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

Abstract

The invention relates to a low-ash rubber-plastic blending medical rubber plug and a preparation method thereof, and belongs to the technical field of medical packaging rubber. The formula of the rubber plug comprises the following components in parts by weight: chlorinated butyl rubber, modified styrene-ethylene / butylene-styrene block copolymer powder, calcined kaolin, precipitated hydrated silicon dioxide, titanium dioxide, carbon black, alkylphenol disulfide and zinc oxide. The preparation method comprises the following steps: firstly, carrying out surface modification on styrene-ethylene / butylene-styrene block copolymer powder and alkyl phosphonium laurate to obtain modified powder; and processing the chlorinated butyl rubber, the modified powder, the filler and the auxiliary agent into the rubber plug through processes of banburying, open milling, vulcanization molding and the like. Through a rubber and plastic blending structure of the modified SEBS powder, high hardness (Shore A hardness is greater than or equal to 48) is realized while low ash content (less than or equal to 15%) is ensured, the adhesion problem caused by insufficient hardness of a traditional low-ash rubber plug is effectively solved, puncture falling scraps are remarkably reduced, and the rubber plug is suitable for packaging high-standard medicines such as biological agents.

Description

A low-ash rubber-plastic blend medical stopper and its preparation method 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: The styrene-ethylene / butene-styrene block copolymer powder and alkyl phosphonium laurate are added to 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 a mixer for mixing. In the second stage, zinc oxide and alkylphenol disulfide are added for mixing. The compound is discharged when the temperature is 120±5℃. The rubber compound is placed in a two-roll mill for two-roll milling, with the rubber being pulled through on both sides once, thinly passed through, and pounded and turned to obtain the compounded rubber of the present invention; S3, preforming, vulcanization, and die-cutting process: the cooled compounded rubber is put into an extruder, the extruded rubber compound 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 stoppers through a die-cutting mold and a punching machine; 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 laurylate is [(C6H 13 3PC 10 H 21 ] + [CH3(CH2) 10 COO] - The structural formula of trihexyloctylphosphonium laurylate is [(C6H 13 )3PC8H17 ] + [CH3(CH2) 10 COO] - The structural formula of trioctyltetradecylphosphonium laurylate is [(C8H 17 3PC 14 H 29 ] + [CH3(CH2) 10 COO] - The structural formula of tripentyltetradecylphosphonium laurylate is [(C5H 11 3PC 14 H 29 ] + [CH3(CH2) 10 COO] - The structural formula of tributyltetradecylphosphonium laurylate is [(C4H9)3PC]. 14 H 29 ] + [CH3(CH2) 10 COO] - The structural formula of trihexyloctadecylphosphonium laurylate 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 was 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 rubber 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 is 29%) and 1 kg of trihexyldecylphosphonium laurate are added to a high-speed mixer and stirred and modified for 30 minutes at 80-100℃ and a speed of 1200R / min to obtain modified styrene-ethylene / butene-styrene block copolymer powder for later use; (2) Preparation of compound rubber: In the first stage, 50 kg of chlorinated butyl rubber, 5 kg of kaolin, 3 kg of precipitated hydrated