CN111528220A - Hydrogel for slowly releasing chlorine dioxide and preparation method thereof - Google Patents

Hydrogel for slowly releasing chlorine dioxide and preparation method thereof Download PDF

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CN111528220A
CN111528220A CN202010318088.7A CN202010318088A CN111528220A CN 111528220 A CN111528220 A CN 111528220A CN 202010318088 A CN202010318088 A CN 202010318088A CN 111528220 A CN111528220 A CN 111528220A
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hydrogel
chlorine dioxide
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CN111528220B (en
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范治平
程萍
王正平
韩军
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Liaocheng University
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Abstract

The invention relates to the technical field related to slow release of chlorine dioxide, and particularly provides a hydrogel for slow release of chlorine dioxide and a preparation method thereof. The invention provides a hydrogel for slowly releasing chlorine dioxide, which is prepared from raw materials including chlorine dioxide, tyramine-grafted polyglutamic acid solution, cysteamine-grafted hyaluronic acid solution, horseradish peroxidase, hydrogen peroxide and alcohol substances; wherein the alcohol substance comprises dihydric alcohol with the relative molecular weight of 2000-5000 and trihydric alcohol with the relative molecular weight of 80-300. According to the invention, tyramine-grafted polyglutamic acid and cysteamine-grafted hyaluronic acid are adopted to form an interpenetrating network structure in a hydrogel system, so that the mechanical strength of the hydrogel is effectively improved; under the synergistic effect of specific dihydric alcohol and trihydric alcohol, a low-temperature-resistant and anti-freezing hydrogel system suitable for the slow release of chlorine dioxide is formed, and the problem that the use condition of a chlorine dioxide solution is limited due to easy icing of the chlorine dioxide solution is avoided.

Description

Hydrogel for slowly releasing chlorine dioxide and preparation method thereof
Technical Field
The invention relates to the technical field related to slow release of chlorine dioxide, and particularly provides a hydrogel for slowly releasing chlorine dioxide and a preparation method thereof.
Background
Chlorine dioxide is an effective antiviral chemical agent, has broad-spectrum antimicrobial effect, has no pain, distortion and mutation causing effects on higher animal cells, has the effect of eliminating formaldehyde, has high safety, is listed as an Al-grade broad-spectrum, safe and high-efficiency disinfectant by the world health organization, and is advocated as a fourth-generation disinfectant. However, the traditional chlorine dioxide slow-release gel is only suitable for the room temperature environment with higher temperature, the slow-release gel cannot release antiviral effective substances due to reasons of icing of chlorine dioxide solution and the like in the low-temperature environment, and the low-temperature environment has poor applicability, so that the application of the gel is limited to a certain extent due to the lack of suitable carriers and formulas.
The gel of the slow-release antibacterial agent mostly adopts artificially synthesized high molecular materials as carriers, but the materials have more synthesis steps and poorer environmental economy, and have potential biological toxicity when being used in the medical field. The traditional gel carrier is only suitable for a room temperature environment, the slow release of the medicine cannot be realized due to reasons such as icing and the like in a low temperature environment, or the slow release effect is poor, a better scheme is provided for solving the problem due to the appearance of the natural polymer-based biological hydrogel, the biocompatibility of the gel carrier is good, the gel carrier can be degraded and absorbed in the nature, the gel carrier can be used for different clinical symptoms when being combined with the medicine, the application prospect is wide, and the disadvantages of poor mechanical property, poor injectability and the like can occur in the using process.
Disclosure of Invention
In order to solve the technical problems, the invention provides a hydrogel for slowly releasing chlorine dioxide in a first aspect, wherein the preparation raw materials comprise chlorine dioxide, tyramine-grafted polyglutamic acid solution, cysteamine-grafted hyaluronic acid solution, horseradish peroxidase, hydrogen peroxide and alcohol substances; wherein the alcohol substance comprises dihydric alcohol with the relative molecular weight of 2000-5000 and trihydric alcohol with the relative molecular weight of 80-300.
As a preferred technical scheme of the invention, the pH value of the hydrogel is 3.5-5.5.
