A self-adhesive material, its preparation method and uses

Abstract

The present invention relates to the field of biomedical materials, and relates to a self-adhesive material, a preparation method thereof and uses thereof. A preparation method of a self-adhesive material provided includes: reacting component A and component B to form a citric acid-based prepolymer; component A is at least one compound having at least two reactive functional groups on the end group or side chain, and the functional groups are the same or different; the functional groups are selected from at least one of hydroxyl group, amino group, mercapto group, epoxy group, carboxyl group, acid anhydride, organic substituent; component B is citric acid and / or its derivative; the reaction includes polycondensation reaction, substitution reaction or transesterification reaction; crosslinking the citric acid-based prepolymer and isocyanate to form a urethane bond or an amide bond; the materials obtained by the above preparation method have good self-adhesiveness between the contact surfaces, can be fixed without suturing, greatly reduce the difficulty of surgical operation and the risk of infection, reduce the damage to tissues, and improve the success rate of the surgery.

Description

Technical Field

[0001] The present invention relates to the field of biomedical materials, and particularly to a self-adhesive material, a preparation method thereof, and uses thereof. Background Art

[0002] Biomembranes in the field of biomedical materials generally serve as materials for replacing and repairing human tissues. Depending on different application scenarios, such as wound dressings, medical adhesives, anti-adhesion membranes, etc. Among them, the function of the anti-adhesion membrane is to prevent tissue adhesion. Tissue adhesion refers to a pathological state in which the contact surfaces of adjacent tissues or organs are connected together by cellulose or newly formed fibrous tissues in scar tissue. It is a common clinical phenomenon after surgery and an inevitable process for patients to heal. The formation of adhesions is usually related to surgery, trauma, inflammation, infection, or foreign bodies in the abdominal cavity, etc. For example, tendon adhesion is closely related to the tendon healing process and can be divided into two mechanisms: endogenous and exogenous healing. Endogenous healing achieves tendon healing through the self-proliferation of fibroblasts on the tendon surface and can prevent tendon adhesion. Exogenous healing involves the generation of new granulation tissue in the subcutaneous tissue and synovium of the tendon at the tendon rupture surface, forming scar tissue and resulting in adhesion. In addition, tendon blood supply and integrity damage, as well as peritendinous tissue inflammatory reactions, are also important reasons for the formation of tendon adhesion. In addition, adhesions may cause various complications such as small intestinal obstruction, secondary infertility, pain at the affected site, or joint movement dysfunction. Due to the serious complications that adhesions may cause, preventing the occurrence of adhesions is of great significance for improving the quality of life of patients and reducing medical costs.

[0003] Currently, the anti-adhesion biomembrane materials used, as a physical barrier, can inhibit adhesion formation by isolating the damaged site from the surrounding tissues, and it has become a commonly used clinical method. Currently, researchers have developed anti-adhesion membranes prepared from a variety of biomaterials, including natural materials (such as collagen, hyaluronic acid), synthetic materials (such as polylactic acid, polyglycolic acid), and composite materials. These materials have improved the tissue repair effect to a certain extent. For example, a decellularized pericardium reported in patent document CN116077739A has a double-sided structure and can effectively block adhesions. A composite nanofiber membrane proposed in CN111714696A has both good biocompatibility and mechanical properties.

[0004] However, the existing anti-adhesion biomembrane materials still have some deficiencies: most anti-adhesion biomembranes need to be sutured and fixed, increasing the difficulty of surgical operation and the risk of infection. In addition, aspects such as the degradation rate, mechanical strength, and tissue biocompatibility of the materials still need to be further optimized. Therefore, developing an anti-adhesion biomaterial with self-adhesion, good biocompatibility, and absorbability is of great significance for improving the tissue repair effect. Summary of the Invention

[0005] Therefore, the technical problem to be solved by the present invention is to overcome the defects of the existing anti-adhesion biofilm materials that need to be sutured and fixed, which increases the difficulty of surgical operation and the risk of infection, and the degradation rate, mechanical strength and tissue biocompatibility are relatively unsatisfactory. Thus, a self-adhesive material, a preparation method thereof and its uses are provided. Due to its self-adhesiveness, the self-adhesive material can be applied without suturing. When used as an anti-adhesion film, it can reduce the difficulty of surgical operation and the risk of infection. Moreover, the self-adhesive material has degradability, can be completely degraded and absorbed in the body of humans or non-human animals, has good biocompatibility, and its mechanical properties can be adjusted. At the same time, it can endow the biomaterial with multifunctions such as luminescence positioning, drug delivery, promoting repair, antibacterial, and promoting angiogenesis.

[0006] For this purpose, the present invention provides the following technical solutions:

[0007] The present invention provides a preparation method of a self-adhesive material, comprising:

[0008] Reacting component A and component B to form a citric acid-based prepolymer; component A is at least one compound having at least two reactive functional groups on the end group or side chain, and the functional groups are the same or different; the functional groups are selected from at least one of hydroxyl group, amino group, mercapto group, epoxy group, carboxyl group, acid anhydride, and organic substituent; component B is citric acid and / or its derivatives; the reaction includes polycondensation reaction, substitution reaction or transesterification reaction;

[0009] Carrying out a cross-linking reaction of urethane bond or amide bond between the citric acid-based prepolymer and isocyanate.

[0010] Optionally, the isocyanate is selected from at least one of 1,6-hexamethylene diisocyanate, isophorone diisocyanate, toluene diisocyanate, lysine diisocyanate, naphthalene diisocyanate, 1,4-cyclohexyl diisocyanate, 4,4'-diphenylmethane diisocyanate or 4,4'-diisocyanatodicyclohexylmethane.

[0011] Optionally, the isocyanate is selected from at least one of 1,6-hexamethylene diisocyanate, lysine diisocyanate and isophorone diisocyanate.

[0012] Optionally, when the citric acid-based prepolymer is in a solid state, before carrying out the cross-linking reaction of urethane bond or amide bond, the citric acid-based prepolymer is dissolved in an organic solvent to obtain a citric acid-based prepolymer solution; isocyanate is added to the citric acid-based prepolymer solution to obtain a mixture, and then the cross-linking reaction of urethane bond or amide bond is carried out;

[0013] The mass percentage of the citric acid-based prepolymer in the citric acid-based prepolymer solution is 30-60%;

[0014] The mass percentage of the isocyanate added is > 0% and ≤ 50% of the citric acid-based prepolymer.

[0015] Optionally, the conditions for the crosslinking reaction of the urethane bond or amide bond are: the temperature is room temperature, the reaction time is 0 - 24 h, and the reaction time > 0 h to ensure that the added organic solvent completely volatilizes.

[0016] Optionally, when preparing the self-adhesive material into a film, it includes spin-coating, solution casting or casting into a film during the crosslinking reaction of the citric acid-based prepolymer and isocyanate to form a urethane bond or amide bond.

[0017] Optionally, the conditions for spin-coating are a rotation speed of 1000 - 3000 rpm / min, a time of 0 - 3 min, and ≠ 0 min.