silica, and 12 kg of modified styrene-ethylene / butene-styrene are added. Block copolymer powder, 1kg titanium dioxide and 0.1kg carbon black are added to the internal mixer and mixed at 80°C for 6 minutes. Then, the remaining 1.5kg zinc oxide and 0.45kg alkylphenol disulfide are added to the second stage and mixed. The rubber compound is discharged when the temperature is 120°C. The rubber compound is put into the open mill for open milling. The left and right blades are pulled once, thin pass, and pounded to obtain the compound of the present invention. (3) Pre-forming, vulcanization and punching process: The cooled compound is put into the extruder. The extruded rubber compound is calendered by the calender to obtain the weight and size of the rubber sheet required for vulcanization. The cut rubber sheet is vulcanized under the high temperature and high pressure of the vulcanizing machine. The vulcanization temperature is 180°C and the vulcanization time is 5 minutes to obtain the molded semi-finished product. The semi-finished products are punched into individual rubber stoppers using a punching die 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°C. 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 was 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 rubber 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 is 29%) and 1 kg of trihexyldecylphosphonium laurate are put into a high-speed mixer and stirred and modified for 30 minutes at 80-100℃ and a speed of 1200R / min to obtain modified styrene-ethylene / butene-styrene block copolymer powder for later use; (2) Preparation of compound rubber: In the first stage, 50 kg of chlorinated butyl rubber and 5 kg of... Kaolin, 3kg precipitated hydrated silica, 10kg modified styrene-ethylene / butene-styrene block copolymer powder, 1kg titanium dioxide, and 0.1kg carbon black were added to a mixer and mixed at 80°C for 6 minutes. Then, the remaining 1.5kg zinc oxide and 0.45kg alkylphenol disulfide were added to the second stage and mixed. The rubber compound was discharged when the temperature was 120°C. The rubber compound was then put into a two-roll mill for two-roll milling. The two mills were pulled on the left and right once, thinly passed through, and pounded and turned to obtain the compound of the present invention. (3) Pre-forming, vulcanization, and punching process: 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 rubber 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 is 29%) and 1 kg of trihexyldecylphosphonium laurate are put into a high-speed mixer and stirred and modified for 30 minutes at 80-100℃ and a speed of 1200R / min to obtain modified styrene-ethylene / butene-styrene block copolymer powder for later use; (2) Preparation of compound rubber: In the first stage, 50 kg of chlorinated butyl rubber and 6 kg of kaolin are mixed with chlorinated butyl rubber and 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 were added to a mixer and mixed at 80°C for 6 min. Then, the remaining 1.5 kg of zinc oxide and 0.45 kg of alkylphenol disulfide were added to the second stage and mixed. The rubber compound was discharged when the temperature was 120°C. The rubber compound was then put into a two-roll mill for two-roll milling. The two mills were pulled on the left and right once, thinly passed through, and pounded and turned to obtain the compound of the present invention. (3) Pre-forming, vulcanization, and punching process: the steps are the same as in Example 1. (4) Cleaning and drying process: the steps are the same as in Example 1.

