CA2308082A1 - Injectable compostion - Google Patents

Injectable compostion Download PDF

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Publication number
CA2308082A1
CA2308082A1 CA002308082A CA2308082A CA2308082A1 CA 2308082 A1 CA2308082 A1 CA 2308082A1 CA 002308082 A CA002308082 A CA 002308082A CA 2308082 A CA2308082 A CA 2308082A CA 2308082 A1 CA2308082 A1 CA 2308082A1
Authority
CA
Canada
Prior art keywords
acid
composition
matter
taxol
pharmaceutical formulation
Prior art date
Legal status (The legal status 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 status listed.)
Abandoned
Application number
CA002308082A
Other languages
French (fr)
Inventor
Paul Handreck
Robyn Elliott
Timothy R. Prout
David R. Carver
Hernita Ewald
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Tapestry Pharmaceuticals Inc
Original Assignee
Paul Handreck
Robyn Elliott
Timothy R. Prout
David R. Carver
Hernita Ewald
Napro Biotherapeutics, Inc.
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
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=25644377&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=CA2308082(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Paul Handreck, Robyn Elliott, Timothy R. Prout, David R. Carver, Hernita Ewald, Napro Biotherapeutics, Inc. filed Critical Paul Handreck
Publication of CA2308082A1 publication Critical patent/CA2308082A1/en
Abandoned legal-status Critical Current

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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
    • 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
    • A61K31/337—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
    • 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
    • A61K47/06—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
    • A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
    • 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

Abstract

A composition of taxol and polyethoxylated castor oil is pH balanced to have a pH less than 8.1 to improve stability. This composition can include an acid, preferably citric acid, to adjust the pH value.
The invention includes a method of formulating a taxol solution for injection by mixing an acid with a carrier material, such as castor oil, to form a carrier solution after which taxol is mixed with the carrier solution to form the taxol solution at a pH of less than 8.1. The method may include the step of slurrying the taxol in alcohol before mixing with the carrier solution.

Description

INJECTABLE COMPOSITION
This invention relates to a solution of taxol having improved stability.
This application is a division of copending Canadian Patent Application No. 2,149,150 filed November 18, 1993.
Taxol is a compound extracted from the bark of a western yew, Taxus brevifolia and known for its antineoplastic activity. It is described for example in The Merck Index, Eleventh Edition 1989, monograph 9049. "TAXOL" is a registered trade-mark for the substance paclitaxel.
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 D16 melanoma and the human X-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 points (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.
5 For further information, reference may be made to the U.S. National Cancer Institute's 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.
It is a disadvantage of a known formulation that the taxol therein degrades, 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.
In accordance with one aspect of the invention claimed in the parent application, there is provided an improvement in a pharmaceutical formulation adapted for use in treating cancer comprising taxol and polyethoxylated castor oil, the improvement comprising an acidifying agent added to the pharmaceutical formulation in a proportion such that the composition has a resulting pH less than or equal to 7Ø
In accordance with an aspect of the present invention, there is provided an article of manufacture comprising a sealable container and a pharmaceutical formulation contained therein, the pharmaceutical formulation comprising taxol; a pharmaceutically acceptable carrier; and an acid in sufficient amount to improve the stability of the taxol such that at least 95% of the taxol potency is retained when the composition is stored at 40°C for seven days; and wherein said pharmaceutical formulation has been sealed in said container for at least seven days.
In accordance with another aspect of the present invention, there is provided a composition of matter produced by the process of (a) obtaining a sealable container; (b) obtaining a pharmaceutical formulation comprising taxol, a pharmaceutically-acceptable carrier, and an acid in sufficient amount to improve the stability of the taxol such that at least 95% of the taxol potency is retained when the composition is stored at 40°C for seven days; (c) placing said pharmaceutical formulation in said sealable container;
(d) sealing said sealable container; and (e) storing said pharmaceutical formulation in said sealed container for at least seven days.
In accordance with an additional aspect of the present invention, there is provided a composition of matter comprising a sealable container and a pharmaceutical formulation contained therein, said pharmaceutical formulation comprising taxol; a pharmaceutically-acceptable carrier; and an acid, said formulation being such that at least 95% of the taxol potency is retained when said formulation is stored at 40°C for seven days; and wherein said pharmaceutical formulation has been sealed in said container for at least seven days.
In accordance with a further aspect of the present invention, there is provided a composition of matter produced by the process of (a) obtaining a sealable container; (b) obtaining a pharmaceutical formulation comprising taxol, a pharmaceutically-acceptable carrier, and an acid, said formulation being such that at least 95% of the taxol potency is retained when said formulation is stored at 40°C for seven days; (c) placing said pharmaceutical formulation in said sealable container; (d) sealing said sealable container; and (e) storing said pharmaceutical formulation in said sealed container for at least seven days.
Accordingly, in a general aspect the invention provides a solution containing taxol, cremophor ELTM
and ethanol, characterized in that the pH of the solution has been adjusted 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 sulfuric acid . The most preferred acid for use in accordance with the present invention is 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 Malefic acid Succinic acid 5 Due to its limited solubility in water, Taxol is usually prepared and administered in a vehicle containing cremophor ELTM (a polyethoxylated castor oil which acts as a solubilizer) and ethanol. A
commercially available solution supplied by Bristol-Myers Squibb (BMS) is formulated with these components and 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 1 to 8, preferably 5 to 7.
In a preferred procedure adopted by the applicant, which it will be clearly understood is non-limiting, the following steps were carried out:
Mixina Instructions Citric acid was dissolved in absolute alcohol, using a ratio of 8 mls of absolute alcohol to 1 gram of citric acid, and the solution was stirred for fifteen (15) minutes.

