Napro Biotherapeutics, Inc.

Timothy R Prout

David Reginald Carver

Hernita A Ewald

Robyn Elliott

Paul Handreck

Donia L Henderson

Christopher T Workman

Charles L Hughes

A pharmaceutical formulation of paclitaxel and polyethoxylated castor oil is disclosed to be relatively acidified to a pH of less than 8.1 and preferably within a pH range of 5 to 7, inclusively. Ethanol is optionally included in the formulation which is adapted for use in a body for the treatment of cancer, A formulation method is disclosed and includes the step of mixing an acid with a carrier material, such as polyethoxylated castor oil, to form a carrier solution after which paclitaxel is added in an amount such that the resulting pH is less than 8.1 and preferably in a pH range of 5 to 7. Ethanol may optionally be slurried with the paclitaxel before mixing with the carrier solution. A variety of acidifying agents, a preferred one being anhydrous citric acid, are described.

Injectable composition

A pharmaceutical formulation of paclitaxel and polyethoxylated castor oil is disclosed to be relatively acidified to a pH of less than 8.1 and preferably within a pH range of 5 to 7, inclusively. Ethanol is optionally included in the formulation which is adapted for use in a body for the treatment of cancer. A formulation method is disclosed and includes the step of mixing an acid with a carrier material, such as polyethoxylated castor oil, to form a carrier solution after which paclitaxel is added in an amount such that the resulting pH is less than 8.1 and preferably in a pH range of 5 to 7. Ethanol may optionally be slurried with the paclitaxel before mixing with the carrier solution. A variety of acidifying agents, a preferred one being anhydrous citric acid, are described.

A pharmaceutical formulation of paclitaxel (also known as taxol) and polyethoxylated castor oil is disclosed to be relatively acidified to a pH of less than 8.1 and preferably within a pH range of 5 to 7, inclusively. Ethanol is optionally included in the formulation which is adapted for use in a body for the treatment of cancer. A formulation method is disclosed and includes the step of mixing an acid with a carrier material, such as polyethoxylated castor oil, to form a carrier solution after which taxol is added in an amount such that the resulting pH is less than 8.1 and preferably in a pH range of 5 to 7. Ethanol may optionally be slurried with the paclitaxel before mixing with the carrier solution. A variety of acidifying agents, a preferred one being anhydrous citric acid, are described.

A pharmaceutical formulation of taxol and polyethoxylated castor oil is disclosed to be relatively acidified to pH of less 8.1 and preferably within a pH range of 5 to 7, inclusively, by an acidifying agent. Ethanol is optionally included in the formulation which is adapted for use in a body for the treatment cancer. A formulation method is disclosed and includes the step of mixing an acid with a carrier material, such as polyethoxylated castor oil, to form a carrier solution after which taxol is added in an amount such that the resulting pH is less than 8.1 and preferably in a pH range of 5 to 7. Ethanol may optionally be slurried with the taxol before mixing with the carrier solution. A variety of acidifying agents, a preferred one being anhydrous citric acid, are described.

Stabilized pharmaceutical composition

A pharmaceutical formulation of taxol and polyethoxylated castor oil is disclosed to be stabilized by reducing its pH to less than 8.1 and preferably within a pH range of 5 to 7, inclusively. Ethanol is optionally included in the formulation which is adapted for use in a body for the treatment of cancer. A formulation method is disclosed and includes the step of reducing the pH of a carrier material, such as polyethoxylated castor oil, to form a carrier solution after which taxol is added in an amount such that the resulting pH is less than 8.1 and preferably in a pH range of 5 to 7. Ethanol may optionally be slurried with the taxol before mixing with the carrier solution.

A pharmaceutical formulation of taxol and polyethoxylated castor oil is disclosed to be relatively acidified to a pH of less than 8.1 and preferably within a pH range of 5 to 7, inclusively, by an acidifying agent. Ethanol is optionally included in the formulation which is adapted for use in a body for the treatment of cancer. A formulation method is disclosed and includes the step of mixing an acid with a carrier material, such as polyethoxylated castor oil, to form a carrier solution after which taxol is added in an amount such that the resulting pH is less than 8.1 and preferably in a pH range of 5 to 7. Ethanol may optionally be slurried with the taxol before mixing with the carrier solution. A variety of acidifying agents, a preferred one being anhydrous citric acid, are described.

A method of processing a feed liquid in the form of an extraction solution containing taxane solutes that is an extraction product of a biomass utilizes at least one semipermeable membrane to remove at least one taxane solute from the solvent by reverse osmosis. The feed liquid is placed in a first region on one side of the membrane and pressure is supplied to transport constitutes of the feed liquid across the membrane to a second region as a first permeate while retaining a first retentate in the first region. The taxane solute may be either retained or transported. Where the taxane solute is transported, the method can further include the use of a second semipermeable membrane of a pore size different from the first membrane and supplying a pressure to transport some of the first permeate across the second membrane as a second permeate while retaining a majority of the desired taxane solute as a second retentate. Here, the first membrane has a pore size which allows transport of the taxane solute while the second membrane has a pore size that retains the taxane solute. A variety of solvents and useable membranes is disclosed.

Reverse osmosis and ultrafiltration methods for solutions to isolate

The present invention is a method that uses an absorption column for the cleavage and recovery of taxanes, which are not normally detected as free taxanes. The method processes a first solution that contains standard detectable taxanes and other undetectable taxane compounds to generate a second solution that contains a higher percentage of detectable standard taxane then the first solution. The first step of this method is loading a column having a first opening and a second opening with an ion exchange media. The next step is placing the first solution in the first opening of the column so that the first solution passes through the ion exchange media in the column and flows to the second opening. Thus, the taxane compounds are converted to standard taxanes by an ion exchange reaction and the second solution is formed. Then the next step is collecting, from the second opening of the column, the second solution and recovering from the second solution a larger percentage of standard taxanes then was detectable in the first solution. The ion exchange media of the present solution is an ion exchange resin. The ion exchange resin can be a mixture of an anion exchange resin and a cation exchange resin. The anion exchange resin is in the OH-form. The cation exchange resin is in the H.sup.+ form. Preferably, the ion exchange resin is alumina.

Method of using ion exchange media to increase taxane yields

A process for the preparation of a compound of formula (I) ##STR1## comprising contacting a mixture containing at least one taxane compound having an ester linkage at the C-13 position with at least one borohydride reducing salt in a reaction solvent in the presence of a Lewis acid.

Processes of converting taxanes into 10-deacetylbaccatin III

The present invention relates to a process of converting partially purified taxane mixtures into Baccatin III. The process for the preparation of Baccatin III includes contacting a mixture containing at least one taxane compound having an ester linkage at the C-13 position with at least one borohydride reducing salt in a reaction solvent in the present of a Lewis acid.

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Boulder, CO, United States of America

Timothy R Prout