JP3429586B2 - Medical rubber composition - Google Patents

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION The present invention is for medical use which is excellent in resealability, needle stickability, hygiene and flexibility, and also has excellent compression set, impact resilience, molding processability and thermoplasticity. The present invention relates to a rubber composition.

[0002]

2. Description of the Related Art Conventionally, as a medical rubber, for example, a rubber sealing material for a medical container is prepared by masticating natural rubber, isoprene rubber, styrene-butadiene rubber and the like, and adding oil, a crosslinking accelerator and other auxiliaries thereto. Kneaded, kneaded, and then rolled into a sheet, which is then fed to a seal mold and heated,
After being pressed and cross-linked, a plurality of connected molded bodies were taken out from the mold, and the individual molded bodies were punched out and separated. The obtained rubber seal material was further washed in order to remove the attached rubber pieces and foreign matters by the punching and deburring steps.

[0003] As described above, the conventional manufacturing of a rubber seal material requires a lot of facilities because of complicated processes, and it takes a lot of time to adjust and manage additives.
It was expensive and poor in productivity.

Further, the rubber seal material obtained by the above-mentioned method has many unnecessary burrs and cannot be reused because it is a cross-linked material, resulting in economical loss.

Furthermore, since the rubber seal material obtained by the above method is added with a crosslinking accelerator which is unsuitable for medical use, for example, when it is brought into contact with a drug solution or blood, these additives are added. May be eluted.

Therefore, in order to comply with the Japanese Pharmacopoeia standards for eluates, alkali and acid cleaning are carried out. However, even if this step is carried out, only those products that pass the specifications can be obtained. is there. Further, when this rubber seal material is thrown away and burned in a disposal process, sulfurous acid gas or the like is generated, which is not preferable.

The type of these rubber sealing materials is selected based on the type of medical container to be sealed. For example, examples of medical containers include glass containers, plastic containers, and plastic bags. For glass containers,
The seal material is caulked from the outside, and the pressure is constantly applied in the direction in which the seal material is tightened, so that the seal material can be used even if the resealability of rubber is somewhat poor. For example, butyl rubber is used.
In the case of a plastic container and a plastic bag, isoprene rubber or butadiene rubber having good resealability is used because these containers are soft and cannot be caulked from the outside.

However, these rubber materials contain additives which are not suitable for medical use as described above. Therefore, many attempts have been made in the past to substitute these rubber materials with thermoplastic elastomers containing no harmful additives and having good resealability (Japanese Patent Publication No. 53-8736). , JP-A-60-83667 and JP-A-5-59287). Among them, styrene elastomers are regarded as promising.

[0009]

However, none of the rubber sealing materials made of thermoplastic elastomers proposed in the past have yet shown the resealing ability equivalent to that of the crosslinked rubber. For example, a composition of polyolefin and rubber as disclosed in JP-A-5-59287 may bring about an unfavorable result that rubber elasticity is deteriorated when the amount of polyolefin is increased to improve fluidity. It has always been the case that a sealing material having a good balance of both performances cannot be practically obtained.

In recent years, the rubber seal material is made of a thermoplastic elastomer, and studies have been made to improve re-sealability in addition to improvement of productivity and safety. Since the rubber seal material made of an elastomer has a characteristic of being thermoplastic as compared with the one formed by a conventional cross-linked rubber, the productivity is improved but the resealability is not good at present.

Further, the conventional rubber seal material is poor in needle sticking property (ease of inserting an injection needle into the rubber seal material), and when a plastic needle is used, a very large sticking pressure is required. There was a problem that the workability was poor. When a steel needle is used, the piercing pressure is reduced, which improves workability, but since it cannot be discarded together with the container, tube, etc., it is necessary to cut the needle portion, which is troublesome. Met. Furthermore, when the needle is pulled out, there is a problem that the liquid in the bag splatters from the hole where the needle was stuck.

There is also a conventional technique whose purpose is to improve the needle stick property. For example, in JP-A-61-131746, a hydrogenated copolymer, a paraffin-based softening agent and an olefin-based resin are used, and the hardness (JIS K6
Disclosed is a stopper for a freeze-dried preparation, which is composed of a thermoplastic elastomer composition of which 301) is 30 to 60. However, the resealability and needle stickability of this stopper are
I'm still not satisfied. Further, the conventional rubber seal material may use a viscous substance as an additive, which may cause a problem of stickiness on the surface.

