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WO1999020635A1 - Sel d'un derive de l'acide bisphosphonique - Google Patents

Sel d'un derive de l'acide bisphosphonique Download PDF

Info

Publication number
WO1999020635A1
WO1999020635A1 PCT/IL1998/000508 IL9800508W WO9920635A1 WO 1999020635 A1 WO1999020635 A1 WO 1999020635A1 IL 9800508 W IL9800508 W IL 9800508W WO 9920635 A1 WO9920635 A1 WO 9920635A1
Authority
WO
WIPO (PCT)
Prior art keywords
alendronic acid
acid salt
dipotassium
pharmaceutical preparation
anhydrous
Prior art date
Application number
PCT/IL1998/000508
Other languages
English (en)
Inventor
Zevulun Tomer
Original Assignee
Unipharm Ltd.
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
Application filed by Unipharm Ltd. filed Critical Unipharm Ltd.
Priority to AU95591/98A priority Critical patent/AU9559198A/en
Publication of WO1999020635A1 publication Critical patent/WO1999020635A1/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
    • C07F9/3804—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)] not used, see subgroups
    • C07F9/3839—Polyphosphonic acids
    • C07F9/3873—Polyphosphonic acids containing nitrogen substituent, e.g. N.....H or N-hydrocarbon group which can be substituted by halogen or nitro(so), N.....O, N.....S, N.....C(=X)- (X =O, S), N.....N, N...C(=X)...N (X =O, S)

Definitions

  • the present invention relates to the anhydrous dipotassium alendronic acid salt and to the dipotassium alendronic acid salt hydrates.
  • Alndronic acid stands for 4-amino-l-hydroxybutyli- dene-1, 1-bisphosphonic acid.
  • Alendronic acid and some of its pharmaceutically acceptable salts are known compounds. Said compounds serve for the treatment of diseases of abnormal (ectopic) depositions of calcium salts and the reduction of bone resorption.
  • diseases there may be mentioned, inter alia, osteoporosis, menopausal osteoporosis, Paget's disease, myosisitis ossificans, Bechterew's disease, malignant hypercalcemia, metastatic bone disease, periodontal disease, cholelithiasis, nephrolithiasis, urolithiasis, urinary calculus, sclerosis, arthritis, bursistis, neuritis and tetany.
  • the present invention thus consists in the anhydrous dipotassium alendronic acid salt and in the dipotassium alendronic acid salt hydrates .
  • the present invention consists also in pharmaceutical preparations comprising as active ingredient the anhydrous dipotassium alendronic acid salt one of the dipotassium alendronic acid salt hydrates.
  • the pharmaceutical preparation may be a tablet, a pellet, a film, sugar or enterocoated tablet or pellet, a capsule, a suspension, a solution, an emulsion, etc. It may comprise in addition to the active ingredient suitable one or more compounds selected among suitable carriers, diluents, fillers, solvents, lubricants, disintegrants, preservatives, emulsifiers, etc.
  • the compounds according to the present invention may be prepared by a reaction of the alendronic acid with potassium hydroxide under suitable reaction conditions.
  • the compound has the molecular formula: C 4 H 11 0 7 NP 2 K 2
  • the compound has the molecular formula C 4 H 11 0 7 NP 2 K 2 .5H 2 0
  • the granulation wetting solution was sprayed on the powder mixture in a fluid bed granulator to obtain a granulate which was then dried in the fluid bed granulator at an inlet temperature of 50°C.
  • the dried granulate was passed through a 16 mesh sieve and mixed in a drum mixer with 4 g of Magnesium Stearate .
  • the granulate was compressed into tablets, each tablet containing 16,8 mg of Dipotassium Alendronic Acid Salt Pentahydrate equivalent to 10 mg of Alendronic Acid.
  • the granulation wetting solution was sprayed on the powder mixture in a fluid bed granulator to obtain a granulate which was then dried in the fluid bed granulator at an inlet temperature of 50°C.
  • the dried granulate was passed through a 16 mesh sieve and mixed in a drum mixer with 4 g of Magnesium Stearate .
  • the granulate was compressed into tablets, each tablet containing 16,8 mg of Dipotassium Alendronic Acid Salt Pentahydrate equivalent to 10 mg of Alendronic Acid.
  • the lubricated mixture was compressed to provide tablets, each containing the equivalent of 10 mg Alendronic acid.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Medicinal Preparation (AREA)

