Developable composite hernia patch as well as preparation method and application thereof

Abstract

The invention provides a developable composite hernia patch as well as a preparation method and application thereof. The developable composite hernia patch comprises a polypropylene patch, and modified fluorine-containing polyarylether and a modified developer which are compounded on the polypropylene patch. Modified fluorine-containing polyarylether grafted with a polyethylene glycol side chain is introduced to the polypropylene patch, and the polyethylene glycol side chain has hydrophilicity and is easy to form a hydration layer, so that the developable composite hernia patch is endowed with excellent anti-adhesion performance. Furthermore, a modified developing agent connected with the modified fluorine-containing polyarylether through a hydrogen bond is introduced, so that the developing agent can be uniformly dispersed, and the position and state of the developable composite hernia patch can be better observed through an imaging means. Through characterization and testing, the developable composite hernia patch provided by the invention has excellent anti-adhesion performance and observability.

Description

Technical Field

[0001] The present invention belongs to the technical field of biomedical polymer preparation, and is particularly applicable to the technical field of high-value medical device manufacturing such as implantation and intervention, and specifically relates to a developable composite hernia patch and its preparation method and application. Background Art

[0002] The traditional repair material for hernia repair surgery is generally a low-cost polypropylene (PP) mesh patch. However, since the PP mesh patch cannot achieve both anti-adhesion and tissue fusion at the same time, it is easy to cause serious complications such as organ adhesion, which limits its application.

[0003] In order to improve the anti-adhesion performance of PP mesh patches, researchers have developed a variety of strategies, including anticoagulant / anti-inflammatory drugs, surface coatings, chemical modifications and composite physical barriers. Among them, composite physical barriers have become the simplest and most effective method to prevent adhesions because they can effectively isolate the contact between the peritoneal injury site and the abdominal contents. The physical barrier materials commonly used in the prior art include hydrogels, degradable polymers and polytetrafluoroethylene (PTFE for short). However, the above three types of physical barrier materials have their own limitations: hydrogels have poor stability and are prone to structural failure under external forces or limb movements; degradable polymers face the problem of mismatch between material degradation and tissue regeneration; although PTFE has good chemical inertness and biocompatibility, its difficult modification and processing characteristics limit its wide application in the field of hernia repair.

[0004] In addition, the position and status of traditional hernia patches cannot be directly observed through conventional imaging methods after implantation, which increases the difficulty of diagnosing postoperative complications (such as displacement, infection or recurrence). Summary of the Invention

[0005] In view of this, the present invention aims to provide a developable composite hernia patch, a preparation method thereof, and its application. The developable composite hernia patch not only has excellent hernia repair ability and anti-adhesion effect, but also has good biocompatibility and long-term durability, and its position and status can be observed by imaging means.

[0006] To achieve this object, the present invention adopts the following technical solutions:

[0007] In a first aspect, the present invention provides a developable composite hernia patch, comprising a polypropylene patch and a modified fluorinated polyarylether and a modified developer composited on the polypropylene patch;

[0008] The modified fluorinated polyarylene ether and the modified developer are connected through hydrogen bonds.

[0009] Preferably, the mass ratio of the modified fluorinated polyarylene ether to the modified developer is 100:(15-40).

[0010] Preferably, the modified fluorinated polyarylene ether is grafted with polyethylene glycol.

[0011] Preferably, the number average molecular weight of the polyethylene glycol is 300 to 5000 g / mol.

[0012] Preferably, the grafting rate of the polyethylene glycol is 30-60%.

[0013] Preferably, the modified developer is obtained by reacting a functionalized developer with a silane coupling agent.

[0014] Preferably, the functionalized developer is a hydroxylated developer.

[0015] Preferably, the developer is selected from any one or more of barium sulfate, tungsten powder, bismuth oxide, bismuth subcarbonate or bismuth oxychloride.

[0016] Preferably, the silane coupling agent is selected from any one or more of 3-ureapropyltriethoxysilane, 3-mercaptopropyltriethoxysilane or 3-aminopropyltrimethoxysilane.

[0017] In a second aspect, the present invention provides a method for preparing the above-mentioned developable composite hernia patch, comprising the following steps:

[0018] A solution comprising modified fluorinated polyarylether and modified developer is sprayed on the surface of a polypropylene patch to obtain a developable composite hernia patch.

[0019] Preferably, the solvent in the solution is selected from any one or more of acetone, dichloromethane, chloroform, N,N-dimethylformamide or N,N-dimethylacetamide.

[0020] Preferably, the concentration of the solution is 40-55 wt%.

[0021] Preferably, the solvent is a mixed solution of acetone and N,N-dimethylformamide.

