A Cu-MOF-based composite antibacterial hydrogel wound dressing and its preparation method

Abstract

The present invention discloses a Cu-MOF-based composite antibacterial hydrogel wound dressing and a preparation method thereof. The Cu-MOF-based composite antibacterial hydrogel wound dressing includes a hydrogel and a chlorogenic acid@Cu-MOF composite material dispersed in the hydrogel; the chlorogenic acid@Cu-MOF composite material includes chlorogenic acid and a Cu-MOF porous material in a mass ratio of 1:2 to 1:5; the hydrogel is a hydrogel with an interpenetrating network structure prepared from polyvinyl alcohol and catechol-modified hydroxypropyl chitosan. The Cu-MOF-based composite antibacterial hydrogel wound dressing of the present invention solves the problems of insufficient antibacterial property, short antibacterial action time, low adhesion strength and adverse effects on wound healing of the existing hydrogel wound dressing for infected wounds.

Description

Technical Field

[0001] The present invention relates to the technical field of medical dressings, and particularly to a Cu-MOF-based composite antibacterial hydrogel wound dressing and a preparation method thereof. Background Art

[0002] Hydrogels have good hydrophilicity, biocompatibility, and a three-dimensional (3D) porous structure similar to the extracellular matrix. As a substitute for traditional dressings such as absorbent cotton gauze and non-woven fabrics, they can provide a good healing environment for wounds and bring a comfortable use experience to patients, making them an "ideal dressing" with great application prospects. However, traditional hydrogels have many weaknesses, such as poor tensile properties, poor adhesion properties, and no antibacterial properties, which limit their application. In recent years, as the requirements for wound care have gradually increased, higher requirements have also been put forward for medical dressings. Tissue deterioration caused by bacterial infection is the most intractable problem faced during wound treatment. Therefore, antibacterial is undoubtedly the most critical and most concerned part during the wound healing process. However, for the antibacterial hydrogel dressings in the prior art, the antibacterial hydrogel dressings for infected wounds have insufficient antibacterial properties, short antibacterial action time, low adhesion strength, and are not conducive to wound healing. Commonly used antibiotics are a common method to combat bacterial infections, but the use of antibiotics has many drawbacks.

[0003] Therefore, it is very necessary to provide a safe and highly efficient antibacterial hydrogel wound dressing. Summary of the Invention

[0004] The purpose of the present invention is to solve the above problems and provide a Cu-MOF-based composite antibacterial hydrogel wound dressing and a preparation method thereof. The Cu-MOF-based composite antibacterial hydrogel wound dressing can solve the problems of insufficient antibacterial properties, short antibacterial action time, low adhesion strength, and being not conducive to wound healing of the hydrogel wound dressings in the prior art for infected wound gel dressings.

[0005] To solve the above technical problems, the technical solution adopted by the present invention is as follows:

[0006] In a first aspect, the present invention provides a Cu-MOF-based composite antibacterial hydrogel wound dressing, which comprises a hydrogel and a chlorogenic acid@Cu-MOF composite material dispersed in the hydrogel; the chlorogenic acid@Cu-MOF composite material comprises chlorogenic acid and a Cu-MOF porous material with a mass ratio of 1:2 to 1:5; the hydrogel is a hydrogel with an interpenetrating network structure prepared from polyvinyl alcohol and catechol-modified hydroxypropyl chitosan.

[0007] Optionally, by mass parts, the raw material components of the Cu-MOF-based composite antibacterial hydrogel wound dressing include 1-5 parts of catechol-modified hydroxypropyl chitosan, 10-20 parts of polyvinyl alcohol, 0.5-5 parts of chlorogenic acid@Cu-MOF composite material, and 100 parts of deionized water.

[0008] Optionally, the Cu-MOF porous material includes one or more of Cu-MOF-199, Cu-MOF-74, Cu-MOF-2, Cu2(BDC)2(BPY), Cu2(BPDC)2(DABCO), Cu2(BTC)2(BPY), or CPL-1.

[0009] Optionally, the chlorogenic acid is an extract of honeysuckle, lonicera japonica, or eucommia ulmoides.

