CN116407681A - 一种可长期控制NGF&bFGF释放的肝素-透明质酸水凝胶及其制备方法与应用 - Google Patents
一种可长期控制NGF&bFGF释放的肝素-透明质酸水凝胶及其制备方法与应用 Download PDFInfo
- Publication number
- CN116407681A CN116407681A CN202310663908.XA CN202310663908A CN116407681A CN 116407681 A CN116407681 A CN 116407681A CN 202310663908 A CN202310663908 A CN 202310663908A CN 116407681 A CN116407681 A CN 116407681A
- Authority
- CN
- China
- Prior art keywords
- heparin
- solution
- ngf
- bfgf
- hyaluronic acid
- 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.)
- Granted
Links
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 title claims abstract description 87
- 229920002674 hyaluronan Polymers 0.000 title claims abstract description 75
- 229960003160 hyaluronic acid Drugs 0.000 title claims abstract description 71
- 239000000017 hydrogel Substances 0.000 title claims abstract description 29
- 238000002360 preparation method Methods 0.000 title claims abstract description 22
- 102100024785 Fibroblast growth factor 2 Human genes 0.000 title claims abstract 20
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 claims abstract description 89
- 229920000669 heparin Polymers 0.000 claims abstract description 78
- 229960002897 heparin Drugs 0.000 claims abstract description 78
- 239000000499 gel Substances 0.000 claims abstract description 63
- 239000002105 nanoparticle Substances 0.000 claims abstract description 61
- 238000000034 method Methods 0.000 claims abstract description 30
- 208000020431 spinal cord injury Diseases 0.000 claims abstract description 25
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 claims abstract description 23
- 210000004556 brain Anatomy 0.000 claims abstract description 19
- 239000002243 precursor Substances 0.000 claims abstract description 16
- 108090000695 Cytokines Proteins 0.000 claims abstract description 13
- 102000004127 Cytokines Human genes 0.000 claims abstract description 13
- 230000004069 differentiation Effects 0.000 claims abstract description 8
- 230000001737 promoting effect Effects 0.000 claims abstract description 8
- 230000012010 growth Effects 0.000 claims abstract description 7
- 230000003993 interaction Effects 0.000 claims abstract description 7
- 238000006845 Michael addition reaction Methods 0.000 claims abstract description 3
- 239000000243 solution Substances 0.000 claims description 87
- 108010025020 Nerve Growth Factor Proteins 0.000 claims description 83
- 102000015336 Nerve Growth Factor Human genes 0.000 claims description 82
- 102000003974 Fibroblast growth factor 2 Human genes 0.000 claims description 67
- 238000000502 dialysis Methods 0.000 claims description 33
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 24
- IBVAQQYNSHJXBV-UHFFFAOYSA-N adipic acid dihydrazide Chemical compound NNC(=O)CCCCC(=O)NN IBVAQQYNSHJXBV-UHFFFAOYSA-N 0.000 claims description 22
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 21
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 20
- 238000003756 stirring Methods 0.000 claims description 16
- 239000008346 aqueous phase Substances 0.000 claims description 15
- 208000029028 brain injury Diseases 0.000 claims description 15
- 210000001178 neural stem cell Anatomy 0.000 claims description 15
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 14
- 125000003277 amino group Chemical group 0.000 claims description 13
- 238000002715 modification method Methods 0.000 claims description 13
- ROOXNKNUYICQNP-UHFFFAOYSA-N ammonium persulfate Chemical compound [NH4+].[NH4+].[O-]S(=O)(=O)OOS([O-])(=O)=O ROOXNKNUYICQNP-UHFFFAOYSA-N 0.000 claims description 12
- 239000012153 distilled water Substances 0.000 claims description 12
- 239000000843 powder Substances 0.000 claims description 12
- 239000011780 sodium chloride Substances 0.000 claims description 12
- 239000000178 monomer Substances 0.000 claims description 11
- 239000000047 product Substances 0.000 claims description 11
- 239000000839 emulsion Substances 0.000 claims description 10
- 239000012071 phase Substances 0.000 claims description 10
- 238000006243 chemical reaction Methods 0.000 claims description 9
