Valve clamping device and preparation method thereof

Abstract

The invention discloses a valve clamping device and a preparation method thereof, the valve clamping device is made of a degradable high polymer material doped with a developing component, and the surface of the valve clamping device is covered with a degradable drug coating. The valve clamping device is safe and non-toxic, can be degraded into water and carbon dioxide in vivo, and has small burden on body organs. The surface of the valve clamping device is coated with a degradable medicine coating, and the risk of causing inflammation, tissue hyperplasia and thrombus after the valve clamping device is implanted into a human body is low. Due to the introduction of the developing component, the valve clamping device can be positioned in vivo in real time by virtue of developing equipment, so that a replacement operation of the valve clamping device can be conveniently carried out as required under specific conditions, such as when the valve clamping device is not completely degraded.

Description

Technical Field

[0001] This invention relates to the field of medical device technology, specifically to a valve clamp and its preparation method. Background Technology

[0002] Valve clips are primarily used in interventional treatment of heart valve diseases, particularly in the treatment of mitral and tricuspid regurgitation. Interventional heart valve treatment techniques have evolved from traditional open-heart surgery to minimally invasive procedures, and valve clips have played a crucial role in this transformation.

[0003] Current valve repair techniques typically use nickel-titanium alloy clips, which are complex to manufacture and remain in the atrium long-term after implantation, posing risks of inflammation, thrombosis, and tissue hyperplasia. Furthermore, if the condition recurs or worsens, traditional nickel-titanium alloy clips are difficult to remove during valve replacement surgery. The inability to accurately locate the clip within the body in real time increases the risks of the replacement surgery and can easily lead to surgical accidents. Summary of the Invention

[0004] The purpose of this invention is to provide a valve clip and its preparation method to simplify the processing technology of the valve clip, optimize the biocompatibility of the valve clip, and reduce the operational difficulty of the valve clip in surgery.

[0005] According to a first aspect of the present invention, a valve clamp is provided, wherein the valve clamp is made of a biodegradable polymer material; the biodegradable polymer material is doped with a radioactive component; and the surface of the valve clamp is covered with a biodegradable drug coating.

[0006] Furthermore, the thickness of the biodegradable drug coating is 5–10 μm.

[0007] Furthermore, the biodegradable polymeric material includes copolymers of one or more of the following polymers: PLA, PGLA, PLLA, PLGA, PGA, PCL, and PBS.

[0008] Furthermore, the biodegradable polymer material is a PCL-PLA copolymer with a molecular weight of 60,000 Da to 80,000 Da.

[0009] Furthermore, the molecular weight of the PCL-PLA copolymer is 65,000 Da to 75,000 Da.

[0010] Furthermore, the developing component includes at least one of iohexol, iopamidol, iopromide, iofluridine, meglumine diatrizoate, iodixanol, iodic acid, tetraiodobenzoate, and p-iodoaniline.

[0011] Furthermore, the mass ratio of the developing component to the biodegradable polymer material is 0.06:1 to 0.07:1.

[0012] Furthermore, the biodegradable drug coating includes at least one of paclitaxel, cyclosporine, rapamycin, emodin, dexamethasone, mitomycin, and actinomycin.

[0013] According to a second aspect of the present invention, a method for preparing a valve clamp as described in the first aspect is provided, the method comprising the following steps:

[0014] The biodegradable polymer material is made into a powder and blended with the developer to obtain a blend;

[0015] Using the blend as a printing medium, 3D printing was performed to obtain valve clamp components, which were then assembled into a valve clamp.

[0016] A biodegradable drug coating is applied to the surface of the assembled valve clamp.

[0017] Compared to existing nickel-titanium alloy clamps, the advantages of this invention are as follows:

[0018] 1. The valve clamp provided by the present invention is made of biodegradable polymer material, which has good biocompatibility. After implantation, it can be degraded into water and carbon dioxide in the body. The degradation rate is appropriate and the burden on organs is small.

[0019] 2. The valve clip provided by the present invention contains a contrast agent, which facilitates the positioning and placement of the clip during surgical installation or replacement. Furthermore, when the clip is not completely degraded in the later stages of implantation, it can be monitored in real time with the aid of a contrast agent, which facilitates surgical replacement of the valve clip as needed after disease recurrence.

[0020] 3. The valve clamp provided by the present invention is coated with a biodegradable drug coating, which can reduce the risk of thrombosis and inflammation, as well as the risk of tissue hyperplasia.

