WO2001019338A1 - Formulations for parenteral use of estramustine phosphate with improved pharmacological properties - Google Patents
Formulations for parenteral use of estramustine phosphate with improved pharmacological properties Download PDFInfo
- 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
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
- 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.
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)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Inorganic Chemistry (AREA)
- Endocrinology (AREA)
- Dermatology (AREA)
- Pulmonology (AREA)
- Reproductive Health (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Immunology (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Priority Applications (15)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR1020027003498A KR20020059405A (ko) | 1999-09-16 | 2000-08-03 | 약리학적 성질이 개선된 에스트라무스틴 포스페이트의비경구 투여용 제형 |
MXPA02002859A MXPA02002859A (es) | 1999-09-16 | 2000-08-03 | Formulaciones para uso parenteral del fosfato de estramustina con propiedades farmacologicas mejoradas. |
EP00956409A EP1212040A1 (en) | 1999-09-16 | 2000-08-03 | Formulations for parenteral use of estramustine phosphate with improved pharmacological properties |
AU68363/00A AU777763B2 (en) | 1999-09-16 | 2000-08-03 | Formulations for parenteral use of estramustine phosphate with improved pharmacological properties |
CA002385063A CA2385063A1 (en) | 1999-09-16 | 2000-08-03 | Formulations for parenteral use of estramustine phosphate with improved pharmacological properties |
IL14840900A IL148409A0 (en) | 1999-09-16 | 2000-08-03 | Formulations for parenteral use of estramustine phosphate with improved pharmacological properties |
SK345-2002A SK3452002A3 (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 |
EA200200369A EA005308B1 (ru) | 1999-09-16 | 2000-08-03 | Препараты эстрамустинфосфата для парентерального применения |
BR0014063-5A BR0014063A (pt) | 1999-09-16 | 2000-08-03 | Formulações papa uso parenteral de fosfato de estramustina com propriedades farmacológicas melhoradas |
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 |
NZ517631A NZ517631A (en) | 1999-09-16 | 2000-08-03 | Formulations for parenteral use of estramustine phosphate with improved pharmacological properties |
HU0202621A HUP0202621A2 (hu) | 1999-09-16 | 2000-08-03 | Javított farmakológiai tulajdonságokkal rendelkező, parenteralis felhasználásra szolgáló ösztramusztin-foszfát készítmények |
NO20021306A NO20021306L (no) | 1999-09-16 | 2002-03-15 | Formuleringer for parenteral bruk av estramustinfosfat med forbedrede formakologiske egenskaper |
HK02108529.1A HK1047227A1 (zh) | 1999-09-16 | 2002-11-26 | 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 |
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 (en) | 2001-03-22 |
Family
ID=10861066
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/EP2000/007679 WO2001019338A1 (en) | 1999-09-16 | 2000-08-03 | Formulations for parenteral use of estramustine phosphate with improved pharmacological properties |
Country Status (20)
Country | Link |
---|---|
EP (1) | EP1212040A1 (ko) |
JP (1) | JP2003509355A (ko) |
KR (1) | KR20020059405A (ko) |
CN (1) | CN1177583C (ko) |
AU (1) | AU777763B2 (ko) |
BR (1) | BR0014063A (ko) |
CA (1) | CA2385063A1 (ko) |
CZ (1) | CZ2002943A3 (ko) |
EA (1) | EA005308B1 (ko) |
GB (1) | GB9921954D0 (ko) |
HK (1) | HK1047227A1 (ko) |
HU (1) | HUP0202621A2 (ko) |
IL (1) | IL148409A0 (ko) |
MX (1) | MXPA02002859A (ko) |
NO (1) | NO20021306L (ko) |
NZ (1) | NZ517631A (ko) |
PL (1) | PL353954A1 (ko) |
SK (1) | SK3452002A3 (ko) |
