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WO1994012198A1 - Injectable taxol composition - Google Patents

Injectable taxol composition Download PDF

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Publication number
WO1994012198A1
WO1994012198A1 PCT/AU1993/000599 AU9300599W WO9412198A1 WO 1994012198 A1 WO1994012198 A1 WO 1994012198A1 AU 9300599 W AU9300599 W AU 9300599W WO 9412198 A1 WO9412198 A1 WO 9412198A1
Authority
WO
WIPO (PCT)
Prior art keywords
acid
solution
taxol
injectable
composition according
Prior art date
Application number
PCT/AU1993/000599
Other languages
French (fr)
Inventor
Robyn Louise Elliott
Gregory Paul Handreck
David Carver
Timothy Prout
Hernita Ewald
Original Assignee
F.H. Faulding & Co. Limited
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by F.H. Faulding & Co. Limited filed Critical F.H. Faulding & Co. Limited
Priority to AU55538/94A priority Critical patent/AU5553894A/en
Publication of WO1994012198A1 publication Critical patent/WO1994012198A1/en

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/12—Carboxylic acids; Salts or anhydrides thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin

Definitions

  • Taxol is a compound extracted from the bark of a western yew, Taxus brev ⁇ folxa and known for its antineoplastic activity. It is described for example in the Merck Index, Eleventh Edition 1989, monograph 9049.
  • taxol was chosen for development as an antineoplastic agent because of its unique mechanism of action and good cytotoxic activity against IP. implanted bl6 melanoma and the human MX-1 mammary tumor xenograft. Taxol is believed to function as a mitotic spindle poison and as a potent inhibitor of cell replication in vitro. Other mitotic spindle poisons (colchicine and podophyllotoxin) inhibit microtubule assembly. Taxol employs a different mechanism of action since it appears to shift the equilibrium of polymerization/depolymerization toward polymer assembly and to stabilize microtubules against depolymerization under conditions which would cause rapid disaggregation of microtubules.
  • taxol entered clinical trials in 1983. Over the past few years, taxol has demonstrated good response rates in treating both ovarian and breast cancer patients who were not benefiting from vinca alkaloid or cisplatin therapy. It has also shown encouraging results in patients with other types of cancer including lung, melanoma, lymphoma, head and neck.
  • NCI National Cancer Institute
  • a known formulation contains taxol, cremophor EL (a polyethoxylated castor oil which acts as a solubilizer) and ethanol. It is a disadvantage of the known formulation that the taxol therein degrades, unless stored at or below 8°C, with the result that the shelf life of the formulation is unsatisfactory, and there is therefore a need for a taxol solution of improved stability.
  • cremophor EL a polyethoxylated castor oil which acts as a solubilizer
  • the invention provides a solution containing taxol, a pharmaceutically acceptable solubilising agent (for example a polyethoxylated castor oil), and a pharmaceutically acceptable organic solvent (such as ethanol), characterized in that the pH of the solution has been adjusted to a pH less than 8.1, preferably into the range 1 to 8 by addition of an acid.
  • a pharmaceutically acceptable solubilising agent for example a polyethoxylated castor oil
  • a pharmaceutically acceptable organic solvent such as ethanol
  • Acids in the form of powders for example citric acid, are preferred over those which contain water, for example sulphuric acid.
  • the most preferred acid for use in accordance with the present invention is anhydrous citric acid but a wide range of acids may be used including the following: Citric acid - Monohydrous
  • taxol Due to its limited solubility in water, taxol is usually prepared and administered in a vehicle containing cremophor EL (a polyethoxylated castor oil which acts as a solubiliser) and ethanol.
  • a solution prepared by the formulation as stated in the NCI Taxol Clinical brochure has a pH of 9.1.
  • the invention essentially teaches addition of an acid to a taxol formulation to adjust its pH into the range below 8.1, preferably 1 to 8, and more preferably 5 to 7.5.
  • Citric acid was dissolved in ethanol (absolute alcohol), using a ratio of 8 mis of absolute alcohol to 1 gram of citric acid, and the solution was stirred for fifteen (15) minutes.
  • Cremophor EL was weighed out into the main mixing vessel.
  • Solution 1 was added to solution 2, and the container used for solution 2 was washed with a minimum quantity of absolute alcohol to ensure complete transfer of the citric acid.
  • Solution 3 was mixed and bubbled with nitrogen for at least 15 minutes.
  • the taxol was weighed out and slurried using absolute alcohol, using a ratio of 8 ml of absolute alcohol to 1 gm of taxol.
  • the slurried taxol was added to solution 3 and the slurrying vessel was washed with a minimum quantity of absolute alcohol.
  • Solution 3 was adjusted to 75% of required volume using absolute alcohol, and thoroughly stirred for at least 45 minutes until completely dissolved. Once completely dissolved, the volume was made up with absolute alcohol and the final solution stirred for 5 minutes.
  • Citric Acid (Anhydrous) 2.O g Taxol 6.Omg Absolute Alcohol to 1.0OmL
  • Cremophor EL 0.5mL Taxol 6mg
  • the solution was filled into clear type 1 glass 5mL vials and sealed with rubber bungs.
  • the solution was stored at 40°C for 7 days.
  • citric acid which is preferably used in the anhydrous form, at pH 5 to 7.5, the formulation at pH 6.1 showing the lowest levels for both total and individual major impurities.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Dermatology (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

