CN107412151A - A kind of phytolectin polysaccharide hydrogel of intelligent control insulin releasing and its preparation and application - Google Patents
A kind of phytolectin polysaccharide hydrogel of intelligent control insulin releasing and its preparation and application Download PDFInfo
- Publication number
- CN107412151A CN107412151A CN201710612832.2A CN201710612832A CN107412151A CN 107412151 A CN107412151 A CN 107412151A CN 201710612832 A CN201710612832 A CN 201710612832A CN 107412151 A CN107412151 A CN 107412151A
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- China
- Prior art keywords
- phytolectin
- hydrogel
- polysaccharide
- added
- insulin
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- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 title claims abstract description 149
- 239000000017 hydrogel Substances 0.000 title claims abstract description 121
- 229920001282 polysaccharide Polymers 0.000 title claims abstract description 99
- 239000005017 polysaccharide Substances 0.000 title claims abstract description 99
- 102000004877 Insulin Human genes 0.000 title claims abstract description 75
- 108090001061 Insulin Proteins 0.000 title claims abstract description 75
- 229940125396 insulin Drugs 0.000 title claims abstract description 75
- 150000004676 glycans Chemical class 0.000 title claims abstract description 66
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- 238000002360 preparation method Methods 0.000 title claims abstract description 23
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- 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 7
- 239000000243 solution Substances 0.000 claims description 53
- 238000006243 chemical reaction Methods 0.000 claims description 48
- 238000003756 stirring Methods 0.000 claims description 39
- 239000007853 buffer solution Substances 0.000 claims description 38
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 30
- 229950003779 propiram Drugs 0.000 claims description 24
- 239000000910 agglutinin Substances 0.000 claims description 17
- 238000004108 freeze drying Methods 0.000 claims description 14
- ZBAFFZBKCMWUHM-UHFFFAOYSA-N propiram Chemical compound C=1C=CC=NC=1N(C(=O)CC)C(C)CN1CCCCC1 ZBAFFZBKCMWUHM-UHFFFAOYSA-N 0.000 claims description 13
- 150000008065 acid anhydrides Chemical class 0.000 claims description 12
- 101710186708 Agglutinin Proteins 0.000 claims description 11
- 101710146024 Horcolin Proteins 0.000 claims description 11
- 101710189395 Lectin Proteins 0.000 claims description 11
- 101710179758 Mannose-specific lectin Proteins 0.000 claims description 11
- 101710150763 Mannose-specific lectin 1 Proteins 0.000 claims description 11
- 101710150745 Mannose-specific lectin 2 Proteins 0.000 claims description 11
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 10
- 239000003814 drug Substances 0.000 claims description 10
- 239000007788 liquid Substances 0.000 claims description 10
- 239000003960 organic solvent Substances 0.000 claims description 10
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 claims description 9
- 235000010523 Cicer arietinum Nutrition 0.000 claims description 8
- 244000045195 Cicer arietinum Species 0.000 claims description 8
- 244000068988 Glycine max Species 0.000 claims description 8
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- 235000010580 Psophocarpus tetragonolobus Nutrition 0.000 claims description 8
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 8
- 240000004922 Vigna radiata Species 0.000 claims description 8
- 235000010721 Vigna radiata var radiata Nutrition 0.000 claims description 8
- 235000011469 Vigna radiata var sublobata Nutrition 0.000 claims description 8
- 238000007654 immersion Methods 0.000 claims description 8
- 229920000945 Amylopectin Polymers 0.000 claims description 7
- 229920000856 Amylose Polymers 0.000 claims description 7
- 241000196324 Embryophyta Species 0.000 claims description 7
- 229920001491 Lentinan Polymers 0.000 claims description 7
- 150000001412 amines Chemical class 0.000 claims description 7
- 229940115286 lentinan Drugs 0.000 claims description 7
- 229910021645 metal ion Inorganic materials 0.000 claims description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- 229920002752 Konjac Polymers 0.000 claims description 6
- 238000004458 analytical method Methods 0.000 claims description 5
- 238000009738 saturating Methods 0.000 claims description 5
- JPSKCQCQZUGWNM-UHFFFAOYSA-N 2,7-Oxepanedione Chemical compound O=C1CCCCC(=O)O1 JPSKCQCQZUGWNM-UHFFFAOYSA-N 0.000 claims description 4
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 claims description 4
- 238000004132 cross linking Methods 0.000 claims description 4
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 claims description 4
- VANNPISTIUFMLH-UHFFFAOYSA-N glutaric anhydride Chemical compound O=C1CCCC(=O)O1 VANNPISTIUFMLH-UHFFFAOYSA-N 0.000 claims description 4
- KKHUSADXXDNRPW-UHFFFAOYSA-N malonic anhydride Chemical compound O=C1CC(=O)O1 KKHUSADXXDNRPW-UHFFFAOYSA-N 0.000 claims description 4
- 239000000203 mixture Substances 0.000 claims description 4
- FALRKNHUBBKYCC-UHFFFAOYSA-N 2-(chloromethyl)pyridine-3-carbonitrile Chemical compound ClCC1=NC=CC=C1C#N FALRKNHUBBKYCC-UHFFFAOYSA-N 0.000 claims description 3
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 claims description 3
- 229920002907 Guar gum Polymers 0.000 claims description 3
- 244000046052 Phaseolus vulgaris Species 0.000 claims description 3
- 235000010627 Phaseolus vulgaris Nutrition 0.000 claims description 3
- 150000008064 anhydrides Chemical class 0.000 claims description 3
- 230000003197 catalytic effect Effects 0.000 claims description 3
- 239000003292 glue Substances 0.000 claims description 3
- 239000000665 guar gum Substances 0.000 claims description 3
- 235000010417 guar gum Nutrition 0.000 claims description 3
- 229960002154 guar gum Drugs 0.000 claims description 3
- 229940014800 succinic anhydride Drugs 0.000 claims description 3
- 229920002527 Glycogen Polymers 0.000 claims description 2
- 108010046016 Peanut Agglutinin Proteins 0.000 claims description 2
- 150000001718 carbodiimides Chemical class 0.000 claims description 2
- 229940096919 glycogen Drugs 0.000 claims description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims 1
- 108010089814 Plant Lectins Proteins 0.000 claims 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 abstract description 41
- 239000008103 glucose Substances 0.000 abstract description 40
- 239000002994 raw material Substances 0.000 abstract description 13
- 239000000463 material Substances 0.000 abstract description 9
- 238000000034 method Methods 0.000 abstract description 9
- 125000002791 glucosyl group Chemical group C1([C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 abstract description 4
- 238000010382 chemical cross-linking Methods 0.000 abstract description 3
- 230000008859 change Effects 0.000 description 20
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- 229910052738 indium Inorganic materials 0.000 description 10
- 229920001223 polyethylene glycol Polymers 0.000 description 10
- -1 polysaccharide Chemical class 0.000 description 9
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 8
- 229910021380 Manganese Chloride Inorganic materials 0.000 description 8
- GLFNIEUTAYBVOC-UHFFFAOYSA-L Manganese chloride Chemical compound Cl[Mn]Cl GLFNIEUTAYBVOC-UHFFFAOYSA-L 0.000 description 8
- 239000001110 calcium chloride Substances 0.000 description 8
- 229910001628 calcium chloride Inorganic materials 0.000 description 8
- 229910001629 magnesium chloride Inorganic materials 0.000 description 8
- 239000011565 manganese chloride Substances 0.000 description 8
- 235000002867 manganese chloride Nutrition 0.000 description 8
- 229940099607 manganese chloride Drugs 0.000 description 8
- 230000009870 specific binding Effects 0.000 description 8
- 230000004913 activation Effects 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 235000017060 Arachis glabrata Nutrition 0.000 description 6
