SI2459176T1 - Crystallization process and bioavailability - Google Patents

Crystallization process and bioavailability Download PDF

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Publication number
SI2459176T1
SI2459176T1 SI201031592T SI201031592T SI2459176T1 SI 2459176 T1 SI2459176 T1 SI 2459176T1 SI 201031592 T SI201031592 T SI 201031592T SI 201031592 T SI201031592 T SI 201031592T SI 2459176 T1 SI2459176 T1 SI 2459176T1
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Slovenia
Prior art keywords
complex
lysine
zoledronic acid
crystalline
water
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Application number
SI201031592T
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English (en)
Slovenian (sl)
Inventor
Mazen Hanna
Ning Shan
Miranda Cheney
David Weyna
Raymond K. Houck
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Gruenenthal Gmbh
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Publication date
Application filed by Gruenenthal Gmbh filed Critical Gruenenthal Gmbh
Publication of SI2459176T1 publication Critical patent/SI2459176T1/en

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/66Phosphorus compounds
    • A61K31/675Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/335Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365Lactones
    • A61K31/375Ascorbic acid, i.e. vitamin C; Salts thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/66Phosphorus compounds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/62Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0053Mouth and digestive tract, i.e. intraoral and peroral administration
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00Drugs for skeletal disorders
    • A61P19/08Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00Drugs for skeletal disorders
    • A61P19/08Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/12Drugs for disorders of the metabolism for electrolyte homeostasis
    • A61P3/14Drugs for disorders of the metabolism for electrolyte homeostasis for calcium homeostasis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • A61P35/04Antineoplastic agents specific for metastasis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • A61P37/02Immunomodulators
    • A61P37/04Immunostimulants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00Drugs for disorders of the blood or the extracellular fluid
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07FACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02Phosphorus compounds
    • C07F9/547Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/645Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having two nitrogen atoms as the only ring hetero atoms
    • C07F9/6503Five-membered rings
    • C07F9/6506Five-membered rings having the nitrogen atoms in positions 1 and 3
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2121/00Preparations for use in therapy
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07BGENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00Indexing scheme relating to specific properties of organic compounds
    • C07B2200/13Crystalline forms, e.g. polymorphs

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Organic Chemistry (AREA)
  • Epidemiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Rheumatology (AREA)
  • Immunology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Oncology (AREA)
  • Obesity (AREA)
  • Cardiology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Endocrinology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Nutrition Science (AREA)
  • Physiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Pyridine Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
SI201031592T 2009-07-31 2010-07-30 Crystallization process and bioavailability SI2459176T1 (en)

Applications Claiming Priority (8)

Application Number Priority Date Filing Date Title
US23022209P 2009-07-31 2009-07-31
US28803609P 2009-12-18 2009-12-18
US30211010P 2010-02-06 2010-02-06
US31287910P 2010-03-11 2010-03-11
US31850310P 2010-03-29 2010-03-29
US35954410P 2010-06-29 2010-06-29
EP10805109.5A EP2459176B1 (en) 2009-07-31 2010-07-30 Crystallization method and bioavailability
PCT/US2010/043892 WO2011014766A2 (en) 2009-07-31 2010-07-30 Crystallization method and bioavailability

Publications (1)

Publication Number Publication Date
SI2459176T1 true SI2459176T1 (en) 2018-01-31

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
SI201031592T SI2459176T1 (en) 2009-07-31 2010-07-30 Crystallization process and bioavailability

