JP2002515046A - 骨粗鬆症を含む閉経後疾患を治療する方法 - Google Patents
骨粗鬆症を含む閉経後疾患を治療する方法Info
- Publication number
- JP2002515046A JP2002515046A JP51283798A JP51283798A JP2002515046A JP 2002515046 A JP2002515046 A JP 2002515046A JP 51283798 A JP51283798 A JP 51283798A JP 51283798 A JP51283798 A JP 51283798A JP 2002515046 A JP2002515046 A JP 2002515046A
- Authority
- JP
- Japan
- Prior art keywords
- idoxifen
- estrogen
- bone
- osteoporosis
- treatment
- Prior art date
- Legal status (The legal status 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 status listed.)
- Pending
Links
- 208000001132 Osteoporosis Diseases 0.000 title claims abstract description 14
- 238000000034 method Methods 0.000 title claims abstract description 11
- 201000010099 disease Diseases 0.000 title claims description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims description 6
- 150000001875 compounds Chemical class 0.000 claims abstract description 19
- 230000002265 prevention Effects 0.000 claims description 8
- JJKOTMDDZAJTGQ-DQSJHHFOSA-N Idoxifene Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN2CCCC2)=CC=1)/C1=CC=C(I)C=C1 JJKOTMDDZAJTGQ-DQSJHHFOSA-N 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims 3
- 125000006306 4-iodophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1I 0.000 claims 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims 1
- 230000000694 effects Effects 0.000 description 21
- 229940011871 estrogen Drugs 0.000 description 19
- 239000000262 estrogen Substances 0.000 description 19
- 206010065687 Bone loss Diseases 0.000 description 18
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 18
- 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 12
- 210000004027 cell Anatomy 0.000 description 11
- 210000000988 bone and bone Anatomy 0.000 description 10
- 229960004622 raloxifene Drugs 0.000 description 10
- 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 10
- 241000700159 Rattus Species 0.000 description 8
- 108091027981 Response element Proteins 0.000 description 8
- 239000000203 mixture Substances 0.000 description 8
- 239000000725 suspension Substances 0.000 description 8
- 239000005089 Luciferase Substances 0.000 description 7
- 239000000556 agonist Substances 0.000 description 7
- 210000000963 osteoblast Anatomy 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 108060001084 Luciferase Proteins 0.000 description 6
- 210000004705 lumbosacral region Anatomy 0.000 description 6
- 238000011552 rat model Methods 0.000 description 6
- 229960001603 tamoxifen Drugs 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 5
- 229950002248 idoxifene Drugs 0.000 description 5
- 150000003839 salts Chemical class 0.000 description 5
- 210000002303 tibia Anatomy 0.000 description 5
- 108700008625 Reporter Genes Proteins 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 208000024172 Cardiovascular disease Diseases 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 208000017657 Menopausal disease Diseases 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- 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 3
- 229930006000 Sucrose Natural products 0.000 description 3
- 239000001913 cellulose Substances 0.000 description 3
- 229920002678 cellulose Polymers 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- 238000009164 estrogen replacement therapy Methods 0.000 description 3
- 238000011049 filling Methods 0.000 description 3
- 239000007903 gelatin capsule Substances 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 229910052500 inorganic mineral Inorganic materials 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 230000010534 mechanism of action Effects 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 239000011707 mineral Substances 0.000 description 3
- 231100000252 nontoxic Toxicity 0.000 description 3
- 230000003000 nontoxic effect Effects 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 235000019198 oils Nutrition 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 239000005720 sucrose Substances 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- 238000001890 transfection Methods 0.000 description 3
- 239000003981 vehicle Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 201000001320 Atherosclerosis Diseases 0.000 description 2
- 208000006386 Bone Resorption Diseases 0.000 description 2
- 108020004414 DNA Proteins 0.000 description 2
- 206010014733 Endometrial cancer Diseases 0.000 description 2
- 206010014759 Endometrial neoplasm Diseases 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 241000713333 Mouse mammary tumor virus Species 0.000 description 2
