JP3065204B2 - Polysulfone resin composition and medical / pharmaceutical device comprising the same - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a novel polysulfone resin composition having a high hygiene property and suitable for long-term preservation of its contents, for example, as a material for containers and the like, and a medical and medical device comprising the composition. The present invention relates to a pharmaceutical device.

[0002]

2. Description of the Related Art The type, performance, quality, test items, test methods, standard values, and the like of medical and pharmaceutical devices are prescribed in the Pharmaceutical Affairs Law, the Japanese Pharmacopoeia and the notification of the Ministry of Health and Welfare.
As the medical technology advances more and more today, products in which various standard values as requirements are added to the above items, methods and numerical values are manufactured.

[0003] Transparent materials used for medical and pharmaceutical purposes are mainly glass products, and for example, they have been combined with molded articles made of natural rubber as a soft elastic body for sealing. However, in recent years, synthetic resins and synthetic rubbers have been studied and marketed as materials for medical and pharmaceutical devices.

[0004]

By the way, there are the following characteristics and problems in the materials of medical and pharmaceutical devices conventionally used widely. Polyvinyl chloride (abbreviated PVC) is a stabilizer added to the resin, for example, a tin-based, cadmium, zinc salt double salt compound or the like, for example, dioctyl phthalate,
Plasticizers such as dioctyl adipate and tricresyl phosphate elute and contaminate pharmaceuticals and drug solutions. In addition to the fact that the PVC raw material monomer remains in the resin, disposal of the resin product may cause environmental destruction. Since polyethylene (abbreviated as PE) has a low softening point, products made from it are tools that cannot be autoclaved. Polypropylene (abbreviation PP) can be sterilized by high-pressure steam, but is difficult to sterilize at high temperature. There is a report that a resin is modified to be transparent and used as a medical material (JP-A-3-16314).
4, ibid., 3-28246). PE and PP are water,
Although it has relatively good resistance to humidity, it has poor gas barrier properties such as oxygen and carbon dioxide.
There is a problem of discoloration. As a method for improving such disadvantages of PE and PP, a saponified product of ethylene and vinyl acetate copolymer component (abbreviated as EVOH) is mixed with PE or PP.
Alternatively, it has been proposed to make a package in which PE, PP and EVOH are laminated (for example, “packaging film, molded container,
Practical heat resistance of bottles: Plastic Age 6 (1992
Year), "High barrier multilayer plastic container: pharmaceutical factory v
ol. 6, No. 12 (1986) "," Plastic gas barrier containers, plastic gas barrier properties and container molding methods: Food packaging vol.32-No.3 "," High gas barrier packaging materials: plastic vol. 38, No. 5 (1987) ",
“Applications and current status of barrier resin containers: plastic vo
l.27, No.5 (1977) "," Barrier composite materials and PVD
C: Compatech vol.15, No.1 (1987) "," Barrier resin for functionalizing packaging materials: Compatech vol.17, No.1
6 (1989) "," Recent functional packaging materials: industrial materials vol.37,
No. 14 (1989) "," Recent trend of functional packaging containers: Science and Industry vol. 61-4 (1987) "), EVOH absorbs water,
Due to its extremely high hygroscopicity, humidity and
The coexistence of moisture has a disadvantage that the effect of shielding gas such as oxygen and air is extremely weak. Glass material is heat resistant, oxygen resistant,
Although it is a material excellent in transparency and the like, there is a problem that alkalis generated from the glass surface and fine particles peeling off the glass contaminate chemicals and chemicals. Polyphenylene ether resin (abbreviation PFE), polyethylene terephthalate (abbreviation PET), polybutylene terephthalate (abbreviation P)
BT) and polycarbonate (PC).
There are problems such as foul odor and formaldehyde generation. Natural rubber (abbreviated as NR) and synthetic rubber isoprene rubber (abbreviated as I
R), butadiene rubber (abbreviated BR), styrene-butadiene copolymer rubber (abbreviated SBR), nitrile rubber (abbreviated N)
BR), butyl rubber (abbreviated IIR), halogenated butyl rubber (BIIR, CIIR), etc. are vulcanized, vulcanization accelerators and reinforcing agents elute and peel when used for medical and pharmaceutical applications. There is a problem that causes chemicals and chemicals to be contaminated. The present inventors have already made IR, BR,
A rubber product in which ultrahigh molecular weight polyethylene is blended with SBR (Japanese Patent Publication No. 5-43740), and a rubber product in which a special vulcanizing agent is combined with IIR (Japanese Patent Application Laid-Open No. 4-213347) are proposed. An object of the present invention is to provide a medical or pharmaceutical device using a novel material which has solved the drawbacks of conventional products, and is particularly highly hygienic and can be used for containers and other devices to improve the contents. A novel polysulfone resin composition suitable for long-term storage of contents without elution or peeling of contaminants, and a medical or pharmaceutical device comprising the same are intended.

