CN108310452B - Temperature-sensitive glucan-based hydrogel and preparation method thereof - Google Patents
Temperature-sensitive glucan-based hydrogel and preparation method thereof Download PDFInfo
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- A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
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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
- A61L26/0014—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing macromolecular materials obtained by reactions only involving carbon-to-carbon unsaturated bonds
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- A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
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- A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
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- A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
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- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/402—Anaestetics, analgesics, e.g. lidocaine
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- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
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- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/41—Anti-inflammatory agents, e.g. NSAIDs
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- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/412—Tissue-regenerating or healing or proliferative agents
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- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
- A61L2300/602—Type of release, e.g. controlled, sustained, slow
Abstract
The invention belongs to the technical field of medical functional dressings, and particularly relates to a temperature-sensitive glucan-based hydrogel and a preparation method thereof. The wound dressing has the characteristics of temperature sensitivity and bacteria resistance, can realize the controllable release of the medicament, flexibly controls the release of the medicament along with the local temperature change of an inflammation part, can adsorb wound exudate, has good biocompatibility and good surface lubricating property, is not easy to cause secondary injury of the wound during clinical replacement, has biodegradability, and cannot cause environmental pollution.
Description
Technical Field
The invention belongs to the field of medical dressings, and particularly relates to a temperature-sensitive glucan-based hydrogel and a preparation method thereof.
Background
Traditional wound dressings such as gauze, absorbent cotton and the like are easily adhered to wound positions, and secondary damage to granulation tissues of wounds is easily caused when the dressings are replaced or removed. The wound dressing can provide and maintain a moist environment around the wound surface, can exchange gas, and can play a role in blocking foreign pollutants, microorganisms and the like. The ideal wound dressing material should be nontoxic, non-adhesive, non-allergic reaction, antibacterial, swelling and absorbing, etc.
The hydrogel is a high molecular network system, has a reticular cross-linked structure, is soft in property, can keep a certain shape, absorbs a large amount of water and has strong water retention capacity. Moreover, the hydrogel has good permeability to water and oxygen and good biocompatibility. The density of the hydrogel is similar to that of organism organ tissues, so that the hydrogel has good mechanical properties and biocompatibility. The hydrogel material is directly contacted with human tissues, can prevent in-vitro microbial infection, control body fluid loss, and can deliver oxygen to wounds to promote wound healing.
However, conventional hydrogels have low porosity, poor gas permeability, low drug loading, and poor mechanical properties, and there is a need for a biosafety method to improve the performance of the conventional hydrogels.
The biological source glucan has the advantages of no toxicity, good biocompatibility and biodegradability, antibiosis and no biological tissue body immunoreaction, and is an ideal hydrogel raw material. The temperature-sensitive glucan-based hydrogel can accelerate or slow down the release of the medicine along with the increase or decrease of the temperature of the wound or the inflammation part, and the controllable release of the medicine is realized.
Disclosure of Invention
Aiming at the problems, the invention provides the temperature-sensitive glucan-based hydrogel dressing which has good moisture retention, air permeability, mechanical property and slow release property and is widely applied to the field of medical dressings.
In order to achieve the purpose, the invention adopts the following technical scheme:
the temperature-sensitive glucan-based hydrogel is a double-network gel formed by temperature-sensitive hydrogel and glucan by using tannic acid as a cross-linking agent.
Preferably, the temperature-sensitive glucan-based hydrogel is a porous temperature-sensitive glucan-based hydrogel.
Preferably, the temperature-sensitive hydrogel is poly-N-isopropylacrylamide hydrogel, polyacrylic acid carbendazim hydrogel, polyhydroxypropyl acrylate hydrogel or polyvinylpyrrolidone hydrogel.
Preferably, the temperature-sensitive glucan-based hydrogel further contains an active pharmaceutical ingredient.
Preferably, the active pharmaceutical ingredient is one or more of small molecule drugs, proteins, peptides, genes, antibodies, anesthetics, vaccines and polysaccharide synthetic inorganic compounds.
Preferably, the small molecular drug is one or more of ciprofloxacin, aspirin, levofloxacin or norfloxacin.
Preferably, the protein is insulin.