[0010] Optionally, the preparation method of the catechol-modified hydroxypropyl chitosan specifically includes the steps of: by mass parts, dissolving 4-20 parts of hydroxypropyl chitosan and 2-4 parts of 3,4-dihydroxybenzaldehyde in 60-80 parts of methanol solution to obtain a first reaction solution; adjusting the pH of the first reaction solution to 3-4, and stirring and reacting at room temperature for 7-8 hours; then dropping 10-20 parts of a methanol solution of sodium borohydride into the first reaction solution until no bubbles are generated to obtain a second reaction solution; then filtering the second reaction solution to obtain a filter residue, and the obtained filter residue is washed and dried to obtain catechol-modified hydroxypropyl chitosan.

[0011] Optionally, when adjusting the pH of the reaction solution to 3-4, the pH regulator used includes one or more of acetic acid, sodium hydroxide, or hydrochloric acid.

[0012] In a second aspect, the present invention provides a preparation method for preparing the Cu-MOF-based composite antibacterial hydrogel wound dressing as described above, including the steps:

[0013] S1. Preparation of the chlorogenic acid@Cu-MOF composite material: Dissolve chlorogenic acid in an organic solvent, then add the Cu-MOF porous material to obtain a first mixed solution, perform ultrasonic treatment on the first mixed solution, then centrifuge, and naturally dry it after the solvent volatilizes to obtain the chlorogenic acid@Cu-MOF composite material; wherein, the concentration of chlorogenic acid dissolved in the organic solvent is 10-100 mg / mL, and the mass ratio of chlorogenic acid to the Cu-MOF porous material is 1:2 to 1:5;

[0014] S2. Preparation of Cu-MOF-based composite antibacterial hydrogel wound dressing: By mass fraction, 1-5 parts of catechol-modified hydroxypropyl chitosan, 10-20 parts of polyvinyl alcohol, and 0.5-5 parts of the chlorogenic acid@Cu-MOF composite material obtained in step S1 are respectively dispersed in 100 parts of deionized water. After mixing evenly, a second mixed solution is obtained. The obtained second mixed solution is transferred to a mold; after subjecting the mold carrying the second mixed solution to freeze-thaw cycles, the reaction product is taken out of the mold to obtain the Cu-MOF-based composite antibacterial hydrogel wound dressing.

[0015] Optionally, in step S2, the number of freeze-thaw cycles is three to five, the freezing temperature of the freeze-thaw cycle is -20 to -10 °C, the freezing time is 12-48 h, the thawing is carried out at room temperature, and the thawing time is 4-6 hours.

[0016] Optionally, the organic solvent includes one or more of ethanol, isopropanol, acetone, ethyl acetate or cyclohexane.

[0017] Optionally, in step S2, for the catechol-modified hydroxypropyl chitosan, its preparation method includes the steps: By mass fraction, 4-20 parts of hydroxypropyl chitosan and 2-4 parts of 3,4-dihydroxybenzaldehyde are dissolved in 60-80 parts of methanol solution to obtain a first reaction solution; the pH of the first reaction solution is adjusted to 3-4, and the reaction is stirred at room temperature for 7-8 hours; then 10-20 parts of a methanol solution of sodium borohydride is added dropwise to the first reaction solution until no bubbles are generated to obtain a second reaction solution; then the second reaction solution is subjected to suction filtration to obtain a filter residue, and the obtained filter residue is washed and dried to obtain the catechol-modified hydroxypropyl chitosan.

[0018] The beneficial effects produced by the present invention at least include:

[0019] In the Cu-MOF-based composite antibacterial hydrogel wound dressing of the present invention, it includes a hydrogel and chlorogenic acid@Cu-MOF composite material dispersed in the hydrogel; the chlorogenic acid@Cu-MOF composite material includes chlorogenic acid and Cu-MOF porous material; the hydrogel is a hydrogel with an interpenetrating network structure prepared from polyvinyl alcohol (PVA) and catechol-modified hydroxypropyl chitosan; chlorogenic acid can exert antibacterial activity by destroying the cell membrane structure of pathogenic bacteria, affect the signal transduction pathway by consuming reactive oxygen species in bacterial cells, and then lead to bacterial apoptosis, thereby playing its antibacterial role. At the same time, chlorogenic acid also has the ability to anti-inflammatory, promote fibroblast proliferation and migration, and promote angiogenesis in skin wounds; in the present invention, PVA and catechol-modified hydroxypropyl chitosan are used to prepare the hydrogel, and the two produce cross-linking through hydrogen bonding between hydroxyl groups to form a matrix material with an interpenetrating network structure, providing a structural basis for the dispersion of the chlorogenic acid@Cu-MOF composite material. See Figure 2 As shown, the hydrogel has a rich cross-linked pore structure; in addition, PVA has good hydrophilicity and biocompatibility, and the catechol-modified hydroxypropyl chitosan used contains polyphenol structures, endowing the hydrogel with good bonding properties and enhancing the adhesion strength, which is convenient for precise fitting on the human skin surface; by loading the antibacterial chlorogenic acid@Cu-MOF composite material in the hydrogel matrix, the hydrogel is endowed with good antibacterial properties and is beneficial to wound healing. Description of the Drawings

