Absorbable patch for uterine muscular layer repair and preparation method thereof

Abstract

The invention relates to the field of medical implant materials, and particularly discloses an absorbable patch for uterine muscular layer repair and a preparation method of the absorbable patch. The invention discloses an absorbable patch for repairing a uterine muscular layer. The absorbable patch is prepared by mixing 2-9.5 parts of poly (L-lactide-caprolactone) and 0.5-8 parts of a biomedical material, the molecular weight of the poly (L-lactide-caprolactone) is 5 to 30 thousand; the preparation method comprises the following steps: mixing a biomedical material stock solution with a poly (L-lactide-caprolactone) stock solution, performing electrostatic spinning, freeze drying or tape casting treatment, and drying to remove an organic solvent, thereby obtaining the absorbable patch for uterine muscular layer repair. The absorbable patch disclosed by the invention not only can be completely degraded in vivo, but also has a similar extracellular matrix structure, can provide muscle cell repair for an injured part of a uterine muscular layer, avoids scar tissues formed by fibrosis, and reduces the risk caused by a secondary operation required by a uterine scar diverticulum.

Description

Technical Field

[0001] This application relates to the field of medical implant materials technology, and more specifically, it relates to an absorbable patch for uterine myometrial repair and a method for preparing the same. Background Technology

[0002] The uterus is the core organ of the female reproductive system, located in the center of the pelvic cavity. It is shaped like an inverted pear, with an inner layer of endometrium, a middle layer of myometrium, and an outer layer of serosal membrane. Its main functions include menstrual cycle formation, embryo implantation, and fetal development. The normal uterine myometrium is mainly composed of abundant smooth muscle tissue and a small amount of collagen fibers. After cesarean section and some open uterine surgeries, the healing of the uterine incision site mainly involves granulation tissue proliferation and fibrotic repair. Normally, smooth muscle cells have poor regenerative capacity. After uterine trauma, local muscle cells are damaged and insufficient to completely regenerate and repair the damaged uterine myometrium. Instead, scar tissue with poor elasticity and contractile function is formed through fibrous proliferation, easily leading to uterine scar diverticula. However, fibrotic scars are malnourished, have poor contractile capacity, and reduced elasticity, increasing the risk of poor implantation and uterine rupture.

[0003] Currently, drug treatments for uterine myometrial repair, such as stem cell therapy, are still in the experimental research stage. Clinical treatment for uterine scar diverticula caused by myometrial damage is mostly surgical, including hysteroscopic scar diverticulum resection, vaginal scar diverticulum excision and suturing, and laparoscopic scar diverticulum excision and repair. While hysteroscopic scar diverticulum resection is quick, leaves no abdominal incision, and is simple to perform, its effectiveness in improving abnormal uterine bleeding is poor, recurrence is common, and it may further thin the remaining myometrium, making it unsuitable for women who wish to preserve fertility. Vaginal or laparoscopic scar diverticulum excision and suturing repairs the diverticulum by removing scar tissue and re-suturing the lower uterine segment. However, the wound healing process is uncertain, and poor healing may lead to diverticulum reformation.

[0004] Therefore, surgical treatment does not completely repair the uterine myometrium, and secondary surgery can easily lead to other problems. Poor repair of damaged organs can lead to abnormalities in the extracellular matrix (ECM), which in turn affects tissue structure. This abnormality can cause cellular imbalance, resulting in persistent fibrosis, impairing organ function, and potentially triggering other diseases. Therefore, there is an urgent need for a medical material to address the problem of damaged uterine myometrium. Summary of the Invention

[0005] To promote the repair of the uterine myometrium, this application provides an absorbable patch for uterine myometrium repair and a method for preparing the same, which can be used for uterine myometrium repair after cesarean section or other uterine incision surgery.

[0006] In a first aspect, this application provides an absorbable patch for uterine myometrial repair, employing the following technical solution: An absorbable patch for uterine myometrial repair comprises the following components in parts by weight: Poly(L-lactide-caprolactone) 2 to 9.5 parts; 0.5–8 parts of biomedical materials; The poly(L-lactide-caprolactone) is prepared by copolymerization of L-lactide and caprolactone, wherein the molar percentage of L-lactide to caprolactone is 10:90 to 95:5. The molecular weight of the poly(L-lactide-caprolactone) is 50,000 to 300,000. The biomedical materials include one or more of the following: fibrinogen, gelatin, collagen, chitosan, silk fibroin, zeolite, and the submucosa of porcine small intestine.

[0007] By adopting the above-mentioned technical solutions, on the one hand, the above-mentioned biomedical materials can quickly bind to or capture platelets after contacting the blood in the myometrium, thereby releasing various growth factors such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF / FGF-2), platelet-derived growth factor (PDGF), and transforming growth factor-β (TGF-β), promoting the regeneration of uterine smooth muscle cells and effectively improving the scar tissue formed by fibrosis in the myometrium.

