Rubber for medical syringe piston, medical syringe cap, drug bottle stopper, etc., and its preparation method and application

Abstract

The present invention discloses a rubber for medical syringe pistons, medical syringe caps, drug bottle stoppers, and the like, as well as a preparation method and application thereof. The present invention uses chlorinated polyethylene rubber and isoprene rubber to compound and co-vulcanize and cross-link to prepare a medical rubber product, and various physical, chemical, biological and mechanical performance indicators all meet national standards for pharmaceutical packaging materials.

Description

Technical Field

[0001] The present invention relates to the field of medical rubber, and in particular to a rubber used for medical syringe pistons, medical syringe protective caps, drug bottle stoppers, etc., as well as a preparation method and application thereof. Background Art

[0002] Prefilled and sealed syringes are integrated drug delivery devices, and the syringe piston is one of its essential components. Since it has both sealing and injection functions, and it is in direct contact with the drug, extremely high requirements are placed on its physical, chemical and biological properties.

[0003] Medical syringe caps are also made of medical rubber materials and are subject to strict restrictions on material selection.

[0004] Since the drug bottle stopper is in direct contact with the drug, it has the same technical requirements as the syringe piston.

[0005] Currently, the primary rubber material used in prefilled syringes, medical syringe caps, and pharmaceutical vial stoppers worldwide is halogenated butyl rubber, manufactured by ExxonMobil (USA) and Bayer (Germany). This specialized rubber exhibits unique and superior properties in terms of drug compatibility, chemical inertness, flexibility, and resilience. This results in high prices for this type of rubber, and the market is dominated by manufacturers and suppliers, severely restricting its application and production.

[0006] Chlorinated polyethylene rubber is similar to halogenated butyl rubber in structure, performance and physical and chemical indicators. It is modified with polyisoprene rubber, and the two have complementary performance advantages. It can completely replace halogenated butyl rubber in the production and application of medical syringe pistons, medical syringe caps and drug bottle stoppers. Summary of the Invention

[0007] The purpose of the present invention is to provide a rubber for medical syringe pistons, medical syringe caps, drug bottle stoppers, etc., which uses chlorinated polyethylene rubber as a main component and isoprene rubber as a toughening agent, and a preparation method and application thereof.

[0008] To achieve the above purpose, the following formula is used: 50-80 parts of chlorinated polyethylene rubber (CM), 20-50 parts of isoprene rubber (IR), 20-90 parts of filler, 1-5 parts of vulcanizing agent, 0.1-5 parts of colorant, and 5-20 parts of silicone resin additive.

[0009] Furthermore, the filler is one or a mixture of any proportion of kaolin, white carbon black, and talc.

[0010] Furthermore, the colorant is titanium dioxide or carbon black, which are mixed or used alone.

[0011] Furthermore, the vulcanizing agent refers to a mixture of thiadiazoles or triazines with peroxides or sulfur, or the use of one of them alone.

[0012] A method for preparing rubber for use as medical syringe pistons, medical syringe caps, drug bottle stoppers, etc., is characterized by comprising the following steps:

[0013] (1) Rubber mixing: Use rubber internal mixer, open mixer, calender and other processing machinery to mix the various components used in the formula evenly to produce mixed rubber sheets.

[0014] (2) Vulcanization molding: at a vulcanization pressure of 160-210kg / cm 2 , under the condition of mold temperature of 155-195℃, put the mixed rubber sheet into the vulcanization mold, and vulcanize for 300-600s to obtain a vulcanized rubber sheet.

[0015] (3) Subsequent processing: The excess rubber edges of the vulcanized rubber sheet are removed by punching and cutting, and the obtained rubber product is cleaned, sterilized, and dried with purified water and injection water to obtain a clean medical rubber seal.

[0016] Chlorinated polyethylene (CM) rubber and isoprene rubber (IR) rubber are used together to replace imported halogenated butyl rubber for medical syringe pistons, medical syringe needle caps and drug bottle stoppers.

