A medical film-coated rubber stopper and a method for manufacturing the same

Abstract

The application discloses a film-coated rubber plug for medicine, which comprises a neck part and a crown part of the rubber plug, the surface of the neck part of the rubber plug is coated with an inert film, the film-coated part extends from the bottom surface of the neck part of the rubber plug to the joint with the crown part, and the top surface of the neck part of the rubber plug is provided with a plurality of connecting protrusions. The application further discloses a preparation method of the film-coated rubber plug for medicine, which comprises the following steps: pretreatment, film pasting, primary vulcanization, primary punching, secondary vulcanization, secondary punching, and obtaining the film-coated rubber plug. The film and the rubber are subjected to electric activation pretreatment before rubber film coating, so that the adhesion strength of the film and the rubber is increased, and the problem of film peeling is reduced. In the application, the film is only subjected to low-temperature vulcanization once, so that the film damage is reduced, the film is not easy to age, the quality of the rubber plug is improved, and the safety of medicine use is ensured.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical packaging materials technology, and in particular to a pharmaceutical coated rubber stopper and its preparation method. Background Technology

[0002] Currently, pharmaceutical injection and infusion drugs are packaged with rubber stoppers. Although pharmaceutical rubber stoppers have excellent cleanliness, chemical stability, airtightness, and biological properties, due to the complex formulation of the stopper and the concentration gradient of the added raw materials, they are easily absorbed, adsorbed, leached, or permeated by some drugs with strong molecular activity after encapsulation, which may lead to the risk of drug deterioration.

[0003] To address the aforementioned issues, coated rubber stoppers have been introduced in recent years, which involve coating the surface of the rubber stopper with a film. The existing manufacturing process for coated rubber stoppers involves attaching a thin film to one side of an extruded rubber sheet, then vulcanizing it in a vulcanizing mold, followed by punching and cleaning to produce a semi-finished product coated with the film. This semi-finished product is then inserted into a secondary molding vulcanizing mold, and rubber material is added on top for a secondary vulcanization. The vulcanized rubber sheet is then punched and cleaned to obtain the final product.

[0004] When using conventional methods for lamination, the following problems often arise: After the film material and rubber are hot-pressed together, they are shaped together in the vulcanization process to form the stopper neck. Due to the difference in material properties, bulging and poor adhesion can easily occur between the film material and the rubber. In the subsequent cleaning process, the film layer is also prone to peeling off, resulting in a low yield. Furthermore, during the vulcanization heat sealing process between the stopper neck and crown, the film has to undergo secondary vulcanization at high temperatures, which can damage the film, make it prone to aging, reduce its shielding performance and service life, and thus affect the quality of the packaged medicine. Summary of the Invention

[0005] The purpose of this invention is to address the shortcomings of the prior art by providing a medical coated rubber stopper and its preparation method.

[0006] To solve the above problems, the technical solution adopted by the present invention is as follows:

[0007] A medical-grade coated rubber stopper includes a neck and a crown. The surface of the neck is covered with a thin film, and the film extends from the bottom surface of the neck to the connection point with the crown. A plurality of connecting protrusions are provided on the top surface of the neck.

[0008] Furthermore, the film is one of ethylene-tetrafluoroethylene copolymer film, polytetrafluoroethylene film, polyethylene film, and polypropylene film.

[0009] A method for preparing a medical-grade coated rubber stopper includes the following steps:

[0010] Step 1) Pretreatment: Electroactivate one side of the membrane surface and electroactivate one side of the film surface;

[0011] Step 2) Film application: The film and the film, after being electro-activated, are flatly bonded together, and a pressure roller is used to heat-press the film and the film together. The temperature of the pressure roller is 70-90℃.

[0012] Step 3) First vulcanization: Place the flat-fitted film-coated sheet into the vulcanizing machine for vulcanization, using the first vulcanization mold to obtain the neck piece of the film-coated rubber stopper.