- 244000105624 Arachis hypogaea Species 0.000 description 6
- 235000010777 Arachis hypogaea Nutrition 0.000 description 6
- 235000018262 Arachis monticola Nutrition 0.000 description 6
- 239000000872 buffer Substances 0.000 description 6
- 239000012153 distilled water Substances 0.000 description 6
- 235000020232 peanut Nutrition 0.000 description 6
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 5
- 239000008280 blood Substances 0.000 description 5
- 210000004369 blood Anatomy 0.000 description 5
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 5
- 239000008057 potassium phosphate buffer Substances 0.000 description 5
- 239000007974 sodium acetate buffer Substances 0.000 description 5
- BHZOKUMUHVTPBX-UHFFFAOYSA-M sodium acetic acid acetate Chemical compound [Na+].CC(O)=O.CC([O-])=O BHZOKUMUHVTPBX-UHFFFAOYSA-M 0.000 description 5
- LUEWUZLMQUOBSB-FSKGGBMCSA-N (2s,3s,4s,5s,6r)-2-[(2r,3s,4r,5r,6s)-6-[(2r,3s,4r,5s,6s)-4,5-dihydroxy-2-(hydroxymethyl)-6-[(2r,4r,5s,6r)-4,5,6-trihydroxy-2-(hydroxymethyl)oxan-3-yl]oxyoxan-3-yl]oxy-4,5-dihydroxy-2-(hydroxymethyl)oxan-3-yl]oxy-6-(hydroxymethyl)oxane-3,4,5-triol Chemical compound O[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@@H](O[C@@H]2[C@H](O[C@@H](OC3[C@H](O[C@@H](O)[C@@H](O)[C@H]3O)CO)[C@@H](O)[C@H]2O)CO)[C@H](O)[C@H]1O LUEWUZLMQUOBSB-FSKGGBMCSA-N 0.000 description 4
- 238000005160 1H NMR spectroscopy Methods 0.000 description 4
- 229920002581 Glucomannan Polymers 0.000 description 4
- SWSHKRHJENMKJJ-UHFFFAOYSA-L O.[Na+].P(=O)(O)(O)[O-].[K+].P(=O)(O)(O)[O-] Chemical compound O.[Na+].P(=O)(O)(O)[O-].[K+].P(=O)(O)(O)[O-] SWSHKRHJENMKJJ-UHFFFAOYSA-L 0.000 description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
- 238000000502 dialysis Methods 0.000 description 4
- 229940046240 glucomannan Drugs 0.000 description 4
- 229910052739 hydrogen Inorganic materials 0.000 description 4
- 239000001257 hydrogen Substances 0.000 description 4
- 239000000252 konjac Substances 0.000 description 4
- BUCIWTBCUUHRHZ-UHFFFAOYSA-K potassium;disodium;dihydrogen phosphate;hydrogen phosphate Chemical compound [Na+].[Na+].[K+].OP(O)([O-])=O.OP([O-])([O-])=O BUCIWTBCUUHRHZ-UHFFFAOYSA-K 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- 230000008961 swelling Effects 0.000 description 4
- XPFJYKARVSSRHE-UHFFFAOYSA-K trisodium;2-hydroxypropane-1,2,3-tricarboxylate;2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound [Na+].[Na+].[Na+].OC(=O)CC(O)(C(O)=O)CC(O)=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O XPFJYKARVSSRHE-UHFFFAOYSA-K 0.000 description 4
- LEAHFJQFYSDGGP-UHFFFAOYSA-K trisodium;dihydrogen phosphate;hydrogen phosphate Chemical compound [Na+].[Na+].[Na+].OP(O)([O-])=O.OP([O-])([O-])=O LEAHFJQFYSDGGP-UHFFFAOYSA-K 0.000 description 4
- 108010062580 Concanavalin A Proteins 0.000 description 3
- WLJVNTCWHIRURA-UHFFFAOYSA-N Heptanedioic acid Natural products OC(=O)CCCCCC(O)=O WLJVNTCWHIRURA-UHFFFAOYSA-N 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000012738 dissolution medium Substances 0.000 description 3
- 231100000252 nontoxic Toxicity 0.000 description 3
- 230000003000 nontoxic effect Effects 0.000 description 3
- OSCBARYHPZZEIS-UHFFFAOYSA-N phenoxyboronic acid Chemical group OB(O)OC1=CC=CC=C1 OSCBARYHPZZEIS-UHFFFAOYSA-N 0.000 description 3
- 229920002627 poly(phosphazenes) Polymers 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- HXMWJLVXIHYART-UHFFFAOYSA-M sodium;2-hydroxypropane-1,2,3-tricarboxylic acid;hydroxide;hydrochloride Chemical compound [OH-].[Na+].Cl.OC(=O)CC(O)(C(O)=O)CC(O)=O HXMWJLVXIHYART-UHFFFAOYSA-M 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 239000004366 Glucose oxidase Substances 0.000 description 2
- 108010015776 Glucose oxidase Proteins 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- 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 description 2
- 108090001090 Lectins Proteins 0.000 description 2
- 102000004856 Lectins Human genes 0.000 description 2
- 239000004372 Polyvinyl alcohol Substances 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- 235000009754 Vitis X bourquina Nutrition 0.000 description 2
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- MKJXYGKVIBWPFZ-UHFFFAOYSA-L calcium lactate Chemical compound [Ca+2].CC(O)C([O-])=O.CC(O)C([O-])=O MKJXYGKVIBWPFZ-UHFFFAOYSA-L 0.000 description 2
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- 239000011591 potassium Substances 0.000 description 2
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- OTNVGWMVOULBFZ-UHFFFAOYSA-N sodium;hydrochloride Chemical compound [Na].Cl OTNVGWMVOULBFZ-UHFFFAOYSA-N 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- RINCXYDBBGOEEQ-UHFFFAOYSA-N succinic anhydride Chemical class O=C1CCC(=O)O1 RINCXYDBBGOEEQ-UHFFFAOYSA-N 0.000 description 2
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 1
- 206010018473 Glycosuria Diseases 0.000 description 1
- 208000013016 Hypoglycemia Diseases 0.000 description 1
- 229910021578 Iron(III) chloride Inorganic materials 0.000 description 1
- WAEMQWOKJMHJLA-UHFFFAOYSA-N Manganese(2+) Chemical compound [Mn+2] WAEMQWOKJMHJLA-UHFFFAOYSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- MJTSOZOWJWOKAY-UHFFFAOYSA-L P(=O)([O-])([O-])O.[Na+].[Na+].P Chemical compound P(=O)([O-])([O-])O.[Na+].[Na+].P MJTSOZOWJWOKAY-UHFFFAOYSA-L 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 238000011938 amidation process Methods 0.000 description 1
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
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- DKAGJZJALZXOOV-UHFFFAOYSA-N hydrate;hydrochloride Chemical compound O.Cl DKAGJZJALZXOOV-UHFFFAOYSA-N 0.000 description 1
- DCPMPXBYPZGNDC-UHFFFAOYSA-N hydron;methanediimine;chloride Chemical compound Cl.N=C=N DCPMPXBYPZGNDC-UHFFFAOYSA-N 0.000 description 1
- 230000002218 hypoglycaemic effect Effects 0.000 description 1
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- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 229910001437 manganese ion Inorganic materials 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
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- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
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- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- LJSOLTRJEQZSHV-UHFFFAOYSA-L potassium;sodium;hydron;hydroxide;phosphate Chemical compound [OH-].[Na+].[K+].OP(O)([O-])=O LJSOLTRJEQZSHV-UHFFFAOYSA-L 0.000 description 1
- 230000008569 process Effects 0.000 description 1
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- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
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- 241000894007 species Species 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/28—Insulins
-
- 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
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Abstract
The invention discloses a kind of phytolectin polysaccharide hydrogel of intelligent control insulin releasing and its preparation method and application.The present invention is using biocompatibility and the preferable natural polysaccharide of degradability as raw material, by the way that chemical crosslinking occurs with phytolectin and the phytolectin polysaccharide hydrogel with loose structure is prepared in the presence of pore-foaming agent.The phytolectin polysaccharide hydrogel can be used for load insulin, so as to be prepared can intelligent control insulin releasing polysaccharide hydrogel.Preparation condition of the present invention is gentle, using materials safety, maintains active and insulin structural stability and bioactivity that phytolectin is specifically bound to glucose molecule, and technique is simple, cheap and easy to get using equipment and raw material.The polysaccharide hydrogel of intelligent control insulin releasing prepared by the present invention, it is expected to as a kind of insulin delivery vector, for intelligent control uelralante, there is larger application prospect in terms for the treatment of diabetes.
