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CN-121971694-A - Hydrogel dressing and preparation method thereof

CN121971694ACN 121971694 ACN121971694 ACN 121971694ACN-121971694-A

Abstract

The application relates to the technical field of medical dressings, in particular to a hydrogel dressing and a preparation method thereof, wherein the hydrogel dressing comprises, by weight, 1-20 parts of bacterial cellulose, 1-10 parts of toluene isocyanate, 0.5-5 parts of modified folic acid, 1-10 parts of metal organic framework nanoparticles and 50-200 parts of solvent. The application carries out external surface precise modification on the copper-based MOFs by the folic acid-polyethylene glycol conjugate, solves the problem of copper ion burst release, maintains the tunnel integrity to ensure the long-acting controllable release of copper ions, constructs a three-dimensional covalent cross-linked network by matching toluene isocyanate, improves the mechanical property and MOFs fixity of hydrogel, combines the advantages of a bionic bracket, wetting and moisturizing, dual antibacterial and biocompatibility of bacterial cellulose, and solves the core problems of poor stability, easiness in hole blocking during folic acid modification, poor copper ion release and control and primary preparation form of related wound products of the existing copper-based MOFs.

Inventors

  • Li Kangyue
  • LI XUEBIN
  • ZHAO XIN

Assignees

  • 杭州端本医药科技有限公司

Dates

Publication Date
20260505
Application Date
20260409

Claims (10)

  1. 1. The hydrogel dressing is characterized by comprising the following components in parts by weight: 1-20 parts of bacterial cellulose; 1-10 parts of toluene isocyanate; 0.5-5 parts of modified folic acid; 1-10 parts of metal organic framework nano particles; 50-200 parts of solvent.
  2. 2. The hydrogel dressing of claim 1, wherein the hydrogel dressing comprises, in parts by weight: 5-10 parts of bacterial cellulose; 2-8 parts of toluene isocyanate; 1-4 parts of modified folic acid; 2-8 parts of metal organic framework nano particles; 80-120 parts of solvent.
  3. 3. The hydrogel dressing of claim 2, wherein the modified folic acid comprises, by weight: 0.5-1.5 parts of folic acid; 2-10 parts of polyethylene glycol; 0.1-1 part of coupling agent; 0.01-0.1 part of catalyst; 10-50 parts of reaction solvent.
  4. 4. A hydrogel dressing according to claim 3, wherein the polyethylene glycol has a molecular weight of 2000-5000Da, the coupling agent is selected from at least one of 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide, dicyclohexylcarbodiimide, N-hydroxysuccinimide, the catalyst is selected from at least one of 4-dimethylaminopyridine, triethylamine, and the reaction solvent is selected from at least one of dimethyl sulfoxide, N-dimethylformamide, phosphate buffer.
  5. 5. The hydrogel dressing of claim 2, wherein the metal-organic framework nanoparticles are copper-based metal-organic frameworks selected from at least one of HKUST-1, NOTT-100, cu-MOF-74, and the metal-organic framework nanoparticles have a particle size of 100-200nm.
  6. 6. A hydrogel dressing according to claim 2, wherein the bacterial cellulose is nano bacterial cellulose having a fiber diameter of 20-100nm and a length of 1-10 μm.
  7. 7. A hydrogel dressing according to claim 2, wherein the solvent is selected from water, phosphate buffer, physiological saline, ethanol or dimethyl sulfoxide.
  8. 8. The hydrogel dressing of claim 2, wherein the modified folic acid is modified on an outer surface of the metal-organic framework nanoparticle to form a modified folic acid modified metal-organic framework nanoparticle, wherein the modified folic acid has a molecular size greater than a pore size of the metal-organic framework nanoparticle.
  9. 9. The method of preparing a hydrogel dressing according to any one of claims 1 to 8, comprising the steps of: S1, preparing modified folic acid, namely dissolving folic acid, polyethylene glycol, a coupling agent and a catalyst in a reaction solvent, reacting for 12-48 hours at 20-40 ℃, and purifying to obtain a folic acid-polyethylene glycol conjugate; S2, preparing metal organic framework nano-particles modified by modified folic acid, namely dispersing the metal organic framework nano-particles in a solvent, adding the modified folic acid obtained in the step S1, reacting for 2-24 hours at 25-60 ℃, and centrifugally washing to obtain the metal organic framework nano-particles modified by the modified folic acid; S3, preparing bacterial cellulose dispersion liquid, namely dispersing bacterial cellulose in a solvent, and homogenizing for 5-30 minutes at the rotating speed of 5000-20000rpm to obtain uniform bacterial cellulose dispersion liquid with the mass percentage concentration of 3-8%; S4, preparing isocyanate-terminated polyethylene glycol, namely mixing toluene isocyanate and polyethylene glycol according to a molar ratio of (2-10): 1, and reacting for 4-24 hours in an anhydrous solvent at 40-80 ℃ under the protection of nitrogen to obtain isocyanate-terminated polyethylene glycol; s5, crosslinking reaction, namely adding the isocyanate-terminated polyethylene glycol obtained in the step S4 into the bacterial cellulose dispersion liquid obtained in the step S3, and reacting for 2-24 hours at 25-60 ℃ to form a crosslinked network; S6, compounding and molding, namely adding the modified folic acid modified metal organic framework nano particles obtained in the step S2 into the crosslinking system obtained in the step S5, uniformly mixing, casting into a mold after ultrasonic defoaming, and standing and molding for 6-24 hours at the temperature of 25-37 ℃ to obtain the hydrogel dressing.
  10. 10. The method of preparing a hydrogel dressing according to claim 9, wherein in step S4, the anhydrous solvent is selected from dimethyl sulfoxide, N-dimethylformamide or toluene.

