WO2023103946A1

WO2023103946A1 - Method for preparing controlled-release coating and coating apparatus therefor

Info

Publication number: WO2023103946A1
Application number: PCT/CN2022/136521
Authority: WO
Inventors: 夏佩佩; 魏征
Original assignee: 易浦润（上海）生物技术有限公司
Priority date: 2021-12-06
Filing date: 2022-12-05
Publication date: 2023-06-15
Also published as: CN116213228A

Abstract

The present invention provides a method for preparing a controlled-release coating and a coating apparatus therefor, wherein the method for preparing the controlled-release coating comprises: step 1), coating a surface of a drug-containing implantable medical instrument with a coating solution; and step 2), curing the surface of the drug-containing implantable medical instrument to obtain the controlled-release coating. In the present invention, the performance of the coating solution can be controlled by means of keeping the temperature of the coating solution at 10-80°C, such that a controlled-release coating with a good controlled-release performance can be obtained.

Description

A method for preparing a controlled-release coating and coating equipment thereof

technical field

The invention relates to the technical field of coating preparation, in particular to a method for preparing a controlled-release coating and coating equipment thereof.

Background technique

In recent years, with the continuous innovation of medical technology, medical devices are also developing rapidly, especially drug-containing implantable medical devices are increasingly used in the treatment of intracranial, cardiac and peripheral blood vessels. The drug release behavior of a medicated implantable medical device affects the efficacy of the device in humans.

However, in the process of drug release, it is difficult to achieve controllable, long-term and stable release. Drugs are easy to accumulate on the outside of the device and cause burst release of drugs in the early stage. In addition, if a degradable material is used as a drug carrier, the degradable material cannot maintain good mechanical properties in the late stage of degradation and collapses, which may easily cause the drug to be released in the later stage.

The release of the drug cannot be precisely controlled, and there are problems such as insufficient long-lasting drug effect, poor stability, and difficult to control drug toxicity, which may bring relatively large side effects to patients, and may even cause life-threatening, hindering or limiting the ability of the drug to be implanted. Into the application of medical devices in the field of drug sustained and controlled release.

Therefore, with the continuous update of clinical needs, the controllable, long-acting, and stable release of drugs is conducive to improving drug efficacy and reducing toxic and side effects, and is of great significance for improving the therapeutic effect of drug-containing implantable medical devices.

Contents of the invention

In order to solve at least one of the technical problems above, the object of the present invention is to provide a method for preparing a controlled-release coating and its coating equipment. By controlling the temperature of the coating solution, a controlled-release coating with good controlled-release performance can be obtained.

For reaching this purpose, the present invention adopts following technical scheme:

A method of preparing a controlled-release coating, comprising:

Step 1), coating the coating solution on the surface of the drug-containing implantable medical device, and keeping the temperature of the coating solution at 10-80°C;

Step 2), curing, drug-containing can be implanted on the surface of the medical device to obtain a controlled-release coating.

In one embodiment, when performing the step 1), the coating method is at least one of dip coating, spray coating and brush coating.

In one embodiment, when performing the step 2), the curing temperature is 20-150° C., and the curing time is less than 10 h.

In one embodiment, before performing the step 1), a loading step is also performed, and the loading step includes: loading the drug-containing implantable medical device on a carrier.

In one of the embodiments, after the loading step and before step 1), a cleaning step is also performed, the cleaning methods include electrostatic adsorption, ion wind blowing, brush removal and rubber roller adsorption at least one of the

In one of the embodiments, after performing step 1) and before performing step 2), a step of removing excess coating liquid is also performed, and the step of removing excess coating liquid includes treating the drug-containing Squeegees and/or dips for implantable medical devices.

In one of the embodiments, the step 1) and the step of removing excess coating liquid are repeated at least once, and a standing step is performed before each repetition, the standing temperature is 10-80°C, and the standing time is less than 1h.

In one of the embodiments, after performing the step of removing excess coating liquid and before performing step 2), a solvent volatilization step is also performed, and the solvent is volatilized at 10-80° C., and the solvent volatilization time is less than 10 h .

In one embodiment, after the step 2), the unloading step is further performed, and the unloading step includes: removing the drug-containing implantable medical device from the carrier.

A kind of coating equipment, described coating equipment is used for implementing the method for preparing controlled-release coating described in any one of above, and described coating equipment comprises: be used for loading the liquid tank of described coating liquid and curing chamber .

