CN111420069A - 一种Gla-ZIFs包合物及其制备方法和应用 - Google Patents
一种Gla-ZIFs包合物及其制备方法和应用 Download PDFInfo
- Publication number
- CN111420069A CN111420069A CN202010442828.8A CN202010442828A CN111420069A CN 111420069 A CN111420069 A CN 111420069A CN 202010442828 A CN202010442828 A CN 202010442828A CN 111420069 A CN111420069 A CN 111420069A
- Authority
- CN
- China
- Prior art keywords
- zif
- gla
- glabridin
- zifs
- solution
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 35
- 239000013153 zeolitic imidazolate framework Substances 0.000 title claims abstract description 31
- 238000002360 preparation method Methods 0.000 title claims abstract description 14
- 239000013154 zeolitic imidazolate framework-8 Substances 0.000 claims abstract description 162
- LBQIJVLKGVZRIW-ZDUSSCGKSA-N glabridin Chemical compound C1([C@H]2CC3=CC=C4OC(C=CC4=C3OC2)(C)C)=CC=C(O)C=C1O LBQIJVLKGVZRIW-ZDUSSCGKSA-N 0.000 claims abstract description 100
- 229940093767 glabridin Drugs 0.000 claims abstract description 99
- PMPYOYXFIHXBJI-ZDUSSCGKSA-N glabridin Natural products C1([C@H]2CC=3C=CC4=C(C=3OC2)CCC(O4)(C)C)=CC=C(O)C=C1O PMPYOYXFIHXBJI-ZDUSSCGKSA-N 0.000 claims abstract description 99
- LBQIJVLKGVZRIW-UHFFFAOYSA-N glabridine Natural products C1OC2=C3C=CC(C)(C)OC3=CC=C2CC1C1=CC=C(O)C=C1O LBQIJVLKGVZRIW-UHFFFAOYSA-N 0.000 claims abstract description 99
- MFLKDEMTKSVIBK-UHFFFAOYSA-N zinc;2-methylimidazol-3-ide Chemical compound [Zn+2].CC1=NC=C[N-]1.CC1=NC=C[N-]1 MFLKDEMTKSVIBK-UHFFFAOYSA-N 0.000 claims abstract description 56
- 239000003814 drug Substances 0.000 claims abstract description 54
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims abstract description 40
- 239000000243 solution Substances 0.000 claims abstract description 39
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 32
- 239000007864 aqueous solution Substances 0.000 claims abstract description 25
- 239000002245 particle Substances 0.000 claims abstract description 22
- 239000011259 mixed solution Substances 0.000 claims abstract description 16
- -1 imidazole compound Chemical group 0.000 claims abstract description 5
- 238000000034 method Methods 0.000 claims description 19
- ONDPHDOFVYQSGI-UHFFFAOYSA-N zinc nitrate Chemical compound [Zn+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O ONDPHDOFVYQSGI-UHFFFAOYSA-N 0.000 claims description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 10
- LXBGSDVWAMZHDD-UHFFFAOYSA-N 2-methyl-1h-imidazole Chemical compound CC1=NC=CN1 LXBGSDVWAMZHDD-UHFFFAOYSA-N 0.000 claims description 8
- 239000002537 cosmetic Substances 0.000 claims description 8
- 239000000463 material Substances 0.000 claims description 8
- 239000002244 precipitate Substances 0.000 claims description 8
- 239000011701 zinc Substances 0.000 claims description 8
- 125000002883 imidazolyl group Chemical group 0.000 claims description 6
- 238000005406 washing Methods 0.000 claims description 6
- YSWBFLWKAIRHEI-UHFFFAOYSA-N 4,5-dimethyl-1h-imidazole Chemical compound CC=1N=CNC=1C YSWBFLWKAIRHEI-UHFFFAOYSA-N 0.000 claims description 4
- 239000008367 deionised water Substances 0.000 claims description 4
- 229910021641 deionized water Inorganic materials 0.000 claims description 4
- 235000013305 food Nutrition 0.000 claims description 4
- 239000000047 product Substances 0.000 claims description 4
- 238000009777 vacuum freeze-drying Methods 0.000 claims description 4
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 claims description 4
- 230000004931 aggregating effect Effects 0.000 claims description 3
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 claims description 2
- 102100029880 Glycodelin Human genes 0.000 claims description 2
- 101000585553 Homo sapiens Glycodelin Proteins 0.000 claims description 2
- 239000006071 cream Substances 0.000 claims description 2
- 239000000686 essence Substances 0.000 claims description 2
- 239000006210 lotion Substances 0.000 claims description 2
- 238000003756 stirring Methods 0.000 claims description 2
- 230000002087 whitening effect Effects 0.000 claims description 2
- 239000013167 zeolitic imidazolate framework-1 Substances 0.000 claims description 2
- 239000013174 zeolitic imidazolate framework-10 Substances 0.000 claims description 2
- 239000013175 zeolitic imidazolate framework-11 Substances 0.000 claims description 2
