An absorbable tissue-reinforcing fiber membrane and a method for producing the same

Abstract

The application relates to an absorbable tissue reinforcing fiber membrane and a preparation method thereof, which comprises the following steps: S1, vacuum drying absorbable material to obtain dried absorbable material; S2, feeding the dried absorbable material into a melt-blowing device to perform melt-blowing to obtain a melt-blowing fiber membrane; and S3, placing the melt-blowing fiber membrane between two flat plate molds to perform heat pressing and shaping treatment to obtain the absorbable tissue reinforcing fiber membrane. The preparation method of the absorbable tissue reinforcing fiber membrane provided by the application combines melt-blowing technology and heat pressing, and through process control, the crystallinity and mechanical rigidity of the material are significantly improved, so that the material can be used as a tissue reinforcing material to provide a supporting effect for cell regeneration; meanwhile, the material has a small diameter and a porous structure, which is very beneficial to cell ingrowth, proliferation and differentiation, and is an excellent tissue repair material.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of implantable medical devices, in particular to an absorbable tissue reinforcing fiber membrane with thin fiber diameter, stable size and high yield strength and a preparation method thereof. BACKGROUND

[0002] In the surgical process of removing lesions from substantial organ tissues (such as lung, liver, gastrointestinal, spleen, pancreas, kidney, etc.) in a living body, subsequent anastomosis or suturing of the disconnected tissues is inevitable. However, when directly suturing these tissues with an automatic anastomat or sutures, the small stress area of the anastomotic nails or sutures can cause secondary damage such as tissue laceration and rupture, and problems such as bleeding, leakage and complications at the needle eye.

[0003] To solve these problems, a tissue reinforcing material is used to pad the sutured (or anastomosed) part of the living body tissue, and then the suturing operation is performed. As an implantable medical device, the tissue reinforcing material is generally a polymer that can be absorbed by the living body, especially an aliphatic polyester or its copolymer, and in particular, polyglycolide (also known as polyglycolic acid, PGA) is highly regarded because of its good biocompatibility and matching degradation period with the tissue growth period. In addition, the structure of the tissue reinforcing material is generally a porous fiber structure, which is beneficial for cell growth and proliferation from the gap part thereof. For example, patent CN 111297512 A proposes a multi-layer tissue repair mesh woven from absorbable fibers. By melting and spinning aliphatic polyester (especially polyglycolide) into fibers, heat setting the fibers, and then weaving the mesh with a specific structure for use in reinforcing fragile tissues, both secondary damage to the living body tissue and leakage can be prevented. Patent CN 105483851B proposes that polyglycolide resin and a second component are respectively extruded, drawn, set, post-treated, and mechanically treated to obtain polyglycolide ultrafine fibers, which are then woven or carded for use in tissue repair patches. Although such a patch structure can meet the clinical requirements to some extent, the fiber structure obtained by the melting and spinning method has a relatively large fiber diameter, and the cell adhesion area is not enough. Based on the characteristics of the extracellular matrix fiber network structure of human body cells (fiber diameter of 0.1um-10μm), from the perspective of bionics, a fiber structure with small fiber diameter is required to increase the cell adhesion surface area and provide a good microenvironment for cell growth.

[0004] As a method for preparing a fiber structure with a small fiber diameter, electrospinning and melt-blowing are known. However, it is not easy to process aliphatic polyester (particularly polyglycolide) into a fiber structure with a small fiber diameter. First, polyglycolide is not easily soluble in common solvents, and electrospinning is not feasible because of the lack of a suitable solvent. Second, although polyglycolide can be melted, there are many difficulties in using a melt-blowing process to prepare polyglycolide into an absorbable tissue-reinforcing fiber membrane suitable for tissue anastomosis (or suturing). An absorbable tissue-reinforcing fiber membrane suitable for tissue anastomosis has a small size deformation (a tensile elongation is usually 10-50%) and a large yield tensile strength when an anastomosis needle penetrates. In the melt-blowing process, the cooling time is short when the melt fibers are gathered into a fiber membrane, the crystallinity is low, and the interaction between the fibers is small, which causes the yield tensile strength of the melt-blown aliphatic polyester fiber membrane to be low and the tensile elongation to be large, and the fiber membrane is macroscopically soft and easily deformed, and the structure is loose. At the same time, the melt-blown aliphatic polyester fiber web also has a relaxation phenomenon of amorphous segments, which further causes the size of the nonwoven fabric to be unstable.

[0005] To solve the problem of the unstable size of the fiber web, Chinese Patent Application No. CN102770593A discloses a size-stable nonwoven fabric fiber web and a manufacturing method. A continuous fiber is formed by using one or more thermoplastic polyesters and an anti-shrinkage agent (a semi-crystalline thermoplastic polymer such as polypropylene and polyamide that forms a dispersed phase with the aliphatic polyester), thereby preparing a size-stable nonwoven fabric fiber web. Although the addition of the anti-shrinkage agent (polypropylene, polyamide, etc.) can reduce the size of the web and stabilize the size, the additive is a non-absorbable polymer, which is a foreign body that exists for a long time and can cause an inflammatory reaction in the body tissue. At the same time, a method for preparing a polyglycolide absorbable tissue-reinforcing fiber membrane using a melt-blowing process has not been reported. Therefore, a method is needed to solve the problems of the poor size stability, low yield tensile strength, and large tensile elongation of the aliphatic polyester melt-blown fiber membrane (particularly the polyglycolide melt-blown fiber membrane) without using an additive, so as to be used as an absorbable tissue-reinforcing fiber membrane. SUMMARY

[0006] Therefore, the present application provides an absorbable tissue-reinforcing fiber membrane, which is prepared by depositing a biodegradable absorbable polymer on a collection surface by a melt-blowing method to form a random cross-wound multi-layer self-adhesive micro-fiber web structure, and then performing a heat-pressing setting treatment.

