An injection seat shell of an implantable drug delivery device and a manufacturing method thereof

Abstract

The present invention discloses an injection seat housing for an implantable drug delivery device and a manufacturing method thereof. The housing is made of epoxy resin AB glue, wherein the epoxy resin AB glue includes component A and component B. The method comprises the following steps: step S1, weighing component A and component B in a mass ratio of 100:30 to 50 and mixing them to obtain the epoxy resin AB glue; step S2, subjecting the epoxy resin AB glue obtained in step S1 to vacuum stirring and degassing in a vacuum stirring and degassing machine; step S3, placing a mold and the epoxy resin AB glue obtained in step S2 in a constant temperature device for heat preservation, and injecting the epoxy resin AB glue into the mold; step S4, shaking the mold obtained in step S3 and then placing it in a drying oven for thermal curing; and step S5, placing the mold obtained in step S4 in a condensing device for rapid cooling and demolding. The present invention can improve the uniformity and transparency of the housing, enhance the degassing effect, increase the success rate of demolding, and reduce medical risks.

Description

Technical Field

[0001] The present invention relates to the technical field of medical instruments, and in particular to an injection seat shell of an implantable drug delivery device and a manufacturing method thereof. Background Art

[0002] As a vascular access device that is completely implanted in the patient's body, the implantable drug delivery device can provide a safe and reliable venous access for patients who require long-term and repeated infusion therapy. Therefore, the selection and production of its shell material is crucial. First, materials that meet medical device standards and have good biocompatibility should be selected to ensure that the shell does not cause rejection reactions or other adverse effects in human tissues; secondly, small and lightweight devices are more suitable for implantation in patients, which can reduce the patient's discomfort and activity restrictions in daily life. Especially for patients who require long-term implantation, reducing the size and weight of the implantable drug delivery device can reduce discomfort and improve the quality of life; in addition, in the specific production process, the shell of the injection seat of the current implantable drug delivery device is usually an injection molded part, and injection molding takes a long time and is mixed. Unevenness will eventually lead to bubbles in the shell, which may further cause holes or pores to form inside the shell, reducing the sealing performance of the shell, and may also cause drug leakage or external environmental substances to enter the device, affecting the stability and effect of the drug. It will also reduce the overall strength and durability of the shell, causing it to crack, deform or fail during use, affecting the function and safety of the device; at the same time, in current practice, complete demoulding is a major problem. Even if demoulding is performed after cooling to room temperature, the completeness is still not high. Demolding is generally achieved by applying a release agent, but this product is used for medical purposes, and the addition of a release agent will introduce new risks of use. Summary of the Invention

[0003] In response to the above technical problems, the present invention provides an injection seat shell of an implantable drug delivery device and a manufacturing method thereof.

[0004] According to a first aspect of one or more embodiments of the present invention, a method for manufacturing an injection seat housing of an implantable drug delivery device is provided, wherein the housing is made of epoxy resin AB glue, the epoxy resin AB glue comprising component A and component B, and the manufacturing method comprises the following steps:

[0005] Step S1, weighing component A and component B respectively in a mass ratio of 100:30 to 50 and mixing them to obtain epoxy resin AB glue;

[0006] Step S2, the epoxy resin AB glue obtained in step S1 is subjected to vacuum stirring and degassing in a vacuum stirring and degassing machine;

[0007] The vacuum stirring and degassing in step S2 includes:

[0008] In the first degassing stage, the mixture is stirred and degassed in a vacuum stirring degassing machine at a speed of 500 to 1200 r / min for 20 to 90 seconds;

[0009] In the second degassing stage, the mixture is stirred and degassed in a vacuum stirring degassing machine at a speed of 1300 to 2000 r / min for 20 to 90 seconds;

[0010] The third degassing stage is to degas in a vacuum stirring degassing machine at a speed of 2100-2300 r / min for 20-90 seconds;

[0011] The fourth degassing stage is to degas the mixture in a vacuum stirring degassing machine at a speed of 2400 to 3000 r / min for 20 to 90 seconds;

