CN115678046A - Oxygen-producing double-network hydrogel, preparation method and application - Google Patents
Oxygen-producing double-network hydrogel, preparation method and application Download PDFInfo
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- CN115678046A CN115678046A CN202211485029.4A CN202211485029A CN115678046A CN 115678046 A CN115678046 A CN 115678046A CN 202211485029 A CN202211485029 A CN 202211485029A CN 115678046 A CN115678046 A CN 115678046A
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Abstract
The invention relates to an oxygen-producing double-network hydrogel, a preparation method and application thereof, belonging to the technical field of medical high polymer materials. Dissolving sodium alginate in water to obtain a sodium alginate solution; dissolving polyvinyl alcohol in water, and adding a cationic cross-linking agent and calcium peroxide microspheres to obtain a mixed solution; the surfaces of the calcium peroxide microspheres are coated with hydrophilic polymers; uniformly mixing the sodium alginate solution with the mixed solution, wherein the cationic cross-linking agent enables the sodium alginate to be cross-linked; then freezing and unfreezing are carried out to ensure that the polyvinyl alcohol is physically crosslinked, and the oxygen-producing double-network hydrogel is obtained. The invention provides an oxygen-producing hydrogel dressing which consists of double-network hydrogel containing calcium peroxide microspheres and catalase solution, wherein the double-network hydrogel consists of the calcium peroxide microspheres, polyvinyl alcohol, sodium alginate and cation solution. The oxygen-producing hydrogel dressing provided by the invention can realize rapid, continuous and controllable oxygen delivery.
Description
Technical Field
The invention relates to the technical field of medical high polymer materials, in particular to an oxygen-producing double-network hydrogel, a preparation method and application thereof.
Background
Diabetes is a chronic metabolic disease, and more than 4.25 million people are affected globally, with a projected population of 6.29 million in 2045 years. Chronic wounds of diabetes are a common complication in diabetics. In diabetic patients, once injury occurs, the damaged blood vessels prevent oxygen from being transmitted to the wound, creating an oxygen deficient environment around the wound. During the inflammatory phase, hypoxia is exacerbated by the accumulation of highly oxygen-consuming inflammatory cells, which in turn severely inhibits angiogenesis, epithelial regeneration and extracellular matrix synthesis, thereby impairing the healing process. Therefore, enhancing oxygenation of wound tissue is critical for chronic diabetic wound healing.
The existing clinical treatment means are systemic hyperbaric oxygen therapy, local hyperbaric oxygen therapy and wearable local hyperbaric oxygen therapy. However, all of the above methods use gaseous oxygen delivery, which is not effective in penetrating the skin, and often depends on an external source, is inconvenient to use, cannot achieve continuous oxygenation, and also has a risk of aerobic poisoning. Topical gaseous oxygen can penetrate only 400 microns, while topical dissolved oxygen can penetrate more than 700 microns through human skin. Therefore, the in-situ delivery of dissolved oxygen has a certain therapeutic potential for diabetic chronic wounds and is widely concerned by researchers. Oxygen-producing hydrogel wound dressings based on perfluorocarbons, microalgae, hydrogen peroxide have been developed. While this type of dressing avoids systemic hyperoxia, oxygen production requires an exogenous condition to trigger, is inconvenient to use, has a limited duration, and is not adjustable.
Chinese patent literature discloses 'an oxygen-producing hydrogel and a preparation method and application thereof', and the application publication number is CN 110464703A. The oxygen-producing hydrogel comprises photosynthetic microalgae and biodegradable hydrogel. The photosynthetic microalgae in the hydrogel utilizes light to decompose water to generate oxygen so as to improve the hypoxic microenvironment of a tumor part and play a role in assisting photodynamic therapy to increase the curative effect. The photosynthetic oxygen-producing hydrogel is limited by illumination conditions, cannot realize continuous oxygen delivery and is not beneficial to wound healing.
