A supramolecular hydrogel based on natural plant ingredients, its preparation and use

Abstract

The application belongs to the field of hydrogel biological medicine, and more particularly discloses a kind of supramolecular hydrogel based on natural plant ingredients, preparation and application thereof.The hydrogel only contains polyphenol, polysaccharide and solvent, and the hydrogel is in-situ gelled only by supramolecular interaction between polyphenol and polysaccharide.The hydrogel of the application can be prepared by simple mixing, and can also be in-situ injected by a syringe.The hydrogel preparation process is simple, the raw material cost is low, and the gelation speed is fast;the hydrogel can effectively adhere to the skin, isolate the contact between the wound and the external environment, avoid the invasion of pathogens, at the same time, it is breathable and moisturizing, can provide a suitable moist environment for wound healing, and can completely and quickly release polyphenol.The hydrogel also has excellent antibacterial, antioxidant, anti-inflammatory and pro-angiogenic functions, so it can accelerate wound healing and accelerate bacterial infection wound healing.

Description

Technical Field

[0001] This invention belongs to the field of hydrogel biomedicine, and more specifically, relates to a supramolecular hydrogel based on natural plant components, its preparation and application. Background Technology

[0002] The skin is the body's first natural barrier, playing a vital role in vital functions and communication with the outside world. While most minor skin wounds heal within weeks, the skin can heal very slowly or not at all when patients experience large-area skin trauma, burns, infected wounds, or ulcers that are difficult to heal due to chronic diseases such as diabetes.

[0003] Hydrogel dressings, due to their three-dimensional network structure, mimicking the physical properties of the extracellular matrix, ability to retain therapeutic biomolecules within their network, and biocompatibility, are considered ideal carriers for therapeutic drugs and are now widely used in skin wound repair. Injectable hydrogels, in particular, are formed through on-site chemical reactions or by the sol-gel phase transition following the injection of a gel precursor. Injectable hydrogels also possess advantages such as high plasticity and ease of handling; they can fill irregular defects with a certain degree of fluidity, exhibiting good conformation to the defect site. Furthermore, the surgical trauma from injection filling is minimal and the procedure is easy to perform. Therefore, they are used even more widely.

[0004] Considering the bacterial infection and abnormal inflammation of chronic wounds, therapeutic molecules, including antibiotics, anti-inflammatory drugs, cytokines, and growth factors, are needed to prepare injectable hydrogel wound dressings. However, most bioactive therapeutic molecules cannot be directly used to construct hydrogels; additional preparation processes such as ultraviolet irradiation, heating, freezing, and the addition of additives (e.g., initiators and cross-linking agents) are required to encapsulate these therapeutic molecules. These complex processes increase preparation time and cost and disrupt the balance of the healing environment of infected wounds. Therefore, there is a need for injectable hydrogel wound dressing systems that are simple to prepare, have low raw material and preparation costs, rapid gelation, and are multifunctional. Summary of the Invention

[0005] To address the aforementioned deficiencies or improvement needs of existing technologies, the present invention aims to provide a supramolecular hydrogel based on natural plant components, its preparation, and its application. This method rapidly obtains a supramolecular hydrogel by thoroughly mixing a polyphenol solution with a natural polysaccharide solution. Compared to existing technologies, the raw materials for this supramolecular hydrogel are selected from natural plants, making them widely available and inexpensive. The hydrogel forms a gel solely through non-covalent supramolecular interactions between polyphenols and natural polysaccharides, thus simplifying the preparation process. It eliminates the need for heating, modification, ultraviolet irradiation, the introduction of chemical cross-linking agents, photoinitiators, or enzymes, and also eliminates the need for expensive and complex equipment. Compared to existing technologies, the supramolecular hydrogel prepared by this invention effectively adheres to the skin and can be injected in situ using a syringe. Furthermore, the supramolecular hydrogel based on natural plant components exhibits high biocompatibility, rapidly releasing polyphenols, thereby providing antibacterial, antioxidant, anti-inflammatory, angiogenesis-promoting, cell proliferation-promoting, wound-healing, and bacterial wound-healing effects.