The present invention solves the above-mentioned conventional problems and resealability, needle stickability, and rubber elasticity (7) at high temperature.
It has excellent physical properties such as compression set at 0 ° C), molding processability and recyclability peculiar to thermoplastic elastomers, less stickiness on the surface, and less costly for the production of medical containers. Or
Rubber composition for medical connecting pipe (hereinafter, simply referred to as medical rubber composition
(Sometimes called things) is intended to provide.

[0014]

As a result of intensive studies, the present inventors have used an elastomer having a specific high molecular weight as one component thereof, and further using a specific amount of a softening agent for an olefin resin and a non-aromatic rubber. It has been found that, by only doing so, a medical rubber composition capable of solving all the conventional problems can be obtained. Further, it was also found that the resealing property and the needle sticking property were dramatically improved by specifying the hardness of the composition, and the present invention could be completed.

That is, the present invention provides a medical treatment prepared in the following mixing ratio of the components (a), (b) and (c) so that the hardness measured according to JIS K6301 is 5 or more and less than 30. For container sealant or medical
A rubber composition for tubing is provided. (A) A block comprising at least two vinyl aromatic compound-based polymer blocks A and at least one conjugated diene compound-based polymer block B and having a number average molecular weight of 150,000 or more. Copolymer and /
Alternatively, 99 to 55 parts by weight of a block copolymer having a number average molecular weight of 150,000 or more obtained by hydrogenating the block copolymer, (b) 1 to 45 parts by weight of a polyolefin resin, and (c) a non-aromatic type 70 to 300 parts by weight of a softening agent for rubber.

In the present invention, the component (a) is styrene /
The above-mentioned medical rubber composition, which is an ethylene / propylene / styrene copolymer, is provided.

In the present invention, the non-aromatic softening agent for rubber is a paraffin-based or naphthene-based process oil,
There is provided the above-mentioned medical rubber composition selected from mineral oil, white oil, oligomers of ethylene and α-olefin, paraffin wax and liquid paraffin.

Further, the present invention provides the above-mentioned medical rubber composition, wherein the compounding ratio of the softening agent for non-aromatic rubber (c) is 75 to 300 parts by weight.

The present invention will be described in more detail below. Component (a) The component (a) in the composition of the present invention is a polymer block A mainly composed of at least two vinyl aromatic compounds.
And a block copolymer having at least one conjugated diene compound as a main component and having a number average molecular weight of 150,000 or more, and / or a number obtained by hydrogenating the block copolymer. It is a block copolymer having an average molecular weight of 150,000 or more.

These block copolymers are disclosed in JP-A-63-112.
A polymer block A mainly composed of at least two vinyl aromatic compounds, as disclosed in Japanese Patent No. 649;
And a polymer block B containing at least one conjugated diene compound as a main component, and further obtained by hydrogenating a block copolymer, if necessary. For example, A-
B-A, B-A-B-A, A-B-B-A, A-B-A
A vinyl aromatic compound-conjugated diene compound block copolymer having a structure such as —BA or a hydrogenated product thereof. Further referring to the block structure, the polymer block A mainly composed of at least two vinyl aromatic compounds is a homopolymer of a vinyl aromatic compound or a vinyl aromatic compound in an amount of more than 50% by weight.
It is preferably composed of a copolymer containing 70% by weight or more. Further, the polymer block B mainly composed of at least one conjugated diene compound which has been optionally hydrogenated is a homopolymer of a conjugated diene compound,
Alternatively, it is composed of a copolymer containing a conjugated diene compound in an amount of more than 50% by weight, preferably 70% by weight or more. Further, the polymer block A containing at least one vinyl aromatic compound as a main component and the polymer block B containing at least one hydrogenated conjugated diene compound as a main component are the molecular chains in the respective polymer blocks. The distribution within is not particularly limited, and may be, for example, random, tapered (in which the monomer component increases or decreases along the molecular chain), partially block-shaped, or any combination thereof. Good.

