Low-ash rubber-plastic blended medical stopper and preparation method thereof

Abstract

The present application relates to a kind of low ash rubber-plastic blend medical rubber plug and its preparation method, belong to medical packaging rubber technical field.The formula of the plug includes chlorinated butyl rubber, modified styrene-ethylene / butylene-styrene block copolymer powder, calcined kaolin, precipitated hydrated silicon dioxide, titanium white, carbon black, alkyl phenol disulfide, zinc oxide by weight portion.First, the modified powder is prepared by surface modification of styrene-ethylene / butylene-styrene block copolymer powder and alkyl phosphonium laurate.Then, chlorinated butyl rubber is processed into plug by mixing, opening, vulcanization forming and other processes with modified powder, filler and auxiliary agent.The present application realizes high hardness (shore A hardness is greater than or equal to 48) while ensuring low ash content (less than or equal to 15%) by modifying the rubber-plastic blend structure of SEBS powder, effectively solves the adhesion problem caused by insufficient hardness of traditional low ash plug, and significantly reduces puncture and shedding, suitable for high-standard drug packaging such as biological preparations.

Description

Technical Field

[0001] This invention belongs to the field of medical packaging materials technology, specifically relating to a low-ash, high-hardness butyl rubber stopper for pharmaceutical packaging and its preparation method, which is particularly suitable for packaging biological agents with strict requirements on puncture force and puncture debris. Background Technology

[0002] Butyl rubber, due to its excellent airtightness and chemical stability, has become a key material for pharmaceutical packaging. With the development of the pharmaceutical industry, biopharmaceuticals are placing higher demands on the performance of rubber stoppers. To meet these requirements, pharmaceutical packaging material manufacturers typically improve the tensile properties of the rubber compound by reducing the ash content of the stoppers. However, this leads to a significant decrease in the hardness of the stoppers, causing problems such as adhesion and deformation during production, transportation, and use, which can affect drug safety. Simply adding plastic substances or non-inorganic fillers can also affect the chemical properties of the stoppers, which is detrimental to the long-term stability of the drugs. Summary of the Invention

[0003] The primary objective of this invention is to provide a low-ash, high-hardness butyl rubber stopper, solving the adhesion problem caused by insufficient hardness after reducing the ash content of traditional rubber stoppers. Another objective is to provide a method for preparing this stopper, ensuring that the product has an ash content ≤15% while maintaining a Shore A hardness ≥48, and significantly improving puncture and chip removal performance.

[0004] The technical solution of this invention is a formulation design for a low-ash rubber-plastic blend medical stopper, comprising the following raw materials by weight: 100 parts of chlorinated butyl rubber, 20-30 parts of modified styrene-ethylene / butene-styrene block copolymer powder (modified SEBS powder), 5-15 parts of calcined kaolin, 4-10 parts of precipitated hydrated silica, 1-3 parts of titanium dioxide, 0.1-0.3 parts of carbon black, 0.5-1.5 parts of alkylphenol disulfide, and 2-5 parts of zinc oxide; wherein the modified styrene-ethylene / butene-styrene block copolymer powder is obtained by surface modification of styrene-ethylene / butene-styrene block copolymer powder and alkylphosphonium laurate at a mass ratio of 6-10:1.

[0005] In the preferred embodiment, 100 parts of chlorinated butyl rubber, 24 parts of modified SEBS powder, 10 parts of calcined kaolin, 6 parts of precipitated hydrated silica, 2 parts of titanium dioxide, 0.2 parts of carbon black, 0.9 parts of alkylphenol disulfide, and 3 parts of zinc oxide are used. The modified styrene-ethylene / butene-styrene block copolymer powder is prepared by surface modification of styrene-ethylene / butene-styrene block copolymer powder and alkyl phosphonium laurate at a mass ratio of 7-9:1.

[0006] In some embodiments, one portion may correspond to an equivalent unit such as 1 kg or 1 g.

[0007] This invention also relates to a method for preparing a low-ash rubber-plastic blend medical stopper, comprising the following steps:

[0008] S1. Preparation of modified styrene-ethylene / butene-styrene block copolymer powder: Styrene-ethylene / butene-styrene block copolymer powder and alkyl phosphonium laurate are put into a high-speed mixer and stirred and modified at high temperature for a period of time to obtain modified styrene-ethylene / butene-styrene block copolymer powder for later use. S2. Preparation of the compound: In the first stage, chlorinated butyl rubber, calcined kaolin, precipitated hydrated silica, modified styrene-ethylene / butene-styrene block copolymer powder, titanium dioxide, and carbon black are added to a mixer for mixing. In the second stage, zinc oxide and alkylphenol disulfide are added for mixing. The rubber compound is discharged when the temperature is 120±5℃. The rubber compound is then put into a two-roll mill for two-roll milling. The mixture is passed through a thin pass, tamped, and turned to obtain the compound of the present invention. S3. Pre-forming, vulcanization, and punching process: The cooled compound is fed into an extruder, and the extruded rubber is calendered by a calender to obtain rubber sheets of the required weight and size for vulcanization. The cut rubber sheets are vulcanized and formed under high temperature and high pressure conditions in a vulcanizing machine to obtain molded semi-finished products. The semi-finished products are punched into individual rubber plugs through punching dies and a punching press. S4. Cleaning and drying process: After cleaning the rubber stoppers with a rubber stopper cleaning machine, hot air drying is carried out in the drying stage, maintaining the drying temperature between 85-95℃, and drying is carried out for 60-120 minutes to obtain the finished product.