[0008] On the other hand, poly(L-lactide-caprolactone) with a molecular weight of 50,000 to 300,000 is prepared by copolymerizing L-lactide and caprolactone in a specific ratio. Poly(L-lactide-caprolactone) has high tensile strength and is suitable for suturing tissues in the myometrium; it has a long support time, with effective tension reaching 3-6 months; it has good biocompatibility and reacts less with tissues; it is completely hydrolyzed and can be completely degraded into water and carbon dioxide.

[0009] Therefore, the absorbable patch prepared by mixing poly(L-lactide-caprolactone) and biomedical materials in the above proportions exhibits good bioactivity, certain mechanical strength, and a controllable degradation rate. It can provide a three-dimensional scaffold for the adhesion and proliferation of smooth muscle cells, thereby repairing the uterine myometrium. Simultaneously, the absorbable patch of this application uses simple raw materials, has high safety, and can provide myocyte repair at the site of uterine myometrial injury, avoiding scar tissue formation due to fibrosis and reducing the risk of needing a second surgery for uterine scar diverticulum.

[0010] Preferably, the absorbable patch for uterine myometrial repair is composed of the following components in parts by weight: 5-8 parts of poly(L-lactide-caprolactone); 2 to 5 portions of biomedical materials.

[0011] Preferably, the poly(L-lactide-caprolactone) is prepared by copolymerization of L-lactide and caprolactone, wherein the molar percentage of L-lactide to caprolactone is 40 to 60. The molecular weight of the poly(L-lactide-caprolactone) is 250,000; The biomedical material is composed of a mixture of collagen and chitosan.

[0012] By adopting the above technical solution, and further changing the concentration and composition ratio of poly(L-lactide-caprolactone) and biomedical materials to obtain suitable mechanical strength and degradation rate, the mechanical strength and degradation rate of absorbable patches can be effectively adjusted. This provides a three-dimensional scaffold for adhesion and proliferation of smooth muscle cells, not only releasing growth factors to promote smooth muscle cell regeneration, but also providing a certain degree of hydrophilicity, enabling better adhesion to tissues, thereby effectively repairing uterine myometrial damage.

[0013] Preferably, the absorbable patch for uterine myometrial repair has a thickness of 0.2–2.0 mm and a porosity of 55–85%.

[0014] By adopting the above technical solution, the absorbable patch of this application has a structure similar to the extracellular matrix. Its good specific surface area and porosity can provide a three-dimensional scaffold for cell adhesion. Combined with biomedical materials, it can induce the proliferation of uterine smooth muscle cells, thus ultimately achieving the complete restoration of uterine structure and function.

[0015] Secondly, this application provides a method for preparing an absorbable patch for uterine myometrial repair, using the following technical solution: A method for preparing an absorbable patch for uterine myometrial repair includes the following steps: (1) After mixing the biomedical material with the first organic solvent, a biomedical material stock solution with a concentration of 50-200 mg / ml is obtained; After mixing poly(L-lactide-caprolactone) with a second organic solvent, a poly(L-lactide-caprolactone) stock solution with a mass fraction of 5-20% is obtained; (2) After mixing the biomedical material stock solution with the poly(L-lactide-caprolactone) stock solution, electrospinning, freeze drying or casting treatment is performed first, and then the organic solvent is removed by drying to obtain an absorbable patch for uterine myometrial repair.

[0016] By employing the above-described technical solution, the biomedical material stock solution and poly(L-lactide-caprolactone) stock solution of the aforementioned concentrations and proportions are mixed, and then subjected to electrospinning, freeze-drying, or casting to provide a three-dimensional scaffold for cell adhesion in the uterine myometrium. The resulting absorbable patch possesses suitable mechanical strength, degradation rate, and biological properties, effectively inducing uterine smooth muscle cell regeneration and improving scar tissue formed due to fibrosis, while also being completely degraded in vivo.

[0017] Meanwhile, the absorbable patch of this application is prepared by electrospinning, freeze drying or casting, which is convenient and simple to operate. The absorbable patch made has good mechanical strength and elasticity, which can meet the mechanical requirements as a uterine myometrial patch.

[0018] Preferably, in step (1), the volume ratio of the biomedical material stock solution to the poly(L-lactide-caprolactone) stock solution is (2-5):(5-8).

[0019] By adopting the above technical solution, a uterine patch with suitable mechanical strength and degradation rate and excellent biological properties can be obtained. Biomedical materials have biocompatibility and rapid degradation rate. Poly(L-lactide-caprolactone) provides mechanical strength while degrading slowly in vivo. The absorbable patch obtained by combining the two has an ideal effect on uterine myometrial repair.

