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CN-121203157-B - POSS-glutathione hybrid material with cartilage protection function, and preparation method and application thereof

CN121203157BCN 121203157 BCN121203157 BCN 121203157BCN-121203157-B

Abstract

The application discloses a POSS-glutathione hybrid material with a cartilage protecting function, and a preparation method and application thereof. The hybrid material takes a rigid three-dimensional nano cage-shaped structure of POSS molecules as a core bracket, and fixes Glutathione (GSH) molecules on the surface of the core bracket through covalent grafting, so as to construct the hybrid material with stable structure and durable function. The preparation method comprises the steps of firstly preparing double-bonded glutathione, and then covalently grafting the double-bonded glutathione with sulfhydryl POSS (POSS-SH) molecules through 'ene-thiol click chemistry reaction'. The hybrid material has a stable structure, can effectively enrich inflammatory sites and improve the bioavailability of GSH, can effectively regulate local inflammatory microenvironment of joints, obviously reduce the level of pro-inflammatory factors, plays a role in maintaining cartilage elasticity and promoting tissue homeostasis, and has good application prospect.

Inventors

  • LU YONG
  • WEI GANG
  • GENG XIAOCHUAN
  • ZHANG KEZHEN
  • WANG HANQI
  • ZHANG JIAHUI

Assignees

  • 上海交通大学医学院附属瑞金医院

Dates

Publication Date
20260508
Application Date
20251128

Claims (9)

  1. 1. The preparation method of the POSS-glutathione hybrid material with the cartilage protection effect is characterized by comprising the following steps of: Sequentially adding glutathione, an organic solvent and triethylamine into a reaction container, adding methacryloyl chloride under inert atmosphere, heating for reaction, cooling after the reaction is finished, dropwise adding a mixture obtained by the reaction into an aqueous solution, separating out solids, sequentially filtering, recrystallizing and drying to obtain doubly-linked glutathione; and 2, dissolving the sulfhydryl POSS, the photoinitiator and the double-bonded glutathione obtained in the step 1 in an organic solvent, then carrying out illumination reaction at room temperature, and removing the solvent by rotary evaporation after the reaction is finished, thus obtaining the POSS-glutathione hybrid material.
  2. 2. The preparation method according to claim 1, wherein the organic solvent in the step 1 is N-methyl-2-pyrrolidone and/or N, N-dimethylformamide.
  3. 3. The preparation method according to claim 1, wherein the feeding molar ratio of glutathione, triethylamine and methacryloyl chloride in the step 1 is 1:1-1.2:1-1.2.
  4. 4. The method according to claim 1, wherein the heating reaction in step 1 is performed at a temperature of 40 to 60 ℃ for a time of 10 to 20 hours.
  5. 5. The process according to claim 1, wherein the organic solvent in the step 2 is one or more of tetrahydrofuran, 1, 4-dioxane and ethylene glycol dimethyl ether, and/or the photoinitiator in the step 2 is at least one selected from 651 photoinitiators, irgacure 2959, irgacure184 and MBF.
  6. 6. The method according to claim 1, wherein the molar ratio of thiol POSS, photoinitiator and doubly linked glutathione in step 2 is 1:0.02-0.1:1.5-2.5, and/or the time of the photoreaction in step 2 is 4-8 hours.
  7. 7. The POSS-glutathione hybrid material prepared by the preparation method of any one of claims 1 to 5.
  8. 8. The use of the POSS-glutathione hybrid material prepared by the preparation method of any one of claims 1-5 in the preparation of products for the treatment of osteoarthritis.
  9. 9. The use of the POSS-glutathione hybrid material prepared by the preparation method of any one of claims 1-5 in the preparation of cartilage-protecting products.

