CN-117084970-B - Supermolecule hydrogel based on natural plant components, preparation and application thereof

CN117084970BCN 117084970 BCN117084970 BCN 117084970BCN-117084970-B

Abstract

The invention belongs to the field of hydrogel biological medicines, and particularly discloses a supermolecule hydrogel based on natural plant components, and preparation and application thereof. The hydrogel only contains polyphenol, polysaccharide and solvent, and the hydrogel is formed into gel in situ only through the supermolecular acting force between the polyphenol and the polysaccharide. The hydrogels of the present invention can be prepared by simple mixing, or can be injected in situ by syringe. The hydrogel has the advantages of simple preparation process, low raw material cost and high gel forming speed, can effectively adhere to skin, isolate the contact between a wound and the external environment, avoid invasion of pathogens, is breathable and moisture-preserving, can provide a moist environment suitable for healing for the wound, and can completely and rapidly release polyphenol. The hydrogel also has excellent antibacterial, antioxidant, anti-inflammatory and angiogenesis promoting functions, so that the wound healing can be accelerated and the bacterial infection wound healing can be accelerated.

Inventors

ZHU JINTAO
CHEN QIANG
DU SHUO
ZHANG LIANBIN

Assignees

华中科技大学

Dates

Publication Date: 20260505
Application Date: 20230830

Claims (6)

1. A supermolecular hydrogel based on natural plant components is characterized by only containing polyphenol, polysaccharide and solvent, wherein the polysaccharide is natural polysaccharide or natural polysaccharide derivative, and the hydrogel is in-situ gelled by supermolecular acting force between the polyphenol and the polysaccharide; the polyphenol is at least one of gallic acid, protocatechuic acid, epigallocatechin gallate and resveratrol; The natural polysaccharide is at least one of starch, carrageenan and chitosan; the natural polysaccharide derivative is at least one of sodium alginate, sodium hyaluronate and chitosan derivative, wherein the chitosan derivative is carboxymethyl chitosan; the supermolecule hydrogel based on the natural plant components is prepared by the following steps: (1) Preparing a polyphenol solution and a polysaccharide solution respectively, wherein the polysaccharide solution is a natural polysaccharide solution or a natural polysaccharide derivative solution, a solvent used by the polyphenol solution is a mixed solvent of water and an organic solvent, the organic solvent is at least one of ethanol and dimethyl sulfoxide, and the organic solvent is used for improving the solubility of polyphenol; (2) Uniformly mixing the polyphenol solution and the polysaccharide solution obtained in the step (1), wherein the uniform mixing mode is in-situ injection, heating is not needed, and the polyphenol and the polysaccharide are subjected to in-situ gel forming through a supermolecular acting force, so that the supermolecular hydrogel based on natural plant components is obtained; The concentration of the polyphenol in the hydrogel is 0.9 wt-27 wt%, the concentration of the polysaccharide in the hydrogel is 0.9-wt-28 wt%, and the weight ratio of the polyphenol to the polysaccharide in the hydrogel is 0.03-30; the in-situ injection is to respectively fill the polyphenol solution and the polysaccharide solution into two syringes of a double-syringe for injection and uniform mixing.
2. The natural plant ingredient based supramolecular hydrogel according to claim 1, wherein the supramolecular forces are hydrogen bonding, hydrophobic forces and pi-pi stacking forces.
3. The natural plant ingredient based supramolecular hydrogel according to claim 1, wherein the interior of the supramolecular hydrogel is a micro-scale porous structure.
4. A method for preparing a supramolecular hydrogel based on natural plant ingredients according to any one of claims 1-3, characterized in that it comprises the following steps: (1) Preparing a polyphenol solution and a polysaccharide solution respectively, wherein the polysaccharide solution is a natural polysaccharide solution or a natural polysaccharide derivative solution, a solvent used by the polyphenol solution is a mixed solvent of water and an organic solvent, the organic solvent is at least one of ethanol and dimethyl sulfoxide, and the organic solvent is used for improving the solubility of polyphenol; (2) Uniformly mixing the polyphenol solution and the polysaccharide solution obtained in the step (1), wherein the uniform mixing mode is in-situ injection, heating is not needed, and the polyphenol and the polysaccharide are subjected to in-situ gel forming through a supermolecular acting force, so that the supermolecular hydrogel based on natural plant components is obtained; The concentration of the polyphenol solution is 40 mg/mL-500 mg/mL, the concentration of the polysaccharide solution is 50 mg/mL-600 mg/mL, and the volume ratio of the polyphenol solution to the polysaccharide solution is 0.5-3; the in-situ injection is to respectively fill the polyphenol solution and the polysaccharide solution into two syringes of a double-syringe for injection and uniform mixing.
5. The method for preparing a supramolecular hydrogel based on natural plant ingredients according to claim 4, wherein the volume ratio of water in the mixed solvent is 60% -80%.
6. Use of a supramolecular hydrogel based on natural plant ingredients according to any one of claims 1-3 for the preparation of a topical formulation for skin that promotes wound healing.