Cremophor EL was weighted 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 5 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 checked and made up as necessary with absolute alcohol and the final solution stirred for 5 minutes.
Exam~l a 1 A solution was prepared with the following formulation:
Formulation: (Sample 1) Cremophor EL 0.5 mL
Citric Acid (Anhydrous) 2.0 mg Taxol 6.0 mg Absolute Alcohol to 1.0 mL
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) Sample 2 per mL
Taxol 6 mg Cremophor EL 0.5 mL
Absolute Alcohol to 1 mL
The solutions were filled into clear type 1 glass 5 mL vials and sealed with rubber bungs.
The solutions were stored at 40°C for 7 (seven) days and the stability results are shown in Table 1.
Sample 1 Sample 2 pH 6.2 9.0 Potency 96.6 86.7 Major individual 0.3% 5.1% impurity Total impurities 2.0% 12.2%
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 0.5 mL
Taxol 6.0 mg Absolute Ethanol to 1 mL
pH adjusted to 6.6 with 1.OM Acetic Acid.
The solution was filled into clear type I glass 5 mL 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.
Sample 3 Sample 2 pH 6.7 9.0 Potency 97.5 86.7 Major individual 0.3% 5.1% impurity Total impurities 2.3% 12.2%
Again the significantly superior stability of the formulation according to the invention (Sample 3) is evident.
It will be clearly understood that the invention in its general aspects is not limited to the specific details referred to hereinabove.

Claims (40)