[0009] The alkylphosphonium laurate is selected from any one of tetradecyltriphenylphosphonium laurate, tributylhexadecylphosphonium laurate, trihexyldecylphosphonium laurate, trioctyltetradecylphosphonium laurate, tripentyltetradecylphosphonium laurate, tributyltetradecylphosphonium laurate, trihexyloctadecylphosphonium laurate, trihexylhexadecylphosphonium laurate, and trihexyldodecylphosphonium laurate.

[0010] The structural formula of tributylhexylphosphonium laurylate is [(C4H9)3PC]. 16 H 33 ] + [CH3(CH2) 10 COO] - ; The structural formula of trihexyldecylphosphonium laurate is [(C6H] 13 3PC 10 H 21 ] + [CH3(CH2) 10 COO] - ; The structural formula of trihexyloctylphosphonium laurylate is [(C6H] 13 )3PC8H 17 ] + [CH3(CH2) 10 COO] - ; The structural formula of trioctyltetradecylphosphonium laurate is [(C8H] 17 3PC 14 H 29 ] + [CH3(CH2) 10 COO] - ; The structural formula of tripentyltetradecylphosphonium laurate is [(C5H] 11 3PC 14 H 29 ] + [CH3(CH2) 10 COO] - ; The structural formula of tributyltetradecylphosphonium laurate is [(C4H9)3PC]. 14 H 29 ] + [CH3(CH2) 10 COO] - ; The structural formula of trihexyloctadecylphosphonium laurate is [(C6H 13 3PC 18 H 37 ] + [CH3(CH2) 10 COO] - ; The structural formula of trihexylhexylphosphonium laurylate is [(C6H 13 3PC 16 H 33 ] + [CH3(CH2) 10 COO] - ; The structural formula of trihexyldodecylphosphonium laurylate is [(C6H 13 3PC 12 H 25 ] + [CH3(CH2) 10 COO] - .

[0011] Furthermore, in step S1, the styrene-ethylene / butene-styrene block copolymer powder contains 25-30% styrene, preferably 29% styrene.

[0012] In step S1, the modified styrene-ethylene / butene-styrene block copolymer powder is prepared by adding styrene-ethylene / butene-styrene block copolymer powder and alkyl phosphonium laurate in a mass ratio of 6-10:1 into a high-speed mixer and stirring at 80-100℃ and a speed of 1000-1200 R / min for 30-45 minutes.

[0013] Furthermore, in step S2, the mixing temperature is 60-80℃ and the mixing time is 4-6 minutes.

[0014] Furthermore, in step S3, the vulcanization temperature is between 170-185℃, and the vulcanization time is between 4-6 minutes.

[0015] Traditional solutions include using coated rubber stoppers (such as fluoroplastic coatings), but the coating process requires secondary molding, which is costly. Other technologies attempt to improve surface bubble problems using hydrotalcite additives (such as calcined zinc-magnesium hydrotalcite), but these additives may increase ash content and have limited effect on hardness improvement. Therefore, developing a rubber stopper that balances low ash content, high hardness, and good puncture resistance is of significant practical importance.

[0016] The present invention has the following beneficial effects: 1. Balance between low ash content and high hardness: Through the reinforcing effect of modified styrene-ethylene / butene-styrene block copolymer, the ash content is ≤15% and the hardness is ≥48 Shore A, overcoming the defects of traditional rubber stoppers.

[0017] 2. Excellent puncture performance: The dense rubber stopper structure significantly reduces puncture force and produces almost zero debris, meeting the requirements of biological agents.

[0018] 3. Cost advantage: No secondary processing with film coating is required, and the production cost is reduced by more than 30% compared with film-coated rubber stoppers.

[0019] 4. Good drug compatibility: After modification, SEBS is evenly dispersed during the vulcanization and crosslinking process and forms a dense structure on the rubber surface, effectively preventing oligomer migration, making it suitable for packaging highly active drugs.

[0020] Highly active pharmaceutical ingredients (PIIs) refer to biological agents and highly sensitive chemical agents, such as cephalosporins and biological vaccines. These drugs are typically encapsulated using diaphragm stoppers to isolate the rubber from the drug, thus ensuring its stability. However, the rigidity of the diaphragm stopper material usually increases the puncture force and the risk of puncture debris. This patent provides a stopper with low ash content and high hardness, while also possessing good puncture performance and stability, meeting the needs of such drugs. Furthermore, the smooth surface and stability of the stopper result in excellent performance during transportation and filling processes.