As the vinyl aromatic compound constituting the block copolymer, for example, one kind or two or more kinds can be selected from styrene, α-methylstyrene, vinyltoluene, p-tertiarybutylstyrene and the like. Among them, styrene is preferable. Is most preferable. Further, as the conjugated diene compound before hydrogenation constituting the conjugated diene compound optionally hydrogenated, for example, butadiene, isoprene, 1,3-pentadiene, 2,3-dimethyl-1,3-butyldiene, etc. 1 type (s) or 2 or more types are selected from the above, and among them, butadiene, isoprene and a combination thereof are preferable. More preferably isoprene, and 1,4-isoprene
Those having a microstructure of 70 to 100% by weight are preferable. If the 1,4-microstructure is less than 70% by weight,
This is not preferable because the oil will bleed. More preferably, the 1,4-microstructure of isoprene is 90 to 100% by weight.

Specific examples of the component (a) include, for example, styrene / butadiene / styrene copolymer (SB
S), styrene / ethylene / butene / styrene copolymer (SEBS), styrene / isoprene / styrene copolymer (SIS), styrene / ethylene / propylene / styrene copolymer (SEPS), among which SEB
S and SEPS are preferred. More preferably, SEPS is good considering the bleeding property of the non-aromatic softener for rubber. The component (a) is preferably hydrogenated with a conjugated diene. Also, a mixture of hydrogenated and non-hydrogenated ones can be used. Here, the component (a) in the present invention is required to have a number average molecular weight of 150,000 or more. If the number average molecular weight is less than 150,000, the resealability deteriorates, which is not preferable.

The component (b) in the composition of the present invention is a polyolefin resin. Specific examples thereof include polyethylene, polypropylene, 4-methylpentene-1, polybutene-1, ethylene / vinyl acetate copolymer, ethylene / acrylic acid ester copolymer, for example,
Ethylene / acrylic acid copolymer, ethylene / methacrylic acid copolymer, ethylene / ethyl acrylate copolymer, ethylene / vinyl silane copolymer, ethylene / methyl acrylate copolymer, ethylene / methyl methacrylate copolymer, etc. Among them, polyethylene and polypropylene are preferable. The component (b) has a melt index (JIS K6760, 23) in consideration of moldability.
It is preferably 0 ° C., 2160 g) of 1 or more. When the melt index is less than 1, the appearance may be deteriorated.

The component (c) in the composition of the present invention is a non-aromatic softening agent for rubber. Specific examples thereof include a saturated hydrocarbon and mixtures thereof represented by C _n H _{2n + 2,} for example, paraffinic and naphthenic process oils, mineral oil, white oil, of ethylene and α- olefin Included are oligomers, paraffin wax and liquid paraffin. Of these, paraffin-based process oil, paraffin wax, and liquid paraffin are preferable.

(Blending ratio) The blending ratio of each component of the composition of the present invention is 99 to 55 parts by weight, preferably 9 parts by weight of the component (a).
5 to 60 parts by weight, (b) component 1 to 45 parts by weight, preferably 5 to 40 parts by weight, (c) component 70 to 300 parts by weight, preferably 100 to 300 parts by weight. Considering the needle stick property, the component (c) is preferably 75 to 300 parts by weight,
More preferably, it is 100 to 300 parts by weight. (A)
If the amount of the component used is less than 55 parts by weight, the resealability will be poor, and if it exceeds 99 parts by weight, the moldability will be poor. If the amount of the component (b) used is less than 1 part by weight, the moldability will be poor, and if it exceeds 45 parts by weight, the resealability will be poor. Further, if the amount of component (c) used is less than 70 parts by weight, resealability and moldability will be poor, and if it is used in excess of 300 parts by weight, bleeding property will be poor.

The composition of the present invention is required to have a hardness specified by JIS K6301 of 5 or more and less than 30. When the hardness is less than 5, the moldability is deteriorated, and when it is 30 or more, the resealability and the needle sticking property are deteriorated, and a liquid scattering phenomenon occurs when the needle is pulled out. Therefore, the blending amounts of the above-mentioned components (a), (b) and (c) are appropriately selected so that the hardness is 5 or more and less than 30 in the prescribed blending ratio. Incidentally, JP-A-61-1317
In the composition of Japanese Patent Publication No. 46, when the hardness is less than 30, "the heat resistance during sterilization is insufficient, mounting on a vial,
Not only will problems occur in the stoppering process, but the appearance of the product will deteriorate and the mechanical strength will also decrease. " However, as a result of diligent studies, the inventors of the present invention specified the blending ratio of the three components, particularly the polyolefin resin and the non-aromatic rubber softening agent, as described above, and specified the hardness to 5 or more and less than 30. In addition to the above, physical properties, appearance, and physical properties are not sacrificed, and integral molding such as injection molding, extrusion molding, insert molding, and two-color molding can be easily performed, and resealability, needle stickability, and hygiene are achieved. I found the amazing fact that you can get something very good.

