Nano copper sulfide based active-targeting thermo-sensitive liposome preparation method and application

A heat-sensitive liposome and active targeting technology, applied in the field of medicine, can solve the problems of large side effects and poor treatment effect, and achieve the effect of small side effects, stable and reliable method, and inhibition of proliferation

Inactive Publication Date: 2018-12-25
HENAN UNIV OF CHINESE MEDICINE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0007] In view of the above situation, in order to overcome the defects of the prior art, the purpose of the present invention is to provide a preparation method and application of activ

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  • Nano copper sulfide based active-targeting thermo-sensitive liposome preparation method and application

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Embodiment 1

[0016] Example 1: The preparation method of active targeting thermosensitive liposome based on nano-copper sulfide of the present invention includes the following steps: (1) Synthesis of stearyl carbenoxolate: 0.235 g of glycyrrhetinic acid in 250 ml In a pear-shaped bottle, add 10ml of N,N-dimethylformamide, then add 0.135g of stearyl alcohol and 0.025g of 4-dimethylaminopyridine into the N,N-dimethylformamide solution and mix well. The reaction was heated in a water bath at ℃ for 1h, and the N,N-dimethylformamide was removed by rotary evaporation. The residue was dissolved in 18ml of water, transferred to a separatory funnel, and 30ml of ethyl acetate was added for extraction; the ethyl acetate extract was collected (layer ), the ethyl acetate was removed by rotary evaporation at 40°C, the residue was washed with 8ml of water, and the washing liquid was freeze-dried to obtain the light yellow powder intermediate product 18-GA; 0.025g 18-GA, 0.14g succinic anhydride and Place ...

Embodiment 2

[0018] Example 2: The preparation method of an active targeting thermosensitive liposome based on nano-copper sulfide of the present invention includes the following steps: (1) Synthesis of stearyl carbenoxolate: 0.588 g of glycyrrhetinic acid in 250 ml In a pear-shaped bottle, add 15ml of N,N-dimethylformamide, then add 0.338g of stearyl alcohol and 0.063g of 4-dimethylaminopyridine into the N,N-dimethylformamide solution and mix well. The reaction was heated in a water bath at ℃ for 1h, and the N,N-dimethylformamide was removed by rotary evaporation. The residue was dissolved in 20ml of water, transferred to a separatory funnel, and 35ml of ethyl acetate was added for extraction; the ethyl acetate extract was collected (layer ), the ethyl acetate was removed by rotary evaporation at 40°C, the residue was washed with 10ml of water, and the washing liquid was freeze-dried to obtain the light yellow powder intermediate product 18-GA; 0.063g 18-GA, 0.34g succinic anhydride and Pl...

Embodiment 3

[0020] Example 3: A preparation method of active targeting thermosensitive liposomes based on nano-copper sulfide of the present invention includes the following steps: (1) Synthesis of stearyl carbenoxolate: 0.47 g of glycyrrhetinic acid in 250 ml In a pear-shaped bottle, add 20ml of N,N-dimethylformamide, then add 0.27g of stearyl alcohol and 0.05g of 4-dimethylaminopyridine to the N,N-dimethylformamide solution and mix well. The reaction was heated in a water bath at ℃ for 1h, and the N,N-dimethylformamide was removed by rotary evaporation. The residue was dissolved in 20ml of water, transferred to a separatory funnel, and 37ml of ethyl acetate was added for extraction; the ethyl acetate extract was collected (layer ), the ethyl acetate was removed by rotary evaporation at 40°C, the residue was washed with 10ml of water, and the washing liquid was freeze-dried to obtain the light yellow powder intermediate product 18-GA; 0.05g 18-GA, 0.28g succinic anhydride and Put 0.02g of...

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Abstract

The invention relates to a nano copper sulfide based active-targeting thermo-sensitive liposome preparation method and application. The liposome is prepared from tumor targeting molecules, copper sulfide nano particles and a chemotherapeutic medicine, wherein the tumor targeting molecules refer to GA (glycyrrhetinic acid), the copper sulfide nano particles are hydrophilic copper sulfide nano particles obtained after povidone modification, and the chemotherapeutic medicine refers to docetaxel. The preparation method includes steps: synthesizing carbenoxolone octadecyl ester; preparing active-targeting thermo-sensitive liposome. The nano copper sulfide based active-targeting thermo-sensitive liposome prepared according to the method is applied to preparation of tumor targeted medicines. By adoption of the tumor targeting molecules as targeting heads, integration of tumor hyperthermia chemotherapy and targeted therapy is realized according to copper sulfide photothermal conversion characteristics. The method is stable, reliable, convenient to use, effective and easy in operation, and rich raw material sources, low cost, low side effects, effectiveness in inhibition of tumor cell proliferation and innovation on medicines for tumor targeted therapy are realized.

Description

Technical field [0001] The invention relates to medicine, in particular to a preparation method and application of an active targeting thermosensitive liposome based on nano copper sulfide. Background technique [0002] In today’s society, the incidence of tumors is increasing year by year, and effective treatment of tumors has become a more frequent topic of discussion in the current pharmaceutical industry. Because the pathophysiological characteristics of tumor tissues are significantly different from normal tissues, they are mainly tumors. The vascular permeability of the site is strong, so macromolecular drugs and carriers can enter the tumor tissue through high permeability and retention effect (EPR effect), and accumulate in the tumor site for a long time and at high concentration. [0003] Heat-sensitive liposomes are made of temperature-sensitive materials whose phase transition temperature is slightly higher than that of normal tissues. When liposomes circulate through th...

Claims

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Application Information

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IPC IPC(8): A61K9/127A61K47/54A61K47/32A61K31/337A61K41/00A61P35/00
CPCA61K9/1277A61K31/337A61K41/0052A61K47/32A61K47/554A61P35/00A61K2300/00
Inventor 祝侠丽李玲华王莎莎贾永艳巴妍妍刘黎明
Owner HENAN UNIV OF CHINESE MEDICINE
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