IL114683A - Use of bisphosphonates together with another active substance in the treatment of delaying bone loss - Google Patents

Use of bisphosphonates together with another active substance in the treatment of delaying bone loss

Info

Publication number: IL114683A
Authority: IL; Israel
Prior art keywords: hydrogen; pharmaceutically acceptable; solvates; hydroxy; acceptable salts
Prior art date: 1994-07-22

Application number

IL11468395A

Other languages

English (en)

Hebrew (he)

Other versions

IL114683A0 (en

Original Assignee

Lilly Co Eli

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1994-07-22

Filing date

1995-07-20

Publication date

2001-06-14

1995-07-20 Application filed by Lilly Co Eli filed Critical Lilly Co Eli

1995-11-27 Publication of IL114683A0 publication Critical patent/IL114683A0/xx

2001-06-14 Publication of IL114683A publication Critical patent/IL114683A/en

Links

229940122361 Bisphosphonate Drugs 0.000 title claims abstract description 36
150000004663 bisphosphonates Chemical class 0.000 title claims abstract description 30
206010065687 Bone loss Diseases 0.000 title claims abstract description 21
239000003112 inhibitor Substances 0.000 title description 3
239000013543 active substance Substances 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims abstract description 82
150000003839 salts Chemical class 0.000 claims abstract description 46
239000012453 solvate Substances 0.000 claims abstract description 29
230000002401 inhibitory effect Effects 0.000 claims abstract description 8
150000001907 coumarones Chemical class 0.000 claims abstract description 4
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 4
-1 cycloheptyl amino Chemical group 0.000 claims description 60
OGSPWJRAVKPPFI-UHFFFAOYSA-N Alendronic Acid Chemical compound NCCCC(O)(P(O)(O)=O)P(O)(O)=O OGSPWJRAVKPPFI-UHFFFAOYSA-N 0.000 claims description 43
229940062527 alendronate Drugs 0.000 claims description 43
229910052739 hydrogen Inorganic materials 0.000 claims description 29
239000001257 hydrogen Substances 0.000 claims description 29
125000003545 alkoxy group Chemical group 0.000 claims description 16
150000002431 hydrogen Chemical group 0.000 claims description 16
125000004423 acyloxy group Chemical group 0.000 claims description 15
125000000719 pyrrolidinyl group Chemical group 0.000 claims description 12
125000003386 piperidinyl group Chemical group 0.000 claims description 11
125000000217 alkyl group Chemical group 0.000 claims description 10
239000003814 drug Substances 0.000 claims description 10
125000002757 morpholinyl group Chemical group 0.000 claims description 10
229910052757 nitrogen Inorganic materials 0.000 claims description 10
125000004433 nitrogen atom Chemical group N* 0.000 claims description 10
125000004356 hydroxy functional group Chemical group O* 0.000 claims description 9
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
125000005333 aroyloxy group Chemical group 0.000 claims description 7
125000005843 halogen group Chemical group 0.000 claims description 7
125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 6
239000002253 acid Substances 0.000 claims description 6
125000005200 aryloxy carbonyloxy group Chemical group 0.000 claims description 6
125000004122 cyclic group Chemical group 0.000 claims description 6
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 6
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 claims description 5
125000004432 carbon atom Chemical group C* 0.000 claims description 5
125000001309 chloro group Chemical group Cl* 0.000 claims description 5
229910052736 halogen Inorganic materials 0.000 claims description 5
WRUUGTRCQOWXEG-UHFFFAOYSA-N pamidronate Chemical compound NCCC(O)(P(O)(O)=O)P(O)(O)=O WRUUGTRCQOWXEG-UHFFFAOYSA-N 0.000 claims description 5
229940046231 pamidronate Drugs 0.000 claims description 5
229940089617 risedronate Drugs 0.000 claims description 5
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 4
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
238000002360 preparation method Methods 0.000 claims description 4
229930192474 thiophene Natural products 0.000 claims description 4
125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 3
229910019142 PO4 Chemical group 0.000 claims description 3
125000001246 bromo group Chemical group Br* 0.000 claims description 3
125000004663 dialkyl amino group Chemical group 0.000 claims description 3
125000001033 ether group Chemical group 0.000 claims description 3
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
150000002367 halogens Chemical group 0.000 claims description 3
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical group [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 3
239000010452 phosphate Chemical group 0.000 claims description 3
125000005605 benzo group Chemical group 0.000 claims description 2
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
125000004193 piperazinyl group Chemical group 0.000 claims description 2
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims 4
WCLJTEXCGGSJJN-UHFFFAOYSA-N 4-(2-piperidin-1-ylethoxy)benzaldehyde Chemical compound C1=CC(C=O)=CC=C1OCCN1CCCCC1 WCLJTEXCGGSJJN-UHFFFAOYSA-N 0.000 claims 1
125000004453 alkoxycarbonyl group Chemical group 0.000 claims 1
238000000034 method Methods 0.000 abstract description 19
239000000203 mixture Substances 0.000 description 27
238000009472 formulation Methods 0.000 description 22
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 22
229960004622 raloxifene Drugs 0.000 description 22
210000000988 bone and bone Anatomy 0.000 description 18
239000004480 active ingredient Substances 0.000 description 16
238000011282 treatment Methods 0.000 description 14
230000000694 effects Effects 0.000 description 13
BFPYWIDHMRZLRN-SLHNCBLASA-N Ethinyl estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1 BFPYWIDHMRZLRN-SLHNCBLASA-N 0.000 description 12
125000002887 hydroxy group Chemical group [H]O* 0.000 description 12
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 12
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
208000001132 Osteoporosis Diseases 0.000 description 9
229920002472 Starch Polymers 0.000 description 9
PSGAAPLEWMOORI-PEINSRQWSA-N medroxyprogesterone acetate Chemical compound C([C@@]12C)CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2CC[C@]2(C)[C@@](OC(C)=O)(C(C)=O)CC[C@H]21 PSGAAPLEWMOORI-PEINSRQWSA-N 0.000 description 9