[0018] Optionally, the thickness of the film is 10 - 500 μm. A thinner film material can better fit the tissue damage site, reduce the foreign body sensation, and the small tensile force can effectively maintain the self-adhesive state.

[0019] Optionally, component A is a hydrophobic compound or a hydrophilic compound;

[0020] And / or, when component A is a hydroxy compound, it includes but is not limited to ethylene glycol, hexanediol, octanediol, polyethylene glycol, bis(4-hydroxyphenyl) disulfide, resveratrol, bis(2-hydroxyethyl) disulfide, isosorbide, xylitol, hydroxyacetate or N-methyldiethanolamine;

[0021] And / or, when component A is an amino- or mercapto-containing amino acid or other compound, it includes but is not limited to serine, phosphoserine, cysteine, glutamine or polyaniline;

[0022] And / or, when component A is an epoxy compound, it includes but is not limited to epoxy soybean oil, epoxy resin, epichlorohydrin or lactide;

[0023] And / or, when component A is a carboxyl- or anhydride-containing compound, it includes but is not limited to folic acid, tartaric acid, adipic acid, succinic acid, fumaric acid, salicylic acid, acetic anhydride or maleic anhydride;

[0024] And / or, when component A is a compound containing an organic substituent, it includes but is not limited to polyphosphazene;

[0025] And / or, the citric acid and / or its derivatives include but are not limited to citric acid, trimethyl citrate, triethyl citrate, tributyl citrate, triethyl acetylcitrate, stearoyl monoglyceride citrate or citric acid luminescent molecule.

[0026] The present invention provides a self - adhesive material prepared by the method for preparing the self - adhesive material described above.

[0027] The present invention provides the use of the self - adhesive material in any one of the following:

[0028] Use in the preparation of a suture - free and / or anti - adhesion biofilm; the suture - free and / or anti - adhesion biofilm is a tissue anti - adhesion film for tendons, abdominal cavity, pelvic cavity, nerves, and spinal regions.

[0029] The technical solution of the present invention has the following advantages:

[0030] 1. A method for preparing a self - adhesive material provided by the present invention includes: reacting component A and component B to form a citric acid - based prepolymer; component A is at least one compound having at least two reactive functional groups on the end group or side chain, and the functional groups are the same or different; the functional groups are selected from at least one of hydroxyl, amino, mercapto, epoxy, carboxyl, acid anhydride, and organic substituents; component B is citric acid and / or its derivatives; the reaction includes polycondensation reaction, substitution reaction, or transesterification reaction; cross - linking the citric acid - based prepolymer and isocyanate to form a urethane bond or an amide bond. The present invention finds that by directly cross - linking the citric acid - based prepolymer with isocyanate, the cross - linking points are urethane bonds or amide bonds. For example, the reaction of an isocyanate group with a hydroxyl group generates a urethane bond for cross - linking. Since the urethane bonds or amide bonds formed by cross - linking improve the hydrogen - bond interaction between the material contact surfaces, the obtained material contact surfaces have good self - adhesiveness. During application, it can be fixed without suturing, greatly reducing the difficulty of surgical operation and the risk of infection. The obtained material can be directly attached to the surface of the defect site, effectively avoiding the disadvantages of the traditional film that needs to be sutured and the inflammation reaction that may be caused by the suture thread wearing the tissue. It greatly simplifies the surgical operation, reduces the damage to the tissue, and improves the success rate of the operation.

[0031] Furthermore, the self - adhesive material also has a satisfactory degradation rate, mechanical strength, and tissue compatibility. The prepared citric acid - based material can be completely degraded in vivo, and the exogenously released citric acid can promote the repair of the defect site through metabolic regulation.

[0032] In summary, compared with the anti - adhesion film prepared by traditional synthetic materials, the citric acid - based material prepared by the present invention has a low production cost, a simple preparation method, better biocompatibility, stronger self - adhesiveness, a simpler operation method, and potential multifunctionality (such as antibacterial, in - vivo imaging, promoting repair, etc.). This material has broad prospects for transformation and application in the field of tissue defect repair, can effectively prevent adhesion, promote tissue regeneration, and improve the postoperative function of patients.

[0033] 2. A method for preparing a self - adhesive material provided by the present invention, wherein the isocyanate is selected from at least one of 1,6 - hexamethylene diisocyanate, isophorone diisocyanate, toluene diisocyanate, lysine diisocyanate, naphthalene diisocyanate, 1,4 - cyclohexyl diisocyanate, 4,4'-diphenylmethane diisocyanate or 4,4'-diisocyanatodicyclohexylmethane. By directly cross - linking the citric acid - based prepolymer with the isocyanate, since the urethane bonds or amide bonds formed by cross - linking enhance the hydrogen - bond interaction between the material contact surfaces, the obtained material contact surfaces have good self - adhesiveness. During application, sutureless fixation can be achieved, greatly reducing the surgical operation difficulty and the infection risk. All of the above isocyanates can achieve this function by adjusting the addition ratio with the prepolymer. Further, because the self - adhesive material needs to have the property of being wrap - able, if it is too hard or too brittle, its wrapping property will be affected. Therefore, if the selected isocyanate has too strong a molecular structure rigidity or too much dosage, it will lead to an increase in the strength of the material, which is not conducive to wrapping, and it is easy to produce an obvious foreign - body sensation in the body and cause an inflammatory reaction. However, the molecular structures of the above isocyanates can ensure that the prepared self - adhesive material has the property of being wrap - able. Further, 1,6 - hexamethylene diisocyanate, lysine diisocyanate and isophorone diisocyanate belong to isocyanates with relatively flexible molecular chain structures, and the prepared self - adhesive material has excellent wrapping properties.

[0034] 3. A method for preparing a self - adhesive material provided by the present invention, including that when the citric acid - based prepolymer is in a solid state, before the cross - linking reaction of urethane bonds or amide bonds, the citric acid - based prepolymer is dissolved in an organic solvent to obtain a citric acid - based prepolymer solution; an isocyanate is added to the citric acid - based prepolymer solution to obtain a mixture, and then the cross - linking reaction of urethane bonds or amide bonds is carried out; the mass percentage of the citric acid - based prepolymer in the citric acid - based prepolymer solution is 30 - 60%; the addition amount of the isocyanate accounts for the mass percentage of the citric acid - based prepolymer of >0% and ≤50%. By controlling the ratio of the citric acid - based prepolymer and the isocyanate, the adhesiveness of the material can be improved. The reason is that the urethane bonds or amide bonds formed by directly cross - linking the citric acid - based prepolymer with the isocyanate enhance the hydrogen - bond interaction between the material contact surfaces, so that the obtained material contact surfaces have good self - adhesiveness. Therefore, the ratio of the citric acid - based prepolymer and the isocyanate will directly affect the content of hydrogen bonds, thereby affecting the adhesive performance of the material. Further, because the self - adhesive material needs to have the property of being wrap - able, if it is too hard or too brittle, its wrapping property will be affected. Therefore, if the dosage of the selected isocyanate is too much, it will lead to an increase in the strength of the material, which is not conducive to wrapping, and it is easy to produce an obvious foreign - body sensation in the body and cause an inflammatory reaction. Selecting the above ratio can prepare a self - adhesive material with better wrapping properties.

