Absorbable anti-adhesion membrane, method of making and use thereof

Abstract

The application discloses an absorbable anti-adhesion membrane and a preparation method and application thereof. The absorbable anti-adhesion membrane comprises three layers of fiber membranes, wherein the first layer of fiber membrane comprises gelatin and optionally chitosan; the second layer of fiber membrane comprises polycaprolactone and gelatin; and the third layer of fiber membrane comprises a hydrophilic polymer and optionally polycaprolactone. The raw materials of the first layer of fiber membrane, the second layer of fiber membrane and the third layer of fiber membrane are respectively prepared into spinning solutions, and then electrostatic spinning is carried out to obtain the absorbable anti-adhesion membrane. The first layer of fiber membrane of the absorbable anti-adhesion membrane can be effectively adhered to the contact surface of the tissue or organ at a surgical wound, and does not need to be sutured and fixed, so that the use is convenient; the second layer of fiber membrane can maintain long-time functional integrity and has good biological shielding effect; the third layer of fiber membrane can effectively reduce the friction and stimulation of the anti-adhesion membrane to other tissues and organs; and the three layers of fiber membranes are cooperated together, so that the use effect of the anti-adhesion membrane is greatly improved.

Description

Technical Field

[0001] This invention relates to the field of postoperative anti-adhesion materials technology, and more specifically, to absorbable anti-adhesion membranes, their preparation methods, and applications. Background Technology

[0002] Postoperative adhesions are among the most common and challenging problems encountered during surgeries in the abdominal cavity, pelvis, and heart. They not only cause serious complications but are also a major reason for the significantly increased probability of complications after secondary surgery. 90% of patients develop adhesions to varying degrees postoperatively, and 60% require anti-adhesion measures. Currently, physical isolation methods are commonly used to prevent postoperative adhesions. Before suturing the surgical wound, surgeons place a layer of anti-adhesion membrane with physical isolation properties between the surgical tissues or organs to prevent adhesion between tissues and organs.

[0003] Currently, anti-adhesion materials used in surgical treatment mainly fall into two categories: non-degradable absorbable materials and biodegradable absorbable materials. Non-degradable absorbable materials, such as polytetrafluoroethylene (PTFE) and cellulose-based anti-adhesion membranes, effectively inhibit adhesion and reduce the risk of secondary surgery. However, the continued presence of these non-degradable materials can lead to inflammatory reactions and fibrosis in surrounding organs and tissues, hindering secondary surgery. Biodegradable absorbable materials have been commercialized and are widely used in surgery, including anti-adhesion membranes, anti-adhesion liquids, and anti-adhesion gels, which have shown some effectiveness in preventing postoperative adhesion. However, anti-adhesion liquids are highly fluid and cannot effectively act as a physical barrier. Their concentration at the wound site decreases due to patient position and drainage, weakening their anti-adhesion effect. Recently, the use of absorbable anti-adhesion membranes as physical barriers to prevent surgical wound adhesion has shown good results.

[0004] Currently, anti-adhesion membranes used clinically include polylactic acid (PLA) anti-adhesion membranes, ethicon-derived cellulose oxide INTERCEED anti-adhesion membranes, and sodium carboxymethyl cellulose (SMC) SEPARFILM anti-adhesion membranes from CENZYNE. However, these anti-adhesion membranes still have some drawbacks. PLA anti-adhesion membranes have poor adhesion to tissues, requiring sutures to fix them to the tissue during surgery, which is not conducive to surgical procedures on deeper lesions. Furthermore, they degrade rapidly, and the degradation products can easily cause acid accumulation and inflammation. Cellulose oxide membranes require thorough hemostasis before use and cannot be used in cases of local bleeding. Sodium carboxymethyl cellulose membranes have a relatively fast absorption cycle and poor mechanical properties and operability in humid environments (Dis Colon Rectum, 2013, 56, 1174-1184). Clinically, medications are sometimes added to improve the anti-adhesion effect, such as dexamethasone, paclitaxel, rapamycin, cortisone, ibuprofen, mitomycin, silver sulfadiazine, heparin sodium, and antibiotics. However, the side effects of these medications can slow down tissue repair and prolong healing time. Furthermore, even with medication, the anti-adhesion rate of the anti-adhesion membrane is generally around 60%, exhibiting a relatively low anti-adhesion effect.

[0005] In summary, the aforementioned problems still urgently need to be solved in the field of preparing medical anti-adhesion membranes. Summary of the Invention

[0006] To address the problems in existing technologies, this invention proposes an absorbable anti-adhesion membrane, its preparation method, and its applications. The first fibrous membrane of this invention effectively adheres to the contact surface of the tissue or organ where the surgical wound is located, eliminating the need for sutures and making it convenient to use. The second fibrous membrane maintains functional integrity for a long time, providing excellent biological shielding. The third fibrous membrane effectively reduces friction between the anti-adhesion membrane and other tissues and organs, ensuring the adhesion stability of the anti-adhesion membrane, and also reducing irritation to other tissues and organs and decreasing the probability of postoperative adhesions. The three fibrous membranes work together to significantly improve the effectiveness of the anti-adhesion membrane.

