Absorbable ligature clip with excellent mechanical property and preparation method thereof

Abstract

The invention discloses an absorbable ligature clip with excellent mechanical properties and a preparation method of the absorbable ligature clip, and belongs to the technical field of absorbable materials and application. The absorbable ligature clip is of a double-layer structure made of different materials and comprises an inner-layer clip body and an outer-layer clip body, the inner-layer clip body is made of a mixture of a glycolide trimethylene carbonate block copolymer (PGA-TMC) and polyglycolide (PGA), and the outer-layer clip body is made of poly (p-dioxo-cyclohexanone) (PPDO); and the outer-layer clamp completely wraps the inner-layer clamp. And the glycolide trimethylene carbonate block copolymer (PGA-TMC) in the inner layer clamp accounts for 10 to 30 percent of the weight of the inner layer clamp. According to the invention, the mixed material of PGA-TMC and PGA is adopted in the inner layer clip, so that the overall rigidity of the ligature clip is reduced to a certain extent, and the mechanical maintenance time is prolonged.

Description

Technical Field

[0001] The present invention relates to the field of absorbable materials and application technology, and in particular to an absorbable ligation clip with excellent mechanical properties and a preparation method thereof. Background Art

[0002] An absorbable ligation clip is a medical device made of biodegradable materials, mainly used to close or ligate tubular tissues such as blood vessels and bile ducts during surgery.

[0003] Currently, ligation clips are mainly divided into three categories: non-absorbable metal clips, non-absorbable polymer clips and absorbable polymer clips.

[0004] Non-absorbable metal clips, mostly made of titanium alloy, offer high strength, corrosion resistance, and biocompatibility. They are widely used in gastrointestinal and vascular surgeries. Comprising a clamp and a tube, they achieve hemostasis through mechanical closure. Their advantages include strong clamping force and high mechanical stability, making them particularly suitable for closing large vessels or thick-walled tissues, providing reliable hemostasis. They also offer excellent long-term safety, as titanium alloy is highly inert and harmless to the human body, and requires no postoperative degradation management. However, their disadvantages include the need for a secondary surgical procedure for removal, imaging interference, and potential complications.

[0005] The non-absorbable polymer clip is a single-layer V-shaped locking structure made of polyoxymethylene (POM). It has excellent biocompatibility and mechanical properties, and has elasticity, puncture function and locking structure. After clamping, it forms a fully closed state and can continue to maintain the clamping force, overcoming most of the disadvantages of titanium metal clips. However, the situation of permanent retention in the body after ligation cannot be changed.

[0006] Absorbable polymer clips do not require secondary surgery for removal, have good biocompatibility, and are free of foreign matter after degradation, reducing the risk of long-term inflammation or stone formation. Based on their structure, they can currently be divided into single and double clips. Single clips are primarily composed of polydioxanone (PPDO). Because the material is relatively soft, single clips have a certain risk of slippage and relatively poor clamping stability. The outer layer of a double clip is primarily composed of polyglycolide (PGA), and the inner layer is composed of PPDO. The presence of PGA provides greater rigidity, reducing the risk of slippage. However, because the PGA material itself is relatively hard, friction can easily cause damage to internal organs in the early stages of implantation. Summary of the Invention

[0007] In response to the above-mentioned shortcomings of the prior art, the purpose of the present invention is to provide an absorbable ligation clip with excellent mechanical properties and a preparation method thereof. The absorbable ligation clip has an inner and outer double-layer structure, the outer layer is made of polydioxanone (PPDO), and the inner layer is made of a mixed material of PGA-TMC and PGA, which reduces the overall rigidity of the ligation clip to a certain extent, thereby improving the mechanical maintenance time.

[0008] To achieve the above object, the technical solutions adopted by the present invention are as follows:

[0009] Disclosed is an absorbable ligation clip with excellent mechanical properties. It has a double-layer structure made of different materials, including an inner clip and an outer clip. The inner clip is made of a mixture of glycolide trimethylene carbonate block copolymer (PGA-TMC) and polyglycolide (PGA), and the outer clip is made of polydioxanone (PPDO). The outer clip completely or partially wraps around the inner clip.

[0010] Furthermore, in the inner layer sandwich material, the weight proportion of glycolide trimethylene carbonate block copolymer (PGA-TMC) is 10-30%, preferably 15-20%.

[0011] Furthermore, the cross section of the inner layer clip is a circular or polygonal structure, and the diameter or cross-sectional thickness of the inner layer clip is 0.5-1.8 mm, preferably 1.0-1.4 mm.