Abstract

La présente invention concerne un sel de l'acide alendronique de dipotassium anhydre, et les hydrates de ce sel de l'acide alendronique de dipotassium, par exemple un pentahydrate du sel de l'acide alendronique de dipotassium. La présente invention concerne également des préparations pharmaceutiques renfermant le sel de l'acide alendronique de dipotassium anhydre ou l'un des hydrates de ce sel d'acide alendronique de dipotassium en tant que principe actif. Cette préparation pharmaceutique peut se présenter sous la forme d'un comprimé, d'une pastille, d'une pellicule, d'un comprimé ou d'une pastille dragéifié ou à enrobage entérique, d'une capsule, d'une suspension, d'une solution, d'une émulsion, etc.
PCT/IL1998/000508 1997-10-21 1998-10-18 Sel d'un derive de l'acide bisphosphonique WO1999020635A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU95591/98A AU9559198A (en) 1997-10-21 1998-10-18 Salt of a bisphosphonic acid derivative

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IL12200997A IL122009A0 (en) 1997-10-21 1997-10-21 Salt of a bisphosphonic acid derivative
IL122009 1997-10-21

Publications (1)

Publication Number Publication Date
WO1999020635A1 true WO1999020635A1 (fr) 1999-04-29

Family

ID=11070773

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IL1998/000508 WO1999020635A1 (fr) 1997-10-21 1998-10-18 Sel d'un derive de l'acide bisphosphonique

Country Status (4)

Country Link
AU (1) AU9559198A (fr)
IL (1) IL122009A0 (fr)
WO (1) WO1999020635A1 (fr)
ZA (1) ZA989552B (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001030788A1 (fr) * 1999-10-26 2001-05-03 A/S Gea Farmaceutisk Fabrik Nouveaux sels d'acide 4- amino-1-hydroxy-butylidene-1,1-bisphosphonique, leur preparation et utilisation
WO2003008425A1 (fr) * 2001-07-16 2003-01-30 Universite Paris 13 Nouveaux derives de bisphosphonates, leurs preparations et utilisations

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4067971A (en) * 1976-05-13 1978-01-10 The Procter & Gamble Company Therapeutic composition
US4113861A (en) * 1977-05-02 1978-09-12 The Procter & Gamble Company Phosphonate pharmaceutical composition
US4922007A (en) * 1989-06-09 1990-05-01 Merck & Co., Inc. Process for preparing 4-amino-1-hydroxybutylidene-1,1-bisphosphonic acid or salts thereof
WO1996039410A1 (fr) * 1995-06-06 1996-12-12 Merck & Co., Inc. Preparations d'alendronate disodique

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4067971A (en) * 1976-05-13 1978-01-10 The Procter & Gamble Company Therapeutic composition
US4113861A (en) * 1977-05-02 1978-09-12 The Procter & Gamble Company Phosphonate pharmaceutical composition
US4922007A (en) * 1989-06-09 1990-05-01 Merck & Co., Inc. Process for preparing 4-amino-1-hydroxybutylidene-1,1-bisphosphonic acid or salts thereof
WO1996039410A1 (fr) * 1995-06-06 1996-12-12 Merck & Co., Inc. Preparations d'alendronate disodique

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
CHEMICAL ABSTRACTS, vol. 093, no. 7, 18 August 1980, Columbus, Ohio, US; abstract no. 063017, DUKHOVNAYA A I: "Toxicology of hydroxyethylidenediphosphonate salts" XP002091317 *
GIG. TR. NAUCHNO-TEKH. PROG. (43OYAD);77; PP.120-1, Sanepidstants.;Moscow; USSR *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001030788A1 (fr) * 1999-10-26 2001-05-03 A/S Gea Farmaceutisk Fabrik Nouveaux sels d'acide 4- amino-1-hydroxy-butylidene-1,1-bisphosphonique, leur preparation et utilisation
WO2003008425A1 (fr) * 2001-07-16 2003-01-30 Universite Paris 13 Nouveaux derives de bisphosphonates, leurs preparations et utilisations

Also Published As

Publication number Publication date
IL122009A0 (en) 1998-03-10
AU9559198A (en) 1999-05-10
ZA989552B (en) 1999-04-22

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