Self-adhesive material, and preparation method therefor and use thereof

Abstract

Provided is a preparation method for a self-adhesive material, the preparation method comprising: reacting a component A with a component B to form a citric acid-based prepolymer, wherein the component A is at least one compound containing at least two reactive functional groups on a terminal group or a side chain, the functional groups being the same or different and selected from at least one of a hydroxyl, an amino, a mercapto, an epoxy group, a carboxyl, an anhydride, and an organic substituent; the component B is citric acid and / or a derivative thereof; and the reaction comprises a polycondensation reaction, a substitution reaction or a transesterification reaction. The citric acid-based prepolymer and an isocyanate are subjected to a cross-linking reaction via an amine-ester bond or an amide bond. The material obtained by means of the preparation method has good self-adhesiveness between contact surfaces thereof, and can be used for suture-free fixation, thereby greatly reducing the difficulty of surgical operation and the risk of infection, reducing damage to tissues, and improving the success rate of surgery.

Description

Self-adhesive material and preparation method and use thereof

[0001] Cross-reference to related applications

[0002] This application claims priority to the Chinese patent application No. 202510194327.5, filed on February 21, 2025, and entitled “Self-adhesive material and preparation method and use thereof”, the entire contents of which are incorporated herein by reference. TECHNICAL FIELD

[0003] The present application relates to the field of biomedical materials, in particular to a self-adhesive material and a preparation method and use thereof. BACKGROUND

[0004] Biological membranes in the field of biomedical materials are generally materials for replacing and repairing human tissues. According to different application scenarios, such as wound dressings, medical adhesives, anti-adhesion membranes, etc. Among them, the function of anti-adhesion membrane is to prevent tissue adhesion. Tissue adhesion refers to the pathological state that the contact surface of adjacent tissues or organs is connected together by fibrous or newly formed fibrous tissue in the scar tissue. It is a common clinical phenomenon after surgery and a necessary process for patient healing. The formation of adhesion is usually related to surgery, trauma, inflammation, infection or foreign bodies in the abdominal cavity, etc. For example, tendon adhesion, which is closely related to the tendon healing process, can be divided into two mechanisms of endogenous and exogenous healing. Endogenous healing can prevent tendon adhesion by proliferation of fibroblasts on the surface of the tendon itself to achieve tendon healing. While exogenous healing involves the generation of new granulation tissue in the subcutaneous tissue and synovial membrane of the tendon at the tendon rupture surface, forming scar tissue and leading to adhesion. In addition, the destruction of tendon blood supply and integrity, and the inflammatory reaction of peritendinous tissue are also important reasons for the formation of tendon adhesion. In addition, adhesion can cause small bowel obstruction, secondary infertility, pain at the site of disease, or joint movement dysfunction and other complications. Due to the serious complications that may be caused by adhesion, preventing the occurrence of adhesion is of great significance to improve the quality of life of patients and reduce medical costs.

[0005] At present, the anti-adhesion biological membrane material used as a physical barrier can inhibit the formation of adhesion by isolating the injury site from the surrounding tissue, which has become a commonly used method in clinical practice. At present, researchers have developed various anti-adhesion membranes prepared from biological materials, including natural materials (such as collagen, hyaluronic acid), synthetic materials (such as polylactic acid, polyglycolic acid) and composite materials. These materials have improved the effect of tissue repair to some extent. For example, the decellularized pericardial membrane reported in patent document CN116077739A has a double-sided structure and can effectively block adhesion. The composite nanofiber membrane proposed in CN111714696A has good biocompatibility and mechanical properties.

[0006] However, the existing anti-adhesion biomembrane materials still have some deficiencies: most of the anti-adhesion biomembrane needs to be fixed by suture, which increases the difficulty of operation and the risk of infection. In addition, the degradation rate, mechanical strength and tissue biocompatibility of the material still need to be further optimized. Therefore, it is of great significance to develop an anti-adhesion biomaterial with self-adhesion, good biocompatibility and absorbability for improving the effect of tissue repair. SUMMARY

[0007] Therefore, the technical problem to be solved by the present application is to overcome the deficiencies in the prior art that the anti-adhesion biomembrane material needs to be fixed by suture, which increases the difficulty of operation and the risk of infection, and the degradation rate, mechanical strength and tissue biocompatibility are difficult to satisfy, thereby providing a self-adhesive material and a preparation method and uses thereof. The self-adhesive material can be suture-free due to its self-adhesion, can reduce the difficulty of operation and the risk of infection when applied to an anti-adhesion membrane, and has degradability, good biocompatibility and adjustable mechanical properties, and can also endow the biomaterial with functions such as luminescent positioning, drug delivery, repair promotion, antibiosis and vascular regeneration.

[0008] To this end, the present application provides the following technical solutions:

[0009] The present application provides a preparation method of a self-adhesive material, comprising:

[0010] 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, anhydride, and organic substituent; component B is citric acid and / or its derivative; the reaction includes polycondensation reaction, substitution reaction or ester exchange reaction;

[0011] crosslinking the citric acid-based prepolymer and isocyanate by urethane bond or amide bond.

[0012] 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'-diphenyl methane diisocyanate or 4,4'-diisocyanate dicyclohexyl methane.

[0013] Optionally, the isocyanate is selected from at least one of 1, 6-hexamethylene diisocyanate, lysine diisocyanate and isophorone diisocyanate.

[0014] Optionally, when the citric acid-based prepolymer is in solid state, the citric acid-based prepolymer is dissolved in an organic solvent to obtain a citric acid-based prepolymer solution before the cross-linking reaction of urethane bond or amide bond; the isocyanate is added into the citric acid-based prepolymer solution to obtain a mixed solution, and then the cross-linking reaction of urethane bond or amide bond is performed;

[0015] The mass percentage of the citric acid-based prepolymer in the citric acid-based prepolymer solution is 30-60%.

[0016] The mass percentage of the isocyanate added in the citric acid-based prepolymer is >0% and ≤50%.

[0017] Optionally, the cross-linking reaction of urethane bond or amide bond is performed at room temperature for 0-24 h, and the reaction time is >0 h to ensure that the added organic solvent is completely volatilized.