Description
Technical field
The invention belongs to biological medicine field of material technology.More particularly, to a kind of intelligent control insulin releasing
Phytolectin-polysaccharide hydrogel and its preparation method and application.
Background technology
Diabetes are a kind of high incidence diseases, and the treatment for diabetes at present depends on subcutaneous note for multiple daily
Insulin is penetrated, but this method can not be according to the release of patients blood glucose level intelligent control insulin, it is therefore desirable to repeatedly note
Insulin is penetrated, but excessive insulin can trigger this acute complications of hypoglycemia, even faint, suffer a shock when serious；Meanwhile
Long term injections insulin also results in the problems such as skin infection, ecchymoma.
Intellectual material is widely paid close attention in recent years, also referred to as environmental response material, if glucose intellectual material is a kind of
The material for making a provisioning response can be changed to internal blood sugar concentration, i.e., it can discharge pancreas islet in time according to the change of blood glucose
Element, so that blood glucose maintains normal level（4~6 mmol/L）.This glucose responding self-regulation system, it is treatment glycosuria
The new thinking of disease, its key are the carrier of load insulin and the switch of response are produced according to change of blood sugar.
At present, had the glucose responding self-regulation system of several comparative maturities, such as glucose oxidase system and
Phenyl boric acid group system etc..However, these systems have some limitations, cause to fail to realize preferable administering effect.
Such as pKa value of the phenyl boric acid group system due to phenyl boric acid group in itself is about 8~9, therefore it is limited in Human Physiology shape
Application under state；Insulin releasing be present because it can not directly receive concentration of glucose change and turn to signal in glucose oxidase system
The problem of response lag.In addition, the patent No. 2007101786.6 disclose a kind of glucose responding type polyphosphazene hydrogel and its
Preparation method, by using poly phosphazene and the phytolectin concanavalin A of the side base containing glucose（Concanavalin
A, Con A）Interaction, by the ratio and the means such as substituent of selection suitable second and the 3rd that improve glucose side base
The aquogel system with the different degrees of cross linking and different moisture content can be obtained.Poly phosphazene is high as a kind of new degradable medical
Molecular material, it is widely used in recent years, but its catabolite is all not nontoxic, there is certain potential safety hazard；
And its preparation technology is cumbersome, raw material is complicated, and many violent reaction conditions can influence activity of the phytolectin to glucose,
So as to influence final using effect.
The content of the invention
It is an object of the invention to overcome above-mentioned the deficiencies in the prior art, there is provided a kind of plant of intelligent control insulin releasing
Thing agglutinin-polysaccharide hydrogel.The hydrogel preparation condition is gentle, using natural polysaccharide materials safety, maintains plant and coagulates
Collection element is to the activity of glucose molecule specific binding and the structural stability and bioactivity of insulin, and technique is simple,
It is cheap and easy to get using equipment and raw material；Meanwhile the hydrogel can further prepare the medicament of intelligent control insulin releasing,
There is certain application prospect in terms for the treatment of diabetes.
It is an object of the invention to provide a kind of phytolectin-polysaccharide hydrogel of intelligent control insulin releasing.
It is a further object of the present invention to provide the preparation method of the phytolectin-polysaccharide hydrogel.
Another object of the present invention is to provide the application of the phytolectin-polysaccharide hydrogel.
The above-mentioned purpose of the present invention is to give realization by the following technical programs：
A kind of preparation method of intelligent control insulin releasing phytolectin-polysaccharide hydrogel, it is raw by polysaccharide and anhydride reaction
Into carboxylated polysaccharide derivative；Carboxylated polysaccharide derivative is added drop-wise in phytolectin again and crosslinks reaction, is planted
Thing agglutinin-polysaccharide hydrogel.
Specifically, by polysaccharide and anhydride reaction, carboxylated polysaccharide derivative is generated；Carboxylated polysaccharide derivative is added dropwise again
Into phytolectin, 1- ethyls-（3- dimethylaminopropyls）Carbodiimide（EDC）WithN- HOSu NHS
（NHS）Catalytic action under cross-linking reaction occurs, obtain phytolectin-polysaccharide hydrogel.
The present invention is the raw material for preparing hydrogel from biocompatibility and the preferable polysaccharide of degradability, by being coagulated with plant
Collection element occurs to be chemically crosslinked and the polysaccharide hydrogel of intelligent control insulin releasing is prepared in the presence of pore-foaming agent, using efficient
Deliver the hydrogel drug delivery system of medicine；Meanwhile from the phytolectin to glucose with specific bond performance with
Polysaccharide prepares a kind of hydrogel of chemical crosslinking by chemical reaction, its have to the concentration of glucose good sensitiveness of change and
Good biocompatibility, catabolite are nontoxic.
Meanwhile the present invention further prepares the porous plant containing cavernous structure to improve the load efficiency of above-mentioned hydrogel
Thing agglutinin-polysaccharide hydrogel；Specifically, pore-foaming agent and carboxylated polysaccharide derivative are added drop-wise in phytolectin simultaneously,
Porous phytolectin-polysaccharide hydrogel containing cavernous structure is made.
Preferably, the polysaccharide is Propiram, amylopectin, guar gum, lentinan, amylose, glycogen or konjaku
The natural polysaccharides such as polysaccharide, their good biocompatibilities and catabolite is nontoxic.
Preferably, the phytolectin is legume lectin element.
It is highly preferred that the legume lectin element is black soya bean agglutinin, mung bean agglutinin, ConA, peanut agglutinin,
Chick-pea agglutinin, phaseolus vulgaris agglutinin or goa bean agglutinin.
Preferably, the acid anhydrides is malonic anhydride, succinic anhydride, glutaric anhydride, adipic anhydride and pimelic acid acid anhydride.
Preferably, the pore-foaming agent be water-soluble preferably polyethylene glycol, it is polyvinyl alcohol, polyvinylpyrrolidone, water-soluble
Property lignin, calcium lactate, poly-ferric chloride, are eliminated so that they form behind cavity easily to be cleaned with water in hydrogel.