[0021] Alkylphosphonium laurate is a hydrophobic quaternary phosphonium salt type ionic liquid. Its characteristics include a large cation (long alkyl chain), a laurate anion, strong hydrophobicity, low volatility, and certain ionic polarity. SEBS has a triblock structure: PS-EB-PS, where PS is the hard segment and EB is the rubber soft segment. In the chlorinated butyl rubber system, the EB segment is in a compatible state, while the PS segment forms a microphase hard domain. Therefore, SEBS itself has a significant polarity difference from CIIR, resulting in high interfacial tension and limited dispersion. However, by rapidly and high-temperature mixing SEBS and alkylphosphonium laurate, under high-temperature and high-speed shearing, the alkylphosphonium laurate physically adsorbs onto SEBS, forming "ion-modified SEBS." Chlorinated butyl rubber has a chlorine-containing structure with C–Cl polar bonds, which can interact with ions through electrostatic or dipole interactions. After adding the modified "ion-modified SEBS", the phosphonium salt cation can generate a dipole-ion interaction with Cl in CIIR, and the laurate ion can generate a hydrophobic interaction with the rubber chain. As a result, SEBS is more finely dispersed in CIIR, transforming what might have been a "coarse phase separation" into a nanoscale microphase dispersion structure. Simultaneously, an "ion-physical composite cross-linking structure" is formed. The phosphonium salt cation weakly binds to the active sites in CIIR, and the phosphonium salt forms ion clusters at the interface. The PS hard segments and ion clusters together form composite physical cross-linking points. Therefore, a dual physical network structure appears in the system: PS hard segment microregions + ion cluster microregions. In summary, SEBS and alkyl phosphonium laurate form an ion-modified core-shell microphase structure under high-speed mixing, constructing a dual physical cross-linking network of "ion clusters + PS hard segments" in CIIR. This reduces interfacial friction and improves fluidity during processing, and increases the effective cross-linking density after vulcanization, thus achieving a synergistic effect of "increased hardness + increased fluidity". Detailed Implementation

[0022] The embodiments of the present invention will be described in detail below with reference to examples. However, those skilled in the art will understand that the following examples are only for illustrating the present invention and should not be regarded as limiting the scope of the present invention.

[0023] Chlorinated butyl rubber uses halogenated butyl rubber, which is used in the rubber stopper industry. The preferred grade is 139 from OAONIzhnekamskneftekhim in Russia. Styrene-ethylene / butene-styrene block copolymer powder is VECTOR8103 from TSRC Corporation Limited, used for surface modification with alkyl phosphonium laurate. Alkylphenol disulfide is preferably JPV-7 from SHIKOKU CHEMICAL CORPERATION in Japan. Calcined kaolin is SX-80A from Inner Mongolia Sanxin Kaolin Co., Ltd. The remaining raw materials have no special requirements and can be commercially available.

[0024] Example 1 Modified styrene-ethylene / butene-styrene block copolymer powder (modified SEBS powder): The mass ratio of styrene-ethylene / butene-styrene block copolymer powder (styrene content of 29%) to trihexyldecylphosphonium laurate is 8:1.

[0025] Compound rubber: 50kg chlorinated butyl rubber, 5kg calcined kaolin, 12kg modified SEBS powder, 3kg precipitated hydrated silica, 1kg titanium dioxide, 0.1kg carbon black, 0.45kg alkylphenol disulfide, and 1.5kg zinc oxide.

[0026] A method for preparing a low-ash rubber-plastic blend medical stopper, the specific process steps are as follows: (1) Preparation of modified styrene-ethylene / butene-styrene block copolymer powder: 8 kg of styrene-ethylene / butene-styrene block copolymer powder (styrene content of 29%) and 1 kg of trihexyldecylphosphonium laurate were added to a high-speed mixer and stirred for 30 minutes at 80-100℃ and 1200 R / min to obtain modified styrene-ethylene / butene-styrene block copolymer powder for later use; (2) Preparation of compound: In the first stage, 50 kg of chlorinated butyl rubber, 5 kg of kaolin, 3 kg of precipitated hydrated silica, 12 kg of modified styrene-ethylene / butene-styrene block copolymer powder, 1 kg of titanium dioxide and 0.1 kg of carbon black are added to the internal mixer and mixed at 80°C for 6 min. In the second stage, the remaining 1.5 kg of zinc oxide and 0.45 kg of alkylphenol disulfide are added and mixed. When the temperature of the rubber compound is 120°C, the rubber compound is discharged and put into the open mill for open milling. The rubber compound is obtained by pulling the blades on both sides once, thinly passing through, tamping and turning. The compound of the present invention is obtained. (3) Pre-forming, vulcanization, and punching process: The cooled compound is fed into an extruder, and the extruded rubber is calendered by a calender to obtain rubber sheets of the required weight and size for vulcanization. The cut rubber sheets are vulcanized and formed under high temperature and high pressure conditions in a vulcanizing machine. The vulcanization temperature is 180℃ and the vulcanization time is 5 minutes to obtain molded semi-finished products. The semi-finished products are punched into individual rubber plugs through punching dies and a punching machine; (4) Cleaning and drying process: After cleaning the rubber stoppers with a rubber stopper cleaning machine, hot air drying is carried out in the drying stage, and the drying temperature is kept between 90℃. The finished product is obtained after drying for 120 minutes.

