NO328734B1 - Anvendelse av ibandroninsyre for fremstilling av medikamenter til behandling og prevensjon av osteoprose - Google Patents
Anvendelse av ibandroninsyre for fremstilling av medikamenter til behandling og prevensjon av osteoprose Download PDFInfo
- Publication number
- NO328734B1 NO328734B1 NO20044195A NO20044195A NO328734B1 NO 328734 B1 NO328734 B1 NO 328734B1 NO 20044195 A NO20044195 A NO 20044195A NO 20044195 A NO20044195 A NO 20044195A NO 328734 B1 NO328734 B1 NO 328734B1
- Authority
- NO
- Norway
- Prior art keywords
- pharmaceutically acceptable
- ibandronic acid
- osteoporosis
- drug
- salts
- Prior art date
Links
- MPBVHIBUJCELCL-UHFFFAOYSA-N Ibandronate Chemical compound CCCCCN(C)CCC(O)(P(O)(O)=O)P(O)(O)=O MPBVHIBUJCELCL-UHFFFAOYSA-N 0.000 title claims description 28
- 229960005236 ibandronic acid Drugs 0.000 title claims description 18
- 239000003814 drug Substances 0.000 title claims description 17
- 208000001132 Osteoporosis Diseases 0.000 title claims description 16
- 229940079593 drug Drugs 0.000 title claims description 16
- 238000011282 treatment Methods 0.000 title claims description 10
- 238000004519 manufacturing process Methods 0.000 title claims description 6
- 230000002265 prevention Effects 0.000 title claims description 6
- 150000003839 salts Chemical class 0.000 claims description 27
- 208000006386 Bone Resorption Diseases 0.000 claims description 13
- 230000024279 bone resorption Effects 0.000 claims description 13
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 12
- 208000035475 disorder Diseases 0.000 claims description 11
- 239000003826 tablet Substances 0.000 claims description 11
- 230000001575 pathological effect Effects 0.000 claims description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 4
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 claims description 4
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical class [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 3
- 235000021355 Stearic acid Nutrition 0.000 claims description 3
- 239000008101 lactose Substances 0.000 claims description 3
- 150000004682 monohydrates Chemical class 0.000 claims description 3
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 3
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims description 3
- 239000008117 stearic acid Substances 0.000 claims description 3
- 239000000454 talc Substances 0.000 claims description 3
- 229910052623 talc Inorganic materials 0.000 claims description 3
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 2
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims description 2
- 239000002202 Polyethylene glycol Substances 0.000 claims description 2
- 229960000913 crospovidone Drugs 0.000 claims description 2
- 239000007941 film coated tablet Substances 0.000 claims description 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 2
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 claims description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 2
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 2
- 229920001223 polyethylene glycol Polymers 0.000 claims description 2
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 claims description 2
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 claims description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 2
- 239000000377 silicon dioxide Substances 0.000 claims description 2
- 235000012239 silicon dioxide Nutrition 0.000 claims description 2
- 229960001866 silicon dioxide Drugs 0.000 claims description 2
- 229960004274 stearic acid Drugs 0.000 claims description 2
- 239000004408 titanium dioxide Substances 0.000 claims description 2
- 201000010099 disease Diseases 0.000 claims 1
- 150000004663 bisphosphonates Chemical class 0.000 description 18
- 229940122361 Bisphosphonate Drugs 0.000 description 17
- 210000000988 bone and bone Anatomy 0.000 description 10
- 229940015872 ibandronate Drugs 0.000 description 7
- -1 alkali metal salts Chemical class 0.000 description 6
- 239000002253 acid Substances 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 239000008194 pharmaceutical composition Substances 0.000 description 5
- 108090000445 Parathyroid hormone Proteins 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 230000003389 potentiating effect Effects 0.000 description 4
- 102000003982 Parathyroid hormone Human genes 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 239000000199 parathyroid hormone Substances 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical class N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 239000004475 Arginine Substances 0.000 description 2
- 208000010392 Bone Fractures Diseases 0.000 description 2
- 206010065687 Bone loss Diseases 0.000 description 2
- 108060001064 Calcitonin Proteins 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical class C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 2
- 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 description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
- 208000037848 Metastatic bone disease Diseases 0.000 description 2
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 208000010191 Osteitis Deformans Diseases 0.000 description 2
- 208000027868 Paget disease Diseases 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 239000008298 dragée Substances 0.000 description 2
- 229940011871 estrogen Drugs 0.000 description 2
- 239000000262 estrogen Substances 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 159000000003 magnesium salts Chemical class 0.000 description 2
- 208000027202 mammary Paget disease Diseases 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- 210000002997 osteoclast Anatomy 0.000 description 2
- 239000008177 pharmaceutical agent Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229940095743 selective estrogen receptor modulator Drugs 0.000 description 2
- 239000000333 selective estrogen receptor modulator Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- SOBHUZYZLFQYFK-UHFFFAOYSA-K trisodium;hydroxy-[[phosphonatomethyl(phosphonomethyl)amino]methyl]phosphinate Chemical class [Na+].[Na+].[Na+].OP(O)(=O)CN(CP(O)([O-])=O)CP([O-])([O-])=O SOBHUZYZLFQYFK-UHFFFAOYSA-K 0.000 description 2
- OGSPWJRAVKPPFI-UHFFFAOYSA-N Alendronic Acid Chemical compound NCCCC(O)(P(O)(O)=O)P(O)(O)=O OGSPWJRAVKPPFI-UHFFFAOYSA-N 0.000 description 1
- 241000972773 Aulopiformes Species 0.000 description 1
- 102000055006 Calcitonin Human genes 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 101000741445 Homo sapiens Calcitonin Proteins 0.000 description 1
- 208000037147 Hypercalcaemia Diseases 0.000 description 1
- 206010020584 Hypercalcaemia of malignancy Diseases 0.000 description 1
- 208000017924 Klinefelter Syndrome Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 208000029725 Metabolic bone disease Diseases 0.000 description 1
- 208000003076 Osteolysis Diseases 0.000 description 1
- 101100272976 Panax ginseng CYP716A53v2 gene Proteins 0.000 description 1
- 102100036893 Parathyroid hormone Human genes 0.000 description 1
- IIDJRNMFWXDHID-UHFFFAOYSA-N Risedronic acid Chemical compound OP(=O)(O)C(P(O)(O)=O)(O)CC1=CC=CN=C1 IIDJRNMFWXDHID-UHFFFAOYSA-N 0.000 description 1
- 241000277284 Salvelinus fontinalis Species 0.000 description 1
- 229930003316 Vitamin D Natural products 0.000 description 1
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 229940062527 alendronate Drugs 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 230000033558 biomineral tissue development Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000004566 building material Substances 0.000 description 1
- 229960004015 calcitonin Drugs 0.000 description 1
- BBBFJLBPOGFECG-VJVYQDLKSA-N calcitonin Chemical compound N([C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(N)=O)C(C)C)C(=O)[C@@H]1CSSC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1 BBBFJLBPOGFECG-VJVYQDLKSA-N 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- ACSIXWWBWUQEHA-UHFFFAOYSA-N clodronic acid Chemical compound OP(O)(=O)C(Cl)(Cl)P(O)(O)=O ACSIXWWBWUQEHA-UHFFFAOYSA-N 0.000 description 1
- 229960002286 clodronic acid Drugs 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 208000021863 corticosteroid-induced osteoporosis Diseases 0.000 description 1
- 210000002249 digestive system Anatomy 0.000 description 1
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
- 235000011180 diphosphates Nutrition 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 210000003238 esophagus Anatomy 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940045644 human calcitonin Drugs 0.000 description 1