- 239000013176 zeolitic imidazolate framework-12 Substances 0.000 claims description 2
- 239000013168 zeolitic imidazolate framework-2 Substances 0.000 claims description 2
- 239000013169 zeolitic imidazolate framework-3 Substances 0.000 claims description 2
- 239000013155 zeolitic imidazolate framework-4 Substances 0.000 claims description 2
- 239000013170 zeolitic imidazolate framework-5 Substances 0.000 claims description 2
- 239000013171 zeolitic imidazolate framework-6 Substances 0.000 claims description 2
- 239000013172 zeolitic imidazolate framework-7 Substances 0.000 claims description 2
- 239000013173 zeolitic imidazolate framework-9 Substances 0.000 claims description 2
- 235000005074 zinc chloride Nutrition 0.000 claims description 2
- 239000011592 zinc chloride Substances 0.000 claims description 2
- NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 claims description 2
- 229910000368 zinc sulfate Inorganic materials 0.000 claims description 2
- 229960001763 zinc sulfate Drugs 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 239000002417 nutraceutical Substances 0.000 claims 2
- 235000021436 nutraceutical agent Nutrition 0.000 claims 2
- 229940079593 drug Drugs 0.000 abstract description 46
- 230000003078 antioxidant effect Effects 0.000 abstract description 15
- 239000013078 crystal Substances 0.000 abstract description 9
- 238000011068 loading method Methods 0.000 abstract description 8
- XUMBMVFBXHLACL-UHFFFAOYSA-N Melanin Chemical compound O=C1C(=O)C(C2=CNC3=C(C(C(=O)C4=C32)=O)C)=C2C4=CNC2=C1C XUMBMVFBXHLACL-UHFFFAOYSA-N 0.000 abstract description 6
- 239000003963 antioxidant agent Substances 0.000 abstract description 6
- 230000002209 hydrophobic effect Effects 0.000 abstract description 6
- 238000000338 in vitro Methods 0.000 abstract description 6
- 230000003834 intracellular effect Effects 0.000 abstract description 6
- 230000002401 inhibitory effect Effects 0.000 abstract description 4
- 230000012010 growth Effects 0.000 abstract description 2
- 238000005538 encapsulation Methods 0.000 description 25
- 210000004027 cell Anatomy 0.000 description 15
- 230000008569 process Effects 0.000 description 10
- 239000012621 metal-organic framework Substances 0.000 description 8
- 238000012377 drug delivery Methods 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 230000005764 inhibitory process Effects 0.000 description 7
- 238000002835 absorbance Methods 0.000 description 6
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 5
- 238000010521 absorption reaction Methods 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 239000012091 fetal bovine serum Substances 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 4
- WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 description 4
- 238000002441 X-ray diffraction Methods 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
- 239000000523 sample Substances 0.000 description 4
- 238000001338 self-assembly Methods 0.000 description 4
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 4
- 238000002411 thermogravimetry Methods 0.000 description 4
- XDFNWJDGWJVGGN-UHFFFAOYSA-N 2-(2,7-dichloro-3,6-dihydroxy-9h-xanthen-9-yl)benzoic acid Chemical compound OC(=O)C1=CC=CC=C1C1C2=CC(Cl)=C(O)C=C2OC2=CC(O)=C(Cl)C=C21 XDFNWJDGWJVGGN-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 3
- WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 108010019160 Pancreatin Proteins 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 102000003425 Tyrosinase Human genes 0.000 description 3
- 108060008724 Tyrosinase Proteins 0.000 description 3
- 239000012296 anti-solvent Substances 0.000 description 3
- 238000005119 centrifugation Methods 0.000 description 3
- 238000000975 co-precipitation Methods 0.000 description 3
- 238000000354 decomposition reaction Methods 0.000 description 3
- MGJZITXUQXWAKY-UHFFFAOYSA-N diphenyl-(2,4,6-trinitrophenyl)iminoazanium Chemical compound [O-][N+](=O)C1=CC([N+](=O)[O-])=CC([N+]([O-])=O)=C1N=[N+](C=1C=CC=CC=1)C1=CC=CC=C1 MGJZITXUQXWAKY-UHFFFAOYSA-N 0.000 description 3
- 239000001963 growth medium Substances 0.000 description 3
- 230000003993 interaction Effects 0.000 description 3
- 229960004502 levodopa Drugs 0.000 description 3
- 230000004060 metabolic process Effects 0.000 description 3
- 229940055695 pancreatin Drugs 0.000 description 3
