Solid lipid nanoparticle or liposome and preparation method thereof

Abstract

The invention provides a solid lipid nanoparticle or a solid liposome which is prepared from a raw material at least containing active medicines, a lipid carrier material, an effervescent acidic material and an effervescent alkaline material, wherein the lipid carrier material is a material in which active medicines are encapsulated. The medical lipid nanoparticle (the solid lipid nanoparticle or the solid liposome) is successfully prepared by virtue of an effervescent dispersion technology. The method is simple and convenient in preparation process, controllable in quality, low in equipment requirement and easy to industrialize. The lipid nanoparticle prepared according to the method can be in a solid state and in a mixed suspension state, is stable in quality and has the particle diameter within a range of 0.050-20 microns, and can be prepared into various solid-type and solution-type preparations so as to meet clinical medication requirements of oral administration, vein injection, inhalation and transdermal delivery.

Description

technical field [0001] The invention relates to a solid lipid nanoparticle or liposome and a preparation method thereof. Background technique [0002] The drug particle dispersion system is divided into a coarse dispersion system and a colloidal dispersion system. The former mainly includes suspensions, microcapsules, microspheres, emulsions, etc.; the latter mainly includes nanoparticles, solid lipid nanoparticles, nanocapsules, nanomicelles, etc. . Particle dispersion system is of great significance in pharmacy: (1) Small particle size and large surface area help to improve the solubility and dissolution rate of insoluble drugs, thereby improving bioavailability; (3) The drug is encapsulated in the carrier, which can improve its stability in vivo and in vitro to a certain extent; (4) Particles of different particle sizes have a certain selective distribution in the body, and are easily phagocytized by the reticuloendothelial system , enriched in liver and spleen and othe...

AI Technical Summary

Problems solved by technology

[0007] There are several deficiencies in the above three preparation processes: (1) Both the melting-homogeneous method and the cooling-homogeneous method require expensive high-pressure homogenizers, and after repeated high-pressure homogenization, it is inevitable that a small amount of iron will be brought into the sample. (2) The disadvantage of the melt-homogeneous method is that most drugs have high solubility at high temperature. As the temperature decreases, a part of the supersaturated drug will redistribute in the phospholipids on the surface of solid lipid nanoparticles. layer, and the other part precipitates out in the water phase; (3) the cooling-homogeneous method is difficult to reduce the particle size, and often only solid lipid nanoparticles with a larger particle size can be obtained; (4) for the nanoemulsion method, if organic If the solvent is an auxiliary emulsifier, the drug that migrates to the external water phase will crystallize out after the organic solvent is evaporated; if cholate or tyloxapol is used as an auxiliary emulsifier, it needs to be removed by dialysis after the preparation, otherwise these emulsifiers May cause hemolysis in vivo

At present, liposome-encapsulated anticancer drugs, new vaccines, etc. have been listed, such as amphotericin liposomes, adriamycin liposomes, paclitaxel liposomes and cisplatin liposomes, etc. (Li Peijun. Characteristics and clinical treatment progress. China Modern Drug Application. 2014,8(5):243-245.), however, there are still only a handful of domestic and foreign liposome formulations on the market; more are still in the laboratory stage , the main reason is that there are several deficiencies in the current preparation process: (1) the degree of industrialization is not high, such as the traditional thin film hydration method, reverse phase evaporation method and other processes have a low level of scale; (2) poor stability, especially Liposome suspensions are prone to aggregation, fusion, and drug leakage during storage; at the same time, natural phospholipids are easily oxidized and hydrolyzed, which makes it difficult to meet the stability requirements of pharmaceutical preparations

(3) Organic residues, toxic organic solvents such as chloroform often used in the process, organic residues in the product are the problem

(4) If nano-liposomes with small particle sizes are obtained, high-pressure homogenization equipment is often required, and repeated high-pressure homogenization will inevitably bring a little iron filings into the sample, which will affect the stability of the sample.

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