JP3153687B2 - Medical infusion plug with excellent heat resistance and recovery properties - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention is rich in flexibility, sealability at the time of needle sticking, self-closing of holes after needle removal, permanent elongation, rubber elasticity, compression set, mechanical strength and safety and health. The present invention relates to a medical infusion plug having excellent thermoplasticity.

[0002]

2. Description of the Related Art Conventionally, medical infusion plugs are prepared by kneading vulcanized rubber such as natural rubber, isoprene rubber, butadiene rubber, butyl rubber, or a blend thereof.
Various fillers, reinforcing agents, oil, sulfur, vulcanization accelerators, and other auxiliaries are added to the mixture, and the mixture is kneaded, supplied to a mold for a plug, and heated and pressurized.

[0003] As described above, the conventional plug requires a large-scale facility because it goes through a complicated process until a molded body is obtained. In addition, since there are many types of additives and complicated adjustments, it is expensive and productivity is high. It was bad. In particular, the vulcanization process with a press mold
Since the vulcanization time is about 10 to 20 minutes, it takes a long time,
Inevitably limited productivity. In addition to this, the plug obtained by the vulcanization method has a lot of unnecessary burrs and has a deburring step, and since it is a vulcanized product, it cannot be reused and is economically lossy. Was. Also, since the stopper obtained by this method is added with sulfur, a vulcanization accelerator and the like during the production, when the stopper comes into contact with the chemical solution in the container to which the stopper is attached, these additives are included in the chemical solution. Could be eluted. Furthermore, if this plug is used and then burned in a disposal process, a toxic gas such as sulfurous acid gas is generated, which is not preferable.

For this reason, in recent years, several proposals have been made for plugs using thermoplastic elastomers as materials for the purpose of improving the above-described productivity, improving safety and health, and making the plugs recyclable. . For example, Japanese Patent Application Laid-Open
-58057, JP-A-59-28965, JP-A-Showa 6
No. 1-64253 discloses butyl rubber and polyester,
A plug obtained by mixing a styrene-based or olefin-based thermoplastic elastomer is disclosed in JP-A-61-1.
No. 31,746 discloses a plug made of a styrene-based thermoplastic elastomer. Also, Japanese Patent Application Laid-Open No. 3-68363
Discloses a resin composition for a plug comprising an olefin resin and a hydrogenated block copolymer. 6
No. 1-24050 discloses a plug made of a thermoplastic elastomer based on a hydrogenated block copolymer, and Japanese Utility Model Laid-Open No. 2-147131 discloses a thermoplastic elastomer material in which a core material of vulcanized rubber is used. A coated plug is disclosed.

However, plugs made of these thermoplastic elastomer materials have low heat resistance, are incorporated into a container during sterilization, and are subjected to 100 ° C. under a certain degree of external stress.
When exposed to the above high temperatures, problems such as deterioration of physical performance or deformation occur. Most of the needles intended for use of these plugs are small diameter metal needles having a diameter of about 1 mmφ. When a large diameter resin needle or the like used for infusion use is inserted, the needle is removed. Later, a problem occurs in which the liquid leaks out. As means for further improvement, a plug in which a vulcanized rubber plug is covered with plastic, and a plug formed by covering a core of vulcanized rubber with a thermoplastic elastomer have been proposed. However, it is still not perfect, and there are problems such as poor productivity as in the case of a plug made of only vulcanized rubber. On the other hand, the present applicant has disclosed Japanese Patent Application Laid-Open No. 63-57663.
In the publication, the materials used in the present invention
For gasket In the present invention, the material is
Newly found to be suitable for the purpose of the present invention
Was.

[0006]

SUMMARY OF THE INVENTION A plug obtained by a conventional vulcanization method solves problems such as productivity and hygiene, and furthermore has excellent flexibility, heat resistance and self-closing property after needle removal. It is an object of the present invention to provide an infusion plug having the same level of recovery characteristics as an infusion plug made of a vulcanized rubber material of a plastic elastomer.