The invention provides a preparation method of the temperature-sensitive glucan-based hydrogel, which comprises the following steps:
(1) preparing 5-10 wt% of aqueous solution containing temperature-sensitive hydrogel monomers and 0.1-1 wt% of N, N-methylene acrylamide, uniformly mixing to obtain mixed solution, adding 3-10 wt% of ammonium persulfate aqueous solution, and uniformly mixing, wherein the volume ratio of the ammonium persulfate aqueous solution to the mixed solution is 1-7: 100;
(2) adding tetramethylethylenediamine into the solution obtained in the step (1), uniformly mixing, and standing to obtain temperature-sensitive hydrogel; the volume ratio of the tetramethylethylenediamine to the solution obtained in the step (1) is 0.8-6: 100;
(3) placing the temperature-sensitive hydrogel into a mixed aqueous solution of tannic acid and glucan and standing to obtain the temperature-sensitive glucan-based hydrogel; in the mixed aqueous solution of the tannic acid and the glucan, the mass fraction of the tannic acid is 0.2-4%, and the mass fraction of the glucan is 1-60%.
Preferably, the temperature-sensitive hydrogel monomer in the step (1) is N-isopropylacrylamide, carbinyl acrylate, hydroxypropyl acrylate or vinyl pyrrolidone.
Preferably, the crosslinking agent in the step (1) is N, N-methylene acrylamide, N-hydroxymethyl acrylamide, diacetone acrylamide or polyethylene glycol diacrylate.
Preferably, the initiator in the step (1) is ammonium persulfate or potassium persulfate.
Preferably, the molecular weight of the glucan is less than or equal to 5000.
Preferably, the standing time in the step (2) is 10-60 min; and (4) standing for 10-60 min.
Preferably, the mixed solution in the step (1) further contains 0.8-4 wt% of NaHCO3And after the step (3) is finished, soaking the obtained temperature-sensitive glucan-based hydrogel in hot water with the temperature of more than or equal to 50 ℃, standing for 1-10 min, and then soaking in cold water to restore the original shape, wherein the temperature of the cold water is 10-30 ℃. NaHCO added3The obtained temperature-sensitive glucan-based hydrogel has a porous structure.
Preferably, after the step (3) is finished, the obtained temperature-sensitive glucan-based hydrogel can be subjected to vacuum freeze drying at-25 to-60 ℃ for 10 to 60 min. And the temperature-sensitive glucan-based hydrogel with a porous structure can be obtained.
Preferably, the mixed solution in the step (1) further contains 0.3 to 4 wt% of polyethylene glycol (PEG), and a step of replacing the PEG in the temperature-sensitive hydrogel with water is further included between the step (2) and the step (3), where the replacement method is as follows: and soaking the temperature-sensitive hydrogel in clear water for 10-30 min, taking out, and soaking in clear water again for 2-6 times. And the temperature-sensitive glucan-based hydrogel with a porous structure can be obtained.
Preferably, the mixed aqueous solution of tannic acid and glucan in the step (3) further contains 0.3-40 wt% of active pharmaceutical ingredients.
The invention has the beneficial effects that:
the temperature-sensitive glucan-based hydrogel dressing provided by the invention has the effects of resisting bacteria and diminishing inflammation, can keep moisture of a wound, can absorb exudate of the wound, and is not adhered to the wound, so that new granulation or epithelial tissues cannot be damaged during dressing change, and the adopted raw materials are safe and have no toxic or side effect.
In addition, the temperature-sensitive glucan-based hydrogel dressing provided by the invention takes tannic acid as a cross-linking agent, and glucan is added to form double-network gel, so that the temperature-sensitive glucan-based hydrogel dressing is high in mechanical property and not easy to damage.
Can realize the controllable release of the medicine, flexibly control the release of the medicine along with the local temperature change of the inflammation part, can adsorb wound exudate, has good biocompatibility and surface lubrication performance, biodegradability and no environmental pollution.
The prepared porous temperature-sensitive glucan-based hydrogel dressing has a porous structure, is better in air permeability, is not easy to breed bacteria, and is more beneficial to wound healing.
Drawings
FIG. 1 is a graph comparing the shape change of the temperature-sensitive dextran-based hydrogel in hot water and cold water, wherein the right graph shows the temperature-sensitive dextran-based hydrogel in cold water, and the left graph shows the temperature-sensitive dextran-based hydrogel at 50 ℃.
FIG. 2 is a graph showing the effect of temperature on the size of hydrogel diameter as measured in example 9.
FIG. 3 is a graph of the stress profile of the hydrogel tested in example 10, where Curve 1 is the stress profile of the dextran-based hydrogel and Curve 2 is the stress profile of the hydrogel without dextran.