[0017] The present invention uses chlorinated polyethylene rubber and isoprene rubber to compound and co-vulcanize and cross-link to prepare medical syringe pistons, medical syringe caps, drug bottle stoppers and other products, and various physical, chemical, biological and mechanical performance indicators meet the national standards for pharmaceutical packaging materials. DETAILED DESCRIPTION

[0018] The following describes the embodiments of the present invention in detail. If no specific techniques or conditions are specified in the embodiments, the experiments were carried out according to the techniques or conditions described in the literature in the field or according to the product specifications. If the manufacturer of the reagents or instruments is not specified, they are all conventional products that can be purchased commercially. Example 1

[0019] The rubber components and weight ratios for use in a medical syringe piston, a medical syringe cap, a drug bottle stopper, etc. of this embodiment are as follows:

[0020] Chlorinated polyethylene rubber 80, polyisoprene rubber 20, talc 20, white carbon black 10, activated magnesium oxide 3, bis-25 peroxide 0.2, triazine TCY 1, titanium dioxide 3, carbon black 0.2, silicone resin 10.

[0021] Preparation method:

[0022] Mixing and refining: Use rubber internal mixers, open mixers, calenders and other processing machinery to mix the various components used in the formula evenly to produce mixed rubber sheets.

[0023] Vulcanization molding: at a vulcanization pressure of 165kg / cm 2 Under the condition of mold temperature of 160℃, the mixed rubber sheet was placed in a vulcanization mold and the vulcanization time was 550s to obtain a vulcanized rubber sheet.

[0024] Subsequent processing: The excess rubber edges of the vulcanized rubber sheet are removed by punching and cutting. The resulting rubber product is cleaned with purified water and injection water, sterilized, and dried before being processed into 5ml syringe pistons or pharmaceutical infusion bottle gaskets 22DP. Example 2

[0025] The components and weight ratios of the rubber used in this embodiment for medical syringe pistons, medical syringe caps, drug bottle stoppers, etc. are as follows:

[0026] Chlorinated polyethylene rubber 55%, polyisoprene rubber 45%, calcined kaolin 50%, talc 30%, white carbon black 20%, activated magnesium oxide 3%, sulfur 0.5%, bis (25) peroxide 0.5%, triazine DB 1

[0027] Titanium dioxide 3%, carbon black 0.3%, silicone resin 20%.

[0028] Preparation method:

[0029] Mixing and refining: Use rubber internal mixers, open mixers, calenders and other processing machinery to mix the various components used in the formula evenly to produce mixed rubber sheets.

[0030] Vulcanization molding: at a vulcanization pressure of 190kg / cm 2 Under the condition of mold temperature of 185℃, the mixed rubber sheet was placed in a vulcanization mold and the vulcanization time was 360s to obtain a vulcanized rubber sheet.

[0031] Subsequent processing: The excess rubber edges of the vulcanized rubber sheet are removed by punching and cutting. The obtained rubber product is cleaned, sterilized, and dried with purified water or injection water, and then processed into a 5ml syringe piston or a sterile powder bottle stopper for injection 20-B. Example 3

[0032] The components and weight ratios of the rubber used in this embodiment for medical syringe pistons, medical syringe caps, drug bottle stoppers, etc. are as follows:

[0033] Chlorinated polyethylene rubber 70, polyisoprene rubber 30, calcined kaolin 40, talc 40, white carbon black 10, activated magnesium oxide 0, alkylphenol disulfide 1.2, thiadiazole 1, titanium dioxide 4, carbon black 0.4, silicone resin 15.

[0034] Preparation method:

[0035] Mixing and refining: Use rubber internal mixers, open mixers, calenders and other processing machinery to mix the various components used in the formula evenly to produce mixed rubber sheets.

[0036] Vulcanization molding: Under the conditions of vulcanization pressure of 205kg / cm2 and mold temperature of 195℃, the mixed rubber sheet is placed in the vulcanization mold for vulcanization time of 300s to obtain a vulcanized rubber sheet.

[0037] Subsequent processing: The excess rubber edges of the vulcanized rubber sheet are removed by punching and cutting. The obtained rubber product is cleaned, sterilized, dried, etc. with purified water and injection water, and then processed into a 5ml syringe piston or injection bottle stopper 32-A. Example 4

[0038] The rubber components and weight ratios for use in a medical syringe piston, a medical syringe cap, a drug bottle stopper, etc. of this embodiment are as follows:

[0039] Chlorinated polyethylene rubber 80, polyisoprene rubber 20, calcined kaolin 10, white carbon black 15, activated magnesium oxide 5, sulfur 0.4, triazine DB 1, titanium dioxide 2, carbon black 0.1, silicone resin 5.