- 239000003995 emulsifying agent Substances 0.000 claims description 9
- 230000004766 neurogenesis Effects 0.000 claims description 9
- YXMISKNUHHOXFT-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) prop-2-enoate Chemical compound C=CC(=O)ON1C(=O)CCC1=O YXMISKNUHHOXFT-UHFFFAOYSA-N 0.000 claims description 8
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 claims description 8
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 claims description 8
- 229920002385 Sodium hyaluronate Polymers 0.000 claims description 8
- 239000007853 buffer solution Substances 0.000 claims description 8
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 claims description 8
- 238000002156 mixing Methods 0.000 claims description 8
- 230000035484 reaction time Effects 0.000 claims description 8
- 229940010747 sodium hyaluronate Drugs 0.000 claims description 8
- YWIVKILSMZOHHF-QJZPQSOGSA-N sodium;(2s,3s,4s,5r,6r)-6-[(2s,3r,4r,5s,6r)-3-acetamido-2-[(2s,3s,4r,5r,6r)-6-[(2r,3r,4r,5s,6r)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2- Chemical compound [Na+].CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 YWIVKILSMZOHHF-QJZPQSOGSA-N 0.000 claims description 8
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 claims description 7
- 208000001738 Nervous System Trauma Diseases 0.000 claims description 7
- 210000003169 central nervous system Anatomy 0.000 claims description 7
- 125000004185 ester group Chemical group 0.000 claims description 7
- 208000028412 nervous system injury Diseases 0.000 claims description 7
- 229910001870 ammonium persulfate Inorganic materials 0.000 claims description 6
- 150000001718 carbodiimides Chemical class 0.000 claims description 6
- 238000004108 freeze drying Methods 0.000 claims description 6
- 239000000203 mixture Substances 0.000 claims description 6
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims description 5
- 239000012620 biological material Substances 0.000 claims description 5
- 230000004048 modification Effects 0.000 claims description 5
- 238000012986 modification Methods 0.000 claims description 5
- 229940053128 nerve growth factor Drugs 0.000 claims description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
- 239000001632 sodium acetate Substances 0.000 claims description 5
- 235000017281 sodium acetate Nutrition 0.000 claims description 5
- 239000006228 supernatant Substances 0.000 claims description 5
- 238000005406 washing Methods 0.000 claims description 5
- 208000012902 Nervous system disease Diseases 0.000 claims description 4
- 230000007547 defect Effects 0.000 claims description 4
- 210000000056 organ Anatomy 0.000 claims description 4
- 238000000527 sonication Methods 0.000 claims description 4
- 238000009210 therapy by ultrasound Methods 0.000 claims description 4
- 238000004506 ultrasonic cleaning Methods 0.000 claims description 4
- NWGKJDSIEKMTRX-AAZCQSIUSA-N Sorbitan monooleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O NWGKJDSIEKMTRX-AAZCQSIUSA-N 0.000 claims description 3
- 239000007864 aqueous solution Substances 0.000 claims description 3
- 238000005119 centrifugation Methods 0.000 claims description 3
- 239000012535 impurity Substances 0.000 claims description 3
- 230000007774 longterm Effects 0.000 claims description 3
- 230000001537 neural effect Effects 0.000 claims description 3
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 3
- 229920000053 polysorbate 80 Polymers 0.000 claims description 3
- 230000008439 repair process Effects 0.000 claims description 3
- 230000002441 reversible effect Effects 0.000 claims description 3
- 230000004083 survival effect Effects 0.000 claims description 3
- 238000001914 filtration Methods 0.000 claims description 2
- 238000012688 inverse emulsion polymerization Methods 0.000 claims description 2
- 239000012528 membrane Substances 0.000 claims description 2
- 238000010526 radical polymerization reaction Methods 0.000 claims description 2
- 238000005303 weighing Methods 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 8
- 239000002244 precipitate Substances 0.000 claims 1
- 230000002194 synthesizing effect Effects 0.000 claims 1