1. An article of manufacture comprising a sealable container and a pharmaceutical formulation contained therein, said pharmaceutical formulation comprising taxol; a pharmaceutically-acceptable carrier; and an acid in sufficient amount to improve the stability of the taxol such that at least 95% of the taxol potency is retained when the composition is stored at 40°C for seven days and wherein said pharmaceutical formulation has been sealed in said container for at least seven days.
2. The article of manufacture of claim 1, wherein said pharmaceutical formulation has a pH between 5 and 7, inclusive.
3. The article of manufacture of claim 1 or 2, further comprising ethanol as a constituent thereof.
4. The article of manufacture of any one of claims 1 to 3, wherein said pharmaceutically-acceptable carrier is polyethoxylated caster oil.
5. The article of manufacture of any one of claims 1 to 4, wherein said pharmaceutical formulation is anhydrous.
6. The article of manufacture of any one of claims 1 to 5, wherein said acid is a mineral acid.
7. The article of manufacture of any one of claims 1 to 5, wherein said acid is an organic acid.
8. The article of manufacture of any one of claims 1 to 5, wherein said acid is acetic acid.
9. The article of manufacture of any one of claims 1 to 5, wherein said acid is citric acid.
10. The article of manufacture of claim 9, wherein said citric acid is anhydrous.
11. A composition of matter produced by the process of:
(a) obtaining a sealable container;
(b) obtaining a pharmaceutical formulation comprising taxol, a pharmaceutically-acceptable carrier, and an acid in sufficient amount to improve the stability of the taxol such that at least 95% of the taxol potency is retained when the composition is stored at 40°C for seven days;
(c) placing said pharmaceutical formulation in said sealable container;
(d) sealing said sealable container; and (e) storing said pharmaceutical formulation in said sealed container for at least seven days.
12. The composition of matter of claim 11, wherein said pharmaceutical formulation has a pH between 5 and 7, inclusive.
13. The composition of matter of claim 11 or 12, further comprising ethanol as a constituent thereof.
14. The composition of matter of any one of claims 11 to 13, wherein said pharmaceutically-acceptable carrier is polyethoxylated caster oil.
15. The composition of matter of any one of claims 11 to 14, wherein said pharmaceutical formulation is anhydrous.
16. The composition of matter of any one of claims 11 to 15, wherein said acid is mineral acid.
17. The composition of matter of any one of claims 11 to 15, wherein said acid is an organic acid.
18. The composition of matter of any one of claims 11 to 15, wherein said acid is acetic acid.
19. The composition of matter of any one of claims 11 to 15, wherein said acid is citric acid.
20. The composition of matter of claim 19, wherein said citric acid is anhydrous.
21. A composition of matter comprising a sealable container and a pharmaceutical formulation contained therein, said pharmaceutical formulation comprising taxol; a pharmaceutically-acceptable carrier; and an acid, said formulation being such that at least 95% of the taxol potency is retained when said formulation is stored at 40°C for seven days; and wherein said pharmaceutical formulation has been sealed in said container for at least seven days.
22. The composition of matter of claim 21, wherein said pharmaceutical formulation has a pH between 5 and 7, inclusive.
23. The composition of matter of claim 21 or 22, further comprising ethanol as a constituent thereof.
24. The composition of matter of any one of claims 21 to 23, wherein said pharmaceutically-acceptable carrier is polyethoxylated caster oil.
25. The composition of matter of any one of claims 21 to 24, wherein said pharmaceutical formulation is anhydrous.
26. The composition of matter of any one of claims 21 to 25, wherein said acid is mineral acid.
27. The composition of matter of any one of claims 21 to 25, wherein said acid is an organic acid.
28. The composition of matter of any one of claims 21 to 25, wherein said acid is acetic acid.
29. The composition of matter of any one of claims 21 to 25, wherein said acid is citric acid.
30. The composition of matter of claim 29, wherein said citric acid is anhydrous.
31. A composition of matter produced by the process of:
(a) obtaining a sealable container;
(b) obtaining a pharmaceutical formulation comprising taxol, a pharmaceutically-acceptable carrier, and an acid, said formulation being such that at least 95% of the taxol potency is retained when said formulation is stored at 40°C for seven days;
(c) placing said pharmaceutical formulation in said sealable container;
(d) sealing said sealable container; and (e) storing said pharmaceutical formulation in said sealed container for at least seven days.
32. The composition of matter of claim 31, wherein said pharmaceutical formulation has a pH between 5 and 7, inclusive.
33. The composition of matter of claim 31 or 32, further comprising ethanol as a constituent thereof.
34. The composition of matter of any one of claims 31 to 33, wherein said pharmaceutically-acceptable carrier is polyethoxylated caster oil.
35. The composition of matter of any one of claims 31 to 34, wherein said pharmaceutical formulation is anhydrous.
36. The composition of matter of any one of claims 31 to 35, wherein said acid is mineral acid.
37. The composition of matter of any one of claims 31 to 35, wherein said acid is an organic acid.
38. The composition of matter of any one of claims 31 to 35, wherein said acid is acetic acid.
39. The composition of matter of any one of claims 31 to 35, wherein said acid is citric acid.
40. The composition of matter of claim 39, wherein said citric acid is anhydrous.
CA002308082A 1992-11-27 1993-11-18 Injectable compostion Abandoned CA2308082A1 (en)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
AUPL6074 1992-11-27
AUPL607492 1992-11-27
US99550192A 1992-12-22 1992-12-22
US07/995,501 1992-12-22
CA002149150A CA2149150C (en) 1992-11-27 1993-11-18 Injectable taxol composition with improved stability