FIG. 4 is a scanning electron micrograph of the porous temperature-sensitive dextran-based hydrogel prepared in example 1.
Detailed Description
EXAMPLE 1 preparation of porous temperature-sensitive dextran-based hydrogel
(1) Preparing 5 mass percent of ammonium persulfate aqueous solution, and then preparing a mixed solution containing 6.6 mass percent of N-isopropylacrylamide and 0.33 mass percent of N, N-methylene acrylamide by using 4.5ml of deionized water. After the obtained mixed solution is uniformly mixed on a rotary oscillator, 135 mu L of the prepared ammonium persulfate aqueous solution is rapidly added and is rapidly and uniformly mixed on the rotary oscillator, and the volume ratio of the added ammonium persulfate solution to the mixed solution is 3: 100.
(2) Adding tetramethylethylenediamine into the solution obtained in the step (1), wherein the volume ratio of tetraethyldiamine to the solution obtained in the step (1) is 2: 100. And quickly and uniformly mixing the obtained solution on a rotary oscillator, quickly pouring the mixture into a mould, and standing for 30min to obtain the temperature-sensitive hydrogel.
(3) Taking out the formed hydrogel from the mold, and standing in a mixed solution containing 0.3 wt% of tannic acid and 10 wt% of dextran for 60min to obtain dextran with average molecular weight of 5000. Standing to obtain the temperature-sensitive glucan-based hydrogel.
(4) Placing the obtained temperature-sensitive glucan-based hydrogel in a vacuum freeze dryer, and freeze-drying at-60 ℃ for 10 min.
Example 2 preparation of porous temperature-sensitive dextran-based hydrogel
(1) Preparing 5 percent of ammonium persulfate aqueous solution by mass, preparing 6.6 percent of N-isopropylacrylamide, 0.33 percent of N, N-methylene acrylamide and 1 percent of NaHCO by using 4.5ml of deionized water3The mixed solution of (1). The obtained mixed solution is oscillated by rotationAfter being mixed uniformly on the device, 135 mul of prepared ammonium persulfate aqueous solution is quickly added and mixed uniformly on a rotary oscillator, and the volume ratio of the added ammonium persulfate solution to the mixed solution is 3: 100.
(2) Adding tetramethylethylenediamine into the solution obtained in the step (1), wherein the volume ratio of tetraethyldiamine to the solution obtained in the step (1) is 2: 100. And quickly and uniformly mixing the obtained solution on a rotary oscillator, quickly pouring the mixture into a mould, and standing for 30min to obtain the temperature-sensitive hydrogel.
(3) Taking out the formed hydrogel from the mold, and standing in a mixed solution containing 0.3 wt% of tannic acid and 3 wt% of glucan for 60min, wherein the average molecular weight of glucan is less than 5000.
(4) Soaking the obtained temperature-sensitive dextran-based hydrogel in 50 deg.C hot water, standing for 5min, and soaking in 10 deg.C cold water to recover its original shape.
Example 3 preparation of porous temperature-sensitive dextran-based hydrogel
(1) 0.1ml of deionized water is used for preparing a potassium persulfate solution with the mass fraction of 3 percent, and 10ml of deionized water is used for preparing a mixed solution containing 5 percent of Carbamyl acrylate and 0.1 percent of N-hydroxymethyl acrylamide. After the obtained mixed solution is uniformly mixed on a rotary oscillator, the prepared potassium persulfate solution is quickly added and is quickly and uniformly mixed on the rotary oscillator.
(2) Adding tetramethylethylenediamine into the solution obtained in the step (1), wherein the volume ratio of tetraethyldiamine to the solution obtained in the step (1) is 0.8: 100. And quickly and uniformly mixing the obtained solution on a rotary oscillator, quickly pouring the mixture into a mould, and standing for 10min to obtain the temperature-sensitive hydrogel.
(3) Taking out the formed hydrogel from the mold, and standing for 60min in a mixed solution containing 0.2 wt% of tannic acid, 1 wt% of glucan and 0.3 wt% of ciprofloxacin, wherein the average molecular weight of glucan is less than 5000. Standing to obtain the temperature-sensitive glucan-based hydrogel.
(4) Placing the obtained temperature-sensitive glucan-based hydrogel in a vacuum freeze dryer, and freeze-drying at-25 ℃ for 60 min.
