WO2001010446A2 - Formulations de phosphate d'estramustine et d'albumine a utilisation par voie parenterale - Google Patents
Formulations de phosphate d'estramustine et d'albumine a utilisation par voie parenterale Download PDFInfo
- Publication number
- WO2001010446A2 WO2001010446A2 PCT/EP2000/007678 EP0007678W WO0110446A2 WO 2001010446 A2 WO2001010446 A2 WO 2001010446A2 EP 0007678 W EP0007678 W EP 0007678W WO 0110446 A2 WO0110446 A2 WO 0110446A2
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- estramustine phosphate
- human albumin
- cancer
- formulation according
- formulation
- Prior art date
Links
Classifications
-
- 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
- A61K31/661—Phosphorus acids or esters thereof not having P—C bonds, e.g. fosfosal, dichlorvos, malathion or mevinphos
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/14—Blood; Artificial blood
- A61K35/16—Blood plasma; Blood serum
-
- 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
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
-
- 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
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
-
- 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
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/475—Quinolines; Isoquinolines having an indole ring, e.g. yohimbine, reserpine, strychnine, vinblastine
-
- 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
- A61K31/555—Heterocyclic compounds containing heavy metals, e.g. hemin, hematin, melarsoprol
-
- 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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
-
- 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
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/38—Albumins
-
- 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
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/42—Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein
-
- 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
- A61P35/00—Antineoplastic agents
Definitions
- the present invention relates to pharmaceutical formulations of estramustine phosphate for parenteral use and, more particularly, to formulations of estramustine phosphate for parenteral use further comprising human albumin.
- Estramustine phosphate (The Merck Index, XII Ed., No. 3749, 1996) is an estradiol-17 ⁇ -phosphate derivative widely known in the art as antitumor agent, currently used in the treatment of advanced adenocarcinoma of the prostate.
- the drug is usually administered orally, preferably at a dose of 10-15 mg/kg/day.
- Intravenous administration is also adopted in some particular cases.
- initial intravenous administration of estramustine phosphate, followed by oral administration has been reported at dosages paralleling the oral administration for the drug, i.e. 300-600 mg daily given intravenously and usually repetitively over for several consecutive days (see, for a reference, British Journal of Urology, 1977, 49, 73-79; J. Urol .108 : 303-306 , 1972; Eur. Clin. Pharmacol. 26(1), 113-119, 1984; Eur. Urol. 1990, 17, 216-218) .
- Estramustine phosphate as well as other well-known cytotoxic compounds used in antitumor therapy are known to cause, or potentially cause, vascular damages at the site of injection when parenterally, in particular intravenously, administered.
- cyclodextrins in the preparation of formulations for parenteral administration of cytotoxic known to cause ulcerative lesions. See, for a reference, US patent No. 5,804,568 in the name of Supergen Inc.
- estramustine phosphate containing human albumin also known in the art are formulations for the intravenous administration of estramustine phosphate containing human albumin, reported to be characterised by fewer local side- effects upon injection of the active (see, for a reference, H. Schutz et al . ; Whypharmazie, II year, issue No. 3, 1988) .
- formulations for parenteral use comprising estramustine phosphate together with human albumin which, unexpectedly, resulted to achieve optimal protection from side-effects even at lower concentrations of human albumin, with respect to the active, compared to the albumin concentration of the prior art formulations .
- estramustine phosphate in admixture with human albumin, wherein the weight ratio between estramustine phosphate and human albumin is from about 1:5 to about 1:0.3, respectively.
- the formulations object of the present invention do not provoke ulcerative damages, nor thrombophlebitis, at the site of injection.
- estramustine phosphate as the active ingredient, we intend any formulation comprising estramustine phosphate either in the acid form or as a pharmaceutically acceptable salt for parenteral administration such as, for instance, a salt with a basic amino acid or with N-methyl glucamine, otherwise referred to as meglu ine .
- estramustine phosphate is in the form of its meglumine salt.
