Healing promoting plaster, preparation method and application

Abstract

The invention discloses a healing-promoting patch, a preparation method and application, and belongs to the field of functional composite materials. The healing promoting application is formed by packaging an upper layer structure, a middle layer structure and a lower layer structure. The upper layer structure is a bioadhesive film; the middle-layer structure is a liquid metal material; and the lower layer structure is a fluorine surface flexible conductive film. The upper-layer structure has good biocompatibility and tissue adhesion, the middle-layer structure has good liquid flow property and excellent drivability, the lower-layer structure has good conductivity, and fluorine on the upper surface of the lower-layer structure has strong electron-withdrawing capability. The healing-promoting application has good biocompatibility, skin adhesion and skin compliance, can be widely applied to the field of medical materials, can change an electric signal of a wound environment through self-power generation, plays a positive role in tissue repair, is beneficial to wound collagen synthesis, inflammation inhibition and wound hair follicle regeneration activation, and has a good healing-promoting effect. The material can be used as a wound application for promoting skin repair and a medical material for repairing other tissues.

Description

Technical Field

[0001] The invention belongs to the field of functional composite materials, and in particular relates to a healing-promoting dressing, a preparation method and an application thereof. Background Art

[0002] The skin is the first line of defense of the human immune system. It is responsible for protecting the body from external attacks, regulating body temperature, and sensing external stimuli. In daily life, the skin is exposed to the outside world and is vulnerable to external attacks. However, wound healing requires a complex and lengthy process, including hemostasis, inflammation, proliferation, and remodeling. However, due to chronic diseases, aging, and other reasons, the skin may become difficult to heal, which will not only affect daily life, but may even endanger life. For this reason, research on promoting wound healing is an important topic for human health and improving the quality of human life.

[0003] The main treatment method for solving the above problems is to bandage and treat wounds with medical materials. It helps to protect the fragile wound environment and avoid secondary injuries. At the same time, the effective ingredients of medical materials help wounds heal quickly. However, such materials with good healing effects still rely on the release of drug ingredients and are not suitable for drug-sensitive people and patients with multiple diseases. For this reason, research on drug-free wound dressings can help meet the needs of specific patients for healthier wound treatment. Electrical stimulation treatment is a healthy treatment method that guides the body to heal itself by activating the organism's own electrical signals. Electrical stimulation treatment of wounds helps promote the proliferation and differentiation of key cells and promotes rapid wound repair. At the same time, it can activate the regeneration of skin organs such as hair follicles, which helps achieve scar-free healing.

[0004] However, the current self-generating conditions of self-generating wound dressings are harsh, relying on skin bending or requiring ultrasonic stimulation (>20000Hz), which limits the places of use and is not suitable for long-term bedridden patients and those who have difficulty moving the injured part, thus affecting the treatment effect. The paper Chem.Eng.J.2024,494,153063 uses polyvinylidene fluoride (PVDF) film to prepare a multifunctional wound dressing on the surface of silver micro-nano hydrogel particles. The dressing has good biocompatibility and antibacterial properties, which helps promote wound healing. However, the self-generating power prepared in this study depends on the pressure stimulation received by PVDF during body movement, which is not suitable for daily use by long-term bedridden patients. The paper J.Mater.Chem.B, 2023, 11, 4318–4329 used carboxymethyl chitosan (CMCS), tannic acid (TA), carbomer (CBM) and piezoelectric FeWO4 micro-nanorods as raw materials to prepare an adhesive piezoelectric antibacterial hydrogel, which promoted the healing of full-thickness skin wounds in mice. However, the preparation of self-generating dressings in this study relies on ultrasound to generate electrical signals, which is not suitable for daily use and has high requirements for treatment equipment.

[0005] Sound waves are generated by the vibration of the sound source, and the number of cycles it completes in one second is called frequency, measured in Hertz (Hz). Sound waves can propagate in all directions with the help of various media (air, liquid, solid), so sound waves are everywhere in production and life, and the known frequency of human voice is 60-1100Hz. The development of self-generating healing materials that can be triggered by daily low-frequency sound waves will help the use of aging and bedridden patients, and will also help to cope with more daily treatment environments and achieve higher healing effects. At present, there are no reports on self-generating wound dressings that can be driven by daily low-frequency sound waves. Therefore, a medical material that can be driven by daily low-frequency sound waves and has good tissue adhesion, biocompatibility, and skin compliance to promote healing is urgently needed to be developed. Summary of the invention

[0006] In order to solve the problems in the prior art, the present invention provides a healing-promoting dressing, a preparation method and an application. The composite material obtained by the present invention can generate electricity by daily low-frequency sound waves, and has tissue adhesion, biocompatibility, and skin flexibility, which can promote rapid wound repair and scar-free wound healing by activating organs such as hair follicles.

[0007] The technical solution of the present invention:

[0008] A healing-promoting dressing comprises an upper, middle and lower three-layer structure; the upper layer structure is a bioadhesive film; the middle layer structure is a liquid metal material; and the lower layer structure is a fluorine-surface flexible conductive film.

[0009] Furthermore, the addition amount of each layer is calculated based on 100 parts by weight of the upper layer, 3-10 parts by weight of the middle layer, and 5-50 parts by weight of the lower layer;

[0010] Furthermore, in the healing-promoting patch, the upper structure has good biocompatibility and tissue adhesion, the middle structure has good liquid flow properties, deformation ability and drivability, the lower structure has good conductivity and the fluorine element on its upper surface has strong electron-withdrawing ability.

[0011] Furthermore, the preparation process of the superstructure is as follows: isophorone diisocyanate, polyetheramine 2000 and an organic tin catalyst are dissolved in acetone in proportion, and stirred at room temperature for 2-3 hours; after heating to 60-70°C, 2,2-dihydroxymethylbutyric acid is added, and the reaction is stirred for 2h-4h; after cooling to room temperature, triethylamine is added, and the reaction is stirred for 1-2h; the temperature is raised to 40-60°C, and oligosaccharide dissolved in deionized water is added, and the reaction is stirred for 6-8 hours; the insoluble matter at the bottom is filtered and dissolved in anhydrous ethanol solution; finally, it is poured into a mold or coated to form a film, and a bioadhesive film is obtained after drying.