[0027] Example 2 Modified styrene-ethylene / butene-styrene block copolymer powder (modified SEBS powder): The mass ratio of styrene-ethylene / butene-styrene block copolymer powder (styrene content of 29%) to trihexyldecylphosphonium laurate is 6:1.

[0028] Compound rubber: 50kg chlorinated butyl rubber, 5kg calcined kaolin, 10kg modified SEBS powder, 3kg precipitated hydrated silica, 1kg titanium dioxide, 0.1kg carbon black, 0.45kg alkylphenol disulfide, and 1.5kg zinc oxide.

[0029] A method for preparing a low-ash rubber-plastic blend medical stopper, the specific process steps are as follows: (1) Preparation of modified styrene-ethylene / butene-styrene block copolymer powder: 6 kg of styrene-ethylene / butene-styrene block copolymer powder (styrene content of 29%) and 1 kg of trihexyldecylphosphonium laurate were added to a high-speed mixer and stirred for 30 minutes at 80-100℃ and 1200 R / min to obtain modified styrene-ethylene / butene-styrene block copolymer powder for later use; (2) Preparation of compound: In the first stage, 50 kg of chlorinated butyl rubber, 5 kg of kaolin, 3 kg of precipitated hydrated silica, 10 kg of modified styrene-ethylene / butene-styrene block copolymer powder, 1 kg of titanium dioxide and 0.1 kg of carbon black are added to the internal mixer and mixed at 80°C for 6 min. In the second stage, the remaining 1.5 kg of zinc oxide and 0.45 kg of alkylphenol disulfide are added and mixed. When the temperature of the rubber compound is 120°C, the rubber compound is discharged and put into the open mill for open milling. The rubber compound is obtained by pulling the blades on both sides once, thinly passing through, pounding and turning. The compound of the present invention is obtained. (3) Pre-forming, vulcanization, and punching processes: Same as in Example 1; (4) Cleaning and drying process: Same as in Example 1.

[0030] Example 3: Modified styrene-ethylene / butene-styrene block copolymer powder (modified SEBS powder): The mass ratio of styrene-ethylene / butene-styrene block copolymer powder (styrene content of 29%) to trihexyldecylphosphonium laurate is 10:1.

[0031] Compound rubber: 50kg chlorinated butyl rubber, 6kg calcined kaolin, 15kg modified SEBS powder, 3kg precipitated hydrated silica, 1kg titanium dioxide, 0.1kg carbon black, 0.45kg alkylphenol disulfide, and 1.5kg zinc oxide.

[0032] A method for preparing a low-ash rubber-plastic blend medical stopper, the specific process steps are as follows: (1) Preparation of modified styrene-ethylene / butene-styrene block copolymer powder: 10 kg of styrene-ethylene / butene-styrene block copolymer powder (styrene content of 29%) and 1 kg of trihexyldecylphosphonium laurate were added to a high-speed mixer and stirred for 30 minutes at 80-100℃ and 1200 R / min to obtain modified styrene-ethylene / butene-styrene block copolymer powder for later use; (2) Preparation of compound: In the first stage, 50 kg of chlorinated butyl rubber, 6 kg of kaolin, 3 kg of precipitated hydrated silica, 15 kg of modified styrene-ethylene / butene-styrene block copolymer powder, 1 kg of titanium dioxide and 0.1 kg of carbon black are added to the internal mixer and mixed at 80°C for 6 min. In the second stage, the remaining 1.5 kg of zinc oxide and 0.45 kg of alkylphenol disulfide are added and mixed. When the temperature of the rubber compound is 120°C, the rubber compound is discharged and put into the open mill for open milling. The rubber compound is obtained by pulling the blades on both sides once, thinly passing through, tamping and turning. The compound of the present invention is obtained. (3) Pre-forming, vulcanization, and punching processes: The steps are the same as in Example 1; (4) Cleaning and drying process: The steps are the same as in Example 1.