229940063222 provera Drugs 0.000 description 9
235000019698 starch Nutrition 0.000 description 9
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
239000002775 capsule Substances 0.000 description 8
239000008107 starch Substances 0.000 description 8
239000003826 tablet Substances 0.000 description 8
239000001913 cellulose Substances 0.000 description 7
235000010980 cellulose Nutrition 0.000 description 7
229920002678 cellulose Polymers 0.000 description 7
239000000243 solution Substances 0.000 description 7
230000024279 bone resorption Effects 0.000 description 6
239000007903 gelatin capsule Substances 0.000 description 6
235000019359 magnesium stearate Nutrition 0.000 description 6
230000002194 synthesizing effect Effects 0.000 description 6
DNXHEGUUPJUMQT-UHFFFAOYSA-N (+)-estrone Natural products OC1=CC=C2C3CCC(C)(C(CC4)=O)C4C3CCC2=C1 DNXHEGUUPJUMQT-UHFFFAOYSA-N 0.000 description 5
208000006386 Bone Resorption Diseases 0.000 description 5
241000700159 Rattus Species 0.000 description 5
230000015572 biosynthetic process Effects 0.000 description 5
229940079593 drug Drugs 0.000 description 5
239000000262 estrogen Substances 0.000 description 5
229940011871 estrogen Drugs 0.000 description 5
210000002997 osteoclast Anatomy 0.000 description 5
208000001685 postmenopausal osteoporosis Diseases 0.000 description 5
239000000843 powder Substances 0.000 description 5
VOPWNXZWBYDODV-UHFFFAOYSA-N Chlorodifluoromethane Chemical compound FC(F)Cl VOPWNXZWBYDODV-UHFFFAOYSA-N 0.000 description 4
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
208000010191 Osteitis Deformans Diseases 0.000 description 4
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 4
208000027868 Paget disease Diseases 0.000 description 4
229910052783 alkali metal Inorganic materials 0.000 description 4
150000001340 alkali metals Chemical class 0.000 description 4
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
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 4
239000003085 diluting agent Substances 0.000 description 4
239000004615 ingredient Substances 0.000 description 4
229910052500 inorganic mineral Inorganic materials 0.000 description 4
208000027202 mammary Paget disease Diseases 0.000 description 4
239000011707 mineral Substances 0.000 description 4
239000000546 pharmaceutical excipient Substances 0.000 description 4
229910052708 sodium Inorganic materials 0.000 description 4
239000011734 sodium Substances 0.000 description 4
239000006188 syrup Substances 0.000 description 4
235000020357 syrup Nutrition 0.000 description 4
238000002560 therapeutic procedure Methods 0.000 description 4
102000055006 Calcitonin Human genes 0.000 description 3
108060001064 Calcitonin Proteins 0.000 description 3
DNXHEGUUPJUMQT-CBZIJGRNSA-N Estrone Chemical compound OC1=CC=C2[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1 DNXHEGUUPJUMQT-CBZIJGRNSA-N 0.000 description 3
208000037147 Hypercalcaemia Diseases 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
230000037396 body weight Effects 0.000 description 3
229960004015 calcitonin Drugs 0.000 description 3
210000004027 cell Anatomy 0.000 description 3
239000003795 chemical substances by application Substances 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
239000000796 flavoring agent Substances 0.000 description 3
239000008187 granular material Substances 0.000 description 3
230000000148 hypercalcaemia Effects 0.000 description 3
208000030915 hypercalcemia disease Diseases 0.000 description 3
230000009245 menopause Effects 0.000 description 3
238000009806 oophorectomy Methods 0.000 description 3
150000007524 organic acids Chemical class 0.000 description 3
150000007530 organic bases Chemical class 0.000 description 3
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
239000011541 reaction mixture Substances 0.000 description 3
238000001356 surgical procedure Methods 0.000 description 3
239000000725 suspension Substances 0.000 description 3
238000003786 synthesis reaction Methods 0.000 description 3
239000000454 talc Substances 0.000 description 3
229910052623 talc Inorganic materials 0.000 description 3
235000012222 talc Nutrition 0.000 description 3
230000001225 therapeutic effect Effects 0.000 description 3
239000003981 vehicle Substances 0.000 description 3
125000006273 (C1-C3) alkyl group Chemical group 0.000 description 2
125000006274 (C1-C3)alkoxy group Chemical group 0.000 description 2
125000004169 (C1-C6) alkyl group Chemical group 0.000 description 2
125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
206010002091 Anaesthesia Diseases 0.000 description 2
239000005711 Benzoic acid Substances 0.000 description 2
208000010392 Bone Fractures Diseases 0.000 description 2
208000020084 Bone disease Diseases 0.000 description 2
QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
206010017076 Fracture Diseases 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 description 2
DKJJVAGXPKPDRL-UHFFFAOYSA-N Tiludronic acid Chemical compound OP(O)(=O)C(P(O)(O)=O)SC1=CC=C(Cl)C=C1 DKJJVAGXPKPDRL-UHFFFAOYSA-N 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
239000000443 aerosol Substances 0.000 description 2
125000005194 alkoxycarbonyloxy group Chemical group 0.000 description 2
230000037005 anaesthesia Effects 0.000 description 2
150000001450 anions Chemical class 0.000 description 2
230000000123 anti-resoprtive effect Effects 0.000 description 2
125000003118 aryl group Chemical group 0.000 description 2
239000002585 base Substances 0.000 description 2
235000010233 benzoic acid Nutrition 0.000 description 2
150000001562 benzopyrans Chemical class 0.000 description 2
230000008416 bone turnover Effects 0.000 description 2
229910052799 carbon Inorganic materials 0.000 description 2
239000000969 carrier Substances 0.000 description 2
210000000845 cartilage Anatomy 0.000 description 2
230000015556 catabolic process Effects 0.000 description 2
238000006243 chemical reaction Methods 0.000 description 2
229960002286 clodronic acid Drugs 0.000 description 2
238000006731 degradation reaction Methods 0.000 description 2
201000010099 disease Diseases 0.000 description 2
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
239000002552 dosage form Substances 0.000 description 2
239000003937 drug carrier Substances 0.000 description 2
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 2
229940009626 etidronate Drugs 0.000 description 2
235000019634 flavors Nutrition 0.000 description 2