Country Status (20)

Country Link
US (5) US8399023B2 (OSRAM)
EP (2) EP2459176B1 (OSRAM)
JP (1) JP5852569B2 (OSRAM)
KR (1) KR101813728B1 (OSRAM)
CN (1) CN102573809B (OSRAM)
AU (2) AU2010278860B2 (OSRAM)
CA (1) CA2769633C (OSRAM)
CY (1) CY1121952T1 (OSRAM)
DK (1) DK2459176T3 (OSRAM)
ES (1) ES2650665T3 (OSRAM)
HR (1) HRP20171755T1 (OSRAM)
HU (1) HUE034784T2 (OSRAM)
IL (1) IL217828B (OSRAM)
IN (1) IN2012DN01216A (OSRAM)
LT (1) LT2459176T (OSRAM)
NO (1) NO2459176T3 (OSRAM)
PL (1) PL2459176T3 (OSRAM)
PT (1) PT2459176T (OSRAM)
SI (1) SI2459176T1 (OSRAM)
WO (1) WO2011014766A2 (OSRAM)

Families Citing this family (68)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2769633C (en) 2009-07-31 2017-06-06 Thar Pharmaceuticals, Inc. Crystallization method and bioavailability
US8980868B2 (en) 2009-07-31 2015-03-17 Thar Pharmaceuticals, Inc. Oral forms of a phosphonic acid derivative
US9169279B2 (en) 2009-07-31 2015-10-27 Thar Pharmaceuticals, Inc. Crystallization method and bioavailability
US20160016982A1 (en) * 2009-07-31 2016-01-21 Thar Pharmaceuticals, Inc. Crystallization method and bioavailability
DK2531200T3 (en) * 2010-02-06 2017-09-11 Gruenenthal Gmbh COSTALLIZATION PROCEDURE AND BIOTA ACCESSIBILITY
WO2012071517A2 (en) 2010-11-24 2012-05-31 Thar Pharmaceuticals, Inc. Novel crystalline forms
US10016445B2 (en) 2012-05-14 2018-07-10 Antecip Bioventures Ii Llc Compositions for oral administration of zoledronic acid or related compounds for treating complex regional pain syndrome
US9675626B2 (en) 2012-05-14 2017-06-13 Antecip Bioventures Ii Llc Compositions for oral administration of zoledronic acid or related compounds for treating complex regional pain syndrome
US9211257B2 (en) 2012-05-14 2015-12-15 Antecip Bioventures Ii Llc Osteoclast inhibitors for knee conditions
US9999628B2 (en) 2012-05-14 2018-06-19 Antecip Bioventures Ii Llc Neridronic acid for treating complex regional pain syndrome
US9949993B2 (en) 2012-05-14 2018-04-24 Antecip Bioventures Ii Llc Compositions for administration of zoledronic acid or related compounds for treating low back pain
US10493085B2 (en) 2012-05-14 2019-12-03 Antecip Bioventures Ii Llc Neridronic acid and other bisphosphonates for treating complex regional pain syndrome and other diseases
US10111837B2 (en) 2012-05-14 2018-10-30 Antecip Bioventures Ii Llc Dosage forms for oral administration of zoledronic acid or related compounds
US9669040B2 (en) 2012-05-14 2017-06-06 Antecip Bioventures Ii Llc Compositions for oral administration of zoledronic acid or related compounds for treating complex regional pain syndrome
US9694023B2 (en) 2012-05-14 2017-07-04 Antecip Bioventures Ii Llc Methods for the safe administration of imidazole or imidazolium compounds
US9867839B2 (en) 2012-05-14 2018-01-16 Antecip Bioventures Ii Llc Osteoclast inhibitors for joint conditions
US9707247B2 (en) 2012-05-14 2017-07-18 Antecip Bioventures Ii Llc Compositions for administration of zoledronic acid or related compounds for treating low back pain
US9867840B2 (en) 2014-05-27 2018-01-16 Antecip Bioventures Ii Llc Compositions for oral administration of zoledronic acid or related compounds for treating complex regional pain syndrome
US9616078B2 (en) 2012-05-14 2017-04-11 Antecip Bioventures Ii Llc Dosage forms for oral administration of zoledronic acid or related compounds for treating disease
US10092581B2 (en) 2014-05-15 2018-10-09 Antecip Bioventures Ii Llc Osteoclast inhibitors such as zoledronic acid for low back pain treatment
US9956238B2 (en) 2014-05-15 2018-05-01 Antecip Bioventures Ii Llc Compositions for administration of zoledronic acid or related compounds for treating low back pain
US8865757B1 (en) 2014-05-28 2014-10-21 Antecip Bioventures Ii Llp Therapeutic compositions comprising imidazole and imidazolium compounds
US10034890B2 (en) 2012-05-14 2018-07-31 Antecip Bioventures Ii Llc Compositions for oral administration of zoledronic acid or related compounds for treating complex regional pain syndrome
US9925203B2 (en) 2012-05-14 2018-03-27 Antecip Bioventures Ii Llc Compositions for administration of zoledronic acid or related compounds for treating low back pain
US9956237B2 (en) 2012-05-14 2018-05-01 Antecip Bioventures Ii Llc Osteoclast inhibitors for knee conditions
US9901589B2 (en) 2012-05-14 2018-02-27 Antecip Bioventures Ii Llc Compositions for oral administration of zoledronic acid or related compounds for treating complex regional pain syndrome
