Hydrogel dressing and preparation method thereof

Abstract

The invention relates to a hydrogel dressing and a preparation method thereof. The hydrogel dressing comprises the following components in percentage by mass: 0.1-3% of a cross-linking agent; 5 to 30% of N-isopropylacrylamide (N-isopropylacrylamide); 5 to 30% of N-[tris (hydroxymethyl) methyl] acrylamide; 0.1 to 2% of boric acid polyaniline; and the balance of deionized water. The dosage of a cascade enzyme initiator is 10-200 U / mL, and the preparation method comprises the following steps: dispersing a cross-linking agent, N-isopropylacrylamide, N-[tris (hydroxymethyl) methyl] acrylamide and boric acid polyaniline in deionized water to form a hydrogel precursor solution, the mass fraction of the cross-linking agent, the mass fraction of the N-isopropylacrylamide, the mass fraction of the N-[tris (hydroxymethyl) methyl] acrylamide and the mass fraction of the boric acid polyaniline are 0.1%-3%, 5%-30%, 5%-30% and 0.1%-2% in sequence, and the balance is deionized water; a cascade enzyme initiator is added into the hydrogel precursor solution for polymerization, the hydrogel dressing is obtained, and the dosage of the cascade enzyme initiator is 10-200 U / mL. According to the hydrogel dressing and the preparation method, the hydrogel dressing has excellent adhesion performance, shrinkage performance, tension resistance and anti-inflammatory / antibacterial performance, has remarkable significance on rapid plugging and regeneration of penetrative fistula, is high in gel forming speed and low in cost, and can effectively improve the production efficiency and reduce the production cost.

Description

Technical Field

[0001] The present invention relates to the technical field of gel dressings, in particular to a hydrogel dressing and a preparation method thereof. Background Art

[0002] Oral oropharyngeal fistula is usually a penetrating soft tissue defect caused by congenital malformation, major head and neck trauma, severe oral inflammation, postoperative radiotherapy for tumors, etc. The incidence rate is as high as 65%, with high morbidity and low cure rate, causing great pain to patients.

[0003] Oral oropharyngeal fistulas are characterized by a variable physiological microenvironment, complex anatomical structure, repeated inflammatory stimulation, and continuous movement. The wound edges are often characterized by high tension and excessive scar deposition, making repair extremely difficult. Traditional surgical treatments often use drug coatings, iodoform / silicone / imported collagen packing, or complex flap transplants. These are accompanied by problems such as poor mechanical strength of the fillers, weak tissue adhesion, low biocompatibility, difficulty in degradation, high prices, and large surgical trauma, placing a significant physical and psychological burden on patients. Therefore, developing a bioactive material that can efficiently and quickly repair oral oropharyngeal fistulas and achieve scarless fistula repair has important social significance and application value.

[0004] At present, traditional wound dressings are mainly used for blocking and anti-inflammatory purposes, and are usually unable to withstand the high tension of penetrating fistulas and reduce scars, resulting in insufficient functionality of these wound dressings and unsatisfactory treatment effects. Summary of the Invention

[0005] In view of this, the purpose of the present invention is to provide a hydrogel dressing and a preparation method, which has excellent adhesion, contraction, tension resistance and anti-inflammatory / antibacterial properties, is of significant significance for the rapid closure and regeneration of through-oral fistulas, and has a fast gelation speed and low cost, which can effectively improve production efficiency and reduce production costs.

[0006] The present invention provides a hydrogel dressing comprising:

[0007] 0.1-3% cross-linking agent;

[0008] 5-30% N-isopropylacrylamide;

[0009] 5-30% N-[tris(hydroxymethyl)methyl]acrylamide;

[0010] 0.1-2% borated polyaniline;

[0011] The rest is deionized water;

[0012] The dosage of cascade enzyme initiator is 10-200 U / m.

[0013] In one embodiment, the cascade enzyme initiator comprises glucose oxidase, ferrous glycine, and glucose.

[0014] In one embodiment, the cross-linking agent is any one or more combinations of acryloyl-hyaluronic acid, xyloglucan, chitosan, chondroitin sulfate, and gelatin.

[0015] In one embodiment, the hydrogel dressing is used for repairing and regenerating penetrating oral fistulas.