- the above formulations are advantageously used for intravenous use.
- these formulations can be administered to patients either as a slow injection, e.g. over about 30 minutes to about 3 hours, or as a bolus injection, also referred to as IV (intravenous) push.
- IV intravenous
- the formulations object of the present invention comprise estramustine phosphate in admixture with human albumin wherein the weight ratio between estramustine phosphate and human albumin is from about 1:4 to about 1:0.4, respectively.
- the said weight ratio between estramustine phosphate and human albumin is from about 1:1 to about 1:0.5, respectively.
- the formulations of the invention provide a very advantageous method for delivering estramustine phosphate intravenously, even when high doses of the active are needed.
- estramustine phosphate as a single infusion dosage of the active exceeding 1300 mg, in admixture with human albumin, wherein the weight ratio between estramustine phosphate and human albumin is from about 1:5 to about 1:0.3, respectively.
- a formulation for parenteral use comprising estramustine phosphate, as a single infusion dosage of the active exceeding 950 mg/m 2 , in admixture with human albumin, wherein the weight ratio between estramustine phosphate and human albumin is from about 1:5 to about 1:0.3, respectively.
- the formulations object of the present invention allow the administration of the active either as a single agent or, alternatively, in combination with known anticancer treatments such as radiation therapy or chemotherapy regimen in combination with cytostatic or cytotoxic agents, antibiotic-type agents, alkylating agents, antimetabolite agents, hormonal agents, e.g. aromatase inhibitors, immunological agents, interferon-type agents, cyclooxygenase inhibitors (e.g.
- COX-2 inhibitors COX-2 inhibitors
- metallomatrixprotease inhibitors telomerase inhibitors
- tyrosine kinase inhibitors anti-growth factor receptor agents
- anti-HER agents anti-EGFR agents
- anti- angiogenesis agents farnesyl transferase inhibitors
- ras- raf signal transduction pathway inhibitors cell cycle inhibitors, other cdks inhibitors, tubulin binding agents, topoisomerase I inhibitors, topoisomerase II inhibitors, and the like.
- the above formulations can be administered in combination with one or more chemotherapeutic agents, optionally within liposomal formulations thereof.
- chemotherapeutic agents are, for instance, taxane, taxane derivatives, CPT-11, camptothecin and derivatives thereof, anthracycline glycosides, e.g. doxorubicin, idarubicin or epirubicin, etoposide, navelbine, vinblastine, carboplatin, cisplatin and the like, optionally within liposomal formulations thereof.
- the above formulations can be also administered in combination with protein kinase inhibitors such as, for instance, the indolinone derivatives disclosed by Sugen in the international patent applications WO 96/40116 and WO 99/61422, which are herewith incorporated by reference.
- the formulations object of the invention can be preferably administered in combination with 3- [4- (2- carboxyethyl-3 , 5-dimethylpyrrol-2-yl)methylidenyl] -2- indolinone and 3 [ (2 , 4-dimethylpyrrol-5-yl)methylidenyl] -2- indolinone, better known as Sugen SU 6668 and SU 5416, respectively .
- the formulations of the invention may be administered sequentially with known anticancer agents when a combination formulation is inappropriate.
- estramustine phosphate in admixture with human albumin, wherein the weight ratio between estramustine phosphate and human albumin is from about 1:5 to about 1:0.3, and one or more chemotherapeutic agents, as a combined preparation for simultaneous, separate or sequential use in anticancer therapy .
- estramustine phosphate was dissolved in different vehicles such as water solution for injection and water solution for injection further containing different amounts of human albumin.
- the following solutions of estramustine phosphate human albumin in a weight ratio of 1:3.3 and of 1:0.8, were prepared and tested.
- Estramustine phosphate in the form of meglumine salt, was administered to groups of rats as a repeated intravenous injection during 3 days. Rats were then sacrificed: a half of the rats at the fourth day and a half at the fifth day. The dose level of estramustine phosphate, in all the different tested solutions, was of 150 mg/kg/day. Clinical observations were recorded daily. Thrombophlebitic side effects resulted in a dark bluish/blackish coloration of the tail during the treatment period.
