CN110404083A - A kind of injection aquagel material and preparation method thereof, application - Google Patents
A kind of injection aquagel material and preparation method thereof, application Download PDFInfo
- Publication number
- CN110404083A CN110404083A CN201910637570.4A CN201910637570A CN110404083A CN 110404083 A CN110404083 A CN 110404083A CN 201910637570 A CN201910637570 A CN 201910637570A CN 110404083 A CN110404083 A CN 110404083A
- Authority
- CN
- China
- Prior art keywords
- injection
- component
- injection aquagel
- aquagel material
- aldehyde radical
- 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
- 238000002347 injection Methods 0.000 title claims abstract description 55
- 239000007924 injection Substances 0.000 title claims abstract description 55
- 239000000463 material Substances 0.000 title claims abstract description 48
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 title claims abstract description 37
- 238000002360 preparation method Methods 0.000 title claims abstract description 12
- 229920001661 Chitosan Polymers 0.000 claims abstract description 21
- 238000000034 method Methods 0.000 claims abstract description 19
- 238000006243 chemical reaction Methods 0.000 claims abstract description 15
- 238000003745 diagnosis Methods 0.000 claims abstract description 15
- -1 dialdehyde polysaccharide Chemical class 0.000 claims abstract description 15
- 229920001282 polysaccharide Polymers 0.000 claims abstract description 14
- 239000005017 polysaccharide Substances 0.000 claims abstract description 14
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims abstract description 13
- 239000002872 contrast media Substances 0.000 claims abstract description 12
- 239000003431 cross linking reagent Substances 0.000 claims abstract description 12
- 230000010354 integration Effects 0.000 claims abstract description 7
- 238000011065 in-situ storage Methods 0.000 claims abstract description 6
- 239000000243 solution Substances 0.000 claims description 17
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 claims description 14
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 11
- 230000001590 oxidative effect Effects 0.000 claims description 9
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 8
- 150000001299 aldehydes Chemical class 0.000 claims description 6
- 239000003153 chemical reaction reagent Substances 0.000 claims description 6
- 229960001845 diodone Drugs 0.000 claims description 6
- 229920002907 Guar gum Polymers 0.000 claims description 5
- 235000010417 guar gum Nutrition 0.000 claims description 5
- 239000000665 guar gum Substances 0.000 claims description 5
- 229960002154 guar gum Drugs 0.000 claims description 5
- NTHXOOBQLCIOLC-UHFFFAOYSA-N iohexol Chemical compound OCC(O)CN(C(=O)C)C1=C(I)C(C(=O)NCC(O)CO)=C(I)C(C(=O)NCC(O)CO)=C1I NTHXOOBQLCIOLC-UHFFFAOYSA-N 0.000 claims description 5
- 229960001025 iohexol Drugs 0.000 claims description 5
- 239000007800 oxidant agent Substances 0.000 claims description 5
- 238000007254 oxidation reaction Methods 0.000 claims description 5
- GOPYZMJAIPBUGX-UHFFFAOYSA-N [O-2].[O-2].[Mn+4] Chemical group [O-2].[O-2].[Mn+4] GOPYZMJAIPBUGX-UHFFFAOYSA-N 0.000 claims description 4
- FOCAUTSVDIKZOP-UHFFFAOYSA-N chloroacetic acid Chemical compound OC(=O)CCl FOCAUTSVDIKZOP-UHFFFAOYSA-N 0.000 claims description 4
- 229940106681 chloroacetic acid Drugs 0.000 claims description 4
- 239000007788 liquid Substances 0.000 claims description 4
- 239000000047 product Substances 0.000 claims description 4
- 239000000725 suspension Substances 0.000 claims description 4
- 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 description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 3
- 229920001503 Glucan Polymers 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 229960000935 dehydrated alcohol Drugs 0.000 claims description 3
- 238000001035 drying Methods 0.000 claims description 3
- 229920002674 hyaluronan Polymers 0.000 claims description 3
- 229960003160 hyaluronic acid Drugs 0.000 claims description 3
- 229910052740 iodine Inorganic materials 0.000 claims description 3
- 239000011630 iodine Substances 0.000 claims description 3
- XQZXYNRDCRIARQ-LURJTMIESA-N iopamidol Chemical compound C[C@H](O)C(=O)NC1=C(I)C(C(=O)NC(CO)CO)=C(I)C(C(=O)NC(CO)CO)=C1I XQZXYNRDCRIARQ-LURJTMIESA-N 0.000 claims description 3
- 229960004647 iopamidol Drugs 0.000 claims description 3
- 238000000746 purification Methods 0.000 claims description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 3
- 235000010493 xanthan gum Nutrition 0.000 claims description 3
- 229920001285 xanthan gum Polymers 0.000 claims description 3
- 239000000230 xanthan gum Substances 0.000 claims description 3
- 229940082509 xanthan gum Drugs 0.000 claims description 3
- SQDAZGGFXASXDW-UHFFFAOYSA-N 5-bromo-2-(trifluoromethoxy)pyridine Chemical compound FC(F)(F)OC1=CC=C(Br)C=N1 SQDAZGGFXASXDW-UHFFFAOYSA-N 0.000 claims description 2
- 229920001287 Chondroitin sulfate Polymers 0.000 claims description 2
- 241000206575 Chondrus crispus Species 0.000 claims description 2
- 229920001353 Dextrin Polymers 0.000 claims description 2
- 239000004375 Dextrin Substances 0.000 claims description 2
- 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 description 2
- 239000003810 Jones reagent Substances 0.000 claims description 2
- 229920002472 Starch Polymers 0.000 claims description 2
- 235000010489 acacia gum Nutrition 0.000 claims description 2
- 239000001785 acacia senegal l. willd gum Substances 0.000 claims description 2
- 229940059329 chondroitin sulfate Drugs 0.000 claims description 2
- 239000012043 crude product Substances 0.000 claims description 2
- 235000019425 dextrin Nutrition 0.000 claims description 2
- 229920000669 heparin Polymers 0.000 claims description 2
- 229960002897 heparin Drugs 0.000 claims description 2
- 229960004359 iodixanol Drugs 0.000 claims description 2
- NBQNWMBBSKPBAY-UHFFFAOYSA-N iodixanol Chemical compound IC=1C(C(=O)NCC(O)CO)=C(I)C(C(=O)NCC(O)CO)=C(I)C=1N(C(=O)C)CC(O)CN(C(C)=O)C1=C(I)C(C(=O)NCC(O)CO)=C(I)C(C(=O)NCC(O)CO)=C1I NBQNWMBBSKPBAY-UHFFFAOYSA-N 0.000 claims description 2
- MIKKOBKEXMRYFQ-WZTVWXICSA-N meglumine amidotrizoate Chemical compound C[NH2+]C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.CC(=O)NC1=C(I)C(NC(C)=O)=C(I)C(C([O-])=O)=C1I MIKKOBKEXMRYFQ-WZTVWXICSA-N 0.000 claims description 2
