Stitchable membrane with adhesion capability and preparation method thereof

Abstract

The invention discloses a stitchable membrane with adhesion capability and a preparation method thereof, and the preparation method specifically comprises the following steps: putting a silk fabric in an alkaline degumming solution for degumming, and cleaning and drying to obtain a substrate; mixing and stirring the macromolecular solute and water to obtain a macromolecular aqueous solution with the mass ratio of 2-5%; mixing and stirring the polymer aqueous solution and a plasticizer, and carrying out vacuum defoaming; obtaining a mixture; the mixture and a substrate are taken for film laying, and a basic film is obtained after freezing and drying; and spraying a silk fibroin aqueous solution and a gelatin aqueous solution on one side of the basic membrane, drying and then crosslinking to obtain the stitchable membrane with the adhesion capability. According to the method, degummed silk is taken as a base material for treatment, and is supplemented with a polymer solution for filling, so that a stitched needle eye can be blocked, and cerebrospinal fluid permeation is prevented.

Description

Technical Field

[0001] The invention relates to the technical field of sewable films, and in particular to a sewable film with adhesion ability and a preparation method thereof. Background Art

[0002] Dura mater defects are common in spinal surgery and neurosurgery. Cerebrospinal fluid leakage after dura mater damage can cause a series of complications. In order to prevent cerebrospinal fluid leakage, it may be necessary to use repair materials to suture the defect in clinical applications to reduce the risk of leakage.

[0003] Currently, the sutureable membranes used in repair materials are mostly polyesters, polymer biomaterials, etc. Polyester materials have good strength and biocompatibility, but the disadvantage is that they are easy to decompose and are acidic, causing tissue damage; polymer biomaterials have good biocompatibility and degradability, but are subject to cost, strength and toughness issues, and their application is limited. Therefore, the preparation of a membrane for suture with high strength, toughness, moderate cost, and excellent biological properties is currently a research hotspot for the treatment of dura mater defects. Summary of the invention

[0004] The object of the present invention is to provide a sutureable film with adhesion ability and a preparation method thereof, so as to overcome the deficiencies in the prior art.

[0005] To achieve the above object, the present invention provides the following technical solutions: The present application discloses a method for preparing a sutureable film with adhesion ability, which specifically comprises the following steps: S1, placing the silk fabric in an alkaline degumming solution for degumming, and washing and drying the silk fabric to obtain a substrate; S2, mixing the polymer solute with water to obtain a polymer aqueous solution with a mass ratio of 2-5%; S3, mixing and stirring the polymer aqueous solution in step S2 and the plasticizer, and vacuum degassing to obtain a mixture; S4, taking the mixture of step S3 and the substrate of step S1 to lay a film, and obtaining a base film after freezing and drying; S5. Spraying a silk fibroin aqueous solution and a gelatin aqueous solution on one side of the base membrane in step S4, and then cross-linking after drying to obtain a sutureable membrane with adhesion ability.

[0006] Preferably, the silk fabric in step S1 is a knitted warp knitted fabric or a knitted weft knitted fabric; and the drying temperature is 25-85°C.

[0007] Preferably, the polymer solute in step S2 includes a combination of one or more of carboxymethyl chitosan, gelatin, collagen, and sodium alginate.

[0008] Preferably, in step S3, the plasticizer is one or more of triethyl citrate, triethyl glycerol, and isopropyl palmitate; the mass ratio of the polymer aqueous solution to the plasticizer is 95:5-98:2; the vacuum degassing time is 2-5 minutes; and the stirring time is 5-10 minutes.

[0009] Preferably, the specific operation of step S4 is as follows: S41, taking the mixture and the substrate according to a mass ratio of the polymer solute in the mixture to the substrate of 10:1 to 25:1; S42, spreading the mixture on the mold according to the proportion, placing a negative base, and spreading the mixture on the base to complete the film laying; S43, after pre-freezing, freezing and drying, a base membrane is obtained; Preferably, in step S43, the pre-freezing time is 3 to 6 hours, and the freezing time is 24 to 48 hours.

[0010] Preferably, the ratio of the mixture to the mold in step S42 is 1 g: 1 cm 2 .

[0011] Preferably, in step S5, the concentrations of the silk fibroin aqueous solution and the gelatin aqueous solution are both 2%, wherein the mass ratio of the silk fibroin aqueous solution to the gelatin aqueous solution is 6:4-4:6, and the drying temperature is 25-85°C.

[0012] Preferably, the aperture of the spray in step S5 is 0.1-1 um and the spraying time is 5-10 min.

