Gemcitabine prodrug compound, bionic nano medicament carrier and preparation method of carrier

A gemcitabine and biomimetic nanotechnology, applied in the field of polymers, can solve the problems of not greatly improving the chemotherapy effect of pancreatic cancer, not effectively realizing effective drug delivery and intelligent controlled release, etc., to achieve intelligent release, increase uptake, and overcome early leakage Effect

A gemcitabine and biomimetic nanotechnology, applied in the field of polymers, can solve the problems of not greatly improving the chemotherapy effect of pancreatic cancer, not effectively realizing effective drug delivery and intelligent controlled release, etc., to achieve intelligent release, increase uptake, and overcome early leakage Effect

CN109970831AActive Publication Date: 2019-07-05WEST CHINA HOSPITAL SICHUAN UNIV
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  • Gemcitabine prodrug compound, bionic nano medicament carrier and preparation method of carrier
  • Gemcitabine prodrug compound, bionic nano medicament carrier and preparation method of carrier
  • Gemcitabine prodrug compound, bionic nano medicament carrier and preparation method of carrier

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0049] The preparation method of the biomimetic drug carrier, comprising:

[0050] S1. Dissolve 10 g of 2-mercaptoethanol and 0.5 g of potassium iodide in a three-necked flask filled with 30 mL of ethyl acetate, and slowly add 1 mL of hydrogen peroxide while stirring. Stirring was continued at room temperature for 2 hours. After the stirring was completed, a saturated saline solution was added, and the aqueous phase was extracted with ethyl acetate, and finally the solvent was removed by rotary evaporation to obtain 2,2'-dithiodiethanol having the structural formula (I),

[0051]

[0052] The reaction equation for S1 is,

[0053]

[0054] S2. Dissolve 5g of 2,2'-dithiodiethanol (I) and 3.9g of triethylamine prepared in S1 in dichloromethane, place in an ice-water bath, and slowly add 3.5g of propylene dropwise under stirring acid chloride. After the dropwise addition was complete, stirring was continued at room temperature for 24 hours. After the reaction is finished...

Embodiment 2

[0085] S1. Dissolve 10 g of 2-mercaptoethanol and 0.5 g of potassium iodide in a three-necked flask filled with 30 mL of ethyl acetate, and slowly add 1 mL of hydrogen peroxide while stirring. Stirring was continued at room temperature for 2 hours. After the stirring was completed, a saturated saline solution was added, and the aqueous phase was extracted with ethyl acetate, and finally the solvent was removed by rotary evaporation to obtain 2,2'-dithiodiethanol having the structural formula (I),

[0086]

[0087] The reaction equation for S1 is,

[0088]

[0089] S2. Dissolve 5g of 2,2'-dithiodiethanol (I) and 3.9g of triethylamine prepared in S1 in dichloromethane, place in an ice-water bath, and slowly add 3.5g of propylene dropwise under stirring acid chloride. After the dropwise addition was complete, stirring was continued at room temperature for 24 hours. After the reaction is finished, add a saturated aqueous common salt solution, extract therein with dichloro...

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Abstract

The invention discloses a gemcitabine prodrug compound, a bionic nano medicament carrier and a preparation method of the carrier. The method comprises the following steps: allowing PEI to react with aprodrug chain segment with reductive response so as to obtain PEI with positive charges on the surface and partial-reacted amino, allowing the obtained PEI to react with a phosphorylcholine chain segment with an aldehyde group, putting the just-obtained PEI into a dialysis bag with MW of 3500, and performing dialyzing for 2 days to remove organic solvent and unreacted small molecules so as to finally obtain the bionic nano medicament carrier with pH / GSH multi-level response. The preparation method of the nano microcarrier is simple and novel. Compared with drug carriers reported in the priorart, in terms of the multi-level response, the phosphorylcholine hydrophilic chain bonded by the carrier is broken under the tumor sourish environment, the PEI with positive charges is exposed, the endocytosis of cells on prodrug molecules is promoted, a large amount of GSH in the cancer cells further decomposes disulfide bonds in the prodrug after the prodrug molecules enter the cancer cells, therelease of the drug is accurately controlled, and the effective release of the drug and the treatment of the tumor cells are realized.

Description

technical field [0001] The invention relates to the field of macromolecules, in particular to a gemcitabine prodrug compound, a bionic nano drug carrier and a preparation method thereof. Background technique [0002] In recent years, nano drug carriers covalently loaded chemotherapy drugs and are sensitive to biological signals (such as low pH value, high glutathione concentration) of tumor tissues have become an important idea for the development of new smart nano-microcarriers. Nevertheless, the applicant found in the study of pancreatic cancer chemotherapy that the existing drug-loaded micelles are not completely ideal, and the effective delivery and intelligent controlled release of drugs from the tissue level to the cell level have not been effectively realized, so this method has not Greatly improve the chemotherapy effect of pancreatic cancer. Contents of the invention [0003] The purpose of the present invention is to overcome the deficiencies of the prior art, e...

Claims

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Application Information

Patent Timeline
05 Jul 2019
Publication
CN109970831A
IPC
C07H19/073; C07H1/00; C08G73/02; C07H19/10; A61P35/00; A61K31/7068; A61K9/107; A61K47/34
CPC
A61K9/1075; A61K31/7068; A61K47/34; A61P35/00; C07H1/00; C07H19/073; C07H19/10; C08G73/0206
Inventors
熊俊杰; 刘续宝