[0012] Furthermore, the upper structure is prepared by solution reaction of raw materials including the following components: 100 parts by weight of isophorone diisocyanate, 200-600 parts by weight of polyetheramine 2000, 7-30 parts by weight of 2,2-dihydroxymethylbutyric acid, 5-21 parts by weight of triethylamine, 20-40 parts by weight of oligomolecular chitosan, 1-3 parts by weight of an organic tin catalyst, 500-1000 parts by weight of acetone, and 500-1000 parts by weight of deionized water.

[0013] Furthermore, the middle layer structure is a gallium-indium alloy with a melting point of -19°C-20°C.

[0014] Furthermore, the preparation process of the lower structure is as follows: prepare a dispersion of liquid metal in an aqueous solution of oligomolecular chitosan by ultrasonic crushing for 20-40 minutes, and set aside; dissolve isophorone diisocyanate, polyetheramine 2000 and an organic tin catalyst in acetone in proportion, and stir and react for 2-3 hours at room temperature; after heating to 60-70°C, add 2,2-dihydroxymethylbutyric acid, and stir and react for 2h-4h; after cooling to room temperature, add triethylamine, and stir and react for 1-2h; heat to 40-60°C, add the reserved liquid metal-oligomolecular chitosan dispersion in proportion, and stir and react for 6-8 hours; filter the insoluble matter at the bottom and dissolve it in anhydrous ethanol solution; pour it into a mold or apply it to form a film, and obtain a flexible conductive film after drying; finally, disperse the fluorine-containing micro-nanoparticles in an ethanol solution to form a fluorine-containing particle dispersion, spray it evenly on the upper surface of the flexible conductive film and dry it to obtain a fluorine-surface flexible conductive film.

[0015] Furthermore, the lower structure is prepared by solution reaction of raw materials including the following components: 100 parts by weight of isophorone diisocyanate, 200-600 parts by weight of polyetheramine 2000, 7-30 parts by weight of 2,2-dihydroxymethylbutyric acid, 5-21 parts by weight of triethylamine, 20-40 parts by weight of oligomeric chitosan, 1-3 parts by weight of organic tin catalyst, 2000-13000 parts by weight of liquid metal, 0.01-0.05 parts by weight of fluorine-containing micro-nanoparticles, 500-1000 parts by weight of acetone, and 500-1000 parts by weight of deionized water.

[0016] Furthermore, the liquid metal is a gallium-indium alloy with a melting point of -19°C-20°C; the fluorine-containing micro-nano particles are one or a mixture of two or more of 500nm-5μm fluorosilicone rubber micro-nano particles, polytetrafluoroethylene micro-nano particles, and polyfluorinated ethylene propylene copolymer micro-nano particles.

[0017] A method for preparing a healing-promoting patch comprises the following steps: using a syringe to drop a middle-layer structure onto the center of a fluorine-containing surface of a lower-layer structure, and rapidly cooling the temperature to below the melting point of liquid metal; finally, using ethanol at low temperature to make the edge of the fluorine-containing surface of the lower-layer structure fit in the central area of ​​an upper-layer structure, thereby achieving encapsulation of the middle-layer structure.

[0018] An application of a healing-promoting dressing, which is used to prepare a healing-promoting dressing that mediates scarless repair and other scar prevention medical materials. The healing-promoting dressing is non-cytotoxic, has good skin adhesion and compliance, can assist wound closure through effective adhesion, promote wound healing and tissue repair; under daily low-frequency sound waves and slight touch, it can drive liquid metal to vibrate and deform to achieve self-generation, and achieve continuous electrical stimulation of the wound, which is beneficial to promote collagen and hair follicle regeneration, reduce wound inflammation, and help reduce scar formation on the wound surface.

[0019] The present invention has the following beneficial effects:

[0020] (1) The dressing structure of the present invention is a multi-layer packaging structure. The upper bioadhesive film has strong skin adhesion, and its edge can be tightly adhered to uninjured skin; the middle layer structure can ensure that the liquid metal can be deformed under drive, which is conducive to the generation of self-electricity; the lower conductive film can provide good conductivity and its adhesion is lower than that of the upper layer, so that no damage to the wound skin will be caused when changing the dressing.

[0021] (2) The dressing of the present invention has good self-generating properties. Driven by daily low-frequency sound waves, the liquid metal in the middle layer of the dressing can vibrate and deform to generate frictional electricity, which helps to improve the electrical signals at the wound site, promote the proliferation and migration of key cells, and promote tissue healing.

[0022] (3) The dressing of the present invention is helped to improve the biocompatibility of the dressing by partially cross-linking isocyanate with oligosaccharides of biomass. The hydroxyl and amino structures in its structure not only help to improve the adhesion of the dressing, but also can be modified on the surface of the gallium-silver alloy to improve its dispersibility, thereby helping to improve the conductivity of the underlying conductive film.

[0023] (4) The fluorine-faced flexible conductive film of the present invention has good conductivity, can realize the effective transmission of electrical signals, and is conducive to the continuous electrical stimulation. At the same time, the fluorine micro-nanoparticles on its surface increase the electronegativity of the material surface and can absorb electrons when rubbing with liquid metal, which helps to achieve the self-generating effect of the application.

