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Mdivi-1 nano long-circulating liposome as well as preparation method and application thereof

A long-circulation liposome and long-circulation technology, which is applied in liposome delivery, pharmaceutical formulations, medical preparations of non-active ingredients, etc., can solve problems such as insoluble in water, short half-life, and large toxic and side effects, and achieve Improve liver cell damage, good anti-hepatic fibrosis, less side effects

Active Publication Date: 2022-06-24
WEST CHINA HOSPITAL SICHUAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, Mdivi-1 is poorly soluble in water, has low bioavailability, short half-life, and severe side effects, which limit its clinical application.

Method used

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  • Mdivi-1 nano long-circulating liposome as well as preparation method and application thereof
  • Mdivi-1 nano long-circulating liposome as well as preparation method and application thereof
  • Mdivi-1 nano long-circulating liposome as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036] Liposomes were prepared using a thin-film hydration method using the method in reference [1]. Lecithin, cholesterol, DSPE-mPEG2000 and Mdivi-1 were dissolved in chloroform methanol solution (chloroform:methanol = 4:1 V / V) so that the concentration of lecithin was 7.5 mM, the concentration of cholesterol was 2 mM, and the concentration of DSPE-mPEG2000 was 0.5 mM , the concentration of Mdivi-1 was 0.125mM, and the film was formed by rotary evaporation under reduced pressure at 37°C in an eggplant-shaped flask; adding normal saline, hydrating at 37°C for 2 hours, and ultrasonicating on ice using a sonicator. Unencapsulated drug was then removed by centrifugation at 18000g for 3 minutes. Then filter with a 0.22 μm pore size filter to obtain Mdivi-1 nanometer long circulating liposomes.

Embodiment 2

[0038] The preparation method and raw materials are the same as those in Example 1, except that the concentration of Mdivi-1 in the chloroform methanol solution is 0.25 mM.

Embodiment 3

[0040] The preparation method and raw materials are the same as those in Example 1, except that the concentration of Mdivi-1 in the chloroform methanol solution is 0.5 mM.

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Abstract

The invention discloses a nano long-circulating liposome, the liposome is formed by entrapment of a pharmaceutical active ingredient by a lipid membrane material, the pharmaceutical active ingredient is Mdivi-1, and the molar mass ratio of the Mdivi-1 to the lipid membrane material is 1: (80-20). The lipid membrane material comprises phospholipid, cholesterol and a long circulating material, and the long circulating material is preferably DSPE-mPEG2000. The Mdivi-1 nano long-circulating liposome provided by the invention is small in hepatotoxicity and few in side effects, has an obvious effect of improving hepatocyte injury compared with a free drug, and also has a better anti-hepatic fibrosis effect.

Description

technical field [0001] The invention belongs to the field of pharmaceutical preparations, and in particular relates to an Mdivi-1 nanometer long-circulating liposome and a preparation method and application thereof. Background technique [0002] Mdivi-1 is a selective cell-permeable inhibitor of mitochondrial fission dynamin-associated GTPases (Drp1) and mitochondrial fission Dynamin I (Dnm1). In vitro experiments confirmed that inhibition of mitochondrial outer membrane permeabilization after treatment of cells with Mdivi-1 resulted in decreased cytochrome c release and inhibited apoptosis. In the study of the circulatory system, Mdivi-1 can improve the prognosis of stroke and protect cells against ischemia-reperfusion injury, suggesting that it has a protective effect on cells, and Mdivi-1 can be used to resist stroke and protect nerves. [0003] In addition, some studies reported that Mdivi-1 is a small molecule compound with anti-hepatic fibrosis activity. However, Mdi...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/127A61K31/517A61P1/16
CPCA61K9/1271A61K31/517A61K47/28A61P1/16Y02A50/30
Inventor 周彦妮万琳冯莉
Owner WEST CHINA HOSPITAL SICHUAN UNIV
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