Tissue-adhesion-resistant polypropylene biomedical monofilament as well as preparation method and application thereof

Abstract

The invention relates to the technical field of medical materials, in particular to a tissue-adhesion-resistant polypropylene biomedical monofilament and a preparation method and application thereof, and the tissue-adhesion-resistant polypropylene biomedical monofilament is composed of a polypropylene monofilament and a tissue-adhesion-resistant functional polymer coating; the tissue adhesion resistant functional polymer coating is formed by carrying out free radical copolymerization on N-acryloyloxy succinimide and a zwitterionic monomer. According to the invention, the polymer with the anti-tissue adhesion function is fixed to the surface of the polypropylene monofilament, and chemical bonding is formed on the surface of the monofilament, so that the problem of coating shedding is solved, and the long-term anti-tissue adhesion effect is maintained. After the monofilaments are woven into the patch, the biomedical patch capable of inhibiting tissue adhesion and inflammatory reaction can be obtained without secondary treatment. Compared with the existing patch modification technology, the method is more suitable for industrialization.

Description

Technical Field

[0001] The invention relates to the technical field of medical materials, and in particular to a polypropylene biomedical monofilament with anti-tissue adhesion, and a preparation method and application thereof. Background Art

[0002] Hernia is a common surgical disease. It is caused by the rupture of the peritoneum supporting the organs, which causes the organs to protrude outward through the gap, forming a local mass. Repair by using patch materials is currently the most widely used method. The implantation of the patch provides sufficient strength support for the weak part, thereby supporting the regeneration of the tissue. The ideal patch material should have good biocompatibility, appropriate mechanical response, antibacterial properties, and no inflammatory response.

[0003] Polypropylene material is cheap, biologically inert, has good mechanical properties, and is chemically stable, so it is widely used as the raw material for various macroporous or mesh patches. Polypropylene patches have the advantages of small surgical wounds and rapid recovery after surgery, and are widely used in clinical practice. However, polypropylene patches also have many disadvantages: due to the rough surface of polypropylene monofilaments, direct contact with tissues or organs can cause severe abdominal adhesions, thereby triggering various infections or inflammatory reactions.

[0004] To make up for this shortcoming, several materials are usually compounded and woven together to prepare a composite patch, which reduces tissue adhesion while meeting mechanical properties, such as compounding polypropylene with degradable materials or with expanded polytetrafluoroethylene materials. Another technical solution is to graft hydrophilic polymers such as polyethylene glycol or zwitterionic polymers onto the patch. Such hydrophilic polymers will form a hydration layer on the surface of the monofilament, thereby inhibiting tissue adhesion and avoiding subsequent tissue adhesion or inflammatory response. However, this method usually processes the patch, which is complicated to operate and only has research value but not mass application value. Summary of the invention

[0005] The purpose of the present invention is to solve the shortcomings of the prior art and to propose a polypropylene biomedical monofilament with anti-tissue adhesion and its preparation method and application. The problem of coating shedding is solved by fixing a polymer with anti-tissue adhesion function to the surface of the polypropylene monofilament and forming a chemical bond on the surface of the monofilament, thereby maintaining a long-term anti-tissue adhesion effect.

[0006] In order to achieve the above object, the present invention adopts the following technical solutions:

[0007] A polypropylene biomedical monofilament with anti-tissue adhesion, which is composed of a polypropylene monofilament and a functional polymer coating with anti-tissue adhesion;

[0008] The anti-tissue adhesion functional polymer coating is formed by free radical copolymerization of N-acryloyloxysuccinimide and zwitterionic monomers, and the structural formula of N-acryloyloxysuccinimide is:

[0009]

[0010] The zwitterionic monomer is [2-(methacryloyloxy)ethyldimethyl-(3-sulfonic acid propyl)amine hydroxide, and its structural formula is:

[0011]

[0012] Preferably, the polypropylene monofilament is subjected to plasma surface treatment and dopamine surface modification, and the diameter of the polypropylene monofilament is 0.1 mm.

[0013] Preferably, the plasma surface treatment process is to use low-temperature plasma to perform surface treatment on the polypropylene monofilament online.

[0014] Preferably, the molar ratio of N-acryloyloxysuccinimide to zwitterionic monomer in the polymer coating with anti-tissue adhesion function is 1:(6-9).