[0024] (5) The middle layer structure of the dressing in the present invention is a gallium-indium alloy with liquid properties, which has good biocompatibility and conductivity, and has extremely strong deformation ability and drivability. It can be deformed by sound waves or slight touch to generate frictional electricity and produce electrical stimulation to the wound. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1 This is a schematic diagram of the healing-promoting dressing adhered to pig skin and wrist skin in Example 1;

[0026] Figure 2 This is the X-ray spectrum image of the cross section of the fluorine surface flexible conductive film in Example 1 (the white dots are gallium elements);

[0027] Figure 3 This is a scanning electron microscope image of the fluorine-containing surface of the fluorine-surface flexible conductive film in Example 1;

[0028] Figure 4 The self-power generation test of the healing-promoting patch in Example 1 under the triggering of a 128 Hz tuning fork (the distance between the tuning fork and the patch is 5 cm);

[0029] Figure 5 This is a picture of the healing-promoting dressing applied to the mouse wound in Example 1;

[0030] Figure 6 This is the H&E staining picture of the healed wound site in Example 1 at 9 days. Specific implementation methods

[0032] Unless otherwise specified, the sources of the reagents used in the embodiments of the present invention can be purchased from the market.

[0033] It should be understood that the specific embodiments described herein are only used to illustrate and explain the present invention and are not intended to limit the present invention. Except for the raw materials used in the embodiments of the present invention, the raw materials components that are identical to the functional groups contained in the raw materials used in the embodiments or contain the same structural units involved in the present invention and are equivalently replaced should all be included in the protection scope of the present invention. The present invention will be further described below in conjunction with specific embodiments.

[0034] The present invention provides drawings of the detection results of some embodiments. Other embodiments and comparative examples adopt the same detection method. Those skilled in the art can directly and unambiguously determine the contents of the embodiments of the present invention through the detection method provided by the present invention.

[0035] The present invention will be further described below in conjunction with the embodiments.

[0036] Example 1

[0037] (1) Preparation of the upper structure bioadhesive film: Weigh 100 parts by weight of isophorone diisocyanate, 400 parts of polyetheramine 2000, and 1 part of dibutyltin dihydrate, add 500 parts of acetone into a three-necked flask to dissolve, and stir at room temperature for 2 hours; after heating to 60°C, add 15 parts of 2,2-dihydroxymethylbutyric acid, and stir for 2 hours; after cooling to room temperature, add 10 parts of triethylamine, and stir for 1 hour; heat to 40°C, add oligosaccharide dissolved in deionized water (500 parts of deionized water and 30 parts of oligosaccharide), and stir for 6 hours; filter the insoluble matter at the bottom and dissolve it in a small amount of anhydrous ethanol solution; finally, cast it into a mold or apply it by scraping to form a film, and obtain the bioadhesive film after drying.

[0038] (2) Preparation of the fluorine surface flexible conductive film of the lower structure: 4800 parts by weight of 6°C gallium-indium alloy was dispersed in a dispersion of an aqueous solution of oligomeric chitosan (500 parts of deionized water and 30 parts of oligomeric chitosan) by ultrasonic grinding, ultrasonicated for 20 minutes, and set aside; 100 parts by weight of isophorone diisocyanate, 400 parts of polyetheramine 2000, and 1 part of dibutyltin diisocyanate were added to a three-necked flask, and 500 parts of acetone were added to dissolve, and the mixture was stirred at room temperature for 2 hours; after the temperature was raised to 60°C, 15 parts of 2,2-dihydroxymethylbutyric acid were added, Stir and react for 2 hours; after cooling to room temperature, add 10 parts of triethylamine and stir and react for 1 hour; heat to 40°C, add the reserved gallium-indium alloy-oligochitosan dispersion in proportion, and stir and react for 6 hours; filter the insoluble matter at the bottom and dissolve it in a small amount of anhydrous ethanol solution; pour it into a mold or apply it to form a film, and obtain a flexible conductive film after drying; finally, evenly spray 0.01 weight parts of 5μm ethanol dispersion of polyfluorinated ethylene propylene copolymer micro-nano particles on the upper surface of the flexible conductive film and dry it to obtain a fluorine surface flexible conductive film.

[0039] (3) Preparation of the healing patch: Cut and weigh 100 parts by weight of the bioadhesive film and 20 parts by weight of the fluorine-surface flexible conductive film; then, use a syringe to drop 5.5 parts by weight of 6°C gallium-indium alloy on the center of the fluorine-containing surface of the fluorine-surface flexible conductive film, and quickly cool it to below the melting point of the liquid metal; finally, at low temperature, use a small amount of ethanol to make the edge of the fluorine-containing surface of the fluorine-surface flexible conductive film fit well in the central area of ​​the bioadhesive film to achieve the encapsulation of the liquid metal. It was pasted on the wound surface, and the wound recovery is shown in Table 1. After 9 days, the skin tissue was taken for H&E staining to observe the regeneration of hair follicles, and the hair follicle activation is shown in Table 2.

[0040] Example 2

[0041] (1) Preparation of the upper structure bioadhesive film: Weigh 100 parts by weight of isophorone diisocyanate, 400 parts of polyetheramine 2000, and 1 part of dibutyltin dihydrate, add 500 parts of acetone into a three-necked flask to dissolve, and stir at room temperature for 2 hours; after heating to 60°C, add 15 parts of 2,2-dihydroxymethylbutyric acid, and stir for 2 hours; after cooling to room temperature, add 10 parts of triethylamine, and stir for 1 hour; heat to 40°C, add oligosaccharide dissolved in deionized water (500 parts of deionized water and 30 parts of oligosaccharide), and stir for 6 hours; filter the insoluble matter at the bottom and dissolve it in a small amount of anhydrous ethanol solution; finally, cast it into a mold or apply it by scraping to form a film, and obtain the bioadhesive film after drying.