[0007] One objective of this invention is to provide an absorbable anti-adhesion membrane, wherein the absorbable anti-adhesion membrane comprises three layers of fiber membrane, wherein:

[0008] The first fibrous membrane includes gelatin and optionally a hemostatic agent;

[0009] The second fibrous membrane consists of polycaprolactone and gelatin;

[0010] The third fibrous membrane comprises a hydrophilic polymer, optionally polycaprolactone.

[0011] In the absorbable anti-adhesion film of the present invention, preferably,

[0012] The second fiber membrane is located in the middle layer of the absorbable anti-blocking membrane;

[0013] The first fiber membrane and the third fiber membrane are located on both sides of the second fiber membrane.

[0014] In the absorbable anti-adhesion film of the present invention, preferably,

[0015] Based on the total weight of the first fibrous membrane as 100%, the gelatin contained therein has a mass fraction of 50wt%-100wt%, preferably 50wt%-90wt%; the hemostatic agent has a mass fraction of 0-50wt%, preferably 10%-50wt%; and / or,

[0016] Based on the total weight of the second fibrous membrane as 100%, it contains polycaprolactone at a mass fraction of 40wt%-90wt%, preferably 50wt%-90wt%, and gelatin at a mass fraction of 10wt%-60wt%, preferably 10wt%-50wt%; and / or,

[0017] Based on the total weight of the third fiber membrane as 100%, the mass fraction of polycaprolactone contained therein is 0-50 wt%, preferably 10%-50 wt%, and the mass fraction of hydrophilic polymer is 50 wt%-100 wt%, preferably 50 wt%-90 wt%.

[0018] In the absorbable anti-adhesion film of the present invention, preferably,

[0019] In the first fibrous membrane, the mass ratio of gelatin to chitosan is 1-2:1; and / or,

[0020] In the second fibrous membrane, the mass ratio of polycaprolactone to gelatin is 1-4:1; and / or,

[0021] In the third fiber membrane, the mass ratio of polycaprolactone to hydrophilic polymer is 1-2:1.

[0022] In the absorbable anti-adhesion film of the present invention, preferably,

[0023] The hemostatic agent is selected from chitosan; and / or,

[0024] The hydrophilic polymer is selected from at least one of polyvinyl alcohol, polyethylene glycol, polyethylene oxide, hyaluronic acid, poly[2-(methacryloyloxy)ethyl phosphocholine], gelatin, or collagen.

[0025] A second objective of this invention is to provide a method for preparing the absorbable anti-adhesion membrane described in one objective of this invention, comprising the following steps:

[0026] The raw materials corresponding to the first, second, and third fiber membranes are respectively prepared into spinning solutions, and then electrospinned and dried to obtain the absorbable anti-adhesion membrane; preferably, the absorbable anti-adhesion membrane is obtained by continuous electrospinning layer by layer.

[0027] In the absorbable anti-adhesion film of the present invention, preferably,

[0028] The method for preparing the first fiber membrane is as follows:

[0029] Gelatin and optionally a hemostatic agent are dissolved in a solvent and electrospinned.

[0030] Preferably, gelatin and hemostatic agent are dissolved in solvents to prepare spinning solution A and spinning solution B, respectively; spinning solution A and spinning solution B are mixed evenly and then electrospun using a single needle to prepare the first fiber membrane; or, spinning solution A and spinning solution B are electrospun separately to prepare the first fiber membrane; or spinning solution A and spinning solution B are added to different solution tanks of an electrospinning device, and multi-needle simultaneous spinning is used to prepare the first fiber membrane.

[0031] More preferably, the concentration of spinning solution A or spinning solution B is independently selected from 0.02 g / mL to 0.2 g / mL, preferably 0.04 g / mL to 0.2 g / mL; more preferably from 0.04 g / mL to 0.1 g / mL.

[0032] In the absorbable anti-adhesion film of the present invention, preferably,

[0033] The preparation method of the second fiber membrane is as follows:

[0034] Polycaprolactone and gelatin are mixed and dissolved in a solvent to prepare spinning solution C; electrospinning is performed on the first fiber membrane to obtain a second fiber membrane; wherein the second fiber membrane is located above the first fiber membrane;

[0035] Preferably, the concentration of the spinning solution C is 0.04 g / mL to 0.2 g / mL; more preferably, it is 0.04 g / mL to 0.15 g / mL.

[0036] In the absorbable anti-adhesion film of the present invention, preferably,

[0037] The preparation method of the third fiber membrane is as follows:

[0038] A hydrophilic polymer and optionally polycaprolactone are added to a solvent and mixed and dissolved to prepare spinning solution D; electrospinning is performed on the second fiber membrane to obtain a third fiber membrane; wherein the third fiber membrane is located above the second fiber membrane;

[0039] Preferably, the concentration of the spinning solution D is 0.01 g / mL-0.8 g / mL, more preferably 0.04 g / mL-0.4 g / mL; and even more preferably 0.04 g / mL-0.2 g / mL.