In one embodiment, the liquid tank is equipped with a first temperature control device, and the first temperature control device includes a first heating element and a first temperature detection and control element, and the first heating element is used to heat the The coating liquid, the first temperature detection and control element is used to detect the temperature of the coating liquid, and control the first heating element to heat or stop heating.

In one embodiment, the liquid tank is provided with an opening, and the liquid tank is also provided with a cover plate that can selectively cover the opening of the liquid tank.

In one embodiment, the liquid tank is also equipped with a liquid removal plate and a selectively openable drain port.

In one of the embodiments, the curing chamber is equipped with a second temperature control device, and the second temperature control device includes a second heating element and a second temperature detection and control element, and the second heating element heats the The curing chamber, the temperature of the curing chamber is detected by the second temperature detection and control element, and the second heating element is controlled to heat or stop heating.

In one embodiment, the curing chamber is further equipped with a first timing element to control the curing time.

In one of the embodiments, the coating equipment further includes a carrier, a first conveyor belt, a second conveyor belt, a mechanical claw, a mechanical claw guide rail, and a lifting rod, the first conveyor belt is arranged adjacent to the liquid tank, and For transporting the carrier along a direction close to the liquid tank, the second conveyor belt is arranged adjacent to the curing chamber for transporting the carrier along a direction away from the curing chamber, so The mechanical claw cooperates to grasp, clamp and release the carrier, and the mechanical claw is arranged in cooperation with the lifting rod. Driven by the lifting rod, the mechanical claw can move up and down, and the lifting rod and the lifting rod The guide rail of the mechanical claw is cooperatingly arranged, and the lifting rod can move left and right along the guide rail of the mechanical claw, thereby driving the mechanical claw to move left and right.

In one of the embodiments, the carrier is in the shape of a rectangular box, the upper end of the carrier is an open structure, and the lower surface of the carrier is provided with hollow holes, and at least one spacer is provided in the carrier. A plate divides the inner cavity of the carrier into a plurality of compartments; or, the carrier is a long cylinder, and a plurality of mutually spaced hooks are arranged on the lower surface of the carrier.

In one of the embodiments, at least one of an electrostatic adsorption device, an ion wind blowing device, a brush and a rubber roller is provided on the transmission path of the first transmission belt; or, between the first transmission belt and the At least one of an electrostatic adsorption device, an ion wind blowing device, a brush and a rubber roller is arranged between the liquid tanks.

In one embodiment, the coating equipment further includes a liquid removal chamber, and a scraper and/or a liquid wetting tool are arranged in the liquid removal chamber.

In one embodiment, the coating equipment further includes a volatilization chamber, and a third conveyor belt is arranged in the volatilization chamber.

In one of the embodiments, the coating equipment further includes a detection device, the detection device is arranged on the transmission path of the second conveyor belt, the detection device includes a distance sensor and an alarm, or the detection device includes Quality sensors and alarms.

Compared with the prior art, the present invention has the following beneficial effects:

In the present invention, by keeping the temperature of the coating liquid at 10-80° C., the performance of the coating liquid can be controlled, so that a controlled-release coating with good controlled-release performance can be obtained.

Description of drawings

Fig. 1 is a schematic structural view of coating equipment in the present invention.

Fig. 2 is a schematic structural view of one of the carriers loaded with drug-containing implantable medical devices in the present invention.

Fig. 3 is a schematic structural view of another carrier loaded with a drug-containing implantable medical device according to the present invention.

Reference signs:

Liquid tank 10, first heating element 11, first temperature detection and control element 12, cover plate 13, volatilization chamber 20, third conveyor belt 21, curing chamber 30, second heating element 31, second temperature detection and control element 32 , Carrier 40, partition 41, hook 42, first conveyor belt 50, second conveyor belt 60, mechanical claw 71, mechanical claw guide rail 72, lifting rod 73, liquid removal chamber 80.

Detailed ways

The technical solutions of the present invention will be further described below through specific embodiments. It should be clear to those skilled in the art that the specific implementation is only to help understand the present invention, and should not be regarded as a specific limitation on the present invention.