[0013] The present invention also discloses a sutureable film with adhesion ability, which is prepared by adopting the preparation method of the sutureable film with adhesion ability as mentioned above; the product structure has 4 layers, which are an adhesive layer, a sealing layer, a base layer and a sealing layer from top to bottom; it can be applied and sutured.

[0014] Beneficial effects of the present invention: 1. The present invention provides a sutureable membrane with adhesion ability. The method uses degummed silk as a substrate for processing and is supplemented with a polymer solution for filling to ensure that the needle holes after suture can be blocked and cerebrospinal fluid penetration can be prevented.

[0015] 2. Using degummed silk as the base material is non-immunogenic, has the ability to enhance the repair and regeneration of cells, blocks the formation of melanin from the source, promotes collagen synthesis, and promotes the metabolism rate of the skin. It is widely available and low-cost.

[0016] 3. The sprayed nanoparticles make the product sticky.

[0017] 4. The product has excellent mechanical properties.

[0018] The features and advantages of the present invention will be described in detail through embodiments in conjunction with the accompanying drawings. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 1 is a structural diagram of a testing device for anti-permeability performance according to an embodiment of the present invention. DETAILED DESCRIPTION

[0020] In order to make the purpose, technical scheme and advantages of the present invention clearer, the present invention is further described in detail below through the accompanying drawings and embodiments. However, it should be understood that the specific embodiments described herein are only used to explain the present invention and are not intended to limit the scope of the present invention. In addition, in the following description, the description of known structures and technologies is omitted to avoid unnecessary confusion of the concept of the present invention.

[0021] Embodiment 1: S1, taking a knitted warp knitted fabric and placing it in a sodium carbonate solution with a concentration of 0.1wt% for degumming, the degumming times are 2, the time is 10min / time, and then washing with water; finally placing it in a stainless steel plate and drying it at 25°C to obtain a substrate; S2, mixing gelatin and aqueous solution at 45°C to obtain a 2% gelatin aqueous solution; S3, taking 2% gelatin aqueous solution and triethyl citrate in a ratio of 95g:5g, mixing and stirring for 5min, and vacuum degassing for 2min to obtain a mixture; S4, spread 50g of the mixture on an area of ​​100cm 2 A mold was prepared, and 0.2 g of the substrate was placed on it; 50 g of the mixture was continued to be spread on the upper layer of the substrate; it was placed in a refrigerator for 3 hours and freeze-dried for 24 hours to obtain a base film; S5. Mix 2% silk fibroin aqueous solution and 2% gelatin aqueous solution in a mass ratio of 6:4 by spraying technology, and then spray it on one side of the base membrane of S4 for 5 minutes and dry at 25°C; the dried product is fumigated with glutaraldehyde for cross-linking to obtain the product; the aperture of the sprayer is 0.1um.

[0022] Product experimental test: The thickness, tensile strength, sewing strength and bonding strength of the membrane were tested.

[0023] 1. Tensile strength / elongation at break test: After rehydrating the silk protein membrane prepared in Example 1 for 1 min, cut the sample into 50 mm × 10 mm strips, and measure the strip thickness D (in mm); then fix the two ends of the strip on the fixture of the universal material testing machine, with a distance of 20 mm between the fixtures. Then stretch the strip at a rate of 50 mm / min until the strip breaks, and record the maximum force F (in N) during this process. The tensile strength T calculation formula is as follows: Where: W is the width of the specimen, 10 mm.

[0024] The elongation at break is the percentage of length change before and after stretching.

[0025] 2. Suture strength: After the silk protein membrane prepared in Example 1 was rehydrated for 1 min, the sample was cut into a 20 mm × 20 mm sample block, and then a 2-0 medical nylon suture was inserted and passed through the sample block at 2 mm from the edge of one end of the sample block to suture into a semi-circle. The sample block and the suture were fixed on the fixture of the universal material testing machine respectively, and the suture was stretched at a rate of 50 mm / min. The maximum force value that pulled the suture out of the sample or caused the sample to be damaged was recorded, which was the suture strength S (N).

[0026] 3. Adhesion strength: Take any sample and cut a circle with a diameter of 3.0 cm ± 0.1 cm.