[0021] 4. The valve clip provided by this invention is made by 3D printing, which is simple and economical. In addition, the valve clip provided by this invention does not contain metal materials, so it does not hinder the patient from undergoing CT, MRT and other examinations, and has few application limitations. Attached Figure Description

[0022] Other features, objects, and advantages of the present invention will become more apparent from the following detailed description of non-limiting embodiments with reference to the accompanying drawings:

[0023] Figure 1 This is a schematic diagram of the valve clamp in a specific embodiment of the present invention.

[0024] Figure 2 This is a schematic diagram of tissue sections taken 1 to 24 weeks after the valve clip is implanted into muscle tissue in a specific embodiment of the present invention. Detailed Implementation

[0025] The following is a more detailed description of a valve clamp and its preparation method according to the present invention, with reference to schematic diagrams, illustrating preferred embodiments of the invention. It should be understood that those skilled in the art can modify the invention described herein while still achieving its advantageous effects. Therefore, the following description should be understood as being of general knowledge to those skilled in the art and is not intended to limit the invention.

[0026] For clarity, not all features of the actual embodiments are described. In the following description, well-known functions and structures are not detailed in detail, as they would obscure the invention with unnecessary detail. It should be understood that in the development of any actual embodiment, numerous implementation details must be made to achieve the developer's specific objectives, such as changes from one embodiment to another according to limitations related to the system or business. Furthermore, it should be understood that such development work may be complex and time-consuming, but is merely routine work for those skilled in the art.

[0027] The invention is described more specifically by way of example in the following paragraphs with reference to the accompanying drawings. The advantages and features of the invention will become clearer from the following description and claims. It should be noted that the drawings are in a very simplified form and use non-precise proportions, and are only used to facilitate and clarify the illustration of the embodiments of the invention.

[0028] In one specific embodiment of the present invention, a valve clamp is provided, the valve clamp being made of PCL-PLA copolymer with a molecular weight of 65,000 to 75,000. Iohexol is doped into the PCL-PLA copolymer, and the mass ratio of iohexol to the PCL-PLA copolymer is 0.065:1. The surface of the valve clamp is coated with a biodegradable drug coating of rapamycin.

[0029] By controlling the molecular weight of the PCL-PLA copolymer, valve clips with different degradation rates can be obtained. Iohexol is a preferred imaging component of this invention; its introduction into the biodegradable polymer material enables the valve clip to be positioned in vivo. The biodegradable drug coating of rapamycin applied to the surface of the valve clip reduces the risk of inflammation or tissue hyperplasia caused by contact between the device and tissue.

[0030] In one specific embodiment of the present invention, a method for preparing the valve clamp as described above is also provided, comprising the following steps:

[0031] A blend was obtained by blending PCL-PLA copolymer powder with a molecular weight of 65,000 to 75,000 with iohexol at a mass ratio of 1:0.065.

[0032] 3D printing of valve clamp components using blends as printing media and assembling them into clamps;

[0033] The clamp is fixed in an ultrasonic spraying machine with a tooling, and after ultrasonic spraying with rapamycin, it is removed to obtain the valve clamp.

[0034] like Figure 1 As shown, the valve clamp obtained by the method of the present invention can have common shapes and structures, and the connection relationships of its various parts are familiar to those skilled in the art and will not be described in detail here.

[0035] To verify the biodegradability of the valve clip provided by this invention, an in vitro degradation experiment was conducted. The specific steps are as follows:

[0036] (1) Grouping

[0037] The study was divided into two groups: a blank control group and an experimental group. The blank control group consisted of 10 clamp samples placed in sealed containers at room temperature for 60 weeks before testing. The experimental group was divided into five time points based on in vitro degradation time: 3 weeks, 5 weeks, 15 weeks, 30 weeks, and 60 weeks. Ten clamp samples were used for testing at each time point, for a total of 30 samples.

[0038] (2) Simulated body fluid immersion in vitro degradation

[0039] All clamps in the experimental groups were vacuum-sealed and labeled. After sterilization by cobalt-60 irradiation, each clamp was placed individually in a 50ml cell culture tube. The sample was then covered with a 30ml volume of prepared simulated body fluid, ensuring complete immersion of the sample. The cell culture tubes were then placed in a constant-temperature cell culture incubator to maintain a physiological temperature of 36℃–38℃, with the immersion solution changed every two weeks.

[0040] (3) Calculate the mass lost and the rate of weight loss.