[0015] The present invention also provides a method for preparing a polypropylene biomedical monofilament with anti-tissue adhesion, comprising the following steps:

[0016] Step 1: Synthesis of functional polymers

[0017] N-acryloyloxysuccinimide, zwitterionic monomers, and solvent are added to a reaction kettle, and an initiator is added, and the reaction is carried out at 70° C. for 8 hours to obtain a functional polymer; wherein the molar ratio of N-acryloyloxysuccinimide to zwitterionic monomers is 1:(6-9), the amount of solvent used is 8 times the total mass of N-acryloyloxysuccinimide and zwitterionic monomers, and the amount of initiator used is 2.5% of the total mass of N-acryloyloxysuccinimide and zwitterionic monomers. After the reaction is completed, the mixture is precipitated with anhydrous ethanol, dissolved with deionized water, and then precipitated with anhydrous ethanol, washed repeatedly for 3 times, filtered, and dried at 60° C. to obtain a functional polymer;

[0018] Step 2: Surface treatment of polypropylene monofilament

[0019] A low-temperature plasma generator is used to perform online surface treatment on polypropylene monofilaments. The polypropylene monofilaments are extracted after plasma treatment and oxidized by air, and then directly introduced into a dopamine aqueous solution for winding, and treated at 60°C for 24 hours to obtain surface-treated polypropylene monofilaments.

[0020] Step 3: Preparation of polypropylene biomedical monofilaments with anti-tissue adhesion

[0021] The functional polymer prepared in step 1 is configured into a functional polymer aqueous solution, the surface-treated polypropylene monofilament obtained in step 2 is unwound, washed in a water tank, dried in a hot air oven at 80°C, introduced into the functional polymer aqueous solution, treated at 60-80°C for 12-36h, unwound, washed with water, and dried to obtain a polypropylene biomedical monofilament with anti-tissue adhesion.

[0022] Preferably, in step 1, the solvent is N,N-dimethylformamide or dimethyl sulfoxide, and the initiator is 2,2-azobisisobutyronitrile.

[0023] Preferably, in step 2, the plasma surface treatment process is as follows: the distance between the polypropylene monofilament and the plasma nozzle is 2.0 cm, the monofilament movement rate is 0.5 m / min, the plasma spraying interval length is 50 cm, and the plasma discharge power is 900 W.

[0024] Preferably, in step 2, the mass percentage of dopamine in the dopamine aqueous solution is 2%. The pH value of the dopamine aqueous solution is 8.

[0025] Preferably, in step three, the functional polymer content in the functional polymer aqueous solution is 8% by weight.

[0026] The invention also provides an application of a tissue-adhesion-resistant polypropylene biomedical monofilament as a medical patch after being woven.

[0027] Compared with the prior art, the present invention has the following beneficial effects:

[0028] 1. The present invention directly performs biocompatibility treatment on the surface of monofilaments, and the obtained monofilaments have the effect of resisting tissue adhesion. After the monofilaments are woven into a patch, a biomedical patch with the function of inhibiting tissue adhesion and inflammatory response can be obtained without secondary treatment. Compared with the existing patch modification technology, the present invention is more suitable for industrialization.

[0029] 2. The present invention first uses plasma to treat the surface of polypropylene monofilaments, and forms a large number of polar groups on the surface of polypropylene monofilaments after air oxidation. Then, the monofilaments are immersed in a dopamine aqueous solution, and dopamine is adsorbed on the surface of the polypropylene monofilaments and oxidized to form a polydopamine layer, so that dopamine and polypropylene have a strong interaction. The synthesized functional polymer has two components, N-succinimide and zwitterions. N-succinimide can react with secondary amines on the surface of polydopamine to form chemical bonds, so that the functional polymer can not fall off from the surface of polypropylene monofilaments during long-term use. The zwitterion segment is hydrophilic and can form a hydration layer in the tissue, which plays a role in inhibiting tissue adhesion, so that the implant material prepared by the monofilament has the effect of inhibiting tissue adhesion and inflammatory response. DETAILED DESCRIPTION

[0030] The technical solutions in the embodiments of the present invention will be described clearly and completely below so that those skilled in the art can better understand the advantages and features of the present invention, thereby making a clearer definition of the protection scope of the present invention. The embodiments described in the present invention are only a part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments in the present invention, all other embodiments obtained by ordinary technicians in the field without creative work are within the scope of protection of the present invention.