- 208000008750 humoral hypercalcemia of malignancy Diseases 0.000 description 1
- 230000000148 hypercalcaemia Effects 0.000 description 1
- 208000030915 hypercalcemia disease Diseases 0.000 description 1
- 201000000916 idiopathic juvenile osteoporosis Diseases 0.000 description 1
- 230000004968 inflammatory condition Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 239000008011 inorganic excipient Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 229960002367 lasofoxifene Drugs 0.000 description 1
- GXESHMAMLJKROZ-IAPPQJPRSA-N lasofoxifene Chemical compound C1([C@@H]2[C@@H](C3=CC=C(C=C3CC2)O)C=2C=CC(OCCN3CCCC3)=CC=2)=CC=CC=C1 GXESHMAMLJKROZ-IAPPQJPRSA-N 0.000 description 1
- 208000029791 lytic metastatic bone lesion Diseases 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 230000001394 metastastic effect Effects 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 230000009456 molecular mechanism Effects 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 235000003170 nutritional factors Nutrition 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000008012 organic excipient Substances 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- WRUUGTRCQOWXEG-UHFFFAOYSA-N pamidronate Chemical compound NCCC(O)(P(O)(O)=O)P(O)(O)=O WRUUGTRCQOWXEG-UHFFFAOYSA-N 0.000 description 1
- 229940046231 pamidronate Drugs 0.000 description 1
- 229960001319 parathyroid hormone Drugs 0.000 description 1
- 108010073509 parathyroid hormone (1-31) Proteins 0.000 description 1
- 108010073230 parathyroid hormone (1-38) Proteins 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 208000001685 postmenopausal osteoporosis Diseases 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 239000000583 progesterone congener Substances 0.000 description 1
- ZDYVRSLAEXCVBX-UHFFFAOYSA-N pyridinium p-toluenesulfonate Chemical compound C1=CC=[NH+]C=C1.CC1=CC=C(S([O-])(=O)=O)C=C1 ZDYVRSLAEXCVBX-UHFFFAOYSA-N 0.000 description 1
- 229960004622 raloxifene Drugs 0.000 description 1
- GZUITABIAKMVPG-UHFFFAOYSA-N raloxifene Chemical compound C1=CC(O)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(O)C=C2S1 GZUITABIAKMVPG-UHFFFAOYSA-N 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 229940089617 risedronate Drugs 0.000 description 1
- 235000019515 salmon Nutrition 0.000 description 1
- 108010068072 salmon calcitonin Proteins 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000003270 steroid hormone Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- OGBMKVWORPGQRR-UMXFMPSGSA-N teriparatide Chemical compound C([C@H](NC(=O)[C@H](CCSC)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@@H](N)CO)C(C)C)[C@@H](C)CC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1N=CNC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1N=CNC=1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CNC=N1 OGBMKVWORPGQRR-UMXFMPSGSA-N 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- WZDGZWOAQTVYBX-XOINTXKNSA-N tibolone Chemical compound C([C@@H]12)C[C@]3(C)[C@@](C#C)(O)CC[C@H]3[C@@H]1[C@H](C)CC1=C2CCC(=O)C1 WZDGZWOAQTVYBX-XOINTXKNSA-N 0.000 description 1
- 229960001023 tibolone Drugs 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 235000019166 vitamin D Nutrition 0.000 description 1
- 239000011710 vitamin D Substances 0.000 description 1
- 150000003710 vitamin D derivatives Chemical class 0.000 description 1
- 229940046008 vitamin d Drugs 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
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
- A61K31/675—Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
-
- 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
- A61K31/662—Phosphorus acids or esters thereof having P—C bonds, e.g. foscarnet, trichlorfon
-
- 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
- A61K31/662—Phosphorus acids or esters thereof having P—C bonds, e.g. foscarnet, trichlorfon
- A61K31/663—Compounds having two or more phosphorus acid groups or esters thereof, e.g. clodronic acid, pamidronic acid
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
- A61K9/2866—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- 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
- A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
-
- 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)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Physical Education & Sports Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Rheumatology (AREA)
- Organic Chemistry (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Nutrition Science (AREA)
- Physiology (AREA)
- Solid-Sorbent Or Filter-Aiding Compositions (AREA)
Description
Foreliggende oppfinnelse vedrører anvendelsen av (1-hyd-roksy-3-(N-metyl-N-pentyl)aminopropyliden-1,1,-bisfonfonin-syre (ibandroninsyre) eller farmasøytisk akseptable salter derav for fremstilling av medikamenter til forebygging eller behandling av forstyrrelser særpreget ved patologisk økning i benresorpsjon, spesielt for å forhindre og be-handle osteoporose, og hvor medikamentet omfatter de trekk som er nevnt i krav 1.
Ben tjener primært som en støtte, og ben er følgelig ofte ansett å være et enkelt byggemateriale. Ben er imidlertid et komplisert biomateriale tilpasset til en bred variasjon av behov, stimulanser og skader som den blir utsatt for. Endoproteser er tilgjengelige som erstatninger for ben og ledd. Endoproteser, selv når biomekanisk svært forfinet, har ikke en aktiv effekt på miljø- og belastningsfaktorer.
Et mangfold av forstyrrelser hos mennesker og pattedyr innebærer eller er assosiert med unormal benresorpsjon. Slike forstyrrelser inkluderer, men er ikke begrenset til, osteoporose, Pagets sykdom, periprostetisk bentap eller osteo-lyse, og hyperkalsemi av ondartet og metastatisk bensykdom. Den meste vanlige av disse forstyrrelsene er osteoporose, som er den mest vanlige manifestering som forekommer post-menopausalt hos kvinner. På grunn av osteoporose, så vel som andre forstyrrelser assosiert med bentap, er kroniske lidelser, er det antatt at egnet terapi vil vanligvis kreve kronisk behandling.
Bisfosfonater, det vil si bisfosfoninsyrer eller farmasøy-tisk akseptable salter derav, er syntetiske analoger av na-turlig forekommende pyrofosfat. På grunn av sin markerte affinitet for fastfasekalsiumfosfat, binder bisfosfonater kraftig til benmineral. Farmakologisk aktive bisfosfonater er godt kjent på fagområdet og er sterke hemmere av benresorpsjon og er derfor nyttige ved behandlingen og forhindring av sykdommer som innebærer unormal benresorpsjon, spesielt osteoporose, Pagets sykdom, hyperkalsemi ved ondar-tethet, og metastatisk og metaboliske benforstyrrelser.
Bisfosfonater som farmasøytiske agenser er for eksempel beskrevet i EP-A-170,228, EP-A-197,478, EP-A-22,751; EP-A-252,504, EP-A-252,505, EP-A-258,618, EP-A-350,002, EP-A-273, 190, WO-A-90/00798, etc.
Farmasøytiske former for bisfosfonater som er i dag på mar-kedet er orale formuleringer (tabletter eller kapsler) eller løsninger for intravenøs injeksjon eller infusjon. De er godt tolerert systemisk når administrert ved terapeu-tiske doser. Bisfosfonater som en klasse er imidlertid ir-riterende for hud og slimhinnemembraner og bivirkninger i fordøyelsessystemet kan oppstå når de gis på en kontinuer-lig basis oralt, som for eksempel uheldige tilstander i spiserøret eller forstyrrelser i den gastrointestinale ka-nalen. Følgelig, og på grunn av sin lave orale biotil-gjengelighet, har den orale administrasjonsveien frem til i dag, måttet følge besværlige anbefalinger for bruk av pasi-enten.
Bisfosfonater kan klassifiseres i to grupper med forskjel-lige virkningsmoduser. Ibandronat tilhører den sterke nit-rogeninneholdende bisfosfonatgruppen [Russell RGG, Rogers MJ. Bisphosphonates: From the laboratory to the clinic and back again. Bone 25(1):97-106 (1999); Rogers MJ, Gordon S, Benford HL, Coxon FP, Luckman SP, Monkkonen J, Frith JC. Cellular Molecular mechanisms of action of bisphosphonates. Cancer 88(12) Suppl: 2961-2978 (2000)]. Ibandronat er en av de mest kraftfulle bisfosfonater som i dag er under klinisk utvikling i osteoporose og metastatiske bensykdommer. Ibandronat er 2, 10, 50 og 500 ganger mer kraftfull enn henholdsvis risedronat, alendronat, pamidronat, og klodro-nat i dyremodeller av benresorpsjon [Muhlbauer R.C., F. Bauss, R. Schenk, M. Janner, E. Bosies, K. Strein, og H. Fleisch. BM 21.0955, a potent new bisphosphonate to inhibit bone resorption. J. Bone Miner. REs. 6: 1003-1011 (1991)].