As a preferable technical scheme of the invention, the grafted polyglutamic acid solution and the cysteamine-grafted hyaluronic acid solution both take 5 wt% chlorine dioxide solution as base solution, and the polyglutamic acid solution and the cysteamine-grafted hyaluronic acid are respectively prepared into solutions.
As a preferred technical scheme of the invention, the concentration of the tyramine grafted polyglutamic acid solution is 100-300 mg/mL; the concentration of the cysteamine grafted hyaluronic acid solution is 100-300 mg/mL; preferably, the volume ratio of the grafted polyglutamic acid solution to the cysteamine-grafted hyaluronic acid solution is 1: (0.5 to 1.5).
As a preferred technical scheme of the invention, the concentration of the hydrogen peroxide is 1-30 mM.
As a preferred technical scheme of the invention, the content of the horseradish peroxidase is 1-50U/mL.
As a preferred technical scheme of the invention, the alcohol substance accounts for 5-25% of the total volume of the hydrogel.
As a preferred technical scheme of the invention, the volume ratio of the dihydric alcohol to the trihydric alcohol is 1: (1.2-4.3).
As a preferred technical scheme of the invention, the structure of the dihydric alcohol is selected from HO (CH)2CH2O)nH、 HO(CH2CH2CH2CH2O)mH、
Figure BDA0002460237510000021
Any one or a combination of more of them, wherein n, m and p are respectively 35-75 independently.
As a preferred technical scheme of the invention, the trihydric alcohol is selected from glycerol and/or trimethylolpropane.
The second aspect of the present invention provides a method for preparing the hydrogel for slowly releasing chlorine dioxide, comprising the steps of: mixing the tyramine-grafted polyglutamic acid solution, the cysteamine-grafted hyaluronic acid solution and the alcohol substances, adding horseradish peroxidase and hydrogen peroxide, adjusting the pH, and standing at room temperature to obtain the required hydrogel.
Compared with the prior art, the hydrogel for slowly releasing chlorine dioxide provided by the invention has the following beneficial effects:
(1) the tyramine-grafted polyglutamic acid and cysteamine-grafted hyaluronic acid are adopted to form an interpenetrating network structure in a hydrogel system, so that the mechanical strength of the hydrogel is effectively improved;
(2) under the synergistic effect of specific dihydric alcohol and trihydric alcohol, a low-temperature-resistant and anti-freezing hydrogel system suitable for the slow release of chlorine dioxide is formed, so that the problem that the use condition of a chlorine dioxide solution is limited due to easy icing of the chlorine dioxide solution is avoided;
(3) various components of the hydrogel system provided by the application are all derived from natural polysaccharide macromolecules or natural polyamino acids from natural sources, and the components are combined to prepare the gel, so that an environment-friendly degradable and absorbable material is obtained, and the defects that the traditional carrier material is easy to pollute the environment and is not easy to recycle are overcome;
(4) the in-situ crosslinking degradable sustained-release gel provided by the invention contains the medicine chlorine dioxide, can realize a longer and adjustable medicine release period of sustained-release time, and the released medicine shows good medicine activity; compared with the existing administration mode, the gel preparation compound can remarkably prolong the drug effect time.
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In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below, it is obvious that the drawings in the following description are only some embodiments of the present invention, and for those skilled in the art, other drawings can be obtained according to the drawings without creative efforts.
FIG. 1: schematic illustration of a hydrogel formed from polyglutamic acid grafted with tyramine and hyaluronic acid grafted with cysteamine;
FIG. 2: example 2 nuclear magnetic spectrum of hyaluronic acid before and after grafting;
FIG. 3: i3 schematic diagram of internal structure of hydrogel;
FIG. 4: fig. 3 is a partially enlarged schematic view of the structure.
Detailed Description
Unless otherwise indicated, implied from the context, or customary in the art, the definitions of terms provided herein control if a definition of a particular term disclosed in the prior art is inconsistent with any definition provided herein. The technical features of the technical solutions provided by the present invention are further clearly and completely described below with reference to the specific embodiments, and the scope of protection is not limited thereto.