[0022] Preferably, the mass ratio of acetone to N,N-dimethylformamide is 1:(3-4).

[0023] Preferably, the spraying adopts an electrostatic spinning method, an ultrasonic spraying method, an inkjet printing method or an atomization deposition method.

[0024] In a third aspect, the present invention provides a use of the above-mentioned developable composite hernia patch in the preparation of hernia repair materials.

[0025] Compared with the prior art, the present invention has the following beneficial effects:

[0026] The present invention provides a developable composite hernia patch comprising a polypropylene patch, a modified fluorinated polyarylether composited on the polypropylene patch, and a modified developer. The polypropylene patch, as a general commercial patch, retains its hernia repair function. The present invention introduces a modified fluorinated polyarylether grafted with polyethylene glycol side chains onto the polypropylene patch. The polyethylene glycol side chains are hydrophilic and easily form a hydration layer, thereby imparting excellent anti-adhesion properties to the developable composite hernia patch. Furthermore, the present invention introduces a modified developer connected to the modified fluorinated polyarylether via hydrogen bonds, which facilitates uniform dispersion of the developer, thereby better observing the position and state of the developable composite hernia patch through imaging means.

[0027] Characterization and testing have shown that the developable composite hernia patch provided by the present invention has excellent anti-adhesion performance and observability. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 This is the hydrogen nuclear magnetic resonance spectrum of the modified fluorinated polyarylene ether powder obtained in Example 1;

[0029] Figure 2 Schematic diagram of the preparation process of the developable composite hernia patch of the present invention;

[0030] Figure 3 This is a comparison chart of the anti-blocking performance test of the products obtained in Example 3 of the present invention and Comparative Example 2;

[0031] Figure 4 CT comparison diagram of the products obtained in Example 3 of the present invention and Comparative Example 1. DETAILED DESCRIPTION

[0032] The following will clearly and completely describe the technical solutions of the present invention in conjunction with the embodiments of the present invention. Obviously, the embodiments described are only some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of the present invention.

[0033] To address the poor anti-adhesion and observability of existing polypropylene patches, the present invention provides a developable composite hernia patch comprising a polypropylene patch, a modified fluorinated polyarylene ether (FPE) and a modified developer composited onto the polypropylene patch. The mass ratio of the modified FPE to the modified developer is 100:(15-40), such as 100:15, 100:20, 100:25, 100:30, 100:35, or 100:40. In the present invention, the modified FPE and the modified developer are linked by hydrogen bonds.

[0034] In the present invention, the polypropylene patch can be a common commercial polypropylene patch, and its source is not specifically limited.

[0035] In the present invention, the modified fluorinated polyarylene ether is prepared by grafting fluorinated polyarylene ether with polyethylene glycol side chains.

[0036] In the present invention, the fluorinated polyarylene ether can be prepared in a manner well known to those skilled in the art.

[0037] Exemplarily, in some embodiments of the present invention, first, under a protective gas atmosphere, the bisphenol monomer, catalyst and azeotropic dehydrating agent are heated to reflux in a solvent to complete the phenolic hydroxyl activation process. In the present invention, the bisphenol monomer is selected from any one or more of biphenol, hydroquinone, bisphenol A or bisphenol S; the protective gas is selected from any one or more of nitrogen, helium, neon or argon; the catalyst is selected from any one or more of potassium carbonate, cesium carbonate, cesium fluoride, sodium carbonate, sodium fluoride, potassium fluoride, calcium hydride or sodium bicarbonate; the azeotropic dehydrating agent is selected from any one or more of benzene, toluene, xylene or cyclohexane; the solvent is selected from any one or more of N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, dimethyl sulfoxide, cyclopentane or diphenyl sulfone. The molar ratio of the bisphenol monomer to the fluorine-containing monomer is 1: (1.02-1.04), and the molar ratio of the catalyst to the bisphenol monomer is (1.1-2): 1. The heating reflux temperature is 140-185° C., preferably 170-175° C., and the heating reflux time is 1.5-4 h, preferably 2.5-3 h.

[0038] After the present invention is heated and refluxed, the obtained material is reacted with a fluorine-containing monomer to obtain a fluorine-containing polyarylene ether. The fluorine-containing monomer is selected from any one or more of hexafluorobenzene, decafluorobiphenyl or decafluorobiphenyl ketone. Specifically, after heating and reflux, the temperature of the reaction system is lowered to room temperature, and then the fluorine-containing monomer is added to the reaction system, and the temperature is raised to react. After the reaction is completed, the mixture is poured into deionized water to obtain a strip-shaped white polymer. After the polymer is crushed into fine particles, it is fully washed with distilled water and ethanol in sequence, and vacuum dried to obtain a fluorine-containing polyarylene ether. The reaction of the present invention is an aromatic nucleophilic substitution reaction, the reaction temperature is 80-100°C, and the reaction time is 10-30h. In the reaction system of the present invention, the mass concentration of the monomer is 15-35wt%, such as 15wt%, 20wt%, 25wt%, 30wt% or 35wt%, etc.