Example 4 preparation of porous temperature-sensitive dextran-based hydrogel
(1) Preparing 10 percent of potassium persulfate solution by using 1ml of deionized water, and preparing 10 percent of hydroxypropyl acrylate, 1 percent of diacetone acrylamide and 0.8 percent of NaHCO by using 20ml of deionized water3The mixed solution of (1). After the obtained mixed solution is uniformly mixed on a rotary oscillator, the prepared potassium persulfate solution is quickly added and is quickly and uniformly mixed on the rotary oscillator.
(2) Adding tetramethylethylenediamine into the solution obtained in the step (1), wherein the volume ratio of tetraethyldiamine to the solution obtained in the step (1) is 6: 100. And quickly and uniformly mixing the obtained solution on a rotary oscillator, quickly pouring the mixture into a mould, and standing for 60min to obtain the temperature-sensitive hydrogel.
(3) Taking out the formed hydrogel from the mold, and standing in a mixed solution containing tannic acid 4 wt%, dextran 60 wt% and insulin 2 wt% for 40min, wherein the average molecular weight of dextran is less than 5000.
(4) Soaking the obtained temperature-sensitive dextran-based hydrogel in 80 deg.C hot water, standing for 1min, and soaking in 30 deg.C cold water to recover its original shape.
Example 5 preparation of porous temperature-sensitive Glucan-based hydrogel
(1) 0.7ml deionized water is used for preparing 7 percent ammonium persulfate solution, 10ml deionized water is used for preparing 8 percent vinyl pyrrolidone, 0.6 percent polyethylene glycol diacrylate and 4 percent NaHCO3The mixed solution of (1). And after the obtained mixed solution is uniformly mixed on a rotary oscillator, quickly adding the prepared ammonium persulfate solution and quickly and uniformly mixing on the rotary oscillator.
(2) Adding tetramethylethylenediamine into the solution obtained in the step (1), wherein the volume ratio of tetraethyldiamine to the solution obtained in the step (1) is 4: 100. And quickly and uniformly mixing the obtained solution on a rotary oscillator, quickly pouring the mixture into a mould, and standing for 40min to obtain the temperature-sensitive hydrogel.
(3) Taking out the formed hydrogel from the mold, and standing in a mixed solution containing 1 wt% of tannic acid, 6 wt% of dextran and 10 wt% of artificial interferon for 10min, wherein the average molecular weight of dextran is less than 5000.
(4) Soaking the obtained temperature-sensitive dextran-based hydrogel in 80 deg.C hot water, standing for 10min, and soaking in 20 deg.C cold water to recover its original shape.
Example 6 preparation of porous temperature-sensitive Glucan-based hydrogel
(1) 0.2ml of deionized water is used for preparing an ammonium persulfate solution with the mass fraction of 4 percent, and 10ml of deionized water is used for preparing a mixed solution containing 7 percent of N-isopropylacrylamide, 0.8 percent of diacetone acrylamide and 0.3 percent of polyethylene glycol. And after the obtained mixed solution is uniformly mixed on a rotary oscillator, quickly adding the prepared ammonium persulfate solution and quickly and uniformly mixing on the rotary oscillator.
(2-1) adding tetramethylethylenediamine into the solution obtained in the step (1), wherein the volume ratio of the tetraethyldiamine to the solution obtained in the step (1) is 1: 100. And quickly and uniformly mixing the obtained solution on a rotary oscillator, quickly pouring the mixture into a mould, and standing for 20min to obtain the temperature-sensitive hydrogel.
(2-2) taking out the formed hydrogel from the mold, then soaking the temperature-sensitive hydrogel in clear water for 10min, then taking out the hydrogel and soaking the hydrogel in clear water again for 6 times, and replacing polyethylene glycol in the temperature-sensitive hydrogel with water.
(3) Placing the hydrogel into a mixed solution containing 0.5 wt% of tannic acid, 20 wt% of dextran and 40% of anesthetic, and standing for 20min, wherein the average molecular weight of dextran is less than 5000.
Example 7 preparation of porous temperature-sensitive Glucan-based hydrogel
(1) 0.6ml of deionized water is used for preparing 6 percent of ammonium persulfate solution, and 10ml of deionized water is used for preparing a mixed solution containing 9 percent of Carbamyl acrylate, 0.2 percent of N-hydroxymethyl acrylamide and 4 percent of polyethylene glycol. And after the obtained mixed solution is uniformly mixed on a rotary oscillator, quickly adding the prepared ammonium persulfate solution and quickly and uniformly mixing on the rotary oscillator.