[0006] To achieve the above objectives, according to one aspect of the present invention, a supramolecular hydrogel based on natural plant components is provided, wherein the supramolecular hydrogel contains only polyphenols, polysaccharides and a solvent, wherein the polysaccharides are natural polysaccharides or natural polysaccharide derivatives; the hydrogel is gelled in situ through supramolecular forces between the polyphenols and the polysaccharides.

[0007] Preferably, the supramolecular forces are hydrogen bonds, hydrophobic forces, and π-π stacking forces.

[0008] Preferably, the polyphenol is at least one selected from gallic acid, protocatechuic acid, epigallocatechin gallate, resveratrol, and tannic acid;

[0009] The natural polysaccharide is at least one of starch, carrageenan and chitosan;

[0010] The natural polysaccharide derivative is at least one of sodium alginate, sodium hyaluronate, and chitosan derivative.

[0011] Preferably, the supramolecular hydrogel has a micron-sized porous structure inside.

[0012] Preferably, the concentration of the polyphenol in the hydrogel is 0.9wt%-27wt%; the concentration of the polysaccharide in the hydrogel is 0.9wt%-28wt%; and the weight ratio of the polyphenol to the polysaccharide in the hydrogel is 0.03-30.

[0013] According to another aspect of the present invention, a method for preparing supramolecular hydrogels based on natural plant components as described in any one of the claims is provided, comprising the following steps:

[0014] (1) Prepare polyphenol solution and polysaccharide solution respectively, wherein the polysaccharide solution is a natural polysaccharide solution or a natural polysaccharide derivative solution; the solvent used for the polyphenol solution is water or a mixture of water and an organic solvent, wherein the organic solvent is at least one of ethanol and dimethyl sulfoxide, and the organic solvent is used to improve the solubility of polyphenol; the solvent used for the polysaccharide solution is water.

[0015] (2) Mix the polyphenol solution and polysaccharide solution obtained in step (1) to allow the polyphenol and polysaccharide to gel in situ through supramolecular forces, thus obtaining a supramolecular hydrogel based on natural plant components.

[0016] Preferably, the concentration of the polyphenol solution is 40 mg / mL-500 mg / mL, and the concentration of the polysaccharide solution is 50 mg / mL-600 mg / mL; the volume ratio of the polyphenol solution to the polysaccharide solution is 0.5-3.

[0017] Preferably, the mixing method is stirring, shaking, or ultrasound, or in-situ injection;

[0018] Preferably, the in-situ injection involves injecting and mixing the polyphenol solution and polysaccharide solution separately into the two syringes of a dual-barrel syringe.

[0019] Preferably, the volume percentage of water in the mixed solvent is 60%-100%.

[0020] According to another aspect of the present invention, the supramolecular hydrogel based on any one of the natural plant components is provided for use in the preparation of topical skin administration formulations that promote wound healing.

[0021] In summary, compared with the prior art, the above-described technical solutions conceived by this invention can achieve the following beneficial effects:

[0022] (1) This invention provides a supramolecular hydrogel based on natural polysaccharides and natural polyphenols. Compared with the prior art, the supramolecular hydrogel in this invention uses widely available and low-cost raw materials, making it suitable for large-scale production.

[0023] (2) This invention provides a supramolecular hydrogel based on natural polysaccharides and natural polyphenols, which can quickly form a gel through the non-covalent supramolecular interaction between polyphenols and natural polysaccharides. Therefore, the preparation process is simple and does not require heating, modification, ultraviolet light irradiation, introduction of chemical crosslinking agents, photoinitiators or enzymes, nor does it require expensive and complex equipment. This solves the problems of complex process, long preparation time and high cost of existing wound healing hydrogels.

[0024] (3) The supramolecular hydrogel based on natural polysaccharides and natural polyphenols provided by the present invention can be injected into the wound in situ with a syringe, and the gel can effectively adhere to and stick to the wound, improving the gel retention and polyphenol utilization efficiency.

[0025] (4) The present invention provides a supramolecular hydrogel based on natural polysaccharides and natural polyphenols, which can effectively isolate the wound from contact with harmful substances in the external environment, avoid infection, and at the same time provide a favorable environment for wound healing by being breathable and moisturizing.

[0026] (5) The supramolecular hydrogel based on natural polysaccharides and natural polyphenols provided by the present invention has high biosafety, can quickly release polyphenols therein for treatment, reduce treatment time, and prevent further deterioration of wounds.