[0020] Figure 1 is the synthesis route diagram of the catechol-modified hydroxypropyl chitosan described in this application.

[0021] Figure 2 is the test diagram of the scanning electron microscope of the hydrogel of the present invention.

[0022] Figure 3 is the comparison diagram of the growth rate of Escherichia coli on the surface of the gel dressings in Example 1 and Comparative Example 1.

[0023] Figure 4 is the comparison diagram of the death rate of Escherichia coli on the gel dressings in Example 1 and Comparative Example 1.

[0024] Figure 5 is the comparison diagram of the adhesion of the gels in Example 1 and Comparative Example 2 on the pig skin surface and the adhesion test after sticking and peeling on the pig skin surface 5 times. Detailed Embodiments

[0025] To facilitate the understanding of the present invention, the present invention will be described more comprehensively below with reference to the relevant drawings. Preferred embodiments of the present invention are shown in the drawings. However, the present invention can be implemented in many different forms and is not limited to the embodiments described herein. On the contrary, these embodiments are provided to make the understanding of the disclosure of the present invention more thorough and comprehensive.

[0026] Unless otherwise defined, all technical and scientific terms used in the present invention have the same meaning as commonly understood by those skilled in the technical field to which the present invention belongs. The terms used in the specification of the present invention are only for the purpose of describing specific embodiments and are not intended to limit the present invention.

[0027] In the present invention, descriptions such as "first", "second", etc. are only for descriptive purposes and cannot be understood as indicating or implying their relative importance or implicitly indicating the quantity of the indicated technical features.

[0028] In a first aspect, the present invention provides a Cu-MOF-based composite antibacterial hydrogel wound dressing, which comprises a hydrogel and chlorogenic acid@Cu-MOF composite material dispersed in the hydrogel; the chlorogenic acid@Cu-MOF composite material comprises chlorogenic acid and Cu-MOF porous material with a mass ratio of 1:2 to 1:5; the hydrogel is a hydrogel with an interpenetrating network structure prepared from polyvinyl alcohol and catechol-modified hydroxypropyl chitosan.

[0029] It should be noted that the Cu-MOF porous material is an inorganic-organic framework material with copper ions as the metal ion center, and the chlorogenic acid is loaded in the pores of the porous structure inside the Cu-MOF porous material. MOF is the abbreviation of Metal Organic Frameworks, which is a class of crystalline porous materials with a periodic network structure formed by the self-assembly of inorganic metal centers (metal ions or metal clusters) and bridging organic ligands. MOF is an organic-inorganic hybrid material, also known as a coordination polymer. It is neither the same as inorganic porous materials nor general organic complexes. It has the rigid characteristics of inorganic materials and the flexible characteristics of organic materials. It has advantages such as high porosity, low density, large specific surface area, regular pore channels, adjustable pore channels, and topological structure diversity and tailoring. It should be noted that the hydrogel with an interpenetrating network structure in the present invention refers to a unique polymer gel formed by the interpenetration and entanglement of two or more polymers through networks. In the present invention, polyvinyl alcohol and catechol-modified hydroxypropyl chitosan used to prepare the hydrogel are both polymers. In the solution, due to the movement of molecular chains and the hydrogen bond interaction between them, they penetrate each other and then form a hydrogel with an interpenetrating structure.

