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Nanometer cluster medicine carrying thermosensitive liposome preparation and making method and application thereof

A heat-sensitive liposome and liposome preparation technology, which is applied in the direction of liposome delivery, radioactive carrier, and preparations for in vivo experiments, can solve the problems of low soft tissue contrast, long imaging time, and high price, and achieve Enhanced effect, enhanced penetration, small metal accumulation toxicity effect

Pending Publication Date: 2020-02-07
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

But its biggest disadvantage is the low soft tissue contrast
MRI is also a non-invasive imaging method widely used in clinical practice. It has high soft tissue contrast and a large penetration depth, but it is expensive and takes a long time to image.

Method used

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  • Nanometer cluster medicine carrying thermosensitive liposome preparation and making method and application thereof
  • Nanometer cluster medicine carrying thermosensitive liposome preparation and making method and application thereof
  • Nanometer cluster medicine carrying thermosensitive liposome preparation and making method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0045] Example 1: Preparation and characterization of blank thermosensitive liposome TSL and gold nanocluster thermosensitive liposome GTSL

[0046]

[0047] Accurately weigh DPPC according to the prescription quantity: DSPE-PEG2000: MPPC=79.5:14:6.5 in a 500mL eggplant-shaped bottle, add 5mL chloroform, shake to dissolve the phospholipids; 35°C rotary evaporation, remove the organic solvent to form a film, continue after film formation Vacuum for 2 hours to completely remove the organic solvent. Then hydrate with physiological saline at 55°C to obtain thick heat-sensitive liposomes, and then ultrasonicate with a probe for 5 minutes, power 30%, and ultrasonication for 1 second at intervals of 2 seconds until the liposomes are transparent and clear, and then the above-mentioned ultrasonicated The liposomes were passed through a 0.22um organic filter about 5 times to obtain blank thermosensitive liposomes.

[0048] The gold coating on the liposome surface was synthesized by ...

Embodiment 2

[0052] Embodiment 2: Characterization of phase transition temperature of thermosensitive liposome TSL and gold nanocluster thermosensitive liposome GTSL

[0053] Take thermosensitive liposomes and gold nanocluster thermosensitive liposomes respectively in a thermal analysis crucible, and analyze and measure them with a differential scanner. The temperature scanning range is 25°C-100°C, and the temperature rise rate is 10°C / min, analyze its phase transition temperature. The result is as Figure 4 shown.

Embodiment 3

[0054] Example 3: Magnetic Fe 3 o 4 Nanoparticles and Magnetic Nanocluster Thermosensitive Liposome Fe 3 o 4 - Preparation and characterization of TSL

[0055] Weigh FeCl 3 ·6H 2 O 21.6165g, FeCl 2 4H 2 O 8.7490g was dissolved in 50ml of deionized water, and 5.5ml of oleic acid was weighed in it, mixed evenly with an electric stirrer, and the mixed solution was heated to 80°C, when the mixed system was fully mixed, the concentration of 25 % ammonia solution 50mL, after reacting for 15min, heat the whole system to 100°C, and keep stirring for 1.5h, then take out the mixed solution, wash with deionized water for 3 times, and wash with absolute ethanol for 2 times to obtain Fe 3 o 4 nanoparticles.

[0056]The phospholipid DPPC:DSPE-PEG2000:MPPC=79.5:14:6.5 (by weight ratio) was dispersed in chloroform and dried under vacuum using a rotary evaporator onto a round bottom flask. Then add pH 4.0 ammonium sulfate (250mM) solution to hydrate the film to obtain thick heat-sens...

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Abstract

The invention discloses a nanometer cluster medicine carrying thermosensitive liposome preparation and a making method and application thereof. The preparation is obtained after impurity removal of nanometer cluster medicine carrying thermosensitive liposome, wherein the nanometer cluster medicine carrying thermosensitive liposome contains a thermosensitive phosphatide component DPPC, a phosphatide component MPPC capable of promoting release, a phosphatide component DSPE-PEG2000 capable of promoting long circulation of the preparation, and a tumor treating medicine; and the liposome is prepared by a film dispersion method, the surface of the liposome is wrapped with a layer of gold nanometer clusters, or the inner part of the liposome is encapsulated with magnetic Fe3O4 nanoparticles. Thepreparation can be used as an antitumor carrier, is connected with an antibody, and is specifically targeted to tumors, through NIR illumination, the medicine is efficiently released at the positionsof the tumors, and through combination with the sensitization effect of thermotherapy and radiotherapy, the treatment effects are improved. The preparation can also be combined with the advantages ofgold and ferrum in the imaging respect of electronic computer tomoscan imaging (CT) / magnetic resonance imaging (MRI) and the like, and can perform medical diagnosis, so that the purpose of achieving multimode pinpoint diagnosis and treatment of the tumor can be realized.

Description

technical field [0001] The invention relates to a liposome preparation and its preparation method and application, in particular to a nano-cluster drug-loaded thermosensitive liposome preparation, its preparation method and application. Background technique [0002] The plasma membrane of thermosensitive liposomes (thermosensitive liposomes) is in a dense colloidal state at normal room temperature, and the drug wrapped in it is difficult to diffuse out, which acts as a drug reservoir; when pre-heated, the temperature reaches the liposome At the phase transition temperature, the liposome membrane changes from a colloidal crystal state to a liquid crystal state, and the permeability of the membrane increases, and the drug embedded in it rapidly diffuses into the target organ, forming a higher drug concentration at the target site, resulting in Thermal targeting. DPPC is the best choice for preparing thermosensitive liposomes because its phase transition temperature is about 4...

Claims

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Application Information

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IPC IPC(8): A61K41/00A61K47/24A61K9/127A61K51/06A61K51/12A61K49/04A61K49/18A61K49/12A61K49/22A61P35/00A61P15/14A61K31/58A61K31/704A61K33/26A61K39/395
CPCA61K9/127A61K9/1277A61K31/58A61K31/704A61K33/26A61K41/0052A61K47/24A61K49/0466A61K49/12A61K49/126A61K49/1812A61K49/227A61K51/06A61K51/1241A61K2039/505A61P15/14A61P35/00C07K16/32
Inventor 沈雁夏云杨文倩叶子璇涂家生何东升
Owner CHINA PHARM UNIV
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