- YHIPILPTUVMWQT-UHFFFAOYSA-N Oplophorus luciferin Chemical compound C1=CC(O)=CC=C1CC(C(N1C=C(N2)C=3C=CC(O)=CC=3)=O)=NC1=C2CC1=CC=CC=C1 YHIPILPTUVMWQT-UHFFFAOYSA-N 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 108010052090 Renilla Luciferases Proteins 0.000 description 2
- 235000021355 Stearic acid Nutrition 0.000 description 2
- 108010090932 Vitellogenins Proteins 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 230000008484 agonism Effects 0.000 description 2
- 230000008485 antagonism Effects 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 230000024279 bone resorption Effects 0.000 description 2
- 230000008416 bone turnover Effects 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 230000004821 effect on bone Effects 0.000 description 2
- 230000002526 effect on cardiovascular system Effects 0.000 description 2
- 230000008030 elimination Effects 0.000 description 2
- 238000003379 elimination reaction Methods 0.000 description 2
- 102000015694 estrogen receptors Human genes 0.000 description 2
- 108010038795 estrogen receptors Proteins 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000006166 lysate Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 238000003305 oral gavage Methods 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 239000000902 placebo Substances 0.000 description 2
- 229940068196 placebo Drugs 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- -1 pyrrolidino, piperidino, 4-methylpiperidino Chemical group 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 229940095743 selective estrogen receptor modulator Drugs 0.000 description 2
- 239000000333 selective estrogen receptor modulator Substances 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000008117 stearic acid Substances 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 210000000689 upper leg Anatomy 0.000 description 2
- 238000011144 upstream manufacturing Methods 0.000 description 2
- 210000004291 uterus Anatomy 0.000 description 2
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 description 1
- 150000000307 17β-estradiols Chemical class 0.000 description 1
- XZIIFPSPUDAGJM-UHFFFAOYSA-N 6-chloro-2-n,2-n-diethylpyrimidine-2,4-diamine Chemical compound CCN(CC)C1=NC(N)=CC(Cl)=N1 XZIIFPSPUDAGJM-UHFFFAOYSA-N 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
- 206010003210 Arteriosclerosis Diseases 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010049003 Fibrinogen Proteins 0.000 description 1
- 102000008946 Fibrinogen Human genes 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 101000574060 Homo sapiens Progesterone receptor Proteins 0.000 description 1
- 101500026551 Homo sapiens Transforming growth factor beta-3 Proteins 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
- 108091026898 Leader sequence (mRNA) Proteins 0.000 description 1
- 208000029725 Metabolic bone disease Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- LOJFGJZQOKTUBR-XAQOOIOESA-N NC(N)=NCCC[C@@H](C(O)=O)NC(=O)CNC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CCC(O)=O)C)CC1=CN=CN1 Chemical compound NC(N)=NCCC[C@@H](C(O)=O)NC(=O)CNC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CCC(O)=O)C)CC1=CN=CN1 LOJFGJZQOKTUBR-XAQOOIOESA-N 0.000 description 1
- 208000035327 Oestrogen receptor positive breast cancer Diseases 0.000 description 1
- BPQQTUXANYXVAA-UHFFFAOYSA-N Orthosilicate Chemical compound [O-][Si]([O-])([O-])[O-] BPQQTUXANYXVAA-UHFFFAOYSA-N 0.000 description 1
- 102000004067 Osteocalcin Human genes 0.000 description 1
- 108090000573 Osteocalcin Proteins 0.000 description 1
- 208000001164 Osteoporotic Fractures Diseases 0.000 description 1
- 108010046016 Peanut Agglutinin Proteins 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 235000009470 Theobroma cacao Nutrition 0.000 description 1
- 244000299461 Theobroma cacao Species 0.000 description 1
- HMNZFMSWFCAGGW-XPWSMXQVSA-N [3-[hydroxy(2-hydroxyethoxy)phosphoryl]oxy-2-[(e)-octadec-9-enoyl]oxypropyl] (e)-octadec-9-enoate Chemical compound CCCCCCCC\C=C\CCCCCCCC(=O)OCC(COP(O)(=O)OCCO)OC(=O)CCCCCCC\C=C\CCCCCCCC HMNZFMSWFCAGGW-XPWSMXQVSA-N 0.000 description 1
- AUYLVPGDOVEOML-UHFFFAOYSA-N [6-hydroxy-2-(4-hydroxyphenyl)-1-benzothiophen-3-yl]-[4-(piperidin-1-ylmethoxy)phenyl]methanone Chemical compound C1=CC(O)=CC=C1C1=C(C(=O)C=2C=CC(OCN3CCCCC3)=CC=2)C2=CC=C(O)C=C2S1 AUYLVPGDOVEOML-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 230000001270 agonistic effect Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 229910001514 alkali metal chloride Inorganic materials 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 229940046836 anti-estrogen Drugs 0.000 description 1