[0007] Further, to facilitate the distinction from the tissue when used in a clinic, a trace amount of a dyeing agent can be added to the absorbable tissue-reinforcing fiber membrane during the melt-blowing process to perform dyeing. The absorbable tissue-reinforcing fiber membrane has a high crystallinity, good size stability, a high yield tensile strength, and a moderate tensile elongation.

[0008] The tissue-reinforcing fiber membrane of the present application is an implantable medical device. In use, the tissue-reinforcing fiber membrane is used for the treatment and repair of irreversible lesions or accidental injuries of fragile organ tissues (such as lung, liver, gastrointestinal, spleen, pancreas, kidney, etc.), solving the problems of liquid leakage from fragile tissue wounds and damage of anastomosis staples. With the repair of the tissue, the tissue-reinforcing material will slowly absorb water and degrade in the body, and the tensile strength will gradually disappear, and finally be degraded into carbon dioxide and water and discharged out of the body.

[0009] The present application adopts melt-blowing method to prepare the fiber membrane. The melt-blowing refers to the process of rapidly stretching the capillary extruded thermoplastic molten filaments by high-speed airflow, and spraying and depositing the molten filaments on a collection surface to form a randomly dispersed self-adhesive micro-fiber network. The melt-blowing method has the characteristics of less process, high efficiency and no need to use solvent. The fiber membrane prepared by the melt-blowing method has a fiber diameter close to the diameter of human collagen fibers (0.5-20um), and the fiber membrane structure has a certain porosity.

[0010] In view of the shortcomings of low initial crystallinity, low yield tensile strength and large tensile elongation of the melt-blown fiber membrane, the present application proposes a hot-pressing setting treatment method. The hot-pressing setting treatment method refers to heating and pressurizing the prepared fiber membrane for a certain time.

[0011] Preferably, the heating temperature is between the glass transition temperature (T g ) and the melting point (T m ) of the polymer, lower than T g , and higher than T m , the molecular chain segment activity is weak; higher than T m , the fiber membrane structure will be damaged. Within the heating temperature range, the molecular chain of the polymer has strong activity, which can be rearranged from disordered amorphous state to ordered crystalline state, showing the increase of fiber crystallinity, solving the problem of low fiber crystallinity in the fiber membrane due to the insufficient recrystallization of the molecular chain during the rapid cooling of the melt-blowing polymer.

[0012] The polymer microstructure will determine the polymer macroscopic performance. The polyglycolide-based semi-crystalline polymer fiber is usually composed of amorphous region, crystalline region and connecting segment. To a certain extent, the increase of the proportion of the regularly arranged and dense crystalline region structure and the improvement of the connecting segment are not only beneficial to reduce the relaxation phenomenon of the amorphous segment and improve the dimensional stability of the fiber film. At the same time, the crystalline structure is also beneficial to the load transmission and better increases the mechanical rigidity of the deformation resistance, so that the heat setting treatment under certain conditions can improve the yield tensile strength of the fiber and reduce the tensile elongation. The heat setting treatment method can improve the contact and adhesion between the fibers and the fiber layers of the melt-blown fiber on the macroscopic level, and further make the structure of the fiber film more compact, so that the interaction force between the fibers in the fiber film can be improved during stretching. Through the improvement of the strength of the fiber itself and the interaction force between the fibers and the fiber layers, the problems of low yield tensile strength and large tensile elongation of the melt-blown fiber film are solved.

[0013] The prepared absorbable tissue reinforcing fiber film has high crystallinity, high yield tensile strength and moderate tensile elongation, and the structure of the fiber film is composed of a plurality of layers of microfibers crossing and winding. The diameter of the microfiber is in the range of 0.1 μm to 20 μm; preferably, the diameter of the microfiber is 1-15 μm, and more preferably, the diameter of the microfiber is 1-10 μm. The number of layers of the multi-layer microfiber web is 1-150 layers, preferably 10-50 layers, and more preferably 10-25 layers.

[0014] The thickness of the fiber film is 0.05-2 mm, preferably 0.1-0.8 mm, and more preferably 0.1-0.25 mm.

[0015] The fiber film has a grammage of 5-200 g / m 2 , preferably 30-150 g / m 2 , and more preferably 60-100 g / m 2 .

[0016] The fiber film has an elongation at break of 5%-200%, preferably an elongation at break of 5%-50%, and more preferably an elongation at break of 10%-30%.

[0017] The absorbable material includes aliphatic polyesters such as polyglycolide, polylactide, polycaprolactone and polyvalerolactone. Preferably, the absorbable material uses polyglycolic acid, and the weight average molecular weight of the polyglycolic acid is 30000-1000000; preferably, the weight average molecular weight of the polyglycolic acid is 30000-400000.

[0018] The dyeing agent includes D&C purple 2, D&C blue 6 and other varieties verified by FDA and widely used for implant dyeing. The content of the dyeing agent is 0-0.3% of the weight of the absorbable material, and the content of the dyeing agent is 0% for the absorbable tissue-reinforcing material without color.

[0019] In addition, the present application provides a preparation method of the above-described absorbable tissue-reinforcing fiber membrane, which comprises the following steps:

[0020] S1, preparing materials: placing the absorbable material resin (or powder, which may contain trace dyeing agent) into a vacuum oven for vacuum drying treatment;

[0021] S2, melt-blown fiber membrane: placing the dried absorbable material powder into a melt-blown device for melt-blown under certain conditions. During melt-blown, the polymer melt is extruded and blown into microfibers by high-speed airflow through a melt-blown die, and then gathered on a receiving roller to form a melt-blown fiber membrane; the temperature of each zone of melt extrusion is between 170°C and 260°C;

[0022] S3, preparing absorbable tissue-reinforcing fiber membrane: performing heat pressing and setting treatment on the melt-blown fiber membrane under certain conditions to improve the crystallinity and strength of the fibers and strengthen the adhesion between the fibers; and obtaining a sheet-shaped absorbable tissue-reinforcing fiber membrane after heat pressing and setting treatment.