US10016446B2 (en) 2012-05-14 2018-07-10 Antecip Bioventures Ii Llc Compositions for oral administration of zoledronic acid or related compounds for treating Paget's disease of bone
US10028969B2 (en) 2012-05-14 2018-07-24 Antecip Bioventures Ii Llc Compositions for oral administration of zoledronic acid or related compounds for treating complex regional pain syndrome
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US9827256B2 (en) 2014-05-27 2017-11-28 Antecip Bioventures Ii Llc Compositions for administration of zoledronic acid or related compounds for treating lower back pain
US10080765B2 (en) 2012-05-14 2018-09-25 Antecip Bioventures Ii Llc Neridronic acid for treating complex regional pain syndrome
US9655908B2 (en) 2012-05-14 2017-05-23 Antecip Bioventures Ii Llc Neridronic acid molecular complex for treating complex regional pain syndrome
US9662343B2 (en) 2012-05-14 2017-05-30 Antecip Bioventures Ii Llc Compositions for oral administration of zoledronic acid or related compounds for treating complex regional pain syndrome
US10028908B2 (en) 2012-05-14 2018-07-24 Antecip Bioventures Ii Llc Compositions for oral administration of zoledronic acid or related compounds for treating complex regional pain syndrome
US10463682B2 (en) 2012-05-14 2019-11-05 Antecip Bioventures Ii Llc Compositions for oral administration of zoledronic acid or related compounds for treating low back pain
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US10413561B2 (en) 2012-05-14 2019-09-17 Antecip Bioventures Ii Llc Neridronic acid and other bisphosphonates for treating complex regional pain syndrome and other diseases
US9770457B2 (en) 2012-05-14 2017-09-26 Antecip Bioventures Ii Llc Neridronic acid for treating bone marrow lesion
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US9795622B2 (en) 2012-05-14 2017-10-24 Antecip Bioventures Ii Llc Neridronic acid for treating pain associated with a joint
US9820999B2 (en) 2012-05-14 2017-11-21 Antecip Bioventures Ii Llc Neridronic acid for treating complex regional pain syndrome
US9999629B2 (en) 2012-05-14 2018-06-19 Antecip Bioventures Ii Llc Compositions for oral administration of zoledronic acid or related compounds for treating complex regional pain syndrome
US10039773B2 (en) 2012-05-14 2018-08-07 Antecip Bioventures Ii Llc Neridronic acid for treating arthritis
US9844559B2 (en) 2012-05-14 2017-12-19 Antecip Bioventures Ii Llc Neridronic acid for treating bone marrow lesions
US9717747B2 (en) 2012-05-14 2017-08-01 Antecip Bioventures Ii Llc Osteoclast inhibitors for knee conditions
US10004756B2 (en) 2014-05-15 2018-06-26 Antecip Bioventures Ii Llc Compositions for oral administration of zoledronic acid or related compounds for treating complex regional pain syndrome
US9789128B2 (en) 2012-05-14 2017-10-17 Antecip Bioventures Ii Llc Compositions for oral administration of zoledronic acid or related compounds for treating complex regional pain syndrome
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US20140349974A1 (en) * 2014-08-12 2014-11-27 Antecip Bioventures Ii Llc Zoledronic acid dosage forms for the treatment of pain
US11654152B2 (en) 2012-05-14 2023-05-23 Antecip Bioventures Ii Llc Compositions for oral administration of zoledronic acid or related compounds for treating disease
US9895383B2 (en) 2012-05-14 2018-02-20 Antecip Bioventures Ii Llc Compositions for oral administration of zoledronic acid or related compounds for treating complex regional pain syndrome
KR20190009428A (ko) * 2013-10-25 2019-01-28 안테씨프 바이오벤쳐스 투 엘엘씨 질병의 치료를 위한, 졸레드론산 또는 관련 화합물의 경구 투여용 조성물
US9127069B1 (en) 2014-06-11 2015-09-08 Antecip Bioventures LLC Compositions comprising rank/rankl antagonists and related compounds for treating pain
US9079927B1 (en) 2014-05-27 2015-07-14 Antecip Bioventures Ii Llc Substituted imidazolium compounds for treating disease
US9688765B2 (en) 2014-06-11 2017-06-27 Antecip Bioventures Ii Llc Methods using RANK/RANKL antagonist antibodies for treating pain
KR20180053384A (ko) * 2015-09-18 2018-05-21 그뤼넨탈 게엠베하 결정화 방법 및 생체이용률
US10195218B2 (en) 2016-05-31 2019-02-05 Grunenthal Gmbh Crystallization method and bioavailability
CN112778365A (zh) * 2020-12-30 2021-05-11 华南理工大学 一种唑来膦酸钙配合物及其制备方法

Family Cites Families (142)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3959361A (en) 1970-03-20 1976-05-25 Joh. A. Benckiser Gmbh Process of producing amino methylene phosphonic acids
US3961934A (en) 1974-12-19 1976-06-08 Monsanto Company Method for increasing the sucrose content of growing plants
ATE72816T1 (de) * 1986-11-21 1992-03-15 Ciba Geigy Ag Neue substituierte alkandiphosphonsaeuren.