[0033] The results of ash content tests and hardness and physical property tests of the vulcanized test pieces for a low-ash rubber-plastic blend medical stopper product according to Embodiments 1, 2, and 3 of the present invention are shown in Table 1 below: Table 1

[0034] Examples 1, 2, and 3 of this invention describe a low-ash rubber-plastic blend medical stopper product. A rapid drug compatibility evaluation was conducted on the product. The drug-grade test product was encapsulated and inverted for 5 days at 60°C and 75% humidity. Turbidity was then tested after dissolution. The results of the diaphragm stopper test are compared in Table 2 below. Table 2

[0035] Examples 1, 2, and 3 of this invention describe a low-ash rubber-plastic blend medical stopper product. Adhesion performance tests were conducted on the product. A certain quantity of the product was placed in an aluminum foil bag and vacuum-sealed under negative pressure (0.1 MPa). The test conditions were: after being placed at 60°C and 75% humidity for 5 days, the product was removed, cooled to room temperature, and then opened. After opening, it was observed whether the product dispersed within 5 minutes. The test results are shown in Table 3 below. Table 3

[0036] The low-ash rubber-plastic blend medical stopper products of Embodiments 1, 2, and 3 of the present invention were tested in accordance with the YBB00052005-2015 standard, and the test indicators are shown in Table 4: Table 4

[0037] Example 4: The difference from Example 1 is that the alkylphosphonium laurate is replaced with tributyltetradecylphosphonium laurate.

[0038] Modified styrene-ethylene / butene-styrene block copolymer powder (modified SEBS powder): The mass ratio of styrene-ethylene / butene-styrene block copolymer powder (styrene content of 29%) to tributyltetradecylphosphonium laurate is 8:1.

[0039] (1) Preparation of modified styrene-ethylene / butene-styrene block copolymer powder: 8 kg of styrene-ethylene / butene-styrene block copolymer powder (styrene content of 29%) and 1 kg of tributyltetradecylphosphonium laurate were added to a high-speed mixer and stirred for 30 minutes at 80-100℃ and 1200 R / min to obtain modified styrene-ethylene / butene-styrene block copolymer powder for later use; (2) Preparation of compound: In the first stage, 50 kg of chlorinated butyl rubber, 5 kg of kaolin, 3 kg of precipitated hydrated silica, 12 kg of modified styrene-ethylene / butene-styrene block copolymer powder, 1 kg of titanium dioxide and 0.1 kg of carbon black are added to the internal mixer and mixed at 80°C for 6 min. In the second stage, the remaining 1.5 kg of zinc oxide and 0.45 kg of alkylphenol disulfide are added and mixed. When the temperature of the rubber compound is 120°C, the rubber compound is discharged and put into the open mill for open milling. The rubber compound is obtained by pulling the blades on both sides once, thinly passing through, tamping and turning. The compound of the present invention is obtained. (3) Pre-forming, vulcanization, and punching processes: The steps are the same as in Example 1; (4) Cleaning and drying process: The steps are the same as in Example 1.

[0040] Example 5: The difference from Example 1 is that the alkylphosphonium laurate is replaced with trihexyloctadecylphosphonium laurate.

[0041] Modified styrene-ethylene / butene-styrene block copolymer powder (modified SEBS powder): The mass ratio of styrene-ethylene / butene-styrene block copolymer powder (styrene content of 29%) to trihexyloctadecylphosphonium laurate is 8:1.

[0042] (1) Preparation of modified styrene-ethylene / butene-styrene block copolymer powder: 8 kg of styrene-ethylene / butene-styrene block copolymer powder (styrene content of 29%) and 1 kg of trihexyloctadecylphosphonium laurate were added to a high-speed mixer and stirred for 30 minutes at 80-100℃ and 1200 R / min to obtain modified styrene-ethylene / butene-styrene block copolymer powder for later use; (2) Preparation of compound: In the first stage, 50 kg of chlorinated butyl rubber, 5 kg of kaolin, 3 kg of precipitated hydrated silica, 12 kg of modified styrene-ethylene / butene-styrene block copolymer powder, 1 kg of titanium dioxide and 0.1 kg of carbon black are added to the internal mixer and mixed at 80°C for 6 min. In the second stage, the remaining 1.5 kg of zinc oxide and 0.45 kg of alkylphenol disulfide are added and mixed. When the temperature of the rubber compound is 120°C, the rubber compound is discharged and put into the open mill for open milling. The rubber compound is obtained by pulling the blades on both sides once, thinly passing through, tamping and turning. The compound of the present invention is obtained. (3) Pre-forming, vulcanization, and punching processes: The steps are the same as in Example 1; (4) Cleaning and drying process: The steps are the same as in Example 1.

