CN112480417A - Natural polymer-based injectable hydrogel and preparation method thereof - Google Patents
Natural polymer-based injectable hydrogel and preparation method thereof Download PDFInfo
- Publication number
- CN112480417A CN112480417A CN201910860343.8A CN201910860343A CN112480417A CN 112480417 A CN112480417 A CN 112480417A CN 201910860343 A CN201910860343 A CN 201910860343A CN 112480417 A CN112480417 A CN 112480417A
- Authority
- CN
- China
- Prior art keywords
- aqueous solution
- polymer
- reaction
- injectable hydrogel
- hyperbranched polymer
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G81/00—Macromolecular compounds obtained by interreacting polymers in the absence of monomers, e.g. block polymers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/16—Macromolecular materials obtained by reactions only involving carbon-to-carbon unsaturated bonds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/20—Polysaccharides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/52—Hydrogels or hydrocolloids
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G65/00—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule
- C08G65/02—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule from cyclic ethers by opening of the heterocyclic ring
- C08G65/32—Polymers modified by chemical after-treatment
- C08G65/329—Polymers modified by chemical after-treatment with organic compounds
- C08G65/337—Polymers modified by chemical after-treatment with organic compounds containing other elements
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/06—Flowable or injectable implant compositions
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Dermatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Transplantation (AREA)
- Inorganic Chemistry (AREA)
- Polymers & Plastics (AREA)
- Organic Chemistry (AREA)
- Dispersion Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Preparation (AREA)
- Materials For Medical Uses (AREA)
Abstract
The invention discloses a natural polymer-based injectable hydrogel and a preparation method thereof. Specifically, the hyperbranched polymer PEGDA-PBA is synthesized to be used as a crosslinking agent of the injectable hydrogel through RAFT active polymerization of polyethylene glycol diacrylate (PEGDA) and phenylboronic acid (PBA); then, the Michael addition reaction is carried out between sulfydryl on sulfhydrylated hyaluronic acid (HA-SH) and double bonds on polyethylene glycol diacrylate (PEGDA), so that the in-situ crosslinking of the hydrogel is realized, the conversion from liquid state to semisolid gel is completed, and the injectable purpose is achieved. The preparation method of the gel is simple, the reaction condition is mild, the biocompatibility is good, and the strength of the gel can be adjusted by controlling the solid content of the hyperbranched polymer.
Description
Technical Field
The invention relates to a natural polymer-based injectable hydrogel and a preparation method thereof, in particular to a method for preparing the injectable hydrogel by carrying out Michael addition reaction on sulfydryl hyaluronic acid (HA-SH) and double bonds on polyethylene glycol diacrylate (PEGDA).
Background
Hyaluronic acid, as a hydrogel material derived from natural sources, has excellent biocompatibility, and is currently applied to tissue engineering relatively mature. However, they are unstable in physicochemical properties and are easily catabolized in vivo.
Phenylboronic acid (PBA) has proved to have excellent properties in terms of drug loading, which can make As-IV obtain firmer combination by combining with the diol structure on the drug (such As astragaloside IV-As-IV), and can destroy the conjugated structure in a slightly acidic environment, thereby promoting the slow release of As-IV, and the properties can be applied to the slow release of the drug.
Polyethylene glycol diacrylate (PEGDA) is considered to be biologically inert ("slate blank") and its mechanical properties can vary over a wide range of moduli. PEGDA is an emerging scaffold for tissue engineering and regenerative medicine, and can be used as a substrate to modify various functional monomers.
The Michael addition reaction of the double bond of PEGDA and the sulfhydryl of HA-SH HAs mild reaction conditions, high reaction speed, quick gelling and convenient in-situ injection.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and aims to produce a three-dimensional network by using the Michael addition reaction between the double bond of PEGDA and the sulfhydryl of HA-SH to prepare the natural polymer-based injectable hydrogel.
The technical purpose of the invention is realized by the following technical scheme.