IE912115A1 (en) * 1990-06-25 1992-01-01 Takeda Chemical Industries Ltd Bisphosphonic acid derivatives, their production and use
HU215124B (hu) 1991-02-26 1998-09-28 Norwich Eaton Pharmaceuticals, Inc. Eljárás csontritkulás (osteoporosis) kezelésére szolgáló ösztrogént és difoszfonátot tartalmazó, szinergetikus hatású gyógyszerkészítmények előállítására
US5431920A (en) * 1993-09-21 1995-07-11 Merck Frosst, Canada, Inc. Enteric coated oral compositions containing bisphosphonic acid antihypercalcemic agents
EP0779812A4 (en) 1994-09-09 1997-09-10 Procter & Gamble METHOD FOR TREATING OSTEOPOROSIS USING BONE-ACTIVE PHOSPHONATES AND PARATHORMONE
US6541454B1 (en) * 1995-04-04 2003-04-01 Yissum Research Development Company Of The Hebrew University Jerusalem Phosphonates, biphosphonates and pharmaceutical compositions containing them
GB9516268D0 (en) 1995-08-08 1995-10-11 Danbiosyst Uk Compositiion for enhanced uptake of polar drugs from the colon
GB9710699D0 (en) 1997-05-24 1997-07-16 Danbiosyst Uk Gastro-retentive controlled release system
AU729912B2 (en) 1997-06-11 2001-02-15 Warner Chilcott Company, Llc Film-coated tablet for improved upper gastrointestinal tract safety
EP0998933A1 (de) 1998-10-09 2000-05-10 Boehringer Mannheim Gmbh Verfahren zur Herstellung von bisphosphonathaltigen pharmazeutischen Zusammensetzungen zur oralen Applikation
ES2301477T3 (es) 1999-02-22 2008-07-01 Merrion Research I Limited Forma de dosificacion oral solida que contiene un potenciador.
US7658938B2 (en) * 1999-02-22 2010-02-09 Merrion Reasearch III Limited Solid oral dosage form containing an enhancer
US8119159B2 (en) * 1999-02-22 2012-02-21 Merrion Research Iii Limited Solid oral dosage form containing an enhancer
SE9901272D0 (sv) 1999-04-09 1999-04-09 Astra Ab New improved formulation
EP1210138A4 (en) 1999-04-22 2003-05-07 Hydro Med Sciences Inc REGULATED BISPHOSPHONATE ADMINISTRATION
ATE293450T1 (de) * 1999-05-21 2005-05-15 Novartis Pharma Gmbh Verwendung von biphosphonsäuren zur behandlung von angiogenese
AR021347A1 (es) * 1999-10-20 2002-07-17 Cipla Ltd Una composicion farmaceutica que contiene acido(s) bisfosfoncio o sal(es) del mismo y un proceso de preparacion de la misma
US6936275B2 (en) * 1999-12-20 2005-08-30 Scolr, Inc. Amino acid modulated extended release dosage form
US6677320B2 (en) * 2000-01-20 2004-01-13 Hoffmann-La Roches Inc. Parenteral bisphosphonate composition with improved local tolerance
AU2001251432A1 (en) * 2000-04-07 2001-10-23 The Board Of Regents Of The University Of Texas System Unique compositions of zwitterionic phospholipids and bisphosphonates and use ofthe compositions as bisphosphate delivery systems with reduced gi toxicity
US6468559B1 (en) * 2000-04-28 2002-10-22 Lipocine, Inc. Enteric coated formulation of bishosphonic acid compounds and associated therapeutic methods
EP1284754B1 (en) * 2000-05-05 2006-01-04 F. Hoffmann-La Roche Ag Gel-like pharmaceutical composition for subcutaneous administration comprising bisphosphonic acids or their salts
SI1296689T1 (sl) 2000-06-20 2006-08-31 Novartis Ag Nacin dajanja pacientu bisfosfonatov
IL153229A0 (en) 2000-06-20 2003-07-06 Novartis Ag Method of administering bisphosphonates
US6476006B2 (en) * 2000-06-23 2002-11-05 Teva Pharmaceutical Industries, Ltd. Composition and dosage form for delayed gastric release of alendronate and/or other bis-phosphonates