- 210000004027 cell Anatomy 0.000 abstract description 21
- 210000002569 neuron Anatomy 0.000 abstract description 12
- 210000000278 spinal cord Anatomy 0.000 abstract description 11
- 230000008569 process Effects 0.000 abstract description 6
- 239000002245 particle Substances 0.000 abstract description 5
- 208000006011 Stroke Diseases 0.000 abstract description 4
- 238000000338 in vitro Methods 0.000 abstract description 3
- 210000003594 spinal ganglia Anatomy 0.000 abstract description 3
- 206010008190 Cerebrovascular accident Diseases 0.000 abstract description 2
- 230000002490 cerebral effect Effects 0.000 abstract description 2
- 238000009826 distribution Methods 0.000 abstract description 2
- 210000001519 tissue Anatomy 0.000 description 15
- 241000700159 Rattus Species 0.000 description 9
- 230000006378 damage Effects 0.000 description 9
- 208000027418 Wounds and injury Diseases 0.000 description 7
- 239000003102 growth factor Substances 0.000 description 6
- 208000014674 injury Diseases 0.000 description 6
- 230000008929 regeneration Effects 0.000 description 6
- 238000011069 regeneration method Methods 0.000 description 6
- 238000003501 co-culture Methods 0.000 description 5
- WOVKYSAHUYNSMH-RRKCRQDMSA-N 5-bromodeoxyuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(Br)=C1 WOVKYSAHUYNSMH-RRKCRQDMSA-N 0.000 description 4
- -1 BDNF Proteins 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 229940099552 hyaluronan Drugs 0.000 description 4
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 4
- 230000003902 lesion Effects 0.000 description 4
- 230000035755 proliferation Effects 0.000 description 4
- 208000024827 Alzheimer disease Diseases 0.000 description 3
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 3
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 3
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 3
- 208000015114 central nervous system disease Diseases 0.000 description 3
- 238000010382 chemical cross-linking Methods 0.000 description 3
- 230000034994 death Effects 0.000 description 3
- 238000010586 diagram Methods 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 230000035876 healing Effects 0.000 description 3
- 238000010166 immunofluorescence Methods 0.000 description 3
- 238000002513 implantation Methods 0.000 description 3
- 210000005036 nerve Anatomy 0.000 description 3
- 210000002241 neurite Anatomy 0.000 description 3
- 102000004196 processed proteins & peptides Human genes 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- 231100000241 scar Toxicity 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 206010002091 Anaesthesia Diseases 0.000 description 2
- 238000012756 BrdU staining Methods 0.000 description 2
- 206010051290 Central nervous system lesion Diseases 0.000 description 2
- 229920001661 Chitosan Polymers 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 101001092197 Homo sapiens RNA binding protein fox-1 homolog 3 Proteins 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 208000028389 Nerve injury Diseases 0.000 description 2
- 239000004698 Polyethylene Substances 0.000 description 2
- 102100035530 RNA binding protein fox-1 homolog 3 Human genes 0.000 description 2
- 210000000683 abdominal cavity Anatomy 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 230000037005 anaesthesia Effects 0.000 description 2
- 210000003050 axon Anatomy 0.000 description 2
- 239000007640 basal medium Substances 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 210000005098 blood-cerebrospinal fluid barrier Anatomy 0.000 description 2
- 230000010261 cell growth Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000013270 controlled release Methods 0.000 description 2
- 238000004132 cross linking Methods 0.000 description 2
- 230000001186 cumulative effect Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 239000004973 liquid crystal related substance Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 238000000691 measurement method Methods 0.000 description 2
- 230000008764 nerve damage Effects 0.000 description 2
- 210000000944 nerve tissue Anatomy 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 230000010412 perfusion Effects 0.000 description 2