- GDOPTJXRTPNYNR-UHFFFAOYSA-N methyl-cyclopentane Natural products CC1CCCC1 GDOPTJXRTPNYNR-UHFFFAOYSA-N 0.000 claims description 2
- ZEYOIOAKZLALAP-UHFFFAOYSA-M sodium amidotrizoate Chemical compound [Na+].CC(=O)NC1=C(I)C(NC(C)=O)=C(I)C(C([O-])=O)=C1I ZEYOIOAKZLALAP-UHFFFAOYSA-M 0.000 claims description 2
- 229950005811 sodium amidotrizoate Drugs 0.000 claims description 2
- 235000019698 starch Nutrition 0.000 claims description 2
- 239000008107 starch Substances 0.000 claims description 2
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 claims 2
- 241001474374 Blennius Species 0.000 claims 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims 1
- 150000001412 amines Chemical class 0.000 claims 1
- RERHJVNYJKZHLJ-UHFFFAOYSA-N bis(2-hydroxyethyl)azanium;2-(3,5-diiodo-4-oxopyridin-1-yl)acetate Chemical compound OCCNCCO.OC(=O)CN1C=C(I)C(=O)C(I)=C1 RERHJVNYJKZHLJ-UHFFFAOYSA-N 0.000 claims 1
- NALMPLUMOWIVJC-UHFFFAOYSA-N n,n,4-trimethylbenzeneamine oxide Chemical compound CC1=CC=C([N+](C)(C)[O-])C=C1 NALMPLUMOWIVJC-UHFFFAOYSA-N 0.000 claims 1
- 230000003647 oxidation Effects 0.000 claims 1
- 229910052708 sodium Inorganic materials 0.000 claims 1
- 239000011734 sodium Substances 0.000 claims 1
- 229940083542 sodium Drugs 0.000 claims 1
- 239000011697 sodium iodate Substances 0.000 claims 1
- 229940032753 sodium iodate Drugs 0.000 claims 1
- 235000015281 sodium iodate Nutrition 0.000 claims 1
- 229940032147 starch Drugs 0.000 claims 1
- 238000005406 washing Methods 0.000 claims 1
- 239000000499 gel Substances 0.000 abstract description 38
- 239000000017 hydrogel Substances 0.000 abstract description 14
- 230000015556 catabolic process Effects 0.000 abstract description 10
- 238000006731 degradation reaction Methods 0.000 abstract description 10
- 238000011161 development Methods 0.000 abstract description 8
- 230000000694 effects Effects 0.000 abstract description 5
- 238000000465 moulding Methods 0.000 abstract description 5
- 238000009833 condensation Methods 0.000 abstract description 4
- 230000005494 condensation Effects 0.000 abstract description 4
- 230000007774 longterm Effects 0.000 abstract description 4
- 239000000700 radioactive tracer Substances 0.000 abstract description 2
- 238000001727 in vivo Methods 0.000 description 8
- 206010028980 Neoplasm Diseases 0.000 description 7
- 239000004372 Polyvinyl alcohol Substances 0.000 description 7
- 239000002262 Schiff base Substances 0.000 description 7
- 229920002451 polyvinyl alcohol Polymers 0.000 description 7
- 150000004753 Schiff bases Chemical class 0.000 description 6
- 238000001959 radiotherapy Methods 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 6
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 5
- PVBALTLWZVEAIO-UHFFFAOYSA-N diodone Chemical compound OC(=O)CN1C=C(I)C(=O)C(I)=C1 PVBALTLWZVEAIO-UHFFFAOYSA-N 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 238000002513 implantation Methods 0.000 description 5
- 229920003023 plastic Polymers 0.000 description 5
- 239000004033 plastic Substances 0.000 description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 5
- 239000002994 raw material Substances 0.000 description 5
- 210000000664 rectum Anatomy 0.000 description 5
- 230000008901 benefit Effects 0.000 description 4
- 230000000052 comparative effect Effects 0.000 description 4
- 238000004132 cross linking Methods 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 4
- 230000029142 excretion Effects 0.000 description 4
- 230000006870 function Effects 0.000 description 4
- 239000003292 glue Substances 0.000 description 4
- 150000004676 glycans Chemical class 0.000 description 4
- 125000006850 spacer group Chemical group 0.000 description 4
- 210000000130 stem cell Anatomy 0.000 description 4
- 239000000654 additive Substances 0.000 description 3
- 230000000996 additive effect Effects 0.000 description 3
- 238000010382 chemical cross-linking Methods 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000002502 liposome Substances 0.000 description 3
- 230000005855 radiation Effects 0.000 description 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
- 238000005303 weighing Methods 0.000 description 3
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 2
- 239000004971 Cross linker Substances 0.000 description 2
- ZNZYKNKBJPZETN-WELNAUFTSA-N Dialdehyde 11678 Chemical compound N1C2=CC=CC=C2C2=C1[C@H](C[C@H](/C(=C/O)C(=O)OC)[C@@H](C=C)C=O)NCC2 ZNZYKNKBJPZETN-WELNAUFTSA-N 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 238000002512 chemotherapy Methods 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 230000002542 deteriorative effect Effects 0.000 description 2
- 229920001971 elastomer Polymers 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 238000002721 intensity-modulated radiation therapy Methods 0.000 description 2
- 230000003902 lesion Effects 0.000 description 2
- 238000011068 loading method Methods 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 210000002307 prostate Anatomy 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 235000010413 sodium alginate Nutrition 0.000 description 2
- 239000000661 sodium alginate Substances 0.000 description 2
- 229940005550 sodium alginate Drugs 0.000 description 2
- 230000007704 transition Effects 0.000 description 2
- 238000002604 ultrasonography Methods 0.000 description 2
- 239000012027 Collins reagent Substances 0.000 description 1
- 244000241257 Cucumis melo Species 0.000 description 1
- 235000015510 Cucumis melo subsp melo Nutrition 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- 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 description 1
- 229920001744 Polyaldehyde Polymers 0.000 description 1
- 229920000604 Polyethylene Glycol 200 Polymers 0.000 description 1
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 description 1
- 229920001030 Polyethylene Glycol 4000 Polymers 0.000 description 1
- 229920002582 Polyethylene Glycol 600 Polymers 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- FJJCIZWZNKZHII-UHFFFAOYSA-N [4,6-bis(cyanoamino)-1,3,5-triazin-2-yl]cyanamide Chemical compound N#CNC1=NC(NC#N)=NC(NC#N)=N1 FJJCIZWZNKZHII-UHFFFAOYSA-N 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 238000004980 dosimetry Methods 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 239000000806 elastomer Substances 0.000 description 1