CA2415643C (en) * 2000-07-17 2010-11-16 Yamanouchi Pharmaceutical Co., Ltd. Pharmaceutical composition for oral use with improved absorption
CA2435552C (en) * 2001-02-06 2010-04-27 The Royal Alexandra Hospital For Children A drug for the treatment of osteonecrosis and for the management of patients at risk of developing osteonecrosis
CA2438848C (en) * 2001-03-01 2011-05-03 Emisphere Technologies, Inc. Compositions for delivering bisphosphonates
JP2004526747A (ja) 2001-04-03 2004-09-02 ザ ロイヤル アレクサンドラ ホスピタル フォー チルドレン 骨移植で使用される医薬
AU2002302555B2 (en) 2001-04-30 2007-08-23 Novologix Gmbh EF-Tu binding agent as antibacterial agent
PL363507A1 (en) * 2001-05-02 2004-11-29 Novartis Ag Pharmaceutical uses of bisphosphonates
CN100345549C (zh) * 2001-05-02 2007-10-31 诺瓦提斯公司 包含双膦酸的药用吸入组合物
EP1392272B1 (en) * 2001-05-11 2014-08-06 Merrion Research III Limited Permeation enhancers
CA2454200A1 (en) 2001-07-17 2003-01-30 Teva Pharmaceutical Industries Ltd. Dosage forms for immediate gastric release of a calcium transport stimulator coupled with delayed gastric release of a bis-phosphonate
DK1443942T3 (da) * 2001-10-19 2008-05-19 Novartis Ag Farmaceutisk sammensætning til anvendelse ved behandling af maligniteter omfattende en kombination af et bisphosphonat, en COX-2 inhibitor og en taxol
JP2005516928A (ja) 2001-12-13 2005-06-09 メルク エンド カムパニー インコーポレーテッド 骨異常のためのビスホスホネート液体製剤
ITMI20020908A1 (it) * 2002-04-29 2003-10-29 Chemi Spa Processo di preparazione di sodio alendronato
KR20140021045A (ko) * 2002-05-10 2014-02-19 에프. 호프만-라 로슈 아게 골다공증 치료 및 예방용 비스포스폰산
CN1665825A (zh) * 2002-05-17 2005-09-07 特瓦制药工业有限公司 用一定的稀释剂制备双膦酸
US20040047835A1 (en) * 2002-09-06 2004-03-11 Cell Therapeutics, Inc. Combinatorial drug therapy using polymer drug conjugates
GB0220885D0 (en) 2002-09-09 2002-10-16 Novartis Ag Organic compounds
US20040138180A1 (en) * 2002-10-03 2004-07-15 Barr Laboratories, Inc. Bisphosphonate composition and process for the preparation thereof
TW200410701A (en) 2002-10-15 2004-07-01 Novartis Ag Method of administering bisphosphonates
ES2530791T3 (es) 2002-12-20 2015-03-05 Hoffmann La Roche Formulación de ibandronato de altas dosis
US20060173009A1 (en) * 2003-01-07 2006-08-03 Hiroyuki Kanoh Agent inducing increase in bone mass
EP1525207A2 (en) * 2003-02-27 2005-04-27 Teva Pharmaceutical Industries Limited Process for purification of zoledronic acid
JP2007524596A (ja) 2003-02-28 2007-08-30 トランスフォーム・ファーマシューティカルズ・インコーポレイテッド 共結晶医薬組成物
JP4923182B2 (ja) 2003-02-28 2012-04-25 マクニール−ピーピーシー・インコーポレーテツド セレコキシブ及びニコチンアミド共結晶並びにこの共結晶を含む医薬組成物
US20040220264A1 (en) * 2003-03-17 2004-11-04 Yu Ruey J Bioavailability and improved delivery of acidic pharmaceutical drugs
GB0310919D0 (en) 2003-05-13 2003-06-18 West Pharm Serv Drug Res Ltd Pharmaceutical compositions
CA2527079A1 (en) 2003-05-29 2005-01-06 Synta Pharmaceuticals, Corp. Heterocyclic compounds for preventing and treating disorders associated with excessive bone loss
EP1567533B1 (en) * 2003-07-03 2009-03-11 Teva Pharmaceutical Industries Ltd. Zoledronic acid crystal forms, zoledronate sodium salt crystal forms, amorphous zoledronate sodium salt, and processes for their preparation
PL1656386T3 (pl) * 2003-08-21 2010-05-31 Sun Pharmaceuticals Ind Ltd Proces wytwarzania związków kwasu difosfonowego
MY141763A (en) * 2003-09-18 2010-06-30 Novartis Ag Pharmaceutical products comprising bisphosphonates
US20050119230A1 (en) * 2003-09-18 2005-06-02 Alexandra Glausch Pharmaceutical products comprising bisphosphonated