[0035] 4. A method for preparing a self - adhesive material provided by the present invention. When the self - adhesive material is prepared into a film, it includes spin - coating a mixed solution of a citric acid - based prepolymer and an isocyanate into a film during the cross - linking reaction of urethane bonds or amide bonds. The conditions for spin - coating are a rotation speed of 1000 - 3000 rpm / min, a time of 0 - 3 min, and ≠0 min. By using the spin - coating method to form a film, the solvent can volatilize rapidly during the rapid rotation process, ensuring that the thickness of the prepared film is controllable and it can be dried quickly.

[0036] 5. A method for preparing a self - adhesive material provided by the present invention. Component A is a hydrophobic compound or a hydrophilic compound. The present invention prepares hydrophilic or hydrophobic materials by changing the structure of component A. In the present invention, when choosing compounds such as octanediol, a hydrophobic anti - adhesion biofilm can be obtained, and when choosing hydrophilic compounds such as polyethylene glycol, a hydrophilic anti - adhesion biofilm can be obtained. BRIEF DESCRIPTION OF THE DRAWINGS

[0037] In order to more clearly illustrate the specific embodiments of the present invention or the technical solutions in the prior art, the following will briefly introduce the drawings required for use in the description of the specific embodiments or the prior art. Obviously, the following - described drawings are some embodiments of the present invention. For those of ordinary skill in the art, without creative efforts, other drawings can also be obtained based on these drawings.

[0038] Figure 1 It is a physical effect diagram of the sutureless anti - adhesion film prepared according to Example 1.

[0039] Figure 2 It is a scanning electron microscope picture of the surface and cross - section of the sutureless anti - adhesion film prepared according to Example 1.

[0040] Figure 3 It is an infrared spectrum diagram of the sutureless anti - adhesion film prepared according to Example 1.

[0041] Figure 4 It is a self - adhesion effect diagram of the sutureless anti - adhesion film prepared according to Example 1.

[0042] Figure 5 It is a statistical chart of the citric acid content released by the sutureless anti - adhesion film prepared from the prepolymer in Example 1 with different mass ratios of isocyanate, and the citric acid content in cells after co - incubation; on the left is the citric acid content released from the sutureless anti - adhesion film into the supernatant; on the right is the citric acid content in cells after co - incubation of the supernatant and cells.

[0043] Figure 6 It is a water contact angle diagram of the sutureless anti - adhesion film prepared according to Example 2.

[0044] Figure 7 Self - adhesion effect diagram of the sutureless anti - adhesion film prepared according to Example 2.

[0045] Figure 8 Fluorescence absorption spectrum of the citrate prepolymer prepared according to Example 3.

[0046] Figure 9 Mechanical properties of the sutureless anti - adhesion film prepared according to Examples 1 - 4.

[0047] Figure 10 Self - adhesion performance of the sutureless anti - adhesion film prepared according to the steps of Examples 1 - 4.

[0048] Figure 11 Cell compatibility of the sutureless anti - adhesion film prepared according to the steps of Examples 1 - 4.

[0049] Figure 12 Anti - protein adhesion effect diagram of the sutureless anti - adhesion film prepared according to Examples 1 - 4.

[0050] Figure 13 In - vivo self - adhesion effect diagram of the sutureless anti - adhesion film prepared according to Examples 2 and 4.

[0051] Figure 14 In - vivo tissue H&E staining section diagram of the sutureless anti - adhesion film prepared according to Example 4.

[0052] Figure 15 In - vivo degradation physical diagram of the sutureless anti - adhesion film prepared according to Example 4.

[0053] Figure 16 Synthesis equation for preparing the citric acid - based prepolymer according to Step 1 of Examples 5 - 7.

[0054] Figure 17 Effect diagram prepared according to the preparation method of Example 8.

[0055] Figure 18 Effect diagram prepared according to the preparation method of Example 9.

[0056] Figure 19 Tensile strength of the sutureless anti - adhesion film prepared according to Example 10.

[0057] Figure 20 Self - adhesion strength of the sutureless anti - adhesion film prepared according to Example 12 and Comparative Example 1. The prepared film material was soaked in PBS with pH = 7.4 to observe the wet - state adhesion performance.

[0058] Figure 21This is a comparison of the self - adhesion properties of the sutureless anti - adhesion membranes prepared according to Example 1 and Example 13. The thickness of the membrane material significantly affects the self - adhesion strength. Detailed implementation mode

[0059] The following embodiments are provided to better understand the present invention further. It is not limited to the best implementation mode, and does not limit the content and protection scope of the present invention. Any product that is the same as or similar to the present invention obtained by anyone under the inspiration of the present invention or by combining the features of the present invention with other prior - art features falls within the protection scope of the present invention.

[0060] For those not specifying specific experimental steps or conditions in the embodiments, the operations or conditions of the conventional experimental steps described in the literature in this field can be followed. For reagents or instruments without indicating the manufacturer, they are all conventional reagent products that can be obtained through commercial purchase.

[0061] The present invention discloses a method for preparing a self - adhesive material, which includes: reacting component A and component B to form a citric acid - based prepolymer; component A is at least one compound containing at least two reactive functional groups on the end group or side chain, and the functional groups are the same or different; the functional groups are selected from at least one of hydroxyl, amino, mercapto, epoxy, carboxyl, acid anhydride, and organic substituents; component B is citric acid and / or its derivatives; the reaction includes polycondensation reaction, substitution reaction or transesterification reaction; cross - linking the citric acid - based prepolymer and isocyanate to form urethane bonds or amide bonds. The present invention finds that isocyanate does not participate in the preparation process of polyester prepolymer. Directly cross - linking isocyanate with the citric acid - based prepolymer at the cross - link points of urethane bonds or amide bonds without thermal cross - linking, the obtained material has self - adhesion. The main reason is that the material mainly forms urethane bonds or amide bonds through isocyanate cross - linking, which can improve the hydrogen - bond interaction between the material contact surfaces to achieve self - adhesion. Therefore, when this material is applied to an anti - adhesion membrane, it can be sutureless, reducing the surgical operation difficulty and infection risk. Moreover, this material also has a relatively satisfactory degradation rate, mechanical strength and tissue compatibility.

[0062] In some embodiments, the isocyanate is selected from at least one of 1,6 - hexamethylene diisocyanate, isophorone diisocyanate, toluene diisocyanate, lysine diisocyanate, naphthalene diisocyanate, 1,4 - cyclohexylene diisocyanate, 4,4'-diphenylmethane diisocyanate, or 4,4'-dicyclohexylmethane diisocyanate. By directly cross - linking the citric acid - based prepolymer with the isocyanate, since the urethane bonds or amide bonds formed by cross - linking enhance the hydrogen - bond interaction between the material contact surfaces, the obtained material contact surfaces have good self - adhesiveness, and sutureless fixation can be avoided during application, greatly reducing the surgical operation difficulty and the infection risk. All of the above isocyanates can achieve this function by adjusting the addition ratio with the prepolymer.

