EA002739B1 - Новые гидратные формы алендроната натрия, способы их получения и фармацевтические композиции - Google Patents
Новые гидратные формы алендроната натрия, способы их получения и фармацевтические композиции Download PDFInfo
- Publication number
- EA002739B1 EA002739B1 EA200100184A EA200100184A EA002739B1 EA 002739 B1 EA002739 B1 EA 002739B1 EA 200100184 A EA200100184 A EA 200100184A EA 200100184 A EA200100184 A EA 200100184A EA 002739 B1 EA002739 B1 EA 002739B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- compound
- amino
- hydroxybutylidene
- sodium
- bisphosphonic acid
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 112
- OGSPWJRAVKPPFI-UHFFFAOYSA-N Alendronic Acid Chemical compound NCCCC(O)(P(O)(O)=O)P(O)(O)=O OGSPWJRAVKPPFI-UHFFFAOYSA-N 0.000 title claims abstract description 46
- 229960004343 alendronic acid Drugs 0.000 title claims abstract description 45
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 8
- 238000004519 manufacturing process Methods 0.000 title description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 216
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 121
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims abstract description 99
- 239000002253 acid Substances 0.000 claims abstract description 52
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims abstract description 50
- 239000011734 sodium Substances 0.000 claims abstract description 50
- 229910052708 sodium Inorganic materials 0.000 claims abstract description 50
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 42
- 150000004682 monohydrates Chemical class 0.000 claims abstract description 32
- CAKRAHQRJGUPIG-UHFFFAOYSA-M sodium;[4-azaniumyl-1-hydroxy-1-[hydroxy(oxido)phosphoryl]butyl]-hydroxyphosphinate Chemical compound [Na+].NCCCC(O)(P(O)(O)=O)P(O)([O-])=O CAKRAHQRJGUPIG-UHFFFAOYSA-M 0.000 claims abstract description 27
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims abstract description 26
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical class [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims abstract description 20
- 238000000634 powder X-ray diffraction Methods 0.000 claims abstract description 18
- 239000000725 suspension Substances 0.000 claims abstract description 14
- 239000002274 desiccant Substances 0.000 claims abstract description 9
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical class [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 claims abstract description 5
- 230000018044 dehydration Effects 0.000 claims abstract description 5
- 238000006297 dehydration reaction Methods 0.000 claims abstract description 5
- 238000006243 chemical reaction Methods 0.000 claims abstract description 4
- 150000003839 salts Chemical class 0.000 claims abstract description 3
- 159000000000 sodium salts Chemical class 0.000 claims abstract description 3
- 150000001875 compounds Chemical class 0.000 claims abstract 100
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims abstract 24
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 claims abstract 12
- PAYGMRRPBHYIMA-UHFFFAOYSA-N sodium;trihydrate Chemical group O.O.O.[Na] PAYGMRRPBHYIMA-UHFFFAOYSA-N 0.000 claims abstract 5
- HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 claims abstract 2
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 27
- 239000000203 mixture Substances 0.000 claims description 27
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 26
- -1 Compound monosodium salt Chemical class 0.000 claims description 26
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 24
- 150000005846 sugar alcohols Polymers 0.000 claims description 19
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 16
