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Intelligent macromolecular amphoteric lipid material as well as synthesis method and application thereof in complex drug delivery preparation

An intelligent polymer and lipid material technology, applied in the field of intelligent liposomes, can solve the problems of inability to release drugs and function, and improve the effect of treating diseases

Inactive Publication Date: 2020-08-11
XIAN LIBANG PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] Although we have successfully encapsulated various drugs in liposomes and sent them to lesions and diseased cells, most conventional liposomes cannot respond to changes in the microenvironment at the cellular level, and liposomes stay intact in many cases The encapsulated drug cannot be released in the micro-organs of the cell, or the liposome drug is decomposed in the lysosome and then excreted out of the cell and cannot function [Baptista ALF and Coutinho PJG, 2003]

Method used

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  • Intelligent macromolecular amphoteric lipid material as well as synthesis method and application thereof in complex drug delivery preparation
  • Intelligent macromolecular amphoteric lipid material as well as synthesis method and application thereof in complex drug delivery preparation
  • Intelligent macromolecular amphoteric lipid material as well as synthesis method and application thereof in complex drug delivery preparation

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Experimental program
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Effect test

Embodiment 1

[0034] 1.1 Liposome preparation

[0035]Prepare large unilamellar liposomes according to the extrusion method published by Hope et al. Take an appropriate amount of phospholipid mixture (lecithin / cholesterol, 55:45 molar ratio) and isotope-labeled cholesteryl ester [3H]-cholesteryl hexadecyl ether (radioactive (radioactivity is 1.33Ci / 4mol)) was co-dissolved in chloroform / methanol, added nitrogen gas in the test tube to dry to form a uniform mixed phospholipid film, and dried overnight in vacuum. Add HBS buffer (20 mmol / L Hepes, 150 mmol / L NaCl, pH 7.5) or HBS buffer containing calcein (100 mM) into the test tube containing the phospholipid membrane, shake rapidly to hydrate and dissolve the phospholipid membrane. The obtained multilamellar vesicles (MLVs) were quick-frozen in liquid nitrogen and then hydrolyzed in 55°C water for 5 rounds. Lamellar liposomes were repeatedly extruded through a double-layer 100 nm pore membrane (Nucleopore) for 10 times to obtain the required l...

Embodiment 2

[0056] 2.1 Drugs and reagents

[0057] Fluorescently labeled phospholipids N-(7-nitro2,1,3-benzoxadiazol-4-yl) phosphatidy lethanolamine (NBD-PE), rhodamine phosphatidy lethanolamine (Rh-PE ), distearoylphosphatidylcholine (DSPC), dipalmitoyl phosphatidylcholine (DPPC) and dimiristoyl phosphatidylg Lycerol (DMPG) was purchased from (Avanti polar lipids company in the United States), lecithin (EPC, 98% purity) and cholesterol (Chol, 98% purity) were provided by Xi’an Libang Pharmaceutical Co., Ltd., and MH medium was a product of Gibco Company in the United States. Poly(2-ethylacrylic acid) (molecular weight: 20,000) was provided by Fu Jingguo, a researcher at the Institute of Chemistry, Henan Academy of Sciences, and the rest of the reagents were of domestic analytical grade.

[0058] 2.2 Drugs and reagents

[0059] Extruder (Canada Lipex Biomembranes Company), LS-50B Fluorescence Spectrophotometer (U.S. Perkin-Elmer Company), Nicomp 370 Laser Scattering Particle Size Analyze...

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Abstract

The invention provides an intelligent macromolecular amphoteric lipid material as well as a synthesis method and an application thereof in a complex drug delivery preparation, belongs to the technicalfield of intelligent liposomes, and aims to solve the problems that different microenvironment changes, such as vascular permeability increase, local acidity increase and local temperature rise and the like, are generated at disease parts of a human body. The novel material disclosed by the invention can change the characteristics of macromolecular configuration along with the changes of the microenvironment of a human body, and the purpose of rapidly releasing drugs at lesion parts is achieved by utilizing the influence of the deformed macromolecular characteristics on the interference capability of a cell phospholipid bilayer membrane, so that the effects of intelligently administering drugs and improving the treatment diseases are achieved.

Description

technical field [0001] The invention relates to the technical field of intelligent liposomes, in particular to a synthesis method of an intelligent polymer amphoteric lipid material and its application in complex drug delivery preparations. Background technique [0002] A large number of animal and clinical experimental data have demonstrated that liposome-encapsulated anticancer drugs, antibiotics and antifungal compounds can improve drug efficacy. The advantage of liposome preparations is that they can change drug metabolism in vivo and organ distribution of drugs, which can significantly reduce the side effects of drugs [Deng YJ, 2007]. In particular, it should be pointed out that liposomes can be selectively enriched in new tumors, infection and inflammation sites, so drugs can be targeted to the lesion together with liposomes [Chonn and Cullis, 1995]. [0003] Although we have successfully encapsulated various drugs in liposomes and sent them to lesions and diseased ce...

Claims

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Application Information

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IPC IPC(8): A61K9/127A61K47/32A61K47/24A61K47/28
CPCA61K9/1271A61K47/24A61K47/28A61K47/32
Inventor 郑岩
Owner XIAN LIBANG PHARMA
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