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Human serum albumin-medicine compound, synthetic method and applications

A technology of human serum albumin and drug complexes, which is applied in the field of medicine to achieve the effects of low toxicity, improved targeting, and improved therapeutic effects

Inactive Publication Date: 2016-03-16
GUANGXI NORMAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] At present, there are no related reports on the complexes of 5-fluorouracil, G-rich oligonucleotide (AS1411) and copper complexes simultaneously transported using human serum albumin (HSA) as a carrier

Method used

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  • Human serum albumin-medicine compound, synthetic method and applications
  • Human serum albumin-medicine compound, synthetic method and applications
  • Human serum albumin-medicine compound, synthetic method and applications

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0043] Example 1: Synthesis of BpT complex

[0044] a) Dissolve 10mmol of 2-benzoylpyridine in 20ml of ethanol (the concentration of solvent ethanol is 50v / v%), stir for 15min at 60℃ to prepare a solution, drop the above solution into 20ml with 10mmol In a solution of thiosemicarbazide in ethanol (the concentration of solvent ethanol is 50v / v%), the reaction was refluxed and stirred at 60°C for 24 hours to obtain a pale yellow precipitate. The obtained pale yellow precipitate was filtered and washed with absolute ethanol and ether 3 times each After drying, the ligand 2-benzoylpyridine thiosemicarbazone is obtained;

[0045] b) Will contain CuBr 2 (223.35mg, 1mmol) 20ml of methanol (the concentration of solvent methanol is 60v / v%), added dropwise to 20ml of ethanol containing 1mmol of 2-benzoylpyridine thiosemicarbazone ligand (the concentration of solvent ethanol is 50v / v) %) in the solution, reflux and stir at 60°C for 2h, filter the reacted solution into a 50ml beaker and seal ...

Embodiment 2

[0051] Example 2: Synthesis of BpT complex

[0052] a) Dissolve 10mmol of 2-benzoylpyridine in 10ml of methanol (the concentration of solvent methanol is 80v / v%), and stir for 15min at 50℃ to prepare a solution. Drop the above solution into 20ml with 10mmol The thiosemicarbazide in ethanol (the concentration of solvent ethanol is 20v / v%) was refluxed and stirred at 80°C for 18h to obtain a pale yellow precipitate. The obtained pale yellow precipitate was filtered and washed with water 3 times. After drying, the preparation was obtained. Body 2-benzoylpyridine thiosemicarbazone;

[0053] b) Will contain CuBr 2 (223.35mg, 1mmol) 20ml of ethanol (solvent ethanol concentration is 40v / v%) solution, added dropwise to 20ml ethanol containing 1mmol 2-benzoylpyridine thiosemicarbazone ligand (solvent ethanol concentration is 70v / v %) in the solution, reflux and stir at 50°C for 2h, filter the reacted solution into a 50ml beaker and seal it with plastic wrap, pierce 30 holes at 8°C and vola...

Embodiment 3

[0054] Example 3: Synthesis of BpT complex

[0055] a) Dissolve 10mmol of 2-benzoylpyridine in 10ml of methanol (the concentration of solvent methanol is 80v / v%), and stir for 15min at 50℃ to prepare a solution. Drop the above solution into 20ml with 10mmol In a solution of thiosemicarbazide in methanol (solvent methanol concentration is 60v / v%), stir for 48h at 35°C to obtain a pale yellow precipitate. The obtained pale yellow precipitate is filtered and washed with methanol 3 times. After drying, Obtain the ligand 2-benzoylpyridine thiosemicarbazone;

[0056] b) Will contain CuBr 2 (223.35mg, 1mmol) 20ml of ethanol (solvent ethanol concentration is 30v / v%) solution, added dropwise to 20ml ethanol containing 1mmol 2-benzoylpyridine thiosemicarbazone ligand (solvent ethanol concentration is 20v / v %) in the solution, stirred at 40°C for 36h, filtered the reaction solution into a 50ml beaker and sealed with plastic wrap, needled 20 holes at 2°C and volatilized for several days to ob...

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Abstract

The invention discloses a human serum albumin-medicine compound, a synthetic method and applications. The human serum albumin-medicine compound employs human serum albumin as a carrier, two sites of tyrosine 161 and histidine 146 in the IB subdomain of the human serum albumin are combined with 5fluorouracil together, the histidine 242 site in the II A subdomain of the human serum albumin is combined with a copper (II) metal complex, and the cysteine 34 site of the human serum albumin is combined with a G-rich oligonucleotide through a cross-linking agent. The obtained compound is subjected to in vivo antineoplastic activity research, results show that a multi-medicine delivery system based on alhumin raises targeting and treatment effects and has lower toxicity when compared with three individual medicines.

Description

Technical field [0001] The present invention relates to the field of medical technology, in particular to a complex of three drugs and human serum albumin, and a synthesis method, synthesis method and application thereof. Background technique [0002] Cancer is a complex disease involving multiple pathways, and its characteristic is that the continuous mutation of cells in a line makes the disease worse. In addition, due to the genetic mutation of tumor cells caused by chemotherapy, the survival rate of tumor cells is increased. Tumors are also facing the challenge of endogenous and acquired resistance to chemotherapeutics. Obviously, a single drug inhibition method is not enough to achieve the purpose of tumor regression. Therefore, multi-targeted combination therapy is becoming an increasingly important strategy for cancer treatment. Through multiple drugs, different signaling pathways of disease cells can be adjusted to overcome resistance to the greatest extent and improve t...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/48A61K31/7088A61P35/00A61K31/513A61K31/555
Inventor 杨峰张振雷齐金旭苟峄张耀王俊
Owner GUANGXI NORMAL UNIV
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