The invention relates to a natural polymer-based injectable hydrogel and a preparation method thereof, which are carried out according to the following steps:
(1) fully dissolving polyethylene glycol diacrylate (PEGDA), phenylboronic acid (PBA), tetraethylthiuram Disulfide (DS) and Azobisisobutyronitrile (AIBN) in an N, N-Dimethylformamide (DMF) solvent, wherein the molar ratio of the four is 30 (10-40) to 1:2, and carrying out RAFT polymerization on the polyethylene glycol diacrylate (PEGDA) and the phenylboronic acid (PBA) in an anhydrous oxygen-free sealed reaction system and in an oil bath to generate a hyperbranched polymer (PEGDA-PBA);
(2) uniformly mixing the aqueous solution of the hyperbranched polymer (PEGDA-PBA) prepared in the step (1) with the aqueous solution of the thiolated hyaluronic acid (HA-SH), wherein the mass ratio of the hyperbranched polymer (PEGDA-PBA) to the thiolated hyaluronic acid (HA-SH) is (10-20): and 1, sufficiently reacting to enable carbon-carbon double bonds on the hyperbranched polymer (PEGDA-PBA) to perform Michael addition reaction with sulfydryl on the sulfhydrylated hyaluronic acid to form a conjugated structure so as to generate the three-dimensional reticular stereo polymer.
In the step (1), the molar ratio of polyethylene glycol diacrylate (PEGDA), phenylboronic acid (PBA), tetraethylthiuram Disulfide (DS) and Azobisisobutyronitrile (AIBN) is 30:20:1: 2.
In the step (1), a two-section one-pot reaction is adopted, polyethylene glycol diacrylate (PEGDA), tetraethylthiuram Disulfide (DS) and Azobisisobutyronitrile (AIBN) are fully dissolved in N, N-Dimethylformamide (DMF) solvent, and the mixture reacts in an anhydrous oxygen-free sealed reaction system and in an oil bath at 70-90 ℃ for 3-5 hours; then adding phenylboronic acid (PBA), and continuing to react for 4-6h in an anhydrous oxygen-free sealed reaction system and in an oil bath at 70-90 ℃.
After the reaction in the step (1) is finished, cooling the system to room temperature, purifying the reaction solution by using a mixed solution of glacial ethyl ether and n-hexane in a volume ratio of 1:1, and washing the lower-layer precipitated liquid by using the glacial ethyl ether.
In the step (2), the mass percent concentration of the aqueous solution of the hyperbranched polymer (PEGDA-PBA) is 10 wt%, the mass percent concentration of the aqueous solution of the thiolated hyaluronic acid (HA-SH) is 1 wt%, and the two are blended according to the volume ratio of 1: 1; fully carrying out the reaction by vortex stirring; the gelling temperature is room temperature, and the gelling time is 3-5 min.
The invention has the beneficial effects that: the hydrogel preparation method is simple, the reaction conditions are mild, the prepared hydrogel has good biocompatibility, the strength of the hydrogel can be adjusted by controlling the solid content of the hyperbranched polymer, and the natural polymer-based injectable hydrogel prepared by the method can be applied to the medical fields of drug sustained release, tissue engineering, regenerative medicine and the like.
Drawings
FIG. 1 shows PEGDA-PBA1H-NMR spectrum;
FIG. 2 is an injectable schematic of a gel of 10 wt% PEGDA-PBA and 1 wt% HA-SH;
FIG. 3 is a time-scanning curve of a gel of 10 wt% PEGDA-PBA and 1 wt% HA-SH;
FIG. 4 is a frequency sweep plot of a gel of 10 wt% PEGDA-PBA and 1 wt% HA-SH.
Detailed Description
The following is a further description of the invention and is not intended to limit the scope of the invention.
The mass of the recovered material was determined in the following examples based on the number average molecular weight 700 of PEGDA-700 and the molar ratio of the individual components.
Example 1
The natural polymer-based injectable hydrogel and the preparation method thereof of the present invention are illustrated by taking the molar ratio of DS: AIBN: PEGDA: PBA ═ 1:2:30:20 as an example:
weighing 0.148g DS, 0.164g AIBN, 1.05g PEGDA-700 in a 50mL flask, and fully dissolving the raw materials with 30mL DMF; sealing the reaction system, repeatedly vacuumizing by using a vacuum nitrogen system and introducing nitrogen for two to three times to ensure that the reaction system has no water and oxygen, and carrying out oil bath at 80 ℃ for 4 hours; 0.148g of PBA is added into the reaction system, the reaction system is repeatedly vacuumized and filled with nitrogen again, and the reaction system is subjected to oil bath at the temperature of 80 ℃ for 5 hours; after the reaction is finished, cooling the reaction system to room temperature; purifying the reaction solution for 2-3 times by using ethyl acetate and n-hexane in a volume ratio of 1:1, and standing to separate out viscous liquid at the lower layer; washing the lower layer liquid with glacial ethyl ether for 2-3 times, and clarifying the upper layer ethyl ether washing liquid; removing the ether at the upper layer, placing the light yellow colloidal product at the lower layer into a small glass bottle, covering a preservative film with a small hole, standing for 2-3 days to volatilize the ether to obtain a polymer, and storing at-20 ℃.
