CA1289886C - Solutions of oxazaphosphorins having improved stability and process for the preparation thereof - Google Patents
Solutions of oxazaphosphorins having improved stability and process for the preparation thereofInfo
- Publication number
- CA1289886C CA1289886C CA000541835A CA541835A CA1289886C CA 1289886 C CA1289886 C CA 1289886C CA 000541835 A CA000541835 A CA 000541835A CA 541835 A CA541835 A CA 541835A CA 1289886 C CA1289886 C CA 1289886C
- Authority
- CA
- Canada
- Prior art keywords
- oxazaphosphorin
- concentration
- solution according
- solution
- oxazaphosphorins
- 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.)
- Expired - Lifetime
Links
- ZZVDXRCAGGQFAK-UHFFFAOYSA-N 2h-oxazaphosphinine Chemical class N1OC=CC=P1 ZZVDXRCAGGQFAK-UHFFFAOYSA-N 0.000 title claims abstract description 32
- 238000002360 preparation method Methods 0.000 title claims abstract description 11
- 238000000034 method Methods 0.000 title claims abstract description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 31
- 125000001340 2-chloroethyl group Chemical group [H]C([H])(Cl)C([H])([H])* 0.000 claims abstract description 7
- -1 2-methanesulfonyloxy-ethyl Chemical group 0.000 claims abstract description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims abstract description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 4
- 239000001257 hydrogen Substances 0.000 claims abstract description 4
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 4
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 claims description 12
- 229960004397 cyclophosphamide Drugs 0.000 claims description 11
- 229960001101 ifosfamide Drugs 0.000 claims description 11
- HOMGKSMUEGBAAB-UHFFFAOYSA-N ifosfamide Chemical compound ClCCNP1(=O)OCCCN1CCCl HOMGKSMUEGBAAB-UHFFFAOYSA-N 0.000 claims description 11
- 239000002904 solvent Substances 0.000 claims description 6
- 239000000126 substance Substances 0.000 claims description 6
- 239000007795 chemical reaction product Substances 0.000 claims description 4
- 235000013350 formula milk Nutrition 0.000 claims 3
- 239000000243 solution Substances 0.000 description 31
- 238000004090 dissolution Methods 0.000 description 8
- 239000000203 mixture Substances 0.000 description 7
- 239000004480 active ingredient Substances 0.000 description 6
- 238000009472 formulation Methods 0.000 description 5
- 230000000474 nursing effect Effects 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 4
- 238000001802 infusion Methods 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 2
- 241000906446 Theraps Species 0.000 description 2
- 238000007792 addition Methods 0.000 description 2
- 239000003708 ampul Substances 0.000 description 2
- 238000011109 contamination Methods 0.000 description 2
- 230000000875 corresponding effect Effects 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 239000000824 cytostatic agent Substances 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 238000011049 filling Methods 0.000 description 2
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 229940058015 1,3-butylene glycol Drugs 0.000 description 1
- CTPDSKVQLSDPLC-UHFFFAOYSA-N 2-(oxolan-2-ylmethoxy)ethanol Chemical compound OCCOCC1CCCO1 CTPDSKVQLSDPLC-UHFFFAOYSA-N 0.000 description 1
- 241001201743 Aseptis Species 0.000 description 1
- 241001024304 Mino Species 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 239000004809 Teflon Substances 0.000 description 1
- 229920006362 Teflon® Polymers 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 235000019437 butane-1,3-diol Nutrition 0.000 description 1
- 230000000711 cancerogenic effect Effects 0.000 description 1