[0042] (2) Preparation of the fluorine-surface flexible conductive film of the lower structure: 2080 parts by weight of -19°C gallium-indium alloy was dispersed in a dispersion of an aqueous solution of oligomeric chitosan (500 parts of deionized water and 30 parts of oligomeric chitosan) by ultrasonic grinding, ultrasonicated for 20 minutes, and set aside; 100 parts by weight of isophorone diisocyanate, 400 parts of polyetheramine 2000, and 1 part of dibutyltin diisocyanate were added to a three-necked flask, and 500 parts of acetone were added to dissolve, and the reaction was stirred at room temperature for 2 hours; after heating to 60°C, 15 parts of 2,2-dihydroxy- Methylbutyric acid, stir and react for 2 hours; after cooling to room temperature, add 10 parts of triethylamine, stir and react for 1 hour; heat to 40°C, add the reserved gallium-indium alloy-oligochitosan dispersion in proportion, stir and react for 6 hours; filter the insoluble matter at the bottom and dissolve it in a small amount of anhydrous ethanol solution; pour it into a mold or apply it to form a film, and obtain a flexible conductive film after drying; finally, evenly spray 0.05 weight parts of 5μm fluorosilicone rubber micro-nano particles in ethanol on the upper surface of the flexible conductive film and dry it to obtain a fluorine surface flexible conductive film.

[0043] (3) Preparation of the healing patch: Cut and weigh 100 parts by weight of the bioadhesive film and 10 parts by weight of the fluorine-surface flexible conductive film; then, use a syringe to drop 4 parts by weight of -19°C gallium-indium alloy on the center of the fluorine-containing surface of the fluorine-surface flexible conductive film, and quickly cool it to below the melting point of the liquid metal; finally, at low temperature, use a small amount of ethanol to make the edge of the fluorine-containing surface of the fluorine-surface flexible conductive film fit well in the central area of ​​the bioadhesive film to achieve the encapsulation of the liquid metal. It was pasted on the wound surface, and the wound recovery is shown in Table 1. After 9 days, the skin tissue was taken for H&E staining to observe the regeneration of hair follicles, and the hair follicle activation is shown in Table 2.

[0044] Example 3

[0045] (1) Preparation of the upper structure bioadhesive film: Weigh 100 parts by weight of isophorone diisocyanate, 200 parts of polyetheramine 2000, and 2 parts of dibutyltin dioxysilicate, add 600 parts of acetone into a three-necked flask to dissolve, and stir at room temperature for 2.5 hours; after heating to 65°C, add 30 parts of 2,2-dihydroxymethylbutyric acid, and stir for 2.5 hours; after cooling to room temperature, add 21 parts of triethylamine, and stir for 1.5 hours; heat to 50°C, add oligosaccharide dissolved in deionized water (600 parts of deionized water and 30 parts of oligosaccharide), and stir for 7 hours; filter the insoluble matter at the bottom and dissolve it in a small amount of anhydrous ethanol solution; finally, cast it into a mold or apply it by scraping to form a film, and obtain the bioadhesive film after drying.

[0046] (2) Preparation of the fluorine-surface flexible conductive film of the lower structure: 2080 parts by weight of 3°C gallium-indium alloy was dispersed in an aqueous solution of oligomolecular chitosan (600 parts of deionized water and 30 parts of oligomolecular chitosan) by ultrasonic grinding, ultrasonicated for 30 minutes, and set aside; 100 parts by weight of isophorone diisocyanate, 200 parts of polyetheramine 2000, and 2 parts of dibutyltin dioxysilicate were added to a three-necked flask, 600 parts of acetone were added to dissolve, and the reaction was stirred at room temperature for 2.5 hours; after heating to 65°C, 30 parts of 2,2-dihydroxymethylbutyl Acid, stir and react for 2.5 hours; after cooling to room temperature, add 21 parts of triethylamine, stir and react for 1.5 hours; heat to 50°C, add the reserved gallium-indium alloy-oligochitosan dispersion in proportion, stir and react for 7 hours; filter the insoluble matter at the bottom and dissolve it in a small amount of anhydrous ethanol solution; pour it into a mold or apply it to form a film, and obtain a flexible conductive film after drying; finally, evenly spray 0.02 weight parts of 5μm polytetrafluoroethylene micro-nano particles in ethanol dispersion on the upper surface of the flexible conductive film and dry it to obtain a fluorine surface flexible conductive film.

[0047] (3) Preparation of healing-promoting patch: Cut and weigh 100 parts by weight of bioadhesive film and 5 parts by weight of fluorine-surface flexible conductive film; then, use a syringe to drop 3 parts by weight of 3°C gallium-indium alloy on the center of the fluorine-containing surface of the fluorine-surface flexible conductive film, and quickly cool it to below the melting point of liquid metal; finally, at low temperature, use a small amount of ethanol to make the edge of the fluorine-containing surface of the fluorine-surface flexible conductive film fit well in the central area of ​​the bioadhesive film to achieve the encapsulation of liquid metal. It was pasted on the wound surface, and the wound recovery is shown in Table 1. After 9 days, the skin tissue was taken for H&E staining to observe the regeneration of hair follicles, and the hair follicle activation is shown in Table 2.

[0048] Example 4

[0049] (1) Preparation of the upper structure bioadhesive film: Weigh 100 parts by weight of isophorone diisocyanate, 200 parts of polyetheramine 2000, and 2 parts of dibutyltin dioxysilicate, add 600 parts of acetone into a three-necked flask to dissolve, and stir at room temperature for 2.5 hours; after heating to 65°C, add 30 parts of 2,2-dihydroxymethylbutyric acid, and stir for 2.5 hours; after cooling to room temperature, add 21 parts of triethylamine, and stir for 1.5 hours; heat to 50°C, add oligosaccharide dissolved in deionized water (600 parts of deionized water and 30 parts of oligosaccharide), and stir for 7 hours; filter the insoluble matter at the bottom and dissolve it in a small amount of anhydrous ethanol solution; finally, cast it into a mold or apply it by scraping to form a film, and obtain the bioadhesive film after drying.

