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Bilobalide B nano lipidosome and preparation method thereof

A nano-liposome and ginkgolide technology, which is applied in the directions of liposome delivery, pharmaceutical formulations, and non-active ingredients medical preparations, can solve the problems of short half-life, poor water solubility, and large toxic and side effects, and achieve uniform quality. , the effect of small particle size and convenient preparation process

Inactive Publication Date: 2019-03-12
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] Purpose of the invention: Aiming at technical problems such as poor water solubility, short half-life and large toxic and side effects in the existing dosage forms of ginkgolide B, this application provides a ginkgolide B nanoliposome preparation with active brain targeting function

Method used

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  • Bilobalide B nano lipidosome and preparation method thereof
  • Bilobalide B nano lipidosome and preparation method thereof
  • Bilobalide B nano lipidosome and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0040] Dissolve 10mg of ginkgolide B, 180mg of egg yolk lecithin, 50mg of cholesterol, 5mg of vitamin E, 65mg of cultured phosphatidylethanolamine, and 35mg of phospholipid polyethylene glycol maleimide in 20mL of absolute ethanol, and ultrasonicate for 10 minutes to form a uniform lipid The lipid solution was transferred to a 250mL round bottom flask, and the above lipid solution was distilled under reduced pressure at 35°C until no ethanol remained, and a uniform lipid film was formed on the inner wall of the round bottom flask. The prepared lipid film was hydrated with 5 mL of phosphate buffered saline (PH=6.0) at 30° C. for 1 hour, and stirred and dispersed evenly under nitrogen protection. The liposome solution was extruded multiple times with a liposome extruder, and passed through polycarbonate membranes with pore sizes of 0.8 μm, 0.4 μm, 0.2 μm, and 0.1 μm in sequence. Under the protection of nitrogen, add disodium hydrogen phosphate solution to increase the pH to 7.2,...

Embodiment 2

[0042] Dissolve 30mg ginkgolide B, 520mg dipalmitoyl lecithin, 140mg cholesterol, 16mg vitamin E, 195mg cultured phosphatidylethanolamine, 100mg phospholipid polyethylene glycol maleimide in 30mL chloroform:methanol=2:1 Mix the solution, ultrasonicate for 20 minutes to form a uniform lipid solution, transfer it to a 500mL round-bottomed flask, and under the protection of nitrogen, distill the above-mentioned lipid solution at 30°C under reduced pressure until no solvent remains, and a uniform lipid solution is formed on the inner wall of the round-bottomed flask. lipid membrane. The prepared lipid film was hydrated with 15 mL of phosphate buffered saline (PH=6.5) at 45° C. for 1 hour, and stirred and dispersed evenly under nitrogen protection. The liposome solution was extruded multiple times with a liposome extruder, and passed through polycarbonate membranes with pore sizes of 0.8 μm, 0.4 μm, 0.2 μm, and 0.1 μm in sequence. Under the protection of nitrogen, add disodium hyd...

Embodiment 3

[0044] Dissolve 50mg of ginkgolide B, 1000mg of soybean lecithin, 230mg of cholesterol, 25mg of vitamin E, 330mg of cultured phosphatidylethanolamine, 170mg of phospholipid polyethylene glycol maleimide in 50mL of dichloromethane, and ultrasonically form a uniform lipid solution , transferred to a 1000mL round bottom flask, and under the protection of nitrogen, the above lipid solution was distilled under reduced pressure at 30°C until no dichloromethane remained, and a uniform lipid film was formed on the inner wall of the round bottom flask. The prepared lipid film was hydrated with 25 mL of phosphate buffered saline (PH=6.8) at 30° C. for 1 hour, and stirred and dispersed evenly under nitrogen protection. The liposome solution was extruded multiple times with a liposome extruder, and passed through polycarbonate membranes with pore sizes of 0.8 μm, 0.4 μm, 0.2 μm, and 0.1 μm in sequence. Under the protection of nitrogen, add disodium hydrogen phosphate solution to increase ...

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Abstract

The invention discloses bilobalide B nano lipidosome. The bilobalide B nano lipidosome comprises bilobalide B, lecithin, cholesterol, vitamin E, phosphatidylethanolamine Pegol, DSPE-PEG-MAL and polypeptide (Cys)-An2. The invention also discloses a preparation method of the lipidosome. Compared with the prior art, (Cys)-An2 with a function being specifically combined with low density lipoprotein receptors on a brain capillary vessel wall is chemically coupled with DSPE-PEG-MAL to prepare a brain target material, and the bilobalide B is coated by using lipidosome prepared from the coupler to establish a novel medicine dose form with long cycling and brain initiative target functions, so that the dispersity of the bilobalide B in water can be significantly improved, and the bioavailability and druggability can be greatly improved.

Description

technical field [0001] The invention relates to a pharmaceutical preparation, in particular to a ginkgolide B nano-liposome with brain active targeting function and a preparation method thereof. Background technique [0002] Cardiovascular and cerebrovascular diseases are a common disease that seriously threatens the health of human beings, especially middle-aged and elderly people over 50 years old. Even if the most advanced and perfect treatment methods are applied, more than 50% of the survivors of cerebrovascular accidents still cannot live fully. Take care of yourself. The number of people who die from cardiovascular and cerebrovascular diseases is as high as 15 million every year in the world, ranking first among various causes of death. Ischemic cerebrovascular disease is the most common and most harmful cardiovascular and cerebrovascular disease, mainly manifested in stroke, ischemia-reperfusion injury, and nerve injury. Ginkgo biloba extract (GBE) is the first-lin...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/127A61K47/42A61K47/24A61K31/365A61P25/00A61P9/10
CPCA61K9/1271A61K9/1277A61K31/365A61K47/24A61K47/42A61P9/10A61P25/00
Inventor 于颖李雄胡宇玉张亚兰邢宇郭传家王云波
Owner CHINA PHARM UNIV