[0043] The results of ash content test and hardness and physical property test of the vulcanized test pieces of the low-ash rubber-plastic blend medical stopper products of Embodiments 1, 4 and 5 of the present invention are shown in Table 5 below: Table 5

[0044] Examples 1, 4, and 5 of this invention describe a low-ash rubber-plastic blend medical stopper product. A rapid drug compatibility evaluation was conducted on the product. After encapsulating the drug-grade test product, it was inverted for 5 days at 60°C and 75% humidity, then dissolved and subjected to a turbidity test. The results of the diaphragm stopper test are compared in Table 6 below. Table 6

[0045] Examples 1, 4, and 5 of this invention describe a low-ash rubber-plastic blend medical stopper product. Adhesion performance tests were conducted on the product. A certain quantity of the product was placed in an aluminum foil bag and vacuum-sealed under a negative pressure of 0.1 MPa. The test conditions were: after being placed at 60°C and 75% humidity for 5 days, the product was removed, cooled to room temperature, and then opened. After opening, it was observed whether the product dispersed within 5 minutes. The test results are shown in Table 7 below. Table 7

[0046] The low-ash rubber-plastic blend medical stopper products of Embodiments 1, 4, and 5 of the present invention were tested in accordance with the YBB00052005-2015 standard, and the test indicators are shown in Table 8: Table 8

[0047] Comparative Example 1 Modified styrene-ethylene / butene-styrene block copolymer powder (modified SEBS powder): Styrene-ethylene / butene-styrene block copolymer powder (styrene content of 29%) is blended with stearic acid at a mass ratio of 8:1.

[0048] Compound rubber: 50kg chlorinated butyl rubber, 5kg calcined kaolin, 12kg modified SEBS powder, 3kg precipitated hydrated silica, 1kg titanium dioxide, 0.1kg carbon black, 0.45kg alkylphenol disulfide, and 1.5kg zinc oxide.

[0049] A method for preparing a low-ash rubber-plastic blend medical stopper, the specific process steps are as follows: (1) Preparation of modified styrene-ethylene / butene-styrene block copolymer powder: 8 kg of styrene-ethylene / butene-styrene block copolymer powder (styrene content of 29%) and 1 kg of stearic acid were added to a high-speed mixer and stirred for 30 minutes at 80-100℃ and 1200 R / min to obtain modified styrene-ethylene / butene-styrene block copolymer powder for later use; (2) Preparation of compound: In the first stage, 50 kg of chlorinated butyl rubber, 5 kg of kaolin, 3 kg of precipitated hydrated silica, 12 kg of modified styrene-ethylene / butene-styrene block copolymer powder, 1 kg of titanium dioxide and 0.1 kg of carbon black are added to the internal mixer and mixed at 80°C for 6 min. In the second stage, the remaining 1.5 kg of zinc oxide and 0.45 kg of alkylphenol disulfide are added and mixed. When the temperature of the rubber compound is 120°C, the rubber compound is discharged and put into the open mill for open milling. The rubber compound is obtained by pulling the blades on both sides once, thinly passing through, tamping and turning. The compound of the present invention is obtained. (3) Pre-forming, vulcanization, and punching process: The cooled compound is fed into an extruder, and the extruded rubber is calendered by a calender to obtain rubber sheets of the required weight and size for vulcanization. The cut rubber sheets are vulcanized and formed under high temperature and high pressure conditions in a vulcanizing machine. The vulcanization temperature is 180℃ and the vulcanization time is 5 minutes to obtain molded semi-finished products. The semi-finished products are punched into individual rubber plugs through punching dies and a punching machine; (4) Cleaning and drying process: After cleaning the rubber stoppers with a rubber stopper cleaning machine, hot air drying is carried out in the drying stage, and the drying temperature is kept between 90℃. The finished product is obtained after drying for 120 minutes.

[0050] Comparative Example 2: Compound rubber: 50kg chlorinated butyl rubber, 5kg calcined kaolin, 10.5kg SEBS powder, 1.5kg trihexyldecylphosphonium laurate, 3kg precipitated hydrated silica, 1kg titanium dioxide, 0.1kg carbon black, 0.45kg alkylphenol disulfide, and 1.5kg zinc oxide.

[0051] A method for preparing a low-ash rubber-plastic blend medical stopper, the specific process steps are as follows: (1) Preparation of compound: In the first stage, 50 kg of chlorinated butyl rubber, 5 kg of calcined kaolin, 10.5 kg of SEBS powder, 1.5 kg of trihexyldecylphosphonium laurate, 3 kg of precipitated hydrated silica, 1 kg of titanium dioxide and 0.1 kg of carbon black are added to the internal mixer and mixed at 80°C for 6 min. In the second stage, the remaining 1.5 kg of zinc oxide and 0.445 kg of alkylphenol disulfide are added and mixed. When the temperature of the rubber compound is 120°C, the rubber compound is discharged and put into the open mill for open milling. The rubber compound is obtained by pulling the blades on both sides once, thinly passing through, tamping and turning. The compound of the present invention is obtained. (2) Pre-forming, vulcanization, and punching process: The cooled compound is fed into an extruder, and the extruded rubber is calendered by a calender to obtain rubber sheets of the required weight and size for vulcanization. The cut rubber sheets are vulcanized under high temperature and high pressure conditions in a vulcanizing machine. The vulcanization temperature is 180℃ and the vulcanization time is 5 minutes to obtain molded semi-finished products. The semi-finished products are punched into individual rubber plugs through punching dies and a punching machine; (3) Cleaning and drying process: After cleaning the rubber stoppers with a rubber stopper cleaning machine, hot air drying is carried out in the drying stage, and the drying temperature is kept between 90℃. The finished product is obtained after drying for 120 minutes.