[0007]

That is, the present invention provides:
(A) a polymer block A composed mainly of at least two vinyl aromatic compound, obtained by hydrogenating at least one conjugated diene compound comprising a polymer block B composed mainly of a block copolymer Number average molecular weight is 5
0,000～250,000 hydrogenated block copolymer
100 parts by weight , (b) the bonding unit is the following formula (1);

[0008]

Embedded image

A polyphenylene ether resin, which is a homopolymer and / or copolymer having a reduced viscosity (0.5 g / dl chloroform solution, measured at 30 ° C.) in the range of 0.15 to 0.70; Parts by weight , (c) 50 to 300 parts by weight of a softener for non-aromatic rubber , (d) 5 to 100 parts by weight of polyolefin hydrocarbon resin ,

The object of the present invention is to provide a medical infusion plug having excellent heat resistance and recovery characteristics, which is formed from a thermoplastic elastomer material and comprises (a), (b), (c) and (d). It is. The hydrogenated block copolymer used as the component (a) in the present invention comprises a polymer block A mainly composed of at least two vinyl aromatic compounds and a polymer block B mainly composed of at least one conjugated diene compound. Which is obtained by hydrogenating a block copolymer consisting of: A (BA) n, B (AB) n, (A-
B) n, (AB) mX [where n is 1 to 10
And m is an integer of 3 to 8, and X represents a polyfunctional residue having m bonds.], Those having a single structure, those having different structures, and hydrogenation rates May be a mixture of different ones. As used herein, the expression “mainly” refers to at least 5
0% by weight or more, preferably 70% by weight or more.

The proportion of the vinyl aromatic compound A constituting the hydrogenated block copolymer is 20 to 40% by weight,
Preferably it is 25 to 35% by weight. Further, these polymer blocks A mainly composed of a vinyl aromatic compound and the polymer blocks B mainly composed of a conjugated diene compound or a hydrogenated product thereof are each a conjugated diene compound or a conjugated diene compound in a molecular chain in each polymer block. The distribution of the hydrogenated product and vinyl aromatic compound is random, tapered (the monomer component increases or decreases along the molecular chain),
The polymer block A mainly composed of the vinyl aromatic compound and the polymer block B mainly composed of a conjugated diene compound or a hydrogenated product thereof may be partially block-shaped or an arbitrary combination thereof. When there are two or more, each of the polymer blocks may have the same structure or different structures.

As the vinyl aromatic compound constituting the block copolymer of the present invention, for example, one or more selected from styrene, α-methylstyrene, vinyltoluene, p-tert-butylstyrene and the like are selected. Of which styrene is preferred. Also, as the conjugated diene compound,
For example, butadiene, isoprene, 1,3-pentadiene, 2,
One or more of 3-dimethyl-1,3-butadiene and the like can be selected, and among them, butadiene, isoprene and a combination thereof are preferable. The polymer block B mainly composed of a conjugated diene compound or a hydrogenated product thereof can be arbitrarily selected in the microstructure of the block. For example, in the case of a polybutadiene block before hydrogenation, 1,2-vinyl 25-55 coupling structure
% By weight, preferably 30 to 50% by weight.

The number average molecular weight of the block copolymer having the above structure is from 50,000 to 250,000.
0, preferably 70,000 to 210,000, more preferably 90,000 to 170,000, and the molecular weight distribution [the ratio of the weight average molecular weight (Mw) to the number average molecular weight (Mn) (Mw / Mn). )] Is 10 or less, preferably 5 or less, more preferably 2 or less. When the number average molecular weight of the above-mentioned block copolymer is less than 50,000, the heat resistance of the obtained plug is lowered, which is not preferable.
The number average molecular weight of the block copolymer is 250,000
If it exceeds 0, the workability and the permanent elongation properties are inferior, and the performance of the obtained plug is undesirably reduced.

The production method of these block copolymers is not limited as long as they have the above-mentioned structure. For example, a lithium catalyst is prepared by the method described in Japanese Patent Publication No. 40-23798. Can be used to synthesize a vinyl aromatic compound-conjugated diene compound block copolymer in an inert solvent. Examples of a method for producing a vinyl aromatic compound-hydrogenated conjugated diene compound block copolymer exhibiting more preferable performance include, for example, JP-B-42-8704 and JP-B-43-66.
The method described in JP-A-36-36 may be used. In particular, in applications requiring high weather resistance and heat aging resistance, use of a titanium-based hydrogenation catalyst is recommended.
No. 3203 and JP-A-60-79005. At that time, the aliphatic double bond derived from the conjugated diene compound accounts for at least 80% or more, preferably 9% or more.
Preferably, 0% or more is hydrogenated, which means that most of the conjugated diene compounds have been morphologically converted to olefinic compounds. For example, a butadiene polymer block converts to a polymer block based on ethylene-butylene.