[0020] Preferably, in step (1), the first organic solvent includes one or more of hexafluoroisopropanol, acetic acid, trifluoroethanol and formic acid.

[0021] Preferably, in step (1), the second organic solvent includes one or more of hexafluoroisopropanol, trifluoroethanol, tetrahydrofuran, and chloroform.

[0022] By adopting the above technical solution, a uniform and appropriately concentrated biomedical material stock solution can be obtained, which is beneficial for subsequent processing. Furthermore, due to the high volatility of the first and second organic solvents, their residual amounts can be reduced to below specified levels through simple drying processes, ensuring the safety of the absorbable patch.

[0023] In summary, this application has the following beneficial effects: 1. Because this application uses a mixture of poly(L-lactide-caprolactone) and biomedical materials to prepare an absorbable patch, on the one hand, the absorbable patch has good biological properties, and the biomedical materials can induce the regeneration of uterine smooth muscle cells, effectively improving scar tissue formed due to fibrosis; on the other hand, by selecting poly(L-lactide-caprolactone) of different molecular weights, and by changing the concentration and composition ratio of poly(L-lactide-caprolactone) and biomedical materials to obtain suitable mechanical strength and degradation rate, the absorbable patch has a certain mechanical strength and degradation rate, which can provide a three-dimensional scaffold for the adhesion and proliferation of smooth muscle cells, thereby effectively repairing uterine myometrial damage; 2. All materials used in the absorbable patch of this application are absorbable. The absorbable patch can be completely degraded in the body, and the degradation time can be controlled according to the ratio of different materials selected. 3. The absorbable patch of this application has a structure similar to the extracellular matrix. Its good specific surface area and porosity can provide a three-dimensional scaffold for cell adhesion. The natural polymer material can induce the proliferation of uterine smooth muscle cells, and ultimately achieve the complete restoration of uterine structure and function. 4. The absorbable patch of this application provides myocyte repair at the site of uterine myometrial injury, avoids scar tissue formation due to fibrosis, and reduces the risk of needing a second surgery due to uterine scar diverticulum. Attached Figure Description

[0024] Figure 1 This is a scanning electron microscope image of the absorbable patch for uterine myometrial repair according to Embodiment 1 of this application; Figure 2 a, b, c, d, and e in the figures are scanning electron microscope images of platelets bound to or captured after contact with blood in Examples 1 to 4 and Comparative Example 1 of this application, respectively. Figure 3 This refers to the adhesion and proliferation ability of smooth muscle cells in Examples 1-4 and Comparative Example 1 of this application. Detailed Implementation

[0025] The present application will be further described in detail below with reference to the embodiments.

[0026] Unless otherwise specified below, all raw materials used in the embodiments of this application are commercially available.

[0027] raw material Procurement Information Fibrinogen (human-derived) Freeze-dried powder; Sigma-Aldrich gelatin Type B, gel strength > 180; Adamas Collagen Type I, derived from cow Achilles tendon; Adamas Life Chitosan 200–400 mPa•s; Adamas Silk fibroin Molecular weight 6–10 kDa; Aladdin zeolite 1~10μm; Alfa submucosa of pig small intestine self made

[0028] Preparation Example 1: A poly(L-lactide-caprolactone) was prepared by the following operation: L-lactide and caprolactone were placed in a reaction vessel, and then dodecanol, the initiator, and stannous octoate, the catalyst were added. The mixture was heated to 140°C and reacted with stirring for 24 hours to obtain a crude polymer. The crude polymer was then removed, dissolved in dichloromethane, and the solution was poured into methanol to precipitate the product. The product was then filtered to obtain the filter material. Finally, the obtained filter material was dried under vacuum at 40°C for 12 hours to obtain poly(L-lactide-caprolactone).

[0029] In the preparation example of this application, the ratio of L-lactide, caprolactone, stannous octoate catalyst and dodecanol initiator is 80g: 20g: 0.5mL: 200μL.

[0030] Tests showed that the molecular weight of poly(L-lactide-caprolactone) is approximately 200,000.

[0031] Preparation Example 2: A poly(L-lactide-caprolactone) was prepared by the following operation: L-lactide and caprolactone were placed in a reaction vessel, and then dodecanol, the initiator, and stannous octoate, the catalyst were added. The mixture was heated to 140°C and reacted with stirring for 24 hours to obtain a crude polymer. The crude polymer was then removed, dissolved in dichloromethane, and the solution was poured into methanol to precipitate the product. The product was then filtered to obtain the filter material. Finally, the obtained filter material was dried under vacuum at 40°C for 12 hours to obtain poly(L-lactide-caprolactone).

[0032] In the preparation example of this application, the ratio of L-lactide, caprolactone, stannous octoate catalyst, and dodecanol initiator is 50g: 50g: 0.5mL: 180μL.