[0012] Furthermore, the surface of the inner layer is smooth or has a partially serrated structure.

[0013] Furthermore, the inner layer clip partially or completely penetrates the space within the outer layer clip.

[0014] Furthermore, the curvatures of the inner layer clip and the outer layer clip at corresponding positions are similar or consistent.

[0015] Furthermore, the glycolide trimethylene carbonate block copolymer (PGA-TMC) is copolymerized by polyglycolide (PGA) and trimethylene carbonate (TMC). The rigid segments of PGA are combined with the flexible segments of TMC to form a glycolide trimethylene carbonate block copolymer with a molecular weight of 70,000-180,000 that has both strength and elasticity.

[0016] Furthermore, the absorbable ligation clamp is a V-shaped structure, including a clamp arm and a clamp arm II, the ends of the clamp arm I and the clamp arm II are fixedly connected, and the front ends (free ends) are detachably connected through a locking structure.

[0017] Furthermore, the method for preparing the absorbable ligation clip with excellent mechanical properties adopts injection molding technology to prepare the absorbable ligation clip, which specifically includes the following steps:

[0018] (1) Designing a double-layer injection mold having an outer cavity and an inner cavity according to the structure of the absorbable ligation clip;

[0019] (2) Weigh a certain weight of the inner layer material and put it into the inner cavity of the mold, and then weigh a certain weight of polydioxanone (PPDO) and put it into the outer cavity of the mold;

[0020] (3) Set the injection temperature of the inner cavity to 215-225°C and the cooling time to 32-50s; set the injection temperature of the outer cavity to 115-120°C and the cooling time to 60-80s;

[0021] (4) First, the material in the inner cavity of the mold is injection molded, and after cooling and shaping, the material in the outer cavity of the mold is injection molded, and after cooling and shaping, the absorbable ligation clip is obtained.

[0022] The design mechanism and beneficial effects of the present invention are as follows:

[0023] 1. The absorbable ligation clip of the present invention has an overall V-shaped structure and an inner and outer double-layer structure. The outer layer is made of polydioxanone (PPDO). In addition, the inner layer innovatively uses a mixed material of PGA-TMC and PGA, which reduces the overall rigidity of the ligation clip to a certain extent, thereby improving the mechanical holding time.

[0024] 2. The optimal addition ratio of PGA-TMC in the inner layer sandwich of the present invention is 15-20 wt.%, and the optimal cross-sectional thickness (diameter) of the inner layer sandwich is 1.0-1.4 mm. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1 Schematic diagram of the structure of the absorbable ligation clip of the present invention.

[0026] Figure 2 Schematic diagram of axial slip force test.

[0027] Figure 3 Schematic diagram of radial slip force test. DETAILED DESCRIPTION

[0028] In order to further illustrate the technical solution of the present invention, the present invention is further described below through examples.

[0029] The present invention provides an absorbable ligation clip with excellent mechanical properties, such as Figure 1 As shown, it is a two-layer structure made of different materials, including an inner layer and an outer layer. The inner layer is made of a mixture of glycolide trimethylene carbonate block copolymer (PGA-TMC) and polyglycolide (PGA), and the outer layer is made of polydioxanone (PPDO). The outer layer completely or partially encapsulates the inner layer. The weight proportion of glycolide trimethylene carbonate block copolymer (PGA-TMC) in the inner layer is 10-30%, preferably 15-20%.

[0030] The glycolide trimethylene carbonate block copolymer (PGA-TMC) is copolymerized by polyglycolide (PGA) and trimethylene carbonate (TMC). The rigid chain segment of PGA is combined with the flexible chain segment of TMC to form a glycolide trimethylene carbonate block copolymer with a molecular weight of 70,000-180,000 that has both strength and elasticity (for preparation, please refer to the patent application number 202111061473.9, invention name "Method for the synthesis of high-stability glycolide-trimethylene carbonate block copolymers").

[0031] Preferably, the cross section of the inner layer clip is a circular or polygonal structure.

[0032] Preferably, the surface of the inner layer is smooth or has a partially serrated structure.

[0033] Preferably, the inner layer clip partially or completely penetrates the space within the outer layer clip.

[0034] Preferably, the curvatures of the inner and outer clips at corresponding positions are similar or consistent.