The invention provides a method for preparing a controlled-release coating, comprising:

In the present invention, the temperature of the coating solution is maintained at 10-80°C. If the temperature is too low, the fluidity of the coating solution will be poor, making it difficult to meet the coating requirements; if the temperature is too high, it will easily cause the solvent in the coating solution to volatilize and affect the concentration of the coating solution.

In the present invention, the coating solution may be a silicone rubber coating solution, including silicone rubber, an organic solvent, a crosslinking agent and a catalyst. The concentration of the silicone rubber is 0.1-0.5%, and the organic solvent is at least one of petroleum ether, alkane reagents and benzene reagents, preferably n-hexane or xylene.

In the present invention, the drug-containing implantable medical device may be a sinus stent, a blood vessel stent, a uterine diaphragm, a urethral stent, a ureteral stent, etc., which are not limited here.

In the present invention, the thickness of the controlled-release coating is 10-200 μm.

When performing step 1), the coating methods include but not limited to dip coating, spray coating and brush coating. No matter what kind of coating method is adopted, it is sufficient to make the controlled-release coating on the surface of the drug-containing implantable medical device uniform and within a preset range.

In one embodiment, the method of coating is dip coating, and the time of each dip coating is 0.1-60s, at least once.

In another embodiment, the method of coating is spraying, the distance between the spray head and the surface of the implantable medical device containing medicine is adjusted, and the time of each spraying is 1-10s, at least once. It can be understood that the time for each spraying is not limited to the above range, and can be adjusted based on actual needs. Additionally, one of the spray head and the medicated implantable medical device may be moved and/or rotated relative to the other to ensure uniform spraying.

In yet another embodiment, the method of coating is brushing, and each brushing is based on ensuring that the corresponding surface of the drug-containing implantable medical device is covered, and brushing is at least once.

When performing step 2), the curing temperature is 20-150°C, and the curing time may be less than 10 hours. Preferably, the curing time is 0.2-6 hours.

Before carrying out step 1), the feeding step can also be carried out. Specifically, the drug-containing implantable medical device is loaded on the carrier, so that in subsequent operations, the operator can be avoided as much as possible from touching the drug-containing implantable medical device, thereby avoiding contamination of the drug-containing implantable medical device. In addition, the carrier is beneficial to realize automatic operation, and a plurality of drug-containing implantable medical devices can be loaded on the carrier, which is beneficial to realize large-scale batch production. After the loading of multiple implantable medical devices containing drugs is completed, they are arranged at intervals to ensure that they will not contact each other in subsequent operations, thereby avoiding mutual adhesion and/or uneven coating between multiple implantable medical devices containing drugs.

After the loading step and before step 1), a cleaning step may also be performed. The cleanliness requirements for drug-containing implantable medical devices are relatively high, and strict control is required to avoid risks caused by dust and impurities on drug-containing implantable medical devices after implantation into the human body. Therefore, after the loading step and before step 1), the drug-containing implantable medical device needs to be cleaned. Cleaning methods include but are not limited to electrostatic adsorption, ion wind blowing, brush removal and rubber roller adsorption. After the cleaning step, it can not only avoid the risks caused by dust, impurities, etc., but also help to increase the binding force between the drug-containing implantable medical device and the controlled-release coating, and is also conducive to obtaining a uniform controlled-release coating, so that This makes the controlled-release coating more stable for the controlled release of drugs.

After performing step 1) and before performing step 2), a step of removing excess coating liquid may also be performed. After completing step 1), due to coating operation errors and other reasons, the coating liquid may be unevenly distributed on the surface of the drug-containing implantable medical device, and/or too thick, and the scraper and the surface of the drug-containing implantable medical device may One of the scraper and the medicated implantable medical device is moved relative to the other by a preset distance between them to perform scraping, thereby removing excess coating fluid. In addition, some drug-containing implantable medical devices may be installed vertically for ease of coating or for other reasons, so that after step 1) is completed, the coating liquid will flow from top to bottom under the action of gravity, making There is excess coating liquid on the lowest point or surface of the drug-containing implantable medical device. If it is not treated, the controlled-release coating formed at this position will be relatively thick. Therefore, it needs to be treated with scraping liquid, so that Remove excess paint. Optionally, in this case, excess coating liquid can also be removed by dipping. Specifically, using a liquid dipping tool, the liquid dipping tool is arranged below the drug-containing implantable medical device, and the two can be relatively close to remove excess coating liquid. According to actual needs, at least one dipping can be performed. In addition, the wetted tool is preferably disposable or replaceable to avoid contamination. Wet implements include, but are not limited to, sponges, lint-free cloths, and cotton swabs.