[0027] (6) When the supramolecular hydrogel based on natural polysaccharides and natural polyphenols provided by the present invention is applied to the wound, it can effectively kill harmful bacteria in and around the wound, prevent further infection caused by bacteria after the wound occurs, and effectively inhibit bacterial regeneration at the wound site, thereby accelerating wound healing.

[0028] (7) The supramolecular hydrogel based on natural polysaccharides and natural polyphenols provided by this invention can effectively remove excess free radicals from the wound when applied to the wound, thereby inhibiting inflammation. This greatly reduces the possibility of adverse complications and helps the wound heal quickly and fully.

[0029] (8) When the supramolecular hydrogel based on natural polysaccharides and natural polyphenols provided by this invention is applied to the wound, it can kill harmful bacteria, inhibit inflammation, thereby accelerating blood circulation around the wound, promoting cell proliferation, migration, angiogenesis and epidermal regeneration, effectively shortening the skin repair time, and reducing the patient's pain and economic loss.

[0030] (9) Preferably, the present invention uses a mixed solvent of water and organic solvent to dissolve polyphenols in order to improve the solubility of polyphenols. Attached Figure Description

[0031] Figure 1 This is a schematic diagram illustrating the application of supramolecular hydrogels based on natural plant components.

[0032] Figure 2 This is a supramolecular hydrogel based on natural plant components prepared in Example 1. It can be seen that an invertible hydrogel can be rapidly formed after stirring for 15 seconds. The production process is simple and low in cost.

[0033] Figure 3 This is a supramolecular hydrogel based on natural plant components prepared in Example 2.

[0034] Figure 4 This is a supramolecular hydrogel based on natural plant components prepared in Example 3.

[0035] Figure 5 This is a supramolecular hydrogel based on natural plant components prepared in Example 4.

[0036] Figure 6 This is a supramolecular hydrogel based on natural plant components prepared in Example 5.

[0037] Figure 7 The image shows a cross-sectional SEM image of the supramolecular hydrogel based on natural plant components prepared in Example 1. It can be seen that the sodium alginate-gallic acid supramolecular hydrogel has a micron-scale porous structure. The interconnected pores of the gel can promote wound healing by rapidly adsorbing blood and tissue exudates.

[0038] Figure 8 The time-scan rheology diagram of the supramolecular hydrogel based on natural plant components in Example 1 shows that the sodium alginate solution always remains in a solution state (storage modulus G' < loss modulus G”), while after the gallic acid solution is added and sheared by the instrument plate for about 15 seconds, the storage modulus G' > loss modulus G” of the mixed system. This is typical gel behavior, indicating that the addition of gallic acid can form a hydrogel after mixing for 15 seconds, and polyphenol supramolecular gels can be prepared quickly.

[0039] Figure 9 To illustrate the adhesion of the supramolecular hydrogel based on natural plant ingredients from Example 1 to different substrates (heart, liver, spleen, stomach, and kidney of BALB / c mice, glass, PP, stainless steel, and PE), the tissue-adhesive sodium alginate-gallic acid supramolecular hydrogel based on natural plant ingredients can form a barrier at the wound site, replacing damaged skin to resist the invasion of external pathogens and providing a moist environment. Good injectability and adhesion also help the sodium alginate-gallic acid supramolecular hydrogel based on natural plant ingredients adapt to irregular skin wounds, improving the hydrogel's retention capacity.

[0040] Figure 10 The image shown is the ATR-FTIR image of the supramolecular hydrogel based on natural plant components in Example 1, compared with gallic acid (3270 cm⁻¹). -1 ) and sodium alginate (3271cm) -1 In comparison, the OH stretching vibration peak of sodium alginate-gallic acid supramolecular hydrogels based on natural plant components redshifted to 3274 cm⁻¹. -1 Furthermore, gallic acid at 1662 cm⁻¹ -1 The typical C=O stretching vibration peak at 1699 cm⁻¹ also redshifted to 1699 cm⁻¹ after gelation. -1The redshift of the aforementioned characteristic functional groups confirms the formation of hydrogen-bonded supramolecular forces between sodium alginate and gallic acid. Furthermore, the sugar rings of natural polysaccharides can form hydrophobic supramolecular forces with the hydrophobic functional groups in the polyphenol structure; π-π stacking supramolecular forces can also form between the benzene rings in polyphenols, collectively forming supramolecular hydrogels based on natural plant components.