(2-1) adding tetramethylethylenediamine into the solution obtained in the step (1), wherein the volume ratio of the tetraethyldiamine to the solution obtained in the step (1) is 2: 100. And quickly and uniformly mixing the obtained solution on a rotary oscillator, quickly pouring the mixture into a mould, and standing for 30min to obtain the temperature-sensitive hydrogel.
(2-2) taking out the formed hydrogel from the mold, then soaking the temperature-sensitive hydrogel in clear water for 30min, then taking out the hydrogel and soaking the hydrogel in clear water again for 2 times, and replacing polyethylene glycol in the temperature-sensitive hydrogel with water.
(3) Placing the hydrogel into a mixed solution containing tannic acid 2 wt%, dextran 40 wt% and vaccine 40 wt%, and standing for 50min, wherein the average molecular weight of dextran is less than 5000.
Example 8 preparation of temperature sensitive Glucan-based hydrogel
(1) Preparing 5 mass percent of ammonium persulfate aqueous solution, and then preparing a mixed solution containing 6.6 mass percent of N-isopropylacrylamide and 0.33 mass percent of N, N-methylene acrylamide by using 4.5ml of deionized water. After the obtained mixed solution is uniformly mixed on a rotary oscillator, 135 mu L of the prepared ammonium persulfate aqueous solution is rapidly added and is rapidly and uniformly mixed on the rotary oscillator, and the volume ratio of the added ammonium persulfate solution to the mixed solution is 3: 100.
(2) Adding tetramethylethylenediamine into the solution obtained in the step (1), wherein the volume ratio of tetraethyldiamine to the solution obtained in the step (1) is 2: 100. And quickly and uniformly mixing the obtained solution on a rotary oscillator, quickly pouring the mixture into a mould, and standing for 30min to obtain the temperature-sensitive hydrogel.
(3) Taking out the formed hydrogel from the mold, and standing in a mixed solution containing 0.3 wt% of tannic acid and 10 wt% of dextran for 60min to obtain dextran with average molecular weight of 5000. Standing to obtain the temperature-sensitive glucan-based hydrogel.
Example 9
This example generally employs the method described in example 1 above to prepare a temperature sensitive dextran-based hydrogel, except that an additional portion of the hydrogel is prepared without dextran, i.e., steps (3) and (4) are eliminated. The temperature was adjusted in a water bath and the change in diameter of the two hydrogels with temperature was measured.
The temperature sensitive glucan-based hydrogel is obviously reduced in warm water at 36-37 ℃ and approaches the temperature of a human body, so that the effect of controllable release of the medicine is achieved.
Example 10
This example generally employs the method described in example 1 above to prepare a dextran-based hydrogel, except that an additional portion of the hydrogel is prepared without dextran, i.e., steps (3) and (4) are eliminated.
And (3) measuring the pressure bearing degree of the two hydrogels by adopting a universal tensile machine. The result shows that the temperature-sensitive hydrogel added with the glucan bears about 20N of pressure compared with the common hydrogel without the glucan, and the mechanical property of the glucan-based hydrogel is obviously improved.
Claims (13)
1. The temperature-sensitive glucan-based hydrogel is characterized in that the temperature-sensitive glucan-based hydrogel is a double-network gel formed by temperature-sensitive hydrogel and glucan by using tannic acid as a cross-linking agent;
the molecular weight of the glucan is less than or equal to 5000.
2. The temperature-sensitive dextran-based hydrogel according to claim 1, wherein said temperature-sensitive dextran-based hydrogel is a porous temperature-sensitive dextran-based hydrogel.
3. The temperature-sensitive dextran-based hydrogel according to claim 1, wherein said temperature-sensitive hydrogel is a poly N-isopropylacrylamide hydrogel, a poly (carbopol acrylate) hydrogel, a poly (hydroxypropyl acrylate) hydrogel or a polyvinylpyrrolidone hydrogel.
4. The temperature-sensitive dextran-based hydrogel according to claim 1, wherein said temperature-sensitive dextran-based hydrogel further comprises an active pharmaceutical ingredient.
5. The temperature-sensitive dextran-based hydrogel according to claim 4, wherein said active drug ingredient is one or more of a small molecule drug, a protein, a peptide, a gene, an antibody, an anesthetic, a vaccine, a polysaccharide or a synthetic inorganic compound.