[0040] In the absorbable anti-adhesion film of the present invention, preferably,

[0041] During electrospinning of the first fiber membrane, the spinning solution extrusion rate is 0.5-10 mL / h, the spinning voltage is 7-30 kV, the receiving distance is 8-30 cm, and the spinning time is 1-4 h; and / or,

[0042] During electrospinning of the second fiber membrane, the extrusion rate of the spinning solution is 0.5-10 mL / h, the spinning voltage is 7-30 kV, the receiving distance is 8-30 cm, and the spinning time is 2-8 h; and / or,

[0043] During electrospinning of the third fiber membrane, the spinning solution extrusion rate is 0.5-10 mL / h, the spinning voltage is 7-30 kV, the receiving distance is 8-30 cm, and the spinning time is 1-4 h; and / or,

[0044] The solvents in the spinning solutions corresponding to the first, second, and third fiber membranes are each independently selected from at least one of hexafluoroisopropanol, trifluoroethanol, chloroform, dichloromethane, acetic acid, trifluoroacetic acid, ethanol, methanol, N,N'-dimethylformamide, N,N'-dimethylacetamide, acetone, and water.

[0045] A third objective of this invention is to provide the application of the absorbable anti-adhesion membrane described in one objective of this invention or the absorbable anti-adhesion membrane prepared by the preparation method described in another objective of this invention in wound anti-adhesion materials, preferably in postoperative anti-adhesion materials.

[0046] When the absorbable anti-adhesion membrane of the present invention is used, the first layer of the fibrous membrane faces the tissue or organ where the surgical wound is located.

[0047] The endpoints and any values ​​of the ranges disclosed in this invention are not limited to the precise ranges or values; these ranges or values ​​should be understood to include values ​​close to these ranges or values. For numerical ranges, the endpoint values ​​of the various ranges, the endpoint values ​​of the various ranges and individual point values, and individual point values ​​can be combined with each other to obtain one or more new numerical ranges, which should be considered as specifically disclosed herein. In the following, various technical solutions can, in principle, be combined with each other to obtain new technical solutions, which should also be considered as specifically disclosed herein.

[0048] Compared with the prior art, the present invention has at least the following advantages:

[0049] (1) The gelatin and optional chitosan fibers in the first layer of the fibrous membrane are attached to the tissue wound. The gelatin fibers can quickly absorb blood to stop bleeding and work together with chitosan to stop bleeding. When attached to the surgical wound, it can quickly stop bleeding and adhere to it. No suture fixation is required, and it can also prevent the anti-adhesion membrane from becoming saturated with blood and losing its function.

[0050] (2) The second layer of fiber membrane can play a biological shielding role. By adjusting the ratio of polycaprolactone and gelatin, the degradation time of the anti-adhesion membrane can be controlled from 1 week to 2 months, ensuring the integrity of the anti-adhesion membrane before tissue healing. Polycaprolactone has high strength, which can provide excellent mechanical properties for the anti-adhesion membrane and avoid breakage during surgical operations. In addition, polycaprolactone has good flexibility, which makes the anti-adhesion membrane prepared by this invention have good compliance and can better adhere to tissues and organs.

[0051] (3) The hydrophilic polymer in the third fibrous membrane can absorb body fluids and form a hydration layer on the surface, which plays a role in water lubrication, reduces the friction between the anti-adhesion membrane and other tissues and organs, ensures the adhesion stability of the anti-adhesion membrane, and can also reduce the stimulation to other tissues and organs. In addition, the hydration layer can reduce the possibility of cell surface proteins and peptides adhering to the membrane surface, and reduce the probability of postoperative adhesion.

[0052] (5) In addition, the addition of gelatin to the second fiber membrane can improve its hydrophilicity as an intermediate layer, which is close to the hydrophilicity of the first and third fiber membranes. This can significantly improve the interfacial bonding force and avoid the delamination of the three fiber membranes without additional molding.

[0053] In summary, it can be seen that the first fibrous membrane of the absorbable anti-adhesion membrane of the present invention can effectively adhere to the contact surface of the tissue or organ where the surgical wound is located without the need for suture fixation, making it convenient to use; the second fibrous membrane can maintain functional integrity for a long time and has a good biological shielding effect; the third fibrous membrane can effectively reduce the friction between the anti-adhesion membrane and other tissues and organs, ensure the adhesion stability of the anti-adhesion membrane, and also reduce the stimulation to other tissues and organs and reduce the probability of postoperative adhesion; the three fibrous membranes work together to greatly improve the effectiveness of the anti-adhesion membrane. Attached Figure Description

[0054] Figure 1 This is a SEM image of the absorbable anti-adhesion membrane prepared in Example 1 of this invention;

[0055] Figure 2 This is a SEM image of the absorbable anti-adhesion membrane prepared in Example 2 of this invention;

[0056] Figure 3 This is a SEM image of the absorbable anti-adhesion membrane prepared in Example 3 of the present invention;

[0057] Figure 4 This is a SEM image of the absorbable anti-adhesion membrane prepared in Example 4 of this invention;

[0058] Figure 5 This is a schematic diagram of the cell permeation experiment of the anti-adhesion membrane of the present invention;

[0059] Figure 6 This is a microscope image (40×) of the bottom of a 24-well plate 3 days after the cells were seeded onto the anti-adhesion membrane.

[0060] Figure 7 This is a SEM image of the back side of the anti-adhesion membrane after cells were seeded on the anti-adhesion membrane one month after the anti-adhesion membrane prepared in Example 1 of this invention was degraded.