In the composition of the present invention, no problem occurs even if a harmless filler such as clay or talc and a lubricant such as wax which are generally used as medical materials are added.

The composition of the present invention includes, for example, (a) to (a) above.
Producing by mixing the component (c) and components that can be added as required using various heating-type kneaders such as a single-screw extruder, a twin-screw extruder, a roll, a Banbury mixer, a Brabender, and a kneader. You can

The composition of the present invention can be widely used in various medical products. For example, it is preferably used as a sealing material for medical containers and various connecting pipes for infusion sets. In particular, it is suitably used as a sealing material for medical containers that requires resealing properties and various connecting pipes such as infusion sets that require resealing properties.

[0030]

EXAMPLES The present invention will be described below with reference to examples, but the present invention is not limited to these examples. Example 1 Styrene-based hydrogenated block copolymer (SEPS, manufactured by Kuraray Co., Ltd., Septon 4055, number average molecular weight = 200,000)
90 parts by weight, polypropylene (Made by Tokuyama Soda Co., Ltd., M
10 parts by weight of S640 and 100 parts by weight of a paraffinic softening agent (CP68N manufactured by Idemitsu Kosan Co., Ltd.) were melt-kneaded at a composition temperature of 200 ° C. with a twin-screw extruder to obtain pellets. The obtained pellets were pressed at 220 ° C. for 7 hours.
It was pressed at 0 kg / cm ² for 10 minutes and then solidified by a cooling press machine at 30 ° C. to obtain a cylindrical molded product having a diameter of 16 mm and a thickness of 6 mm.

Example 2 A molded product was obtained in the same manner as in Example 1 except that polyethylene (J240 manufactured by Asahi Kasei Kogyo Co., Ltd.) was used instead of polypropylene.

Example 3 Paraffin-based softener (CP68 manufactured by Idemitsu Kosan Co., Ltd.)
A molded product was obtained in the same manner as in Example 1 except that the addition amount of N) was 200 parts by weight.

Example 4 Styrene-based hydrogenated block copolymer (SEPS, Kuraray Co., Ltd., Septon 4055, number average molecular weight = 200,000)
95 parts by weight, polypropylene (Made by Tokuyama Soda Co., Ltd., M
S640) 5 parts by weight and a paraffinic softener (manufactured by Idemitsu Kosan Co., Ltd., CP68N) 80 parts by weight were used to obtain a molded product in the same manner as in Example 1.

Example 5 Styrene-based hydrogenated block copolymer (SEPS, Kuraray Co., Ltd., Septon 4055, number average molecular weight = 200,000)
60 parts by weight, polypropylene (Made by Tokuyama Soda Co., Ltd., M
A molded product was obtained in the same manner as in Example 1 except that 40 parts by weight of S640 and 270 parts by weight of a paraffinic softening agent (CP68N manufactured by Idemitsu Kosan Co., Ltd.) were used.

Example 6 Styrene-based hydrogenated block copolymer (SEPS, Kuraray Co., Ltd., Septon 4055, number average molecular weight = 200,000)
Instead of styrene-based hydrogenated block copolymer (SEP
S, manufactured by Kuraray Co., Ltd., Septon 4077, number average molecular weight = 260,000) was used to obtain a molded product in the same manner as in Example 1.

Comparative Example 1 Styrene-based hydrogenated block copolymer (SEPS, manufactured by Kuraray Co., Ltd., Septon 4055, number average molecular weight = 200,000)
Instead of styrene-based hydrogenated block copolymer (SEB
S, manufactured by Asahi Chemical Industry Co., Ltd., Tuftec H1272, number average molecular weight = 140,000), except that Example 1 was used.
A molded product was obtained in the same manner as in.

