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CN-121971686-A - Medical tissue adhesive based on mussel mucin and preparation method thereof

CN121971686ACN 121971686 ACN121971686 ACN 121971686ACN-121971686-A

Abstract

The invention discloses a medical tissue adhesive based on mussel mucin and a preparation method thereof, wherein the medical tissue adhesive comprises modified mussel mucin, a TA-Fe@Ser compound, a quaternary ammonium salt chitosan/sodium silicate/glycyrrhizinate compound, sodium hexametaphosphate, ferric trichloride, a surfactant and PBS buffer solution, the modified mussel mucin is obtained by sequentially reacting mussel mucin with cysteine hydrochloride and phenylalanine methyl ester hydrochloride, and the TA-Fe@Ser compound is obtained by coordination self-assembly of sericin, tannic acid and Fe 3+ . The medical tissue adhesive provided by the invention has the multiple functions of Gao Jiangshi adhesion, antibiosis, anti-inflammation, antioxidation and the like.

Inventors

  • CHEN LEI
  • JIANG LEI
  • CUI HAITAO
  • LI XIN

Assignees

  • 贝壳派创新科技（深圳）有限公司

Dates

Publication Date
20260505
Application Date
20260407

Claims (10)

  1. 1. Medical tissue adhesive based on mussel mucin is characterized by comprising the following components in parts by weight: 2.0-4.0 parts by mass of modified mussel mucin; 1.0 to 2.5 parts by mass of TA-Fe@Ser compound; 0.5 to 1.5 parts by mass of quaternary ammonium salt chitosan/sodium sulfanilate/glycyrrhizic acid compound; sodium hexametaphosphate 0.1-0.5 weight portions; 0.005-0.025 parts by mass of ferric trichloride; 0.1-0.3 part by mass of surfactant; 91-97 parts by mass of PBS buffer solution; the modified mussel mucin is obtained by sequentially reacting mussel mucin with cysteine hydrochloride and phenylalanine methyl ester hydrochloride; The TA-Fe@Ser compound is prepared by self-assembling sericin, tannic acid and Fe 3+ through coordination; the quaternary ammonium salt chitosan/sodium sulmore gluconate/glycyrrhizic acid compound is prepared by clathrating glycyrrhizic acid in sodium sulmore gluconate to obtain sodium sulmore gluconate/glycyrrhizic acid clathrate, and then carrying out polymerization reaction on the quaternary ammonium salt chitosan and the sodium sulmore gluconate/glycyrrhizic acid clathrate.
  2. 2. The mussel adhesive-based medical tissue adhesive of claim 1, wherein the preparation of the modified mussel adhesive comprises the steps of: 1) Adding mussel mucin into MES buffer solution, and stirring until the mussel mucin is completely dissolved; 2) Slowly adding cysteine hydrochloride into the solution, simultaneously adding a composite coupling agent, and then carrying out light-shielding reaction for 10-16 hours at 1-5 ℃; 3) Adding phenylalanine methyl ester hydrochloride into the reaction liquid, supplementing a small amount of compound coupling agent, and continuing to react for 8-10 hours at 1-5 ℃ in a dark place; 4) After the reaction is finished, the obtained reaction solution is dialyzed and purified in a dark place, and freeze-dried in a dark place, so that the modified mussel mucin is obtained.
  3. 3. The mussel mucin-based medical tissue adhesive according to claim 2, wherein the mass ratio of mussel mucin to cysteine hydrochloride to phenylalanine methyl ester hydrochloride is 1 (0.15-0.25) to 0.1-0.2 in the preparation process of the modified mussel mucin.