According to actual needs, step 1) and the steps of removing excess coating liquid can be repeated at least once to achieve multiple coatings. That is, after completing step 1) and the step of removing excess coating liquid in sequence, repeat step 1) and the step of removing excess coating liquid at least one more time, and then proceed to the subsequent steps. It should be noted that a standing step is required before each repetition. The standing temperature is 10-80° C., and the standing time can be less than 1 hour. Preferably, the standing time is 2-30 minutes. The purpose of standing is to allow The solvent is at least partially volatilized, which facilitates the next coating. During the resting step, the drug-containing implantable medical device may be in a static state or in a slowly moving state. After completing the last step 1) and the step of removing excess coating liquid, proceed to the next step. It can be understood that when only one coating is required, after step 1) and the step of removing excess coating liquid are completed, the subsequent steps can be directly entered without a standing step. Of course, in other embodiments, the step of standing still may not be provided.

After performing the step of removing excess coating liquid and before performing step 2), a solvent volatilization step may also be performed. The solvent is volatilized at 10-80° C., and the solvent volatilization time may be less than 10 h, preferably, the volatilization time is 0.2-6 h.

After performing step 2), the unloading step may also be performed, that is, removing the drug-containing implantable medical device from the carrier.

As shown in FIG. 1 , the present invention also provides a coating device for implementing the above preparation method, including: a liquid tank 10 for loading coating liquid and a curing chamber 30 . The coating solution loaded in the liquid tank 10 is used to coat the surface of the drug-containing implantable medical device; after the coating is completed, the drug-containing implantable medical device is placed in the curing chamber 30, and the surface coating solution is cured to obtain Controlled release coating.

As mentioned above, the temperature of the coating solution is kept at 10-80°C. If the temperature is too low, the fluidity of the coating solution will be poor and it will be difficult to meet the coating requirements; if the temperature is too high, the solvent in the coating solution will easily volatilize , affecting the concentration of the coating solution. In order to keep the temperature of the coating liquid within the above range, the liquid tank 10 is equipped with a first temperature control device. The first temperature control device comprises a first heating element 11 and a first temperature detection control element 12, the first heating element 11 is used to heat the coating liquid, the first temperature detection control element 12 is used to detect the temperature of the coating liquid, and controls the first The heating element 11 heats up or stops heating. Understandably, in order to keep the temperature of the coating liquid at 10-80° C., it may be necessary to cool the coating liquid. The first temperature control device also includes a first cooling element, the first cooling element is used for cooling the coating liquid, and the first temperature detection and control element 12 is used for detecting the temperature of the coating liquid, and controlling the first cooling element to cool or stop cooling.

Methods of application include, but are not limited to, dipping, spraying, and brushing. No matter what kind of coating method is adopted, it is sufficient to make the controlled-release coating on the surface of the drug-containing implantable medical device uniform and within a preset range.

In one embodiment, the method of coating is dip coating, and dip coating can be realized by directly immersing the drug-containing implantable medical device into the coating liquid in the liquid tank 10 . The time of dipping each time is 0.1-60s, that is, the time of immersing in the coating solution in the liquid tank 10 is 0.1-60s each time, and when the dipping time is reached, the drug-containing implantable medical device is removed from the liquid tank 10 take out. Dip coat at least once. Understandably, in order to facilitate the drug-containing implantable medical device to enter the liquid tank 10, the liquid tank 10 is provided with an opening, which makes the coating liquid in the liquid tank 10 easy to volatilize. In order to avoid volatilization of the coating liquid as much as possible, the liquid tank 10 is also equipped with a cover plate 13 that can selectively cover the opening of the liquid tank 10. After the drug-containing implantable medical device enters the liquid tank 10, or after it is taken out of the liquid tank 10, the cover plate 13 covers the opening of the liquid tank 10 to avoid volatilization of the coating solution as much as possible. When the drug-containing implantable medical device enters the liquid tank 10 , the cover plate 13 is opened to allow the drug-containing implantable medical device to pass through the opening of the liquid tank 10 . In addition, the remaining coating solution in the liquid tank 10 may be unfavorable for the next coating, for example, the opening of the liquid tank 10 may introduce impurities, dust, etc., and for example, the solvent volatilizes through the opening of the liquid tank 10, which will cause The concentration of the coating solution does not match the preset concentration. Based on this, the liquid tank 10 is also equipped with a liquid removal plate and a selectively openable liquid discharge port. After the coating is completed, open the drain port and cooperate with the scraping operation of the liquid removal plate to remove the residual coating liquid. Further, it can also be washed with a solvent. In addition, before the next coating, do a good job of replenishing the liquid. The coating liquid can be replenished through the opening of the liquid tank 10 , or a liquid inlet can be provided on the liquid tank 10 . It can be understood that it may mean that after the coating of a batch of drug-containing implantable medical devices is completed, the coating liquid is replaced, and the next batch of drug-containing implantable medical devices is coated with the replaced coating liquid. Alternatively, the coating solution may be replaced after the coating solution has been used for a preset number of times. In addition, the shape of the liquid tank 10 can be designed according to the shape of the drug-containing implantable medical device and its arrangement.