[0005]

Means for Solving the Problems The present invention provides means for solving the problems by (1) at least one kind of an isobutylene-isoprene copolymer-based elastic material.
1 or more of polysulfone resin per 100 parts by weight
A polysulfone resin composition for medical and pharmaceutical plugs, comprising at least 40 parts by weight , (2) at least one kind of isobutylene-isoprene copolymer elastic body and one kind of polysulfone resin A mixture or an alloy containing the above.
Medical, pharmaceuticals plug body for polysulfone-based resin composition of the mounting, (3) polysulfone-based resin (-Ph-SO ₂ -Ph-S
(1) wherein the repeating unit is-) _n (where n means an integer of 2 to 1000 ).
Or polysulfo for medical and pharmaceutical plugs according to (2)
Resin-based resin composition and (4) isobutylene-isoprene copolymer-based elastic
Tylene-isoprene copolymer rubber, chlorinated isobutylene-
Isoprene copolymer rubber, brominated isobutylene-isoprene
Copolymer rubber or isobutylene-isoprene-divinyl
The above, characterized by containing a benzene copolymer rubber
Medical or pharmaceutical stopper according to any of (1) to (3)
A polysulfone-based resin composition for body use. Again
Akira describes (5) isobutylene-isoprene copolymer-based elastomer as (-P
_{h-SO 2 -Ph-O-)} n [where n is an integer of 2 to 1000] polysulfone to repeating unit
Polysulfone-based resin composition comprising a resin, (6) isobutylene - 1 or more kinds of isoprene copolymer based elastic body
99 to 1% by weight and at least one kind of polysulfone resin
99% by weight of the polysulfo according to the above (5).
Emissions-based resin composition, (7) isobutylene - 1 or more kinds of isoprene copolymer based elastic body
A mixture comprising the above and one or more polysulfone resins
Or (5), characterized in that it is a compound or an alloy.
Or (8) the polysulfone resin composition according to (6 ), wherein the isobutylene-isoprene copolymer-based elastic material is
Tylene-isoprene copolymer rubber, chlorinated isobutylene-
Isoprene copolymer rubber, brominated isobutylene-isoprene
Copolymer rubber or isobutylene-isoprene-divinyl
The above, characterized by containing a benzene copolymer rubber
(5) The polysulfone resin according to any one of (7) to (7).
Composition, (9) above (5) to (8 isobutylene according to any one of - isoprene copolymer based elastic body and medical consisting polysulfone resin composition comprising a polysulfone-based resin, pharmaceutical appliances and characterized in that (10) medical, pharmaceutical appliances are plug
To the (9) for medical according pharmaceuticals instrument, and (11) medical, pharmaceutical appliances syringes, the (9) for medical, wherein it is an infusion set or a container, medical
Provide a medical device.

[0006]

The isobutylene-isoprene copolymer-based elastic body (hereinafter sometimes abbreviated as IIR elastic body) according to the present invention refers to an isobutylene-isoprene copolymer rubber (IIR),
Rubber obtained by reacting chlorine with isobutylene-isoprene copolymer rubber (CIIR), rubber obtained by reacting bromine with isobutylene-isoprene copolymer rubber (BIIR), isobutylene-isoprene-divinylbenzene copolymer rubber (abbreviated as D)
VIIR), IIR, CIIR, BII
It is an elastic body obtained by vulcanizing R, DVIIR with one or more vulcanizing agents such as sulfur, zinc white, magnesium, an amine compound, an organic peroxide, a maleimide compound and the like.

The IIR elastic body according to the present invention has an isoprene group content of 4.5% by weight or less and an average molecular weight of 10,000 to 650,000.
For example, for 100 parts by weight of IIR, sulfur,
For example, t-butylperoxyisopropyl, n-butyl-4,4'-bis (t-butylperoxide) valerate, 1,1-di (t-butylperoxy) 3,3,5-
Organic peroxides such as trimethylcyclohexane; maleimides such as N, N'-m-phenylenebismaleimide; vulcanizing agents such as zinc white; and dipentamethylenethiuram tetrasulfide, zinc diethyldithiocarbamate, and tetramethylthiurammono Vulcanization accelerators such as sulfide and tetramethylthiuram disulfide are added in an amount of 0.
It can be produced by known means such as vulcanization by adding 5 to 2 parts by weight and applying heat and pressure, for example.

The elastic body of BIIR and CIIR according to the present invention is prepared by adding zinc oxide and magnesium oxide, for example, an organic amine compound having an amino group and a carboxyl group in the molecule to 100 parts by weight of BIIR and CIIR. It can be produced by adding 1 to 5 parts by weight of a vulcanization accelerator, a vulcanization accelerator similar to the case of the IIR elastic body, and heating and pressurizing.

The elastic body of the DVIIR according to the present invention is DV
It can be produced by blending 0.5 to 2 parts by weight of the same organic peroxide as that of the IIR with 100 parts by weight of the IIR, and vulcanizing by heating and pressing.

As a specific method for vulcanizing the elastic body according to the present invention, preparing the resin composition of the present invention, and molding from the composition, the raw rubber is mixed with the above-mentioned various compounding agents in advance, and the mixture is mixed. After performing dynamic vulcanization by pressurizing and heating at 160 to 220 ° C with a null mixer or a mixing and extruding machine, mixing with a polysulfone resin or mixing and alloying, or vulcanizing agent A vulcanization accelerator, a polysulfonic acid, and vulcanization in a mold.

The polysulfone resin according to the present invention is an ultrahigh molecular weight resin having a bond of an aromatic hydrocarbon group and a sulfonyl group (—SO ₂ —) as a main component. Examples of the aromatic hydrocarbon group include a phenyl group and a phenylene group. The number of phenyl groups or phenylene groups bonded to one sulfonyl group is one or two to seven, and in the latter case, a biphenyl group, a bisphenylalkane group, a triphenyl group, or the like is used. The polysulfone resin of the present invention has, as constituents, an oxy group (-O-), a thio group (-S) in addition to a phenyl group, a phenylene group or a sulfonyl group.
-), A lower alkyl group such as a carbonyl group (-CO-) or a methyl group.