[0050] (2) Preparation of the fluorine-surface flexible conductive film of the lower structure: 4800 parts by weight of 3°C gallium-indium alloy was dispersed in a dispersion of an aqueous solution of oligomeric chitosan (600 parts of deionized water and 30 parts of oligomeric chitosan) by ultrasonic grinding, ultrasonicated for 30 minutes, and set aside; 100 parts by weight of isophorone diisocyanate, 200 parts of polyetheramine 2000, and 2 parts of dibutyltin dioxysilicate were added to a three-necked flask and 600 parts of acetone were added to dissolve, and the reaction was stirred at room temperature for 2.5 hours; after heating to 65°C, 30 parts of 2,2-dihydroxymethane were added butyric acid, stirring and reacting for 3 hours; after cooling to room temperature, adding 21 parts of triethylamine, stirring and reacting for 2 hours; heating to 50°C, adding the reserved gallium-indium alloy-oligochitosan dispersion in proportion, stirring and reacting for 7 hours; filtering the insoluble matter at the bottom and dissolving it in a small amount of anhydrous ethanol solution; pouring it into a mold or coating it with a scraper to form a film, and obtaining a flexible conductive film after drying; finally, spraying 0.05 weight parts of 1 μm polytetrafluoroethylene micro-nano particles in ethanol evenly on the upper surface of the flexible conductive film and drying it to obtain a fluorine-surface flexible conductive film.

[0051] (3) Preparation of healing-promoting patch: Cut and weigh 100 parts by weight of bioadhesive film and 20 parts by weight of fluorine-surface flexible conductive film; then, use a syringe to drop 5.5 parts by weight of 3°C gallium-indium alloy on the center of the fluorine-containing surface of the fluorine-surface flexible conductive film, and quickly cool it to below the melting point of liquid metal; finally, at low temperature, use a small amount of ethanol to make the edge of the fluorine-containing surface of the fluorine-surface flexible conductive film fit well in the central area of ​​the bioadhesive film to achieve the encapsulation of liquid metal. It was pasted on the wound surface, and the wound recovery is shown in Table 1. After 9 days, the skin tissue was taken for H&E staining to observe the regeneration of hair follicles, and the hair follicle activation is shown in Table 2.

[0052] Example 5

[0053] (1) Preparation of the upper structure bioadhesive film: Weigh 100 parts by weight of isophorone diisocyanate, 300 parts of polyetheramine 2000, and 3 parts of dibutyltin dioxysilicate, add 800 parts of acetone into a three-necked flask to dissolve, and stir at room temperature for 3 hours; after heating to 70°C, add 22 parts of 2,2-dihydroxymethylbutyric acid, and stir for 3 hours; after cooling to room temperature, add 15 parts of triethylamine, and stir for 2 hours; heat to 60°C, add oligosaccharide dissolved in deionized water (800 parts of deionized water and 30 parts of oligosaccharide), and stir for 8 hours; filter the insoluble matter at the bottom and dissolve it in a small amount of anhydrous ethanol solution; finally, cast it into a mold or apply it by scraping to form a film, and obtain the bioadhesive film after drying.

[0054] (2) Preparation of the fluorine-surface flexible conductive film of the lower structure: 7000 parts by weight of 6°C gallium-indium alloy was dispersed in a dispersion of an aqueous solution of oligomeric chitosan (800 parts of deionized water and 30 parts of oligomeric chitosan) by ultrasonic grinding, ultrasonicated for 40 minutes, and set aside; 100 parts by weight of isophorone diisocyanate, 300 parts of polyetheramine 2000, and 3 parts of dibutyltin dioxysilicate were added to a three-necked flask, 800 parts of acetone were added to dissolve, and the reaction was stirred at room temperature for 3 hours; after heating to 70°C, 22 parts of 2,2-dihydroxymethane were added butyric acid, stirring and reacting for 3 hours; after cooling to room temperature, adding 15 parts of triethylamine, stirring and reacting for 2 hours; heating to 60°C, adding the reserved gallium-indium alloy-oligochitosan dispersion in proportion, stirring and reacting for 8 hours; filtering the insoluble matter at the bottom and dissolving it in a small amount of anhydrous ethanol solution; pouring it into a mold or coating it with a scraper to form a film, and obtaining a flexible conductive film after drying; finally, spraying 0.01 weight parts of 1 μm fluorosilicone rubber micro-nano particles in ethanol evenly on the upper surface of the flexible conductive film and drying it to obtain a fluorine-surface flexible conductive film.

[0055] (3) Preparation of healing-promoting patch: Cut and weigh 100 parts by weight of bioadhesive film and 30 parts by weight of fluorine-surface flexible conductive film; then, use a syringe to drop 7.5 parts by weight of 6°C gallium-indium alloy on the center of the fluorine-containing surface of the fluorine-surface flexible conductive film, and quickly cool it to below the melting point of liquid metal; finally, at low temperature, use a small amount of ethanol to make the edge of the fluorine-containing surface of the fluorine-surface flexible conductive film fit well in the central area of ​​the bioadhesive film to achieve the encapsulation of liquid metal. It was pasted on the wound surface, and the wound recovery is shown in Table 1. After 9 days, the skin tissue was taken for H&E staining to observe the regeneration of hair follicles, and the hair follicle activation is shown in Table 2.

[0056] Example 6

[0057] (1) Preparation of the upper structure bioadhesive film: Weigh 100 parts by weight of isophorone diisocyanate, 600 parts of polyetheramine 2000, and 3 parts of dibutyltin dioxysilicate, add 900 parts of acetone into a three-necked flask to dissolve, and stir at room temperature for 3 hours; after heating to 70°C, add 7 parts of 2,2-dihydroxymethylbutyric acid, and stir for 4 hours; after cooling to room temperature, add 5 parts of triethylamine, and stir for 2 hours; heat to 60°C, add oligosaccharide dissolved in deionized water (900 parts of deionized water and 30 parts of oligosaccharide), and stir for 8 hours; filter the insoluble matter at the bottom and dissolve it in a small amount of anhydrous ethanol solution; finally, cast it into a mold or apply it by scraping to form a film, and obtain the bioadhesive film after drying.