[0033] Tests showed that the molecular weight of poly(L-lactide-caprolactone) is approximately 150,000.

[0034] Preparation Example 3: A poly(L-lactide-caprolactone) was prepared by the following operation: L-lactide and caprolactone were placed in a reaction vessel, and then dodecanol, the initiator, and stannous octoate, the catalyst were added. The mixture was heated to 140°C and reacted with stirring for 24 hours to obtain a crude polymer. The crude polymer was then removed, dissolved in dichloromethane, and the solution was poured into methanol to precipitate the product. The product was then filtered to obtain the filter material. Finally, the obtained filter material was dried under vacuum at 40°C for 12 hours to obtain poly(L-lactide-caprolactone).

[0035] In the preparation example of this application, the ratio of L-lactide, caprolactone, stannous octoate catalyst and dodecanol initiator is 40g: 60g: 0.5mL: 220μL.

[0036] Tests showed that the molecular weight of poly(L-lactide-caprolactone) is approximately 250,000.

[0037] Preparation Example 4: A poly(L-lactide-caprolactone) was prepared by the following operation: L-lactide and caprolactone were placed in a reaction vessel, and then dodecanol, the initiator, and stannous octoate, the catalyst were added. The mixture was heated to 140°C and reacted with stirring for 24 hours to obtain a crude polymer. The crude polymer was then removed, dissolved in dichloromethane, and the solution was poured into methanol to precipitate the product. The product was then filtered to obtain the filter material. Finally, the obtained filter material was dried under vacuum at 40°C for 12 hours to obtain poly(L-lactide-caprolactone).

[0038] In the preparation example of this application, the ratio of L-lactide, caprolactone, stannous octoate catalyst and dodecanol initiator is 10g: 90g: 0.5mL: 150μL.

[0039] Tests showed that the molecular weight of poly(L-lactide-caprolactone) is approximately 100,000.

[0040] Preparation Example 5: A poly(L-lactide-caprolactone) was prepared by the following operation: L-lactide and caprolactone were placed in a reaction vessel, and then dodecanol, the initiator, and stannous octoate, the catalyst were added. The mixture was heated to 140°C and reacted with stirring for 24 hours to obtain a crude polymer. The crude polymer was then removed, dissolved in dichloromethane, and the solution was poured into methanol to precipitate the product. The product was then filtered to obtain the filter material. Finally, the obtained filter material was dried under vacuum at 40°C for 12 hours to obtain poly(L-lactide-caprolactone).

[0041] In the preparation example of this application, the ratio of L-lactide, caprolactone, stannous octoate catalyst and dodecanol initiator is 70g: 30g: 0.5mL: 200μL.

[0042] Tests showed that the molecular weight of poly(L-lactide-caprolactone) is approximately 200,000.

[0043] Preparation Example 6: A poly(L-lactide-caprolactone) was prepared by the following operation: L-lactide and caprolactone were placed in a reaction vessel, and then dodecanol, the initiator, and stannous octoate, the catalyst were added. The mixture was heated to 140°C and reacted with stirring for 24 hours to obtain a crude polymer. The crude polymer was then removed, dissolved in dichloromethane, and the solution was poured into methanol to precipitate the product. The product was then filtered to obtain the filter material. Finally, the obtained filter material was dried under vacuum at 40°C for 12 hours to obtain poly(L-lactide-caprolactone).

[0044] In the preparation example of this application, the ratio of L-lactide, caprolactone, stannous octoate catalyst, and dodecanol initiator is 5g: 95g: 0.5mL: 220μL.

[0045] Tests showed that the molecular weight of poly(L-lactide-caprolactone) is approximately 250,000.

[0046] Preparation Example 7: A poly(L-lactide-caprolactone) was prepared by the following operation: L-lactide and caprolactone were placed in a reaction vessel, and then dodecanol, the initiator, and stannous octoate, the catalyst were added. The mixture was heated to 140°C and reacted with stirring for 24 hours to obtain a crude polymer. The crude polymer was then removed, dissolved in dichloromethane, and the solution was poured into methanol to precipitate the product. The product was then filtered to obtain the filter material. Finally, the obtained filter material was dried under vacuum at 40°C for 12 hours to obtain poly(L-lactide-caprolactone).

[0047] In the preparation example of this application, the ratio of L-lactide, caprolactone, catalyst stannous octoate, and initiator dodecanol is 97g: 3g: 0.5mL: 220μL.

[0048] Tests showed that the molecular weight of poly(L-lactide-caprolactone) is approximately 250,000.

[0049] Example 1: An absorbable patch for uterine myometrial repair, the components and their corresponding weights (g) are shown in the table below.