- 238000012869 ethanol precipitation Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- AZKVWQKMDGGDSV-UHFFFAOYSA-N genipin Natural products COC(=O)C1=COC(O)C2C(CO)=CCC12 AZKVWQKMDGGDSV-UHFFFAOYSA-N 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 238000002786 image-guided radiation therapy Methods 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 229960002358 iodine Drugs 0.000 description 1
- DGAIEPBNLOQYER-UHFFFAOYSA-N iopromide Chemical group COCC(=O)NC1=C(I)C(C(=O)NCC(O)CO)=C(I)C(C(=O)N(C)CC(O)CO)=C1I DGAIEPBNLOQYER-UHFFFAOYSA-N 0.000 description 1
- 229960002603 iopromide Drugs 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229920005615 natural polymer Polymers 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 229920002523 polyethylene Glycol 1000 Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000002861 polymer material Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- NPRDHMWYZHSAHR-UHFFFAOYSA-N pyridine;trioxochromium Chemical compound O=[Cr](=O)=O.C1=CC=NC=C1.C1=CC=NC=C1 NPRDHMWYZHSAHR-UHFFFAOYSA-N 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000002271 resection Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000002893 slag Substances 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- AVPCPPOOQICIRJ-UHFFFAOYSA-L sodium glycerol 2-phosphate Chemical compound [Na+].[Na+].OCC(CO)OP([O-])([O-])=O AVPCPPOOQICIRJ-UHFFFAOYSA-L 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 230000007480 spreading Effects 0.000 description 1
- 238000003892 spreading Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000012876 topography Methods 0.000 description 1
Classifications
-
- 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
- A61K49/00—Preparations for testing in vivo
- A61K49/0002—General or multifunctional contrast agents, e.g. chelated agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/04—X-ray contrast preparations
- A61K49/0433—X-ray contrast preparations containing an organic halogenated X-ray contrast-enhancing agent
- A61K49/0447—Physical forms of mixtures of two different X-ray contrast-enhancing agents, containing at least one X-ray contrast-enhancing agent which is a halogenated organic compound
- A61K49/0457—Semi-solid forms, ointments, gels, hydrogels
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
- A61K49/08—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by the carrier
- A61K49/10—Organic compounds
- A61K49/12—Macromolecular compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
- A61K49/18—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes
- A61K49/1803—Semi-solid preparations, e.g. ointments, gels, hydrogels
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/22—Echographic preparations; Ultrasound imaging preparations ; Optoacoustic imaging preparations
- A61K49/222—Echographic preparations; Ultrasound imaging preparations ; Optoacoustic imaging preparations characterised by a special physical form, e.g. emulsions, liposomes
-
- 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
- A61K9/0024—Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue
-
- 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
-
- 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
- C08J3/02—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
-
- 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
-
- 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
- C08J2405/00—Characterised by the use of polysaccharides or of their derivatives not provided for in groups C08J2401/00 or C08J2403/00
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Radiology & Medical Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Polymers & Plastics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Dispersion Chemistry (AREA)
- Biomedical Technology (AREA)
- Inorganic Chemistry (AREA)
- Neurosurgery (AREA)
- Dermatology (AREA)
- Physics & Mathematics (AREA)
- Acoustics & Sound (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Materials Engineering (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicinal Preparation (AREA)
- Materials For Medical Uses (AREA)
Abstract
The present invention relates to medical macromolecular materials technical fields, to solve, existing injectable hydrogel condensation is slow, intensity is low, biocompatibility and biodegradability are poor, the problem of being unfavorable for the fixed point molding and long-term motion tolerance of gel after injecting, a kind of injection aquagel material is provided, the injection aquagel material injects in-situ preparation using duplex injection technique by component A and B component in equal volume；The component A is carboxymethyl chitosan, and the B component is obtained by dialdehyde polysaccharide and auxiliary crosslinking agent, aldehyde radical contrast material reaction.The exercise tolerance of injection aquagel material of the invention is good, meet bio-compatible and biodegradable requirement on; it is also equipped with the function of multi-modal development, controlled degradation; achieve the effect that integrate protection, tracer, customize treatment etc. multi-functional, have broad application prospects in diagnosis and treatment integration field.
Description
Technical field
The present invention relates to medical macromolecular materials technical field more particularly to a kind of injection aquagel material and its preparations
Method, application.
Background technique
Diagnosis and treatment integration is a kind of emerging medical technology that the diagnosing and treating of disease combines, and passes through diagnosis
The combination of component and therapeutic component while being expected to have now found that disease in fact, treats precisely, in time, avoids further deteriorating.This
It is particularly important for cancer.The treatment means of cancer are usually operation, chemotherapy, radiotherapy.Chemotherapy, the side effect of radiotherapy are big,
Tumor tissues are difficult in surgical procedure.Therefore fixed point treatment is carried out to lesion during diagnosis, be expected in early detection
It gives and timely and effectively treats, reduce the probability for deteriorating, spreading.
