do not discolor after irradiation with gamma rays. Here, polyethylene wax is particularly preferably used because it has a particularly high ability to prevent drug adsorption.

Examples of pigments include blueing agents such as ultramarine blue and cyanine blue.

The medical device of the present invention can be obtained by melt-mixing the above-mentioned composition using a kneading machine such as a roll or an extruder, and then molding the mixture into a medical device by injection molding, extrusion molding, or the like. Generally, each additive is blended with polybutadiene, mixed with a mixing device such as a mixer, and then melted and kneaded with an extruder to form pellets.
The pellets are directly injection molded or extruded into molded products. The molded product is assembled into a medical device, packaged, and subjected to radiation sterilization. As the radiation, gamma rays from a cobalt-60 radiation source are preferably used. The amount of irradiation is 5 megarads or less, preferably 0.5 to 4 megarads, and excessive irradiation causes deterioration of the molded product, so it is preferable to avoid it. The irradiation may be performed in vacuum, in an inert gas such as nitrogen, or in air, and is performed at a temperature of 80° C. or lower, preferably room temperature or lower.

Examples of radiation-resistant medical instruments obtainable according to the present invention include, in particular, tubes for transporting liquids; Examples include, but are not limited to, infusion bags and the like. Specifically, it is meaningful to use the composition of the present invention when it has a part that should come into contact with a liquid containing a drug.

Next, the present invention will be explained in more detail by giving preferred examples.

[Example 1] Syndiotactic 1.2 polybutadiene (trade name JS
R-RB810 manufactured by Nippon Gosei Rubber Co., Ltd.) as a hindered amine (2,2,6,6-titramethyl-4-biveridyl H,2,3,4-butanetetracarboxylate (
A tube with an outer diameter of 3.3 mm and an inner diameter of 2.1 mm (hereinafter referred to as tube 1) was prepared by adding 0.3% by weight of MARK-LA-57 (product name: MARK-LA-57, manufactured by Adeka Argus Chemical Co., Ltd.) by weight.
That's what it means. )It was created.

[Example 2] (2,2,6,6-tetramethyl-4-piperidyl) 1
．． 2. Poly((6-(1,1,3,3-tetramethylbutyl)imino-1,3°5-triazine-2,4-di-μ) instead of 3°4-butanetetracarboxylate
(2,2,6,6-titramedyl-4-piperidyl)imino)hexamethylene ((2゜2.6.6-tetramethyl-4-piperidyl)imino)] (Product name CHI
In the same manner as in Example 1, except that MASSORB944 (manufactured by Nippon Ciba Geigy) was added at a weight ratio of 0.3χ,
A tube of the same size as in Example 1 (hereinafter referred to as tube 2) was obtained.

[Example 3] (2,2,6,6-tetramethyl-4-piperidyl) 1
．． Poly((6-(1,1,3,3-tetramethylbutyl)imino-1,3°5-triazine-2,4-diyμ) instead of 2,3°4-butanetetracarboxylate
The weight ratio of (2,2,6,6-tetramethyl-4-piperidyl)imino)hexamethylene ((2゜2.6.6-tetramethyl-4-piperidyl)imino) is 0.
．． Example 1 was prepared in the same manner as in Example 1 except that 1% was added.
A tube of the same size (hereinafter referred to as tube 3) was obtained.

[Example 4] (2,2゜6.6-tetramethyl-4-piperidyl) 1,2,3.
The weight ratio of 4-butanetetracarboxylate is 0.
3% was added, and paraffin wax (trade name SP-0145 manufactured by Nippon Seiro Co., Ltd.) was added as a lubricant at a weight ratio of 0.5% to the syndiotactic 1.2 polybutadiene, and the size was the same as in Example 1. A tube (hereinafter referred to as tube 4) was obtained.

[Example 5] Syndiotactic 1.2 polybutadiene with poly((6
-(1,1,3,3-tetramethylbutyl)imide 1,
3゜5-triazine-2,4-diμ) (2,2,
0.3% by weight of 6,6-tetramethyl-4-piperidyl)imino)hexamethylene ((2゜2.6.6-tetramethyl-4-piperidyl)imino) was added,
In addition, 9-octadecaneamide (C1) is used as a lubricant.
(CI+□)? Cl1=CI (C8t) TCON
II□] (trade name: RMI 0.0 manufactured by Lion Akzo) was added at a weight ratio of 0.5χ to syndiotactic 1.2 polybutadiene, and a tube of the same size as Example 1 (hereinafter referred to as tube 5) was added. I got it.

