Low-precipitate rubber plug formula

Abstract

The invention relates to the technical field of medicinal rubber plugs, and provides a low-precipitate rubber plug formula which comprises the following raw materials in parts by weight: 100 parts of EXXPRO3433 special elastomer, 50-80 parts of calcined kaolin, 2-3 parts of alkylphenol disulfide resin, 3-5 parts of zinc oxide, 1-3 parts of magnesium oxide, 2-3 parts of titanium dioxide and 0.1-0.3 part of carbon black. Alkylbenzene disulfide resin is used as a vulcanizing agent, the dosage of the alkylbenzene disulfide resin and the dosage of zinc oxide are accurately adjusted, the preparation processes of raw material matching, mixing, preforming, vulcanization forming, edge removing, cleaning, packaging and the like are carried out, the process parameters are strictly controlled, the appropriate vulcanization speed is achieved, and it is guaranteed that low free sulfur and zinc ions in the formula are leached out; and the composition has good compatibility with drugs, can ensure the stability of the drugs, and does not pollute the drugs during long-term storage.

Description

Technical Field

[0001] The invention relates to the technical field of medicinal rubber plugs, in particular to a formula of low-precipitate rubber plugs. Background Art

[0002] Medicine is a special commodity that is directly related to human health and safety. In addition to the intrinsic properties of the medicine, the packaging of the medicine, especially the packaging materials that are in direct contact with the medicine, also plays a decisive role in the medicine.

[0003] As a packaging material that directly contacts drugs, the internal cleanliness of rubber plugs has a great impact on drugs. Because the formula of butyl rubber plugs is complex and many types of raw materials are used, after being encapsulated with some drugs with relatively strong molecular activity, the internal components of the rubber plugs will be separated out, resulting in compatibility problems between the rubber plugs and drugs. When in contact with drugs for a long time, the small molecules in the rubber plugs will migrate into the drugs and contaminate the drugs, which can easily lead to drug failure or drug safety problems. The more prominent ones are some cephalosporins, some large infusions, and many Chinese medicine injection preparations.

[0004] Therefore, it has become a development trend for rubber bottle stoppers to select suitable materials to manufacture rubber bottle stoppers with low precipitation and reduce the possibility of precipitation. Summary of the invention

[0005] In view of the deficiencies in the prior art, the present invention provides a low-precipitate rubber stopper formula, which solves the problem that traditional rubber bottle stoppers have high precipitates and are prone to adverse effects on drugs after long-term use.

[0006] To achieve the above objectives, the present invention is implemented through the following technical scheme: a low precipitate rubber plug formula, comprising the following raw materials in parts by weight: 100 parts of EXXPRO3433 special elastomer, 50-80 parts of calcined kaolin, 2-3 parts of alkylphenol disulfide resin, 3-5 parts of zinc oxide, 1-3 parts of magnesium oxide, 2-3 parts of titanium dioxide and 0.1-0.3 parts of carbon black.

[0007] Preferably, the following raw materials are included in parts by weight: 100 parts of EXXPRO3433 special elastomer, 65 parts of calcined kaolin, 2 parts of alkylphenol disulfide resin, 4 parts of zinc oxide, 2 parts of magnesium oxide, 2 parts of titanium dioxide and 0.2 parts of carbon black.

[0008] Preferably, a method for preparing a low-precipitate rubber plug comprises the following steps:

[0009] S1. Mixing: After the incoming raw materials have passed the inspection, they are accurately mixed according to the formula, and the mixed raw materials are put into the internal mixer for internal mixing. The mixed rubber materials are transferred to the open mixer for internal mixing, and various raw materials are fully mixed;

[0010] S2. Preforming: The mixed rubber is extruded by an extruder, the extruded rubber is calendered by a calender, and after calendering, it is cooled to room temperature and then cut into pieces;

[0011] S3. Vulcanization molding: The rubber pieces are chemically cross-linked and vulcanized in the vulcanization equipment;

[0012] S4. Edge removal: The vulcanized rubber sheet is punched out using a punching die to obtain a low-precipitate rubber plug.