In diagnosis and treatment integrated material development process, the information content that multi-modal developing relation to material can monitor in vivo,
Directly influence the accuracy of diagnosis.Tumour is in hardness and the otherness of perienchyma is small, without coating and boundary, and it is swollen
Tumor tissue is easily movable, and difficulty has fixed position.This allows for being difficult to completely identification and tumor resection position during operation, causes hidden
Suffer from.Therefore, during diagnosis, with one kind can developing materials pathological tissues are marked, allow operation when accurately identify
Lesion achievees the purpose that precisely to treat.On the other hand, if the developing materials of implantation can degradation in vivo, can avoid subsequent take
It performs the operation out.Ideally, different according to the treatment cycle demand of different patients, if the time of degradation is controllable, it is expected to realize
Personalized customization treatment, for different sufferers, suitably there is the time in design in vivo.In view of tumour now disease incidence year by year on
Rise, develop it is a integrate label, identification, protection, treatment diagnosis and treatment material with significant realistic meaning.
In recent years, hydrogel material has become the brand-new material of bio-medical field, it is in drug delivery system, group weaver
Cheng Xue and environment-responsive technical field of biological material are all applied.Hydrogel is a kind of polymer with three-dimensional crosslinked network,
Property with high-moisture, soft bullet.Injectable hydrogel is to be injected the colloidal sol of liquid using sol-gel transition point
After entering in vivo, is changed using stimuli responsives such as temperature, pH value, form gel in vivo.It can be to avoid operation implantation, pole
Big reduces costs, and mitigates sufferer pain.
Traditional injection aquagel is mostly temperature sensitive hydrogel, completes sol-gel transition using body temperature.But thermo-sensitive gel
Substantially it is a kind of physical crosslinking type gel, there are the disadvantages such as condensation is slow, intensity is low, is unfavorable for the fixed point molding of gel after injection
With long-term motion tolerance.Use duplex injection technique matrix and crosslinking agent can be sent into body in a manner of two component co-injections
It is interior, chemical crosslinking gel is formed in situ in vivo, can solve the problem that physical gel plastic rate is slow and gel strength is weak.
But most of chemical cross-linking agents have bio-toxicity, and the Biological cross-linker genipin cross-linked reaction time is too long, is unable to satisfy note
Penetrate the fixed point molding effect of rear gel.Therefore exploitation has the chemical crosslinking gel rubber system of biological safety particularly important.This generation
It records just, artificial glass is used as using polyvinyl alcohol (PVA) hydrogel and polyvinylpyrrolidone (PVP) hydrogel of cross-linking radiation
The research of body is very mature.They are proven to have reliable biological safety, but difficult due to being artificial synthesized macromolecule
With degradation.In recent years, research finds that, using natural bioabsorbable polymer material as gel-in-matrix, can get both biocompatibility and life
Biodegradable, such as sodium alginate, hyaluronic acid, xanthan gum, glucan.
" the temperature sensitive type injection aquagel of load fat stem cell excretion body and its preparation are disclosed in Chinese patent literature
The temperature sensitive type of methods and applications ", application publication number CN109568665A, the load fat stem cell excretion body of the invention can be infused
Jetting gel includes temperature sensitive type injection aquagel and fat stem cell excretion body, and the temperature sensitive type injection aquagel contains shell
Glycan, nanometer hydroxyapatite-collagen and sodium β-glycerophosphate.But the temperature sensitive type of the load fat stem cell excretion body can
It injects hydrogel and there are the disadvantages such as condensation is slow, intensity is low, be unfavorable for the fixed point molding and long-term motion tolerance of gel after injection.
Summary of the invention
The condensation of existing injectable hydrogel is slow, intensity is low, biocompatibility and biodegradable in order to overcome by the present invention
Property it is poor, be unfavorable for after injection the fixed point molding of gel and the problem of long-term motion tolerance, provide a kind of exercise tolerance it is good,
Bio-compatible and biodegradability are high, have the injection aquagel material of multi-modal development, controlled degradation function.
The present invention also provides a kind of preparation methods of injection aquagel material, and raw material biological polyoses are from a wealth of sources, at
This cheap, gel being cross-linked to form using schiff base reaction has the fireballing advantage of plastic, and step is easy, medicament obtained
It is easy to maintain.
The present invention also provides a kind of application of injection aquagel material in diagnosis and treatment integration.
To achieve the goals above, the invention adopts the following technical scheme:
A kind of injection aquagel material, which is characterized in that the injection aquagel material is by component A and B component using double
Connection injection technique injects in-situ preparation in equal volume；The component A be carboxymethyl chitosan, the B component by dialdehyde polysaccharide with
Auxiliary crosslinking agent, aldehyde radical contrast material reaction obtain.
The present invention is modified it using biological polyoses as raw material, be chemically crosslinked two components can, is prepared into pure natural life
Object polysaccharide-based injection aquagel；Its mechanism of degradation is studied, design different formulations keep gel degradation expectable, realize to customize and control
It treats；Diodone, liposome microbubble are loaded, tracing in vivo is enhanced, constructs MR, CT, the multi-modal developing system of ultrasound.The present invention
Provided injection aquagel is the gel being cross-linked to form using schiff base reaction, has the fireballing advantage of plastic, and seat
Husband's alkali key is a kind of dynamic reversible covalent bond, assigns gel self-healing properties, and resistance to sports fatigue is good.Moreover, compared to penta 2
The cross-linked network of the small molecules cross-link agent such as aldehyde, macromolecular polyaldehyde has higher integrality and controllability, to assign
Give gel preferably elasticity and gel strength.In addition, the great amount of hydroxy group active site having on biological polyoses chain, is drug loading
Bring possibility.Therefore, using biological polyoses as raw material, had in diagnosis and treatment integration based on the injectable hydrogel of schiff base reaction
There is very big application prospect.