Further, the polymer block A mainly composed of a vinyl aromatic compound and, if necessary, the vinyl aromatic compound copolymerized with the polymer block B mainly composed of a conjugated diene compound or a hydrogenated product thereof, Although there is no particular limitation on the hydrogenation rate of the aromatic double bond derived therefrom,
0% or less is preferable. The hydrogenation rate of the hydrogenated block copolymer can be easily known by infrared spectroscopy or nuclear magnetic resonance analysis.

Next, the polyphenylene ether resin used as the component (b) of the present invention is an essential component for improving the compression set and the permanent elongation strain of the obtained plug, and the bonding unit is represented by the formula (1). , Reduced viscosity (0.5g
/ Dl chloroform solution, measured at 30 ° C.)
Those having a range of 0.70, preferably 0.20 to 0.60 are used. Known polyphenylene ether resins can be used. Specific examples include poly (2,6-dimethyl-1,4-phenylene ether), poly (2-methyl-6ethyl-1,4-phenylene ether), and poly (2,6-diphenyl-1,4). -Phenylene ether), poly (2-methyl-6-phenyl-1,4-phenylene ether), poly (2,6-dichloro-1,4-phenylene ether) and the like.
Also, a polyphenylene ether copolymer such as a copolymer of 2,6-dimethylphenol and other phenols (for example, 2,3,6-trimethylphenol or 2-methyl-6-butylphenol) can be used. Among them, poly (2,6-dimethyl-1,4-phenylene ether), 2,6-dimethylphenol and 2,3,6-trimethylphenol are preferable, and poly (2,6-dimethyl-1,4-phenylene) is more preferable. Ether) is preferred.

In the case of poly (2,6-dimethyl-1,4-phenylene ether), its reduced viscosity (0.5 g / dl)
Chloroform solution, 30 ° C measurement) is 0.15 to 0.7
0 is preferable, and more preferably 0.20 to 0.20.
It is in the range of 0.60. The amount of component (b) can be suitably selected in the range of 20 to 150 parts by weight per 100 parts by weight of component (a). If the compounding amount exceeds 150 parts by weight, the hardness of the obtained plug is increased, and the rubber elasticity is deteriorated, which is not preferable. If the amount is less than 20 parts by weight, rubber elasticity at high temperature [compression set (100 ° C. × 22)
Time)], which is not preferred.

Next, the softener for non-aromatic rubber used as the component (c) of the present invention is useful for adjusting the hardness of the obtained plug and imparting flexibility. The non-aromatic rubber softener used here can be a liquid paraffin, and the impurities such as aromatic hydrocarbons and sulfur compounds contained in the petroleum lubricating oil fraction are removed with sulfuric anhydride or fuming sulfuric acid, and purified. It is a colorless, transparent, tasteless and odorless oil composed of saturated hydrocarbons. In the present invention, as the component (c), in addition to the liquid paraffin described above, a petroleum softener approved by the FDA (United States Food and Drug Administration) can also be used.

The compounding amount of the softener of the component (c) is 50 to 300 parts by weight, preferably 100 to 250 parts by weight, per 100 parts by weight of the component (a). If the amount is more than 300 parts by weight, bleed-out of oil is likely to occur, and the obtained plug may be tacky, which is not preferable. Further, the mechanical strength is also reduced, which is not preferable. Further, if the amount is less than 50 parts by weight, it is not preferable from the viewpoint of imparting flexibility and economy.