[0031] A polypropylene biomedical monofilament with anti-tissue adhesion, which is composed of a polypropylene monofilament and a functional polymer coating with anti-tissue adhesion;

[0032] The anti-tissue adhesion functional polymer coating is formed by free radical copolymerization of N-acryloyloxysuccinimide and zwitterionic monomers, and the structural formula of N-acryloyloxysuccinimide is:

[0033]

[0034] The zwitterionic monomer is [2-(methacryloyloxy)ethyldimethyl-(3-sulfonic acid propyl)amine hydroxide, and its structural formula is:

[0035]

[0036] Among them, the polypropylene monofilament is subjected to plasma surface treatment and dopamine surface modification, and the diameter of the polypropylene monofilament is 0.1 mm; the plasma surface treatment process is to use low-temperature plasma to perform surface treatment on the polypropylene monofilament online; the molar ratio of N-acryloyloxysuccinimide and zwitterionic monomer in the polymer coating with anti-tissue adhesion function is 1:(6-9).

[0037] The present invention also provides a method for preparing a polypropylene biomedical monofilament with anti-tissue adhesion, comprising the following steps:

[0038] Step 1: Synthesis of functional polymers

[0039] N-acryloyloxysuccinimide, zwitterionic monomer, solvent are added to a reaction kettle, and an initiator is added, and the reaction is carried out at 70°C for 8 hours to obtain a functional polymer; wherein the molar ratio of N-acryloyloxysuccinimide to zwitterionic monomer is 1:(6-9), the amount of solvent is 8 times the total mass of N-acryloyloxysuccinimide and zwitterionic monomer, and the amount of initiator is 2.5% of the total mass of N-acryloyloxysuccinimide and zwitterionic monomer. After the reaction is completed, it is precipitated with anhydrous ethanol, dissolved with deionized water and then precipitated with anhydrous ethanol, washed repeatedly for 3 times, filtered, and dried at 60°C to obtain a functional polymer. wherein the solvent is N,N-dimethylformamide or dimethyl sulfoxide; and the initiator is 2,2-azobisisobutyronitrile.

[0040] Step 2: Surface treatment of polypropylene monofilament

[0041] The polypropylene monofilament was subjected to online surface treatment using a low-temperature plasma generator. The polypropylene monofilament was extracted after plasma treatment and oxidized by air, then directly introduced into a dopamine aqueous solution for winding, and treated at 60°C for 24 hours to obtain a surface-treated polypropylene monofilament. The plasma surface treatment process is as follows: the distance between the polypropylene monofilament and the plasma nozzle is 2.0 cm, the monofilament movement rate is 0.5 m / min, the plasma jet width is 50 cm, and the plasma discharge power is 900 W. The mass percentage of dopamine in the dopamine aqueous solution is 2%, and the pH value is 8.

[0042] Step 3: Preparation of polypropylene biomedical monofilaments with anti-tissue adhesion

[0043] The functional polymer prepared in step 1 is prepared into a functional polymer aqueous solution, the surface-treated polypropylene monofilament obtained in step 2 is unwound, washed in a water tank, dried in a hot air oven at 80° C., introduced into the functional polymer aqueous solution, treated at 60-80° C. for 12-36 hours, unwound, washed with water, and dried to obtain a polypropylene biomedical monofilament with anti-tissue adhesion. In the functional polymer aqueous solution, the mass percentage content of the functional polymer is 8%.

[0044] The invention also provides an application of a tissue-adhesion-resistant polypropylene biomedical monofilament as a medical patch after being woven.

[0045] In this embodiment, the test method for the anti-tissue adhesion of polypropylene biomedical monofilament is:

[0046] Polypropylene biomedical monofilament was woven into a patch and cut into samples of 1.0 cm*2.0 cm. SD rats weighing about 250 g were selected, and an incision was made in the midline of the abdominal wall. The patch was implanted and fixed to the defect site. The animals were killed on the 60th day, and a tension tester was used to test the maximum force required to destroy tissue-patch adhesion.

[0047] The present invention is further described below with reference to the examples.