Ibandronat hemmer benresorpsjon uten å hemme minerali-seringen (Miihlbauer R.C., F. Bauss, R. Schenk, M. Janner, E. Bosies, K. Strein, og H. Fleisch. BM 21.0955, a potent new bisphosphonate to inhibit bone resorption. J. Bone Miner. Res. 6; 1003-1011 (1991)). Det har vært vist å senke osteoklastaktivitet, og således hemmer bendestruksjon. Ved høye doser re-duserer den også antallet osteoklaster (Miihlbauer R.C., F. Bauss, R. Schen, M. Janner, E. Bosies, K. Strein, og H. Fleisch. BM 21.0955, a potent new bisphosphonate to inhibit bone resoption. J. Bone Miner. Res. 6; 1003-1011 (1991)).
Som beskrevet blir bisfosfonater akseptert å gi sterk effekt ved håndteringen av osteoporose. Gitte administra-sjonsbegrensninger assosiert med lav oral biotilgjengelig-het og faren for gastrointestinale effekter foreligger imidlertid en klar åpning for en kur som byr på forbedret beleilighet og fleksibilitet, som fører til et høyere an-vendelighetsnivå og bedre pasient behandling/tilfredsstill-het. Intermitterende kurer slik som for eksempel en ukent-lig administrasjon, har vært beskrevet på fagområdet, men slike intermitterende behandlinger fører ikke til de øns-kede resultatene.
Det har nå blitt funnet at forhindringen eller behandlingen av forstyrrelser særpreget ved patologisk økning i benresorpsjon slik som osteoporose, kan forbedres ved månedlig administrasjon av 150 mg av et bisfonsfonat eller farmasøy-tisk akseptabelt salt derav, spesielt ved en månedlig administrasjon av ibandronat, det vil si ibandroninsyre eller et farmasøytisk akseptabelt salt derav.
Foreliggende oppfinnelse vedrører således anvendelsen av ibandroninsyre eller et farmasøytisk akseptabelt salt derav, for fremstillingen av medikamenter for forebygging eller behandling av lidelser særpreget ved patologisk økning i benresorpsjon, hvori medikamentet a) omfatter en effektiv dose på omkring 150 mg ibandroninsyre eller et akseptabelt salt derav og b) medikamentet er tilrettelagt for å bli administrert oralt en dag per måned.
Før det kliniske ibandronat utviklingsprogrammet ble stilt ferdig, hadde ingen bisfosfonat vist mulig benbruddreduk-sjonseffektivitet med et medikamentfritt interval lengre enn den daglige administrasjon. I korthet kan det opplyses at det er ganske uventet at fordelen ved redusert benbrudd kan oppnås fra månedlig administrasjon av oral ibandronat med en enkel tablett administrasjonsplan.
Ibandroninsyre eller farmasøytisk akseptable salter derav kan således anvendes for fremstillingen av et medikament for forhindring eller behandling av forstyrrelser særpreget ved patologisk økning i benresorpsjon, for eksempel osteoporose .
Uttrykket "farmasøytisk akseptabel" som benyttet heri betyr saltene eller chelaterende agenser som er akseptable med hensyn til toksisitet.
Uttrykket "farmasøytisk akseptabelt salt" viser til ammoniakksalter, alkaliske metallsalter slik som kalium og natrium (inkludert mono-, di- og tri-natrium) salter (som er foretrukket) , jordalkalimetallsalter slik som kalsium og magnesiumsalter, salter med organiske baser slik som dicykloheksylaminsalter, N-metyl-D-glukamin, og salter med amino-syrer slik som arginin, lysin og lignende.
Uttrykket "forstyrrelser særpreget ved patologisk økning i benresorpsjon" viser til medisinsk beskrevne lidelser med eller uten en identifiserbar årsak (slik som post-menopau-sal osteoporose, idiopatisk juvenil osteoporose, osteoporose assosiert med Klinefelter's syndrom, mannlig osteoporose, osteoporose grunnet ernæringsfaktorer, organtrans-plantasjons relatert osteoporose, immobilitet assosiert osteoporose, betennelsestilstander og kortikosteroid indusert osteoporose).
Uttrykket "medikament" viser til en farmasøytisk sammensetning. Uttrykket omfatter enkelt- eller flerlags admini-strasjonsopplegg.
Medikamentet blir fortrinnsvis administrert på en dag per måned. Medikamentet blir fortrinnsvis administrert som en enkel dose.
Uttrykket "effektiv dose" viser til omtrent 50 til omtrent 250 mg, mest foretrukket til omtrent 100 til omtrent 150 mg, av ibandroninsyre eller et farmasøytisk akseptabelt salt derav. Som bemerket kan den effektive dosen være enkel dose.
"Bisfosfoninsyrer og farmasøytisk akseptable salter derav" som farmasøytiske agenser er beskrevet i for eksempel US patentnumrene 4,509,612, 4,666,895, 4,719,203, 4,777,163, 5,002,937, 4,971,958 og 4,958,839 og i europeisk patent-søknader nr. 252,504 og 252,505.
Fremgangsmåter for fremstilling av bisfosfoninsyrer og far-masøytisk akseptable salter derav kan finnes i, for eksempel US patentnumrene 3,962,432, 4,054,598, 4,267,108, 4,327,039, 4,407,761, 4,621,077, 4,624,947, 4,746,654, 4,922,077, 4,970,335, 5,019,651, 4,761,406, 4,876,248; i J. Org. Chem. 32, 4111 (1967) og europeisk patentsøknad 252,504. Eksempler på basesalter av bisfosfoninsyrer inkluderer ammoniakksalter, alkaliske metallsalter slik som kalium og natrium (inkludert mono-, di- og tri-natrium) salter (som er foretrukket), jordalkalimetallsalter slik som kalsium- og magnesiumsalter, salter med organiske baser slik som dicykloheksylaminsalter, N-metyl-D-glukamin, og salter med aminosalter slik som arginin, lysin og lignende. Ikke-toksiske, fysiologisk akseptable salter er foretrukket. Saltene kan fremstilles ved fremgangsmåter kjent på fagområdet, slik som beskrevet i europeisk patentsøknad 252,504 eller i US patentnummer 4,922,077.
Medikamentet omfatter fortrinnsvis 150 mg ibandroninsyre eller et farmasøytisk akseptabelt salt derav. Medikamentet blir fortrinnsvis administrert som en enkel dose.
Ibandroninsyre(l-hydroksy-3-(N-metyl-N-pentyl)aminopropyli-den-1,1-bisfosfoninsyre) eller fysiologisk kompatible salter derav er spesielt foretrukket, for eksempel ibandroninsyre, mononatriumsalt, monohydrat.
Ibandroninsyre og de farmasøytisk akseptable saltene kan administreres alene eller i kombinasjon med andre benaktive stoffer, enten i fastkombinasjoner eller separat både fy-sisk og i tid, inkludert hormoner, slik som et steroidhor-mon, for eksempel et østrogen; en partiell østrogenagonist, eller østrogen-gestagenkombinasjon; en kalsitonin eller analog eller derivat derav, for eksempel laks, ål eller hu-man kalsitonin paratyroidhormon eller analoger derav, for eksempel PTH (1-84), PTH (1-34), PTH (1-36), PTH (1-38), PTH (1-31)NH2 eller PPTS 893; en SERM (Selektiv østrogenre-septormodulator), for eksempel raloksifen, lasofoksifen, TSE-434, FC1271, tibolon, vitamin D eller en analog. Slike ytterligere benaktive stoffer kan administreres oftere enn bisfosfonatet.