[0018] Optionally, when the self-adhesive material is prepared into a film, the mixed solution of the citric acid-based prepolymer and the isocyanate is spin-coated, solution-casted or flow-casted into a film during the cross-linking reaction of urethane bond or amide bond.

[0019] Optionally, the spin-coating is performed at a rotation speed of 1000-3000 rpm / min for 0-3 min, and the time is ≠0 min.

[0020] Optionally, the thickness of the film is 10-500 μm. The thinner film material can better fit the tissue damage site, reduce the foreign body sensation, and effectively maintain the self-adhesive state under the small tension effect.

[0021] Optionally, the component A is a hydrophobic compound or a hydrophilic compound.

[0022] When the component A is a hydroxyl 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-methyl diethanolamine.

[0023] When the component A is an amino acid or other compound containing amino or mercapto, it includes but is not limited to serine, phosphoserine, cysteine, glutamine or polyaniline.

[0024] When the component A is an epoxy compound, it includes but is not limited to epoxidized soybean oil, epoxy resin, epichlorohydrin or lactide.

[0025] When the component A is a compound containing carboxyl 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.

[0026] and / or, when the component A is an organic substituent-containing compound, includes but is not limited to polyphosphazene;

[0027] 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, stearyl monoglyceride citrate or citric acid luminescent molecules.

[0028] The application provides a self-adhesive material prepared by the self-adhesive material preparation method.

[0029] The application provides the use of the self-adhesive material in any one of the following:

[0030] In the preparation of a suture-free and / or anti-adhesion biological membrane; the suture-free and / or anti-adhesion biological membrane is a tissue anti-adhesion membrane for tendons, abdominal cavities, pelvic cavities, nerves and spinal parts.

[0031] The technical scheme of the application has the following advantages:

[0032] 1. The self-adhesive material preparation method provided by the application comprises: 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 a hydroxyl group, an amino group, a mercapto group, an epoxy group, a carboxyl group, an acid anhydride and an organic substituent; component B is citric acid and / or its derivatives; the reaction includes polycondensation, substitution or ester exchange; and the citric acid-based prepolymer and isocyanate are subjected to cross-linking reaction of urethane bond or amide bond; the application research shows that, by directly cross-linking the citric acid-based prepolymer with isocyanate, the cross-linking points are urethane bond or amide bond, for example, isocyanate groups react with hydroxyl groups to form urethane bond cross-linking, the urethane bond or amide bond formed by cross-linking improves the hydrogen bond interaction between the contact surfaces of the material, so that the obtained material has good self-adhesion between the contact surfaces, can be fixed without suture in application, greatly reduces the operation difficulty and infection risk, the obtained material can be directly attached to the surface of the defect part, effectively avoids the defects that the traditional membrane needs to be sutured and the suture line may cause inflammatory reaction due to abrasion of the tissue, greatly simplifies the operation, reduces the damage to the tissue and improves the success rate of the operation;

[0033] Further, 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 exogenous citric acid released by degradation can promote the repair of the defect part through metabolic regulation;

[0034] In summary, compared with the anti-adhesion film prepared by traditional synthetic materials, the citric acid-based material prepared in the application has low manufacturing cost, simple preparation method, better biocompatibility, stronger self-adhesion, simpler operation method and potential multifunctionality (such as antibacterial, in vivo imaging, repair promotion, etc.). The material has broad application prospects in the field of tissue defect repair, can effectively prevent adhesion, promote tissue regeneration and improve the postoperative function of patients.

[0035] 2. The self-adhesive material preparation method provided in the application, wherein the isocyanate is at least one selected from 1,6-hexamethylene diisocyanate, isophorone diisocyanate, toluene diisocyanate, lysine diisocyanate, naphthalene diisocyanate, 1,4-cyclohexyl diisocyanate, 4,4'-diphenyl methane diisocyanate or 4,4'-diisocyanate dicyclohexyl methane. By directly cross-linking the citric acid-based prepolymer with isocyanate, the urethane bond or amide bond formed by cross-linking improves the hydrogen bond interaction between the contact surfaces of the material, so that the obtained material has good self-adhesion between the contact surfaces, and can be fixed without suture in application, greatly reducing the operation difficulty and infection risk. The above-mentioned isocyanates can realize this function by adjusting the addition ratio with the prepolymer. Further, because the self-adhesive material needs to have a winding performance, if it is too hard or too brittle, it will affect its winding performance, therefore, if the molecular structure of the selected isocyanate is too strong or the amount is too much, it will cause the strength of the material to rise, which is not conducive to winding, and the implanted body is easy to produce obvious foreign body sensation, which is easy to cause inflammation reaction, and the molecular structure of the above-mentioned isocyanate can ensure that the prepared self-adhesive material has a winding performance, and further, 1,6-hexamethylene diisocyanate, lysine diisocyanate and isophorone diisocyanate belong to isocyanates with flexible molecular chain structure, and the prepared self-adhesive material has excellent winding performance.

[0036] 3. The self-adhesive material preparation method provided in the present application, comprising: when the citric acid-based prepolymer is in a solid state, dissolving the citric acid-based prepolymer in an organic solvent to obtain a citric acid-based prepolymer solution before cross-linking reaction of urethane bond or amide bond is performed; adding isocyanate to the citric acid-based prepolymer solution to obtain a mixed solution, and then performing cross-linking reaction of urethane bond or amide bond; the mass percentage of the citric acid-based prepolymer in the citric acid-based prepolymer solution is 30-60%; and the mass percentage of the isocyanate added to the citric acid-based prepolymer is >0% and ≤50%. By controlling the ratio of the citric acid-based prepolymer and the isocyanate, the adhesion of the material can be improved, because the urethane bond or amide bond formed by directly cross-linking the citric acid-based prepolymer with the isocyanate improves the hydrogen bond interaction between the contact surfaces of the material, so that the obtained material has good self-adhesion between the contact surfaces, and therefore the ratio of the citric acid-based prepolymer and the isocyanate will directly affect the content of the hydrogen bond, thereby affecting the adhesion of the material. Further, because the self-adhesive material needs to have a winding performance, if it is too hard or too brittle, the winding performance will be affected, and therefore if the amount of the isocyanate used is too much, the strength of the material will increase, which is not conducive to winding, and the material implanted in the body is easy to produce obvious foreign body sensation and easily cause inflammatory reaction. By selecting the above ratio, a self-adhesive material with better winding performance can be prepared.