[0030] The Cu-MOF-based composite antibacterial hydrogel wound dressing described in the present invention includes a hydrogel and a chlorogenic acid@Cu-MOF composite material dispersed in the hydrogel; the chlorogenic acid@Cu-MOF composite material includes chlorogenic acid and a Cu-MOF porous material; the hydrogel is a hydrogel with an interpenetrating network structure made of polyvinyl alcohol (PVA) and catechol-modified hydroxypropyl chitosan; chlorogenic acid can exert its antibacterial activity by destroying the cell membrane structure of pathogens, and by consuming the reactive oxygen species in bacterial cells, affecting the signal transduction pathway, thereby causing bacterial apoptosis, thereby exerting its antibacterial effect. At the same time, chlorogenic acid also has the ability to resist inflammation, promote fibroblast proliferation and migration, and promote angiogenesis in skin wounds; in the present invention, PVA and catechol-modified hydroxypropyl chitosan are used to prepare the hydrogel, and the two are cross-linked through hydrogen bonding between hydroxyl groups to form a matrix material with an interpenetrating network structure, providing a structural basis for the dispersion of the chlorogenic acid@Cu-MOF composite material, see Figure 2 As shown, the hydrogel has a rich cross-linked pore structure; in addition, PVA has good hydrophilicity and biocompatibility, and the catechol-modified hydroxypropyl chitosan contains a polyphenol structure, which gives the hydrogel good bonding properties and improves the adhesion strength, facilitating precise fitting on the surface of human skin; the chlorogenic acid@Cu-MOF composite material with antibacterial properties is loaded in the hydrogel matrix, giving the hydrogel good antibacterial properties and facilitating wound healing.

[0031] Optionally, the raw material components of the Cu-MOF-based composite antibacterial hydrogel wound dressing include, by mass, 1-5 parts of catechol-modified hydroxypropyl chitosan (CHCS), 10-20 parts of polyvinyl alcohol (PVA), 0.5-5 parts of chlorogenic acid@Cu-MOF composite material, and 100 parts of deionized water.

[0032] Specifically, for example, the mass fraction of the catechol-modified hydroxypropyl chitosan (CHCS) can be 1 part, 2 parts, 3 parts, 4 parts or 5 parts, the mass fraction of the polyvinyl alcohol can be 10 parts, 11 parts, 12 parts, 13 parts, 14 parts, 15 parts, 16 parts, 17 parts, 18 parts, 19 parts or 20 parts, and the mass fraction of the chlorogenic acid@Cu-MOF composite material can be 0.5 parts, 1 part, 1.5 parts, 2 parts, 2.5 parts, 3 parts, 3.5 parts, 4 parts, 4.5 parts or 5 parts.

[0033] Optionally, the Cu-MOF porous material includes one or more of Cu-MOF-199, Cu-MOF-74, Cu-MOF-2, Cu2(BDC)2(BPY), Cu2(BPDC)2(DABCO), Cu2(BTC)2(BPY) or CPL-1.

[0034] Optionally, in some embodiments, the chlorogenic acid is an extract of honeysuckle, Lonicera japonica or Eucommia ulmoides. Loading the chlorogenic acid antibacterial drug into the Cu-MOF porous material endows the finally prepared Cu-MOF-based composite antibacterial hydrogel wound dressing with excellent and sustained antibacterial and wound-healing properties. Compared with traditional antibiotics, it has fewer adverse reactions, higher safety, lower raw material cost and is easier to obtain. Preferably, the chlorogenic acid is derived from honeysuckle, which is extracted from natural plants, further improving the safety performance of the Cu-MOF-based composite antibacterial hydrogel wound dressing. In other embodiments, the chlorogenic acid can also be sourced from known suppliers in the art or prepared by well-known methods.

[0035] Specifically, Figure 1 is the synthesis route diagram of the catechol-modified hydroxypropyl chitosan. The preparation method of the catechol-modified hydroxypropyl chitosan specifically includes the steps of: dissolving 4-20 parts of hydroxypropyl chitosan and 2-4 parts of 3,4-dihydroxybenzaldehyde in 60-80 parts of a methanol solution (methanol: water = 1:2); adjusting the pH of the reaction solution to 3-4 and stirring the reaction at room temperature for 7 hours; slowly dropping 10-20 parts of a methanol solution of sodium borohydride into the above reaction solution until no bubbles are generated; then filtering the reaction solution, and washing and drying the obtained filter residue to obtain catechol-modified hydroxypropyl chitosan (CHCS). Among them, the methanol solution of sodium borohydride is prepared by adding sodium borohydride to a methanol solution, wherein the concentration of sodium borohydride is 0.15 g / mL, and the addition ratio of methanol to water in the methanol solution is 1:1.