[0052] Comparative Example 3: Modified polyethylene powder (modified PE powder): The mass ratio of polyethylene powder to trihexyldecylphosphonium laurate is 8:1.

[0053] Compound rubber: 50kg chlorinated butyl rubber, 5kg calcined kaolin, 12kg modified PE powder, 3kg precipitated hydrated silica, 1kg titanium dioxide, 0.1kg carbon black, 0.45kg alkylphenol disulfide, and 1.5kg zinc oxide.

[0054] A method for preparing a low-ash rubber-plastic blend medical stopper, the specific process steps are as follows: (1) Preparation of modified polyethylene powder: 8 kg of polyethylene powder and 1 kg of trihexyldecylphosphonium laurate were added to a high-speed mixer and stirred for 30 minutes at 80-100℃ and 1200 R / min to obtain modified polyethylene powder for later use. (2) In the first stage, 50 kg of chlorinated butyl rubber, 5 kg of kaolin, 3 kg of precipitated hydrated silica, 12 kg of modified polyethylene powder, 1 kg of titanium dioxide and 0.1 kg of carbon black are added to the internal mixer and mixed at 80°C for 6 min. In the second stage, the remaining 1.5 kg of zinc oxide and 0.45 kg of alkylphenol disulfide are added and mixed. When the rubber compound temperature is 120°C, the rubber compound is discharged and put into the open mill for open milling. The rubber compound is then passed through the mill once on each side, and then pounded and turned to obtain the compound of the present invention. (3) Pre-forming, vulcanization, and punching process: The cooled compound is fed into an extruder, and the extruded rubber is calendered by a calender to obtain rubber sheets of the required weight and size for vulcanization. The cut rubber sheets are vulcanized and formed under high temperature and high pressure conditions in a vulcanizing machine. The vulcanization temperature is 180℃ and the vulcanization time is 5 minutes to obtain molded semi-finished products. The semi-finished products are punched into individual rubber plugs through punching dies and a punching machine; (4) Cleaning and drying process: After cleaning the rubber stoppers with a rubber stopper cleaning machine, hot air drying is carried out in the drying stage, and the drying temperature is kept between 90℃. The finished product is obtained after drying for 120 minutes.

[0055] Comparative Example 4 Compound: 50kg chlorinated butyl rubber, 3.5kg calcined kaolin, 0.5kg stearic acid, 3kg precipitated hydrated silica, 1kg titanium dioxide, 0.1kg carbon black, 0.45kg alkylphenol disulfide, 2kg dimethyl silicone oil, and 1.5kg zinc oxide.

[0056] A method for preparing a low-ash rubber-plastic blend medical stopper, the specific process steps are as follows: (1) Preparation of compound: 50kg chlorinated butyl rubber, 3.5kg calcined kaolin, 0.5kg stearic acid, 1kg titanium dioxide, 0.1kg carbon black, 2kg dimethyl silicone oil, 1.5kg zinc oxide and 0.45kg alkylphenol disulfide are added to the internal mixer. After mixing, the rubber compound is discharged when the temperature is 120℃. The rubber compound is put into the open mill for open milling. The mixture is passed through the left and right sides once, thinly passed through, and pounded and turned to obtain the compound of the present invention. (2) Pre-forming, vulcanization, and punching process: The cooled compound is fed into an extruder, and the extruded rubber is calendered by a calender to obtain rubber sheets of the required weight and size for vulcanization. The cut rubber sheets are vulcanized under high temperature and high pressure conditions in a vulcanizing machine. The vulcanization temperature is 180℃ and the vulcanization time is 5 minutes to obtain molded semi-finished products. The semi-finished products are punched into individual rubber plugs through punching dies and a punching machine; (4) Cleaning and drying process: After cleaning the rubber stoppers with a rubber stopper cleaning machine, hot air drying is carried out in the drying stage, and the drying temperature is kept between 90℃. The finished product is obtained after drying for 120 minutes.

[0057] The results of ash content tests and hardness and physical property tests of the vulcanized test pieces of the low-ash rubber-plastic blend medical stopper products of Comparative Examples 1, 2, 3, and 4 of the present invention are shown in Table 9 below: Table 9

[0058] The low-ash rubber-plastic blend medical stopper products of Comparative Examples 1, 2, 3, and 4 of the present invention underwent rapid evaluation for drug compatibility. After encapsulating the drug-grade test product, it was inverted for 5 days at 60°C and 75% humidity, then dissolved and subjected to turbidity testing. The test results for the diaphragm stopper are shown in Table 10 below. Table 10

[0059] Comparative Examples 1, 2, 3, and 4 of this invention describe low-ash rubber-plastic blend medical stopper products. Adhesion performance tests were conducted on the products. A certain number of products were placed in aluminum foil bags and vacuum-sealed under a negative pressure of 0.1 MPa. The test conditions were: after being placed at 60°C and 75% humidity for 5 days, the products were removed, cooled to room temperature, and then opened. After opening, it was observed whether the products dispersed within 5 minutes. The test results are shown in Table 11 below. Table 11