[0012] Step S3: placing the mold and the epoxy resin AB glue obtained in step S2 in a constant temperature device for heat preservation, and injecting the epoxy resin AB glue into the mold;

[0013] Step S4: shaking the mold after completing step S3, and then placing it in a drying oven for heat curing;

[0014] Wherein, the step S4 includes:

[0015] The first heat curing stage: curing at 60-90°C for 30-60 minutes;

[0016] Second heat curing stage: curing at 90-180°C for 30-60 minutes;

[0017] Step S5: placing the mold after step S4 into a cooling device for rapid cooling and demoulding. Preferably, the component A includes epoxy resin and an auxiliary agent, and the component B is a curing agent.

[0018] Preferably, the vacuum stirring and degassing machine performs vacuum stirring and degassing at -0.5 to 5 kPa.

[0019] Preferably, step S3 includes:

[0020] The mold and the epoxy resin AB glue obtained in step S2 are kept at a constant temperature of 30 to 80° C. for 20 to 60 minutes.

[0021] Preferably, step S3 includes:

[0022] The thermostatically controlled epoxy resin AB glue is slowly injected into the mold along the edge.

[0023] Preferably, step S4 includes:

[0024] The mold is shaken in an oscillator at 50-100 V for 30 seconds to 3 minutes, and then placed in a drying oven for thermal curing.

[0025] Preferably, the step S5 comprises: rapidly cooling the mold to 30-60° C. within 1-5 minutes using a condensing device.

[0026] According to a second aspect of one or more embodiments of the present invention, the present invention further provides an injection seat shell of an implantable drug delivery device, wherein the injection seat shell of the implantable drug delivery device is prepared by an optional manufacturing method of the injection seat shell of the implantable drug delivery device.

[0027] The present invention selects epoxy resin components A and B, reduces the glue ratio to improve the uniformity and transparency of the shell, adopts vacuum stirring degassing after mixing to improve the degassing effect, and maintains the mold and epoxy resin AB glue at a constant temperature before pouring the mold to avoid the generation of new bubbles. The rapid cooling method can increase the success rate of demoulding and the integrity of the product, thereby reducing medical risks. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] The present invention will be further described below with reference to the accompanying drawings.

[0029] Figure 1 Schematic diagram of the production process of the present invention;

[0030] Figure 2 This is a schematic diagram of the shape of the injection seat shell of the implantable drug delivery device of the present invention;

[0031] Figure 3 It is a histogram of the residual bubble rate under different degassing means in the present invention. DETAILED DESCRIPTION

[0032] The technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, rather than all 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.

[0033] In the description of the present invention, it should be understood that the directions or positional relationships indicated by the terms "front", "rear", "left", "right", "up", "down", etc. are based on the directions or positional relationships shown in the accompanying drawings, and are only for the convenience of describing the present invention and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific direction, be constructed and operated in a specific direction, and therefore cannot be understood as a limitation on the present invention.

[0034] See also Figure 1 , the present invention provides a technical solution:

[0035] A method for manufacturing an injection seat housing of an implantable drug delivery device, wherein the housing is made of epoxy resin AB glue, the epoxy resin AB glue comprising component A and component B, and the method comprises the following steps:

[0036] Step S1, weighing component A and component B respectively in a mass ratio of 100:30 to 50 and mixing them to obtain epoxy resin AB glue;

[0037] Step S2, the epoxy resin AB glue obtained in step S1 is subjected to vacuum stirring and degassing in a vacuum stirring and degassing machine;

[0038] Step S3: placing the mold and the epoxy resin AB glue obtained in step S2 in a constant temperature device for heat preservation, and injecting the epoxy resin AB glue into the mold;

[0039] Step S4: shaking the mold in step S3 and then placing it in a drying oven for thermal curing;

[0040] Step S5: placing the mold after step S4 into a condensation device for rapid cooling and demoulding.