[0041] Figure 11 The graph shows the DPPH free radical scavenging efficiency of the supramolecular hydrogels based on natural plant ingredients in Examples 1-5. All the supramolecular hydrogels based on natural plant ingredients have a DPPH free radical scavenging efficiency greater than 60%, indicating that the polyphenols released by the supramolecular hydrogels based on natural plant ingredients have excellent antioxidant capacity. Therefore, supramolecular hydrogels based on natural plant ingredients can also be used to remove excess reactive oxygen species in skin wounds.

[0042] Figure 12 The antibacterial properties of the supramolecular hydrogels based on natural plant ingredients in Examples 1-5 show that the supramolecular hydrogels based on natural plant ingredients described in Examples 1-5 can kill Staphylococcus aureus and have excellent antibacterial properties.

[0043] Figure 13 The image shows the therapeutic effect of the supramolecular hydrogel based on natural plant components in Example 1 on a mouse whole-skin injury model infected with Staphylococcus aureus. Due to the excellent antibacterial properties of the supramolecular hydrogel, it significantly reduced the bacterial load in the infected wound. At the same time, the antioxidant properties of polyphenols can also remove excess ROS from the wound, reduce skin wound inflammation, and thus significantly promote wound healing.

[0044] Figure 14 The supramolecular hydrogel based on natural plant components in Example 1 was used to treat wound tissue in a mouse whole-skin injury model on day 14 of treatment with HE and Masson staining. The wound in the treatment group showed more epidermal, dermal, sebaceous gland, sweat gland and collagen deposition. At the same time, the sodium alginate-gallic acid supramolecular hydrogel also promoted angiogenesis. Detailed Implementation

[0045] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the invention. Furthermore, the technical features involved in the various embodiments of this invention described below can be combined with each other as long as they do not conflict with each other.

[0046] This invention discloses a supramolecular hydrogel based on natural plant components, comprising only polyphenols, natural polysaccharides, and a solvent. The hydrogel forms in situ through supramolecular interactions between the polyphenols and natural polysaccharides, requiring no heating, modification, ultraviolet irradiation, introduction of chemical cross-linking agents, photoinitiators, or enzymes, and eliminating the need for expensive and complex equipment. The hydrogel can be prepared through simple mixing or injected in situ using a syringe.

[0047] In some embodiments, the polyphenols are natural plant polyphenols and their derivatives, specifically at least one selected from gallic acid, protocatechuic acid, epigallocatechin gallate, resveratrol, and tannic acid. The concentration of the polyphenols in the hydrogel is 0.9 wt%-27 wt%. The solvent used is water or a mixture of water and an organic solvent, wherein the organic solvent is at least one selected from ethanol and dimethyl sulfoxide, and the organic solvent is used to improve the solubility of the polyphenols.

[0048] In some embodiments, the supramolecular hydrogel based on natural plant components contains natural polysaccharides that are natural plant polysaccharides and their derivatives, including at least one of sodium alginate, starch, carrageenan, sodium hyaluronate, chitosan, and chitosan derivatives, and the concentration of the natural polysaccharide in the hydrogel is 0.9wt%-28wt%.

[0049] In some embodiments, the supramolecular hydrogel based on natural plant components is mixed with the polyphenol solution and the polysaccharide solution using one or a combination of stirring, shaking, and sonication. The temperature range for mixing the polyphenol solution and the polysaccharide solution is 4℃-70℃.

[0050] In some embodiments, the supramolecular hydrogel based on natural plant components forms a gel through supramolecular interactions between polyphenols and natural polysaccharides, specifically hydrogen bonds, hydrophobic interactions, and π-π stacking interactions.

[0051] The method for preparing supramolecular hydrogels based on natural plant components described in this invention involves thoroughly mixing a polyphenol solution with a natural polysaccharide solution to obtain a hydrogel; after mixing, the weight ratio of polyphenols to polysaccharides ranges from 0.3 to 30.

[0052] The supramolecular hydrogel based on natural plant components described in this invention includes the following steps:

[0053] (1) Prepare polyphenol solution and natural polysaccharide solution. The solvent used for polyphenol solution is water or a mixture of water and organic solvent. The organic solvent is at least one of ethanol and dimethyl sulfoxide. The organic solvent is used to improve the solubility of polyphenol. The solvent used for natural polysaccharide solution is water.