- 238000002955 isolation Methods 0.000 claims description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 10
- 150000001298 alcohols Chemical class 0.000 claims description 10
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 9
- 239000003960 organic solvent Substances 0.000 claims description 9
- 239000012024 dehydrating agents Substances 0.000 claims description 7
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 7
- 150000004683 dihydrates Chemical class 0.000 claims description 6
- 208000001132 Osteoporosis Diseases 0.000 claims description 3
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 claims description 3
- 239000002904 solvent Substances 0.000 claims description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims 7
- 230000003993 interaction Effects 0.000 claims 7
- 150000004677 hydrates Chemical class 0.000 claims 2
- NIFIFKQPDTWWGU-UHFFFAOYSA-N pyrite Chemical compound [Fe+2].[S-][S-] NIFIFKQPDTWWGU-UHFFFAOYSA-N 0.000 claims 2
- 229910052683 pyrite Inorganic materials 0.000 claims 2
- 239000011028 pyrite Substances 0.000 claims 2
- 150000002170 ethers Chemical class 0.000 claims 1
- 239000011877 solvent mixture Substances 0.000 claims 1
- 239000000843 powder Substances 0.000 abstract description 14
- DUYCFMAOEDAKDN-UHFFFAOYSA-M sodium (4-amino-1-hydroxy-1-phosphonobutyl)-hydroxyphosphinate hydrate Chemical compound O.[Na+].NCCCC(O)(P(O)(O)=O)P(O)([O-])=O DUYCFMAOEDAKDN-UHFFFAOYSA-M 0.000 abstract 4
- 206010065687 Bone loss Diseases 0.000 abstract 1
- DCSBSVSZJRSITC-UHFFFAOYSA-M alendronate sodium trihydrate Chemical compound O.O.O.[Na+].NCCCC(O)(P(O)(O)=O)P(O)([O-])=O DCSBSVSZJRSITC-UHFFFAOYSA-M 0.000 description 92
- AQAZLLYAEFBJMU-UHFFFAOYSA-N (4-amino-1-hydroxy-1-phosphonobutyl)phosphonic acid;hydrate Chemical compound O.NCCCC(O)(P(O)(O)=O)P(O)(O)=O AQAZLLYAEFBJMU-UHFFFAOYSA-N 0.000 description 31
- 239000000243 solution Substances 0.000 description 25
- 238000003756 stirring Methods 0.000 description 23
- 238000001035 drying Methods 0.000 description 21
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 20
- 239000000126 substance Substances 0.000 description 17
- 238000002329 infrared spectrum Methods 0.000 description 16
- 230000004580 weight loss Effects 0.000 description 16
- 239000002808 molecular sieve Substances 0.000 description 13
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 13
- 238000010992 reflux Methods 0.000 description 12
- 238000010521 absorption reaction Methods 0.000 description 10
- 238000009835 boiling Methods 0.000 description 10
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 10
- 239000007787 solid Substances 0.000 description 9
- 238000001816 cooling Methods 0.000 description 8
- 238000002083 X-ray spectrum Methods 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 239000007791 liquid phase Substances 0.000 description 4
- 239000003937 drug carrier Substances 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- SOBHUZYZLFQYFK-UHFFFAOYSA-K trisodium;hydroxy-[[phosphonatomethyl(phosphonomethyl)amino]methyl]phosphinate Chemical compound [Na+].[Na+].[Na+].OP(O)(=O)CN(CP(O)([O-])=O)CP([O-])([O-])=O SOBHUZYZLFQYFK-UHFFFAOYSA-K 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 208000006386 Bone Resorption Diseases 0.000 description 2
- 208000020084 Bone disease Diseases 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 208000010191 Osteitis Deformans Diseases 0.000 description 2
- 208000027868 Paget disease Diseases 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 230000024279 bone resorption Effects 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 208000027202 mammary Paget disease Diseases 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 229910052698 phosphorus Inorganic materials 0.000 description 2