An injectable solution of taxol of improved stability has a pH less than 8.1, preferably 1 to 8, more preferably 5 to 7.5. The pH is adjusted by addition of an acid, preferably citric acid, and the preferred composition comprises taxol, Cremophor EL (TM), citric acid and ethanol.

Description

INJECTABLETAXOLCOMPOSITION This invention relates to a solution of taxol having improved stability.
BACKGROUND OF THE INVENTION Taxol is a compound extracted from the bark of a western yew, Taxus brev±folxa and known for its antineoplastic activity. It is described for example in the Merck Index, Eleventh Edition 1989, monograph 9049.
In 1977, taxol was chosen for development as an antineoplastic agent because of its unique mechanism of action and good cytotoxic activity against IP. implanted bl6 melanoma and the human MX-1 mammary tumor xenograft. Taxol is believed to function as a mitotic spindle poison and as a potent inhibitor of cell replication in vitro. Other mitotic spindle poisons (colchicine and podophyllotoxin) inhibit microtubule assembly. Taxol employs a different mechanism of action since it appears to shift the equilibrium of polymerization/depolymerization toward polymer assembly and to stabilize microtubules against depolymerization under conditions which would cause rapid disaggregation of microtubules. The interference with the polymerization/depolymerization cycle in cells appears to interfere with both the replication and migration of cells. After extensive preclinical screening in mouse tumor models, taxol entered clinical trials in 1983. Over the past few years, taxol has demonstrated good response rates in treating both ovarian and breast cancer patients who were not benefiting from vinca alkaloid or cisplatin therapy. It has also shown encouraging results in patients with other types of cancer including lung, melanoma, lymphoma, head and neck.
For further information, reference may be made to the U.S. National Cancer Institute (NCI) Clinical Brochure for Taxol, revised July 1991, and papers presented at the Second National Cancer Institute Workshop on Taxol and Taxus held in Alexandria, Virginia USA on September 23-24, 1992.
BRIEF DESCRIPTION OF THE INVENTION
A known formulation contains taxol, cremophor EL (a polyethoxylated castor oil which acts as a solubilizer) and ethanol. It is a disadvantage of the known formulation that the taxol therein degrades, unless stored at or below 8°C, with the result that the shelf life of the formulation is unsatisfactory, and there is therefore a need for a taxol solution of improved stability.
Accordingly, .in" a general aspect the invention provides a solution containing taxol, a pharmaceutically acceptable solubilising agent (for example a polyethoxylated castor oil), and a pharmaceutically acceptable organic solvent (such as ethanol), characterized in that the pH of the solution has been adjusted to a pH less than 8.1, preferably into the range 1 to 8 by addition of an acid.
Acids in the form of powders, for example citric acid, are preferred over those which contain water, for example sulphuric acid. The most preferred acid for use in accordance with the present invention is anhydrous citric acid but a wide range of acids may be used including the following: Citric acid - Monohydrous
Citric acid - Anhydrous Citric acid - Hydrous Acetic acid Formic acid Ascorbic acid
Aspartic acid Benzene sulphonic acid Benzoic acid Hydrochloric acid Sulphuric acid
Phosphoric acid Nitric acid Tartaric acid Diatrizoic acid Glutamic acid Lactic acid
Maleic acid Succinic acid
DETAILED DESCRIPTION OF THE INVENTION