[0013] Preferably, in S1, the banburying temperature is controlled at 100-120° C., the banburying time is 10-15 minutes, the open-mixing roll temperature is controlled at 40-60° C., and the open-mixing time is 5-8 minutes.

[0014] Preferably, the extrusion temperature of the extruder in S2 is 80-100°C, and the calendering roller temperature is 60-80°C.

[0015] Preferably, the rubber material cut into pieces in S2 is stored in an environment with a temperature of 20-25° C. and a humidity of 40%-60% for future use.

[0016] Preferably, in S3, the vulcanization temperature is 150-170° C., the vulcanization pressure is 10-15 MPa, and the vulcanization time is 10-15 minutes.

[0017] Preferably, S4 further comprises washing the obtained rubber plug with pure water or deionized water, and packaging and storing the rubber plug in a ziplock bag after drying.

[0018] The present invention provides a low-precipitate rubber plug formula, which has the following beneficial effects:

[0019] The raw rubber of the present invention uses EXXPRO3433 special elastomer as a core matrix material, uses alkyl phenyl phenoxide disulfide resin as a vulcanizing agent, accurately mixes the dosage of alkyl phenyl phenoxide disulfide resin and zinc oxide, achieves a suitable vulcanization speed, ensures lower leaching of free sulfur and zinc ions in the formula, has good compatibility with drugs, can ensure the stability of drugs, and does not contaminate drugs during long-term storage. DETAILED DESCRIPTION

[0020] The following will be combined with the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of the present invention.

[0021] Embodiment 1:

[0022] The embodiment of the present invention provides a low-precipitate rubber plug formula, including 100 parts of EXXPRO3433 special elastomer, 50 parts of calcined kaolin, 2 parts of alkylphenol disulfide resin, 3 parts of zinc oxide, 1 part of magnesium oxide, 2 parts of titanium dioxide, and 0.1 part of carbon black.

[0023] A method for preparing a low-precipitate rubber plug comprises the following steps:

[0024] Mixing: put the weighed raw materials into an internal mixer, set the rotor speed of the internal mixer to 30 rpm, control the internal mixing temperature at 100°C, and mix for 10 minutes; then transfer to an open mixer, set the roller temperature at 40°C, and mix for 5 minutes;

[0025] Preforming: The mixed rubber is extruded by an extruder, the extruder screw speed is 20 rpm, and the extrusion temperature is 80°C; it is calendered by a calender, the calender roller temperature is 60°C, and the calender roller line speed is 5 m / min. After cooling to room temperature (cooling rate 5°C / min), the pieces are cut and stored in an environment with a temperature of 20°C and a humidity of 40%;

[0026] Vulcanization molding: Vulcanization in vulcanization equipment, vulcanization temperature 150℃, vulcanization pressure 10MPa, vulcanization time 10 minutes;

[0027] Edge removal: Use punching die to punch, punching pressure 5MPa;

[0028] Cleaning: Use pure water, the water temperature is 30℃, and the cleaning time is 3 minutes.

[0029] Specifically, in the mixing stage, the temperature and time of internal and open mixing are precisely controlled to ensure uniform dispersion of the raw materials and form a stable internal structure, laying a solid foundation for the subsequent performance of the rubber plug. In the preforming step, the parameter settings of extrusion, calendering and cooling pieces ensure the accuracy and consistency of rubber molding, making the rubber plug accurate in size and smooth in appearance. In the vulcanization molding stage, the specific vulcanization temperature, pressure and time range are used to achieve perfect cross-linking of the rubber, further optimize the mechanical properties of the rubber plug, and give it good sealing, compression resistance and rebound performance. Finally, the cleaning process after edge removal combined with appropriate drying and self-sealing bag packaging and storage not only completely removes impurities on the surface of the rubber plug, but also prevents secondary pollution by isolating it from the external environment, thereby maintaining the low precipitation and high cleanliness of the rubber plug to the greatest extent.