[0040] Preparation method:

[0041] Mixing and refining: Use rubber internal mixers, open mixers, calenders and other processing machinery to mix the various components used in the formula evenly to produce mixed rubber sheets.

[0042] Vulcanization molding: Under the conditions of vulcanization pressure of 190kg / cm2 and mold temperature of 175℃, the mixed rubber sheet is placed in the vulcanization mold and the vulcanization time is 500s to obtain the vulcanized rubber sheet.

[0043] Subsequent processing: The excess rubber edges of the vulcanized rubber sheet are removed by punching and cutting. The obtained rubber product is cleaned with purified water and injection water, sterilized, and dried, and then processed into cone head caps for pre-filled syringes or gaskets for medicinal infusion bottles 22DP. Example 5

[0044] The rubber components and weight ratios for use in a medical syringe piston, a medical syringe cap, a drug bottle stopper, etc. of this embodiment are as follows:

[0045] Chlorinated polyethylene rubber 55%, polyisoprene rubber 45%, calcined kaolin 50%, talc 20%, white carbon black 30%, activated magnesium oxide 6%, sulfur 0.6%, bis (25%) peroxide 0.5%, thiadiazole 1%, triazine TCY 1%, titanium dioxide 3%, carbon black 0.25%, silicone resin 20

[0046] Preparation method:

[0047] Mixing and refining: Use rubber internal mixers, open mixers, calenders and other processing machinery to mix the various components used in the formula evenly to produce mixed rubber sheets.

[0048] Vulcanization molding: Under the conditions of vulcanization pressure of 205kg / cm2 and mold temperature of 188℃, the mixed rubber sheet is placed in the vulcanization mold and the vulcanization time is 400s to obtain the vulcanized rubber sheet.

[0049] Subsequent processing: The excess rubber edges of the vulcanized rubber sheet are removed by punching and cutting, and the obtained rubber product is cleaned, sterilized, and dried with purified water and injection water, and then processed into cone-shaped protective caps for prefilled syringes or sterile powder bottle stoppers for injection 20-B. Example 6

[0050] The components and weight ratios of the rubber used in this embodiment for medical syringe pistons, medical syringe caps, drug bottle stoppers, etc. are as follows:

[0051] Chlorinated polyethylene rubber 70, polyisoprene rubber 30, calcined kaolin 60, talc 30, alkylphenol disulfide 1.5, triazine DB 1, titanium dioxide 4, carbon black 0.35, silicone resin 15.

[0052] Preparation method:

[0053] Mixing and refining: Use rubber internal mixers, open mixers, calenders and other processing machinery to mix the various components used in the formula evenly to produce mixed rubber sheets.

[0054] Vulcanization molding: Under the conditions of vulcanization pressure of 210kg / cm2 and mold temperature of 180℃, the mixed rubber sheet is placed in the vulcanization mold for 450s to obtain a vulcanized rubber sheet.

[0055] Subsequent processing: The excess rubber edges of the vulcanized rubber sheet are removed by punching and cutting, and the obtained rubber product is cleaned, sterilized, and dried with purified water and injection water, and then processed into cone-shaped protective caps for prefilled syringes or stoppers 32-A for injection bottles.

[0056] Product inspection results:

[0057] Corresponding embodiment 1 2 3 4 5 6 Inspection items Inspection standards 5ml syringe piston 5ml syringe piston 5ml syringe piston Cone head cap Cone head cap Needle cap Compatibility between piston and push rod (For threaded pistons only) Add an appropriate amount of this product, connect the push rod and piston, and fully insert the piston into a pre-filled syringe lubricated with silicone oil and half-filled with water. Expel any air, replace the needle cap on the syringe, and slowly withdraw it approximately 3 mm. The push rod should remain stable and not separate from the piston. Comply with regulations Comply with regulations Comply with regulations —— —— —— Piston lubricity Take an appropriate amount of this product, insert the piston into the syringe barrel lubricated with silicone oil, and use the push rod to push the piston into the entire syringe barrel. The push rod piston should move smoothly without sudden pauses. Comply with regulations Comply with regulations Comply with regulations —— —— —— Piston sliding performance Take an appropriate amount of this product, place the plunger into a syringe lubricated with silicone oil, and push the plunger at a speed of 100mm / min±5mm / min. The initial force for piston sliding and the sustained force for piston sliding should meet the requirements. Comply with regulations Comply with regulations Comply with regulations —— —— —— Body tightness Take an appropriate amount of this product and fill the syringe halfway with water. Insert the plunger into the syringe, remove the protective cap to expel any remaining air, and then block the needle with the needle cap. Apply 30N of axial pressure to the plunger plug inside the syringe through the plunger and maintain this pressure for 5 seconds. Ensure there is no leakage at the contact area between the needle and the needle seat, and at the contact area between the plunger and the syringe barrel. No leakage No leakage No leakage No leakage No leakage No leakage Needle cap removal force Take an appropriate amount of this product, fix the needle cap and syringe needle into the upper and lower fixtures of the testing machine, and test at a speed of 100mm / min±5mm / min. The needle cap removal force should be between 4.0-45.0N. —— —— —— —— —— Comply with regulations (6.0N-12.4N) ash content Take 1.0g of this product and determine it according to the rubber ash determination method "YBB00262005-2015". The remaining residue shall not exceed 50%. 24.32% 46.35% 44.33% 22.46% 46.89% 44.36% Volatile sulfur compounds* Take this product and determine it according to the method for the determination of volatile sulfides (YBB00302004-2015). It should meet the requirements. ≤50µg Na2S / 20cm 2 > <25µg <25µg <25µg <25µg <25µg <25µg Insoluble particles Take 10 capsules of this product, add 50 ml of water for particle inspection, and measure according to the method for determination of insoluble particles in packaging materials (YBB00272004-2015) under the item of medicinal rubber stoppers. Every 1 ml shall contain no more than 60 particles larger than 10 μm, and no more than 6 particles larger than 25 μm. >10μm, 5 particles. >25μm, 0 particles. >10μm, 4 particles. >25μm, 0 particles. >10μm, 6 particles. >25μm, 1 particle. —— —— —— Clarity and color The solution should be clear and colorless. If turbid, it should not be thicker than the standard turbidity solution No. 2. If colored, it should not be darker than the yellow-green standard colorimetric solution No. 5. <0.5 standard turbidity solution, colorless <0.5 standard turbidity solution, colorless <0.5 standard turbidity solution, colorless <0.5 standard turbidity solution, colorless <0.5 standard turbidity solution, colorless <0.5 standard turbidity solution, colorless pH change Take 20 ml of the test solution and blank solution respectively, add 1 ml of potassium chloride solution (1-1000) respectively, and determine according to the law (General Rules 0631 of the 2015 edition of the Chinese Pharmacopoeia). The difference between the two shall not exceed 1.0. 