[0061] Figure 8 This is a SEM image of the back side of the anti-adhesion membrane after the anti-adhesion membrane prepared in Example 2 of this invention has been degraded for one month and cells have been seeded on the anti-adhesion membrane.

[0062] Figure 9 This is a SEM image of the back side of the anti-adhesion membrane after the anti-adhesion membrane prepared in Example 3 of this invention has been degraded for one month and cells have been seeded on the anti-adhesion membrane.

[0063] Figure 10 This is a SEM image of the back side of the anti-adhesion membrane after the anti-adhesion membrane prepared in Example 4 of this invention has been degraded for one month and cells have been seeded on the anti-adhesion membrane.

[0064] Explanation of reference numerals in the attached figures:

[0065] 1-Cells, 2-Anti-adhesion membrane, 3-Upper culture medium, 4-Lower culture medium. Detailed Implementation

[0066] The present invention will now be described in detail with reference to the accompanying drawings and embodiments. It should be noted that the following embodiments are only used to further illustrate the present invention and should not be construed as limiting the scope of protection of the present invention. Some non-essential improvements and adjustments made by those skilled in the art based on the content of the present invention are still within the scope of protection of the present invention.

[0067] It should also be noted that the various specific technical features described in the following embodiments can be combined in any suitable manner without contradiction. To avoid unnecessary repetition, the various possible combinations will not be described separately in this invention.

[0068] Furthermore, various embodiments of the present invention can be combined in any way, as long as they do not violate the spirit of the present invention. The resulting technical solutions are part of the original disclosure of this specification and also fall within the protection scope of the present invention.

[0069] Unless otherwise specified, the raw materials used in the examples and comparative examples are all disclosed in the prior art, such as those that can be directly purchased or prepared according to the preparation methods disclosed in the prior art.

[0070] Example 1

[0071] 1. Dissolve gelatin and chitosan separately in hexafluoroisopropanol and stir magnetically at room temperature for 12 hours. The concentration of gelatin solution (spinning solution A) is 0.04 g / mL and the concentration of chitosan solution (spinning solution B) is 0.02 g / mL. Mix the gelatin solution and chitosan solution at a mass ratio of 1:1 and stir evenly. Then add the mixture to an electrospinning machine to prepare the first fiber membrane M1. The extrusion rate of the electrospinning solution is 1 mL / h, the spinning voltage is 16 kV, the spinning distance is 12 cm, and the spinning time is 1 hour.

[0072] 2. Polycaprolactone and gelatin were dissolved in trifluoroethanol at a mass ratio of 1:1. The solution was stirred at 60°C for 6 hours to obtain spinning solution C, with a concentration of 0.08 g / mL. This solution was added to an electrospinning machine, and a second fiber membrane was spun on fiber membrane M1 to obtain composite membrane M2. The extrusion rate of the spinning solution was 1.2 mL / h, the spinning voltage was 18 kV, the spinning distance was 10 cm, and the spinning time was 5 hours.

[0073] 3. Polycaprolactone and polyethylene glycol were dissolved in chloroform at a mass ratio of 1:1. The solution was magnetically stirred at room temperature for 12 hours to obtain spinning solution D. The concentration of spinning solution D was 0.06 g / mL. The solution was added to an electrospinner to prepare a third fiber membrane on the composite membrane M2, resulting in composite fiber membrane M3. The extrusion rate of the spinning solution was 0.8 mL / h, the spinning voltage was 15 kV, the spinning distance was 10 cm, and the spinning time was 1.5 h.

[0074] 4. The obtained composite fiber membrane M3 was dried in a fume hood at room temperature for 48 hours to allow the residual solvent to fully evaporate. It was then packaged and sterilized to obtain an absorbable anti-blocking membrane. The corresponding SEM image is shown below. Figure 1 As shown.

[0075] The absorbable anti-adhesion membrane has a wet mechanical strength of 9.2 MPa, exhibiting elasticity and capable of withstanding large deformations encountered during clinical procedures and tissue growth without damage. The water contact angle of the absorbable anti-adhesion membrane is 68.3°. Animal experiments showed that the anti-adhesion membrane can rapidly stop bleeding, adheres to the wound without sutures, is easy to use, and did not shift during tissue growth, achieving an anti-adhesion rate of 93.1%.

[0076] Example 2

[0077] 1. Dissolve gelatin in trifluoroethanol and stir magnetically at room temperature for 8 hours to obtain a gelatin solution with a concentration of 0.1 g / mL. Add the gelatin solution to an electrospinning machine to prepare the first fiber membrane M1. The extrusion rate of the spinning solution is 0.8 mL / h, the spinning voltage is 10 kV, the spinning distance is 8 cm, and the spinning time is 1 hour.

[0078] 2. Polycaprolactone and gelatin were dissolved in trifluoroethanol at a mass ratio of 3:2. The solution was stirred at room temperature for 12 hours to obtain spinning solution C, which had a concentration of 0.15 g / mL. This solution was then added to an electrospinning machine, and a second fiber membrane was spun on fiber membrane M1 to obtain composite membrane M2. The extrusion rate of the spinning solution was 0.5 mL / h, the spinning voltage was 25 kV, the spinning distance was 20 cm, and the spinning time was 6 hours.