[0027] Take the Tyvek ring and moisten it by spraying a small amount of saline with a spray bottle; Take the test sample and place it on the Tyvek ring with the text facing up. The center of the test sample and the ring should coincide. Gently press the test sample until it is completely adhered to the surface of the ring. There should be no bubbles or gaps visible to the naked eye. Place the sample face down in saline to rehydrate for 30 seconds, take it out, and turn it over; place the ring face down in saline to continue rehydrating for 30 seconds; take it out, and use filter paper to remove water droplets on the surface of the sample and the ring; Take a PVC tape disc and stick it on the upper surface of the test sample. The center of the test sample and the disc should coincide. Use a roller to roll back and forth 5 times in both directions of a "cross" shape just above the tape disc; place the ring face up on the test module of the tensile testing machine, and after fixing it, apply pressure to the sample through the ring hole at a speed of 50mm / min, and record the maximum pressure value of the sample falling off the ring.

[0028] 4. Anti-penetration performance: Sampling: Cut the sample to a size of 3.2~3.4cm in diameter; Place the sample between two PVC pipes and use aluminum foil tape to glue the pipe and the sample together (eg. Figure 1 Inject a water column of standard quality into the upper part of the pipe and keep it for 1 minute to observe whether it penetrates.

[0029] Embodiment 2: S1. Take a knitted warp knitted fabric, place it in a sodium carbonate solution with a concentration of 0.1wt% for degumming, the degumming times are 2, the time is 10min / time, and then wash it with water; finally, place it in a stainless steel plate and dry it at 85°C to obtain a substrate; S2, mixing carboxymethyl chitosan and the aqueous solution at 45° C. and stirring to obtain a carboxymethyl chitosan aqueous solution containing 5% of the solute; S3, 5% carboxymethyl chitosan aqueous solution and triethyl glycerol were mixed in a ratio of 98 g:2 g, stirred for 10 min, and vacuum degassed for 5 min to obtain a mixture; S4, spread 50g of the mixture on an area of ​​100cm 2 A mold was prepared, and 0.2 g of the substrate was placed on it; 50 g of the mixture was continued to be spread on the upper layer of the substrate; the mixture was placed in a refrigerator for 6 hours and freeze-dried for 48 hours to obtain a base film; S5, mixing a 2% silk fibroin aqueous solution and a 2% gelatin aqueous solution in a mass ratio of 4:6 by spraying technology, and then spraying the mixture on one side of the base membrane for 10 minutes, drying at 85° C., and fumigating with glutaraldehyde for cross-linking to obtain a product; Among them, the aperture of the sprayer is 1um.

[0030] Embodiment 3: S1, taking a knitted weft-knitted fabric, placing it in a sodium carbonate solution with a concentration of 0.1wt% for degumming, the degumming times are 2, the time is 10min / time, and then washing with water; finally placing it in a stainless steel plate and drying it at 60°C to obtain a substrate; S2, dissolving 1.44 g collagen and 1.44 g carboxymethyl chitosan in 93.12 g water to obtain a 3% aqueous solution of a polymer solute; S3, 3% polymer solute aqueous solution B and isopropyl palmitate were mixed and stirred at a ratio of 96 g:4 g for 7 min, and vacuum degassed for 3 min to obtain a mixture; S4, spread 50g of the mixture on an area of ​​100cm 2 A mold was prepared, and 0.2 g of the substrate was placed on it; 50 g of the mixture was continued to be spread on the upper layer of the substrate; the mixture was placed in a refrigerator for 4 hours and freeze-dried for 36 hours to obtain a base film; S5, mixing a 2% silk fibroin aqueous solution and a 2% gelatin aqueous solution in a mass ratio of 5:5 by spraying technology, and then spraying the mixture on one side of the base membrane for 7.5 minutes, drying at 60° C., and fumigating with glutaraldehyde for cross-linking to obtain a product; Among them, the aperture of the sprayer is 0.5um.

[0031] Embodiment 4: S1, taking a knitted weft-knitted fabric, placing it in a sodium carbonate solution with a concentration of 0.1wt% for degumming, the degumming times are 2, the time is 10min / time, and then washing with water; finally placing it in a stainless steel plate at 37°C to dry to obtain a substrate; S2, dissolving 2.88 g of sodium alginate in 93.12 g of water to obtain a 3% sodium alginate aqueous solution; S3, 96 g of 3% sodium alginate aqueous solution, 2 g of isopropyl palmitate and 2 g of triethyl palmitate were mixed and stirred for 7 min, and vacuum degassed for 3 min to obtain a mixture; S4, spread 50g of the mixture on an area of ​​100cm 2 A mold was prepared, and 0.2 g of the substrate was placed on it; 50 g of the mixture was continued to be spread on the substrate; the mixture was placed in a refrigerator for 4 hours, and then freeze-dried for 36 hours to obtain a base film; S5. A 2% silk fibroin aqueous solution and a 2% gelatin aqueous solution were mixed in a mass ratio of 5:5 by spraying technology, and then sprayed on one side of the base membrane for 5 minutes. The mixture was dried at 37°C, and then fumigated with glutaraldehyde for cross-linking to obtain the product.