- a score system based on tail coloration and its extension was used to evaluate the different tested formulations.
- the score system considered estramustine phosphate water solution as the positive control (i.e. marked toxicity) .
- Water for injection was administered to the control group as negative control (i.e. no toxicity signs).
- Estramustine phosphate in a water solution induced, at the used dose, local irritant effects at the injection site after the first administration and marked toxicity signs at the end of the experiment.
- Albumin containing formulations showed no toxicity signs even when albumin was present at very low concentrations. Histological evaluation of the tail of the rats treated with the formulations containing albumin did not reveal any damage when compared to the tails of the control group.
- estramustine phosphate in a water solution containing human albumin induced markedly less local irritant effects when compared with a water solution of the same.
- One particularly preferred schedule for administering the formulation of estramustine phosphate according to the invention is a single infusion given once weekly to a maximal dose of 4000 mg or 3500 mg/m 2 .
- Another preferred schedule is the administration of a single drug infusion once every two to four weeks .
- One schedule may be preferred over another in consideration of schedules with other optional concomitant therapy. These schedules may repeat in serial or as repetitive fashion.
- the formulations of the present invention are useful in antitumor therapy, particularly in the treatment of prostate cancer, breast cancer, melanoma, lung cancer, pancreatic cancer, colorectal cancer, ovarian cancer and cancers of the brain.
- the formulations object of the present invention are prepared according to conventional techniques adopted in the preparation of pharmaceutical forms for parenteral use.
- a proper amount of estramustine phosphate either as a dry powder or into a lyophilised form, is dissolved in a pharmaceutically acceptable solution for parenteral use and then admixed with a proper amount of human albumin, either as a dry powder or as a commercially available solution, e.g. human albumin 25%, 20% or 5%, optionally properly diluted.
- estramustine phosphate in the form of a suitable salt such as, for instance, N-methyl glucamine salt
- a suitable amount of sterile water or aqueous dextrose solution e.g. 5% dextrose in water for intravenous administration
- a proper amount of powdered human albumin e.g. 5% dextrose in water for intravenous administration
- the above admixture is then stirred, sterilised, and subsequently lyophilised according to conventional techniques .
- the freeze-dried formulation is prepared and stored in vials for injection; the addition of a proper amount of sterile water or of a physiological solution for parenteral use enables the preparation of the final formulation to be injected.
- estramustine phosphate for instance as N-methyl-glucamine salt and under lyophilized form, is added to a proper amount of water or of a physiological solution for parenteral use already containing human albumin.
- the preparation of the final formulation to be injected is prepared just before its use, by reconstituting the lyophilized form containing the active principle, for instance estramustine phosphate N-methyl- glucamine salt, in the presence of a physiological solution for parenteral use containing a proper amount of human albumin.
- the active principle for instance estramustine phosphate N-methyl- glucamine salt
- estramustine phosphate or salts thereof under lyophilized form, and a physiological solution for parenteral use containing human albumin.
- the above methods are also suitable for preparing high dosages estramustine phosphate formulations whilst maintaining the desired weight ratio between the components .
- the unit strength of the formulation to be injected depended on the concentration of the active in the solution itself and, of course, on the filling volume of the vials used to prepare the final formulation.
- formulations of the present invention may optionally contain pharmaceutically acceptable excipients for parenteral administration such as, for instance, bulking agents, e.g. lactose or mannitol, pH buffering agents, anti-oxidant agents, preservative agents, tonicity adjusters and the like.
- pharmaceutically acceptable excipients for parenteral administration such as, for instance, bulking agents, e.g. lactose or mannitol, pH buffering agents, anti-oxidant agents, preservative agents, tonicity adjusters and the like.
