Paclitaxel palmitate liposome and preparation method thereof

A technology of palmitate and paclitaxel, applied in the field of medicine, can solve the problems of liver and kidney function and reproductive function damage, poor compatibility of infusion equipment, frequent allergic reactions, etc., so as to overcome the poor drugability, improve antitumor properties, and improve drug concentration. high effect

Active Publication Date: 2016-08-17
SHANGHAI WEI ER BIOPHARM TECH CO LTD +3
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although "Taxol" has solved the problem that paclitaxel is insoluble in water and has shown good anti-tumor effect, but because of the addition of a large amount of solubilizer polyoxyethylene castor oil with toxic side effects in the prescription, resulting in The preparation has many defects: ①Frequent allergic reactions: Taxol instructions and literature (Gao Peng, Tu Jiasheng, Polyoxyethylene castor oil and its safety research progress. Pharmacy and Clinical Research, 2010,18(1):59-63. ) pointed out that polyoxyethylene castor oil is an active substance, which causes the body to release histamine with allergic effects, which leads to the occurrence of allergic reactions. Reaction is the biggest safety hazard of Taxol; ② Poor compatibility with infusion equipment: literature reports (Zhang Hong, Yang Fengmin, Wu Jing, et al.

Method used

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  • Paclitaxel palmitate liposome and preparation method thereof
  • Paclitaxel palmitate liposome and preparation method thereof
  • Paclitaxel palmitate liposome and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0063] Example 1: Comparative evaluation of series of different paclitaxel fatty acid esters in vivo efficacy tests

[0064] Chinese patent CN1202166A and literature (Shaukat Ali, Imran Ahmad etc., Hydrolyzablehydrophobic taxanes: synthesis and anti-cancer activities, Anti-Cancer Drugs, 2001, 12:117-128; Walter R.Perkins, Imran Ahmad etc., Novel therapeutic nano-resicles ( ): trapping poorly water soluble compounds, International Journal of Pharmaceutics 2000, 200:27–39), which records a kind of α-bromo-based fatty acid ester of paclitaxel, and the carbon chain length of the fatty acid covered is paclitaxel between C6-C16 Fatty acid ester prodrug; U.S. patent (US 7,235,583B1) and international patent (WO 00 / 53231), have studied a paclitaxel fatty acid ester and its preparation, and its fatty acid length is C8-C26. The above-mentioned patent documents have recorded paclitaxel fatty acid ester prodrugs with fatty acid carbon chain lengths between C6-C26, but no differential rese...

Embodiment 2

[0085] Example 2: Study on the druggability of paclitaxel palmitate in different formulations

[0086] The druggability and antitumor effect of liposomes, polymer micelles, fat emulsions, and nanoparticles were compared and studied respectively. For the sake of conservatism, the fixed drug loading was 3 mg / ml for parallel comparison. With reference to the current clinical dosage of paclitaxel ( The total dosage for adults is about 400mg each time), and the drug loading of 3mg / ml is only a lower requirement. On this basis, research on related preparations is carried out, and the main research programs and results are summarized as follows:

[0087] 1. Study on the druggability of preparations

[0088] 1.1 Liposome

[0089] Weigh 300mg of paclitaxel palmitate, 3.5g of high-purity egg yolk lecithin (EPCS), 0.3g of DSPE-PEG2000, add 3g of propylene glycol, heat and dissolve at 65°C to obtain an organic phase; weigh 85g of water for injection, heat to 65°C, Stir and dissolve to ...

Embodiment 3

[0113] Example 3: Importance of Propylene Glycol Infusion for Paclitaxel Palmitate Liposome Development

[0114] Commonly used liposome preparation methods include thin film evaporation, reverse evaporation, and ethanol injection. Among them, thin film evaporation has poor controllability and cumbersome steps in large-scale production. Therefore, we plan to use relatively simple reverse evaporation and ethanol injection. Injection method to prepare liposomes. But for paclitaxel palmitate, reverse evaporation method and ethanol injection method all can't realize the preparation of this liposome well, when selecting propylene glycol to inject, just received fundamental effect. In Example 2 above, good liposomes can be prepared by injecting a small amount of propylene glycol, so taking this as an example, the commonly used reverse evaporation method and ethanol injection method are respectively verified using the same prescription. The methods and results are as follows:

[011...

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Abstract

The invention belongs to the technical field of medicine, and particularly relates to a paclitaxel palmitate liposome and a preparation method thereof. Paclitaxel palmitate is obtained through esterification of palmitic acid and 2'-bit hydroxyl of the paclitaxel and belongs to a paclitaxel prodrug. The prodrug overcomes the defect of poor lipid solubility of the paclitaxel, and accordingly, the problem of poor druggability of paclitaxel nano-preparations is solved substantially. Aiming at the special physicochemical property of the paclitaxel palmitate, matching between formula composition and preparation technology is researched, the paclitaxel palmitate liposome, which does not contain polyoxyethylated castor oil and is safe, stable in quality and simple to prepare, is developed in a real sense, and the solid foundation is laid for further research and application of the paclitaxel in the anti-tumor field.

Description

Technical field: [0001] The invention relates to the technical field of medicine, in particular to a paclitaxel palmitate liposome and a preparation method thereof. Background technique: [0002] Paclitaxel (Paclitaxe1) is a diterpenoid compound extracted from Taxaceae plants. Hexahydroxytaxane-11-en-9-one-4,10-diacetate-2-benzoate-13[(2,R,3,S)-N-benzoyl-3- Phenylisoserine]. This product is a white crystalline powder, odorless, tasteless, insoluble in water, and poorly fat-soluble, almost not absorbed after oral administration. Due to its poor fat solubility and water solubility, it has brought difficulties to the development and application of clinical preparations. The related research began in the late 1950s and lasted for more than 30 years. Until December 1992, the FDA approved for the first time the paclitaxel injection of Bristol-Myers Squibb, which was named "Taxol", which was widely used in various malignant tumors such as ovarian cancer, cervical cancer, breast ...

Claims

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Application Information

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IPC IPC(8): A61K31/337A61K9/127A61K47/24A61K47/10A61K9/19A61P35/00
CPCA61K9/127A61K9/19A61K31/337A61K47/10A61K47/24A61K9/0019A61K9/08A61K9/1277A61K47/02A61K47/26A61K47/28A61P35/00
Inventor 单彬周琴琴余侬
Owner SHANGHAI WEI ER BIOPHARM TECH CO LTD
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