Description

Supermolecule hydrogel based on natural plant components, preparation and application thereof Technical Field The invention belongs to the field of hydrogel biological medicines, and in particular relates to a supermolecule hydrogel based on natural plant components, and preparation and application thereof. Background Skin is the first natural barrier of the human body and plays a very important role in performing life activities and communicating with the outside. Although most minor skin wounds heal within weeks, the rate of skin self-healing can be very slow, even non-healing, when patients develop extensive skin wounds, burns, infectious wounds, and hard-to-heal ulcers caused by chronic diseases such as diabetes. Hydrogel dressings are now widely used for skin wound repair because of their three-dimensional network structure, physical properties mimicking the extracellular matrix, the ability to retain therapeutic biomolecules in their network, and biocompatibility, as ideal carriers for loading therapeutic drugs. The injectable hydrogel is formed by on-site chemical reaction or sol-gel phase transition after gel precursor injection, has the advantages of high plasticity, convenient operation and the like, can fill irregular defect parts through certain fluidity, has good anastomosis with the defect parts, and has small and easy operation after injection filling. And thus are more widely used. In view of bacterial infection and abnormal inflammation of chronic wounds, therapeutic molecules including antibiotics, anti-inflammatory drugs, cytokines, growth factors, etc. are required to prepare injectable hydrogel wound dressings. However, most therapeutic molecules with biological effects cannot be used directly to construct hydrogels, and additional preparation processes such as uv light irradiation, heating, freezing, and addition of additives (e.g., initiators and cross-linking agents) must be performed to encapsulate these therapeutic molecules. These complex processes increase the preparation time and cost and disrupt the balance of the infected wound healing environment. Therefore, a multifunctional injectable hydrogel wound dressing system with simple preparation process, low raw material and preparation cost and high gelation speed is needed. Disclosure of Invention In view of the above-mentioned drawbacks or improvements of the prior art, an object of the present invention is to provide a supramolecular hydrogel based on natural plant components, which is obtained rapidly by sufficiently mixing a polyphenol solution with a natural polysaccharide solution, and which has a raw material selected from natural plants, a wide source and a low cost, compared with the prior art; the hydrogel can be formed by only depending on non-covalent supermolecular acting force formed by polyphenol and natural polysaccharide, so that the preparation process is simple, heating, modification, ultraviolet irradiation, introduction of chemical cross-linking agent, photoinitiator or enzyme are not needed, and expensive and complex equipment is not needed. Compared with the prior art, the prepared supermolecule hydrogel based on natural plant components can effectively adhere to skin, and can be injected in situ by using a syringe. The supramolecular hydrogel based on natural plant components has high biological safety, and can rapidly release polyphenol therein, so that the supramolecular hydrogel has the effects of resisting bacteria, resisting oxidation, resisting inflammation, promoting angiogenesis, promoting cell proliferation, promoting wound healing and promoting wound healing of bacterial infection. In order to achieve the above object, according to one aspect of the present invention, there is provided a supramolecular hydrogel based on natural plant components, the supramolecular hydrogel comprising only polyphenols, polysaccharides and solvents, the polysaccharides being natural polysaccharides or natural polysaccharide derivatives, the hydrogel being gelled in situ by the supramolecular forces between the polyphenols and the polysaccharides. Preferably, the supramolecular forces are hydrogen bonding, hydrophobic forces and pi-pi stacking forces. Preferably, the polyphenol is at least one of gallic acid, protocatechuic acid, epigallocatechin gallate, resveratrol and tannic acid; The natural polysaccharide is at least one of starch, carrageenan and chitosan; the natural polysaccharide derivative is at least one of sodium alginate, sodium hyaluronate and chitosan derivative. Preferably, the supramolecular hydrogel is internally of a micron-sized porous structure. Preferably, the concentration of the polyphenol in the hydrogel is 0.9-27 wt%, the concentration of the polysaccharide in the hydrogel is 0.9-28 wt%, and the weight ratio of the polyphenol to the polysaccharide in the hydrogel is 0.03-30. According to another aspect of the present invention, there is provided a method for preparing a supramolecular hydr