[0041] The injection seat of the implantable drug delivery device manufactured by the present invention is as follows Figure 2 As shown, it is provided with a medicine inlet and a medicine outlet, and a cavity is left inside to accommodate the medicine liquid. Figure 2 As a form of the injection seat of the implantable drug delivery device, it is only used to facilitate the understanding of those skilled in the art and does not constitute a limitation on the specific form of the shell in the present invention. Those skilled in the art can use the manufacturing method provided in the present invention to manufacture the same, similar or significantly different implantable drug delivery device injection seat shell, as long as it conforms to the general understanding of the technicians in this field of the implantable drug delivery device injection seat shell.

[0042] In step S1, epoxy resin AB glue is selected to ensure biocompatibility, facilitate implantation of the housing into the human body, and reduce potential rejection reactions. Epoxy resin AB glue is another name for a two-liquid mixed hardening glue. One liquid is the glue, also known as component A, and the other is the hardener, also known as component B. The two liquids must be mixed to harden. Component A is typically an acrylic modified epoxy or epoxy resin, or contains catalysts and other additives. Component B is a modified amine or other hardener, or contains catalysts and other additives.

[0043] In one specific embodiment, Component A includes an epoxy resin and an additive, while Component B is a curing agent. Experimentation has shown that this formulation reduces costs and raw material requirements while ensuring product performance. Where conditions permit, the present invention does not limit the specific compositions of Components A and B. In another specific embodiment, Component A is primarily composed of a bisphenol epoxy resin and also includes a hydantoin epoxy resin; Component B is primarily composed of a low-molecular-weight polyamide and also includes 4,4'-diaminodiphenyl sulfone, which can improve the thermal stability and aging resistance of the epoxy resin AB adhesive.

[0044] In step S1, mixing component A and component B in a certain proportion can change the shape, performance and curing time of the finished product. Too much component A and too little component B will cause curing difficulties or even no curing. Too little component A and too much component B will cause curing too quickly, or even curing without complete mixing, which is inconvenient for other steps and has poor uniformity and transparency. When component A and component B are mixed in a mass ratio range of 100:51 to 80, the finished shell will have flocculent stripes, affecting the appearance of the product. The present invention adopts a mass ratio of 100:30 to 50 for mixing component A and component B, and the finished shell is uniform and transparent.

[0045] In step S2, the epoxy resin AB glue that completes step S1 is vacuum stirred and deaerated by a vacuum stirring degassing machine to minimize bubbles. The presence of bubbles in the injection seat housing of the implantable drug delivery device may cause holes or pores to form inside the housing, reducing the sealing performance of the housing. It may also cause drug leakage or external environmental substances to enter the inside of the device, affecting the stability and effect of the drug. It can also reduce the overall strength and durability of the housing, causing it to break, deform or fail during use, affecting the function and safety of the device. Therefore, it is necessary to minimize the generation of bubbles. Current deaeration methods mainly include heating deaeration and ultrasonic deaeration. Heating deaeration can cause the glue to solidify prematurely, affecting subsequent operations such as mold reversing. Although ultrasonic deaeration can reduce bubbles, the ultrasonic time is long and it is impossible to completely eliminate bubbles, particularly dense and tiny bubbles. The present invention adopts vacuum stirring deaeration, and a low pressure or negative pressure environment is generated by a vacuum stirring deaerator. Under the state of high-speed rotation, the bubbles in the epoxy resin AB glue are removed by the effect of stirring force.

[0046] In order to test the vacuum stirring degassing effect, this application used six degassing methods to conduct experiments. The degassing effects are shown in Table 1, where the residual bubble rate can be referred to Figure 3 .

[0047] Table 1 Degassing effects of different degassing methods

[0048]

[0049] When using single-stage degassing, when the speed of the vacuum stirring degassing machine is lower than 1400r / min, the epoxy resin AB glue is prone to uneven mixing, flocs are present, and it is in a translucent state, affecting the uniformity of the appearance of the finished product; when the speed of the vacuum stirring degassing machine exceeds 3000r / min, the epoxy resin AB glue is mixed evenly and large bubbles are basically removed, but it is difficult to remove dense small bubbles, and even cause the dense small bubbles to increase, which will affect the appearance and other performance of the finished product and increase medical risks.