[0063] Furthermore, since the self - adhesive material needs to have the property of being wrap - able, if it is too hard or too brittle, its wrapping property will be affected. Therefore, if the molecular structure of the selected isocyanate is too rigid or the dosage is too much, it will lead to an increase in the strength of the material, which is not conducive to wrapping, and it is easy to produce an obvious foreign - body sensation in the body and trigger an inflammatory reaction. However, the molecular structures of the above - mentioned isocyanates can ensure that the prepared self - adhesive material has the wrapping property.

[0064] In a preferred embodiment, the isocyanate is selected from at least one of 1,6 - hexamethylene diisocyanate, lysine diisocyanate, and isophorone diisocyanate. Compared with diisocyanates with branched or cyclic structures, the molecular chains of 1,6 - hexamethylene diisocyanate, lysine diisocyanate, and isophorone diisocyanate have less rigidity. Therefore, when adjusting the ratio, the upper limit of their addition amount is higher, more hydrogen - bond structures can be introduced, and the self - adhesive property of the material is correspondingly increased.

[0065] In some embodiments, when the citric acid-based prepolymer is in a solid state, before the crosslinking reaction of urethane bonds or amide bonds, the citric acid-based prepolymer is dissolved in an organic solvent to obtain a citric acid-based prepolymer solution; an isocyanate is added to the citric acid-based prepolymer solution to obtain a mixture, and then the crosslinking reaction of urethane bonds or amide bonds is carried out; the mass percentage of the citric acid-based prepolymer in the citric acid-based prepolymer solution is 30-60%; the addition amount of the isocyanate accounts for more than 0% and ≤50% of the mass of the citric acid-based prepolymer. Further, the mass percentage of the citric acid-based prepolymer in the citric acid-based prepolymer solution can be any value among 30%, 33%, 35%, 38%, 40%, 43%, 45%, 48%, 50%, 53%, 55%, 58%, 60% or the range value between any two values; the addition amount of the isocyanate accounts for the mass of the citric acid-based prepolymer can be any value among 0.01%, 0.1%, 0.5%, 1%, 5%, 8%, 10%, 13%, 15%, 18%, 20%, 23%, 25%, 28%, 30%, 33%, 35%, 38%, 40%, 45%, 48%, 50% or the range value between any two values. By controlling the ratio of the citric acid-based prepolymer to the isocyanate, the adhesiveness of the material can be improved. The reason is that the urethane bonds or amide bonds formed by directly crosslinking the citric acid-based prepolymer with the isocyanate enhance the hydrogen bond interaction between the material contact surfaces, making the obtained material contact surfaces have good self-adhesiveness. Therefore, the ratio of the citric acid-based prepolymer to the isocyanate will directly affect the content of hydrogen bonds, thereby affecting the adhesion performance of the material. Further, because the self-adhesive material needs to have the winding performance, if it is too hard or too brittle, its winding performance will be affected. Therefore, if too much isocyanate is used, the strength of the material will increase, which is not conducive to winding, and it is easy to produce obvious foreign body sensation in the body and cause inflammatory reactions. By selecting the above ratio, a self-adhesive material with better winding performance can be prepared.

[0066] In some embodiments, the prepolymer prepared with citric acid as component B is in a solid state and needs to be dissolved in an anhydrous organic solvent. Examples of suitable organic solvents include acetone, dioxane, cyclohexane or isopropyl ether, etc. The mass ratio of the prepolymer to the organic solvent is 30-60%, and the preferred organic solvent is dioxane. In one embodiment, the prepolymer prepared with citric acid ester as component B is in a liquid state and does not need to be dissolved in an organic solvent.

[0067] In some embodiments, the conditions for the crosslinking reaction of the urethane bond or amide bond are as follows: the temperature is room temperature, for 0 to 24 h, and the reaction time > 0 h to ensure that the added organic solvent completely volatilizes. Further, the reaction time can be any value greater than 0 min, 10 min, 20 min, 30 min, 40 min, 50 min, 60 min, 1.5 h, 2 h, 2.5 h, 3 h, 3.5 h, 4 h, 4.5 h, 5 h, 5.5 h, 6 h, 6.5 h, 7 h, 7.5 h, 8 h, 8.5 h, 9 h, 10 h, 11 h, 12 h, 13 h, 14 h, 15 h, 16 h, 17 h, 18 h, 19 h, 20 h, 21 h, 22 h, 23 h, 24 h or a range value between any two values. By using the method of the present invention, the temperature is room temperature, no heating is required, and the reaction is rapid. The temperature range of room temperature is 10 - 30 °C, including but not limited to 10 °C, 15 °C, 20 °C, 25 °C, 30 °C.

[0068] In some embodiments, when preparing the self - adhesive material into a film, it includes spin - coating, solution casting or casting into a film during the crosslinking reaction of the citric acid - based prepolymer and isocyanate to form a urethane bond or amide bond.

[0069] In some embodiments, the conditions for spin - coating are as follows: the rotation speed is 1000 - 3000 rpm / min, the time is 0 - 3 min, and ≠ 0 min. Further, the rotation speed can be any value among 1000 rpm / min, 1100 rpm / min, 1200 rpm / min, 1500 rpm / min, 1800 rpm / min, 2000 rpm / min, 2200 rpm / min, 2500 rpm / min, 2800 rpm / min, 3000 rpm / min or a range value between any two values; the time can be any value among 0.01 min, 0.1 min, 0.5 min, 0.8 min, 1 min, 1.2 min, 1.5 min, 1.8 min, 2.0 min, 2.2 min, 2.5 min, 2.8 min, 3 min or a range value between any two values.

[0070] Further, in some embodiments, after spin - coating, solution casting or casting into a film, it is further crosslinked under ultraviolet light irradiation, so that a photo - crosslinkable or 3D - printable film material can be prepared. The conditions for ultraviolet light irradiation can be 365 nm ultraviolet light irradiation for 1 - 3 min.

[0071] In some embodiments, the component A is a hydroxy compound, including but not limited to polyols and ethers. The polyols such as diols. The diols include but are not limited to C2-C20, C2-C12 or C2-C6 aliphatic alkane diols, including α,ω-n-alkane diols or α,ω-alkene diols. Further, the hydroxy compound includes but is not limited to ethylene glycol, hexanediol, octanediol, polyethylene glycol, bis(4-hydroxyphenyl) disulfide, resveratrol, bis(2-hydroxyethyl) disulfide, isosorbide, xylitol, hydroxyacetate or N-methyldiethanolamine.

[0072] In some embodiments, when the component A is an amino- or mercapto-containing amino acid or other compound, it includes but is not limited to serine, phosphoserine, cysteine, glutamine, polyaniline, etc.

[0073] In some embodiments, when the component A is an epoxy compound, it includes but is not limited to epoxy soybean oil, epoxy resin, epichlorohydrin, lactide, etc.

[0074] In some embodiments, when the component A is a carboxyl- or anhydride-containing compound, it includes but is not limited to folic acid, tartaric acid, adipic acid, succinic acid, fumaric acid, salicylic acid, acetic anhydride, maleic anhydride, etc.