Preparing PEGDA-PBA into 10 wt% aqueous solution, preparing HA-SH into 1 wt% aqueous solution, blending according to the volume ratio of 1:1, and performing vortex stirring to obtain gel.
Example 2
The natural polymer-based injectable hydrogel and the preparation method thereof of the present invention are illustrated by taking the molar ratio of DS: AIBN: PEGDA: PBA ═ 1:2:30:40 as an example:
weighing 0.148g DS, 0.164g AIBN, 1.05g PEGDA-700 in a 50mL flask, and fully dissolving the raw materials with 30mL DMF; sealing the reaction system, repeatedly vacuumizing by using a vacuum nitrogen system and introducing nitrogen for two to three times to ensure that the reaction system has no water and oxygen, and carrying out oil bath at 80 ℃ for 4 hours; 0.296g of PBA is added into the reaction system, the reaction system is repeatedly vacuumized and filled with nitrogen again, and the reaction system is subjected to oil bath for 5 hours at the temperature of 80 ℃; after the reaction is finished, cooling the reaction system to room temperature; purifying the reaction solution for 2-3 times by using ethyl acetate and n-hexane in a volume ratio of 1:1, and standing to separate out viscous liquid at the lower layer; washing the lower layer liquid with glacial ethyl ether for 2-3 times, and clarifying the upper layer ethyl ether washing liquid; removing the ether at the upper layer, placing the light yellow colloidal product at the lower layer into a small glass bottle, covering a preservative film with a small hole, standing for 2-3 days to volatilize the ether to obtain a polymer, and storing at-20 ℃.
Preparing PEGDA-PBA into 10 wt% aqueous solution, preparing HA-SH into 1 wt% aqueous solution, blending according to the volume ratio of 1:1, and performing vortex stirring to obtain gel.
Example 3
The natural polymer-based injectable hydrogel and the preparation method thereof of the present invention are illustrated by taking the molar ratio of DS: AIBN: PEGDA: PBA ═ 1:2:30:10 as an example:
weighing 0.148g DS, 0.164g AIBN, 1.05g PEGDA-700 in a 50mL flask, and fully dissolving the raw materials with 30mL DMF; sealing the reaction system, repeatedly vacuumizing by using a vacuum nitrogen system and introducing nitrogen for two to three times to ensure that the reaction system has no water and oxygen, and carrying out oil bath at 80 ℃ for 4 hours; 0.074g of PBA is added into the reaction system, the reaction system is repeatedly vacuumized and nitrogen is introduced, and the reaction system is subjected to oil bath at 80 ℃ for 5 hours; after the reaction is finished, cooling the reaction system to room temperature; purifying the reaction solution for 2-3 times by using ethyl acetate and n-hexane in a volume ratio of 1:1, and standing to separate out viscous liquid at the lower layer; washing the lower layer liquid with glacial ethyl ether for 2-3 times, and clarifying the upper layer ethyl ether washing liquid; removing the ether at the upper layer, placing the light yellow colloidal product at the lower layer into a small glass bottle, covering a preservative film with a small hole, standing for 2-3 days to volatilize the ether to obtain a polymer, and storing at-20 ℃.
Preparing PEGDA-PBA into 10 wt% aqueous solution, preparing HA-SH into 1 wt% aqueous solution, blending according to the volume ratio of 1:1, and performing vortex stirring to obtain gel.
By using1The chemical structure of the hyperbranched polymer PEGDA-PBA prepared in example 1 of the invention is characterized by H NMR, and as can be seen from figure 1, strong chemical shifts exist between 7.5 ppm and 8ppm, which are proton signals from a large number of grafted PBA benzene rings, thereby proving that PBA is successfully grafted on PEGDA, namely the hyperbranched polymer PEGDA-PBA is successfully synthesized; and the double bond peak near 6.0-6.5ppm indicates that the prepared hyperbranched polymer PEGDA-PBA still has carbon-carbon double bonds capable of generating Michael addition reaction as a crosslinking agent.
As can be seen from FIG. 2, the natural polymer-based hydrogel obtained in example 1 of the present invention was injectable.