125000002541 furyl group Chemical group 0.000 description 2
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
238000010191 image analysis Methods 0.000 description 2
230000005764 inhibitory process Effects 0.000 description 2
230000002452 interceptive effect Effects 0.000 description 2
230000000670 limiting effect Effects 0.000 description 2
230000007774 longterm Effects 0.000 description 2
239000002609 medium Substances 0.000 description 2
WSFSSNUMVMOOMR-BJUDXGSMSA-N methanone Chemical compound O=[11CH2] WSFSSNUMVMOOMR-BJUDXGSMSA-N 0.000 description 2
150000007522 mineralic acids Chemical class 0.000 description 2
125000001624 naphthyl group Chemical group 0.000 description 2
235000005985 organic acids Nutrition 0.000 description 2
201000008482 osteoarthritis Diseases 0.000 description 2
208000005368 osteomalacia Diseases 0.000 description 2
230000001009 osteoporotic effect Effects 0.000 description 2
239000001267 polyvinylpyrrolidone Substances 0.000 description 2
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
230000003389 potentiating effect Effects 0.000 description 2
230000004044 response Effects 0.000 description 2
206010039073 rheumatoid arthritis Diseases 0.000 description 2
239000007787 solid Substances 0.000 description 2
239000000126 substance Substances 0.000 description 2
125000001424 substituent group Chemical group 0.000 description 2
229960001603 tamoxifen Drugs 0.000 description 2
125000001544 thienyl group Chemical group 0.000 description 2
150000003577 thiophenes Chemical class 0.000 description 2
229940019375 tiludronate Drugs 0.000 description 2
210000000689 upper leg Anatomy 0.000 description 2
210000004291 uterus Anatomy 0.000 description 2
238000005303 weighing Methods 0.000 description 2
125000004209 (C1-C8) alkyl group Chemical group 0.000 description 1
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 1
VMZKWNQITYDWEE-UHFFFAOYSA-N 1-[2-[4-(7-methoxy-3-phenyl-2h-chromen-2-yl)phenoxy]ethyl]piperidine Chemical compound O1C2=CC(OC)=CC=C2C=C(C=2C=CC=CC=2)C1C(C=C1)=CC=C1OCCN1CCCCC1 VMZKWNQITYDWEE-UHFFFAOYSA-N 0.000 description 1
FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical class C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 1
AUVALWUPUHHNQV-UHFFFAOYSA-N 2-hydroxy-3-propylbenzoic acid Chemical class CCCC1=CC=CC(C(O)=O)=C1O AUVALWUPUHHNQV-UHFFFAOYSA-N 0.000 description 1
VFJFQJKZWLXQQX-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-2-[4-(2-piperidin-1-ylethoxy)phenyl]-2h-chromen-7-ol Chemical compound C1=CC(O)=CC=C1C1=CC2=CC=C(O)C=C2OC1C(C=C1)=CC=C1OCCN1CCCCC1 VFJFQJKZWLXQQX-UHFFFAOYSA-N 0.000 description 1
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
FIYLLNDHLJCAAC-UHFFFAOYSA-N 4-[2-[4-(2-piperidin-1-ylethoxy)phenyl]-2h-chromen-3-yl]phenol Chemical compound C1=CC(O)=CC=C1C1=CC2=CC=CC=C2OC1C(C=C1)=CC=C1OCCN1CCCCC1 FIYLLNDHLJCAAC-UHFFFAOYSA-N 0.000 description 1
125000004861 4-isopropyl phenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
244000215068 Acacia senegal Species 0.000 description 1
235000006491 Acacia senegal Nutrition 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
241000416162 Astragalus gummifer Species 0.000 description 1
LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
206010006187 Breast cancer Diseases 0.000 description 1
208000026310 Breast neoplasm Diseases 0.000 description 1
206010006298 Breast pain Diseases 0.000 description 1
108010001789 Calcitonin Receptors Proteins 0.000 description 1
102100038520 Calcitonin receptor Human genes 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
208000014311 Cushing syndrome Diseases 0.000 description 1
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
ZQZFYGIXNQKOAV-OCEACIFDSA-N Droloxifene Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=C(O)C=CC=1)\C1=CC=C(OCCN(C)C)C=C1 ZQZFYGIXNQKOAV-OCEACIFDSA-N 0.000 description 1
LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
DBVJJBKOTRCVKF-UHFFFAOYSA-N Etidronic acid Chemical compound OP(=O)(O)C(O)(C)P(O)(O)=O DBVJJBKOTRCVKF-UHFFFAOYSA-N 0.000 description 1
KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 1
BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
229920000084 Gum arabic Polymers 0.000 description 1
206010020100 Hip fracture Diseases 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
206010020584 Hypercalcaemia of malignancy Diseases 0.000 description 1
201000002980 Hyperparathyroidism Diseases 0.000 description 1
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 1
YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 description 1
JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
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 description 1
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
241000124008 Mammalia Species 0.000 description 1
229930195725 Mannitol Natural products 0.000 description 1
208000006662 Mastodynia Diseases 0.000 description 1
208000029725 Metabolic bone disease Diseases 0.000 description 1
206010027452 Metastases to bone Diseases 0.000 description 1
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
229920000168 Microcrystalline cellulose Polymers 0.000 description 1
229910002651 NO3 Inorganic materials 0.000 description 1
206010028980 Neoplasm Diseases 0.000 description 1
NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
206010030247 Oestrogen deficiency Diseases 0.000 description 1
206010049088 Osteopenia Diseases 0.000 description 1
XNKLGNLAIBORDD-UHFFFAOYSA-N P(O)(OC(C)(O)OP(O)=O)=O Chemical compound P(O)(OC(C)(O)OP(O)=O)=O XNKLGNLAIBORDD-UHFFFAOYSA-N 0.000 description 1
LPYFOKNUDJNHQB-UHFFFAOYSA-N P(O)(OC(NC1CCCCCC1)OP(O)=O)=O Chemical compound P(O)(OC(NC1CCCCCC1)OP(O)=O)=O LPYFOKNUDJNHQB-UHFFFAOYSA-N 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 1
229920001214 Polysorbate 60 Polymers 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical class C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 1
XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
206010039984 Senile osteoporosis Diseases 0.000 description 1
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
235000021355 Stearic acid Nutrition 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
229930006000 Sucrose Natural products 0.000 description 1
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical compound OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 description 1
229920001615 Tragacanth Polymers 0.000 description 1
GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
208000002495 Uterine Neoplasms Diseases 0.000 description 1
IHGLINDYFMDHJG-UHFFFAOYSA-N [2-(4-methoxyphenyl)-3,4-dihydronaphthalen-1-yl]-[4-(2-pyrrolidin-1-ylethoxy)phenyl]methanone Chemical compound C1=CC(OC)=CC=C1C(CCC1=CC=CC=C11)=C1C(=O)C(C=C1)=CC=C1OCCN1CCCC1 IHGLINDYFMDHJG-UHFFFAOYSA-N 0.000 description 1
MVJKHVLZZWTOKH-UHFFFAOYSA-L [Na+].P(OC(NC1CCCCCC1)OP([O-])=O)([O-])=O.[Na+] Chemical compound [Na+].P(OC(NC1CCCCCC1)OP([O-])=O)([O-])=O.[Na+] MVJKHVLZZWTOKH-UHFFFAOYSA-L 0.000 description 1
238000010521 absorption reaction Methods 0.000 description 1
235000010489 acacia gum Nutrition 0.000 description 1
DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
239000011149 active material Substances 0.000 description 1
235000010443 alginic acid Nutrition 0.000 description 1
229920000615 alginic acid Polymers 0.000 description 1
125000001931 aliphatic group Chemical group 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
150000001412 amines Chemical class 0.000 description 1
229910021529 ammonia Inorganic materials 0.000 description 1
238000004458 analytical method Methods 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
238000003556 assay Methods 0.000 description 1
125000004429 atom Chemical group 0.000 description 1
150000007514 bases Chemical class 0.000 description 1
230000009286 beneficial effect Effects 0.000 description 1
230000008901 benefit Effects 0.000 description 1
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
230000002146 bilateral effect Effects 0.000 description 1
230000037182 bone density Effects 0.000 description 1
244000309464 bull Species 0.000 description 1
KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
229960003773 calcitonin (salmon synthetic) Drugs 0.000 description 1
239000011575 calcium Substances 0.000 description 1
229910052791 calcium Inorganic materials 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
239000000378 calcium silicate Substances 0.000 description 1
229910052918 calcium silicate Inorganic materials 0.000 description 1
229960003340 calcium silicate Drugs 0.000 description 1
235000012241 calcium silicate Nutrition 0.000 description 1
OYACROKNLOSFPA-UHFFFAOYSA-N calcium;dioxido(oxo)silane Chemical compound [Ca+2].[O-][Si]([O-])=O OYACROKNLOSFPA-UHFFFAOYSA-N 0.000 description 1
201000011510 cancer Diseases 0.000 description 1
150000001721 carbon Chemical group 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
239000001768 carboxy methyl cellulose Substances 0.000 description 1
125000002091 cationic group Chemical group 0.000 description 1
150000001768 cations Chemical class 0.000 description 1
230000003915 cell function Effects 0.000 description 1
210000003541 chondroclast Anatomy 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
GKIRPKYJQBWNGO-OCEACIFDSA-N clomifene Chemical compound C1=CC(OCCN(CC)CC)=CC=C1C(\C=1C=CC=CC=1)=C(\Cl)C1=CC=CC=C1 GKIRPKYJQBWNGO-OCEACIFDSA-N 0.000 description 1
229960003608 clomifene Drugs 0.000 description 1
239000003246 corticosteroid Substances 0.000 description 1
229960001334 corticosteroids Drugs 0.000 description 1
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
230000003111 delayed effect Effects 0.000 description 1
OWZREIFADZCYQD-NSHGMRRFSA-N deltamethrin Chemical compound CC1(C)[C@@H](C=C(Br)Br)[C@H]1C(=O)O[C@H](C#N)C1=CC=CC(OC=2C=CC=CC=2)=C1 OWZREIFADZCYQD-NSHGMRRFSA-N 0.000 description 1
230000001627 detrimental effect Effects 0.000 description 1
239000008121 dextrose Substances 0.000 description 1
150000001991 dicarboxylic acids Chemical class 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-M dihydrogenphosphate Chemical compound OP(O)([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-M 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
230000002222 downregulating effect Effects 0.000 description 1
229950004203 droloxifene Drugs 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
230000001804 emulsifying effect Effects 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
230000002708 enhancing effect Effects 0.000 description 1
230000003628 erosive effect Effects 0.000 description 1
229960002568 ethinylestradiol Drugs 0.000 description 1
LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
229940093471 ethyl oleate Drugs 0.000 description 1
125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
238000011156 evaluation Methods 0.000 description 1
238000011049 filling Methods 0.000 description 1
239000012530 fluid Substances 0.000 description 1
125000001153 fluoro group Chemical group F* 0.000 description 1
235000013305 food Nutrition 0.000 description 1
235000013355 food flavoring agent Nutrition 0.000 description 1
235000003599 food sweetener Nutrition 0.000 description 1
230000006870 function Effects 0.000 description 1
238000003304 gavage Methods 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
239000003862 glucocorticoid Substances 0.000 description 1
230000002710 gonadal effect Effects 0.000 description 1
210000004349 growth plate Anatomy 0.000 description 1
125000000623 heterocyclic group Chemical group 0.000 description 1
125000003707 hexyloxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
208000008750 humoral hypercalcemia of malignancy Diseases 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
229940071870 hydroiodic acid Drugs 0.000 description 1
229910052588 hydroxylapatite Inorganic materials 0.000 description 1
238000003384 imaging method Methods 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
125000002346 iodo group Chemical group I* 0.000 description 1
150000002500 ions Chemical class 0.000 description 1
230000007794 irritation Effects 0.000 description 1
125000002510 isobutoxy group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])O* 0.000 description 1
125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 1
229960003299 ketamine Drugs 0.000 description 1
239000008101 lactose Substances 0.000 description 1
239000007788 liquid Substances 0.000 description 1
239000011344 liquid material Substances 0.000 description 1
229940057995 liquid paraffin Drugs 0.000 description 1
229910052744 lithium Inorganic materials 0.000 description 1
238000011866 long-term treatment Methods 0.000 description 1
239000007937 lozenge Substances 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
230000001050 lubricating effect Effects 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