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
CA002149150A Division CA2149150C (en) 1992-11-27 1993-11-18 Injectable taxol composition with improved stability

Publications (1)

Publication Number Publication Date
CA2308082A1 true CA2308082A1 (en) 1994-06-09

Family

ID=25644377

Family Applications (2)

Application Number Title Priority Date Filing Date
CA002308082A Abandoned CA2308082A1 (en) 1992-11-27 1993-11-18 Injectable compostion
CA002149150A Expired - Lifetime CA2149150C (en) 1992-11-27 1993-11-18 Injectable taxol composition with improved stability

Family Applications After (1)

Application Number Title Priority Date Filing Date
CA002149150A Expired - Lifetime CA2149150C (en) 1992-11-27 1993-11-18 Injectable taxol composition with improved stability

Country Status (12)

Country Link
US (7) US5733888A (en)
EP (4) EP0674510B1 (en)
JP (1) JP2880292B2 (en)
AT (2) ATE274347T1 (en)
AU (1) AU5612694A (en)
CA (2) CA2308082A1 (en)
DE (2) DE69333605T2 (en)
DK (2) DK0835657T3 (en)
ES (2) ES2119996T3 (en)
GR (1) GR3027724T3 (en)
PT (1) PT835657E (en)
WO (2) WO1994012031A1 (en)