[0036] Optionally, when adjusting the pH of the reaction solution to 3-4, the pH regulator used includes one or more of acetic acid, sodium hydroxide or hydrochloric acid.

[0037] Another object of the present invention is to provide a preparation method of a Cu-MOF-based composite antibacterial hydrogel wound dressing for preparing the Cu-MOF-based composite antibacterial hydrogel wound dressing as described above, including the steps of:

[0038] S1. Preparation of chlorogenic acid@Cu-MOF composite material: Dissolve chlorogenic acid in an organic solvent, then add Cu-MOF porous material to obtain a first mixed solution. Ultrasonically treat the first mixed solution, then centrifuge it, and let it air-dry naturally after the solvent evaporates to obtain a Cu-MOF porous material loaded with chlorogenic acid, which is the chlorogenic acid@Cu-MOF composite material; wherein, the concentration of chlorogenic acid dissolved in the organic solvent is 10-100 mg / mL, and the mass ratio of chlorogenic acid to Cu-MOF porous material is 1:2 to 1:5;

[0039] S2. Preparation of Cu-MOF-based composite antibacterial hydrogel wound dressing: By mass, 1-5 parts of catechol-modified hydroxypropyl chitosan, 10-20 parts of polyvinyl alcohol (PVA), and 0.5-5 parts of the chlorogenic acid@Cu-MOF composite material obtained in step S1 are respectively dispersed in 100 parts of deionized water. After mixing evenly, a second mixed solution is obtained. The obtained second mixed solution is transferred to a mold; after the mold carrying the second mixed solution undergoes freeze-thaw cycles, the reaction product is taken out of the mold to obtain the Cu-MOF-based composite antibacterial hydrogel wound dressing.

[0040] In the present invention, a Cu-MOF porous material with a porous structure is used as a carrier to load chlorogenic acid with bactericidal and wound-healing promoting properties. Then, the Cu-MOF porous material loaded with chlorogenic acid is dispersed in a hydrogel to obtain a Cu-MOF-based composite antibacterial hydrogel wound dressing with intelligent response, which has good antibacterial properties, a long antibacterial action time, a good binding force with the wound, and promotes wound healing. In the preparation method of the present invention, polyvinyl alcohol and catechol-modified hydroxypropyl chitosan are used to prepare the hydrogel. Polyvinyl alcohol has good hydrophilicity and biocompatibility. Through freeze-thaw cycles of freezing and thawing, polyvinyl alcohol forms crystals, which improves the crosslinking strength between it and catechol-modified hydroxypropyl chitosan, and further improves the mechanical properties of the hydrogel matrix; the selection of catechol-modified hydroxypropyl chitosan introduces catechol groups into the obtained wound dressing, improves the adhesion performance of the obtained wound dressing, can closely combine with wound tissues, avoids biological contact between the wound and bacteria and other microorganisms in the air, and promotes the rapid healing of the wound.

[0041] Among them, the number of cycles of the freeze-thaw cycle is three to five times. The freezing temperature of the freeze-thaw cycle is -20 to -10 °C, the freezing time is 12-48 h, the thawing is carried out at room temperature, and the thawing time is 4-6 hours.

[0042] Optionally, the organic solvent includes one or more of ethanol, isopropanol, acetone, ethyl acetate, or cyclohexane.

[0043] See Figure 1As shown in the figure, specifically, the preparation method of the catechol-modified hydroxypropyl chitosan includes the steps: by mass fraction, dissolving 4-20 parts of hydroxypropyl chitosan and 2-4 parts of 3,4-dihydroxybenzaldehyde in 60-80 parts of methanol solution to obtain a first reaction solution; wherein, the ratio of the added parts of methanol to water in the solution is 1:2; adjusting the pH of the first reaction solution to 3-4, and stirring and reacting at room temperature for 7-8 hours; then dropping 10-20 parts of a methanol solution of sodium borohydride into the first reaction solution until no bubbles are generated to obtain a second reaction solution; then filtering the second reaction solution to obtain a filter residue, and the obtained filter residue is washed and dried to obtain catechol-modified hydroxypropyl chitosan (CHCS).