230000036210 malignancy Effects 0.000 description 1
239000000594 mannitol Substances 0.000 description 1
235000010355 mannitol Nutrition 0.000 description 1
239000011159 matrix material Substances 0.000 description 1
230000007246 mechanism Effects 0.000 description 1
230000010534 mechanism of action Effects 0.000 description 1
230000001404 mediated effect Effects 0.000 description 1
210000004914 menses Anatomy 0.000 description 1
125000005341 metaphosphate group Chemical group 0.000 description 1
229920000609 methyl cellulose Polymers 0.000 description 1
239000001923 methylcellulose Substances 0.000 description 1
235000010981 methylcellulose Nutrition 0.000 description 1
235000019813 microcrystalline cellulose Nutrition 0.000 description 1
239000008108 microcrystalline cellulose Substances 0.000 description 1
229940016286 microcrystalline cellulose Drugs 0.000 description 1
229910021424 microcrystalline silicon Inorganic materials 0.000 description 1
239000002480 mineral oil Substances 0.000 description 1
235000010446 mineral oil Nutrition 0.000 description 1
238000002156 mixing Methods 0.000 description 1
239000013642 negative control Substances 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
230000000474 nursing effect Effects 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
235000008390 olive oil Nutrition 0.000 description 1
239000004006 olive oil Substances 0.000 description 1
150000002895 organic esters Chemical class 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
230000011164 ossification Effects 0.000 description 1
230000001599 osteoclastic effect Effects 0.000 description 1
235000006408 oxalic acid Nutrition 0.000 description 1
XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 description 1
125000004115 pentoxy group Chemical group [*]OC([H])([H])C([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
239000002304 perfume Substances 0.000 description 1
208000028169 periodontal disease Diseases 0.000 description 1
239000008024 pharmaceutical diluent Substances 0.000 description 1
CMPQUABWPXYYSH-UHFFFAOYSA-N phenyl phosphate Chemical compound OP(O)(=O)OC1=CC=CC=C1 CMPQUABWPXYYSH-UHFFFAOYSA-N 0.000 description 1
239000006187 pill Substances 0.000 description 1
239000013641 positive control Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000011591 potassium Substances 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
201000009395 primary hyperaldosteronism Diseases 0.000 description 1
239000000583 progesterone congener Substances 0.000 description 1
230000002035 prolonged effect Effects 0.000 description 1
239000003380 propellant Substances 0.000 description 1
238000011321 prophylaxis Methods 0.000 description 1
125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
230000001681 protective effect Effects 0.000 description 1
HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 1
BKXVVCILCIUCLG-UHFFFAOYSA-N raloxifene hydrochloride Chemical compound [H+].[Cl-].C1=CC(O)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(O)C=C2S1 BKXVVCILCIUCLG-UHFFFAOYSA-N 0.000 description 1
238000011552 rat model Methods 0.000 description 1
238000011084 recovery Methods 0.000 description 1
230000009467 reduction Effects 0.000 description 1
230000002829 reductive effect Effects 0.000 description 1
230000000452 restraining effect Effects 0.000 description 1
108010068072 salmon calcitonin Proteins 0.000 description 1
239000012056 semi-solid material Substances 0.000 description 1
239000000377 silicon dioxide Substances 0.000 description 1
235000012239 silicon dioxide Nutrition 0.000 description 1
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
FAPWRFPIFSIZLT-UHFFFAOYSA-M sodium chloride Inorganic materials [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
239000011343 solid material Substances 0.000 description 1
239000000600 sorbitol Substances 0.000 description 1
235000010356 sorbitol Nutrition 0.000 description 1
206010041569 spinal fracture Diseases 0.000 description 1
238000013223 sprague-dawley female rat Methods 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
229910001220 stainless steel Inorganic materials 0.000 description 1
239000010935 stainless steel Substances 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
150000003431 steroids Chemical class 0.000 description 1
238000003756 stirring Methods 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
125000000547 substituted alkyl group Chemical group 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
125000003375 sulfoxide group Chemical group 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
230000002459 sustained effect Effects 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
239000007916 tablet composition 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
210000001519 tissue Anatomy 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
235000010487 tragacanth Nutrition 0.000 description 1
239000000196 tragacanth Substances 0.000 description 1
229940116362 tragacanth Drugs 0.000 description 1
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 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
229950000212 trioxifene Drugs 0.000 description 1
230000007306 turnover Effects 0.000 description 1
206010046766 uterine cancer Diseases 0.000 description 1
235000015112 vegetable and seed oil Nutrition 0.000 description 1
239000008158 vegetable oil Substances 0.000 description 1
229920002554 vinyl polymer Polymers 0.000 description 1
230000003442 weekly effect Effects 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1
BPICBUSOMSTKRF-UHFFFAOYSA-N xylazine Chemical compound CC1=CC=CC(C)=C1NC1=NCCCS1 BPICBUSOMSTKRF-UHFFFAOYSA-N 0.000 description 1
229960001600 xylazine Drugs 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
- 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
- A61K31/13—Amines
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
- A61K31/343—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
- A61K31/382—Heterocyclic compounds having sulfur as a ring hetero atom having six-membered rings, e.g. thioxanthenes
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
- A61K31/405—Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- 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
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- 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
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00