[0050]

[0051] The above-mentioned method for preparing absorbable patches for uterine myometrial repair includes the following steps: (1) After mixing the biomedical material with the first organic solvent, a biomedical material stock solution with a mass fraction of 100 mg / ml is obtained; The first organic solvent was prepared by mixing hexafluoroisopropanol and 10×DMEM culture medium at a volume ratio of 9:1.

[0052] Poly(L-lactide-caprolactone) was mixed with hexafluoroisopropanol to obtain a 10% (w / w) poly(L-lactide-caprolactone) stock solution. (2) The biomedical material stock solution and the poly(L-lactide-caprolactone) stock solution were mixed at a volume ratio of 3:7 and then added to the same syringe of the electrospinning machine for electrospinning. The positive spinning pressure was 15kV, the negative spinning pressure was -2kV, the receiving distance was 12cm, the spinning solution propulsion speed was 2ml / h, and the scanning speed was 15cm / min. Finally, the absorbable patch crude product for uterine myometrial repair was obtained on the roller receiving device.

[0053] The crude absorbable patch for uterine myometrial repair was dried in a vacuum drying oven for 24 hours to remove residual organic solvents. After cutting and packaging, it was sterilized with an electron beam to obtain the absorbable patch for uterine myometrial repair.

[0054] Example 2: An absorbable patch for uterine myometrial repair, the components and their corresponding weights (g) are shown in the table below.

[0055]

[0056] The above-mentioned method for preparing absorbable patches for uterine myometrial repair includes the following steps: (1) After mixing the biomedical material with the first organic solvent, a biomedical material stock solution with a mass fraction of 90 mg / ml is obtained; The first organic solvent is a mixture of formic acid and acetic acid in a volume ratio of 30:70.

[0057] Poly(L-lactide-caprolactone) was mixed with tetrahydrofuran to obtain a 9% (w / w) poly(L-lactide-caprolactone) stock solution. (2) The biomedical material stock solution and the poly(L-lactide-caprolactone) stock solution were mixed at a volume ratio of 2:8 and poured onto a flat polytetrafluoroethylene plate. Using a coater with a blade gap height of 500 μm, the mixture was uniformly coated at a speed of 20 mm / s. The mixture was then dried at room temperature in a fume hood for 2 h, and then transferred to a vacuum oven at 35 °C for 12 h. After peeling off the film, the mixture was soaked in a 0.1% EDC ethanol solution for crosslinking for 2 h. After removal, it was rinsed with ethanol / water to obtain a crude absorbable patch for uterine myometrial repair.

[0058] The crude absorbable patch for uterine myometrial repair was dried in a vacuum drying oven for 36 hours to remove residual organic solvents. After cutting and packaging, it was sterilized with an electron beam to obtain the absorbable patch for uterine myometrial repair.

[0059] Example 3: An absorbable patch for uterine myometrial repair, the components and their corresponding weights (g) are shown in the table below.

[0060]

[0061] The above-mentioned method for preparing absorbable patches for uterine myometrial repair includes the following steps: (1) After mixing the biomedical material with trifluoroethanol, a biomedical material stock solution with a mass fraction of 110 mg / ml was obtained.

[0062] Poly(L-lactide-caprolactone) was mixed with tetrahydrofuran to obtain a 9% (w / w) poly(L-lactide-caprolactone) stock solution. (2) The biomedical material stock solution and poly(L-lactide-caprolactone) stock solution were mixed at a volume ratio of 5:5, poured into a petri dish and pre-frozen in a -80℃ freezer for 24 hours. Then the mixture was transferred to a freeze dryer with a cold trap of -85℃, a vacuum of 20Pa, and a shelf temperature starting from -40℃ and slowly increased to 20℃ within 48 hours. The total drying time was 60 hours, and the crude absorbable patch for uterine myometrial repair was obtained.

[0063] The crude absorbable patch for uterine myometrial repair was dried in a vacuum drying oven for 48 hours to remove residual organic solvents. After cutting and packaging, it was sterilized with an electron beam to obtain the absorbable patch for uterine myometrial repair.

[0064] Example 4: An absorbable patch for uterine myometrial repair, the components and their corresponding weights (g) are shown in the table below.

[0065]

[0066] The above-mentioned method for preparing absorbable patches for uterine myometrial repair includes the following steps: (1) After mixing the biomedical material with the first organic solvent, a biomedical material stock solution with a mass fraction of 120 mg / ml is obtained.

[0067] The first organic solvent is a mixture of acetic acid and hexafluoroisopropanol in a volume ratio of 40:60.