[0044] Example 1:

[0045] Preparation of catechol-modified hydroxypropyl chitosan (CHCS):

[0046] Dissolve 6 parts of hydroxypropyl chitosan and 3 parts of 3,4-dihydroxybenzaldehyde in 60 parts of methanol solution (methanol: water = 1:2). Dropwise add acetic acid to adjust the pH of the reaction solution to about 3-4, and stir and react at room temperature for 7 hours. Slowly drop 15 parts of a methanol solution of sodium borohydride (concentration 0.15 g / ml) (methanol: water = 1:1) into the above reaction solution until no bubbles are generated. Filter the above reaction solution, and the obtained filter residue is washed and dried to obtain catechol-modified hydroxypropyl chitosan (CHCS).

[0047] Preparation of chlorogenic acid@Cu-MOF composite material: Dissolve chlorogenic acid in an organic solvent, then add Cu-MOF porous material to obtain a first mixed solution, perform ultrasonic treatment on the first mixed solution for 30 min, then centrifuge, and naturally dry it after the solvent volatilizes to obtain chlorogenic acid@Cu-MOF composite material; wherein, the Cu-MOF porous material is selected as Cu-MOF-199, the concentration of chlorogenic acid dissolved in the organic solvent is 80 mg / mL, and the mass ratio of chlorogenic acid to Cu-MOF porous material is 1:3;

[0048] Preparation of Cu-MOF-based composite antibacterial hydrogel wound dressing:

[0049] Dissolve 3 parts of the catechol-modified hydroxypropyl chitosan (CHCS) prepared in Example a, 15 parts of polyvinyl alcohol (PVA), and 0.25 parts of chlorogenic acid (CA) in 100 parts of deionized water, mix evenly and transfer to a mold. Place the mold at -20 °C and freeze for 20 hours, then thaw at room temperature for 4 hours, repeat three times, and take it out of the mold to obtain an antibacterial and wound-healing promoting hydrogel wound dressing.

[0050] Example 2:

[0051] Preparation of catechol-modified hydroxypropyl chitosan (CHCS):

[0052] Dissolve 9 parts of hydroxypropyl chitosan and 3 parts of 3,4-dihydroxybenzaldehyde in 60 - 80 parts of methanol solution (methanol:water = 1:2). Dropwise add acetic acid to adjust the pH of the reaction solution to about 3 - 4, and stir the reaction at room temperature for 7 hours. Slowly dropwise add 16 parts of sodium borohydride (concentration 0.15 g / ml) methanol solution (methanol:water = 1:1) to the above reaction solution until no bubbles are generated. Filter the above reaction solution by suction, and the obtained filter residue is washed and dried to obtain catechol-modified hydroxypropyl chitosan (CHCS).

[0053] Preparation of chlorogenic acid@Cu-MOF composite material:

[0054] Dissolve chlorogenic acid in an organic solvent, then add Cu-MOF porous material to obtain a first mixed solution. Ultrasonically treat the first mixed solution for 30 min, then centrifuge it. After the solvent volatilizes, let it dry naturally to obtain chlorogenic acid@Cu-MOF composite material; wherein, the Cu-MOF porous material is selected as Cu-MOF-199, the concentration of chlorogenic acid dissolved in the organic solvent is 90 mg / mL, and the mass ratio of chlorogenic acid to Cu-MOF porous material is 1:4.

[0055] Preparation of Cu-MOF-based composite antibacterial hydrogel wound dressing:

[0056] Dissolve 2 parts of catechol-modified hydroxypropyl chitosan (CHCS) obtained in this example, 18 parts of polyvinyl alcohol (PVA), and 0.2 part of chlorogenic acid (CA) in 100 parts of deionized water. After mixing evenly, transfer it to a mold. Place the mold at -20 °C and freeze it for 20 hours, then thaw it at room temperature for 4 hours, repeat three times, and take it out of the mold to obtain a hydrogel wound dressing with antibacterial and wound-healing promotion properties.