0.36 0.41 0.32 0.29 0.33 0.42 absorbance Take an appropriate amount of the test solution and use the blank solution as a control. According to the UV-visible spectrophotometry method (General Chapter 0401 of the Chinese Pharmacopoeia 2015 Edition), the absorbance shall not be greater than 0.1 in the wavelength range of 220-360nm. 0.036 0.025 0.042 0.028 0.033 0.022 Oxidizable substances Accurately measure 20 ml of the test solution and add 20 ml of 0.002 mol / L potassium permanganate titrant and 2 ml of dilute sulfuric acid. Boil for 3 minutes, cool rapidly, add 0.1 g of potassium iodide, and allow to stand in the dark for 5 minutes. Titrate with sodium thiosulfate titrant (0.01 mol / L) until the solution turns light brown. Add 5 drops of starch indicator solution and titrate until colorless. Repeat the same procedure for a separate blank solution. The difference in the consumption of sodium thiosulfate titrant (0.01 mol / L) between the two should not exceed 3.0 ml. 0.37ml 0.22ml 0.27ml 0.14ml 0.26ml 0.19ml Conductivity Within 5 hours of preparing the test solution, measure the conductivity using a conductivity meter: Rinse the measuring electrode (bright platinum electrode or black platinum electrode) with water several times, then rinse the electrode at least twice with blank solution. The conductivity of the blank solution should not exceed 3.0 μS / cm (20°C ± 1°C). Rinse the electrode at least twice with the test solution, then measure the conductivity of the test solution. It should not exceed 40.0 μS / cm. If the measurement is not performed at 20°C ± 1°C, temperature correction should be performed. 2.04μS / cm 2.56μS / cm 2.10μS / cm 1.83μS / cm 1.99μS / cm 2.63μS / cm Non-volatile matter Accurately measure 100 ml of the test solution and blank solution, place them in evaporating dishes at constant weight, evaporate to dryness in a water bath, and dry at 105°C to constant weight. The difference between the two should not exceed 4.0 mg. 0.4mg / 100ml 0.5mg / 100ml 0.4mg / 100ml 0.4mg / 100ml 0.4mg / 100ml 0.5mg / 100ml heavy metal Accurately measure 10 ml of the test solution, add 2 ml of acetate buffer (PH3.5), and check according to the law (Chinese Pharmacopoeia 2015 Edition General Chapter 0821 First Method), the heavy metal content shall not exceed one part per million. <0.5ppm <0.5ppm <0.5ppm <0.5ppm <0.5ppm <0.5ppm ammonium ions Accurately measure 10 ml of the test solution, add 2 ml of alkaline potassium mercury iodide test solution, and let it stand for 15 minutes. No color should appear. If color appears, compare it with a control solution made by adding 2.0 ml of ammonium chloride solution (31.5 mg of ammonium chloride is dissolved in an appropriate amount of ammonia-free water and diluted to 1000.0 ml), 8 ml of blank extract, and 2 ml of alkaline potassium mercury iodide test solution. The color should not be darker (0.0002%). Comply with regulations Comply with regulations Comply with regulations Comply with regulations Comply with regulations Comply with regulations zinc ion Take the test solution, filter it with a filter membrane with a pore size of 0.45μm, accurately measure 10ml of the filtrate, add 1ml of 2mol / L hydrochloric acid and 3 drops of potassium ferrocyanide test solution (weigh 4.2g of potassium ferrocyanide trihydrate, dissolve and dilute to 100ml with water, shake well, and the product should be freshly prepared before use) and mix. It should not be turbid; if it is turbid, compare it with 3.0ml of standard zinc solution (weigh 44.0mg of zinc sulfate heptahydrate, dissolve and dilute to 1000.0ml with freshly boiled and cooled water, and the product should be freshly prepared before use), add 7ml of blank control solution and compare it with 1ml of 2mol / L hydrochloric acid and 3 drops of potassium ferrocyanide test solution. The color should not be darker (0.0003%). Comply with regulations Comply with regulations Comply with regulations Comply with regulations Comply with regulations Comply with regulations Pyrogens* Take this product, add sodium chloride injection according to the irregular shape ratio, place in a high-pressure steam sterilizer at 115℃±2℃, maintain for 30 minutes, and measure according to the pyrogen test method (YBB00022003-2015), which should comply with the regulations. Comply with regulations Comply with regulations Comply with regulations Comply with regulations Comply with regulations Comply with regulations Acute systemic toxicity test** Take this product, add sodium chloride injection according to the irregular shape ratio, place in a high-pressure steam sterilizer at 115℃±2℃, maintain for 30 minutes, and measure according to the acute systemic toxicity test method (YBB00042003-2015), which should comply with the regulations. Comply with regulations Comply with regulations Comply with regulations Comply with regulations Comply with regulations Comply with regulations Hemolysis** Take this product and measure it according to the hemolysis test method (YBB00032003-2015). The hemolysis rate should comply with the regulations. Comply with regulations Comply with regulations Comply with regulations Comply with regulations Comply with regulations Comply with regulations

