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CN-121971381-A - Oxidative response hydrogel carrying medlar glycopeptide and preparation method and application thereof

CN121971381ACN 121971381 ACN121971381 ACN 121971381ACN-121971381-A

Abstract

The invention discloses an oxidation-responsive hydrogel carrying medlar glycopeptide, and a preparation method and application thereof, and belongs to the technical field of biological medicines. The oxidation-responsive hydrogel comprises in-situ hydrogel formed by crosslinking a hydrogel bracket component A and a component B and embedded oxidation-responsive microspheres thereof, wherein the oxidation-responsive microspheres comprise a gelatin network formed by crosslinking gelatin and an oxidation-responsive crosslinking agent, and medlar glycopeptides wrapped by the gelatin network. The invention also discloses a preparation method of the oxidation-responsive hydrogel carrying the medlar glycopeptide and application of the oxidation-responsive hydrogel in preparation of medicines for preventing or/and treating oral diseases.

Inventors

  • MOU YANDONG
  • ZENG CHUANJIE
  • YUAN LUN
  • WANG NI
  • SUN LEI

Assignees

  • 四川省医学科学院·四川省人民医院

Dates

Publication Date
20260505
Application Date
20260408

Claims (10)

  1. 1. The oxidation-responsive hydrogel carrying the medlar glycopeptide is characterized by comprising an in-situ hydrogel formed by crosslinking a hydrogel bracket component A and a hydrogel bracket component B and oxidation-responsive microspheres embedded by the in-situ hydrogel, wherein the mass ratio of the hydrogel bracket component A to the hydrogel bracket component B to the oxidation-responsive microspheres is 100:100-200:1-3; the hydrogel bracket component A comprises at least one of oxidized hyaluronic acid, oxidized sodium alginate, oxidized starch and oxidized dextran, and the hydrogel bracket component B comprises at least one of chitosan, carboxymethyl chitosan and gelatin; The oxidation-responsive microspheres comprise a gelatin network formed by crosslinking gelatin and an oxidation-responsive crosslinking agent, wherein the gelatin network is wrapped with medlar glycopeptide, and the mass ratio of the medlar glycopeptide to the gelatin to the oxidation-responsive crosslinking agent is 2-6:20:1.
  2. 2. The oxidation-responsive hydrogel carrying a lycium barbarum glycopeptide of claim 1, wherein the oxidation-responsive cross-linking agent comprises at least one of a ketal, an arylborate, a peroxyoxalate, and a thioether.
  3. 3. The method for producing an oxidation-responsive hydrogel carrying a lycium barbarum glycopeptide according to claim 1 or 2, comprising the steps of: Firstly preparing oxidation-responsive microspheres by adopting an emulsion template method, and then mixing the aqueous solution of the hydrogel bracket component A and the aqueous solution of the hydrogel bracket component B with the oxidation-responsive microspheres to obtain the oxidation-responsive hydrogel carrying the medlar glycopeptide.
  4. 4. The method for producing an oxidation-responsive hydrogel carrying a lycium barbarum glycopeptide according to claim 3, wherein the method for producing the oxidation-responsive microsphere by using the emulsion template method comprises the steps of: S1, preparing an oxidation-responsive cross-linking agent reaction solution, namely dissolving an oxidation-responsive cross-linking agent, a carbodiimide coupling agent and an N-hydroxysuccinimide compound in an organic solvent, and stirring at room temperature for an activation reaction to obtain the oxidation-responsive cross-linking agent reaction solution; S2, emulsifying, namely dissolving medlar glycopeptide and gelatin in water to form a water phase, then adding an oil phase material and a surfactant into the water phase, mixing and emulsifying to obtain emulsion; and S3, crosslinking, namely adding an oxidation-responsive crosslinking agent reaction solution into the emulsion for crosslinking, and after the reaction is finished, collecting precipitate through solid-liquid separation, washing and freeze-drying to obtain the oxidation-responsive microsphere carrying the medlar glycopeptide.
  5. 5. The method for producing an oxidation-responsive hydrogel carrying a lycium barbarum glycopeptide according to claim 4, wherein in step S1, the carbodiimide coupling agent comprises 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride, and the N-hydroxysuccinimide compound comprises N-hydroxysuccinimide; wherein the mass ratio of the oxidation responsive cross-linking agent, the carbodiimide coupling agent and the N-hydroxysuccinimide compound is 1:1.0-1.5:0.8-1.0; The concentration of the oxidation-responsive cross-linking agent in the oxidation-responsive cross-linking agent reaction solution is 10-15 mg/mL; The activation reaction time is 3-12 hours.
  6. 6. The method for producing an oxidation-responsive hydrogel carrying a lycium barbarum glycopeptide of claim 4, wherein in step S2, the oil phase material comprises paraffin wax, and the surfactant comprises span 80; The concentration of gelatin in the water phase is 10-30 mg/mL; the volume ratio of the oil phase material to the surfactant is 40-50:3-4; the volume ratio of the water phase to the oil phase is 1.2-1.5:1; in step S2, emulsification is performed under heating.
  7. 7. The method for producing an oxidation-responsive hydrogel carrying a lycium barbarum glycopeptide according to claim 4, wherein in the step S3, the reaction solution of the oxidation-responsive crosslinking agent is added dropwise to the emulsion, and the reaction is stirred in an ice bath for 3 to 12 hours.
  8. 8. The method for preparing an oxidation-responsive hydrogel carrying a medlar glycopeptide according to any one of claims 3 to 7, wherein the concentration of the aqueous solution of the hydrogel scaffold component a is 5 to 10wt% and the concentration of the aqueous solution of the hydrogel scaffold component B is 3 to 8wt%.
  9. 9. The use of an oxidation-responsive hydrogel carrying a lycium barbarum glycopeptide according to claim 1 or 2, for the preparation of a medicament for preventing or/and treating an oral disease associated with a highly oxidizing environment.
  10. 10. The use of an oxidation-responsive hydrogel for encapsulating a lycium barbarum glycopeptide according to claim 9, wherein the oral cavity disease associated with a highly oxidizing environment comprises at least one of periodontitis, peri-implantitis, and radiojaw necrosis.