Families Citing this family (105)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ATE274347T1 (en) * 1992-11-27 2004-09-15 Mayne Pharma Usa Inc STABLE INJECTABLE PACLITAXEL SOLUTION
TW406020B (en) * 1993-09-29 2000-09-21 Bristol Myers Squibb Co Stabilized pharmaceutical composition and its method for preparation and stabilizing solvent
FR2710534B1 (en) * 1994-09-28 1996-07-05 Bristol Myers Squibb Co Stabilization solvent, pharmaceutical composition containing it, and process for its preparation.
NL9500340A (en) * 1995-02-22 1996-10-01 Yew Tree Pharmaceuticals B V Stabilized paclitaxel solution and pharmaceutical preparation containing said solution
DE19536165A1 (en) * 1995-09-28 1997-04-03 Basf Ag Process for cleaning alkoxylated fats
US6395770B1 (en) 1995-10-26 2002-05-28 Baker Norton Pharmaceuticals, Inc. Method and compositions for administering taxanes orally to human patients
US6964946B1 (en) * 1995-10-26 2005-11-15 Baker Norton Pharmaceuticals, Inc. Oral pharmaceutical compositions containing taxanes and methods of treatment employing the same
US6245805B1 (en) * 1995-10-26 2001-06-12 Baker Norton Pharmaceuticals, Inc. Method, compositions and kits for increasing the oral bioavailability of pharmaceutical agents
AU724842B2 (en) * 1995-12-21 2000-09-28 Genelabs Technologies, Inc. Taxane composition and method
US6515016B2 (en) 1996-12-02 2003-02-04 Angiotech Pharmaceuticals, Inc. Composition and methods of paclitaxel for treating psoriasis
US20030157187A1 (en) * 1996-12-02 2003-08-21 Angiotech Pharmaceuticals, Inc. Compositions and methods for treating or preventing inflammatory diseases
US6495579B1 (en) 1996-12-02 2002-12-17 Angiotech Pharmaceuticals, Inc. Method for treating multiple sclerosis
CA2275889C (en) 1996-12-30 2008-03-18 Battelle Memorial Institute Formulation and method for treating neoplasms by inhalation
US6727280B2 (en) * 1997-01-07 2004-04-27 Sonus Pharmaceuticals, Inc. Method for treating colorectal carcinoma using a taxane/tocopherol formulation
US6458373B1 (en) * 1997-01-07 2002-10-01 Sonus Pharmaceuticals, Inc. Emulsion vehicle for poorly soluble drugs
US20030105156A1 (en) * 1997-01-07 2003-06-05 Nagesh Palepu Method for administration of a taxane/tocopherol formulation to enhance taxane therapeutic utility
US20030087954A1 (en) * 1997-01-07 2003-05-08 Sonus Pharmaceuticals, Inc. Method of treating bladder carcinoma using a Taxane/Tocopherol formulation
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.
IL131217A0 (en) * 1998-03-10 2001-01-28 Napro Biotherapeutics Inc Novel methods and compositions for delivery of taxanes
US5922754A (en) * 1998-10-02 1999-07-13 Abbott Laboratories Pharmaceutical compositions containing paclitaxel
DE19983660T1 (en) 1998-10-20 2001-09-13 Ben Venue Lab Inc Methods for purifying solvents useful in the manufacture of pharmaceutical compositions
US6071952A (en) * 1998-12-02 2000-06-06 Mylan Pharmaceuticals, Inc. Stabilized injectable pharmaceutical compositions containing taxoid anti-neoplastic agents
US6040330A (en) * 1999-01-08 2000-03-21 Bionumerik Pharmaceuticals, Inc. Pharmaceutical formulations of taxanes
US6410255B1 (en) * 1999-05-05 2002-06-25 Aurora Biosciences Corporation Optical probes and assays
EP1591437B1 (en) 1999-05-14 2009-11-25 Nereus Pharmaceuticals, Inc. Interleukin-1 and tumor necrosis factor-alpha modulators, syntheses of said modulators and methods of using said modulators
DE19925211B4 (en) * 1999-06-01 2006-01-12 PBS Pharmaceutical Bulk Substances SA Kit for the preparation of a formulation of paclitaxel
CO5271755A1 (en) * 2000-01-20 2003-04-30 Baker Norton Pharma PURIFICATION OF POLYOXYETHYLED CASTOR OILS WITH ACTIVATED CARBON
JP2003521545A (en) * 2000-02-02 2003-07-15 フロリダ・ステイト・ユニバーシティ・リサーチ・ファウンデイション・インコーポレイテッド Taxane formulation with improved solubility
WO2001062919A1 (en) 2000-02-23 2001-08-30 Aurora Biosciences Corporation Modified fluorescent proteins
JP4922507B2 (en) * 2000-08-10 2012-04-25 武田薬品工業株式会社 Pharmaceutical composition
AU2001278705A1 (en) 2000-08-10 2002-02-25 Takeda Chemical Industries Ltd. Pharmaceutical composition
AU2002243228B2 (en) * 2000-11-16 2007-08-02 The Regents Of The University Of California Marine actinomycete taxon for drug and fermentation product discovery
EP1337273A2 (en) * 2000-11-28 2003-08-27 Transform Pharmaceuticals, Inc. Pharmaceutical formulations comprising paclitaxel, derivatives, and pharmaceutically acceptable salts thereof
WO2002080940A2 (en) 2001-04-06 2002-10-17 Cytorex Biosciences, Inc. Pharmacologically active strong acid solutions
KR100774366B1 (en) * 2001-09-10 2007-11-08 주식회사 중외제약 Injectable composition of paclitaxel