- the obtained solution was then brought to the final volume of 10 ml with water so as to reach a final concentration of 30 mg/ml of estramustine phosphate and 100 mg/ml of human albumin (1:3.3 weight ratio respectively).
- Example 1 The formulation described in Example 1 was also prepared by dissolving the commercially available Estracyt ® freeze- dried formulation containing 300 mg/vial of the active. The reconstitution of the formulation was made by using 10 ml of a 100 mg/ml human albumin solution so as to obtain a final concentration of 30 mg/ml of estramustine phosphate and 100 mg/ml of human albumin (1:3.3 weight ratio respectively) .
- the albumin solution could be prepared either by dissolving in water a proper amount of human albumin as a dry powder or by properly diluting a commercially available human albumin solution.
- the obtained solution was then brought to the final volume of 10 ml with water so as to reach a final concentration of 30 mg/ml of estramustine phosphate and 25 mg/ml of human albumin (1:0.8 weight ratio respectively).
- Example 4 The formulation described in Example 3 was also prepared by dissolving the commercially available Estracyt ® freeze- dried formulation containing 300 mg/vial of the active. The reconstitution of the formulation was made by using 10 ml of a 25 mg/ml human albumin solution so as to obtain a final concentration of 30 mg/ml of estramustine phosphate and 25 mg/ml of human albumin (1:0.8 weight ratio respectively) .
- the albumin solution could be prepared either by dissolving in water a proper amount of human albumin as a dry powder or by properly diluting a commercially available human albumin solution.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Zoology (AREA)
- Engineering & Computer Science (AREA)
- Hematology (AREA)
- Cell Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Inorganic Chemistry (AREA)
- Immunology (AREA)
- Dermatology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Molecular Biology (AREA)
- General Chemical & Material Sciences (AREA)
- Gastroenterology & Hepatology (AREA)
- Biomedical Technology (AREA)
- Biotechnology (AREA)
- Developmental Biology & Embryology (AREA)
- Virology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Priority Applications (13)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
NZ517632A NZ517632A (en) | 1999-08-09 | 2000-08-03 | Formulations for parenteral use of estramustine phosphate and albumin |
EA200200234A EA200200234A1 (ru) | 1999-08-09 | 2000-08-03 | Препараты для парентерального применения эстрамустин фосфата и альбумина |
KR1020027001700A KR20020019967A (ko) | 1999-08-09 | 2000-08-03 | 에스트라무스틴 포스페이트 및 알부민의 비경구용 제형 |
BR0013276-4A BR0013276A (pt) | 1999-08-09 | 2000-08-03 | Formulação farmacêutica para uso parenteral que compreende fosfato de estramustina, como ingrediente ativo |
SK178-2002A SK1782002A3 (en) | 1999-08-09 | 2000-08-03 | Formulations for parenteral use of estramustine phosphate and albumin |
JP2001514963A JP2003506408A (ja) | 1999-08-09 | 2000-08-03 | エストラムスチンリン酸及びアルブミンの非経口使用のための配合物 |
CA002380312A CA2380312A1 (fr) | 1999-08-09 | 2000-08-03 | Formulations de phosphate d'estramustine et d'albumine a utilisation par voie parenterale |
HU0202645A HUP0202645A3 (en) | 1999-08-09 | 2000-08-03 | Fornulations for parenteral use of estramustine phosphate and albumin |
MXPA02001395A MXPA02001395A (es) | 1999-08-09 | 2000-08-03 | Formulaciones para uso parenteral de estramustinfosfato y albumina. |