- 239000011148 porous material Substances 0.000 description 3
- 238000001878 scanning electron micrograph Methods 0.000 description 3
- 230000035040 seed growth Effects 0.000 description 3
- 238000001179 sorption measurement Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 235000001674 Agaricus brunnescens Nutrition 0.000 description 2
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 2
- 244000303040 Glycyrrhiza glabra Species 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- 229930182555 Penicillin Natural products 0.000 description 2
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 2
- 230000002292 Radical scavenging effect Effects 0.000 description 2
- 229910006069 SO3H Inorganic materials 0.000 description 2
- 238000003917 TEM image Methods 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 230000001186 cumulative effect Effects 0.000 description 2
- VFLDPWHFBUODDF-FCXRPNKRSA-N curcumin Chemical compound C1=C(O)C(OC)=CC(\C=C\C(=O)CC(=O)\C=C\C=2C=C(OC)C(O)=CC=2)=C1 VFLDPWHFBUODDF-FCXRPNKRSA-N 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 230000003061 melanogenesis Effects 0.000 description 2
- 239000013081 microcrystal Substances 0.000 description 2
- 229940049954 penicillin Drugs 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 239000012488 sample solution Substances 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000012086 standard solution Substances 0.000 description 2
- 229960005322 streptomycin Drugs 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000002211 ultraviolet spectrum Methods 0.000 description 2
- 230000004580 weight loss Effects 0.000 description 2
- OCZVHBZNPVABKX-UHFFFAOYSA-N 1,1-diphenyl-2-(2,4,6-trinitrophenyl)hydrazine;ethanol Chemical compound CCO.[O-][N+](=O)C1=CC([N+](=O)[O-])=CC([N+]([O-])=O)=C1NN(C=1C=CC=CC=1)C1=CC=CC=C1 OCZVHBZNPVABKX-UHFFFAOYSA-N 0.000 description 1
- XIOUDVJTOYVRTB-UHFFFAOYSA-N 1-(1-adamantyl)-3-aminothiourea Chemical compound C1C(C2)CC3CC2CC1(NC(=S)NN)C3 XIOUDVJTOYVRTB-UHFFFAOYSA-N 0.000 description 1
- SRDYZYPCNSKEHD-UHFFFAOYSA-N 2-azido-n-benzyl-7h-purin-6-amine Chemical compound C=12NC=NC2=NC(N=[N+]=[N-])=NC=1NCC1=CC=CC=C1 SRDYZYPCNSKEHD-UHFFFAOYSA-N 0.000 description 1
- SMBRHGJEDJVDOB-UHFFFAOYSA-N 2-methylpropanimidamide;dihydrochloride Chemical compound Cl.Cl.CC(C)C(N)=N SMBRHGJEDJVDOB-UHFFFAOYSA-N 0.000 description 1
- KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 102100021202 Desmocollin-1 Human genes 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000371 Esterases Proteins 0.000 description 1
- 235000006200 Glycyrrhiza glabra Nutrition 0.000 description 1
- 101000968043 Homo sapiens Desmocollin-1 Proteins 0.000 description 1
- 101000880960 Homo sapiens Desmocollin-3 Proteins 0.000 description 1
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- 229910021536 Zeolite Inorganic materials 0.000 description 1
- 238000004847 absorption spectroscopy Methods 0.000 description 1
- PQLVXDKIJBQVDF-UHFFFAOYSA-N acetic acid;hydrate Chemical compound O.CC(O)=O PQLVXDKIJBQVDF-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 229940009456 adriamycin Drugs 0.000 description 1
- 230000003698 anagen phase Effects 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 238000002792 antioxidant assay Methods 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- CDQSJQSWAWPGKG-UHFFFAOYSA-N butane-1,1-diol Chemical compound CCCC(O)O CDQSJQSWAWPGKG-UHFFFAOYSA-N 0.000 description 1
- 229960001948 caffeine Drugs 0.000 description 1
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- VSJKWCGYPAHWDS-FQEVSTJZSA-N camptothecin Chemical compound C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-FQEVSTJZSA-N 0.000 description 1
- 229940127093 camptothecin Drugs 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000003889 chemical engineering Methods 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- GVPFVAHMJGGAJG-UHFFFAOYSA-L cobalt dichloride Chemical compound [Cl-].[Cl-].[Co+2] GVPFVAHMJGGAJG-UHFFFAOYSA-L 0.000 description 1
- 229910000361 cobalt sulfate Inorganic materials 0.000 description 1
- 229940044175 cobalt sulfate Drugs 0.000 description 1
- KTVIXTQDYHMGHF-UHFFFAOYSA-L cobalt(2+) sulfate Chemical compound [Co+2].[O-]S([O-])(=O)=O KTVIXTQDYHMGHF-UHFFFAOYSA-L 0.000 description 1
- 238000013267 controlled drug release Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 229940109262 curcumin Drugs 0.000 description 1