Landscapes

Health & Medical Sciences (AREA)
General Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Chemical & Material Sciences (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Medicinal Chemistry (AREA)
Animal Behavior & Ethology (AREA)
Pharmacology & Pharmacy (AREA)
Epidemiology (AREA)
Physical Education & Sports Medicine (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Chemical Kinetics & Catalysis (AREA)
Organic Chemistry (AREA)
General Chemical & Material Sciences (AREA)
Orthopedic Medicine & Surgery (AREA)
Rheumatology (AREA)
Obesity (AREA)
Diabetes (AREA)
Hematology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Control Of Motors That Do Not Use Commutators (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

IL11468395A 1994-07-22 1995-07-20 Use of bisphosphonates together with another active substance in the treatment of delaying bone loss IL114683A (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US27936394A	1994-07-22	1994-07-22

Publications (2)

Publication Number	Publication Date
IL114683A0 IL114683A0 (en)	1995-11-27
IL114683A true IL114683A (en)	2001-06-14

Family

ID=23068631

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
IL11468395A IL114683A (en)	1994-07-22	1995-07-20	Use of bisphosphonates together with another active substance in the treatment of delaying bone loss

Country Status (23)

Country	Link
US (1)	US20010051636A1 (fr)
EP (1)	EP0693285B1 (fr)
JP (1)	JPH0840911A (fr)
KR (1)	KR960003726A (fr)
CN (1)	CN1079671C (fr)
AT (1)	ATE212846T1 (fr)
AU (1)	AU693235B2 (fr)
BR (1)	BR9503406A (fr)
CA (1)	CA2154414A1 (fr)
CZ (1)	CZ189195A3 (fr)
DE (1)	DE69525291T2 (fr)
DK (1)	DK0693285T3 (fr)
ES (1)	ES2168336T3 (fr)
HU (1)	HUT72754A (fr)
IL (1)	IL114683A (fr)
NO (1)	NO308194B1 (fr)
NZ (1)	NZ272608A (fr)
PL (1)	PL181304B1 (fr)
PT (1)	PT693285E (fr)
RU (1)	RU2149631C1 (fr)
TW (1)	TW398975B (fr)
UA (1)	UA41909C2 (fr)
ZA (1)	ZA956029B (fr)