[0037] 4. The self-adhesive material preparation method provided in the present application, when the self-adhesive material is prepared into a film, comprising: spin coating the mixed solution of the citric acid-based prepolymer and the isocyanate during the cross-linking reaction of urethane bond or amide bond; and the spin coating condition is that the rotation speed is 1000-3000 rpm / min, and the time is 0-3 min and ≠0 min. By using the spin coating method to prepare the film, the solvent can be quickly volatilized in the process of rapid rotation, so that the thickness of the prepared film can be controlled and quickly dried.

[0038] 5. The self-adhesive material preparation method provided in the present application, wherein component A is a hydrophobic compound or a hydrophilic compound; by changing the structure of component A, a hydrophilic or hydrophobic material can be prepared. In the present application, by selecting octanediol compounds, a hydrophobic anti-adhesion biological film can be obtained, and by selecting polyethylene glycol hydrophilic compounds, a hydrophilic anti-adhesion biological film can be obtained. BRIEF DESCRIPTION OF DRAWINGS

[0039] In order to more clearly illustrate the specific embodiments of the present application or the technical solutions in the prior art, the drawings needed in the following description of the specific embodiments or the prior art will be briefly introduced. Obviously, the drawings in the following description are some embodiments of the present application, and other drawings can also be obtained by those skilled in the art without creative labor.

[0040] Figure 1 is a photograph of the sutureless anti-adhesion film prepared according to Example 1.

[0041] Figure 2 is a scanning electron microscope image of the surface and cross-section of the sutureless anti-adhesion film prepared according to Example 1.

[0042] Figure 3 is an infrared spectrum of the sutureless anti-adhesion film prepared according to Example 1.

[0043] Figure 4 is a photograph of the self-adhesion of the sutureless anti-adhesion film prepared according to Example 1.

[0044] Figure 5 is a bar graph of the citric acid content released from the sutureless anti-adhesion film prepared according to Example 1 from different mass ratios of isocyanate, and the intracellular citric acid content after co-incubation; the left side is the citric acid content released into the supernatant from the sutureless anti-adhesion film; the right side is the intracellular citric acid content after co-incubation of the supernatant with cells.

[0045] Figure 6 is a water contact angle graph of the sutureless anti-adhesion film prepared according to Example 2.

[0046] Figure 7 is a photograph of the self-adhesion of the sutureless anti-adhesion film prepared according to Example 2.

[0047] Figure 8 is a fluorescence absorption spectrum of the citrate ester prepolymer prepared according to Example 3.

[0048] Figure 9 is the mechanical property of the sutureless anti-adhesion film prepared according to Examples 1-4.

[0049] Figure 10 is the self-adhesion property of the sutureless anti-adhesion film prepared according to the steps of Examples 1-4.

[0050] Figure 11 is the cell compatibility of the sutureless anti-adhesion film prepared according to the steps of Examples 1-4.

[0051] Figure 12 is a photograph of the anti-protein adhesion effect of the sutureless anti-adhesion film prepared according to Examples 1-4.

[0052] Figure 13 is a photograph of the in vivo self-adhesion effect of the sutureless anti-adhesion film prepared according to Example 2 and Example 4.

[0053] Figure 14 is an H&E staining section of the tissue in vivo of the sutureless anti-adhesion film prepared according to Example 4.

[0054] Figure 15 is a photograph of the degradation in vivo of the sutureless anti-adhesion film prepared according to Example 4.

[0055] Figure 16 is a synthesis equation of the citric acid-based prepolymer prepared according to Step 1 of Examples 5-7.

[0056] Figure 17 is a photograph of the preparation method according to Example 8.

[0057] Figure 18 is a picture of the effect prepared according to the preparation method of Example 9.

[0058] Figure 19 is the tensile strength of the suture-free anti-adhesion film prepared according to Example 10.

[0059] Figure 20 is the self-adhesion strength of the suture-free anti-adhesion film prepared according to Example 12 and Comparative Example 1, and the film material prepared is immersed in PBS with pH = 7.4 to observe the wet-state adhesion performance.

[0060] Figure 21 is a comparison of the self-adhesion performance of the suture-free anti-adhesion film prepared according to Example 1 and Example 13, and the film material thickness significantly affects the self-adhesion strength. DETAILED DESCRIPTION

[0061] The following examples are provided to better enable those skilled in the art to further understand and practice the application, and are not intended to limit the scope of the application described and claimed herein, nor are they intended to limit the scope of the disclosure. Any product prepared according to the teachings of this application, or any modification thereof, or any other product or method that is equivalent thereto, falls within the scope of this application.

[0062] If the specific experimental steps or conditions are not specified in the examples, they can be carried out according to the conventional experimental steps described in the literature in the art. If the reagents or instruments used are not specified by the manufacturer, they are all conventional reagent products that can be obtained commercially.

[0063] The embodiment of the present application discloses a self-adhesive material preparation method, comprising: 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, the functional groups are the same or different; the functional groups are selected from at least one of hydroxyl, amino, mercapto, epoxy, carboxyl, anhydride, and organic substituent; component B is citric acid and / or its derivative; the reaction includes polycondensation reaction, substitution reaction or ester exchange reaction; and the citric acid-based prepolymer and isocyanate are subjected to cross-linking reaction of urethane bond or amide bond. The present application finds that isocyanate does not participate in the preparation process of polyester prepolymer, and isocyanate is directly cross-linked with citric acid-based prepolymer at the cross-linking point of urethane bond or amide bond, without the need for thermal cross-linking, and the obtained material has self-adhesion, the reason is mainly that the material mainly forms urethane bond or amide bond through isocyanate cross-linking, which can improve the hydrogen bond interaction between the contact surfaces of the material to realize self-adhesion, so that when the material is applied to an anti-adhesion film, it can be suture-free to reduce the difficulty of surgical operation and the risk of infection, and the material also has a satisfactory degradation rate, mechanical strength and tissue compatibility.