Specific examples of the repeating unit of the polysulfone resin according to the present invention are shown below. In the following examples a to w, abbreviations mean the following. Ph: phenyl group or phenylene group, —SO ₂ —: sulfonyl group, —O—:
Oxy group, -S-: thio group, -CO-: carbonyl group,
CH ₃ —: a methyl group. n: 2 to 1000 integer _{a: (- Ph-SO 2} -) n b: (- Ph-SO 2 -Ph-) n c: (- Ph-SO 2 -Ph-Ph-SO 2 -Ph) n _{d: (- Ph-SO 2} -Ph-Ph-Ph-SO 2 -P
_{h) n e: (- Ph} -SO 2 -Ph-Ph-Ph-SO 2 -)
_{n f: (- Ph-SO} 2 -Ph-O-) n g: (- Ph-SO 2 -Ph-SO 2 -Ph-O-) n h: (- Ph-SO 2 -Ph-SO 2 - Ph-O-Ph
_{-O-) n i: (- PhSO} 2 -Ph-PhSO 2 -Ph-O
_{-) n j: (- Ph} -SO 2 -Ph-Ph-SO 2 -Ph-O
_{-Ph-O-) n k: (} - Ph-SO 2 -Ph-Ph-SO 2 -Ph-O
_{-Ph-Ph-O-) n l} : (- Ph-SO 2 -Ph-Ph-O-Ph-O-)
_{n m: (- Ph-SO} 2 -Ph-O-Ph-O-Ph-O
_{-) n n: (- Ph} -SO 2 -Ph-O-Ph-Ph-O-)
_{n o: (- Ph-SO} 2 -Ph-CH 2 -Ph-SO 2 -
Ph-O-) _n p: _{[- Ph-SO 2 -Ph-Ph} -O-Ph-C (C
_{H 3) (CH 3) -Ph} -O- ] _n q: _{[- Ph-SO 2 -Ph-O} -Ph-C (Ph)
(Ph) -Ph-O-] _{n r: (- Ph-SO} 2 -Ph-S-) n s: (- Ph-SO 2 -Ph-O-Ph─CO-Ph-
_{O-) n t: (- Ph} -SO 2 -Ph-O-Ph-O-) n u: _{[- Ph-SO 2 -Ph-O} -Ph-C (CH 3)
(CH ₃₎ -Ph-O-] _{n v: (- Ph-Ph} -SO 2 -Ph-Ph-SO 2 -P
h-O-) _n w: _{[- (CH 3) (CH 3} ) -Ph-SO 2 -Ph
_{(CH 3) (CH 3)} -O-Ph-CO-Ph-O- ]
_n

The polysulfone resin according to the present invention is a polymer having a repeating unit as described above as a main component, and is a conventionally known technique, for example, Japanese Patent Publication Nos. 45-21318 and 46-46.
-21458, 47-617, 53-25879,
56-2091, 61-12930, JP-A-52-2
96700, 53-10696, 59-1293
0, 63-21030, 63-243128, JP-A-1-315422, 1-318040, 3-41
120, 3-95200, 4-335030, 5
It can be produced by polymerization according to the technology described in JP-A-9453. The average molecular weight of the polysulfone resin is 5,0
The method is often employed in which the resin is polymerized in a polar organic solvent using an alkaline catalyst. However, the polysulfone resin used in the present invention is:
It is preferable that the raw material compound, low molecular weight oligomer, inorganic compound (mostly NaCl) and the like are removed as much as possible by repeating solvent washing, warm water washing and the like. Various known techniques can be applied to such a means for purifying the polysulfone resin. The polysulfonic acid resin according to the present invention is tough,
High-strength, heat-resistant, clave-resistant, abrasion-resistant, light-white, transparent resin with excellent resistance to acids, alkalis, and salt solutions, high temperature in detergents and hydrocarbons Can withstand conditions. In addition, steam resistance, hot water resistance 130 ℃,
Since it has the property that it can endure autoclave sterilization for 30 minutes repeatedly, it is very advantageous to use it for medical and pharmaceutical instruments.

As the polysulfonic acid resin of the present invention, a resin to which a relatively high molecular weight stabilizer is added is preferable.
As such a stabilizer, for example, tetrakis [methylene (3,5-di-t-butyl-4-hydroxyphenyl) propionate] methane: trade name Irganox 1
010 (manufactured by Ciba-Geigy), triethylene glycol-bis-3- (2-t-butyl-4-hydroxy-
5-Methylphenyl) propionate: trade name Irganox 245 (manufactured by Ciba-Geigy), bis (2,6)
-Di-t-butyl-4-methylphenyl) pentaeristol diphosphite: trade name Adeostab PEP-3
6 (manufactured by Asahi Denka Co., Ltd.), N, N'-m-phenylenebismaleimide, tocopherol, and the like. One or more of these may be used in an amount of 0.01 to 0.5 parts by weight based on 100 parts by weight of the polysulfonic acid resin. It is preferable to add a part.

The composition of the present invention comprises the above-mentioned IIR elastic body and a polysulfone resin. Further, each of the IIR elastic body and the polysulfone-based resin may be used alone or in combination. The polysulfonic acid resin is blended in an amount of 99 to 1% by weight, preferably 95 to 5% by weight with respect to the IIR elastic body. It is desirable to select this mixing ratio in accordance with the type of medical or pharmaceutical device and the degree of hardness and softness suitable for the device. For example, when applied as a medical or pharmaceutical device plug, it is preferable to blend 5 to 40 parts by weight of a polysulfonic acid resin with respect to 100 parts by weight of an IIR elastic body. Particularly preferably, it is 5 to 30 parts by weight.
If the amount is less than 5 parts by weight, properties suitable for the intended purpose, such as elasticity, cannot be obtained, and if it exceeds 40 parts by weight, the physical properties as a plug, for example, the physical properties required for puncturing a syringe needle Because it lacks. Also for medical use,
When used for the container body of pharmaceutical equipment, BIIR, CIIR, D
2 to 100 parts by weight, preferably 5 to 50 parts by weight of an elastic material selected from VIIR is mixed or alloyed. It becomes a heat-resistant, highly elastic resin body, and has high heat resistance as a medical device or a pharmaceutical device. Therefore, it becomes a container or device that can repeatedly perform heat sterilization, high-pressure autoclave sterilization, and ethylene oxide sterilization. Therefore, it is suitable to be formed into a surgical instrument, a syringe, a syringe / container and the like. It has also been found that the film can be used as a material for bags for infusions and the like, and can also be suitably used as a storage container for high trolley infusions containing glucose and amino acids. In the case of film formation, it is preferable to mix a processing aid, a graft copolymer, and the like with the composition of the present invention.