[0075] In some embodiments, when the component A is a compound containing an organic substituent, it includes but is not limited to polyphosphazene, etc.

[0076] In some embodiments, the citric acid and / or its derivatives include but are not limited to citric acid, trimethyl citrate, triethyl citrate, tributyl citrate, triethyl acetylcitrate, stearoyl monoglyceride citrate, citric acid luminescent molecules (such as CA-Cys).

[0077] In some embodiments, the component A is a hydrophobic compound or a hydrophilic compound. When the component A is a hydrophilic compound (such as polyethylene glycol), the prepared material is a hydrophilic material. When the component A is a hydrophobic compound (such as octanediol), the prepared material is a hydrophobic material.

[0078] In some embodiments, when the component A containing an amino acid reacts with citric acid to generate a fluorescent luminescent group, a material with fluorescent function can be prepared for applications such as biological imaging and localization.

[0079] In some embodiments, by adjusting the ratio of the citric acid-based prepolymer or isocyanate, or the molecular structure of the isocyanate, the mechanical strength of the material can be regulated, and the strength of the tissue adhesion prevention film can be significantly improved.

[0080] In some embodiments, the functional groups on the side chains of the citric acid-based prepolymer can also be loaded with drugs such as antibacterial, nerve regeneration-promoting, or tissue repair-promoting drugs, or various drugs can be encapsulated during the crosslinking process to adapt to the repair of different defect sites, thereby preparing materials with drug delivery functions, such as tissue adhesion prevention membranes.

[0081] In some embodiments, component A of the dicarboxylic acid, unsaturated fatty acid, or acid anhydride can react with citric acid to prepare a photocrosslinkable citric acid-based prepolymer. Materials adapted to the sizes and shapes of different defect sites can be prepared by 3D printing, and can be used to prepare tissue adhesion prevention membranes with photocrosslinking or 3D printing functions.

[0082] In some embodiments, using citric acid as component B, the molar ratio of it to a compound with hydroxyl, amino, mercapto, epoxy, carboxyl, acid anhydride, organic substituent, etc. in the side chain or end group of component A is 1 to 2, the polymerization temperature is 140 to 160 °C, the polymerization time is 0 to 6 h and greater than 0 h, and the rotation speed is 100 to 1000 rpm / min. Further, the polymerization temperature can be any value among 140, 142, 145, 148, 150, 153, 155, 158, 160 °C or the range value between any two values. The rotation speed can be any value among 100, 200, 500, 600, 800, 1000 rpm / min or the range value between any two values. The reaction time can be any value among 0.1 min, 1 min, 5 min, 10 min, 20 min, 0.5 h, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h or the range value between any two values.

[0083] In some embodiments, using a citric acid ester as component B, the molar ratio of it to a compound with a hydroxyl group in the side chain or end group of component A is 1 to 2, the polymerization temperature is 140 to 160 °C, the polymerization time is 0 to 48 h and greater than 0 h, and the rotation speed is 100 to 1000 rpm / min. Further, the polymerization temperature can be any value among 140, 142, 145, 148, 150, 153, 155, 158, 160 °C or the range value between any two values. The rotation speed can be any value among 100, 200, 500, 600, 800, 1000 rpm / min or the range value between any two values. The reaction time can be any value among 0.1 min, 1 min, 5 min, 10 min, 20 min, 0.5 h, 1 h, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 48 h or the range value between any two values.

[0084] The embodiments of the present invention provide the use of the self - adhesive material in any of the following:

[0085] (1) Use in the preparation of a suture - free and / or anti - adhesion biofilm;

[0086] (2) The suture - free and / or anti - adhesion biofilm can be used as a tissue anti - adhesion film for tendons, abdominal cavity, pelvic cavity, nerves, and spinal regions.

[0087] Alcohols such as hexanediol, octanediol, cyclohexane, etc., and cysteine used in the following examples are of analytical purity.

[0088] Example 1

[0089] An example of preparing a citric acid - based polymer by polycondensation reaction of citric acid and polyol and cross - linking into a film with diisocyanate.

[0090] (1) Add 10 g of citric acid and 7 g of 1,6 - hexanediol to a flask, set the rotation speed at 800 rpm / min, react at 140 °C for 3 h, precipitate the reactant with deionized water, and obtain a citric acid ester prepolymer by freeze - drying;

[0091] (2) Accurately quantify the mass of the prepolymer, add cyclohexane to obtain a prepolymer solution with a mass fraction of 50%;

[0092] (3) Take 1 g of the prepolymer solution and add 1,6 - hexamethylene diisocyanate accounting for 20% of the mass of the prepolymer (i.e., add 100 mg of 1,6 - hexamethylene diisocyanate to 0.5 g of the prepolymer), spin - coat at a speed of 1000 rpm / min on a spin coater for 1 min to form a film, and remove the film after drying to obtain a suture - free anti - adhesion film.

[0093] Perform various index detections on the obtained suture - free anti - adhesion film, and the detection results are as follows:

[0094] Figure 1 It is a physical effect picture of the suture - free anti - adhesion film prepared according to step (3) of Example 1.

[0095] Figure 2 It is a scanning electron microscope picture of the surface and thickness of the suture - free anti - adhesion film prepared according to step (3) of Example 1. As can be seen from the figure, the film prepared by this preparation method is dense, the surface is flat, and there are no pore structures, which can effectively prevent the ingrowth of fibroblasts.

[0096] Figure 3 It is an infrared spectrum diagram of the suture - free anti - adhesion film (cross - linked group) prepared according to step (3) of Example 1 and the citric acid ester prepolymer (non - cross - linked group) prepared according to step (1). The picture shows that in the cross - linked group, at 1535 cm -1A new characteristic peak appears at [specific location], which is attributed to the characteristic absorption peak of -NH- in the urethane, indicating that the film is prepared by chemical crosslinking.

[0097] Figure 4 It is the self - adhesion effect diagram of the suture - free anti - adhesion film prepared according to Example 1. The picture shows that the films can be overlapped together through hydrogen - bond interaction with each other, and self - winding occurs, thus eliminating the experimental steps of suturing.

[0098] Figure 5 It is the statistical chart of the citric acid content released by the suture - free anti - adhesion film prepared by the prepolymer prepared according to Example 1 with different mass ratios of isocyanate, and the citric acid content in cells after co - incubation; Figure 5 On the left side of [chart] is the citric acid content released by the suture - free anti - adhesion film into the supernatant; Figure 5 On the right side of [chart] is the citric acid content in cells after co - incubation of the supernatant and cells. The specific method is as follows: According to step (3) of Example 1, add different mass percentages (0%, 5%, 10%, 15%, 20%) of 1,6 - hexamethylene diisocyanate to the prepolymer solution prepared in step (2), cross - link to form a self - adhesive anti - adhesion film. Immerse an 8 - mm - diameter film in 1 mL of PBS (pH = 7.4), place it in an incubator at 37 °C for 24 h to obtain an extract, and then detect the citric acid content in the supernatant of the extract. Under the same conditions, extract with the culture medium, take the supernatant and co - culture with mouse embryonic fibroblasts (NIH / 3T3), that is, add 10,000 cells per well in a 96 - well plate and co - culture for 24 h. After 24 h, replace 100 μL of the above - mentioned extract per well and continue co - culture for 24 h, then wash with PBS at pH = 7.4, lyse, centrifuge, and determine the citric acid content in cells. The results show that the film with a high degree of cross - linking degrades slowly, and the released citric acid content is also relatively small, resulting in a corresponding decrease in the citric acid content in cells.