[0016] The present invention also provides a method for preparing a hydrogel dressing, which is characterized in that the method is used to prepare the hydrogel dressing described above, comprising the following steps:

[0017] Dispersing a crosslinker, N-isopropylacrylamide, N-[tris(hydroxymethyl)methyl]acrylamide, and borated polyaniline in deionized water to form a hydrogel precursor solution, wherein the mass fractions of the crosslinker, N-isopropylacrylamide, N-[tris(hydroxymethyl)methyl]acrylamide, and borated polyaniline are 0.1-3%, 5-30%, 5-30%, and 0.1-2%, respectively, and the remainder is deionized water;

[0018] A cascade enzyme initiator is added to the hydrogel precursor solution for polymerization to obtain the hydrogel dressing, wherein the amount of the cascade enzyme initiator is 10-200 U / mL.

[0019] In one embodiment, the time for adding the cascade enzyme to the hydrogel precursor solution for polymerization is not less than 10 minutes.

[0020] The hydrogel dressing and preparation method provided by the present invention have excellent adhesion, contraction, tension resistance and anti-inflammatory / antibacterial properties, and are of significant significance for the rapid closure and regeneration of penetrating fistulas. In addition, the hydrogel dressing has a fast gelling speed and low cost, which can effectively improve production efficiency and reduce production costs. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the following briefly introduces the drawings required for use in the embodiments. It should be understood that the following drawings only illustrate certain embodiments of the present invention and therefore should not be regarded as limiting the scope. For ordinary technicians in this field, other relevant drawings can be obtained based on these drawings without paying any creative work.

[0022] Figure 1 This is a schematic diagram of the process for preparing the hydrogel dressing provided by the present invention.

[0023] Figure 2Molecular diagrams of the raw materials of the hydrogel (b-PNITH) and the hydrogel dressing of the present invention, wherein a) is the molecular diagram of the hydrogel precursor solution, and b) is the molecular diagram of the hydrogel dressing (THMA: N-[tris(hydroxymethyl)methyl]acrylamide; NIPAM: N-isopropylacrylamide; b-PANi: borated polyaniline; CSMA: acryloyl chondroitin sulfate).

[0024] Figure 3 The mechanical property curves of the hydrogel dressing prepared in Example 1 are as follows: a) is the uniaxial tensile stress-strain curve of hydrogels with different proportions; b) is the uniaxial compressive stress-strain curve of hydrogels with different proportions.

[0025] Figure 4 This is a graph showing the change in lap shear stress versus displacement for hydrogel dressings of different proportions in Example 2.

[0026] Figure 5 This is a temperature comparison diagram of the hydrogel dressing formed in Example 3 under near-infrared light stimulation, where a) does not contain borated polyaniline, and b) contains borated polyaniline.

[0027] Figure 6 These are images showing the temperature-sensitive contraction performance of the hydrogel dressing formed in Example 3: a. Contraction images of the hydrogel at 25°C, 37°C, and 46°C; b. Comparative images of the hydrogel dressing applied to mouse skin after 2 hours of contraction.

[0028] Figure 7 The diagrams show the effects of treating penetrating oral fistulas according to Example 3: a) shows the effects of oral fistulas at 0 days, 4 days, 7 days and 11 days without treatment; b) shows the effects of treating oral fistulas with the hydrogel dressing prepared in Example 3 at 4 days, 7 days and 11 days.

[0029] Figure 8 These are H&E images of the hydrogel excipient prepared in Example 3 during treatment, where a) is for 4 days of treatment, b) is for 7 days of treatment, and c) is for 11 days of treatment. DETAILED DESCRIPTION

[0030] Specific embodiments of the present invention will be described in detail below with reference to the accompanying drawings. It should be understood that the described embodiments are merely some, and not all, of the embodiments of the present invention. All other embodiments derived by persons of ordinary skill in the art based on the description of the present invention without inventive effort are intended to fall within the scope of protection of the present invention.

[0031] In the description of the present invention, unless otherwise specified or limited, the terms "disposed," "installed," and "connected" should be understood broadly. For example, they may refer to fixed, detachable, or integral connections; mechanical or electrical connections; and direct or indirect connections through an intermediary. Those skilled in the art will understand the specific meanings of these terms based on the specific circumstances.

[0032] The directions or positional relationships indicated by terms such as "upper", "lower", "left", "right", "front", "back", "top", "bottom", "inside" and "outside" are based on the directions or positional relationships shown in the accompanying drawings, or are the directions or positional relationships in which the inventive product is usually placed when in use. They are only for the convenience and simplification of description, and do not indicate or imply that the device or element referred to must have a specific direction, be constructed and operate in a specific direction. Therefore, they should not be understood as limiting the present invention.