- 235000012754 curcumin Nutrition 0.000 description 1
- 239000004148 curcumin Substances 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- VFLDPWHFBUODDF-UHFFFAOYSA-N diferuloylmethane Natural products C1=C(O)C(OC)=CC(C=CC(=O)CC(=O)C=CC=2C=C(OC)C(O)=CC=2)=C1 VFLDPWHFBUODDF-UHFFFAOYSA-N 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- HNPSIPDUKPIQMN-UHFFFAOYSA-N dioxosilane;oxo(oxoalumanyloxy)alumane Chemical compound O=[Si]=O.O=[Al]O[Al]=O HNPSIPDUKPIQMN-UHFFFAOYSA-N 0.000 description 1
- VSJKWCGYPAHWDS-UHFFFAOYSA-N dl-camptothecin Natural products C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)C5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-UHFFFAOYSA-N 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 230000009881 electrostatic interaction Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 229930003935 flavonoid Natural products 0.000 description 1
- 150000002215 flavonoids Chemical class 0.000 description 1
- 235000017173 flavonoids Nutrition 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 150000002460 imidazoles Chemical class 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- PSCMQHVBLHHWTO-UHFFFAOYSA-K indium(iii) chloride Chemical compound Cl[In](Cl)Cl PSCMQHVBLHHWTO-UHFFFAOYSA-K 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 239000002085 irritant Substances 0.000 description 1
- 231100000021 irritant Toxicity 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 230000000324 neuroprotective effect Effects 0.000 description 1
- 239000013110 organic ligand Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000004792 oxidative damage Effects 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 229940126586 small molecule drug Drugs 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 239000010457 zeolite Substances 0.000 description 1
Images
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
- A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/69—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6949—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L29/00—Foods or foodstuffs containing additives; Preparation or treatment thereof
- A23L29/015—Inorganic compounds
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L29/00—Foods or foodstuffs containing additives; Preparation or treatment thereof
- A23L29/03—Organic compounds
- A23L29/045—Organic compounds containing nitrogen as heteroatom
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
-
- 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
- A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/52—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an inorganic compound, e.g. an inorganic ion that is complexed with the active ingredient
-
- 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
- A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/54—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
- A61K47/545—Heterocyclic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
- A61K8/25—Silicon; Compounds thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/494—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with more than one nitrogen as the only hetero atom
- A61K8/4946—Imidazoles or their condensed derivatives, e.g. benzimidazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/4973—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom
- A61K8/498—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom having 6-membered rings or their condensed derivatives, e.g. coumarin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/02—Preparations for care of the skin for chemically bleaching or whitening the skin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/10—Washing or bathing preparations
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
- C07D493/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G83/00—Macromolecular compounds not provided for in groups C08G2/00 - C08G81/00
- C08G83/008—Supramolecular polymers
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Polymers & Plastics (AREA)
- Nutrition Science (AREA)
- Food Science & Technology (AREA)
- Birds (AREA)
- Inorganic Chemistry (AREA)
- Dermatology (AREA)