[0079] 3. Polycaprolactone and poly[2-(methacryloyloxy)ethylphosphocholine] were dissolved in a hexafluoroisopropanol / dichloromethane composite solvent. The volume ratio of hexafluoroisopropanol to dichloromethane was 1:1, and the mass ratio of polycaprolactone to polyethylene glycol was 1:2. The solution was magnetically stirred at room temperature for 8 hours to obtain spinning solution D, with a concentration of 0.04 g / mL. This solution was added to an electrospinning machine to prepare a third fiber membrane on the composite membrane M2, resulting in composite fiber membrane M3. The extrusion rate of the spinning solution was 2 mL / h, the spinning voltage was 12 kV, the spinning distance was 12 cm, and the spinning time was 2 hours.

[0080] 4. The obtained composite fiber membrane M3 was placed in a vacuum oven at 60℃ and dried for 12 hours to allow the residual solvent to fully evaporate. It was then packaged and sterilized to obtain an absorbable anti-blocking membrane. The corresponding SEM image is shown below. Figure 2 As shown.

[0081] The absorbable anti-adhesion membrane has a wet mechanical strength of 9.7 MPa, exhibiting elasticity and capable of withstanding large deformations encountered during clinical procedures and tissue growth without being damaged. The water contact angle of the absorbable anti-adhesion membrane is 64.1°. Animal experiments showed that the anti-adhesion membrane, with a small amount of blood adsorbed, adheres to the wound without the need for sutures, simplifying the operation, and achieving an anti-adhesion rate of 86.5%.

[0082] Example 3

[0083] 1. Gelatin and chitosan were separately dissolved in 80℃ hot water and magnetically stirred for 10 hours. The concentration of the gelatin solution was 0.08 g / mL, and the concentration of the chitosan solution was 0.04 g / mL. The gelatin and chitosan solutions were mixed at a 1:1 mass ratio and stirred evenly. Then, the mixture was added to an electrospinning machine to prepare the first fibrous membrane M1. The extrusion rate of the spinning solution was 1 mL / h, the spinning voltage was 14 kV, the spinning distance was 12 cm, and the spinning time was 4 hours.

[0084] 2. Polycaprolactone and gelatin were dissolved in trifluoroethanol at a mass ratio of 7:3. The solution was stirred at room temperature for 12 hours to obtain spinning solution C, which had a concentration of 0.1 g / mL. This solution was then added to an electrospinning machine, and a second fiber membrane was spun on fiber membrane M1 to obtain composite membrane M2. The extrusion rate of the spinning solution was 1 mL / h, the spinning voltage was 15 kV, the spinning distance was 13 cm, and the spinning time was 8 hours.

[0085] 3. Polyvinyl alcohol was dissolved in hot water at 80℃ to obtain a solution concentration of 0.15 g / mL. The solution was magnetically stirred at room temperature for 8 hours to obtain spinning solution D. This solution was then added to an electrospinning machine to prepare a third fiber membrane on the composite membrane M2, resulting in composite fiber membrane M3. The extrusion rate of the spinning solution was 0.5 mL / h, the spinning voltage was 16 kV, the spinning distance was 10 cm, and the spinning time was 3 hours.

[0086] 4. The obtained composite fiber membrane M3 was placed in a vacuum oven at 60℃ and dried for 12 hours to allow the residual solvent to fully evaporate. It was then packaged and sterilized to obtain an absorbable anti-blocking membrane. The corresponding SEM image is shown below. Figure 3 As shown.

[0087] The absorbable anti-adhesion membrane has a wet mechanical strength of 9.1 MPa, exhibiting elasticity and capable of withstanding large deformations encountered during clinical procedures and tissue growth without being damaged. The water contact angle of the absorbable anti-adhesion membrane is 61.2°. Animal experiments have shown that this anti-adhesion membrane can rapidly stop bleeding, adheres to the wound without sutures, is easy to use, and achieves an anti-adhesion rate of 90.1%.

[0088] Example 4

[0089] 1. Gelatin was dissolved in trifluoroethanol to a concentration of 0.07 g / mL, and chitosan was dissolved in acetic acid to a concentration of 0.06 g / mL. The solutions were magnetically stirred for 12 hours. The gelatin and chitosan solutions were then added to two separate syringes, and spun using two needles to prepare a blended fiber membrane, resulting in fiber membrane M1. The extrusion rate of the gelatin solution was 1 mL / h, and the spinning voltage was 16 kV. The extrusion rate of the chitosan solution was 0.7 mL / h, and the spinning voltage was 16 kV. The spinning distance was 12 cm for both solutions, and the spinning time was 4 hours.

[0090] 2. Polycaprolactone and gelatin were dissolved in trifluoroethanol at a mass ratio of 4:1. The solution was stirred at room temperature for 12 hours to obtain spinning solution C, which had a concentration of 0.12 g / mL. This solution was then added to an electrospinning machine, and a second fiber membrane was spun on fiber membrane M1 to obtain composite membrane M2. The extrusion rate of the spinning solution was 2 mL / h, the spinning voltage was 30 kV, the spinning distance was 20 cm, and the spinning time was 4 hours.