In another embodiment, the method of coating is spray coating. The liquid tank 10 is equipped with a spray head for spraying the coating liquid loaded in the liquid tank 10 on the surface of the drug-containing implantable medical device. Adjust the distance between the spray head and the surface of the drug-containing implantable medical device to a preset distance, each spraying time is the preset time, for example, 1-10s, and spray at least once. To ensure uniform spraying, one of the spray head and the medicated implantable medical device may be moved and/or rotated relative to the other.

In yet another embodiment, the application is by brushing. The liquid tank 10 is equipped with a brush for dipping the coating liquid in the liquid tank 10, and brushing on the surface of the drug-containing implantable medical device, each brushing is to ensure that the corresponding surface of the drug-containing implantable medical device is covered Subject to at least one brush.

The curing chamber 30 is equipped with a second temperature control device, and the second temperature control device includes a second heating element 31 and a second temperature detection and control element 32 . The curing chamber 30 is heated by the second heating element 31 , and the temperature of the curing chamber 30 is detected by the second temperature detection and control element 32 , and the second heating element 31 is controlled to heat or stop heating. It will be appreciated that cooling of the curing chamber 30 may be required in order to maintain the curing temperature at 20-150°C. The second temperature control device also includes a second cooling element, the second cooling element is used to cool the solidification chamber 30, the second temperature detection control element 32 is used to detect the temperature of the solidification chamber 30, and controls the second cooling element to refrigerate or stop Refrigeration. In addition, the curing chamber 30 is also equipped with a first timing element to control the curing time, and the curing time is 0.2-6 hours.

In order to prevent the operator from touching the implantable medical device containing medicine as much as possible, the coating equipment also includes a carrier 40 . The drug-containing implantable medical device can be in the shape of sheet, rod, tube, etc., or other irregular shapes, and the loading method of the carrier 40 is designed based on the shape and related structure of the drug-containing implantable medical device. After the drug-containing implantable medical device is loaded on the carrier 40, in subsequent operations, contact with the drug-containing implantable medical device can be avoided as much as possible, so that contamination of the drug-containing implantable medical device can be avoided as much as possible.

As shown in FIG. 2 , the drug-containing implantable medical device is in the shape of a sheet, and the carrier 40 is in the shape of a rectangular box. The upper end of the carrier 40 is an open structure, and the lower surface of the carrier 40 is provided with perforated holes. At least one partition 41 is arranged inside the carrier 40 to divide the inner cavity of the carrier 40 into a plurality of compartments, and a sheet-shaped implantable medical device containing medicine is tiled in each compartment. If dip coating is adopted, the carrier 40 and the drug-containing implantable medical device are immersed in the coating liquid as a whole, and the upward surface of the drug-containing implantable medical device can be evenly coated with the coating liquid, and then the carrier 40 together with the drug-containing The implanted medical device is taken out as a whole, and the excess coating liquid flows out through the hollow hole. After the drug-containing implantable medical device is turned over, it is immersed in the coating liquid again, and the dip coating can be repeated according to actual needs. If spraying or brushing is used, spray or brush the upward facing surface of the drug-containing implantable medical device, and then turn the drug-containing implantable medical device over, and then spray or brush again, according to actual needs Repeat by spraying or brushing. In order to avoid the accumulation of coating liquid on the surface of the carrier 40, affecting the coating, turning over or taking out of the drug-containing implantable medical device, the surface of the carrier 40 can be surface treated, for example, a coating is provided to prevent accumulation Apply liquid.