NZ545804A (en) * 2003-09-19 2009-09-25 Wisconsin Alumni Res Found Pharmaceutical compositions and methods comprising combinations of 2-alkylidene-19-or-vitamin D derivatives and a bisphosphonate
WO2005048979A2 (en) 2003-10-06 2005-06-02 Torrent Pharmaceuticals Limited Pharmaceutical composition having casing with multiple micro tablets
CN1886105A (zh) 2003-10-14 2006-12-27 德马全兹股份有限公司 经增强的亲水药物的经皮给药
AR046773A1 (es) 2003-12-23 2005-12-21 Novartis Ag Formulaciones farmaceuticas de bisfosfonatos
WO2005063717A1 (en) 2003-12-26 2005-07-14 Natco Pharma Limited An improved process for the preparation of zoledronic acid
JP2007532577A (ja) 2004-04-07 2007-11-15 ダーマトレンズ,インコーポレイティド 塩基性浸透促進剤と共に用いるための経皮デリバリー・システム
US20080287400A1 (en) * 2004-05-24 2008-11-20 Richard John Dansereau Low Dosage Forms Of Risedronate Or Its Salts
AU2011218625B2 (en) 2004-05-24 2014-03-20 Theramex HQ UK Limited Dosage forms of risedronate
DK1753395T3 (da) 2004-05-24 2010-11-08 Warner Chilcott Co Llc Enterisk, fast, oral doseringsform af et bisphosphonat, der indeholder et chelateringsmiddel
US7645459B2 (en) * 2004-05-24 2010-01-12 The Procter & Gamble Company Dosage forms of bisphosphonates
US20080286359A1 (en) * 2004-05-24 2008-11-20 Richard John Dansereau Low Dosage Forms Of Risedronate Or Its Salts
US7645460B2 (en) * 2004-05-24 2010-01-12 The Procter & Gamble Company Dosage forms of risedronate
US20050289182A1 (en) 2004-06-15 2005-12-29 Sand Hill Systems Inc. Document management system with enhanced intelligent document recognition capabilities
US20060069069A1 (en) * 2004-07-15 2006-03-30 Nanobac Pharmaceuticals, Inc. Methods and compositions for the administration of calcium chelators, bisphosponates and/or citrate compounds and their pharmaceutical uses
WO2006020009A1 (en) 2004-07-23 2006-02-23 The Procter & Gamble Company Solid oral dosage form of a bisphosphonate containing a chelating agent
WO2006018033A1 (en) 2004-08-20 2006-02-23 Mepha Ag Formulations of bisphosphonates
US20060068010A1 (en) * 2004-09-30 2006-03-30 Stephen Turner Method for improving the bioavailability of orally delivered therapeutics
US20060134190A1 (en) * 2004-12-16 2006-06-22 Banner Pharmacaps Inc. Formulations of bisphosphonate drugs with improved bioavailability
US20060178439A1 (en) 2005-01-04 2006-08-10 Mohakhud Pradeep K Crystalline form of zoledronic acid
KR100815040B1 (ko) * 2005-01-31 2008-03-18 주식회사종근당 비스포스포네이트계 약물의 경구흡수 개선을 위한약제학적 조성물
ATE511835T1 (de) * 2005-02-17 2011-06-15 Hadasit Med Res Service Biophosphonate zur behandlung von endometriose
BRPI0606280A2 (pt) 2005-03-17 2009-06-09 Elan Pharma Int Ltd composições de bisfosfonato nanoparticulado
AR057291A1 (es) 2005-05-06 2007-11-28 Medichem Sa Proceso para la preparacion de acidos bisfosfonicos geminales y las sales y/o hidratos farmaceuticamente aceptables de los mismos, una composicion farmaceutica que los contiene y el uso de esta en el tratamiento de la osteoporosis
US20070014319A1 (en) 2005-07-15 2007-01-18 Zetetic Institute Continuously Tunable External Cavity Diode Laser Sources With High Tuning And Switching Rates And Extended Tuning Ranges
AR054673A1 (es) 2005-07-28 2007-07-11 Gador Sa Una forma cristalina del acido zoledronico, un proceso para su obtencion y la composicion farmaceutica que la comprende
US20070049557A1 (en) * 2005-08-24 2007-03-01 Hashim Ahmed Solid pharmaceutical dosage forms comprising bisphosphonates and modified amino acid carriers