The words "preferred", "preferably", "more preferred", and the like, in the present invention, refer to embodiments of the invention that may provide certain benefits, under certain circumstances. However, other embodiments may be preferred, under the same or other circumstances. Furthermore, the recitation of one or more preferred embodiments does not imply that other embodiments are not useful, nor is it intended to exclude other embodiments from the scope of the invention.
The invention provides a hydrogel for slowly releasing chlorine dioxide, which is prepared from raw materials including chlorine dioxide, tyramine-grafted polyglutamic acid solution, cysteamine-grafted hyaluronic acid solution, horseradish peroxidase, hydrogen peroxide and alcohols; preferably, the pH of the hydrogel is 3.5-5.5; more preferably 4.5.
The tyramine grafted polyglutamic acid (PGA-Ty) is prepared by grafting tyramine into polyglutamic acid molecules by adopting an aqueous phase method; the molecular structure of polyglutamic acid (PGA) is a kind of nylon-4 derivatives, and a carboxyl group is grafted on the carbon at the 4-position of the repeating unit. PGA has numerous properties, such as: water solubility, degradability, edibility, human and environment friendliness, and the like.
The preparation process of the tyramine-grafted polyglutamic acid is not particularly limited, and can be prepared by a method well known to those skilled in the art, and in one embodiment, the preparation method of the tyramine-grafted polyglutamic acid is as follows: dissolving polyglutamic acid in distilled water, and adding tyramine hydrochloride; EDC and NHS are added into the mixed solution to initiate the reaction, and the pH value of the system is adjusted to be 4.8 by 1M sodium hydroxide and hydrochloric acid solution along with the reaction; stirring at room temperature overnight, adjusting the pH value of the system to 7, transferring the reaction solution into a dialysis bag with the cutoff molecular weight of 1000Da, dialyzing in 100mM sodium chloride solution for 2 days, dialyzing in a mixed solution of water and ethanol (volume ratio is 3:1) for 1 day, dialyzing in pure water for 1 day, finally lyophilizing the dialyzed and purified product solution to form a white flocculent sample, and freezing and storing at 4 ℃ to obtain the required tyramine grafted polyglutamic acid, wherein the weight ratio of tyramine hydrochloride to polyglutamic acid is 1: (1-1.2); the weight ratio of tyramine hydrochloride, EDC and NHS is 1: (4-5): (2.4-2.9); the specific reaction process and principle are shown in the reaction formula (1).
Figure BDA0002460237510000041
The cysteamine-grafted hyaluronic acid (HA-CA) is prepared by grafting cysteamine into hyaluronic acid molecules by an aqueous phase method, the Hyaluronic Acid (HA) is an acidic mucopolysaccharide and is a disaccharide unit consisting of D-glucuronic acid and N-acetylglucosamine, and the hyaluronic acid HAs a unique molecular structure and excellent biocompatibility, and shows a plurality of important physiological functions in a body, such as joint lubrication, permeability regulation of a blood vessel wall, protein regulation, water electrolyte diffusion and operation promotion, wound healing promotion and the like.
The specific preparation process of the cysteamine-grafted hyaluronic acid is not particularly limited, and can be prepared by a method well known to those skilled in the art, and in one embodiment, the specific preparation method of the cysteamine-grafted hyaluronic acid is as follows: weighing hyaluronic acid, dissolving in deionized water, stirring at constant temperature by using a magnetic stirrer until the hyaluronic acid is completely dissolved, weighing cysteamine hydrochloride, 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS) in distilled water, activating at room temperature for 1h, adding an activating solution into a hyaluronic acid solution, stirring at room temperature overnight, transferring a reaction solution into a dialysis bag, dialyzing with distilled water for 3 days, finally freeze-drying a dialyzed and purified product solution to form a white flocculent sample, and freezing and storing at 4 ℃ to obtain the required cysteamine grafted hyaluronic acid, wherein the weight ratio of the cysteamine hydrochloride to the hyaluronic acid is 1: (1-1.3); the weight ratio of the cysteamine hydrochloride, the EDC and the NHS is 1: (1.45-1.75): (1-1.2); the specific reaction process and principle are shown in the reaction formula (2).
