CN115068674A - Functional hydrogel dressing and preparation method thereof - Google Patents
Functional hydrogel dressing and preparation method thereof Download PDFInfo
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- CN115068674A CN115068674A CN202210801915.7A CN202210801915A CN115068674A CN 115068674 A CN115068674 A CN 115068674A CN 202210801915 A CN202210801915 A CN 202210801915A CN 115068674 A CN115068674 A CN 115068674A
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- A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
- A61L26/0061—Use of materials characterised by their function or physical properties
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- A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
- A61L26/0009—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing macromolecular materials
- A61L26/0023—Polysaccharides
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- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
- A61L2300/216—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials with other specific functional groups, e.g. aldehydes, ketones, phenols, quaternary phosphonium groups
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Abstract
The invention relates to the field of biomedicine, and provides a functional hydrogel dressing and a preparation method thereof. A method of making a functional hydrogel dressing comprising: uniformly mixing a chitosan substance solution, a curcumin solution and an oxidized sodium alginate solution to form hydrogel, wherein the chitosan substance is at least one selected from chitosan and chitosan derivatives. A functional hydrogel dressing prepared by the method of any one of the preceding embodiments. The functional hydrogel dressing provided by the application has the effect of remarkably promoting wound healing.
Description
Technical Field
The invention relates to the technical field of biomedicine, in particular to a functional hydrogel dressing and a preparation method thereof.
Background
The hydrogel contains a large amount of water, is swollen but not dissolved after absorbing water, can absorb wound exudate when being used for the wound dressing, plays a role in autolysis debridement, can isolate external bacteria, can play a role in moisturizing, provides a moist healing microenvironment, and promotes wound healing. Patent CN110151681A discloses a preparation method of curcumin hydrogel microspheres based on nanoemulsion, which does not mention the application field and effect of the hydrogel microspheres, the curcumin hydrogel microspheres of the nanoemulsion successfully load curcumin into hydrogel, but the preparation process of the hydrogel microspheres is complex, the requirements on the emulsification condition of curcumin emulsion and the condition of mixing curcumin emulsion and ammonium alginate are high, and the temperature, stirring speed and other process parameters which play an important role in hydrogel microsphere formation need to be controlled in the preparation process. Patent CN113057177A discloses a preparation method of a nano-modified titanium dioxide-chitosan-curcumin antibacterial compound, which introduces curcumin to enhance the antibacterial activity of a high molecular material prepared from chitosan, but the preparation method uses an antibacterial compound obtained by crosslinking chitosan with glutaraldehyde with cytotoxicity, so that the application of the antibacterial compound in the biomedical field is limited. Patent CN113813443A discloses a preparation method of a dextran-based hydrogel dressing loaded with curcumin, which loads curcumin microparticles to achieve the expectation of slow release of curcumin, but the preparation process of the hydrogel dressing involves more raw material modification and complicated steps, thus seriously limiting the popularization and application of the hydrogel dressing.
Most of the existing biomedical dressings are traditional chemically crosslinked hydrogel or functional substances added in other high molecular material polymers, the existing technology adopts a complicated chemical treatment method, the preparation process flow is not only complicated and not easy to operate, but also the bioactivity of the functional substances is greatly reduced, the biological safety of the biomedical dressings is also greatly reduced, and therefore the use effect of the biomedical dressings is influenced, and the popularization and the application of the biomedical dressings are limited. For example, curcumin-loaded biological dressings mostly adopt a fussy chemical treatment method to prepare curcumin into curcumin micelles or curcumin microspheres and the like, and then add the curcumin micelles or curcumin microspheres into a biological dressing base material, and the process solves the problems that the operation steps are fussy, the flow is complex, the biological activity of curcumin is seriously influenced, and the bioavailability of curcumin is reduced.
In view of this, the invention is particularly proposed.
Disclosure of Invention
The invention aims to provide a functional hydrogel dressing and a preparation method thereof.
The invention is realized by the following steps:
in a first aspect, the present invention provides a method for preparing a functional hydrogel dressing, comprising:
uniformly mixing a chitosan substance solution, a curcumin solution and an oxidized sodium alginate solution to form hydrogel, wherein the chitosan substance is selected from at least one of chitosan and chitosan derivatives.
In an optional embodiment, the chitosan solution and the curcumin solution are uniformly mixed to obtain a mixed solution, and then the oxidized sodium alginate solution and the mixed solution are uniformly mixed to form the hydrogel.