Egnede farmasøytiske sammensetninger er kjent på fagområdet og har vært beskrevet for eksempel i US patent nr. 6,143,326 og 6,294,196.
For fremstillingen av tabletter, belagte tabletter, dragéer eller harde gelatinkapsler, kan ibandroninsyre blandes sam-men med farmasøytisk inerte, uorganiske eller organiske eksipienser. Eksempler på egnede eksipienser for tabletter,
dragéer eller harde gelatinkapsler inkluderer laktose,
maisstivelse eller derivater derav, talkum eller stearinsyre eller salter derav.
Farmasøytiske sammensetninger kan også inneholde konser-veringsmidler, solubiliseringsmidler, stabiliseringsmidler, fuktemidler, emulgeringsmidler, søtestoffer, fargemidler, luktemidler, salter for variasjon av osmotisk trykk, buf-fere, belegningsagenser eller antioksidanter. De kan også inneholde andre terapeutisk nyttige agenser. Den farmasøy-tiske sammensetningen er fortrinnsvis en filmbelagt tablett hvori tablettkjernen omfatter 150 mg ibandroninsyre eller et farmasøytisk akseptabelt salt derav som definert ovenfor og en eller flere farmasøytisk akseptable eksipienser valgt fra gruppen bestående av laktose, polyvinylpyrrolidon, mikrokrystallinsk cellulose, krospovidon, stearinsyre, silikondioksid og tablettkjernen omfatter en eller flere farma-søytisk akseptable eksipienser valgt fra gruppen bestående av hydroksypropylmetylcellulose, titandioksid, talkum og polyetylenglykol 6.000. Disse sammensetningene er kjent på fagområdet og beskrevet for eksempel i US patent nr. 6,143,326 og 6,294,196.
Oppfinnelsen vil nå bli forklart med henvisning til eksem-plifiserte utførelser.
Eksempler
Eksempel 1: Farmasøytisk sammensetning
Eksemplet viser sammensetningen av en 50 mg tablett. Sammensetningen og fremstilling av disse tablettene er kjent på fagområdet og beskrevet i for eksempel i US patentnumrene 6,143,326 og 6,294,196.
Andre sammensetningene kan fremstilles ved å justere ingre-diensene ifølge mengden bisfosfonat, for eksempel ibandroninsyre, mononatriumsalt, monohydrat.
Claims (5)
1. Anvendelse av en ibandroninsyre eller farmasøytisk akseptabelt salt derav for fremstilling av et medikament egnet for forebygging eller behandling av forstyrrelser særpreget ved patologisk økning i benresorpsjon hvori medikamentet a) omfatter en effektiv dose på omkring 150 mg ibandroninsyre eller et farmasøytisk akseptabelt salt derav; og b) medikamentet er tilrettelagt for å bli administrert oralt en dag per måned.
2. Anvendelse ifølge krav 1 hvor sykdommen er osteoporose .
3. Anvendelse ifølge krav 1 eller 2, hvori ibandroninsy-ren foreligger i form av sitt mononatriumsalt, monohydrat.
4. Anvendelse ifølge et hvilket som helst av kravene 1 til 3, hvori medikamentet er en filmbelagt tablett hvori tablettkjernen omfatter 150 mg ibandroninsyre eller et far-masøytisk akseptabelt salt derav som definert i kravene 1 til 3, og en eller flere farmasøytisk akseptable eksipienser valgt fra gruppen bestående av laktose, polyvinylpyrrolidon, mikrokrystallinsk cellulose, krospovidon, stearinsyre, silikondioksid og tablettkjernen omfatter en eller flere farmasøytisk akseptable eksipienser valgt fra gruppen bestående av hydroksypropylmetylcellulose, titandioksid, talkum og polyetylenglykol 6.000.
5. Anvendelse ifølge et hvilket som helst av kraven 1 til 4, hvori medikamentet blir administrert som en enkel dose.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP02010136 | 2002-05-10 | ||
PCT/EP2003/004629 WO2003095029A1 (en) | 2002-05-10 | 2003-05-02 | Bisphosphonic acid for the treatment and prevention of osteoporosis |
Publications (2)
Publication Number | Publication Date |
---|---|
NO20044195L NO20044195L (no) | 2004-10-01 |
NO328734B1 true NO328734B1 (no) | 2010-05-03 |
Family
ID=29414669
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO20044195A NO328734B1 (no) | 2002-05-10 | 2004-10-01 | Anvendelse av ibandroninsyre for fremstilling av medikamenter til behandling og prevensjon av osteoprose |
NO20100477A NO331024B1 (no) | 2002-05-10 | 2010-03-31 | Anvendelse av risendroninsyre for forebygging eller behandling av osteoporose |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO20100477A NO331024B1 (no) | 2002-05-10 | 2010-03-31 | Anvendelse av risendroninsyre for forebygging eller behandling av osteoporose |
Country Status (33)
Country | Link |
---|---|
US (5) | US7410957B2 (no) |
EP (4) | EP2851105A1 (no) |
JP (5) | JP2005522526A (no) |
KR (7) | KR20060058151A (no) |
CN (2) | CN1939314A (no) |
AR (2) | AR039978A1 (no) |
AT (1) | ATE376444T1 (no) |
AU (2) | AU2003229770B2 (no) |
BR (1) | BR0308901A (no) |
CA (2) | CA2481142C (no) |
CY (2) | CY1108105T1 (no) |
DE (1) | DE60317061T2 (no) |
DK (2) | DK1506041T3 (no) |
EC (1) | ECSP045335A (no) |
ES (2) | ES2532393T3 (no) |
GT (1) | GT200300107A (no) |
HK (1) | HK1080409A1 (no) |
HR (1) | HRP20040906B1 (no) |
IL (3) | IL164371A0 (no) |
MX (1) | MXPA04009586A (no) |
MY (2) | MY146809A (no) |
NO (2) | NO328734B1 (no) |
NZ (2) | NZ556278A (no) |
PA (1) | PA8573101A1 (no) |
PE (1) | PE20040440A1 (no) |
PL (2) | PL399493A1 (no) |
PT (2) | PT1880744E (no) |
RU (2) | RU2329809C2 (no) |
SI (2) | SI1506041T1 (no) |
TW (1) | TWI347188B (no) |
UY (1) | UY27802A1 (no) |
WO (1) | WO2003095029A1 (no) |
ZA (1) | ZA200407950B (no) |
Families Citing this family (30)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20070148228A1 (en) * | 1999-02-22 | 2007-06-28 | Merrion Research I Limited | Solid oral dosage form containing an enhancer |
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 |
CN100479823C (zh) * | 2001-12-21 | 2009-04-22 | 宝洁公司 | 双膦酸盐在制造药物套盒中的用途以及用于增加骨质的套盒 |
US20050070504A1 (en) * | 2001-12-21 | 2005-03-31 | The Procter & Gamble Co. | Risedronate compositions and their methods of use |
AU2003226148A1 (en) * | 2002-04-05 | 2003-10-27 | Merck & Co., Inc. | Method for inhibiting bone resorption with an alendronate and vitamin d formulation |
ES2532393T3 (es) * | 2002-05-10 | 2015-03-26 | F. Hoffmann-La Roche Ag | Acidos bisfosfónicos para tratamiento y prevención de osteoporosis |
NZ536273A (en) † | 2002-12-20 | 2007-08-31 | Hoffmann La Roche | High dose ibandronate formulation |