Due to its limited solubility in water, taxol is usually prepared and administered in a vehicle containing cremophor EL (a polyethoxylated castor oil which acts as a solubiliser) and ethanol. A solution prepared by the formulation as stated in the NCI Taxol Clinical brochure (the known formulation) has a pH of 9.1. As indicated above, the invention essentially teaches addition of an acid to a taxol formulation to adjust its pH into the range below 8.1, preferably 1 to 8, and more preferably 5 to 7.5.
In a preferred procedure adopted by the applicant, which it will be clearly understood is non- limiting, the following steps were carried out:-
Mixing Instructions SOLUTION 1
Citric acid was dissolved in ethanol (absolute alcohol), using a ratio of 8 mis of absolute alcohol to 1 gram of citric acid, and the solution was stirred for fifteen (15) minutes.
SOLUTION 2
Cremophor EL was weighed out into the main mixing vessel.
SOLUTION 3
Solution 1 was added to solution 2, and the container used for solution 2 was washed with a minimum quantity of absolute alcohol to ensure complete transfer of the citric acid. Solution 3 was mixed and bubbled with nitrogen for at least 15 minutes. The taxol was weighed out and slurried using absolute alcohol, using a ratio of 8 ml of absolute alcohol to 1 gm of taxol. The slurried taxol was added to solution 3 and the slurrying vessel was washed with a minimum quantity of absolute alcohol. Solution 3 was adjusted to 75% of required volume using absolute alcohol, and thoroughly stirred for at least 45 minutes until completely dissolved. Once completely dissolved, the volume was made up with absolute alcohol and the final solution stirred for 5 minutes.
EXAMPLE 1
A solution was prepared with the following formulation:
Formulation: (Sample 1) Cremophor EL 0.5mL
Citric Acid (Anhydrous) 2.O g Taxol 6.Omg Absolute Alcohol to 1.0OmL
The pH of this solution was determined as 6.1.
The stability of this sample was compared with a sample prepared by the formulation stated in the NCI Taxol Clinical brochure (as follows) which had a pH of 9.1. (Sample 2)
Sam le 2 er mL
Figure imgf000006_0001
The solutions were filled into clear type 1 glass 5mL vials and sealed with rubber bungs. The solutions were stored at 40°C for 7 (seven) days and the stability results are shown as follows:-
PH
Potency
Major individual impurity
Total impurities
Figure imgf000007_0001
Clearly Sample 1 showed significantly increased stability over Sample 2.
EXAMPLE 2
A solution was prepared with the following formulation:
Formulation - Sample 3
Cremophor EL 0.5mL Taxol 6mg
Absolute alcohol to lmL pH adjusted to 6.6 with 1.0M Acetic Acid.
The solution was filled into clear type 1 glass 5mL vials and sealed with rubber bungs. The solution was stored at 40°C for 7 days.
The stability results obtained are compared to those seen with Sample 2.
Figure imgf000007_0002
Again the significantly superior stability of the formulation according to the invention (Sample 3) is evident. FURTHER TRIALS
The following Tables 1, 2 and 3 summarise further trials in which formulations containing Cremophor EL, Taxol and absolute alcohol were brought to the specified pH levels by addition of the specified acids, and tested for stability at 40°C over 4 weeks.
TABLE 1 - TOTAL IMPURITIES (BY HPLC AREA NORMALISATION)
Figure imgf000008_0001
anhydrous TABLE 2 - MAJOR IMPURITIES (BY HPLC AREA NORMALISATION)
Figure imgf000009_0001
TABLE 3 - POTENCY (HPLC)
Figure imgf000009_0002
It is clear that the best performance is achieved by citric acid, which is preferably used in the anhydrous form, at pH 5 to 7.5, the formulation at pH 6.1 showing the lowest levels for both total and individual major impurities.
It will be clearly understood that the invention in its general aspects is not limited to the specific details referred to hereinabove.