Next, the polyolefin-based hydrocarbon resin used as the component (d) of the present invention is useful for improving the processability and / or heat resistance of the obtained plug, for example, polyethylene, isotactic polypropylene, propylene and the like. Other minor copolymers of α -olefins, such as propylene-ethylene copolymer, propylene-1-hexene copolymer, propylene-4-methyl-1-pentene copolymer, and poly (4-methyl-1 -Pentene), polybutene-1 and the like. MFR (ASTM-D-1) when isotactic polypropylene or a copolymer thereof is used as the polyolefin resin.
238-L condition, 230 ° C) is 0.1 to 50 g / 10
Min, especially 0.5 to 30 g / 10 min can be suitably used. The amount of the component (d) is 10
The amount is 5 to 100 parts by weight, preferably 5 to 50 parts by weight based on 0 parts by weight. If the blending amount exceeds 100 parts by weight, the hardness of the obtained plug becomes too high and the flexibility is lost.
Not only can a rubbery product not be obtained, but also rubber elasticity (compression set) and permanent elongation strain at high temperatures deteriorate, which is not preferable. In addition, if the rubber does not have rubber elasticity in order to maintain the self-closing property of the hole after removing the needle of the stopper, liquid leakage will occur. This is because the rubber elasticity that holds the pressure is lost.

Next, by blending a polystyrene resin as the component (e) in the composition of the present invention within a range of 5 to 50 parts by weight with respect to 100 parts by weight of the component (a), the composition is effective for moldability. is there. As the polystyrene resin, those obtained by a known radical polymerization method or ionic polymerization method can be suitably used, and the number average molecular weight is 5,000 to 500,000,
Preferably, it is in the range of 10,000 to 400,000. The molecular weight distribution [ratio (Mw / Mn) between weight average molecular weight (Mw) and number average molecular weight (Mn)] is preferably 10 or less.

Further, as a component of the medical infusion plug of the present invention, a hindered amine light stabilizer, if necessary,
UV absorbers, antioxidants, inorganic fillers, coloring agents, silicone oils and the like can be added. As a method for producing the hydrogenated block copolymer composition used as the material of the medical infusion stopper of the present invention, a method used in the production of a usual resin composition or the production of a rubber composition can be adopted. Compounding can be carried out using a melt kneader such as a screw extruder, a twin screw extruder, a Banbury mixer, a heating roll, a Brabender, various kneaders and the like. At this time, the order of addition of each component is not limited. For example, all components are premixed by a mixer such as a Henschel mixer or a blender and melt-composited by the above mixer, or arbitrary components are premixed and mixed in a master batch. And then adding the remaining components to form a melt composite.

Then, the composite medical transport of the present invention is provided.
The liquid plug can be molded by a commonly used thermoplastic resin molding machine, and various molding methods such as injection molding, extrusion molding, blow molding, calendar molding, and compression molding can be applied. Injection molding is preferred as an efficient method for manufacturing the plug.

[0024]

The test methods in Examples and Comparative Examples are as follows. (1) The hardness was measured with a type A according to JIS-K-6301. (2) The tensile strength [kgf / cm ² ] and elongation [%]
In accordance with IS-K-6301, a test piece used was a 2 mm-thick injection sheet punched out with a No. 3 dumbbell. (3) The permanent compression set [%] was defined as a residual strain after 25% deformation at 100 ° C. for 22 hours according to JIS-K-6301. (4) Permanent elongation strain [%] is based on JIS-K-6301, and the test piece is a 2 mm thick injection sheet.
What was punched out with a No. 1 type dumbbell was used. The retention time at 1/2 elongation at break elongation [%] is indicated by residual elongation after 10 minutes. (5) In the self-closure test after removing the needle, a plug sample is attached to the lower part of the water tank, water is poured into the water tank to a height of 20 cm from the plug, and an infusion needle is quickly placed at the center of the plug. Insert and leave for 30 minutes. After 30 minutes, pull out the needle,
Check the amount of leakage.

The evaluation was performed in three stages: ○: water leakage from the needle hole stopped immediately after needle removal, Δ: water leakage from the needle hole but stopped within 10 minutes, × A case where water leakage from the needle hole did not stop for more than 10 minutes. The plug sample used was 5 m as shown in FIG.
25mmφ disk with a thickness of 5mm
Injection molding of a 2 mm minimum diameter and a 1 mm deep truncated cone with a frustum-shaped concavity is performed as a heat sterilization process that is expected to be performed during actual production. The test was performed on the sample subjected to the heat treatment for 30 minutes and the sample not subjected to the heat treatment at all.