For example, prostate cancer radiotherapy can bring damage to prostate surrounding normal tissue, even with state-of-the-art technology as adjusted
Strong radiotherapy (Intensity modulated radiation therapy, IMRT) and image-guided radiotherapy (Image guided
Radiation therapy, IGRT) etc., the surrounding tissues such as rectum can be preferably protected, but with the increase of Radiotherapy dosimetry, rectum
Antetheca still will receive high dose radiation.Therefore, Radio-oncologist trial is created between prostate and rectum with bioinert material
One " temporary space " is made to reduce the dose of radiation that rectum is subject to, referred to as " interval " (" Spacing ") technology.Injectable water-setting
Glue has biocompatibility and biodegradability, is avoided that operation implantation spacer, this technology is significantly simplified, significant to drop
Low patient suffering, and for the Radio-oncologist for being familiar with close-range treatment, injection operation is easily mastered.If water-setting glue material
Material has the function of multi-modal development, then not only has the function of protecting rectum in this technical application, can also instruct shadow
As diagnosis, gel location, form are monitored over the course for the treatment of.
Preferably, the carboxymethyl chitosan is made in accordance with the following methods: by chitosan sodium hydroxide 50~80
The chitosan suspension of 1~3h is swollen at DEG C；Chloroacetic acid is dissolved in isopropanol, is added drop-wise to chitosan at 60~90 DEG C
In suspension, after reacting 3~4h, crude product is obtained；It is washed, it is dry, obtain carboxymethyl chitosan.
Preferably, the dialdehyde polysaccharide is made in accordance with the following methods: biological polyoses are soluble in water, it is dripped in dark
Increase sodium iodide solution, react 2 at room temperature~for 24 hours, centrifugal filtering liquid, then be settled out product with dehydrated alcohol is drying to obtain
Dialdehyde polysaccharide.
The groups such as hydroxyl how rich in, amino in natural polysaccharide can obtain schiff bases by simple reaction treatment
Aldehyde radical, amino needed for reaction.
Preferably, the biological polyoses are selected from sodium alginate, hyaluronic acid, heparin, chondroitin sulfate, glucan, melon
One of your glue, xanthan gum, starch, dextrin, Arabic gum and carragheen；It is preferred that guar gum.
Preferably, the aldehyde radical contrast agent is oxidizing through aldehyde radicalization by diodone, purification is made.It is described to mention
It is pure to be purified for pillar layer separation.
Preferably, the diodone is selected from Iopromide, Iopamidol, cardiografin, Iohexol, Sodium Amidotrizoate, iodine
One of carburetion and Iodixanol；It is preferred that Iopamidol；
Preferably, the aldehyde radical oxidant be selected from activated manganese dioxide, sodium metaperiodate, Swern reagent, DMP reagent,
One of TEMPO reagent, Jones reagent and Collins reagent；It is preferred that sodium metaperiodate and activated manganese dioxide.
Preferably, the aldehyde radical oxidant is sodium metaperiodate, oxidization time is controlled in 2~6h.
Preferably, the aldehyde radical oxidant is activated manganese dioxide, oxidizing temperature is 50~80 DEG C, and oxidization time is
6~12h.
A kind of preparation method of injection aquagel material, comprising the following steps:
(1) carboxymethyl chitosan solution for configuring 1~5wt%, obtains component A；
(2) in the dialdehyde polysaccharide solution of 1~5wt%, auxiliary crosslinking agent solution and aldehyde radical contrast agent is added, obtains B group
Point；The auxiliary crosslinking agent include polyvinyl alcohol 1798, polyvinyl alcohol 1788, polyvinyl alcohol 1750, PEG-200, PEG-400,
PEG-600, PEG-1000, PEG4000, PEG-10000 etc., preferred polyvinyl alcohol 1798 in this patent；The step is in room temperature item
Part hybrid reaction；On the basis of mixed total volume, the volume fraction of each component are as follows: carboxymethyl chitosan 30%~50%；
Dialdehyde polysaccharide 20%~35%；Auxiliary crosslinking agent 10%~15%；Aldehyde radical contrast agent 5%~10%；
(3) using duplex injection technique by component A and B component, isometric injection can in-situ preparation injectable water-setting in the several seconds
Glue material；The gel being cross-linked to form using schiff base reaction has the fireballing advantage of plastic.
The present invention with the modified chitosan of water-solubleization for the first component, with the biological polyoses after aldehyde grouping modified, modification
Diodone, liposome microbubble, auxiliary crosslinker solution be the second component, two components by duplex injection form mix after amino
Schiff bases cross-linking reaction occurs with aldehyde radical and forms gel, contrast agent is grafted on gel molecular chain in the form chemically reacted, makes
Hydrogel spacer load C T contrast agent, acoustic contrast agent, it can be achieved that multi-modal development, monitored for flexible after implantation, with
Track provides basis, with the progress of entire treatment cycle, can play development Detectable effects, it can be achieved that when development duration is with degradation
Long synchronism.
A kind of application of injection aquagel material in diagnosis and treatment integration.
Therefore, the invention has the following beneficial effects:
(1) exercise tolerance of injection aquagel material of the invention is good, meets bio-compatible and biodegradable requirement
On, it is also equipped with the function of multi-modal development, controlled degradation, reaches and integrates protection, tracer, customizes treatment etc. multi-functional
Effect；
(2) raw material biological polyoses are from a wealth of sources, low in cost, the gel being cross-linked to form using schiff base reaction, have plastic speed
Fast advantage is spent, step is easy, and medicament obtained is easy to maintain, is expected to realize industrialized production and clinical application；
(3) gel degradation is expectable, realizes and customizes treatment, loads diodone, liposome microbubble, enhances tracing in vivo,
Construct MR, CT, the multi-modal developing system of ultrasound, can be provided for the biomedical applications of such natural polymer theoretical direction with
Experiment basis is implanted into hydrogel spacer in the form of injection, avoids operation implantation bring pain and cost, and have opposite
Faster learning curve, it is significant to clinic conversion, it has broad application prospects in diagnosis and treatment integration field.
Detailed description of the invention
Fig. 1 is the low range SEM figure of injection aquagel material made from embodiment 1.
Fig. 2 is the high magnification SEM figure of injection aquagel material made from embodiment 1.
Fig. 3 is the storage modulus (G ') of injection aquagel material made from embodiment 1-5, loss modulus (G ") with frequency
Variation diagram.
Specific embodiment
Below by specific embodiment, and in conjunction with attached drawing, the technical solutions of the present invention will be further described.
In the present invention, if not refering in particular to, all devices and raw material is commercially available or the industry is common are following
Method in embodiment is unless otherwise instructed conventional method in that art.