Specifically, the preparation method of above-mentioned phytolectin-polysaccharide hydrogel comprises the following steps：
S1. according to polysaccharide：Organic solvent=0.1~1g：10~100mL ratio, polysaccharide is added into organic solvent, in room temperature
Stirring and dissolving；
S2. according to acid anhydrides organic solvent=1~10mg：1~10mL ratio, acid anhydrides is added into organic solvent, is stirred at room temperature
Dissolving；
S3. step S2 is obtained into solution and is added in step S1 to obtain mixed liquor, according to mixed liquor：Organic amine=11~110mL：1~
20mg ratio, organic amine is added dropwise into mixed liquor, reaction is stirred at room temperature 1~24 hour；It is after reaction terminates, reaction solution is saturating
Analysis, obtains carboxylated polysaccharide derivative after freeze-drying；
S4. according to carboxylated polysaccharide derivative：Cushioning liquid=0.1~1g：1~10mL, it is more that carboxylated is added into cushioning liquid
Sugar derivatives, dissolving is stirred at room temperature；
S5. according to phytolectin：Buffer solution=0.1~10mg：0.1~2mL ratio, plant is sequentially added into buffer solution
Agglutinin, stirring and dissolving, 4 DEG C are placed 1~10 hour；
S6. according to pore-foaming agent：Buffer solution=1~10mg：1~10mL ratio, pore-foaming agent is added into buffer solution, is stirred in room temperature
Mix dissolving；
S7. the solution that solution step S5, S6 obtained is added drop-wise to step S4 obtains mixed liquor, and reaction 1~10 is stirred at room temperature
Hour；
S8. according to 1- ethyls-(3- dimethylaminopropyls) carbodiimide hydrochloride（EDC·HCl）：N- HOSu NHS
（NHS）：Buffer solution=5~50mg：1~10mg：0.1~1mL ratio, EDCHCl and NHS is added to buffer solution, then will be upper
State solution to be added drop-wise in the mixed liquor that S7 is obtained, at room temperature stirring reaction 1~2 hour；After obtaining hydrogel, soaked with cushioning liquid
Bubble several times, then takes out hydrogel freeze-drying, phytolectin-polysaccharide hydrogel is made；
Step S4, the pH of buffer solution described in S5, S6 or S8 is 4~7.
Preferably, the organic solvent be dimethyl sulfoxide (DMSO),N,N- dimethylformamide, formamide, acetonitrile.
Preferably, acid anhydrides described in step S2 is malonic anhydride, succinic anhydride, glutaric anhydride, adipic anhydride and pimelic acid acid anhydride.
Preferably, organic amine described in step S3 is ethamine, diethylamine and triethylamine.
Preferably, step S5 is according to metal ion：Buffer solution：Phytolectin=0.03~3mg：0.1~2mL：0.1~
10mg ratio, metal ion and phytolectin are added into buffer solution.
The purpose that each metal ion species are added in step S5 is in order to activate phytolectin, so as to improve phytolectin
The ability combined with glucose occurrence features.
More preferably, the metal ion is magnesium chloride, the one or more in calcium chloride or manganese chloride.
It is highly preferred that magnesium chloride in metal ion described in the S5：Calcium chloride：Manganese chloride=0.01~1mg：0.01~
1mg：0.01~1mg.
In order that polysaccharide fully dissolves, the degree of polysaccharide cross-linking reaction is improved, polysaccharide needs to dissolve certain time in the solution
Polysaccharide segment could be caused to be fully extended；Preferably, room temperature described in step S1~S8 is 15~40 DEG C；The condition of the stirring
To be stirred 1~24 hour under the conditions of 300~1000 rpm/min.
Preferably, in order to keep acid anhydrides and the reactive activity of polysaccharide hydroxyl, acid anhydrides is anhydrous acid anhydrides in step S2；Step
It is to remove acid anhydrides and caused water byproduct during polysaccharide hydroxyl reaction using the purpose of organic amine in S3, improves reaction
Degree.
Preferably, the temperature being freeze-dried described in step S3 or S8 is 0~-60 DEG C, and the time is 1~24 hour, its mesh
Be polysaccharide derivates is completed drying at low temperature, ensure that its activity will not change, and be maximally maintained water
The space structure of gel.
The purpose of step S3 dialysis is to remove solvent and unreacted raw material, dialysed using the pure water of routine；It is excellent
Selection of land, dialysis described in step S3 are the bag filter for being 500~50000 with the molecular weight that dams, and ensure to remove the same of small molecular weight impurity
Shi Buhui gives polysaccharide derivates to come, and dialysis time is 1~5 day.
Step S4, cushioning liquid is used in S5, S6 or S8（PH=4~7）As reaction dissolvent, avoid joining in following protein
With reaction in send out conformational change protedogenous.Cushioning liquid commonly used in the art can be selected（PH=4~7）；Preferably,
The buffer solution is acetic acid-sodium acetate buffer（pH4.0）, citric acid-sodium citrate buffer solution（pH4.4）, citric acid-hydrogen-oxygen
Change sodium-hydrochloride buffer（pH5.3）, disodium hydrogen phosphate-phosphate sodium dihydrogen buffer solution（pH7.4）, disodium hydrogen phosphate-biphosphate
Potassium buffer solution（pH6.2）Or potassium dihydrogen phosphate-sodium hydrate buffer solution（pH6.8）Deng.
In order to obtain chemically crosslinked aquagel of the present invention, the chemical reaction described in step S8 derives for carboxylated polysaccharide
In thing-COOH group and phytolectin in-NH2Under EDC and NHS catalytic action, obtained by amidation process
Phytolectin-polysaccharide hydrogel of chemical crosslinking；The purpose for obtaining repeatedly being soaked with buffer solution again after hydrogel is in order to clear
The water soluble pore formers remained in the greatest extent in hydrogel are removed, hole are left in its original position, so as to obtain the plant of loose structure
Thing agglutinin-polysaccharide hydrogel.
Meanwhile phytolectin-the polysaccharide hydrogel being prepared by above-mentioned preparation method is also in the scope of the present invention
It is interior.
Because phytolectin-polysaccharide hydrogel of the present invention is as a kind of hydrogel drug delivery of high-efficiency delivery medicine
System and phytolectin have the performance of specific binding glucose, have preferable sensitiveness to concentration of glucose change, can
Further prepare the medicine of intelligent control insulin.Therefore, phytolectin-polysaccharide hydrogel of the present invention is preparing treatment
Application in diabetes medicament is also in the scope of the present invention.
In addition, the present invention also provides a kind of medicament of intelligent control insulin releasing, the medicament is by insulin load
It is prepared in above-mentioned phytolectin-polysaccharide hydrogel.
Specifically, by phytolectin-polysaccharide hydrogel in room temperature（15~40 DEG C）Under the conditions of be soaked in insulin solutions
In, prepare phytolectin-polysaccharide hydrogel of load insulin.
Preferably, the soak time is 1~10 hour, and the concentration of insulin solutions is 1~20 mmol/L.
It is so as to realize the mechanism of intelligent control insulin releasing with polysaccharide hydrogel load insulin of the invention：Containing pancreas
The polysaccharide hydrogel of island element, it is in glucose solution because phytolectin combines the ability of free glucose molecule higher than knot
The ability of glucose unit on polysaccharide chain is closed, so as to promote hydrogel volume to expand and uelralante.
Compared with prior art, the present invention has the advantages that：
（1）The invention provides a kind of phytolectin-polysaccharide hydrogel, its preparation condition is gentle, using materials safety, keeps
The activity and the structural stability and bioactivity of insulin that phytolectin is specifically bound to glucose molecule, and work
Skill is simple, cheap and easy to get using equipment and raw material.
（2）Load insulin polysaccharide hydrogel prepared by the present invention has the sensitiveness to concentration of glucose change, i.e. root
The intelligent control uelralante according to the change of concentration of glucose, it is expected to as a kind of insulin delivery vector, for intelligent tune
Uelralante is controlled, there is larger application prospect in terms for the treatment of diabetes.
