CN113072716A - Preparation method of photo-crosslinked chitosan hydrogel - Google Patents
Preparation method of photo-crosslinked chitosan hydrogel Download PDFInfo
- Publication number
- CN113072716A CN113072716A CN202110287161.3A CN202110287161A CN113072716A CN 113072716 A CN113072716 A CN 113072716A CN 202110287161 A CN202110287161 A CN 202110287161A CN 113072716 A CN113072716 A CN 113072716A
- Authority
- CN
- China
- Prior art keywords
- chitosan
- photo
- lipoic acid
- dissolving
- hydrogel
- 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
- 229920001661 Chitosan Polymers 0.000 title claims abstract description 104
- 239000000017 hydrogel Substances 0.000 title claims abstract description 57
- 238000002360 preparation method Methods 0.000 title claims abstract description 15
- 239000000243 solution Substances 0.000 claims abstract description 30
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 26
- 238000004132 cross linking Methods 0.000 claims abstract description 20
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 14
- 239000003960 organic solvent Substances 0.000 claims abstract description 12
- 150000001408 amides Chemical class 0.000 claims abstract description 9
- 239000003054 catalyst Substances 0.000 claims abstract description 6
- 238000001035 drying Methods 0.000 claims abstract description 5
- 238000002156 mixing Methods 0.000 claims abstract description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 60
- AGBQKNBQESQNJD-UHFFFAOYSA-N alpha-Lipoic acid Natural products OC(=O)CCCCC1CCSS1 AGBQKNBQESQNJD-UHFFFAOYSA-N 0.000 claims description 51
- 235000019136 lipoic acid Nutrition 0.000 claims description 51
- 229960002663 thioctic acid Drugs 0.000 claims description 51
- AGBQKNBQESQNJD-SSDOTTSWSA-N (R)-lipoic acid Chemical compound OC(=O)CCCC[C@@H]1CCSS1 AGBQKNBQESQNJD-SSDOTTSWSA-N 0.000 claims description 15
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 claims description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 9
- 239000008367 deionised water Substances 0.000 claims description 8
- 229910021641 deionized water Inorganic materials 0.000 claims description 8
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims description 8
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 6
- -1 hexafluorophosphate Chemical compound 0.000 claims description 5
- 238000003756 stirring Methods 0.000 claims description 5
- 239000000203 mixture Substances 0.000 claims description 4
- AZKVWQKMDGGDSV-BCMRRPTOSA-N Genipin Chemical compound COC(=O)C1=CO[C@@H](O)[C@@H]2C(CO)=CC[C@H]12 AZKVWQKMDGGDSV-BCMRRPTOSA-N 0.000 claims description 3
- AZKVWQKMDGGDSV-UHFFFAOYSA-N genipin Natural products COC(=O)C1=COC(O)C2C(CO)=CCC12 AZKVWQKMDGGDSV-UHFFFAOYSA-N 0.000 claims description 3
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- 238000000502 dialysis Methods 0.000 abstract description 7
- 238000006243 chemical reaction Methods 0.000 abstract description 5
- 230000009286 beneficial effect Effects 0.000 abstract description 2
- 239000002207 metabolite Substances 0.000 abstract description 2
- 235000015097 nutrients Nutrition 0.000 abstract description 2
- 239000011148 porous material Substances 0.000 abstract description 2
- 239000007864 aqueous solution Substances 0.000 abstract 1
- 230000005540 biological transmission Effects 0.000 abstract 1
- 239000007809 chemical reaction catalyst Substances 0.000 abstract 1
- 231100000252 nontoxic Toxicity 0.000 abstract 1
- 230000003000 nontoxic effect Effects 0.000 abstract 1
- 239000000126 substance Substances 0.000 abstract 1
- 238000004108 freeze drying Methods 0.000 description 8
- 230000005855 radiation Effects 0.000 description 6
- 239000002994 raw material Substances 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 5
- 239000000499 gel Substances 0.000 description 5
- 230000008439 repair process Effects 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 239000007821 HATU Substances 0.000 description 2
- 230000003078 antioxidant effect Effects 0.000 description 2
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 1
- VQNDBXJTIJKJPV-UHFFFAOYSA-N 2h-triazolo[4,5-b]pyridine Chemical compound C1=CC=NC2=NNN=C21 VQNDBXJTIJKJPV-UHFFFAOYSA-N 0.000 description 1
- 208000005156 Dehydration Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 1
- 208000028389 Nerve injury Diseases 0.000 description 1
