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WO2001019338A1 - Formulations pour usage parenteral d'estramustine phosphate a proprietes pharmacologiques ameliorees - Google Patents

Formulations pour usage parenteral d'estramustine phosphate a proprietes pharmacologiques ameliorees Download PDF

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Publication number
WO2001019338A1
WO2001019338A1 PCT/EP2000/007679 EP0007679W WO0119338A1 WO 2001019338 A1 WO2001019338 A1 WO 2001019338A1 EP 0007679 W EP0007679 W EP 0007679W WO 0119338 A1 WO0119338 A1 WO 0119338A1
Authority
WO
WIPO (PCT)
Prior art keywords
estramustine phosphate
cancer
sulfoalkyl ether
human albumin
cyclodextrin
Prior art date
Application number
PCT/EP2000/007679
Other languages
English (en)
Inventor
Lorena Muggetti
Paolo Colombo
Alessandro Martini
Giovanni Buzzi
Original Assignee
Pharmacia Italia S.P.A.
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
Priority to SK345-2002A priority Critical patent/SK3452002A3/sk
Priority to EP00956409A priority patent/EP1212040A1/fr
Priority to PL00353954A priority patent/PL353954A1/xx
Priority to JP2001522973A priority patent/JP2003509355A/ja
Priority to EA200200369A priority patent/EA005308B1/ru
Priority to CA002385063A priority patent/CA2385063A1/fr
Priority to HU0202621A priority patent/HUP0202621A2/hu
Priority to BR0014063-5A priority patent/BR0014063A/pt
Priority to AU68363/00A priority patent/AU777763B2/en
Priority to KR1020027003498A priority patent/KR20020059405A/ko
Application filed by Pharmacia Italia S.P.A. filed Critical Pharmacia Italia S.P.A.
Priority to IL14840900A priority patent/IL148409A0/xx
Priority to NZ517631A priority patent/NZ517631A/en
Priority to HK02108529.1A priority patent/HK1047227A1/zh
Priority to MXPA02002859A priority patent/MXPA02002859A/es
Publication of WO2001019338A1 publication Critical patent/WO2001019338A1/fr
Priority to NO20021306A priority patent/NO20021306L/no