- Botany (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Mycology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明提供了一种Gla‑ZIFs包合物及其制备方法和应用,该包合物以咪唑酯骨架结构材料ZIFs为载体,将光甘草定包裹在其中,形成Gla‑ZIFs包合物。在制备Gla‑ZIFs包合物时,首先,将光甘草定的乙醇溶液逐渐加入到含Zn2+和/或In3+和/或Co2+的水溶液中形成混合溶液,从而生成光甘草定微晶颗粒;然后,将咪唑基化合物加入到上述混合溶液中,Zn2+和/或In3+和/或Co2+和咪唑基化合物通过配位形成ZIFs,并在微晶颗粒表面生长、聚集,同时将Gla包裹在其中,从而形成Gla‑ZIFs包合物。以ZIF‑8为例,制备得到的Gla‑ZIF‑8包合物的包封率高达98.67%,并表现出pH可控的药物释放行为,显示出平和的体外抗氧化能力和显著提高的胞内抗氧化活性,Gla‑ZIF‑8抑制黑色素生成的能力明显增强,实验还验证了晶种生长的ZIF‑8载药途径对疏水性药物的适用性。
Description
技术领域
本发明属于制药、化工生物领域,特别涉及一种Gla-ZIFs包合物及其制备方法和应用。
背景技术
光甘草定(Glabridin,Gla)是一种广泛存在于光果甘草根茎中的黄酮类活性物质,结构式如图1所示。光甘草定是小极性分子,水溶性差,易溶于乙醇、丙二醇、丁二醇等有机溶剂。临床研究显示光甘草定具有广泛的生理功能,如:抗炎、心血管保护作用、神经保护、调节能量消耗和代谢、抗癌。
来源于植物光果甘草的光甘草定因其具有丰富多样的生物活性越来越成为人们研究和关注的热点,然而,其存在着水溶性差、遇光热易分解、化学稳定度低、代谢快、半衰期短、难以被生物体吸收和利用等缺点。为了解决药物传递过程中药效降低和药物释放的难题,开发更加安全高效的药物递送系统迫在眉睫。
金属有机骨架材料(metal-organic frameworks,MOFs)由金属离子和有机配体通过自组装而形成。MOFs之所以被越来越多地作为药物递送系统载体应用于生物研究领域,是因为其孔隙率高、比表面积大、孔径可调以及表面可进行功能化修饰的特点,可以提高药物的负载量,增强药物分子的稳定性,将药物安全有效的传递至靶向部位。MOFs可以将大量的药物递送至靶向细胞附近,然而大部分MOFs在水性介质中稳定性差、易崩解。因此,寻求合适的MOFs材料作为药物递送载体仍面临许多挑战。
在MOFs中,由沸石和咪唑自组装形成的咪唑酯骨架结构材料ZIFs(ZeoliteImidazolate Frameworks,ZIFs)是较为特殊的一类。目前尚未有采用ZIFs包覆光甘草定的报道。
发明内容
本发明的目的是提供一种Gla-ZIFs包合物及其制备方法和应用,选取ZIFs对光甘草定进行包封,解决了光甘草定因水溶性差、遇光热易分解、化学稳定度低、代谢快、半衰期短,而难以被生物体吸收和利用的问题。
本发明的目的是通过以下技术方案实现的:
一种Gla-ZIFs包合物,以咪唑酯骨架结构材料ZIFs为载体,将光甘草定包裹在其中,形成Gla-ZIFs包合物。所述ZIFs为ZIF-1、ZIF-2、ZIF-3、ZIF-4、ZIF-5、ZIF-6、ZIF-7、ZIF-8、ZIF-9、ZIF-10、ZIF-11、ZIF-12中任意一种。
所述Gla-ZIFs包合物的制备方法,包括以下步骤:
首先,将光甘草定的乙醇溶液逐渐加入到含Zn2+和/或In3+和/或Co2+的水溶液中形成混合溶液,从而生成光甘草定微晶颗粒;
然后,将咪唑基化合物加入到上述混合溶液中,Zn2+和/或In3+和/或Co2+和咪唑基通过配位形成ZIF-n,并在微晶颗粒表面生长、聚集,同时将药物Gla包裹在其中,从而形成Gla-ZIFs包合物;
所述咪唑基化合物包括咪唑(imidazolate,IM)、苯丙咪唑(benzimidazolate,PhIM)、2-甲基咪唑(2-methylimidazolate,2-MeIM)。
所述的Gla-ZIFs包合物在化妆品、药品、保健品和食品中的应用。
进一步的,所述含Zn2+的水溶液选用硝酸锌水溶液、硫酸锌水溶液或氯化锌水溶液,含Co2+的水溶液选用氯化钴或硫酸钴,含In3+的水溶液选用氯化铟等。
本发明的另一方面:
一种Gla-ZIF-8包合物的制备方法,包括以下方法:
首先,将光甘草定的乙醇溶液逐渐加入到含Zn2+的水溶液中形成混合溶液,由于光甘草定的疏水性,加入到水溶液中会析出微晶,从而生成光甘草定微晶颗粒;
然后,将2-甲基咪唑加入到上述混合溶液中,Zn2+和2-MeIM通过配位形成ZIF-8,并在微晶颗粒表面生长、聚集,同时将药物Gla包裹在其中,从而形成Gla-ZIF-8包合物。
进一步的,向混合溶液中加入2-甲基咪唑后,室温条件下反应20~40min,而后通过离心分离,得到白色沉淀物,再使用去离子水洗涤该白色沉淀物以去除其表面残留物,经真空冷冻干燥得到粉末状的Gla-ZIF-8包合物。
本发明的另一方面:
所述的Gla-ZIF-8包合物在化妆品、药品、保健品和食品中的应用。
进一步的,所述化妆品为美白化妆品,包括化妆水、乳液、精华、膏霜、面膜及皮肤清洁产品。
咪唑酯骨架结构材料ZIFs有很多种,经研究其中12种适合疏水药物小分子包裹载入,见下表:
其中ZIF-8载体对于光甘草定的包封率达到98%以上,高于其他载体。
由于Zn2+和2-MeIM之间存在更强的相互作用力,确保了ZIF-8在水溶液中具备更优异的稳定性。另一方面,ZIF-8在酸性条件下易发生崩解,可以作为pH刺激的药物递送系统的载体材料,递送药物至靶向部位发挥疗效。
纵观ZIF-n的合成机理和方案,大致可以分为以下两类。其一,将预先制备好的ZIF-n加入到含有药物的溶媒中,通过ZIF-n的吸附特性,实现对药物分子的包覆。但这一工艺仅适用于粒径小于ZIF-n孔径的小分子药物,对于颗粒较大的药物不能实现有效封装。另外,通过吸附作用装载的药物容易在传递过程中泄漏,且药物的释放过程易发生突释行为。第二种方法是一步原位封装,即在ZIF-n自组装形成的过程中将药物分子载入其中。这样就避免了因药物分子大小而出现的包覆问题,且不易发生药物泄漏和药物突释。但此方案仅限于具备-NH3、-COOH、-SO3H等特殊官能团的药物分子,例如阿霉素、喜树碱、咖啡因等。
本发明相比现有技术的有益效果为:
1、现有技术中ZIF-n的两种合成机理均具有一定限制性,通过吸附作用装载药物,药物的包封效果取决于载体孔径的大小和数量,会造成包封率低且药物容易吸附在载体表面,在药物传递过程中极易发生泄漏。另外,在ZIF-n自组装过程中装载药物,药物分子和药物载体间必须存在强相互作用力,这取决于药物分子本身是否具有-NH3、-COOH、-SO3H等特定的官能团。与之相反,本发明开发出的制备方法打破其限制,提出了一个晶种生长的思路来实现ZIF-n对疏水性药物的封装,针对所有疏水性药物,都可以制备出具有高包封率的ZIF-n载药系统,并且工艺简捷有效、绿色安全;
2、本发明利用ZIF-n对光甘草定进行包封,是通过抗溶剂共沉淀法进行制备的,首先,将光甘草定的乙醇溶液逐渐加入到含有Zn2+和/或In3+和/或Co2+的水溶液中,由于溶解度的差异性,生成了光甘草定的微晶颗粒。然后,将咪唑基加入到上述混合溶液中,Zn2+和咪唑基通过配位形成ZIF-n,并在微晶颗粒表面生长,同时将药物包裹其中。随着Gla-ZIFs的不断生长、聚集、沉降,离心得到白色沉淀物,即为所述的Gla-ZIFs包合物;
3、本发明实施例制备Gla-ZIF-8包合物的包封率达到98.67±0.43%,本发明所述晶种生长的ZIF-8装载工艺能够实现对药物极高的包封率;并且制备得到的Gla-ZIF-8呈现梭形或十字交叉花状结构,通过UV、Zeta、FTIR、XRD、TGA对Gla-ZIF-8进行表征,证实了ZIF-8对光甘草定成功封装;
4、经测定,由于ZIF-8的包封作用,增强了Gla-ZIF-8抑制黑色素生成的能力;胞内抗氧化活性远远高于游离光甘草定。这是因为ZIF-8的包封增强了与细胞间的相互吸引,提高了细胞的内化作用,改善了药物的生物利用度。
构成本发明的一部分的附图用来提供对本发明的进一步解释,本发明的示意性实施例及其说明用于解释本发明,并不构成对本发明的不当限定。
附图说明
图1为光甘草定的结构式;
图2为光甘草定标准曲线;
图3为Gla-ZIF-8的TEM和SEM图像;
图4为光甘草定、ZIF-8和Gla-ZIF-8的紫外光谱;
图5为ZIF-8和Gla-ZIF-8的Zeta电位;
图6为光甘草定、ZIF-8和Gla-ZIF-8的红外光谱;
图7为光甘草定、ZIF-8和Gla-ZIF-8的XRD图;
图8为光甘草定和Gla-ZIF-8的热重变化图;
图9为Gla-ZIF-8在PBS(pH 7.4和5.4)中的光甘草定的体外释放曲线;
图10为游离光甘草定和Gla-ZIF-8对抑制酪氨酸酶活性;
图11为游离光甘草定和Gla-ZIF-8对DPPH自由基清除活性;
图12为游离光甘草定、ZIF-8、Gla-ZIF-8的DCF荧光动力学曲线(A)和CAA值(B)。
具体实施方式
试验材料:光甘草定(Gla),湖南佳木生物科技有限公司;二甲基咪唑(2-MIM)、六水合硝酸锌(Zn(NO3)2·6H2O)、2,2-二苯基-1-苦基肼基(DPPH),萨恩化学技术(上海)有限公司;2',7'-二氯荧光黄双乙酸(DCFH-DA)、2-脒基丙烷二盐酸盐(ABAP),美国Sigma-Aldrich公司;蘑菇酪氨酸酶(25KU)、左旋多巴(L-DOPA),上海吉至生化有限公司;CCK-8试剂盒(CCK-8),美国MP公司;DMEM培养基、胎牛血清(FBS),美国Gibco公司;0.25%胰酶(含0.53mM EDTA·4Na)、PBS(0.01M,pH 7.4)、青霉素(10,000U/mL)、链霉素(10,000U/mL),美国Hyclone公司。其他分析纯的试剂购自北京化工厂。
人胃癌细胞(MGC80-3)取自北京协和医学院细胞资源中心,采用DMEM细胞培养基,配方为10%胎牛血清(FBS)、1%双抗(100U/mL链霉素和100U/mL青霉素)。在37℃,5%CO2的条件下恒温培养。更换培养基的时间间隔为24h,0.25%的胰酶消化贴壁细胞,1000r离心收集细胞,然后进行传代或备用。