As described above, the composition comprising the IIR elastic body and the polysulfone resin of the present invention may be a mixture or an alloy. Further, a processing aid can be added to improve the processability and moldability of the mixture and the alloy. Examples of such processing aids include higher fatty acids such as arachidic acid and behenic acid; metal soaps such as zinc stearate, calcium stearate and aluminum stearate; fatty acid amides such as styrene bisstearyl amide; ,
Higher fatty acid esters such as ethylenebisoleic acid amide, behenic acid amide, and stearic acid amide: for example, long-chain fatty acid esters having 20 to 24 carbon atoms, sorbitan fatty acid esters, and the like, and waxes: microcrystalline wax, polyethylene wax, and the like. High molecular weight polyethylenes, alcohols having 16 to 18 carbon atoms,
Graft copolymer, block copolymer (for example, butadiene-styrene-block copolymer and hydrogenated product of the copolymer, polydimethylsiloxane-polyethylene oxide) By blending at least 20 parts by weight of one or more selected from block copolymers, ethylene-glycidyl methacrylate graft copolymers, etc., it is possible to obtain a very uniform alloy and improve processability. it can.

Means for mixing and kneading the IIR elastic body and the polysulfone resin according to the present invention to form an alloy include:
It can be carried out at a temperature of 120 to 380 ° C. using a conventionally known device, for example, an internal mixer, a single-screw or twin-screw extruder, and a uniform mixture or alloy is obtained. Alternatively, it can be directly extruded to obtain a medical or pharmaceutical device. The products molded as medical and pharmaceutical devices according to the present invention are both Japanese Pharmacopoeia (12th revision)
48. Rubber stopper test method for infusion, 49. It is a medical and pharmaceutical device that conforms to the infusion plastic container test method, Notification Nos. 301, 413, and 442 of the Ministry of Health and Welfare, and can be a syringe, a syringe / container, and an infusion set device. In addition, the container has excellent characteristics as a container for medicines and liquid medicines, which can maintain the quality of the contents medicine for a long period of time.

[0018]

The present invention will be described below in more detail with reference to examples, but the present invention is not limited to these examples. [Polysulfonic acid polymerization: 1] In a 10,000 ml autoclave, 358 g of NaHS (concentration: 47% by weight), NaOH
(Concentration: 48% by weight) 225 g, CH ₃ COONa123
g, 19 g of Na ₂ CO ₃ and N-methylpyrrolidone 23
76 g was charged and stirred at 130 ° C. for 3 hours while flowing nitrogen gas. After cooling the mixture to 70 ° C.,
297 g of N-methylpyrrolidone and 4,4-
A mixture with 878.5 g of dichlorodiphenylsulfone is mixed in with stirring and heated at a temperature of 260 ° C. for 4 hours to carry out polymerization. Next, the mixture was cooled with stirring at a rate of 1 ° C./min to 120 ° C., and 9 g of acetic acid and N-methylpyrrolidone 258 were added.
The polymer was gradually poured into 3 g with stirring to precipitate the polymer in the form of fine particle powder.
Wash with 00 ml and then with 1000 ml of methanol.
Irganox 1010 was added to 100 parts by weight of the obtained polymer.
After adding 0.1 parts by weight, the mixture is dried in a vacuum. The obtained resin amount was 632 g, and the glass transition temperature was 192 ° C. The resin is pale yellow and transparent, and the repeating unit is (-Ph-SO ₂
—Ph—S—) _n , that is, the repeating unit r described above. This resin is abbreviated as resin r.

[Examples 1 to 3 and Comparative Examples 1 and 2] IIR
[Product name: JSR Butyl 365, manufactured by Nippon Synthetic Rubber Co., Ltd., 2.0 mol% of unsaturation, ML _{1 + 8} 100 ° C. 4
2] To 100 parts by weight, the polysulfone resin r obtained above was blended in a ratio shown in Table 1 below (parts in the table means parts by weight), and the mixture was mixed with an internal mixer and a twin-screw extruder. The mixture was kneaded and dispensed with two rolls to prepare a mixed dough.

[0020]

[Table 1]

In Table 1 above,-are as follows. PE: low-density polyethylene, Shorex M22
2. Softening point 92 ° C, manufactured by Showa Denko KK Filler: Trade name Whitetex: Souther
n Clay. 2,5-dimethyl-2,5-di (t-butylperoxy) hexane. N, N'-m-phenylenebismaleimide. Microcrystalline wax (melting point: 110 ° F., manufactured by Nippon Seiro Co., Ltd.). γ-mercaptotrimethoxysilane: A-189 (trade name) manufactured by Nippon Unicar.

Oscillating the mixed dough obtained above
With a disc rheometer (abbreviated as ORR) testing machine, Japan Rubber Association, VOL. 40 (1967) p874,
According to ASTM D-2705 and SRIS 3102, a vibration type vulcanization test [giving a small angular vibration (torsional vibration) of rotary reciprocating motion, measuring the corresponding stress as a torque value, and obtaining the maximum torque value (c), And the minimum torque (b) are obtained], and the results are shown in Table 2.