JP2005515187A (en) * 2001-11-26 2005-05-26 スーパージェン インコーポレイテッド Process for the preparation of pharmaceutical compositions using polyoxyethylated castor oil
AU2002357012A1 (en) * 2001-11-27 2003-06-10 Transform Pharmaceuticals, Inc. Oral pharmaceutical formulations comprising paclitaxel, derivatives and methods of administration thereof
US6476068B1 (en) * 2001-12-06 2002-11-05 Pharmacia Italia, S.P.A. Platinum derivative pharmaceutical formulations
RU2004119557A (en) * 2001-12-20 2005-04-20 Бристол-Маерс Сквибб Компани (Us) PHARMACEUTICAL COMPOSITIONS OF ORAL-ACTIVE DERIVATIVES OF TAXANA WITH INCREASED BIOAVAILABILITY
CZ294371B6 (en) * 2002-06-10 2004-12-15 Pliva - Lachema, A. S. Stabilized pharmaceutical composition based on polyoxyethylated castor oil and process for preparing thereof
US7176232B2 (en) 2002-06-24 2007-02-13 The Regents Of The University Of California Salinosporamides and methods for use thereof
CA2491216C (en) * 2002-06-26 2012-01-03 Medigene Oncology Gmbh Method of producing a cationic liposomal preparation comprising a lipophilic compound
AU2003302721B2 (en) * 2002-08-02 2009-10-08 Beyondspring Pharmaceuticals, Inc. Dehydrophenylahistins and analogs thereof and the synthesis of dehydrophenylahistins and analogs thereof
US7919497B2 (en) * 2002-08-02 2011-04-05 Nereus Pharmaceuticals, Inc. Analogs of dehydrophenylahistins and their therapeutic use
US7935704B2 (en) * 2003-08-01 2011-05-03 Nereus Pharmaceuticals, Inc. Dehydrophenylahistins and analogs thereof and the synthesis of dehydrophenylahistins and analogs thereof
AU2003296908A1 (en) * 2002-09-27 2004-05-04 Nereus Pharmaceuticals, Inc. Macrocyclic lactams
US20040122081A1 (en) * 2002-11-08 2004-06-24 Gogate Uday Shankar Pharmaceutical compositions and methods of using taxane derivatives
WO2004072104A2 (en) * 2003-02-11 2004-08-26 Northwestern University Methods and materials for nanocrystalline surface coatings and attachment of peptide amphiphile nanofibers thereon
EP1638552B1 (en) * 2003-06-20 2011-03-02 Nereus Pharmaceuticals, Inc. Use of (3.2.0) heterocyclic compounds and analogs thereof for the treatment of cancer
ZA200600473B (en) * 2003-06-20 2007-04-25 Univ California Salinosporamides and methods for use thereof
US20050016926A1 (en) * 2003-07-24 2005-01-27 Dabur Research Foundation Stabilized formulation
CA2445420A1 (en) * 2003-07-29 2005-01-29 Invitrogen Corporation Kinase and phosphatase assays
US7619059B2 (en) * 2003-07-29 2009-11-17 Life Technologies Corporation Bimolecular optical probes
US7727752B2 (en) * 2003-07-29 2010-06-01 Life Technologies Corporation Kinase and phosphatase assays
US20050208095A1 (en) * 2003-11-20 2005-09-22 Angiotech International Ag Polymer compositions and methods for their use
WO2005061474A1 (en) * 2003-12-12 2005-07-07 Quiral Química Do Brasil Process for the preparation of anhydrous and hydrated active pharmaceutical ingredients (apis); stable pharmaceutical compositions prepared from the same and uses of said compositions
ATE509018T1 (en) * 2004-01-23 2011-05-15 Nereus Pharmaceuticals Inc BISINDOLPYRROLES SUITABLE AS ANTIMICROBIAL AGENT
KR20050099311A (en) * 2004-04-09 2005-10-13 에이엔에이치 케어연구소(주) Composition for injection comprising anticancer drug
US7579371B2 (en) 2004-04-30 2009-08-25 Nereus Pharmaceuticals, Inc. Methods of using [3.2.0] heterocyclic compounds and analogs thereof
AU2005283141B2 (en) 2004-04-30 2012-05-10 Nereus Pharmaceuticals, Inc. (3.2.0) heterocyclic compounds and methods of using the same
US7361683B2 (en) * 2004-11-24 2008-04-22 Yung Shin Pharm. Ind., Co., Ltd Paclitaxel aqueous injection solution and methods for preparing the same
WO2006060676A1 (en) 2004-12-03 2006-06-08 Dana Farber Cancer Institute Compositions and methods for treating neoplastic diseases
WO2006126825A1 (en) * 2005-05-23 2006-11-30 Choongwae Pharma Corporation Composition comprising tetrafluorobenzyl derivatives or salts of thereof for injection
KR20080030024A (en) * 2005-06-17 2008-04-03 호스피라 오스트레일리아 피티와이 리미티드 Liquid pharmaceutical formulations of docetaxel
ATE556046T1 (en) 2005-07-21 2012-05-15 Nereus Pharmaceuticals Inc INTERLEUKIN-1 AND TUMOR NECROSIS FACTOR A MODULATORS, SYNTHESIS OF SUCH MODULATORS AND METHODS USING SUCH MODULATORS
KR101420445B1 (en) 2005-08-31 2014-07-16 아브락시스 바이오사이언스, 엘엘씨 Compositions comprising poorly water soluble pharmaceutical agents and antimicrobial agents
US8034765B2 (en) 2005-08-31 2011-10-11 Abraxis Bioscience, Llc Compositions and methods for preparation of poorly water soluble drugs with increased stability
BRPI0600194A (en) * 2006-01-30 2007-10-23 Quiral Quimica Do Brasil S A docetaxel-containing pharmaceutical compositions and a degradation inhibitor and process for obtaining same