US20050261250A1 (en) * | 2004-05-19 | 2005-11-24 | Merck & Co., Inc., | Compositions and methods for inhibiting bone resorption |
CN101022812A (zh) * | 2004-08-23 | 2007-08-22 | 特瓦制药工业有限公司 | 固体和晶体伊班膦酸钠及其制备方法 |
CA2594802C (en) * | 2005-02-01 | 2012-11-27 | Uwe Eiermann | Ibandronate polymorph a |
RU2387661C2 (ru) * | 2005-02-01 | 2010-04-27 | Ф.Хоффманн-Ля Рош Аг | Полиморфная модификация в ибандроната |
US20070049557A1 (en) * | 2005-08-24 | 2007-03-01 | Hashim Ahmed | Solid pharmaceutical dosage forms comprising bisphosphonates and modified amino acid carriers |
EP2007397B1 (en) * | 2006-04-07 | 2013-07-24 | Merrion Research III Limited | Solid oral dosage form containing an enhancer |
EP2010506B1 (en) | 2006-04-20 | 2010-08-04 | F. Hoffmann-La Roche AG | Diazepan derivatives modulators of chemokine receptors |
AU2007335156A1 (en) * | 2006-12-20 | 2008-06-26 | Mylan Pharmaceuticals Ulc | Pharmaceutical composition comprising a hot-melt granulated lubricant |
TW200950799A (en) * | 2008-05-07 | 2009-12-16 | Merrion Res Iii Ltd | Compositions of GnRH related compounds and processes of preparation |
EP2210596A1 (en) | 2009-01-22 | 2010-07-28 | Laboratorios Liconsa, S.A. | Pharmaceutical composition of ibandronate sodium salt or a hydrate thereof |
US20100215743A1 (en) * | 2009-02-25 | 2010-08-26 | Leonard Thomas W | Composition and drug delivery of bisphosphonates |
EP3295935B1 (en) * | 2009-07-31 | 2020-07-22 | Grünenthal GmbH | Crystallization method and bioavailability |
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 |
US20110182985A1 (en) * | 2010-01-28 | 2011-07-28 | Coughlan David C | Solid Pharmaceutical Composition with Enhancers and Methods of Preparing thereof |
WO2011120033A1 (en) * | 2010-03-26 | 2011-09-29 | Merrion Research Iii Limited | Pharmaceutical compositions of selective factor xa inhibitors for oral administration |
WO2012071517A2 (en) | 2010-11-24 | 2012-05-31 | Thar Pharmaceuticals, Inc. | Novel crystalline forms |
CA2819234A1 (en) | 2011-01-07 | 2012-07-12 | Merrion Research Iii Limited | Pharmaceutical compositions of iron for oral administration |
JP5874545B2 (ja) * | 2011-06-20 | 2016-03-02 | アステラス製薬株式会社 | 経口投与用医薬組成物 |
WO2016120378A1 (en) | 2015-01-29 | 2016-08-04 | Novo Nordisk A/S | Tablets comprising glp-1 agonist and enteric coating |
CN107011380A (zh) * | 2016-01-28 | 2017-08-04 | 臧伟 | 一种二膦酸衍生物及含二膦酸衍生物的组合物治疗骨折的应用 |
WO2017208070A1 (en) | 2016-05-31 | 2017-12-07 | Grünenthal GmbH | Bisphosphonic acid and coformers with lysin, glycin, nicotinamide for treating psoriatic arthritis |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2001015703A1 (en) * | 1999-09-02 | 2001-03-08 | Merck & Co., Inc. | Method for inhibiting bone resorption |
WO2001082903A1 (en) * | 2000-04-28 | 2001-11-08 | Lipocine, Inc. | Enteric coated formulation of bisphosphonic acid compounds and associated therapeutic methods |
Family Cites Families (128)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US500937A (en) * | 1893-07-04 | Conduit railway insulator | ||
US124314A (en) * | 1872-03-05 | Improvement in preparing paper for buildings | ||
DE2405254C2 (de) | 1974-02-04 | 1982-05-27 | Henkel KGaA, 4000 Düsseldorf | Verwendung von 3-Amino-1-Hydroxypropan-1, 1-diphosphonsäure oder ihrer wasserlöslichen Salze bei der Beeinflußung von Calciumstoffwechselstörungen im menschlichen oder tierischen Körper |
DE2534391C2 (de) | 1975-08-01 | 1983-01-13 | Henkel KGaA, 4000 Düsseldorf | 1-Hydroxy-3-aminoalkan-1,1-diphosphonsäuren |
DE2745083C2 (de) | 1977-10-07 | 1985-05-02 | Henkel KGaA, 4000 Düsseldorf | Hydroxydiphosphonsäuren und Verfahren zu deren Herstellung |
US4252742A (en) | 1979-07-13 | 1981-02-24 | Ciba-Geigy Corporation | Chemical process for the preparation of 2,6-dialkylcyclohexylamines from 2,6-dialkylphenols |
DE2943498C2 (de) | 1979-10-27 | 1983-01-27 | Henkel KGaA, 4000 Düsseldorf | Verfahren zur Herstellung von 3-Amino-1-hydroxypropan-1,1-diphosphonsäure |
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 |
FR2531088B1 (fr) | 1982-07-29 | 1987-08-28 | Sanofi Sa | Produits anti-inflammatoires derives de l'acide methylenediphosphonique et leur procede de preparation |
US4509612A (en) | 1982-09-28 | 1985-04-09 | Applied Power Inc. | Latch mechanism for a tilt-cab truck |
JPS59145179A (ja) | 1983-01-11 | 1984-08-20 | Ricoh Co Ltd | 補充交換用部品を検知可能にした事務機器 |
IT1195993B (it) | 1984-01-12 | 1988-11-03 | Gentili Ist Spa | Forme farmaceutiche a base di difosfonati |
DE3428524A1 (de) | 1984-08-02 | 1986-02-13 | Boehringer Mannheim Gmbh, 6800 Mannheim | Neue diphosphonsaeurederivate, verfahren zu deren herstellung und diese verbindungen enthaltende arzneimittel |
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 |
US4812311A (en) | 1984-12-21 | 1989-03-14 | The Procter & Gamble Company | Kit for use in the treatment of osteoporosis |
DE3512536A1 (de) | 1985-04-06 | 1986-10-16 | Boehringer Mannheim Gmbh, 6800 Mannheim | Neue diphosphonsaeure-derivate, verfahren zu deren herstellung und diese verbindungen enthaltende arzneimittel |
US4761406A (en) | 1985-06-06 | 1988-08-02 | The Procter & Gamble Company | Regimen for treating osteoporosis |
DE3540150A1 (de) | 1985-11-13 | 1987-05-14 | Boehringer Mannheim Gmbh | Neue diphosphonsaeurederivate, verfahren zu deren herstellung und diese verbindungen enthaltende arzneimittel |
DE3623397A1 (de) | 1986-07-11 | 1988-01-14 | Boehringer Mannheim Gmbh | Neue diphosphonsaeurederivate, verfahren zu deren herstellung und diese verbindungen enthaltende arzneimittel |
DE3626058A1 (de) | 1986-08-01 | 1988-02-11 | Boehringer Mannheim Gmbh | Neue diphosphonsaeurederivate, verfahren zu deren herstellung und diese verbindungen enthaltende arzneimittel |
DE3640938A1 (de) | 1986-11-29 | 1988-06-01 | Boehringer Mannheim Gmbh | Neue diphosphonsaeurederivate, verfahren zu deren herstellung und diese verbindung enthaltende arzneimittel |
US4973576A (en) | 1987-03-10 | 1990-11-27 | Yamanouchi Pharmaceutical Co., Ltd. | Bisphophonic acid derivatives and pharmaceutical compositions containing the same |