Figure BDA0002460237510000051
In one embodiment, the weight ratio of the grafted polyglutamic acid solution to the cysteamine-grafted hyaluronic acid solution is 1: (0.5 to 1.5); preferably, the weight ratio of the grafted polyglutamic acid solution to the cysteamine-grafted hyaluronic acid solution is 1: (0.8 to 1.2); more preferably, the volume ratio of the grafted polyglutamic acid solution to the cysteamine-grafted hyaluronic acid solution is 1: 1.
the grafted polyglutamic acid solution and the cysteamine-grafted hyaluronic acid solution are both prepared into solutions by respectively taking 5 wt% chlorine dioxide solution as base solution; the concentration of the tyramine grafted polyglutamic acid solution is 30-300 mg/mL; preferably 40-100 mg/mL; further preferably 40-70 mg/mL; the concentration of the cysteamine grafted hyaluronic acid solution is 100-300 mg/mL; 30-300 mg/mL; preferably 40-100 mg/mL; further preferably 40-70 mg/mL; the invention is not particularly limited to the manufacturer of the chlorine dioxide solution, and in one embodiment, the chlorine dioxide solution is obtained from Haemax reagent, Shanghai.
Preferably, the content of the chlorine dioxide solution is 70-90 wt% of the hydrogel.
The content of the horseradish peroxidase is 1-50U/mL; preferably 5-30U/mL; further preferably 5-20U/mL; due to good biocompatibility and high stability of horseradish peroxidase (HRP), the HRP is widely applied to an enzyme-crosslinked hydrogel system, in the presence of hydrogen peroxide, phenol-derivatized polymers can form a crosslinked network under the catalysis of horseradish peroxidase, and HRP-mediated hydrogels are generally applied to natural high molecular materials, such as hyaluronic acid, dextran, gelatin, chitosan and the like; synthetic polymer materials, such as poly (l-glutamic acid) and four-arm PPO-PEO, are also suitable for an enzyme crosslinking method to obtain related hydrogel, but the clinical application of the synthetic polymer materials is greatly limited due to complicated synthetic steps and potential toxicity of additives.
The concentration of the hydrogen peroxide is 1-30 mM; preferably 5 to 20 mM; more preferably 7 to 15 mM.
The invention adopts tyramine grafted polyglutamic acid and cysteamine grafted hyaluronic acid, under the action of hydrogen peroxide and horseradish peroxidase, the system is subjected to in-situ crosslinking, namely phenolic hydroxyl is introduced to a polyglutamic acid macromolecular chain, the phenolic hydroxyl is catalyzed by oxidase to carry out oxidative crosslinking, and the hyaluronic acid containing sulfhydryl is subjected to oxidative crosslinking to form interpenetrating network hydrogel, the process is shown in figure 1, and two new covalent bonds appear in the crosslinking process: one is a carbon-carbon bond formed between two adjacent carbon atoms on the benzene ring; one is a carbon-oxygen bond between the ortho-carbon atom and the phenolic oxygen atom. The HA-CA can also influence the self-crosslinking process due to the existence of hydrogen peroxide, and finally forms a stable crosslinked disulfide bond; the formed two networks have synergistic effect, so that the mechanical strength and the drug slow-release capacity of the hydrogel are improved; the preparation method can overcome the toxicity brought by a chemical cross-linking agent, can solve the defect of poor physical cross-linking effect, and can realize non-toxic and harmless degradation of self materials; in addition, in order to reduce the influence of hydrogen peroxide on the system, the technical scheme of the application adopts hydrogen peroxide with lower concentration.
The alcohol substance comprises dihydric alcohol with the relative molecular weight of 2000-5000 and trihydric alcohol with the relative molecular weight of 80-300; preferably, the alcohol substance accounts for 5-25% of the total volume of the hydrogel; preferably 8-20%; further preferably 10-16%; more preferably 14%.
The structure of the dihydric alcohol is selected from HO (CH)2CH2O)nH、HO(CH2CH2CH2CH2O)mH、
Figure BDA0002460237510000061
Any one or a combination of more of the above, wherein n, m and p are respectively 35-75 independently; preferably, the dihydric alcohol is any one or combination of PEG4000, PEG6000, PEG 8000; more preferably, the glycol is PEG 4000.
