JP2746882B2 - Modified polysiloxane-coated rubber stopper for pharmaceuticals and method for producing the same - Google Patents

Description

Description: TECHNICAL FIELD The present invention relates to a rubber stopper for a medical drug in which a surface of a rubber stopper is coated with a specific modified organopolysiloxane composition by cross-linking to improve its surface properties. About. [Prior art] Improve the surface characteristics of a molded rubber material to obtain various effects such as reducing surface friction resistance, imparting solvent resistance, water repellency, ozone resistance, and removing tackiness. Conventionally, various methods have been proposed. For example, a method of keeping in a chlorine gas, bromine gas or sodium sulfonate solution (see Japanese Patent Publication No. 57-3807), a method of keeping in a fluorine gas atmosphere (Japanese Patent Publication No. 58-1964, Japanese Patent Application Laid-Open No. No. 218830), polyorganosiloxane containing hydroxyl groups bonded to two or more silicon atoms in one molecule, polydiorganosiloxane having both ends hydroxyl-blocked, polyorganohydrodienesiloxane, epoxy-containing siloxane, amino group or alkoxy group A method of applying a polyorganosiloxane composition comprising a siloxane having the formula (1) to the surface of a rubber and curing the same (see Japanese Patent Publication No. 56-47864): 0.1 to 10% by weight of an organosilicon compound which can move little by little in the rubber Method for producing medical or sanitary rubber products by incorporating them into rubber (Japanese Patent Publication No.
No. 30089), a method of cross-linking a silicone raw rubber containing a hydroxyl group or a methoxy group in a molecule to coat the surface of a rubber molded product (see JP-A-57-96837), furthermore, polydimethylsiloxane or its dimethyl A method for producing a rubber stopper in which dimethylsiloxane in which a part of the groups is substituted with a phenyl group, a vinyl group, an amino group, a fluorine-containing group, a polyether group, an alkylallyl group or a fatty acid group is cross-linked (Japanese Patent Laid-Open No.
-182418). The present inventors have already proposed in JP-A-56-104672 that the rubber surface is coated with a silane coupling agent containing an amino group. However, when a sanitary rubber product is manufactured by such a conventional technique, problems such as stickiness and adsorptivity remaining or the applied polysilicon composition being mixed as foreign matter into pharmaceuticals and foods and entering the human body. It was difficult to say that the rubber product was excellent in hygiene. Although it is a good method to coat the surface of a sanitary rubber product with a thin polysiloxane, it is a good method, but in addition to uneven coating thickness and film, foreign matter and fine particles are generated due to peeling of the coated product, insufficient friction resistance, etc. However, there is also a problem in that it is unsuitable for attachment to machinery and equipment. In recent years, there has been a strong demand for a sanitary rubber stopper that is easy to handle for automatic operation. Accordingly, the present inventors have disclosed in Japanese Patent Application No. 62-154272, "One or more groups selected from the group consisting of an acryloyl group, a vinyloxy group, a maleimide group and a phenylketone group in the molecule. And a modified polysiloxane-coated sanitary rubber product comprising a modified polysiloxane composition containing a modified organopolysiloxane having cross-linking and adhesion to the rubber surface. This rubber product is excellent as a sanitary rubber product which has solved the above problems. [Problems to be Solved by the Invention] By the way, in the invention described in the specification of Japanese Patent Application No. 62-154272, there was a tendency that the slidability was slightly lowered in a long