[0068] Poly(L-lactide-caprolactone) was mixed with chloroform to obtain a 12% (w / w) poly(L-lactide-caprolactone) stock solution. (2) Biomedical material stock solution and poly(L-lactide-caprolactone) stock solution were added to two syringes of an electrospinning machine at a volume ratio of 4:6 for coaxial electrospinning. The outer shell solution was the submucosa of porcine small intestine, and the inner core solution was PLCL1090. The spinning positive voltage was 17kV, the spinning negative voltage was -2kV, the receiving distance was 12cm, the propulsion speed of the outer shell and the inner core spinning solution was 2ml / h and 3ml / h, respectively, and the scanning speed was 30cm / min. Finally, a crude absorbable patch for uterine myometrial repair was obtained on a roller receiving device.

[0069] The crude absorbable patch for uterine myometrial repair was dried in a vacuum drying oven for 24 hours to remove residual organic solvents. After cutting and packaging, it was sterilized with an electron beam to obtain the absorbable patch for uterine myometrial repair.

[0070] Example 5: An absorbable patch for uterine myometrial repair differs from Example 3 in that the biomedical material is fibrinogen (human-derived).

[0071] Examples 6-7: An absorbable patch differs from Example 3 in that the components and their corresponding weights (g) are shown in the table below.

[0072]

[0073] Comparative Example 1: An absorbable patch is prepared from poly(L-lactide-caprolactone) prepared in Preparation Example 5, wherein the molecular weight of poly(L-lactide-caprolactone) is 300,000.

[0074] The above-mentioned method for preparing absorbable patches for uterine myometrial repair includes the following steps: (1) After mixing poly(L-lactide-caprolactone) with an organic solvent, a poly(L-lactide-caprolactone) stock solution with a mass fraction of 10% was obtained; The organic solvent is a mixture of hexafluoroisopropanol and tetrahydrofuran in a volume ratio of 50:50.

[0075] (2) Pour the poly(L-lactide-caprolactone) stock solution onto a flat polytetrafluoroethylene plate, use a coater and set the blade gap height to 450 μm, and coat it at a uniform speed of 25 mm / s. Place it in a fume hood and dry it at room temperature for 2 h, then transfer it to a vacuum oven at 35 °C and dry it for 12 h to obtain the crude absorbable patch for uterine myometrial repair.

[0076] The crude absorbable patch for uterine myometrial repair was dried in a vacuum drying oven for 48 hours to remove residual organic solvents. After cutting and packaging, it was sterilized with an electron beam to obtain the absorbable patch for uterine myometrial repair.

[0077] Comparative Example 2: An absorbable patch, which differs from Example 3 in that the poly(L-lactide-caprolactone) is the poly(L-lactide-caprolactone) prepared in Preparation Example 6.

[0078] Comparative Example 3: An absorbable patch, which differs from Example 3 in that the poly(L-lactide-caprolactone) is the poly(L-lactide-caprolactone) prepared in Preparation Example 7.

[0079] Performance testing: I. Using the absorbable patch for uterine myometrial repair prepared in the embodiments of this application and the absorbable patch prepared in the comparative example as samples, tensile strength, elongation at break, and tear strength were tested. The test methods are as follows: Tensile strength and elongation at break: The test was conducted according to the method specified in GB / T 1040.3-2006. The specimen was a strip with a width of 20 mm and a length of 60 mm. The tensile speed was 100 mm / min. The tensile strength and elongation at break were measured.

[0080] Suture strength: Referring to standard ISO 7198-1998, the specimen size is 40 mm × 40 mm. A test point is marked 10 mm from the edge on the middle of one side of each specimen. Using 4-0 medical nylon suture, a semi-loop is formed by passing the suture through the test point. The suture is then fixed to the upper clamp of a tensile testing machine, with the lower clamp holding the edge of the specimen. The suture strength is measured at a rate of 100 mm / min.

[0081] Tear strength: According to GB / T 16578.1-2008, the specimen size is 150mm×50mm. A 75mm long cut is made parallel to the length direction in the center of one 50mm side of the specimen. The two sides of the specimen cut are clamped into the upper and lower fixtures of the tensile testing machine, with the cutting line aligned with the center line of the fixture. The tear strength is measured at a rate of 100 mm / min.

[0082] The test results for tensile strength, elongation at break, elongation at break, and tear strength of the samples are shown in the table below.

[0083] Test Project Group Tensile strength (MPa) Elongation at break (%) Suture strength (N) Tear strength (N) Example 1 10.79 75 6.16 18.57 Example 2 5.75 100 10.02 17.91 Example 3 6.69 130 19.62 17.8 Example 4 5.13 58 5.87 8.61 Example 5 7.06 121 16.35 12.3 Example 6 7.58 124 23.26 23.44 Example 7 4.55 103 12.56 15.2 Comparative Example 1 10.97 146 11.71 24.68 Comparative Example 2 3.56 160 10.3 9.58 Comparative Example 3 10.57 75 29.53 32.6

[0084] Analysis of the data in the table above shows that the absorbable patch prepared with pure poly(L-lactide-caprolactone) in Comparative Example 1 exhibits higher tensile strength and elongation at break. This may be because the addition of biomedical materials complicates the solution composition, causing changes in the crystallinity of the poly(L-lactide-caprolactone) during patch molding, thus affecting the tensile strength and elongation at break. Furthermore, suture strength and tear strength are related to the patch thickness. In Examples 1-4 and Comparative Example 1, patches prepared with the same solution volume showed differences in thickness, resulting in varying suture and tear strengths.