US8129527B2 (en) * 2006-11-03 2012-03-06 Nereus Pharmacuticals, Inc. Analogs of dehydrophenylahistins and their therapeutic use
WO2008095195A2 (en) * 2007-02-02 2008-08-07 Nereus Pharmaceuticals, Inc. Lyophilized formulations of salinosporamide a
FR2912745A1 (en) * 2007-02-19 2008-08-22 Centre Nat Rech Scient NEW INDOLE-DERIVED COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
US20090017167A1 (en) * 2007-07-11 2009-01-15 Herbalife International Inc. Mixture and beverage made therefrom for protecting cellular hydration
US8394816B2 (en) * 2007-12-07 2013-03-12 Irene Ghobrial Methods of using [3.2.0] heterocyclic compounds and analogs thereof in treating Waldenstrom's Macroglobulinemia
KR101053780B1 (en) * 2008-02-29 2011-08-02 동아제약주식회사 Single liquid stable pharmaceutical composition containing docetaxel
WO2009140287A1 (en) 2008-05-12 2009-11-19 Nereus Pharmaceuticals, Inc. Salinosporamide derivatives as proteasome inhibitors
ES2344674B1 (en) * 2008-08-07 2011-06-29 Gp Pharm, S.A. INJECTABLE PHARMACEUTICAL COMPOSITION OF TAXANOS.
US9198968B2 (en) * 2008-09-15 2015-12-01 The Spectranetics Corporation Local delivery of water-soluble or water-insoluble therapeutic agents to the surface of body lumens
US8257722B2 (en) 2008-09-15 2012-09-04 Cv Ingenuity Corp. Local delivery of water-soluble or water-insoluble therapeutic agents to the surface of body lumens
US8128951B2 (en) 2008-09-15 2012-03-06 Cv Ingenuity Corp. Local delivery of water-soluble or water-insoluble therapeutic agents to the surface of body lumens
US8114429B2 (en) 2008-09-15 2012-02-14 Cv Ingenuity Corp. Local delivery of water-soluble or water-insoluble therapeutic agents to the surface of body lumens
TWI438009B (en) * 2010-02-19 2014-05-21 Teikoku Pharma Usa Inc Taxane pro-emulsion formulations and methods making and using the same
SG185389A1 (en) 2010-05-03 2012-12-28 Teikoku Pharma Usa Inc Non-aqueous taxane pro-emulsion formulations and methods of making and using the same
WO2012130819A1 (en) 2011-03-29 2012-10-04 Sanofi Otamixaban formulations with improved stability
CA2841864A1 (en) * 2011-07-11 2013-01-17 Claude MERCURE Novel anti-cancer isocarbostyril alkaloid conjugates
US9956385B2 (en) 2012-06-28 2018-05-01 The Spectranetics Corporation Post-processing of a medical device to control morphology and mechanical properties
JO3685B1 (en) 2012-10-01 2020-08-27 Teikoku Pharma Usa Inc Non-aqueous taxane nanodispersion formulations and methods of using the same
EP2777691A1 (en) 2013-03-14 2014-09-17 Pharmachemie B.V. Taxoid - Purification of Liquid Excipients
JP2016513699A (en) * 2013-03-15 2016-05-16 エピザイム，インコーポレイティド Injection formulation for the treatment of cancer
US10525171B2 (en) 2014-01-24 2020-01-07 The Spectranetics Corporation Coatings for medical devices
EP3628640B1 (en) 2014-09-02 2023-08-09 Hub Therapeutics Methods of making a deuterated or a non-deuterated molecule and pharmaceutical formulations for treatment
US20170290765A1 (en) * 2014-09-17 2017-10-12 Epizyme, Inc. Injectable formulations for treating cancer
US10751317B2 (en) 2014-10-08 2020-08-25 Pacific Northwest Research Institute Methods and compositions for increasing the potency of antifungal agents
JP6904570B2 (en) 2015-03-06 2021-07-21 ビヨンドスプリング ファーマシューティカルズ，インコーポレイテッド How to treat brain tumors
SG11201707127VA (en) 2015-03-06 2017-09-28 Beyondspring Pharmaceuticals Inc Method of treating cancer associated with a ras mutation
CN109516981B (en) 2015-07-13 2019-10-22 大连万春布林医药有限公司 Pune's cloth woods composition
US10561766B2 (en) * 2015-09-15 2020-02-18 W. L. Gore & Associates, Inc. Drug composition and coating
RU2753543C1 (en) 2016-02-08 2021-08-17 Бейондспринг Фармасьютикалс, Инк. Compositions containing tucaresol or analogues thereof
SG11201810872UA (en) 2016-06-06 2019-01-30 Beyondspring Pharmaceuticals Inc Composition and method for reducing neutropenia
US11633393B2 (en) 2017-01-06 2023-04-25 Beyondspring Pharmaceuticals, Inc. Tubulin binding compounds and therapeutic use thereof
KR20190109479A (en) 2017-02-01 2019-09-25 비욘드스프링 파마수티컬스, 인코포레이티드. How to reduce neutropenia
US10226423B1 (en) * 2017-12-20 2019-03-12 RxOMEG Therapeutics LLC Colchicine drug-to-drug interactions
CA3089226A1 (en) 2018-01-24 2019-08-01 Beyondspring Pharmaceuticals, Inc. Composition and method for reducing thrombocytopenia via the administration of plinabulin
MX2020010036A (en) 2018-03-28 2021-03-02 Herbalife Int Of America Inc Acetylation of polysaccharides.
BR112021005104A2 (en) * 2018-10-16 2021-06-08 US Nano Food & Drug INC intratumoral injection formulation
AU2021257738A1 (en) 2020-04-13 2022-05-19 US Nano Food & Drug INC Basic chemotherapeutic intratumour injection formulation