- 208000028990 Skin injury Diseases 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 238000005452 bending Methods 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 125000002228 disulfide group Chemical group 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 230000008764 nerve damage Effects 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 231100000241 scar Toxicity 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- 208000020431 spinal cord injury Diseases 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 238000009281 ultraviolet germicidal irradiation Methods 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J3/00—Processes of treating or compounding macromolecular substances
- C08J3/02—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques
- C08J3/03—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques in aqueous media
- C08J3/075—Macromolecular 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
- A61L27/20—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
-
- 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
- A61L27/56—Porous materials, e.g. foams or sponges
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
- C08B37/0006—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid
- C08B37/0024—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid beta-D-Glucans; (beta-1,3)-D-Glucans, e.g. paramylon, coriolan, sclerotan, pachyman, callose, scleroglucan, schizophyllan, laminaran, lentinan or curdlan; (beta-1,6)-D-Glucans, e.g. pustulan; (beta-1,4)-D-Glucans; (beta-1,3)(beta-1,4)-D-Glucans, e.g. lichenan; Derivatives thereof
- C08B37/0027—2-Acetamido-2-deoxy-beta-glucans; Derivatives thereof
- C08B37/003—Chitin, i.e. 2-acetamido-2-deoxy-(beta-1,4)-D-glucan or N-acetyl-beta-1,4-D-glucosamine; Chitosan, i.e. deacetylated product of chitin or (beta-1,4)-D-glucosamine; Derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J3/00—Processes of treating or compounding macromolecular substances
- C08J3/28—Treatment by wave energy or particle radiation
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J2305/00—Characterised by the use of polysaccharides or of their derivatives not provided for in groups C08J2301/00 or C08J2303/00
- C08J2305/08—Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Dispersion Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Transplantation (AREA)
- Organic Chemistry (AREA)
- Polymers & Plastics (AREA)
- Animal Behavior & Ethology (AREA)
- Dermatology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Materials Engineering (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention provides a preparation method of photo-crosslinking chitosan hydrogel, which comprises the steps of mixing a chitosan ethanol solution with a lipoic acid-organic solvent solution, adding an amide reaction catalyst after the chitosan ethanol solution and the lipoic acid-organic solvent solution are uniformly mixed, carrying out dialysis and drying treatment after complete reaction to obtain water-soluble chitosan, dissolving the water-soluble chitosan in an aqueous solution, and obtaining the hydrogel under ultraviolet irradiation. The water solution of the water-soluble chitosan prepared by the invention can be quickly gelled under the ultraviolet irradiation, does not need to add other catalysts, is safe and nontoxic, has good biocompatibility, better mechanical strength and good pore structure, and is beneficial to the transmission and transportation of nutrient substances and the discharge of metabolites.
Description
Technical Field
The invention relates to the technical field of hydrogel preparation, in particular to a preparation method of photo-crosslinking chitosan hydrogel.
Background
Chitosan is the only basic polysaccharide in nature, has good biocompatibility and biodegradability, can be widely applied to repairing of wound tissues (such as skin, nerves and the like), can effectively eliminate scar tissues, but has poor water solubility, and the application of the chitosan is severely limited, so that the preparation of water-soluble chitosan is one of the development directions of the chitosan.
Lipoic acid is a sulfur-containing fatty acid, is called as 'super antioxidant', has a more durable antioxidant effect, and can protect nerve cells in nerve injury caused by diabetes and prevent inflammation caused by protein deposition.
The hydrogel is a three-dimensional network formed by water-insoluble highly-crosslinked hydrophilic polymerization, has good action effect and application prospect in the fields of skin injury repair, spinal cord injury repair and the like similar to soft tissues, can effectively fill damaged areas due to rapid forming of the photo-crosslinked hydrogel and no need of adding other catalysts in the forming process, and is widely applied in the field of biological materials, but the water solubility of chitosan is poor, so that the photo-crosslinking property of the hydrogel is limited.