[0023] The atmosphere of the heat pressing and setting treatment includes air, vacuum and nitrogen; the heat pressing and setting treatment mode includes online heat pressing and setting and offline heat pressing and setting; and the heat pressing and setting treatment is performed under certain temperature and pressure conditions. The conditions of the heat pressing and setting treatment are as follows: temperature is 70-120°C, pressure is 0.1-5 MPa, and time is 10S-300S; preferably, the temperature is 80-100°C, the pressure is 0.1-3 MPa, and the time is 30S-120S; more preferably, the temperature is 80-90°C, the pressure is 0.5-1 MPa, and the time is 30S-60S. If the heat pressing and setting temperature is lower than 70°C, the crystallinity and strength of the fibers and the adhesion between the fibers cannot be effectively improved in a short time; if the heating temperature exceeds 120°C, the microfibers in the patch may be melted; if the heat pressing and setting pressure is lower than 0.1 MPa, the fiber membrane cannot be effectively prevented from fluffing; and if the heat pressing and setting pressure exceeds 5 MPa, the fiber membrane may be deformed and the porosity may be reduced. If the heat pressing and setting time is lower than 10S, the crystallinity of the fibers cannot be effectively improved; and if the heat pressing and setting time exceeds 300S, the fiber membrane may become hard.

[0024] Due to the excellent comprehensive performance of the absorbable tissue reinforcing fiber membrane, after a specific sterilization treatment, an antibacterial absorbable tissue reinforcing fiber membrane with advantages of mechanical performance, medical performance and antibacterial performance can be obtained, so as to play a great role as a tissue reinforcing material in biological tissue suture operation.

[0025] Specifically, the method comprises the following steps:

[0026] A preparation method of an absorbable tissue reinforcing fiber membrane, comprising the following steps:

[0027] S1, vacuum drying the absorbable material to obtain dried absorbable material;

[0028] S2, putting the dried absorbable material into a melt-blowing device for melt-blowing to obtain a melt-blown fiber membrane;

[0029] S3, placing the melt-blown fiber membrane between two flat plate molds and performing hot pressing and shaping treatment in a hot press to obtain an absorbable tissue reinforcing fiber membrane.

[0030] Further, the absorbable material in S1 comprises an absorbable material resin and an optional dyeing agent.

[0031] Preferably, the absorbable material resin is at least one of aliphatic polyester and copolymer of polyester, and preferably the aliphatic polyester is at least one of polyglycolide, polylactide, polycaprolactone and glycolide-lactide copolymer.

[0032] Further, the absorbable material resin is polyglycolic acid, and preferably the weight average molecular weight of the polyglycolic acid is 30000-1000000, and more preferably the weight average molecular weight of the polyglycolic acid is 30000-400000.

[0033] Further, the dyeing agent in S1 is a dyeing agent verified by FDA for human body implants, and preferably the dyeing agent is D&C violet 2 and / or D&C blue 6.

[0034] Preferably, the content of the dyeing agent is 0-0.3% of the weight of the absorbable material, and preferably 0.1-0.2%.

[0035] Further, the temperature of the vacuum drying in S1 is 90-100℃, and the time is more than 8h, so that the water content of the dried absorbable material is less than 100ppm.

[0036] Further, the melt extrusion temperature of the melt-blowing in S2 is 180℃-260℃, and after the absorbable material is melt-extruded and blown into fibers by air flow, the melt-blown fiber membrane is formed on the receiving roller.

[0037] Preferably, the temperature of the extruder I zone is set to 180-210℃, the temperature of the extruder II zone is set to 200-230℃, the temperature of the extruder III zone is set to 220-250℃, and the temperature of the melt-blowing die is set to 240-260℃ during melt-blowing.

[0038] More preferably, the temperature of the extruder I zone is set to 180℃, the temperature of the extruder II zone is set to 220℃, the temperature of the extruder III zone is set to 240℃, and the temperature of the melt-blowing die is set to 250℃ during melt-blowing.

[0039] Further, the atmosphere of the heat-pressing setting treatment in S3 comprises air, vacuum and nitrogen; and the heat-pressing setting treatment is either online or offline.

[0040] Preferably, the temperature of the heat-pressing setting treatment in S3 is 70-120℃, preferably 80-100℃, and more preferably 80-90℃.

[0041] Preferably, the pressure of the heat-pressing setting treatment in S3 is 0.1-5MPa, preferably 0.1-3MPa, and more preferably 0.5-1MPa.

[0042] Preferably, the time of the heat-pressing setting treatment in S3 is 10S-300S, preferably 30S-120S, and more preferably 30S-60S.

[0043] The present application also protects the absorbable tissue-reinforcing fiber membrane prepared by the method for preparing the absorbable tissue-reinforcing fiber membrane, which is composed of a plurality of layers of microfiber mesh stacks, and the microfiber mesh is composed of cross-wound microfibers.

[0044] Further, the diameter of the microfiber is 0.1μm-15μm, preferably 1-15μm, and more preferably 1-10μm.

[0045] Preferably, the number of layers of the microfiber mesh is 1-150 layers, preferably 10-50 layers, and more preferably 15-25 layers.

[0046] Preferably, the thickness of the absorbable tissue-reinforcing fiber membrane is 0.05-2mm, preferably 0.1-0.8mm, and more preferably 0.1-0.25mm.