- 231100000315 carcinogenic Toxicity 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- PWOQRKCAHTVFLB-UHFFFAOYSA-N cyclophosphamide hydrate Chemical compound O.ClCCN(CCCl)P1(=O)NCCCO1 PWOQRKCAHTVFLB-UHFFFAOYSA-N 0.000 description 1
- 230000001085 cytostatic effect Effects 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 239000003978 infusion fluid Substances 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 108010025647 phosphate-binding proteolipid Proteins 0.000 description 1
- UNQNIRQQBJCMQR-UHFFFAOYSA-N phosphorine Chemical compound C1=CC=PC=C1 UNQNIRQQBJCMQR-UHFFFAOYSA-N 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- IOVGROKTTNBUGK-SJCJKPOMSA-N ritodrine Chemical compound N([C@@H](C)[C@H](O)C=1C=CC(O)=CC=1)CCC1=CC=C(O)C=C1 IOVGROKTTNBUGK-SJCJKPOMSA-N 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 239000011800 void material Substances 0.000 description 1
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
- A61K9/08—Solutions
-
- 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
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/66—Phosphorus compounds
- A61K31/675—Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Dermatology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Detergent Compositions (AREA)
- Cosmetics (AREA)
- Macromolecular Compounds Obtained By Forming Nitrogen-Containing Linkages In General (AREA)
- Paper (AREA)
- Carbon And Carbon Compounds (AREA)
- Food Preservation Except Freezing, Refrigeration, And Drying (AREA)
- Inks, Pencil-Leads, Or Crayons (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE3623369 | 1986-07-11 | ||
| DEP3623369.2 | 1986-07-11 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1289886C true CA1289886C (en) | 1991-10-01 |
Family
ID=6304930
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000541835A Expired - Lifetime CA1289886C (en) | 1986-07-11 | 1987-07-10 | Solutions of oxazaphosphorins having improved stability and process for the preparation thereof |
Country Status (16)
| Country | Link |
|---|---|
| US (1) | US4952575A (enExample) |
| EP (1) | EP0254902B1 (enExample) |
| JP (1) | JPS6323888A (enExample) |
| KR (1) | KR880001282A (enExample) |
| AT (1) | ATE66609T1 (enExample) |
| AU (1) | AU598282B2 (enExample) |
| CA (1) | CA1289886C (enExample) |
| DE (2) | DE3722043A1 (enExample) |
| DK (1) | DK168322B1 (enExample) |
| ES (1) | ES2038623T3 (enExample) |
| FI (1) | FI86690C (enExample) |
| GR (1) | GR3002618T3 (enExample) |
| IE (1) | IE59897B1 (enExample) |
| IL (1) | IL83141A (enExample) |
| PT (1) | PT85293B (enExample) |
| ZA (1) | ZA875059B (enExample) |
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5051257A (en) * | 1989-05-09 | 1991-09-24 | Pietronigro Dennis D | Antineoplastic solution and method for treating neoplasms |
| RO113611B1 (ro) * | 1990-08-03 | 1998-09-30 | Asta Pharma Ag | Preparate solide de ifosfamida, administrate oral si procedeu de obtinere |
| US5227373A (en) * | 1991-10-23 | 1993-07-13 | Bristol-Myers Squibb Co. | Lyophilized ifosfamide compositions |
| WO1999018973A2 (de) * | 1997-10-13 | 1999-04-22 | Stada Arzneimittel Ag | Flüssige darreichungsformen oxazaphosphorinhaltiger pharmazeutischer produkte |
| US7205404B1 (en) * | 1999-03-05 | 2007-04-17 | Metabasis Therapeutics, Inc. | Phosphorus-containing prodrugs |
| AUPQ849900A0 (en) * | 2000-06-30 | 2000-07-27 | Dbl Australia Pty Ltd. | Injectable composition |
| US6613927B1 (en) | 2002-02-08 | 2003-09-02 | American Pharmaceutical Partners, Inc. | Sterile lyophilized ifosfamide and associated methods |
| EA008776B1 (ru) * | 2002-09-05 | 2007-08-31 | Бхарат Сирумс Энд Вэксинс Лтд. | Жидкая стабильная композиция оксазафосфорина с месной |
| US7199111B2 (en) * | 2002-12-02 | 2007-04-03 | Bharat Serums & Vaccines Ltd. | Aqueous ifosfamide compositions for parenteral administration and a process for their preparations |