Disclosure of Invention
In view of the above, the present invention is directed to a method for preparing a photo-crosslinked chitosan hydrogel, in which lipoic acid is grafted onto chitosan through an amide reaction to obtain water-soluble chitosan, the modified chitosan contains disulfide groups of lipoic acid, and disulfide bonds are broken and reconstructed under ultraviolet illumination to form the photo-crosslinked chitosan hydrogel, thereby effectively solving the problems of poor water solubility, limitation of photo-crosslinking property, and the like of the existing chitosan.
In order to achieve the purpose, the technical scheme of the invention is realized as follows:
a preparation method of photo-crosslinking chitosan hydrogel comprises the following steps:
1) dissolving chitosan in an acetic acid solution, dissolving thioctic acid in an organic solvent, then mixing, stirring to uniformly mix, adding an amide catalyst, reacting for a period of time, dialyzing in deionized water to remove unreacted lipoic acid, acetic acid and the organic solvent, and drying to obtain lipoic acid modified chitosan;
2) and dissolving the lipoic acid modified chitosan in water, and reacting under the irradiation of ultraviolet light to obtain the photocrosslinking chitosan hydrogel.
Optionally, the solvent for dissolving lipoic acid in step 1) is one of methanol, ethanol, chloroform, and diethyl ether.
Optionally, the dissolving of chitosan in acetic acid solution in step 1) comprises: according to the concentration of 1-4 wt% chitosan, the chitosan is dissolved in 1-2% acetic acid solution by volume fraction.
Optionally, the COOH group of the lipoic acid and NH on the chitosan in the step 1)2The molar ratio of the base groups is 1: 2-10.
Optionally, the amide catalyst in step 1) is one of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide/N-hydroxysuccinimide (EDC/NHS), genipin, EDC/1-Hydroxybenzotriazole (HOBT), O-benzotriazol-tetramethyluronium Hexafluorophosphate (HBTU), 2- (7-azabenzotriazole) -N, N' -tetramethyluronium Hexafluorophosphate (HATU), 1H-benzotriazol-1-yl oxo-tris (dimethylamino) phosphonium hexafluorophosphate (BOP).
Optionally, the wavelength of the ultraviolet light in the step 2) is 200-400 nm.
Optionally, the dissolving of the lipoic acid modified chitosan in step 2) in water comprises: the lipoic acid modified chitosan is dissolved in water according to the concentration of 0.5-2% (W/V).
Compared with the prior art, the preparation method of the photo-crosslinking chitosan hydrogel has the following advantages:
the lipoic acid modified chitosan with good water solubility is obtained by grafting lipoic acid to chitosan through an amide reaction, and then photocrosslinking chitosan hydrogel is formed under the irradiation of ultraviolet light.
Drawings
The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate an embodiment of the invention and, together with the description, serve to explain the invention and not to limit the invention. In the drawings:
FIG. 1 is an IR spectrum of a chitosan modified with lipoic acid (CS-LA) in example 1 of the present invention;
FIG. 2 is a gel forming process of lipoic acid modified chitosan (CS-LA) in example 3 of the present invention;
FIG. 3 shows gel forming time of lipoic acid modified chitosan (CS-LA) in different proportions in examples 2, 3 and 6 of the present invention;
FIG. 4 shows the micro-morphology of photo-crosslinked chitosan hydrogel (CS-LA hydrogel) after freeze-drying in example 3 of the present invention;
FIG. 5 is an SEM photograph of cells grown on a photo-crosslinked chitosan hydrogel (CS-LA hydrogel) in example 4 of the present invention;
FIG. 6 is a graph showing the mechanical properties of a photo-crosslinked chitosan hydrogel (CS-LA hydrogel) in example 5 of the present invention.
Detailed Description
It should be noted that the embodiments and features of the embodiments may be combined with each other without conflict.
The present invention will be described in detail below with reference to the drawings and examples.