[0047] Further, the absorbable tissue-reinforcing fiber membrane satisfies at least one of the following (1)-(4):

[0048] (1) The crystallinity of the absorbable tissue-reinforcing fiber membrane is 70%-80%;

[0049] (2) the weight of the absorbable tissue-reinforcing fiber membrane is 5-200 g / m 2 , preferably 30-150 g / m 2 , and more preferably 60-100 g / m 2 ;

[0050] (3) the yield tensile strength of the absorbable tissue-reinforcing fiber membrane is 2-30 MPa, preferably 6-30 MPa, and more preferably 10-20 MPa;

[0051] (4) the elongation at break of the absorbable tissue-reinforcing fiber membrane is 10%-200%, preferably 10%-50%, and more preferably 10%-30%.

[0052] The present application also protects an antibacterial absorbable tissue-reinforcing fiber membrane, which is obtained by treating the absorbable tissue-reinforcing fiber membrane according to the following steps:

[0053] Step 1: obtaining a solution of triclosan, putting it into a carrier, and obtaining a triclosan-impregnated carrier;

[0054] Step 2: putting the triclosan-impregnated carrier and the absorbable tissue-reinforcing fiber membrane into a container, sealing the container, and providing the wall of the container with air-permeable holes to obtain a sample to be sterilized;

[0055] Step 3: putting the sample to be sterilized into a sterilization device to perform ethylene oxide sterilization, and obtaining a sterilized absorbable tissue-reinforcing fiber membrane;

[0056] Step 4: performing ethylene oxide resolution on the sterilized absorbable tissue-reinforcing fiber membrane to obtain an antibacterial absorbable tissue-reinforcing fiber membrane.

[0057] In step 1, triclosan is dissolved in a volatile solvent to obtain the solution of triclosan; the volatile carboxylic acid is a monobasic carboxylic acid or a dibasic carboxylic acid with a boiling point lower than 150°C under normal pressure, such as at least one of formic acid, acetic acid, propionic acid, or malonic acid. The volatile carboxylic acid is mixed with a volatile solvent to obtain a solution of the volatile carboxylic acid, and the volatile solvent is at least one of ethyl acetate or ethanol.

[0058] For the solution of triclosan, filter paper or kraft paper can be used as the carrier; for the solution of the volatile carboxylic acid, polyurethane sponge, polyvinyl alcohol sponge, or cellulose sponge can be used as the carrier.

[0059] In step 3, the ethylene oxide sterilization is preferably performed at a temperature of 40-70°C, a humidity of 30%-70%, and a pressure maintained at -20-10 kpa.

[0060] Advantages:

[0061] (1) The absorbable tissue-reinforcing fiber membrane of the present application is a multi-layer melt-blown self-adhesive micro-fiber sheet structure after heat-pressing setting treatment, has higher crystallinity, high yield tensile strength and suitable elongation, and has fewer preparation process steps and high efficiency;

[0062] (2) The fiber diameter in the absorbable tissue-reinforcing fiber membrane of the present application is ≤10 um, the micro-fiber not only makes the fiber membrane more flexible, but also increases the cell-adhesion surface area, which is helpful for cell ingrowth, proliferation and differentiation, and is beneficial to tissue healing;

[0063] (3) The absorbable tissue-reinforcing fiber membrane of the present application is very suitable for specific ethylene oxide sterilization treatment, and an antibacterial absorbable tissue-reinforcing fiber membrane with excellent performance is obtained, which has excellent mechanical properties of the sheet material and outstanding antibacterial effect;

[0064] (4) The absorbable tissue-reinforcing fiber membrane of the present application has high yield tensile strength and suitable elongation, which not only facilitates the penetration of anastomosis nails, but also effectively strengthens the postoperative fragile tissue wound to resist the tensile and compressive force of suturing or anastomosis, and prevents further damage to the fragile tissue.

[0065] In summary, the absorbable tissue-reinforcing fiber membrane provided by the present application uses melt-blown process and heat-pressing in combination, and through process control, the crystallinity and mechanical rigidity of the material are significantly improved, so that it can be used as a tissue-reinforcing material to provide support for cell regeneration; at the same time, it has a small diameter and porous structure, which is very beneficial to cell ingrowth, proliferation and differentiation, and is an ideal tissue repair material. BRIEF DESCRIPTION OF DRAWINGS

[0066] In order to more clearly illustrate the technical solutions of the present application, the following will briefly introduce the drawings. Obviously, the drawings described below only relate to some embodiments of the present application, and are not a limitation on the present application.

[0067] Figure 1 is the appearance and straightness front view of a sample provided by an embodiment 1 of the present application;

[0068] Figure 2 is the appearance and straightness side view of a sample provided by an embodiment 1 of the present application;

[0069] Figure 3 is the SEM image (500 times magnification) of the surface of the absorbable tissue-reinforcing fiber membrane provided by an embodiment 1 of the present application;

[0070] Figure 4 is the effect photo of the absorbable tissue-reinforcing fiber membrane provided by an embodiment 1 of the present application after the anastomat is tested on the foam.

[0071] Figure 5 is a product XRD comparison chart of Example 1, Example 2 and Comparative Example 1, Comparative Example 2 of the present application;

[0072] Figure 6 is a tensile property comparison chart of Example 1 and Comparative Example 1 of the present application;

[0073] Figure 7 is an SEM chart of the cross section of the absorbable tissue-reinforcing fiber membrane provided in Example 2 of the present application (magnification 250 times);

[0074] Figure 8 is an SEM chart of the cross section of the absorbable tissue-reinforcing fiber membrane provided in Example 3 of the present application (magnification 250 times). DETAILED DESCRIPTION

[0075] The preferred embodiments of the present application will be described in more detail below. Although the preferred embodiments of the present application are described below, it is understood that the present application can be implemented in various forms and should not be limited by the embodiments set forth herein. In the examples, unless a specific technique or condition is specified, the technique or condition described in the literature in the art or according to the product manual is used. In the examples, unless a manufacturer is specified, a conventional product available on the market is used. In the following examples, unless otherwise specified, "%" means weight percent, and "parts" means weight parts.