[0039] After obtaining the fluorinated polyarylene ether, in some embodiments of the present invention, the fluorinated polyarylene ether, polyethylene glycol monomethyl ether, a catalyst, and a solvent are placed in a three-necked flask equipped with a mechanical stirrer under a protective gas atmosphere for heating reaction. The protective gas is selected from one or more of nitrogen, helium, neon, or argon; the catalyst is selected from one or more of potassium carbonate, cesium carbonate, cesium fluoride, sodium carbonate, sodium fluoride, potassium fluoride, calcium hydride, or sodium bicarbonate; and the solvent is selected from one or more of N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, dimethyl sulfoxide, sulfolane, or diphenyl sulfone. The molar ratio of the fluorinated polyarylether to polyethylene glycol monomethyl ether is 1:(0.5-1), such as 1:0.5, 1:0.8 or 1:1; the molar ratio of the catalyst to polyethylene glycol monomethyl ether is (1.1-2):1, such as 1.1:1, 1.3:1, 1.5:1, 1.8:1 or 2:1. The temperature of the above-mentioned heating reaction is 60-100°C, preferably 80-100°C, and the reaction time is 8-32 hours, preferably 16-24 hours. After the reaction is completed, the solution is poured into warm water to precipitate a strip-like crude product, which is then crushed, purified with ethanol and ultrapure water, and dried to obtain the modified fluorinated polyarylether.

[0040] In the present invention, the number average molecular weight of the grafted polyethylene glycol in the modified fluorinated polyarylene ether is 300 to 5000 g / mol, such as 300 g / mol, 350 g / mol, 500 g / mol, 1000 g / mol, 3000 g / mol or 5000 g / mol.

[0041] The number average molecular weight of the polyethylene glycol monomethyl ether is 300 to 5000 g / mol, and can be specifically selected from any one or more of polyethylene glycol monomethyl ether (average Mn=350 g / mol), polyethylene glycol monomethyl ether (average Mn=750 g / mol), polyethylene glycol monomethyl ether (average Mn=1900 g / mol), and polyethylene glycol monomethyl ether (average Mn=5000 g / mol). In the above technical solution for preparing the modified fluorinated polyarylene ether, polyethylene glycol monomethyl ether cannot be arbitrarily replaced with other substances. For example, if it is replaced with polyethylene glycol dimethyl ether, cross-linking will easily occur, affecting the solubility of the modified fluorinated polyarylene ether, thereby affecting its solution processing performance, and thus it cannot be composited with the PP patch by electrospinning.

[0042] In the present invention, the polyethylene glycol grafting ratio in the modified fluorinated polyarylene ether is 30-60%. If the polyethylene glycol grafting ratio is too low, the hydrophilic groups are insufficient and the anti-adhesion effect cannot be achieved; if it is too high, the ether bonds in the fluorinated polyarylene ether backbone are degraded, affecting the overall performance.

[0043] Among them, when polyethylene glycol monomethyl ether (average Mn=350g / mol) is used, the polyethylene glycol grafting rate is 59.8%; when polyethylene glycol monomethyl ether (average Mn=750g / mol) is used, the polyethylene glycol grafting rate is 50.5%; when polyethylene glycol monomethyl ether (average Mn=1000g / mol) is used, the polyethylene glycol grafting rate is 41.1%; when polyethylene glycol monomethyl ether (average Mn=1500g / mol) is used, the polyethylene glycol grafting rate is 36.6%; when polyethylene glycol monomethyl ether (average Mn=5000) is used, the polyethylene glycol grafting rate is 32.1%.

[0044] In the present invention, the modified developer is obtained by reacting a functionalized developer with a silane coupling agent.

[0045] Wherein, the functionalized developer is a hydroxylated developer. Exemplarily, the developer is reacted with an oxidant (such as H2O2) under heating conditions to obtain a hydroxylated developer. The ratio of the developer to the oxidant is 1g: (1-2)mL, the temperature of the heating conditions is 100-140°C, and the reaction time is 8-24h. The developer can make the developable composite hernia patch have a developing function, and can be specifically selected from any one or more of barium sulfate, tungsten powder, bismuth oxide, bismuth basic carbonate or bismuth oxychloride. The present invention functionally modifies the developer to facilitate its formation of hydrogen bonds with the modified fluorinated polyarylene ether, which is beneficial for its uniform dispersion in the spinning solution.