[0054] (2) Mix the polyphenol solution and natural polysaccharide solution obtained in step (1) to allow the polyphenol and natural polysaccharide to gel in situ through supramolecular forces, thus obtaining a supramolecular hydrogel based on natural plant components.

[0055] The supramolecular hydrogel based on natural plant components described in this invention, in situ injection includes using a double-barreled syringe to inject a polyphenol solution and a natural polysaccharide solution to the wound to form a hydrogel, and using a syringe to inject the formed supramolecular hydrogel based on natural plant components into the wound. Figure 1 This is a schematic diagram of a bi-barrel injection process for supramolecular hydrogels based on natural plant components.

[0056] The application of the supramolecular hydrogel based on natural plant components prepared in this invention in topical skin drug delivery formulations.

[0057] The aforementioned topical skin medication is specifically a topical skin medication used for antibacterial, antioxidant, anti-inflammatory, angiogenesis-promoting, cell proliferation-promoting, wound healing-promoting, and bacterial wound healing.

[0058] The following are specific embodiments.

[0059] Example 1

[0060] A method for preparing supramolecular hydrogels based on natural plant components includes the following steps:

[0061] A. Dissolve gallic acid in a certain amount of water-ethanol (7:3, v / v) to prepare a 5% solution.

[0062] B. Dissolve sodium alginate in a certain amount of water to prepare a 15% solution by mass.

[0063] C. Mix gallic acid solution and sodium alginate solution at a volume ratio of 2.5:1, stir for 15 seconds to form a hydrogel. The concentration of gallic acid in the hydrogel is 3.3 wt%, and the concentration of sodium alginate is 4.0 wt%.

[0064] Figure 2 This is a supramolecular hydrogel based on natural plant components prepared in Example 1. It can be seen that an invertible hydrogel can be rapidly formed after stirring for 15 seconds. The production process is simple and low in cost.

[0065] Example 2

[0066] A method for preparing supramolecular hydrogels based on natural plant components includes the following steps:

[0067] A. Dissolve protocatechuic acid in a certain amount of water-dimethyl sulfoxide (8:2, v / v) to prepare a 10% solution.

[0068] B. Dissolve sodium hyaluronate in a certain amount of water to prepare a 30% solution.

[0069] C. Mix the protocatechuic acid solution and the sodium hyaluronate solution in a volume ratio of 1:1, stir for 15 seconds to form a hydrogel. The concentration of protocatechuic acid in the hydrogel is 4.2 wt%, and the concentration of sodium hyaluronate is 12.5 wt%.

[0070] Figure 3 The supramolecular hydrogel based on natural plant components prepared in Example 2 has the following antioxidant properties: Figure 11 As shown, its antibacterial properties are as follows: Figure 12 As shown.

[0071] Example 3

[0072] A method for preparing supramolecular hydrogels based on natural plant components includes the following steps:

[0073] A. Dissolve tannic acid in a certain amount of water to prepare a solution with a mass fraction of 30%.

[0074] B. Dissolve carboxymethyl chitosan in a certain amount of water to prepare a solution with a mass fraction of 8%.

[0075] C. Mix tannic acid and carboxymethyl chitosan solutions at a volume ratio of 1:2, stir for 15 seconds, let stand for 24 hours to form a hydrogel. The concentration of tannic acid in the hydrogel is 8.7 wt%, and the concentration of carboxymethyl chitosan is 4.6 wt%.

[0076] Figure 4 The supramolecular hydrogel based on natural plant components prepared in Example 3 has the following antioxidant properties: Figure 11 As shown, its antibacterial properties are as follows: Figure 12 As shown.

[0077] Example 4

[0078] A method for preparing supramolecular hydrogels based on natural plant components includes the following steps:

[0079] A. Dissolve epigallocatechin gallate in a certain amount of water-ethanol (6:4, v / v) to prepare a 6% solution by mass.

[0080] B. Dissolve starch in a certain amount of water to prepare a 10% solution.

