High polymer material degradable hemostatic clip and manufacturing method thereof

Abstract

The invention discloses a degradable hemostatic clip made of a high polymer material and a manufacturing method of the degradable hemostatic clip. According to the degradable hemostatic clip, Mg-Zn-Ga series metal alloys with different contents and a degradable functional polymer organic compound PLGA are combined to form a metal-polymer two-phase structure, so that the problems that a traditional titanium clip is non-degradable and can cause inflammation, imaging interference and the like after being retained in a body for a long time are solved, the clamping force of the high polymer material hemostatic clip (such as PLA / PGA) is improved, and the hemostatic clip has a good application prospect. Different types of PLGA can be prepared according to different monomer ratios, the degradation degree is different along with different monomer ratios, and the in-vivo degradation period of the disposable hemostatic clip is guaranteed.

Description

Technical Field

[0001] The present invention belongs to the field of medical devices, and specifically relates to a hemostatic clip that achieves controllable degradation through metal-polymer composite materials and structural design. The hemostatic clip is suitable for closing blood vessels or tissues in minimally invasive surgeries such as laparoscopy and endoscopy, avoiding secondary surgery for removal. Background Art

[0002] The main function of a disposable hemostatic clip is to achieve hemostasis by clamping blood vessels or tissues and blocking blood flow. It is usually made of medical stainless steel and has a pair of jaws and a handle. The design of the jaws enables it to firmly clamp blood vessels or tissues to ensure hemostasis. The design of the handle allows doctors to easily control the use of the hemostatic clip. Since the performance of medical devices directly affects the safety and treatment effects of patients, it is crucial to improve clinical safety and effectiveness. Achieving the degradability of hemostatic clips can significantly improve the reliability of the devices and reduce the risk of complications. Research on new materials and new design concepts will help promote the advancement of interventional medical device technology and promote the development of more efficient and controllable medical devices. Research on degradable hemostatic clips will help enhance the competitiveness of the entire industry chain and promote the healthy development of my country's medical device industry.

[0003] Traditional hemostatic clips are bulky and complex to operate, making them difficult to adapt to the narrow confines of the clamp channel. While traditional hemostatic clips (such as titanium alloy clips) possess high mechanical properties, they must remain permanently in the body, potentially leading to inflammatory reactions, imaging interference (such as CT / MRI artifacts), and psychological burden on patients. Early absorbable hemostatic clips were mostly made of polymer materials such as polylactic acid (PLA) and polyglycolic acid (PGA), but their mechanical strength was insufficient, resulting in a short-lived clamping force and prone to failure before tissue healing. Furthermore, there is a significant mismatch between degradation rate and healing cycle. For example, PLA has a long degradation period (6-24 months), which can cause delayed inflammation.

[0004] A single material cannot achieve both mechanical strength and controllable degradation. Magnesium alloys exhibit a rapid initial degradation rate, but incomplete degradation occurs later due to the accumulation of corrosion products. While suitable for short-term hemostasis, researchers have leveraged the excellent biodegradability and mechanical properties of magnesium alloys to develop pure magnesium and magnesium-based composite hemostatic clips. However, the processing of magnesium alloy hemostatic clips is complex and time-consuming, and the precision and efficiency of the finished product need to be improved. Traditional magnesium alloy composites use hydrofluoric acid for passivation, and the decomposed fluoride ions can also have adverse effects on the human body. Some magnesium alloy hemostatic clips present a risk of postoperative migration or slippage in clinical use, potentially leading to wound bleeding or secondary surgery. Zinc alloys, by adjusting their composition (such as adding calcium and strontium), have a longer degradation cycle, making them suitable for long-term clamping applications. Iron alloys degrade more slowly, but composite coatings can balance mechanical properties and degradation rate, making them suitable for high-strength applications such as vascular closure. Magnesium alloys are used for minimally invasive procedures such as laparoscopy to meet short-term degradation requirements, but the degradation rate is uncontrollable. Adding polymer coatings can achieve this degradation rate control.

