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DSPE-PEG-FA-modified nanometer paclitaxel liposome and preparation method thereof

A technology of phosphatidylethanolamine and polyethylene glycol, which is applied in the directions of liposome delivery, medical preparations of inactive ingredients, and pharmaceutical formulations, can solve the problem of low efficacy of folic acid-paclitaxel nanoliposomes, affecting drug efficacy, problems such as low drug efficacy, to achieve the effects of good drug encapsulation efficiency, good colloidal stability, and high encapsulation efficiency

Inactive Publication Date: 2014-01-15
李红霞
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] The one, the raw material used for preparing liposome only has stearic acid, lacks cholesterol and other substances that have a stabilizing effect on the liposome membrane, resulting in stronger fluidity of the liposome membrane, and the encapsulated medicine is easy to leak;
[0009] The second is that folic acid-coupled paclitaxel liposomes only connect folic acid and fatty acids, and there is no polyethylene glycol connection in the middle. Drug metabolism, increase in vivo circulation time and other advantages;
[0010] Third, the particle sizes of the two liposomes produced are relatively large, respectively 374.3±54.9nm and 369.3±49.3nm, so the drug efficacy is very low: the IC of A549 cells (lung adenocarcinoma cells) 50 1.86±0.13μg / ml, 0.21±0.02μg / ml, respectively
[0024] Because the folic acid-paclitaxel nanoliposomes prepared by the above literature methods have low drug efficacy, which affects the clinical use effect, or uses substances that are not allowed for clinical use

Method used

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  • DSPE-PEG-FA-modified nanometer paclitaxel liposome and preparation method thereof
  • DSPE-PEG-FA-modified nanometer paclitaxel liposome and preparation method thereof
  • DSPE-PEG-FA-modified nanometer paclitaxel liposome and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0125] Example 1 Preparation of folic acid-coupled nano-paclitaxel drug (1)

[0126] 1. Instruments and materials

[0127] 1.1 Instrument

[0128] High performance liquid chromatography (ShimadzuLC-10AT, Shimadzu, Japan, including SPD-10A UV detection); N2000 chromatography workstation (Zhejiang Zhida); Zetasizer 3000 laser particle analyzer (Malvern, UK); ultrasonic cleaning machine (JP-010S , Shenzhen Jiemeng); freeze dryer (FD-1A-50, Chengdu Bilang); rotary evaporator (RE-501, Beijing Laiheng); electric constant temperature drying oven (101-3, Beijing Jiuhenglong)

[0129] 1.2 Drugs

[0130] Paclitaxel (Nanjing Kanghai Pharmaceutical Co., Ltd., content 98.6%); egg yolk lecithin (Germany avantipolar lipids company); cholesterol (Sinopharm Chemical Reagent Co., Ltd.); company); paclitaxel reference substance (National Institute for the Control of Pharmaceutical and Biological Products, content 99.08%); methanol and acetonitrile are chromatographic alcohols, and other reage...

Embodiment 2

[0158] Example 2 Preparation of Folic Acid-Coupled Nano-paclitaxel Drug (2)

[0159] The method is the same as in Example 1, but when preparing nano-paclitaxel liposomes, fluorescein isothiocyanate (FITC) is not added to the raw materials, and other materials are the same as in Example 1.

experiment example 1

[0160] Experimental Example 1 In Vitro Cell Experimental Study of Folic Acid-Coupled Nano-paclitaxel Targeted Therapy for Ovarian Cancer

[0161] 1. Experimental materials

[0162] SKOV3 cells, a gift from Professor Li Chunhai of the Academy of Military Medical Sciences;

[0163] SKOV3 / TAX, induced by our laboratory, according to SudimackJJ, Adams D, RotaruJ, et al. Folate receptor-mediated liposomal delivery of alipophilic boron agent to tumor cells in vitro for neutron capturetherapy. Pharm Res, 2002, 19(10): 1502-1508;

[0164] BALB / c female nude mice were purchased from the Animal Department of Peking University Health Science Center;

[0165] Culture medium RPM I-1640 (Sigma), folic acid-free RPM I-1640 medium (GIBCO), folate receptor monoclonal antibody MOV18 (Enzo Life Science), and apoptosis detection kit were purchased from Beijing Baosai Company;

[0166] Folic acid conjugated nano-paclitaxel: Example 1.

[0167] 2. Experimental method

[0168] 2.1 Immunohistoch...

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Abstract

The invention relates to a DSPE-PEG2000-FA-modified nanometer paclitaxel liposome. A molar ratio of the DSPE-PEG2000-FA to egg yolk lecithin is 0.05% to 0.15%, and a particle size of the liposome is less than 150 nm. A preparation method of the DSPE-PEG2000-FA-modified nanometer paclitaxel liposome comprises the following steps: first, preparing a DSPE-PEG2000-FA into a DSPE-PEG2000-FA micelle; second, performing incubation on the DSPE-PEG2000-FA micelle and a paclitaxel liposome together to obtain a DSPE-PEG2000-FA-modified nanometer paclitaxel liposome. Materials, which are forbidden to be used in clinical practice, are not used as crude materials in the present invention. According to the invention, the DSPE-PEG2000-FA-modified nanometer paclitaxel liposome has a small particle size, and the content of the DSPE-PEG2000-FA is low; besides, the DSPE-PEG2000-FA-modified nanometer paclitaxel liposome has good drug entrapment efficiency and good colloid stability. Moreover, the DSPE-PEG2000-FA-modified nanometer paclitaxel liposome can be absorbed effectively by an ovarian cancer cell having properties of sensitiveness to folic acid (+) and drug resistance, and the cytotoxicity of folic acid dependence is displayed; therefore, the efficacy of the DSPE-PEG2000-FA-modified nanometer paclitaxel liposome is stronger than that of a paclitaxel injection.

Description

technical field [0001] The invention relates to a medicine for treating tumors, in particular to a nano-paclitaxel liposome modified by phosphatidylethanolamine-polyethylene glycol 2000-folate and a preparation method thereof; Applications in cancer drugs. Background technique [0002] When cytotoxic drugs are used for chemotherapy of tumors, the failure of chemotherapy is often caused by the failure of the drugs to reach an effective concentration in the tumor site, and the toxicity and side effects will also increase. [0003] Ovarian cancer is the culprit of gynecological tumors, with a high mortality rate. Because more than 90% of ovarian cancers are folate receptor-positive, with a high expression level, while normal ovarian epithelial folate receptors are negative, in folate receptor (folic acid)-mediated targeted therapy for ovarian cancer, drugs are combined with folic acid to utilize The overexpression of folate receptors in tumor cells, with folate receptors as t...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/127A61K31/337A61K47/34A61K47/22A61K47/24A61P35/00A61P15/08
Inventor 李红霞佟玲霞程光
Owner 李红霞
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