[0046] After obtaining the hydroxylated developer, the developer is reacted with a silane coupling agent under heating conditions. After the reaction is completed, the reaction mixture is cooled to room temperature and centrifuged 3 to 5 times using toluene to obtain the modified developer. The heating temperature is 100 to 140°C, and the reaction time is 8 to 24 hours. The silane coupling agent is specifically selected from any one or more of 3-ureapropyltriethoxysilane, 3-mercaptopropyltriethoxysilane, or 3-aminopropyltrimethoxysilane.

[0047] In summary, the present invention introduces a modified fluorinated polyarylene ether grafted with polyethylene glycol side chains onto a polypropylene patch. Leveraging the hydrophilicity of the polyethylene glycol side chains, the present invention imparts excellent anti-adhesion properties to the developable composite hernia patch. Furthermore, the present invention introduces a modified developer. While imparting a developing function to the developable composite hernia patch, the functional groups on its surface (determined by the type of silane coupling agent, such as amino or thiol) readily form hydrogen bonds with the polyethylene glycol side chains in the modified fluorinated polyarylene ether, improving the dispersibility of the modified developer and enabling better imaging of the position and status of the developable composite hernia patch.

[0048] The present invention also provides a method for preparing the above-mentioned developable composite hernia patch, comprising the following steps:

[0049] A solution comprising modified fluorinated polyarylether and modified developer is sprayed on the surface of a polypropylene patch to obtain a developable composite hernia patch.

[0050] In the present invention, the preparation of the modified fluorinated polyarylene ether and the modified developer is described above and will not be repeated here.

[0051] The solvent in the above solution provides a liquid environment, and can be specifically selected from any one or more of acetone, dichloromethane, chloroform, N,N-dimethylformamide or N,N-dimethylacetamide. The concentration of the solution is 40-55wt%, such as 40wt%, 42wt%, 45wt%, 47wt%, 50wt%, 52wt% or 55wt%. In some embodiments of the present invention, the solvent is preferably a mixed solution of acetone and N,N-dimethylformamide. Compared with a single solvent, the combination of the two can make the solvent evaporate at an appropriate speed, thereby ensuring the spinning rate and fiber morphology. The mass ratio of acetone to N,N-dimethylformamide is 1:(3-4), such as 1:3, 1:3.2, 1:3.5, 1:3.7 or 1:4.

[0052] In the present invention, the spraying method can be an electrostatic spinning method, an ultrasonic spraying method, an inkjet printing method or an atomization deposition method.

[0053] Taking electrospinning technology as an example, the present invention uses a solution including modified fluorinated polyarylether and modified developer as the spinning solution, and controls its concentration to be 40-55wt%, then pours the spinning solution into a syringe for electrospinning, and uses a polypropylene patch as the receiving surface to obtain a developable composite hernia patch. The electrospinning uses a 21G metal needle, the distance between the spinning needle and the metal collecting roller is 9-18cm, the spinning voltage is 10-25kV, the temperature inside the spinning machine is 18-60℃, the humidity is 20-60%, and the liquid feeding rate is 0.8-1.5mL / h. For the specific flow diagram, please refer to Figure 1 .

[0054] The solution is obtained by mixing modified fluorinated polyarylether, modified barium sulfate developer and solvent, and the mixing time is 0.5 to 1 hour.

[0055] It can be seen that the preparation method of the developable composite hernia patch provided by the present invention is simple, does not require complicated equipment, and is easy to achieve industrial or industrial production.

[0056] The present invention also provides a use of the developable composite hernia patch in preparing a hernia repair material.

[0057] Characterization and testing have shown that the present invention's developable composite hernia patch, when used as a repair material for abdominal wall hernias in animals, exhibits superior anti-adhesion properties compared to a single polypropylene patch. The patch was placed in contact with the abdominal cavity, while the composite modified fluorinated polyarylether and modified developer were placed in contact with the side facing away from the abdominal cavity. Furthermore, the developable composite hernia patch exhibited superior imaging effects.

[0058] In addition, the reducing substance content test and cytotoxicity test of the water extracts revealed that the developable composite hernia patch provided by the present invention has excellent biocompatibility.

[0059] In order to further illustrate the present invention, the following examples are provided for detailed description. The experimental raw materials used in the following examples of the present invention are all commonly available commercial products.