In an optional embodiment, the manner of uniformly mixing the oxidized sodium alginate solution and the mixed solution is as follows:
and dropwise adding the oxidized sodium alginate solution into the mixed solution.
In an alternative embodiment, the curcumin solution is obtained by dissolving curcumin in an organic solvent;
preferably, the organic solvent is an alcohol;
preferably, the organic solvent is propylene glycol.
In an optional embodiment, the molar ratio of the chitosan substance to the sodium alginate oxide is 2-10: 1;
preferably, the molar ratio of the curcumin to the sodium alginate oxide is 0.01-0.1: 1.
In an optional embodiment, the mass concentration of the chitosan substance solution is 1.5-5%, the mass concentration of the oxidized sodium alginate is 10-20%, and the mass concentration of the curcumin solution is 8-12%.
In an optional embodiment, the volume ratio of the chitosan substance solution to the curcumin solution is 10-50: 1, and the volume ratio of the mixed solution to the oxidized sodium alginate solution is 4-10: 1.
In an alternative embodiment, the derivative of chitosan comprises at least one of carboxymethyl chitosan, hydroxypropyl chitosan, and chitosan quaternary ammonium salt.
In a second aspect, the present invention provides a functional hydrogel dressing prepared by the method according to any one of the preceding embodiments.
The invention has the following beneficial effects:
(1) the hydrogel preparation process is simple and mild, does not need an intermediate chemical reaction treatment process, and can form gel only by preparing a plurality of raw materials into a solution with a proper concentration and mixing the solution according to a proper proportion.
(2) The hydrogel is formed in situ, is suitable for wound surfaces with complex shapes, and has obvious advantages for burn, ulcer and laser postoperative repair treatment.
(3) The hydrogel is formed by amide bonds and intermolecular hydrogen bonds, toxic micromolecular cross-linking agents and initiators are not needed to be added in the gel forming process, and the biological safety of the obtained hydrogel is high.
(4) The hydrogel system of the invention is introduced with the micromolecule substance curcumin with the functions of anti-inflammation, antioxidation, antibacterial, antifungal, antiulcer and the like, thereby enhancing the efficacy of the polysaccharide-based hydrogel.
(5) The functional micromolecule substance curcumin introduced by the hydrogel disclosed by the invention forms hydrogen bonds with chitosan substances and oxidized sodium alginate molecules, and the functional micromolecules participate in the formation of the gel, are not simply doped, are not easy to fall off, cannot be released suddenly in the using process, play a role of slowly releasing, improve the utilization rate and achieve the best effect of promoting wound repair.
(6) The hydrogel disclosed by the invention has multiple functions of resisting inflammation, resisting oxidation, inhibiting bacteria, resisting ulcer and the like, has a good effect of promoting wound repair, and can be used in the field of wound repair treatment.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings needed to be used in the embodiments will be briefly described below, it should be understood that the following drawings only illustrate some embodiments of the present invention and therefore should not be considered as limiting the scope, and for those skilled in the art, other related drawings can be obtained according to the drawings without inventive efforts.
FIG. 1 is a graph showing the results of verification of cytotoxic staining in Experimental example 1;
FIG. 2 is a graph showing the results of experiments in Experimental example 2 for verifying the presence or absence of hemolytic reaction of hydrogel;
fig. 3 is a diagram of the results of animal wound experiments in experimental example 3, which proves that hydrogel promotes wound healing.
Detailed Description
In order to make the objects, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below. The examples, in which specific conditions are not specified, were conducted under conventional conditions or conditions recommended by the manufacturer. The reagents or instruments used are conventional products which are not indicated by manufacturers and are commercially available.
The functional hydrogel dressing and the preparation method thereof provided in the examples of the present application are described in detail below.
The embodiment of the application provides a preparation method of a functional hydrogel dressing, which comprises the following steps:
uniformly mixing a chitosan substance solution, a curcumin solution and an oxidized sodium alginate solution to form hydrogel, wherein the chitosan substance is at least one selected from chitosan and chitosan derivatives.