Brief description of the drawings
Fig. 1 is the process chart of preparation method of the present invention；
Fig. 2 is the reaction mechanism figure of preparation method of the present invention；
Fig. 3 is the embodiment of the present invention 1（a）Propiram raw material and（b）The hydrogen nuclear magnetic resonance spectrogram of carboxylated Propiram derivative（1H
NMR）；
Fig. 4 is the embodiment of the present invention 1（a）Propiram raw material,（b）Carboxylated Propiram derivative and（c）ConA-Pu Lu
The infrared spectrogram of blue hydrogel（FTIR）；
Fig. 5 is the embodiment of the present invention 1（a）It is unactivated and（b）ConA-Propiram hydrogel is activated in various concentrations grape
Swelling ratio figure in the dissolution medium of sugar（Solvent is PBS（PH=7.4, it is increased that swelling ratio is defined as hydrogel during swelling equilibrium
Weight（mg）With the weight of lyophilized rear gel（mg）The ratio between）；
Fig. 6 is activation ConA-Propiram hydrogel of the load insulin of the embodiment of the present invention 1 in different glucose
The accumulative release rate curve of insulin in dissolution medium（Accumulative release rate is defined as the accumulative insulin weight discharged of hydrogel
Amount（mg）With the insulin weight loaded in hydrogel（mg）The ratio between）.
Fig. 7 is the pore-foaming agent polyethylene glycol of the embodiment of the present invention 1（PEG）Activation ConA-Propiram hydrogel is inhaled
The influence figure of attached Insulin energy：（a）PEG activation ConA-Propiram hydrogel is not added with,（b）Add PEG work
Change ConA-Propiram hydrogel（Insulin load rate is defined as the insulin weight loaded in hydrogel（μg）With it is dry
The weight of dry hydrogel（mg）The ratio between）.
Embodiment
The present invention is further explained with reference to specific embodiment, but specific embodiment is not to the present invention
It is limited in any way.Unless stated otherwise, reagent involved in embodiment, method are reagent commonly used in the art and method.
Unless stated otherwise, reagent involved in embodiment is purchased in market.
The present invention prepares and provides a kind of polysaccharide hydrogel of intelligent control insulin releasing and preparation method thereof, its technique
Route is as shown in figure 1, the synthesis of carboxylated polysaccharide derivative and its reaction equation to be chemically reacted with phytolectin are distinguished
As shown in Figures 2 and 3.Following examples concrete example explanation.
Embodiment 1
1st, ConA-Propiram hydrogel of load insulin is prepared
（1）0.2 gram of pulullan polysaccharide is weighed, is named as PUL, is placed in 20 milliliters of dimethyl sulfoxide (DMSO)s, it is small in 15 DEG C of dissolving stirrings 2
When；
（2）3 milligrams of succinic anhydrides are weighed, are placed in 1 milliliter of dimethyl sulfoxide (DMSO), are dissolved 4 hours in 15 DEG C；
（3）By step（2）Obtain solution and be added to step（1）Obtained mixed liquor, then 16 milligrams of triethylamines are added dropwise in mixed liquor,
In 15 DEG C of stirring reactions 1 hour.After reaction terminates, by reaction solution from the bag filter distilled water that molecular weight is 1,000 that dams
Dialysis, carboxylated polysaccharide derivative is obtained after -20 DEG C of freeze-dryings, is named as CPUL；
（4）Weigh 0.3 gram of step（3）Obtained CPUL, it is dissolved in 2 milliliters of acetic acid-sodium acetate buffer（pH4.0）In, in 15
DEG C stirring and dissolving 12 hours；
（5）0.01 milligram of magnesium chloride, 0.01 milligram of calcium chloride, 0.01 milligram of manganese chloride are weighed in 0.1 milliliter of acetic acid-sodium acetate
Buffer solution（pH4.0）In, then weigh 0.1 milligram of ConA and add in above-mentioned solution, stirring and dissolving, it is placed in 8 in 4 DEG C of refrigerators
Hour；
（6）2 milligrams of polyethylene glycol are weighed, are dissolved in 2 milliliters of acetic acid-sodium acetate buffer（pH4.0）In, in 15 DEG C of stirring and dissolvings
10 hours；
（7）By step（5）、（6）Obtained solution is added drop-wise to step（4）Solution obtains mixed liquor, the two is fully contacted, in 15
DEG C stirring reaction 10 hours.
（8）10 milligrams of EDCHCl and 10 milligram of NHS are weighed, are added to 0.1mL acetic acid-sodium acetate buffer（pH4.0）
Middle dissolving, then be added drop-wise to（7）In obtained mixed liquor, stir, reacted 1 hour at 15 DEG C.After obtaining hydrogel, with acetic acid-second
Sour sodium buffer solution（pH4.0）Repeatedly immersion, each soak time are 12 hours, then take out -20 DEG C of freeze-dryings of hydrogel, system
Obtain porous ConA-Propiram hydrogel.
（9）By step（8）Porous ConA-the polysaccharide hydrogel is soaked in insulin solutions at 15 DEG C,
Prepare ConA-Propiram hydrogel of load insulin.
2nd, result
（1）Fig. 3 is Propiram raw material and carboxylated Propiram derivative1H NMR spectras.Contrast Propiram raw material1H NMR
Spectrogram（Fig. 3 a）, carboxylated polysaccharide derivative1In H NMR spectras（Fig. 3 b）, H1 signal peak on pulullan polysaccharide chain（A peaks）
Drifted about to high field direction, show that change occurs in carboxylated Propiram derivative H1 chemical environment.And occur in fig 3b
Two-CH2The signal peak of-group, i.e. b peaks（2.62ppm）With c peaks（2.44ppm）, they are attributed to the general Shandong of carboxylated respectively
Two-CH that blue derivative is connected with-COOH group2- group.Therefore,1H NMR methods more confirm to synthesize carboxylated Propiram
Derivative.Further pass through1H NMR integration methods, to the H1 peaks of carboxylated polysaccharide derivative（A peaks）With two-CH2- group peak（b
With c peaks）Integrated, according to formula（1）Calculate in carboxylated polysaccharide derivative-substitution value of COOH group is 0.2.Substitution
The definition of degree：In carboxylated polysaccharide derivative in average each glucose unit-number of COOH group.
DS=N -COOH /N Glc=I b,c/(4I a)（1）
In formula, DS is the-substitution value of COOH group in carboxylated polysaccharide derivative, N-COOHIt is-the number of COOH group,N GlcIt is
The number of glucose unit,I b,cWithI aThe respectively integral area at the integral area sum at b and c peaks and a peaks.
（2）Fig. 4 is that the FTIR of Propiram raw material, carboxylated polysaccharide derivative and ConA-Propiram hydrogel is composed
Figure.Contrast the FTIR spectrograms of Propiram raw material（Fig. 4 a）, in the FTIR spectrograms of carboxylated polysaccharide derivative（Fig. 4 b）,
1723cm-1Place occurs-characteristic absorption peak of COOH group, show to synthesize carboxylated polysaccharide derivative.The absworption peak is in knife
Disappeared in the FTIR spectrograms of legumin-Propiram hydrogel（Fig. 4 c）, show carboxylated polysaccharide derivative-COOH group and knife
- the NH of beans agglutinin2Reacted.
（3）Fig. 5 be it is unactivated and activation ConA-Propiram hydrogel different glucose release be situated between
Swelling ratio figure in matter, ConA hydrogel prepared after calcium ion and manganese ion activation show higher molten
Swollen ratio, show that activating ConA-Propiram hydrogel has the performance of specific binding to glucose.