[0023]

[Table 2]

As shown in Table 2, Example 1 has a larger difference in torque value [(c)-(b)] than doughs of Comparative Examples 1 and 2.
Since the length is large, it is understood that the rubber is a highly elastic body. Further, in Example 2 in which the amount of the resin A was increased, and in Example 3 in which the silane coupling agent was added, the torque value and the Hs value were higher than those in Example 1 due to the effects of the addition.

Next, using each of the doughs obtained above, a rubber stopper for medicine shown in FIG. 1 was molded under vulcanization conditions: temperature of 170 ° C. for 10 minutes. FIG. 1 is a schematic cross-sectional view of a specific example in which the rubber stopper is applied to a glass bottle, showing a state in which the rubber stopper 1 is inserted into a glass bottle 2 and wound with an aluminum cap 4, 3 is a drug, and 5 is a pharmaceutical. Needle insertion part, 6 is head space, 7
Indicates an injection needle. For each rubber stopper, a test method according to the 12th revised Japanese Pharmacopoeia and a special hygiene test used by the present inventors were conducted. The results are shown in Tables 3 and 4. A special hygiene test is performed as follows.

Other special hygiene test Amount of fine particles (test of the amount of particles generated from rubber stopper): Put 10 rubber stoppers in a hard glass bottle, add 300 ml of dust-free water, wrap the container opening with a film, And vibrates at about 2 revolutions / second for 20 seconds. Then, after standing still for one hour, the number of fine particles in water is measured by a light shielding type automatic fine particle measuring device (manufactured by HIAC). The presence of fine particles of 5 μm or more in the injection solution is an important item because it causes problems such as blockage of blood vessels.

Separation of rubber fragments (Fragmentati
on); 5 ml of water is put into a bottle (10 ml capacity) shown as 2 in FIG. 1, a rubber stopper 1 is stoppered, and then an aluminum cap 4 is tightened. Test needle [22G (0.70 × 32m
m)] is filled with 2 ml of water, and is passed through the needle insertion portion 5 of the rubber stopper 20 times. At the time of the 20th penetration, the water in the syringe is poured into the bottle, and then the injection needle is pulled out. After vibrating inside the bottle, remove the rubber stopper, filter the contents,
Count the number of rubber pieces on the filter paper. This test method is an improvement of the method of British Standard 3263 (abbreviated as BS), and the standard of BS is 3 rubber pieces or less, but the industry currently requires less than 2 rubber pieces.

Chemical leakage: 500 ml of water is put into the bottle 2 of FIG. 1, the rubber stopper 1 is stoppered, and the aluminum cap 4 is tightened. After heating this to 121 ° C. for 30 minutes in a container,
Rocket needle 7 (JMS 200
No., rocket needle with infusion set), leave it for 1 hour while keeping the bottle upside down, then pierce with an air needle, let out 400 ml of water in the bottle, and at this point pull out the rocket needle from the rubber stopper Observe and measure the liquid leakage (ml) at this time.

Water repellency (Water repellenc)
y); 500 ml of distilled water is put into the bottle 2 of FIG. 1, the rubber stopper 1 is stoppered, and the aluminum cap 4 is tightly wound. Next, it is placed in a pressure-resistant heating vessel and steamed at a temperature of 121 ° C. for 30 minutes.
After standing at room temperature for an hour, the inner wall of the bottle is observed. At this time, those that do not recognize water droplets are accepted.

Injection needle puncture resistance test (Determin
Injection needle 7 (21. SWG outer diameter 0.81 mm, length 38 mm)
Is measured with a measuring device (tension type rubber tensile tester) when it penetrates the rubber stopper at a speed of 20 cm / min. This test is a modification of the corresponding test of BS.
BS standard value is 1000g or less.

Water Vapor Permeability Test 8 ml of a 2% by weight saline solution was placed in the glass bottle shown in FIG. 1, the rubber stopper 1 was closed, and the aluminum cap 4 was further tightened. After storing this glass bottle in a desiccator containing silica gel at room temperature for 6 months, the change in weight is measured, and the water vapor transmission amount (g) of the rubber stopper is measured. The average value of five samples is taken, and 1 g or less is regarded as a pass. It is a voluntary standard test of the present inventors.

Gas Component Test in Headspace 8 ml of a 2% by weight saline solution was placed in the glass bottle 2 of FIG.
The rubber stopper 1 is stoppered, and the aluminum cap 4 is further tightened. The glass bottle is steam-heated in a pressure vessel at a temperature of 121 ± 1 ° C. for 60 minutes and then left for about 10 hours. Next, 5 ml of the gas in the head space 6 in the bottle is sampled with a gas syringe, and this is measured by gas chromatography. Column: 10% OV-101 (180-200 mesh W
HP), carrier gas He 50 ml / min, column temperature 1
The presence or absence of the peak at 00 to 200 ° C. (4 ° C./min. Temperature rise) and the magnitude are observed. This test is a test for examining the generation of trace amounts of gas by rubber and compounding agents, which has become a problem in recent years.

Alkali-resistant solution test: Put 10 rubber stoppers in an alkali-resistant container, and add 10 times the weight of the rubber stopper to sodium carbonate.
After adding the 0.5% by weight solution, the rubber stopper is stoppered and the aluminum cap is tightened. Next, the temperature is 121 ° C in a high pressure vessel.
And heat for 30 minutes. After leaving to cool to room temperature, the rubber stopper was removed after cooling, and the test solution was placed in a quartz cell at 430 nm and 650 nm.
Measure the transmittance in the visible part of nm. Pass 95% or more. This test is a basic test for examining the relationship between rubber and a chemical solution, and rubber products with low transmittance are unsuitable.