According to the method provided by the invention, the raw materials are dissolved in the solvent at normal temperature and normal pressure to form the solution, and the in-situ hydrogel loaded with curcumin can be quickly formed only by mixing a plurality of solutions according to a designed proportion, so that the bioactivity effect of the curcumin is maximally exerted. The curcumin is introduced into the method, not only because the curcumin has the effects of resisting bacteria, promoting vascularization and the like, but also most importantly, hydrogen bonds are formed among the curcumin, chitosan substances and ammonium alginate oxide molecules, and the curcumin can stabilize the three-dimensional network structure of the hydrogel. The method can prepare blocky hydrogel with a determined shape and hydrogel with an indefinite shape by adjusting the concentration and the mixing ratio of the solutions, can be applied to the wound surface with a regular shape, and has more obvious advantages when being applied to the wound surface with an irregular shape or a cave type wound surface. The hydrogel dressing provided by the invention is used for the wound surface, has the isolation barrier effect of the traditional dressing, provides a moist microenvironment beneficial to wound surface tissue healing, has the anti-inflammatory, antibacterial and vascularization promoting effects, and is a novel functional wound surface dressing.
The preparation method provided by the application has the following advantages:
(1) the hydrogel preparation process is simple and mild, does not need an intermediate chemical reaction treatment process, and can be formed by preparing a plurality of raw materials into a solution with appropriate concentration and mixing the solution according to an appropriate proportion.
(2) The hydrogel is formed in situ, is suitable for wound surfaces with complex shapes, and has obvious advantages for postoperative repair treatment of burns, ulcers and lasers.
(3) The hydrogel is formed by amide bond and intermolecular hydrogen bond, toxic micromolecular cross-linking agents and initiators are not needed to be added in the forming process, and the biological safety of the obtained hydrogel is high.
(4) The hydrogel system of the invention introduces micromolecular substance curcumin with anti-inflammatory, antioxidant, antibacterial, antifungal, antiulcer and other functions, and enhances the efficacy of the polysaccharide-based hydrogel.
(5) The functional micromolecule substance curcumin introduced by the hydrogel disclosed by the invention forms hydrogen bonds with chitosan substances and oxidized sodium alginate molecules, and the functional micromolecules participate in the formation of the gel, are not simply doped, are not easy to fall off, cannot be released suddenly in the using process, play a role of slowly releasing, improve the utilization rate and achieve the best effect of promoting wound repair.
(6) The hydrogel disclosed by the invention has multiple functions of resisting inflammation, resisting oxidation, inhibiting bacteria, resisting ulcer and the like, has a good effect of promoting wound repair, and can be used in the field of wound repair treatment.
Preferably, in order to ensure sufficient crosslinking to obtain hydrogel with stable performance, the dosage ratio of the chitosan substance to the oxidized sodium alginate is 2-10: 1 (such as 2:1, 4:1, 6:1, 8:1 or 10: 1).
Preferably, in order to obtain a dressing with a better wound healing promoting effect, the dosage ratio of the curcumin to the sodium alginate oxide is 0.01-0.1: 1(0.01:1, 0.05:1 or 0.1: 1).
The preparation method of the functional hydrogel dressing provided in the examples of the present application is further described below:
s1 preparation of solution
Dissolving chitosan in solvent such as glacial acetic acid or hydrochloric acid, deionized water, etc. to obtain solution with mass concentration of 1.5-5%.
The chitosan material is at least one of chitosan and chitosan derivative; the chitosan derivative includes but is not limited to at least one of carboxymethyl chitosan, hydroxypropyl chitosan, chitosan quaternary ammonium salt and other polysaccharides.
Curcumin is dissolved in an organic solvent to prepare a curcumin solution with the mass concentration of 8-12% (such as 8%, 10% or 12%).
Preferably, the curcumin is dissolved, the adopted organic solvent does not influence the hydrogel system and has no adverse effect on wound healing, and the organic solvent for dissolving the curcumin is alcohol; further, the alcohol is propylene glycol.
The oxidized sodium alginate is prepared into a solution with the mass concentration of 10-20% (such as 10%, 15% or 20%) in deionized water for later use.
S2, solution mixing reaction
And mixing the three solutions prepared in the step S1 for reaction.
Preferably, the specific operations for ensuring that hydrogel with good stability can be obtained and that curcumin can be doped more uniformly are as follows:
uniformly mixing the solution of the chitosan substances and the curcumin solution to obtain a mixed solution, and uniformly mixing the oxidized sodium alginate solution and the mixed solution to form the hydrogel.