（4）Fig. 6 is release of the activation ConA-Propiram hydrogel in different glucose of load insulin
The accumulative release rate curve map of insulin in medium.The hydrogel be can be seen that in glucose solution medium, insulin adds up
Release rate is above its accumulative release rate in PBS solution, and the accumulative release rate of insulin is with grape in dissolution medium
The increase of sugared concentration and increase.These results show that the hydrogel shows preferably intelligently to adjust according to the change of concentration of glucose
Control the performance of insulin releasing.
（6）Fig. 7 is the activation ConA-Propiram hydrogel absorption insulin for being not added with and adding pore-foaming agent PEG
Performance map, compared with the hydrogel for being not added with PEG（Fig. 7 a）, the hydrogel for adding PEG shows higher insulin load
Rate（Fig. 7 b）, show that PEG addition is favorably improved the performance of hydrogel load insulin.
Embodiment 2
1st, peanut agglutinin-amylopectin hydrogel of load insulin is prepared
（1）0.5 gram of amylopectin is weighed, is named as AMYP, is placed in 50 millilitersN,NIn-dimethylformamide, stirred in 30 DEG C of dissolvings
Mix 24 hours；
（2）5 milligrams of malonic anhydrides are weighed, are placed in 5 millilitersN,NIn-dimethylformamide, dissolved 24 hours in 30 DEG C；
（3）By step（2）Obtain solution and be added to step（1）Obtained mixed liquor, then 10 milligrams of diethylamine are added dropwise in mixed liquor,
In 30 DEG C of stirring reactions 24 hours.It is after reaction terminates, reaction solution is saturating with the bag filter distilled water that molecular weight is 50,000 that dams
Analysis, carboxylated polysaccharide derivative is obtained after -30 DEG C of freeze-dryings, is named as CAMYP；
（4）Weigh 0.5 gram of step（3）Obtained CAMYP, it is dissolved in 5 milliliters of disodium hydrogen phosphate-phosphate sodium dihydrogen buffer solution
（pH7.4）In, dissolved 24 hours in 30 DEG C；
（5）0.04 milligram of magnesium chloride, 0.04 milligram of calcium chloride, 0.05 milligram of manganese chloride are weighed in 1 milliliter of disodium hydrogen phosphate-phosphorus
Acid dihydride sodium buffer solution（pH7.4）In, then weigh 2 milligrams of peanut agglutinins and add in above-mentioned solution, stirring and dissolving, it is placed in 4 DEG C
4 hours in refrigerator；
（6）5 milligrams of polyvinyl alcohol are weighed, are dissolved in 5 milliliters of disodium hydrogen phosphate-phosphate sodium dihydrogen buffer solution（pH7.4）In, in 15
DEG C stirring and dissolving 24 hours；
（7）By step（5）、（6）Obtained solution is added drop-wise to step（4）Solution obtains mixed liquor, the two is fully contacted, in 30
DEG C reaction 5 hours.
（8）20 milligrams of EDCHCl and 5 milligram of NHS are weighed, are added to 0.5mL disodium hydrogen phosphates-sodium dihydrogen phosphate buffering
Liquid（pH7.4）Middle dissolving, then be added drop-wise to（7）In obtained mixed liquor, stir, reacted 1.5 hours at 30 DEG C.Obtain hydrogel
Afterwards, with disodium hydrogen phosphate-phosphate sodium dihydrogen buffer solution（pH7.4）Repeatedly immersion 24 hours, each soak time are 24 hours, so
- 30 DEG C of freeze-dryings of hydrogel are taken out afterwards, and porous peanut agglutinin-amylopectin hydrogel is made.
（9）By step（8）Porous peanut agglutinin-the polysaccharide hydrogel is soaked in insulin solutions at 30 DEG C,
Prepare peanut agglutinin-amylopectin hydrogel of load insulin.
2nd, result is shown, gained peanut agglutinin-amylopectin hydrogel has the performance of specific binding to glucose,
And the hydrogel is shown preferably according to the performance of the change intelligent control insulin releasing of concentration of glucose.
Embodiment 3
1st, chick-pea agglutinin-Guar hydrogel of load insulin is prepared
（1）0.8 gram of guar gum is weighed, is named as GUA, is placed in 40 milliliters of formamides, in 35 DEG C of stirring and dissolvings 15 hours；
（2）10 milligrams of succinic anhydrides are weighed, are placed in 10 milliliters of formamides, are dissolved 12 hours in 35 DEG C；
（3）By step（2）Obtain solution and be added to step（1）Obtained mixed liquor, then 15 milligrams of triethylamines are added dropwise in mixed liquor,
Reacted 12 hours in 35 DEG C.After reaction terminates, reaction solution is dialysed with the bag filter distilled water that molecular weight is 10,000 that dams ,-
Carboxylated polysaccharide derivative is obtained after 60 DEG C of freeze-dryings, is named as CGUA；
（4）Weigh 0.1 gram of step（3）Obtained CGUA, it is dissolved in 1 milliliter of citric acid-sodium hydroxide-hydrochloride buffer
（pH5.3）In, in 35 DEG C of stirring and dissolvings 10 hours；
（5）0.05 milligram of magnesium chloride, 0.05 milligram of calcium chloride, 0.05 milligram of manganese chloride are weighed in 0.2 milliliter of citric acid-hydrogen-oxygen
Change sodium-hydrochloride buffer（pH5.3）In, then claim 10 milligrams of chick-pea agglutinins to add in above-mentioned solution, stirring and dissolving, it is placed in 4
6 hours in DEG C refrigerator；
（6）10 milligrams of polyvinylpyrrolidones are weighed, are dissolved in 10 milliliters of citric acid-sodium hydroxide-hydrochloride buffer（pH5.3）
In, in 35 DEG C of stirring and dissolvings 12 hours；
（7）By step（5）、（6）Obtained solution is added drop-wise to step（4）Solution obtains mixed liquor, the two is fully contacted, in 35
DEG C stirring reaction 8 hours.
（8）5 milligrams of EDCHCl and 6 milligram of NHS are weighed, are added to 0.4mL citric acids-sodium hydroxide-hydrochloride buffer
（pH5.3）Middle dissolving, then be added drop-wise to（7）In obtained mixed liquor, stir, reacted 1.2 hours at 35 DEG C.After obtaining hydrogel,
With citric acid-sodium hydroxide-hydrochloride buffer（pH5.3）Repeatedly immersion, each soak time are 10 hours, then take out water-setting
- 60 DEG C of freeze-dryings of glue, are made porous chick-pea agglutinin-Guar hydrogel.
（9）By step（8）The porous chick-pea agglutinin-polysaccharide hydrogel is soaked in insulin solutions at 35 DEG C
In, prepare chick-pea agglutinin-Guar hydrogel of load insulin.
2nd, result is shown, gained chick-pea agglutinin-Guar hydrogel has the performance of specific binding to glucose,
And the hydrogel is shown preferably according to the performance of the change intelligent control insulin releasing of concentration of glucose.
