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Preparation and application of hybrid nano-formulation based on tumor extensive metabolism regulation

A nano-formulation and metabolic regulation technology, applied in the field of medicine, can solve the problems of limited use and high risk of toxic and side effects

Active Publication Date: 2020-05-12
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the use of such cationic non-viral vectors is also limited due to the high risk of toxic side effects due to their positive surface charges

Method used

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  • Preparation and application of hybrid nano-formulation based on tumor extensive metabolism regulation
  • Preparation and application of hybrid nano-formulation based on tumor extensive metabolism regulation
  • Preparation and application of hybrid nano-formulation based on tumor extensive metabolism regulation

Examples

Experimental program
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Effect test

Embodiment 1

[0055] Example 1: Preparation of low molecular weight heparin-gemcitabine-cholesterol conjugate / PEI (10kDa) / miR-206 (metabolism regulation gene) and PSS / PEI (10kDa) / miR-206 mixed nano-preparation

[0056] Take the low molecular weight heparin-gemcitabine-cholesterol conjugate, PEI (10kDa) and miR-206 according to the mass ratio of 20:5:1, and dissolve the low molecular weight heparin-gemcitabine-cholesterol conjugate and PEI (10kDa) in ultra- pure water. The PEI aqueous solution and miR-206 were mixed and stirred for 30 seconds, then allowed to stand for 30 minutes, and then injected into an aqueous solution of low molecular weight heparin-gemcitabine-cholesterol conjugate under stirring conditions, stirred for 30 seconds and then left to stand for 30 minutes to obtain a ternary composite nano drug. Take PSS, PEI (10kDa) and miR-206 according to the mass ratio of 5:3:1, and dissolve PSS and PEI (10kDa) in ultrapure water respectively. The PEI aqueous solution and miR206 were ...

Embodiment 2

[0057] Example 2: Preparation of low molecular weight heparin-gemcitabine-cholesterol conjugate / chitosan / miR-206 and PSS / chitosan / miR-206 mixed nano-preparation

[0058] Take the low molecular weight heparin-gemcitabine-cholesterol conjugate, chitosan and miR-206 according to the mass ratio of 100:5:1, and dissolve the low molecular weight heparin-gemcitabine-cholesterol conjugate and chitosan in sodium chloride respectively Injection. Mix the chitosan solution and miR-206 for 10 seconds and let it stand for 40 minutes, then inject the low molecular weight heparin-gemcitabine-cholesterol conjugate solution under stirring conditions, stir for 30 seconds and let it stand for 30 minutes to obtain a ternary composite nano drug . Take PSS, chitosan and miR-206 according to the mass ratio of 10:5:1, and dissolve PSS and chitosan in sodium chloride injection respectively. The chitosan solution and miR206 were mixed and stirred for 10 seconds, then left to stand for 40 minutes, and ...

Embodiment 3

[0059] Embodiment 3: Preparation of low molecular weight heparin-gemcitabine-cholesterol conjugate / chitosan / miR-9 (metabolism regulation gene) and PSS / chitosan / miR-9 mixed nano drug system

[0060] Take the low molecular weight heparin-gemcitabine-cholesterol conjugate, chitosan and miR-9 according to the mass ratio of 100:8:1, and dissolve the low molecular weight heparin-gemcitabine-cholesterol conjugate and chitosan in ultrapure water respectively . Chitosan aqueous solution and miR-9 were mixed and stirred for 30 seconds, then allowed to stand for 60 minutes, then injected with low molecular weight heparin-gemcitabine-cholesterol conjugate aqueous solution under stirring conditions, stirred for 30 seconds and then left to stand for 60 minutes to obtain a ternary composite nano drug . Take PSS, chitosan and miR-9 according to the mass ratio of 20:6:1, and dissolve PSS and chitosan in ultrapure water respectively. Chitosan aqueous solution and miR-9 were mixed and stirred ...

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Abstract

The invention discloses a hybrid nano-formulation for promoting normalization of tumor blood vessels based on tumor extensive metabolism regulation and application thereof. A nano self-assembly technology based on electrostatic interaction and hydrogen bonding is used to obtain the hybrid nano-formulation. Heparin polysaccharide macromolecules that having VEGF inhibitory activity and derivatives and active biological macromolecules thereof, or active substance targeting vascular endothelial cells are assembled with non-viral gene carriers and metabolic regulation related gene drugs to construct stable nano-drugs targeting tumor cells and tumor vascular endothelial cells, separately. After the hybrid nano-formulation formed only by physically mixing the two ternary assembled nano-drugs areadministered in the manner of beat, significant metabolic regulation effects of tumor cells and tumor vascular endothelial cells, promoting normalization of tumor blood vessels, and the multiple therapeutic effects of tumor proliferation inhibition can be obtained. The three effects are synergistic and complement each other to enhance the effectiveness.

Description

technical field [0001] The invention relates to the technical field of medicine, in particular to the preparation and application of a mixed nano-preparation based on tumor pan-metabolism regulation. Background technique [0002] Cancer is one of the major diseases leading to human death today, in which tumor blood vessels play a key role in the development and metastasis of tumors. However, the most commonly used anti-tumor treatment methods such as chemotherapy and radiotherapy have weak regulation on tumor blood vessels, which brings huge difficulties to clinical anti-tumor treatment. An imbalance of pro-angiogenic and anti-angiogenic signals in the tumor microenvironment can lead to structural and functional abnormalities in solid tumor vasculature (Zhigang Liu, Yifan Wang, Yuhui Huang, Betty Y.S. Kim, Hong Shan, Depei Wu, Wen Jiang, TumorVasculatures: A New Target for Cancer Immunotherapy, Trends in Pharmacological Sciences, Volume 40, Issue 9, 2019, Pages613-623.), th...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K48/00A61K47/69A61K47/61A61K45/00A61K31/727B82Y5/00B82Y30/00B82Y40/00
CPCA61K48/0041A61K48/005A61K47/61A61K47/6931A61K45/00A61P35/00B82Y5/00B82Y30/00B82Y40/00A61K31/727A61K2300/00
Inventor 熊慧姚静刘小妍
Owner CHINA PHARM UNIV
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