The trihydric alcohol is selected from glycerol and/or trimethylolpropane; preferably, the triol is glycerol.
The volume ratio of the dihydric alcohol to the trihydric alcohol is 1: (1.2-4.3); preferably, the volume ratio of diol to triol is 1: (1.7-3.5); further preferably, the volume ratio of the dihydric alcohol to the trihydric alcohol is 1: (2.1-2.9); more preferably, the volume ratio of diol to triol is 1: 2.5.
in the experimental process, the applicant finds that under the synergistic action of specific dihydric alcohol and trihydric alcohol, particularly under the synergistic action of PEG4000 and glycerol, the volume ratio of the PEG4000 to the glycerol is controlled to be 1: (2.1-2.9) the pH of the system is between 4-5; the hydrogel system which is suitable for the slow release of chlorine dioxide and is resistant to low temperature and frost is favorably formed, the injectability of the hydrogel system formed by the hydrogel system and other components in the hydrogel is better, and the operability in the actual use process is better, which probably is because the viscosity and the hydroxyl value of organic components of the system are adjusted by PEG4000 and glycerol, so that the hydration among different components in the system is improved, the freezing temperature of the hydrogel is reduced, and the injectability of the hydrogel system is improved.
The second aspect of the present invention provides a preparation method of the hydrogel for slowly releasing chlorine dioxide, comprising the steps of: mixing the polyglutamic acid solution grafted by tyramine, the hyaluronic acid solution grafted by cysteamine and the alcohol substance, adding horseradish peroxidase and hydrogen peroxide, adjusting the pH, and standing at room temperature to obtain the required hydrogel.
Preferably, the preparation method of the hydrogel for slowly releasing chlorine dioxide comprises the following steps: adding PGA-Ty solution and HA-CA solution into PBS, adding alcohol, dissolving to obtain solution, adding HRP, adjusting pH, and adding H2O2Rapidly stirring to form drug-loaded gel, standing overnight at room temperature to ensure crosslinkingThe reaction is completely finished; during the gel formation process, the gel time is tested by a small bottle tilting method, namely, the sample can be judged to reach the gel state if no fluid flow is observed within one minute after the sample bottle is inverted.
The reagent for adjusting the pH is citric acid/sodium dihydrogen phosphate; preferably, the total addition of citric acid/sodium dihydrogen phosphate accounts for 7-9% of the total volume of the hydrogel; further preferably, the weight ratio of citric acid/sodium dihydrogen phosphate is 1: (0.8 to 1.2).
Example 1
Example 1 of the present invention provides tyramine-grafted polyglutamic acid (PGA-Ty) prepared by: dissolving 1g of polyglutamic acid in 50 ml of distilled water, and then adding 1.076g of tyramine hydrochloride; 4.457g EDC and 2.674g NHS were added into the mixed solution to initiate reaction; the pH value of the system is regulated to be stable at 4.8 by 1M sodium hydroxide and hydrochloric acid solution along with the reaction; stirring at room temperature overnight, and after adjusting the pH value of the system back to 7, transferring the reaction solution into a dialysis bag with the cutoff molecular weight of 1000 Da; dialyzing in 100mM sodium chloride solution for 2 days, dialyzing in mixed solution of water and ethanol (volume ratio of 3:1) for 1 day, and finally dialyzing in pure water for 1 day; the dialyzed and purified product solution is finally freeze-dried to form a white flocculent sample, and the white flocculent sample is frozen and stored at 4 ℃, and the test yield is about 86 percent.
Example 2
Example 2 of the present invention provides a cysteamine-grafted hyaluronic acid (HA-CA), which is prepared by the following steps: weighing 2g of hyaluronic acid, dissolving in 100ml of deionized water, and stirring at constant temperature by using a magnetic stirrer until the hyaluronic acid is completely dissolved; weighing 1.68g of cysteamine hydrochloride, 2.73g of EDC and 1.72g of NHS, dissolving in 100ml of distilled water, activating at room temperature for 1h (pH 4.8), adding the activated solution into hyaluronic acid solution, and stirring at room temperature overnight; transferring the reaction solution into a dialysis bag for 3 days by distilled water dialysis, finally freeze-drying the dialyzed and purified product solution to form a white flocculent sample, freezing and storing the white flocculent sample at 4 ℃, and testing the yield to be about 92 percent, wherein the nuclear magnetic spectrogram before and after hyaluronic acid grafting is shown in figure 2, and the peak is generated between 2.6 and 2.8.