[0091] 3. Polyvinyl alcohol and hyaluronic acid were dissolved in hot water at 70℃, with a polyvinyl alcohol to hyaluronic acid mass ratio of 2:1 and a total solution concentration of 0.8 g / mL. The solution was magnetically stirred at room temperature for 8 hours to obtain spinning solution D. This solution was then added to an electrospinning machine to prepare a third fiber membrane on the composite membrane M2, resulting in composite fiber membrane M3. The spinning solution extrusion rate was 1 mL / h, the spinning voltage was 18 kV, the spinning distance was 15 cm, and the spinning time was 2 hours.

[0092] 4. The obtained composite fiber membrane M3 was dried in a fume hood at room temperature for 48 hours to allow the residual solvent to fully evaporate. It was then packaged and sterilized to obtain an absorbable anti-blocking membrane. The corresponding SEM image is shown below. Figure 4 As shown.

[0093] This absorbable anti-adhesion membrane has a wet mechanical strength of 10 MPa, exhibiting elasticity and capable of withstanding large deformations encountered during clinical procedures and tissue growth without being damaged. The water contact angle of this absorbable anti-adhesion membrane is 57.2°. Animal experiments have shown that this anti-adhesion membrane can rapidly stop bleeding, adheres to the wound without sutures, is easy to use, and achieves an anti-adhesion rate of 91.1%.

[0094] from Figure 1-4 As can be seen from the SEM images, the anti-adhesion membranes prepared in Examples 1-4 have fiber diameters between 1 and 3 micrometers, which can play a shielding role, and porosity between 70% and 90%, which can facilitate the exchange of gases and nutrients.

[0095] Figure 5 This is a schematic diagram of the cell permeation through the anti-adhesion membrane experiment of the present invention; it includes cells 1, anti-adhesion membrane 2, upper culture medium 3 and lower culture medium 4; Figure 6 Three days after the cells were seeded onto the anti-adhesion membrane prepared in Example 1, the bottom of the 24-well plate was photographed under a microscope (40×), which shows that it has a good shielding effect on the cells.

[0096] After one month of degradation, the anti-adhesion membranes prepared in Examples 1-4 were used to seed cells onto the membranes. Specific results are as follows: Figure 7-10 ,from Figure 7-10 It can be observed that the anti-adhesion membranes prepared in Examples 1-4 still maintain their cell-shielding effect after one month of degradation, ensuring the function of the anti-adhesion membrane. Therefore, the absorbable anti-adhesion membrane of the present invention has good application effects as a wound anti-adhesion material.

[0097] Comparative Example 1

[0098] 1. Gelatin and chitosan were separately dissolved in hexafluoroisopropanol and magnetically stirred at room temperature for 12 hours. The concentration of the gelatin solution was 0.04 g / mL, and the concentration of the chitosan solution was 0.02 g / mL. The gelatin and chitosan solutions were then mixed at a 1:1 mass ratio and stirred until homogeneous. The mixture was then fed into an electrospinning machine to prepare the first fibrous membrane M1. The spinning solution extrusion rate was 1 mL / h, the spinning voltage was 16 kV, the spinning distance was 12 cm, and the spinning time was 1 hour.

[0099] 2. Polycaprolactone and gelatin were dissolved in trifluoroethanol at a mass ratio of 1:1. The solution was stirred at 60°C for 6 hours to obtain spinning solution C, with a concentration of 0.08 g / mL. This solution was added to an electrospinning machine, and a second fiber membrane was spun on fiber membrane M1 to obtain composite membrane M2. The extrusion rate of the spinning solution was 1.2 mL / h, the spinning voltage was 18 kV, the spinning distance was 10 cm, and the spinning time was 5 hours.

[0100] 3. Place the obtained composite fiber membrane M2 in a fume hood at room temperature and dry for 48 hours to allow the residual solvent to fully evaporate. Then package and sterilize to obtain an absorbable anti-adhesion membrane.

[0101] The absorbable anti-adhesion membrane has a wet mechanical strength of 7.4 MPa, exhibiting elasticity and capable of withstanding large deformations encountered during clinical procedures and tissue growth without being damaged. The water contact angle of the absorbable anti-adhesion membrane is 68.3°. Animal experiments showed that the anti-adhesion membrane could rapidly stop bleeding and adhere to the wound without the need for sutures; however, during tissue growth, the anti-adhesion membrane shifted, and the anti-adhesion rate was only 80.1%.

[0102] Comparative Example 2

[0103] 1. Polycaprolactone and gelatin were dissolved in trifluoroethanol at a mass ratio of 1:1. The solution was stirred at 60°C for 6 hours to obtain spinning solution C, with a concentration of 0.08 g / mL. This solution was then added to an electrospinning machine to obtain nanofiber membrane M2. The extrusion rate of the spinning solution was 1.2 mL / h, the spinning voltage was 18 kV, the spinning distance was 10 cm, and the spinning time was 5 hours.

[0104] 2. Place the obtained nanofiber membrane M2 in a fume hood at room temperature and dry for 48 hours to allow the residual solvent to fully evaporate. Then package and sterilize to obtain an absorbable anti-adhesion membrane.