WO (1) | WO2001019338A1 (ko) |
ZA (1) | ZA200201743B (ko) |
Cited By (3)
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 (en) * | 2017-11-09 | 2020-03-26 | Abon Pharmaceuticals, Llc | Intravenous delivery systems for chemotherapy drugs |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1984002270A1 (en) * | 1982-12-13 | 1984-06-21 | Leo Ab | Microfine particles having target-seeking properties |
US5134127A (en) * | 1990-01-23 | 1992-07-28 | University Of Kansas | Derivatives of cyclodextrins exhibiting enhanced aqueous solubility and the use thereof |
WO1996009072A1 (en) * | 1994-09-22 | 1996-03-28 | Pharmacia Ab | Estramustine formulations with improved pharmaceutical properties |
US5804568A (en) * | 1992-06-19 | 1998-09-08 | Supergen, Inc. | Pharmaceutical formulation |
WO1998051282A1 (en) * | 1997-05-13 | 1998-11-19 | Imarx Pharmaceutical Corp. | Solid porous matrices and methods of making and using the same |
-
1999
- 1999-09-16 GB GBGB9921954.5A patent/GB9921954D0/en not_active Ceased
-
2000
- 2000-08-03 CN CNB008129525A patent/CN1177583C/zh not_active Expired - Fee Related
- 2000-08-03 NZ NZ517631A patent/NZ517631A/en unknown
- 2000-08-03 WO PCT/EP2000/007679 patent/WO2001019338A1/en not_active Application Discontinuation
- 2000-08-03 PL PL00353954A patent/PL353954A1/xx not_active Application Discontinuation
- 2000-08-03 SK SK345-2002A patent/SK3452002A3/sk unknown
- 2000-08-03 BR BR0014063-5A patent/BR0014063A/pt not_active IP Right Cessation
- 2000-08-03 MX MXPA02002859A patent/MXPA02002859A/es unknown
- 2000-08-03 KR KR1020027003498A patent/KR20020059405A/ko not_active Application Discontinuation
- 2000-08-03 HU HU0202621A patent/HUP0202621A2/hu unknown
- 2000-08-03 CZ CZ2002943A patent/CZ2002943A3/cs unknown
- 2000-08-03 CA CA002385063A patent/CA2385063A1/en not_active Abandoned
- 2000-08-03 JP JP2001522973A patent/JP2003509355A/ja not_active Withdrawn
- 2000-08-03 EA EA200200369A patent/EA005308B1/ru not_active IP Right Cessation
- 2000-08-03 AU AU68363/00A patent/AU777763B2/en not_active Ceased
- 2000-08-03 IL IL14840900A patent/IL148409A0/xx unknown
- 2000-08-03 EP EP00956409A patent/EP1212040A1/en not_active Withdrawn
-
2002
- 2002-03-01 ZA ZA200201743A patent/ZA200201743B/en unknown
- 2002-03-15 NO NO20021306A patent/NO20021306L/no not_active Application Discontinuation
- 2002-11-26 HK HK02108529.1A patent/HK1047227A1/zh unknown
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1984002270A1 (en) * | 1982-12-13 | 1984-06-21 | Leo Ab | Microfine particles having target-seeking properties |
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 (en) * | 1994-09-22 | 1996-03-28 | Pharmacia Ab | Estramustine formulations with improved pharmaceutical properties |
WO1998051282A1 (en) * | 1997-05-13 | 1998-11-19 | Imarx Pharmaceutical Corp. | Solid porous matrices and methods of making and using the same |
Cited By (3)
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 (en) * | 2017-11-09 | 2020-03-26 | Abon Pharmaceuticals, Llc | Intravenous delivery systems for chemotherapy drugs |
Also Published As
Publication number | Publication date |
---|---|
CZ2002943A3 (cs) | 2002-08-14 |
HK1047227A1 (zh) | 2003-02-14 |
KR20020059405A (ko) | 2002-07-12 |
HUP0202621A2 (hu) | 2002-12-28 |
EP1212040A1 (en) | 2002-06-12 |
MXPA02002859A (es) | 2003-07-21 |
CN1374858A (zh) | 2002-10-16 |
NO20021306L (no) | 2002-04-24 |
AU777763B2 (en) | 2004-10-28 |
AU6836300A (en) | 2001-04-17 |
NZ517631A (en) | 2004-01-30 |
CA2385063A1 (en) | 2001-03-22 |
EA005308B1 (ru) | 2004-12-30 |
JP2003509355A (ja) | 2003-03-11 |
SK3452002A3 (en) | 2002-08-06 |
ZA200201743B (en) | 2003-05-28 |