Example 3
Embodiment 3 of the present invention provides a hydrogel for slowly releasing chlorine dioxide, wherein the preparation raw materials include a polyglutamic acid solution grafted with tyramine, a hyaluronic acid solution grafted with cysteamine, horseradish peroxidase, hydrogen peroxide and alcohol substances; the content of horseradish peroxidase is 10U/mL; the concentration of hydrogen peroxide is 10 mM; the alcohol substance accounts for 14 percent of the total volume of the hydrogel; adjusting the concentration of the polyglutamic acid solution grafted by tyramine and the concentration of the hyaluronic acid solution grafted by cysteamine and the volume ratio of the polyglutamic acid solution grafted by tyramine and the hyaluronic acid solution grafted by cysteamine to form different hydrogels for slowly releasing chlorine dioxide, wherein the specific concentration and volume ratio are shown in the following table 1;
the grafted polyglutamic acid solution and the cysteamine-grafted hyaluronic acid solution are prepared by respectively taking 5 wt% chlorine dioxide solution as base solution and preparing the polyglutamic acid solution and the cysteamine-grafted hyaluronic acid; the content of the chlorine dioxide solution is 80 wt% of the hydrogel; the alcohol substances comprise dihydric alcohol and trihydric alcohol; the volume ratio of the dihydric alcohol to the trihydric alcohol is 1: 2.5; the dihydric alcohol is PEG 4000; the trihydric alcohol is glycerol;
the preparation method of the hydrogel for slowly releasing chlorine dioxide comprises the following steps: adding PGA-Ty solution and HA-CA solution into PBS, adding alcohol, dissolving to obtain solution, adding HRP, adjusting pH to 4.5, and adding H2O2Quickly stirring to form a drug-loaded gel, standing overnight at room temperature to ensure complete crosslinking reaction; in the process of forming the gel, the gel time is tested by adopting a small bottle inclination method, namely, the sample can be judged to reach the gel state if no fluid flow is observed within one minute after the sample bottle is inverted; the reagent used to adjust the pH is citric acid/sodium dihydrogen phosphate; the weight ratio of citric acid/sodium dihydrogen phosphate is 1: 1.
TABLE 1
Figure BDA0002460237510000081
Figure BDA0002460237510000091
Example 4
Example 4 of the present invention provides a hydrogel for the sustained release of chlorine dioxide, which is embodied in the same manner as the system I3 of example 3, except that glycerin is not included.
Example 5
Embodiment 5 of the present invention provides a hydrogel for slowly releasing chlorine dioxide, which is the same as the system I3 in embodiment 3, except that the diol is PEG 6000.
Example 6
Example 6 of the present invention provides a hydrogel for sustained release of chlorine dioxide, which is embodied in the same manner as the system I3 of example 3, except that the diol is PEG 8000.
Performance evaluation
1. Testing the internal appearance of the hydrogel: selecting the hydrogel I3 in example 3 as a sample, firstly freezing the sample in a refrigerator at-20 ℃ to ice, and then freeze-drying the sample in a freeze dryer to obtain an SEM sample; placing the freeze-dried sample on the surface of an SEM objective table, bonding and fixing the sample by using a conductive adhesive tape to form a conductive path, and spraying gold on the fixed sample for 1 minute to form a compact gold-plated film on the surface of the sample; observing the appearance of the sample under 5KV accelerating voltage; it should be noted that the internal morphology of the sample is easily damaged during the freeze-drying preparation process, and in order to truly reflect the internal structural morphology of the gel, the sample should be brittle when frozen into a solid state.
The test results are shown in fig. 3 to 4, and it can be seen that the hydrogel has a porous structure inside and has good penetrability among pores; fig. 4 is an enlarged view of a portion of the structure of fig. 3.