Disclosure of Invention
The invention provides an oxygen-producing hydrogel dressing for improving the problem that the existing oxygen-producing hydrogel can not continuously deliver oxygen, which consists of double-network hydrogel containing calcium peroxide microspheres and catalase solution, wherein the double-network hydrogel consists of calcium peroxide microspheres, polyvinyl alcohol, sodium alginate and cation solution. The oxygen-producing hydrogel dressing provided by the invention can realize rapid, continuous and controllable delivery of oxygen so as to promote the healing of diabetic chronic wounds.
According to a first aspect of the present invention, there is provided a method for preparing an oxygen-generating double-network hydrogel, comprising the steps of:
(1) Dissolving sodium alginate in water to obtain a sodium alginate solution; dissolving polyvinyl alcohol in water, and adding a cationic cross-linking agent and calcium peroxide microspheres to obtain a mixed solution; the surfaces of the calcium peroxide microspheres are coated with hydrophilic polymers; the calcium peroxide microspheres are used for reacting with water to generate hydrogen peroxide, and the hydrogen peroxide is used for generating oxygen;
(2) Uniformly mixing the sodium alginate solution obtained in the step (1) with the mixed solution, wherein the cationic cross-linking agent enables the sodium alginate to be cross-linked; then freezing and unfreezing are carried out, so that the polyvinyl alcohol is physically crosslinked, and the oxygen-producing double-network hydrogel is obtained.
Preferably, the mass ratio of the polyvinyl alcohol to the sodium alginate to the calcium peroxide microspheres is (5-10): (1-2): (0.5-1).
Preferably, the mass ratio of the cationic cross-linking agent to the mass of the sodium alginate is 0.5-1;
preferably, the cationic cross-linking agent is calcium chloride or magnesium chloride.
Preferably, the hydrophilic polymer is polyethylene glycol.
According to another aspect of the present invention, there is provided an oxygen generating double network hydrogel prepared by any one of the methods.
Preferably, in the hydrogel, the mass ratio of the polyvinyl alcohol to the sodium alginate to the cationic cross-linking agent to the calcium peroxide microspheres is (2.5-5): (0.5-1): (0.25-1): (0.25-0.5).
According to another aspect of the present invention, there is provided the use of said oxygen-generating double-network hydrogel for the preparation of a wound dressing.
Preferably, the application is specifically: soaking the double-network hydrogel in a catalase solution, and then taking out the double-network hydrogel to adhere catalase to the double-network hydrogel; the calcium peroxide microspheres in the double-network hydrogel react with water to generate hydrogen peroxide, and the hydrogen peroxide and catalase generate oxygen.
Preferably, the volume of the catalase in the catalase solution accounts for 0.2-6%;
preferably, the soaking time is 30-120min.
According to another aspect of the present invention, there is provided a wound dressing comprising said oxygen-producing double-network hydrogel, and further comprising a separate catalase solution.
Generally, compared with the prior art, the above technical solution conceived by the present invention mainly has the following technical advantages:
(1) The oxygen-producing hydrogel dressing provided by the invention integrates the excellent functions and biological activities of all raw materials, can deliver oxygen, can quickly absorb wound exudate, and provides a moist environment for promoting healing for a wound. Wherein the oxygen is obtained by reacting calcium peroxide with water to generate hydrogen peroxide, and further decomposing the hydrogen peroxide to generate oxygen under the action of catalase.
(2) The oxygen-producing hydrogel has a modulus similar to that of skin tissue, is soft and conformable, and is easy to use.
(3) The oxygen-producing hydrogel dressing can deliver oxygen for up to seven days and keep stable, and in addition, the oxygen production rate and the oxygen production amount can be regulated and controlled by changing the content of catalase and the quality of calcium peroxide, so that the customized design of the wound dressing can be realized, and a more intelligent treatment mode is provided for the treatment of chronic wounds of diabetes.
(4) The oxygen-generating function of the oxygen-generating hydrogel dressing is derived from microspheres obtained by modifying calcium peroxide with hydrophilic polymers, and the microspheres can quickly react with water to generate oxygen under the action of the hydrophilic polymers, so that the wound is in a high-oxygen environment in time, and the wound healing is further facilitated.