[0030] Embodiment 2:

[0031] The embodiment of the present invention provides a low-precipitate rubber plug formula, including 100 parts of EXXPRO3433 special elastomer, 65 parts of calcined kaolin, 2.5 parts of alkylphenol disulfide resin, 4 parts of zinc oxide, 2 parts of magnesium oxide, 2.5 parts of titanium dioxide, and 0.2 parts of carbon black.

[0032] A method for preparing a low-precipitate rubber plug comprises the following steps:

[0033] Mixing: The raw materials were put into the internal mixer, the rotor speed of the internal mixer was 40 rpm, the internal mixing temperature was 110°C, and the internal mixing time was 13 minutes; then the raw materials were transferred to the open mixer, the temperature of the open mixing roller was 50°C, and the open mixing time was 6.5 minutes;

[0034] Preforming: extrusion of rubber compound, extruder screw speed 25 rpm, extrusion temperature 90°C, calendering, calender roller temperature 70°C, calender roller linear speed 7.5 m / min, cooling (cooling rate 7.5°C / min) and storage in an environment with a temperature of 22°C and a humidity of 50% after cutting;

[0035] Vulcanization molding: vulcanization temperature 160°C, vulcanization pressure 12.5MPa, vulcanization time 12.5 minutes;

[0036] Edge removal: Punching by punching die, punching pressure 6.5MPa;

[0037] Cleaning: Deionized water, water temperature 35°C, cleaning time 4 minutes.

[0038] Embodiment three:

[0039] The embodiment of the present invention provides a low-precipitate rubber plug formula, including 100 parts of EXXPRO3433 special elastomer, 80 parts of calcined kaolin, 3 parts of alkylphenol disulfide resin, 5 parts of zinc oxide, 3 parts of magnesium oxide, 3 parts of titanium dioxide, and 0.3 parts of carbon black.

[0040] A method for preparing a low-precipitate rubber plug comprises the following steps:

[0041] Mixing: put into internal mixer, the rotor speed of internal mixer is 50 rpm, the internal mixing temperature is 120℃, and the internal mixing time is 15 minutes; switch to open mixer, the temperature of open mixing roller is 60℃, and the open mixing time is 8 minutes;

[0042] Preforming: extrusion of rubber compound, extruder screw speed 30 rpm, extrusion temperature 100°C; calendering, calender roller temperature 80°C, calender roller line speed 10 m / min, cooling (cooling rate 10°C / min) and storage in an environment with a temperature of 25°C and a humidity of 60% after cutting;

[0043] Vulcanization molding: vulcanization temperature 170℃, vulcanization pressure 15MPa, vulcanization time 15 minutes;

[0044] Edge removal: Punching by punching die, punching pressure 8MPa;

[0045] Cleaning: Use pure water, the water temperature is 40℃, and the cleaning time is 5 minutes.

[0046] Comparative example: The traditional butyl rubber plug formula includes 100 parts of butyl rubber, 2.5 parts of carbon black, 0.8 parts of stearic acid, 2.5 parts of zinc oxide, 0.8 parts of accelerator M, and 1.5 parts of sulfur.

[0047] The preparation method comprises:

[0048] Mixing: Put butyl rubber into a mixer for mixing. After mixing for 10 minutes, add carbon black, stearic acid, zinc oxide and accelerator M. Continue mixing for 6 minutes and then transfer the rubber to an open mixer for mixing. At this time, add sulfur and mix for 3 minutes to ensure uniformity.

[0049] Preforming: The mixed rubber is extruded through an extruder, and the extruded rubber is calendered by a calender, and then naturally cooled to room temperature;

[0050] Vulcanization molding: Vulcanize in the vulcanizing equipment for 12 minutes.

[0051] Edge removal: Use a punching die to punch out the butyl rubber plug.