CA1339805C (en) | 1988-01-20 | 1998-04-07 | Yasuo Isomura | (cycloalkylamino)methylenebis(phosphonic acid) and medicines containing the same as an active |
DE3822650A1 (de) | 1988-07-05 | 1990-02-01 | Boehringer Mannheim Gmbh | Neue diphosphonsaeurederivate, verfahren zu deren herstellung und diese verbindungen enthaltende arzneimittel |
US4958839A (en) | 1988-07-12 | 1990-09-25 | Guzik Technical Enterprises, Inc. | Disc clamp employing resilient cone for spreading balls |
DE3825654A1 (de) * | 1988-07-28 | 1990-02-01 | Bosch Gmbh Robert | Sicherheitseinrichtung an einer handwerkzeugmaschine |
JP2691914B2 (ja) | 1988-09-09 | 1997-12-17 | 株式会社リコー | 画像形成装置 |
US5018651A (en) | 1988-12-27 | 1991-05-28 | Hull Harold L | Side or end dump article carrier |
US4922077A (en) | 1989-01-31 | 1990-05-01 | Raytheon Company | Method of laser marking metal packages |
DE3917153A1 (de) * | 1989-05-26 | 1990-11-29 | Boehringer Mannheim Gmbh | Neue diphosphonsaeurederivate, verfahren zu deren herstellung und diese verbindungen enthaltende arzneimittel |
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 |
JP2985205B2 (ja) | 1990-01-25 | 1999-11-29 | ミノルタ株式会社 | 画像形成装置 |
JPH03226767A (ja) | 1990-01-31 | 1991-10-07 | Minolta Camera Co Ltd | 画像形成装置管理システム |
US5335048A (en) | 1990-01-30 | 1994-08-02 | Minolta Camera Kabushiki Kaisha | Efficient control system of image forming apparatus |
US5356887A (en) | 1990-01-31 | 1994-10-18 | Merck & Co., Inc. | Pharmaceutical compositions containing insoluble calcium salts of amino-hydroxybutylidene bisphoshonic acids |
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 |
JPH04151765A (ja) | 1990-10-16 | 1992-05-25 | Fujitsu Ltd | ファクシミリ装置の消耗品自動発注方式 |
KR100274734B1 (ko) | 1991-11-22 | 2000-12-15 | 제이코버스 코넬리스 레이서 | 리제드로네이트 지연-방출성 조성물 |
WO1993011786A1 (en) | 1991-12-17 | 1993-06-24 | Procter & Gamble Pharmaceuticals, Inc. | Methods for the treatment of osteoporosis using bisphosphonates and parathyroid hormone |
JPH05224479A (ja) | 1992-02-10 | 1993-09-03 | Toshiba Corp | 画像形成装置 |
TW237386B (no) | 1992-04-15 | 1995-01-01 | Ciba Geigy | |
WO1994000129A1 (en) | 1992-06-30 | 1994-01-06 | Procter & Gamble Pharmaceuticals, Inc. | Use of phosphonates for the treatment of osteoporosis |
JPH06111039A (ja) | 1992-09-25 | 1994-04-22 | Toray Ind Inc | 光学読み取り識別マークの記録方法 |
US5358941A (en) * | 1992-12-02 | 1994-10-25 | Merck & Co., Inc. | Dry mix formulation for bisphosphonic acids with lactose |
JPH06250802A (ja) | 1993-02-22 | 1994-09-09 | Ricoh Co Ltd | プリンタ |
FR2703590B1 (fr) | 1993-04-05 | 1995-06-30 | Sanofi Elf | Utilisation de derives d'acide bisphosphonique pour la preparation de medicaments destines a favoriser la reparation osseuse . |
US5510517A (en) * | 1993-08-25 | 1996-04-23 | Merck & Co., Inc. | Process for producing N-amino-1-hydroxy-alkylidene-1,1-bisphosphonic acids |
US5431920A (en) * | 1993-09-21 | 1995-07-11 | Merck Frosst, Canada, Inc. | Enteric coated oral compositions containing bisphosphonic acid antihypercalcemic agents |
JPH07239825A (ja) | 1994-02-28 | 1995-09-12 | Canon Inc | 状態通報方法およびそれを用いたネットワークシステム |
TW390813B (en) | 1994-04-29 | 2000-05-21 | Merck & Co Inc | Wet granulation formulation for bisphosphonic acids |
US20010007863A1 (en) | 1998-06-18 | 2001-07-12 | Merck & Co., Inc. | Wet granulation formulation for bisphosphonic acids |
GB9408775D0 (en) | 1994-05-04 | 1994-06-22 | Ciba Geigy Ag | Use of certain methanebisphosphonic acid derivatives to prevent prothesis loosening and prothesis migration |
US5462932A (en) | 1994-05-17 | 1995-10-31 | Merck & Co., Inc. | Oral liquid alendronate formulations |
JPH07325514A (ja) | 1994-05-30 | 1995-12-12 | Ricoh Co Ltd | サプライ発注システム |
JPH08152825A (ja) | 1994-11-30 | 1996-06-11 | Mita Ind Co Ltd | 画像形成装置の管理システム |
JPH08152814A (ja) | 1994-11-30 | 1996-06-11 | Mita Ind Co Ltd | 画像形成装置の管理システム |
FR2727629A1 (fr) | 1994-12-06 | 1996-06-07 | Sanofi Sa | Trousse pour cycle de traitement de l'osteoporose |
JP3261900B2 (ja) | 1994-12-13 | 2002-03-04 | 村田機械株式会社 | ファクシミリ装置 |
ES2262145T3 (es) | 1994-12-28 | 2006-11-16 | Gador S.A. | Composicion anabolica para la masa osea que comprende olpadronato. |
JPH08211792A (ja) | 1995-02-03 | 1996-08-20 | Mita Ind Co Ltd | 画像形成装置の管理システム |
CN1181012A (zh) * | 1995-02-17 | 1998-05-06 | 麦克公司 | 减小非椎骨骨折危险的方法 |
US20010051616A1 (en) | 1995-02-17 | 2001-12-13 | David B. Karpf | Method of lessening the risk of vertebral fractures |
JPH08315052A (ja) | 1995-05-18 | 1996-11-29 | Ricoh Co Ltd | 自動発注システム |
JPH08310007A (ja) | 1995-05-19 | 1996-11-26 | Oki Data:Kk | シリアルプリンタ |
JPH09120238A (ja) | 1995-10-25 | 1997-05-06 | Canon Inc | 出力装置 |
JPH09156123A (ja) | 1995-12-04 | 1997-06-17 | Brother Ind Ltd | プリンタ |
JPH09185474A (ja) | 1995-12-27 | 1997-07-15 | Fuji Xerox Co Ltd | 印刷管理装置 |
JP3363680B2 (ja) | 1995-12-28 | 2003-01-08 | ブラザー工業株式会社 | カートリッジの真偽判別方法及びそれを利用した出力装置 |
JPH09259355A (ja) | 1996-03-21 | 1997-10-03 | Oki Electric Ind Co Ltd | 梱包された商品の確認処理システム |
DE19615812A1 (de) * | 1996-04-20 | 1997-10-23 | Boehringer Mannheim Gmbh | Pharmazeutische Zubereitung enthaltend Diphosphonsäuren zur oralen Applikation |
US5930553A (en) | 1997-04-25 | 1999-07-27 | Hewlett-Packard Company | Image forming and office automation device consumable with memory |
US5730715A (en) | 1996-06-14 | 1998-03-24 | Becton Dickinson And Company | Method for the iontophoretic administration of bisphosphonates |
US5781405A (en) * | 1996-09-30 | 1998-07-14 | Gateway 2000, Inc. | Electronic device having rotatably mounted infrared device with a pair of pegs fitting into a pair of holes |
US6572874B1 (en) | 1998-05-15 | 2003-06-03 | Umd, Inc. | Vaginal delivery of bisphosphonates |
US6905701B2 (en) | 1997-06-11 | 2005-06-14 | Umd, Inc. | Formulations for transmucosal vaginal delivery of bisphosphonates |
US5994329A (en) * | 1997-07-22 | 1999-11-30 | Merck & Co., Inc. | Method for inhibiting bone resorption |
DE122007000063I1 (de) * | 1997-07-22 | 2007-12-20 | Merck & Co Inc | Alendronate zur Behandlung von Osteoporose |
US6015801A (en) | 1997-07-22 | 2000-01-18 | Merck & Co., Inc. | Method for inhibiting bone resorption |