[0076] The test methods used below include:

[0077] 1. Appearance

[0078] The appearance of the tissue fiber membrane was evaluated by visual observation, and the tensile sample was placed on a platform, and the stiffness of the sample was observed after 5 minutes.

[0079] 2. Thickness:

[0080] A digital micrometer thickness gauge (Shanghai Siwei Instrument Manufacturing Co., Ltd.) was used to randomly measure the thickness of the fiber membrane surface at three points, and the average value was taken as the thickness of the fiber membrane.

[0081] 3. Gram weight (p)

[0082] The test method for the gram weight was to measure the weight of the sample under test per unit area, ignoring the thickness of the tissue fiber membrane. The weight m of the sample under test was measured using a balance with an accuracy of more than one thousandth, the size of the sample under test was measured using a steel ruler, and the area S of the sample under test was calculated, and the average value was taken by testing in parallel for three times. The gram weight of the fiber membrane was calculated according to formula (1).

[0083]

[0084] 4. SEM image of fiber membrane

[0085] The surface of the sample was photographed by a scanning electron microscope (FEI Prisma E, USA) to obtain the SEM image of the fiber membrane.

[0086] 5. Crystal structure analysis

[0087] The fiber membrane was subjected to wide-angle X-ray diffraction test by an X-ray diffractometer (Ultima IV, Japan Rigaku) with a scanning angle of 5-90°.

[0088] 6. Tensile properties

[0089] The fiber membrane was cut into a sample to be tested with a size of 60 mm x 10 mm, and the two ends of the long side of the sample were clamped by a universal material testing machine (UTM18268, Shenzhen Sanechips Longsys Technology Co., Ltd.) with a clamping length of 10 mm on each side. The sample was stretched at a rate of 150 mm / min until it broke, and 3 samples were repeatedly tested in each group.

[0090] The tensile strength corresponding to the yield of the sample was taken as the yield tensile strength, f was the average yield tensile strength of the sample, A was the average cross-sectional area of the sample, and the average yield tensile strength σ of the sample was calculated according to formula (2).

[0091]

[0092] The distance between the two clamps of the sample was L (L = 40 mm), the average tensile elongation of the sample was Δl, and the average elongation rate ε of the sample was calculated according to formula (3).

[0093]

[0094] Example 1

[0095] This embodiment takes polyglycolic acid (PGA resin) as an example of the absorbable material, and is described in detail, but the present application is not limited to polyglycolic acid.

[0096] The absorbable tissue reinforcing fiber membrane was prepared by the following steps:

[0097] S1, preparing materials: the PGA resin with a weight average molecular weight of 400000 was uniformly mixed with 0.03% D&C blue No. 6, and then vacuum dried at 100°C for 12h in a vacuum drying box to make the water content of the material less than 100ppm;

[0098] S2, melt-blown melt-blown fiber film: the dried PGA resin was quickly put into the hopper of the extruder for melt extrusion melt blowing. When melt blowing, the temperature of the extruder I zone was set to 180°C, the temperature of the II zone was set to 220°C, the temperature of the III zone was set to 240°C, and the temperature of the melt blowing die was set to 250°C. The extrusion amount was adjusted by the gear pump, and the receiving roller winding speed was adjusted to prepare a PGA melt-blown fiber film with a thickness of 0.20 mm.

[0099] S3, preparation of absorbable tissue reinforcing fiber film: the melt-blown fiber film prepared in S2 was placed between two flat plates and treated at a temperature of 80°C and a pressure of 0.5 MPa for 60 seconds to obtain an absorbable tissue reinforcing fiber film.

[0100] The fiber film prepared in this example had no fluff and wrinkle on the surface and was overall straight and crisp. A 60 mm x 10 mm tensile sample was placed on the platform, and the sample did not bend and sag. The photo taken after 5 minutes is shown in Figure 1 、 Figure 2 .

[0101] The fiber film prepared in this example had a thickness of 0.196 mm as tested by a digital display micrometer thickness tester. The fiber film had a grammage of 90 g / m 2 .

[0102] The SEM image of the surface of the absorbable tissue reinforcing fiber film obtained in this example is shown in Figure 3 . As can be seen from Figure 3 , the absorbable tissue reinforcing fiber film is composed of a plurality of fibers with a diameter of about 5-7 um, which is suitable for use as a tissue reinforcing material.

[0103] The fiber film was cut into a 60 mm x 20 mm sample to be tested, and an anastomosis test was performed on the foam to simulate tissue using a stapler (Shaid (Xiamen) Medical Instrument Co., Ltd.). As shown in Figure 4 , from the photos of the anastomosis effect, it can be seen that all the anastomosis staples penetrated the absorbable tissue reinforcing fiber film without any missed staples, and all the anastomosis staples had a good "B-type" staple formation effect.

[0104] Example 2

[0105] In this example, polyglycolic acid (PGA resin) was used as the absorbable material to prepare an absorbable tissue reinforcing fiber film, and the steps were as follows:

[0106] S1, the materials were the same as in Example 1.

[0107] S2, melt-blown melt-blown fiber film: the dried PGA resin is quickly put into the hopper of the extruder for melt extrusion melt blowing. When melt blowing, the temperature of the extruder I zone is set to 180°C, the temperature of the II zone is set to 220°C, the temperature of the III zone is set to 240°C, and the temperature of the melt blowing die is set to 250°C. The extrusion amount is adjusted by a gear pump, and the take-up roll speed is adjusted to prepare a PGA melt-blown fiber film with a thickness of about 0.140 mm.

[0108] S3, preparation of absorbable tissue-reinforcing fiber film: the melt-blown fiber film prepared in S2 is placed between two flat plates, treated at a temperature of 90°C and a pressure of 0.5 MPa for 30 S to obtain an absorbable tissue-reinforcing fiber film.