[0058] Corresponding embodiment 5 2 6 3 1 4 Inspection items Inspection standards Sterile powder bottle stopper for injection 20-B Sterile powder bottle stopper for injection 20-B Injection bottle stopper 32-A Injection bottle stopper 32-A Medical infusion bottle gasket 22DP Medical infusion bottle gasket 22DP Puncture debris Take 10 pieces of this product and measure them according to the first method of the determination of chip dropping after puncture of injection stoppers and gaskets (YBB00332004-2015). The number of chip dropping should not exceed 20. —— —— 3 5 —— —— puncture force Take 10 bottles of this product and measure them according to the first method of the test method for the puncture force of injection stoppers and gaskets (YBB00322004-2015). The average puncture force shall not exceed 75N, and the puncture force of each stopper shall not exceed 80N. No stopper should be pushed into the bottle during the puncture process. —— —— Comply with regulations Comply with regulations —— —— Sealing and trocar retention Take 10 bottles of this product and place them in an autoclave (not submerged in water) at 121°C ± 2°C for 30 minutes. Cool to room temperature. Take another 10 matching glass injection bottles, add water to the marked capacity, and securely plug them with the aforementioned rubber stoppers. Then, attach the matching aluminum caps and cap them. Use a puncture device that complies with the requirements of the "Test Method for the Puncture Force of Rubber Stoppers and Gaskets for Injections" (YBB00322004-2015). Puncture the rubber stopper vertically. With the puncture device piercing the stopper, hang the bottle upside down with a 0.5 kg weight suspended from the puncture device. The puncture device should remain intact for 4 hours, and there should be no leakage from the punctured stopper. —— —— Comply with regulations Comply with regulations —— —— Puncture debris Take an appropriate amount of this product and measure the number of chips dropped according to the second method of the injection stopper and gasket puncture determination method (YBB00332004-2015). The number of chips dropped should not exceed 5. 0 0 —— —— —— —— puncture force Take 10 bottles of this product and measure them according to the second method of the method for measuring the puncture force of injection stoppers and gaskets (YBB00322004-2015). The force required to puncture the stopper shall not exceed 10N. Comply with regulations Comply with regulations —— —— —— —— The tightness between the stopper and the container Take 10 bottles of this product, place them in a beaker, add water and boil for 5 minutes, remove them, dry them at 70°C for 1 hour, and set aside. Take another 10 matching injection bottles, add water to the marked capacity, plug them tightly with the above stoppers, add the matching aluminum caps, and press the caps. Place them in a high-pressure steam sterilizer at 121°C ± 2°C for 30 minutes, cool to room temperature, and let them stand for 24 hours. Invert the above sample and place it in a container with a vacuum device containing 10% methylene blue solution. Evacuate to a vacuum degree of 25kPa and maintain for 30 minutes. Return the vacuum device to normal pressure and let it stand for another 30 minutes. Remove them, rinse the outer wall of the bottle with water, and observe that the methylene blue solution does not penetrate into the bottle. No leakage No leakage —— —— —— —— Self-sealing Take samples from the test for tightness between stoppers and containers and, using a needle conforming to the second method of the test method for the puncture force of stoppers and gaskets for injections (YBB00332004-2015), vertically puncture the stoppers at different puncture sites. Puncture each stopper three times, replacing the needle after every 10 punctures. Invert the sample and place it in a container equipped with a vacuum device containing 10% methylene blue solution. Evacuate to a vacuum of 25 kPa and maintain for 30 minutes. Return the vacuum device to atmospheric pressure and allow the sample to sit for another 30 minutes. Remove the sample and rinse the outer wall of the bottle with water. Observe that the methylene blue solution has not seeped into the bottle. No leakage No leakage —— —— —— —— Puncture debris Take 10 pieces of this product and measure them according to the third method of the method for measuring the chip drop after puncture of injection stoppers and gaskets (YBB00332004-2015). The number of chip drops shall not exceed 20. —— —— —— —— 4 5 puncture force Take 10 test samples, open the pull ring, and use a plastic puncture device to measure the puncture force of injection stoppers and gaskets according to the third method (YBB00322004-2015). —— —— —— —— Comply with regulations Comply with regulations Sealing and trocar retention The average puncture force shall not exceed 75N, and the puncture force of each stopper shall not exceed 80N. No stopper should be pushed into the bottle during the puncture process. —— —— —— —— Comply with regulations Comply with regulations ash content Take 1.0g of this product and determine it according to the rubber ash determination method "YBB00262005-2015". The remaining residue shall not exceed 50%. 46.76% 46.17% 44.29% 44.24% 24.26% 22.38% Volatile sulfur compounds* Take this product and determine it according to the method for the determination of volatile sulfides (YBB00302004-2015). It should meet the requirements. ≤50µg Na2S / 20cm 2 > <25µg <25µg <25µg <25µg <25µg <25µg Insoluble particles <![CDATA[Take several complete rubber stoppers equivalent to a surface area of 100 cm 2 and determine them according to the method for the determination of insoluble particles in packaging materials (under the item of medicinal rubber stoppers in YBB00272004-2015). The number of particles above 10 μm per 1 ml shall not exceed 30, and the number of particles above 25 μm shall not exceed 3.]]> —— —— >10μm, 5 particles. >25μm, 0 particles. >10μm, 4 particles. >25μm, 0 particles. —— —— Insoluble particles <![CDATA[Take several complete rubber stoppers equivalent to a surface area of 100 cm 2 . Determine according to the method for the determination of insoluble particles in packaging materials (under the item of medicinal rubber stoppers in YBB00272004-2015). The number of particles above 10 μm per 1 ml shall not exceed 60, and the number of particles above 25 μm shall not exceed 6.]]