需要说明的是,在不冲突的情况下,本发明中的实施例及实施例中的特征可以相互组合。下面将参考附图并结合实施例来详细说明本发明。
实施例1
本实施例通过抗溶剂共沉淀法制备Gla-ZIF-8包合物。
首先,分别配制光甘草定的乙醇溶液(2mg/mL)、硝酸锌水溶液(30mg/mL)和二甲基咪唑水溶液(66mg/mL),在剧烈搅拌状态下,先向50mL硝酸锌溶液中加入10mL光甘草定溶液,再加入50mL二甲基咪唑溶液,室温下反应30min。离心分离,得到白色沉淀物Gla-ZIF-8,去离子水洗涤2-3次,去除Gla-ZIF-8表面的残留物。将Gla-ZIF-8真空冷冻干燥成粉末,即得到所述Gla-ZIF-8包合物。
取200μL HCl(1M)酸解10mg Gla-ZIF-8粉末,用乙醇将上述溶液稀释至2mL,HPLC检测,根据公式(1)和光甘草定的标准曲线计算Gla-ZIF-8的包封率(DLE)。
包封率(%)=Gla-ZIF-8中光甘草定的质量/光甘草定的总添加量×100%......(1)
用乙醇配置浓度梯度为20、40、80、100、160、200μg/mL的光甘草定标准溶液,HPLC检测光甘草定标准溶液,绘制光甘草定标准曲线,并求其回归方程。
高效液相色谱仪(LC-20A,日本岛津)色谱条件:色谱柱:Venusil XBP C18反向色谱柱(4.6×250mm,5um),流动相为乙腈:2%乙酸水(50:50);流速为1mL/min;柱温为30℃;进样体积为20μL,检测波长为282nm。见表1所示,在20-200ug/mL之间呈良好的线性关系(R2=0.9996)。
表1光甘草定的浓度与峰面积
根据光甘草定的标准曲线(图2),由公式(1)可以计算出Gla-ZIF-8的包封率(DLE)为98.67±0.43%。晶种生长的ZIF-8装载工艺能够实现对药物极高的包封率。
根据上述计算结果说明本实施例所述的制备方法打破了现有ZIF-8载药的限制条件,针对所有疏水性药物,都可以制备出具有高包封率的ZIF-8载药系统。
实施例2
本实施例对实施例1制备得到的Gla-ZIF-8包合物进行表征测定。
采用紫外可见吸收光谱(UV)(UV-2450,日本岛津)检测光甘草定甲醇溶液、ZIF-8水溶液和Gla-ZIF-8水溶液的光谱特性。微量Gla-ZIF-8水溶液滴加在铜网/硅片上,室温干燥后,通过透射电镜(TEM)(HT7700,日本日立)/扫描电镜(SEM)(S-4700,Hitachi)观察Gla-ZIF-8的形貌和尺寸大小。采用纳米粒径电位分析仪(Nano-ZS 2000,英国莫尔文仪器)测量适当浓度的ZIF-8、Gla-ZIF-8水溶液的表面电荷。称取适量的光甘草定、ZIF-8、Gla-ZIF-8的干燥粉末,在4000-400cm-1范围内进行红外(FTIR)(Nicolet 6700,赛默飞世尔科技有限公司)分析。称取适量的光甘草定、ZIF-8和Gla-ZIF-8的干燥粉末,分别平铺在样品台上,采用X射线晶体衍射(XRD)(D8 ADVANCE,德国布鲁克AXS有限公司)分析晶型变化的情况。称取适量的ZIF-8、Gla-ZIF-8的干燥粉末,分别置于样品坩埚中,在25-1000℃范围内进行热重分析(TGA)(DSC1,梅特勒公司)。
图3分别是光甘草定微晶颗粒(A)和Gla-ZIF-8的TEM(B、C)和SEM图像(D)。光甘草定在水相中形成棒状的微晶颗粒,随后ZIF-8依附在晶体表面生长、聚集,将药物包覆其中,从而形成Gla-ZIF-8。从图3中可以看出,Gla-ZIF-8呈现梭形或十字交叉花状结构,Gla-ZIF-8的尺寸大小为3μm左右。
图4是光甘草定、ZIF-8和Gla-ZIF-8的UV光谱。其中,光甘草定在282nm处有最大吸收峰,而ZIF-8和Gla-ZIF-8在此波段均没有紫外吸收。结果表明,ZIF-8的包封作用掩盖了光甘草定的特征峰,进一步证明了ZIF-8将光甘草定包覆其中。
ZIF-8和Gla-ZIF-8的Zeta电位如图5所示。ZIF-8的Zeta电位(+3.8mV)与Gla-ZIF-8的Zeta电位(+2.67mV)相差不大,且均表现出正电性,表明光甘草定被ZIF-8严密地载入其中。
图6是光甘草定、ZIF-8和Gla-ZIF-8的红外分析结果。在3340、1520和1480、1270cm-1处观察到光甘草定的特征吸收峰,对应于O-H、芳环骨架和C–O–C键的伸缩振动。ZIF-8的特征峰出现在3177和1566cm-1处,对应于芳香族C-H键咪唑环上的C-N键的伸缩振动。Gla-ZIF-8在3220和1568cm-1处的特征峰分别对应于芳族C–H键和咪唑环上的C–N键,这刚好与ZIF-8的特征峰重合。值得注意的是,Gla-ZIF-8中并没有发现光甘草定的特征峰,再次证实了ZIF-8实现了对光甘草定的封装。
XRD的结果也为Gla-ZIF-8的形成提供了证据。从图7中可以看出,ZIF-8的特征峰位置出现在10.54、12.80和18.00等处。光甘草定在2θ值为15.02、16.54、18.16、19.88、20.06和21.13处有较强的特征峰。在Gla-ZIF-8的XRD谱图中,出现了ZIF-8的特征峰(10.38和12.72),而光甘草定在19.88处的最大特征峰被掩盖,表明ZIF-8成功地包封了光甘草定。特别地,Gla-ZIF-8和CCM-ZIF-8在2θ值(10.38、11.00、11.58、12.72、13.48、15.12、16.66、17.06、18.00)处显示出形貌相同的特征峰,表明我们制备的ZIF-8包合物具有独特的晶型和结构。
图8是光甘草定和Gla-ZIF-8的热重变化图。在40-350℃的温度范围内,光甘草定的重量损失仅为6.54%,而Gla-ZIF-8的重量损失为24.31%。当温度从350℃升至390℃时,游离光甘草定急剧降解,40分钟内光甘草定的重量损失高达88.69。与之相反,当温度升至580℃时,仍有69.30%的Gla-ZIF-8稳定存在。由此可以得出,ZIF-8的保护性包封增强了光甘草定的热稳定性能,有效地避免了光甘草定在高温下的快速分解。
实施例3
本实施例对实施例1制备得到的Gla-ZIF-8包合物进行体外药物释放性能及多项生物活性的测定。
Gla-ZIF-8体外药物释放性能的测定:
分别精密称量10mg Gla-ZIF-8粉末,分散于pH为5.0和7.4的50mL PBS溶液(0.02M,10%乙醇)中。考虑到光甘草定在水溶液中易分解的特性,通过在PBS溶液中添加吐温-80(1.0wt%)来改善光甘草定的稳定性,以便于监测释放出的光甘草定。37℃下保持振荡,在每个预定时间,离心收集一定体积的上清液用于HPLC分析,并补加等体积的新鲜溶液。计算不同pH条件下光甘草定的累计释放量,并绘制随时间变化的药物释放曲线。
分别在在pH值pH 5.0和pH 7.4的PBS溶液中评估Gla-ZIF-8的pH响应性药物释放行为。为了提高光甘草定的溶解性,向PBS溶液中添加10%乙醇。如图9所示,在pH 5.0的PBS溶液中,72h内Gla-ZIF-8的累积药物释放达到80.08%。相比之下,在pH 7.4的PBS溶液中,72h内Gla-ZIF-8仅释放20.82%的姜黄素。特别地,在pH 7.4的PBS溶液中的Gla-ZIF-8具有非常缓慢的药物释放速率。与之相比,在pH 5.0条件下的Gla-ZIF-8显示出持续、高效的药物释放速率。Gla-ZIF-8的这种pH可控的药物释放特性,对开发刺激性药物递送系统具有重要参考价值。
Gla-ZIF-8抑制黑色素生成的能力测定:
使用L-DOPA作为底物,分别对游离光甘草定和包合物Gla-ZIF-8的酪氨酸酶活性抑制效果、抑制黑色素生成能力进行评估。将适量光甘草定、Gla-ZIF-8分别溶解在乙醇中,并用PBS溶液(0.05mM,pH=6.8)稀释成浓度0.025–2.5μg/mL的溶液。将1mLL-DOPA(1.0mM)的PBS溶液和0.5mL上述样品溶液充分混合,37℃下振荡5分钟。然后,将0.5mL酪氨酸酶(100U/mL,来源于蘑菇)的PBS溶液加入上述混合溶液中并在37℃继续振荡10分钟。选取1mL L-DOPA溶液、0.5mL酪氨酸酶溶液和0.5mLPBS的混合溶液作为对照组。采用UV测量475nm处的吸光度,根据公式2计算抑制率。
抑制率(100%)=(1-测试组吸光度/对照组吸光度)×100%......(2)
酪氨酸酶能够催化L-DOPA生成黑色素,光甘草定可通过抑制酪氨酸酶活性来减少黑色素的产生。通过检测475nm下吸光度的变化情况,评估游离态光甘草定和Gla-ZIF-8抑制黑色素生成的能力。如图10所示,随着浓度的升高,游离态光甘草定和Gla-ZIF-8的抑制百分比都逐渐增加。当光甘草定浓度低于0.5μg/ml时,游离态和包合物的抑制百分比无明显差异。当浓度在1-2.5μg/ml之间时,Gla-ZIF-8的抑制百分比略高于游离态。这可能是由于包合物的形成提高了Gla-ZIF-8在PBS溶液中的分散性。相反地,游离光甘草定由于水溶性差,在水相中分散程度低,导致抑制黑色素生成的效果不佳。
Gla-ZIF-8的体外抗氧化活性测定:
用乙醇分别配制光甘草定、Gla-ZIF-8溶液,药物浓度为2.5-80μg/mL。避光条件下,向1mL DPPH乙醇溶液(0.2mM)中加入0.5mL上述样品溶液,室温反应30min。选取1mLDPPH溶液和0.5mL乙醇的混合溶液作为对照组。通过UV测定底物DPPH在517nm处的吸光度,并根据以下公式计算各个样品的自由基清除能力。
DPPH清除率(100%)=(1-测试组溶液吸光度/对照组溶液吸光度)×100%......(3)
通过DPPH清除实验评价光甘草定的体外抗氧化活性。图11是不同浓度的游离光甘草定和Gla-ZIF-8与相应的DPPH自由基清除率的变化曲线。随着浓度的增加,游离光甘草定和Gla-ZIF-8对DPPH自由基的清除率也不断增加,且包合物的清除率低于游离态。当浓度为20μg/mL时,Gla-ZIF-8的清除率为24.42%,略高于游离态在5μg/mL的清除率(22.47%)。类似地,当浓度为40μg/mL时,游离光甘草定的清除率为44.91%,接近于Gla-ZIF-8在80μg/mL时的清除率(45.31%)。DPPH的清除率越高表明抗氧化活性越好,游离光甘草定表现出比包合物Gla-ZIF-8更优异的抗氧化性能,这可能是由于ZIF-8的包封作用阻碍了光甘草定与自由基之间的相互作用。