Embodiment 4
1st, black soya bean agglutinin-lentinan hydrogel of load insulin is prepared
（1）0.1 gram of lentinan is weighed, is named as LEN, is placed in 10 milliliters of acetonitriles, in 20 DEG C of stirring and dissolvings 10 hours；
（2）8 milligrams of glutaric anhydrides are weighed, are placed in 2 milliliters of acetonitriles, are dissolved 10 hours in 20 DEG C；
（3）By step（2）Obtain solution and be added to step（1）Obtained mixed liquor, then 20 milligrams of diethylamine are added dropwise in mixed liquor,
In 20 DEG C of stirring reactions 10 hours.It is after reaction terminates, reaction solution is saturating with the bag filter distilled water that molecular weight is 20,000 that dams
Analysis, carboxylated polysaccharide derivative is obtained after -50 DEG C of freeze-dryings, is named as CLEN；
（4）Weigh 0.4 gram of step（3）Obtained CLEN, it is dissolved in 5 milliliters of citric acid-sodium citrate buffer solution（pH4.4）In,
In 20 DEG C of stirring and dissolvings 15 hours；
（5）1 milligram of magnesium chloride, 1 milligram of calcium chloride, 0.04 milligram of manganese chloride are weighed in 2 milliliters of citric acid-buffered sodium citrate
Liquid（pH4.4）In, then weigh 5 milligrams of black soya bean agglutinins and add in above-mentioned solution, stirring and dissolving, it is placed in 4 DEG C of refrigerators 5 hours；
（6）8 milligrams of water-soluble lignins are weighed, are dissolved in 7 milliliters of citric acid-sodium citrate buffer solution（pH4.4）In, in 20 DEG C
Dissolving 15 hours；
（7）By step（5）、（6）Obtained solution is added drop-wise to step（4）Solution obtains mixed liquor, the two is fully contacted, in 20
DEG C stirring reaction 1 hour.
（8）4 milligrams of EDCHCl and 8 milligram of NHS are weighed, are added to 0.2mL citric acids-sodium citrate buffer solution
（pH4.4）Middle dissolving, then be added drop-wise to（7）In obtained mixed liquor, stir, reacted 0.5 hour at 20 DEG C.After obtaining hydrogel,
With citric acid-sodium citrate buffer solution（pH4.4）Immersion repeatedly immersion, each soak time is 8 hours, then takes out water-setting
- 50 DEG C of freeze-dryings of glue, are made porous black soya bean agglutinin-lentinan hydrogel.
（9）By step（8）The porous black soya bean agglutinin-polysaccharide hydrogel is soaked in insulin solutions at 20 DEG C,
Prepare black soya bean agglutinin-lentinan hydrogel of load insulin.
2nd, result is shown, gained black soya bean agglutinin-lentinan hydrogel has the performance of specific binding to glucose,
And the hydrogel is shown preferably according to the performance of the change intelligent control insulin releasing of concentration of glucose.
Embodiment 5
1st, goa bean agglutinin-amylose hydrogel of load insulin is prepared
（1）0.4 gram of amylose is weighed, is named as AMY, is placed in 60 milliliters of dimethyl sulfoxide (DMSO)s, is dissolved 16 hours in 25 DEG C；
（2）9 milligrams of adipic anhydrides are weighed, are placed in 8 milliliters of dimethyl sulfoxide (DMSO)s, are dissolved 16 hours in 25 DEG C；
（3）By step（2）Obtain solution and be added to step（1）Obtained mixed liquor, then 12 milligrams of ethamine are added dropwise in mixed liquor, in
25 DEG C of stirring reactions 8 hours.It is after reaction terminates, reaction solution is saturating from the bag filter distilled water that molecular weight is 40,000 that dams
Analysis, carboxylated polysaccharide derivative is obtained after -40 DEG C of freeze-dryings, is named as CAMY；
（4）Weigh 0.6 gram of step（3）Obtained CAMY, it is dissolved in 6 milliliters of disodium hydrogen phosphate-potassium phosphate buffer
（pH6.2）In, in 25 DEG C of stirring and dissolvings 14 hours；
（5）Weigh 0.08 milligram of magnesium chloride, 0.08 milligram of calcium chloride, 0.08 milligram of manganese chloride in 0.7 milliliter disodium hydrogen phosphate-
Potassium phosphate buffer（pH6.2）In, then weigh 6 milligrams of goa bean agglutinins and add in above-mentioned solution, stirring and dissolving, it is placed in
1 hour in 4 DEG C of refrigerators；
（6）1 milligram of calcium lactate is weighed, is dissolved in 2 milliliters of disodium hydrogen phosphate-potassium phosphate buffer（pH6.2）In, in 25 DEG C
Stirring and dissolving 9 hours；
（7）By step（5）、（6）Obtained solution is added drop-wise to step（4）Solution obtains mixed liquor, the two is fully contacted, in 25
DEG C stirring reaction 7 hours.
（8）50 milligrams of EDCHCl and 1 milligram of NHS are weighed, are added to 1mL disodium hydrogen phosphates-potassium phosphate buffer
（pH6.2）Middle dissolving, then be added drop-wise to（7）In obtained mixed liquor, stir, reacted 2 hours at 25 DEG C.After obtaining hydrogel, use
Disodium hydrogen phosphate-potassium phosphate buffer（pH6.2）Repeatedly immersion, each soak time are 15 hours, and -40 DEG C of freezings are dry
It is dry, porous goa bean agglutinin-amylose hydrogel is made.
（9）By step（8）The porous goa bean agglutinin-polysaccharide hydrogel is soaked in insulin solutions at 25 DEG C
In, prepare goa bean agglutinin-amylose hydrogel of load insulin.
2nd, result is shown, gained goa bean agglutinin-amylose hydrogel has the property of specific binding to glucose
Can, and the hydrogel is shown preferably according to the performance of the change intelligent control insulin releasing of concentration of glucose.
Embodiment 6
1st, mung bean agglutinin-konjac glucomannan hydrogel of load insulin is prepared
（1）1 gram of SKGM is weighed, is named as KJC, is placed in 100 milliliters of dimethyl sulfoxide (DMSO)s, in 40 DEG C of stirring and dissolvings 1 hour；
（2）1 milligram of pimelic acid acid anhydride is weighed, is placed in 6 milliliters of dimethyl sulfoxide (DMSO)s, is dissolved 1 hour in 40 DEG C；
（3）By step（2）Obtain solution and be added to step（1）Obtained mixed liquor, then 17 milligrams of ethamine are added dropwise in mixed liquor, in
40 DEG C are reacted 15 hours.After reaction terminates, reaction solution is dialysed with the bag filter distilled water that molecular weight is 500 that dams, 0 DEG C of freezing
Carboxylated polysaccharide derivative is obtained after drying, is named as CKJC；
（4）Weigh 1 gram of step（3）Obtained CKJC, it is dissolved in 10 milliliters of potassium dihydrogen phosphate-sodium hydrate buffer solution（pH6.8）
In, dissolved 1 hour in 40 DEG C；
（5）1 milligram of magnesium chloride, 1 milligram of calcium chloride, 1 milligram of manganese chloride are weighed in 0.5 milliliter of potassium dihydrogen phosphate-sodium hydroxide
Buffer solution（pH6.8）In, then weigh 8 milligrams of mung bean agglutinins and add in above-mentioned solution, stirring and dissolving, it is placed in 10 in 4 DEG C of refrigerators
Hour；
（6）9 milligrams of poly-ferric chlorides are weighed, are dissolved in 1 milliliter of potassium dihydrogen phosphate-sodium hydrate buffer solution（pH6.8）In, in 40
DEG C dissolving 1 hour；
（7）By step（5）、（6）Obtained solution is added drop-wise to step（4）Solution obtains mixed liquor, the two is fully contacted, in 40
DEG C reaction 6 hours.
（8）30 milligrams of EDCHCl and 9 milligram of NHS are weighed, are added to 0.6mL potassium dihydrogen phosphates-sodium hydrate buffer solution
（pH6.8）Middle dissolving, then be added drop-wise to（7）In obtained mixed liquor, stir, reacted 0.5 hour at 40 DEG C.After obtaining hydrogel,
With potassium dihydrogen phosphate-sodium hydrate buffer solution（pH6.8）Repeatedly immersion, each soak time are 1 hour, then take out hydrogel
0 DEG C of freeze-drying, is made porous mung bean agglutinin-konjac glucomannan hydrogel.
（9）By step（8）The porous mung bean agglutinin-polysaccharide hydrogel is soaked in insulin solutions at 40 DEG C,
Prepare mung bean agglutinin-konjac glucomannan hydrogel of load insulin.