[0013] Step 4) First punching: Punch the neck of the coated rubber stopper to obtain the neck of the coated rubber stopper for later use;

[0014] Step 5) Secondary vulcanization: Place the neck of the coated rubber stopper into the second vulcanization mold, place unvulcanized rubber above the neck of the rubber stopper, and perform secondary molding and vulcanization. The neck and crown of the rubber stopper are integrated to obtain a coated rubber stopper sheet.

[0015] Step 6) Secondary punching: The coated rubber stopper is punched and cleaned to obtain the coated rubber stopper.

[0016] Furthermore, in step 1), the electrical activation discharge power is 1-4 kW, and the processing time is 15-60 s.

[0017] Furthermore, in step 3), the primary vulcanization temperature is 120-150℃, the pressure is 15-25 MPa, and the time is 10-15 min; in step 5), the secondary vulcanization temperature is 150-170℃, the pressure is 15-25 MPa, and the time is 10-15 min.

[0018] Furthermore, the first vulcanizing mold includes a first upper mold and a first lower mold. The first upper mold is provided with a first upper mold cavity, and the first lower mold is provided with a first lower mold cavity. In the mold-closed state, the first upper mold cavity and the first lower mold cavity cooperate to form a molding cavity. The first upper mold and the first lower mold are respectively provided with heating cavities, and the heating cavities are provided with heating holes, which are connected to heat transfer pipes.

[0019] Furthermore, the second vulcanizing mold includes a second upper mold, a middle mold, and a second lower mold. The second upper mold has a second upper mold cavity, the middle mold has a middle mold cavity, and the second lower mold has a second lower mold cavity. In the closed state, the second upper mold cavity, the middle mold cavity, and the second lower mold cavity cooperate to form a molding cavity. The second upper mold and the middle mold are provided with heating chambers, and the heating chambers are provided with heating holes that are connected to heat transfer pipes. The second lower mold is provided with cooling chambers, and the cooling chambers are provided with cooling holes that are connected to refrigeration pipes.

[0020] The beneficial effects of adopting the above technical solution are as follows:

[0021] Compared with the previous rubber stopper coating process, the present invention pre-treats the membrane and the film with electro-activation (surface corona) before rubber coating, so that the surface of the membrane is roughened and the surface activity is increased, thereby increasing the bonding strength. The other side of the membrane needs to be in direct contact with the drug, so no surface treatment is required. The extremely low surface tension can reduce the adsorption of the drug. The film has good density, which can ensure good shielding performance and stability with the drug.

[0022] Corona treatment (also known as electrical discharge treatment) involves applying a high voltage and high frequency of 2-100kV and 2-10kHz to a discharge electrode, generating a large amount of plasma gas ozone. This ozone interacts directly or indirectly with the molecules on the surface of polymer materials, causing polar groups such as carbonyl groups and nitrogen-containing groups to be generated on the molecular chains of the polymer materials, increasing the surface tension. The strong ion impact roughens the surface of the polymer materials, removing oil, moisture and dirt, and significantly improving the adhesion of the polymer material surface.

[0023] The film surface is subjected to corona treatment. During the discharge treatment process, in addition to electrons and ions, there are also intermediate excitation species such as free radicals and ozone, as well as ultraviolet and visible light emitted by the excitation species. These lights interact with the polymer surface, modify the rubber surface, and introduce functional groups through cross-linking and oxidation to improve the adhesion of the rubber.

[0024] The rubber stopper undergoes two vulcanization processes. The first is a low-temperature vulcanization, during which the membrane material and rubber undergo chemical cross-linking and become tightly bonded to each other. During the second high-temperature vulcanization, the coated part is kept in a normal or low-temperature environment to avoid damage to the membrane, making the membrane less prone to aging, improving product quality, and ensuring medication safety. Attached Figure Description

[0025] Figure 1 This is a schematic diagram of the rubber stopper structure in this invention;

[0026] Figure 2 This is a schematic diagram of the neck structure of the rubber stopper in this invention;

[0027] Figure 3 This is a schematic diagram of the structure of the first vulcanizing mold in this invention;

[0028] Figure 4 This is a schematic diagram of the structure of the second vulcanizing mold in this invention.

