• 专利标题:   Preparing target-photothermal-photodynamic hypericin-folate-fluorinated graphene polymer nanocomposite comprises e.g. mixing graphene oxide dispersion, hydrofluoric acid, ultrasonically treating, and transferring into autoclacve.
  • 专利号:   CN109045298-A
  • 发明人:   WANG B, YAO S, HU J, CHEN B, WAN J, HU Z
  • 专利权人:   UNIV ZHEJIANG SCI TECH
  • 国际专利分类:   A61K041/00, A61K047/52, A61K047/54, A61P035/00
  • 专利详细信息:   CN109045298-A 21 Dec 2018 A61K-041/00 201923 Pages: 8 Chinese
  • 申请详细信息:   CN109045298-A CN11000805 30 Aug 2018
  • 优先权号:   CN11000805

▎ 摘  要

NOVELTY - Preparing target-photothermal-photodynamic hypericin-folate-fluorinated graphene polymer nanocomposite comprises e.g. (ii) mixing 1-3 mg/ml graphene oxide dispersion, and 35-45 wt.% hydrofluoric acid, ultrasonically treating to obtain a mixed solution, (ii) transferring the mixture obtained in the step (i) to a polytetrafluoroethylene-lined autoclave, maintaining at 180-200 degrees C for 30-40 hours, and naturally cooling the autoclave to room temperature, (iii) using microporous membrane filtration for step (ii) to obtain the product, repeatedly washing, centrifuging, filtering to make the solution finally neutral, and freeze-drying to obtain fluorinated graphene, (iv) taking fluorinated graphene, adding deionized water, ultrasonically vibrating for 1-2 hours under ice bath conditions, peeling off fluorinated graphite sheet to obtain a brownish yellow dispersion, and removing precipitate by centrifugation to obtain aqueous solution of fluorinated graphene, and (v) dialyzing in dialysis bag. USE - The target-photothermal-photodynamic hypericin-folate-fluorinated graphene polymer nanocomposite is useful for cancer cell therapy. ADVANTAGE - The method: realizes the synergistic effect of targeted therapy, tumor hyperthermia, and chemotherapy; increases the stability; and does not have a significant effect on cells during the later experiments. DETAILED DESCRIPTION - Preparing target-photothermal-photodynamic hypericin-folate-fluorinated graphene polymer nanocomposite comprises (ii) mixing 40-60 ml of 1-3 mg/ml graphene oxide dispersion, and 0.5-0.75 ml of 35-45 wt.% hydrofluoric acid, ultrasonically treating for 1-2 minutes to obtain a mixed solution, (ii) transferring the mixture obtained in the step (i) to a polytetrafluoroethylene-lined autoclave, maintaining at 180-200 degrees C for 30-40 hours, and naturally cooling the autoclave to room temperature, (iii) using microporous membrane filtration for step (ii) to obtain the product, repeatedly washing, centrifuging, filtering to make the solution finally neutral, and then freeze-drying to obtain fluorinated graphene, (iv) taking fluorinated graphene, adding deionized water, ultrasonically vibrating for 1-2 hours under ice bath conditions, peeling off fluorinated graphite sheet to obtain a brownish yellow dispersion, and removing the precipitate by centrifugation to obtain an aqueous solution of fluorinated graphene, (v) dialyzing the fluorinated aqueous graphene solution in dialysis bag having a molecular weight of 8000-14000 for 2 to 3 days to obtain a purified fluorinated graphene dispersion, freeze-drying to obtain purified fluorinated graphene, (vi) taking 100-150 mg fluorinated graphene, dispersing it in 80-120 ml deionized water, ultrasonically dispersing uniformly, then adding 5-7 g sodium hydroxide, 5-7 g sodium hypochlorite, and ultrasonically bathing for 2-3 hours for converting the hydroxy groups on the graphene fluoride sheet into carboxy groups, reacting completely, neutralizing with dilute hydrochloric acid, repeatedly washing, centrifuging, collecting the upper black solution, and dialyzing for 40-50 hours with deionized water for removing the unreacted water-soluble substance, (vii) adding 0.5-0.8 g folic acid to the solution obtained in the step (vi), ultrasonically dispersing uniformly, them adding 125-127 mg 1-ethyl-(3-dimethylaminopropyl) carbodiimide, and 182.5-184.5 mg nitrogen-hydroxy succinimide, stirring, ultrasonically processing for 2-3 hours, then dialyzing with sodium bicarbonate solution of pH 7-9, changing water every 3-5 hours, and dialyzing for 40-50 hours to obtain a black solution, (viii) removing the water in the black solution by rotary evaporation, repeatedly washing with acetone, and then drying under vacuum at 40-50 degrees C to obtain folic acid-modified fluorinated graphene, (ix) taking 64.8-66.8 mg folic acid-modified fluorinated graphene, dispersing it in 40-60 ml deionization, then adding 6.05-6.25 mg hypericin, 2.76-2.96 mg 1-ethyl-(3- dimethylaminopropyl) carbodiimide hydrochloride, and 0.30-0.32 mg 4-dimethylaminopyridine, and stirring, and reacting overnight, and (x) filtering the solution obtained in the step (ix) through an ultrafiltration filter, and then freeze-drying to obtain a finished product.