- 229920000573 polyethylene Polymers 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 238000004445 quantitative analysis Methods 0.000 description 2
- 108700005467 recombinant KCB-1 Proteins 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 230000000717 retained effect Effects 0.000 description 2
- 210000000130 stem cell Anatomy 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- WCDDVEOXEIYWFB-VXORFPGASA-N (2s,3s,4r,5r,6r)-3-[(2s,3r,5s,6r)-3-acetamido-5-hydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-4,5,6-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@@H]1C[C@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](C(O)=O)O[C@@H](O)[C@H](O)[C@H]1O WCDDVEOXEIYWFB-VXORFPGASA-N 0.000 description 1
- SQDAZGGFXASXDW-UHFFFAOYSA-N 5-bromo-2-(trifluoromethoxy)pyridine Chemical compound FC(F)(F)OC1=CC=C(Br)C=N1 SQDAZGGFXASXDW-UHFFFAOYSA-N 0.000 description 1
- IYMAXBFPHPZYIK-BQBZGAKWSA-N Arg-Gly-Asp Chemical compound NC(N)=NCCC[C@H](N)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(O)=O IYMAXBFPHPZYIK-BQBZGAKWSA-N 0.000 description 1
- 229920001287 Chondroitin sulfate Polymers 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 206010018341 Gliosis Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 102000006386 Myelin Proteins Human genes 0.000 description 1
- 108010083674 Myelin Proteins Proteins 0.000 description 1
- 102000007072 Nerve Growth Factors Human genes 0.000 description 1
- 102000010410 Nogo Proteins Human genes 0.000 description 1
- 108010077641 Nogo Proteins Proteins 0.000 description 1
- 102100029826 Reticulon-4 receptor Human genes 0.000 description 1
- 208000030886 Traumatic Brain injury Diseases 0.000 description 1
- 206010052428 Wound Diseases 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 210000001130 astrocyte Anatomy 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 229940059329 chondroitin sulfate Drugs 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 238000004624 confocal microscopy Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000003431 cross linking reagent Substances 0.000 description 1
- 230000000093 cytochemical effect Effects 0.000 description 1
- 210000001947 dentate gyrus Anatomy 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- ZHNUHDYFZUAESO-UHFFFAOYSA-N formamide Substances NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 230000000971 hippocampal effect Effects 0.000 description 1
- 229940014041 hyaluronate Drugs 0.000 description 1
- DCPMPXBYPZGNDC-UHFFFAOYSA-N hydron;methanediimine;chloride Chemical compound Cl.N=C=N DCPMPXBYPZGNDC-UHFFFAOYSA-N 0.000 description 1
- 230000003832 immune regulation Effects 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 210000005012 myelin Anatomy 0.000 description 1
- 230000001991 pathophysiological effect Effects 0.000 description 1
- 229920001606 poly(lactic acid-co-glycolic acid) Polymers 0.000 description 1
- 229940117828 polylactic acid-polyglycolic acid copolymer Drugs 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 239000012474 protein marker Substances 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 230000001172 regenerating effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000009529 traumatic brain injury Effects 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
Images
Classifications
-
- 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
- C08B37/006—Heteroglycans, i.e. polysaccharides having more than one sugar residue in the main chain in either alternating or less regular sequence; Gellans; Succinoglycans; Arabinogalactans; Tragacanth or gum tragacanth or traganth from Astragalus; Gum Karaya from Sterculia urens; Gum Ghatti from Anogeissus latifolia; Derivatives thereof
- C08B37/0063—Glycosaminoglycans or mucopolysaccharides, e.g. keratan sulfate; Derivatives thereof, e.g. fucoidan
- C08B37/0075—Heparin; Heparan sulfate; Derivatives thereof, e.g. heparosan; Purification or extraction methods thereof
-
- 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
- A61L27/14—Macromolecular materials