[0029] In the diagram: 1. Neck; 2. Crown; 3. Membrane; 4. Connecting protrusion; 5. First upper mold; 6. First lower mold; 7. Heating chamber; 8. Heat transfer pipe; 9. Second upper mold; 10. Middle mold; 11. Second lower mold; 12. Cooling chamber; 13. Refrigeration pipe. Detailed Implementation

[0030] The embodiments of the present invention will be described in further detail below with reference to the accompanying drawings and examples. The following examples are for illustrative purposes only and should not be construed as limiting the scope of the invention.

[0031] like Figure 1-4 The figure shows a specific embodiment of a medical-grade coated rubber stopper disclosed in this invention. This embodiment includes a neck 1 and a crown 2 of the stopper, which are formed by vulcanization and hot pressing. The surface of the neck 1 of the stopper is covered with a thin film 3, which extends from the bottom surface of the neck 1 to the connection with the crown 2. The top surface of the neck 1 of the stopper is provided with multiple connecting protrusions 4, which not only facilitates the connection with the crown during secondary vulcanization, but also does not affect the room temperature setting of the neck coated part. The bottom of the neck 1 of the stopper can be a two-pronged, three-pronged, or four-pronged structure or other commonly used structures.

[0032] Furthermore, the film 3 is any one of ethylene-tetrafluoroethylene copolymer film, polytetrafluoroethylene film, polyethylene film, and polypropylene film.

[0033] Furthermore, the rubber stopper is a medical rubber stopper. In this invention, chlorobutyl rubber stopper is selected, which is existing technology and will not be described in detail here.

[0034] A method for preparing a medical-grade coated rubber stopper includes the following steps:

[0035] Step 1) Pretreatment: Electroactivate one side of the diaphragm surface and electroactivate one side of the film surface. Electroactivating one side of the diaphragm surface roughens the surface, increases the surface area, and improves the adhesion. Electroactivating the film surface involves the release of free radicals, ozone, and other intermediate excitation species, as well as ultraviolet and visible light emitted by these excitation species, in addition to electrons and ions. These light interact with the polymer surface, modifying the rubber surface and introducing functional groups through crosslinking and oxidation, thereby improving the adhesiveness of the rubber.

[0036] Step 2) Film application: The film and the film, after being electro-activated, are flatly bonded together, and a pressure roller is used to heat-press the film and the film together. The temperature of the pressure roller is 70-90℃.

[0037] Step 3) First vulcanization: Place the flat-fitted film-coated sheet into the vulcanizing machine for vulcanization, using the first vulcanization mold to obtain the neck piece of the film-coated rubber stopper.

[0038] Step 4) First punching: Punch the neck piece of the coated rubber stopper to obtain the neck 1 of the coated rubber stopper for later use;

[0039] Step 5) Secondary vulcanization: Place the neck 1 of the coated rubber stopper into the second vulcanization mold, place unvulcanized rubber above the neck 1 of the rubber stopper, and perform secondary molding and vulcanization. The neck 1 and crown 2 of the rubber stopper are integrated to obtain the coated rubber stopper sheet.

[0040] Step 6) Secondary punching: The coated rubber stopper is punched and cleaned to obtain the coated rubber stopper.

[0041] Furthermore, in step 1), the electrical activation discharge power is 1-4 kW, and the processing time is 15-60 s.

[0042] Furthermore, in step 3), the primary vulcanization temperature is 120-150℃, the pressure is 15-25 MPa, and the time is 10-15 min; in step 5), the secondary vulcanization temperature is 150-170℃, the pressure is 15-25 MPa, and the time is 10-15 min.