BRPI0616081A2 (pt) * 2005-09-12 2011-06-07 Reddy S Lab Inc triidrato cristalino de ácido zoledrÈnico
JO3006B1 (ar) 2005-09-14 2016-09-05 Janssen Pharmaceutica Nv املاح ليسين مبتكرة من مشتقات حامض 4-((فينوكسي الكيل)ثيو) فينوكسي الخليك
US7473684B2 (en) * 2005-09-16 2009-01-06 Selamine Limited Bisphosphonate formulation
US20070088161A1 (en) * 2005-10-19 2007-04-19 Stockel Richard F Novel chelated bisphosphonates for use as pharmaceutical agents
WO2007069049A2 (en) 2005-12-16 2007-06-21 Wockhardt Ltd Processes for the preparation of pure zoledronic acid
WO2007083240A2 (en) * 2006-01-20 2007-07-26 Aurobindo Pharma Limited An improved process for the preparation of bisphosphonic acids
BRPI0707516A2 (pt) * 2006-02-06 2011-05-10 Cypress Bioscience Inc composiÇÕes que compreendem um bisfosfonato e um antifolato
WO2007096896A1 (en) * 2006-02-20 2007-08-30 Alembic Limited An improved process for the preparation of biphosphonic derivatives
CN101443341A (zh) * 2006-03-21 2009-05-27 雅宝公司 制造二膦酸的方法
CA2648594C (en) 2006-04-07 2012-10-16 Merrion Research Iii Limited Solid oral dosage form containing an enhancer
US20090075941A1 (en) * 2006-04-21 2009-03-19 The Uab Research Foundation Treating neoplasms
WO2007125521A2 (en) 2006-05-02 2007-11-08 Ranbaxy Laboratories Limited Polymorphic form of zoledronic acid and processes for their preparation
WO2007146234A2 (en) 2006-06-09 2007-12-21 Merrion Research Ii Limited Solid oral dosage form containing an enhancer
US20100047306A1 (en) * 2006-10-05 2010-02-25 Novartis Ag Pharmaceutical compositions comprising bisphosponates
EP1923394A1 (en) 2006-11-16 2008-05-21 Sandoz A/S Reagent and use thereof for the production of bisphosphonates
JP2010510194A (ja) 2006-11-17 2010-04-02 ベシンズ・ヘルスケアー ビスホスホネート化合物を含む薬剤組成物
EP1925621A1 (en) 2006-11-27 2008-05-28 Novartis AG Crystalline forms of zoledronic acid
US20080139514A1 (en) * 2006-11-29 2008-06-12 Subhash Pandurang Gore Diphosphonic acid pharmaceutical compositions
KR100775440B1 (ko) * 2006-12-20 2007-11-12 동우신테크 주식회사 리세드로네이트 나트륨 헤미펜타히드레이트의 제조방법
US8974801B2 (en) * 2006-12-21 2015-03-10 Amphastar Pharmaceuticals Inc. Long term sustained release pharmaceutical composition containing aqueous suspension of bisphosphonate
TW200843802A (en) 2007-02-09 2008-11-16 Drugtech Corp Compositions for improving gastrointestinal nutrient and drug absorption
ES2704439T3 (es) 2007-03-20 2019-03-18 Scf Pharma Inc Composiciones que comprenden monoglicéridos de ácidos grasos poliinsaturados o derivados de los mismos y usos de los mismos
US20090023683A1 (en) * 2007-07-16 2009-01-22 Chandrasekhar Kocherlakota Complexes comprising zoledronic acid and cyclodextrins
WO2009018834A1 (en) 2007-08-06 2009-02-12 Pharmathen S.A. Pharmaceutical composition containing bisphosphonate and method for the preparation thereof
KR101165455B1 (ko) 2007-09-10 2012-07-12 한스바이오메드 주식회사 인산칼슘 마이크로스피어 약물전달체 및 이의 제조방법
WO2009042179A1 (en) 2007-09-24 2009-04-02 Teva Pharmaceutical Industries Ltd. Crystalline forms of ibandronic acid and processeses for the preparation thereof
ES2731881T3 (es) 2007-09-25 2019-11-19 Formulex Pharma Innovations Ltd Composiciones que comprenden compuestos activos lipófilos y método para su preparación
US20090082312A1 (en) * 2007-09-25 2009-03-26 Protia, Llc Deuterium-enriched zoledronic acid
ITPA20070034A1 (it) 2007-10-30 2009-04-30 Tetrapharm S R L Bifosfonati geminali, loro preparazione e loro impiego in campo oncologico.