Drawings
Figure 1 is a functional schematic of an oxygen-producing hydrogel dressing of the present invention.
Fig. 2 is an oxygen generating effect of calcium peroxide microspheres in the oxygen generating hydrogel dressing of the present invention.
Fig. 3 is an oxygen production rate regulating effect of the oxygen-producing hydrogel dressing of the present invention.
Figure 4 is the sustained oxygen production results of the oxygen-producing hydrogel dressing of the present invention.
FIG. 5 is a graph showing the therapeutic effect of the oxygen-producing hydrogel dressing of the present invention on diabetic chronic wounds.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is described in further detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and do not limit the invention. In addition, the technical features involved in the respective embodiments of the present invention described below may be combined with each other as long as they do not conflict with each other.
The invention relates to an oxygen-producing hydrogel dressing which is composed of double-network hydrogel containing calcium peroxide microspheres and catalase solution. The double-network hydrogel is composed of calcium peroxide microspheres, polyvinyl alcohol, sodium alginate and a cationic solution. The catalase solution consists of catalase and sterilized water. The double-network hydrogel containing the calcium peroxide microspheres is obtained by freezing, thawing and multiple times of circulating physical crosslinking, and then can be applied to wounds after being soaked in catalase solution for a certain time.
Preferably, the calcium peroxide microspheres are prepared by the following method: dissolving calcium peroxide powder in polyethylene glycol 400 solution at a certain ratio, adding deionized water and hydrochloric acid, and stirring at normal temperature for 24h. The resulting solution was centrifuged, filtered with ethanol, and dried at room temperature to obtain a powder.
Preferably, the oxygen-producing hydrogel dressing is prepared according to the following method: sodium alginate is dissolved in deionized water in a certain proportion to be used as a component A, polyvinyl alcohol 124 is dissolved in deionized water in a certain proportion at high temperature, and then calcium chloride with certain mass is added to be used as a component B. And respectively carrying out high-speed centrifugal defoaming on the component A and the component B, and then adding a certain mass of calcium peroxide microspheres into the component B to obtain the component C. And uniformly mixing the component A and the component C according to a certain proportion, pouring the mixture into a mould, and performing multiple freezing and thawing cycles to obtain the final hydrogel.
Preferably, the components of the double-network hydrogel consist of (2.5-5%) polyvinyl alcohol, (0.5-1%) sodium alginate, (0.25-1%) calcium chloride and (0.25-0.5%) calcium peroxide microspheres. Preferably, the components of the catalase solution are composed of liquid catalase and sterilized water mixed in a volume ratio of (0.2-6%).
Preferably, the soaking time is 30-120min.
Example 1
(1) The synthesis method of the calcium peroxide microspheres comprises the following steps:
at normal temperature, 1g of calcium peroxide is dissolved in 15ml of polyethylene glycol 400, 10ml of deionized water and 15ml of 0.5M hydrochloric acid are added, stirring is carried out for 24 hours, centrifugation is carried out, then filtration is carried out for three times by using ethanol, and drying is carried out at normal temperature.
(2) The synthesis method of the oxygen-generating hydrogel comprises the following steps:
at room temperature, 0.2g of sodium alginate was dissolved in 9.8g of deionized water. 1g of polyvinyl alcohol 124 is dissolved in 9g of deionized water at 90 ℃, 0.2g of calcium chloride is added to the solution and dissolved in the solution, and after centrifugal deaeration, 0.12g of calcium peroxide microspheres are further added to the solution. The above solutions were mixed in a volume ratio of 1. The hydrogel was thawed by freezing at-20 ℃ for two cycles (as shown in FIG. 1).
(3) The synthesis method of the oxygen-generating hydrogel dressing comprises the following steps:
at room temperature, 40. Mu.l of liquid catalase was dissolved in 10ml of sterilized water and mixed well. And then soaking the obtained oxygen-producing hydrogel in a prepared catalase solution for 120min to obtain the oxygen-producing hydrogel dressing.