[0043] Furthermore, the first vulcanizing mold includes a first upper mold 5 and a first lower mold 6. The first upper mold 5 is provided with a first upper mold cavity, and a groove is provided at the top of the first upper mold cavity for forming the connecting protrusion 4 of the rubber stopper neck 1. The first lower mold 6 is provided with a first lower mold cavity for forming the bottom structure of the rubber stopper neck. In the mold-closed state, the first upper mold cavity and the first lower mold cavity cooperate to form the compression molding cavity of the rubber stopper neck 1. The first upper mold 5 and the first lower mold 6 are respectively provided with heating cavities 7. The heating cavities 7 are provided with heating holes, and the heating holes are connected to the heat transfer pipe 8 for introducing a heat medium to vulcanize the rubber at high temperature.

[0044] Furthermore, the second vulcanizing mold includes a second upper mold 9, a middle mold 10, and a second lower mold 11. The second upper mold 9 is provided with a second upper mold cavity for molding the crown 2 of the rubber stopper. The middle mold 10 is provided with a middle mold cavity for molding the connection between the crown 2 and the neck 1 of the rubber stopper. The second lower mold 11 is provided with a second lower mold cavity for placing the neck 1 of the rubber stopper. In the mold-closed state, the second upper mold cavity, the middle mold cavity, and the second lower mold cavity cooperate to form the molding cavity of the rubber stopper. The second upper mold 9 and the middle mold 10 are provided with heating chambers 7, and the heating chambers 7 are provided with heating holes. The heating hole is connected to the heat transfer pipe 8. The rubber in the second upper mold 9 and the middle mold 10 is vulcanized and connected under high temperature and high pressure. The second lower mold 11 is provided with a cooling chamber 12. The cooling chamber 12 is provided with cooling holes. The cooling holes are connected to the refrigeration pipe 13. Cooling liquid is introduced into the cooling chamber 12 through the refrigeration pipe 13. The temperature of the cooling liquid is 15-25℃, which ensures that the second lower mold 11 is in a normal temperature or low temperature state. This can prevent the outer film of the rubber stopper neck 1 from being subjected to secondary high temperature during the secondary vulcanization process, reduce film damage and aging, and ensure its shielding performance and service life.

[0045] Furthermore, the vulcanizing machine is selected from one of the following: a vacuum vulcanizing machine, a conventional molding vulcanizing machine, or an injection vulcanizing machine.

[0046] Example 1

[0047] This invention discloses a specific embodiment of a medical-grade coated rubber stopper. The embodiment includes a neck 1 and a crown 2 of the stopper, which are formed by vulcanization and hot pressing. The surface of the neck 1 of the stopper is coated with an ethylene-tetrafluoroethylene copolymer film, and the coated portion extends from the bottom surface of the neck 1 to the connection with the crown 2. The top surface of the neck 1 of the stopper is provided with a plurality of connecting protrusions 4.

[0048] This invention also discloses a method for preparing a medical-grade coated rubber stopper, comprising the following steps:

[0049] Step 1) Pretreatment: Electroactivate one side of the membrane surface with an electroactivation discharge power of 1 kW and a treatment time of 15 s; electroactivate one side of the film surface with an electroactivation discharge power of 1 kW and a treatment time of 60 s.

[0050] Step 2) Film application: The film and the film, after being electro-activated, are flatly bonded together, and a pressure roller is used to heat-press the film and the film together. The temperature of the pressure roller is 80℃.

[0051] Step 3) First vulcanization: Place the flat-fitted film sheet into the vulcanizing machine for vulcanization. Use the first vulcanization mold, the vulcanization temperature is 130℃ (temperature of the first upper mold and the first lower mold), the pressure is 20Mpa, and the time is 10min to obtain the neck piece of the film-coated rubber stopper.