The needle for infusion is a commercially available needle, and a plastic needle having a maximum diameter of about 4 mm was used. In addition, each compounded component is as follows. (1) <Component (a-1)> having a structure of hydrogenated polybutadiene-polystyrene-hydrogenated polybutadiene-polystyrene,
Bound styrene content 31% by weight, number average molecular weight 45,000
A hydrogenated block copolymer having a molecular weight distribution of 1.18, a 1,2 bond amount of polybutadiene before hydrogenation of 37% by weight, and a hydrogenation rate of 99% was obtained by the method described in JP-A-61-33132. It was synthesized using a system hydrogenation catalyst.

<Component (a-2)> It has a structure of hydrogenated polybutadiene-polystyrene-hydrogenated polybutadiene-polystyrene, the amount of bound styrene is 22% by weight, the number average molecular weight is 78,000, and the molecular weight distribution is 1. 1
8. A hydrogenated block copolymer having a 1,2 bond content of polybutadiene before hydrogenation of 36% by weight and a hydrogenation rate of 99% was obtained by the method disclosed in
Synthesis was carried out using a Ti-based hydrogenation catalyst described in JP-A-33132.

<Component (a-3)> It has a structure of hydrogenated polybutadiene-polystyrene-hydrogenated polybutadiene-polystyrene, the amount of bound styrene is 33% by weight, the number average molecular weight is 136,000, and the molecular weight distribution is 1. 2
0, a hydrogenated block copolymer having a 1,2 bond amount of polybutadiene before hydrogenation of 38% by weight and a hydrogenation rate of 99% was obtained by the method disclosed in
Synthesis was carried out using a Ti-based hydrogenation catalyst described in JP-A-33132.

<Component (a-4)> having the structure of polystyrene-hydrogenated polybutadiene-polystyrene,
Bound styrene content 29% by weight, number average molecular weight 113,00
A hydrogenated block copolymer having a molecular weight distribution of 1.08, a 1,2 bond amount of polybutadiene before hydrogenation of 41% by weight, and a hydrogenation rate of 99% was obtained by the method described in JP-A-61-33132. It was synthesized using a system hydrogenation catalyst.

<Component (a-5)> (polystyrene-hydrogenated polybutadiene) having a structure of ₄ Si, a bound styrene content of 30% by weight, a number average molecular weight of 201,000, a molecular weight distribution of 1.36, A hydrogenated block copolymer having a 1,2 bond content of polybutadiene of 40% by weight and a hydrogenation rate of 99% was synthesized using a Ti-based hydrogenation catalyst described in JP-A-61-33132.

<Component (a-6)> having the structure of polystyrene-hydrogenated polyisoprene-polystyrene,
34% by weight of bound styrene, number average molecular weight 141,00
0, molecular weight distribution 1.20, 1,4 bond amount of polyisoprene before hydrogenation is 94% by weight, 3,4 bond amount is 6% by weight,
A hydrogenated block copolymer of a styrene / isoprene block copolymer having a hydrogenation rate of 99% of polyisoprene was obtained by the method disclosed in
Synthesis was carried out using a Ti-based hydrogenation catalyst described in JP-A-33132. (2) Component (b) As the polyphenylene ether resin, poly (2,6-dimethyl-1,4-phenylene) ether <reduced viscosity;
0.54> was synthesized. (3) Component (c) Diana Process Oil PW-380 manufactured by Idemitsu Kosan Co., Ltd. [paraffin-based process oil, kinematic viscosity: 381.6 cst
(40 ° C.), 30.1 cst (10 ° C.), ring analysis; C _{N
= 27%, C P = 73} %] (4) the component (d) manufactured by Asahi Kasei Corporation polypropylene resin, M1600 [MFR
(230 ° C., 2.16 kg) 14 g / 10 min] (5) Component (e) Asahi Kasei's polystyrene resin, polystyrene 685 [M
FR (200 ° C, 5.0 kg) 2 g / 10 min]

[0032]

Examples 1 to 6 As a hydrogenated block copolymer (a-
Using 4), each component shown in Table 1 was mixed with a Henschel mixer, and then melt-kneaded with a twin screw extruder having a diameter of 30 mm at 270 ° C to obtain pellets of a thermoplastic elastomer. This was evaluated as an injection molded product, and the results are shown in Table 1.