2nd, result is shown, gained mung bean agglutinin-konjac glucomannan hydrogel has the performance of specific binding to glucose,
And the hydrogel is shown preferably according to the performance of the change intelligent control insulin releasing of concentration of glucose.
Above-described embodiment is the preferable embodiment of the present invention, but embodiments of the present invention are not limited by examples detailed above
System, other any Spirit Essences without departing from the present invention with made under principle change, modification, replacement, combine, simplification,
Equivalent substitute mode is should be, is included within protection scope of the present invention.
Claims (10)
1. a kind of preparation method of phytolectin-polysaccharide hydrogel of intelligent control insulin releasing, it is characterised in that will be more
Sugar and anhydride reaction, generate carboxylated polysaccharide derivative；Carboxylated polysaccharide derivative is added drop-wise in phytolectin again, in 1-
Ethyl-（3- dimethylaminopropyls）Carbodiimide andNCross-linking reaction occurs under the catalytic action of-HOSu NHS, obtains
To phytolectin-polysaccharide hydrogel.
2. preparation method according to claim 1, it is characterised in that drip pore-foaming agent and carboxylated polysaccharide derivative simultaneously
It is added in phytolectin, porous phytolectin-polysaccharide hydrogel containing cavernous structure is made.
3. preparation method according to claim 1, it is characterised in that the polysaccharide be Propiram, amylopectin, guar gum,
Lentinan, amylose, glycogen or konjaku.
4. preparation method according to claim 1, it is characterised in that the phytolectin is black soya bean agglutinin, mung bean coagulates
Collect element, ConA, peanut agglutinin, chick-pea agglutinin, phaseolus vulgaris agglutinin or goa bean agglutinin.
5. preparation method according to claim 1 or claim 2, it is characterised in that specifically comprise the following steps：
S1. according to polysaccharide：Organic solvent=0.1~1g：10~100mL ratio, polysaccharide is added into organic solvent, in room temperature
Stirring and dissolving；
S2. according to acid anhydrides：Organic solvent=1~10mg：1~10mL ratio, acid anhydrides is added into organic solvent, is stirred in room temperature
Mix dissolving；
S3. step S2 is obtained into solution and is added in step S1 to obtain mixed liquor, according to mixed liquor：Organic amine=11~110mL：1~
20mg ratio, organic amine is added dropwise into mixed liquor, reaction is stirred at room temperature 1~24 hour；It is after reaction terminates, reaction solution is saturating
Analysis, obtains carboxylated polysaccharide derivative after freeze-drying；
S4. according to carboxylated polysaccharide derivative：Cushioning liquid=0.1~1g：1~10mL, it is more that carboxylated is added into cushioning liquid
Sugar derivatives, dissolving is stirred at room temperature；
S5. according to phytolectin：Buffer solution=0.1~10mg：0.1~2mL ratio, plant is sequentially added into buffer solution
Agglutinin, stirring and dissolving, 4 DEG C are placed 1~10 hour；
S6. according to pore-foaming agent：Buffer solution=1~10mg：1~10mL ratio, pore-foaming agent is added into buffer solution, is stirred in room temperature
Mix dissolving；
S7. the solution that solution step S5, S6 obtained is added drop-wise to step S4 obtains mixed liquor, and reaction 1~10 is stirred at room temperature
Hour；
S8. according to EDCHCl：NHS：Buffer solution=5~50mg：1~10mg：0.1~1mL ratio, added to buffer solution
EDCHCl and NHS, then above-mentioned solution is added drop-wise in the mixed liquor that S7 is obtained, at room temperature stirring reaction 1~2 hour；Obtain
After hydrogel, with cushioning liquid immersion several times, hydrogel freeze-drying is then taken out, phytolectin-polysaccharide water-setting is made
Glue；
Step S4, the pH of buffer solution described in S5, S6 or S8 is 4~7.
6. preparation method according to claim 5, it is characterised in that the organic solvent be dimethyl sulfoxide,N,N- dimethyl
Formamide, formamide or acetonitrile；Acid anhydrides described in step S2 is malonic anhydride, succinic anhydride, glutaric anhydride, adipic anhydride or heptan two
Acid anhydrides；Organic amine described in step S3 is ethamine, diethylamine or triethylamine.
7. preparation method according to claim 5, it is characterised in that step S5 is according to metal ion：Buffer solution：Plant lectin
Element=0.03~3mg：0.1~2mL：0.1~10mg ratio, metal ion and phytolectin are added into buffer solution.
8. phytolectin-polysaccharide hydrogel that any one of claim 1~7 preparation method is prepared.
9. phytolectin-polysaccharide hydrogel described in claim 8 is preparing the application in treating diabetes medicament.
10. a kind of medicament of intelligent control insulin releasing, it is characterised in that be described in claim 8 by insulin load
It is prepared in phytolectin-polysaccharide hydrogel.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109879977A (en) * | 2019-01-30 | 2019-06-14 | 中山大学 | A kind of amphiphilic polysaccharide derivative and its preparation method and application containing cholesterol and phytolectin group |
| CN111440331A (en) * | 2020-03-20 | 2020-07-24 | 华南农业大学 | Chitosan-based cell targeted adhesion controlled-release hydrogel and preparation method and application thereof |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20030220254A1 (en) * | 2002-03-29 | 2003-11-27 | Texas Tech University System | Composition and method for preparation of an oral dual controlled release formulation of a protein and inhibitor |
| CN101450996A (en) * | 2007-12-07 | 2009-06-10 | 北京化工大学 | Glucose responding type polyphosphazene hydrogel and preparation method thereof |
| CN103613681A (en) * | 2013-12-10 | 2014-03-05 | 中山大学 | Tea polysaccharide derivative 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 |
| CN105832656A (en) * | 2016-05-25 | 2016-08-10 | 暨南大学 | Nitric oxide-loaded carboxylation chitosan-polyethyleneimine hydrogel and preparation method and application thereof |
-
2017
- 2017-07-25 CN CN201710612832.2A patent/CN107412151B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20030220254A1 (en) * | 2002-03-29 | 2003-11-27 | Texas Tech University System | Composition and method for preparation of an oral dual controlled release formulation of a protein and inhibitor |
| CN101450996A (en) * | 2007-12-07 | 2009-06-10 | 北京化工大学 | Glucose responding type polyphosphazene hydrogel and preparation method thereof |
| CN103613681A (en) * | 2013-12-10 | 2014-03-05 | 中山大学 | Tea polysaccharide derivative 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 |
| CN105832656A (en) * | 2016-05-25 | 2016-08-10 | 暨南大学 | Nitric oxide-loaded carboxylation chitosan-polyethyleneimine hydrogel and preparation method and application thereof |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109879977A (en) * | 2019-01-30 | 2019-06-14 | 中山大学 | A kind of amphiphilic polysaccharide derivative and its preparation method and application containing cholesterol and phytolectin group |
| CN109879977B (en) * | 2019-01-30 | 2022-03-04 | 中山大学 | Amphiphilic polysaccharide derivative containing cholesterol and phytohemagglutinin groups and preparation method and application thereof |
| CN111440331A (en) * | 2020-03-20 | 2020-07-24 | 华南农业大学 | Chitosan-based cell targeted adhesion controlled-release hydrogel and preparation method and application thereof |
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