[0052] Step 4) First punching: Punch the neck piece of the coated rubber stopper to obtain the neck of the coated rubber stopper for later use;

[0053] Step 5) Secondary vulcanization: Place the neck 1 of the coated rubber stopper into the second vulcanization mold, place the unvulcanized rubber above the neck 1 of the rubber stopper, and perform secondary molding and vulcanization. The vulcanization temperature is 160℃ (the temperature of the second upper mold and the middle mold, and the temperature of the second lower mold is 20℃), the pressure is 25Mpa, and the time is 15min. The neck 1 and the crown 2 of the rubber stopper are integrated to obtain the coated rubber stopper sheet.

[0054] Step 6) Secondary punching: The coated rubber stopper is punched and cleaned to obtain the coated rubber stopper.

[0055] Example 2

[0056] The difference from Example 1 is that in step 1) of the preparation method of the coated rubber stopper, the pretreatment is as follows: one side surface of the membrane is electroactivated with an electroactivation discharge power of 2 kW and a treatment time of 15 s, and one side surface of the film is electroactivated with an electroactivation discharge power of 2 kW and a treatment time of 60 s.

[0057] Example 3

[0058] The difference from Example 1 is that in step 1) of the preparation method of the coated rubber stopper, the pretreatment is as follows: one side surface of the membrane is electro-activated with an electro-activation discharge power of 3 kW and a treatment time of 15 s, and one side surface of the film is electro-activated with an electro-activation discharge power of 3 kW and a treatment time of 60 s.

[0059] Example 4

[0060] The difference from Example 1 is that in step 1) of the preparation method of the coated rubber stopper, the pretreatment is as follows: one side surface of the membrane is electro-activated with an electro-activation discharge power of 4 kW and a treatment time of 15 s, and one side surface of the film is electro-activated with an electro-activation discharge power of 4 kW and a treatment time of 60 s.

[0061] Comparative Example 1

[0062] The difference from Example 1 is that the preparation method of the coated rubber stopper does not involve electroactivation treatment of the diaphragm and the film.

[0063] Comparative Example 2

[0064] The difference from Example 2 is that in step 5) of the preparation method of the coated rubber stopper: the neck 1 of the coated rubber stopper is placed in the second vulcanization mold, and unvulcanized rubber is placed above the neck 1 of the rubber stopper. Secondary molding and vulcanization is carried out. The vulcanization temperature is 160℃ (the temperature of the second upper mold, middle mold and second lower mold), the pressure is 25Mpa and the time is 15min. The neck 1 and the crown 2 of the rubber stopper are integrated to obtain the coated rubber stopper sheet.

[0065] The performance of the rubber stoppers prepared in Examples 1-4 and Comparative Examples 1-2 was tested, and the test results are shown in Table 1.

[0066] 1. Appearance: Take 1000 pieces of this product and inspect them according to GB / T2828.1-2012 "Sampling Procedures for Inspection by Attributes - Part 1: Sampling Schemes for Lot Inspection Retrieved by Acceptable Quality Limit (AQL)".

[0067] Appearance pass rate = (Total number of rubber stoppers inspected - Number of rubber stoppers with unacceptable appearance) / Total number of rubber stoppers inspected * 100%

[0068] 2. Coating strength: Take 1000 pieces of this product and stack them naturally in an open stainless steel cup. Place them in a high-pressure steam sterilizer at 121±2℃ for 30 minutes. Remove them and place them in a 60℃ oven for 60 minutes. Remove them and allow them to cool naturally to room temperature in the air. Observe that there should be no delamination between the film layer and the adhesive layer.

[0069] The pass rate of the coating composite strength is calculated as follows: (Total number of rubber plugs tested - Number of rubber plugs with bulging or delamination in the membrane layer) / Total number of rubber plugs tested * 100%.

[0070] Table 1. Test Structure for Coated Rubber Stoppers

[0071]

[0072] As shown in Table 1, electro-activation treatment of the film and the film can effectively reduce phenomena such as bulging, poor adhesion, and film peeling between the film and the rubber, and enhance the bonding strength between the film and the rubber. Furthermore, the film does not undergo secondary high-temperature vulcanization, which can effectively reduce film damage and improve product quality.