  4. 4. The mussel mucin-based medical tissue adhesive according to claim 2, wherein in the steps 2) and 3), the compound coupling agent is a mixture of EDC, HCl and NHS in a mass ratio of 2:1, in the step 2), the added cysteine hydrochloride is added in a mass ratio of EDC, HCl and NHS of (0.15-0.25): 0.02-0.03): 0.01-0.015, and in the step 3), the added phenylalanine methyl ester hydrochloride is added in a mass ratio of EDC, HCl and NHS of (0.1-0.2): 0.01-0.02): 0.005-0.01.
  5. 5. The mussel adhesive based medical tissue adhesive of claim 1, wherein the preparation of the TA-fe@ser complex comprises the steps of: Dissolving sericin in PBS buffer solution, slowly adding tannic acid, stirring at room temperature for 20-40 min, slowly adding ferric trichloride, stirring at room temperature for 20-40 min, ending the reaction, dialyzing the obtained reaction solution, and freeze-drying to obtain TA-Fe@Ser compound.
  6. 6. The medical tissue adhesive based on mussel mucin according to claim 5, wherein in the preparation process of the TA-Fe@Ser compound, the mass ratio of sericin to tannic acid to ferric trichloride is 1 (0.2-0.4) (0.01-0.03).
  7. 7. The mussel adhesive based medical tissue adhesive of claim 1, wherein the preparation of the quaternary ammonium salt chitosan/sodium sulfacetamide/glycyrrhizic acid complex comprises the steps of: ① Dissolving sodium sulfanilate in PBS buffer solution, slowly adding glycyrrhizic acid, stirring at 38-42 ℃ for reaction for 3-4 hours, and naturally cooling to room temperature to obtain a solution containing sodium sulfanilate/glycyrrhizic acid clathrate; ② Slowly adding the quaternary ammonium salt chitosan, stirring at room temperature for reaction for 1-2 hours, and freeze-drying the obtained reaction liquid to obtain the quaternary ammonium salt chitosan/sodium sulfanilate/glycyrrhizic acid compound.
  8. 8. The mussel adhesive protein-based medical tissue adhesive according to claim 7, wherein the mass ratio of the quaternary ammonium salt chitosan to the sodium glycose to the glycyrrhizic acid is 1:1 (0.75-0.85).
  9. 9. The mussel adhesive based medical tissue adhesive of claim 1, wherein the surfactant is a mixture of poloxamer 407 and tween 80 in a mass ratio of 3:1.
  10. 10. A method of preparing a mussel adhesive based medical tissue adhesive according to claim 1, comprising the steps of: a) Dissolving a certain proportion of modified mussel mucin and TA-Fe@Ser compound in a partial proportion of PBS buffer solution to obtain a solution A; Dissolving a proportioned amount of quaternary ammonium salt chitosan/sodium sulfanyl sulfate/glycyrrhizic acid compound in a partial proportioned amount of PBS buffer solution to obtain a solution B; Dissolving a proportioning amount of sodium hexametaphosphate in a partial proportioning amount of PBS buffer solution to obtain a solution C; dissolving a proportioning amount of surfactant into a partial proportioning amount of PBS buffer solution to obtain a solution D; dissolving a proportional amount of ferric trichloride into a partial proportional amount of PBS buffer solution to obtain a solution E; b) Adding the solution A into a reaction container, then adding the solution D, and stirring for 3-8 minutes at room temperature; c) Then adding the solution B, and stirring for 5-15 minutes at room temperature; d) Slowly dripping the solution C, and stirring for 3-8 minutes at room temperature; e) Then slowly dripping the solution E, continuously stirring for 5-10 minutes after dripping, standing and defoaming for 5-10 minutes to obtain the medical tissue adhesive.

