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CN-122005903-A - Temperature-sensitive hydrogel dressing and preparation method and application thereof

CN122005903ACN 122005903 ACN122005903 ACN 122005903ACN-122005903-A

Abstract

The invention discloses a temperature-sensitive hydrogel dressing and a preparation method and application thereof, wherein the method comprises the steps of preparing an alkynyl temperature-sensitive block copolymer, azidated mussel protein, an alkynyl MOF@QK nano enzyme complex, an ROS responsive HA-ss-RGD complex and a traditional Chinese medicine yellow wine extract; and (3) covalently assembling the components through click chemistry to obtain a precursor solution. The dressing is in-situ glued at body temperature, strong-effect wet tissue adhesion is realized through mussel protein, long-effect ROS removal and QK peptide sustained release are realized through MOF@QK, RGD peptide release as required is realized through ROS responsive rupture of phenylboronic acid ester bonds of HA-ss-RGD, and multi-target cooperative regulation and control are realized through traditional Chinese medicine extracts. The invention combines nano enzyme catalysis, ROS responsive drug release and traditional Chinese medicine multi-target regulation, and the characteristics cooperate to obviously promote the healing of chronic wounds, so as to prepare the oxidative stress related chronic wound repair material.

Inventors

  • ZUO CHAO
  • ZHANG XUEPING
  • FAN YING

Assignees

  • 十堰市太和医院（湖北医药学院附属医院）

Dates

Publication Date
20260512
Application Date
20260316

Claims (10)

  1. 1. The preparation method of the temperature-sensitive hydrogel dressing is characterized by comprising the following steps of: S1, preparing an alkynyl temperature-sensitive block copolymer Alk-PNIPAM-PEG-PNIPAM-Alk; S2, preparing azide functionalized mussel protein N 3 -MFP; s3, preparing an alkynyl metal organic framework@healing promoting peptide compound Alk-MOF@QK, wherein the metal organic framework has superoxide dismutase-like and catalase-like activities, and the inside of the metal organic framework is loaded with angiogenesis promoting peptide QK; s4, preparing an ROS responsive peptide-hyaluronic acid complex HA-ss-RGD, wherein the complex is used for covalently connecting angiogenesis promoting peptide RGD with hyaluronic acid through phenylboronic acid ester bonds; S5, preparing a traditional Chinese medicine extract TCME, wherein the traditional Chinese medicine extract is prepared from papaya, achyranthes root, dipsacus root, chinese herbaceous peony, yam rhizome, combined spicebush root, gastrodia tuber, astragalus root, clematis root, chinese angelica, ledebouriella root, trogopterus dung, stiff silkworm and artificial tiger bone as raw materials through soaking and extracting with yellow wine; S6, dissolving the alkynyl temperature-sensitive block copolymer prepared in the S1 into a solvent at 4-10 ℃, adding the azide functionalized mussel protein prepared in the S2, the alkynyl metal organic framework@healing-promoting peptide compound prepared in the S3, the ROS responsive peptide-hyaluronic acid compound prepared in the S4 and the traditional Chinese medicine extract prepared in the S5, and performing an azide-alkynyl cycloaddition click chemical reaction under the catalysis of a copper salt catalyst to connect the azide functionalized mussel protein and the alkynyl metal organic framework@healing-promoting peptide compound to the temperature-sensitive block copolymer through covalent triazole rings to obtain a precursor solution, thus obtaining a final product.
  2. 2. The preparation method of the temperature-sensitive hydrogel dressing according to claim 1, wherein in the step S1, the alkynyl temperature-sensitive block copolymer is prepared by using HO-PNIPAM-PEG-PNIPAM-OH as a raw material and carrying out esterification reaction with 4-pentynoic acid under DCC/DMAP catalysis, the reaction temperature is 25 ℃, and the reaction time is 24 hours.
  3. 3. The method for preparing the temperature-sensitive hydrogel dressing according to claim 1, wherein in the step S2, the azide-functionalized mussel protein is prepared by reacting natural mussel podophyllotoxin protein with azide-PEG 4 -NHS ester in PBS buffer solution with pH of 7.4 for 12 hours at room temperature, and after the reaction, dialyzing, freeze-drying and purifying.
  4. 4. The method of preparing a temperature-sensitive hydrogel dressing according to claim 1, wherein step S3 comprises: s3-1, synthesizing Mn-MOF of manganese-porphyrin metal organic framework nano particles, namely dissolving tetra (4-carboxyphenyl) porphyrin and MnCl 2 ·4H 2 O in DMF, adding benzoic acid, performing solvothermal reaction at 80 ℃ for 24 hours, and centrifugally washing to obtain the Mn-MOF; S3-2, incubating Mn-MOF and angiogenesis peptide QK in PBS for 24 hours under 4 ℃ vibration, and centrifugally washing to obtain MOF@QK; S3-3, dispersing MOF@QK in DMF, adding alkynyl-PEG 4 -NHS ester and triethylamine, reacting for 6 hours at room temperature, and centrifugally washing to obtain Alk-MOF@QK.
  5. 5. The method of claim 1, wherein in step S4, the HA-ss-RGD is prepared by connecting a thiolated RGD peptide with thiolated hyaluronic acid by a bifunctional crosslinking agent Mal-PhB-OEG-PhB-Mal containing phenylboronic acid ester bond, and the reaction is performed under nitrogen protection and light-shielding conditions.
  6. 6. The method for preparing the temperature-sensitive hydrogel dressing according to claim 1, wherein in the step S5, the preparation of the traditional Chinese medicine extract comprises the steps of taking equal parts of papaya, achyranthes root, teasel root, chinese herbaceous peony, yam rhizome, combined spicebush root, gastrodia tuber, astragalus root, clematis root, chinese angelica, ledebouriella root, trogopterus dung, stiff silkworm and artificial tiger bone, cleaning, removing impurities, airing, adding yellow wine, sealing, soaking for 20-30 days, filtering, concentrating and drying to obtain the traditional Chinese medicine extract.
  7. 7. The method for preparing the temperature-sensitive hydrogel dressing according to claim 1, wherein in the step S6, the mass ratio of the alkynyl temperature-sensitive block copolymer, the azide-functionalized mussel protein, the alkynyl metal-organic framework@healing-promoting peptide complex, the ROS-responsive peptide-hyaluronic acid complex and the traditional Chinese medicine extract is 100 (1-4): 3-10): 2-8): 1-6.
  8. 8. The method for preparing the temperature-sensitive hydrogel dressing according to claim 1, wherein in the step S6, the copper salt catalyst is a CuSO 4 /sodium ascorbate system, the reaction is carried out for 1-2 hours at 4-10 ℃, and the mass volume fraction of the alkynyl temperature-sensitive block copolymer in the precursor solution is 12-18%.
  9. 9. A temperature-sensitive hydrogel dressing, characterized in that it is prepared according to the method for preparing a temperature-sensitive hydrogel dressing according to any one of claims 1-8.
  10. 10. The use of the temperature-sensitive hydrogel dressing of claim 9 in chronic refractory wounds.