[0073] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A method for preparing a medical-grade coated rubber stopper, comprising a neck (1) and a crown (2) of the stopper, characterized in that, The neck (1) surface of the rubber stopper is covered with a thin film (3), and the film extends from the bottom surface of the neck (1) of the rubber stopper to the connection with the crown (2). The top surface of the neck (1) of the rubber stopper is provided with multiple connecting protrusions (4). The method for preparing the medical-grade coated rubber stopper is characterized by comprising the following steps: Step 1) Pretreatment: Electroactivate one side of the membrane surface and electroactivate one side of the film surface; Step 2) Film application: The film and the film, after being electro-activated, are flatly bonded together, and a pressure roller is used to heat-press the film and the film together. The temperature of the pressure roller is 70-90℃. Step 3) First vulcanization: Place the flat-fitted film-coated sheet into the vulcanizing machine for vulcanization, using the first vulcanization mold to obtain the neck piece of the film-coated rubber stopper. Step 4) First punching: Punch the neck piece of the coated rubber stopper to obtain the neck (1) of the coated rubber stopper for later use; Step 5) Secondary vulcanization: Place the neck (1) of the coated rubber stopper into the second vulcanization mold, place unvulcanized rubber above the neck (1) of the rubber stopper, and perform secondary molding and vulcanization. The neck (1) of the rubber stopper and the crown (2) are integrated to obtain the coated rubber stopper sheet. Step 6) Secondary punching: The coated rubber stopper is punched and cleaned to obtain the coated rubber stopper; The second vulcanizing mold includes a second upper mold (9), a middle mold (10), and a second lower mold (11). The second upper mold (9) is provided with a second upper mold cavity for molding the crown (2) of the rubber stopper. The middle mold (10) is provided with a middle mold cavity for molding the connection between the crown (2) and the neck (1) of the rubber stopper. The second lower mold (11) is provided with a second lower mold cavity for placing the neck (1) of the rubber stopper. In the mold-closed state, the second upper mold cavity, the middle mold cavity, and the second lower mold cavity cooperate to form a molding cavity. The second upper mold (9) and the middle mold (10) are provided with heating chambers (7). The heating chambers (7) are provided with heating holes, which are connected to a heat transfer pipe (8). The second lower mold (11) is provided with a cooling chamber (12). The cooling chambers (12) are provided with cooling holes, which are connected to a refrigeration pipe (13).

2. The method for preparing a medical-grade coated rubber stopper according to claim 1, characterized in that, The film (3) is any one of ethylene-tetrafluoroethylene copolymer film, polytetrafluoroethylene film, polyethylene film and polypropylene film.

3. The method for preparing a medical-grade coated rubber stopper according to claim 1, characterized in that, In step 1), the electrical activation discharge power is 1-4 kW, and the processing time is 15-60 s.

4. The method for preparing a medical-grade coated rubber stopper according to claim 1, characterized in that, In step 3), the primary vulcanization temperature is 120-150℃, the pressure is 15-25 MPa, and the time is 10-15 min; in step 5), the secondary vulcanization temperature is 150-170℃, the pressure is 15-25 MPa, and the time is 10-15 min.

5. The method for preparing a medical-grade coated rubber stopper according to claim 1, characterized in that, The first vulcanizing mold includes a first upper mold (5) and a first lower mold (6). The first upper mold (5) is provided with a first upper mold cavity, and the first lower mold (6) is provided with a first lower mold cavity. In the mold-closed state, the first upper mold cavity and the first lower mold cavity cooperate to form a molding cavity. The first upper mold (5) and the first lower mold (6) are respectively provided with heating cavities (7). The heating cavities (7) are provided with heating holes, and the heating holes are connected to the heat transfer pipe (8).

6. The method for preparing a medical-grade coated rubber stopper according to claim 1, characterized in that, The temperature of the coolant in the cooling chamber (12) is 15-25℃.

Images