[0057] Example 3:

[0058] Preparation of catechol-modified hydroxypropyl chitosan (CHCS):

[0059] Dissolve 10 parts of hydroxypropyl chitosan and 2.5 parts of 3,4-dihydroxybenzaldehyde in 60 - 80 parts of methanol solution (methanol:water = 1:2). Dropwise add acetic acid to adjust the pH of the reaction solution to about 3 - 4, and stir the reaction at room temperature for 7 hours. Slowly dropwise add 13 parts of sodium borohydride (concentration 0.15 g / ml) methanol solution (methanol:water = 1:1) to the above reaction solution until no bubbles are generated. Filter the above reaction solution by suction, and the obtained filter residue is washed and dried to obtain catechol-modified hydroxypropyl chitosan (CHCS).

[0060] Preparation of Chlorogenic Acid@Cu-MOF Composite Material:

[0061] Dissolve chlorogenic acid in an organic solvent, then add Cu-MOF porous material to obtain a first mixed solution. Ultrasonically treat the first mixed solution for 30 min, then centrifuge. After the solvent volatilizes, air-dry naturally to obtain the chlorogenic acid@Cu-MOF composite material; wherein, the Cu-MOF porous material is selected as Cu-MOF-199, the concentration of chlorogenic acid dissolved in the organic solvent is 90 mg / mL, and the mass ratio of chlorogenic acid to Cu-MOF porous material is 1:5.

[0062] Preparation of Cu-MOF-based Composite Antibacterial Hydrogel Wound Dressing:

[0063] Dissolve 4 parts of the catechol-modified hydroxypropyl chitosan (CHCS) prepared in this example, 14 parts of polyvinyl alcohol (PVA), and 0.4 part of chlorogenic acid (CA) in 100 parts of deionized water. After mixing evenly, transfer to a mold. Place the mold at -20 °C for 20 hours, then thaw at room temperature for 4 hours, repeat three times, and take out from the mold to obtain the hydrogel wound dressing with antibacterial and wound-healing promotion properties.

[0064] Comparative Example 1:

[0065] Preparation of Hydrogel Wound Dressing without Antibacterial Effect:

[0066] Dissolve 3 parts of the catechol-modified hydroxypropyl chitosan (CHCS) prepared in Example 1 and 15 parts of polyvinyl alcohol (PVA) in 100 parts of deionized water. After mixing evenly, transfer to a mold. Place the mold at -20 °C for 20 hours, then thaw at room temperature for 4 hours, repeat three times, and take out from the mold to obtain the hydrogel wound dressing without antibacterial effect.

[0067] Comparative Example 2:

[0068] Preparation of Hydrogel Wound Dressing without Adhesion Function:

[0069] Dissolve 18 parts of polyvinyl alcohol (PVA) and 0.25 part of the chlorogenic acid@Cu-MOF composite material prepared in Example 1 in 100 parts of deionized water. After mixing evenly, transfer to a mold. Place the mold at -20 °C for 20 hours, then thaw at room temperature for 4 hours, repeat three times, and take out from the mold to obtain the hydrogel wound dressing with no adhesion function.

[0070] Test Example:

[0071] Using Escherichia coli as the test object, under the same test conditions, the antibacterial performance tests were respectively carried out on the wound dressings obtained in Example 1 and Comparative Example 1. SeeFigure 3 As shown, with the prolongation of the cultivation time, the number of cells per unit area of Escherichia coli on the wound dressing obtained in Example 1 slightly increased, but overall it was less than the number of cells per unit area on the wound dressing of Comparative Example 1. The growth rate of Escherichia coli on the wound dressing obtained in Example 1 was less than the growth rate of Escherichia coli on the gel dressing surface of Comparative Example 1. See Figure 4 As shown, overall, the bacterial death rate in the wound dressing of Example 1 was higher than that in the wound dressing of Comparative Example 1. It shows that the Cu-MOF-based composite antibacterial hydrogel wound dressing obtained in the present invention has better antibacterial performance and the ability to promote wound healing.