[0035] Furthermore, the absorbable ligation clip is generally V-shaped and includes a clamp arm I and a clamp arm II. The distal ends of the clamp arms I and II are fixedly connected, and the front ends (free ends) are detachably connected via a locking structure. The specific features of the locking structure are not limited, as long as they can achieve the locking purpose, such as a locking structure that cooperates with a buckle and a slot.

[0036] Preferably, the cross-sectional diameter or cross-sectional thickness of the inner layer is 0.5-1.8 mm, preferably 1.0-1.4 mm.

[0037] Comparative Example 1:

[0038] The structure of the V-shaped absorbable ligation clip in this case is referenced Figure 1 The inner layer of the clip is made of polyglycolide (PGA), and the outer layer of the clip is made of polydioxanone (PPDO). The absorbable ligation clip is prepared by injection molding technology, which specifically includes the following steps:

[0039] (1) A double-layer injection mold with an outer cavity and an inner cavity is designed according to the structure of the absorbable ligation clip; the diameters of the inner layer of the designed ligation clip are 0.5, 0.8, 1.0, 1.2, 1.4, 1.6 and 1.8 mm.

[0040] (2) Weighing the required amount of polyglycolide (PGA) and placing it into the inner cavity of the mold, and then weighing the required amount of polydioxanone (PPDO) and placing it into the outer cavity of the mold;

[0041] (3) Set the injection temperature of the inner cavity to 220-225°C and the cooling time to 20-30s; set the injection temperature of the outer cavity to 115-120°C and the cooling time to 60-80s;

[0042] (4) Injection molding: First, the material in the inner cavity of the mold is injection molded, and after cooling and shaping, the material in the outer cavity of the mold is injection molded, and after cooling and shaping, the absorbable ligation clip is obtained.

[0043] The slippage force degradation test of the ligation clip sample prepared in Comparative Example 1 was performed as follows:

[0044] 1. Slip force test:

[0045] Slippage force refers to the force required to release a clip after closing a blood vessel. After using a ligature clip to ligate tissue, it can fail due to mishandling during surgery or due to internal organs squeezing and falling. Slippage force is an indicator of clip strength.

[0046] Select the supporting fixture that can be moved up and down on the tensile testing machine and cut the end of the rubber tube to a uniform size of 2 mm. Set the gauge length of the auxiliary fixture to 50 mm. Under this condition, close the ligature clamp to the rubber tube fracture to conduct a step-by-step test of the axial and radial slippage force.

[0047] according to Figure 2 The experimental device is built by the axial slip force test schematic shown in the figure, and the experimental device is built by referring to the Figure 3 The radial slip force test schematic shown configures the corresponding test environment.

[0048] Start the testing machine and run the program at a standard test speed of 50 mm / min until the ligation clip is observed to slip off the rubber tube. The system automatically stops recording data.

[0049] 2. Degradation test:

[0050] Before the degradation test begins (at time zero), determine the initial values ​​for all samples. Test the degradation samples at each test period. Sampling intervals are set at: 0, 3, 10, 14, 21, and 28 days. Number of samples: 3 tests at each sampling point.

[0051] 3. Test results:

[0052] The V-shaped ligation clip of Comparative Example 1 and the Tianzhu V-clip (produced by Beijing Tianzhu Changyun Medical Technology Co., Ltd.) were subjected to comparative slippage force and degradation tests. The test results are shown in Table 1.

[0053] Table 1

[0054]

[0055]

[0056] In the comparative example in Table 1, the ligation clip with an inner clamp diameter of 1.6 mm may break directly when the slippage force value is 15.89, and the ligation clip with an inner clamp diameter of 1.8 mm may break directly when the slippage force value is 17.33.

[0057] The data results in Table 1 show that: as the thickness (diameter) of the inner layer of the V-shaped ligation clamp in Comparative Example 1 increases, the anti-slip force in the initial stage of degradation becomes greater. When the thickness of the inner layer is 0.8-1.0 mm, its clamping stability is significantly improved compared with the Tianzhu V clamp. However, due to the relatively fast degradation rate of PGA materials, as the content of PGA materials increases, the rigidity of the product increases while there is a disadvantage of a fast degradation rate, which will lead to a significant decrease in mechanical properties after 14 days. In terms of pure PGA materials, the current optimal inner layer thickness is 0.8-1.0 mm.