[0085] The tensile strength of Comparative Example 2 was too low and the elongation at break was too high, while the tensile strength of Comparative Example 3 was too low and the elongation at break was too high. This was because the ratio of the two monomers in poly(L-lactide-caprolactone) was too high and too low, respectively, and neither of them could obtain a patch with suitable mechanical strength.

[0086] At the same time, by Figure 1 It is known that electrospinning forms a network structure in which fibers interweave, so the tensile strength of Example 1 is relatively high. However, due to the low strength of the fibers, the elongation at break and the stitch strength of the patch obtained by electrospinning are also slightly lower.

[0087] II. Using the absorbable patch for uterine myometrial repair prepared in the embodiments of this application and the absorbable patch prepared in the comparative example as samples, the thickness and porosity were tested. The test methods are as follows: Thickness was measured using a thickness gauge, and porosity was measured using the mercury intrusion porosimetry method (GB / T 21650.2-2008 Determination of pore size distribution and porosity of solid materials by mercury intrusion porosimetry and gas adsorption method - Part 2: Analysis of mesopores and macropores by gas adsorption method).

[0088] The results of the thickness and porosity tests on the samples are shown in the table below.

[0089] Test Project Group Thickness (mm) Porosity (%) Example 1 0.45 63 Example 2 0.27 57 Example 3 1.06 79 Example 4 0.37 66 Example 5 1.12 81 Example 6 0.86 76 Example 7 0.95 79 Comparative Example 3 0.99 83 Data analysis of the table above shows that regardless of whether electrospinning, freeze-drying, or casting is used, the resulting material is a porous absorbable patch. In electrospinning, the fibers are interlocked and stacked to form a porous structure. In freeze-drying and casting, solvent evaporation forms the porous structure, with freeze-drying producing a denser and more stable pore structure. This is because the pre-freezing process in freeze-drying freezes the solvent, and the drying process directly changes the solvent from a solid to a gaseous state. In contrast, in casting, the solvent evaporation process is accompanied by solute deformation, pore collapse, and closure.

[0090] Regarding thickness, the thickness of the patch obtained by freeze drying is greater than that obtained by other processes. This is because slight shrinkage may occur during the solution freezing process. In order to ensure the continuity and uniformity of the patch thickness, the height of the solution added before freeze drying cannot be too low.

[0091] III. Using the patches prepared in Examples 1-4 and Comparative Example 1 of this application as samples, platelet binding or capture capacity was tested. The test methods are as follows: Take sterilized samples from each group and cut them into 1cm × 1cm pieces. Completely immerse the samples in anticoagulated pig blood. Incubation conditions should follow the guidelines in YY / T 1649.1-2019 Medical Devices and Platelet Interaction Tests Part 1: In Vitro Platelet Counting Method: temperature (37±1)℃, shaking speed 60r / min, and time (60±5)min. After incubation, remove the samples, gently blot away excess blood with absorbent paper, and dry them. Observe under a scanning electron microscope.

[0092] Results of the ability of Examples 1-4 and Comparative Example 1 to bind or capture platelets after contact with blood are as follows: Figure 2 As shown. By Figure 2It can be seen that, except for the patch obtained in Comparative Example 1, a large number of platelets adhered to the patches obtained in the other examples. The reason for this may be that the porous structure is the structural basis for platelet adhesion. All patches in each group have a porous structure; the porous structure is formed by the interlocking and stacking of fibers during electrospinning, and also by the formation of a porous structure due to solvent evaporation in patches obtained by freeze-drying and solution casting. Each patch provides sites for platelet attachment. Therefore, the platelet capture capacity depends on whether the material contains platelet-affinity groups. The biomedical materials used in the embodiments of this application all have good biocompatibility, while biomedical materials often lack biocompatibility.

[0093] Therefore, by Figure 2 It is known that the patches prepared by mixing poly(L-lactide-caprolactone) and biomedical materials in Examples 1 to 4 of this application have superior platelet capture ability compared with the patch prepared by pure poly(L-lactide-caprolactone) in Comparative Example 1.

[0094] In Examples 1-4, Examples 3 and 4 had relatively high biomedical material content, resulting in a greater amount of captured platelets. Scanning electron microscopy (SEM) images showed platelets stacked to a certain height, which was more pronounced in the SEM image of the patch obtained in Example 3. In contrast, the patch obtained in Example 2 had a lower biomedical material content, with only one or several layers of platelets adhering to the patch. The platelet-capturing ability of the patch obtained in Example 1 was higher than that in Example 2, which is related to the higher biomedical material content in Example 1.