[0041] Before the experiment, all clamps in both groups were vacuum-dried at 25°C for 48 hours until constant weight. Each clamp was weighed individually using an electronic balance (denoted as W0) and labeled, with an accuracy of 0.1 mg. The clamps in the experimental group were then placed in simulated body fluid for in vitro degradation according to the above standards. At 3, 5, 15, 30, and 60 weeks after in vitro degradation, 10 clamps were taken out at each time point, rinsed three times with deionized water, vacuum-dried at 25°C for 48 hours until constant weight, and weighed using the same electronic balance, denoted as W1. Weight loss rate = [initial mass W0 - degraded mass W1] / W0 × 100% (n = 10). The control group clamps were placed in a sealed container at room temperature for 60 weeks, and their mass was measured and weight loss rate calculated using the same method. The changes in mass loss and weight loss rate of the clamps at different time points during in vitro degradation are shown in Table 1.

[0042] Table 1. Changes in mass loss and weight loss rate of the clamp at different time points during in vitro degradation.

[0043]

[0044] Using the t-test, there were no statistically significant differences in quality between the control group and the experimental group before and after 3, 5, and 15 weeks (P > 0.05); however, there were statistically significant differences in quality before and after 30 and 60 weeks (P < 0.05).

[0045] Implants typically undergo endothelialization in vivo, a process that often takes more than three months. Therefore, rapid degradation is detrimental to ensure their strength and stability within the body. As shown in Table 1, the in vitro degradation results indicate that complete degradation of the clamp may take more than two years. However, because the in vitro degradation process lacks the phagocytic and enzymatic metabolic processes of in vivo cells and tissue fluid, the degradation process and rate differ between in vitro and in vivo. Therefore, the in vitro degradation results cannot be equated with the actual in vivo application of the clamp and have certain limitations. Nevertheless, the in vitro degradation process can, to some extent, illustrate the degradation characteristics and rate changes of the clamp in vivo.

[0046] The raw materials of the valve clamp provided by the present invention are prepared into test samples through the following steps and then subjected to biological performance testing: the blend of PCL-PLA copolymer powder and iohexol is made into a glass slide and coated with a biodegradable drug coating of rapamycin to obtain the test sample.

[0047] 1. Hemolysis test:

[0048] The hemolysis experiment involved collecting 10 mL of blood from the heart of a healthy New Zealand rabbit and adding 0.5 mL of 20 g / L potassium oxalate solution to prepare fresh anticoagulated rabbit blood. 8 mL of this fresh anticoagulated rabbit blood was diluted with 10 mL of physiological saline. Test samples (2.2 cm × 2.6 cm) were placed in a 50 mL saline beaker containing 10 mL of physiological saline. For the negative control group, 10 mL of sodium chloride injection was added to each tube; for the positive control group, 10 mL of distilled water was added to each tube. Three tubes were run in parallel for each group. After incubating all tubes in a 37°C water bath for 30 min, 0.2 mL of diluted rabbit blood was added to each tube, gently mixed, and incubated at 37°C for another 60 min. Pour out 800g of liquid from the tube and centrifuge for 5 minutes. Collect the supernatant after 5 minutes of centrifugation and measure the absorbance at 545nm using an ELISA reader. Calculate the hemolysis rate: Hemolysis rate (%) = 100*(AB) / (CB); where: A: absorbance of the test sample; B: absorbance of the negative control; C: absorbance of the positive control. The experimental results are shown in Table 2.

[0049] Table 2 Results of the hemolysis test

[0050] sample absorbance Hemolysis rate % negative control 0.022 0 Positive control 1.297 100 Test sample 0.036 1.09

[0051] The calculation results in Table 2 show that the hemolysis rate of the test sample was 1.09%, which meets the requirement of GB / T16886.4-2003 that the hemolysis rate of the sample should be <5%.

[0052] 2. Muscle implantation experiment:

[0053] The tests were conducted according to the methods recommended in the national standard GB / T 16886.6-2015 "Biological evaluation of medical devices - Part 6: Local reaction test after implantation".

[0054] Healthy adult rabbits were used as experimental animals in this experiment. After routine disinfection of the skin, the experimental samples were implanted into the muscles approximately 2 cm from the spine on both sides of the midline. At 1, 4, 12, and 24 weeks post-implantation, the animals were euthanized painlessly with an excess of CO2. The implants and surrounding tissues were excised for macroscopic observation, fixed in 10% neutral buffered formalin, and then dissected. PCL-PLA slides were retained, and the dissected tissue blocks were dehydrated with graded alcohol gradients, embedded in paraffin, sectioned, stained with hematoxylin and eosin (HE), and subjected to histopathological observation and evaluation. The histological observations of the experimental samples from 1 to 24 weeks post-implantation are as follows: Figure 2 As shown.