Example 1
A preparation method of photo-crosslinking chitosan hydrogel specifically comprises the following steps:
1) dissolving a certain amount of Chitosan (CS) in 1% (W/V) acetic acid solution to obtain 1 wt% chitosan solution; dissolving thioctic acid in methanol, adding it to the above chitosan solution, wherein the thioctic acid has COOH group and NH on chitosan2The molar ratio of the base is 1:2, EDC/NHS is added after stirring and mixing evenly, reaction is carried out for 1h, then dialysis is carried out in deionized water to remove unreacted lipoic acid, acetic acid and organic solvent, and the steps are carried outFreeze drying to obtain thioctic acid modified chitosan (CS-LA);
2) 0.1g of CS-LA is dissolved in 20mL of water and is irradiated under the ultraviolet radiation with the wavelength of 365nm to obtain the photo-crosslinking chitosan hydrogel (CS-LA hydrogel).
The chitosan before and after modification in this example was subjected to infrared testing, and the test results are shown in fig. 1.
As can be seen from FIG. 1, the peak of the amide in-plane bending vibration in the CS-LA infrared region was found, and it was found that the peak was found to be at 567cm-1The peak is the characteristic peak of S-S bond, which proves that the amide reaction occurs between the chitosan and the lipoic acid, and the LA is successfully grafted to the chitosan.
Example 2
A preparation method of photo-crosslinking chitosan hydrogel specifically comprises the following steps:
1) dissolving Chitosan (CS) in 1% (W/V) acetic acid solution to obtain 4% chitosan solution, dissolving thioctic acid in diethyl ether, and adding into the above chitosan solution, wherein the COOH group of thioctic acid and NH on chitosan2The molar ratio of the raw materials is 1:4, the raw materials are stirred to be uniformly mixed, EDC/HOBT is added to react for 12 hours, then dialysis is carried out in deionized water to remove unreacted lipoic acid, acetic acid and organic solvent, and freeze drying treatment is carried out to obtain lipoic acid modified chitosan (CS-LA);
2) 0.1g of CS-LA is dissolved in 20mL of water and is irradiated under the ultraviolet radiation with the wavelength of 365nm to obtain the photo-crosslinking chitosan hydrogel (CS-LA hydrogel).
Example 3
A preparation method of photo-crosslinking chitosan hydrogel specifically comprises the following steps:
1) dissolving Chitosan (CS) in 1% (W/V) acetic acid solution to obtain 2% chitosan solution, dissolving thioctic acid in ethanol, and adding into the chitosan solution, wherein the COOH group of thioctic acid and NH on chitosan2The molar ratio of the raw materials is 1:6, EDC/NHS is added after the raw materials are uniformly mixed by stirring, the mixture reacts for 4 hours, then the dialysis is carried out in deionized water to remove the unreacted lipoic acid, acetic acid and organic solvent, and the freezing and drying treatment is carried out to obtain the lipoic acid modified shellGlycans (CS-LA);
2) 0.1g of CS-LA is dissolved in 10mL of water and is irradiated under the ultraviolet radiation with the wavelength of 365nm to obtain the photo-crosslinking chitosan hydrogel (CS-LA hydrogel).
The lipoic acid modified chitosan (CS-LA) of this example was tested for gelling, and the results are shown in FIG. 2.
As shown in FIG. 2, the CS-LA of this example was dissolved in water and then successfully formed into hydrogel by UV irradiation, indicating its photocrosslinking property.
The microscopic morphology of the CS-LA hydrogel obtained in this example after freeze-drying was tested, and the test results are shown in FIG. 4.
As can be seen from FIG. 4, the hydrogel obtained in this example has a good pore structure after freeze-drying, which is beneficial to the delivery of nutrients and the discharge of metabolites during the tissue engineering repair process.