Comparative Example 2 Styrene-based hydrogenated block copolymer (SEPS, manufactured by Kuraray Co., Ltd., Septon 4055, number average molecular weight = 200,000)
Instead of styrene-based hydrogenated block copolymer (SEP
S, manufactured by Kuraray Co., Ltd., Septon 4033, number average molecular weight = 100,000) was used to obtain a molded product in the same manner as in Example 1.

Comparative Example 3 Paraffin softener (CP68 manufactured by Idemitsu Kosan Co., Ltd.)
Example 1 except that the amount of N) added was 20 parts by weight.
A molded product was obtained in the same manner as in.

Comparative Example 4 Styrene-based hydrogenated block copolymer (SEPS, Kuraray Co., Ltd., Septon 4055, number average molecular weight = 200,000)
50 parts by weight of polypropylene (made by Tokuyama Soda Co., Ltd.,
Example 1 except that MS640) was 50 parts by weight.
A molded product was obtained in the same manner as in.

Comparative Example 5 Styrene-based hydrogenated block copolymer (SEPS, Kuraray Co., Ltd., Septon 4055, number average molecular weight = 200,000)
Was obtained in the same manner as in Example 1 except that 100 parts by weight and 100 parts by weight of a paraffinic softener (manufactured by Idemitsu Kosan Co., Ltd., CP68N) were used.

Comparative Example 6 Paraffin softener (CP68 manufactured by Idemitsu Kosan Co., Ltd.)
A molded product was obtained in the same manner as in Example 1 except that the amount of N) added was 350 parts by weight.

Comparative Example 7 Paraffin softener (CP68 manufactured by Idemitsu Kosan Co., Ltd.)
A molded product was obtained in the same manner as in Example 1 except that the addition amount of N) was 80 parts by weight and the hardness of the composition was 35.

Comparative Example 8 Isoprene rubber (Califlex I manufactured by Shell Co., Ltd.
R307) 80 parts by weight, butadiene rubber (manufactured by Asahi Kasei Corporation, Diene NF35) 20 parts by weight, organic peroxide (manufactured by NOF CORPORATION, Perhexa 3M) 0.5 parts by weight, crosslinking aid (Shin Nakamura Chemical Co., Ltd.) Made, NK ester 1G) 3
Parts by weight, 1 part by weight of stearic acid (F-3, manufactured by Kawaken Fine Chemical Co., Ltd.) and 5 parts by weight of calcined clay (Satinton W, manufactured by Engelhard Minerals Co., Ltd.) at 50 ° C.
After kneading with an oven roll of No. 1 and heating at 160 ° C for 7 minutes with a hot press machine, then solidify with a cooling press molding machine at 30 ° C to obtain a cylindrical molded product with a diameter of 16 mm and a thickness of 6 mm. It was Add 3% of this with an aqueous solution of 1% sodium carbonate.
Boil for 5 hours, linearize with 0.1N sulfuric acid aqueous solution for 5 minutes,
It was washed with pure water and dried at 80 ° C. for 4 hours to obtain a molded product.

The molded articles obtained in the above Examples and Comparative Examples were tested for compression set, impact resilience, resealability, needle stickability, hardness and eluate. Further, based on the composition of each Example or Comparative Example, another molded product was manufactured using a press molding machine under the same conditions as above, and its moldability and bleeding property were tested. The test method is described below.

