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Preparation method of vesicle-loaded multivescular liposome

A multivesicular liposome and vesicle technology, applied in the field of medicine, can solve the problems of loss of biological activity, structural damage, loss of activity, etc., and achieve the effects of improving biological activity, ensuring slow release, and extending half-life

Active Publication Date: 2017-07-07
YANTAI UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the structure of biological macromolecules is relatively complex, and it is easy to undergo chemical degradation or physical changes due to in vivo and external environments in the process of preparation, storage or release, thereby losing activity, especially the preparation of multivesicular liposomes using W / O / With the double emulsion method, at the oil-water interface, protein and polypeptide drugs are prone to structural damage, resulting in the loss of part of their biological activity

Method used

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  • Preparation method of vesicle-loaded multivescular liposome
  • Preparation method of vesicle-loaded multivescular liposome
  • Preparation method of vesicle-loaded multivescular liposome

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preparation example Construction

[0026] The present invention provides a novel preparation method for the preparation of substances such as drugs, proteins and polypeptides or active ingredients that can be released with delayed characteristics, that is, a preparation method of multivesicular liposomes loaded with vesicles is provided. Proceed as follows:

[0027] (1) Preparation of three-phase solution

[0028] Solution A: prepare the inner aqueous phase containing vesicles and sucrose for embedding small molecule drugs and / or biomacromolecule drugs;

[0029] Wherein, the solution A contains a sucrose mass concentration of 2-10% (w / v);

[0030] Solution B: preparing a lipid phase containing lipids and organic solvents;

[0031] Wherein, the lipids include dioleoylphosphatidylcholine, dipalmitoylphosphatidylglycerol, cholesterol and triolein; the percentage of the dioleoylphosphatidylcholine in the total lipid mass is 20-60% %, the percentage of the triolein in the total lipid mass is 5-20%, the percentage...

Embodiment 1

[0054] Multivesicular Liposomes of Gelatin Nanoparticles Loaded with Exenatide

[0055] (1) Preparation of solution A: 1 part of the inner aqueous phase of gelatin nanoparticles loaded with exenatide and the osmotic pressure regulator, specifically dispersing the prepared nanoparticles in the aqueous phase in which the osmotic pressure regulator is dissolved;

[0056] Preparation solution B: containing 200 parts of lipid organic solvent;

[0057] Prepare solution C: an external aqueous phase containing an osmotic pressure regulator and an auxiliary emulsifier;

[0058] (2) Combine and mix solution A and solution B, and stir at 12000 rpm to obtain W / O colostrum;

[0059] Wherein, the volume ratio of solution A and solution B is 1:0.5-1:20;

[0060] Solution A contains sucrose with a mass concentration of 2-10% (w / v);

[0061] The mass concentration of dipalmitoylphosphatidylglycerol in solution B is 0.01-1% (w / v);

[0062] (3) Disperse the W / O colostrum into solution C at a...

Embodiment 2

[0070] Multivesicular liposomes of mPEG-PLGA micelles loaded with huperzine A

[0071] (1) Preparation of solution A: 1 part of mPEG-PLGA micelles loaded with huperzine A and the internal water phase of the osmotic pressure regulator, specifically dispersing the prepared nanoparticles in the aqueous phase in which the osmotic pressure regulator is dissolved middle;

[0072] Solution B: contains 200 parts of lipid organic solvent;

[0073] Solution C: an external aqueous phase containing an osmotic pressure regulator and an auxiliary emulsifier;

[0074] (2) Combine and mix solution A and solution B, and stir at 12000 rpm to obtain W / O colostrum;

[0075] Wherein, the volume ratio of solution A and solution B is 1:0.5-1:20;

[0076] Solution A contains sucrose with a mass concentration of 2-10% (w / v);

[0077] The mass concentration of dipalmitoylphosphatidylglycerol in solution B is 0.01-1% (w / v);

[0078] (3) Disperse the W / O colostrum into solution C at a shear rate of ...

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Abstract

The invention relates to a preparation method of a vesicle-loaded multivescular liposome. The preparation method comprises the steps of adopting nanoscale vesica and an osmotic pressure regulator as an inner water phase and an organic solvent of a lipid with good biocompatibility as an oil phase, dispersing the inner water phase into the oil phase to form a W / O primary emulsion; dispersing the primary emulsion into an outer water phase containing the osmotic pressure regulator and an auxiliary emulsifier to form a W / O / W compound emulsion; and transferring the compound emulsion to the same outer water phase and removing an organic solvent through rotary evaporation or nitrogen introduction to obtain a multivescular liposome suspension. According to a multivescular liposome preparation, the encapsulation efficiency of a loaded drug can be ensured, the biological activity of biomacromolecules can be improved, the immunogenicity is reduced, the burst effect is reduced and sustained slow release of the drug is ensured.

Description

technical field [0001] The invention relates to a method for preparing multivesicular liposomes loaded with vesicles, belonging to the technical field of medicine. Background technique [0002] Multivesicular liposomes (Multivesicular, MVLs) are a relatively mature sustained-release preparation developed at present. In 1983, the British Skyepharma PLC company adopted the depot foam technology (Depo Foam) TM ) was successfully developed. It is composed of multiple aqueous chambers in the form of non-concentric circles, each chamber is separated by a lipid bilayer, and neutral lipids are distributed as fixed connectors at the junctions of adjacent chambers, so that Form a solid topology. As a carrier of hydrophilic drugs, multivesicular liposomes can greatly improve the encapsulation efficiency of water-soluble drugs and reduce leakage. The spherical structure can still maintain its original shape to achieve the purpose of sustained release. [0003] At present, the report...

Claims

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Application Information

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IPC IPC(8): A61K9/127A61K9/107A61K9/51A61K47/42A61K38/22A61K47/24A61K47/34A61K31/4748A61P27/02A61P27/06A61P29/00A61P9/10A61P35/00A61P1/16A61P25/00
CPCA61K9/0002A61K9/1075A61K9/1273A61K9/1277A61K9/5169A61K31/4748A61K38/22A61K47/24A61K47/34
Inventor 慕宏杰孙考祥王毅云
Owner YANTAI UNIV
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