[0072] The wound dressing obtained in Example 1 and the wound dressing obtained in Comparative Example 2 were respectively covered on the surface of pig skin. After 1-5 paste-peel cycles, the adhesion between the wound dressing obtained in Example 1 and the wound dressing obtained in Comparative Example 2 and the surface of pig skin was tested. See Figure 5 As shown, at the first paste, the adhesion between the wound dressing obtained in Example 1 and the surface of pig skin was greater than the adhesion between the wound dressing obtained in Comparative Example 2 and pig skin; after 5 paste-peel cycle tests, the adhesion between the wound dressing obtained in Example 1 and the surface of pig skin was still greater than the adhesion between the wound dressing obtained in Comparative Example 2 and pig skin. It shows that the Cu-MOF-based composite antibacterial hydrogel wound dressing obtained in the present invention has good biocompatibility and good adhesion strength to the skin.

[0073] The technical features of the above embodiments can be combined arbitrarily. For the sake of brevity of description, not all possible combinations of the technical features in the above embodiments are described. However, as long as there is no contradiction in the combination of these technical features, it should be considered as the scope recorded in this specification.

[0074] The above embodiments only represent the preferred embodiments of the present invention, and the description is relatively specific and detailed, but it should not be understood as a limitation to the scope of the invention patent. It should be noted that for those of ordinary skill in the art, without departing from the concept of the present invention, several modifications and improvements can still be made, and these all belong to the protection scope of the present invention. Therefore, the protection scope of the invention patent should be subject to the appended claims.

Claims

1. Application of a Cu-MOF based composite antibacterial hydrogel for wound dressings, characterized in that, The preparation method of the Cu-MOF-based composite antibacterial hydrogel wound dressing includes the steps: S1. Preparation of chlorogenic acid@Cu-MOF composite material: Dissolve chlorogenic acid in an organic solvent, then add Cu-MOF porous material to obtain a first mixed solution. Ultrasonically treat the first mixed solution, then centrifuge it. After the solvent volatilizes, air-dry it naturally to obtain the chlorogenic acid@Cu-MOF composite material. Among them, the concentration of chlorogenic acid dissolved in the organic solvent is 10-100 mg / mL, and the mass ratio of chlorogenic acid to Cu-MOF porous material is 1:2 to 1:

5. S2. Preparation of the Cu-MOF-based composite antibacterial hydrogel wound dressing: By mass, disperse 1-5 parts of catechol-modified hydroxypropyl chitosan, 10-20 parts of polyvinyl alcohol, and 0.5-5 parts of the chlorogenic acid@Cu-MOF composite material obtained in step S1 in 100 parts of deionized water respectively. After mixing evenly, obtain a second mixed solution, and transfer the obtained second mixed solution to a mold. After subjecting the mold containing the second mixed solution to freeze-thaw cycles, take out the reaction product from the mold to obtain the Cu-MOF-based composite antibacterial hydrogel wound dressing. In step S2, for the preparation method of the catechol-modified hydroxypropyl chitosan, the steps include: By mass, dissolve 4-20 parts of hydroxypropyl chitosan and 2-4 parts of 3,4-dihydroxybenzaldehyde in 60-80 parts of methanol solution to obtain a first reaction solution. Adjust the pH of the first reaction solution to 3-4, and stir and react at room temperature for 7-8 hours. Then, dropwise add 10-20 parts of a methanol solution of sodium borohydride to the first reaction solution until no bubbles are generated to obtain a second reaction solution. Then, perform suction filtration on the second reaction solution to obtain a filter residue. After washing and drying the obtained filter residue, the catechol-modified hydroxypropyl chitosan is obtained.

2. The application according to claim 1, characterized in that, In step S2, the number of freeze-thaw cycles is three to five times. The freezing temperature of the freeze-thaw cycle is -20 to -10 °C, the freezing time is 12-48 h, the thawing is carried out at room temperature, and the thawing time is 4-6 hours.

3. The application according to claim 1, wherein The organic solvent includes one or more of ethanol, isopropanol, acetone, ethyl acetate, or cyclohexane.

4. The application according to claim 1, characterized in that, The Cu-MOF porous material includes one or more of Cu-MOF-199, Cu-MOF-74, Cu-MOF-2, Cu2(BDC)2(BPY), Cu2(BPDC)2(DABCO), Cu2(BTC)2(BPY), or CPL-1.

5. The application according to claim 1, wherein The chlorogenic acid is an extract of honeysuckle, lonicera japonica, or eucommia ulmoides.

6. The application according to claim 1, wherein When adjusting the pH of the reaction solution to 3-4, the pH regulator used includes one or more of acetic acid, sodium hydroxide, or hydrochloric acid.

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