[0048] Example 1

[0049] Step 1: Synthesis of functional polymers

[0050] 42.3 g of N-acryloyloxysuccinimide and 419 g of zwitterionic monomer, 3.7 kg of solvent N, N-dimethylformamide were added into a reactor, and 11.5 g of initiator 2,2-azobisisobutyronitrile was added, and the reaction was carried out at 70° C. for 8 hours. After the reaction was completed, it was precipitated with anhydrous ethanol, dissolved with deionized water, and then precipitated with anhydrous ethanol. After repeated washing for 3 times, it was filtered and dried at 60° C. to obtain a functional polymer.

[0051] Step 2: Surface treatment of polypropylene monofilament

[0052] A polypropylene monofilament with a diameter of 0.1 mm was selected. A low-temperature plasma generator was used to perform online surface treatment on the polypropylene monofilament. The plasma surface treatment process is as follows: the distance between the polypropylene monofilament and the plasma nozzle is 2.0 cm, the monofilament movement rate is 0.5 m / min, the plasma jet width is 50 cm, and the plasma discharge power is 900 W. The polypropylene monofilament is led out after plasma treatment, and after being oxidized by air, it is directly introduced into the dopamine aqueous solution for winding. The mass percentage content of dopamine in the dopamine aqueous solution is 2%, and the pH value of the aqueous solution is 8. The surface-treated polypropylene monofilament is obtained by treating at 60°C for 24 hours.

[0053] Step 3: Preparation of polypropylene biomedical monofilaments with anti-tissue adhesion

[0054] The functional polymer prepared in step 1 is prepared into an aqueous functional polymer solution with a mass percentage of 8%. The surface-treated polypropylene monofilament obtained in step 2 is unwound, washed in a water tank, dried in a hot air oven at 80°C, introduced into the functional polymer aqueous solution, treated at 60°C for 12h, unwound, washed with water, and dried to obtain a polypropylene biomedical monofilament with anti-tissue adhesion.

[0055] The polypropylene biomedical monofilament was woven into a patch and placed in an animal body for 60 days. Testing showed that the maximum force required to destroy tissue network adhesion was 0.5N.

[0056] Example 2

[0057] In this embodiment, step 1 and step 2 are the same as those in embodiment 1. The difference is that in step 3, the surface-treated polypropylene monofilament is treated in the functional polymer aqueous solution at 60° C. for 36 hours.

[0058] The polypropylene biomedical monofilament was woven into a patch and placed in an animal body for 60 days. Testing showed that the maximum force required to destroy tissue network adhesion was 0.3N.

[0059] Example 3

[0060] In this embodiment, step 1 and step 2 are the same as those in embodiment 1. The difference is that in step 3, the surface-treated polypropylene monofilament is treated in the functional polymer aqueous solution at 80° C. for 24 hours.

[0061] The polypropylene biomedical monofilament was woven into a patch and placed in an animal's body for 60 days. Testing showed that the maximum force required to destroy tissue network adhesion was 0.3N.

[0062] Example 4

[0063] Step 1, add 42.3g N-acryloyloxysuccinimide and 628.5g zwitterionic monomer, 5.4kg solvent dimethyl sulfoxide into a reactor, and add 16.8g initiator 2,2-azobisisobutyronitrile, and react at 70°C for 8h; after the reaction, precipitate with anhydrous ethanol, dissolve with deionized water and then precipitate with anhydrous ethanol, wash repeatedly 3 times and filter, and dry at 60°C to obtain a functional polymer.

[0064] Step 2 and step 3 are the same as those in Example 1.

[0065] The polypropylene biomedical monofilament was woven into a patch and placed in an animal's body for 60 days. Testing showed that the maximum force required to destroy tissue network adhesion was 0.8N.

[0066] Comparative Example:

[0067] After the unsurface-modified polypropylene monofilaments were woven into a patch, it was placed in the animal's body for 60 days. After testing, the maximum force required to destroy the tissue network adhesion was 2.8N.

[0068] In summary, the present invention solves the problem of coating shedding and maintains a long-term anti-tissue adhesion effect by fixing the polymer with anti-tissue adhesion function to the surface of the polypropylene monofilament and forming a chemical bond on the surface of the monofilament.

[0069] The description and practice disclosed in the present invention are easy to think and understand for ordinary technicians in the technical field, and several improvements and modifications can be made without departing from the principles of the present invention. Therefore, modifications or improvements made without departing from the spirit of the present invention should also be regarded as the protection scope of the present invention.