Water absorption test: Crosslinked rubber product was treated at a temperature of 1
Dry at 05 ° C under normal pressure for 3 hours. Next, after being left in a desiccator containing a desiccant for about 1 hour, the weight (A) is precisely weighed. Next, the rubber stopper is immersed in purified water 10 times as much as the rubber stopper, and steam-heated as it is in a pressure vessel at a temperature of 121 ± 1 ° C. for 30 minutes. After cooling, only the rubber stopper was left in a desiccator for 30 minutes to remove water on the surface, the weight (B) at that time was weighed, and ([(B)-
(A) / (A)] × 100) (%) is determined, and 2% by weight or less is regarded as acceptable.

Adsorption test of drug solution: Isosorbite nitrate (drug for ischemic heart disease, melting point: 72 ° C., manufactured by Nippon Pharmaceutical Co., Ltd.) was diluted to 0.040% by weight with physiological saline, and 3 ml of this solution was accurately poured into a 10 ml bottle. , A rubber stopper was capped, an aluminum cap was fastened and left standing for 24 hours in an inverted state. This is subjected to a high performance liquid chromatograph (manufactured by HLPC), and the amount of isosorbite nitrate is measured to obtain the adsorbed weight loss. Column: FINEPAK SILC18 (trade name, manufactured by JASCO Corporation), mobile phase methanol: water = 7: 3, flow rate 1 ml / min,
Detector UVIDEC100-IV (trade name, manufactured by JASCO Corporation, 220 nm)

[0036]

[Table 3]

[0037]

[Table 4]

As shown in Tables 3 and 4, all of the products of the present invention conform to the standard values of the 12th revised Japanese Pharmacopoeia. In addition, it can be seen that it is an excellent rubber stopper that can also be used for special self-test items as containers and devices that can handle the latest pharmaceuticals. On the other hand, the products of Comparative Examples 1 and 2 show a problematic result in several items such as pH, evaporation residue, and fine particle amount.

Embodiment 4 BIIR (EXXON CH)
ML1 _{+ 8} 125 ° C 50, bromine content 0.6% by weight) 100 parts by weight, activated zinc white (manufactured by Sakai Chemical Industry Co., Ltd.) 1.0 part by weight, N, N'-m-phenylene 2.0 parts by weight of bismaleimide (manufactured by Kawaguchi Chemical Industry Co., Ltd.)
Insoluble sulfur (0.2 parts by weight manufactured by Nippon Kaizoku Co., Ltd. was mixed with an internal mixer and kneaded at a temperature of 160 ° C. for 7 minutes to obtain a dynamic vulcanizate. A separately purified polysulfone resin (trade name: UDEL) POLYSULFONE,
The repeating unit manufactured by Union Carbide is u: [-
_{Ph-SO 2 -Ph-O-} Ph-C (CH 3) (C
H ₃ ) -Ph-O-] _n washed twice with a solvent obtained by heating N-methylpyrrolidone: water = 1: 0.5]
100 parts by weight, 1 part by weight of ethylene bisstearic acid amide (manufactured by Nippon Kasei Co., Ltd.), 5 parts by weight of styrene-butadiene-ethylene copolymer and 5 parts by weight of maleic anhydride 5 parts by weight of block copolymer (prototype) An alloy was formed at a temperature of 160 to 220 ° C. using a mixer and a twin extruder. Next, a uniform film plate was obtained through a T-tie. 0.4mm thick. As a result of measuring the physical properties in accordance with JIS K6301, the tensile strength was 213 kg / cm ² and the elongation was 21.
0%, and measure the oxygen gas permeation amount (GT made by Yanagimoto Seisakusho)
R), at a temperature of 20 ° C and 100cc in a dry state
/ m was ² · 24hrs / atm. The oxygen gas permeation amount of the BIIR vulcanized film plate before kneading is 300 cc / m ² · 24.
Since it was hrs / atm, it is understood that the gas barrier property against oxygen was improved by mixing the IIR elastic body and the polysulfone resin according to the present invention. In addition, about the alloyed product of BIIR of this invention and a polysulfonic acid resin, 49. of the 12th revision Japanese Pharmacopoeia. A test was conducted in accordance with the plastic container test method for infusion, and the results are shown in Table 5 below.

Embodiment 5 CIIR (JSR CHLO)
ROBUTYL 1068, trade name, manufactured by Nippon Synthetic Rubber Co., Ltd., ML _{1 + 8} 125 ° C. 50, halogen content 1.
2 parts by weight), 100 parts by weight of activated zinc flower (manufactured by Sakai Chemical Industry Co., Ltd.) and 1.0 part by weight of zinc diethyldithiocarbamate were mixed by an internal mixer, and then kneaded at a temperature of 160 ° C. for 7 minutes. And a dynamic vulcanizate was obtained. Separately purified polysulfonic acid [trade name VICTRE]
X PES, manufactured by ICI, wherein the repeating unit is f: (−
Those _{Ph-SO 2 -Ph-O-)} n, tetrahydrofuran: water: acetic acid = 20: 5: further washed one] 400 parts by weight with acetone washed with 0.1 heated solvent, styrene - ethylene 10 parts by weight of a styrene block copolymer (manufactured by Shiil Chemical Co., Ltd.) and 30 parts by weight of polyethylene terephthalate (Kuraray Co., Ltd., polyethylene terephthalate, grade KS700) were heated to 160-220 using an internal mixer and a twin extruder. ° C
Was used as an alloy. Next, 0.4m thick through T-tie
m was obtained. About the film
Physical properties were measured in accordance with IS K6301. As a result, the tensile strength was 256 kg / cm ² , the elongation was 180%, and the oxygen gas permeation amount was measured in the same manner as in Example 4.
/ m was ² · 24hrs / atm. FIG. 2 shows the prepared infusion solution container. In FIG. 2, 8 is an injection, 9 is a container mouth, 1
0 indicates a welding stopper, 11 indicates a heat-welded portion, and 12 indicates a suspension. In addition, 49. of the 12th revision Japanese Pharmacopoeia. A test was conducted in accordance with the plastic container test method for infusion, and the results are shown in Table 5 below. As shown in Table 5, the product according to the present invention has passed the standard values of the 12th revised Japanese Pharmacopoeia.