[Comparative Example 1] (2,2,6,6-tetramethyl-4-piperidyl) 1
．． A tube of the same size as in Example 1 (hereinafter referred to as Chepro) was obtained in the same manner as in Example I except that 2.3°4-butanetetracarboxylate was not added.

The above six types of tubes were irradiated with T-rays under the following conditions in an atmospheric atmosphere.

・Radiation source: Cobalt 60 ・Irradiation dose: 2 megarads [Comparative Example 2] Example 1 using an extruder using soft polyvinyl chloride as the material
A tube of the same size (hereinafter referred to as tube 7) was obtained.

(Comparative Example 3) A tube of the same size as in Example 1 (hereinafter referred to as tube 8) was obtained using an extruder using an ethylene-vinyl acetate copolymer as a material.

[Comparative Example 4] Styrenic elastomer (Cariflex TR1102
A tube of the same size as in Example 1 (hereinafter referred to as tube 9) was obtained using an extruder using a tube (manufactured by Shell Chemical Co., Ltd.) as a material.

The following experiments were conducted on the nine types of tubes thus obtained.

■ Inner surfaces of 8 types of tubes (10c) excluding drug adsorption experimental tube 6
+s x 10 cm ) was brought into contact with a 50 ug/d nitroglycerin solution for 10 minutes, and the residual rate of nitroglycerin was determined and calculated using a liquid chromatography machine (manufactured by Kaiho Co., Ltd.). Table 1 shows the results.

Table 1 Nitroglycerin Remaining Rate As is clear from Table 1, all the tubes according to the present invention exhibited a higher drug adsorption suppressing effect than the comparative example.

(2) Coloring experiment after T-ray irradiation The degree of coloring of each tube after T-ray irradiation was visually determined.

As a result, tube 6 was considerably yellowed, but tubes 1 to 5 were all only slightly yellowed. Moreover, all of tubes 1 to 5 showed a tendency to decolor over time.

■ I pressed the approximate center of each tube with an inner blocking clamp, left it for 24 hours, and then released the clamp.
remained occluded for more than 1 minute. - All of the tubes 4.5 according to the second invention immediately returned to their pre-pressed shapes.

■ Extractables test Cut a 15g piece from each tube and add 150g of distilled water.
After boiling at d for 30 minutes, distilled water was added to make the solution 150/d, and this was used as a test solution.

Consumption amount of 0,0IN potassium permanganate (Mn04) required to neutralize 10 aft of test solution and pl of test solution
Table 2 shows the consumption amount required for neutralization of distilled water as a control and the value when the pH is taken as a reference value. A small piece of the same size was also cut from the PvC tube of Comparative Example 2 and subjected to the same measurement.

As shown in Margin Table 2 Eluate Experiment Table 2 below, it can be seen that the problematic elution amount from the tube of the present invention is at an extremely low level.

[Effects of the Invention] Since the polybutadiene composition provided by the present invention has almost no polar groups, it has the effect of being difficult to adsorb fat-soluble drug components such as nitroglycerin. Therefore, it can be suitably used for materials such as tubes for administering drug-containing liquids into the body and bags containing drug-containing liquids inside. Furthermore, since it has sufficient flexibility, it can be particularly suitably used as a material for things that require deformation in shape, such as tubes. Also, since it contains hindered amine as a stabilizer, it will not be colored or deteriorated even when exposed to radiation, making it particularly suitable for use as a material for medical instruments that require radiation sterilization. I can do it.

Claims (8)

[Claims] (1) A radiation-resistant polybutadiene composition containing 0.01 to 2 parts by weight of hindered amine in 100 parts by weight of polybutadiene. (2) The radiation-resistant polybutadiene composition according to claim 1, further comprising a lubricant. (3) The molecular weight of hindered amine is 700 to 10,00
The radiation-resistant polybutadiene composition according to claim 1 or 2, wherein the radiation-resistant polybutadiene composition is 0. (4) The radiation-resistant polybutadiene composition according to any one of claims 1 to 3, wherein the lubricant is a saturated hydrocarbon type or an amide type lubricant. (5) A medical device molded from the radiation-resistant polybutadiene composition according to any one of claims 1 to 4 and sterilized by radiation. (6) The medical device according to claim 5, which contains a liquid containing a drug. (7) The medical device according to claim 5, comprising a portion that comes into contact with a liquid containing a drug. (8) The medical device according to claim 7, which is a tube for transporting liquid.