[0099] Example 2

[0100] The difference between this example and Example 1 is that 1,6 - hexamethylene diisocyanate is replaced with lysine diisocyanate in equal mass to prepare a film with adjustable strength.

[0101] The obtained suture - free anti - adhesion film is subjected to various index detections, and the detection results are as follows:

[0102] The obtained suture - free anti - adhesion film is subjected to water contact angle detection. The detection method is based on the national standard GB / T 30693 - 2014. Figure 6 It is the water contact angle picture of the suture - free anti - adhesion film prepared according to Example 2. The results show that the water contact angle of the film is 109.5°, indicating that the introduction of the long alkyl chain of hexanediol makes the film hydrophobic and has an anti - fouling effect.

[0103] Figure 7 It is the self - adhesion effect diagram and adhesion stability test of the suture - free anti - adhesion membrane prepared according to Example 2. The detection method is as follows: Wrap the suture - free anti - adhesion membrane outside a 1 mL syringe to simulate the wrapping effect at the tendon site. The length of the material membrane is slightly longer than the circumference of the syringe. Through the self - lap of the membrane with the membrane, the membrane material can stably wrap the outer surface of the syringe without falling off (see Figure 7 on the left side). Further, soak the whole in PBS with pH = 7.4 in a shaker at 37 °C for 1 month and then observe. The results show ( Figure 7 on the right side) that even in a wet environment, the membrane still has a good wrapping effect on the syringe surface and does not fall off, indicating that the membrane has good long - term stability in a wet environment and has the potential for application in the in - vivo wet environment.

[0104] Example 3

[0105] An example of preparing a citric acid - based polymer by polycondensation reaction of citric acid and amino acid and cross - linking with diisocyanate to prepare an imaging film.

[0106] (1) Add 10 g of citric acid and 6 g of cysteine into a flask, set the rotation speed at 800 rpm / min, react at 140 °C for 4 h, precipitate the reactant with deionized water, and obtain a citric acid ester prepolymer by freeze - drying;

[0107] Precisely quantify the mass of the prepolymer, add cyclohexane to obtain a prepolymer solution with a mass fraction of 50%;

[0108] (3) Take 1 g of the prepolymer solution and add 1,6 - hexamethylene diisocyanate accounting for 20% of the mass of the prepolymer. Spin - coat on a spin coater at a speed of 1000 rpm / min for 1 min to form a film. After the film is dried, take it off to obtain a suture - free anti - adhesion membrane.

[0109] Perform fluorescence absorption spectrum detection on the citric acid ester prepolymer obtained in step (1). The excitation wavelength is 350 nm and the emission wavelength is 420 nm. The detection results are as Figure 8 shown, Figure 8 is the fluorescence absorption spectrum of the citric acid ester prepolymer prepared according to the steps of Example 3. This proves that molecules containing amino groups such as amino acids react with citric acid to generate fluorescent groups. By using different amino acids or molecules containing amino groups, a series of photoluminescent fluorescent molecules can be obtained, which can be used to prepare a series of citric acid - based degradable polymer photoluminescent suture - free anti - adhesion membranes with adjustable excitation and emission wavelengths (visible - near infrared) for applications such as bioimaging.

[0110] Example 4

[0111] Example of preparing a citric acid-based polymer by transesterification reaction of a citrate with a polyol and crosslinking into a film with a diisocyanate.

[0112] (1) Add 10 g of triethyl citrate and 6 g of 1,6-hexanediol to a flask, set the rotation speed to 800 rpm / min, react at 140 °C for 24 h, precipitate the reactant with deionized water, and obtain a liquid citrate prepolymer by freeze-drying.

[0113] (2) Take 1 g of the prepolymer solution and add 1,6-hexamethylene diisocyanate accounting for 20% of the prepolymer mass. Spin-coat for 1 min at a speed of 1000 rpm on a spin coater to form a film. After the film is dried, remove it to obtain a sutureless anti-adhesion film.

[0114] Example 5

[0115] Example of preparing a citric acid-based polymer by polycondensation reaction of citric acid with a polyol and an acid anhydride, and crosslinking into a film with a diisocyanate and ultraviolet light.

[0116] (1) Add 8 g of citric acid, 2 g of maleic anhydride and 7 g of octanediol to a flask, set the rotation speed to 800 rpm / min, react at 140 °C for 3 h, precipitate the reactant with deionized water, and obtain a citrate prepolymer by freeze-drying.

[0117] (2) Accurately quantify the mass of the prepolymer and add cyclohexane to obtain a 50% prepolymer solution by mass fraction.

[0118] (3) Take 1 g of the prepolymer solution and add 1,6-hexamethylene diisocyanate accounting for 5% of the prepolymer mass. Spin-coat for 1 min at a speed of 1000 rpm on a spin coater to form a film, and further crosslink with ultraviolet light at 365 nm for 3 min. After the film is dried, remove it to obtain a sutureless anti-adhesion film.

[0119] Example 6

[0120] Example of preparing a citric acid-based polymer by polycondensation reaction of citric acid with a polyamine and crosslinking into a film with a diisocyanate.

[0121] (1) Add 10 g of citric acid and 6 g of hexamethylenediamine to a flask, set the rotation speed to 800 rpm / min, react at 140 °C for 3 h, precipitate the reactant with deionized water, and obtain a citrate prepolymer by freeze-drying.

[0122] (2) Accurately quantify the mass of the prepolymer and add cyclohexane to obtain a 50% prepolymer solution by mass fraction.

[0123] (3) Take 1 g of the prepolymer solution and add 1,6 - hexamethylene diisocyanate, which accounts for 10% of the mass of the prepolymer. Spin - coat it on a spin coater at a speed of 1000 rpm / min for 1 min to form a film. After the film is dried, remove it to obtain a suture - free anti - adhesion film.

[0124] Example 7

[0125] An example of preparing a citric acid - based polymer by polycondensation reaction of citric acid and polycarboxylic acid and cross - linking into a film with diisocyanate.

[0126] (1) Add 10 g of citric acid and 7 g of adipic acid into a flask. Set the rotation speed at 800 rpm / min and react at 140 °C for 3 h. Precipitate the reactant with deionized water and obtain a citric acid ester prepolymer by freeze - drying.

[0127] (2) Accurately quantify the mass of the prepolymer and add cyclohexane to obtain a 50% prepolymer solution by mass fraction.

[0128] (3) Take 1 g of the prepolymer solution and add 1,6 - hexamethylene diisocyanate, which accounts for 10% of the mass of the prepolymer. Spin - coat it on a spin coater at a speed of 1000 rpm / min for 1 min to form a film. After the film is dried, remove it to obtain a suture - free anti - adhesion film.