[0041]

[Table 5]

[Polymerization of polysulfonic acid: 2] 3000 m
306 g (1 mol) of bis (3,5-dimethyl-4-hydroxyphenyl) sulfone, 1000 ml of chlorobenzene and 450 ml of sulfolane were added to a three-necked flask with stirring, and the mixture was stirred and heated to 60 ° C. under a nitrogen gas atmosphere.
250.5 g of an OH (45% by weight) solution was gradually added, and 5
Chlorobenzene was removed by azeotropic addition of 0 ml of purified water, and heating was continued to a temperature of 120 to 140 ° C. When the reaction reached 145 ° C, it was cooled to 130 ° C and bis (4-
Fluorophenyl) ketone (218 g)
And react for 8 hours. The polymerization reaction product was cooled, and a large amount of methanol was poured under stirring to precipitate a resin, which was filtered, washed with acetone and warm water, and dried under vacuum. 450 g resin
Repeating unit w: [-(CH ₃ ) (CH ₃ ) Ph-S
_{O 2 -Ph (CH 3) (} CH 3) -O-Ph-CO-P
hO-] _n , glass transition temperature 240 ° C. This resin is abbreviated as resin w.

[Polymerization of polysulfonic acid: 3] 4000 m
149 g of 4,4'-diphenol in a three-necked flask
234 g of 4,4'-dichlorodiphenylsulfone, 121.6 g of anhydrous potassium carbonate and 1200 g of N, N'-dimethylacetamide were charged, and the reactor was boiled in a nitrogen gas atmosphere to boil N, N'-dimethylacetamide and water. Let out. After conducting the polymerization reaction for about 4 hours, it is cooled,
The potassium carbonate is filtered off, a large amount of methanol is poured under stirring to precipitate a resin body, washed with methanol and warm water, and dried under vacuum. The amount of the obtained resin was 340 g. Glass transition temperature 220 ° C. In the resin, the repeating unit has the n: (-
A _{Ph-SO 2 -Ph-O-} Ph-Ph-O-) n, it referred to the resin as n.

Examples 6 to 10 Various polysulfone resins and IIR elastic bodies were blended in the ratios (parts by weight) shown in Table 6. After previously mixing each raw material powder, the mixture was dynamically vulcanized at an extruder temperature of 180 to 220 ° C., and then formed into an injection cylinder shape shown in FIG. In FIG. 3, 13 is an injection cylinder, 14
Represents a stopper, 15 represents an injection needle, and 16 represents a pusher bar. The obtained syringe was tested according to the Ministry of Health and Welfare Notification No. 442. Table 7 shows the results.

[0045]

[Table 6]

[0046]

[Table 7]

In the above examples of the present invention, any one of the resins having a repeating unit of r, n, w, u, and f as the polysulfonic acid resin and the IIR elastic body are IIR, BIIR,
Although examples of combinations each of which is one of CIIR and DVIIR are shown, in the present invention, any combination of one or more of all polysulfone-based resins and any combination of one or more of IIR is also available. It is equally effective. Specifically, the above-mentioned repeating unit may be any one or all of polysulfonic acids of a to w, IIR, BII
R, CIIR and DVIIR are combined with any one or all of them.

The following is a summary of embodiments of the present invention. (1) Isobutylene-isoprene copolymer elastic material 1
A polysulfone-based resin composition comprising 95 to 5% by weight of at least one kind and at least 5 to 95% by weight of at least one kind of polysulfone-based resin. (2) Isobutylene-isoprene copolymer-based elastic material 1
5 to 4 parts by weight of polysulfone resin per 100 parts by weight
A medical or pharmaceutical instrument stopper comprising a polysulfone-based resin composition mixed with 0 parts by weight. (3) Isobutylene-isoprene copolymer-based elastic material 1
5 to 3 parts by weight of polysulfone-based resin to 100 parts by weight or more
A medical or pharmaceutical instrument stopper comprising a polysulfone-based resin composition mixed with 0 parts by weight. (4) For medical and pharmaceutical use comprising a polysulfone-based resin composition in which 2 to 100 parts by weight of at least one type of isobutylene-isoprene copolymer-based elastic material is blended with respect to at least one type of polysulfone-based resin and at least 100 parts by weight. Appliances. (5) For medical or pharmaceutical use comprising a polysulfone resin composition obtained by blending 5 to 50 parts by weight of at least one kind of isobutylene-isoprene copolymer-based elastic material with respect to at least one kind of polysulfone resin to 100 parts by weight. Appliances. (6) The IIR and the repeating unit are represented by (-Ph-SO ₂ -P
The polysulfone resin composition according to the above (1), which is blended with a polysulfone resin represented by hS-) _n (where n represents an integer of 1 to 2000). (7) BIIR and repeating unit (-Ph-SO ₂ -
Ph-O-Ph-C ( CH 3) (CH 3) -Ph-O
-] _N (where n means an integer of 1 to 2000) and a polysulfone resin represented by the formula (1).
The polysulfone-based resin composition as described above. (8) The CIIR and the repeating unit are represented by (-Ph-SO _2-
The polysulfone-based resin composition according to the above (1), which is blended with a polysulfone resin represented by Ph-O-) _n [where n represents an integer of 1 to 2000]. (9) BIIR and a repeating unit are represented by (-Ph-SO _2-
Ph-O-Ph-Ph-O-) _n [where n is 1 to 200
[Indicating an integer of 0]. (10) CIIR and a repeating unit are (− (CH ₃ ))
_{(CH 3) Ph-SO 2} -Ph (CH 3) (CH 3) -
O-Ph-CO-Ph-O-) _n [where n is 1 to 200
[Indicating an integer of 0]. (11) DVIIR, wherein the repeating unit is [-Ph-SO
_{2 -Ph-O-Ph-C} (CH 3) (CH 3) -Ph-
O-) _n [where n means an integer of 1 to 2000] and the repeating unit represented by (-Ph
The polysulfone-based resin composition according to the above (1), which is blended with a polysulfone resin represented by —SO ₂ —Ph—O—) _n (where n represents an integer of 1 to 2000). (12) DVIIR, wherein the repeating unit is (-Ph-SO
₂ -Ph-O-) _n [where n is an integer of 1 to 2,000] polysulfone resin and a recurring unit represented by _{(-Ph-SO 2 -Ph-O} -Ph-Ph-O-) n
The polysulfone resin composition according to the above (1), wherein the polysulfone resin composition is blended with a polysulfone resin represented by the formula (1), wherein n represents an integer of 2 to 2000. (13) DVIIR and a repeating unit represented by (-Ph-SO
₂ -Ph-O-) _{n wherein n} represents an integer of 2 to 2000. The polysulfone resin composition according to the above (1), which is blended with a polysulfone resin represented by the formula:

The medical and pharmaceutical devices according to the present invention are:
The following effects are obtained. 1) High hygiene properties that meet the specifications of the Japanese Pharmacopoeia. 2) Oxygen permeability barrier properties. 3) Peeling of fine particles and rubber fragments, leakage of chemicals, water repellency, needle stick resistance, water vapor transmission, head. Excellent hygiene with regard to space gas, alkali solution resistance, water absorption, and chemical solution adsorption.

[Brief description of the drawings]

FIG. 1 is a schematic cross-sectional view showing a specific example in which a rubber stopper for a chemical solution according to the present invention is applied to a glass bottle.

FIG. 2 is a sectional view of an infusion container according to the present invention.

FIG. 3 is a cross-sectional view of a syringe according to the present invention.

[Explanation of symbols]

1 rubber stopper, 2 glass bottle, 3 medicine,
4 Aluminum cap, 5 Needles, 6 Headspace, 7 Needles, 8 Injections, 9
Container mouth, 10 welding tap, 11 heat welding part,
12 Suspension, 13 Syringe barrel, 14 Slumber, 15 Injection needle, 16 Push rod.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI // (C08L 15/02 81:06) (C08L 23/22 81:06) (58) Investigated field (Int.Cl. ⁷ , DB name) C08L 1/00-101/16 A61J 1/00 A61L 31/00 A61M 5/18

Claims (11)

(57) [Claims] 1. A isobutylene - a polysulfone-based resin relative to 100 parts by weight of one or more isoprene copolymer based elastic body
Medical and pharmaceutical products containing at least one and 5 to 40 parts by weight
Polysulfone-based resin composition for plugs . 2. Isobutylene-isoprene copolymer elasticity
Contains at least one kind of body and at least one kind of polysulfone resin
Mixture or medical, pharmaceuticals plug body for polysulfone-based resin composition according to claim 1, wherein you being a alloy product was composed. 3. The method according to claim 1, wherein the polysulfone resin is (-Ph-SO _2).
-Ph-S-) _n (where n means an integer of 2 to 1000 )
3. The medical or pharmaceutical plug according to claim 1 or 2, wherein the unit is a repeating unit.
-Body polysulfone resin composition. 4. Elasticity of isobutylene-isoprene copolymer
Isobutylene-isoprene copolymer rubber, chlorinated iso
Butylene-isoprene copolymer rubber, brominated isobutylene
-Isoprene copolymer rubber or isobutylene-isoprene
- Medical according to any one of claims 1 to 3, characterized that you containing divinylbenzene copolymer rubber
And polysulfone resin compositions for plugs for pharmaceuticals . 5. Elasticity of isobutylene-isoprene copolymer
Body and _{(-Ph-SO 2 -Ph-O-} ) n [where n is 2
Which means an integer of 1000 )
A polysulfone-based resin composition containing a sulfone-based resin . 6. Elasticity of isobutylene-isoprene copolymer
1 to 99% by weight of at least one body and 1% of polysulfone resin
The polysulfone-based resin composition according to claim 5, comprising 1 to 99% by weight or more . 7. Elasticity of isobutylene-isoprene copolymer
Contains at least one kind of body and at least one kind of polysulfone resin
Characterized in that it is a mixture or an alloy of
The polysulfone resin set according to claim 5 or 6.
Adult. 8. An isobutylene-isoprene copolymer elasticity
Isobutylene-isoprene copolymer rubber, chlorinated iso
Butylene-isoprene copolymer rubber, brominated isobutylene
-Isoprene copolymer rubber or isobutylene-isoprene
-Characterized by containing divinylbenzene copolymer rubber
The police according to any one of claims 5 to 7,
Rufone resin composition. 9. The method according to claim 5, wherein
Isobutylene-Isoprene Copolymer Elastic Material and Police
Polysulfone resin composition containing rufone resin
Medical / pharmaceutical equipment consisting of products. 10. The medical or pharmaceutical device is a plug.
The medical and pharmaceutical device according to claim 9, characterized in that: 11. The medical or pharmaceutical device is a syringe or an infusion.
10. The container according to claim 9, wherein the container is a set or a container.
Medical and pharmaceutical equipment.