Embodiment 1
(1) accurate weighing 10.0g chitosan, 10g sodium hydroxide are in three-necked flask, addition 100mL isopropanol solvent, at 50 DEG C
Swelling 3 hours；Accurate weighing 10.0g chloroacetic acid is simultaneously dissolved in 20mL isopropanol.Chloroacetic acid solution is slowly added dropwise to shell
12h is reacted in glycan lye；Pour into 200mL dehydrated alcohol washed product, filtering, drying to obtain carboxymethyl chitosan；
(2) accurate weighing 1.0g guar gum is dissolved in 100mL water, and 10ml sodium periodate solution is added dropwise in dark at room temperature
(0.1g/mL) reacts 2h.Centrifugation is removed slag, and ethanol precipitation goes out product, dry dialdehyde guar gum；
(3) 10mL iohexol injection is measured, 1mL sodium periodate solution (0.1g/mL) is added dropwise in dark at room temperature and reacts 1h；
Aldehyde radical Iohexol solution is obtained after column chromatography separating purification；
(4) by above-mentioned carboxymethyl chitosan be configured to 5.0mL mass fraction be 2% solution to get component A；
(5) above-mentioned dialdehyde guar gum is made into the solution that 3.0mL mass fraction is 2%, and it is molten that 1.5mL polyvinyl alcohol 1798 is added
The iohexol injection formation B component of liquid (2wt%), 0.5mL aldehyde radical；
(6) the two component mixed liquor of A, B of difference draws equal amounts, injects to obtain hydrogel spacer, as injectable by duplex
Hydrogel material.
From timing when starting injection, terminates when stopping and flowing to colloidal sol, be calculated as gel time.
It after gel is freezed, is placed in freeze drier and drains, xerogel is made.Xerogel surface metal spraying is handled, with
Its surface topography is observed under scanning electron microscope, SEM figure is as depicted in figs. 1 and 2, it can be seen from the figure that the injection aquagel
Material has intensive hole configurations, and at 5 μm or so, hole is perfect in aperture.Hole configurations can keep large quantity of moisture, be drug
Load provides possibility, and the concentration of hole and degree of perfection affect the intensity of its gel body.This is gel tool
There is the reason of higher Drug loading capacity and gel strength.
Embodiment 2- embodiment 5
Embodiment 2- embodiment 5 the difference from embodiment 1 is that, in step (5), the formula of B component is different, referring to table 1, remaining
Technique is identical.
Comparative example 1
Comparative example 1 the difference from embodiment 1 is that, in step (5), the formula of B component is different, and referring to table 1, remaining technique is complete
It is identical.
The B component formula and gel time of table 1. embodiment 1-5 and comparative example 1
| Number | Carboxymethyl chitosan | Aldehyde radical polysaccharide | Auxiliary crosslinking agent | Gel time |
| Embodiment 1 | 5mL | 1mL | 3.5mL | 76-106s |
| Embodiment 2 | 5mL | 2mL | 2.5mL | 23-42s |
| Embodiment 3 | 5mL | 3mL | 1.5mL | 8-15s |
| Embodiment 4 | 5mL | 4mL | 0.5mL | 25-36s |
| Embodiment 5 | 5mL | 4.5mL | 0 | 32-39s |
| Comparative example 1 | 5mL | 10mL | 0 | 72-96s |
As can be seen from Table 1, gel time is related with crosslinking agent additive amount, this is because the additional amount of crosslinking agent influences finally
The mixed concentration of two components, concentration is higher, and reaction is faster.But since amino and aldehyde radical are reaction with same mole, when group ratio is 1:
Reactivity is best when 1.Therefore, to will appear gel time elongated after additive amount is more than the group number of amino.
Injection aquagel material made from embodiment 1-5 is placed in advanced expansion rheometer, scanning constant strain and temperature
Degree tests the relationship of modulus and frequency, as a result as shown in Figure 3: as the additional amount of aldehyde radical polysaccharide increases, in elasticity modulus presentation
The trend risen, it means that the increase of gel elastomer.After additive amount is more than a certain range, elasticity is no longer further increased, this
It is because amino is depleted that the degree of cross linking does not continue to increase.For the material to implant it is necessary to have with tissue
Similar modulus.The modulus of most of soft tissue can be in the region in 2000-5000Pa, the modulus of this gel just, fit
It shares and makees diagnosis and treatment integrated material.
The foregoing is merely presently preferred embodiments of the present invention, is not intended to limit the present invention in any form, and is not surpassing
There are also other variations and modifications under the premise of technical solution documented by claim out.
Claims (10)
1. a kind of injection aquagel material, which is characterized in that the injection aquagel material is used by component A and B component
Duplex injection technique injects in-situ preparation in equal volume；The component A is carboxymethyl chitosan, and the B component is by dialdehyde polysaccharide
It is obtained with auxiliary crosslinking agent, aldehyde radical contrast material reaction.
2. a kind of injection aquagel material according to claim 1, which is characterized in that the carboxymethyl chitosan according to
Following methods are made: chitosan sodium hydroxide is swollen to the chitosan suspension of 1~3h at 50~80 DEG C；By chloroacetic acid
It is dissolved in isopropanol, is added drop-wise at 60~90 DEG C in chitosan suspension, after reacting 3~4h, obtain crude product；Through washing
It washs, it is dry, obtain carboxymethyl chitosan.
3. a kind of injection aquagel material according to claim 1, which is characterized in that the dialdehyde polysaccharide according to
Lower section method be made: biological polyoses are soluble in water, sodium periodate solution is added dropwise in dark, at room temperature react 2~for 24 hours, from
The heart takes clear liquid, then is settled out product with dehydrated alcohol, is drying to obtain dialdehyde polysaccharide.
4. a kind of injection aquagel material according to claim 3, which is characterized in that the biological polyoses are selected from seaweed
Sour sodium, hyaluronic acid, heparin, chondroitin sulfate, glucan, guar gum, xanthan gum, starch, dextrin, Arabic gum and carragheen
One of.
5. a kind of injection aquagel material according to claim 1, which is characterized in that the aldehyde radical contrast agent is by iodine
Contrast agent is oxidizing through aldehyde radicalization, purification is made.