term. Therefore, the present invention has a coating excellent in adhesiveness to the rubber surface, has no exfoliated matter, is excellent in hygiene, and is improved by improving the main raw material, the crosslinking production apparatus, the production conditions and the like. An object of the present invention is to provide an inexpensive rubber stopper for pharmaceuticals, which has heat resistance and stable lubricating properties over a long period of time, is easy to attach to machinery and equipment, can sufficiently cope with automation, and is inexpensive, and an efficient production method thereof. (Means for Solving the Problems) The present inventors have found that silicone oils, i.e., linear polysiloxanes, have the lowest tissue reaction in biological systems, are inert and have very low toxicity, and have a friction coefficient of 0.23-0.3. (25 ℃)
Focusing on the fact that, in addition to having the best lubricity, which is inferior to spindle oil, it also has excellent heat resistance, and to maintain these favorable characteristics, the basic structure of polysiloxane The bond is maintained as it is, and a partial substituent is introduced into the molecule of the organopolysiloxane to form a modified organopolysiloxane (hereinafter also referred to as a modified polysiloxane). The coating is strong and adheres to the rubber surface. The modified polysiloxane composition containing this modified polysiloxane with improved lipophilicity is applied to a rubber surface and then crosslinked to form a process of the present invention that forms a coating adhered to the rubber surface. That is, the present invention relates to the general formula (Where R ₁ is an unsubstituted or fluorine-substituted alkyl group having 1 to 7 carbon atoms, phenyl group, or phenylalkyl group; R ₂ is an alkyl group having 1 to 4 carbon atoms; An alkenyl group, and Y represents a hydrogen group, a hydroxyl group, an epoxy group,
Selected from an acetoxy group, an acetyl group, an alkoxy group having 1 to 3 carbon atoms and an amino group, wherein the X and Y substituents are each directly bonded to silicon or bonded via an alkylene group; _1, n ₂ and m well even zero thickness n _{2 integers, 1 ≦ n 1 + n 2} ≦ 40, and _{20 ≦ n 1 + n 2 +} m ≦ 7
A modified polysiloxane composition having an average molecular weight of 2,000 to 5,000,000 and a total of 0.001 to 5 mol% of X and Y substituents in the molecule at 80 ° C. A modified polysiloxane-coated rubber stopper for pharmaceuticals, which is cross-linked at the following low temperature. Further, the present invention, as a means for realizing the rubber stopper for pharmaceuticals, a mixture of the modified polysiloxane composition and a volatile solvent is applied to the surface of a molded rubber, and after the solvent is evaporated, the surface of the coating layer is applied. Provided is a method for producing a modified polysiloxane-coated rubber stopper for pharmaceuticals, characterized in that the modified polysiloxane is crosslinked and adhered at a low temperature of 80 ° C. or less by applying energy. The present invention can be obtained at lower cost than the modified organopolysiloxane having one or more of acryloyl, vinyloxy, maleimide and phenylketone groups proposed in Japanese Patent Application No. 62-154272. The polysiloxane represented by the general formula is used as a coating material. General formula Here, R ₁ is an unsubstituted alkyl group having 1 to 7 carbon atoms, that is, a methyl group, an ethyl group, etc., and a fluorinated alkyl group, a phenyl group, a phenylalkyl group in which at least one hydrogen atom of the alkyl group is substituted with a fluorine atom. Any of the groups. R ₂ is an alkyl group having 1 to 4 carbon atoms, that is, a methyl group,
Either an ethyl group, a propyl group, or a butyl group. X is an alkenyl group such as a vinyl group, an allyl group, a butenyl group and the like. Y is selected from a hydrogen group, a hydroxyl group, an epoxy group, an acetoxy group, an acetyl group, an alkoxy group having 1 to 3 carbon atoms, and an amino group, and is within 4 types. X substituent, Y