- A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
- A61L27/227—Other specific proteins or polypeptides not covered by A61L27/222, A61L27/225 or A61L27/24
-
- 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
-
- 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
- A61L27/58—Materials at least partially resorbable by the body
-
- 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
- C08B37/006—Heteroglycans, i.e. polysaccharides having more than one sugar residue in the main chain in either alternating or less regular sequence; Gellans; Succinoglycans; Arabinogalactans; Tragacanth or gum tragacanth or traganth from Astragalus; Gum Karaya from Sterculia urens; Gum Ghatti from Anogeissus latifolia; Derivatives thereof
- C08B37/0063—Glycosaminoglycans or mucopolysaccharides, e.g. keratan sulfate; Derivatives thereof, e.g. fucoidan
- C08B37/0072—Hyaluronic acid, i.e. HA or hyaluronan; Derivatives thereof, e.g. crosslinked hyaluronic acid (hylan) or hyaluronates
-
- 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
- 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
- A61L2300/414—Growth factors
-
- 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
-
- 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
- A61L2430/00—Materials or treatment for tissue regeneration
- A61L2430/32—Materials or treatment for tissue regeneration for nerve reconstruction
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Dermatology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Transplantation (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Polymers & Plastics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Materials Engineering (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Dispersion Chemistry (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
Abstract
Description
Claims (16)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202310663908.XA CN116407681B (zh) | 2023-06-07 | 2023-06-07 | 一种可长期控制NGF&bFGF释放的肝素-透明质酸水凝胶及其制备方法与应用 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202310663908.XA CN116407681B (zh) | 2023-06-07 | 2023-06-07 | 一种可长期控制NGF&bFGF释放的肝素-透明质酸水凝胶及其制备方法与应用 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN116407681A true CN116407681A (zh) | 2023-07-11 |
CN116407681B CN116407681B (zh) | 2023-08-11 |
Family
ID=87059659
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202310663908.XA Active CN116407681B (zh) | 2023-06-07 | 2023-06-07 | 一种可长期控制NGF&bFGF释放的肝素-透明质酸水凝胶及其制备方法与应用 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN116407681B (zh) |
Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101036809A (zh) * | 2007-04-17 | 2007-09-19 | 孙勇 | 肝素明胶纳米颗粒及肝素微胶囊化心脏封堵器的制备方法 |
CN101905038A (zh) * | 2010-05-21 | 2010-12-08 | 中国医学科学院生物医学工程研究所 | 负载生长因子的胶原基复合材料及其制造方法和应用 |
CN104399085A (zh) * | 2014-11-07 | 2015-03-11 | 山东大学 | 叶酸修饰的肝素-维生素e琥珀酸酯聚合物及其合成方法 |
CN106902392A (zh) * | 2017-03-01 | 2017-06-30 | 西南交通大学 | 载肝素/多聚赖氨酸纳米粒子透明质酸水凝胶的制备方法 |
WO2017159943A1 (ko) * | 2016-03-17 | 2017-09-21 | 중앙대학교 산학협력단 | 화학반응을 통하여 결합된 섬유아세포 증식인자-헤파린 복합체 및 이의 제조 방법 |
CN112933293A (zh) * | 2020-11-06 | 2021-06-11 | 浙江大学 | 一种治疗中枢神经损伤的可注射水凝胶及其制备方法 |
CN114306242A (zh) * | 2021-12-29 | 2022-04-12 | 广州佰斯伦医疗器械有限公司 | 含生长因子纳米凝胶的脂质体微粒及其制备方法和应用 |
-
2023
- 2023-06-07 CN CN202310663908.XA patent/CN116407681B/zh active Active
Patent Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101036809A (zh) * | 2007-04-17 | 2007-09-19 | 孙勇 | 肝素明胶纳米颗粒及肝素微胶囊化心脏封堵器的制备方法 |
CN101905038A (zh) * | 2010-05-21 | 2010-12-08 | 中国医学科学院生物医学工程研究所 | 负载生长因子的胶原基复合材料及其制造方法和应用 |
CN104399085A (zh) * | 2014-11-07 | 2015-03-11 | 山东大学 | 叶酸修饰的肝素-维生素e琥珀酸酯聚合物及其合成方法 |
WO2017159943A1 (ko) * | 2016-03-17 | 2017-09-21 | 중앙대학교 산학협력단 | 화학반응을 통하여 결합된 섬유아세포 증식인자-헤파린 복합체 및 이의 제조 방법 |
CN106902392A (zh) * | 2017-03-01 | 2017-06-30 | 西南交通大学 | 载肝素/多聚赖氨酸纳米粒子透明质酸水凝胶的制备方法 |
CN112933293A (zh) * | 2020-11-06 | 2021-06-11 | 浙江大学 | 一种治疗中枢神经损伤的可注射水凝胶及其制备方法 |
CN114306242A (zh) * | 2021-12-29 | 2022-04-12 | 广州佰斯伦医疗器械有限公司 | 含生长因子纳米凝胶的脂质体微粒及其制备方法和应用 |
Non-Patent Citations (4)
Title |
---|