Claims

CLAIMS :
1. A composition comprising taxol, a pharmaceutically acceptable solubilising agent, an acid and a pharmaceutically acceptable organic solvent, said composition having a pH less than 8.1.
2. A composition according to claim 1 comprising taxol, a polyethoxylated castor oil, an acid and ethanol, said composition having a pH in the range 1 to 8.
3. A .composition according to claim 2 having a pH in the range 5 to 7.5.
4. A composition according to claim 2 having a pH in the range 5 to 7.
5. A composition according to claim 4 having a pH of about 6.1.
6. A composition according to claim 2 in which the acid is chosen from the group consisting of:
Citric acid - Monohydrous
Citric acid - Anhydrous
Citric acid - Hydrous Acetic acid
Formic acid
Ascorbic acid
Aspartic acid
Benzene sulphonic acid Benzoic acid
Hydrochloric acid
Sulphuric acid
Phosphoric acid
Nitric acid Tartaric acid
Diatrizoic acid Glutamic acid Lactic acid Maleic acid Succinic acid
7. A composition according to claim 6 in which the acid is citric acid.
8. A composition according to claim 2 in which the polyethoxylated castor oil is Cremophor EL (TM) .
9. A method of formulating an injectable taxol solution of improved stability which comprises the following steps:
(a) mixing acid with a carrier material to form a first solution
(b) mixing taxol with the first solution to form a taxol solution having a pH of less than 8.1.
10. A method according to claim 9 wherein the carrier is ethanol.
11. A method according to claim 10 wherein polyethoxylated castor oil is included as a solubilizer.
12. An injectable composition comprising taxol,
Cremophor EL (TM), citric acid and ethanol having a pH in the range 1 to 8.
13. An injectable composition according to claim 12 having a pH in the range 5 to 7.5.
14. An injectable composition according to claim 13 having a pH in the range 5 to 7.
15. An injectable composition according to claim 14 having a pH about 6.1.
16. A method of formulating an injectable taxol solution of improved stability which comprises the following steps:
(a) dissolving anhydrous citric acid in ethanol to form a first solution
(b) mixing Cremophor EL (TM) with the first solution to form a second solution
(c) mixing taxol with ethanol to form a slurry
(d) mixing the slurry with the second solution to form a third solution
(e) adding ethanol to make up the volume of the third solution to form an injectable solution having a pH from 5 to 7.5.
17. A method according to claim 16 wherein the pH of the injectable solution is from 5 to 7.
18. A method according to claim 17 wherein the pH of the injectable solution is about 6.1.
PCT/AU1993/000599 1992-11-27 1993-11-25 Injectable taxol composition WO1994012198A1 (en)

Priority Applications (1)

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AUPL6074 1992-11-27
AUPL607492 1992-11-27

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CN (2) CN1096673A (en)
AU (1) AU5553894A (en)
IL (2) IL107776A0 (en)
IN (1) IN176188B (en)
NZ (1) NZ258044A (en)
WO (1) WO1994012198A1 (en)
ZA (1) ZA938844B (en)