[0060] The low-ash rubber-plastic blend medical stopper products of Comparative Examples 1, 2, 3, and 4 of this invention were tested according to the YBB00052005-2015 standard, and the test indicators are shown in Table 12: Table 12

Claims

1. A low-ash rubber-plastic blend medical stopper, characterized in that, The product comprises, by weight, the following raw materials: 100 parts chlorinated butyl rubber, 20-30 parts modified styrene-ethylene / butene-styrene block copolymer powder, 5-15 parts calcined kaolin, 4-10 parts precipitated hydrated silica, 1-3 parts titanium dioxide, 0.1-0.3 parts carbon black, 0.5-1.5 parts alkylphenol disulfide, and 2-5 parts zinc oxide; wherein the modified styrene-ethylene / butene-styrene block copolymer powder is composed of styrene-ethylene / butene-styrene... The block copolymer powder is prepared by surface modification with alkyl phosphonium laurate at a mass ratio of 6-10:1; the alkyl phosphonium laurate is selected from any one of tributylhexadecyl phosphonium laurate, trihexyldecyl phosphonium laurate, trihexyloctyl phosphonium laurate, trioctyltetradecyl phosphonium laurate, tripentyltetradecyl phosphonium laurate, tributyltetradecyl phosphonium laurate, trihexyloctadecyl phosphonium laurate, trihexylhexadecyl phosphonium laurate, and trihexyldodecyl phosphonium laurate.

2. The low-ash rubber-plastic blend medical stopper according to claim 1, characterized in that: 100 parts of chlorinated butyl rubber, 24 parts of modified styrene-ethylene / butene-styrene block copolymer powder, 10 parts of calcined kaolin, 6 parts of precipitated hydrated silica, 2 parts of titanium dioxide, 0.2 parts of carbon black, 0.9 parts of alkylphenol disulfide, and 3 parts of zinc oxide.

3. The method for preparing the low-ash rubber-plastic blend medical stopper according to any one of claims 1-2, characterized in that, Includes the following steps: S1. Preparation of modified styrene-ethylene / butene-styrene block copolymer powder: Styrene-ethylene / butene-styrene block copolymer powder and alkyl phosphonium laurate are put into a high-speed mixer and stirred and modified at high temperature for a period of time to obtain modified styrene-ethylene / butene-styrene block copolymer powder for later use. S2. Preparation of compound: In the first stage, chlorinated butyl rubber, calcined kaolin, precipitated hydrated silica, modified styrene-ethylene / butene-styrene block copolymer powder, titanium dioxide, and carbon black are added to the internal mixer for mixing. In the second stage, zinc oxide and alkylphenol disulfide are added for mixing. When the rubber compound temperature is 120±5℃, the rubber compound is discharged and put into a two-roll mill for two-roll milling. The mixture is obtained by pulling the blades on both sides once, thinly passing through, and tamping and turning. S3. Pre-forming, vulcanization, and punching process: The cooled compound is fed into an extruder, and the extruded rubber is calendered into rubber sheets by a calender. The cut rubber sheets are vulcanized in a vulcanizer under high temperature and high pressure to obtain molded semi-finished products. The semi-finished products are punched into individual rubber plugs by punching dies and a punching press. S4. Cleaning and drying process: After cleaning the rubber stoppers with a rubber stopper cleaning machine, hot air drying is carried out in the drying stage, maintaining the drying temperature between 85-95℃, and drying is carried out for 60-120 minutes to obtain the finished product.

4. The method for preparing low-ash rubber-plastic blend medical stoppers according to claim 3, characterized in that, In step S1, the styrene content in the styrene-ethylene / butene-styrene block copolymer powder is 25-30%.

5. The method for preparing low-ash rubber-plastic blend medical rubber stoppers according to claim 4, characterized in that, In step S1, the modified styrene-ethylene / butene-styrene block copolymer powder is prepared by adding styrene-ethylene / butene-styrene block copolymer powder and alkyl phosphonium laurate into a high-speed mixer at a mass ratio of 6-10:1 and stirring at 80-100℃ and a speed of 1000-1200 R / min for 30-45 minutes.

6. The method for preparing low-ash rubber-plastic blend medical stoppers according to claim 3, characterized in that, In step S2, the mixing temperature is 60-80℃ and the mixing time is 4-6 minutes.

7. The method for preparing low-ash rubber-plastic blend medical stoppers according to claim 3, characterized in that, In step S3, the vulcanization temperature is between 170-185℃ and the vulcanization time is between 4-6 minutes.

8. A medical rubber stopper, characterized in that, The low-ash rubber-plastic blend medical stopper prepared by the method described in any one of claims 3-7 has an ash content ≤15% and a Shore A hardness ≥48.

Images