Families Citing this family (32)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CN1167437A (zh) *	1994-11-29	1997-12-10	赫彻斯特马里恩鲁斯公司	用三芳基-乙烯衍生物治疗和预防骨质疏松的方法
AU712711B2 (en) *	1994-11-29	1999-11-11	Hoechst Marion Roussel, Inc.	Method of using triaryl-ethylene derivatives in the treatment and prevention of osteoporosis
EP0722727A1 (fr) *	1995-01-20	1996-07-24	Eli Lilly And Company	Dérivés de la benzofuranne pour inhiber la fibrose utérine
US5554600A (en) *	1995-01-20	1996-09-10	Eli Lilly And Company	Methods for inhibiting endometriosis
US5512583A (en) *	1995-01-30	1996-04-30	Eli Lilly And Company	Methods of decreasing serum calcium levels
US6479517B1 (en) *	1995-02-28	2002-11-12	Eli Lilly And Company	Phosphorous-containing benzothiophenes
US5616571A (en) *	1995-06-06	1997-04-01	Merck & Co., Inc.	Bisphosphonates prevent bone loss associated with immunosuppressive therapy
US5958969A (en) *	1996-10-10	1999-09-28	Eli Lilly And Company	Benzo b!thiophene compounds, intermediates, formulations, and methods
GB2324726A (en) *	1997-05-01	1998-11-04	Merck & Co Inc	Combination Therapy for the Treatment of Osteoporosis
US7005428B1 (en)	1998-06-11	2006-02-28	Endorecherche, Inc.	Medical uses of a selective estrogen receptor modulator in combination with sex steroid precursors
US6465445B1 (en)	1998-06-11	2002-10-15	Endorecherche, Inc.	Medical uses of a selective estrogen receptor modulator in combination with sex steroid precursors
WO2002007733A2 (fr) *	2000-07-19	2002-01-31	Eli Lilly And Company	Procede servant a ameliorer la densite de mineraux osseux
US7560490B2 (en) *	2001-01-23	2009-07-14	Gador S.A.	Composition comprising bisphosphonates for prevention and/or treatment of metabolic diseases of bones, process for preparing such composition and use thereof
NZ527157A (en) *	2001-03-01	2005-04-29	Emisphere Tech Inc	Compositions for delivering bisphosphonates
RU2192639C1 (ru) *	2001-04-05	2002-11-10	Дальневосточный государственный медицинский университет	Способ прогнозирования нарушений в постменопаузальном периоде
RU2387451C2 (ru) *	2002-05-10	2010-04-27	Ф.Хоффманн-Ля Рош Аг	Бисфосфоновые кислоты, предназначенные для лечения и профилактики остеопороза
TR200300510A2 (tr) *	2003-04-18	2004-11-22	Sanovel �La� Sanay� Ve T�Caret A.�.	Dağılan alendronat mikropartikül formülasyonu
PT3395338T (pt) *	2003-09-12	2019-07-23	Amgen Inc	Formulação de dissolução rápida de cinacalcet hcl
KR100557086B1 (ko) *	2003-11-14	2006-03-03	한미약품 주식회사	랄록시펜과 비스포스포네이트의 상호 염
CA2555406A1 (fr) *	2004-02-19	2005-09-01	Teva Pharmaceutical Industries, Ltd.	Therapie amelioree utilisant une combinaison de raloxifene et d'alendronate
FR2875807B1 (fr)	2004-09-30	2006-11-17	Servier Lab	Forme cristalline alpha du ranelate de strontium, son procede de preparation, et les compositions pharmaceutiques qui la contiennent
CN1304401C (zh) *	2004-12-28	2007-03-14	浙江工业大学	一种阿伦膦酸的制备方法
KR101313702B1 (ko)	2005-02-03	2013-10-04	와이어쓰	제피티니브 및/또는 에를로티니브 내성암 치료용 약제학적 조성물
GB0506708D0 (en) *	2005-04-01	2005-05-11	Queen Mary & Westfield College	Use of calcitonin as combined treatment therapy for the management of inflammatory disease conditions
EP1942937A1 (fr)	2005-11-04	2008-07-16	Wyeth	Combinaisons antineoplasiques a base d'inhibiteur de mtop, d'herceptine et/ou de khi-272
US8022216B2 (en)	2007-10-17	2011-09-20	Wyeth Llc	Maleate salts of (E)-N-{4-[3-chloro-4-(2-pyridinylmethoxy)anilino]-3-cyano-7-ethoxy-6-quinolinyl}-4-(dimethylamino)-2-butenamide and crystalline forms thereof
BRPI0914790A2 (pt)	2008-06-17	2015-10-20	Wyeth Llc	uso de um composto de vinorelbina e um composto de hki-272, composição farmacêutica e produto e kit para o tratamento de neoplasma
US8669273B2 (en)	2008-08-04	2014-03-11	Wyeth Llc	Antineoplastic combinations of 4-anilino-3-cyanoquinolines and capecitabine
DK3000467T3 (da)	2009-04-06	2023-03-27	Wyeth Llc	Behandling med neratinib mod brystkræft
RS56042B1 (sr)	2010-06-10	2017-09-29	Seragon Pharmaceuticals Inc	Modulatori estrogenih receptora i njihove upotrebe
WO2013090829A1 (fr)	2011-12-14	2013-06-20	Aragon Pharmaceuticals, Inc.	Modulateurs des récepteurs des œstrogènes et ses utilisations
US20210392934A1 (en) *	2016-03-10	2021-12-23	Enzymotec Ltd.	Lipid compositions and uses thereof

Family Cites Families (17)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US2914563A (en)	1957-08-06	1959-11-24	Wm S Merrell Co	Therapeutic composition
US3274213A (en)	1961-09-05	1966-09-20	Upjohn Co	Alkoxy-substituted 2-phenyl-1-(tertiary-aminoalkoxy)phenyl-3, 4-dihydronaphthalenes
BE637389A (fr)	1962-09-13
US4400543A (en)	1975-10-28	1983-08-23	Eli Lilly And Company	3-Phenyl-4-benzoyl-1,2-dihydronaphthalenes
US4230862A (en)	1975-10-28	1980-10-28	Eli Lilly And Company	Antifertility compounds
US4133814A (en)	1975-10-28	1979-01-09	Eli Lilly And Company	2-Phenyl-3-aroylbenzothiophenes useful as antifertility agents
US4323707A (en)	1975-10-28	1982-04-06	Eli Lilly And Company	Antifertility compounds
DE3046719C2 (de)	1980-12-11	1983-02-17	Klinge Pharma GmbH, 8000 München	1,1,2-Triphenyl-but-1-en-Derivate, Verfahren zu ihrer Herstellung und Arzneimittel
US4418068A (en)	1981-04-03	1983-11-29	Eli Lilly And Company	Antiestrogenic and antiandrugenic benzothiophenes
US5139786A (en)	1989-07-07	1992-08-18	Ciba-Geigy Corporation	Topical formulations
DE69023844T2 (de)	1989-09-06	1996-06-20	Merck & Co Inc	Acyloxymethylester der Bisphonsäuren als Knochenresorptions-Inhibitoren.
EP0470310B1 (fr)	1990-08-09	1995-11-29	Council of Scientific and Industrial Research	Benzopyrannes et procédé pour leur production
JPH04312526A (ja)	1991-04-09	1992-11-04	Fujisawa Pharmaceut Co Ltd	骨疾患治療剤
JP3157882B2 (ja) *	1991-11-15	2001-04-16	帝国臓器製薬株式会社	新規なベンゾチオフエン誘導体
TW366342B (en) *	1992-07-28	1999-08-11	Lilly Co Eli	The use of 2-phenyl-3-aroylbenzothiophenes in inhibiting bone loss
EP0675723A4 (fr) *	1992-12-23	1998-08-05	Merck & Co Inc	Therapie utilisant des bisphosphonates et des strogenes en vue de traiter et de prevenir la resorption osseuse.
US5591753A (en) *	1994-01-28	1997-01-07	Eli Lilly And Company	Combination treatment for osteoporosis