IL14774500A IL147745A0 (en) | 1999-08-09 | 2000-08-03 | Formulations for parenteral use of estramustine phosphate and albumin |
AU62809/00A AU6280900A (en) | 1999-08-09 | 2000-08-03 | Formulations for parenteral use of estramustine phosphate and albumin |
EP00949471A EP1206266A2 (fr) | 1999-08-09 | 2000-08-03 | Formulations de phosphate d'estramustine et d'albumine a utilisation par voie parenterale |
NO20020631A NO20020631D0 (no) | 1999-08-09 | 2002-02-08 | Formuleringer for parenteral bruk av estramustinfosfat og albumin |
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB9918779.1 | 1999-08-09 | ||
GBGB9918779.1A GB9918779D0 (en) | 1999-08-09 | 1999-08-09 | Formulations for parenteral use of estramustine phosphate and albumin |
ITMI99A001998 | 1999-09-27 | ||
IT99MI001998 IT1313629B1 (it) | 1999-09-27 | 1999-09-27 | Formulazioni di estramustina fosfato ed albumina per uso parenterale |
Publications (2)
Publication Number | Publication Date |
---|---|
WO2001010446A2 true WO2001010446A2 (fr) | 2001-02-15 |
WO2001010446A3 WO2001010446A3 (fr) | 2001-05-25 |
Family
ID=26315835
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/EP2000/007678 WO2001010446A2 (fr) | 1999-08-09 | 2000-08-03 | Formulations de phosphate d'estramustine et d'albumine a utilisation par voie parenterale |
Country Status (17)
Country | Link |
---|---|
EP (1) | EP1206266A2 (fr) |
JP (1) | JP2003506408A (fr) |
KR (1) | KR20020019967A (fr) |
CN (1) | CN1511037A (fr) |
AU (1) | AU6280900A (fr) |
BR (1) | BR0013276A (fr) |
CA (1) | CA2380312A1 (fr) |
CZ (1) | CZ2002376A3 (fr) |
EA (1) | EA200200234A1 (fr) |
HU (1) | HUP0202645A3 (fr) |
IL (1) | IL147745A0 (fr) |
MX (1) | MXPA02001395A (fr) |
NO (1) | NO20020631D0 (fr) |
NZ (1) | NZ517632A (fr) |
PL (1) | PL353406A1 (fr) |
SK (1) | SK1782002A3 (fr) |
WO (1) | WO2001010446A2 (fr) |
Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR100426450B1 (ko) * | 2002-03-16 | 2004-04-13 | 박래옥 | 구연산, 알부민 및 아연을 함유한 항암 조성물 |
JP2006524632A (ja) * | 2002-12-09 | 2006-11-02 | アメリカン バイオサイエンス、インコーポレイテッド | 組成物及び薬物送達方法 |
DE102006024528A1 (de) * | 2006-05-23 | 2007-11-29 | Albupharm Heidelberg Gmbh & Co. Kg | Neue, an der Tumorphysiologie orientierte Formulierung eines Zytostatikums, insbesondere von cis-Platin |
US7595293B2 (en) | 2003-04-11 | 2009-09-29 | Novo Nordisk A/S | Stable pharmaceutical compositions |
US7794748B2 (en) | 2003-01-31 | 2010-09-14 | Yamanouchi Pharmaceutical Co., Ltd. | Stable oral solid drug composition |
US9364772B2 (en) | 2003-04-08 | 2016-06-14 | Novo Nordisk A/S | Regeneration of chromatographic stationary phases |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1984002270A1 (fr) * | 1982-12-13 | 1984-06-21 | Leo Ab | Particules microfines ayant des proprietes de recherche de cible |
WO1998051282A1 (fr) * | 1997-05-13 | 1998-11-19 | Imarx Pharmaceutical Corp. | Matrices poreuses solides, leur procede de fabrication et leur utilisation |
-
2000
- 2000-08-03 EA EA200200234A patent/EA200200234A1/ru unknown
- 2000-08-03 SK SK178-2002A patent/SK1782002A3/sk unknown
- 2000-08-03 MX MXPA02001395A patent/MXPA02001395A/es unknown
- 2000-08-03 PL PL00353406A patent/PL353406A1/xx not_active Application Discontinuation
- 2000-08-03 NZ NZ517632A patent/NZ517632A/en unknown
- 2000-08-03 AU AU62809/00A patent/AU6280900A/en not_active Abandoned
- 2000-08-03 BR BR0013276-4A patent/BR0013276A/pt not_active IP Right Cessation
- 2000-08-03 WO PCT/EP2000/007678 patent/WO2001010446A2/fr not_active Application Discontinuation