PL353954A1 (en) | 2003-12-15 |
EA200200369A1 (ru) | 2002-08-29 |
CN1177583C (zh) | 2004-12-01 |
BR0014063A (pt) | 2004-06-29 |
GB9921954D0 (en) | 1999-11-17 |
IL148409A0 (en) | 2002-09-12 |
NO20021306D0 (no) | 2002-03-15 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
EP1214078B1 (en) | Formulations for parenteral use of estramustine phosphate and amino acids | |
US6730664B1 (en) | Formulations for parenteral use of estramustine phosphate and sulfoalkyl ether cyclodextrins | |
EP1206266A2 (en) | Formulations for parenteral use of estramustine phosphate and albumin | |
AU777763B2 (en) | Formulations for parenteral use of estramustine phosphate with improved pharmacological properties | |
WO2001076603A1 (fr) | Compositions medicamenteuses contenant un derive de camptothecine et un agent de regulation de ph | |
ZA200201955B (en) | Formulations for parenteral use of estramustine phosphate and albumin. | |
ITMI991998A1 (it) | Formulazioni di estramustina fosfato ed albumina per uso parenterale |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AK | Designated states |
Kind code of ref document: A1 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: A1 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) | ||
WWE | Wipo information: entry into national phase |
Ref document number: 68363/00 Country of ref document: AU |
|
WWE | Wipo information: entry into national phase |
Ref document number: 148409 Country of ref document: IL |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2002/01743 Country of ref document: ZA Ref document number: 200201743 Country of ref document: ZA |
|
WWE | Wipo information: entry into national phase |
Ref document number: 517631 Country of ref document: NZ |
|
WWE | Wipo information: entry into national phase |
Ref document number: 3452002 Country of ref document: SK |
|
ENP | Entry into the national phase |
Ref document number: 2001 522973 Country of ref document: JP Kind code of ref document: A |
|
WWE | Wipo information: entry into national phase |
Ref document number: PA/a/2002/002859 Country of ref document: MX |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2385063 Country of ref document: CA Ref document number: 008129525 Country of ref document: CN Ref document number: 1020027003498 Country of ref document: KR Ref document number: PV2002-943 Country of ref document: CZ |
|
WWE | Wipo information: entry into national phase |
Ref document number: 10070430 Country of ref document: US |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2000956409 Country of ref document: EP |
|
WWE | Wipo information: entry into national phase |
Ref document number: IN/PCT/2002/532/CHE Country of ref document: IN |
|
WWE | Wipo information: entry into national phase |
Ref document number: 200200369 Country of ref document: EA |
|
WWP | Wipo information: published in national office |
Ref document number: 2000956409 Country of ref document: EP |
|
WWP | Wipo information: published in national office |
Ref document number: 1020027003498 Country of ref document: KR |
|
WWP | Wipo information: published in national office |
Ref document number: PV2002-943 Country of ref document: CZ |
|
WWP | Wipo information: published in national office |
Ref document number: 517631 Country of ref document: NZ |
|
WWG | Wipo information: grant in national office |
Ref document number: 517631 Country of ref document: NZ |
|
WWG | Wipo information: grant in national office |
Ref document number: 68363/00 Country of ref document: AU |
|
WWW | Wipo information: withdrawn in national office |
Ref document number: 2000956409 Country of ref document: EP |