[0050] Under the action of centrifugal force, bubbles in epoxy resin AB glue are pushed to the periphery, thereby separating from the colloid. Small bubbles have a smaller radius and are subject to less centrifugal force. Therefore, segmented vacuum stirring degassing can increase the speed to target small bubbles and optimize the degassing effect. When the degassing stage is divided into two stages, the number of large bubbles and dense small bubbles is significantly reduced, but small bubbles still exist at more than 50%. When the degassing stage is divided into three stages, dense small bubbles can be gradually removed by gradually increasing the rotation speed. Specifically, in the first degassing stage, the degassing is carried out at a speed of 500-1200 r / min in the vacuum stirring degassing machine for 20-90 seconds, and the epoxy resin AB glue is evenly mixed; in the second degassing stage, the degassing is carried out at a speed of 1300-2000 r / min in the vacuum stirring degassing machine for 20-90 seconds, and basically no large bubbles exist in the epoxy resin AB glue; in the third degassing stage, the degassing is carried out at a speed of 2100-2300 r / min in the vacuum stirring degassing machine for 20-90 seconds to further remove small bubbles in the epoxy resin AB glue. The number of small bubbles is reduced by 67% compared with the two-stage degassing.

[0051] When the vacuum stirring degassing is divided into four stages, the dense small bubbles can also be gradually removed by increasing the speed step by step. Specifically, in the first degassing stage, the degassing is carried out at a speed of 500-1200 r / min in the vacuum stirring degassing machine for 20-90s, and it can be further preferably carried out at a speed of 800-1200 r / min; in the second degassing stage, the degassing is carried out at a speed of 1300-2000 r / min in the vacuum stirring degassing machine for 20-90s, and basically no large bubbles exist in the epoxy resin AB glue; in the third degassing stage, the degassing is carried out at a speed of 2100-2100 r / min in the vacuum stirring degassing machine. Stirring at a speed of 2300 r / min for 20 to 90 seconds has shown that the small bubbles in the epoxy resin AB glue are reduced at this time. It can be further preferred to stir and deaerate at a speed of 2100 to 2200 r / min. At this time, the small bubbles in the epoxy resin AB glue can be reduced by 67%; the fourth deaeration stage is to stir at a speed of 2400 to 3000 r / min in a vacuum stirring deaerator for 20 to 90 seconds. Practice has shown that at this time, there are basically no bubbles remaining in the epoxy resin AB glue and no new bubbles are generated. It can be further preferred to stir and deaerate at a speed of 2400 to 2600 r / min. Generally speaking, in order to improve the effect of stirring and deaeration, the stirring time must be extended, but stirring for too long will cause the glue material to stratify, affecting curing and the performance of the final product. Therefore, segmented stirring can gradually remove bubbles extending from the outer layer to the inner layer, ensuring that bubbles at each level are completely removed. At the same time, an extremely short high-speed rotation time is guaranteed to avoid stratification of the glue material. This method can achieve a zero-bubble effect and greatly save time and cost.

[0052] In one embodiment, the vacuum stirring degassing machine performs vacuum stirring degassing at 5 to 10 kPa. In another embodiment, the vacuum stirring degassing machine performs vacuum stirring degassing at -0.5 to 5 kPa. A low pressure or negative pressure environment can further improve the degassing effect.

[0053] In step S3, the mold and the epoxy resin AB glue obtained in step S2 are placed in a constant temperature device for insulation, and the epoxy resin AB glue is then injected into the mold. Practice has shown that when there is a temperature difference between the mold and the epoxy resin AB glue that has been mixed and degassed, new bubbles are likely to form during the injection of the epoxy resin AB glue into the mold, and the glue may also be unevenly distributed. Therefore, maintaining the two at the same temperature before injection can improve the final shell molding effect.