[0129] Figure 16 It is the synthesis equation for preparing the citric acid - based prepolymer according to the steps (1) of Examples 5 - 7.

[0130] Example 8

[0131] Prepare a suture - free anti - adhesion film in the same way as in Example 2, except that the film is spin - coated at a speed of 500 rpm / min.

[0132] Result: Observe the state of the spin - coated film. Since the prepolymer solution is hydrophobic and has a high viscosity, it is difficult to coat the film evenly at a low rotation speed. See Figure 17 .

[0133] Example 9

[0134] Prepare a suture - free anti - adhesion film in the same way as in Example 4, except that the ratio of 1,6 - hexamethylene diisocyanate added to the prepolymer is 100%.

[0135] Result: Since the ratio of isocyanate is too high, the reaction rate between the prepolymer and isocyanate is too fast, and the spin - coating solution cures quickly, making it difficult to spin - coat. See Figure 18 .

[0136] Example 10

[0137] The difference between this example and Example 1 is that toluene diisocyanate is used to replace 1,6 - hexamethylene diisocyanate in equal mass.

[0138] Result: Due to the excessive rigidity of the molecular structure of toluene diisocyanate, the strength of the prepared film is as high as 33.68 MPa, making it impossible to bend for self - winding and not being well - matched with the surrounding tissues when implanted in the body, which is likely to cause inflammatory reactions and is not suitable for in - vivo applications. See Figure 19 .

[0139] Example 11

[0140] The suture - free anti - adhesion film is prepared in the same way as in Example 1, except that polyethylene glycol 1000 is used to replace 1,6 - hexanediol in equal mass. However, at this cross - linking ratio, film - forming cannot occur.

[0141] Example 12

[0142] The suture - free anti - adhesion film is prepared in the same way as in Example 1, except that (3) 1 g of the prepolymer solution is taken and 1,6 - hexamethylene diisocyanate accounting for 5% of the mass of the prepolymer is added.

[0143] Result: Due to the too - low cross - linking ratio, there are insufficient hydrogen - bonding sites for self - adhesion performance, so the self - adhesion performance of the material is poor. It shows self - adhesion effect in the dry state, but once immersed in PBS with pH = 7.4, the self - adhesion part shifts and falls off, losing the self - adhesion effect. See Figure 20 .

[0144] Example 13

[0145] The suture - free anti - adhesion film is prepared in the same way as in Example 1, except that the system of the film - forming solution is enlarged by 5 times, that is, 5 g of the prepolymer solution is added with 1,6 - hexamethylene diisocyanate accounting for 20% of the mass of the prepolymer (i.e., 2.5 g of the prepolymer is added with 500 mg of hexamethylene diisocyanate), and then spin - coated into a film.

[0146] Result: The thickness of the coating is measured with a vernier caliper, about 720 μm. The too - thick film material leads to too large surface tension of the film, and the hydrogen - bonding effect at the film - bonding part cannot maintain a good self - adhesion effect, so the film material loses its self - adhesion performance. At the same time, due to the relatively thick film material, there is an obvious foreign - body sensation when contacting with skin tissues, which is not suitable for use inside tissues. While the coating thickness of the film material in Example 1 is about 100 μm, which can effectively self - adhere at the finger part and does not crack even when bent, having good self - adhesion performance. Therefore, the thickness of the film material is also closely related to the self - adhesion performance. See Figure 21 .

[0147] Comparative Example 1

[0148] The sutureless anti-adhesion film was prepared in the same manner as in Example 1, except that isocyanate crosslinking was not used and only thermal crosslinking was used. That is, 1 g of the prepolymer solution was spin-coated on a spin coater at a speed of 1000 rpm / min for 1 min to form a film, which was then thermally crosslinked in an oven at 80 °C. After the film was dried, it was taken down to obtain the sutureless anti-adhesion film.

[0149] Results: With thermal crosslinking, the film material was only crosslinked by ester bonds, lacking hydrogen bond sites, and the self-adhesive performance of the material was poor, as shown in Figure 20 .

[0150] Experimental Example 1 This experimental example investigated the various properties of the sutureless anti-adhesion films prepared in Examples 1 to 4.

[0151] The detection method was as follows: The film material was made into a spline with a width of 1.5 cm and a length of 4 cm, placed on a universal testing machine, and clamped at positions 0.5 cm above and below, and stretched at a rate of 50 mm / min. The results were as shown in Figure 9 . Figure 9 The mechanical properties of the sutureless anti-adhesion films prepared according to Examples 1 to 4 are shown. Their tensile strength was 50 - 100 KPa, which could be regulated by controlling the molecular structure of the isocyanate, matching the mechanical properties of commercially available materials, and meeting the support requirements at the tendon injury site.

[0152] The detection method was as follows: Two sutureless anti-adhesion films prepared in the same way were overlapped face to face, and a uniform pressure was applied to the entire overlapping surface. It was recommended that the applied pressure could reach 1 MPa, in a T shape, as shown in the left side of Figure 10 . The strength of the bonding site was measured with reference to the national standard GB / T 2791-1995.

[0153] As shown in Figure 10 The right side shows the self-adhesive performance of the sutureless anti-adhesion films prepared according to the steps of Examples 1 to 4. The results showed that the prepared films had self-adhesiveness, with a strength of 0.14 - 0.22 MPa, and their bonding strength could be adjusted by controlling the molecular structure of the isocyanate.

[0154] The detection method was as follows: The sutureless anti-adhesion films (8 mm in diameter) prepared in each example were separately immersed in 1 mL of DMEM culture medium and placed in an incubator at 37 °C for 24 h to obtain the extract. Then, the extract was taken to replace an equal volume of the cell supernatant and co-cultured with mouse embryonic fibroblasts (NIH / 3T3). That is, 10,000 cells were added to each well of a 96-well plate for co-culture for 24 h. After 24 h, 100 μL of the extract was replaced in each well and co-cultured for another 24 h. Then, CCK8 was used to measure the absorbance value at OD 600 nm. Among them, the all-alive group was replaced with cell culture medium, and the all-dead group was replaced with sterile water. The cell survival rate calculation formula was as follows:

[0155] Cell viability = (OD 材料组 - OD 全死组 ) / (OD 全活组 - OD 全死组 ) × 100%.

[0156] As Figure 11 is the cytotoxicity of the sutureless anti - adhesion membrane prepared according to the steps of Examples 1 - 4. The results show that the cell viability of all groups is higher than 70%, indicating that the citric acid - based sutureless anti - adhesion membrane prepared by this preparation method has good biocompatibility and can be used for further in - vivo characterization.

[0157] (4) Anti - protein adhesion effect

[0158] The detection method is as follows: Place the 8 - mm - diameter membranes prepared in each example in the wells of a 48 - well plate. Prepare a 2 - mg / mL solution of FITC - labeled BSA with PBS, and add 200 μL to each well. At the same time, set a control group, and the control group uses a commercially available membrane material (Seprafilm®). Incubate at 37 °C for 2 h, wash with PBS, and then observe with a fluorescence microscope.