[0064] 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'-diisocyanatodicyclohexylmethane. By using isocyanate to directly crosslink the citric acid-based prepolymer, the urethane bond or amide bond formed by crosslinking improves the hydrogen bond interaction between the material contact surfaces, so that the obtained material contact surfaces have good self-adhesion, which can be fixed without suture in application, greatly reducing the difficulty of surgical operation and the risk of infection. The above-mentioned isocyanates can achieve this function by adjusting the addition ratio with the prepolymer.

[0065] Further, because the self-adhesive material needs to have a winding performance, if it is too hard or too brittle, it will affect its winding performance, therefore, if the molecular structure of the selected isocyanate is too strong or the amount is too much, it will cause the strength of the material to rise, which is not conducive to winding, and the implanted body is easy to produce obvious foreign body sensation, which is easy to trigger inflammatory reaction, and the molecular structure of the above-mentioned isocyanate can ensure that the self-adhesive material prepared has a winding performance.

[0066] In a preferred embodiment, the isocyanate is selected from at least one of 1,6- hexamethylene diisocyanate, lysine diisocyanate and isophorone diisocyanate. The molecular structure of 1,6-hexamethylene diisocyanate, lysine diisocyanate and isophorone diisocyanate is smaller than that of diisocyanate with branched or cyclic structure, so the rigidity of its molecular chain is smaller, therefore, when the ratio is adjusted, the upper limit of its addition amount is higher, more hydrogen bond structures can be introduced, so that the self-adhesion performance of the material is also increased accordingly.

[0067] In some embodiments, when the citric acid-based prepolymer is in a solid state, the citric acid-based prepolymer is dissolved in an organic solvent to obtain a citric acid-based prepolymer solution before the cross-linking reaction of urethane bond or amide bond is performed; 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 performed; the mass percentage of the citric acid-based prepolymer in the citric acid-based prepolymer solution is 30-60%; and the mass percentage of the isocyanate added to the citric acid-based prepolymer is >0% and ≤50%. Further, the mass percentage of the citric acid-based prepolymer in the citric acid-based prepolymer solution can be any one of 30%, 33%, 35%, 38%, 40%, 43%, 45%, 48%, 50%, 53%, 55%, 58%, 60% or a range value between any two of them; and the mass percentage of the isocyanate added to the citric acid-based prepolymer can be any one of 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 a range value between any two of them. By controlling the ratio of the citric acid-based prepolymer and the isocyanate, the adhesion of the material can be improved, because the urethane bond or amide bond formed by the direct cross-linking of the isocyanate and the citric acid-based prepolymer improves the hydrogen bond interaction between the contact surfaces of the material, so that the obtained material has good self-adhesion between the contact surfaces, and therefore the ratio of the citric acid-based prepolymer and the isocyanate will directly affect the content of the hydrogen bond, thereby affecting the adhesion performance of the material. Further, because the self-adhesive material needs to have a winding performance, if it is too hard or too brittle, it will affect the winding performance, and if the amount of isocyanate used is too much, it will cause the strength of the material to rise, which is not conducive to winding, and it is easy to produce obvious foreign body sensation in the body and easily cause inflammation. By selecting the above ratio, a self-adhesive material with better winding performance can be prepared.

[0068] In some embodiments, the prepolymer prepared with citric acid as component B is in a solid state and needs to be dissolved in 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 optional 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.

[0069] In some embodiments, the cross-linking reaction of the urethane bond or amide bond is carried out at room temperature for 0-24 h and for a reaction time >0 h, ensuring complete evaporation of the added organic solvent. Further, the reaction time can be >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 any range between any two of the listed values. Using the method of the present application, the reaction is rapid at room temperature without the need for heating, and the temperature range at room temperature is 10-30 °C, including but not limited to 10 °C, 15 °C, 20 °C, 25 °C, 30 °C.

[0070] In some embodiments, when the self-adhesive material is prepared as a film, the mixture of citric acid-based prepolymer and isocyanate is spin-coated, solution-cast, or flow-cast into a film during the cross-linking reaction of the urethane bond or amide bond.

[0071] In some embodiments, the spin-coating is carried out at a rotation speed of 1000-3000 rpm / min for a time of 0-3 min, and ≠0 min. Further, the rotation speed can be any one of 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 any range between any two of the listed values; and the time can be any one of 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 any range between any two of the listed values.

[0072] Further, in some embodiments, after spin-coating, solution-casting, or flow-casting into a film, the film is further cross-linked under UV light, thereby preparing a photo-cross-linkable or 3D-printable film material. The UV light can be 365 nm UV light for 1-3 min.

[0073] In some embodiments, the component A is a hydroxyl compound, including but not limited to polyols, ethers. The polyols are, for example, diols. The diols include but are not limited to C2-C20, C2-C12, or C2-C6 aliphatic alkane diols, including a, ω- n-alkane diols or a, ω-alkene diols. Further, the hydroxyl compounds include but are not limited to ethylene glycol, hexanediol, octanediol, polyethylene glycol, bis(4-hydroxyphenyl)disulfide, resveratrol, bis(2-hydroxyethyl)disulfide, isosorbide, xylitol, glycolate, or N-methyldiethanolamine.

[0074] In some embodiments, the component A is an amino acid or other compound containing amino or sulfhydryl groups, including but not limited to serine, phosphoserine, cysteine, glutamine, polyaniline, etc.

[0075] In some embodiments, the component A is an epoxy compound, including but not limited to epoxidized soybean oil, epoxy resin, epichlorohydrin, lactide, etc.

[0076] In some embodiments, the component A is a carboxyl or anhydride containing compound, including but not limited to folic acid, tartaric acid, adipic acid, succinic acid, fumaric acid, salicylic acid, acetic anhydride, maleic anhydride, etc.

[0077] In some embodiments, the component A is an organic substituent containing compound, including but not limited to polyphosphazene, etc.

[0078] In some embodiments, the citric acid and / or its derivatives include but are not limited to citric acid, trimethyl citrate, triethyl citrate, tributyl citrate, acetyl triethyl citrate, stearyl monoglyceryl citrate, citric acid luminescent molecules (such as CA-Cys).

[0079] 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.

[0080] In some embodiments, when the component A containing amino acid reacts with citric acid, a fluorescent luminescent group can be generated, and a material with fluorescent function can be prepared for applications such as biological imaging and positioning.

[0081] In some embodiments, by adjusting the ratio of citric acid-based prepolymer or isocyanate, or the molecular structure of isocyanate, the mechanical strength of the material can be controlled, and the strength for tissue adhesion prevention membrane can be significantly improved.