[0109] The surface of the absorbable tissue-reinforcing fiber film is free of fuzz and wrinkles, and the whole is crisp, which is composed of 13 layers of microfiber web stacks to form a film with a thickness of 0.135 mm, and the microfiber web is a porous structure composed of 6-8 um microfibers crossing and winding. Figure 7 The fiber film has a grammage of 80 g / m 2 The tensile strength is 18 MPa, and the elongation at break is 25%.

[0110] Example 3

[0111] This example takes polylactide as the absorbable material for detailed description, but the present application is not limited to this material.

[0112] Preparation of absorbable tissue-reinforcing fiber film, the steps are as follows:

[0113] S1, preparation of materials: polylactide resin with a weight average molecular weight of 300000 is dried in a vacuum drying oven at 100°C for 12 h to reduce the water content to less than 100 ppm;

[0114] S2, melt-blown melt-blown fiber film: the dried material is quickly put into the hopper of the extruder for melt extrusion melt blowing. When melt blowing, the temperature of the extruder I zone is set to 190°C, the temperature of the II zone is set to 220°C, the temperature of the III zone is set to 240°C, and the temperature of the melt blowing die is set to 250°C. The extrusion amount is adjusted by a gear pump, and the take-up roll speed is adjusted to prepare a melt-blown fiber film with a thickness of 0.15 mm.

[0115] S3, preparation of absorbable tissue-reinforcing fiber film: the melt-blown fiber film prepared in S2 is placed between two flat plates, treated at a temperature of 100°C and a pressure of 0.8 MPa for 60 S to obtain an absorbable tissue-reinforcing fiber film.

[0116] The surface of the absorbable tissue-reinforcing fiber film is free of fuzz and wrinkles, and the whole is crisp, which is composed of 11 layers of microfiber web stacks to form a film with a thickness of 0.13 mm, and the microfiber web is a porous structure composed of 3-8 um microfibers crossing and winding.Figure 8 The crystallinity was 65% by XRD test and calculation. The absorbable tissue reinforcement fiber membrane had a grammage of 65 g / m 2 , a tensile strength at yield of 8 MPa, and an elongation at break of 15%.

[0117] Example 4

[0118] The absorbable tissue reinforcement fiber membrane prepared in Example 1 was treated according to the following steps:

[0119] Step 1: An acetic acid ethyl acetate solution with a molar concentration of 0.5 mol / L was prepared, and a triclosan ethyl acetate solution with a molar concentration of 0.1 mol / L was prepared; a polyurethane sponge was immersed in the acetic acid ethyl acetate solution for 5-20 s to obtain a sponge with acetic acid / ethyl acetate solution; DuPont Tyvek paper was used as a carrier, immersed in the triclosan ethyl acetate solution for 5-20 s, and dried for 12-36 h to obtain triclosan-containing Tyvek paper.

[0120] Step 2: The sponge with acetic acid / ethyl acetate solution and the absorbable tissue reinforcement fiber membrane prepared in Example 1 were placed in the same blister box, and the triclosan-containing Tyvek paper soaked and dried was placed on the blister box and sealed to obtain a sample to be sterilized by EO. The sample to be sterilized by EO was placed in an ethylene oxide sterilization device for ethylene oxide sterilization. The sterilization parameters are shown in the following table:

[0121] Table 1 Sterilization parameters

[0122]

[0123]

[0124] Step 3: The sterilized absorbable tissue reinforcement fiber membrane was subjected to ethylene oxide resolution. Specifically, it was placed in an EO resolution chamber for 2 days of forced resolution. Thus, an absorbable tissue reinforcement fiber membrane with uniform antibacterial agent and slow and controllable release of antibacterial agent in vivo was obtained.

[0125] Comparative Example 1

[0126] This comparative example was prepared according to Example 1, except that the S3 step of heat setting was not performed, and a comparative fiber membrane was obtained.

[0127] The fiber membrane prepared in this comparative example had no fuzz on the surface, but had slight wrinkles, and was soft and flexible as a whole.

[0128] The SEM image of the comparative fiber membrane was similar to that of Example 1, with a fiber diameter of 5-7 um. The thickness and grammage of the fiber membrane were also close to those of Example 1.

[0129] Comparative Example 2

[0130] The comparative example was prepared according to example 1, the only difference was that the heat setting process in step S3 was carried out at 70℃ and 0.5MPa for 60s, and the comparative fiber membrane was obtained.

[0131] The fiber membrane prepared in the comparative example had no fuzz and wrinkle on the surface, and had a certain stiffness.

[0132] The SEM image of the comparative fiber membrane was similar to that of example 1, and the fiber diameter was 5-7um. The thickness and the gram weight of the fiber membrane were also close to those of example 1. The tensile strength at yield of the absorbable tissue reinforcing fiber membrane was 5MPa, and the elongation at break was 50%.

[0133] Comparative example 3

[0134] The comparative example was prepared according to example 1, the only difference was that the melt blowing in step S2 was carried out at 160℃, 180℃ and 220℃ in zones I, II and III respectively, and the temperature of the melt blowing die was set to 240℃. It was found through experiments that many melt drops appeared during melt blowing, and the fiber was relatively thick, so the melt blown fiber membrane could not be successfully obtained.

[0135] Performance comparison test

[0136] The tensile sample of 60mm x 10mm corresponding to the fiber membrane prepared in comparative example 1 was placed on the platform, and the sample was bent and sagged. The photo taken after 5 minutes is shown in Figure 1 、 Figure 2 as compared.

[0137] The SEM image of the comparative fiber membrane was similar to that of example 1, and the fiber diameter was 5-7um. The thickness and the gram weight of the fiber membrane were also close to those of example 1, indicating that the heat setting process did not significantly change the fiber diameter distribution, thickness and gram weight.