Preferably, in order to ensure that the hydrogel dressing with good performance can be further obtained, the oxidized sodium alginate solution is added into the mixed solution in a dropwise adding mode, and the reaction container is vibrated in the dropwise adding process of the oxidized sodium alginate so that the oxidized sodium alginate and the chitosan or the derivative of the chitosan are fully crosslinked.
Furthermore, the volume ratio of the chitosan substance solution to the curcumin solution is 10-50: 1, and the volume ratio of the mixed solution to the oxidized sodium alginate solution is 4-10: 1.
The embodiment of the application also provides a functional hydrogel dressing which is prepared by adopting the preparation method provided by the application. The functional hydrogel dressing is suitable for wound surface with complex shape, and has good effect for postoperative rehabilitation of burn, ulcer and laser.
The features and properties of the present invention are described in further detail below with reference to examples.
Example 1
Weighing a certain mass of oxidized sodium alginate, and dissolving the oxidized sodium alginate in deionized water to prepare an oxidized sodium alginate solution with a mass concentration of 15% for later use; weighing chitosan with a certain mass, dissolving the chitosan in glacial acetic acid to prepare a chitosan solution with the mass concentration of 2% for later use; then weighing a certain mass of curcumin, and dissolving the curcumin in propylene glycol to prepare a 10% curcumin solution. Respectively weighing chitosan solution and curcumin solution, mixing the chitosan solution and curcumin solution according to the volume ratio of 50:1 to form uniform mixed solution, dripping oxidized sodium alginate solution into the mixed solution according to the volume ratio of 4:1, shaking and mixing the solution uniformly to form hydrogel within 10 seconds. According to characterization tests, the hydrogel has no cytotoxicity, the hemolysis rate is 1.51%, and no hemolysis reaction exists.
Example 2
Weighing a certain mass of oxidized sodium alginate, and dissolving the oxidized sodium alginate in deionized water to prepare an oxidized sodium alginate solution with the mass concentration of 10% for later use; weighing a certain mass of carboxymethyl chitosan, dissolving in deionized water to prepare a carboxymethyl chitosan solution with the mass concentration of 3% for later use; then weighing a certain mass of curcumin, and dissolving the curcumin in propylene glycol to prepare a 10% curcumin solution. Respectively weighing carboxymethyl chitosan solution and curcumin solution, mixing according to the volume ratio of 20:1 to form uniform mixed solution, dripping oxidized sodium alginate solution into the mixed solution according to the volume ratio of 8:1, shaking and mixing uniformly to form hydrogel in 30 s. According to characterization tests, the hydrogel has no cytotoxicity, the hemolysis rate is 1.63%, and no hemolysis reaction exists.
Example 3
Weighing a certain mass of oxidized sodium alginate, and dissolving the oxidized sodium alginate in deionized water to prepare an oxidized sodium alginate solution with the mass concentration of 20% for later use; weighing a certain mass of chitosan quaternary ammonium salt, dissolving in deionized water to prepare a chitosan quaternary ammonium salt solution with the mass concentration of 5% for later use; then weighing a certain mass of curcumin, and dissolving the curcumin in propylene glycol to prepare a 10% curcumin solution. Respectively weighing chitosan quaternary ammonium salt solution and curcumin solution, mixing according to the volume ratio of 10:1 to form uniform mixed solution, then dripping sodium alginate oxide solution into the mixed solution according to the volume ratio of 10:1, shaking and mixing uniformly to form hydrogel in 60 s. The hydrogel has no cytotoxicity, the hemolytic rate is 1.87% and no hemolytic reaction through characterization tests.
Comparative example 1
This comparative example is essentially the same as example 1, except that: preparing curcumin into curcumin microspheres; mixing the curcumin microspheres with the chitosan solution and the oxidized sodium alginate according to the mass ratio of the chitosan to the curcumin of 10: 1.
Comparative example 2
This comparative example is substantially the same as comparative example 1 except that: the curcumin microspheres are replaced by curcumin micelles.
Experimental example 1
The hydrogel prepared in example 1 was used as an experimental group, and no other material was added as a negative control group. The experimental group and the negative control group are respectively cultured with the cells for 3 days under the same experimental conditions, and the survival condition of the cells is observed under a fluorescence microscope after staining. As shown in fig. 1.
From FIG. 1, it can be seen that the number of cells after 3 days of co-culture of the gel of the present invention and the cells was not significantly different from that of the control group, indicating that the gel of the present invention was not cytotoxic.