[0105] The absorbable anti-adhesion membrane has a wet mechanical strength of 6.9 MPa, exhibiting elasticity and capable of withstanding large deformations encountered during clinical procedures and tissue growth without damage. The water contact angle of the absorbable anti-adhesion membrane is 77.6°. Animal experiments showed that during surgery, the anti-adhesion membrane absorbed a significant amount of blood, resulting in weak adhesion, displacement, and the need for sutures; the anti-adhesion rate reached 70.4%.

[0106] Comparative Example 3

[0107] 1. Polycaprolactone and gelatin were dissolved in trifluoroethanol at a mass ratio of 1:1. The solution was stirred at 60°C for 6 hours to obtain spinning solution C, with a concentration of 0.08 g / mL. This solution was then added to an electrospinning machine with a nanofiber membrane M2. The extrusion rate of the spinning solution was 1.2 mL / h, the spinning voltage was 18 kV, the spinning distance was 10 cm, and the spinning time was 5 hours.

[0108] 2. Polycaprolactone and polyethylene glycol were dissolved in chloroform at a mass ratio of 1:1. The solution was magnetically stirred at room temperature for 12 hours to obtain spinning solution D. The concentration of spinning solution D was 0.06 g / mL. The solution was added to an electrospinner to prepare a second fiber membrane on the nanofiber membrane M2, resulting in a composite fiber membrane M3. The extrusion rate of the spinning solution was 0.8 mL / h, the spinning voltage was 15 kV, the spinning distance was 10 cm, and the spinning time was 1.5 h.

[0109] 3. Place the obtained composite fiber membrane M3 in a fume hood at room temperature and dry for 48 hours to allow the residual solvent to fully evaporate. Then package and sterilize to obtain an absorbable anti-adhesion membrane.

[0110] The absorbable anti-adhesion membrane has a wet mechanical strength of 7.8 MPa, exhibiting elasticity and capable of withstanding large deformations encountered during clinical procedures and tissue growth without damage. The water contact angle of the absorbable anti-adhesion membrane is 72.6°. Animal experiments showed that the anti-adhesion membrane absorbed a significant amount of blood, failed to adhere properly, shifted, requiring sutures, and achieved an anti-adhesion rate of 77.8%.

[0111] By comparing Example 1 with Comparative Example 1, it can be seen that Comparative Example 1, due to the lack of a third fibrous membrane, experienced increased friction between its anti-adhesion membrane and other tissues and organs, and the anti-adhesion membrane shifted during use.

[0112] Comparing Example 1 with Comparative Example 3, it can be seen that Comparative Example 3, lacking a first fibrous membrane, produced an anti-adhesion membrane that absorbed a significant amount of blood, making it unable to adhere and requiring suturing.

[0113] Compared with Examples 1, 1 and 3, Comparative Example 2 shows that when Comparative Example 2 only has a second layer of fiber membrane, the anti-adhesion membrane it prepared adsorbed more blood, could not adhere, required suturing, and the anti-adhesion rate further decreased.

[0114] In summary, the three fiber membranes in the absorbable anti-adhesion membrane of the present invention work together to produce an anti-adhesion membrane with better wet mechanical strength and better anti-adhesion rate.

[0115] The present invention has been described in detail above with reference to specific embodiments and exemplary examples; however, these descriptions should not be construed as limiting the present invention. Those skilled in the art will understand that various equivalent substitutions, modifications, or improvements can be made to the technical solutions and embodiments of the present invention without departing from the spirit and scope of the invention, and all such modifications and improvements fall within the scope of the present invention. The scope of protection of the present invention is defined by the appended claims.

[0116] All publications, patent applications, patents, and other references mentioned in this specification are incorporated herein by reference. Unless otherwise defined, all technical and scientific terms used in this specification have the meanings commonly understood by those skilled in the art. In case of conflict, the definitions in this specification shall prevail.

[0117] When this specification uses the prefixes “known to those skilled in the art,” “prior art,” or similar terms to derive materials, substances, methods, steps, apparatus, or components, the objects derived from such prefixes cover those commonly used in the art at the time of this application, but also include those that are not currently commonly used but will become generally recognized in the art as suitable for similar purposes.

[0118] In the context of this specification, except where expressly stated otherwise, any matters or issues not mentioned shall apply directly to those known in the art without any modification.

Claims

1. An absorbable anti-adhesion film, characterized in that: The absorbable anti-adhesion membrane comprises three layers of fiber membrane, wherein: The first fibrous membrane includes gelatin and a hemostatic agent, the hemostatic agent being chitosan; The second fibrous membrane consists of polycaprolactone and gelatin; The third fibrous membrane comprises a hydrophilic polymer, optionally polycaprolactone; The second fiber membrane is located in the middle layer of the absorbable anti-blocking membrane; The first fiber membrane and the third fiber membrane are located on both sides of the second fiber membrane; Based on the total weight of the first layer of fiber membrane as 100%, the mass fraction of gelatin contained therein is 50wt%-90wt%; the mass fraction of hemostatic agent is 10%-50wt%. Based on the total weight of the second layer of fiber membrane as 100%, the mass fraction of polycaprolactone contained therein is 40wt%-90wt%, and the mass fraction of gelatin is 10wt%-60wt%. Based on the total weight of the third fiber membrane as 100%, the mass fraction of polycaprolactone contained therein is 0-50 wt%, and the mass fraction of hydrophilic polymer is 50 wt%-100 wt%. A method for preparing an absorbable anti-adhesion membrane includes the following steps: The raw materials corresponding to the first, second, and third fiber membranes are respectively prepared into spinning solutions, and then electrospinning and drying are performed to obtain the absorbable anti-adhesion membrane.