Example 4
A preparation method of photo-crosslinking chitosan hydrogel specifically comprises the following steps:
1) dissolving Chitosan (CS) in 1% (W/V) acetic acid solution to obtain 4% chitosan solution, dissolving thioctic acid in chloroform, and adding into the chitosan solution, wherein the COOH group of thioctic acid and NH on chitosan2The molar ratio of the components is 1:6, after stirring and mixing the components evenly, genipin is added to react for 8 hours, then dialysis is carried out in deionized water to remove unreacted lipoic acid, acetic acid and organic solvent, and freeze drying treatment is carried out to obtain lipoic acid modified chitosan (CS-LA);
2) 0.1g of CS-LA is dissolved in 10mL of water and is irradiated under the ultraviolet radiation with the wavelength of 400nm to obtain the photo-crosslinking chitosan hydrogel (CS-LA hydrogel).
L929 cells were seeded on the surface of the CS-LA hydrogel of this example, and after three days of culture, dehydration treatment and freeze-drying, the growth and adhesion of the cells on the gel were observed under a scanning electron microscope, and the test results are shown in FIG. 5.
As can be seen from FIG. 5, the cells spread well on the surface of the CS-LA hydrogel of this example, indicating that the hydrogel has good cell compatibility.
Example 5
A preparation method of photo-crosslinking chitosan hydrogel specifically comprises the following steps:
1) dissolving Chitosan (CS) in 2% (W/V) acetic acid solution to obtain 1% chitosan solution, dissolving thioctic acid in ethanol, and adding into the chitosan solution, wherein the COOH group of thioctic acid and NH on chitosan2The molar ratio of the raw materials is 1:4, the raw materials are stirred to be uniformly mixed, EDC/NHS is added to react for 8 hours, then dialysis is carried out in deionized water to remove unreacted lipoic acid, acetic acid and organic solvent, and freeze drying treatment is carried out to obtain lipoic acid modified chitosan (CS-LA);
2) 0.1g of CS-LA is dissolved in 10mL of water and is irradiated under the ultraviolet radiation with the wavelength of 365nm to obtain the photo-crosslinking chitosan hydrogel (CS-LA hydrogel).
The mechanical properties of the photo-crosslinked chitosan hydrogel (CS-LA hydrogel) of this example were tested, and the test results are shown in FIG. 6.
As can be seen from FIG. 6, the CS-LA hydrogel of this example has good compression resistance and can maintain the basic form of the hydrogel in a compressed state.
Example 6
A preparation method of photo-crosslinking chitosan hydrogel specifically comprises the following steps:
1) dissolving Chitosan (CS) in 2% (W/V) acetic acid solution to obtain 1% chitosan solution, dissolving thioctic acid in ethanol, and adding into the chitosan solution, wherein the COOH group of thioctic acid and NH on chitosan2The molar ratio of the components is 1:8, the mixture is stirred to be uniformly mixed, HATU is added to react for 8 hours, then dialysis is carried out in deionized water to remove unreacted lipoic acid, acetic acid and organic solvent, and freeze drying treatment is carried out to obtain lipoic acid modified chitosan (CS-LA);
2) 0.1g of CS-LA is dissolved in 5mL of water and is irradiated under the ultraviolet radiation with the wavelength of 200nm to obtain the photo-crosslinking chitosan hydrogel (CS-LA hydrogel).
The gel forming time of the lipoic acid modified chitosan (CS-LA) in different proportions in examples 2, 3 and 6 of the invention is tested, and the test result is shown in figure 3.
As can be seen from FIG. 3, the CS-LA solutions of examples 2, 3 and 6 of the present invention can rapidly gel within several tens of seconds, which is convenient and fast.
The present invention is not limited to the above preferred embodiments, and any modifications, equivalent substitutions, improvements, etc. within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (7)
1. A preparation method of photo-crosslinking chitosan hydrogel is characterized by comprising the following steps:
1) dissolving chitosan in an acetic acid solution, dissolving thioctic acid in an organic solvent, then mixing, stirring to uniformly mix, adding an amide catalyst, reacting for a period of time, dialyzing in deionized water to remove unreacted lipoic acid, acetic acid and the organic solvent, and drying to obtain lipoic acid modified chitosan;
2) and dissolving the lipoic acid modified chitosan in water, and reacting under the irradiation of ultraviolet light to obtain the photocrosslinking chitosan hydrogel.
2. The method for preparing photo-crosslinked chitosan hydrogel according to claim 1, wherein the solvent for dissolving lipoic acid in step 1) is one of methanol, ethanol, chloroform, and diethyl ether.