[0138] The X-ray diffraction patterns of example 1, example 2 and comparative examples 1 and 2 are shown in Figure 5 From the Figure 5 , it can be seen that the fiber membranes prepared in example 1 and example 2 have the same crystal structure, and the crystal structure of the fiber membrane is perfect, and two obvious diffraction peaks appear at positions 22.0° and 28.7° in the XRD pattern, which correspond to the (110) and (020) planes of PGA crystal respectively. According to the analysis and calculation, the crystallinity of the fiber membrane prepared in example 1 is about 75%, and the crystallinity of the fiber membrane prepared in example 1 is about 80%.

[0139] The fiber membrane of the comparative example 1 has a very different XRD diffraction pattern from the fiber membranes of the example 1 and the example 2. Since the fiber membrane is not subjected to the heat-pressing process, the XRD spectrum of the fiber membrane presents a broad diffraction peak, which indicates that the crystalline structure of the fiber membrane is imperfect and the crystallinity is low. This confirms the argument that the crystallinity is low due to the rapid cooling of the molecular chains during the melt-blown process.

[0140] The fiber membrane of the comparative example 2 is subjected to the heat-pressing process at a low temperature. The XRD spectrum of the fiber membrane presents a single broad peak near 21.8°, but the peak corresponding to the (020) plane is not present. According to the analysis and calculation, the crystallinity of the fiber membrane prepared in the comparative example 2 is about 50%.

[0141] The fiber membrane prepared in the example 1 has a high crystallinity. Such a high crystallinity and perfect crystalline structure not only facilitate the transmission of load, but also have greater mechanical rigidity, which is manifested in the appearance of the fiber membrane. Figure 1 、 Figure 2 At the same time, the fiber membrane has a large yield tensile strength, and the average yield tensile strength is 19.10 MPa. The tensile elongation is appropriate, and the average tensile elongation is 28.83%.

[0142] The fiber membrane of the comparative example 1 is soft and not stiff, and is easily deformed under external force, as shown in Figure 1 、 Figure 2 In addition, the structure of the fiber membrane of the comparative example 1 is mainly loose and amorphous, which leads to poor performance of the material in resisting deformation under external force. The mechanical rigidity of the fiber membrane is insufficient, and the tensile elongation is large. The yield tensile strength is small, and the average yield tensile strength is only 3.13 MPa. The tensile elongation is very large, and the average tensile elongation is 359.83%, as shown in Figure 6

[0143] The above experimental results show that the absorbable tissue reinforcing fiber membrane prepared in the example has a high crystallinity, a good stiffness, and solves the problem of softness and easy deformation of the melt-blown aliphatic polyester fiber membrane. At the same time, the fiber membrane has a high yield tensile strength and an appropriate tensile elongation. The absorbable tissue reinforcing fiber membrane prepared in the example is suitable for the penetration of the anastomosis needle during the anastomosis process. It not only provides sufficient mechanical support before the tissue is completely repaired, but also effectively improves the problem of anastomosis failure caused by the difficulty of penetration during the clinical use.

[0144] The above detailed description of the preferred embodiments of the present application, but the present application is not limited to the specific details in the above-described embodiments, within the technical concept of the present application, the technical solutions of the present application can be variously modified, and these simple modifications all belong to the protection scope of the present application.

[0145] ​It should be further noted that any technically feasible combination of the various technical features described in the above embodiments is possible, provided that the combination does not contradict itself. In order to avoid unnecessary repetition, the present application does not describe each and every possible combination of the various technical features.

[0146] Furthermore, any combination of the various embodiments of the present application is possible, provided that the combination does not contradict itself, and should be considered as being disclosed by the present application.

Claims

1. A method for preparing an absorbable tissue-reinforcing fiber membrane, characterized by: It comprises the following steps: S1, vacuum drying the absorbable material to obtain dried absorbable material; the absorbable material comprises absorbable material resin, and the absorbable material resin is polyglycolic acid, and the weight average molecular weight of the polyglycolic acid is 30000-1000000; S2, putting the dried absorbable material into a melt blowing device to melt blow to obtain a melt blown fiber film; the melt blowing melt extrusion zone temperature is 180-260 DEG C; after the absorbable material is melt extruded and blown into fibers by airflow, the fibers are deposited on a receiving roller to form a melt blown fiber film; during melt blowing, the extruder I zone temperature is set to 180-210 DEG C, the II zone temperature is set to 200-230 DEG C, the III zone temperature is set to 220-250 DEG C, and the melt blowing die temperature is set to 240-260 DEG C; S3, placing the melt blown fiber film between two flat plate molds and performing hot pressing and setting treatment in a hot press; the hot pressing and setting treatment temperature is 70-120 DEG C, the hot pressing and setting treatment pressure is 0.1-5 MPa, and the hot pressing and setting treatment time is 30 S-120 S to obtain an absorbable tissue reinforcing fiber film.

2. The method for preparing the absorbable tissue-reinforced fiber membrane according to claim 1, characterized in that: The absorbable material in S1 comprises absorbable material resin and optionally a dyeing agent; the dyeing agent is a dyeing agent verified by FDA for human body implants.

3. The method for preparing the absorbable tissue-reinforced fiber membrane according to claim 2, characterized in that: The dyeing agent is D&C violet 2 and / or D&C blue 6.

4. The method for preparing the absorbable tissue-reinforced fiber membrane according to claim 2, characterized in that: The content of the dyeing agent is 0-0.3% of the weight of the absorbable material.

5. The method for preparing the absorbable tissue-reinforcing fiber membrane according to claim 4, characterized in that: The content of the dyeing agent is 0.1-0.2% of the weight of the absorbable material.

6. The method for preparing the absorbable tissue-reinforced fiber membrane according to claim 1, characterized in that: The weight average molecular weight of the polyglycolic acid is 30000-400000.