- 2000-08-03 JP JP2001514963A patent/JP2003506408A/ja not_active Withdrawn
- 2000-08-03 CA CA002380312A patent/CA2380312A1/fr not_active Abandoned
- 2000-08-03 CN CNA008114420A patent/CN1511037A/zh active Pending
- 2000-08-03 KR KR1020027001700A patent/KR20020019967A/ko not_active Application Discontinuation
- 2000-08-03 CZ CZ2002376A patent/CZ2002376A3/cs unknown
- 2000-08-03 EP EP00949471A patent/EP1206266A2/fr not_active Withdrawn
- 2000-08-03 HU HU0202645A patent/HUP0202645A3/hu unknown
- 2000-08-03 IL IL14774500A patent/IL147745A0/xx unknown
-
2002
- 2002-02-08 NO NO20020631A patent/NO20020631D0/no not_active Application Discontinuation
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1984002270A1 (fr) * | 1982-12-13 | 1984-06-21 | Leo Ab | Particules microfines ayant des proprietes de recherche de cible |
WO1998051282A1 (fr) * | 1997-05-13 | 1998-11-19 | Imarx Pharmaceutical Corp. | Matrices poreuses solides, leur procede de fabrication et leur utilisation |
Non-Patent Citations (1)
Title |
---|
HARTMUT SCHUTZ ET AL.: "ESTRAMUSTIN I.V.:OPTIMALE APPLIKATIONSWEISE ZUR VERH]TUNG VON VENENWANDSCH[DEN" KRANKENHAUSPHARMAZIE, vol. 9, no. 3, - 1988 XP002157640 cited in the application * |
Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR100426450B1 (ko) * | 2002-03-16 | 2004-04-13 | 박래옥 | 구연산, 알부민 및 아연을 함유한 항암 조성물 |
JP2006524632A (ja) * | 2002-12-09 | 2006-11-02 | アメリカン バイオサイエンス、インコーポレイテッド | 組成物及び薬物送達方法 |
US7794748B2 (en) | 2003-01-31 | 2010-09-14 | Yamanouchi Pharmaceutical Co., Ltd. | Stable oral solid drug composition |
US9364772B2 (en) | 2003-04-08 | 2016-06-14 | Novo Nordisk A/S | Regeneration of chromatographic stationary phases |
US7595293B2 (en) | 2003-04-11 | 2009-09-29 | Novo Nordisk A/S | Stable pharmaceutical compositions |
DE102006024528A1 (de) * | 2006-05-23 | 2007-11-29 | Albupharm Heidelberg Gmbh & Co. Kg | Neue, an der Tumorphysiologie orientierte Formulierung eines Zytostatikums, insbesondere von cis-Platin |
WO2007134595A2 (fr) * | 2006-05-23 | 2007-11-29 | Albupharm Heidelberg Gmbh & Co. Kg | Nouvelle formulation d'un cytostatique, en particulier le cis-platine, orientée en fonction de la physiologie tumorale |
WO2007134595A3 (fr) * | 2006-05-23 | 2008-10-16 | Albupharm Heidelberg Gmbh & Co | Nouvelle formulation d'un cytostatique, en particulier le cis-platine, orientée en fonction de la physiologie tumorale |
Also Published As
Publication number | Publication date |
---|---|
SK1782002A3 (en) | 2002-05-09 |
EA200200234A1 (ru) | 2002-06-27 |
WO2001010446A3 (fr) | 2001-05-25 |
NZ517632A (en) | 2004-02-27 |
HUP0202645A2 (hu) | 2002-12-28 |
CZ2002376A3 (cs) | 2002-06-12 |
AU6280900A (en) | 2001-03-05 |
PL353406A1 (en) | 2003-11-17 |
CA2380312A1 (fr) | 2001-02-15 |
BR0013276A (pt) | 2004-08-03 |
IL147745A0 (en) | 2002-08-14 |
KR20020019967A (ko) | 2002-03-13 |
NO20020631L (no) | 2002-02-08 |
JP2003506408A (ja) | 2003-02-18 |
HUP0202645A3 (en) | 2004-06-28 |
CN1511037A (zh) | 2004-07-07 |
NO20020631D0 (no) | 2002-02-08 |
EP1206266A2 (fr) | 2002-05-22 |
MXPA02001395A (es) | 2002-08-12 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
EP1214078B1 (fr) | Formulations pour une utilisation parenterale de phosphate d'estramustine et d'acides amines | |
US6730664B1 (en) | Formulations for parenteral use of estramustine phosphate and sulfoalkyl ether cyclodextrins | |
EP1206266A2 (fr) | Formulations de phosphate d'estramustine et d'albumine a utilisation par voie parenterale | |