Each substituent is bonded directly to the silicon atom or via a linear alkylene group, the sum of the number of X substituents and the number of Y substituents in the molecule is in the range of 1 to 40, and the number of Y substituents is 0
Alternatively, the total sum of the X substituent and the Y substituent is 0.001 to 5 mol%. A large sum of the X substituent and the Y substituent,
The cross-linking / adhesive strength of the coating to the base rubber surface is increased, and peeling of the coated polysiloxane is reduced. However, if it exceeds 5 mol%, it tends to exhibit surface water absorption, adsorptivity, and toxicity, so it is used for pharmaceuticals. It is not preferable as a rubber stopper. Also, 0.00
If it is less than 1 mol%, the crosslinking / adhesive strength will be poor. In the present invention, as R ₁ and R ₂ , a fluorine-substituted or unsubstituted alkyl group having 1 to 4 carbon atoms and a phenyl group are bonded to a silicon atom directly or via an alkylene group, and Is preferably 95 mol% or more in the polymer molecule, and the main component is a bond in which the bond between carbon and silicon is linear. When a large amount of the cyclic branch or network is contained, the viscosity increases and the coating on the rubber surface becomes uneven. The total amount of the phenyl group in the polymer molecule is preferably 15 mol% or less, and if it exceeds 15 mol%, the adhesive force and the sliding property of the polysiloxane coating on the rubber surface are inferior. The modified polysiloxane of the present invention has an average molecular weight of 2,000 to
5,000,000, and the degree of polymerization is 1 ≦ n ₁ + n ₂ ≦ 40 (where n ₂ may be 0) and 20 ≦ n ₁ +
n ₂ + m ≦ 70,000 is preferred. If the polymerization degree is less than 20, it is not preferable because it is easily volatilized and aging, and if it exceeds 70,000, the viscosity becomes too high and the compatibility with the solvent is reduced, and it is not preferable to form a uniform and desired thickness coating. . Various specific examples of the modified polysiloxane of the present invention as described above are given in Examples below, but are not limited to only Examples. The modified polysiloxane of the present invention can be produced by a known technique such as hydrolysis, transesterification, dehydration, substitution, condensation, or polymerization reaction in a solvent. An aromatic ketone compound as a sensitizer and / or an organic peroxide as a low-temperature radical cross-linking agent can be added to the polysiloxane composition of the present invention for cross-linking at low temperature and in a short time. . In addition, antioxidants,
An oiliness improver may be added. As the aromatic ketone compound used as a sensitizer,
Acetophenone type, benzoyl ether type, benzyl ketal type compounds, such as acetophenone, propiophenone, 4,4'-bis (dimethylamino) benzophenone, 3 or 4 methylacetophenone, 3 or 4 pentylacetophenone, 4,4 '-Dimethoxybenzophenone,
Benzyl, benzoyl propyl ether, benzoin ethyl ether, benzoin methyl ether, benzoin isobutyl ether, 2,2'-diethoxyacetophenone, 2-hydroxy-2-methylpropiophenone, 4'-isopropyl-2-hydroxy- 2-methylpropiophenone, benzyldimethyl ketal, 3,3 '
Dimethyl-4-ethoxybenzophenone, benzophenone, 2,5-dimethyl-2,5-di (3-methylbenzoylperoxy) hexane, tetramethyldisilylbenzophenone, benzoin etherified product at both ends of dimethylpolysiloxane, Examples thereof include dibenzophenone etherified products of both ends of dimethyldisiloxane, 1-hydroxycyclohexylphenyl ketone, and the like. Activation by such a compound is disclosed in JP-B-50-1597 and JP-A-50-138081.
The sensitizer may be used in a small amount of 0.1 to 3% by weight with respect to the polysiloxane. A sensitizer and a polysiloxane are used, for example, in JP-A-54-48.