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

[0034] According to Embodiments 1, 2, and 3 of this invention, a low-ash rubber-plastic blend medical stopper product was tested for rapid drug compatibility. 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 shown 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: Unlike Example 1, 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, and 3 kg of precipitated hydrated silica were added. 12kg of modified styrene-ethylene / butene-styrene block copolymer powder, 1kg of titanium dioxide, and 0.1kg of carbon black were added to a mixer and mixed at 80°C for 6 minutes. Then, the remaining 1.5kg of zinc oxide and 0.45kg of alkylphenol disulfide were added to the second stage and mixed. The rubber compound was discharged when the temperature was 120°C. The rubber compound was then put into a two-roll mill for two-roll milling. The two mills were pulled on the left and right once, thinly passed through, and pounded and turned to obtain the compound of the present invention. (3) Preforming, vulcanization, and die-cutting process: 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: Unlike Example 1, 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, and 3 kg of precipitated hydrated silica were added. 12kg of modified styrene-ethylene / butene-styrene block copolymer powder, 1kg of titanium dioxide, and 0.1kg of carbon black were added to a mixer and mixed at 80°C for 6 minutes. Then, the remaining 1.5kg of zinc oxide and 0.45kg of alkylphenol disulfide were added to the second stage and mixed. The rubber compound was discharged when the temperature was 120°C. The rubber compound was then put into a two-roll mill for two-roll milling. The two mills were pulled on the left and right once, thinly passed through, and pounded and turned to obtain the compound of the present invention. (3) Preforming, vulcanization, and die-cutting process: 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 tests and hardness and physical property tests 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] According to Examples 1, 4, and 5 of this invention, a low-ash rubber-plastic blend medical stopper product was tested for rapid drug compatibility. 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 shown 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 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 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 according to 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): The mass ratio of styrene-ethylene / butene-styrene block copolymer powder (styrene content of 29%) to stearic acid was 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 rubber 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 is 29%) and 1 kg of stearic acid are put into a high-speed mixer and stirred and modified for 30 minutes at 80-100℃ and a speed of 1200R / min to obtain modified styrene-ethylene / butene-styrene block copolymer powder for later use; (2) Preparation of compound rubber: In the first stage, 50 kg of chlorinated butyl rubber, 5 kg of kaolin, 3 kg of precipitated hydrated silica, and 12 kg of modified styrene-ethylene / butene-styrene block copolymer are mixed. After mixing polymer powder, 1kg titanium dioxide and 0.1kg carbon black in a mixer at 80°C for 6 minutes, the remaining 1.5kg zinc oxide and 0.45kg alkylphenol disulfide are added in the second stage and mixed. The rubber compound is discharged when the temperature is 120°C. The rubber compound is put into a rolling mill for rolling. The rolling mill is rolled once on each side, thinly passed through, and pounded to obtain the compound of the present invention. (3) Pre-forming, vulcanization and punching process: The cooled compound is put into an extruder. The extruded rubber compound is calendered by a calender to obtain the weight and size of the rubber sheet required for vulcanization. The cut rubber sheet is vulcanized under high temperature and high pressure conditions in a vulcanizing machine. The vulcanization temperature is 180°C and the vulcanization time is 5 minutes to obtain the molded semi-finished product. The semi-finished products are punched into individual rubber stoppers using a punching die 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°C. The finished product is obtained after drying for 120 minutes.

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

[0051] A method for preparing a low-ash rubber-plastic blend medical rubber stopper, the specific process steps are as follows: (1) Preparation of the 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 a 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. After mixing, the rubber compound is discharged when the temperature is 120℃. The rubber compound is put into a two-roll mill for two-roll milling. The two rolls are pulled once on each side, thinly passed through, and pounded and turned to obtain the mixed rubber compound of the present invention. (2) Pre-forming, vulcanization and punching process: The cooled mixed rubber compound is put into an extruder. The extruded rubber compound is calendered by a calender to obtain the weight and size of the rubber sheet required for vulcanization. The cut rubber sheet is vulcanized and formed under the high temperature and high pressure of the vulcanizing machine. The vulcanization temperature is 180℃ and the vulcanization time is 5min to obtain the molded semi-finished product. The semi-finished product is punched into individual rubber stoppers by punching mold and 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. The drying temperature is kept between 90℃ and the drying is carried out for 120min to obtain the finished product.

[0052] Comparative Example 3: Modified polyethylene powder (modified PE powder): The mass ratio of polyethylene powder to trihexyldecylphosphonium laurylate was 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 rubber 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 are added to a high-speed mixer and stirred and modified for 30 minutes at 80-100℃ and a speed of 1200 R / min to obtain modified polyethylene powder for later use; (2) 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 a mixer and mixed at 80℃ for 6 minutes. After adding the remaining 1.5 kg of zinc oxide and 0.45 kg of alkylphenol disulfide to the second stage for mixing, the rubber compound is discharged when the temperature is 120°C. The rubber compound is then put into a two-roll mill for two-roll milling. The two rolls are pulled once on each side, thinly passed through, and pounded to obtain the compound of the present invention. (3) Pre-forming, vulcanization, and punching process: The cooled compound is put into an extruder. The extruded rubber compound is calendered by a calender to obtain the weight and size of the rubber sheet required for vulcanization. The cut rubber sheet is vulcanized under high temperature and high pressure conditions in a vulcanizing machine. The vulcanization temperature is 180°C and the vulcanization time is 5 minutes to obtain the molded semi-finished product. The semi-finished product is punched into individual rubber stoppers by a punching die 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. The drying temperature is kept between 90°C and the drying time is 120 minutes to obtain the finished product.