[0058] Example 1:

[0059] Unlike Comparative Example 1, this example uses a mixture of glycolide-trimethylene carbonate block copolymer (PGA-TMC) and polyglycolide (PGA) as the inner layer material, and polydioxanone (PPDO) as the outer layer material. The absorbable ligation clip is manufactured using injection molding technology. The glycolide-trimethylene carbonate block copolymer (PGA-TMC) is a copolymer of PGA (polyglycolide) and TMC (trimethylene carbonate). The rigid segments of PGA combine with the flexible segments of TMC to form a material with both strength and elasticity.

[0060] The test results of Comparative Example 1 show that using pure PGA as the inner layer material is prone to fracture due to excessive rigidity and a drastic decrease in mechanical properties due to its rapid degradation rate. This example adds a certain amount of PGA-TMC to the inner layer material to reduce rigidity while increasing toughness, thereby providing longer-term stability for the ligation clamp. The PGA-TMC addition levels in the absorbable ligation clamp are 5wt.%, 10wt.%, 15wt.%, 20wt.%, and 30wt.%.

[0061] The process of preparing absorbable ligation clip samples is as follows:

[0062] (1) A double-layer injection mold with an outer cavity and an inner cavity was designed based on the structure of the absorbable ligation clip. The diameter of the inner layer of the designed ligation clip was 1.0 mm, the injection molding weight of the inner layer was 50 g, and the mixing ratio of the two materials of the inner layer was shown in Table 2.

[0063] Table 2

[0064] Types of raw materials 1#、 2# 3# 4# 5# PGA 47.5g 45g 42.5g 40g 35g PGA-TMC 2.5g 5g 7.5g 10g 15g

[0065] (2) Weigh 50 g of the inner layer material and put it into the inner cavity of the mold, and then weigh 50 g of polydioxanone (PPDO) and put it into the outer cavity of the mold;

[0066] (3) Set the injection temperature of the inner cavity to 215-225°C and the cooling time to 32-50s; set the injection temperature of the outer cavity to 115-120°C and the cooling time to 60-80s;

[0067] (4) Injection molding: First, the material in the inner cavity of the mold is injection molded, and after cooling and shaping, the material in the outer cavity of the mold is injection molded, and after cooling and shaping, the absorbable ligation clip is obtained.

[0068] The slippage force degradation test of the V-shaped ligation clip sample prepared in Example 1 was performed as follows:

[0069] 1. Slip force test: The test process is the same as that of Comparative Example 1.

[0070] 2. Degradation test:

[0071] Before the degradation test begins (time zero), the initial values ​​of all samples should be measured directly. Degradation samples should be tested at each test period. Sampling intervals were set at: 0 days, 3 days, 10 days, 14 days, 21 days, and 28 days. Number of samples: 3 tests were taken at each sampling point. The test results are shown in Table 3.

[0072] Table 3

[0073]

[0074]

[0075] The results in Table 3 show that as the PGA-TMC content in the inner clamp increases, the proportion of introduced flexible segments increases, and its initial clamping force decreases (but still exceeds that of the Tianzhu V-clamp). When the PGA-TMC content increases to 30%, the initial clamping force decreases by nearly 40%. From the perspective of clamping stability, the addition of PGA-TMC improves clamping stability, thereby reducing the risk of slippage during degradation. For example, in the case of sample 5, after 28 days of degradation, its closing force is nearly doubled compared to the Tianzhu V-clamp.

[0076] Example 2:

[0077] Based on the experiments in Example 1, inner layer sandwiches with varying thicknesses (diameters) were prepared and tested, with PGA-TMC additions of 15 wt.%, 20 wt.%, and 30 wt.%. The inner layer sandwich diameters were 0.5 mm, 0.8 mm, 1.0 mm, 1.2 mm, and 1.4 mm, respectively. The test results for the inner layer sandwiches with PGA-TMC additions of 15 wt.%, 20 wt.%, and 30 wt.% are shown in Tables 4-6.

[0078] Table 4 Test results when the amount of PGA-TMC added is 15%

[0079]

[0080]

[0081] The results in Table 4 show that as the thickness of the inner layer material increases, the slippage force of the ligation clip increases. However, as the thickness of the inner layer increases, its rigidity also gradually increases. When the thickness is 1.6 mm or above, the ligation clip cannot maintain its mechanical properties for 10 days or more due to its excessive rigidity.

[0082] Table 5 Test results when the addition amount of PGA-TMC is 20%

[0083]

[0084] The results in Table 5 show that as the PGA-TMC content in the inner clip increases, the initial stiffness decreases, but the mechanical retention improves, providing better clamping force over a longer period of time. However, for a thickness of 1.8 mm, due to excessive stiffness, fracture may occur after 14 days.