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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
    • 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
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/40—Cyclodextrins; Derivatives 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
    • A61K47/30—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
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • 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 with improved pharmacological properties and, more particularly, to formulations of estramustine phosphate for parenteral use further comprising sulfoalkyl ether cyclodextrins and 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. For example, initial intravenous administration of estramustine phosphate, followed by oral administration, has been reported at dosages paralleling the oral administration for the drug, i.e.
  • 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 for instance hydroxypropyl-cyclodextrin
  • Cyclodextrin derivatives such as sulfoalkyl ether cyclodextrins are known in the art as solubilizing agents for insoluble or poorly soluble drugs (see, for a reference, US 5,134,127 in the name of the University of Kansas) .
  • 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) .
  • estramustine phosphate in admixture with a sulfoalkyl ether cyclodextrin and human albumin .
  • the formulations object of the present invention do not provoke ulcerative damages, nor thrombophlebitis, at the site of injection.
  • estramustine phosphate formulations of the invention result to be endowed with unexpected pharmacological properties, expressed in terms of toxicity at the site of injection, markedly improved with respect to formulations containing, as a single protective excipient, a sulfoalkyl ether cyclodextrin or, alternatively, human albumin.
  • 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 meglumine .
  • estramustine phosphate is in the form of its meglumine salt.
  • sulfoalkyl ether cyclodextrin we refer to any cyclodextrin of the above type wherein alkyl stands for straight or branched C 1 -C 6 alkyl group such as methyl, ethyl, n.propyl, isopropyl, n.butyl, isobutyl, sec-butyl, tert-butyl, n.pentyl, n.hexyl and the like.
  • the formulation of the present invention comprises estramustine phosphate in admixture with sulfobutyl ether ⁇ -cyclodextrin.
  • the weight ratio between estramustine phosphate and sulfoalkyl ether cyclodextrin is comprised from about 1:0.5 to about 1:5, respectively.
  • the above formulations are advantageously used for intravenous use .
  • these formulations of the invention 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.
  • estramustine phosphate is in lyophilised form and the parenterally acceptable carrier or diluent is a physiological solution for parenteral use containing the sulfoalkyl ether cyclodextrin and the human albumin, or
  • estramustine phosphate and sulfoalkyl ether cyclodextrin are in lyophilised form and the parenterally acceptable carrier or diluent is a physiological solution for parenteral use containing the human albumin.
  • the invention also provides a product which comprises estramustine phosphate in lyophilised form and a physiological solution for parenteral use containing human albumin.
  • the formulations of the invention also 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 g, in admixture with a sulfoalkyl ether cyclodextrin and human albumin.
  • estramustine phosphate as a single infusion dosage of the active exceeding 950 mg/m ' , in admixture with a sulfoalkyl ether cyclodextrin and human albumin.
  • 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 .
  • formulations of the invention may be administered sequentially with known anticancer agents when a combination formulation is inappropriate.
  • estramustine phosphate in admixture with a sulfoalkyl ether cyclodextrin and human albumin 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 sulfobutyl ether ⁇ -cyclodextrin and human albumin.
  • formulations of estramustine phosphate in admixture with sulfobutyl ether ⁇ -cyclodextrin only or, alternatively, with human albumin only were used for comparison.
  • 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.
  • estramustine phosphate 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.
  • estramustine phosphate water solution (b) was administered to the control group as negative control (i.e. no toxicity signs) .
  • Histological evaluation was carried out on the tail of the rats treated with the composition of the invention. Estramustine phosphate in a water solution (b) 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.
  • estramustine phosphate in a water solution containing sulfoalkyl ether cyclodextrin and human albumin induced markedly less local irritant effects when compared with a water solution of estramustine phosphate itself. Even more surprisingly, the formulation of the invention produced less local irritant effects also in comparison to analogous solutions of estramustine phosphate containing sulfoalkyl ether cyclodextrin only or human albumin only.
  • 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 is dissolved in a pharmaceutically acceptable solution for parenteral use and then admixed with a proper amount of a sulfoalkyl ether cyclodextrin, for instance sulfobutyl ether ⁇ -cyclodextrin.
  • the above solution is 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 sulfobutyl ether ⁇ -cyclodextrin is dissolved in a suitable amount of sterile water or aqueous dextrose solution, e.g. 5% dextrose in water for intravenous administration.
  • each of the ingredients of the invention such as sulfoalkyl ether cyclodextrin and human albumin, each independently as a powder or into a suitable solution, can be admixed in any order to the active, already dissolved into a proper solution or in the form of a dry powder.
  • the formulations of the invention can also be prepared by admixing the active with the aforementioned ingredients already properly combined as above indicated. The final freeze-dried formulation is then prepared and stored in vials for injection; the addition of a proper amount of sterile water or a physiological solution for parenteral use enables the preparation of the final formulation to be injected.
  • the above method is 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.
  • 300 mg of estramustine phosphate were weighed in a beaker and dispersed by means of magnetic stirring in 5 ml of water. 120.8 mg of N-methyl-glucamine were then added under stirring to the watery dispersion of the active and, after a few minutes, a clear solution was obtained.
  • Example 1 The formulation described in Example 1 was also prepared by solubilization of the commercially available Estracyt ® freeze-dried formulation containing 300 mg/vial of the active. The reconstitution of the formulation was made using 10 ml of a 31.25 mg/ml sulfobutyl ether ⁇ - cyclodextrin solution so as to obtain a final concentration of 30 mg/ml of estramustine phosphate and 31.25 mg/ml of cyclodextrin (1:1 weight ratio - 1:0.25 molar ratio respectively) .
  • estramustine phosphate 300 mg were weighed in a beaker and dispersed by means of magnetic stirring in 5 ml of water. 120.8 mg of N-methyl-glucamine were then added under stirring to the watery dispersion of the active and, after a few minutes, a clear solution was obtained. 0.250 ml of a commercially available solution of human albumin at 25% concentration were added whilst maintaining the solution under stirring.
  • 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 6.25 mg/ml of human albumin (1:0.21 weight ratio respectively).
  • Example 3 The formulation described in Example 3 was also prepared by solubilization of 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 6.25 mg/ml human albumin solution so as to obtain a final concentration of 30 mg/ml of estramustine phosphate and 6.25 mg/ml of human albumin (1:0.21 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.
  • 300 mg of estramustine phosphate were weighed in a beaker and dispersed by means of magnetic stirring in 5 ml of water. 120.8 mg of N-methyl-glucamine were then added under stirring to the watery dispersion of the active and, after a few minutes, a clear solution was obtained.
  • the 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, 31.25 mg/ml of sulfobutyl ether ⁇ -cyclodextrin and 6.25 mg/ml of human albumin.
  • the weight ratio between the components of the solution were as follows: estramustine phosphate : sulfobutyl ether ⁇ - cyclodextrin: human albumin 1:1:0.21 respectively.
  • Example 4 The formulation described in Example 4 was also prepared by solubilization of 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 solution containing 31.25 mg/ml of sulfobutyl ether ⁇ -cyclodextrin and 6.25 mg/ml of human albumin so as to reach a final concentration of 30 mg/ml of the active.
  • the weight ratio between the components of the solution were as follows: estramustine phosphate: sulfobutyl ether ⁇ -cyclodextrin: human albumin 1:1:0.21 respectively.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
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  • Pharmacology & Pharmacy (AREA)
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  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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  • Inorganic Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
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  • Gastroenterology & Hepatology (AREA)
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  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