| CA2580202A1 (en) * | 2004-09-13 | 2006-03-23 | Bharat Serums & Vaccines Ltd. | Stable emulsion compositions for intravenous administration having antimicrobial preservative efficacy |
| EP3623364A1 (en) | 2014-02-13 | 2020-03-18 | Ligand Pharmaceuticals, Inc. | Prodrug compounds and their uses |
| US20150320774A1 (en) * | 2014-05-09 | 2015-11-12 | AuroMedics Pharma LLC | Formulations of cyclophosphamide liquid concentrate |
| CN106687118A (zh) | 2014-07-02 | 2017-05-17 | 配体药物公司 | 前药化合物及其用途 |
| WO2016005962A2 (en) | 2014-07-11 | 2016-01-14 | Dr. Reddy’S Laboratories Limited | Stable liquid formulations of cyclophosphamide and processes |
| US10849916B2 (en) | 2014-07-11 | 2020-12-01 | Dr. Reddys Laboratories Limited | Stable liquid formulations of cyclophosphamide and its impurities |
| US10993952B2 (en) | 2015-02-16 | 2021-05-04 | Leiutis Pharmaceuticals Pvt. Ltd. | Stable ready to use cyclophosphamide liquid formulations |
| WO2019139919A1 (en) | 2018-01-09 | 2019-07-18 | Ligand Pharmaceuticals, Inc. | Acetal compounds and therapeutic uses thereof |
| US20230310468A1 (en) * | 2020-08-17 | 2023-10-05 | Sandoz Ag | Parenteral pharmaceutical composition comprising cyclophosphamide and a mixture of liquids |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3530147A1 (de) * | 1985-08-23 | 1987-02-26 | Bayer Ag | Verwendung von diazaphosphorinen zur bekaempfung von endoparasiten |
-
1987
- 1987-07-03 DE DE19873722043 patent/DE3722043A1/de not_active Withdrawn
- 1987-07-03 ES ES198787109559T patent/ES2038623T3/es not_active Expired - Lifetime
- 1987-07-03 AT AT87109559T patent/ATE66609T1/de not_active IP Right Cessation
- 1987-07-03 DE DE8787109559T patent/DE3772482D1/de not_active Expired - Lifetime
- 1987-07-03 EP EP87109559A patent/EP0254902B1/de not_active Expired - Lifetime
- 1987-07-07 JP JP62167976A patent/JPS6323888A/ja active Granted
- 1987-07-09 IL IL83141A patent/IL83141A/xx not_active IP Right Cessation
- 1987-07-09 PT PT85293A patent/PT85293B/pt unknown
- 1987-07-10 FI FI873064A patent/FI86690C/fi not_active IP Right Cessation
- 1987-07-10 CA CA000541835A patent/CA1289886C/en not_active Expired - Lifetime
- 1987-07-10 AU AU75549/87A patent/AU598282B2/en not_active Expired
- 1987-07-10 DK DK359387A patent/DK168322B1/da not_active IP Right Cessation
- 1987-07-10 ZA ZA875059A patent/ZA875059B/xx unknown
- 1987-07-10 IE IE186787A patent/IE59897B1/en not_active IP Right Cessation
- 1987-07-11 KR KR1019870007481A patent/KR880001282A/ko not_active Ceased
-
1989
- 1989-02-06 US US07/307,230 patent/US4952575A/en not_active Expired - Lifetime
-
1991
- 1991-08-29 GR GR91401184T patent/GR3002618T3/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| DK168322B1 (da) | 1994-03-14 |
| GR3002618T3 (en) | 1993-01-25 |
| DK359387A (da) | 1988-01-12 |
| EP0254902A2 (de) | 1988-02-03 |
| DK359387D0 (da) | 1987-07-10 |
| ES2038623T3 (es) | 1993-08-01 |
| KR880001282A (ko) | 1988-04-22 |
| FI86690B (fi) | 1992-06-30 |
| FI86690C (fi) | 1992-10-12 |
| PT85293B (pt) | 1990-03-30 |
| IL83141A (en) | 1992-11-15 |
| AU598282B2 (en) | 1990-06-21 |
| ATE66609T1 (de) | 1991-09-15 |
| IL83141A0 (en) | 1987-12-31 |
| DE3772482D1 (de) | 1991-10-02 |
| FI873064A0 (fi) | 1987-07-10 |
| FI873064L (fi) | 1988-01-12 |
| EP0254902A3 (en) | 1988-08-03 |
| US4952575A (en) | 1990-08-28 |
| AU7554987A (en) | 1988-01-14 |
| IE59897B1 (en) | 1994-04-20 |
| ZA875059B (en) | 1988-02-24 |
| JPH0543711B2 (enExample) | 1993-07-02 |
| IE871867L (en) | 1988-01-11 |
| JPS6323888A (ja) | 1988-02-01 |
| DE3722043A1 (de) | 1988-01-14 |
| PT85293A (de) | 1987-08-01 |
| EP0254902B1 (de) | 1991-08-28 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKEX | Expiry |