[0060] The testing method involved in the present invention is as follows:

[0061] (1) Test for reducing substance content in aqueous extracts: According to GB / T 14233.1-2022 “Test methods for medical infusion, transfusion, and injection equipment, Part 1: Chemical analysis methods”, the reducing substance content in aqueous extracts of the final products obtained in the examples and comparative examples was tested using an indirect titration method with an extraction ratio of 0.2 g / mL, an extraction temperature of 37°C, and an extraction time of 72 h.

[0062] (2) Cytotoxicity test: Cytotoxicity tests of the final products obtained in the examples and comparative examples were performed in accordance with GB / T 16886.5-2017 “Biological evaluation of medical devices, Part 5: In vitro cytotoxicity tests”.

[0063] The grafting rate of polyethylene glycol involved below can be calculated based on the nuclear magnetic resonance hydrogen spectrum of the modified fluorinated polyarylene ether powder, and can be specifically calculated according to the following formula:

[0064] Grafting rate (%) = [(c peak area / (PEG-OH polymerization degree × 4)) / ((a+b peak area) / (2 × 4))] × 100%;

[0065] Among them, the a+b peak area involved is the sum of the peak areas of peak a and peak b, both of which are characteristic peaks of the benzene ring, among which peak a corresponds to 7.00~7.08ppm, and peak b corresponds to 7.35~7.44ppm; the c peak in the c peak area corresponds to the characteristic peak of the methylene on the PEG segment at 3.61ppm; the PEG-OH polymerization degree refers to the number of repeating units of polyethylene glycol in polyethylene glycol monomethyl ether.

[0066] Example 1

[0067] 34.244g bisphenol A (0.15mol), 24.878g anhydrous potassium carbonate (0.18mol), 483.720g N,N-dimethylacetamide, and 161.240g cyclohexane were placed in a 1000mL three-necked flask equipped with a mechanical stirrer and a water separator. The atmosphere in the flask was replaced with argon and stirred at room temperature for 30 minutes. The oil bath was heated to 175°C and refluxed with water for 3 hours, with water continuously flowing back into the water separator. After completion of this process, the remaining cyclohexane was completely distilled off, and the oil bath was allowed to cool to room temperature. Then, 51.119g (0.153mol) of decafluorobiphenyl was added. The oil bath was heated to 80°C, mechanically stirred at 250 rpm, and the reaction continued for 24 hours. After the reaction was completed, the solution was poured into warm water to precipitate a strip-like crude product, which was purified by ethanol and ultrapure water five times each and dried to obtain a fluorinated polyarylene ether powder (number average molecular weight of 54,000 g / mol).

[0068] 6.30 g (0.005 mol) of the obtained fluorinated polyarylether powder, 4.64 g (0.0132 mol) of polyethylene glycol monomethyl ether (average Mn = 350), 0.51 g (0.012 mol) of CaH2, 0.070 g (0.0012 mol) of KF and 45 mL of DMAc were placed in a 100 mL three-necked flask equipped with a mechanical stirrer. The atmosphere in the flask was replaced with argon and stirred at room temperature for 30 minutes. The reaction was then carried out at 100°C for 24 hours. After the reaction was completed, the solution was poured into warm water to precipitate a strip of crude product. After crushing, the product was purified by ethanol and ultrapure water 5 times each and dried to obtain a modified fluorinated polyarylether powder. Its H NMR spectrum is shown as follows: Figure 1 As shown, the polyethylene glycol grafting rate is 59.8%, and the calculation formula is (4.33 / (7.25×4)) / (2 / 8)×100%.

[0069] Barium sulfate (12 g) and H₂O₂ (30%, 60 mL) were heated (100°C) and refluxed for 10 hours in a single-necked round-bottom flask to obtain hydroxyl-modified barium sulfate. Subsequently, hydroxylated barium sulfate (6 g), 3-aminopropyltrimethoxysilane (6 g), and toluene (60 mL) were placed in a single-necked round-bottom flask and heated (110°C) and refluxed for 20 hours. After the reaction mixture cooled to room temperature, it was centrifuged five times with toluene to obtain the modified barium sulfate developer.

[0070] Weigh 1.8 g of the obtained modified fluorinated polyarylether powder, 0.4 g of modified barium sulfate developer and 6 g of a mixed solvent of acetone and N,N-dimethylformamide in a mass ratio of 1:3, and ultrasonically mix for 1 hour to obtain a spinning solution. Pour the spinning solution into a syringe and pass it through an electrospinning machine (model: Yunfan Technology YFSP-T) to prepare a porous fiber membrane. In the electrospinning process, a 21G metal needle is used, the electrospinning spacing is 9 cm, the spinning voltage is 20KV, the temperature in the spinning machine is 30°C, the humidity is 30%, the liquid feeding rate is 1.0 mL / h, and the polypropylene mesh is used as the receiving surface. After all the spinning solution is exhausted, vacuum dry it at 40°C overnight to obtain a developable composite hernia patch. The flow diagram is as follows Figure 2 shown.