[0055] One week after implantation, the experimental sample showed significant inflammation and tissue hyperplasia, with extensive angiogenesis. At 4, 12, and 24 weeks post-implantation, the inflammatory cells around the implant gradually disappeared, and a stable fibrous encapsulation gradually formed. Microscopic observation of the surrounding muscle tissue revealed no obvious abnormalities. This indicates that the experimental sample and surrounding muscle tissue stabilized with prolonged implantation time. The absence of necrosis or inflammatory reaction suggests that the experimental sample was non-toxic to the surrounding muscle tissue, and the local response after implantation was good.

[0056] In summary, in a specific embodiment of the present invention, a valve clip and its preparation method are provided. The valve clip is made of a biodegradable polymer material with good biocompatibility. After implantation, it can degrade into water and carbon dioxide in the body at a suitable degradation rate, resulting in minimal burden on organs. Furthermore, the valve clip provided by the present invention contains a contrast agent, which facilitates positioning and placement of the clip during surgical installation or replacement. Even when the clip is not fully degraded in the later stages of implantation, real-time monitoring can be achieved using contrast agents, facilitating surgical replacement of the valve clip as needed after disease recurrence. Additionally, the valve clip provided by the present invention is coated with a biodegradable drug coating, which can reduce the risk of thrombosis and inflammation, as well as the risk of tissue hyperplasia.

[0057] Furthermore, the valve clip provided by this invention is made using 3D printing, which is simple and cost-effective. In addition, the valve clip provided by this invention does not contain any metal materials, so it does not hinder the patient from undergoing CT, MRI and other examinations, and has few limitations in application.

[0058] The valve clamp provided by this invention contains a contrast agent, which facilitates the positioning and placement of the clamp during surgical installation or replacement, and enables real-time monitoring in the later stages of clamp implantation.

[0059] The valve clamp provided by this invention has a biodegradable drug coating on its surface, which can reduce the risk of thrombosis and inflammation, and reduce the risk of tissue hyperplasia.

[0060] The valve clamp components provided by this invention are prepared by 3D printing, which is simple and economical.

[0061] The above are merely preferred embodiments of the present invention and do not constitute any limitation on the present invention. Any equivalent substitutions or modifications made by those skilled in the art to the technical solutions and content disclosed in the present invention without departing from the scope of the present invention shall be deemed to have remained within the protection scope of the present invention.

Claims

1. A valve clamp, characterized in that, The valve clamp is made of a biodegradable polymer material; the biodegradable polymer material is doped with a radioactive component; and the surface of the valve clamp is covered with a biodegradable drug coating.

2. The valve clamp according to claim 1, characterized in that, The thickness of the biodegradable drug coating is 5–10 μm.

3. The valve clamp according to claim 1, characterized in that, The biodegradable polymeric material includes copolymers of one or more of the following polymers: PLA, PGLA, PLLA, PLGA, PGA, PCL, and PBS.

4. The valve clamp according to claim 3, characterized in that, The biodegradable polymer material is a PCL-PLA copolymer with a molecular weight of 60,000 Da to 80,000 Da.

5. The valve clamp according to claim 4, characterized in that, The molecular weight of the PCL-PLA copolymer is 65,000 Da to 75,000 Da.

6. The valve clamp according to claim 1, characterized in that, The developing components include at least one of iohexol, iopamidol, iopromide, iodofol, meglumine diatrizoate, iodixanol, iodoxacic acid, tetraiodobenzoate, and p-iodoaniline.

7. The valve clamp according to claim 6, characterized in that, The mass ratio of the developing component to the biodegradable polymer material is 0.06:1 to 0.07:

1.

8. The valve clamp according to claim 1, characterized in that, The biodegradable drug coating includes at least one of paclitaxel, cyclosporine, rapamycin, emodin, dexamethasone, mitomycin, and actinomycin.

9. The method for preparing the valve clamp according to any one of claims 1 to 8, characterized in that, Includes the following steps: The biodegradable polymer material is made into a powder and blended with the developer to obtain a blend; Using the blend as a printing medium, 3D printing was performed to obtain valve clamp components, which were then assembled into a valve clamp. The biodegradable drug coating is applied to the surface of the assembled valve clamp.

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