[0082] In some embodiments, the functional groups of the side chains of the citric acid-based prepolymer can also load antibacterial, nerve regeneration promoting, or tissue repair promoting drugs, or load various drugs during the crosslinking process to adapt to the repair of different defect sites, so as to prepare materials with drug delivery function, such as tissue anti-adhesion membranes.

[0083] In some embodiments, component A of dicarboxylic acid, unsaturated fatty acid or anhydride can react with citric acid to prepare a light-crosslinkable citric acid-based prepolymer, which can be prepared by 3D printing to adapt to the size and shape of different defect sites, and can be used to prepare tissue anti-adhesion membranes with light crosslinking or 3D printing function.

[0084] In some embodiments, citric acid is used as component B, the molar ratio of which to the compound containing hydroxyl, amino, mercapto, epoxy, carboxyl, anhydride, organic substituent, etc. in the side chain or end group of component A is 1-2, the polymerization temperature is 140-160°C, the polymerization time is 0-6h and greater than 0h, and the rotation speed is 100-1000rpm / min. Further, the polymerization temperature can be any one of 140, 142, 145, 148, 150, 153, 155, 158, 160°C or a range value between any two of them. The rotation speed can be any one of 100, 200, 500, 600, 800, 1000rpm / min or a range value between any two of them. The reaction time can be any one of 0.1min, 1min, 5min, 10min, 20min, 0.5h, 1h, 2h, 3h, 4h, 5h, 6h or a range value between any two of them.

[0085] In some embodiments, citric acid ester is used as component B, the molar ratio of which to the compound containing hydroxyl in the side chain or end group of component A is 1-2, the polymerization temperature is 140-160°C, the polymerization time is 0-48h and greater than 0h, and the rotation speed is 100-1000rpm / min. Further, the polymerization temperature can be any one of 140, 142, 145, 148, 150, 153, 155, 158, 160°C or a range value between any two of them. The rotation speed can be any one of 100, 200, 500, 600, 800, 1000 rpm / min or a range value between any two of them. The reaction time can be any one of the following values: 0.1min, 1min, 5min, 10min, 2omin, 0.5h, 1h, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 48h or a range value between any two of them.

[0086] The application provides use of the self-adhesive material in any one of the following:

[0087] (1) use in preparation of a suture-free and / or anti-adhesion biological membrane;

[0088] (2) the suture-free and / or anti-adhesion biological membrane can be used as a tissue anti-adhesion membrane for tendons, abdominal cavities, pelvic cavities, nerves and spinal parts.

[0089] The alcohol used in the following examples, such as hexanediol, octanediol, cyclohexane and the like, and cysteine is of analytical purity.

[0090] Example 1

[0091] An example of preparing a citric acid-based polymer by polycondensation of citric acid and polyols, and cross-linking of diisocyanate to form a film.

[0092] (1) 10 g of citric acid and 7 g of 1,6-hexanediol are added to a flask, and the rotation speed is set to 800 rpm / min, and reacted at 140°C for 3 h; the reaction product is precipitated with deionized water, and citrate pre-polymer is obtained by freeze-drying;

[0093] (2) the mass of the pre-polymer is accurately measured, and cyclohexane is added to obtain a pre-polymer solution with a mass fraction of 50%;

[0094] (3) 1 g of the pre-polymer solution is taken and 1,6-hexamethylene diisocyanate accounting for 20% of the mass of the pre-polymer (i.e. 0.5 g of the pre-polymer is added with 100 mg of 1,6-hexamethylene diisocyanate), and a film is formed on a spin coater at a speed of 1000 rpm / min for 1 min; after the film is dried, it is taken off to obtain a suture-free anti-adhesion film.

[0095] The obtained suture-free anti-adhesion film is detected for various indexes, and the detection results are as follows:

[0096] Fig. 1 is a practical effect diagram of the suture-free anti-adhesion film prepared according to step (3) of Example 1.

[0097] Fig. 2 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 2, from which it can be seen that the film prepared by the preparation method has a dense and smooth surface without pore structure, and can effectively prevent the growth of fibroblasts.

[0098] Fig. 3 is an infrared spectrum of the suture-free anti-adhesion film (cross-linking group) prepared according to step (3) of Example 1 and the citrate pre-polymer (non-cross-linking group) prepared according to step (1), and the picture shows that the cross-linking group has a new characteristic peak at 1535 cm -1 , which is attributed to the characteristic absorption peak of -NH- in urethane, indicating that the film is prepared by chemical cross-linking.

[0099] Figure 4 is a self-adhesion effect diagram of the suture-free anti-adhesion film prepared according to Example 1, the picture shows that the film can be overlapped together by hydrogen bonding with each other, self-winding occurs, and the experimental step of suture can be omitted.

[0100] Figure 5 is a statistical diagram of the citric acid content released by the suture-free anti-adhesion film prepared by different mass ratios of isocyanate of the prepolymer prepared according to Example 1, and the citric acid content in the cells after co-incubation; the left side of Figure 5 is the citric acid content released into the supernatant by the suture-free anti-adhesion film; the right side of Figure 5 is the citric acid content in the cells after co-incubation of the supernatant with the cells. The specific method is as follows: according to the step (3) of Example 1, the self-adhesive anti-adhesion film formed after crosslinking of the prepolymer solution prepared in step (2) by adding different mass percentages of 1, 6-hexamethylene diisocyanate (0%, 5%, 10%, 15%, 20%) is immersed in 1 mL of PBS (pH = 7.4) with a diameter of 8 mm, and placed in a 37°C incubator for 24 h to obtain the leaching solution, and then the citric acid content in the supernatant of the leaching solution is detected. Under the same conditions, the culture solution is leached, the supernatant is co-cultured with mouse embryonic fibroblasts (NIH / 3T3), i.e. 10,000 cells are added per well of 96T for co-culture for 24 h, 100 μL of the above leaching solution is replaced per well after 24 h, and co-culture is continued for 24 h, then washed with PBS with pH = 7.4, lysed and centrifuged, and the citric acid content in the cells is determined. The results show that the film with high crosslinking degree degrades slowly, and the released citric acid content is also correspondingly less, thereby resulting in a corresponding decrease in the citric acid content in the cells.