2. The absorbable anti-adhesion film according to claim 1, characterized in that: Based on the total weight of the second fibrous membrane as 100%, it contains 50wt%-90wt% polycaprolactone and 10wt%-50wt% gelatin; and / or, Based on the total weight of the third fiber membrane as 100%, it contains 10%-50 wt% polycaprolactone and 50 wt%-90 wt% hydrophilic polymer.

3. The absorbable anti-adhesion film according to claim 1, characterized in that: The hemostatic agent is selected from chitosan; and / or, The hydrophilic polymer is selected from at least one of polyvinyl alcohol, polyethylene glycol, polyethylene oxide, hyaluronic acid, poly[2-(methacryloyloxy)ethyl phosphocholine], gelatin, or collagen.

4. The absorbable anti-adhesion film according to claim 1, characterized in that: The method for preparing the first fiber membrane is as follows: Gelatin and optionally a hemostatic agent are dissolved in a solvent and then electrospun.

5. The absorbable anti-adhesion film according to claim 4, characterized in that: The method for preparing the first fiber membrane is as follows: Gelatin and hemostatic agent are dissolved in solvents to prepare spinning solution A and spinning solution B, respectively. Spinning solution A and spinning solution B are mixed evenly and then electrospun using a single needle to prepare the first fiber membrane. Alternatively, spinning solution A and spinning solution B are electrospun separately to prepare the first fiber membrane.

6. The absorbable anti-adhesion film according to claim 5, characterized in that: The method for preparing the first fiber membrane is as follows: Gelatin and hemostatic agent are dissolved in solvents to prepare spinning solution A and spinning solution B, respectively; spinning solution A and spinning solution B are mixed evenly and then electrospun with a single needle to prepare the first fiber membrane; or, spinning solution A and spinning solution B are electrospun separately to prepare the first fiber membrane. The concentration of spinning solution A or spinning solution B is independently selected from 0.02 g / mL to 0.2 g / mL.

7. The absorbable anti-adhesion film according to claim 6, characterized in that: The concentration of spinning solution A or spinning solution B is independently 0.04 g / mL to 0.2 g / mL.

8. The absorbable anti-adhesion film according to claim 7, characterized in that: The concentration of spinning solution A or spinning solution B is independently 0.04 g / mL to 0.1 g / mL.

9. The absorbable anti-adhesion film according to claim 1, characterized in that: The preparation method of the second fiber membrane is as follows: Polycaprolactone and gelatin are mixed and dissolved in a solvent to prepare spinning solution C; electrospinning is performed on the first fiber membrane to obtain the second fiber membrane.

10. The absorbable anti-adhesion film according to claim 9, characterized in that: The concentration of the spinning solution C is 0.04 g / mL to 0.2 g / mL.

11. The absorbable anti-adhesion film according to claim 10, characterized in that: The concentration of the spinning solution C is 0.04 g / mL to 0.15 g / mL.

12. The absorbable anti-adhesion film according to claim 1, characterized in that: The preparation method of the third fiber membrane is as follows: A hydrophilic polymer and optionally polycaprolactone are added to a solvent and mixed and dissolved to prepare spinning solution D; electrospinning is performed on the second fiber membrane to obtain the third fiber membrane.

13. The absorbable anti-adhesion film according to claim 12, characterized in that: The concentration of the spinning solution D is 0.01 g / mL to 0.8 g / mL.

14. The absorbable anti-adhesion film according to claim 13, characterized in that: The concentration of the spinning solution D is 0.04 g / mL to 0.4 g / mL.

15. The absorbable anti-adhesion film according to claim 14, characterized in that: The concentration of the spinning solution D is 0.04 g / mL to 0.2 g / mL.

16. The absorbable anti-adhesion film according to claim 1, characterized in that: During electrospinning of the first fiber membrane, the spinning solution extrusion rate is 0.5-10 mL / h, the spinning voltage is 7-30 kV, the receiving distance is 8-30 cm, and the spinning time is 1-3 h; and / or, During electrospinning of the second fiber membrane, the extrusion rate of the spinning solution is 0.5-10 mL / h, the spinning voltage is 7-30 kV, the receiving distance is 8-30 cm, and the spinning time is 2-8 h; and / or, During electrospinning of the third fiber membrane, the spinning solution extrusion rate is 0.5-10 mL / h, the spinning voltage is 7-30 kV, the receiving distance is 8-30 cm, and the spinning time is 1-3 h; and / or, The solvents in the spinning solutions corresponding to the first, second, and third fiber membranes are each independently selected from at least one of hexafluoroisopropanol, trifluoroethanol, chloroform, dichloromethane, acetic acid, trifluoroacetic acid, ethanol, methanol, N,N'-dimethylformamide, N,N'-dimethylacetamide, acetone, and water.

17. The use of the absorbable anti-adhesion membrane according to any one of claims 1-16 in wound anti-adhesion materials.

18. The application according to claim 17, characterized in that: Application of absorbable anti-adhesion membranes in postoperative anti-adhesion materials.

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