As shown in Figure 3, the drug-containing implantable medical device is in the form of a sheet, and the drug-containing implantable medical device is provided with a through hole, the carrier 40 is a long column, and the lower surface of the carrier 40 is provided with A plurality of hooks 42 spaced apart from each other, and the hooks 42 cooperate with the through holes, so that the drug-containing implantable medical device is hung on the carrier 40 . By using the mounting method, the contact area between the drug-containing implantable medical device and the carrier 40 can be minimized, and the influence of the carrier on the coating can be reduced as much as possible, which is conducive to the uniformity of the coating solution on the surface of the drug-containing implantable medical device coated. A lanyard can also be further provided. After the lanyard is passed through the through hole, it is knotted to form a rope loop, and then the rope loop is mounted on the hook 42, which can further reduce the contact area between the drug-containing implantable medical device and the carrier 40 . If dip coating is adopted, the carrier 40 drives the drug-containing implantable medical device to immerse in the coating solution, and the carrier 40 itself can be located outside the coating solution as much as possible, thereby avoiding the accumulation of coating solution on the carrier 40 as much as possible, and can be based on actual conditions. Requires repeated dipping. If spraying or brushing is used, the carrier 40 can drive the drug-containing implantable medical device to rotate 180°, and one of the main surfaces of the drug-containing implantable medical device is opposite to the nozzle or brush. Tool 40 drives the drug-containing implantable medical device to rotate 180°, so that the other main surface is opposite to the nozzle or brush, so that the other main surface can be sprayed or brushed, and spraying or brushing can be repeated according to actual needs. It can be understood that in other unshown embodiments, other shapes but provided with through holes can also be used to mount the drug-containing implantable medical device, which is not limited here.

Please refer to FIG. 1 again. After the carrier 40 is set, it is beneficial to realize automatic operation and realize large-scale mass production. On the one hand, the carrier 40 can be loaded with a plurality of implantable medical devices containing medicines, and on the other hand, the carrier 40 is suitable for use with automatic devices. Specifically, the coating equipment further includes a first conveyor belt 50 , a second conveyor belt 60 , a mechanical claw 71 , a mechanical claw guide rail 72 and a lifting rod 73 . The first conveyor belt 50 is disposed adjacent to the liquid tank 10 for transporting the carrier 40 in a direction close to the liquid tank 10 . That is, after the drug-containing implantable medical device is loaded on the carrier 40, the carrier 40 is matched with one end of the first conveyor belt 50, and the first conveyor belt 50 transports the carrier 40 together with the drug-containing implantable medical device to the second conveyor belt 50. The other end of a conveyor belt 50 makes the carrier 40 and the implantable medical device containing medicine approach the liquid tank 10 as a whole. The second conveyor belt 60 is disposed adjacent to the curing chamber 30 and is used for transporting the carrier 40 in a direction away from the curing chamber 30 . That is, the carrier 40 cooperates with one end of the second conveyor belt 60, and the second conveyor belt 60 transports the carrier 40 together with the drug-containing implantable medical device to the other end of the second conveyor belt 60, so that the carrier 40 together with the drug-containing implantable The whole medical device is far away from the curing chamber 30, so that it is convenient for the operator to unload the material. If a higher curing temperature is selected, the material can be kept away from the curing chamber 30 during blanking, so as not to be scalded by the curing chamber 30 at a higher temperature. In addition, during the output process, the drug-containing implantable medical device naturally cools down, which can also prevent the operator from being scalded by the drug-containing implantable medical device at a higher temperature, which is beneficial for the operator to unload. The mechanical claw 71 can be opened or clamped, and the mechanical claw 71 is arranged with the elevating rod 73. Driven by the elevating rod 73, the mechanical claw 71 can move up and down. Move left and right along the mechanical claw guide rail 72, thereby driving the mechanical claw 71 to move left and right, so that the mechanical claw 71 can grab, clamp and release the carrier 40, and when clamping the carrier 40, it can drive the carrier 40 up and down, left and right Move, so as to drive the drug-containing implantable medical device to enter different sections, and complete the corresponding process in the corresponding section. For example, after the first conveyor belt 50 transports the carrier 40 together with the drug-containing implantable medical device to the other end of the first conveyor belt 50, the mechanical gripper 71 can move the carrier 40 together with the drug-containing implantable medical device to the liquid tank 10, and can move up and down relative to the liquid tank 10 to complete the coating. For another example, after curing is completed, the mechanical gripper 71 can move the carrier 40 together with the implantable medical device containing medicine to one end of the second conveyor belt 60 .