Description

Oxidative response hydrogel carrying medlar glycopeptide and preparation method and application thereof Technical Field The invention belongs to the technical field of biological medicines, and particularly relates to an oxidation-responsive hydrogel carrying medlar glycopeptide, and a preparation method and application thereof. Background Oral health is an important sign of human physical and mental health. The incidence rate of the oral diseases is high, so that normal functions such as chewing, speech, attractive appearance and the like are affected, social difficulties and psychological disorders can be caused, and the oral diseases are closely related to various systemic diseases. The jawbone is used as an important supporting structure of the maxillofacial region and plays a key role in maintaining the appearance of the face, realizing the chewing function, participating in physiological activities such as pronunciation and the like. The jawbone defect can cause the loss of the function of the oromandibular system, which seriously affects the life quality and the working capacity of patients. The main methods for clinically treating the jawbone defect at present comprise autologous or allogeneic bone grafting, bone substitute grafting, stem cell tissue engineering bone, stretching and osteogenesis technologies and the like, but the methods have certain limitations, such as donor area injury, immune rejection, unstable osteogenesis effect, complex operation, long treatment course and the like. Therefore, searching for a safe, effective and easy-to-operate jaw defect repair method becomes an important research direction in the current oral medicine field. The lycium barbarum glycopeptide is a main active component of lycium barbarum, and has various biological activities of anti-inflammatory, immunoregulation, antioxidation, osteogenesis promotion and the like. Researches show that the medlar glycopeptide can promote proliferation, migration and osteogenic differentiation of human periodontal ligament stem cells through ERK1/2 and other signal channels, inhibit the activity of osteoclast cells, and further slow down alveolar bone resorption. In addition, the prebiotic property can promote the generation of short chain fatty acid by regulating the metabolism of intestinal flora, further up-regulate the expression of bone formation related factor BMP-2, activate transcription factor RUNX2 and promote bone formation. At present, the medlar glycopeptide is loaded into biological materials for treating oral diseases, but the defects of over-quick drug release, short material retention time, insufficient curative effect maintenance and the like still exist. Active oxygen (e.g., superoxide, hydroxyl radicals, etc.) plays an important role in the progression of oral disease. Appropriate levels of reactive oxygen species are involved in cell signaling and antibacterial defenses, but excessive accumulation can lead to oxidative stress, triggering tissue damage and pathological changes. Active oxygen is one of the key factors responsible for bone destruction in oral diseases such as periodontitis, peri-implant inflammation, and radioosteonecrosis. Therefore, a delivery system capable of responding to the active oxygen level in the focus microenvironment and realizing the controllable release of the medlar glycopeptide is constructed, and the method has important clinical significance. Therefore, the bone repair method capable of responding to active oxygen and controlling the release of the medlar glycopeptide has the characteristics of targeted drug release, long-acting maintenance, good biocompatibility and simple operation, and becomes a technical problem to be solved by the technicians in the field. Disclosure of Invention The invention aims to provide an oxidation-responsive hydrogel carrying medlar glycopeptide, which solves the problems of uncontrollable drug effect release, short material retention time, unsatisfactory osteogenesis effect and the like in the prior art. The second object of the present invention is to provide a method for producing the oxidation-responsive hydrogel carrying a lycium barbarum glycopeptide. The third object of the present invention is to provide an application of the oxidation-responsive hydrogel carrying a lycium barbarum glycopeptide. In order to achieve the above purpose, the technical scheme adopted by the invention is as follows: The invention discloses an oxidation-responsive hydrogel carrying medlar glycopeptide, which comprises in-situ hydrogel formed by crosslinking a hydrogel bracket component A and a hydrogel bracket component B, and oxidation-responsive microspheres embedded by the in-situ hydrogel, wherein the mass ratio of the hydrogel bracket component A to the hydrogel bracket component B to the oxidation-responsive microspheres is 100:100-200:1-3; the hydrogel bracket component A comprises at least one of oxidized hyaluronic acid, oxidized sodium alginate, ox