6. The temperature-sensitive dextran-based hydrogel according to claim 5, wherein the preferred small molecule drug is one or more of ciprofloxacin, aspirin, levofloxacin or norfloxacin.
7. A method of preparing a temperature-sensitive dextran-based hydrogel according to any of claims 1-6, comprising the steps of:
(1) preparing an aqueous solution containing 5-10 wt% of temperature-sensitive hydrogel monomer and 0.1-1 wt% of cross-linking agent, uniformly mixing to obtain a mixed solution, adding an initiator aqueous solution with the mass fraction of 3-10%, and uniformly mixing, wherein the volume ratio of the initiator aqueous solution to the mixed solution is 1-7: 100;
(2) adding tetramethylethylenediamine into the solution obtained in the step (1), uniformly mixing, and standing to obtain temperature-sensitive hydrogel; the volume ratio of the tetramethylethylenediamine to the solution obtained in the step (1) is 0.8-6: 100;
(3) placing the temperature-sensitive hydrogel into a mixed aqueous solution of tannic acid and glucan and standing to obtain the temperature-sensitive glucan-based hydrogel; in the mixed aqueous solution of the tannic acid and the glucan, the mass fraction of the tannic acid is 0.2-4%, and the mass fraction of the glucan is 1-60%.
8. The method according to claim 7, wherein the temperature-sensitive hydrogel monomer is N-isopropylacrylamide, carbinyl acrylate, hydroxypropyl acrylate, or vinyl pyrrolidone; the cross-linking agent is N, N-methylene acrylamide, N-hydroxymethyl acrylamide, diacetone acrylamide or polyethylene glycol diacrylate; the initiator is ammonium persulfate or potassium persulfate.
9. The method according to claim 7, wherein the standing time in the step (2) is 10-60 min; and (4) standing for 10-60 min.
10. The method as claimed in claim 7, wherein the mixed aqueous solution of tannic acid and glucan of step (3) further comprises 0.3 to 40% by weight of an active pharmaceutical ingredient.
11. The method according to any one of claims 7 to 10, wherein the mixed solution of step (1) further comprises 0.8 to 4% by weight of NaHCO3And after the step (3) is finished, soaking the obtained temperature-sensitive glucan-based hydrogel in hot water with the temperature of more than or equal to 50 ℃, standing for 1-10 min, and then soaking in cold water to restore the original shape, wherein the temperature of the cold water is 10-30 ℃.
12. The method according to any one of claims 7 to 10, wherein after the completion of step (3), the temperature-sensitive glucan-based hydrogel obtained is subjected to vacuum freeze drying at-25 to-60 ℃ for 10 to 60 min.
13. The method according to any one of claims 7 to 10, wherein the mixed solution in step (1) further contains 0.3 to 4 wt% of polyethylene glycol, and further comprises a step of replacing the polyethylene glycol in the temperature-sensitive hydrogel with water between step (2) and step (3), wherein the replacement method comprises: and soaking the temperature-sensitive hydrogel in clear water for 10-30 min, taking out, and soaking in clear water again for 2-6 times.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103347901A (en) * | 2010-11-29 | 2013-10-09 | 生物科技药物学会 | Glucan compositions |
| CN104530336A (en) * | 2015-01-17 | 2015-04-22 | 杨俊� | Method for synthesizing heat-sensitive and biodegradable hydrogel |
| CN105462142A (en) * | 2016-01-15 | 2016-04-06 | 复旦大学 | Thermo-sensitive type interpenetrating polymer network hydrogel material and preparation method and application thereof |
| CN106039382A (en) * | 2016-05-25 | 2016-10-26 | 东华大学 | Glucan-based transparent hydrogel dressing and preparation method thereof |
-
2018
- 2018-04-11 CN CN201810318950.7A patent/CN108310452B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103347901A (en) * | 2010-11-29 | 2013-10-09 | 生物科技药物学会 | Glucan compositions |
| CN104530336A (en) * | 2015-01-17 | 2015-04-22 | 杨俊� | Method for synthesizing heat-sensitive and biodegradable hydrogel |
| CN105462142A (en) * | 2016-01-15 | 2016-04-06 | 复旦大学 | Thermo-sensitive type interpenetrating polymer network hydrogel material and preparation method and application thereof |
| CN106039382A (en) * | 2016-05-25 | 2016-10-26 | 东华大学 | Glucan-based transparent hydrogel dressing and preparation method thereof |
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