854,57-207622,57-131230, JP-B-51-4879
It is preferable to use as a condensate condensed by a known technique described in 4, 52-32913, 58-25679. The details of such a condensation reaction will be described in Examples described later. As the organic peroxide used as the low-temperature radical crosslinking agent, an organic peroxide whose result increases when used in combination with an aromatic ketone compound, for example, 1,1-di (t-butylperoxy) -3,3 , 5-trimethylcyclohexane,
t-butylcumyl peroxide, dicumyl peroxide, 2,5-dimethyl-2,5-di (t-butylperoxy)
Hexane or the same hexyne-3, t-butylperoxyisopropyl carbonate, benzoyl peroxide,
Di-t-butyl peroxide, 2,2'-di-t-butylperoxybutane, diisobutyl peroxide, 3-benzoylper-oxy-3-methylbutyltriethylsilane, pertrimellitic acid tri-t-butyl ester, 3,
3 ', 4,4'-tetra (t-butylperoxycarbonyl) benzophenone, di-t-butylperoxide,
t-butyl peroxybenzoate, 2,5-di (t-
Butylperoxy) 2,5-dimethylhexane and the like. These low-temperature radical crosslinking agents are preferably added in an amount of 0.01 to 3 parts by weight based on 100 parts of the modified polysiloxane. When no sensitizer or cross-linking agent is used, the total amount of the X substituent and the Y substituent bonded to the molecule is 0.2 to 5 mol%, preferably 1 to 5 mol%, and particularly preferably 0.1 to 5 mol%. It is preferable to use a modified polysiloxane close to 5 mol% or to increase the amount of light energy to be irradiated in order to satisfy the chemical and physical properties required for a rubber stopper for a drug as a target. In the present invention, examples of the rubber used as a raw material of a molded rubber stopper having a modified polysiloxane coating formed on its surface include diene rubbers such as isobrene rubber (IR), butadiene rubber (BR), styrene butadiene rubber (SBR), and natural rubber. Known crosslinking agents, crosslinking activators, reinforcing agents, etc. for known rubbers such as olefin rubbers such as butyl rubbers (IIR, BIIR, CIIR), ethylene propylene rubber and ethylene propylene terpolymer (EPM and EPDM), and thermoplastic elastomers What was compounded by heating, cross-linking and molding the additives is used. Next, a specific method for coating the rubber surface with the modified polysiloxane composition will be described. The modified polysiloxane composition is preferably coated with a fluidity of 30,000 cps or less. In order to form a uniform coating on the surface of the molded rubber, it is preferable to apply a diluted solution having a polysiloxane concentration of 0.001 to 3% by weight on the rubber surface, and to apply a coating thickness of 0.1 to 50 μm. Solvents having low boiling point and low toxicity at a boiling point of 100 ° C. or lower, for example, methyl ethyl ketone, diethyl ketone, isopropyl ketone, toluene, acetone, 1,1,1
One or a mixture of two or more of trifluoroethane, isopropyl alcohol, hexane, trichlorotrifluoroethane, trichloromonofluoromethane, dichlorodifluoromethane, and etrahydrofuran is used. As a coating method, any of spraying, brushing, and dipping in a dilute solution may be used, but a method of repeating spraying several times is suitable for obtaining a uniform and thin coating. In this case, you may coat | cover using what changed the combination of the solvent and the modified polysiloxane composition. Subsequently, the solvent is evaporated, usually at 90 ° C. or lower.
Even at a temperature of 90 ° C. or less, there are almost no organic peroxides that generate radicals and exhibit a crosslinking effect. Next, the modified polysiloxane composition is crosslinked and adhered to the surface of the molded rubber by applying energy to the surface of the coating layer. Light or heat can be used as energy. Preferred treatment conditions at this time are a temperature of 80 ° C. or less and a treatment time of 10 minutes or less, particularly preferably room temperature at 0.02 ° C.
This is a processing within 1 minute. As the light energy, ultraviolet light, electron beam, laser light (YAG laser, wavelength 10.6μ), etc. are used. However, considering equipment costs, low pressure, high pressure or ultra high pressure mercury lamp, argon, neon, hydrogen or nitrogen, etc. Easy to use discharge tubes, xenon lamps, xenon-mercury lamps. For example, a lamp in which mercury and argon gas are sealed in a quartz glass tube has ultraviolet rays of 220 to 400 nm centered on 360 nm, and 400 to 80 nm.