[0005] Based on this, the present invention provides a metal-polymer degradable hemostatic clip to resolve the contradiction between insufficient strength of polymer materials and uncontrollable degradation rate. Summary of the Invention

[0006] The purpose of the present invention is to address the deficiencies of the prior art and provide a polymer material degradable hemostatic clip and a method for making the same, which can effectively meet the requirements of degradation cycle and hemostatic clip clamping force strength.

[0007] The technical solutions adopted in the present invention are as follows:

[0008] A method for making a polymer-based biodegradable hemostatic clip includes selecting a Mg-Zn-Zr-Ca alloy (4% Zn, 0.9% Zr, 0.4% Ca, with the balance being Mg) and balancing mechanical properties with degradation rate. Specifically, under argon protection, pure magnesium and alloying elements are melted (melting temperature 700-750°C), stirred until uniform, and then poured into a preheated mold (210-260°C) to form the magnesium alloy matrix.

[0009] The magnesium alloy substrate is subjected to phytic acid passivation treatment to form a dense magnesium phytic acid composite passivation layer, namely, a MgF2 nanolayer (thickness 1-3 μm) on the surface.

[0010] The initial degradation rate was mitigated by controlling the PLGA monomer content (70-90% LA 10-30% GA). The PLGA solution was evenly coated on the surface of the passivated magnesium alloy substrate using an electrostatic spraying device (voltage 30 kV, nozzle diameter 0.3 mm) to form a sustained-release layer with a thickness of 10-20 μm. The degradation cycle was 2-5 months.

[0011] Afterwards, the hemostatic clip may be obtained by vacuum drying at 60° C. for 12 hours.

[0012] Furthermore, the hemostatic clip is V-shaped with serrated edges (depth 500-600 μm, spacing 1 mm) to ensure the required clamping force. The cutting angle is usually 35°.

[0013] Furthermore, the outer layer is coated with chitosan with a mass concentration of 2-5% to promote blood coagulation and antibacterial properties.

[0014] The hemostatic clip prepared by the method of the present invention not only meets the mechanical properties, but also has a magnesium alloy matrix (degradation in 1-2 months) and a PLGA coating (degradation in 2-5 months) that work together to match the tissue healing cycle; the magnesium alloy provides initial strength (tensile strength > 300 MPa), and the PLGA / chitosan coating enhances wound healing ability. BRIEF DESCRIPTION OF THE DRAWINGS

[0015] Figure 1 This is a schematic diagram of the structure of the polymer material degradable hemostatic clip of the present invention;

[0016] Figure 2 Schematic diagram of gradient degradation mechanism;

[0017] Figure 3 This is a graph showing the experimental data of 20-week degradation rate comparison. DETAILED DESCRIPTION

[0018] The technical solution of the present invention is further described below with reference to the accompanying drawings and specific embodiments. The components of the Mg-Zn-Zr-Ca alloy described in the embodiment are as follows: Zn 4%, Zr 0.9%, Ca 0.4%, and the balance Mg by weight.

[0019] Example 1

[0020] A polymer-based biodegradable hemostatic clip and its manufacturing method include the following steps: injection molding a (Mg-Zn-Zr-Ca) magnesium alloy substrate into a V-shaped clip, with a single clip length of 1 cm (±0.5 mm) and a magnesium phytate composite passivation layer of 2 μm thickness. PLGA (90:10) is sprayed onto the clip to form a 15 μm-thick sustained-release layer, followed by vacuum drying at 60° for 12 hours. A 2% chitosan solution can then be applied to the surface. Mechanical properties were tested using ASTM F2392 standards, simulating a 5 mm silicone blood vessel. The clamping force was 5.5 N, and the tensile strength was initially 12 MPa, maintaining 8.2 MPa after 8 weeks. The clip exhibited no plastic deformation after 1000 opening and closing cycles. In vitro, in simulated body fluid (PBS, 37°C, pH 7.4), the mass loss rate was 15% (PLGA layer) at 2 weeks, with no significant corrosion of the magnesium alloy substrate. The mass loss rate was 45% at 6 weeks (most of the PLGA layer degraded, 10% of the magnesium alloy degraded), and 65% at 10 weeks (complete degradation of the PLGA layer and 30% of the magnesium alloy degraded). Complete degradation occurred in 14 weeks for the magnesium alloy and 16 weeks for the entire structure. Animal experiments (rat liver hemostasis) showed no inflammatory response 14 weeks after surgery, and degradation products were completely absorbed.