Description

POSS-glutathione hybrid material with cartilage protection function, and preparation method and application thereof Technical Field The application belongs to the technical field of biomedicine, and particularly relates to a POSS-glutathione hybrid material with a cartilage protecting effect, and a preparation method and application thereof. Background Osteoarthritis (OA) is a chronic degenerative disease of an anatomic disorder characterized by abnormal metabolism of joint tissue and cartilage degradation, and is the degenerative joint disease with the highest global disability rate. The prevalence rate of the elderly population over 60 years old is up to 62.2%, and the risk of illness in women, especially after menopause, is 60% -80% higher than in men. Notably, early-onset osteoarthritis cases under 45 years old increase by 17%. OA significantly reduces the quality of life of patients, is a major disabling disease, affecting walking and even losing independent lifestyle when severe. Pain in OA does not occur infrequently. Early may be post-activity pain and later progression to resting pain and nocturnal pain, meaning that the patient is afflicted even at rest. The daily activities of walking, going up and down stairs, squatting and rising become extraordinarily difficult and painful. Advanced patients may be able to move only to a very small extent, even relying entirely on walkers or wheelchairs. The reduced movement due to pain results in rapid atrophy of muscles surrounding the joint (e.g., the quadriceps thigh), which further weakens the stability of the joint, creating a "pain-reduced movement-muscular atrophy-less stable-more painful" vicious circle. More than half (58.49%) of osteoarthritis patients present with anxiety depression symptoms. Night pain and joint stiffness can severely interfere with sleep, resulting in the inability of the patient to go deep sleep. Long-term sleep deprivation exacerbates pain sensitivity, cognitive decline, and mood disorders, forming another vicious circle. Traditional medicines (such as NSAIDs patch, acetaminophen, aspirin, ibuprofen, etc.) mainly exert analgesic effects on diseases, and cannot delay the progress of the diseases, but the method of injecting hyaluronic acid into joint cavities can temporarily improve joint functions, but the curative effect is difficult to last. Oxidative stress is one of the core pathological mechanisms of osteoarthritis cartilage degeneration, and intervention strategies directed against this pathway have important therapeutic value. Glutathione (GSH) has significant potential in terms of antioxidant stress as an antioxidant molecule capable of effectively scavenging active oxygen and reducing inflammatory reactions, but its direct application is limited by inherent chemical instability and extremely short half-life in the joint cavity, resulting in low bioavailability. More critical, GSH cannot reach the deep cartilage, resulting in limited protection of the deep cartilage. Based on the technical problems, the inventor provides a POSS-glutathione hybrid material. The material utilizes POSS nano-scaffold to enhance stability and half-life of GSH, deliver GSH to deep cartilage, and improve availability. Is expected to realize long-acting and targeted oxidation-resistant treatment of full-layer cartilage in the joint cavity, and provides a brand new treatment scheme for overcoming the cartilage degradation of OA. Disclosure of Invention The application aims to provide a glutathione hybridization material based on oligomeric cage silsesquioxane (POSS) and application thereof in cartilage protection aiming at the defects of the prior art. The hybrid material takes a rigid three-dimensional nano cage-shaped structure of POSS molecules as a core bracket, and fixes Glutathione (GSH) molecules on the surface of the core bracket through covalent grafting, so as to construct the hybrid material with stable structure and durable function. In order to achieve the above purpose, the present application adopts the following technical scheme: in a first aspect, the application provides a method for preparing a POSS-glutathione hybrid material with a cartilage protecting function, comprising the following steps: Sequentially adding glutathione, an organic solvent and triethylamine into a reaction container, adding methacryloyl chloride under inert atmosphere, heating for reaction, cooling after the reaction is finished, dropwise adding a mixture obtained by the reaction into an aqueous solution, separating out solids, sequentially filtering, recrystallizing and drying to obtain doubly-linked glutathione; Step 2, dissolving the sulfhydryl POSS (POSS-SH) and the doubly linked glutathione obtained in the step 1 in an organic solvent, then carrying out illumination reaction at room temperature, and removing the solvent by rotary evaporation after the reaction is finished to obtain a POSS-glutathione hybrid material; preferably, the organic solvent