CN-121971794-A - Primary cell effect hydrogen-producing antioxidant hydrogel microneedle patch and preparation and application thereof

CN121971794ACN 121971794 ACN121971794 ACN 121971794ACN-121971794-A

Abstract

The invention belongs to the technical field of medical materials, and particularly discloses a primary cell effect hydrogen-producing antioxidant hydrogel microneedle patch and preparation and application thereof; preparing a needle point solution, preparing a lower substrate solution, preparing an upper substrate solution, preparing a microneedle patch primary product, and salting out the microneedle patch primary product by using a sulfate solution to obtain the hydrogen-producing antioxidant hydrogel microneedle patch based on a primary cell effect. The invention adopts the primary cell effect hydrogen-producing antioxidant hydrogel microneedle patch and the preparation and application thereof, and the patch can spontaneously produce therapeutic microcurrent and hydrogen in a wound microenvironment, and cooperate with photo-thermal antibacterial and pharmaceutical activities, so as to realize multi-mechanism synergistic treatment of chronic difficult-to-heal wounds such as diabetes mellitus.

Inventors

QI HOUJUAN
SHI DONGJIE
HUANG ZHANHUA
YAO JIAWEI
JIA GUANGYAN
ZHANG YANAN

Assignees

东北林业大学

Dates

Publication Date: 20260505
Application Date: 20260407

Claims (9)

1. The preparation method of the hydrogen-generating antioxidant hydrogel microneedle patch by using the galvanic effect is characterized by comprising the following steps of: step S1, weighing polyvinyl alcohol, hydroformylation bacterial cellulose, quaternized chitosan and silver nanowires, and respectively dissolving the polyvinyl alcohol, the hydroformylation bacterial cellulose, the quaternized chitosan and the silver nanowires in deionized water to obtain polyvinyl alcohol solution, hydroformylation bacterial cellulose solution, quaternized chitosan solution and silver nanowire dispersion liquid; S2, taking a polyvinyl alcohol solution and silver nanowire dispersion liquid, stirring and mixing uniformly at the stirring temperature of 85-95 ℃ and the stirring speed of 400-800 r/min, cooling to 50-60 ℃, and adding a conductive electrothermal material, a hypoglycemic agent and an anti-inflammatory drug to obtain a needlepoint solution; Step S3, taking a polyvinyl alcohol solution, an hydroformylation bacterial cellulose solution and a quaternized chitosan solution, stirring and mixing uniformly at the temperature of 85-95 ℃ and the speed of 400-800 r/min, cooling to 50-60 ℃, and adding a cathode material silver nanowire, a conductive electrothermal material, a hypoglycemic and an anti-inflammatory drug to obtain a lower substrate solution; S4, taking a polyvinyl alcohol solution, an hydroformylation bacterial cellulose solution and a quaternized chitosan solution, stirring and mixing uniformly at the temperature of 85-95 ℃ and the speed of 400-800 r/min, cooling to 50-60 ℃, and adding anode material zinc particles, conductive electrothermal materials, hypoglycemic agents and anti-inflammatory drugs to obtain an upper substrate solution; S5, injecting the needle point solution into a microneedle mould, centrifuging to fill the needle point cavity with the needle point solution, sucking off the redundant solution, putting the needle point solution into a refrigerator for freezing and shaping, taking out the solution, thawing the solution at room temperature, adding the lower substrate solution, putting the solution into the refrigerator again for freezing and shaping, thawing the solution at room temperature, finally adding the upper substrate solution, and performing repeated cycle freezing and thawing treatment to obtain a microneedle patch primary product; and S6, salting out the initial product of the microneedle patch by using a sulfate solution to obtain the hydrogen-producing antioxidant hydrogel microneedle patch based on the primary cell effect.
2. The preparation method of the hydrogen-generating antioxidative hydrogel microneedle patch by using a galvanic cell effect according to claim 1 is characterized in that in the step S1, the mass percentage concentration of a polyvinyl alcohol solution is 12.5-40%, the mass percentage concentration of an aldehyde bacteria cellulose solution is 0.05-0.5%, and the mass percentage concentration of a quaternized chitosan solution is 0.05-0.3%.
3. The preparation method of the primary cell effect hydrogen-producing antioxidant hydrogel microneedle patch according to claim 1, wherein in the step S2, the volume usage ratio of the polyvinyl alcohol solution to the silver nanowire dispersion is 8-10:1; In the step S3, the volume and the dosage ratio of the polyvinyl alcohol solution, the hydroformylation bacterial cellulose solution, the quaternized chitosan solution and the silver nanowire dispersion liquid are 6-9:0.5-1:0.5-1:1; In the step S4, the volume and the volume use ratio of the polyvinyl alcohol solution, the hydroformylation bacterial cellulose solution and the quaternized chitosan solution are 6-9:0.5-3:2-4.
4. The preparation method of the hydrogen-generating antioxidant hydrogel microneedle patch with the galvanic effect is characterized in that in the step S2, the step S3 and the step S4, the addition amount of the conductive electrothermal material is 0.1-0.5% based on the mass of the conductive electrothermal material corresponding to the total solution, the conductive electrothermal material comprises one or more of MXene, polypyrrole, polyaniline and carbon nano tubes, the addition amount of the hypoglycemic and anti-inflammatory drugs is 0.1-1% based on the mass of the conductive electrothermal material corresponding to the total solution, and the hypoglycemic and anti-inflammatory drugs comprise one or more of metformin hydrochloride, insulin and analogues thereof, amoxicillin, alpha-lipoic acid, quercetin, curcumin and growth factors.
5. The preparation method of the hydrogen-generating antioxidant hydrogel microneedle patch by using the galvanic cell effect is characterized in that in the step S5, the length of the needle tip of a microneedle mould is 400-800 mu m, the shape of the needle tip of the microneedle mould is a cone, a triangular pyramid or a regular quadrangular pyramid, the centrifugal rotating speed is 3000-8000 r/min, and the centrifugal time is 3-6 min.
6. The method for preparing the hydrogen-generating antioxidant hydrogel microneedle patch by using the galvanic effect according to claim 1, wherein in the step S5, the cyclic freezing and thawing is performed for at least 3 times, the freezing temperature is-15 to-40 ℃, the freezing time is 8-14 h, and the thawing time is 2-4 h.
7. The preparation method of the hydrogen-generating antioxidative hydrogel microneedle patch by using the galvanic cell effect, which is disclosed in claim 1, is characterized in that in the step S4, the mass concentration of an anode material in an upper substrate solution is 0.5-4%, and in the step S3, the mass concentration of a cathode material in a lower substrate solution is 0.05-0.2%.
8. The method for preparing the hydrogen-generating and oxidation-resistant hydrogel microneedle patch by using the galvanic effect according to claim 1, wherein in the step S6, the concentration of a sulfate solution is 1-10M, and the sulfate is one or more of sodium sulfate, ammonium sulfate, magnesium sulfate and calcium sulfate.
9. A galvanic-effect hydrogen-producing antioxidant hydrogel microneedle patch prepared by the method for preparing a galvanic-effect hydrogen-producing antioxidant hydrogel microneedle patch according to any one of claims 1 to 8.

