Lenvatinib liposome, pharmaceutical composition thereof, preparation method thereof and prescription process optimization method

A lenvatinib and liposome technology, applied in the field of medicine, can solve the problem of low bioavailability of lenvatinib

Pending Publication Date: 2021-04-06
SHAOXING UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] The purpose of the present invention is to provide a kind of lenvatinib liposome and pharmaceutical composition thereof and its preparation method and prescription process optimization method based on the foundation and present situation of prior art, utilize lenvatinib liposome, actively target Immunotherapy to immune cells, while solving the problem of low bioavailability of existing lenvatinib

Method used

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  • Lenvatinib liposome, pharmaceutical composition thereof, preparation method thereof and prescription process optimization method
  • Lenvatinib liposome, pharmaceutical composition thereof, preparation method thereof and prescription process optimization method
  • Lenvatinib liposome, pharmaceutical composition thereof, preparation method thereof and prescription process optimization method

Examples

Experimental program
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Embodiment 1

[0040]Example 1 Sialic acid - Tenxin - stearate (SA-PG10-C18Synthesis and characterization

[0041]SA-PG according to the present invention10-C18Preparation process: First, the proportion of the feed is sialic acid (SA) / ten polyglycerol - stearate (Pg10-C18) / N-hydroxybutyimide (NHS) / 1-ethyl-(3-dimethylaminopropyl) carbonitidinimide hydrochloride (EDC) / triethylamine (TEA) = 2: 1: 2: 4: 4 (molar ratio); Sa is dissolved in 5 mL of formamide (FA), adding EDC / NHS, activation of EDC / NHS, at 4 ° C for 90min, at this time, the system is clarified; then dissolved in 2 ml of FA PG in PG10-C18In the addition of the reaction system, TEA was added, and the reaction was stirred at room temperature for 48 h, and the reaction solution was clarified; then the reaction solution was transferred to the dialysis bag (intercept molecular weight 10 kDa), and the dialysis medium was concentrated hydrochloric acid (V / V, 1: 100) system, The dialysis volume is 1000 ml dialysis, and the dialysis med...

Embodiment 2

[0045]Example 2LEN UV detection wavelength determination and standard curve

[0046]First, it is prepared by isopropanol / water (90 / 10 V / V) to formulate the Laut Dibini (LEN) drug solution, the drug concentration is 0.1 mg / ml. Then, with isopropanol / water (90 / 10 V / V) as a white solvent, 200 to 800 nm full-wavelength scanning is performed with a UV2700 ultraviolet spectrophotometer to 0.1 mg / ml of a Len drug solution, and the optimum Len ultraviolet detection wavelength is determined.

[0047]Precision, 10.0 mg of Len raw materials, placed in a 100 mL volumetric flask, dissolved in isopropanol / water (90 / 10V / V) and diluted to the scale, and manufactured by 100 μg · ml of mass concentration-1LEN solution as a reserve. Squeezing the stock solution 0.5, 1.0, 2.0, 3.0, 4.0 ml, respectively, in a 10 ml volumetric flask, diluted with isopropanol / water (90 / 10 V / V) to the scale, i.e., the mass concentration is 5.0, 10.0, respectively. 20.0, 30.0, 40.0 μg · ml-1Len series standard...

Embodiment 3

[0050]Example 3 Method for preparing a lug niterni

[0051]The Len Liposomes according to the present invention are prepared by the classic liposome, and their groups are HSPC / CH / SA-PG.10-C18 / LEN = 100 mg / 33 mg / 33 mg / 5 mg, 10 ml of liposomes were prepared. Precision-priced placed HSPC, CH and SA-PG10-C18Placed in a 500 ml round bottom flask, 10 ml of anhydrous ethanol, completely dissolved HSPC, CH and SA-PG10-C18Thereafter, the water bath was heated at 65 ° C, the rotation was 30 rpm, and the vacuum was 0.09 MPa conditions, the water-evaporation was removed, a lipid film was formed on the round bottom flask; then, the precision weighed 5 mg LEN, completely dissolved in 10 ml In aqueous solution containing 10% ethanol, the Len solution was added to the round bottom flask, and the lipid film was 30 min under a rotational speed of 30 rpm. The lipid film was hydrated at room temperature atmospheric pressure; dispersed the liposomes using ultrasonic cell pulverizer, using 100W d...

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Abstract

The invention provides a lenvatinib (Len) liposome, a pharmaceutical composition thereof, a preparation method thereof and a prescription process optimization method. The liposome contains lenvatinib, phospholipid, an amphiphilic derivative, cholesterol and a gradient establishing substance, wherein the weight ratio of cholesterol to phospholipid is 1:2-1:10, the weight ratio of lenvatinib to phospholipid is 1:10-1:40, the weight ratio of the amphiphilic derivative to the phospholipid is 1:2-1:10, the phospholipid is glycerophospholipid or sphingomyelin, the gradient adopts a pH gradient method or an amine gradient method, and the concentration of the gradient establishing substance solution is 100-300mM. The Len liposome can actively target a tumor site through an SA-Siglec1 pathway, has the advantages of high encapsulation efficiency, high stability, high active targeting, high tumor inhibition rate and the like, and has good clinical application potential and product development value.

Description

Technical field[0001]The present invention belongs to the field of medical technology, and more particularly to a Merogenini liposome and a pharmaceutical composition and a preparation method thereof and a process optimization method thereof.Background technique[0002]The mortality of liver cancer is in the second place worldwide, and the healing effect of late liver cancer is especially good. Therefore, there is a major social and economic benefit of targeted drugs for liver cancer, especially targeted drugs for advanced liver cancer.[0003][0004]LeNvatinib, Len, its structure is formula (II), is a multi-target tyrosine kinase inhibitor, which can act on vascular endothelial growth factor receptors 1 to 3 (VEGFR 1 ~ 3) Fibroblast growth factor receptors 1 to 4 (FGFR 1 to 4), RET, KIT, and platelet-derived growth factor alpha (PDGFR-α) or the like to produce neovascular inhibition and anti-tumor effects. In February 2015, Japanese Weiluki Company has developed mesylate, Levima (Lenvim...

Claims

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Application Information

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IPC IPC(8): A61K9/127A61K47/26A61K47/24A61K47/28A61K47/12A61K31/47A61P35/00
CPCA61K9/1277A61K47/26A61K47/24A61K47/28A61K47/12A61K31/47A61P35/00
Inventor 骆翔周艳艳俞燕娜吴梦琦朱柯武沈润溥吴春雷邓莉平杜奎蔡涛余乐茂
Owner SHAOXING UNIVERSITY
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