Claims

1. A polypropylene biomedical monofilament with anti-tissue adhesion, It is characterized in that It is composed of polypropylene monofilament and a functional polymer coating with anti-tissue adhesion; The anti-tissue adhesion functional polymer coating is formed by free radical copolymerization of N-acryloyloxysuccinimide and zwitterionic monomers, and the structural formula of N-acryloyloxysuccinimide is: The zwitterionic monomer is [2-(methacryloyloxy)ethyldimethyl-(3-sulfonic acid propyl)amine hydroxide, and its structural formula is:

2. The anti-tissue adhesion polypropylene biomedical monofilament according to claim 1, It is characterized in that The polypropylene monofilament is subjected to plasma surface treatment and dopamine surface modification, and the diameter of the polypropylene monofilament is 0.1 mm.

3. The anti-tissue adhesion polypropylene biomedical monofilament according to claim 2, It is characterized in that The plasma surface treatment process is to use low-temperature plasma to perform surface treatment on polypropylene monofilaments online.

4. The anti-tissue adhesion polypropylene biomedical monofilament according to claim 1, It is characterized in that The molar ratio of N-acryloxysuccinimide to zwitterionic monomer in the polymer coating with anti-tissue adhesion function is 1:(6-9).

5. The method for preparing the anti-tissue adhesion polypropylene biomedical monofilament according to claim 1, It is characterized in that The steps include: Step 1: Synthesis of functional polymers N-acryloyloxysuccinimide, zwitterionic monomers, and solvent are added to a reaction kettle, and an initiator is added, and the reaction is carried out at 70° C. for 8 hours to obtain a functional polymer; wherein the molar ratio of N-acryloyloxysuccinimide to zwitterionic monomers is 1:(6-9), the amount of solvent used is 8 times the total mass of N-acryloyloxysuccinimide and zwitterionic monomers, and the amount of initiator used is 2.5% of the total mass of N-acryloyloxysuccinimide and zwitterionic monomers. After the reaction is completed, the mixture is precipitated with anhydrous ethanol, dissolved with deionized water, and then precipitated with anhydrous ethanol, washed repeatedly for 3 times, filtered, and dried at 60° C. to obtain a functional polymer; Step 2: Surface treatment of polypropylene monofilament A low-temperature plasma generator is used to perform online surface treatment on polypropylene monofilaments. The polypropylene monofilaments are extracted after plasma treatment and oxidized by air, and then directly introduced into a dopamine aqueous solution for winding, and treated at 60°C for 24 hours to obtain surface-treated polypropylene monofilaments. Step 3: Preparation of polypropylene biomedical monofilaments with anti-tissue adhesion The functional polymer prepared in step 1 is configured into a functional polymer aqueous solution, the surface-treated polypropylene monofilament obtained in step 2 is unwound, washed in a water tank, dried in a hot air oven at 80°C, introduced into the functional polymer aqueous solution, treated at 60-80°C for 12-36h, unwound, washed with water, and dried to obtain a polypropylene biomedical monofilament with anti-tissue adhesion.

6. The method for preparing the anti-tissue adhesion polypropylene biomedical monofilament according to claim 5, It is characterized in that In step 1, the solvent is N,N-dimethylformamide or dimethyl sulfoxide, and the initiator is 2,2-azobisisobutyronitrile.

7. The method for preparing the anti-tissue adhesion polypropylene biomedical monofilament according to claim 5, It is characterized in that In step 2, the plasma surface treatment process is as follows: the distance between the polypropylene monofilament and the plasma nozzle is 2.0 cm, the monofilament movement rate is 0.5 m / min, the plasma spraying interval length is 50 cm, and the plasma discharge power is 900W.

8. The method for preparing the anti-tissue adhesion polypropylene biomedical monofilament according to claim 5, It is characterized in that In step 2, the mass percentage of dopamine in the dopamine aqueous solution is 2%. The pH value of the dopamine aqueous solution is 8.

9. The method for preparing the anti-tissue adhesion polypropylene biomedical monofilament according to claim 5, It is characterized in that In step 3, the functional polymer content in the functional polymer aqueous solution is 8% by weight.

10. Use of the anti-tissue adhesion polypropylene biomedical monofilament according to any one of claims 1 to 4 as a medical patch after weaving.

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