2. Characterization of the injectability of the hydrogel: performing injectability characterization on all samples in the example 3 and the hydrogel samples obtained in the examples 4-6, namely observing whether the hydrogel can be used in an injection mode; 100 specimens are taken from each sample, and the evaluation grade and standard of the injectability are as follows: a level: the number of samples which can not be injected is 0-5; b stage: the number of samples which can not be injected is 6-17; c level: the number of samples which are not injectable is 18-40; d stage: the number of samples with nonejection is more than or equal to 41;
3. characterization of hydrogel low temperature resistance: all the samples in the example 3 and the hydrogel samples obtained in the examples 4 to 6 are subjected to low temperature resistance characteristic characterization, the obtained hydrogel is cylindrical, the samples are placed at room temperature and-10 ℃ for 2 hours respectively, then a compression experiment test is performed at room temperature and-10 ℃ respectively by using a universal material tester (WDW-50, Jinan Hengle instruments Co., Ltd.), the compression rate of the tester is set to be 20mm/min, and whether the hydrogel is broken or not is observed when the compression percentage is 20% (the compression percentage is calculated by dividing the compression deformation height of the sample by the original height of the sample).
TABLE 1
Figure BDA0002460237510000101
The foregoing is a preferred embodiment of the present invention, and it will be apparent to those skilled in the art that variations, modifications, substitutions and alterations can be made in the embodiment without departing from the principles and spirit of the invention.

Claims (10)

1. The hydrogel capable of slowly releasing chlorine dioxide is characterized in that raw materials for preparing the hydrogel comprise chlorine dioxide, tyramine grafted polyglutamic acid solution, cysteamine grafted hyaluronic acid solution, horseradish peroxidase, hydrogen peroxide and alcohol substances; wherein the alcohol substance comprises dihydric alcohol with the relative molecular weight of 2000-5000 and trihydric alcohol with the relative molecular weight of 80-300.
2. The hydrogel for slowly releasing chlorine dioxide according to claim 1, wherein the hydrogel has a pH of 3.5 to 5.5.
3. The hydrogel for slowly releasing chlorine dioxide according to claim 1 or 2, wherein the grafted polyglutamic acid solution and the cysteamine-grafted hyaluronic acid solution are both solutions prepared by using 5 wt% chlorine dioxide solution as a base solution and preparing the polyglutamic acid solution and the cysteamine-grafted hyaluronic acid into the solutions respectively.
4. The hydrogel for slowly releasing chlorine dioxide as claimed in claim 3, wherein the concentration of the tyramine-grafted polyglutamic acid solution is 100-300 mg/mL; the concentration of the cysteamine grafted hyaluronic acid solution is 100-300 mg/mL; preferably, the volume ratio of the grafted polyglutamic acid solution to the cysteamine-grafted hyaluronic acid solution is 1: (0.5 to 1.5).
5. The hydrogel for slowly releasing chlorine dioxide as claimed in claim 1 or 2, wherein the concentration of hydrogen peroxide is 1-30 mM.
6. The hydrogel capable of slowly releasing chlorine dioxide according to claim 1 or 2, wherein the content of horseradish peroxidase is 1-50U/mL.
7. The hydrogel capable of slowly releasing chlorine dioxide according to claim 1 or 2, wherein the alcohol substance accounts for 5-25% of the total volume of the hydrogel.
8. The hydrogel for slowly releasing chlorine dioxide as claimed in any one of claims 1 to 6, wherein the volume ratio of the dihydric alcohol to the trihydric alcohol is 1: (1.2-4.3).
9. The hydrogel for slowly releasing chlorine dioxide as claimed in any one of claims 1 to 6, wherein the structure of the diol is selected from HO (CH)2CH2O)nH、HO(CH2CH2CH2CH2O)mH、
Figure FDA0002460237500000011
Any one or a combination of more of them, wherein n, m and p are respectively 35-75 independently.
10. A method for preparing the hydrogel for slowly releasing chlorine dioxide according to any one of claims 1 to 9, comprising the steps of: mixing the tyramine-grafted polyglutamic acid solution, the cysteamine-grafted hyaluronic acid solution and the alcohol substances, adding horseradish peroxidase and hydrogen peroxide, adjusting the pH, and standing at room temperature to obtain the required hydrogel preparation.
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