It should be noted that drug-containing implantable medical devices need to have a high degree of cleanliness to avoid risks caused by dust and impurities on drug-containing implantable medical devices after implantation into the human body. At least one of an electrostatic adsorption device, an ion wind blowing device, a brush and a rubber roller is arranged on the transmission path of the first transmission belt 50, so that the implantable medical device containing medicine can be cleaned. Optionally, at least one of an electrostatic adsorption device, an ion wind blowing device, a hair brush and a rubber roller can also be arranged between the first conveyor belt 50 and the liquid tank 10, so that when the carrier 40 is moved to the first After the other end of the conveyor belt 50, the carrier 40 is grasped by the mechanical claw 71, and by moving, the carrier 40 and the implantable medical device containing the drug are sent to the corresponding device for cleaning, and then coating is carried out after cleaning operate. After cleaning, it can not only avoid the risks caused by dust and impurities, but also help to increase the binding force between the drug-containing implantable medical device and the controlled-release coating, and also help to obtain a uniform controlled-release coating, so that The controlled release coating is more stable for the controlled release of the drug.

The coating apparatus also includes a liquid removal chamber 80 . In one embodiment, a scraper is provided in the liquid removal chamber 80 , and one of the scraper and the implantable medical device containing medicine moves relative to the other to scrape off excess coating liquid. In another embodiment, a liquid-wetting tool is provided in the liquid-removing chamber 80 to remove excess coating liquid. In yet another embodiment, the liquid removal chamber 80 is provided with a scraper and a liquid wetting tool at the same time. After the excess liquid is removed by a scraper and/or a dipping tool, the coating liquid is evenly distributed on the surface of the drug-containing implantable medical device with a moderate thickness, which is conducive to the formation of a uniform and preset thickness of the controlled-release coating. Among them, the liquid-wetting tool is preferably disposable or replaceable to avoid contamination. Wet implements include, but are not limited to, sponges, lint-free cloths, and cotton swabs.

After the excess liquid is removed, if repeated coating is required, the mechanical gripper 71 holds the carrier 40, so that the implantable medical device containing medicine is left to stand in the liquid removal chamber 80 at a temperature of 10-80°C. The standing time is 0.5-30min. The purpose of standing is to let the solvent evaporate at least partially, which is beneficial to the next coating. Alternatively, after the excess liquid is removed, the mechanical claw 71 clamps the carrier 40 and slowly moves it from the liquid removal chamber 80 to the liquid tank 10 , and the rest is completed during the slow movement. Alternatively, the coating equipment is additionally provided with a static chamber, and the carrier and the implantable medical device containing medicine are moved into the static chamber to complete the static state. If there is no need for repeated coating, or after the last coating and excess liquid removal process has been completed, the mechanical claw 71 drives the carrier 40 to move to the next working section. If the ambient temperature meets the requirements, no additional temperature control is required; if the ambient temperature does not meet the requirements, a third temperature control device can be set to increase or decrease the temperature so that the standing temperature is 10-80°C. In addition, the second timing element can be set to control the resting time, and the moving speed can also be adjusted so that when the moving is in place, the resting time is just reached.

The coating device also includes a volatilization chamber 20, in which the drug-containing implantable medical device is placed in the volatilization chamber 20 after excess coating liquid is removed and before curing, so that the solvent is volatilized. The solvent in the coating solution evaporates at 10-80°C, understandably, if the ambient temperature meets the requirements, no additional temperature control is required. If the ambient temperature does not meet the requirements, the volatilization chamber 20 is also equipped with a fourth temperature control device, which makes the solvent volatilize at 10-80° C. by raising or lowering the temperature. In addition, in order to facilitate the discharge of the volatilized solvent, the volatilization chamber 20 is in an open state. In addition, the volatilization chamber 20 is also equipped with a third timing element to control the volatilization time, and the volatilization time is 0.2-6h.