[0101] Example 2

[0102] The difference between this example and Example 1 is that the 1, 6-hexamethylene diisocyanate is replaced by lysine diisocyanate to prepare a film with adjustable strength.

[0103] The obtained suture-free anti-adhesion film is detected for various indexes, and the detection results are as follows:

[0104] The obtained suture-free anti-adhesion film is detected for water contact angle, and the detection method is according to the national standard GB / T 30693-2014, Figure 6 is the water contact angle picture of the suture-free anti-adhesion film prepared according to Example 2, and the results show that the water contact angle of the film is 109.5°, which indicates that the introduction of hexanediol long alkyl chain makes the film hydrophobic and has the effect of anti-fouling.

[0105] Figure 7 is a self-adhesion effect diagram and adhesion stability test of the sutureless anti-adhesion film prepared according to Example 2. The detection method is as follows: the sutureless anti-adhesion film is wrapped outside a 1 mL syringe to simulate the wrapping effect at the tendon site. The length of the film is slightly longer than the circumference of the syringe. The film material can be stably wrapped around the outer surface of the syringe without falling off through the self-lapping of the film and the film (see the left side of Figure 7). After further soaking the whole in PBS with pH = 7.4 at 37°C in a shaker for 1 month, it is observed that the film still has a good wrapping effect on the surface of the syringe even in a wet environment, and no falling off occurs, which indicates that the film has good long-term stability in a wet environment and has the potential for application in a wet environment in vivo.

[0106] Example 3

[0107] An example of preparing a citric acid-based polymer by polycondensation of citric acid and amino acids, and cross-linking with diisocyanate to prepare an imageable film.

[0108] (1) 10 g of citric acid and 6 g of cysteine are added to a flask, and the rotation speed is set to 800 rpm / min. The reaction is carried out at 140°C for 4 h. The reaction product is precipitated with deionized water, and the citrate prepolymer is obtained by freeze-drying;

[0109] (2) The mass of the prepolymer is accurately measured, and cyclohexane is added to obtain a prepolymer solution with a mass fraction of 50%;

[0110] (3) 1 g of the prepolymer solution is taken and 1,6-hexamethylene diisocyanate is added at a percentage of 20% of the mass of the prepolymer. The film is formed on a spin coater at a speed of 1000 rpm / min for 1 min. After the film is dried, it is taken off to obtain a sutureless anti-adhesion film.

[0111] The citrate prepolymer obtained in step (1) is detected by fluorescence absorption spectrum. The excitation wavelength is 350 nm, and the emission wavelength is 420 nm. The detection result is shown in Figure 8, which is the fluorescence absorption spectrum of the citrate prepolymer prepared according to the steps of Example 3. This proves that the reaction of molecules containing amino groups such as amino acids and citric acid can generate fluorescent light 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 high molecular photoluminescent sutureless anti-adhesion films with adjustable excitation and emission wavelengths (visible light-near infrared) for biological imaging and other applications.

[0112] Example 4

[0113] An example of preparing a citric acid-based polymer by ester exchange reaction of citrate and polyol, and cross-linking with diisocyanate to form a film.

[0114] ​(1) Add 10g of triethyl citrate and 6g of 1,6-hexanediol to a flask, set the rotation speed to 800rpm / min, react at 140℃ for 24h, precipitate the reactants with deionized water, and obtain liquid citrate prepolymer by freeze drying.

[0115] (2) Take 1g of prepolymer solution and add 1,6-hexamethylene diisocyanate accounting for 20% of the mass of prepolymer. Spin coat the film on a spin coater at a speed of 1000rpm / min for 1min. After the film dries, remove it to obtain a stitch-free anti-adhesion film.

[0116] Example 5

[0117] An example of preparing citric acid-based polymers, diisocyanates, and UV crosslinking films by polycondensation reaction of citric acid with polyols and anhydrides.

[0118] (1) Add 8g citric acid, 2g maleic anhydride and 7g octanediol to a flask, set the rotation speed to 800rpm / min, react at 140℃ for 3h, precipitate the reactants with deionized water, and obtain the citric acid ester prepolymer by freeze drying.

[0119] (2) Accurately quantify the mass of the prepolymer and add cyclohexane to obtain a prepolymer solution with a mass fraction of 50%;

[0120] (3) Take 1g of prepolymer solution and add 1,6-hexamethylene diisocyanate accounting for 5% of the mass of prepolymer. Spin coat the film on a spin coater at a speed of 1000rpm / min for 1min. Then, irradiate with 365nm ultraviolet light for 3min for further crosslinking. After the film dries, remove it to obtain a stitch-free anti-adhesion film.

[0121] Example 6

[0122] An example of preparing citric acid-based polymers by polycondensation reaction of citric acid and polyamines, and crosslinking diisocyanates into films.

[0123] (1) Add 10g citric acid and 6g hexamethylenediamine to a flask, set the rotation speed to 800rpm / min, react at 140℃ for 3h, precipitate the reactants with deionized water, and obtain the citric acid ester prepolymer by freeze drying.

[0124] (2) Accurately quantify the mass of the prepolymer and add cyclohexane to obtain a prepolymer solution with a mass fraction of 50%;

[0125] (3) Take 1g of prepolymer solution and add 1,6-hexamethylene diisocyanate accounting for 10% of the mass of prepolymer. Spin coat the film on a spin coater at a speed of 1000rpm / min for 1min. After the film dries, remove it to obtain a stitch-free anti-adhesion film.

[0126] Example 7

[0127] Examples of citric acid-based polymers prepared by polycondensation of citric acid with polycarboxylic acid and crosslinked by diisocyanate to form a film.

[0128] (1) 10 g of citric acid and 7 g of adipic acid were added to a flask, and the rotation speed was set to 800 rpm / min. The reaction was carried out at 140°C for 3 h. The reaction product was precipitated with deionized water, and a citric acid ester prepolymer was obtained by freeze-drying;

[0129] (2) The mass of the prepolymer was accurately measured, and cyclohexane was added to obtain a prepolymer solution with a mass fraction of 50%;

[0130] (3) 1 g of the prepolymer solution was added to 1,6-hexamethylene diisocyanate at a mass percentage of 10% of the prepolymer. The film was formed on a spin coater at a speed of 1000 rpm / min for 1 min. After the film was dried, it was removed to obtain a suture-free anti-adhesion film.