AU777763B2 (en) | Formulations for parenteral use of estramustine phosphate with improved pharmacological properties | |
ZA200201955B (en) | Formulations for parenteral use of estramustine phosphate and albumin. | |
US20040014729A1 (en) | Use of estramustine phosphate in the treatment of bone metastasis |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AK | Designated states |
Kind code of ref document: A2 Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CR CU CZ DE DK DM DZ EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT TZ UA UG US UZ VN YU ZA ZW |
|
AL | Designated countries for regional patents |
Kind code of ref document: A2 Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG |
|
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
AK | Designated states |
Kind code of ref document: A3 Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CR CU CZ DE DK DM DZ EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT TZ UA UG US UZ VN YU ZA ZW |
|
AL | Designated countries for regional patents |
Kind code of ref document: A3 Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG |
|
WWE | Wipo information: entry into national phase |
Ref document number: 147745 Country of ref document: IL |
|
WWE | Wipo information: entry into national phase |
Ref document number: PV2002-376 Country of ref document: CZ |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2380312 Country of ref document: CA |
|
WWE | Wipo information: entry into national phase |
Ref document number: 1782002 Country of ref document: SK |
|
WWE | Wipo information: entry into national phase |
Ref document number: 1020027001700 Country of ref document: KR Ref document number: 008114420 Country of ref document: CN |
|
WWE | Wipo information: entry into national phase |
Ref document number: PA/a/2002/001395 Country of ref document: MX |
|
WWE | Wipo information: entry into national phase |
Ref document number: 62809/00 Country of ref document: AU |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2000949471 Country of ref document: EP |
|
WWE | Wipo information: entry into national phase |
Ref document number: 517632 Country of ref document: NZ Ref document number: 200200234 Country of ref document: EA |
|
WWE | Wipo information: entry into national phase |
Ref document number: IN/PCT/2002/358/CHE Country of ref document: IN |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2002/01955 Country of ref document: ZA Ref document number: 200201955 Country of ref document: ZA |
|
WWP | Wipo information: published in national office |
Ref document number: 1020027001700 Country of ref document: KR |
|
WWE | Wipo information: entry into national phase |
Ref document number: 10048463 Country of ref document: US |
|
WWP | Wipo information: published in national office |
Ref document number: 2000949471 Country of ref document: EP |
|
WWP | Wipo information: published in national office |
Ref document number: PV2002-376 Country of ref document: CZ |
|
REG | Reference to national code |
Ref country code: DE Ref legal event code: 8642 |
|
WWP | Wipo information: published in national office |
Ref document number: 517632 Country of ref document: NZ |
|
WWG | Wipo information: grant in national office |
Ref document number: 517632 Country of ref document: NZ |
|
WWW | Wipo information: withdrawn in national office |
Ref document number: 2000949471 Country of ref document: EP |
|
WWR | Wipo information: refused in national office |
Ref document number: PV2002-376 Country of ref document: CZ |