It emits 0nm visible light and 800nm or more infrared rays (heat rays),
Since the efficiency of generating ultraviolet light is 10% or less, the modified polysiloxane composition can crosslink and adhere to the rubber surface in 2 to 60 seconds. As described above, ultraviolet irradiation is the most economically advantageous because it requires only small equipment and short processing time. In the case of heat energy, generally performed in the case of heating such a rubber molded body, heating at a temperature of 100 ° C. or more by radiant heat using air as a medium,
It takes a longer time than light irradiation, and there is a risk that the rubber surface layer is oxidized and deteriorated. Incidentally, a reaction catalyst or a radical generator may be added to the modified polysiloxane composition, and a method of crosslinking / adhering by heating at a low temperature may be adopted.However, such an additive may have coloring property and toxicity. However, it is not optimal as a rubber stopper for pharmaceuticals. By crosslinking and adhering the modified polysiloxane as described above, the surface of the pharmaceutical rubber stopper of the present invention has both rubber elasticity and plasticity, unlike metals and plastics. The raw material rubber plug of the present invention has a surface friction coefficient of 1 to 4 or more.By forming a modified polysiloxane coating, this can be reduced to 1/10 to 1/50. Glidability has been stable for a long time. Furthermore, the product of the present invention is excellent in hygiene as a medical rubber stopper that satisfies the conditions specified in the Japanese Pharmacopoeia 11th Edition (for example, fine particles of injections). [Examples] Examples 1 to 6 and Comparative Examples 1 to 3 a) Rubber compounding and molding BR (JSR BR01: manufactured by Japan Synthetic Rubber) 100 parts Titanium oxide 15 parts Zinc Hua No. 1 1 part 2,5-dimethyl-2 , 5-di (t-butylperoxy)
Hexane 1 part According to SRIS 3602 (1972)
It is compounded with a roll, and then subjected to crosslinking molding at a temperature of 170 ° C. for 10 minutes. The rubber stopper shown in FIG. 1 and the stopper for a syringe shown in FIG. 2 (diameter 15.3 mm, length 7.7 mm, hereinafter referred to as stopper) Abbreviated). b) Coating of polysiloxane on rubber surface Modified polysiloxane according to the present invention having the composition shown in Table 1 (Examples 1 to 6), silicone oil (Comparative Examples 1 and 2) and silicone rubber (Comparative Examples) Example 3)
Were prepared in the form of a 0.1% by weight toluene solution. The coating solution is applied to the foot 1 of the rubber stopper shown in FIG.
Once and the top surface portion 2 was evenly spray-coated once. The slide stopper 3 in FIG. 2 is a sliding portion in the syringe barrel, and the whole was immersed in the coating solution for 1 second and then pulled up. Next, both were heated and dried in a hot air circulating oven at 60-80 ° C. The thickness of each coating was about 1 μm. c) Coating formation by adhesion crosslinking
Using a 00 μm fluorescent lamp (output: 4 W, calcium halophosphate), three passes at a distance of 5 to 10 cm are performed for about 10 seconds to uniformly irradiate the polysiloxane to cross-link and adhere the coating layer. Formed. d) Evaluation test The following evaluation tests were performed on the product of the present invention and the comparative product obtained as described above. Table 2 shows the results. i) Test for peeling off amount of polysiloxane from rubber surface Put 10 rubber stoppers in a 500 ml jar, add 300 ml of non-particulate water, and gently shake with the container for 20 minutes. 60 as it is
After standing still for a minute, the solution is
(Manufactured by AC) at a constant flow rate of 8 ml / min, and count the number of particles having a particle size of 5 to 7 μm. It represents the average of three measurements. ii) Sliding value test The resistance to moving in a syringe with a push rod attached to a stopper is shown by a measurement method (kg) using an autograph DCD-100 (manufactured by Shimadzu Corporation). In addition, the untreated (with the rubber surface) stopper in the form of FIG. 2 required a force of 8 to 5 kg. iii) Polysiloxane adhesion test 100 ml of chloroform was added to five rubber stoppers, and the mixture was vibrated for about 5 minutes. The amount of silicon in the extracted polysiloxane was measured by atomic absorption spectrometry, and the amount of polysiloxane (μg) was obtained from the calibration curve.
Is shown by the calculated value. iv) Eluent test According to the rubber stopper test for infusion in the Japanese Pharmacopoeia, 11th edition, use purified water 10 times the amount of rubber stopper, at 121 ° C and 60 ° C.