Example 2
(1) The synthesis method of the calcium peroxide microspheres comprises the following steps:
at normal temperature, 1g of calcium peroxide is dissolved in 15ml of polyethylene glycol 400, 10ml of deionized water and 15ml of 0.5M hydrochloric acid are added, stirring is carried out for 24 hours, centrifugation is carried out, then filtration is carried out for three times by using ethanol, and drying at normal temperature is carried out.
(2) The synthesis method of the oxygen-generating hydrogel comprises the following steps:
at room temperature, 0.1g of sodium alginate was dissolved in 9.9g of deionized water. 0.5g of polyvinyl alcohol 124 is dissolved in 9.5g of deionized water at 90 ℃, 0.1g of calcium chloride is added to the solution and dissolved in the solution, and after centrifugal defoaming, 0.20g of calcium peroxide microspheres are further added. The above solutions were mixed in a volume ratio of 1. Placing the mixture at the temperature of minus 20 ℃ for freezing and unfreezing for two cycles to obtain the hydrogel. As shown in figure 1, the oxygen-producing hydrogel is a double-network hydrogel, wherein the first network is a polyvinyl alcohol network and is formed by repeated freeze-thaw cycle crystallization and crosslinking. The second network is a sodium alginate network and is formed by calcium ion crosslinking. In addition, a part of calcium ions in the polyvinyl alcohol network interact with polyvinyl alcohol chains to further carry out ionic crosslinking.
(3) The synthesis method of the oxygen-generating hydrogel dressing comprises the following steps:
at room temperature, 100. Mu.l of liquid catalase was dissolved in 10ml of sterilized water and mixed well. And soaking the obtained oxygen-producing hydrogel in a prepared catalase solution for 30min to obtain the oxygen-producing hydrogel dressing.
Example 3
(1) The synthesis method of the calcium peroxide microspheres comprises the following steps:
at normal temperature, 1g of calcium peroxide is dissolved in 15ml of polyethylene glycol 400, 10ml of deionized water and 15ml of 0.5M hydrochloric acid are added, stirring is carried out for 24 hours, centrifugation is carried out, then filtration is carried out for three times by using ethanol, and drying is carried out at normal temperature.
(2) The synthesis method of the oxygen-generating hydrogel comprises the following steps:
at room temperature, 0.15g of sodium alginate was dissolved in 9.85g of deionized water. 0.75g of polyvinyl alcohol 124 is dissolved in 9.25g of deionized water at 90 ℃, 0.15g of calcium chloride is added to the solution and dissolved in the solution, and after centrifugal deaeration, 0.08g of calcium peroxide microspheres are further added to the solution. The above solutions were mixed in a volume ratio of 1. The hydrogel was thawed by freezing at-20 ℃ for two cycles (as shown in FIG. 1).
(3) The synthesis method of the oxygen-generating hydrogel dressing comprises the following steps:
at room temperature, 20. Mu.l of liquid catalase was dissolved in 10ml of sterilized water and mixed well. And soaking the obtained oxygen-producing hydrogel in a prepared catalase solution for 60min to obtain the oxygen-producing hydrogel dressing.
Example 4 oxygen generation performance test: the oxygen production effect of the microspheres and hydrogel was tested by a dissolved oxygen electrode.
(1) Characterization of oxygen production performance of calcium peroxide microspheres
As can be seen from FIG. 2, under the same conditions, the oxygen-generating performance of the PEG-modified calcium peroxide PEG @ CPO is obviously higher than that of the CPO within 60 minutes. After catalase, both PEG @ CPO and CPO showed significant increases in dissolved oxygen production concentrations. In addition, PEG @ CPO reaches the upper limit of dissolved oxygen within only 10 minutes, which is beneficial to keep the wound in a high oxygen level state and promote wound healing.
(2) Characterization of oxygen production rate of oxygen-producing hydrogel
As can be seen from FIG. 3, the oxygen production rate of the hydrogel was controlled by varying the catalase content under otherwise identical conditions.
(3) Characterization of continuous oxygen production performance of oxygen-producing hydrogel
As can be seen from FIG. 4, the oxygen-producing hydrogel prepared in example 1 can continuously release oxygen for up to 7 days.