[0081] C. Mix epigallocatechin gallate solution and starch solution at a volume ratio of 1:1, stir for 15 seconds, let stand for 24 hours to form a hydrogel. The concentration of epigallocatechin gallate in the formed hydrogel is 2.8 wt%, and the concentration of starch is 4.6 wt%.

[0082] Figure 5 The supramolecular hydrogel based on natural plant components prepared in Example 4 has the following antioxidant properties: Figure 11 As shown, its antibacterial properties are as follows: Figure 12 As shown.

[0083] Example 5

[0084] A method for preparing supramolecular hydrogels based on natural plant components includes the following steps:

[0085] A. Dissolve resveratrol in a certain amount of water-dimethyl sulfoxide (7:3, v / v) to prepare a 4% solution by mass.

[0086] B. Dissolve carrageenan in a certain amount of water to prepare a 15% solution by mass.

[0087] C. Mix resveratrol solution and carrageenan solution at a volume ratio of 1:1, stir for 15 seconds, let stand for 12 hours to form a hydrogel. The concentration of resveratrol in the formed hydrogel is 1.8 wt%, and the concentration of carrageenan is 6.8 wt%.

[0088] Figure 6 The supramolecular hydrogel based on natural plant components prepared in Example 5 has the following antioxidant properties: Figure 11 As shown, its antibacterial properties are as follows: Figure 12 As shown.

[0089] Figure 7 The image shows a cross-sectional SEM image of the supramolecular hydrogel based on natural plant components prepared in Example 1. It can be seen that the sodium alginate-gallic acid supramolecular hydrogel has a micron-scale porous structure. The interconnected pores of the gel can promote wound healing by rapidly adsorbing blood and tissue exudates.

[0090] Figure 8 The time-scanning rheological diagram of the supramolecular hydrogel based on natural plant components in Example 1 shows that the sodium alginate solution always remains in a solution state (storage modulus G' < loss modulus G”). However, after adding gallic acid solution and shearing it by the instrument plate for about 15 seconds, the storage modulus G' > loss modulus G” of the mixed system. This is typical gel behavior, indicating that a hydrogel can be formed after mixing for 15 seconds after adding gallic acid, and polyphenol supramolecular gels can be prepared quickly.

[0091] Figure 9 To illustrate the adhesion of the supramolecular hydrogel based on natural plant ingredients from Example 1 to different substrates (heart, liver, spleen, stomach, and kidney of BALB / c mice, glass, PP, stainless steel, and PE), the tissue-adhesive sodium alginate-gallic acid supramolecular hydrogel based on natural plant ingredients can form a barrier at the wound site, replacing damaged skin to resist the invasion of external pathogens and providing a moist environment. Good injectability and adhesion also help the sodium alginate-gallic acid supramolecular hydrogel based on natural plant ingredients adapt to irregular skin wounds, improving the hydrogel's retention capacity.

[0092] Figure 10 The image shown is the ATR-FTIR image of the supramolecular hydrogel based on natural plant components in Example 1, compared with gallic acid (3270 cm⁻¹). -1 ) and sodium alginate (3271cm) -1 In contrast, the OH stretching vibration peaks of sodium alginate-gallic acid supramolecular hydrogels based on natural plant components merged and redshifted to 3274 cm⁻¹. -1 Furthermore, gallic acid at 1662 cm⁻¹ -1 The typical C=O stretching vibration peak at 1699 cm⁻¹ also redshifted to 1699 cm⁻¹ after gelation. -1 The redshift of the aforementioned characteristic functional groups confirms the formation of hydrogen-bonded supramolecular forces between sodium alginate and gallic acid. Furthermore, the sugar rings of natural polysaccharides can form hydrophobic supramolecular forces with the hydrophobic functional groups in the polyphenol structure; π-π stacking supramolecular forces can also form between the benzene rings in polyphenols, collectively forming supramolecular hydrogels based on natural plant components.

[0093] Figure 11 The graph shows the DPPH free radical scavenging efficiency of the supramolecular hydrogels based on natural plant ingredients in Examples 1-5. All the supramolecular hydrogels based on natural plant ingredients have a DPPH free radical scavenging efficiency greater than 60%, indicating that the polyphenols released by the supramolecular hydrogels based on natural plant ingredients have excellent antioxidant capacity. Therefore, supramolecular hydrogels based on natural plant ingredients can also be used to remove excess reactive oxygen species in skin wounds.