The eluate heated for one minute was tested. Table 2 also shows the obtained results and the standard values determined by the local government. e) Test results As shown in Table 2, in Examples 1 to 6 of the present invention, the modified polysiloxane adhered, cross-linked and adhered to the surface of the rubber stopper and the stopper, so that the movement in the cylinder was easily operated. Even when vibrated in water, the amount of fine particles from which polysiloxane has separated is small. This indicates that the modified polysiloxane is less likely to be exfoliated and become fine particles and to be mixed as foreign matter into the medicine. On the other hand, the silicone oil (Comparative Example 1) easily peels off the silicone oil to form fine particles in water. Silicone rubber (Comparative Example 3) is a rubber stopper that has a small amount of peeled rubber but has a high sliding value and is difficult to handle, and a syringe stopper does not become a practical product unless silicone oil is applied to its surface. Although not shown in Table 2, the amount of ultraviolet irradiation was reduced to 3
In seconds, the amount of fine particles increased in all of Examples 1 to 3. Accordingly, it has been found that a suitable amount of ultraviolet light is effective for crosslinking adhesion. Examples 7 to 13 and Comparative Example 4 Both ends of the molecular chain were blocked with a trimethylsilyl group, the methylvinylsiloxane unit was 3 mol%, the balance was dimethylsiloxane unit, and the viscosity at 25 ° C was 20%.
A crosslinking agent or a sensitizer shown in Table 3 was blended in 100 g of polydimethylsiloxane of 00 cps in a ratio shown in Table 3 and mixed uniformly. Next, a mixture of toluene and isopropyl alcohol (1: 1) was added to the mixture to prepare a 0.3% by weight solution. The solution was applied to rubber stoppers and slip stoppers produced in the same manner as in Examples 1 to 6, and dried in the same manner as in Examples 1 to 6. Next, the coating was formed by crosslinking and bonding under the processing conditions shown in Table 4. For the obtained coated rubber stoppers and stoppers (Examples 7 to 13) and the uncoated rubber stoppers and stoppers (Comparative Example 4) as comparative products, the amount of peeling (in this case, rubber) was the same as in Example 1. (Fine particles) and the sliding value were measured. Table 4 shows the results. As is evident from the results in Table 4, the processing conditions of Examples 9 to 13 are simple and require only a short time, and the obtained products have a small amount of polysiloxane peeling, good hygiene, and low sliding values. That is, the product is easy to handle because it has no tackiness. Examples 7 and 8 are slightly inferior in performance. Comparative Example 4 without coating has a very large sliding value and a large amount of fine particles peeled off from the rubber surface. Since the sliding value is large with rubber alone, a syringe in which silicone oil is applied to the inner surface of a syringe barrel and the surface of a rubber stopper is generally commercially available. In this case, the weight regulation of the soluble matter of trifluorotrichloroethane in Notification 442 of the Ministry of Health and Welfare is applied. Example 3 IIR (JSR Butyl 365, trade name, manufactured by Nippon Butyl) 100 parts Zinc flower 2 parts Stearic acid 1 part Clay (Burgess Iceberg, trade name, manufactured by Burges Pigment) 60 parts Processing aid (Hiwax 110P) , Trade name, Mitsui Petrochemical) 1.5 parts Magnesium oxide (Kyowa Mag 100, trade name, manufactured by Kyowa Chemical Industry) 3 parts White carbon (Carplex 1120, trade name, manufactured by Shionogi Pharmaceutical) 10 parts Titanium oxide 5 parts sulfur 0.8 parts 0.7 parts of zinc di-n-butyldithiocarbamate 0.7 parts of zinc diethyldithiocarbamate The above composition was applied to a SRIS 3603 (1