[0058] (2) Preparation of the fluorine surface flexible conductive film of the lower structure: 8500 parts by weight of 11°C gallium-indium alloy was dispersed in a dispersion of an aqueous solution of oligomeric chitosan (900 parts of deionized water and 30 parts of oligomeric chitosan) by ultrasonic grinding, ultrasonicated for 30 minutes, and set aside; 100 parts by weight of isophorone diisocyanate, 600 parts of polyetheramine 2000, and 2 parts of dibutyltin dioxysilicate were added to a three-necked flask, 900 parts of acetone were added to dissolve, and the reaction was stirred at room temperature for 3 hours; after heating to 70°C, 7 parts of 2,2-dihydroxymethylbutyric acid were added. , stirring and reacting for 4 hours; after cooling to room temperature, adding 5 parts of triethylamine, stirring and reacting for 2 hours; heating to 60°C, adding the reserved gallium-indium alloy-oligochitosan dispersion in proportion, stirring and reacting for 8 hours; filtering the insoluble matter at the bottom and dissolving it in a small amount of anhydrous ethanol solution; pouring it into a mold or coating it with a scraper to form a film, and obtaining a flexible conductive film after drying; finally, spraying 0.03 weight parts of 2μm polyfluorinated ethylene propylene copolymer micro-nano particles in ethanol evenly on the upper surface of the flexible conductive film and drying it to obtain a fluorine surface flexible conductive film.

[0059] (3) Preparation of the healing patch: Cut and weigh 100 parts by weight of the bioadhesive film and 40 parts by weight of the fluorine-surface flexible conductive film; then, use a syringe to drop 8.5 parts by weight of 11°C gallium-indium alloy on the center of the fluorine-containing surface of the fluorine-surface flexible conductive film, and quickly cool it to below the melting point of the liquid metal; finally, at low temperature, use a small amount of ethanol to make the edge of the fluorine-containing surface of the fluorine-surface flexible conductive film fit well in the central area of ​​the bioadhesive film to achieve the encapsulation of the liquid metal. It was pasted on the wound surface, and the wound recovery is shown in Table 1. After 9 days, the skin tissue was taken for H&E staining to observe the regeneration of hair follicles, and the hair follicle activation is shown in Table 2.

[0060] Example 7

[0061] (1) Preparation of the upper structure bioadhesive film: Weigh 100 parts by weight of isophorone diisocyanate, 360 parts of polyetheramine 2000, and 3 parts of dibutyltin dioxysilicate, add 1000 parts of acetone into a three-necked flask to dissolve, and stir at room temperature for 3 hours; after heating to 70°C, add 13.3 parts of 2,2-dihydroxymethylbutyric acid, and stir for 4 hours; after cooling to room temperature, add 9 parts of triethylamine, and stir for 2 hours; heat to 60°C, add oligosaccharide dissolved in deionized water (1000 parts of deionized water and 40 parts of oligosaccharide), and stir for 8 hours; filter the insoluble matter at the bottom and dissolve it in a small amount of anhydrous ethanol solution; finally, cast it into a mold or apply it by scraping to form a film, and obtain the bioadhesive film after drying.

[0062] (2) Preparation of the fluorine surface flexible conductive film of the lower structure: 12500 parts by weight of 16°C gallium-indium alloy was dispersed in a dispersion of an aqueous solution of oligomeric chitosan (1000 parts of deionized water and 40 parts of oligomeric chitosan) by ultrasonic grinding, ultrasonicated for 30 minutes, and set aside; 100 parts by weight of isophorone diisocyanate, 360 parts of polyetheramine 2000, and 2 parts of dibutyltin dioxysilicate were added to a three-necked flask, and 1000 parts of acetone were added to dissolve, and the reaction was stirred at room temperature for 3 hours; after heating to 70°C, 13.3 parts of 2,2-dihydroxymethane were added. butyric acid, stirring and reacting for 4 hours; after cooling to room temperature, adding 9 parts of triethylamine, stirring and reacting for 2 hours; heating to 60°C, adding the reserved gallium-indium alloy-oligochitosan dispersion in proportion, stirring and reacting for 8 hours; filtering the insoluble matter at the bottom and dissolving it in a small amount of anhydrous ethanol solution; pouring it into a mold or coating it with a scraper to form a film, and obtaining a flexible conductive film after drying; finally, spraying 0.04 weight parts of 1μm polyfluorinated ethylene propylene copolymer micro-nano particles in ethanol evenly on the upper surface of the flexible conductive film and drying it to obtain a fluorine-surface flexible conductive film.

[0063] (3) Preparation of the healing patch: Cut and weigh 100 parts by weight of the bioadhesive film and 50 parts by weight of the fluorine-surface flexible conductive film; then, use a syringe to drop 10 parts by weight of a 16°C gallium-indium alloy on the center of the fluorine-containing surface of the fluorine-surface flexible conductive film, and quickly cool it to below the melting point of the liquid metal; finally, at low temperature, use a small amount of ethanol to make the edge of the fluorine-containing surface of the fluorine-surface flexible conductive film fit well in the central area of ​​the bioadhesive film to achieve the encapsulation of the liquid metal. It was pasted on the wound surface, and the wound recovery is shown in Table 1. After 9 days, the skin tissue was taken for H&E staining to observe the regeneration of hair follicles, and the hair follicle activation is shown in Table 2.

[0064] Example 8

[0065] (1) Preparation of the upper structure bioadhesive film: Weigh 100 parts by weight of isophorone diisocyanate, 450 parts of polyetheramine 2000, and 1.5 parts of dibutyltin dioxysilicate, add 1000 parts of acetone into a three-necked flask to dissolve, and stir at room temperature for 3 hours; after heating to 70°C, add 16.7 parts of 2,2-dihydroxymethylbutyric acid, and stir for 4 hours; after cooling to room temperature, add 11 parts of triethylamine, and stir for 2 hours; heat to 60°C, add oligosaccharide dissolved in deionized water (1000 parts of deionized water and 20 parts of oligosaccharide), and stir for 8 hours; filter the insoluble matter at the bottom and dissolve it in a small amount of anhydrous ethanol solution; finally, cast it into a mold or apply it by scraping to form a film, and obtain the bioadhesive film after drying.