- 239000012266 salt solution Substances 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 229940062527 alendronate Drugs 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000000536 complexating effect Effects 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 238000001139 pH measurement Methods 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- XTUSEBKMEQERQV-UHFFFAOYSA-N propan-2-ol;hydrate Chemical compound O.CC(C)O XTUSEBKMEQERQV-UHFFFAOYSA-N 0.000 description 1
- 239000012086 standard solution Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- ISIJQEHRDSCQIU-UHFFFAOYSA-N tert-butyl 2,7-diazaspiro[4.5]decane-7-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC11CNCC1 ISIJQEHRDSCQIU-UHFFFAOYSA-N 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 150000004684 trihydrates Chemical class 0.000 description 1
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)]
-
- 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)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Physical Education & Sports Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US9831398P | 1998-08-27 | 1998-08-27 | |
| US12974399P | 1999-04-16 | 1999-04-16 | |
| US14446199P | 1999-07-19 | 1999-07-19 | |
| PCT/US1999/019838 WO2000012517A1 (en) | 1998-08-27 | 1999-08-27 | Novel hydrate forms of alendronate sodium, processes for manufacture thereof, and pharmaceutical compositions thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EA200100184A1 EA200100184A1 (ru) | 2001-10-22 |
| EA002739B1 true EA002739B1 (ru) | 2002-08-29 |
Family
ID=27378576
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EA200100184A EA002739B1 (ru) | 1998-08-27 | 1999-08-27 | Новые гидратные формы алендроната натрия, способы их получения и фармацевтические композиции |
Country Status (30)
| Country | Link |
|---|---|
| US (2) | US6281381B1 (enExample) |
| EP (1) | EP1107974B1 (enExample) |
| JP (2) | JP2002523514A (enExample) |
| KR (2) | KR20010079701A (enExample) |
| AT (1) | ATE334993T1 (enExample) |
| AU (1) | AU5698899A (enExample) |
| BG (1) | BG65329B1 (enExample) |
| BR (1) | BR9913472A (enExample) |
| CA (1) | CA2341459A1 (enExample) |
| CZ (1) | CZ2001629A3 (enExample) |
| DE (1) | DE69932620T2 (enExample) |
| DK (1) | DK1107974T3 (enExample) |
| EA (1) | EA002739B1 (enExample) |
| EE (1) | EE04552B1 (enExample) |
| ES (1) | ES2270613T3 (enExample) |
| HR (1) | HRP20010129A2 (enExample) |
| HU (1) | HUP0203078A3 (enExample) |
| IL (1) | IL141423A (enExample) |
| IS (1) | IS5864A (enExample) |
| LT (1) | LT4888B (enExample) |
| LV (1) | LV12720B (enExample) |
| NO (1) | NO20010957L (enExample) |
| NZ (1) | NZ510682A (enExample) |
| PL (1) | PL346347A1 (enExample) |
| PT (1) | PT1107974E (enExample) |
| RO (1) | RO122854B1 (enExample) |
| SI (1) | SI20581B (enExample) |
| SK (1) | SK2482001A3 (enExample) |
| WO (1) | WO2000012517A1 (enExample) |
| YU (1) | YU14701A (enExample) |
Families Citing this family (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE455121T1 (de) * | 2001-07-16 | 2010-01-15 | Univ Paris 13 | Herstellungsverfahren von derivate von bisphosphonaten |
| GB2383042A (en) * | 2001-10-18 | 2003-06-18 | Cipla Ltd | Amorphous alendronate sodium |
| WO2003057136A2 (en) * | 2001-12-24 | 2003-07-17 | Teva Pharmaceutical Industries Ltd. | Dosage form with a core tablet of active ingredient sheathed in a compressed annular body of powder or granular material, and process and tooling for producing it |
| US20040052843A1 (en) * | 2001-12-24 | 2004-03-18 | Lerner E. Itzhak | Controlled release dosage forms |