Gla-ZIF-8的胞内抗氧化活性:
胰酶消化,离心收集对数生长期的MGC80-3细胞,计数,调整细胞浓度至4000个/mL。在96孔板中接种90μL细胞悬液,培养12h,每孔加入10μL含光甘草定/ZIF-8/Gla-ZIF-8的DMEM培养基,保持光甘草定的最终浓度为4μg/mL和相同含量的ZIF-8,继续培养24h。PBS清洗2-3次,每孔加入100μL 25μM DCFH-DA的DMEM培养基(不含FBS),继续培养1h。PBS清洗2-3次,每孔加入100μL 600μMABAP的PBS溶液,每5min酶标仪检测一次,检测时长1h,激发波长485nm,发射波长535nm。对照组仅添加DCFH-DA和ABAP,空白组仅添加DCFH-DA。绘制时间-荧光强度的曲线,通过积分计算面积∫A,然后根据公式4计算CAA值。
CAA=100-((∫As-∫Ab)/(∫Ac-∫Ab))×100..............................(4)
其中,∫As表示实验组,∫Ac表示对照组,∫Ab表示空白组。
通过氧化MGC80-3细胞模型评估光甘草定、ZIF-8和Gla-ZIF-8在活细胞中的抗氧化活性(CAA)。ABAP可以在细胞内产生过氧化氢自由基,建立细胞氧化模型。DCFH-DA能够被细胞内化,经由细胞内酯酶转化为DCFH。进一步地,非荧光性的DCFH可以被ABAP氧化成具有荧光特性的DCF,通过DCF的荧光强度反映自由基引起的氧化损伤程度。相反地,添加抗氧化剂后,可以根据DCF荧光强度的降低程度来反映药物的抗氧化能力。图12(A)是光甘草定、ZIF-8和Gla-ZIF-8的DCF荧光动力学曲线,对照组为仅添加DCFH-DA和ABAP,空白组为仅添加ABAP。荧光强度的逐渐增强表明ABAP持续不断地将DCFH氧化成DCF。光甘草定作为抗氧化剂能够阻断这一过程。特别地,DCF荧光动力学曲线的趋势越平缓,说明外源添加物的抗氧化活性越高。与游离光甘草定和ZIF-8相比,Gla-ZIF-8展现出最强的抗氧化能力。如图12(B)所示,根据公式4计算光甘草定、ZIF-8和Gla-ZIF-8的CAA值。与ZIF-8(9.12)和光甘草定(14.35)相比,Gla-ZIF-8具有最大的CAA值(69.08),进一步表明ZIF-8的包封增强了Gla-ZIF-8的胞内抗氧化活性。这可能是由于Gla-ZIF-8的表面呈正电位,而细胞膜表面为负电位,容易发生静电相互作用,进而促进了细胞对Gla-ZIF-8的吸收。
综上,本发明通过抗溶剂共沉淀法成功制备了Gla-ZIF-8,具有98.67%的极高包封率。TEM和SEM的图像显示,Gla-ZIF-8具有规则、统一的梭形或十字交叉花状结构,尺寸大小为3μm左右。通过UV、Zeta、FTIR、XRD、TGA对Gla-ZIF-8进行表征,证实了ZIF-8对光甘草定成功封装。由于ZIF-8的包封作用,增强了Gla-ZIF-8抑制黑色素生成的能力。此外,Gla-ZIF-8的体外抗氧化活性略低于游离态,而胞内抗氧化活性远远高于游离光甘草定。这是因为ZIF-8的包封增强了与细胞间的相互吸引,提高了细胞的内化作用,改善了药物的生物利用度。此外,Gla-ZIF-8的成功制备证实了晶种生长的ZIF-8载药工艺对疏水性药物的适用性。
Claims (10)
1.一种Gla-ZIFs包合物,其特征在于,所述包合物以咪唑酯骨架结构材料ZIFs为载体,将光甘草定包裹在其中,形成Gla-ZIFs包合物;所述ZIFs为ZIF-1、ZIF-2、ZIF-3、ZIF-4、ZIF-5、ZIF-6、ZIF-7、ZIF-8、ZIF-9、ZIF-10、ZIF-11、ZIF-12中任意一种。
2.一种Gla-ZIFs包合物的制备方法,其特征在于,所述制备方法包括以下步骤:
首先,将光甘草定的乙醇溶液逐渐加入到含Zn2+和/或In3+和/或Co2+的水溶液中形成混合溶液,从而生成光甘草定微晶颗粒;
然后,将咪唑基化合物加入到上述混合溶液中,Zn2+和/或In3+和/或Co2+和咪唑基通过配位形成ZIFs,并在微晶颗粒表面生长、聚集,同时将药物Gla包裹在其中,从而形成Gla-ZIFs包合物;
所述咪唑基化合物包括咪唑、苯丙咪唑和2-甲基咪唑。
3.一种如权利要求1所述的Gla-ZIFs包合物在化妆品、药品、保健品和食品中的应用。
4.一种Gla-ZIF-8包合物的制备方法,其特征在于,所述制备方法包括以下方法:
首先,将光甘草定的乙醇溶液逐渐加入到含Zn2+的水溶液中形成混合溶液,从而生成光甘草定微晶颗粒;
然后,将2-甲基咪唑加入到上述混合溶液中,Zn2+和2-甲基咪唑通过配位形成ZIF-8,并在微晶颗粒表面生长、聚集,同时将药物Gla包裹在其中,从而形成Gla-ZIF-8包合物。
5.根据权利要求4所述Gla-ZIF-8包合物的制备方法,其特征在于,向混合溶液中加入2-甲基咪唑后,室温条件下反应20~40min,而后通过离心分离,得到白色沉淀物,再使用去离子水洗涤该白色沉淀物以去除其表面残留物,经真空冷冻干燥得到粉末状的Gla-ZIF-8包合物。
6.根据权利要求4所述Gla-ZIF-8包合物的制备方法,其特征在于,所述含Zn2+的水溶液包括硝酸锌、氯化锌、硫酸锌水溶液。
7.根据权利要求4所述Gla-ZIF-8包合物的制备方法,其特征在于,所述制备方法为:
分别配制浓度为2mg/mL光甘草定的乙醇溶液、30mg/mL硝酸锌水溶液和66mg/mL 2-甲基咪唑水溶液,在剧烈搅拌状态下,先向50mL硝酸锌溶液中加入5~15mL光甘草定溶液,再加入25-75mL二甲基咪唑溶液,室温下反应30min;离心分离,得到白色沉淀物Gla-ZIF-8,去离子水洗涤2-3次,去除Gla-ZIF-8表面的残留物,将Gla-ZIF-8真空冷冻干燥成粉末,即得到所述Gla-ZIF-8包合物。
8.一种由权利要求4-7所述制备方法得到的Gla-ZIF-8包合物。
9.一种如权利要求8所述的Gla-ZIF-8包合物在化妆品、药品、保健品和食品中的应用。
10.根据权利要求9所述Gla-ZIF-8的应用,其特征在于,所述化妆品为美白化妆品,包括化妆水、乳液、精华、膏霜、面膜及皮肤清洁产品。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202010442828.8A CN111420069A (zh) | 2020-05-22 | 2020-05-22 | 一种Gla-ZIFs包合物及其制备方法和应用 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202010442828.8A CN111420069A (zh) | 2020-05-22 | 2020-05-22 | 一种Gla-ZIFs包合物及其制备方法和应用 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN111420069A true CN111420069A (zh) | 2020-07-17 |
Family
ID=71552920
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202010442828.8A Pending CN111420069A (zh) | 2020-05-22 | 2020-05-22 | 一种Gla-ZIFs包合物及其制备方法和应用 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN111420069A (zh) |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN111437399A (zh) * | 2020-05-27 | 2020-07-24 | 山东大学 | 一种基因与化学小分子共递送系统及在肿瘤治疗中的应用 |
CN113331425A (zh) * | 2021-06-07 | 2021-09-03 | 中国农业大学 | 一种软骨多糖缓释剂及其制备方法与应用 |
CN114177301A (zh) * | 2021-12-21 | 2022-03-15 | 四川大学华西医院 | 一种包含氨甲环酸的组合物及其在制备用于治疗黄褐斑的药物中的用途 |
CN115040505A (zh) * | 2022-06-24 | 2022-09-13 | 河南科技大学 | 一种光甘草定复合物及其制备方法和应用 |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN104307482A (zh) * | 2014-10-14 | 2015-01-28 | 中国科学院宁波材料技术与工程研究所 | 功能化zif类型金属有机骨架多孔材料、其制备方法与应用 |
CN109985247A (zh) * | 2019-04-03 | 2019-07-09 | 河南科技学院 | 一种用于药物释放的杂化金属有机骨架化合物的制备方法 |
-
2020
- 2020-05-22 CN CN202010442828.8A patent/CN111420069A/zh active Pending
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN104307482A (zh) * | 2014-10-14 | 2015-01-28 | 中国科学院宁波材料技术与工程研究所 | 功能化zif类型金属有机骨架多孔材料、其制备方法与应用 |
CN109985247A (zh) * | 2019-04-03 | 2019-07-09 | 河南科技学院 | 一种用于药物释放的杂化金属有机骨架化合物的制备方法 |
Non-Patent Citations (2)
Title |
---|