[0066] (2) Preparation of the fluorine-surface flexible conductive film of the lower structure: 4800 parts by weight of 6°C gallium-indium alloy was dispersed in a dispersion of an aqueous solution of oligomeric chitosan (1000 parts of deionized water and 20 parts of oligomeric chitosan) by ultrasonic grinding, ultrasonicated for 30 minutes, and set aside; 100 parts by weight of isophorone diisocyanate, 450 parts of polyetheramine 2000, and 2 parts of dibutyltin dioxysilicate were added to a three-necked flask, and 1000 parts of acetone were added to dissolve, and the reaction was stirred at room temperature for 3 hours; after heating to 70°C, 16.7 parts of 2,2-dihydroxymethylbutyl Acid, stir and react for 4 hours; after cooling to room temperature, add 11 parts of triethylamine, stir and react for 2 hours; heat to 60°C, add the reserved gallium-indium alloy-oligochitosan dispersion in proportion, stir and react for 8 hours; filter the insoluble matter at the bottom and dissolve it in a small amount of anhydrous ethanol solution; pour it into a mold or apply it to form a film, and obtain a flexible conductive film after drying; finally, evenly spray 0.04 weight parts of 500nm polyfluorinated ethylene propylene copolymer micro-nano particles in ethanol on the upper surface of the flexible conductive film and dry it to obtain a fluorine surface flexible conductive film.

[0067] (3) Preparation of the healing patch: Cut and weigh 100 parts by weight of the bioadhesive film and 20 parts by weight of the fluorine-surface flexible conductive film; then, use a syringe to drop 5.5 parts by weight of 6°C gallium-indium alloy on the center of the fluorine-containing surface of the fluorine-surface flexible conductive film, and quickly cool it to below the melting point of the liquid metal; finally, at low temperature, use a small amount of ethanol to make the edge of the fluorine-containing surface of the fluorine-surface flexible conductive film fit well in the central area of ​​the bioadhesive film to achieve the encapsulation of the liquid metal. It was pasted on the wound surface, and the wound recovery is shown in Table 1. After 9 days, the skin tissue was taken for H&E staining to observe the regeneration of hair follicles, and the hair follicle activation is shown in Table 2.

[0068] Comparative Example 1

[0069] The bioadhesive film of Example 1 was directly attached to the wound of mice, and the wound recovery was shown in Table 1. After 9 days, the skin tissue was taken for H&E staining to observe the regeneration of hair follicles, and the activation was shown in Table 2.

[0070] Comparative Example 2

[0071] The fluorine-surface flexible conductive film of Example 1 was directly attached to the wound of mice, and the wound recovery was shown in Table 1. After 9 days, the skin tissue was taken for H&E staining to observe the regeneration of hair follicles, and its activation was shown in Table 2.

[0072] Comparative Example 3

[0073] The other conditions of Example 1 (1) were kept unchanged. During the preparation of the patch, no liquid metal was added. A small amount of ethanol was directly used to make the edge of the fluorine-containing surface of the fluorine-surface flexible conductive film fit well with the central area of ​​the bioadhesive film. Finally, the patch was applied to the wound of the mouse. The wound recovery was shown in Table 1. After 9 days, the skin tissue was taken for H&E staining to observe the regeneration of hair follicles. The activation was shown in Table 2.

[0074] Table 1 Wound healing rate

[0075]

[0076]

[0077] Table 2 Hair follicle regeneration (9 days)

[0078] Is there hair follicle regeneration? Example 1 yes Example 2 yes Example 3 yes Example 4 yes Example 5 yes Example 6 yes Example 7 yes Example 8 yes Comparative Example 1 no Comparative Example 2 no Comparative Example 3 no

[0079] By comparing Table 1 and Table 2, since the patches of Comparative Examples 1, 2 and 3 cannot achieve self-generation and cannot generate electrical stimulation to the wound, the wound heals slowly and new hair follicles cannot be generated. This proves that the self-generation of the self-healing patch promotes wound repair and activates hair follicles, and helps mediate scar-free repair.

[0080] Figure 1 The healing-promoting patch can achieve good adhesion on pig skin and human wrist, and does not fall off when the skin is bent, indicating that it has good tissue adhesion and skin compliance, which helps it adapt to the complex daily treatment environment. Figure 2 The energy spectrum image shows that the metal elements in the gallium-indium alloy in Example 1 do not aggregate in a large area in the flexible conductive film on the fluorine surface, which proves that the liquid metal can be evenly dispersed, which is beneficial to the rapid and uniform transmission of electrical signals and the realization of uniform and stable electrical stimulation. Figure 3 Scanning electron microscopy images show that polyfluorinated ethylene propylene copolymer micro-nano particles are uniformly adhered to the surface of the film, indicating that the introduction of fluorine-containing micro-nano particles improves the surface roughness, and the uniform introduction of fluorine elements helps to improve the material's electron-absorbing ability, which is beneficial to the generation of spontaneous electricity.

[0081] Figure 4The healing-promoting patch generates dynamic voltage when triggered by a 128HZ tuning fork, proving that driven by everyday low-frequency sound waves, the healing-promoting patch can achieve self-generation, which helps to produce therapeutic effects by changing the electrical signals at the wound site. Figure 5 The healing-promoting dressing can be directly applied to the skin and wounds of mice without the aid of additional materials, which helps ensure the continued effectiveness of treatment. Figure 6 H&E staining of the healing wound site showed clear new hair follicles, proving that the healing-promoting dressing can activate wound hair follicles and mediate scarless wound healing.