GUIHUA LIU ET AL.: "A cocktail of growth factors released from a heparin hyaluronic-acid hydrogel promotes the myogenic potential of human urine-derived stem cells in vivo", ACTA BIOMATERIALIA, vol. 107, pages 50 - 64, XP086129417, DOI: 10.1016/j.actbio.2020.02.005 * |
TAE HO KIM ET AL.: "Dual growth factor-immobilized microspheres for tissue reinnervation: in vitro and preliminary in vivo studies", JOURNAL OF BIOMATERIALS SCIENCE, POLYMER EDITION,, vol. 26, pages 322 - 337 * |
YANQING WU ET AL.: "Dual Delivery of bFGF- and NGF-Binding Coacervate Confers Neuroprotection by Promoting Neuronal Proliferation", CELLULAR PHYSIOLOGY AND BIOCHEMISTRY, vol. 47, pages 948 - 956 * |
尚俊奎等: "应用神经组织工程治疗脊髓和周围神经损伤的新策略", 中国医疗器械信息, vol. 22, pages 5 - 12 * |
Also Published As
Publication number | Publication date |
---|---|
CN116407681B (zh) | 2023-08-11 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Sarrigiannidis et al. | A tough act to follow: Collagen hydrogel modifications to improve mechanical and growth factor loading capabilities | |
JP5255274B2 (ja) | 精製両親媒性ペプチド組成物およびその使用 | |
Zheng et al. | Neuro-regenerative imidazole-functionalized GelMA hydrogel loaded with hAMSC and SDF-1α promote stem cell differentiation and repair focal brain injury | |
Wan et al. | CHITIN—A promising biomaterial for tissue engineering and stem cell technologies | |
Ghane et al. | Design of hydrogel-based scaffolds for the treatment of spinal cord injuries | |
King et al. | The use of injectable forms of fibrin and fibronectin to support axonal ingrowth after spinal cord injury | |
Wang et al. | Combination of hyaluronic acid hydrogel scaffold and PLGA microspheres for supporting survival of neural stem cells | |
Wang et al. | Injectable silk sericin scaffolds with programmable shape-memory property and neuro-differentiation-promoting activity for individualized brain repair of severe ischemic stroke | |
Choi et al. | Gelatin-based micro-hydrogel carrying genetically engineered human endothelial cells for neovascularization | |
JP7384767B2 (ja) | コラーゲンに基づく治療送達系 | |
Meco et al. | Impact of elastin-like protein temperature transition on PEG-ELP hybrid hydrogel properties | |
US20050282747A1 (en) | Methods and compositions for wound healing | |
CN115521627A (zh) | 一种结构蛋白/透明质酸复合微纳米颗粒及颗粒水凝胶材料和应用 | |
Luong et al. | In situ functionalization of poly (hydroxyethyl methacrylate) cryogels with oligopeptides via β-cyclodextrin–adamantane complexation for studying cell-instructive peptide environment | |
CN111407921A (zh) | 一种医用水凝胶敷料、其制备方法及应用 | |
US9623044B2 (en) | Chitosan hydrogel for repairing nerve tissue | |
Nair et al. | Polysaccharide-based hydrogels for targeted drug delivery | |
CN108042793B (zh) | 包埋gdnf的多核-单壳微球缓释系统的制备方法 | |
Ren et al. | Hyaluronic acid/polylysine hydrogel as a transfer system for transplantation of neural stem cells | |
CN116407681B (zh) | 一种可长期控制NGF&bFGF释放的肝素-透明质酸水凝胶及其制备方法与应用 | |
Xu et al. | A self-assembled dynamic extracellular matrix-like hydrogel system with multi-scale structures for cell bioengineering applications | |
CN114288469A (zh) | 一种双重交联胶原蛋白填充剂的组成和制备方法及应用 | |
CN114773692B (zh) | 一种可长期控制ngf释放的活性生物凝胶及其应用 | |
CN114432498B (zh) | 一种骨修复材料及其制备方法和应用 | |
Thakur et al. | Hydrogels: characterization, drug delivery, and tissue engineering applications |
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 | ||
GR01 | Patent grant | ||
GR01 | Patent grant | ||
TR01 | Transfer of patent right |
Effective date of registration: 20231212 Address after: Building 2, 2nd Floor, No. 29 Yongxing Road, Daxing District, Beijing, 102600 Patentee after: Beijing north central United Institute of Medicine Address before: The 100069 Beijing Fengtai District right outside the West No. 10 Patentee before: CAPITAL MEDICAL University |
|
TR01 | Transfer of patent right | ||
TR01 | Transfer of patent right |
Effective date of registration: 20231227 Address after: Room 723, 6 / F, building 5, courtyard 121, Majiabao East Road, Fengtai District, Beijing 100068 Patentee after: Beijing Zhishu Biotechnology Co.,Ltd. Address before: Building 2, 2nd Floor, No. 29 Yongxing Road, Daxing District, Beijing, 102600 Patentee before: Beijing north central United Institute of Medicine |
|
TR01 | Transfer of patent right |