[0131] FIG. 16 is a synthesis equation for preparing a citric acid-based prepolymer according to step (1) of Examples 5-7.

[0132] Example 8

[0133] The suture-free anti-adhesion film was prepared in the same manner as in Example 2, except that the film was formed by spin coating at a speed of 500 rpm / min.

[0134] Results: The state of the spin-coated film was observed. Since the prepolymer solution is hydrophobic and has high viscosity, it is difficult to uniformly coat the coating at a low rotation speed. See FIG. 17.

[0135] Example 9

[0136] The suture-free anti-adhesion film was prepared in the same manner as in Example 4, except that 1,6-hexamethylene diisocyanate was added at a ratio of 100% of the prepolymer.

[0137] Results: Since the ratio of isocyanate is too high, the reaction rate of the prepolymer with isocyanate is too fast, and the spin coating solution is quickly solidified, making it difficult to spin coat. See FIG. 18.

[0138] Example 10

[0139] The difference between this example and Example 1 is that toluene diisocyanate is used instead of 1,6-hexamethylene diisocyanate.

[0140] Results: Since the toluene diisocyanate molecule has too much rigidity, the strength of the prepared film is as high as 33.68 MPa, making it impossible to bend and self-wind, and it does not fit the surrounding tissue when implanted in the body, easily causing an inflammatory response, making it unsuitable for in vivo applications. See FIG. 19.

[0141] Example 11

[0142] The sutureless anti-adhesion film was prepared in the same manner as in Example 1, except that polyethylene glycol 1000 was used instead of 1,6-hexanediol in an equal amount, but no film was formed at this cross-linking ratio.

[0143] Example 12

[0144] The sutureless anti-adhesion film was prepared in the same manner as in Example 1, except that (3) 1 g of the prepolymer solution was added with 1,6-hexamethylene diisocyanate accounting for 5% of the mass percentage of the prepolymer.

[0145] Results: Due to the low cross-linking ratio, there are not enough hydrogen bond sites for self-adhesion performance, so the material has poor self-adhesion performance. In the dry state, self-adhesion occurs, but once soaked in PBS with pH = 7.4, the self-adhesion site shifts and falls off, losing the self-adhesion effect, as shown in Figure 20.

[0146] Example 13

[0147] The sutureless anti-adhesion film was prepared in the same manner as in Example 1, except that the film-forming solution system was expanded 5 times, i.e. 5 g of the prepolymer solution was added with 1,6-hexamethylene diisocyanate accounting for 20% of the mass percentage of the prepolymer (i.e. 2.5 g of the prepolymer was added with 500 mg of hexamethylene diisocyanate), and then spin-coated into a film.

[0148] Results: The coating thickness was measured using a vernier caliper, which was about 720 μm. The excessive thickness of the film material resulted in excessive surface tension of the film, and the hydrogen bond effect at the film bonding site could not maintain good self-adhesion effect, and the film material lost the self-adhesion performance. At the same time, due to the thick film material, there was a clear foreign body sensation when in contact with the skin tissue, which was not suitable for use inside the tissue. The coating thickness of the film material of Example 1 was about 100 μm, which could effectively self-adhere at the finger part, and the film did not break when bent, having good self-adhesion performance. Therefore, the thickness of the film material was closely related to the self-adhesion performance, as shown in Figure 21.

[0149] Comparative Example 1

[0150] The sutureless anti-adhesion film was prepared in the same manner as in Example 2, except that no isocyanate cross-linking was used, and only thermal cross-linking was used, i.e. 1 g of the prepolymer solution was spin-coated into a film on a spin coater at a speed of 1000 rpm / min for 1 min, and then placed in an 80°C oven for thermal cross-linking. After the film was dried, it was taken out to obtain the sutureless anti-adhesion film.

[0151] Results: Using thermal cross-linking, the film material was only cross-linked by ester bonds, lacking hydrogen bond sites, and the material had poor self-adhesion performance, as shown in Figure 20.

[0152] Experimental Example 1: This experimental example examines the various properties of the sutureless anti-adhesion films prepared in Examples 1-4.

[0153] (1) Mechanical properties

[0154] The testing method was as follows: A strip of membrane material, 1.5 cm wide and 4 cm long, was prepared and placed on a universal testing machine with 0.5 cm clamps at the top and bottom, and stretched at a rate of 50 mm / min. The results are shown in Figure 9. Figure 9 shows the mechanical properties of the sutureless anti-adhesion membranes prepared according to Examples 1-4. Their tensile strength is 50-100 kPa, which can be controlled by adjusting the isocyanate molecular structure, matching the mechanical properties of commercially available materials and meeting the requirements for support at tendon injury sites.

[0155] (2) Self-adhesive

[0156] The testing method is as follows: Two pieces of the same type of non-seamless anti-adhesion film are used and overlapped face to face. Uniform pressure is applied to the entire overlap surface. It is recommended that the pressure applied can reach 1 MPa, in a T-shape, as shown on the left side of Figure 10. The strength of the adhesive joint is measured, referring to the national standard GB / T 2791-1995.

[0157] Figure 10 on the right shows the self-adhesive properties of the stitchless anti-adhesion film prepared according to the steps of Examples 1 to 4. The results show that the prepared film has self-adhesive properties and a strength of 0.14 to 0.22 MPa. Its adhesive strength can be adjusted by regulating the molecular structure through isocyanate.

[0158] (3) Cytotoxicity

[0159] The detection method was as follows: Each sutureless anti-adhesion membrane (8 mm diameter) prepared in each example was immersed in 1 mL of DMEM culture medium and incubated at 37°C for 24 h to obtain an extract. Then, the extract was used to replace an equal volume of cell supernatant and co-cultured with mouse embryonic fibroblasts (NIH / 3T3). Specifically, 10,000 cells were added to each well of 96T cells and co-cultured for 24 h. After 24 h, 100 μL of the extract was replaced in each well, and co-cultured for another 24 h. The results were then obtained using CCK8 at OD... 600 The absorbance was measured at nm. For the fully viable cells, cell culture medium was replaced, while for the completely dead cells, sterile water was used. Cell viability was calculated using the following formula: Cell viability = (OD0)0 材料组 -OD 全死组 ) / (OD 全活组 -OD 全死组 )×100%.