[0032] Among them, the aperture of the sprayer is 0.5um.

[0033] Comparative Example 1: The difference between this comparative example and Example 1 is that the drying temperature of steps S1 and S5 is 105°C. Comparative Example 2: The difference between this comparative example and Example 1 is that the drying temperature in steps S1 and S5 is 10°C; Comparative Example 3: The difference between this comparative example and Example 1 is that: in step S2, gelatin and aqueous solution are mixed and stirred at 45° C. to obtain a gelatin aqueous solution with a solute content of 1%; Comparative Example 4: The difference between this comparative example and Example 1 is that: in step S2, gelatin and aqueous solution are mixed and stirred at 45° C. to obtain a gelatin aqueous solution with a solute content of 7%, and the rest is the same as Example 1; Comparative Example 5: The difference between this comparative example and Example 1 is that: in step S3, 2% gelatin aqueous solution and triethyl citrate are mixed and stirred at a ratio of 99 g:1 g for 5 min, and vacuum degassing is performed for 2 min; Comparative Example 6: The difference between this comparative example and Example 1 is that in step S3, 2% gelatin aqueous solution B and triethyl citrate are mixed and stirred at a ratio of 93 g:7 g for 5 min, and vacuum degassing is performed for 2 min; Comparative Example 7: The difference between this comparative example and Example 1 is that in step S3, the degassing time of step S3 is 1 min. Comparative Example 8: The difference between this comparative example and Example 1 is that in step S3, the stirring time of step S3 is 3 minutes. Comparative Example 9: The difference between this comparative example and Example 1 is that in step S4, 50 g of the mixture is spread on an area of ​​100 cm 2 A mold was prepared, and 0.4 g of the substrate was placed on it; 50 g of the mixture was continued to be spread on the substrate; the mixture was placed in a refrigerator for 3 hours and freeze-dried for 24 hours; Comparative Example 10: The difference between this comparative example and Example 1 is that in step S4, 50 g of the mixture is spread on an area of ​​100 cm 2 A mold was prepared, and a negative substrate of 0.067 g was placed on it; 50 g of the mixture was continued to be spread on the upper layer of the substrate; the mixture was placed in a refrigerator for 3 hours and freeze-dried for 24 hours; Comparative Example 11: The difference between this comparative example and Example 1 is that in step S4, 50 g of the mixture is spread on an area of ​​100 cm 2 A mold was prepared, and a 0.2 g substrate was placed on it; 50 g of the mixture was continued to be spread on the substrate; the mixture was placed in a refrigerator for 1 hour, and then freeze-dried for 20 hours; Comparative Example 12: The difference between this comparative example and Example 1 is that in step S5, a 2% silk fibroin aqueous solution and a 2% gelatin aqueous solution are mixed in a mass ratio of 7:3 by spraying technology, then sprayed on one side of the base membrane and dried at 25°C; the aperture of the sprayer is 0.1 um.

[0034] Comparative Example 13: The difference between this comparative example and Example 1 is that in step S5, a 2% silk fibroin aqueous solution and a 2% gelatin aqueous solution are mixed in a mass ratio of 3:7 by spraying technology, and then sprayed on one side of the base membrane and dried at 25°C. The aperture of the sprayer is 0.1 um.

[0035] Comparative Example 14: The difference between this comparative example and Example 1 is that in step S5, a 2% silk fibroin aqueous solution and a 2% gelatin aqueous solution are mixed in a mass ratio of 6:4 by spraying technology, and then sprayed on one side of the base membrane and dried at 25°C. The aperture of the sprayer is 0.2 um.

[0036] Comparative Example 15: The only difference between this comparative example and Example 1 is that in step S5, the spraying time is 1 min.

[0037] Comparative Example 16: The only difference between this comparative example and Example 1 is that in step S5, the spraying time is 15 minutes.