> >10μm, 6 particles. >25μm, 1 particle. >10μm, 8 particles. >25μm, 0 particles. —— —— —— —— Clarity and color The solution should be clear and colorless. If turbid, it should not be thicker than the standard turbidity solution No. 2. If colored, it should not be darker than the yellow-green standard colorimetric solution No. 5. <0.5 standard turbidity solution, colorless <0.5 standard turbidity solution, colorless <0.5 standard turbidity solution, colorless <0.5 standard turbidity solution, colorless <0.5 standard turbidity solution, colorless <0.5 standard turbidity solution, colorless pH change Take 20 ml of the test solution and blank solution respectively, add 1 ml of potassium chloride solution (1-1000) respectively, and determine according to the law (General Rules 0631 of the 2015 edition of the Chinese Pharmacopoeia). The difference between the two shall not exceed 1.0. 0.42 0.43 0.38 0.35 0.26 0.46 absorbance Take an appropriate amount of the test solution and use the blank solution as a control. According to the UV-visible spectrophotometry method (General Chapter 0401 of the Chinese Pharmacopoeia 2015 Edition), the absorbance shall not be greater than 0.1 in the wavelength range of 220-360nm. 0.026 0.019 0.026 0.031 0.039 0.024 Oxidizable substances Accurately measure 20 ml of the test solution and add 20 ml of 0.002 mol / L potassium permanganate titrant and 2 ml of dilute sulfuric acid. Boil for 3 minutes, cool rapidly, add 0.1 g of potassium iodide, and allow to stand in the dark for 5 minutes. Titrate with sodium thiosulfate titrant (0.01 mol / L) until the solution turns light brown. Add 5 drops of starch indicator solution and titrate until colorless. Repeat the same procedure for a separate blank solution. The difference in the consumption of sodium thiosulfate titrant (0.01 mol / L) between the two should not exceed 3.0 ml. 0.42ml 0.31ml 0.22ml 0.24ml 0.33ml 0.45ml Conductivity Within 5 hours of preparing the test solution, measure the conductivity using a conductivity meter: Rinse the measuring electrode (bright platinum electrode or black platinum electrode) with water several times, then rinse the electrode at least twice with blank solution. The conductivity of the blank solution should not exceed 3.0 μS / cm (20°C ± 1°C). Rinse the electrode at least twice with the test solution, then measure the conductivity of the test solution. It should not exceed 40.0 μS / cm. If the measurement is not performed at 20°C ± 1°C, temperature correction should be performed. 1.88μS / cm 1.53μS / cm 2.67μS / cm 2.80μS / cm 2.03μS / cm 2.41μS / cm Non-volatile matter Accurately measure 100 ml of the test solution and blank solution, place them in evaporating dishes at constant weight, evaporate to dryness in a water bath, and dry at 105°C to constant weight. The difference between the two should not exceed 4.0 mg. 0.5mg / 100ml 0.5mg / 100ml 0.3mg / 100ml 0.4mg / 100ml 0.4mg / 100ml 0.3mg / 100ml heavy metal Accurately measure 10 ml of the test solution, add 2 ml of acetate buffer (PH3.5), and check according to the law (Chinese Pharmacopoeia 2015 Edition General Chapter 0821 First Method), the heavy metal content shall not exceed one part per million. <0.5ppm <0.5ppm <0.5ppm <0.5ppm <0.5ppm <0.5ppm ammonium ions Accurately measure 10 ml of the test solution, add 2 ml of alkaline potassium mercury iodide test solution, and let it stand for 15 minutes. No color should appear. If color appears, compare it with a control solution made by adding 2.0 ml of ammonium chloride solution (31.5 mg of ammonium chloride is dissolved in an appropriate amount of ammonia-free water and diluted to 1000.0 ml), 8 ml of blank extract, and 2 ml of alkaline potassium mercury iodide test solution. The color should not be darker (0.0002%). Comply with regulations Comply with regulations Comply with regulations Comply with regulations Comply with regulations Comply with regulations zinc ion Take the test solution, filter it with a filter membrane with a pore size of 0.45μm, accurately measure 10ml of the filtrate, add 1ml of 2mol / L hydrochloric acid and 3 drops of potassium ferrocyanide test solution (weigh 4.2g of potassium ferrocyanide trihydrate, dissolve and dilute to 100ml with water, shake well, and the product should be freshly prepared before use) and mix. It should not be turbid; if it is turbid, compare it with 3.0ml of standard zinc solution (weigh 44.0mg of zinc sulfate heptahydrate, dissolve and dilute to 1000.0ml with freshly boiled and cooled water, and the product should be freshly prepared before use), add 7ml of blank control solution and compare it with 1ml of 2mol / L hydrochloric acid and 3 drops of potassium ferrocyanide test solution. The color should not be darker (0.0003%). Comply with regulations Comply with regulations Comply with regulations Comply with regulations Comply with regulations Comply with regulations Pyrogens* Take this product, add sodium chloride injection according to the irregular shape ratio, place in a high-pressure steam sterilizer at 115℃±2℃, maintain for 30 minutes, and measure according to the pyrogen test method (YBB00022003-2015), which should comply with the regulations. Comply with regulations Comply with regulations Comply with regulations Comply with regulations Comply with regulations Comply with regulations Acute systemic toxicity test** Take this product, add sodium chloride injection according to the irregular shape ratio, place in a high-pressure steam sterilizer at 115℃±2℃, maintain for 30 minutes, and measure according to the acute systemic toxicity test method (YBB00042003-2015), which should comply with the regulations. Comply with regulations Comply with regulations Comply with regulations Comply with regulations Comply with regulations Comply with regulations Hemolysis** Take this product and measure it according to the hemolysis test method (YBB00032003-2015). The hemolysis rate should comply with the regulations. Comply with regulations Comply with regulations Comply with regulations Comply with regulations Comply with regulations Comply with regulations