[0160] As shown in Figure 11 is the cytotoxicity of the sutureless anti-adhesion film prepared according to the steps of Examples 1-4, the results show that the cell survival rate of all groups is higher than 70%, which indicates that the citric acid-based sutureless anti-adhesion film prepared by the preparation method has good biocompatibility and can be used for further characterization in vivo.

[0161] (4) Anti-protein adhesion effect

[0162] The detection method is as follows: place the film prepared in each example with a diameter of 8 mm in the holes of a 48-well plate, prepare a FITC-labeled BSA solution with PBS to 2 mg / mL, add 200 microliters to each well, and set up a control group, which uses a commercially available film material . Incubate at 37°C for 2 h, wash with PBS, and then observe under a fluorescence microscope.

[0163] As shown in Figure 12 is the anti-protein adhesion effect diagram of the sutureless anti-adhesion film prepared according to the steps of Examples 1-4, the results shows that the citric acid-based sutureless anti-adhesion film prepared by the preparation method can effectively prevent protein adhesion on its surface, and has good anti-adhesion effect. Experimental Example 2

[0164] Application in tendon injury model: SD rats weighing about 200-250 g were used to make animal models of tendon injury in vivo. The rats were anesthetized with sodium pentobarbital, the hair on the surface of the Achilles tendon was removed, and iodophor was used for disinfection. The skin was cut longitudinally along the Achilles tendon, and the Achilles tendon was transversely cut and disconnected. A film with a size of 1.0 cm x 2.0 cm was used to wrap the Achilles tendon, and then the skin was sutured and disinfected again. The film is the sutureless anti-adhesion film prepared according to the steps of Examples 2 and 4, and the control group is sutured with surgical thread.

[0165] As shown in Figure 13 is the wrapping effect diagram of the sutureless anti-adhesion film prepared according to Examples 2 and 4 at the tendon injury site of the rat, the results show that the film prepared by the method of Examples 2 and 4 can effectively wrap the tendon injury site, without the need for suturing, greatly shortening the operation time and avoiding the risk of infection, while the control group needs to be sutured to ensure the butt joint repair.

[0166] Figure 14 is an H&E staining section of the tissue wrapped with the sutureless anti-adhesion film prepared according to Example 4 at the tendon injury site of the rat after 1 day, the results show that a large number of inflammatory cell infiltration phenomenon occurs in the control group, while the film prepared by the method of Example 4 has good biocompatibility in vivo. There is an obvious gap between the tendon and the muscle, indicating that the citric acid-based sutureless anti-adhesion film has good anti-adhesion effect in vivo, and can effectively avoid the occurrence of fibrous adhesion.

[0167] Figure 15 is a macroscopic observation of the sutureless anti-adhesion film prepared according to Example 4 after wrapping the site of tendon injury in rats for 9 weeks, which shows that the film is completely degraded at 9W, indicating that the citric acid-based anti-adhesion film prepared by this method is completely degradable in vivo, has good biocompatibility, and does not accumulate in the internal tissues or organs of the human body.

[0168] Obviously, the above examples are only examples for the purpose of clarity, and are not limitations on the embodiments. Based on the above description, other different forms of changes or variations can also be made by those of ordinary skill in the art. It is not necessary and impossible to exhaust all the embodiments here. The obvious changes or variations derived therefrom are still within the protection scope of the present application.

Claims

1. A method for preparing a self-adhesive material, characterized in that, include: Component A and component B are reacted to form a citric acid-based prepolymer; Component A is at least one compound having at least two reactive functional groups on its terminal group or side chain, wherein 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 substituent; Component B is citric acid and / or its derivatives; the reaction includes polycondensation, substitution or transesterification. The citric acid prepolymer and isocyanate are cross-linked by urethane or amide bonds.

2. The method for preparing the 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, or 4,4'-diisocyanate dicyclohexylmethane.

3. The method for preparing the 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 the self-adhesive material according to any one of claims 1-3, characterized in that, When the citric acid-based prepolymer is in a solid state, before carrying out the cross-linking reaction of urethane or amide bonds, 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 or amide bonds is carried out. The citric acid-based prepolymer solution contains 30-60% by mass of citric acid-based prepolymer. The amount of isocyanate added is >0% and ≤50% of the mass percentage of the citric acid-based prepolymer.

5. The method for preparing the self-adhesive material according to any one of claims 1-3, characterized in that, The conditions for the crosslinking reaction of the urethane or amide bonds are: room temperature, reaction time of 0-24 h, and reaction time > 0 h.

6. The method for preparing the self-adhesive material according to any one of claims 1-3, characterized in that, When preparing the self-adhesive material into a film, the process includes spin coating, solution casting, or casting a mixture of citric acid prepolymer and isocyanate during a crosslinking reaction of urethane or amide bonds.

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

8. The method for preparing a self-adhesive material according to any one of claims 1-3, characterized in that, 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, hexanediol, octanediol, polyethylene glycol, bis(4-hydroxyphenyl) disulfide, resveratrol, bis(2-hydroxyethyl) disulfide, isosorbide, xylitol, glycolic acid ester or N-methyldiethanolamine; And / or, when component A is an amino acid or other compound containing an amino or 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, epoxidized soybean oil, epoxy resin, epichlorohydrin, or lactide; And / or, when component A is a compound containing a carboxyl group or an anhydride, including but not limited to folic acid, tartaric acid, adipic acid, succinic acid, fumaric acid, salicylic acid, acetic anhydride or maleic anhydride; And / or, when component A is a compound containing organic substituents, it includes, but is not limited to, polyphosphazenes; And / or, the citric acid and / or its derivatives include, but are not limited to, citric acid, trimethyl citrate, triethyl citrate, tributyl citrate, acetylated 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 as described in any one of claims 1-8.

10. The self-adhesive material of claim 9 is used in the following ways: In the preparation of sutureless and / or anti-adhesion biofilms; the sutureless and / or anti-adhesion biofilms are intended for use as tissue anti-adhesion membranes for tendons, abdominal cavity, pelvic cavity, nerves, and spinal regions.

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