Title:  Oil-in-water emulsion for encapsulating paclitaxel

United States Patent:  6,348,491

Assignee:  National Science Council (Taipei, TW)

Filed:  October 29, 1999

Foreign Application Priority Data:  Jul 01, 1999[TW] (88111153)

An oil-in-water emulsion for encapsulating paclitaxel including (a) triglyceride , (b) emulsifier including phosphatidyl choline (PC), non-ionic surfactant and polyethyleneglycol-modified disteaoyl phosphatidylethanolamine (PEG-M-DSPE), and (c) pharmaceutically acceptable aqueous solution.

DETAILED DESCRIPTION OF THE INVENTION

The oil-in-water emulsion of the invention can be prepared by vigorously mixing triglyceride, emulsifier and paclitaxel in pharmaceutically acceptable aqueous solution, followed by filtering. Specifically, triglyceride, emulsifiers and paclitaxel are first dissolved in a suitable solvent such as chloroform or methanol to obtain a homogeneous solution. The organic solution is then removed and the pharmaceutically acceptable aqueous solution is added. The resulting solution is then vigorously oscillated by using for example a vortex, followed by filtering to obtain an emulsion in which the paclitaxel is encapsulated therein. According to the invention, the concentration of the paclitaxel in the emulsion can reach 0.75-1.75 mg/ml.

The triglyceride is used as the core lipid and is a triglyceride of saturated or unsaturated C₆ -C₁₈ fatty acid, and is preferably tricaproin or tricaprylin. A mixture of tricaproin and tricaprylin in a ratio of 3:1 (w/w) is more preferable.

The weight ratio between core lipid and the emulsion is preferably from 1:0.6 to 1:1.5, and more preferably ranges from 1:1 to 1:1.5.

The weight ratio between phosphatidyl cholin and non-ionic surfactant is preferably from 1:0.3 to 1:1, and more preferably 1:0.5.

The weight ratio among phosphatidyl cholin, non-ionic surfactant and polyethyleneglycol-modified disteaoyl phosphatidylethanolamine is preferably 1:0.4-1:0.1-0.2, and more preferably 1:0.5:0.12.

The pharmaceutically acceptable aqueous solution can be glycerol solution, glucose solution and physiological saline solution. A 2.5% glycerol solution is preferred.

The non-ionic surfactant can be Tween 80, Tween 20 and Pluronic F68. Tween 80 is preferred according to the invention.

The polyethyleneglycol-modified phosphatidylethanolamine is a phosphatidylethanolamine treated by polyethyleneglycol. Preferably, the polyethylene glycol has a molecular weight between 600 and 5000, more preferably a molecular weight of about 2000. Moreover, the preferred polyethyleneglycol-modified phosphatidylethanolamine is polyethylene-modified disteraoyl phosphatidylethanolamine.

Claim 1 of 21 Claims

What is claimed is:

1. An oil-in-water emulsion for encapsulating paclitaxel comprising:

triglyceride;

emulsifier comprising phosphatidyl choline, non-ionic surfactant and polyethyleneglycol-modified phosphatidylethanolamine; and

pharmaceutically acceptable aqueous solution;

wherein the weight ratio of said triglyceride and said emulsifier ranges between 1:1 to 1:1.5 and said triglyceride is homogeneously dispersed in said pharmaceutically acceptable aqueous solution.

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