US6124314A (en) | 1997-10-10 | 2000-09-26 | Pfizer Inc. | Osteoporosis compounds |
SE9703691D0 (sv) | 1997-10-10 | 1997-10-10 | Astra Ab | Pharmaceutical compositions |
JP3065053B2 (ja) | 1998-01-06 | 2000-07-12 | セイコーエプソン株式会社 | 機器監視システム、ローカル監視装置、統合監視装置、機器監視方法、及び、プログラムを格納したコンピュータ可読媒体 |
EP1088333A4 (en) | 1998-06-24 | 2005-08-10 | Merck & Co Inc | METHOD AND COMPOSITIONS FOR CONNECTING OSTEOPROSIS |
US6816968B1 (en) | 1998-07-10 | 2004-11-09 | Silverbrook Research Pty Ltd | Consumable authentication protocol and system |
IT1303672B1 (it) | 1998-07-28 | 2001-02-23 | Nicox Sa | Sali nitrati di farmaci attivi nei disordini ossei |
US6494562B1 (en) | 1998-09-03 | 2002-12-17 | Hewlett-Packard Company | Method and apparatus for identifying a sales channel |
FR2784031B1 (fr) | 1998-10-02 | 2002-02-01 | Sanofi Elf | Utilisation de derives de l'acide bisphosphonique pour la preparation d'un medicament destine au traitement des boiteries |
EP0998932A1 (de) * | 1998-10-09 | 2000-05-10 | Boehringer Mannheim Gmbh | Feste pharmazeutische Darreichungsform enthaltend Diphosphonsäure oder deren Salze und Verfahren zu ihrer Herstellung |
EP0998933A1 (de) | 1998-10-09 | 2000-05-10 | Boehringer Mannheim Gmbh | Verfahren zur Herstellung von bisphosphonathaltigen pharmazeutischen Zusammensetzungen zur oralen Applikation |
US6331533B1 (en) | 1998-11-16 | 2001-12-18 | Merck & Co., Inc. | Method for inhibiting dental resorptive lesions |
PT1135140E (pt) | 1998-12-04 | 2005-10-31 | Roche Diagnostics Gmbh | Utilizacao de ibandronato para a promocao da integracao ossea de endoproteses |
TW442666B (en) | 1998-12-22 | 2001-06-23 | Minolta Co Ltd | Zoom lens system |
WO2000042665A1 (de) * | 1999-01-11 | 2000-07-20 | Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. | Mos-leistungsbauelement und verfahren zum herstellen desselben |
DK1165184T3 (da) | 1999-04-09 | 2004-04-13 | Karobio Ab | Estrogenreceptor-beta antagonisme og knoglesygdomme |
SE9901272D0 (sv) | 1999-04-09 | 1999-04-09 | Astra Ab | New improved formulation |
CA2308532C (en) | 1999-05-12 | 2005-11-29 | Gador S.A. | Use of bisphosphonates for the treatment of osteogenesis imperfecta |
WO2000071104A2 (en) | 1999-05-21 | 2000-11-30 | Novartis Ag | Use of bisphosphonic acids for treating angiogenesis |
US6965411B1 (en) | 1999-06-24 | 2005-11-15 | Jones Richard A | Remote camera positioner |
AR024462A1 (es) | 1999-07-01 | 2002-10-02 | Merck & Co Inc | Tabletas farmaceuticas |
US6903836B2 (en) | 1999-09-10 | 2005-06-07 | Hewlett-Packard Development Company, L.P. | Hard copy cost recovery systems, an apparatus for tracking usage information for a hard copy device, hard copy devices, and a usage accounting method |
US6793934B1 (en) * | 1999-12-08 | 2004-09-21 | Shire Laboratories, Inc. | Solid oral dosage form |
US6285060B1 (en) * | 1999-12-30 | 2001-09-04 | Siliconix Incorporated | Barrier accumulation-mode MOSFET |
JP2001253827A (ja) | 2000-02-15 | 2001-09-18 | Pfizer Prod Inc | 骨粗鬆症を治療するための組成物および方法 |
US20020004218A1 (en) * | 2000-03-31 | 2002-01-10 | Rodan Gideon A. | Methods for identifying compounds useful for inhibiting geranylgeranyl diphosphate synthase |
AU2001251391A1 (en) | 2000-04-06 | 2001-10-23 | Acorda Therapeutics, Inc. | Compositions and methods for promoting neural regeneration |
GB0012209D0 (en) | 2000-05-19 | 2000-07-12 | Novartis Ag | Organic compounds |
ATE304856T1 (de) | 2000-06-20 | 2005-10-15 | Novartis Pharma Gmbh | Methode zur verabreichung von biphosphonaten |
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 |
KR100863146B1 (ko) | 2000-07-17 | 2008-10-14 | 아스텔라스세이야쿠 가부시키가이샤 | 경구 흡수 개선 의약 조성물 |
US6638920B2 (en) * | 2000-07-21 | 2003-10-28 | Merck & Co., Inc. | Compositions and methods of preventing or reducing the risk or incidence of skeletal injuries in horses |
US6750213B2 (en) | 2000-10-19 | 2004-06-15 | Merck & Co., Inc. | Estrogen receptor modulators |
BRPI0116865B8 (pt) | 2001-01-23 | 2021-05-25 | Gador Sa | composição compreendendo bisfosfonatos para prevenção e/ou tratamento de doenças metabólicas dos ossos, processo para preparar tal composição e uso desta |
AR034199A1 (es) | 2001-02-01 | 2004-02-04 | Riderway Corp | Composicion farmacologica liquida para el tratamiento de enfermedades oseas y procedimientos para su elaboracion |
US7425549B2 (en) | 2001-02-06 | 2008-09-16 | The Royal Alexandra Hospital For Children | Drug for the treatment of osteonecrosis and for the management of patients at risk of developing osteonecrosis |
JP4354698B2 (ja) | 2001-03-01 | 2009-10-28 | エミスフェアー・テクノロジーズ・インク | ビスホスホネートデリバリー用組成物 |
US6838584B2 (en) | 2001-05-10 | 2005-01-04 | Merck & Co., Inc. | Estrogen receptor modulators |
US6998678B2 (en) * | 2001-05-17 | 2006-02-14 | Infineon Technologies Ag | Semiconductor arrangement with a MOS-transistor and a parallel Schottky-diode |
US20030139378A1 (en) | 2001-12-13 | 2003-07-24 | Daifotis Anastasia G. | Liquid bisphosphonate formulations for bone disorders |
CN100479823C (zh) * | 2001-12-21 | 2009-04-22 | 宝洁公司 | 双膦酸盐在制造药物套盒中的用途以及用于增加骨质的套盒 |
US20050070504A1 (en) | 2001-12-21 | 2005-03-31 | The Procter & Gamble Co. | Risedronate compositions and their methods of use |
DE10207309B4 (de) * | 2002-02-21 | 2015-07-23 | Infineon Technologies Ag | MOS-Transistoreinrichtung |
US7488496B2 (en) * | 2002-03-06 | 2009-02-10 | Christer Rosen | Effervescent compositions comprising bisphosphonates and methods related thereto |
MXPA04008800A (es) | 2002-03-13 | 2004-11-26 | Merck & Co Inc | Derivados de 4-azasteroides fluorados como moduladores del receptor de androgenos. |
AU2003226148A1 (en) | 2002-04-05 | 2003-10-27 | Merck & Co., Inc. | Method for inhibiting bone resorption with an alendronate and vitamin d formulation |
ES2532393T3 (es) * | 2002-05-10 | 2015-03-26 | F. Hoffmann-La Roche Ag | Acidos bisfosfónicos para tratamiento y prevención de osteoporosis |
NZ536273A (en) * | 2002-12-20 | 2007-08-31 | Hoffmann La Roche | High dose ibandronate formulation |
GB0424543D0 (en) * | 2004-11-05 | 2004-12-08 | Varintelligent Bvi Ltd | Driving method for high frame rate display system |