[0071] Example 2

[0072] The preparation process of the fluorinated polyarylene ether powder is the same as that in Example 1.

[0073] 6.30 g (0.005 mol) of the obtained fluorinated poly(arylene ether) powder, 9.9 g (0.0132 mol) of polyethylene glycol monomethyl ether (average Mn = 750), 0.51 g (0.012 mol) of CaH2, 0.070 g (0.0012 mol) of KF, and 45 mL of DMAc were placed in a 100 mL three-necked flask equipped with a mechanical stirrer. The atmosphere in the flask was replaced with argon, and the mixture was stirred at room temperature for 30 minutes. The reaction was then carried out at 100°C for 24 hours. After the reaction was completed, the solution was poured into warm water to precipitate a crude product in the form of strips. The product was then crushed, purified in ethanol and then in ultrapure water five times each, and dried to obtain a modified fluorinated poly(arylene ether) powder with a polyethylene glycol grafting ratio of 50.5%.

[0074] The preparation process of the modified barium sulfate developer is the same as that of Example 1.

[0075] The preparation process of the developable composite hernia patch is the same as that in Example 1.

[0076] Example 3

[0077] The preparation process of the fluorinated polyarylene ether powder is the same as that in Example 1.

[0078] 6.30 g (0.005 mol) of the obtained fluorinated poly(arylene ether) powder, 25.08 g (0.0132 mol) of polyethylene glycol monomethyl ether (average Mn = 1900), 0.51 g (0.012 mol) of CaH2, 0.070 g (0.0012 mol) of KF, and 45 mL of DMAc were placed in a 100 mL three-necked flask equipped with a mechanical stirrer. The atmosphere in the flask was replaced with argon, and the mixture was stirred at room temperature for 30 minutes. The mixture was then reacted at 100°C for 24 hours. After the reaction was completed, the solution was poured into warm water to precipitate a crude product in the form of strips. The product was then crushed, purified in ethanol and then in ultrapure water five times each, and dried to obtain a modified fluorinated poly(arylene ether) powder with a polyethylene glycol grafting ratio of 36.6%.

[0079] The preparation process of the modified barium sulfate developer is consistent with that of Example 1

[0080] The preparation process of the developable composite hernia patch is the same as that in Example 1.

[0081] Example 4

[0082] The preparation process of the fluorinated polyarylene ether powder is the same as that in Example 1.

[0083] 6.30 g (0.005 mol) of the obtained fluorinated poly(arylene ether) powder, 66.0 g (0.0132 mol) of polyethylene glycol monomethyl ether (average Mn = 5000), 0.51 g (0.012 mol) of CaH2, 0.070 g (0.0012 mol) of KF, and 45 mL of DMAc were placed in a 100 mL three-necked flask equipped with a mechanical stirrer. The atmosphere in the flask was replaced with argon, and the mixture was stirred at room temperature for 30 minutes. The mixture was then reacted at 100°C for 24 hours. After the reaction was completed, the solution was poured into warm water to precipitate a crude product in the form of strips. The product was then crushed, purified in ethanol and ultrapure water five times each, and dried to obtain a modified fluorinated poly(arylene ether) powder with a polyethylene glycol grafting efficiency of 32.1%.

[0084] The preparation process of the modified barium sulfate developer is the same as that of Example 1.

[0085] The preparation process of the developable composite hernia patch is the same as that in Example 1.

[0086] Example 5

[0087] 34.244 g (0.15 mol) of bisphenol A, 24.878 g (0.18 mol) of anhydrous potassium carbonate, 483.720 g of N,N-dimethylacetamide, and 161.240 g of cyclohexane were placed in a 1000 mL three-necked flask equipped with a mechanical stirrer and a water separator. The atmosphere in the flask was replaced with argon and stirred at room temperature for 30 min. The oil bath was heated to 175°C and refluxed with water for 3 h, with water continuously flowing back into the water separator. This represents the deprotonation process. After this process, the remaining cyclohexane was completely distilled off, the oil bath cooled to room temperature, and 28.466 g (0.153 mol) of hexafluorobenzene was added. The oil bath was heated to 80°C and mechanically stirred at 250 rpm for 24 h. This represents the aromatic nucleophilic substitution process. After the reaction was completed, the solution was poured into warm water to precipitate a strip-like crude product, which was purified by ethanol and ultrapure water five times each and dried to obtain a fluorinated polyarylene ether powder (number average molecular weight of 54,000 Da).