3. The method for preparing photo-crosslinked chitosan hydrogel according to claim 1, wherein said dissolving chitosan in acetic acid solution in step 1) comprises: according to the concentration of 1-4 wt% chitosan, the chitosan is dissolved in 1-2% acetic acid solution by volume fraction.
4. The method for preparing photo-crosslinked chitosan hydrogel according to claim 1, wherein the COOH group of lipoic acid in the step 1)And NH on chitosan2The molar ratio of the base groups is 1: 2-10.
5. The method for preparing the photo-crosslinking chitosan hydrogel according to claim 1, wherein the amide catalyst in step 1) is one of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide/N-N-hydroxysuccinimide, genipin, EDC/1-hydroxybenzotriazole, O-benzotriazole-tetramethylurea hexafluorophosphate, 2- (7-azabenzotriazole) -N, N, N ', N' -tetramethylurea hexafluorophosphate, and 1H-benzotriazol-1-yl oxo tris (dimethylamino) phosphonium hexafluorophosphate.
6. The method for preparing photo-crosslinked chitosan hydrogel according to claim 1, wherein the wavelength of the ultraviolet light in the step 2) is 200-400 nm.
7. The method for preparing photo-crosslinked chitosan hydrogel according to claim 1, wherein said step 2) of dissolving said lipoic acid modified chitosan in water comprises: the lipoic acid modified chitosan is dissolved in water according to the concentration of 0.5-2% (W/V).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110287161.3A CN113072716A (en) | 2021-03-17 | 2021-03-17 | Preparation method of photo-crosslinked chitosan hydrogel |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110287161.3A CN113072716A (en) | 2021-03-17 | 2021-03-17 | Preparation method of photo-crosslinked chitosan hydrogel |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN113072716A true CN113072716A (en) | 2021-07-06 |
Family
ID=76612781
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202110287161.3A Pending CN113072716A (en) | 2021-03-17 | 2021-03-17 | Preparation method of photo-crosslinked chitosan hydrogel |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN113072716A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113929790A (en) * | 2021-11-02 | 2022-01-14 | 江南大学 | Natural polysaccharide material capable of being processed at low temperature and recycled, preparation and application |
| CN114736317A (en) * | 2022-04-29 | 2022-07-12 | 湖南巴德医药科技有限公司 | Modified chitosan gel and preparation method and application thereof |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20100255097A1 (en) * | 2007-12-21 | 2010-10-07 | Sigea S.R.L. | Polysaccharide derivatives of lipoic acid, and their preparation and use as skin cosmetics and medical devices |
| CN103756020A (en) * | 2013-12-16 | 2014-04-30 | 武汉纺织大学 | Preparation method for nanometer composite supermolecular hydrogel with photosensitivity |
| CN109180970A (en) * | 2018-08-30 | 2019-01-11 | 武汉理工大学 | A kind of citric acid cross-linked chitosan and the hydrogel of dopamine and preparation method thereof |
| CN110234314A (en) * | 2016-12-15 | 2019-09-13 | 芬欧汇川集团 | The method of dry acellular tissue extract and the dried hydrogel comprising nanometer fibril cellulose and acellular tissue extract in the hydrogel comprising nanometer fibril cellulose |
| CN111035801A (en) * | 2020-01-14 | 2020-04-21 | 青岛科技大学 | Silver nanocluster based chitosan hydrogel dressing and preparation method and application thereof |
-
2021
- 2021-03-17 CN CN202110287161.3A patent/CN113072716A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20100255097A1 (en) * | 2007-12-21 | 2010-10-07 | Sigea S.R.L. | Polysaccharide derivatives of lipoic acid, and their preparation and use as skin cosmetics and medical devices |
| CN103756020A (en) * | 2013-12-16 | 2014-04-30 | 武汉纺织大学 | Preparation method for nanometer composite supermolecular hydrogel with photosensitivity |
| CN110234314A (en) * | 2016-12-15 | 2019-09-13 | 芬欧汇川集团 | The method of dry acellular tissue extract and the dried hydrogel comprising nanometer fibril cellulose and acellular tissue extract in the hydrogel comprising nanometer fibril cellulose |