[0085] Table 6 Test results when the addition amount of PGA-TMC is 30%

[0086]

[0087] The results in Table 6 show that the initial force value continues to decrease with the increase of PGA-TMC content. When the inner layer thickness is less than 1.0 mm, it is basically not much different from the original Tianzhu V-clip.

[0088] The results of the above examples and comparative examples demonstrate that using a blend of PGA-TMC and PGA in the inner clip reduces the overall rigidity of the ligation clip to a certain extent, thereby improving the mechanical holding time. The optimal PGA-TMC ratio in the inner clip is 15-20 wt.%, and the optimal inner clip cross-sectional thickness (diameter) is 1.0-1.4 mm.

[0089] The foregoing shows and describes the principal features and advantages of the present invention. It will be apparent to those skilled in the art that the present invention is not limited to the details of the exemplary embodiments described above and that the present invention can be embodied in other specific forms without departing from the spirit or essential characteristics of the present invention. Therefore, the embodiments should be considered in all respects as illustrative and non-restrictive, and the scope of the present invention is defined by the appended claims, not the foregoing description, and all variations that come within the meaning and range of equivalents of the claims are intended to be embraced therein.

Claims

1. An absorbable ligation clip with excellent mechanical properties, characterized by: The absorbable ligation clip has a double-layer structure with different materials, including an inner layer clip and an outer layer clip, wherein: the inner layer clip material is a mixture of glycolide trimethylene carbonate block copolymer (PGA-TMC) and polyglycolide (PGA), and the outer layer clip material is polydioxanone (PPDO); the outer layer clip completely or partially wraps the inner layer clip.

2. The absorbable ligation clip with excellent mechanical properties according to claim 1, characterized in that: In the inner layer sandwich material, the weight proportion of glycolide trimethylene carbonate block copolymer (PGA-TMC) is 10-30%.

3. The absorbable ligation clip with excellent mechanical properties according to claim 1, characterized in that: The cross section of the inner layer clip is a circular or polygonal structure, and the diameter or cross-sectional thickness of the inner layer clip is 0.5-1.8 mm.

4. The absorbable ligation clip with excellent mechanical properties according to claim 1, characterized in that: The surface of the inner layer is smooth or has a partially serrated structure.

5. The absorbable ligation clip with excellent mechanical properties according to claim 1, characterized in that: The inner layer clip partially or completely penetrates the space inside the outer layer clip.

6. The absorbable ligation clip with excellent mechanical properties according to claim 1, characterized in that: The curvatures of the inner layer clip and the outer layer clip at corresponding positions are similar or consistent.

7. The absorbable ligation clip with excellent mechanical properties according to claim 1, characterized in that: The glycolide trimethylene carbonate block copolymer (PGA-TMC) is copolymerized by polyglycolide (PGA) and trimethylene carbonate (TMC). The rigid segments of PGA are combined with the flexible segments of TMC to form a glycolide trimethylene carbonate block copolymer with both strength and elasticity.

8. The absorbable ligation clip with excellent mechanical properties according to claim 1, characterized in that: The absorbable ligation clamp is a V-shaped structure, comprising a clamp arm I and a clamp arm II. The ends of the clamp arm I and the clamp arm II are fixedly connected, and the front ends (free ends) are detachably connected via a locking structure.

9. The method for preparing the absorbable ligation clip with excellent mechanical properties according to any one of claims 1 to 8, characterized in that: The method adopts injection molding technology to prepare an absorbable ligation clip, which specifically includes the following steps: (1) Designing a double-layer injection mold having an outer cavity and an inner cavity according to the structure of the absorbable ligation clip; (2) Weigh the required weight of the inner layer material and put it into the inner cavity of the mold, and then weigh the required weight of polydioxanone (PPDO) and put it into the outer cavity of the mold; (3) Setting the injection temperature and cooling time of the inner and outer cavities; (4) First, the material in the inner cavity of the mold is injection molded, and after cooling and shaping, the material in the outer cavity of the mold is injection molded, and after cooling and shaping, the absorbable ligation clip is obtained.

10. The method for preparing the absorbable ligation clip with excellent mechanical properties according to claim 9, characterized in that: In step (3), the injection molding temperature of the inner cavity is set to 215-225°C, and the cooling time is set to 32-50s; the injection molding temperature of the outer cavity is set to 115-120°C, and the cooling time is set to 60-80s.

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