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

[0056] A method for preparing a low-ash rubber-plastic blend medical rubber stopper, the specific process steps are as follows: (1) Preparation of compound rubber: 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 a mixer. After mixing, the rubber is discharged when the temperature of the rubber compound is 120℃. The rubber compound is put into a two-roll mill for two-roll milling. The two rolls are pulled once on each side, thinly passed through, and pounded and turned to obtain the compound rubber of the present invention; (2) Pre-forming, vulcanization, and punching process: The cooled compound rubber is put into an extruder. The extruded rubber is calendered by a calender to obtain the weight and size of the rubber sheet required for vulcanization. The cut rubber sheet is vulcanized and formed under high temperature and high pressure conditions in a vulcanizing machine. The vulcanization temperature is 180℃ and the vulcanization time is 5min to obtain the molded semi-finished product. The semi-finished products are punched into individual rubber stoppers using a punching die 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°C. The finished product is obtained after drying for 120 minutes.

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

[0058] The present invention provides comparative examples 1, 2, 3, and 4 of 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 turbidity testing. The results of the diaphragm stopper test 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 negative pressure (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 raw materials include, by weight, the following: 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 obtained by mixing styrene-ethylene / butene-styrene block copolymer powder with alkyl phosphonium laurate and then performing surface modification.

2. The low-ash rubber-plastic blend medical stopper according to claim 1, characterized in that: The mixture comprises 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. The modified styrene-ethylene / butene-styrene block copolymer powder is prepared by surface modification of styrene-ethylene / butene-styrene block copolymer powder and alkylphosphonium laurate at a mass ratio of 6-10:

1.

3. The low-ash rubber-plastic blend medical stopper according to claim 1 or 2, characterized in that: The alkylphosphonium laurate is selected from any one of tributylhexadecylphosphonium laurate, trihexyldecylphosphonium laurate, trihexyloctylphosphonium laurate, trioctyltetradecylphosphonium laurate, tripentyltetradecylphosphonium laurate, tributyltetradecylphosphonium laurate, trihexyloctadecylphosphonium laurate, trihexylhexadecylphosphonium laurate, and trihexyldodecylphosphonium laurate.

4. The method for preparing the low-ash rubber-plastic blend medical stopper according to any one of claims 1-3, characterized in that, The process includes the following steps: S1, Preparation of modified styrene-ethylene / butene-styrene block copolymer powder: The styrene-ethylene / butene-styrene block copolymer powder and alkyl phosphonium laurate are added to 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 a mixer for mixing. In the second stage, zinc oxide and alkylphenol disulfide are added for mixing. The temperature of the rubber compound is maintained at 1°C. The rubber compound is discharged at 20±5℃ and placed into a two-roll mill for two-roll milling. The rubber is then passed through a thin mill and pounded to obtain the compound of the present invention. S3, Pre-forming, vulcanization, and die-cutting process: The cooled compound is fed into an extruder and extruded. The extruded rubber is calendered into rubber sheets by a calender. The cut rubber sheets are vulcanized in a vulcanizing machine under high temperature and high pressure to obtain molded semi-finished products. The semi-finished products are punched into individual rubber stoppers by a die-cutting mold and a stamping machine. S4, Cleaning and drying process: After cleaning the rubber stoppers with a rubber stopper cleaning machine, they are dried with hot air in the drying stage. The drying temperature is maintained between 85-95℃ and the drying process is carried out for 60-120 minutes to obtain the finished product.

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

6. The method for preparing low-ash rubber-plastic blend medical rubber stoppers according to claim 5, 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.

7. The method for preparing low-ash rubber-plastic blend medical stoppers according to claim 6, characterized in that, 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.

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

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

10. 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 4-9 has an ash content ≤15% and a Shore A hardness ≥48.

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