US8737985B2 (en) * 2007-11-26 2014-05-27 Wavemarket, Inc. Methods and systems for zone creation and adaption
AU2008328797B2 (en) 2007-11-30 2011-11-03 Novartis Ag C2-C5-Alkyl-imidazole-bisphosphonates
EP2217260B1 (en) 2007-12-04 2016-11-09 Ben-Gurion University Of The Negev Research And Development Authority Amphiphilic peptide matrices for treatment of osteoporosis
EP2255199A1 (en) * 2008-02-19 2010-12-01 Jovesis Inc. Microparticle compositions to modify cancer promoting cells
AU2009217982B2 (en) 2008-02-26 2013-04-11 Takeda Pharmaceutical Company Limited Fused heterocyclic derivative and use thereof
FR2928270B1 (fr) 2008-03-10 2011-01-21 Erytech Pharma Formulation methode pour la prevention ou le traitement des metastases osseuses et autres maladies de l'os
AU2009232033A1 (en) 2008-04-04 2009-10-08 Novartis Ag Pharmaceutical composition with bisphosphonate
JP2009302891A (ja) 2008-06-13 2009-12-24 Sony Corp 情報処理装置
JP2011529901A (ja) 2008-07-31 2011-12-15 味の素株式会社 リセドロネートまたはその塩の低投与量形態
US8008329B2 (en) * 2008-08-01 2011-08-30 Dong Wha Pharmaceutical Co., Ltd. Method of treating or preventing osteoporosis comprising administering to a patient in need thereof an effective amount of pharmacuetical composition comprising benzamidine derivative or it's salt, and bisphosphonate
WO2010060619A1 (en) 2008-11-26 2010-06-03 Synthon B.V. Process for making zoledronic acid
US20100158905A1 (en) 2008-12-19 2010-06-24 Nuon Therapeutics, Inc. Combination therapy of arthritis with tranilast
AR075613A1 (es) 2009-02-25 2011-04-20 Merrion Res Iii Ltd Composicion y suministro de drogas de bifosfonato. metodo de tratamiento
US20160016982A1 (en) 2009-07-31 2016-01-21 Thar Pharmaceuticals, Inc. Crystallization method and bioavailability
US9169279B2 (en) 2009-07-31 2015-10-27 Thar Pharmaceuticals, Inc. Crystallization method and bioavailability
CA2769633C (en) * 2009-07-31 2017-06-06 Thar Pharmaceuticals, Inc. Crystallization method and bioavailability
US8980868B2 (en) 2009-07-31 2015-03-17 Thar Pharmaceuticals, Inc. Oral forms of a phosphonic acid derivative
US20110182985A1 (en) * 2010-01-28 2011-07-28 Coughlan David C Solid Pharmaceutical Composition with Enhancers and Methods of Preparing thereof
DK2531200T3 (en) 2010-02-06 2017-09-11 Gruenenthal Gmbh COSTALLIZATION PROCEDURE AND BIOTA ACCESSIBILITY
WO2011132826A1 (en) 2010-04-19 2011-10-27 Snu R&Db Foundation Transdermal drug delivery system and pharmaceutical composition for preventing or treating bone diseases
US8946199B2 (en) * 2010-04-26 2015-02-03 Ketan Desai Co-administration of steroids and Zoledronic acid to prevent and treat side effects from Zoledronic acid infusion
WO2012071517A2 (en) 2010-11-24 2012-05-31 Thar Pharmaceuticals, Inc. Novel crystalline forms
CN102070668B (zh) 2010-12-23 2013-07-24 蚌埠丰原医药科技发展有限公司 一种利用相转移催化剂制备唑来膦酸及其钠盐的方法
US8993057B2 (en) 2011-10-22 2015-03-31 Masoud Salavati-Niasari Method for preparing silica-dysprosium oxide core-shell nanoparticles
US20140349974A1 (en) 2014-08-12 2014-11-27 Antecip Bioventures Ii Llc Zoledronic acid dosage forms for the treatment of pain
US20130303486A1 (en) 2012-05-14 2013-11-14 Herriot Tabuteau Compositions Comprising Zoledronic Acid or Related Compounds for Relieving Pain Associated with Arthritis
CN103070668A (zh) 2013-01-02 2013-05-01 北京工业大学 心脏年龄检测仪及其检测方法
CN114159580A (zh) 2013-10-04 2022-03-11 加利福尼亚大学董事会 采用llp2a-二膦酸盐/酯偶联物和间充质干细胞治疗炎症
KR20180053384A (ko) 2015-09-18 2018-05-21 그뤼넨탈 게엠베하 결정화 방법 및 생체이용률
US10195218B2 (en) 2016-05-31 2019-02-05 Grunenthal Gmbh Crystallization method and bioavailability

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