1995
- 1995-07-19 PL PL95309693A patent/PL181304B1/pl unknown
- 1995-07-19 NZ NZ272608A patent/NZ272608A/xx active IP Right Revival
- 1995-07-19 TW TW084107488A patent/TW398975B/zh not_active IP Right Cessation
- 1995-07-19 ZA ZA956029A patent/ZA956029B/xx unknown
- 1995-07-19 UA UA95073400A patent/UA41909C2/uk unknown
- 1995-07-20 AT AT95305083T patent/ATE212846T1/de not_active IP Right Cessation
- 1995-07-20 RU RU95114385A patent/RU2149631C1/ru active
- 1995-07-20 DK DK95305083T patent/DK0693285T3/da active
- 1995-07-20 DE DE69525291T patent/DE69525291T2/de not_active Expired - Fee Related
- 1995-07-20 HU HU9502193A patent/HUT72754A/hu unknown
- 1995-07-20 PT PT95305083T patent/PT693285E/pt unknown
- 1995-07-20 KR KR1019950021267A patent/KR960003726A/ko not_active Ceased
- 1995-07-20 ES ES95305083T patent/ES2168336T3/es not_active Expired - Lifetime
- 1995-07-20 IL IL11468395A patent/IL114683A/en not_active IP Right Cessation
- 1995-07-20 NO NO952890A patent/NO308194B1/no not_active IP Right Cessation
- 1995-07-20 CZ CZ951891A patent/CZ189195A3/cs unknown
- 1995-07-20 EP EP95305083A patent/EP0693285B1/fr not_active Expired - Lifetime
- 1995-07-20 AU AU27112/95A patent/AU693235B2/en not_active Ceased
- 1995-07-21 CN CN95108916A patent/CN1079671C/zh not_active Expired - Fee Related
- 1995-07-21 BR BR9503406A patent/BR9503406A/pt not_active Application Discontinuation
- 1995-07-21 JP JP7185512A patent/JPH0840911A/ja not_active Withdrawn
- 1995-07-21 CA CA002154414A patent/CA2154414A1/fr not_active Abandoned
2000
- 2000-03-08 US US09/520,737 patent/US20010051636A1/en not_active Abandoned

Also Published As

Publication number	Publication date
NO308194B1 (no)	2000-08-14
IL114683A0 (en)	1995-11-27
PL309693A1 (en)	1996-02-05
CN1119940A (zh)	1996-04-10
NZ272608A (en)	2000-05-26
JPH0840911A (ja)	1996-02-13
PT693285E (pt)	2002-06-28
KR960003726A (ko)	1996-02-23
ZA956029B (en)	1997-01-20
EP0693285A2 (fr)	1996-01-24
NO952890L (no)	1996-01-23
HU9502193D0 (en)	1995-09-28
UA41909C2 (uk)	2001-10-15
PL181304B1 (pl)	2001-07-31
NO952890D0 (no)	1995-07-20
DE69525291T2 (de)	2002-09-19
BR9503406A (pt)	1996-02-27
TW398975B (en)	2000-07-21
AU693235B2 (en)	1998-06-25
RU2149631C1 (ru)	2000-05-27
DK0693285T3 (da)	2002-05-27
DE69525291D1 (de)	2002-03-21
EP0693285A3 (fr)	1998-05-06
CN1079671C (zh)	2002-02-27
AU2711295A (en)	1996-02-01
CZ189195A3 (en)	1996-06-12
ATE212846T1 (de)	2002-02-15
HUT72754A (en)	1996-05-28
ES2168336T3 (es)	2002-06-16
EP0693285B1 (fr)	2002-02-06
US20010051636A1 (en)	2001-12-13
CA2154414A1 (fr)	1996-01-23

Legal Events

Date	Code	Title
2001-11-25	FF	Patent granted
2002-02-10	KB	Patent renewed
2006-04-10	MM9K	Patent not in force due to non-payment of renewal fees

Publication	Publication Date	Title
EP0693285B1 (fr)	2002-02-06	Composition pharmaceutique contenant un bisphosphonate et un agent anti-resorptif pour inhiber la perte osseuse
EP1438957B1 (fr)	2007-04-11	Raloxifène destinée au traitement de l'ostéoporose post-ménopause
AU702575B2 (en)	1999-02-25	Methods of use for inhibiting bone loss and lowering serum cholesterol
AU677700B2 (en)	1997-05-01	Methods for inhibiting endometriosis
AU692490B2 (en)	1998-06-11	Methods of inhibiting dysfunctional uterine bleeding
EP0771200B1 (fr)	2000-02-09	Utilisation du raloxifene et de ses analogues dans la fabrication d'un medicament pour le traitement des maladies virales
JP2001253827A (ja)	2001-09-18	骨粗鬆症を治療するための組成物および方法
JPH07304674A (ja)	1995-11-21	タモキシフェンおよびタモキシフェン類似体の子宮刺激作用を最小限にするための方法
US5545661A (en)	1996-08-13	Methods for inhibiting bone loss with bis-pyrone oxovanadium compounds
US5547685A (en)	1996-08-20	Methods for inhibiting bone loss with vanadyl sulfate
CA2412373A1 (fr)	2002-01-31	Procede servant a ameliorer la densite de mineraux osseux
AU701946B2 (en)	1999-02-11	Methods for bone healing and fracture repair
US20030216358A1 (en)	2003-11-20	Method for enhancing bone mineral density gain
ES2242731T3 (es)	2005-11-16	Aplicacion de derivados de xantina para la preparacion de un medicamento destinado a la prevencion o tratamiento de la osteoporosis.
MXPA01001699A (en)	2002-06-05	Compositions and methods for treating osteoporosis