6. a kind of injection aquagel material according to claim 5, which is characterized in that it is general that the diodone is selected from iodine
One of sieve amine, Iopamidol, cardiografin, Iohexol, Sodium Amidotrizoate, iodized oil and Iodixanol；The aldehyde radicalization oxidation
Agent is selected from activated manganese dioxide, sodium metaperiodate, Swern reagent, DMP reagent, TEMPO reagent, Jones reagent and Collins examination
One of agent.
7. a kind of injection aquagel material according to claim 6, which is characterized in that the aldehyde radical oxidant is height
Sodium iodate, oxidization time are controlled in 2~6h.
8. a kind of injection aquagel material according to claim 6, which is characterized in that the aldehyde radical oxidant is to live
Property manganese dioxide, oxidizing temperature be 50~80 DEG C, oxidization time be 6~12h.
9. a kind of preparation method of injection aquagel material a method as claimed in any one of claims 1-8, which is characterized in that including with
Lower step:
(1) carboxymethyl chitosan solution for configuring 1~5wt%, obtains component A；
(2) in the dialdehyde polysaccharide solution of 1~5wt%, auxiliary crosslinking agent solution and aldehyde radical contrast agent is added, obtains B group
Point；
(3) using duplex injection technique by component A and B component, isometric injection can in-situ preparation injection aquagel material
Material.
10. a kind of application of injection aquagel material a method as claimed in any one of claims 1-8 in diagnosis and treatment integration.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910637570.4A CN110404083B (en) | 2019-07-15 | 2019-07-15 | Injectable hydrogel material and preparation method and application thereof |
| PCT/CN2019/100764 WO2021007899A1 (en) | 2019-07-15 | 2019-08-15 | Injectable hydrogel material and preparation method therefor and use thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910637570.4A CN110404083B (en) | 2019-07-15 | 2019-07-15 | Injectable hydrogel material and preparation method and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN110404083A true CN110404083A (en) | 2019-11-05 |
| CN110404083B CN110404083B (en) | 2021-03-09 |
Family
ID=68361486
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910637570.4A Active CN110404083B (en) | 2019-07-15 | 2019-07-15 | Injectable hydrogel material and preparation method and application thereof |
Country Status (2)
| Country | Link |
|---|---|
| CN (1) | CN110404083B (en) |
| WO (1) | WO2021007899A1 (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111228579A (en) * | 2020-01-21 | 2020-06-05 | 赛克赛斯生物科技股份有限公司 | Injectable hydrogel, preparation method and application thereof, and joint lubricant |
| CN111803707A (en) * | 2020-06-05 | 2020-10-23 | 上海大学 | Polysaccharide-based fiber composite in-situ pore-forming injectable hydrogel and preparation method thereof |
| CN112048079A (en) * | 2020-09-08 | 2020-12-08 | 西北大学 | Carboxymethyl chitosan-alginate injectable double-network temperature-sensitive hydrogel and preparation method and application thereof |
| WO2021258725A1 (en) * | 2020-06-22 | 2021-12-30 | 北京大学深圳医院 | Method for preparing injectable and degradable anti-fracturing supramolecular hydrogel |
| CN114209645A (en) * | 2021-12-17 | 2022-03-22 | 大连大学 | Preparation method of CS-KOS temperature-sensitive hydrogel for slowly releasing k-carrageenan oligosaccharides |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113024845A (en) * | 2021-03-17 | 2021-06-25 | 广西医科大学 | Preparation method of aldehyde hydrazine cross-linked antibacterial hydrogel dressing |
| CN113754794B (en) * | 2021-08-10 | 2022-12-23 | 武汉纺织大学 | Carboxymethyl chitosan fluid with good antibacterial property and high-temperature resistance and capable of being processed and preparation method thereof |
| CN114230812A (en) * | 2021-12-07 | 2022-03-25 | 广东省科学院健康医学研究所 | Functional hydrogel and preparation method and application thereof |
| CN114230678B (en) * | 2021-12-13 | 2023-09-01 | 珠海通桥医疗科技有限公司 | Photocrosslinked hydrogel embolism system for intravascular treatment and application method |
| CN114452436B (en) * | 2022-03-15 | 2022-08-23 | 四川大学 | Collagen-based injectable self-repairing hydrogel and preparation method thereof |
| CN114796620B (en) * | 2022-04-24 | 2023-09-29 | 广东顺德工业设计研究院(广东顺德创新设计研究院) | Interpenetrating network hydrogel used as medical implant material and preparation method and application thereof |
| CN114939098B (en) * | 2022-05-19 | 2023-09-26 | 明德南加(成都)生物技术有限公司 | Exosome-loaded hydrogel and preparation method and application thereof |
| CN115177748B (en) * | 2022-08-01 | 2024-11-01 | 北京大学口腔医学院 | Application of ioversol in preparation of body surface contrast agent and body surface contrast agent |
| CN115651220A (en) * | 2022-10-28 | 2023-01-31 | 合肥师范学院 | Prussian blue/chitosan/sodium alginate composite hydrogel as well as preparation method and application thereof |
| CN116421745B (en) * | 2023-06-14 | 2023-08-29 | 中国人民解放军总医院第一医学中心 | Abdominal bleeding point delay imaging contrast agent |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101439206A (en) * | 2007-11-22 | 2009-05-27 | 郭倩 | Preparation of enzyme-catalyzed rapid-solidified hydrogel and use thereof |
| CN105833344A (en) * | 2016-04-26 | 2016-08-10 | 青岛慧生惠众生物科技有限公司 | Application of injectable hydrogel in preparing intraocular filling materials |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9132207B2 (en) * | 2009-10-27 | 2015-09-15 | Spine Wave, Inc. | Radiopaque injectable nucleus hydrogel compositions |
| NZ599524A (en) * | 2009-11-09 | 2014-04-30 | Spotlight Technology Partners Llc | Polysaccharide based hydrogels |
| CN103937014B (en) * | 2014-04-10 | 2016-05-25 | 北京爱美客生物科技有限公司 | Shitosan dual network rapid response type injection aquagel and preparation method thereof |
| CN104479150A (en) * | 2014-10-29 | 2015-04-01 | 上海大学 | Preparation method of multiple cross-linked polysaccharide injectable hydrogel |