Experimental example 2
The hydrogel prepared in example 1 was used as an experimental group, a neutral phosphate buffer solution was used as a negative control group, and deionized water was used as a positive control group to perform a hemolysis experiment. The results of the experiment are shown in FIG. 2.
As can be seen from FIG. 2, the results of the blood-lysing test showed that the gel of the present invention had the same hemolysis as that of the negative control group, indicating that the gel of the present invention had no hemolysis reaction.
Experimental example 3
Animal skin wound repair test, the wound of a rat treated with the hydrogel prepared in example 1 of the present application was used as an experimental group, and the wound of a rat not treated with the gel was used as a control group, and wound healing conditions were observed after the 3 rd and 7 th days. The results of the experiment are shown in FIG. 3.
As can be seen from FIG. 3, the hydrogel provided by the embodiment of the invention has an obvious repairing effect on the wound surface.
Experimental example 4
The hydrogel provided in example 1 and comparative examples 1 and 2 was subjected to wound repair effect experiments. The results of the experiment are shown in the following table.
Compared with the two comparative examples 1 and 2, the hydrogel prepared by the preparation method provided by the invention has the advantages that compared with the existing mode of preparing the curcumin into micelles and microspheres, the hydrogel prepared by dissolving the curcumin in the organic solvent can better retain the activity of the curcumin, so that the hydrogel has a better effect of promoting wound healing.
In summary, the preparation method provided by the application is simple and convenient to operate, and the activity of curcumin can be ensured to the maximum extent in the preparation process. The three-dimensional network structure of the prepared hydrogel is mainly constructed by natural polysaccharide and derivatives thereof, and functional micromolecule substances are introduced to stabilize the three-dimensional network structure of the hydrogel and simultaneously improve the application effect of the polysaccharide-based hydrogel. The hydrogel contains a large amount of water, is swollen by water absorption but not dissolved, can absorb wound exudate when used for the wound dressing, plays a role in autolysis debridement, can isolate external bacteria, can play a role in moisturizing, provides a moist healing microenvironment, and promotes wound healing. The curcumin in the prepared hydrogel is not easy to burst due to the hydrogen bond between the curcumin, chitosan and sodium alginate oxide, has the characteristic of slow release, and has good promotion effect on wound healing.
The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention, and various modifications and changes may be made by those skilled in the art. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (10)
1. A method of making a functional hydrogel dressing, comprising:
uniformly mixing a chitosan substance solution, a curcumin solution and an oxidized sodium alginate solution to form hydrogel, wherein the chitosan substance is at least one selected from chitosan and chitosan derivatives.
2. The method for preparing the functional hydrogel dressing according to claim 1, wherein the solution of the chitosan substance and the curcumin solution are uniformly mixed to obtain a mixed solution, and then the oxidized sodium alginate solution and the mixed solution are uniformly mixed to form the hydrogel.
3. The method for preparing the functional hydrogel dressing according to claim 2, wherein the oxidized sodium alginate solution and the mixed solution are uniformly mixed in a manner that:
and dropwise adding the oxidized sodium alginate solution into the mixed solution.
4. The method for preparing the functional hydrogel dressing according to claim 2, wherein the curcumin solution is obtained by dissolving curcumin in an organic solvent.
5. The method of claim 4, wherein the organic solvent is an alcohol;
preferably, the organic solvent is propylene glycol.
6. The preparation method of the functional hydrogel dressing according to any one of claims 2 to 5, wherein the dosage molar ratio of the chitosan substance to the sodium alginate oxide is 10-20: 1;
preferably, the molar ratio of the curcumin to the sodium alginate oxide is 0.01-0.1: 1.
7. The method for preparing the functional hydrogel dressing according to any one of claims 2 to 5, wherein the mass concentration of the chitosan substance solution is 1.5 to 5%, the mass concentration of the oxidized sodium alginate is 10 to 20%, and the mass concentration of the curcumin solution is 8 to 12%.
8. The preparation method of the functional hydrogel dressing according to claim 7, wherein the volume ratio of the chitosan solution to the curcumin solution is 10-50: 1, and the volume ratio of the mixed solution to the sodium alginate oxide solution is 4-10: 1.
9. The method of any one of claims 1 to 5, wherein the derivative of chitosan comprises at least one of carboxymethyl chitosan, hydroxypropyl chitosan and chitosan quaternary ammonium salt.
10. A functional hydrogel dressing prepared by the preparation method of any one of claims 1 to 8.
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