979), and cross-linked at a temperature of 150 ° C. for 15 minutes to prepare a rubber stopper shown in FIG. 1 and a syringe stopper shown in FIG. The modified polysiloxane composition shown in Table 5 was diluted with a 1: 1 solution of isopropyl alcohol: ethyl ether to obtain a 0.3% by weight solution, and the molded article obtained above was immersed in the solution for 2 seconds, pulled up and dried. Then, a coating layer was formed by crosslinking and bonding in the same manner as in Examples 1 to 6 to form a coating. With respect to the obtained coated rubber stoppers / plugs (Examples 14 to 20, Comparative Example 5), the amount of polysiloxane peeled off and the sliding value were measured in the same manner as in Example 1. The obtained results are also shown in Table 5. As is clear from the results in Table 5, in Examples 14, 18, and 20 in which cross-linking was performed by ultraviolet irradiation with a fluorescent lamp, the bonding to the rubber surface was strong and did not peel off. On the other hand, Examples 15, 16, 17, and 19, which were crosslinked and adhered by heating, had a disadvantage that the treatment time was long. In Comparative Example 5, since the polysiloxane was a sulfide, the coated rubber product had a bad smell and was unsuitable. The sliding value of the coated product of Comparative Example 6 changed from 0.6 to 1.0 kg after about 2 months. The following polysiloxane compositions were used in Table 5 below. Viscosity 1, blocked by dimethylvinylsilyl groups at both ends
100 cps of 300 cps polydimethylsiloxane, (CH ₃ ) ₃ SiO _1/2
Unit 43 mol%, SiO ₂ unit 50 mol%, and (CH ₂ CHCH) (C
H ₃ ) 5 g of polyorganosiloxane composed of 5 mol% of SiO units, particle size 10 having both ends blocked with trimethylsilyl groups
Obtained by uniformly mixing 5 g of 0 cps polymethylhydrogensiloxane and 2 g of butenyltriacetylsilane Ethoxy-methyl-γ-trichlorovinylpolysiloxane at both ends (n = 32) 100 g Hydroxy-allyl-methyl-polysiloxane at both ends (vinyl content 0.15 mol%) 32 g Organopolysiloxane (CH ₃ ). (CH ₂ CHCH ) SiO
Unit 0.2 _{mol%, (CH 3) 2 -SiO} , 99.8 mol% viscosity 530cp
s100g. Dimethylpolysiloxane having hydroxyl groups at both ends (n
= 180) 13g. 100 g of dimethylsiloxane-methylvinylsiloxane copolymer (vinyl group content 0.18 mol%, viscosity 300 cps) with dimethylvinylsilyl groups at both ends. 8 g of dimethylsiloxane and methylhydrogensiloxane copolymer having a trimethylsilyl group blocked at both terminals (molar ratio of silicon-bonded hydrogen atom to methyl group: 1/30, viscosity: 20 cps). 4'-isopropyl-
0.1 g of 2-hydroxy-2-methylpropiophenone. Both ends are blocked with a trimethylsilyl group in 95 g of a methylphenylvinylsiloxane oil consisting of 97 mol% of dimethylsiloxane units capped at divinylmethylsilyl groups and 3 mol% of diphenylsiloxane units,
8 g of a mercaptoalkyl group-containing organopolysiloxane comprising 5 mol% of mercaptopropyl (methyl) siloxane units and 50 mol% of dimethylsiloxane units. [Effects of the Invention] The rubber stopper for pharmaceuticals of the present invention has a coating that is strong and has improved adhesion to rubber in order to crosslink and adhere the modified polysiloxane composition coated on the surface of the rubber body to the surface. And
As a result, it is non-toxic, has excellent lubricity, does not exfoliate the modified polysiloxane, and since these properties are stable for a long period of time, it is easy to handle, and it is easy to handle. It has a high degree of hygiene that meets the standards for stoppers. Therefore, the pharmaceutical rubber stopper of the present invention is a powder formulation,
It can be used for rubber stoppers for pharmaceuticals such as freeze-dried preparations and liquid injections, slip stoppers for syringes, rubber stoppers for medical instruments such as artificial kidney devices and other artificial internal organs, and sealing materials. For example, the syringe stopper according to the present invention has good slidability, so that it can be easily moved in a cylinder, and does not peel off, so that no fine particles are generated. In addition, it is convenient to apply the rubber stopper of the present invention to an injection drug because the amount of fine particles is small and, for example, when the rubber stopper is used for a rubber stopper of a freeze-dried preparation, automatic stoppering can be easily performed. Furthermore, in the production of the rubber stopper for pharmaceuticals of the present invention, the modified polysiloxane can be obtained at a low cost, and the cross-linking and adhesion treatment step can be continuously performed in a short time of only seconds and with a simple apparatus. Has the advantage of high cost and low cost.