L'invention concerne une formulation pharmaceutique renfermant un excipient ou diluant acceptable par voie parentérale, de l'estramustine phosphate, une cyclodextrine de sulfoalkyl éther et de l'albumine humaine. La formulation peut être administrée selon un schéma posologique chimiothérapeutique combiné, en association avec un ou plusieurs agents chimiomothérapeutiques. La formulation permet aussi d'administrer l'estramustine phosphate sans effets secondaires au site d'injection.
PCT/EP2000/007679 1999-09-16 2000-08-03 Formulations pour usage parenteral d'estramustine phosphate a proprietes pharmacologiques ameliorees WO2001019338A1 (fr)

Priority Applications (15)

Application Number Priority Date Filing Date Title
AU68363/00A AU777763B2 (en) 1999-09-16 2000-08-03 Formulations for parenteral use of estramustine phosphate with improved pharmacological properties
PL00353954A PL353954A1 (en) 1999-09-16 2000-08-03 Formulations for parenteral use of estramustine phosphate with improved pharmacological properties
JP2001522973A JP2003509355A (ja) 1999-09-16 2000-08-03 薬理学的特性が改善されたリン酸エストラムスチン塩の非経口的使用のための処方
EA200200369A EA005308B1 (ru) 1999-09-16 2000-08-03 Препараты эстрамустинфосфата для парентерального применения
CA002385063A CA2385063A1 (fr) 1999-09-16 2000-08-03 Formulations pour usage parenteral d'estramustine phosphate a proprietes pharmacologiques ameliorees
HU0202621A HUP0202621A2 (hu) 1999-09-16 2000-08-03 Javított farmakológiai tulajdonságokkal rendelkező, parenteralis felhasználásra szolgáló ösztramusztin-foszfát készítmények
BR0014063-5A BR0014063A (pt) 1999-09-16 2000-08-03 Formulações papa uso parenteral de fosfato de estramustina com propriedades farmacológicas melhoradas
SK345-2002A SK3452002A3 (en) 1999-09-16 2000-08-03 Formulations for parenteral use of estramustine phosphate with improved pharmacological properties
EP00956409A EP1212040A1 (fr) 1999-09-16 2000-08-03 Formulations pour usage parenteral d'estramustine phosphate a proprietes pharmacologiques ameliorees
KR1020027003498A KR20020059405A (ko) 1999-09-16 2000-08-03 약리학적 성질이 개선된 에스트라무스틴 포스페이트의비경구 투여용 제형
IL14840900A IL148409A0 (en) 1999-09-16 2000-08-03 Formulations for parenteral use of estramustine phosphate with improved pharmacological properties
NZ517631A NZ517631A (en) 1999-09-16 2000-08-03 Formulations for parenteral use of estramustine phosphate with improved pharmacological properties
HK02108529.1A HK1047227A1 (zh) 1999-09-16 2000-08-03 具有改進藥理學性質的非腸胃道使用的雌莫司汀磷酸鹽製劑
MXPA02002859A MXPA02002859A (es) 1999-09-16 2000-08-03 Formulaciones para uso parenteral del fosfato de estramustina con propiedades farmacologicas mejoradas.
NO20021306A NO20021306L (no) 1999-09-16 2002-03-15 Formuleringer for parenteral bruk av estramustinfosfat med forbedrede formakologiske egenskaper

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB9921954.5 1999-09-16
GBGB9921954.5A GB9921954D0 (en) 1999-09-16 1999-09-16 Formulations for parenteral use of estramustine phosphate with improved pharmacological properties

Publications (1)

Publication Number Publication Date
WO2001019338A1 true WO2001019338A1 (fr) 2001-03-22

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PCT/EP2000/007679 WO2001019338A1 (fr) 1999-09-16 2000-08-03 Formulations pour usage parenteral d'estramustine phosphate a proprietes pharmacologiques ameliorees