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FR2710534A1 (en) * 1994-09-28 1995-04-07 Bristol Myers Squibb Co Stabilisation solvent, pharmaceutical composition containing it and process for preparing it
EP0674510A4 (en) * 1992-11-27 1995-08-12 Napro Biotherapeutics Inc Injectable composition.
NL9500340A (en) * 1995-02-22 1996-10-01 Yew Tree Pharmaceuticals B V Stabilized paclitaxel solution and pharmaceutical preparation containing said solution
ES2095802A1 (en) * 1993-09-29 1997-02-16 Bristol Myers Squibb Co Stabilized pharmaceutical composition and stabilizing solvent.
US5686488A (en) * 1995-08-25 1997-11-11 Alcon Laboratories, Inc. Polyethoxylated castor oil products as anti-inflammatory agents
WO1997041850A1 (en) * 1996-05-02 1997-11-13 Yeong Wook Song Paclitaxel for the treatment of rheumatic diseases
EP0876145A1 (en) * 1995-12-21 1998-11-11 Genelabs Technologies, Inc. Taxane composition and method
WO1998053810A1 (en) * 1997-05-30 1998-12-03 Man Woo Han Pharmaceutical injection solution containing taxol
WO1998057630A1 (en) * 1997-06-13 1998-12-23 Laboratoires Thissen (L.T.B.) Pharmaceutical form for administering paclitaxel, method for preparing a ready-for-use paclitaxel composition and thereof
US6045808A (en) * 1997-01-31 2000-04-04 Pharmacia & Upjohn Company Method for removing high boiling solvents from drug formulations by vacuum drying
WO2000032186A2 (en) * 1998-12-02 2000-06-08 Mylan Pharmaceuticals, Inc. Stabilized injectable pharmaceutical compositions containing taxoid anti-neoplastic agents
KR100330373B1 (en) * 1996-05-28 2002-11-07 주식회사한국신약 Pharmaceutical composition for injection containing taxol
KR100358934B1 (en) * 1996-09-13 2003-01-29 주식회사한국신약 Pharmaceutical composition of injection containing taxol for
WO2003022247A1 (en) * 2001-09-10 2003-03-20 Choongwae Pharma Corporation Injectable composition of paclitaxel
US6919370B2 (en) 2000-11-28 2005-07-19 Transform Pharmaceuticals, Inc. Pharmaceutical formulations comprising paclitaxel, derivatives, and pharmaceutically acceptable salts thereof
JP2005534656A (en) * 2002-06-10 2005-11-17 プリヴァ−ラチェマ アー．エス． Stabilized pharmaceutical composition based on polyoxyethylated castor oil and process for its production
EP1904052A1 (en) * 2005-06-17 2008-04-02 Hospira Australia Pty Ltd Liquid pharmaceutical formulations of docetaxel
JP2012072188A (en) * 2002-06-26 2012-04-12 Medigene Ag Method for producing cationic liposome comprising lipophilic compound
US9308180B2 (en) 2005-08-31 2016-04-12 Abraxis Bioscience, Llc Compositions and methods for preparation of poorly water soluble drugs with increased stability
US11529441B2 (en) 2015-09-15 2022-12-20 W. L. Gore & Associates, Inc. Drug composition and coating

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE19536165A1 (en) * 1995-09-28 1997-04-03 Basf Ag Process for cleaning alkoxylated fats
CN1101677C (en) * 1997-05-30 2003-02-19 韩万愚 Pharmaceutical injection solution containing taxol
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CN103432109B (en) * 2013-09-01 2015-09-23 吴静 The pharmaceutical composition of paclitaxel