[0021] Example 2

[0022] A polymer-based biodegradable hemostatic clip and its manufacturing method include the following steps: injection molding a (Mg-Zn-Zr-Ca) magnesium alloy substrate into a V-shaped clip body, with a single clip length of 1 cm (±0.5 mm) and a magnesium phytate composite passivation layer of 2 μm thickness. PLGA (80:20) is then sprayed onto the clip body to form a 15 μm-thick sustained-release layer. The clip is then vacuum-dried at 60° for 12 hours, and then coated with a 2% chitosan solution. Mechanical properties were tested using ASTM F2392 standards, simulating a 5 mm silicone blood vessel. The clamping force was 5.3 N, and the tensile strength was initially 11 MPa, maintaining 7.8 MPa after 8 weeks. The clip exhibited no plastic deformation after 1000 opening and closing cycles. In vitro, in simulated body fluid (PBS, 37°C, pH 7.4), the mass loss rate was 22% (PLGA layer) at 2 weeks, with no significant corrosion of the magnesium alloy substrate. The mass loss rate was 57% at 6 weeks (most of the PLGA layer degraded, 19% of the magnesium alloy degraded), and 82% at 10 weeks (complete degradation of the PLGA layer and 50% of the magnesium alloy degraded). Complete degradation occurred in 13 weeks for the magnesium alloy and 14 weeks for the entire structure. Animal experiments (rat liver hemostasis) showed no inflammatory response 14 weeks after surgery, and degradation products were completely absorbed.

[0023] Example 3

[0024] A polymer-based biodegradable hemostatic clip and its manufacturing method include the following steps: injection molding a (Mg-Zn-Zr-Ca) magnesium alloy substrate into a V-shaped clip body, with a single clip length of 1 cm (±0.5 mm) and a magnesium phytate composite passivation layer of 2 μm thickness. PLGA (70:30) is then sprayed onto the clip body to form a 15 μm-thick sustained-release layer. The clip is then vacuum-dried at 60° for 12 hours, and then coated with a 2% chitosan solution. Mechanical properties were tested using ASTM F2392 standards, simulating a 5 mm silicone blood vessel. The clamping force was 4.9 N, and the tensile strength was initially 10.2 MPa, maintaining 6.8 MPa after 8 weeks. The clip exhibited no plastic deformation after 1000 opening and closing cycles. In vitro, in simulated body fluid (PBS, 37°C, pH 7.4), the mass loss rate was 34% (PLGA layer) at 2 weeks, with no significant corrosion of the magnesium alloy substrate. The mass loss rate was 64% at 6 weeks (most of the PLGA layer degraded, 10% of the magnesium alloy degraded). The mass loss rate was 86% at 10 weeks (complete degradation of the PLGA layer, % degradation of the magnesium alloy). Complete degradation occurred in 10 weeks for the magnesium alloy and 13 weeks for the entire structure. Animal experiments (rat liver hemostasis) showed no inflammatory response 14 weeks after surgery, and degradation products were completely absorbed.

[0025] Comparative Example 1

[0026] A polymer-based biodegradable hemostatic clip and its production method include the following steps: Using a pure polymer hemostatic clip as an example, a PLGA (50:50) + 2% chitosan composition is used. A 3D-printed V-shaped clip body with a 0.1mm thick chitosan layer is molded onto the inner surface with anti-slip teeth (80μm deep, staggered in a diamond pattern). The outer layer is coated with a 20μm thick polycaprolactone (PCL) sustained-release layer (electrostatically sprayed). The clip has a clamping force of 3.8N (lower than the magnesium-PLGA clip, but sufficient for superficial vessels). The initial tensile strength is 8MPa, decreasing to 3MPa after 4 weeks. The 4-week mass loss rate is 30% (the PCL layer delays initial degradation). The complete degradation time is 18 weeks (the PLGA matrix). Endoscopic surgery testing demonstrated a 92% clipping success rate after 15 consecutive firings. Degradation synchrony: the clip loosened 12 weeks after surgery, matching the healing cycle of the digestive tract mucosa.