[0088] The preparation process of the modified fluorinated polyarylene ether powder was the same as that in Example 3. The polyethylene glycol grafting rate was 36.6%.

[0089] The preparation process of the modified barium sulfate developer is the same as that of Example 1.

[0090] The preparation process of the developable composite hernia patch is the same as that in Example 1.

[0091] Example 6

[0092] 34.244 g (0.15 mol) of bisphenol A, 24.878 g (0.18 mol) of anhydrous potassium carbonate, 483.720 g of N,N-dimethylacetamide, and 161.240 g of cyclohexane were placed in a 1000 mL three-necked flask equipped with a mechanical stirrer and a water separator. The atmosphere in the flask was replaced with argon and stirred at room temperature for 30 min. The oil bath was heated to 175°C and refluxed with water for 3 h, with water continuously flowing back into the water separator. This represents the deprotonation process. After this process, the remaining cyclohexane was completely evaporated, the oil bath cooled to room temperature, and 55.404 g (0.153 mol) of decafluorobiphenyl ketone was added. The oil bath was heated to 80°C and mechanically stirred at 250 rpm for 24 h. This represents the aromatic nucleophilic substitution process. After the reaction was completed, the solution was poured into warm water to precipitate a strip-like crude product, which was purified by ethanol and ultrapure water five times each and dried to obtain a fluorinated polyarylene ether powder (number average molecular weight of 54,000 Da).

[0093] The preparation process of the modified fluorinated polyarylene ether powder was the same as that in Example 3. The polyethylene glycol grafting rate was 36.6%.

[0094] The preparation process of the modified barium sulfate developer is the same as that of Example 1.

[0095] The preparation process of the developable composite hernia patch is the same as that in Example 1.

[0096] Comparative Example 1 (no developer added)

[0097] The preparation process of the fluorinated polyarylene ether powder is the same as that in Example 1.

[0098] The preparation process of the modified fluorinated polyarylene ether powder was the same as that in Example 3. The polyethylene glycol grafting rate was 36.6%.

[0099] 1.8 g of the modified fluorinated polyarylene ether powder was weighed and mixed with a 1:3 mass ratio of acetone and N,N-dimethylformamide solvent to form a spinning solution. This solution was then poured into a syringe and passed through an electrospinning machine (Yunfan Technology YFSP-T) to prepare a fiber membrane. The electrospinning process employed a 21G metal needle, a 9 cm electrospinning pitch, a spinning voltage of 20 kV, a temperature of 30°C, a humidity of 30%, and a liquid feed rate of 1.0 mL / h. A polypropylene mesh served as the receiving surface. After the spinning solution was exhausted, a modified fluorinated polyarylene ether / polypropylene composite hernia repair patch was obtained.

[0100] Comparative Example 2 (fluorinated polyarylene ether not modified)

[0101] The preparation process of the fluorinated polyarylene ether powder is the same as that in Example 1.

[0102] The preparation process of the modified barium sulfate developer is the same as that of Example 1.

[0103] 1.8 g of the obtained fluorinated polyarylene ether powder, 0.4 g of modified barium sulfate developer, and a 1:3 mass ratio of acetone and N,N-dimethylformamide mixed solvent were weighed and mixed to obtain a spinning solution. This solution was then poured into a syringe and passed through an electrospinning machine (Yunfan Technology YFSP-T) to prepare a porous fiber membrane. The electrospinning process employed a 21G metal needle, a 9 cm electrospinning pitch, a spinning voltage of 20 kV, a temperature of 30°C, a humidity of 30%, and a liquid feed rate of 1.0 mL / h. A polypropylene mesh served as the receiving surface. After the spinning solution was completely exhausted, a developable fluorinated polyarylene ether / polypropylene composite hernia repair patch was obtained.

[0104] The test results of reducing substances of the water extracts of the final products obtained in the above examples and comparative examples are shown in Table 1 below:

[0105] Table 1

[0106]

[0107]

[0108] The final products obtained in the above examples and comparative examples were subjected to cytotoxicity testing, where negative results were obtained by not receiving any treatment and positive results were obtained by adding 10 wt% DMSO to the culture medium. The test results are shown in Table 2 below (cell viability ≥ 70% is considered low cytotoxicity):

[0109] Table 2

[0110] Group Cell survival rate (%) Negative 100 Positive 0.5 Example 1 87 Example 2 93 Example 3 85 Example 4 86 Example 5 87 Example 6 94 Comparative Example 1 86 Comparative Example 2 92

[0111] As shown in Tables 1 and 2, there is no difference in the reducing substance content and cytotoxicity of the water extracts of the Examples and Comparative Examples.