ZEXUN LIU ET AL.: "Crystal-Seeded Growth of pH-Responsive Metal–Organic Frameworks for Enhancing Encapsulation, Stability, and Bioactivity of Hydrophobicity Compounds", 《ACS BIOMATER.SCI.ENG.》 * |
刘泽勋: "锌基--有机杂化材料负载天然活性小分子药物及其生物活性研究", 《北京化工大学 硕士学位论文》 * |
Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN111437399A (zh) * | 2020-05-27 | 2020-07-24 | 山东大学 | 一种基因与化学小分子共递送系统及在肿瘤治疗中的应用 |
CN111437399B (zh) * | 2020-05-27 | 2021-07-09 | 山东大学 | 一种基因与化学小分子共递送系统及在肿瘤治疗中的应用 |
CN113331425A (zh) * | 2021-06-07 | 2021-09-03 | 中国农业大学 | 一种软骨多糖缓释剂及其制备方法与应用 |
CN113331425B (zh) * | 2021-06-07 | 2022-06-14 | 中国农业大学 | 一种软骨多糖缓释剂及其制备方法与应用 |
CN114177301A (zh) * | 2021-12-21 | 2022-03-15 | 四川大学华西医院 | 一种包含氨甲环酸的组合物及其在制备用于治疗黄褐斑的药物中的用途 |
CN115040505A (zh) * | 2022-06-24 | 2022-09-13 | 河南科技大学 | 一种光甘草定复合物及其制备方法和应用 |
CN115040505B (zh) * | 2022-06-24 | 2024-01-30 | 河南科技大学 | 一种光甘草定复合物及其制备方法和应用 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN111420069A (zh) | 一种Gla-ZIFs包合物及其制备方法和应用 | |
Han et al. | Photothermy-strengthened photocatalytic activity of polydopamine-modified metal-organic frameworks for rapid therapy of bacteria-infected wounds | |
Soomro et al. | Natural drug physcion encapsulated zeolitic imidazolate framework, and their application as antimicrobial agent | |
Al-Zaqri et al. | Biosynthesis of zirconium oxide nanoparticles using Wrightia tinctoria leaf extract: Characterization, photocatalytic degradation and antibacterial activities | |
Chakraborty et al. | Rapid eradication of human breast cancer cells through trackable light-triggered CO delivery by mesoporous silica nanoparticles packed with a designed photoCORM | |
Barick et al. | Nanoscale assembly of mesoporous ZnO: A potential drug carrier | |
KR101846085B1 (ko) | 금속-유기 골격체를 이용한 화장품 성분의 안정화 방법 | |
Zhang et al. | Dual stimuli-responsive smart fibrous membranes for efficient photothermal/photodynamic/chemo-therapy of drug-resistant bacterial infection | |
Saranya et al. | Facile one pot microwave-assisted green synthesis of Fe2O3/Ag nanocomposites by phytoreduction: potential application as sunlight-driven photocatalyst, antibacterial and anticancer agent | |
CN101891783B (zh) | 黄酮-金属络合微球及其制备方法与应用 | |
Liu et al. | Smart “on-off” responsive drug delivery nanosystems for potential imaging diagnosis and targeted tumor therapy | |
Latifi et al. | Drug delivery by micro and meso metal-organic frameworks | |
CN113751079B (zh) | 一种生物材料负载的钙钛矿-二氧化钛纳米复合光催化剂及其构建方法和应用 | |
Khasevani et al. | Green synthesis of ternary carbon dots (CDs)/MIL-88B (Fe)/Bi2S3 nanocomposite via MOF templating as a reusable heterogeneous nanocatalyst and nano-photocatalyst | |
Cao et al. | Chitosan coated biocompatible zeolitic imidazolate framework ZIF-90 for targeted delivery of anticancer drug methotrexate | |
Ayodhya et al. | Green synthesis of CeO2 NPs using Manilkara zapota fruit peel extract for photocatalytic treatment of pollutants, antimicrobial, and antidiabetic activities | |
Zhou et al. | Codelivery of epigallocatechin-3-gallate and diallyl trisulfide by near-infrared light-responsive mesoporous polydopamine nanoparticles for enhanced antitumor efficacy | |
CN114009444A (zh) | 一种新型多功能Janus型介孔二氧化硅纳米药肥的制备及应用 | |
Kumar et al. | Centella asiatica mediated facile green synthesis of nano zinc oxide and its photo-catalytic and biological properties | |
Chen et al. | Polymerization-induced self-assembly of tea polyphenols into open-mouthed nanoparticles for active delivery systems and stable carbon bowls | |
Shi et al. | Drug delivery system and in vitro release of luteolin based on magnetic nanocomposite (Fe3O4@ ZIF‐67) | |
Chung et al. | Preparation of TiO2-loaded nanocapsules and their sun protection behaviors | |
Cai et al. | An investigation of IRMOF-16 as a pH-responsive drug delivery carrier of curcumin | |
Ma et al. | Solid SiO2-sealed mesoporous silica for synergistically combined use of inorganic and organic filters to achieve safe and effective skin protection from all-band UV radiation | |
Guan et al. | Cu-MOFs based photocatalyst triggered antibacterial platform for wound healing: 2D/2D Schottky junction and DFT calculation |
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 | ||
WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20200717 |
|
WD01 | Invention patent application deemed withdrawn after publication |