The rheological properties of the hydrogel prepared in example 1 were also tested. FIG. 3 is a time-scan plot of a gel of 10 wt% PEGDA-PBA and 1 wt% HA-SH, under the test conditions: adding silicon oil to hold water at 37 ℃, carrying out 1% strain, and testing for 15 min. As can be seen from the results in FIG. 3, G' and G "have a point of intersection at 170s, indicating that a sol-gel transition has occurred and then the gel state is maintained. In addition, the gel strength increased gradually with time after gelling under the time sweep test carried out for 15min, with a final strength of 280Pa under the test conditions, which is favourable for gel injection. FIG. 4 is a frequency sweep plot of a gel formed from 10 wt% PEGDA-PBA and 1 wt% HA-SH at 37 deg.C under 1% strain with silicone oil added and frequency ranging from 0 to 100 rad/s. And after the time scanning test is finished, the frequency scanning is continued without changing the sample. As can be seen from the results in FIG. 4, the gel substantially maintained the gel state with increasing frequency, indicating that our gel was not easily damaged. Thus, it was confirmed that the hydrogel prepared according to the present invention was injectable.
Similar test results were obtained by performing the same test on samples prepared in other examples of the present invention.
The preparation of the natural polymer-based injectable hydrogel can be realized by adjusting the process parameters according to the content of the invention, and the performance of the hydrogel is basically consistent with that of the embodiment of the invention.
The invention has been described in an illustrative manner, and it is to be understood that any simple variations, modifications or other equivalent changes which can be made by one skilled in the art without departing from the spirit of the invention fall within the scope of the invention.
Claims (10)
1. A natural polymer-based injectable hydrogel, characterized by: the preparation method comprises the following steps:
(1) fully dissolving polyethylene glycol diacrylate, phenylboronic acid, tetraethylthiuram disulfide and azobisisobutyronitrile into an N, N-dimethylformamide solvent, wherein the molar ratio of the four is 30 (10-40) to 1:2, and carrying out RAFT polymerization on the polyethylene glycol diacrylate and the phenylboronic acid in an anhydrous oxygen-free sealed reaction system and in an oil bath to generate a hyperbranched polymer;
(2) uniformly mixing the aqueous solution of the hyperbranched polymer prepared in the step (1) with the aqueous solution of the thiolated hyaluronic acid, wherein the mass ratio of the hyperbranched polymer to the thiolated hyaluronic acid is (10-20): and 1, sufficiently reacting to enable the carbon-carbon double bonds on the hyperbranched polymer and the sulfydryl on the sulfhydrylated hyaluronic acid to generate Michael addition reaction to form a conjugated structure so as to generate the three-dimensional reticular stereo polymer.
2. The natural polymer-based injectable hydrogel according to claim 1, wherein: in the step (1), the molar ratio of the polyethylene glycol diacrylate, the phenylboronic acid, the tetraethylthiuram disulfide and the azobisisobutyronitrile is 30:20:1: 2.
3. The natural polymer-based injectable hydrogel according to claim 1, wherein: in the step (1), a two-section one-pot reaction is adopted, polyethylene glycol diacrylate, tetraethylthiuram disulfide and azobisisobutyronitrile are fully dissolved in an N, N-dimethylformamide solvent, and the mixture reacts in an anhydrous oxygen-free sealed reaction system and an oil bath at 70-90 ℃ for 3-5 hours; then adding phenylboronic acid, and continuously reacting for 4-6h in an anhydrous oxygen-free sealed reaction system and in an oil bath at 70-90 ℃.
4. The natural polymer-based injectable hydrogel according to claim 1, wherein: after the reaction in the step (1) is finished, cooling the system to room temperature, purifying the reaction solution by using a mixed solution of glacial ethyl ether and n-hexane in a volume ratio of 1:1, and washing the lower-layer precipitated liquid by using the glacial ethyl ether.
5. The natural polymer-based injectable hydrogel according to claim 1, wherein: in the step (2), the mass percent concentration of the hyperbranched polymer aqueous solution is 10 wt%, the mass percent concentration of the thiolated hyaluronic acid (HA-SH) aqueous solution is 1 wt%, and the hyperbranched polymer aqueous solution and the thiolated hyaluronic acid (HA-SH) aqueous solution are mixed according to the volume ratio of 1: 1; fully carrying out the reaction by vortex stirring; the gelling temperature is room temperature, and the gelling time is 3-5 min.