[0059] Although the embodiments of the present invention have been shown and described above, it will be understood that the above embodiments are illustrative and are not to be construed as limitations on the present invention. A person skilled in the art may change, modify, replace and modify the above embodiments within the scope of the present invention without departing from the principles and purpose of the present invention.

Claims

1. A rubber for medical syringe pistons, medical syringe caps, and drug bottle stoppers, characterized in that: It is composed of the following components and parts by weight: 50-80 parts of chlorinated polyethylene rubber (CM), 20-50 parts of isoprene rubber (IR), 20-90 parts of filler, 1-5 parts of vulcanizing agent, 0.1-5 parts of colorant, and 5-20 parts of silicone resin.

2. The rubber for medical syringe pistons, medical syringe caps, and drug bottle stoppers according to claim 1, characterized in that: The filler is one or a mixture of kaolin, white carbon black and talcum powder in any proportion.

3. The rubber for medical syringe pistons, medical syringe caps, and drug bottle stoppers according to claim 1, characterized in that: The vulcanizing agent is a mixture of thiadiazoles or triazines with peroxides or sulfur, or one of them is used alone.

4. The rubber for medical syringe pistons, medical syringe caps, and drug bottle stoppers according to claim 1, characterized in that: The colorant is titanium dioxide or carbon black, which can be mixed or used alone.

5. A method for preparing a rubber for use as a medical syringe piston, a medical syringe cap, or a drug bottle stopper according to any one of claims 1 to 4, characterized in that: The following steps are involved: (1) Mixing and refining rubber: Using rubber internal mixer, open mixer and calender processing machinery to mix the various components used in the formula evenly to prepare mixed rubber sheets; (2) Vulcanization molding: Place the mixed rubber sheet into a vulcanization mold under a vulcanization pressure of 160-210 kg / cm2 and a mold temperature of 155-195°C for a vulcanization time of 300-600 seconds to obtain a vulcanized rubber sheet; (3) Subsequent processing: The excess rubber edges of the vulcanized rubber sheet are removed by punching and cutting. The obtained rubber product is cleaned, sterilized and dried with purified water and injection water to obtain a clean medical rubber seal.