[0054] In one specific embodiment, the mold and the epoxy resin AB glue completed in step S1 are kept at a constant temperature of 30 to 80° C. for 20 minutes. In another specific embodiment, the mold and the epoxy resin AB glue completed in step S1 are kept at a constant temperature of 30 to 80° C. for 20 to 60 minutes to ensure that there is no temperature difference between the two.

[0055] In one embodiment, the thermostated epoxy resin AB glue is slowly injected into the mold along the edges to minimize air bubbles and ensure even glue distribution. The speed of injection is controlled to avoid excessive speed or slowness to ensure that the glue fills every corner of the mold. A slow, even injection method can be used, or vibration or tapping the mold can be used to help expel air and ensure more even glue filling.

[0056] In step S4, the mold after step S3 is shaken and then placed in a drying oven for thermal curing. Shaking can reduce bubbles that appear after the glue is injected into the mold and improve the uniformity of the glue distribution.

[0057] In one embodiment, the mold can be shaken in an oscillator at 50-100 V for 3-5 minutes and then placed in a drying oven for heat curing. In another embodiment, the mold can be shaken in an oscillator at 50-100 V for 30 seconds to 3 minutes and then placed in a drying oven for heat curing to reduce the curing time.

[0058] In the current shell manufacturing process, room temperature curing or single-stage thermal curing is usually used. In order to test the curing effect, this application used seven curing methods to conduct experiments. The curing results are shown in Table 2.

[0059] Table 2 Degassing effects corresponding to different degassing methods

[0060]

[0061] When using room temperature curing, it usually takes a long time, and the time varies depending on the different ratios and total amount of AB glue, but generally speaking, it takes at least 48 hours to fully cure. When cured at room temperature for 24 hours, the hand test shows that the outer layer is sticky, the middle layer is sticky, and the outer layer has a hardness of 32.3. Under normal conditions, the higher the temperature, the more time can be saved when curing at elevated temperatures. However, according to experiments, although single-stage heat curing can shorten the curing time, it is very easy to cause implosion by raising the temperature at one time, which affects the normal cross-linking between the molecules of the AB glue, greatly reducing the mechanical strength of the final product. In addition, the curing inside and outside are inconsistent, and the hardness of the center layer is greatly different from that of the outer layer, making it difficult for the center layer to fully cure. As shown in Table 2, when the drying oven was set to 70°C for curing for 60 minutes, the outer layer was cured while the center layer was not cured. When the drying oven was set to 70°C for curing for 150 minutes, the center layer was still sticky when touched, and the hardness increased slightly, but still did not exceed 50D / HA. This shows that when the temperature does not meet the standard, the center layer is difficult to be completely cured. When the drying oven was set to 180°C for curing for 60 minutes, the outer layer was cured and the hardness exceeded 90D / HA, but the center layer was still sticky to the touch, and the hardness difference between the center layer and the outer layer was still large. When the drying oven was set to 180°C for curing for 150 minutes, the center layer was slightly sticky when touched, and the hardness reached 72.6D / HA.

[0062] The present invention uses segmented thermal curing to address the shortcomings of traditional curing. In one specific embodiment, thermal curing is divided into two stages: the first curing stage: curing at 40°C for 60 minutes; the second curing stage: curing at 70°C for 60 minutes. As a result, the outer layer is cured while the core layer is uncured. Furthermore, while the hardness of the outer layer exceeds 90D / HA, the hardness of the core layer is only 63.4D / HA.

[0063] In another specific embodiment, the thermal curing is divided into two stages: the first curing stage: curing at 70°C for 30 minutes; the second curing stage: curing at 150°C for 60 minutes. As a result, both the inner and outer layers are fully cured and the hardness exceeds 90D / HA. At the same time, the curing time is shortened to 90 minutes, which improves the curing efficiency. The segmented curing method achieves layer-by-layer curing, making the inner and outer layers more uniform without affecting the mechanical strength of the product. Analysis found that the first thermal curing stage: curing at 60-90°C for 30-60 minutes is mainly used to avoid excessive internal stress, while the second thermal curing stage: curing at 90-180°C for 30-60 minutes can achieve a better crosslinking density.