[0038] Table 1 Strength test comparison It can be seen from Example 1 and Comparative Example 1 that when the temperature is too high, the obtained film is relatively brittle; when the temperature is too low in Comparative Example 2, the drying speed is too slow and the efficiency is too low, so this parameter is not selected; In the preparation process of Comparative Example 3, the polymer tends to be relatively dilute, the silk fabric cannot float on it, and the product cannot be obtained; The membrane plugging layer prepared in Comparative Example 4 was too thick, and swelled too much after absorbing water, resulting in liquid leakage; Comparative Example 5 used less plasticizer, and the resulting film was extremely brittle and could not be tested or used; It can be seen from Example 1 and Comparative Example 6 that too much plasticizer addition will soften the film but reduce its strength; During the preparation of Comparative Examples 7 and 8, it was found that the test time was insufficient to obtain a uniform film; It can be seen from Example 1 and Comparative Example 9 that under the same film laying area, the higher the quality of the substrate A, the thicker the product. During the test of the final product, the outer plugging layer cracks first; It can be seen from Example 1 and Comparative Example 10 that the substrate is too thin and the product strength is too low; In comparative example 11, it was found during the test that the film was not completely dried; By comparing Example 1 with Comparative Examples 13 and 12, it can be seen that the parameters outside the scope of the claims have poor viscosity. Gelatin and silk fibroin have electrostatic interactions to form viscous gels, with large ratio deviations and weak electrostatic interactions; Comparative Example 14 has a large spray aperture, a small area in contact with tissue, and low viscosity; Comparative Example 15 had a short spraying time and less product was sprayed out; In Comparative Example 16, increasing the spray time did not result in better viscosity, so this parameter was not selected.

[0039] This product also has excellent adhesion and can be tightly fixed to the defect site after being sutured with the tissue, preventing the problem of cerebrospinal fluid leaking through the suture needle eye.

[0040] Finally, it should be noted that the above description is only a preferred embodiment of the present invention and is not intended to limit the protection scope of the present invention. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A method for preparing a sutureable film having adhesion ability, characterized in that: The specific steps include: S1, placing the silk fabric in an alkaline degumming solution for degumming, and washing and drying the silk fabric to obtain a substrate; S2, mixing the polymer solute with water to obtain a polymer aqueous solution with a mass ratio of 2-5%; S3, mixing and stirring the polymer aqueous solution in step S2 and the plasticizer, and vacuum degassing to obtain a mixture; S4, taking the mixture of step S3 and the substrate of step S1 to lay a film, and obtaining a base film after freezing and drying; S5. Spraying a silk fibroin aqueous solution and a gelatin aqueous solution on one side of the base membrane in step S4, and then cross-linking after drying to obtain a sutureable membrane with adhesion ability.

2. A method for preparing a sutureable film with adhesion ability as claimed in claim 1, characterized in that: The silk fabric in step S1 is a knitted warp knitted fabric or a knitted weft knitted fabric; the drying temperature is 25-85°C.

3. The method for preparing a sutureable film with adhesion ability as claimed in claim 1, characterized in that: The polymer solute in step S2 includes a combination of one or more of carboxymethyl chitosan, gelatin, collagen, and sodium alginate.

4. The method for preparing a sutureable film with adhesion ability as claimed in claim 1, characterized in that: In step S3, the plasticizer is one or more of triethyl citrate, triethyl glycerol, and isopropyl palmitate; the mass ratio of the polymer aqueous solution to the plasticizer is 95:5-98:2; and the vacuum degassing time is 2-5 minutes.

5. The method for preparing a sutureable film with adhesion ability as claimed in claim 1, characterized in that: The specific operations of step S4 are as follows: S41, taking the mixture and the substrate according to a mass ratio of the polymer solute in the mixture to the substrate of 10:1 to 25:1; S42, spreading the mixture on the mold according to the proportion, placing a negative base, and spreading the mixture on the base to complete the film laying; S43, after pre-freezing, freezing and drying, a base membrane is obtained.

6. A method for preparing a sutureable film with adhesion according to claim 5, characterized in that: In step S43, the pre-freezing time is 3 to 6 hours, and the freezing time is 24 to 48 hours.

7. A method for preparing a sutureable film with adhesion according to claim 5, characterized in that: The ratio of the mixture to the mold in step S42 is 1g:1cm 2 .

8. The method for preparing a sutureable film with adhesion ability as claimed in claim 1, characterized in that: In step S5, the concentrations of the silk fibroin aqueous solution and the gelatin aqueous solution are both 2%, wherein the mass ratio of the silk fibroin aqueous solution to the gelatin aqueous solution is 6:4-4:6, and the drying temperature is 25-85°C.

9. The method for preparing a sutureable film with adhesion ability as claimed in claim 1, characterized in that: In step S5, the aperture of the spray is 0.1-1 μm and the time is 5-10 min.

10. A sutureable film having adhesion capability, characterized in that: The film is prepared by the method for preparing a sutureable film with adhesion ability as described in claims 1 to 9.

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