| CN109180970A (en) * | 2018-08-30 | 2019-01-11 | 武汉理工大学 | A kind of citric acid cross-linked chitosan and the hydrogel of dopamine and preparation method thereof |
| CN111035801A (en) * | 2020-01-14 | 2020-04-21 | 青岛科技大学 | Silver nanocluster based chitosan hydrogel dressing and preparation method and application thereof |
Non-Patent Citations (2)
| Title |
|---|
| LUO QIANG ET AL.: "Redox response, antibacterial and drug package capacities of chitosan-alpha-lipoic acid conjugates", 《INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES》, vol. 154, 23 November 2019 (2019-11-23), pages 1166 - 1174 * |
| SONG LI ET AL.: "Single component Pluronic F127-lipoic acid hydrogels with self-healing and multi-responsive properties", 《EUROPEAN POLYMER JOURNAL》, vol. 115, 26 March 2019 (2019-03-26), pages 346 - 355, XP085701123, DOI: 10.1016/j.eurpolymj.2019.03.051 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113929790A (en) * | 2021-11-02 | 2022-01-14 | 江南大学 | Natural polysaccharide material capable of being processed at low temperature and recycled, preparation and application |
| CN114736317A (en) * | 2022-04-29 | 2022-07-12 | 湖南巴德医药科技有限公司 | Modified chitosan gel and preparation method and application thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US11384162B2 (en) | Catechol group modified biomacromolecular scaffold material and preparation method thereof | |
| CN111303459B (en) | Preparation method of hyaluronic acid based double-crosslinked hydrogel | |
| CN106188442B (en) | Chitosan derivative hydrogel and preparation method thereof | |
| CN110240712A (en) | The high stretching of tissue adhesion a kind of, high viscosity, self-healing double-network hydrogel and its preparation method and application | |
| CN110522948B (en) | Injectable hydrogel and preparation method and application thereof | |
| CN113072716A (en) | Preparation method of photo-crosslinked chitosan hydrogel | |
| CN110201219A (en) | A kind of composite hydrogel and preparation method thereof of injectable and quick-gelatinizing | |
| CN109180970B (en) | Citric acid crosslinked chitosan and dopamine hydrogel and preparation method thereof | |
| CN106267337B (en) | A kind of preparation method of DOPA amido function-graded material | |
| CN113416326B (en) | Injectable hydrogel and preparation method and application thereof | |
| CN111072997A (en) | High-strength self-healing hydrogel based on modified hyaluronic acid and preparation method thereof | |
| CN110157012A (en) | A kind of preparation method of high-intensity and high-tenacity gelatin based aquagel | |
| CN109125808A (en) | A kind of biodegradable collagen-based cornea substitute and preparation method thereof | |
| CN114874455B (en) | Construction method of neutral-dissolution modified collagen and gel with self-assembly capability and photocrosslinking capability | |
| CN105646894B (en) | A kind of preparation method of the hydrogel based on polyamidoamine dendrimer | |
| CN110698866A (en) | Ultrasonic-mediated silk fibroin composite collagen hydrogel and preparation method thereof | |
| CN114272433A (en) | Gelatin-based biomedical adhesive and preparation method thereof | |
| CN1155347C (en) | Absorbable artificial dura meter of brain and its preparing process | |
| CN109762184A (en) | A kind of preparation method of collagen hydrogels | |
| Wang et al. | Fabrication, characterization and potential application of biodegradable polydopamine-modified scaffolds based on natural macromolecules | |
| CN113929792A (en) | Aldehyde modified hyaluronic acid (sodium) and synthesis method and application thereof | |
| CN114702698A (en) | Double-crosslinking self-healing hydrogel and preparation method thereof | |
| CN116178751A (en) | Self-healing hydrogel and preparation method thereof | |
| CN114381015A (en) | Injectable and self-repairing hydrogel and preparation method and application thereof | |
| CN115746412A (en) | Water-soluble chitosan composite hydrogel and preparation method and application thereof |
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: 20210706 |
|
| RJ01 | Rejection of invention patent application after publication |