Example 5
Diabetic animal wound healing test: and evaluating the wound healing effect of the oxygen-producing hydrogel PSC in vivo based on a full-thickness diabetic wound mouse model. In brief, a wound having a diameter of 8mm was first created on the dorsal skin of a diabetic mouse, and then three measures, i.e., no treatment, PVA/SA hydrogel treatment, and PSC oxygen-producing hydrogel treatment, were performed on the wound. Wound status was recorded at day 0, 2, 4, 7 and 14, respectively. From FIG. 5, it can be found that the wound surface shrinkage speed of the PSC group is faster than that of the control group and the PVA/SA group, which indicates that the PSC oxygen-generating hydrogel prepared in example 1 has a better diabetic wound repair effect.
It will be understood by those skilled in the art that the foregoing is only a preferred embodiment of the present invention, and is not intended to limit the invention, and that any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the scope of the present invention.
Claims (10)
1. The preparation method of the oxygen-producing double-network hydrogel is characterized by comprising the following steps:
(1) Dissolving sodium alginate in water to obtain a sodium alginate solution; dissolving polyvinyl alcohol in water, and adding a cationic cross-linking agent and calcium peroxide microspheres to obtain a mixed solution; the surface of the calcium peroxide microsphere is coated with a hydrophilic polymer; the calcium peroxide microspheres are used for reacting with water to generate hydrogen peroxide, and the hydrogen peroxide is used for generating oxygen;
(2) Uniformly mixing the sodium alginate solution obtained in the step (1) with the mixed solution, wherein the cationic cross-linking agent enables the sodium alginate to be cross-linked; then freezing and unfreezing are carried out, so that the polyvinyl alcohol is physically crosslinked, and the oxygen-producing double-network hydrogel is obtained.
2. The preparation method of the oxygen-generating double-network hydrogel as claimed in claim 1, wherein the mass ratio of the polyvinyl alcohol, the sodium alginate and the calcium peroxide microspheres is (5-10): (1-2): (0.5-1).
3. The method for preparing an oxygen generating double-network hydrogel according to claim 1, wherein the mass ratio of the cationic cross-linking agent to the mass of the sodium alginate is 0.5 to 1;
preferably, the cationic cross-linking agent is calcium chloride or magnesium chloride.
4. The method of preparing an oxygen-generating double-network hydrogel according to claim 1, wherein the hydrophilic polymer is polyethylene glycol.
5. An oxygen-generating double-network hydrogel prepared by the method of any one of claims 1 to 4.
6. The oxygen-generating double-network hydrogel according to claim 5, wherein the hydrogel comprises polyvinyl alcohol, sodium alginate, a cationic cross-linking agent and calcium peroxide microspheres in a mass ratio of (2.5-5): (0.5-1): (0.25-1): (0.25-0.5).
7. Use of an oxygen-generating double-network hydrogel according to claim 5 or 6 for the preparation of a wound dressing.
8. The application according to claim 7, characterized in that it is specifically: soaking the double-network hydrogel in a catalase solution, and then taking out the double-network hydrogel to adhere catalase to the double-network hydrogel; the calcium peroxide microspheres in the double-network hydrogel react with water to generate hydrogen peroxide, and the hydrogen peroxide and catalase generate oxygen.
9. The use of claim 8, wherein the catalase solution comprises catalase in an amount of 0.2% to 6% by volume;
preferably, the soaking time is 30-120min.
10. A wound dressing comprising the oxygen-producing double network hydrogel of claim 5 or 6 and further comprising a separate catalase solution.
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| CN117599228A (en) * | 2024-01-23 | 2024-02-27 | 浙江大学医学院附属第二医院 | Multifunctional dressing patch for eyes |
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| CN117599228A (en) * | 2024-01-23 | 2024-02-27 | 浙江大学医学院附属第二医院 | Multifunctional dressing patch for eyes |
| CN117599228B (en) * | 2024-01-23 | 2024-04-02 | 浙江大学医学院附属第二医院 | Multifunctional dressing patch for eyes |
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