[0052] The rubber plug precipitate detection was carried out for the above three embodiments and comparative examples, and the precipitate in the rubber plug was quantitatively analyzed by high performance liquid chromatography, and the specific steps were as follows: the rubber plug sample was placed in a specific simulated extraction medium, such as physiological saline, and soaked for 72 hours at room temperature and under shaking conditions, and then the soaking liquid was filtered through a 0.45 μm filter membrane and detected by HPLC, and the type and content of the precipitate in the rubber plug sample were compared and calculated according to the chromatographic peak retention time and peak area of ​​the known standard substance;

[0053] The test results are as follows: under the above-mentioned test conditions, the total amount of precipitates of the low-precipitate rubber stoppers prepared in the three embodiments is less than 10 μg / mL, wherein the main precipitates are a very small amount of unreacted alkylphenol disulfide resin and its decomposition products, with a content in the microgram level, and the dissolution amount of other inorganic substances such as kaolin and titanium dioxide is extremely low and almost negligible; the traditional butyl rubber stoppers are tested and the total amount of precipitates is as high as 40 μg / mL or more. In addition to containing a large amount of unreacted promoters and their derivatives, there are also precipitates of substances such as stearic acid. These precipitates may not only affect the quality of the drug, but also pose potential safety risks, which is in sharp contrast to the low-precipitate rubber stoppers in the embodiments.

[0054] In summary, the rubber plug of the present invention has good chemical stability and low precipitation characteristics, and can effectively avoid contamination of drugs.

[0055] Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions and variations may be made to the embodiments without departing from the principles and spirit of the present invention, and that the scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. A low-precipitate rubber plug formula, characterized in that: The invention comprises the following raw materials in parts by weight: 100 parts of EXXPRO3433 special elastomer, 50-80 parts of calcined kaolin, 2-3 parts of alkylphenol disulfide resin, 3-5 parts of zinc oxide, 1-3 parts of magnesium oxide, 2-3 parts of titanium dioxide and 0.1-0.3 parts of carbon black.

2. A low precipitate rubber plug formula according to claim 1, characterized in that: The invention comprises the following raw materials in parts by weight: 100 parts of EXXPRO3433 special elastomer, 65 parts of calcined kaolin, 2 parts of alkylphenol disulfide resin, 4 parts of zinc oxide, 2 parts of magnesium oxide, 2 parts of titanium dioxide and 0.2 parts of carbon black.

3. A method for preparing a low-precipitate rubber plug, using a low-precipitate rubber plug formula as described in any one of claims 1-2, characterized in that: The following steps are involved: S1. Mixing: After the incoming raw materials have passed the inspection, they are accurately mixed according to the formula, and the mixed raw materials are put into the internal mixer for internal mixing. The mixed rubber materials are transferred to the open mixer for internal mixing, and various raw materials are fully mixed; S2. Preforming: The mixed rubber is extruded by an extruder, the extruded rubber is calendered by a calender, and after calendering, it is cooled to room temperature and then cut into pieces; S3. Vulcanization molding: The rubber pieces are chemically cross-linked and vulcanized in the vulcanization equipment; S4. Edge removal: The vulcanized rubber sheet is punched out using a punching die to obtain a low-precipitate rubber plug.

4. The method for preparing a low-precipitate rubber plug according to claim 3, characterized in that: In S1, the banburying temperature is controlled at 100-120° C., the banburying time is 10-15 minutes, the open-mixing roll temperature is controlled at 40-60° C., and the open-mixing time is 5-8 minutes.

5. The method for preparing a low-precipitate rubber plug according to claim 3, characterized in that: The extrusion temperature of the extruder in S2 is 80-100°C, and the temperature of the calendering roller is 60-80°C.

6. The method for preparing a low-precipitate rubber plug according to claim 3, characterized in that: The cut rubber material in S2 is stored in an environment with a temperature of 20-25° C. and a humidity of 40%-60% for later use.

7. The method for preparing a low-precipitate rubber plug according to claim 3, characterized in that: In the S3, the vulcanization temperature is 150-170° C., the vulcanization pressure is 10-15 MPa, and the vulcanization time is 10-15 minutes.

8. The method for preparing a low-precipitate rubber plug according to claim 3, characterized in that: The step S4 further comprises washing the obtained rubber plug with pure water or deionized water, and packaging and storing the rubber plug in a ziplock bag after drying.