7. The method of making absorbable tissue reinforcing fiber mesh according to any one of claims 1-6, wherein: The vacuum drying temperature in S1 is 90-100 DEG C, and the time is more than 8 h, so that the water content of the dried absorbable material is less than 100 ppm.

8. The method for preparing the absorbable tissue-reinforced fiber membrane according to claim 1, characterized in that: During melt blowing in S2, the extruder I zone temperature is set to 180 DEG C, the II zone temperature is set to 220 DEG C, the III zone temperature is set to 240 DEG C, and the melt blowing die temperature is set to 250 DEG C.

9. The method for preparing the absorbable tissue-reinforced fiber membrane according to claim 8, characterized in that: The atmosphere of the hot pressing and setting treatment in S3 comprises air, vacuum and nitrogen; the hot pressing and setting treatment mode is online hot pressing and setting or offline hot pressing and setting.

10. The method for preparing the absorbable tissue-reinforced fiber membrane according to claim 9, characterized in that: The hot pressing and setting treatment temperature in S3 is 80-100 DEG C.

11. The method for preparing the absorbable tissue-reinforced fiber membrane according to claim 10, characterized in that: The hot pressing and setting treatment temperature in S3 is 80-90 DEG C.

12. The method for preparing the absorbable tissue-reinforced fiber membrane according to claim 9, characterized in that: The hot pressing and setting treatment pressure in S3 is 0.1-3 MPa.

13. The method for preparing the absorbable tissue-reinforced fiber membrane according to claim 12, characterized in that: The hot pressing and setting treatment pressure in S3 is 0.5-1 MPa.

14. The method for preparing the absorbable tissue-reinforced fiber membrane according to claim 9, characterized in that: The hot pressing and setting treatment time in S3 is 30 S-60 S.

15. Absorbable tissue-reinforcing fiber membrane prepared by the production method according to any one of claims 1 to 9, characterized by: The absorbable tissue reinforcing fiber film is composed of a plurality of layers of microfiber web stacks, and the microfiber web is composed of cross-wound microfibers.

16. The absorbable tissue reinforcing fiber membrane of claim 15, wherein: The diameter of the microfiber is 0.1-15 μm.

17. The absorbable tissue reinforced fibrous membrane of claim 16, wherein: The diameter of the microfiber is 1-15 μm.

18. The absorbable tissue reinforced fibrous membrane of claim 17, wherein: The diameter of the microfiber is 1-10 μm.

19. The absorbable tissue reinforcing fiber membrane of claim 16, wherein: The number of layers of the microfiber web is 1-150 layers.

20. The absorbable tissue reinforcing fiber membrane of claim 16, wherein: The number of layers of the microfiber web is 10-50 layers.

21. The absorbable tissue reinforced fibrous membrane of claim 20, wherein: The number of layers of the microfiber web is 15-25 layers.

22. The absorbable tissue reinforcing fiber membrane of claim 16, wherein: The thickness of the absorbable tissue reinforcing fiber film is 0.05-2 mm.

23. The absorbable tissue reinforced fibrous membrane of claim 22, wherein: The thickness of the absorbable tissue-reinforcing fiber membrane is 0.1-0.8mm.

24. The absorbable tissue reinforcing fiber membrane of claim 23, wherein: The thickness of the absorbable tissue-reinforcing fiber membrane is 0.1-0.25mm.

25. The absorbable tissue reinforcing fiber membrane according to any one of claims 15-24, wherein: The absorbable tissue-reinforcing fiber membrane satisfies at least one of the following (1)-(4): (1) The crystallinity of the absorbable tissue-reinforcing fiber membrane is 70%-80%; (2) the absorbable tissue-reinforcing fiber membrane has a grammage of 5-200 g / m 2 ; (3) The yield tensile strength of the absorbable tissue-reinforcing fiber membrane is 2-30MPa; (4) The elongation at break of the absorbable tissue-reinforcing fiber membrane is 10%-200%.

26. The absorbable tissue reinforcing fiber membrane of claim 25, wherein: The absorbable tissue-reinforcing fiber film has a grammage of 30 to 150 g / m 2 .

27. The absorbable tissue reinforced fibrous membrane of claim 26, wherein: The absorbable tissue-reinforcing fiber film has a grammage of 60 to 100 g / m 2 .

28. The absorbable tissue reinforcing fiber membrane of claim 25, wherein: The yield tensile strength of the absorbable tissue-reinforcing fiber membrane is 6-30MPa.

29. The absorbable tissue reinforcing fiber membrane of claim 28, wherein: The yield tensile strength of the absorbable tissue-reinforcing fiber membrane is 10-20MPa.

30. The absorbable tissue reinforcing fiber membrane of claim 25, wherein: The elongation at break of the absorbable tissue-reinforcing fiber membrane is 10%-50%.

31. The absorbable tissue reinforcing fiber membrane of claim 30, wherein: The elongation at break of the absorbable tissue-reinforcing fiber membrane is 10%-30%.

32. An absorbable tissue-reinforcing fiber film loaded with an antibacterial agent, characterized by: The absorbable tissue-reinforcing fiber membrane is treated according to the following steps: Step 1: obtain a solution of triclosan, put it into a carrier, and obtain a triclosan-containing carrier; Step 2: put the triclosan-containing carrier and the absorbable tissue-reinforcing fiber membrane into a container, seal the container, and provide the wall of the container with air-permeable holes to obtain a sample to be sterilized; Step 3: put the sample to be sterilized into a sterilization device, perform ethylene oxide sterilization, and obtain a sterilized absorbable tissue-reinforcing fiber membrane; Step 4: perform ethylene oxide analysis on the sterilized absorbable tissue-reinforcing fiber membrane to obtain an absorbable tissue-reinforcing fiber membrane loaded with an antibacterial agent.

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