[0027] Comparative Example 2

[0028] A polymer-based biodegradable hemostatic clip and its manufacturing method include the following steps: Using a pure magnesium alloy hemostatic clip as an example, the clip is constructed from pure magnesium alloy + 2% chitosan, with a 3D-printed V-shaped clip body and a 0.1mm thick chitosan layer. The inner surface is molded with anti-slip teeth (80μm deep, staggered in a diamond pattern), and the outer layer is coated with a 20μm thick polycaprolactone (PCL) sustained-release layer (electrostatically sprayed). The clip exhibits a clamping force of 4.5N and an initial tensile strength of 12MPa, which drops to 3MPa after three weeks. The four-week mass loss rate is 50% (the PCL layer delays initial degradation), indicating excessive degradation in the early stages. Endoscopic surgery testing demonstrated a 94% clipping success rate after 15 consecutive firings. Degradation synchrony revealed minimal clamping force eight weeks after surgery, making it suitable for rapid wound healing. Furthermore, the degradation rate is approximately 94%, which falls short of complete degradation.

[0029] The embodiments described above are merely some preferred embodiments of the present invention and are not intended to limit the present invention. Persons skilled in the art may make various changes and modifications without departing from the spirit and scope of the present invention. Therefore, any technical solution obtained by equivalent substitution or equivalent transformation falls within the scope of protection of the present invention.

Claims

1. A method for making a polymer-based degradable hemostatic clip, characterized in that: include: Mg-Zn-Zr-Ca alloy is selected to form a magnesium alloy matrix; It is subjected to phytic acid passivation treatment to form a dense magnesium phytate composite passivation layer on the surface; The PLGA solution is evenly coated on the surface of the magnesium alloy substrate after passivation treatment to form a sustained-release layer, and then dried to obtain a polymer material degradable hemostatic clip.

2. The method for making a polymer degradable hemostatic clip according to claim 1, characterized in that: The components of the Mg-Zn-Zr-Ca alloy are as follows: 4% Zn, 0.9% Zr, 0.4% Ca, and the balance Mg by mass.

3. The method for making a polymer degradable hemostatic clip according to claim 1, characterized in that: The thickness of the magnesium phytate composite passivation layer is 1-3 μm.

4. The method for making a polymer degradable hemostatic clip according to claim 1, characterized in that: The initial degradation rate is alleviated by controlling the monomer ratio in the PLGA solution to 70-90% LA and 10-30% GA, so that the degradation period of the hemostatic clip is 2-5 months.

5. The method for making a polymer degradable hemostatic clip according to claim 1, characterized in that: The thickness of the sustained-release layer is 10-20 μm.

6. The method for making a polymer degradable hemostatic clip according to claim 1, characterized in that: The hemostatic clip has a V-shaped structure with a serrated edge, a serration depth of 500-600 μm, a spacing L of 1 mm, and an inclination angle α of 35° to ensure the clamping force requirement.

7. The method for making a polymer degradable hemostatic clip according to claim 1, characterized in that: Chitosan with a mass concentration of 2-5% is then applied outside the sustained-release layer to promote blood coagulation and antibacterial properties.

8. The method for making a polymer degradable hemostatic clip according to claim 1, characterized in that: Including magnesium alloy hot extrusion molding, PLGA electrostatic spraying, specifically including the following: Under argon protection, pure magnesium and alloy elements are melted at a melting temperature of 700-750°C, stirred until uniform, and poured into a mold preheated to 210-260°C to form a magnesium alloy matrix; After passivation treatment with phytic acid, the PLGA solution is evenly sprayed on the surface of the magnesium alloy substrate by using an electrostatic spraying method, and after vacuum drying, the chitosan solution is coated and dried.

9. A polymer material degradable hemostatic clip, characterized in that: The method is prepared by the method according to any one of claims 1 to 8.

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