[0095] III. Examples 1-4 and Comparative Example 1 were used as samples for cell adhesion and proliferation tests. The test methods are as follows: Sterilized samples were placed in 96-well plates, and uterine smooth muscle cells were then seeded into the plates. After stabilization, the plates were incubated at 37°C with 5% CO2 for different time periods. After incubation, the 96-well plates were removed, washed with PBS, and CCK-8 solution was added. The plates were then placed in a cell culture incubator at 37°C with 5% CO2 for further incubation. Finally, the absorbance (OD) values ​​were read using a microplate reader (450 nm). Parallel samples were prepared for each group of samples.

[0096] The results of smooth muscle cell adhesion and proliferation on different substrates are shown in the figure. Figure 3 After implantation, cells undergo adhesion and proliferation. The OD value after 4 hours essentially reflects the number of cells adhering to the patch. The OD value increases continuously over time, indicating continuous cell proliferation on and within the patch. The patch possesses an extracellular matrix-like structure, and its excellent specific surface area and porosity provide a three-dimensional scaffold for cell adhesion. The addition of biomedical materials increases the patch's porosity, making it easier for smooth muscle cells to proliferate within the patch. Higher biomedical material content results in a higher cell proliferation rate, such as... Figure 3 The results showed that the patch obtained in Example 3 had the highest OD value among all groups after 7 days of cultivation. However, considering the overall performance of the patch, namely mechanical strength, degradation rate and biological properties, the amount of biomedical material added should be within a suitable range (8:2 to 5:5).

[0097] This specific embodiment is merely an explanation of this application and is not intended to limit it. After reading this specification, those skilled in the art can make modifications to this embodiment without contributing any inventive step, but such modifications are protected by patent law as long as they fall within the scope of the claims of this application.

Claims

1. An absorbable patch for uterine myometrial repair, characterized in that, It consists of the following components in parts by weight: Poly(L-lactide-caprolactone) 2 to 9.5 parts; 0.5–8 parts of biomedical materials; The poly(L-lactide-caprolactone) is prepared by copolymerization of L-lactide and caprolactone, wherein the molar percentage of L-lactide to caprolactone is 10:90 to 95:

5. The molecular weight of the poly(L-lactide-caprolactone) is 50,000 to 300,000. The biomedical materials include one or more of the following: fibrinogen, gelatin, collagen, chitosan, silk fibroin, zeolite, and the submucosa of porcine small intestine.

2. The absorbable patch for uterine myometrial repair according to claim 1, characterized in that, It consists of the following components in parts by weight: 5-8 parts of poly(L-lactide-caprolactone); 2 to 5 portions of biomedical materials.

3. The absorbable patch for uterine myometrial repair according to claim 1, characterized in that, The poly(L-lactide-caprolactone) is prepared by copolymerization of L-lactide and caprolactone, wherein the molar percentage of L-lactide to caprolactone is 40 to 60. The molecular weight of the poly(L-lactide-caprolactone) is 250,000; The biomedical material is composed of a mixture of collagen and chitosan.

4. The absorbable patch for uterine myometrial repair according to claim 1, characterized in that, The absorbable patch used for uterine myometrial repair has a thickness of 0.2–2.0 mm and a porosity of 55–85%.

5. The method for preparing the absorbable patch for uterine myometrial repair as described in any one of claims 1 to 4, characterized in that, Includes the following steps: (1) After mixing the biomedical material with the first organic solvent, a biomedical material stock solution with a concentration of 50-200 mg / ml is obtained; After mixing poly(L-lactide-caprolactone) with a second organic solvent, a poly(L-lactide-caprolactone) stock solution with a mass fraction of 5-20% is obtained; (2) After mixing the biomedical material stock solution with the poly(L-lactide-caprolactone) stock solution, electrospinning, freeze drying or casting treatment is performed first, and then the organic solvent is removed by drying to obtain an absorbable patch for uterine myometrial repair.

6. The method for preparing the absorbable patch for uterine myometrial repair according to claim 5, characterized in that, In step (1), the volume ratio of the biomedical material stock solution to the poly(L-lactide-caprolactone) stock solution is (2-5):(5-8).

7. The method for preparing the absorbable patch for uterine myometrial repair according to claim 5, characterized in that, In step (1), the first organic solvent includes one or more of hexafluoroisopropanol, acetic acid, trifluoroethanol and formic acid.

8. The method for preparing the absorbable patch for uterine myometrial repair according to claim 5, characterized in that, In step (1), the second organic solvent includes one or more of hexafluoroisopropanol, trifluoroethanol, tetrahydrofuran, and chloroform.

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