[0033] The terms "first," "second," "third," etc. are merely used to distinguish between elements of similar nature and do not indicate or imply relative importance or a particular order.

[0034] The terms "comprises," "comprising," or any other variations thereof, are intended to cover a non-exclusive inclusion of elements other than the listed elements and may also include additional elements not specifically listed.

[0035] Example 1

[0036] See also Figures 1 to 3 The hydrogel dressing provided in this embodiment comprises: 1 wt% CSMA (acryloyl-modified chondroitin sulfate), 30 wt% N-isopropylacrylamide, 5 wt% N-[tris(hydroxymethyl)methyl]acrylamide, 0.5 wt% borated polyaniline, and 63.5 wt% deionized water. The preparation method comprises uniformly dispersing the above ingredients in deionized water to form a hydrogel precursor solution, adding glucose oxidase (50 U / mL), ferrous glycine (100 μg / mL), and glucose (100 μg / mL) to form an initiator system for a cascade enzyme initiator, and then polymerizing for 10 minutes. The resulting hydrogel dressing exhibits an elongation at break exceeding 1000% and can withstand compression exceeding 90%. Its adhesion strength (lap shear strength) exceeds 14 kPa. It exhibits significant photothermal sensitivity and shrinkage properties. The prepared hydrogel was applied to a 1.5 cm diameter perforated oral fistula model in New Zealand white rabbits. The hydrogel was able to firmly adhere to the wound surface, while exerting anti-inflammatory, antibacterial, tension-resistant, and fibrosis-reducing effects. The wound healing rate exceeded 75% within 7 days, significantly accelerating the healing process of perforated oral fistulas.

[0037] Example 2

[0038] See also Figure 1 and Figure 4 The hydrogel dressing provided in this embodiment comprises 0.5 wt% CSMA, 20 wt% N-isopropylacrylamide, 15 wt% N-[tris(hydroxymethyl)methyl]acrylamide, 1 wt% borated polyaniline, and the remainder deionized water. The preparation method comprises uniformly dispersing the above ingredients in deionized water to form a hydrogel precursor solution, and then adding glucose oxidase (30 U / mL), ferrous glycine (50 μg / mL), and glucose (50 μg / mL) to form an initiator system for the cascade enzyme initiator. The polymerization time is extended to 15 minutes. The hydrogel dressing obtained by this method exhibits an elongation at break exceeding 700% and can withstand compression exceeding 90%. It also exhibits an adhesion strength exceeding 18 kPa. It also maintains significant photothermal sensitivity and contractility. In a New Zealand white rabbit model of penetrating oral fistula, the wound healing rate exceeded 80% after 7 days, effectively accelerating wound healing.

[0039] Example 3

[0040] See also Figures 5 to 8 The hydrogel dressing provided in this embodiment comprises 3 wt% CSMA, 10 wt% N-isopropylacrylamide, 10 wt% N-[tris(hydroxymethyl)methyl]acrylamide, 0.5 wt% borated polyaniline, and the remaining mass fraction of deionized water. The preparation method comprises uniformly dispersing the above ingredients in deionized water to form a hydrogel precursor solution, and then adding a cascade enzyme initiation system consisting of glucose oxidase (50 U / mL), ferrous glycine (100 μg / mL), and glucose (100 μg / mL). The polymerization and gelation time is 10 minutes. The hydrogel dressing obtained in this embodiment exhibits an elongation at break exceeding 400% and can withstand compression exceeding 90%. It also exhibits an adhesion strength exceeding 7 kPa. It also maintains significant photothermal sensitivity and shrinkage properties. During the healing process of penetrating oral fistulas in New Zealand white rabbits, partial shedding occurred due to insufficient adhesion strength, resulting in a wound healing rate exceeding 55% after 7 days.

[0041] Example 4

[0042] See also Figure 1The hydrogel dressing provided in this embodiment comprises 1 wt% CSMA, 30 wt% N-isopropylacrylamide, 5 wt% N-[tris(hydroxymethyl)methyl]acrylamide, and the remaining wt% deionized water to form a hydrogel precursor solution. The preparation method comprises uniformly dispersing the above components in deionized water and adding an initiator system consisting of a cascade enzyme initiator consisting of glucose oxidase (50 U / mL), ferrous glycine (100 μg / mL), and glucose (100 μg / mL). The polymerization time is 10 minutes. The resulting hydrogel dressing has an elongation at break exceeding 1000% and can withstand compression exceeding 90%. Its adhesion strength (lap shear strength) exceeds 10 kPa.

