• 专利标题:   Nano super-molecule used for preparing camptothecin loaded nano super-molecule for treating cancer, comprises beta-cyclodextrin modified graphene and adamantane modified hyaluronic acid.
  • 专利号:   CN103920160-A, CN103920160-B
  • 发明人:   CAO Y, LIU Y, ZHANG Y
  • 专利权人:   UNIV NANKAI
  • 国际专利分类:   A61K031/4745, A61K047/04, A61K047/36, A61K047/40, A61P035/00, C08B037/08
  • 专利详细信息:   CN103920160-A 16 Jul 2014 A61K-047/40 201467 Chinese
  • 申请详细信息:   CN103920160-A CN10170073 25 Apr 2014
  • 优先权号:   CN10170073

▎ 摘  要

NOVELTY - Nano super-molecule comprises beta-cyclodextrin modified graphene and adamantane modified hyaluronic acid, where thickness of cyclodextrin modified graphene is 2.5 nm, and 1g of graphene is modified with 0.28 g of beta-cyclodextrin and 7.7 part of hyaluronic acid is modified by one part of ethylenediamine adamantine. The nano super-molecule is prepared by combining cyclodextrin modified graphene with adamantane-modified hyaluronic acid, where thickness of nano super-molecule is 4.5 nm, and size is 50-100 nm. USE - Nano super-molecule used for preparing camptothecin loaded nano super-molecule (claimed) for treating cancer. ADVANTAGE - The nano super-molecule is prepared in simple and cost-effective manner, and is easy in transportation. DETAILED DESCRIPTION - INDEPENDENT CLAIMS are included for: a method for preparing nano super-molecule, which involves preparing N-(2-aminoethyl)adamantane-1-carboxamide by dissolving ethylenediamine in 1,4-dioxane solvent, and then adding di-tert-butyl dicarbonate (Boc) dropwise to the obtained solution; keeping the obtained reaction for 24 hours at room temperature; removing solvent form the obtained mixture by distillation under reduced pressure; dissolving the obtained residue in deionized water, and then removing insoluble matter by filtration; washing the obtained filtrate twice, and then extracted with methylene chloride; collecting the obtained organic phase, and then drying the obtained material over anhydrous sodium sulfate; evaporating solvent from the obtained material to obtain oily compound single-Boc protected ethylenediamine; dissolving adamantane-1-carbonyl chloride in methylene chloride, and then adding triethylamine dropwise to the obtained solution; adding single-Boc protected ethylenediamine to the obtained solution, and then keeping the reaction mixture overnight at room temperature; washing the obtained reaction mixture wit hydrochloric acid and sodium chloride solution thrice; coolecting the obtained organic phase, and then drying over anhydrous sodium sulfate; drying the obtained material under reduced pressure; separating and purifying the obtained material by eluting through 200-300 mesh silica gel column by using methylene chloride-ethyl acetate mixtures (3:2) as eluent; dissolving the purified compound in dichloromethane, and then adding trifluoroacetic acid dropwise to the obtained mixture; keeping the obtained mixture overnight at room temperature with stirring; evaporating the obtained reaction mixture under reduced pressure; adding sodium hydroxide solution (5 mole^/L; 20 ml) to the obtained material with stirring for 1 hour; removing water by distillation under reduced pressure, and then extracting the obtained material with chloroform; washing the obtained solution with sodium chloride solution, and then collecting organic phase; removing solvent from the obtained material under reduced pressure, and then drying the obtained material over sodium sulfate; drying the obtained material under vacuum to obtain white solid product of N-(2-aminoethyl)adamantane-1-carboxamide; preparing adamantane-modified hyaluronic acid (HA-Ada) by dissolving sodium hyaluronate in deionised water, and then passing the obtained material through cation exchange resin column to obtain hyaluronic acid; dissolving the obtained hyaluronic acid in dimethyl sulfoxide (DMSO) by heating; cooling the obtained solution at room temperature, and then adding triethylamine to the obtained solution with stirring for 10 minutes at room temperature; adding ethyl chloroformate to the obtained solution with stirring at room temperature for 1 hour; adding N-(2-aminoethyl)adamantane-1-carboxamide to the obtained solution with stirring at room temperature for 24 hours; diluting the obtained reaction mixture with deionized water; dalysing the obtained mixture 8-14 kdalton molecular weight cut-off's dialysis bag with sodium chloride solution (0.1 mole^/L) for 24 hours, and then dialyzing with deionized water for 7 days; lyophilizing the obtained dialysate to obtain HA-Ada; preparing nano super-molecule by adding HA-Ada to cyclodextrin-modified graphene in aqueous medium; sonicating the obtained mixture ultrasonically for half an hour at room temperature; diluting the obtained solution with deionized water; filtering the obtained material by using 0.45 m filtration membrane; collecting the obtained filtrate to obtain the finished product; and a method of preparing targeted hydrophobic anticancer medicine, which involves loading the obtained nano super-molecule with camptothecin by dissolving the camptothecin in DMSO solution, and then adding dropwise to the aqueous solution of nano super-molecule at room temperature; stirring the obtained mixture overnight; centrifuging the obtained mixture for 5 minutes to remove insoluble camptothecin; filtering the obtained material with 0.45 microns water film filter to remove the insoluble solid; dialyzing the obtained filtrate with 8-14 kdalton molecular weight cut-off's dialysis bag with microns water for 24 hours; filtering the obtained material by using 0.45 m filtration membrane; collecting the obtained filtrate to obtain the camptothecin loaded nano super-molecule.