[0112] The present invention tests the final products obtained in Example 3 and Comparative Example 2, and the specific method is as follows:

[0113] Thirty-six female Sprague-Dawley rats (110-130 g, 4 / 5 weeks old) were randomly divided into six groups (n=6) to establish an abdominal wall hernia model. In vivo experiments were conducted in accordance with the Guide for the Care and Use of Laboratory Animals of the Changchun Institute of Applied Chemistry, Chinese Academy of Sciences. All animal experiments were approved by the Animal Ethics Committee of the Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, with the corresponding animal experiment ethics code 2023-0167. Sprague-Dawley rats were anesthetized with 5% isoflurane, and after skin preparation, they were transferred to the operating table and maintained with 1.5% isoflurane. The rats were placed with their abdomen facing upwards, and the abdominal skin preparation site was disinfected with iodine. The abdomen was bisected along the midline, and abdominal wall tissue was removed to create a full-thickness abdominal wall defect measuring 8 mm × 10 mm. A patch sample was implanted to fill the defect and closed with 5-0 absorbable sutures. In vivo anti-adhesion testing was performed with the composite modified fluoropolyarylether and modified imaging agent in contact with the side facing away from the peritoneal cavity.

[0114] The results are as follows Figure 3 As shown, it was found that both the patch materials provided by Example 3 and Comparative Example 2 filled the abdominal wall defect without forming a hernia sac. Among them, the Comparative Example 2 group (left picture) had more adhesion to the small intestine, while the Example 3 group (right picture) had almost no adhesion.

[0115] The present invention performs CT test on the final products obtained in Example 3 and Comparative Example 1. The results are as follows Figure 4 As shown, it was found that the composite hernia patch of Example 3 (right figure) had a developing function, while the composite hernia patch of Comparative Example 1 (left figure) had no developing function.

[0116] The above description of the disclosed embodiments will enable one skilled in the art to implement or use the present invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the present invention. Therefore, the present invention is not limited to the embodiments shown herein but is to be construed in the widest manner consistent with the principles and novel features disclosed herein.

Claims

1. A developable composite hernia patch, characterized in that: The invention comprises a polypropylene patch and a modified fluorinated polyarylether and a modified developer compounded on the polypropylene patch; The modified fluorinated polyarylene ether is grafted with polyethylene glycol; The modified fluorinated polyarylene ether and the modified developer are connected through hydrogen bonds.

2. The developable composite hernia patch according to claim 1, characterized in that: The mass ratio of the modified fluorinated polyarylene ether to the modified developer is 100:(15-40).

3. The developable composite hernia patch according to claim 1 or 2, characterized in that: The number average molecular weight of the polyethylene glycol is 300 to 5000 g / mol; The grafting rate of the polyethylene glycol is 30-60%.

4. The developable composite hernia patch according to any one of claims 1 to 3, characterized in that: The modified developer is obtained by reacting a functional developer with a silane coupling agent.

5. The developable composite hernia patch according to claim 4, characterized in that: The functionalized developer is a hydroxylated developer; The developer is selected from any one or more of barium sulfate, tungsten powder, bismuth oxide, bismuth subcarbonate or bismuth oxychloride; The silane coupling agent is selected from any one or more of 3-ureapropyltriethoxysilane, 3-mercaptopropyltriethoxysilane or 3-aminopropyltrimethoxysilane.

6. A method for preparing a developable composite hernia patch according to any one of claims 1 to 5, characterized in that: The following steps are involved: A solution comprising modified fluorinated polyarylether and modified developer is sprayed on the surface of a polypropylene patch to obtain a developable composite hernia patch.

7. The preparation method according to claim 6, characterized in that The solvent in the solution is selected from any one or more of acetone, dichloromethane, chloroform, N,N-dimethylformamide or N,N-dimethylacetamide; The concentration of the solution is 40-55 wt%.

8. The preparation method according to claim 7, characterized in that The solvent is a mixed solution of acetone and N,N-dimethylformamide; The mass ratio of the acetone to N,N-dimethylformamide is 1:(3-4).

9. The preparation method according to any one of claims 6 to 8, characterized in that The spraying adopts an electrostatic spinning method, an ultrasonic spraying method, an inkjet printing method or an atomization deposition method.

10. Use of the developable composite hernia patch according to any one of claims 1 to 5 or the developable composite hernia patch prepared according to the preparation method according to any one of claims 6 to 9 in the preparation of hernia repair materials.

Images