[0159] As Figure 12 is the anti - protein adhesion effect diagram of the sutureless anti - adhesion membrane prepared according to the steps of Examples 1 - 4. The results show that the citric acid - based sutureless anti - adhesion membrane prepared by this preparation method can effectively prevent protein adhesion on its surface and play a good role in anti - adhesion.

[0160] Experimental Example 2 This experimental example examines the anti - adhesion effect of the sutureless anti - adhesion membrane in a tendon injury model

[0161] Application in tendon injury model: Use SD rats weighing about 200 - 250 g to establish an in - vivo tendon injury animal model. Anesthetize the rats with sodium pentobarbital, remove the hair on the surface of the Achilles tendon, disinfect with iodophor, longitudinally incise the skin along the Achilles tendon, make a transverse cut and severance at the Achilles tendon site, wrap it with a membrane with a size of 1.0 cm × 2.0 cm (width × length), and then suture the skin and disinfect again. The membrane is the sutureless anti - adhesion membrane prepared according to the steps of Examples 2 and 4, and the control group is sutured with surgical thread.

[0162] As Figure 13 is the wrapping effect diagram of the sutureless anti - adhesion membrane prepared according to Examples 2 and 4 at the tendon injury site of rats. The results show that the membranes prepared by the methods of Examples 2 and 4 can effectively wrap the tendon injury site, without the need for suture, greatly shortening the operation time and avoiding the risk of infection, while the control group requires surgical suture to ensure docking repair.

[0163] Figure 14It is the tissue H&E staining section of the sutureless anti-adhesion membrane prepared according to Example 4 after being wrapped around the tendon injury site of rats for 1 day. The results show that a large number of inflammatory cell infiltrations occurred in the control group, while the membrane prepared by the method of Example 4 has good biocompatibility in vivo. And there is an obvious gap between the tendon and the muscle, indicating that the citric acid-based sutureless anti-adhesion membrane has good anti-adhesion effect in vivo and can effectively avoid the occurrence of fibrous adhesion phenomenon.

[0164] Figure 15 It is the gross observation diagram of the sutureless anti-adhesion membrane prepared according to Example 4 after being wrapped around the tendon injury site of rats for 9 weeks. The results show that the membrane is completely degraded at 9 W. This result indicates that the citric acid-based anti-adhesion membrane prepared by this method is completely biodegradable in vivo, has good biocompatibility, and will not accumulate in human internal tissues or organs.

[0165] Obviously, the above embodiments are only examples given for clear illustration, rather than limitations on the implementation manners. For those of ordinary skill in the art, other different forms of changes or alterations can be made based on the above description. It is not necessary and impossible to enumerate all the implementation manners here. And the obvious changes or alterations derived therefrom are still within the protection scope of the present invention.

Claims

1. A method for preparing a self-adhesive material, characterized in that: include: reacting component A and component B to form a citric acid based prepolymer; Component A is at least one compound having at least two reactive functional groups on the terminal group or side chain, the functional groups being the same or different; the functional groups being at least one selected from hydroxyl, amino, thiol, epoxy, carboxyl, anhydride, and organic substituents; component B is citric acid and / or its derivatives; the reaction comprises polycondensation, substitution, or transesterification; The citric acid-based prepolymer and isocyanate are subjected to a urethane bond or an amide bond cross-linking reaction.

2. The method for preparing a self-adhesive material according to claim 1, characterized in that: The isocyanate is selected from at least one of 1,6-hexamethylene diisocyanate, isophorone diisocyanate, toluene diisocyanate, lysine diisocyanate, naphthalene diisocyanate, 1,4-cyclohexyl diisocyanate, 4,4'-diphenylmethane diisocyanate and 4,4'-diisocyanate dicyclohexylmethane.

3. The method for preparing a self-adhesive material according to claim 2, characterized in that: The isocyanate is selected from at least one of 1,6-hexamethylene diisocyanate, lysine diisocyanate and isophorone diisocyanate.

4. The method for preparing a self-adhesive material according to any one of claims 1 to 3, characterized in that: When the citric acid-based prepolymer is in a solid state, before the cross-linking reaction of the urethane bond or the amide bond is carried out, the citric acid-based prepolymer is dissolved in an organic solvent to obtain a citric acid-based prepolymer solution; isocyanate is added to the citric acid-based prepolymer solution to obtain a mixed solution, and then the cross-linking reaction of the urethane bond or the amide bond is carried out; The mass percentage of the citric acid-based prepolymer in the citric acid-based prepolymer solution is 30-60%; The mass percentage of the isocyanate added to the citric acid-based prepolymer is greater than 0% and less than or equal to 50%.

5. The method for preparing a self-adhesive material according to any one of claims 1 to 3, characterized in that: The conditions for the cross-linking reaction of the urethane bond or amide bond are: the temperature is room temperature, the reaction time is 0 to 24 h, and the reaction time is greater than 0 h.

6. The method for preparing a self-adhesive material according to any one of claims 1 to 3, characterized in that: When the self-adhesive material is prepared into a film, the mixed solution of citric acid-based prepolymer and isocyanate is subjected to spin coating, solution casting or tape casting to form a film during the cross-linking reaction of urethane bonds or amide bonds.

7. The method for preparing a self-adhesive material according to claim 6, characterized in that: The spin coating conditions are as follows: a rotation speed of 1000-3000 rpm / min, a time of 0-3 min, and ≠0 min; And or, the film has a thickness of 10-500 μm.

8. The method for preparing a self-adhesive material according to any one of claims 1 to 3, characterized in that: The component A is a hydrophobic compound or a hydrophilic compound; And / or, when component A is a hydroxy compound, it includes but is not limited to ethylene glycol, hexylene glycol, octanediol, polyethylene glycol, bis(4-hydroxyphenyl) disulfide, resveratrol, bis(2-hydroxyethyl) disulfide, isosorbide, xylitol, glycolate or N-methyldiethanolamine; and / or, when component A is an amino acid or other compound containing an amino group or a thiol group, including but not limited to serine, phosphoserine, cysteine, glutamine or polyaniline; and / or, when component A is an epoxy compound, it includes but is not limited to epoxy soybean oil, epoxy resin, epichlorohydrin or lactide; and / or, when component A is a compound containing a carboxyl group or anhydride, it includes but is not limited to folic acid, tartaric acid, adipic acid, succinic acid, fumaric acid, salicylic acid, acetic anhydride or maleic anhydride; And / or, when the component A is a compound containing an organic substituent, it includes but is not limited to polyphosphazene; And / or, the citric acid and / or its derivatives include but are not limited to citric acid, trimethyl citrate, triethyl citrate, tributyl citrate, acetyl triethyl citrate, stearoyl monoglyceride citrate or citric acid luminescent molecules.

9. A self-adhesive material prepared by the method for preparing a self-adhesive material according to any one of claims 1 to 8.

10. The self-adhesive material according to claim 9 is used for the following purposes: The invention relates to a use of a suture-free and / or anti-adhesion biofilm in the preparation of a suture-free and / or anti-adhesion biofilm; the suture-free and / or anti-adhesion biofilm is used as a tissue anti-adhesion membrane for tendons, abdominal cavity, pelvic cavity, nerves, and spinal cord.

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