Description

Temperature-sensitive hydrogel dressing and preparation method and application thereof Technical Field The invention relates to the technical field of hydrogel dressing, in particular to a temperature-sensitive hydrogel dressing, and a preparation method and application thereof. Background The pathological microenvironment of chronic difficult-to-heal wound surfaces (such as diabetic feet and pressure ulcers) is characterized by sustained inflammation, high-level Reactive Oxygen Species (ROS) accumulation, angiogenesis disorder and extracellular matrix degradation, the high-oxidative stress state leads to fibroblast aging and endothelial cell dysfunction, so that 'ROS burst, cell injury, inflammation aggravation and more ROS generation' vicious circle is formed, although the traditional intelligent thermosensitive hydrogel dressing has realized strong wet tissue adhesion by introducing mussel protein, realizes ROS responsive on-demand release healing promotion signals by RGD peptide-hyaluronic acid complex connected by phenylboronic acid ester bonds, realizes long-acting ROS clearance by metal organic frame nano-enzyme, and primarily solves the problems of dynamic matching of signal supply and microenvironment, the healing promotion signals are still limited to the effects of single or two factors, the wound surface repair is a complex physiological process involving multiple targets such as inflammatory regulation, angiogenesis, cell proliferation, matrix and the like, the regulation and control effects of the single or two factors are still limited, and the complete and clinical overall regulation and overall regulation of the complex microenvironment is difficult to realize, so that the critical requirements of complete and the complete clinical regulation on complex microenvironment are met, the requirements of the traditional wound surfaces can be realized, the long-acting ROS release promotion signals can be realized, the promotion and the promotion of the slow-acting repair technologies can be realized, the key requirements are also can be realized, the key requirements are overcome, and the promotion of the effective healing has the promotion of the effective wound surface has the good healing has the good effect and the effect. Disclosure of Invention The invention aims to solve the technical problem of how to construct a dressing which can not only remove ROS for a long time, but also release healing promoting signals according to the needs, and can also provide multi-target and multi-channel cooperative regulation and control effects. In order to solve the technical problems, the invention adopts the following technical scheme: The preparation method of the temperature-sensitive hydrogel dressing comprises the following steps: S1, preparing an alkynyl temperature-sensitive block copolymer Alk-PNIPAM-PEG-PNIPAM-Alk; S2, preparing azide functionalized mussel protein N 3 -MFP; s3, preparing an alkynyl metal organic framework@healing promoting peptide compound Alk-MOF@QK, wherein the metal organic framework has superoxide dismutase-like and catalase-like activities, and the inside of the metal organic framework is loaded with angiogenesis promoting peptide QK; s4, preparing an ROS responsive peptide-hyaluronic acid complex HA-ss-RGD, wherein the complex is used for covalently connecting angiogenesis promoting peptide RGD with hyaluronic acid through phenylboronic acid ester bonds; S5, preparing a traditional Chinese medicine extract TCME, wherein the traditional Chinese medicine extract is prepared from papaya, achyranthes root, dipsacus root, chinese herbaceous peony, yam rhizome, combined spicebush root, gastrodia tuber, astragalus root, clematis root, chinese angelica, ledebouriella root, trogopterus dung, stiff silkworm and artificial tiger bone as raw materials through soaking and extracting with yellow wine; S6, dissolving the alkynyl temperature-sensitive block copolymer prepared in the S1 into a solvent at 4-10 ℃, adding the azide functionalized mussel protein prepared in the S2, the alkynyl metal organic framework@healing-promoting peptide compound prepared in the S3, the ROS responsive peptide-hyaluronic acid compound prepared in the S4 and the traditional Chinese medicine extract prepared in the S5, and performing an azide-alkynyl cycloaddition click chemical reaction under the catalysis of a copper salt catalyst to connect the azide functionalized mussel protein and the alkynyl metal organic framework@healing-promoting peptide compound to the temperature-sensitive block copolymer through covalent triazole rings to obtain a precursor solution, thus obtaining a final product. In the preparation method of the thermosensitive hydrogel dressing, in the step S1, the alkynyl thermosensitive block copolymer is prepared by taking HO-PNIPAM-PEG-PNIPAM-OH as a raw material, and carrying out esterification reaction with 4-pentynoic acid under DCC/DMAP catalysis, wherein the reaction temperature is 25