Test Method The compression set was tested according to (JIS K6301). The heat treatment was performed at 70 ° C. for 22 hours. The impact resilience was tested according to (BS standard 903). The resealability was obtained by attaching the obtained molded product to a pseudo medical infusion bag (plastic bag), inserting a plastic needle with a diameter of 4 mm (made by Terumo Corp.) for 1 hour, and then leaking the liquid for 10 minutes. Was observed. Evaluation method A +: No scattering of liquid, no liquid leakage at all;
A: There was a slight amount of liquid splattering and no liquid leakage at all; A
-: Liquid splattered, no liquid leakage at all; B: Liquid leakage at about bleeding out; C: Liquid leakage at about 1 to 2 drops Needle pricking was performed by using the obtained molded product as a pseudo medical infusion bag (plastic). It was attached to a bag) and the ease of inserting a 4 mm diameter plastic needle (made by Terumo Corp.) was compared. Evaluation method A +: Very easy to stab; A: Easy to stab;
A-: Slightly stinging; B: Very stinging;
C: Not stabbed The hardness was measured according to JIS K6 using a 6 mm thick test piece.
It carried out according to 301. The eluate test (pH test, potassium permanganate reducing substance) was carried out in accordance with the Japanese Pharmacopoeia, rubber stopper test method for infusion. The pass value of the eluate test is the pH test 1.
It is 0 or less and 2.0 ml or less of a reducing substance of potassium permanganate. As for moldability, a test piece of 160 × 130 × 6 mm was press-molded, and then the distortion state of the molded product was observed. Evaluation method ○: No molding distortion; ×: Molding distortion was observed. After bleeding, a molded product of 90 × 50 × 3 mm was press-molded and allowed to stand for 1 day, and then neutral white fine paper (75 g /
m ² ) was brought into close contact with the test piece and allowed to stand at room temperature for 24 hours.
The state of the oil transferred to the paper was observed. Evaluation method ○: No oil transfer; ×: Oil transfer

The test results are shown in Table 1. From the results shown in Table 1, it is clear that the molded products obtained in the examples of the present invention are superior in various properties as compared with the comparative examples.

[0047]

[Table 1]

[0048]

[Table 2]

[0049]

INDUSTRIAL APPLICABILITY According to the present invention, various physical properties such as resealability, needle stickability, and rubber elasticity at high temperature (compression set at 70 ° C.) are excellent, and molding processability and recyclability characteristic of thermoplastic elastomers are achieved. The present invention provides a medical rubber composition which has less surface tackiness and does not require much manufacturing cost. In addition, the composition of the present invention does not contain impurities that affect safety and health, and does not require a complicated post-treatment to remove the impurities. INDUSTRIAL APPLICABILITY The composition of the present invention can be applied to various medical products, and can be suitably used, for example, in medical sealing materials and connecting pipes.

─────────────────────────────────────────────────── --- Continuation of the front page (56) References JP-A-1-284546 (JP, A) JP-A-1-304147 (JP, A) JP-A-5-171002 (JP, A) JP-A-61- 131746 (JP, A) JP, 7-149999 (JP, A) (58) Fields investigated (Int.Cl. ⁷ , DB name) C08L 53/02 A61J 1/05

Claims (5)

(57) [Claims] 1. The following (a), so that the hardness measured according to JIS K6301 is 5 or more and less than 30:
A rubber composition for a sealant for a medical container prepared in a blending ratio of components (b) and (c): (a) a polymer block A containing at least two vinyl aromatic compounds as a main component, and at least 1 Block copolymer mainly composed of individual conjugated diene compounds and having a number average molecular weight of 150,000 or more, and /
Alternatively, 99 to 55 parts by weight of a block copolymer having a number average molecular weight of 150,000 or more obtained by hydrogenating the block copolymer, (b) 1 to 45 parts by weight of a polyolefin resin, and (c) a non-aromatic type 70 to 300 parts by weight of a softening agent for rubber. 2. The following (a), so that the hardness measured according to JIS K6301 is 5 or more and less than 30:
A rubber composition for a medical connecting pipe prepared in a mixing ratio of components (b) and (c): (a) a polymer block A containing at least two vinyl aromatic compounds as a main component and at least one conjugate A block copolymer consisting of a diene compound-based polymer block B and having a number average molecular weight of 150,000 or more;
Alternatively, 99 to 55 parts by weight of a block copolymer having a number average molecular weight of 150,000 or more obtained by hydrogenating the block copolymer, (b) 1 to 45 parts by weight of a polyolefin resin, and (c) a non-aromatic type 70 to 300 parts by weight of a softening agent for rubber. Wherein (a) component is a styrene / ethylene / propylene / styrene copolymer according to claim 1 or 2,
Set composition as described in. 4. The non-aromatic softening agent for rubber is selected from paraffinic and naphthenic process oils, mineral oils, white oils, oligomers of ethylene and α-olefins, paraffin wax and liquid paraffin. 1 to 3 described in any one of
Set Narubutsu. Wherein (c) the mixing ratio of the non-aromatic rubber softener is 75 to 300 parts by weight, the set composition as claimed in any one of claims 1 to 4.