[0094] Figure 12 The antibacterial properties of the supramolecular hydrogels based on natural plant ingredients in Examples 1-5 show that the supramolecular hydrogels based on natural plant ingredients described in Examples 1-5 can kill Staphylococcus aureus and have excellent antibacterial properties.

[0095] Figure 13The image shows the therapeutic effect of the supramolecular hydrogel based on natural plant components in Example 1 on a mouse whole-skin injury model infected with Staphylococcus aureus. Due to the excellent antibacterial properties of the supramolecular hydrogel, it significantly reduced the bacterial load in the infected wound. At the same time, the antioxidant properties of polyphenols can also remove excess ROS from the wound, reduce skin wound inflammation, and thus significantly promote wound healing.

[0096] Figure 14 The supramolecular hydrogel based on natural plant components in Example 1 was used to treat wound tissue in a mouse whole-skin injury model on day 14 of treatment with HE and Masson staining. The wound in the treatment group showed more epidermal, dermal, sebaceous gland, sweat gland and collagen deposition. At the same time, the sodium alginate-gallic acid supramolecular hydrogel also promoted angiogenesis.

[0097] Those skilled in the art will readily understand that the above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. A supramolecular hydrogel based on natural plant components, characterized in that, The supramolecular hydrogel contains only polyphenols, polysaccharides, and solvents, wherein the polysaccharides are natural polysaccharides or natural polysaccharide derivatives; the hydrogel is gelled in situ through supramolecular forces between the polyphenols and the polysaccharides. 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; the chitosan derivative is carboxymethyl chitosan. The supramolecular hydrogel based on natural plant components was prepared through the following steps: (1) Prepare polyphenol solution and polysaccharide solution respectively, wherein the polysaccharide solution is a natural polysaccharide solution or a natural polysaccharide derivative solution; the solvent used in the polyphenol solution is a mixed solvent of water and an organic solvent, wherein the organic solvent is at least one of ethanol and dimethyl sulfoxide, and the organic solvent is used to improve the solubility of polyphenol; the solvent used in the polysaccharide solution is water; (2) Mix the polyphenol solution and polysaccharide solution obtained in step (1) in situ without heating, so that the polyphenol and polysaccharide can form a gel in situ through supramolecular forces, thus obtaining a supramolecular hydrogel based on natural plant components. 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 involves injecting and mixing the polyphenol solution and polysaccharide solution separately into the two syringes of a double-barreled syringe.

2. The supramolecular hydrogel based on natural plant components as described in claim 1, characterized in that, The supramolecular forces are hydrogen bonds, hydrophobic forces, and π-π stacking forces.

3. The supramolecular hydrogel based on natural plant components as described in claim 1, characterized in that, The supramolecular hydrogel has a micron-sized porous structure inside.

4. The method for preparing supramolecular hydrogels based on natural plant components according to any one of claims 1-3, characterized in that, Includes the following steps: (1) Prepare polyphenol solution and polysaccharide solution respectively, wherein the polysaccharide solution is a natural polysaccharide solution or a natural polysaccharide derivative solution; the solvent used in the polyphenol solution is a mixed solvent of water and an organic solvent, wherein the organic solvent is at least one of ethanol and dimethyl sulfoxide, and the organic solvent is used to improve the solubility of polyphenol; the solvent used in the polysaccharide solution is water; (2) Mix the polyphenol solution and polysaccharide solution obtained in step (1) in situ without heating, so that the polyphenol and polysaccharide can form a gel in situ through supramolecular forces, thus obtaining a supramolecular hydrogel based on natural plant components. The concentration of the polyphenol solution is 40 mg / mL-500 mg / mL, and the concentration of the polysaccharide solution is 50 mg / mL-600 mg / mL; the volume ratio of the polyphenol solution to the polysaccharide solution is 0.5-3. The in-situ injection involves injecting and mixing the polyphenol solution and polysaccharide solution separately into the two syringes of a double-barreled syringe.

5. The method for preparing supramolecular hydrogels based on natural plant components as described in claim 4, characterized in that, In the mixed solvent, water accounts for 60%-80% by volume.

6. The use of the supramolecular hydrogel based on natural plant components as described in any one of claims 1-3 for the preparation of topical skin drug delivery formulations that promote wound healing.

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