-
2003
- 2003-05-02 ES ES07014362.3T patent/ES2532393T3/es not_active Expired - Lifetime
- 2003-05-02 RU RU2004129324/15A patent/RU2329809C2/ru not_active IP Right Cessation
- 2003-05-02 KR KR1020067008979A patent/KR20060058151A/ko not_active Application Discontinuation
- 2003-05-02 CA CA2481142A patent/CA2481142C/en not_active Expired - Fee Related
- 2003-05-02 AT AT03722591T patent/ATE376444T1/de active
- 2003-05-02 KR KR1020097004578A patent/KR20090029312A/ko active Application Filing
- 2003-05-02 KR KR1020097019891A patent/KR20090106663A/ko active Search and Examination
- 2003-05-02 NZ NZ556278A patent/NZ556278A/en not_active IP Right Cessation
- 2003-05-02 BR BR0308901-0A patent/BR0308901A/pt not_active Application Discontinuation
- 2003-05-02 CA CA2763775A patent/CA2763775C/en not_active Expired - Fee Related
- 2003-05-02 PL PL399493A patent/PL399493A1/pl unknown
- 2003-05-02 DK DK03722591T patent/DK1506041T3/da active
- 2003-05-02 KR KR1020137034838A patent/KR20140021045A/ko active Application Filing
- 2003-05-02 KR KR1020047015694A patent/KR100642961B1/ko active IP Right Review Request
- 2003-05-02 EP EP14184790.5A patent/EP2851105A1/en not_active Withdrawn
- 2003-05-02 EP EP10179327A patent/EP2308563A1/en not_active Ceased
- 2003-05-02 DK DK07014362.3T patent/DK1880744T3/en active
- 2003-05-02 KR KR1020157010154A patent/KR20150053811A/ko not_active Application Discontinuation
- 2003-05-02 KR KR1020127011286A patent/KR20120065435A/ko not_active Application Discontinuation
- 2003-05-02 SI SI200331018T patent/SI1506041T1/sl unknown
- 2003-05-02 NZ NZ535705A patent/NZ535705A/en not_active IP Right Cessation
- 2003-05-02 WO PCT/EP2003/004629 patent/WO2003095029A1/en active Application Filing
- 2003-05-02 CN CNA2006101363686A patent/CN1939314A/zh active Pending
- 2003-05-02 PT PT70143623T patent/PT1880744E/pt unknown
- 2003-05-02 MX MXPA04009586A patent/MXPA04009586A/es active IP Right Grant
- 2003-05-02 PT PT03722591T patent/PT1506041E/pt unknown
- 2003-05-02 EP EP20070014362 patent/EP1880744B1/en not_active Revoked
- 2003-05-02 JP JP2004503108A patent/JP2005522526A/ja active Pending
- 2003-05-02 AU AU2003229770A patent/AU2003229770B2/en not_active Ceased
- 2003-05-02 CN CNB038075652A patent/CN100551377C/zh not_active Expired - Fee Related
- 2003-05-02 PL PL03371346A patent/PL371346A1/xx not_active Application Discontinuation
- 2003-05-02 SI SI200332418T patent/SI1880744T1/sl unknown
- 2003-05-02 ES ES03722591T patent/ES2294277T3/es not_active Expired - Lifetime
- 2003-05-02 RU RU2008103617/14A patent/RU2387451C2/ru not_active IP Right Cessation
- 2003-05-02 EP EP03722591A patent/EP1506041B1/en not_active Revoked
- 2003-05-02 DE DE60317061T patent/DE60317061T2/de not_active Expired - Lifetime
- 2003-05-06 TW TW092112340A patent/TWI347188B/zh not_active IP Right Cessation
- 2003-05-06 US US10/430,007 patent/US7410957B2/en not_active Expired - Fee Related
- 2003-05-06 PA PA20038573101A patent/PA8573101A1/es unknown
- 2003-05-07 PE PE2003000447A patent/PE20040440A1/es not_active Application Discontinuation
- 2003-05-08 MY MYPI20071758A patent/MY146809A/en unknown
- 2003-05-08 MY MYPI20031738A patent/MY140080A/en unknown
- 2003-05-08 AR ARP030101609A patent/AR039978A1/es not_active Application Discontinuation
- 2003-05-09 UY UY27802A patent/UY27802A1/es not_active Application Discontinuation
- 2003-05-09 GT GT200300107A patent/GT200300107A/es unknown
-
2004
- 2004-06-09 IL IL17437104A patent/IL164371A0/xx unknown
- 2004-10-01 HR HR20040906 patent/HRP20040906B1/xx not_active IP Right Cessation
- 2004-10-01 NO NO20044195A patent/NO328734B1/no not_active IP Right Cessation
- 2004-10-01 EC EC2004005335A patent/ECSP045335A/es unknown
- 2004-10-01 ZA ZA2004/07950A patent/ZA200407950B/en unknown
- 2004-10-03 IL IL164371A patent/IL164371A/en active IP Right Grant
- 2004-11-29 US US10/998,849 patent/US7192938B2/en not_active Expired - Fee Related
-
2006
- 2006-01-05 HK HK06100194.8A patent/HK1080409A1/xx not_active IP Right Cessation
- 2006-03-27 US US11/390,227 patent/US20060166938A1/en not_active Abandoned
-
2007
- 2007-07-06 AR ARP070103036A patent/AR061845A2/es not_active Application Discontinuation
-
2008
- 2008-01-11 CY CY20081100046T patent/CY1108105T1/el unknown
- 2008-06-16 US US12/139,587 patent/US7718634B2/en not_active Expired - Fee Related
- 2008-11-17 JP JP2008293614A patent/JP5813911B2/ja not_active Expired - Fee Related
-
2010
- 2010-02-08 AU AU2010200438A patent/AU2010200438B2/en not_active Ceased
- 2010-03-31 NO NO20100477A patent/NO331024B1/no not_active IP Right Cessation
- 2010-04-08 US US12/756,376 patent/US20100197637A1/en not_active Abandoned
- 2010-04-22 IL IL205262A patent/IL205262A/en unknown
-
2013
- 2013-04-19 JP JP2013088493A patent/JP6067466B2/ja not_active Expired - Lifetime
- 2013-12-02 JP JP2013249105A patent/JP5837552B2/ja not_active Expired - Lifetime
-
2014
- 2014-12-22 JP JP2014258163A patent/JP2015083592A/ja active Pending
-
2015
- 2015-03-30 CY CY20151100307T patent/CY1116233T1/el unknown
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2001015703A1 (en) * | 1999-09-02 | 2001-03-08 | Merck & Co., Inc. | Method for inhibiting bone resorption |
WO2001082903A1 (en) * | 2000-04-28 | 2001-11-08 | Lipocine, Inc. | Enteric coated formulation of bisphosphonic acid compounds and associated therapeutic methods |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
NO328734B1 (no) | Anvendelse av ibandroninsyre for fremstilling av medikamenter til behandling og prevensjon av osteoprose | |
AU2012202489B2 (en) | Bisphosphonic acid for the treatment and prevention of osteoporosis | |
MX2011013867A (es) | Bisfosfonatos utiles en la prevencion y el tratamiento de resorcion osea anormal. |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
CHAD | Change of the owner's name or address (par. 44 patent law, par. patentforskriften) |
Owner name: ATNAHS PHARMA UK LIMITED, GB |
|
CREP | Change of representative |
Representative=s name: OSLO PATENTKONTOR AS, POSTBOKS 7007 M, 0306 |
|
MM1K | Lapsed by not paying the annual fees |