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1990010443A1 (en) * 1989-03-09 1990-09-20 University Of Kansas Derivatives of taxol, pharmaceutical compositions thereof and methods for the preparation thereof
EP0428376A1 (en) * 1989-11-14 1991-05-22 Florida State University Method for preparation of taxol using an oxazinone
EP0505047A1 (en) * 1991-03-18 1992-09-23 Virginia Tech Intellectual Properties, Inc. Rearranged taxol compounds and method of using in testing of in vivo activity
US5157049A (en) * 1988-03-07 1992-10-20 The United States Of America As Represented By The Department Of Health & Human Services Method of treating cancers sensitive to treatment with water soluble derivatives of taxol
AU1888792A (en) * 1991-04-19 1992-11-17 University Of Mississippi, The Methods and compositions for isolating taxanes

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2601675B1 (en) * 1986-07-17 1988-09-23 Rhone Poulenc Sante TAXOL DERIVATIVES, THEIR PREPARATION AND THE PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
NZ224497A (en) * 1987-05-18 1990-04-26 Janssen Pharmaceutica Nv Pharmaceutical composition comprising flunarizine

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5157049A (en) * 1988-03-07 1992-10-20 The United States Of America As Represented By The Department Of Health & Human Services Method of treating cancers sensitive to treatment with water soluble derivatives of taxol
WO1990010443A1 (en) * 1989-03-09 1990-09-20 University Of Kansas Derivatives of taxol, pharmaceutical compositions thereof and methods for the preparation thereof
EP0428376A1 (en) * 1989-11-14 1991-05-22 Florida State University Method for preparation of taxol using an oxazinone
EP0505047A1 (en) * 1991-03-18 1992-09-23 Virginia Tech Intellectual Properties, Inc. Rearranged taxol compounds and method of using in testing of in vivo activity
AU1888792A (en) * 1991-04-19 1992-11-17 University Of Mississippi, The Methods and compositions for isolating taxanes