Description

Hydrogel dressing and preparation method thereof Technical Field The invention relates to the technical field of medical dressing, in particular to a hydrogel dressing and a preparation method thereof. Background The chronic refractory wound surface is one of the most serious complications of diabetics, wherein diabetic foot ulcers are particularly typical, and the core pathological characteristics of the chronic refractory wound surface are that the wound surface is subjected to local continuous inflammatory reaction, impaired angiogenesis capacity, insufficient collagen deposition and repeated infection, so that the life quality of the patients is seriously reduced, extremely high disability rate is caused, and meanwhile, heavy social medical burden is caused. The traditional gauze, hydrocolloid dressing, foam dressing and the like are mainly used as the wound dressing in the conventional clinical practice at present, the core functions of the wound dressing are concentrated on physical isolation of the wound, absorption of seepage and maintenance of moist microenvironment of the wound, the capacity of actively regulating and controlling the microenvironment of the wound is generally lacking, the biological behaviors such as proliferation and migration of key cells related to wound repair cannot be effectively promoted, the regeneration process of damaged tissues is difficult to accelerate, the biological activity is lacking, and the healing promoting effect on chronic difficultly healed wound is very limited. To impart active healing-promoting biological functions to a wound dressing, researchers focused the direction of research on active ions with defined biological regulation, where copper ions are a key regulator in the wound healing process as demonstrated by a large number of studies. Copper ions can effectively promote local angiogenesis of a wound surface, collagen synthesis, epithelialization process and tissue matrix remodeling by up-regulating the expression of various core growth factors such as vascular endothelial growth factors, fibroblast growth factors and the like, so that wound surface healing is remarkably accelerated. However, when the copper ions are directly applied to wound surface treatment, the method still faces a plurality of fundamental technical challenges, namely firstly, uncontrollable release process, easy rapid release of the copper ions in wound surface exudates, local concentration sudden rise, even cytotoxicity and oxidative stress injury initiation, secondly, short effect time, frequent dressing change for maintaining the local effective treatment concentration of the wound surface, increase of treatment cost and aggravation of pain of patients, thirdly, lack of targeting, difficult effective enrichment of the copper ions at the wound surface part and low bioavailability. To solve the problem of controlled release of copper ions, MOFs (Metal-Organic Frameworks, metal-organic framework materials) are introduced into the field of research as an emerging class of biomaterial carriers. MOFs are porous crystal materials formed by self-assembling metal ions/metal clusters and organic ligands through coordination bonds, have ultrahigh specific surface area, precisely controllable pore channel size and chemical composition, and are ideal active ingredient loading and controlled release carriers. Wherein, copper-based MOFs can be loaded with copper ions and can be slowly released as required, and are used as a first-choice target. However, copper-based MOFs have the fatal defect in the practical application of wound treatment that the stability is extremely poor in a physiological environment containing protein, protein molecules in wound exudates are easy to cause rapid collapse of MOFs structures, so that carried copper ions are rapidly released, the toxicity problem of directly using copper salts is reappeared, and the slow release potential of MOFs cannot be exerted. Aiming at the stability bottleneck of the copper-based MOFs, the prior research has been carried out to explore the related technology, small molecular folic acid is introduced as a modifier in the synthesis process of the copper-based MOFs, the hydrophobicity of the MOFs is improved through folic acid doping, the degradation rate of the MOFs in a serum-containing culture medium is slowed down, the release of copper ions is slower than that of the unmodified MOFs, and a better healing-promoting effect is shown in a diabetic mouse wound surface model. The technical scheme has the remarkable and unresolved core contradiction that folic acid molecules can enter and occupy the pore space of MOFs while improving the stability of the MOFs, so that serious pore blockage is caused, the specific surface area of the material is greatly reduced, the loading capacity of the MOFs as a carrier is greatly limited, other therapeutic agents such as antibiotics, growth factors and the like are difficult to load simultaneously,