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Hyaluronic acid modified picrasma quassioides total alkaloid hybrid lipid nano preparation, and preparation method and applications thereof

A total alkaloid and lipid nanotechnology, which is applied to medical preparations with non-active ingredients, medical preparations containing active ingredients, anti-inflammatory agents, etc., can solve the problem of high toxicity and lack of targeting of total alkaloids of bitterwood , poor water solubility and other issues, to achieve good loading performance, improve anti-inflammatory activity, and reduce toxicity

Active Publication Date: 2019-05-07
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, no alkaloid monomers with excellent activity in bitter wood have been found, and the total alkaloid parts of bitter wood are still used clinically [Chen Meng. Research on the active components of bitter wood alkaloids [D]. Yantai University, 2007.]
The total alkaloids of bitter

Method used

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  • Hyaluronic acid modified picrasma quassioides total alkaloid hybrid lipid nano preparation, and preparation method and applications thereof
  • Hyaluronic acid modified picrasma quassioides total alkaloid hybrid lipid nano preparation, and preparation method and applications thereof
  • Hyaluronic acid modified picrasma quassioides total alkaloid hybrid lipid nano preparation, and preparation method and applications thereof

Examples

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[0057] Example 1

[0058] Synthesis of BzPGA: Dissolve 10 g of γ-PGA with a molecular weight of 1 million Da in 200 mL of deionized water, and add 3% (w / v) cetyltrimethylammonium chloride aqueous solution to excess with stirring until no precipitation occurs. , Stir for 5min, filter with sand core funnel, wash the white precipitate with an appropriate amount of hot deionized water until the dripping filtrate is free of bubbles, freeze-dry to obtain white solid powder γ-PGA-CTA; take 2g of the above γ-PGA-CTA and 1.036 g NaHCO 3 Dry in a desiccator overnight to remove trace water, add to 60mL of anhydrous nitromethylpyrrolidone (NMP), add 1.88mL of benzyl bromide under ice bath, react at 55°C for 8h until the solution is slightly clear; cool to room temperature and remove excess by suction filtration NaHCO 3 And NaCl, the filtrate was poured into a mixed solution of 200mL methanol and 100mL 1% HCl, stirred for 0.5h under an ice bath, filtered with a sand core funnel, and the filte...

Example Embodiment

[0059] Example 2

[0060] mPEG-b-C 16 Synthesis:

[0061] (1) Dissolve 5g of mPEG-OH in 50mL of anhydrous toluene, remove water azeotropically for 2-3h under argon protection, cool to room temperature, add anhydrous dichloromethane dropwise under ice bath until the solution is clear; add under stirring 0.520mL of triethylamine, then 0.290mL of methanesulfonyl chloride was added dropwise. After 18 hours of reaction in an ice bath, the insoluble methanesulfonic acid hydrochloride was removed by suction and precipitated with excess ether; the above product was added to a round bottom flask, and 85mL was added 25% ammonia water, sealed with a sealing film, stirred at 20°C for 4 days, the reaction solution was volatilized in a fume hood until the wet pH test paper did not change color; 5M sodium hydroxide was added dropwise to adjust the pH to 13, dichloride Methane was extracted 3 times (3×25mL), washed with concentrated brine, dried with anhydrous sodium sulfate, concentrated by rota...

Example Embodiment

[0063] Example 3

[0064] Investigate the influence of different L / P values ​​on particle size and PDI

[0065] Prepare 10 mL of 4 mg / mL BzPGA / DMSO solution as the organic phase; prepare 10 mL of 10% ethanol aqueous solution with soy lecithin concentration of 0, 0.04, 0.08, 0.15, 0.24 mg / mL, and ultrasonicate in a water bath for 3-5 minutes before preparation , The water bath is heated to 65°C as the water phase; the BzPGA solution is injected into the water phase solution at a speed of 30mL / h with a micro syringe pump. During the injection, the water phase is kept at 65°C, the injection volume is 1mL, and the injection is completed at low speed. Then vortex at high speed for 3 minutes to evaporate the ethanol to disperse the soy lecithin to prevent the soy lecithin from being wrapped in the core. Then slowly stir for 2 hours to room temperature, and transfer the solution to an Amicon Ultra-15 ultrafiltration tube for ultrafiltration and centrifugation. The rotation speed is 2000r...

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Abstract

The invention relates to a picrasma quassioides total alkaloid hybrid lipid nano preparation, and discloses a hyaluronic acid modified picrasma quassioides total alkaloid hybrid lipid nano preparation, and a preparation method and applications thereof. Poly(gamma-glutamic acid)benzyl ester (gamma-BzPGA) can be taken as a nuclear material; amphiphilic compounds, such as soya bean lecithin containing 98% of phosphatidylcholine (PC) and 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE) can be taken as a surfactant; hyaluronic acid (HA) or polyethylene glycol-b-palmitic acid (PEG-b-C16) canbe taken as a shell material; and a carrier can be used for loading picrasma quassioides total alkaloid. The preparation method is mature and efficient in technology, so that possibility can be provided for the preparing of picrasma quassioides total alkaloid complex active components and other active monomer nano preparations.

Description

technical field [0001] The present invention relates to total alkaloid hybrid lipid nano-preparation of bitter wood, in particular to hyaluronic acid (HA) or PEGylated total alkaloid hybrid lipid nano-preparation of bitter wood and its preparation method Background technique [0002] Core-shell nanoparticles (Core-shell nanoparticles) consist of one material as its core and another material as its shell wrapped around the outside of the core through non-covalent interactions. It was first used as a lipid-polymer Lipid-polymer hybrid NPs was proposed by Chinese scholar Zhang Liangfang in 2009. Based on polymer micelles and liposomes, the author designed and synthesized a new type of lipid-polymer hybrid NPs for large quantities of fat-soluble drugs. A new type of preparation between body and micelles, the related research results were published in ACS nano, the top journal of American nano preparations [ZhangL, Chan J M, Gu F X, et al.Self-assembled lipid-polymer hybrid nanop...

Claims

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Application Information

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IPC IPC(8): A61K36/185A61K9/51A61K47/61A61K47/69A61K47/24A61K47/14A61P19/02A61P29/00A61K135/00
Inventor 曲玮柳文媛刘博文冯锋刘富垒李聪
Owner CHINA PHARM UNIV
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