From these results, it was found that the medical infusion stopper of the present invention was excellent in compression set and permanent elongation strain at 100 ° C., and also excellent in self-closing property of a hole after needle removal.

[0034]

Comparative Examples 1-4 As a hydrogenated block copolymer (a-
Using 4), the components shown in Table 1 were kneaded in the same manner as in Examples 1 to 5, molded, and evaluated. The results are shown in Table 1. From these results, it was found that a plug molded with a thermoplastic elastomer outside the scope of the present invention was inferior in compression set and permanent elongation strain at 100 ° C., and was also inferior in self-closing property of a hole after needle removal.

[0035]

Examples 7 to 10 As hydrogenated block copolymers (a-
2) Using (a-3), (a-5), and (a-6), the components shown in Table 2 were kneaded in the same manner as in Examples 1 to 5,
It was molded and evaluated. The results are shown in Table 2. From these results, if the structure of the hydrogenated block copolymer is within the range described in the present invention, the medical infusion plug of the present invention is 100%.
It was found to be excellent in compression set and permanent elongation set at ℃, and also excellent in self-closing property of the hole after needle removal.

[0036]

Comparative Example 5 Using (a-1) as a hydrogenated block copolymer, the components shown in Table 2 were kneaded in the same manner as in Examples 1 to 5, molded and evaluated. The results are shown in Table 2. From this result, it was found that a plug molded from a thermoplastic elastomer having a number average molecular weight of less than 50,000 of the hydrogenated block copolymer used was inferior in the self-closing property of the hole after needle removal, which was not preferable.

[0037]

Examples 11 and 12 The medical infusion stoppers obtained in Examples 4 and 9 were subjected to a material and dissolution test in accordance with the rubber stopper test method for infusion according to the Twelfth Revised Japanese Pharmacopoeia Law. Was. Table 3 shows the results. From this result, the medical use of the present invention
The infusion plug was found to meet the standards.

[0038]

[Table 1]

[0039]

[Table 2]

[0040]

[Table 3]

[0041]

The heat resistance, self-closing property of the hole after needle removal, permanent elongation, rubber elasticity and compression set required for medical infusion plugs have been improved. As it does not contain sulfur, there is no sulfur elution in the chemical solution or blood that comes in contact with the plug, and it is non-toxic because it does not contain heavy metals such as zinc, and it does not react with free sulfur and metals. It is a target.

Since the medical infusion plug of the present invention can be injection-molded, the molding time is greatly reduced as compared with the conventional one including a vulcanization step, and the mold releasability is good, so that the productivity is excellent. Further, when injection molding is performed by the cold runner method, the runner portion and the sprue portion after molding are thermoplastic elastomers, so that they can be recycled and are economical.

[Brief description of the drawings]

[1] transportation of medical of the present invention used in a self-occlusive test
It is sectional drawing and a front view of a stopper for liquids .

[Explanation of symbols]

 1 Cross section 2 Front view

──────────────────────────────────────────────────続 き Continued on the front page (58) Field surveyed (Int. Cl. ⁷ , DB name) A61J 1/05 A61L 31/00 C08L 9/06

Claims (1)

(57) [Claims] 1. A (a) and the polymer block A mainly composed of at least two vinyl aromatic compound, and a block copolymer comprising a polymer block B mainly comprising at least one conjugated diene compound hydrogen 100 parts by weight of a hydrogenated block copolymer having a number average molecular weight of 50,000 to 250,000 obtained by addition , (b) a bonding unit represented by the following formula (1); (Here, R1, R2, R3, and R4 are each selected from the group consisting of hydrogen, halogen, hydrocarbon, and substituted hydrocarbon group, and may be the same or different . )
20 to 150 parts by weight of a polyphenylene ether resin which is a homopolymer and / or a copolymer having a reduced viscosity (0.5 g / dl chloroform solution, measured at 30 ° C.) in the range of 0.15 to 0.70 . (C) 50 to 300 parts by weight of a softener for a non-aromatic rubber , (d) 5 to 100 parts by weight of a polyolefin-based hydrocarbon resin , and (a), (b), (c) and (d), Self-occlusion after needle removal made of thermoplastic elastomer material
Excellent medical infusion plug.