Family Cites Families (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS552421B2 (en) * 1971-08-06 1980-01-19
FR2601675B1 (en) * 1986-07-17 1988-09-23 Rhone Poulenc Sante TAXOL DERIVATIVES, THEIR PREPARATION AND THE PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
US4942184A (en) * 1988-03-07 1990-07-17 The United States Of America As Represented By The Department Of Health And Human Services Water soluble, antineoplastic derivatives of taxol
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
US4960790A (en) * 1989-03-09 1990-10-02 University Of Kansas Derivatives of taxol, pharmaceutical compositions thereof and methods for the preparation thereof
US5136060A (en) * 1989-11-14 1992-08-04 Florida State University Method for preparation of taxol using an oxazinone
KR0158697B1 (en) * 1990-02-15 1998-11-16 어니스트 지. 포스너 Method of frying oil treatment using an alumina and amorphous silica composition
TW223634B (en) * 1991-03-18 1994-05-11 Kingston David G I
FR2678833B1 (en) * 1991-07-08 1995-04-07 Rhone Poulenc Rorer Sa NEW PHARMACEUTICAL COMPOSITIONS BASED ON DERIVATIVES OF THE TAXANE CLASS.
US5254580A (en) * 1993-01-19 1993-10-19 Bristol-Myers Squibb Company 7,8-cyclopropataxanes
ATE274347T1 (en) * 1992-11-27 2004-09-15 Mayne Pharma Usa Inc STABLE INJECTABLE PACLITAXEL SOLUTION
NZ258044A (en) * 1992-11-27 1995-12-21 Faulding F H & Co Ltd Pharmaceutical composition comprising taxol, solubilising agent, an acid and an organic solvent
US5281727A (en) * 1992-11-27 1994-01-25 Napro Biotherapeutics, Inc. Method of using ion exchange media to increase taxane yields
TW406020B (en) * 1993-09-29 2000-09-21 Bristol Myers Squibb Co Stabilized pharmaceutical composition and its method for preparation and stabilizing solvent
US5733388A (en) 1994-08-11 1998-03-31 Daido Tokiushuko Kabushiki Kaisha Steel composition for bearings and method of producing the same

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