6. A preparation method of natural polymer-based injectable hydrogel is characterized by comprising the following steps: the method comprises the following steps:
(1) fully dissolving polyethylene glycol diacrylate, phenylboronic acid, tetraethylthiuram disulfide and azobisisobutyronitrile into an N, N-dimethylformamide solvent, wherein the molar ratio of the four is 30 (10-40) to 1:2, and carrying out RAFT polymerization on the polyethylene glycol diacrylate and the phenylboronic acid in an anhydrous oxygen-free sealed reaction system and in an oil bath to generate a hyperbranched polymer;
(2) uniformly mixing the aqueous solution of the hyperbranched polymer prepared in the step (1) with the aqueous solution of the thiolated hyaluronic acid, wherein the mass ratio of the hyperbranched polymer to the thiolated hyaluronic acid is (10-20): and 1, sufficiently reacting to enable the carbon-carbon double bonds on the hyperbranched polymer and the sulfydryl on the sulfhydrylated hyaluronic acid to generate Michael addition reaction to form a conjugated structure so as to generate the three-dimensional reticular stereo polymer.
7. The method for preparing the natural polymer-based injectable hydrogel according to claim 6, wherein: in the step (1), the molar ratio of the polyethylene glycol diacrylate, the phenylboronic acid, the tetraethylthiuram disulfide and the azobisisobutyronitrile is 30:20:1: 2.
8. The method for preparing the natural polymer-based injectable hydrogel according to claim 6, wherein: in the step (1), a two-section one-pot reaction is adopted, polyethylene glycol diacrylate, tetraethylthiuram disulfide and azobisisobutyronitrile are fully dissolved in an N, N-dimethylformamide solvent, and the mixture reacts in an anhydrous oxygen-free sealed reaction system and an oil bath at 70-90 ℃ for 3-5 hours; then adding phenylboronic acid, and continuously reacting for 4-6h in an anhydrous oxygen-free sealed reaction system and in an oil bath at 70-90 ℃.
9. The method for preparing the natural polymer-based injectable hydrogel according to claim 6, wherein: after the reaction in the step (1) is finished, cooling the system to room temperature, purifying the reaction solution by using a mixed solution of glacial ethyl ether and n-hexane in a volume ratio of 1:1, and washing the lower-layer precipitated liquid by using the glacial ethyl ether.
10. The method for preparing the natural polymer-based injectable hydrogel according to claim 6, wherein: in the step (2), the mass percent concentration of the hyperbranched polymer aqueous solution is 10 wt%, the mass percent concentration of the thiolated hyaluronic acid (HA-SH) aqueous solution is 1 wt%, and the hyperbranched polymer aqueous solution and the thiolated hyaluronic acid (HA-SH) aqueous solution are mixed according to the volume ratio of 1: 1; fully carrying out the reaction by vortex stirring; the gelling temperature is room temperature, and the gelling time is 3-5 min.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910860343.8A CN112480417A (en) | 2019-09-11 | 2019-09-11 | Natural polymer-based injectable hydrogel and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910860343.8A CN112480417A (en) | 2019-09-11 | 2019-09-11 | Natural polymer-based injectable hydrogel and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN112480417A true CN112480417A (en) | 2021-03-12 |
Family
ID=74919862
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910860343.8A Pending CN112480417A (en) | 2019-09-11 | 2019-09-11 | Natural polymer-based injectable hydrogel and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN112480417A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114773608A (en) * | 2022-04-18 | 2022-07-22 | 南京工业大学 | Long-acting hyaluronic acid for treating osteoarthritis and preparation method thereof |
| CN116162290A (en) * | 2023-03-09 | 2023-05-26 | 深圳丹伦基因科技有限公司 | Porous microcarrier, preparation method and application thereof |
| JP7463127B2 (en) | 2020-02-25 | 2024-04-08 | 株式会社日本触媒 | Crosslinked polymer, gel composition, cell culture material, method for producing cell population, and method for separating cell population |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20130059925A1 (en) * | 2010-03-09 | 2013-03-07 | Hemant Ravindran Nair | Biodegradable Polymeric Hydrogel Composition |
| CN105176080A (en) * | 2015-07-28 | 2015-12-23 | 南京微腾生物科技有限公司 | Injectable hydrogel with good biocompatibility, preparation method and applications |