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EP (1) EP1212040A1 (fr)
JP (1) JP2003509355A (fr)
KR (1) KR20020059405A (fr)
CN (1) CN1177583C (fr)
AU (1) AU777763B2 (fr)
BR (1) BR0014063A (fr)
CA (1) CA2385063A1 (fr)
CZ (1) CZ2002943A3 (fr)
EA (1) EA005308B1 (fr)
GB (1) GB9921954D0 (fr)
HK (1) HK1047227A1 (fr)
HU (1) HUP0202621A2 (fr)
IL (1) IL148409A0 (fr)
MX (1) MXPA02002859A (fr)
NO (1) NO20021306L (fr)
NZ (1) NZ517631A (fr)
PL (1) PL353954A1 (fr)
SK (1) SK3452002A3 (fr)
WO (1) WO2001019338A1 (fr)
ZA (1) ZA200201743B (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8574551B2 (en) 2005-11-28 2013-11-05 Verrow Pharmaceuticals, Inc. Compositions useful for reducing nephrotoxicity and methods of use thereof
US9215679B2 (en) 2010-09-21 2015-12-15 Telefonaktiebolaget L M Ericsson (Publ) Air-interface timing synchronization sharing
WO2019094819A3 (fr) * 2017-11-09 2020-03-26 Abon Pharmaceuticals, Llc Systèmes d'administration par voie intraveineuse pour médicaments de chimiothérapie

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* Cited by examiner, † Cited by third party
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
US5134127A (en) * 1990-01-23 1992-07-28 University Of Kansas Derivatives of cyclodextrins exhibiting enhanced aqueous solubility and the use thereof
WO1996009072A1 (fr) * 1994-09-22 1996-03-28 Pharmacia Ab Formulations d'estramustine possedant des proprietes pharmacologiques ameliorees
US5804568A (en) * 1992-06-19 1998-09-08 Supergen, Inc. Pharmaceutical formulation
WO1998051282A1 (fr) * 1997-05-13 1998-11-19 Imarx Pharmaceutical Corp. Matrices poreuses solides, leur procede de fabrication et leur utilisation

Patent Citations (5)

* Cited by examiner, † Cited by third party
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
US5134127A (en) * 1990-01-23 1992-07-28 University Of Kansas Derivatives of cyclodextrins exhibiting enhanced aqueous solubility and the use thereof
US5804568A (en) * 1992-06-19 1998-09-08 Supergen, Inc. Pharmaceutical formulation
WO1996009072A1 (fr) * 1994-09-22 1996-03-28 Pharmacia Ab Formulations d'estramustine possedant des proprietes pharmacologiques ameliorees
WO1998051282A1 (fr) * 1997-05-13 1998-11-19 Imarx Pharmaceutical Corp. Matrices poreuses solides, leur procede de fabrication et leur utilisation

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8574551B2 (en) 2005-11-28 2013-11-05 Verrow Pharmaceuticals, Inc. Compositions useful for reducing nephrotoxicity and methods of use thereof
US9215679B2 (en) 2010-09-21 2015-12-15 Telefonaktiebolaget L M Ericsson (Publ) Air-interface timing synchronization sharing
WO2019094819A3 (fr) * 2017-11-09 2020-03-26 Abon Pharmaceuticals, Llc Systèmes d'administration par voie intraveineuse pour médicaments de chimiothérapie

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GB9921954D0 (en) 1999-11-17
PL353954A1 (en) 2003-12-15
KR20020059405A (ko) 2002-07-12
HUP0202621A2 (hu) 2002-12-28
BR0014063A (pt) 2004-06-29
CN1177583C (zh) 2004-12-01
EA200200369A1 (ru) 2002-08-29
CN1374858A (zh) 2002-10-16
AU6836300A (en) 2001-04-17
NO20021306D0 (no) 2002-03-15
JP2003509355A (ja) 2003-03-11
CZ2002943A3 (cs) 2002-08-14
IL148409A0 (en) 2002-09-12
HK1047227A1 (zh) 2003-02-14
NZ517631A (en) 2004-01-30
CA2385063A1 (fr) 2001-03-22
ZA200201743B (en) 2003-05-28
NO20021306L (no) 2002-04-24
AU777763B2 (en) 2004-10-28
EA005308B1 (ru) 2004-12-30
SK3452002A3 (en) 2002-08-06
MXPA02002859A (es) 2003-07-21
EP1212040A1 (fr) 2002-06-12

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