Description

Primary cell effect hydrogen-producing antioxidant hydrogel microneedle patch and preparation and application thereof Technical Field The invention belongs to the technical field of medical materials, and particularly relates to a hydrogen-generating antioxidant hydrogel microneedle patch with a primary cell effect, and preparation and application thereof. Background Chronic refractory wounds, such as diabetic foot ulcers, are a significant challenge in the world of medical health due to their complex pathological microenvironment, including sustained high oxidative stress, susceptibility to secondary infections, localized hypoxia, and inflammatory disorders. Traditional dressings and methods of treatment tend to have limited effectiveness. The microneedle technology can minimally invasive penetrate through the stratum corneum, establish a drug delivery channel, improve the drug permeation efficiency, and has been widely applied to the field of wound healing. However, most of the existing drug-loaded microneedles can only realize passive release of drugs, have a single treatment mechanism, are difficult to cooperatively cope with multiple pathological factors of diabetes wounds, and lack active response capability to dynamic wound microenvironment. Furthermore, therapies that rely on external oxygen may exacerbate wound hypoxia, whereas long-term use of antimicrobial agents is prone to drug resistance. Electrical stimulation has been demonstrated to promote fibroblast migration, accelerate vascular regeneration, and modulate inflammatory responses as an effective physical intervention to improve the healing process. However, most current electrical stimulation therapy protocols rely on external power sources or complex devices, with significant limitations in portability, persistence, intelligence, and patient self-management. Therefore, the dressing which can realize self-power supply and continuously generate therapeutic electric stimulation by utilizing the endogenous environment of the wound is developed, and has important clinical significance and application prospect. Therefore, the development of a novel intelligent wound dressing which can accurately respond to the wound microenvironment, has self-powered characteristics and integrates a multidimensional treatment mechanism is urgently needed in the field so as to realize the efficient regulation and comprehensive management of chronic refractory wounds such as diabetic wounds and solve the key problems of strong external dependence, single action mechanism, contradiction between antibacterial and tissue repair requirements and the like in the current treatment. Disclosure of Invention The invention aims to provide a primary cell effect hydrogen-producing antioxidant hydrogel microneedle patch, and preparation and application thereof, wherein the patch can spontaneously produce therapeutic microcurrent and hydrogen in a wound microenvironment, and cooperate with photo-thermal antibacterial and pharmaceutical activities, so as to realize multi-mechanism synergistic treatment of chronic difficult-to-heal wounds such as diabetes mellitus. In order to achieve the above purpose, the invention provides a preparation method of a primary cell effect hydrogen-producing antioxidant hydrogel microneedle patch, which comprises the following steps: Step S1, weighing a certain amount of polyvinyl alcohol (PVA), aldehyde bacterial cellulose (OBC), quaternized Chitosan (QCS) and silver nanowires (AgNWs), respectively dissolving in deionized water to obtain a polyvinyl alcohol (PVA) solution, an aldehyde bacterial cellulose (OBC) solution, a Quaternized Chitosan (QCS) solution and silver nanowire (AgNWs) dispersion liquid with certain mass percentage concentration; s2, weighing a polyvinyl alcohol solution and a silver nanowire dispersion liquid, stirring and uniformly mixing at the stirring temperature of 85-95 ℃ and the stirring speed of 400-800 r/min, cooling to 50-60 ℃, and adding a conductive electrothermal material, a hypoglycemic agent and an anti-inflammatory drug to obtain a needlepoint solution; Step S3, taking a polyvinyl alcohol solution, an hydroformylation bacterial cellulose solution, a quaternized chitosan solution and a silver nanowire dispersion liquid, stirring and mixing uniformly at the temperature of 85-95 ℃ and the speed of 400-800 r/min, cooling to 50-60 ℃, and adding a conductive electrothermal material, a hypoglycemic agent and an anti-inflammatory drug to obtain a lower substrate solution; S4, taking a polyvinyl alcohol solution, an hydroformylation bacterial cellulose solution and a quaternized chitosan solution, stirring and mixing uniformly at the temperature of 85-95 ℃ and the speed of 400-800 r/min, cooling to 50-60 ℃, and adding conductive electrothermal materials, zinc particles and compounds thereof, hypoglycemic and anti-inflammatory drugs to obtain an upper substrate solution; S5, injecting the needle point solution into a micron