• 专利标题:   Preparation of doxorubicin-loaded polyethyleneimine-modified graphene quantum dots involves adding doxorubicin powder to graphene quantum dot-polyethyleneimine aqueous solution, mixing uniformly and dialyzing using deionized water.
  • 专利号:   CN108671239-A
  • 发明人:   DENG X, XU J, XIE Z, SHEN N, SUN M
  • 专利权人:   UNIV SHANGHAI
  • 国际专利分类:   A61K047/69, A61K047/58, A61K031/704, A61P035/00
  • 专利详细信息:   CN108671239-A 19 Oct 2018 A61K-047/69 201902 Pages: 17 Chinese
  • 申请详细信息:   CN108671239-A CN10386098 26 Apr 2018
  • 优先权号:   CN10386098

▎ 摘  要

NOVELTY - Preparation of doxorubicin-loaded polyethyleneimine-modified graphene quantum dots involves adding 10 mg dried graphene quantum dot powder to a reactor, adding 1 mL anhydrous N,N-dimethylformamide and 3 mL thionyl chloride, stirring, drying, washing with anhydrous tetrahydrofuran, ultrasonically processing for at least 10 minutes, evaporating to dryness, dispersing the resultant product in 3 mL anhydrous dimethylformamide, ultrasonically processing for at least 10 minutes, adding 100 mg polyethyleneimine and 500 mu L triethylamine, stirring, centrifuging to remove the lower layer precipitate, collecting the upper black solution, dialyzing in water to obtain aqueous solution of graphene quantum dot-polyethyleneimine complex, adding doxorubicin powder, mixing uniformly to obtain quantum dot-polyethyleneimine-doxorubicin product, dialyzing using deionized water for 3-5 days, and replacing dialyzate every 8 hours until the free doxorubicin is completely removed. USE - Preparation of doxorubicin-loaded polyethyleneimine-modified graphene quantum dots. ADVANTAGE - The method enables safe and stable preparation of doxorubicin-loaded polyethyleneimine-modified graphene quantum dots with high drug encapsulation efficiency. DETAILED DESCRIPTION - Preparation of doxorubicin-loaded polyethyleneimine-modified graphene quantum dots involves adding 10 mg dried graphene quantum dot powder to a reactor, adding 1 mL anhydrous N,N-dimethylformamide and 3 mL thionyl chloride, stirring for at least 24 hours in an oil bath of 60 degrees C or more under anhydrous condition, drying the resultant reaction mixture in a vacuum oven, washing with anhydrous tetrahydrofuran, ultrasonically processing for at least 10 minutes, evaporating to dryness using a rotary evaporator, repeating at least twice to remove unreacted thionyl chloride from the product mixture, obtaining purified product, dispersing the purified product in 3 mL anhydrous dimethylformamide, ultrasonically processing for at least 10 minutes, adding 100 mg polyethyleneimine and 500 mu L triethylamine, stirring at 85 degrees C or more in an oil bath for at least 96 hours, obtaining graphene quantum dot-polyethyleneimine product, centrifuging at 10000 rpm or more in a centrifuge for at least 5 minutes to remove the lower layer precipitate, collecting the upper black solution, dialyzing in deionized water with 8000-14000 Da-dialysis bag for 3-5 days to remove unbonded polyethyleneimine to obtain aqueous solution of graphene quantum dot-polyethyleneimine complex, adding 8 mL obtained complex to a reactor, adding 3.5 mg doxorubicin powder, mixing uniformly at 1000 rpm or more under normal temperature and dark condition for at least 24 hours to obtain quantum dot-polyethyleneimine-doxorubicin product, dialyzing in a dialysis bag with molecular weight of 3500 Da using deionized water for 3-5 days, replacing dialyzate every 8 hours until the free doxorubicin is completely removed and obtaining quantum dot-polyethyleneimine-doxorubicin nanocomposite particles. The graphene quantum dot powder is obtained by adding 4 g carbon fibers to a 250 mL-reactor, adding mixture of 95 %mass or more 135 mL concentrated sulfuric acid and 65 %mass or more 45 mL concentrated nitric acid, ultrasonically processing for at least 1 hour under normal-temperature water bath, refluxing in oil bath of 80 degrees C or more, heating for at least 24 hours, cooling the resultant reaction mixture to room temperature, diluting with 800 mL deionized water, centrifuging with a centrifuge at 6000 rpm or more for at least 30 minutes, separating and removing lower layer sediment, collecting upper black liquid, performing vacuum suction filtration using a membrane having pore size of 0.22 mu m or more, removing larger particles, obtaining acid solution of graphene quantum dots, dialyzing in a dialysis bag having a molecular weight of 3500 Da in deionized water to neutral, evaporating the dialyzed residual solution to dryness at 60 degrees C or more using a rotary evaporator, grinding and drying.