| ITMI20020146A1 (it) * | 2002-01-29 | 2003-07-29 | Lyogen Ltd | Alendronato monosodico amorfo e processo per la sua preparazione |
| US20050176685A1 (en) * | 2002-04-05 | 2005-08-11 | Daifotis Anastasia G. | Method for inhibiting bone resorption with an alendronate and vitamin d formulation |
| US20080249068A1 (en) * | 2002-09-05 | 2008-10-09 | Deluca Hector F | Method of Extending the Dose Range of Vitamin D Compounds |
| US20050113343A1 (en) * | 2003-10-14 | 2005-05-26 | Pliva - Research And Development Ltd. | Solid-state form of alendronate sodium and preparation thereof |
| US20050181043A1 (en) * | 2004-02-12 | 2005-08-18 | Indranil Nandi | Alendronate salt tablet compositions |
| US20050261250A1 (en) * | 2004-05-19 | 2005-11-24 | Merck & Co., Inc., | Compositions and methods for inhibiting bone resorption |
| PT1753395E (pt) | 2004-05-24 | 2010-10-21 | Warner Chilcott Co Llc | Forma entérica sólida de dosagem oral de um bisfosfonato contendo um agente quelante |
| CZ296937B6 (cs) * | 2004-09-02 | 2006-07-12 | Zentiva, A. S | Trisodná sul kyseliny 4-amino-1-hydroxybutyliden-1,1-bisfosfonové |
| DE602005016292D1 (de) * | 2004-10-29 | 2009-10-08 | Sandoz Ag | Verfahren zur herstellung von glatiramer |
| US20060134190A1 (en) * | 2004-12-16 | 2006-06-22 | Banner Pharmacaps Inc. | Formulations of bisphosphonate drugs with improved bioavailability |
| CZ297262B6 (cs) * | 2004-12-28 | 2006-10-11 | Zentiva, A. S. | Trisodná sul kyseliny 4-amino-1-hydroxybutyliden-1,1-bisfosfonové |
| US8003820B2 (en) * | 2005-10-20 | 2011-08-23 | Dr. Reddy's Laboratories Limited | Process for preparing bisphosphonic acids |
| AR058168A1 (es) * | 2005-11-07 | 2008-01-23 | Merck & Co Inc | Sintesis del alendronato de sodio trihidratado |
| NZ598071A (en) * | 2006-10-27 | 2013-08-30 | Signal Pharm Llc | Uses of and pharmaceutical compositions comprising 4-[9-(tetrahydro-furan-3-yl)-8-(2,4,6-trifluoro-phenylamino)-9h-purin-2-ylamino]-cyclohexan-1-ol compounds |
| ES2392890T3 (es) * | 2006-11-22 | 2012-12-14 | Eisai R&D Management Co., Ltd. | Sal sódica de un compuesto disacarídico, procedimiento para la producción de la misma y uso de la misma |
| US20090076144A1 (en) * | 2007-09-17 | 2009-03-19 | Protia, Llc | Deuterium-enriched bazedoxifene |
| US20090118238A1 (en) * | 2007-09-17 | 2009-05-07 | Protia, Llc | Deuterium-enriched alendronate |
| US20090170815A1 (en) * | 2007-12-28 | 2009-07-02 | Roxane Laboratories Incorporated. | Alendronate oral liquid formulations |
| WO2011054182A1 (zh) * | 2009-11-03 | 2011-05-12 | Liu Li | 丹参酮ⅱa磺酸钠水合物及其制备方法和用途 |
| TWI846166B (zh) | 2013-11-15 | 2024-06-21 | 美商阿克比治療有限公司 | {[5-(3-氯苯基)-3-羥基吡啶-2-羰基]胺基}乙酸之固體型式，其組合物及用途 |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3016289A1 (de) | 1980-04-28 | 1981-10-29 | Henkel KGaA, 4000 Düsseldorf | Verfahren zur herstellung von omega -amino-1-hydroxyalkyliden-1,1-bis-phosphonsaeuren |
| IT1201087B (it) * | 1982-04-15 | 1989-01-27 | Gentili Ist Spa | Bifosfonati farmacologicamente attivi,procedimento per la loro preparazione e relative composizioni farmaceutiche |
| US4639338A (en) * | 1984-08-06 | 1987-01-27 | Ciba-Geigy Corporation | Preparation of crystalline disodium 3-amino-1-hydroxypropane-1,1-diphosphonate pentahydrate |
| DE3434667A1 (de) * | 1984-09-21 | 1986-04-03 | Henkel KGaA, 4000 Düsseldorf | 4-dimethylamino-1-hydroxybutan-1,1-diphosphonsaeure, deren wasserloesliche salze, verfahren zu ihrer herstellung sowie ihre verwendung |
| IT1196315B (it) * | 1984-10-29 | 1988-11-16 | Gentili Ist Spa | Procedimento per la preparazione di acidi difosfonici |
| US4711800A (en) * | 1985-06-06 | 1987-12-08 | Divincenzo Maureen | Needlecraft with metallic substrate |