[0064] In step S5, the mold that completes step S4 is placed in a condensing device for rapid cooling and demoulding. Currently, achieving complete demoulding after the glue solidifies is a major problem. Even if demoulding is performed after cooling to room temperature, the integrity is still not high. Therefore, demoulding is generally achieved by applying a release agent, but this product is used for medical purposes, and the increase of a release agent can introduce new risks of use. The present invention adopts a rapid cooling method, utilizing the performance difference of the mold and epoxy resin AB glue facing low temperatures, so that the two are separated, increasing the success rate of demoulding and the integrity of the product. For the medical industry, it is also possible to reduce the risk of the product by not introducing new substances.

[0065] In one embodiment, the mold can also be rapidly cooled to 10-20° C. within 5-10 minutes using a condensation device. In another embodiment, the mold can be rapidly cooled to 30-60° C. within 1-5 minutes using a condensation device to further improve condensation efficiency.

[0066] Various modifications to these embodiments will be readily apparent to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the invention.

Claims

1. A method for manufacturing an injection seat housing of an implantable drug delivery device, wherein the housing is made of epoxy resin AB glue, the epoxy resin AB glue comprising component A and component B, characterized in that: The method comprises the following steps: Step S1, weighing component A and component B respectively in a mass ratio of 100:30 to 50 and mixing them to obtain epoxy resin AB glue; Step S2, the epoxy resin AB glue obtained in step S1 is subjected to vacuum stirring and degassing in a vacuum stirring and degassing machine, wherein the vacuum stirring and degassing is performed at a pressure of 5 to 10 kPa; The vacuum stirring and degassing in step S2 includes: In the first degassing stage, the mixture is stirred and degassed in a vacuum stirring foaming machine at a speed of 500 to 1200 r / min for 20 to 90 seconds; In the second degassing stage, the mixture is stirred and degassed in a vacuum stirring degassing machine at a speed of 1300 to 2000 r / min for 20 to 90 seconds; The third degassing stage is to degas in a vacuum stirring degassing machine at a speed of 2100-2300 r / min for 20-90 seconds; The fourth degassing stage is to degas in a vacuum stirring degassing machine at a speed of 2400 to 3000 r / min for 20 to 90 seconds; Step S3: placing the mold and the epoxy resin AB glue obtained in step S2 in a constant temperature device at a temperature of 30 to 80° C. for 20 minutes, and then injecting the epoxy resin AB glue into the mold; Step S4, shaking the mold injected with the epoxy resin AB glue in step S3, and then placing it in a drying oven for thermal curing; Wherein, the step S4 includes: The first heat curing stage: curing at 60-90°C for 30-60 minutes; Second heat curing stage: curing at 90-180°C for 30-60 minutes; Step S5: placing the mold after step S4 into a cooling device for rapid cooling and demoulding; The component A includes epoxy resin and auxiliary agents, and the component B is a curing agent.

2. The method for manufacturing an injection seat housing of an implantable drug delivery device according to claim 1, characterized in that: The step S3 comprises: The thermostatically controlled epoxy resin AB glue is slowly injected into the mold along the edge.

3. The method for manufacturing an injection seat housing of an implantable drug delivery device according to claim 1, characterized in that: The step S4 comprises: The mold is shaken in an oscillator at 50-100 V for 30 seconds to 3 minutes, and then placed in a drying oven for thermal curing.

4. The method for manufacturing an injection seat housing of an implantable drug delivery device according to claim 1, characterized in that: The step S5 includes: rapidly cooling the mold to 30-60° C. within 1-5 minutes using a cooling device.

5. An injection seat housing of an implantable drug delivery device, characterized in that: The injection seat shell of the implantable drug delivery device is prepared by the manufacturing method of the injection seat shell of the implantable drug delivery device according to any one of claims 1 to 4.

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