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a sectional view showing the shape of a rubber stopper for pharmaceuticals (rubber stopper for freeze-dried preparation) according to an embodiment of the present invention, and FIG. 2 is for a syringe according to the embodiment of the present invention. It is sectional drawing which shows the shape of a seal stopper. 1: Foot of rubber stopper, 2: Top of rubber stopper, 3: Sliding part in syringe barrel

Claims (1)

(57) [Claims] General formula (Where R ₁ is an unsubstituted or fluorine-substituted alkyl group having 1 to 7 carbon atoms, phenyl group, or phenylalkyl group; R ₂ is an alkyl group having 1 to 4 carbon atoms; An alkenyl group, and Y represents a hydrogen group, a hydroxyl group, an epoxy group,
Selected from an acetoxy group, an acetyl group, an alkoxy group having 1 to 3 carbon atoms and an amino group, wherein the X and Y substituents are each directly bonded to silicon or bonded via an alkylene group; _1, n ₂ and m well even zero thickness n _{2 integers, 1 ≦ n 1 + n 2} ≦ 40, and _{20 ≦ n 1 + n 2 +} m ≦ 7
A modified polysiloxane composition having an average molecular weight of 2,000 to 5,000,000 and a total of 0.001 to 5 mol% of X and Y substituents in the molecule at 80 ° C. Modified polysiloxane-coated pharmaceutical rubber stoppers which are cross-linked at the following low temperatures. 2. The rubber stopper for a modified polysiloxane-coated pharmaceutical according to claim 1, wherein the modified polysiloxane composition is added with an organic peroxide and / or an aromatic ketone compound. 3. The modified polysiloxane according to claim 1 or 2, wherein the sum of the number of X substituents and the number of Y substituents is 1 to 40 in the modified polysiloxane molecule, and the number of Y substituents is 4 or less. Siloxane-coated pharmaceutical rubber stopper. 4. General formula (Where R ₁ is an unsubstituted or fluorine-substituted alkyl group having 1 to 7 carbon atoms, phenyl group, or phenylalkyl group; R ₂ is an alkyl group having 1 to 4 carbon atoms; An alkenyl group, and Y represents a hydrogen group, a hydroxyl group, an epoxy group,
Selected from an acetoxy group, an acetyl group, an alkoxy group having 1 to 3 carbon atoms and an amino group, wherein the X and Y substituents are each directly bonded to silicon or bonded via an alkylene group; _1, n ₂ and m well even zero thickness n _{2 integers, 1 ≦ n 1 + n 2} ≦ 40, and _{20 ≦ n 1 + n 2 +} m ≦ 7
A modified polysiloxane composition having an average molecular weight of 2,000 to 5,000,000, and a total of 0.001 to 5 mol% of X and Y substituents in the molecule and a volatile solvent. After applying the mixture to the surface of the molded rubber and evaporating the solvent,
A method for producing a modified polysiloxane-coated rubber stopper for pharmaceuticals, characterized in that the modified polysiloxane is crosslinked and adhered at a low temperature of 80 ° C. or less by applying energy to the surface of the coating layer. 5. The method for producing a modified polysiloxane-coated pharmaceutical rubber stopper according to claim 4, wherein the modified polysiloxane composition is added with an organic peroxide and / or an aromatic ketone compound. 6. The modified polysiloxane according to claim 4 or 5, wherein the sum of the number of X substituents and the number of Y substituents is 1 to 40 in the molecule of the modified polysiloxane, and the number of the Y substituents is 4 or less. A method for producing siloxane-coated rubber stoppers for pharmaceuticals. 7. 4. The method according to claim 4, wherein the means for applying energy includes irradiating an electron beam, an ultraviolet ray or a laser beam or heating.
Item 7. A method for producing a rubber stopper for a pharmaceutical product coated with a modified polysiloxane according to any one of Items 6 to 6.