[0082] The healing-promoting patch provided by the present invention can be directly attached to the surface of the wound skin, and can achieve self-generation under the stimulation of daily low-frequency sound waves. Its power generation effect has the efficacy of promoting wound healing. At the same time, it helps to activate the regeneration of wound hair follicles and mediate scarless wound repair. The patch has good biocompatibility and skin compliance, and does not require the aid of drugs to achieve good therapeutic effects. It overcomes the dependence of traditional self-generating patches on body movement and skin bending, and is potentially suitable for patients with drug sensitivity, aging, multiple diseases, and long-term bedridden patients, and has important development value and significance.

[0083] Those skilled in the art should understand that the above description is only a specific embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the protection scope of the present invention.

Claims

1. A healing-promoting dressing, characterized in that: The healing-promoting dressing is encapsulated by three layers of structures: upper, middle and lower. The upper layer is a bioadhesive film; the middle layer is a liquid metal material; and the lower layer is a fluorine-surface flexible conductive film.

2. A healing-promoting patch according to claim 1, characterized in that: The added amount of each layer is calculated based on the weight of the upper layer being 100 parts by weight, the middle layer being 3-10 parts by weight, and the lower layer being 5-50 parts by weight; in the healing-promoting dressing, the upper structure has good biocompatibility and tissue adhesion, the middle structure has good liquid flow properties, deformation ability and driveability, the lower structure has good conductivity and the fluorine element on its upper surface has strong electron-withdrawing ability.

3. A healing-promoting dressing according to any one of claims 1-2, characterized in that: The preparation process of the upper structure is as follows: isophorone diisocyanate, polyetheramine 2000 and an organic tin catalyst are dissolved in acetone in proportion, and stirred at room temperature for 2-3 hours; after heating to 60-70° C., 2,2-dihydroxymethylbutyric acid is added, and stirred for 2 hours to 4 hours; after cooling to room temperature, triethylamine is added, and stirred for 1-2 hours; after heating to 40-60° C., oligosaccharide dissolved in deionized water is added, and stirred for 6-8 hours; The insoluble matter at the bottom is filtered and dissolved in an anhydrous ethanol solution; finally, it is poured into a mold or scraped to form a film, and a bioadhesive film is obtained after drying.

4. A healing-promoting dressing according to claim 3, characterized in that: The upper structure is prepared by solution reaction of raw materials including the following components: 100 parts by weight of isophorone diisocyanate, 200-600 parts by weight of polyetheramine 2000, 2,2-dihydroxymethylbutyric acid is 7-30 parts by weight, triethylamine is 5-21 parts by weight, oligomeric chitosan is 20-40 parts by weight, an organic tin catalyst is 1-3 parts by weight, acetone is 500-1000 parts by weight, and deionized water is 500-1000 parts by weight.

5. A healing-promoting dressing according to any one of claims 1-2, characterized in that: The middle layer structure is a gallium-indium alloy with a melting point of -19°C-20°C.

6. A healing-promoting patch according to claim 1-2, characterized in that: The preparation process of the lower structure is as follows: preparing a dispersion of liquid metal in an aqueous solution of oligomolecular chitosan by ultrasonic crushing for 20-40 minutes, and setting aside; dissolving isophorone diisocyanate, polyetheramine 2000 and an organic tin catalyst in acetone in proportion, and stirring and reacting at room temperature for 2-3 hours; heating to 60-70° C., adding 2,2-dihydroxymethylbutyric acid, and stirring and reacting for 2 hours to 4 hours; cooling to room temperature, adding triethylamine, and stirring and reacting for 1-2 hours; heating to 40-60° C., adding a liquid metal-oligomolecular chitosan dispersion in proportion, and stirring and reacting for 6-8 hours; filtering the insoluble matter at the bottom and dissolving it in an anhydrous ethanol solution; pouring into a mold or coating to form a film, and obtaining a flexible conductive film after drying; Finally, the fluorine-containing micro-nano particles are dispersed in an ethanol solution to form a fluorine-containing particle dispersion, which is evenly sprayed on the upper surface of the flexible conductive film and dried to obtain a fluorine-surface flexible conductive film.

7. A healing-promoting dressing according to claim 6, characterized in that: The lower structure is prepared by solution reaction of raw materials including the following components: 100 parts by weight of isophorone diisocyanate, 200-600 parts by weight of polyetheramine 2000, 7-30 parts by weight of 2,2-dihydroxymethylbutyric acid, 5-21 parts by weight of triethylamine, 20-40 parts by weight of oligomeric chitosan, 1-3 parts by weight of an organic tin catalyst, 2000-13000 parts by weight of a liquid metal, and 0.01-0.05 parts by weight of fluorine-containing micro-nanoparticles. The acetone is 500-1000 parts by weight, and the deionized water is 500-1000 parts by weight.

8. A healing-promoting dressing according to claim 7, characterized in that: The liquid metal is a gallium-indium alloy with a melting point of -19°C-20°C; the fluorine-containing micro-nano particles are one or a mixture of two or more of 500nm-5μm fluorosilicone rubber micro-nano particles, polytetrafluoroethylene micro-nano particles, and polyfluorinated ethylene propylene copolymer micro-nano particles.

9. A method for preparing a healing-promoting dressing according to any one of claims 1 to 8, characterized in that: The following steps are involved: The middle-layer structure is dropped onto the center of the fluorine-containing surface of the lower-layer structure using a syringe, and the temperature is quickly lowered to below the melting point of the liquid metal. Finally, ethanol is used at low temperature to make the edge of the fluorine-containing surface of the lower-layer structure fit into the central area of ​​the upper-layer structure, thereby achieving encapsulation of the middle-layer structure.

10. Use of a healing-promoting patch according to any one of claims 1 to 8 or a healing-promoting patch obtained by the preparation method according to claim 9, characterized in that: Used to prepare healing-promoting dressings that mediate scar-free repair and other medical materials for scar prevention.

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