[0043] Example 5

[0044] See also Figure 1 The hydrogel dressing provided in this embodiment comprises 0.1 wt% CSMA, 5 wt% N-isopropylacrylamide, 5 wt% N-[tris(hydroxymethyl)methyl]acrylamide, and 0.1 wt% borated polyaniline uniformly dispersed in deionized water to form a hydrogel precursor solution. A cascade enzyme initiator system consisting of glucose oxidase (10 U / mL), ferrous glycine (20 μg / mL), and glucose (20 μg / mL) is then added. After uniform mixing, the solution is polymerized to form the hydrogel dressing. The gelation time exceeds 1 hour. The elongation at break exceeds 1500%. The compression recovery rate is only 50%. The adhesion strength (lap shear strength) exceeds 5 kPa.

[0045] It is understandable that the hydrogel prepared by replacing acryloyl chondroitin sulfate with any one or more combinations of acryloyl hyaluronic acid, xyloglucan, chitosan, and gelatin has similar properties.

[0046] As can be seen from the above description, the hydrogel dressing and preparation method provided by the present invention can address a series of problems such as high tension, severe infection, and fibrosis at the site of perforated oral fistulas. By rationally introducing functional components, the material possesses excellent adhesion, contractility, tensile strength, and anti-inflammatory / antibacterial properties. This is of significant significance for the rapid closure and regeneration of perforated oral fistulas, effectively sealing wounds, resisting tension, reducing inflammation and fibrosis, and providing corresponding mechanical support. The excellent antioxidant properties of this hydrogel dressing can effectively reduce oxidative stress during the healing process of perforated oral fistulas and accelerate wound healing. In addition, the contractility of the hydrogel dressing promotes cell migration, proliferation, and growth at the edge of the fistula, significantly shortening the time it takes to heal the wound. This has broad application prospects and promotional value. The versatility of the hydrogel dressing makes it suitable not only for perforated oral fistulas but also has certain application potential for other fistulas (such as intestinal fistulas, anal fistulas, etc.) and high-tension wounds, demonstrating its universal applicability.

[0047] The foregoing description is merely a specific embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any modifications or substitutions that can be readily conceived by a person skilled in the art within the technical scope disclosed herein are intended to be encompassed within the scope of protection of the present invention. Therefore, the scope of protection of the present invention shall be determined by the appended claims.

Claims

1. A hydrogel dressing, characterized in that: Includes quality scores of: 0.1-3% cross-linking agent; 5-30% N-isopropylacrylamide; 5-30% N-[tris(hydroxymethyl)methyl]acrylamide; 0.1-2% borated polyaniline; The rest is deionized water; The dosage of cascade enzyme initiator is 10-200 U / mL.

2. The hydrogel dressing according to claim 1, wherein The cascade enzyme initiator comprises glucose oxidase, ferrous glycine and glucose.

3. The hydrogel dressing according to claim 1, wherein The cross-linking agent is any one or more combinations of acryloyl hyaluronic acid, xyloglucan, chitosan, chondroitin sulfate, and gelatin.

4. The hydrogel dressing according to claim 1, wherein The hydrogel dressing is used for repairing and regenerating penetrating oral fistulas.

5. A method for preparing a hydrogel dressing, characterized in that: The preparation of the hydrogel dressing according to any one of claims 1 to 3 comprises the following steps: Dispersing a crosslinker, N-isopropylacrylamide, N-[tris(hydroxymethyl)methyl]acrylamide, and borated polyaniline in deionized water to form a hydrogel precursor solution, wherein the mass fractions of the crosslinker, N-isopropylacrylamide, N-[tris(hydroxymethyl)methyl]acrylamide, and borated polyaniline are 0.1-3%, 5-30%, 5-30%, and 0.1-2%, respectively, and the remainder is deionized water; A cascade enzyme initiator is added to the hydrogel precursor solution for polymerization to obtain the hydrogel dressing, wherein the amount of the cascade enzyme initiator is 10-200 U / mL.

6. The method for preparing a hydrogel dressing according to claim 1, wherein: The time for adding the cascade enzyme to the hydrogel precursor solution for polymerization is not less than 10 minutes.

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