Description

Medical tissue adhesive based on mussel mucin and preparation method thereof Technical Field The invention relates to a medical tissue adhesive based on mussel mucin and a preparation method thereof, belonging to the technical field of medical tissue adhesives. Background In clinical practice, closure of surgical incisions traditionally relies on sutures and staples, but this approach inevitably penetrates the tissue, causes secondary damage, forms an eye-of-the-needle scar, and is time consuming to operate. In addition, suturing is difficult to achieve a complete barrier to bodily fluids, nor is it actively involved in the wound healing process. Tissue adhesives have been attracting attention as an emerging alternative to wound closure because of their ease of operation, low trauma, avoidance of secondary injury from suturing, and the like. The ideal medical tissue adhesive needs to meet the multifunctional requirements, such as having enough wet tissue adhesive strength, resisting skin tension, ensuring firm incision closure, having good biocompatibility, not inhibiting tissue healing, and the like. Mussel mucin, also known as mussel foot protein, is a protein secreted by marine mussels and has a particular viscosity. The adhesion of mussel mucin is mainly derived from the abundant dopa group, the dopa group is converted from tyrosine residues through modification of hydroxyl groups, and catechol functional groups on side groups are key structures of functional diversity and high affinity. Research shows that mussel mucin has good adhesiveness and biocompatibility and can effectively promote wound healing, so that mussel mucin is widely applied to medical tissue adhesives at present. However, the existing mussel mucin tissue adhesives have insufficient performance in certain aspects, such as insufficient antibacterial performance, inability to well control bacterial infection, insufficient oxidation resistance, easy oxidation and inactivation, and the like. Therefore, there is a need to develop a medical tissue adhesive based on mussel adhesive protein with Gao Jiangshi adhesion, antibacterial, anti-inflammatory, antioxidant and other functions. Disclosure of Invention Aiming at the problems existing in the prior art, the invention aims to provide a medical tissue adhesive based on mussel mucin and a preparation method thereof. In order to achieve the above purpose, the present invention adopts the following technical scheme: a medical tissue adhesive based on mussel mucin has the following composition and proportion: 2.0-4.0 parts by mass of modified mussel mucin; 1.0 to 2.5 parts by mass of TA-Fe@Ser compound; 0.5 to 1.5 parts by mass of quaternary ammonium salt chitosan/sodium sulfanilate/glycyrrhizic acid compound; sodium hexametaphosphate 0.1-0.5 weight portions; 0.005-0.025 parts by mass of ferric trichloride; 0.1-0.3 part by mass of surfactant; 91-97 parts by mass of PBS buffer solution; the modified mussel mucin is obtained by sequentially reacting mussel mucin with cysteine hydrochloride and phenylalanine methyl ester hydrochloride; The TA-Fe@Ser compound is prepared by self-assembling sericin, tannic acid and Fe 3+ through coordination; the quaternary ammonium salt chitosan/sodium sulmore gluconate/glycyrrhizic acid compound is prepared by clathrating glycyrrhizic acid in sodium sulmore gluconate to obtain sodium sulmore gluconate/glycyrrhizic acid clathrate, and then carrying out polymerization reaction on the quaternary ammonium salt chitosan and the sodium sulmore gluconate/glycyrrhizic acid clathrate. In one embodiment, the preparation of the modified mussel mucin comprises the following steps: 1) Adding mussel mucin into MES buffer solution (0.1M, pH 6.0), and stirring to dissolve completely; 2) Slowly adding cysteine hydrochloride into the solution, simultaneously adding a composite coupling agent, and then carrying out light-shielding reaction for 10-16 hours at 1-5 ℃; 3) Adding phenylalanine methyl ester hydrochloride into the reaction liquid, supplementing a small amount of compound coupling agent, and continuing to react for 8-10 hours at 1-5 ℃ in a dark place; 4) After the reaction is finished, the obtained reaction solution is dialyzed and purified in a dark place, and freeze-dried in a dark place, so that the modified mussel mucin is obtained. In a preferred scheme, in the preparation process of the modified mussel mucin, the mass ratio of the mussel mucin to cysteine hydrochloride to phenylalanine methyl ester hydrochloride is 1 (0.15-0.25) to 0.1-0.2. In a preferred scheme, in the steps 2) and 3), the compound coupling agent is a mixture of EDC-HCl (1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride) and NHS (N-hydroxysuccinimide) in a mass ratio of 2:1, in the step 2), the added cysteine hydrochloride is added, the mass ratio of EDC-HCl to NHS is (0.15-0.25): 0.02-0.03): 0.01-0.015, and in the step 3), the added phenylalanine methyl ester hydrochloride is added, the mass