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US6306894B1 (en) 1992-11-27 2001-10-23 Napro Biotherapeutics, Inc. Injectable composition
EP0674510A4 (en) * 1992-11-27 1995-08-12 Napro Biotherapeutics Inc Injectable composition.
EP0674510A1 (en) * 1992-11-27 1995-10-04 Napro Biotherapeutics, Inc. Injectable composition
US6140359A (en) * 1992-11-27 2000-10-31 Napro Biotherapeutics, Inc. Injectable composition
EP1500393A1 (en) * 1992-11-27 2005-01-26 Mayne Pharma (USA) Inc. Injectable composition containing taxol
EP1384474A1 (en) * 1992-11-27 2004-01-28 Napro Biotherapeutics, Inc. Injectable composition containing taxol
US5977164A (en) * 1992-11-27 1999-11-02 Napro Biotherapeutics, Inc. Stabilized pharmaceutical composition
EP0835657A1 (en) * 1992-11-27 1998-04-15 Napro Biotherapeutics, Inc. Injectable composition
US5972992A (en) * 1992-11-27 1999-10-26 Napro Biotherapeutics, Inc. Injectable composition
ES2095802A1 (en) * 1993-09-29 1997-02-16 Bristol Myers Squibb Co Stabilized pharmaceutical composition and stabilizing solvent.
FR2710534A1 (en) * 1994-09-28 1995-04-07 Bristol Myers Squibb Co Stabilisation solvent, pharmaceutical composition containing it and process for preparing it
NL9500340A (en) * 1995-02-22 1996-10-01 Yew Tree Pharmaceuticals B V Stabilized paclitaxel solution and pharmaceutical preparation containing said solution
US5686488A (en) * 1995-08-25 1997-11-11 Alcon Laboratories, Inc. Polyethoxylated castor oil products as anti-inflammatory agents
EP0876145A4 (en) * 1995-12-21 1999-04-21 Genelabs Tech Inc Taxane composition and method
EP0876145A1 (en) * 1995-12-21 1998-11-11 Genelabs Technologies, Inc. Taxane composition and method
WO1997041850A1 (en) * 1996-05-02 1997-11-13 Yeong Wook Song Paclitaxel for the treatment of rheumatic diseases
KR100330373B1 (en) * 1996-05-28 2002-11-07 주식회사한국신약 Pharmaceutical composition for injection containing taxol
KR100358934B1 (en) * 1996-09-13 2003-01-29 주식회사한국신약 Pharmaceutical composition of injection containing taxol for
US6045808A (en) * 1997-01-31 2000-04-04 Pharmacia & Upjohn Company Method for removing high boiling solvents from drug formulations by vacuum drying
WO1998053810A1 (en) * 1997-05-30 1998-12-03 Man Woo Han Pharmaceutical injection solution containing taxol
BE1011216A3 (en) * 1997-06-13 1999-06-01 Thissen En Abrege L T B Lab Pharmaceutical form for the administration of paclitaxel, method of preparation of a composition paclitaxel ready to employment and use thereof.
WO1998057630A1 (en) * 1997-06-13 1998-12-23 Laboratoires Thissen (L.T.B.) Pharmaceutical form for administering paclitaxel, method for preparing a ready-for-use paclitaxel composition and thereof
WO2000032186A3 (en) * 1998-12-02 2000-11-16 Mylan Pharmaceuticals Inc Stabilized injectable pharmaceutical compositions containing taxoid anti-neoplastic agents
WO2000032186A2 (en) * 1998-12-02 2000-06-08 Mylan Pharmaceuticals, Inc. Stabilized injectable pharmaceutical compositions containing taxoid anti-neoplastic agents
US6919370B2 (en) 2000-11-28 2005-07-19 Transform Pharmaceuticals, Inc. Pharmaceutical formulations comprising paclitaxel, derivatives, and pharmaceutically acceptable salts thereof
US7186751B2 (en) 2001-09-10 2007-03-06 Choongwae Pharma Corporation Injectable composition of paclitaxel
KR100774366B1 (en) * 2001-09-10 2007-11-08 주식회사 중외제약 Injectable composition of paclitaxel
WO2003022247A1 (en) * 2001-09-10 2003-03-20 Choongwae Pharma Corporation Injectable composition of paclitaxel
JP2005534656A (en) * 2002-06-10 2005-11-17 プリヴァ−ラチェマ アー．エス． Stabilized pharmaceutical composition based on polyoxyethylated castor oil and process for its production
JP2012072188A (en) * 2002-06-26 2012-04-12 Medigene Ag Method for producing cationic liposome comprising lipophilic compound
EP1904052A1 (en) * 2005-06-17 2008-04-02 Hospira Australia Pty Ltd Liquid pharmaceutical formulations of docetaxel
EP2138164A1 (en) * 2005-06-17 2009-12-30 Hospira Australia Pty Ltd Liquid pharmaceutical formulations of docetaxel
EP2308467A3 (en) * 2005-06-17 2011-06-22 Hospira Australia Pty Ltd Liquid pharmaceutical formulations of docetaxel
EP1904052A4 (en) * 2005-06-17 2008-12-10 Hospira Australia Pty Ltd Liquid pharmaceutical formulations of docetaxel
US9308180B2 (en) 2005-08-31 2016-04-12 Abraxis Bioscience, Llc Compositions and methods for preparation of poorly water soluble drugs with increased stability
US11529441B2 (en) 2015-09-15 2022-12-20 W. L. Gore & Associates, Inc. Drug composition and coating

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CN1096673A (en) 1994-12-28
ZA938844B (en) 1994-08-02
AU5553894A (en) 1994-06-22
AU5196793A (en) 1994-06-09
KR100371062B1 (en) 2003-04-21
NZ258044A (en) 1995-12-21
IL126178A0 (en) 1999-05-09
CN1095266A (en) 1994-11-23
IL107776A0 (en) 1994-02-27
IN176188B (en) 1996-02-24
CN1047305C (en) 1999-12-15
AU667142B2 (en) 1996-03-07

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