| CN107987285A (en) * | 2016-10-26 | 2018-05-04 | 天津大学 | A kind of conduction injection aquagel and preparation method thereof |
| CN109666107A (en) * | 2017-10-16 | 2019-04-23 | 天津大学 | Polyethylene glycol -3- methacryl dopamine the dissaving polymer and preparation method thereof of catechol modification |
-
2019
- 2019-09-11 CN CN201910860343.8A patent/CN112480417A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20130059925A1 (en) * | 2010-03-09 | 2013-03-07 | Hemant Ravindran Nair | Biodegradable Polymeric Hydrogel Composition |
| CN105176080A (en) * | 2015-07-28 | 2015-12-23 | 南京微腾生物科技有限公司 | Injectable hydrogel with good biocompatibility, preparation method and applications |
| CN107987285A (en) * | 2016-10-26 | 2018-05-04 | 天津大学 | A kind of conduction injection aquagel and preparation method thereof |
| CN109666107A (en) * | 2017-10-16 | 2019-04-23 | 天津大学 | Polyethylene glycol -3- methacryl dopamine the dissaving polymer and preparation method thereof of catechol modification |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP7463127B2 (en) | 2020-02-25 | 2024-04-08 | 株式会社日本触媒 | Crosslinked polymer, gel composition, cell culture material, method for producing cell population, and method for separating cell population |
| CN114773608A (en) * | 2022-04-18 | 2022-07-22 | 南京工业大学 | Long-acting hyaluronic acid for treating osteoarthritis and preparation method thereof |
| CN116162290A (en) * | 2023-03-09 | 2023-05-26 | 深圳丹伦基因科技有限公司 | Porous microcarrier, preparation method and application thereof |
| CN116162290B (en) * | 2023-03-09 | 2024-05-28 | 深圳丹伦基因科技有限公司 | Porous microcarrier, preparation method and application thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN112480417A (en) | Natural polymer-based injectable hydrogel and preparation method thereof | |
| CN107428930B (en) | Method for producing low-concentration gel using gel precursor cluster, and gel obtained by the production method | |
| JP6106686B2 (en) | Water-insoluble gel composition and method for producing the same | |
| Geng et al. | Hierarchically designed injectable hydrogel from oxidized dextran, amino gelatin and 4-arm poly (ethylene glycol)-acrylate for tissue engineering application | |
| Jejurikar et al. | Degradable alginate hydrogels crosslinked by the macromolecular crosslinker alginate dialdehyde | |
| CN110522948B (en) | Injectable hydrogel and preparation method and application thereof | |
| CN109734851B (en) | Temperature-sensitive polymer, synthesis method thereof and temperature-sensitive injectable hydrogel | |
| CN112759774B (en) | Mechanically-enhanced gelatin frozen hydrogel and preparation method and application thereof | |
| CN113416326B (en) | Injectable hydrogel and preparation method and application thereof | |
| JP2017505366A (en) | Production of cross-linked poly α-1,3-glucan solution and poly α-1,3-glucan film produced therefrom | |
| CN109503768A (en) | A kind of preparation method of high tough sticky weather-resistance polyethylene alcohol radical double-network hydrogel | |
| CN106632855A (en) | Multifunctional high-strength gel and preparation method thereof | |
| MarieáVasquez | Hyperbranched PEG-based multi-NHS polymer and bioconjugation with BSA | |
| CN113248743B (en) | Biocompatible degradable three-dimensional cellulose gel, and preparation method and application thereof | |
| CN104231286B (en) | Double cross connection situ-gel based on modified PAMAM dendritic and preparation | |
| CN115040702B (en) | Temperature-sensitive injectable antibacterial hydrogel filler and preparation method thereof | |
| CN114437373B (en) | Amino acid composite free radical polymerization type hydrogel and preparation method and application thereof | |
| CN112480389B (en) | Low-oxygen responsive injectable hydrogel and preparation method thereof | |
| CN107840955B (en) | Conductive adhesive and preparation method thereof | |
| CN112538174B (en) | Injectable zwitterionic hydrogel and preparation method thereof | |
| JP2010174145A (en) | Method for producing xanthan gel and xanthan hydrogel | |
| CN113769159A (en) | Anhydrous calcium phosphate bone cement and preparation method thereof | |
| CN108586682B (en) | Hyperbranched polymer and preparation method thereof | |
| CN108623763B (en) | Hydrogel based on linear copolymers and use thereof | |
| CN115109275B (en) | Dynamic crosslinking degradable hydrogel, preparation method and application |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20210312 |
|
| RJ01 | Rejection of invention patent application after publication |