In one embodiment, the drug-containing implantable medical device is placed in the volatilization chamber 20 to allow the solvent to volatilize. After the volatilization is completed, the drug-containing implantable medical device is moved to the curing chamber 30 . In another embodiment, the volatilization chamber 20 is provided with a third conveyor belt 21. After the drug-containing implantable medical device enters the volatilization chamber 20, it cooperates with the third conveyor belt 21, and the third conveyor belt 21 will The medical equipment moves from one end of the third conveyor belt 21 to the other end of the third conveyor belt 21. By setting the moving speed, the movement completion time matches the solvent volatilization time, that is, when it moves to the other end of the guide rail 21, the solvent volatilization process is completed. . Understandably, in this case, the third timing element can be omitted.

The coating equipment may also include a detection device for detecting whether the thickness of the control coating meets the requirements. The detection device is arranged on the conveying path of the second conveying belt 60 . In one embodiment, the detection device includes a distance sensor and an alarm. The distance sensor is used to detect the distance between the distance sensor and the implantable medical device containing the drug. If the detection distance is not equal to the preset distance, it indicates that the drug may be If the thickness of the controlled-release coating on the surface of the implanted medical device does not meet the requirements, the alarm will sound an alarm, and the operator will discard the drug-containing implantable medical device. In another embodiment, the detection device includes a quality sensor and an alarm. The quality sensor is used to detect the quality of the drug-containing implantable medical device. If the detected quality is not equal to the preset quality, it indicates that the drug-containing implantable medical device If the thickness of the controlled-release coating on the surface does not meet the requirements, the alarm will sound an alarm, and the operator will scrap the drug-containing implantable medical device.

The applicant declares that the above description is only a specific embodiment of the present invention, but the scope of protection of the present invention is not limited thereto, and those skilled in the art should understand that any person skilled in the art should be aware of any disclosure in the present invention Within the technical scope, easily conceivable changes or substitutions all fall within the scope of protection and disclosure of the present invention.

Claims

A method for preparing a controlled-release coating, characterized in that it comprises:

Step 1), coating the coating solution on the surface of the drug-containing implantable medical device, and keeping the temperature of the coating solution at 10-80°C;

Step 2), curing, drug-containing can be implanted on the surface of the medical device to obtain a controlled-release coating.
The method for preparing a controlled-release coating according to claim 1, characterized in that, when performing the step 1), the coating method is at least one of dip coating, spray coating and brush coating.
The method for preparing a controlled-release coating according to claim 1, characterized in that, when performing the step 2), the curing temperature is 20-150° C., and the curing time is less than 10 h.
The method for preparing a controlled-release coating according to claim 1, characterized in that, after carrying out the step 1) and before carrying out the step 2), the step of removing excess coating liquid is also carried out, and the removing The step of removing excess coating fluid includes scraping and/or dipping the medicated implantable medical device.
The method for preparing a controlled-release coating according to claim 4, wherein the step 1) and the step of removing excess coating liquid are repeated at least once, and the step of standing still is carried out before each repetition. The temperature is 10-80°C, and the standing time is less than 1h.
The method for preparing a controlled-release coating according to claim 4, wherein, after carrying out the step of removing excess coating liquid, and before carrying out the step 2), a solvent volatilization step is also carried out, and in 10- The solvent is volatilized at 80° C., and the solvent volatilization time is less than 10 h.
A kind of coating equipment, it is characterized in that, described coating equipment is used for implementing the method for preparing controlled-release coating described in any one of claim 1-6, and described coating equipment comprises: for loading described coating liquid tank and curing chamber.
The coating equipment according to claim 7, wherein the liquid tank is equipped with a first temperature control device, the first temperature control device includes a first heating element and a first temperature detection and control element, the The first heating element is used to heat the coating liquid, and the first temperature detection and control element is used to detect the temperature of the coating liquid and control the first heating element to heat or stop heating.
The coating equipment according to claim 7, wherein the curing chamber is equipped with a second temperature control device, the second temperature control device includes a second heating element and a second temperature detection and control element, through The second heating element heats the curing chamber, the temperature of the curing chamber is detected by the second temperature detection and control element, and the second heating element is controlled to heat or stop heating.
The coating equipment according to claim 9, characterized in that, the curing chamber is further equipped with a first timing element to control the curing time.