| 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 |
| US5019651A (en) * | 1990-06-20 | 1991-05-28 | Merck & Co., Inc. | Process for preparing 4-amino-1-hydroxybutylidene-1,1-bisphosphonic acid (ABP) or salts thereof |
| US5159108A (en) * | 1990-09-18 | 1992-10-27 | Merck & Co., Inc. | Process for preparing an antihypercalcemic agent |
| US5039819A (en) * | 1990-09-18 | 1991-08-13 | Merck & Co., Inc. | Diphosphonate intermediate for preparing an antihypercalcemic agent |
| ATE289199T1 (de) * | 1995-06-06 | 2005-03-15 | Merck & Co Inc | Formulierungen mit dem wasserfreien mononatriumsalz von alendronat und deren verwendung zur behandlung von knochenkrankheiten |
| EP0837863A4 (en) | 1995-06-06 | 1999-06-16 | Merck & Co Inc | DISODIUM ALENDRONATE PREPARATIONS |
-
1999
- 1999-08-27 HR HR20010129A patent/HRP20010129A2/hr not_active Application Discontinuation
- 1999-08-27 SI SI9920070A patent/SI20581B/sl not_active IP Right Cessation
- 1999-08-27 PT PT99944004T patent/PT1107974E/pt unknown
- 1999-08-27 BR BR9913472-1A patent/BR9913472A/pt not_active Application Discontinuation
- 1999-08-27 CA CA002341459A patent/CA2341459A1/en not_active Abandoned
- 1999-08-27 YU YU14701A patent/YU14701A/sh unknown
- 1999-08-27 DE DE69932620T patent/DE69932620T2/de not_active Expired - Fee Related
- 1999-08-27 AU AU56988/99A patent/AU5698899A/en not_active Abandoned
- 1999-08-27 KR KR1020017002535A patent/KR20010079701A/ko not_active Ceased
- 1999-08-27 PL PL99346347A patent/PL346347A1/xx not_active Application Discontinuation
- 1999-08-27 NZ NZ510682A patent/NZ510682A/en not_active IP Right Cessation
- 1999-08-27 IL IL14142399A patent/IL141423A/xx not_active IP Right Cessation
- 1999-08-27 US US09/384,145 patent/US6281381B1/en not_active Expired - Fee Related
- 1999-08-27 WO PCT/US1999/019838 patent/WO2000012517A1/en not_active Ceased
- 1999-08-27 RO ROA200100219A patent/RO122854B1/ro unknown
- 1999-08-27 AT AT99944004T patent/ATE334993T1/de not_active IP Right Cessation
- 1999-08-27 EP EP99944004A patent/EP1107974B1/en not_active Expired - Lifetime
- 1999-08-27 JP JP2000567539A patent/JP2002523514A/ja not_active Withdrawn
- 1999-08-27 KR KR1020077004456A patent/KR20070034132A/ko not_active Ceased
- 1999-08-27 DK DK99944004T patent/DK1107974T3/da active
- 1999-08-27 CZ CZ2001629A patent/CZ2001629A3/cs unknown
- 1999-08-27 EA EA200100184A patent/EA002739B1/ru not_active IP Right Cessation
- 1999-08-27 HU HU0203078A patent/HUP0203078A3/hu unknown
- 1999-08-27 SK SK248-2001A patent/SK2482001A3/sk unknown
- 1999-08-27 EE EEP200100126A patent/EE04552B1/xx not_active IP Right Cessation
- 1999-08-27 ES ES99944004T patent/ES2270613T3/es not_active Expired - Lifetime
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2001
- 2001-02-26 LT LT2001016A patent/LT4888B/lt not_active IP Right Cessation
- 2001-02-26 BG BG105292A patent/BG65329B1/bg unknown
- 2001-02-26 NO NO20010957A patent/NO20010957L/no not_active Application Discontinuation
- 2001-02-26 IS IS5864A patent/IS5864A/is unknown
- 2001-04-05 LV LVP-01-26A patent/LV12720B/en unknown
- 2001-07-03 US US09/898,756 patent/US6696601B2/en not_active Expired - Fee Related
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2009
- 2009-02-18 JP JP2009035788A patent/JP2009143955A/ja active Pending
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| MM4A | Lapse of a eurasian patent due to non-payment of renewal fees within the time limit in the following designated state(s) |
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| MM4A | Lapse of a eurasian patent due to non-payment of renewal fees within the time limit in the following designated state(s) |
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