| CN106109400A (en) * | 2016-07-22 | 2016-11-16 | 金陵科技学院 | A kind of oral drugs hydrogel slow-released carrier and preparation method and applications |
| CN109694484B (en) * | 2017-10-20 | 2021-08-27 | 四川大学华西医院 | Immunologic adjuvant and preparation method thereof |
-
2019
- 2019-07-15 CN CN201910637570.4A patent/CN110404083B/en active Active
- 2019-08-15 WO PCT/CN2019/100764 patent/WO2021007899A1/en active Application Filing
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101439206A (en) * | 2007-11-22 | 2009-05-27 | 郭倩 | Preparation of enzyme-catalyzed rapid-solidified hydrogel and use thereof |
| CN105833344A (en) * | 2016-04-26 | 2016-08-10 | 青岛慧生惠众生物科技有限公司 | Application of injectable hydrogel in preparing intraocular filling materials |
Non-Patent Citations (3)
| Title |
|---|
| LIHONG FAN ET AL.: "Preparation and characterization of Oxidized Konjac Glucomannan/Carboxymethyl Chitosan/Graphene Oxide hydrogel", 《INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES》 * |
| RIHAM R. MOHAMED ET AL.: "Synthesis, characterization and applications of N-quaternized chitosan/poly(vinyl alcohol) hydrogels", 《INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES》 * |
| 李丹丹等: "基于席夫碱反应的氧化葡聚糖/胺化羧甲基壳聚糖双组分水凝胶粘合剂", 《中国组织工程研究》 * |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111228579A (en) * | 2020-01-21 | 2020-06-05 | 赛克赛斯生物科技股份有限公司 | Injectable hydrogel, preparation method and application thereof, and joint lubricant |
| CN111228579B (en) * | 2020-01-21 | 2021-12-03 | 赛克赛斯生物科技股份有限公司 | Injectable hydrogel, preparation method and application thereof, and joint lubricant |
| CN111803707A (en) * | 2020-06-05 | 2020-10-23 | 上海大学 | Polysaccharide-based fiber composite in-situ pore-forming injectable hydrogel and preparation method thereof |
| WO2021258725A1 (en) * | 2020-06-22 | 2021-12-30 | 北京大学深圳医院 | Method for preparing injectable and degradable anti-fracturing supramolecular hydrogel |
| CN112048079A (en) * | 2020-09-08 | 2020-12-08 | 西北大学 | Carboxymethyl chitosan-alginate injectable double-network temperature-sensitive hydrogel and preparation method and application thereof |
| CN114209645A (en) * | 2021-12-17 | 2022-03-22 | 大连大学 | Preparation method of CS-KOS temperature-sensitive hydrogel for slowly releasing k-carrageenan oligosaccharides |
| CN114209645B (en) * | 2021-12-17 | 2023-11-07 | 大连大学 | Preparation method of CS-KOS temperature-sensitive hydrogel for slowly releasing k-carrageenan oligosaccharides |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2021007899A1 (en) | 2021-01-21 |
| CN110404083B (en) | 2021-03-09 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN110404083A (en) | A kind of injection aquagel material and preparation method thereof, application | |
| Tan et al. | Development of alginate-based hydrogels: Crosslinking strategies and biomedical applications | |
| Gholamali | Stimuli-responsive polysaccharide hydrogels for biomedical applications: a review | |
| Khan et al. | Recent advances of emerging green chitosan-based biomaterials with potential biomedical applications: A review | |
| El-Husseiny et al. | Smart/stimuli-responsive hydrogels: Cutting-edge platforms for tissue engineering and other biomedical applications | |
| Ye et al. | Advances in hydrogels based on dynamic covalent bonding and prospects for its biomedical application | |
| CN110124117B (en) | Injectable hydrogel and preparation method thereof | |
| JPH11505734A (en) | Injectable hydrogel composition | |
| CN102827446B (en) | Temperature response type injectable hydrogel and preparation method and usage thereof | |
| CN104922675A (en) | Preparation method of graphene oxide composite material mediated by carboxymethyl chitosan and modified by hyaluronic acid | |
| CN115554462B (en) | Anti-swelling injectable hydrogel adhesive and preparation method thereof | |
| CN109021169A (en) | A kind of sodium alginate polymer, novel alga acid natremia pipe embolism chemical therapeutic composition and its preparation method and application | |
| CN111870806A (en) | Magnetic control microneedle robot and preparation method, use method and application thereof | |
| CN107693838A (en) | A kind of medical injectable gel and preparation method thereof | |
| US20240076266A1 (en) | Iodine labeled hydrogels and precursors thereof with improved properties | |
| BR112021011574A2 (en) | HYALURONIC ACID MODIFIED BY ALDEHYDE, METHOD FOR PREPARING IT AND APPLICATIONS THEREOF | |
| CN106750416B (en) | It is a kind of to possess self-healing and the injection aquagel of pH response performance and its preparation method and application | |
| CN106139166B (en) | Chitosan derivatives are the MRI contrast agent and preparation method of carrier | |
| US10376469B2 (en) | Microspheres containing therapeutic agents and related methods of use | |
| US20240115759A1 (en) | Medical tissue adhesive and preparation method thereof | |
| CN107595767A (en) | It is a kind of to possess to antibacterial injection aquagel of electro photoluminescence and pH double-response performances and its preparation method and application | |
| US20240075190A1 (en) | Iodinated crosslinked hydrogels and methods of forming the same | |
| Wang et al. | Chitosan‐based hydrogels | |
| US11229604B2 (en) | Microspheres containing therapeutic agents and related methods of use | |
| CN108421042B (en) | Preparation method of light-operated degradable hydrogel |
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: 20230113 Address after: Room 703, Unit 3, Building 1, No. 13, Nangonghe Road, Linping Street, Linping District, Hangzhou City, Zhejiang Province, 310000 Patentee after: Hangzhou Bitai Biomedical Technology Co.,Ltd. Address before: 310014 No. 18 Chao Wang Road, Xiacheng District, Zhejiang, Hangzhou Patentee before: JIANG University OF TECHNOLOGY |
|
| TR01 | Transfer of patent right |