- 230000001833 anti-estrogenic effect Effects 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000008365 aqueous carrier Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 239000008135 aqueous vehicle Substances 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 238000005415 bioluminescence Methods 0.000 description 1
- 230000029918 bioluminescence Effects 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- XAAHAAMILDNBPS-UHFFFAOYSA-L calcium hydrogenphosphate dihydrate Chemical compound O.O.[Ca+2].OP([O-])([O-])=O XAAHAAMILDNBPS-UHFFFAOYSA-L 0.000 description 1
- PASHVRUKOFIRIK-UHFFFAOYSA-L calcium sulfate dihydrate Chemical compound O.O.[Ca+2].[O-]S([O-])(=O)=O PASHVRUKOFIRIK-UHFFFAOYSA-L 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 238000012761 co-transfection Methods 0.000 description 1
- 238000011278 co-treatment Methods 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 108010049937 collagen type I trimeric cross-linked peptide Proteins 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000012669 compression test Methods 0.000 description 1
- 230000001054 cortical effect Effects 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 238000009547 dual-energy X-ray absorptiometry Methods 0.000 description 1
- 239000008157 edible vegetable oil Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 201000006828 endometrial hyperplasia Diseases 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000009585 enzyme analysis Methods 0.000 description 1
- 239000000328 estrogen antagonist Substances 0.000 description 1
- 201000007281 estrogen-receptor positive breast cancer Diseases 0.000 description 1
- 230000001076 estrogenic effect Effects 0.000 description 1
- 229940012952 fibrinogen Drugs 0.000 description 1
- 230000020764 fibrinolysis Effects 0.000 description 1
- 239000000796 flavoring agent Substances 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
- 235000011187 glycerol Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 210000004349 growth plate Anatomy 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229940041476 lactose 100 mg Drugs 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 238000000504 luminescence detection Methods 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 230000009245 menopause Effects 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 239000002687 nonaqueous vehicle Substances 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 238000009806 oophorectomy Methods 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 230000011164 ossification Effects 0.000 description 1
- 210000002997 osteoclast Anatomy 0.000 description 1
- 230000000577 osteoprotective effect Effects 0.000 description 1
- 201000008968 osteosarcoma Diseases 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- 239000011505 plaster Substances 0.000 description 1
- 238000013001 point bending Methods 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 208000001685 postmenopausal osteoporosis Diseases 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 150000003856 quaternary ammonium compounds Chemical class 0.000 description 1
- 230000001850 reproductive effect Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000002207 retinal effect Effects 0.000 description 1
- 125000006413 ring segment Chemical group 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000005204 segregation Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 229940035044 sorbitan monolaurate Drugs 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 239000003270 steroid hormone Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 230000007306 turnover Effects 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 230000002485 urinary effect Effects 0.000 description 1
- 230000001836 utereotrophic 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
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
- A61K31/138—Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine
-
- 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
- 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
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
- A61P5/30—Oestrogens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Physical Education & Sports Medicine (AREA)
- Rheumatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Diabetes (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Endocrinology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pyrrole Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Saccharide Compounds (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US2543996P | 1996-09-06 | 1996-09-06 | |
| US60/025,439 | 1996-09-06 | ||
| US5066697P | 1997-06-24 | 1997-06-24 | |
| US60/050,666 | 1997-06-24 | ||
| PCT/US1997/015474 WO1998009519A1 (en) | 1996-09-06 | 1997-09-03 | Method of treating post menopausal diseases, including osteoporosis |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JP2002515046A true JP2002515046A (ja) | 2002-05-21 |
Family
ID=26699738
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP51283798A Pending JP2002515046A (ja) | 1996-09-06 | 1997-09-03 | 骨粗鬆症を含む閉経後疾患を治療する方法 |
| JP51283898A Pending JP2002515047A (ja) | 1996-09-06 | 1997-09-03 | 新規方法 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP51283898A Pending JP2002515047A (ja) | 1996-09-06 | 1997-09-03 | 新規方法 |
Country Status (16)
| Country | Link |
|---|---|
| EP (2) | EP0927029A4 (zh) |
| JP (2) | JP2002515046A (zh) |
| KR (2) | KR20000068473A (zh) |
| CN (2) | CN1236313A (zh) |
| AR (1) | AR008155A1 (zh) |
| AU (2) | AU4409797A (zh) |
| BR (2) | BR9711676A (zh) |
| CA (2) | CA2264943A1 (zh) |
| CO (2) | CO5070658A1 (zh) |
| CZ (1) | CZ76699A3 (zh) |
| IL (1) | IL128645A0 (zh) |
| NO (2) | NO991097D0 (zh) |
| PL (2) | PL332278A1 (zh) |
| TR (2) | TR199900506T2 (zh) |
| TW (1) | TW411273B (zh) |
| WO (2) | WO1998009619A1 (zh) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU5749998A (en) * | 1997-02-11 | 1998-08-26 | Novo Nordisk A/S | Methods for treatment or prophylaxis of menopausal symptoms |
| GB9827121D0 (en) * | 1998-12-09 | 1999-02-03 | Orion Corp | Agent for lowering endothelin levels |
| DE19905961A1 (de) * | 1999-02-12 | 2000-08-17 | Stefan Neubauer | Verwendung von Östrogenen zur Behandlung der Herzinsuffizienz |
| US6528681B2 (en) * | 2000-04-05 | 2003-03-04 | Bristol-Meyers Squibb Pharma Company | Halogenated triphenylethylene derivatives as selective estrogen receptor modulators |
| TWI303990B (en) | 2000-10-17 | 2008-12-11 | Pfizer Prod Inc | New use of estrogen agonists/antagonists for improving vascular health |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2196003A (en) * | 1986-09-11 | 1988-04-20 | Nat Res Dev | Iodo-and bromo-tamoxifen derivatives |
| ES2112994T3 (es) * | 1992-09-15 | 1998-04-16 | Merrell Pharma Inc | Analogos de clomifeno no metabolizables utilizados en el tratamiento de tumores resistentes al tamoxifeno. |
| US6197789B1 (en) * | 1995-06-07 | 2001-03-06 | Neorx Corporation | Prevention and treatment of cardiovascular pathologies with tamoxifen analogues |
| US5681835A (en) * | 1994-04-25 | 1997-10-28 | Glaxo Wellcome Inc. | Non-steroidal ligands for the estrogen receptor |
| US5604248A (en) * | 1994-05-05 | 1997-02-18 | Eli Lilly And Company | Method for minimizing the uterotrophic effect of tamoxifen and tamoxifen analogs |
| US5470883A (en) * | 1994-05-23 | 1995-11-28 | Stromberg; Brent V. | Method of treating peripheral vasoconstriction with tamoxifen citrate |
| HN1996000101A (es) * | 1996-02-28 | 1997-06-26 | Inc Pfizer | Terapia combinada para la osteoporosis |
| US6069175A (en) * | 1996-11-15 | 2000-05-30 | Pfizer Inc. | Estrogen agonist/antagonists treatment of atherosclerosis |
-
1997
- 1997-08-29 AR ARP970103968A patent/AR008155A1/es unknown
- 1997-09-03 KR KR1019997001861A patent/KR20000068473A/ko not_active Application Discontinuation
- 1997-09-03 BR BR9711676A patent/BR9711676A/pt not_active Application Discontinuation
- 1997-09-03 TR TR1999/00506T patent/TR199900506T2/xx unknown
- 1997-09-03 WO PCT/US1997/015475 patent/WO1998009619A1/en not_active Application Discontinuation
- 1997-09-03 PL PL97332278A patent/PL332278A1/xx unknown
- 1997-09-03 AU AU44097/97A patent/AU4409797A/en not_active Abandoned
- 1997-09-03 JP JP51283798A patent/JP2002515046A/ja active Pending
- 1997-09-03 EP EP97942388A patent/EP0927029A4/en not_active Withdrawn
- 1997-09-03 WO PCT/US1997/015474 patent/WO1998009519A1/en not_active Application Discontinuation
- 1997-09-03 TR TR1999/00504T patent/TR199900504T2/xx unknown
- 1997-09-03 PL PL97332038A patent/PL332038A1/xx unknown
- 1997-09-03 CN CN97199493A patent/CN1236313A/zh active Pending
- 1997-09-03 JP JP51283898A patent/JP2002515047A/ja active Pending
- 1997-09-03 CA CA002264943A patent/CA2264943A1/en not_active Abandoned
- 1997-09-03 CA CA002264775A patent/CA2264775A1/en not_active Abandoned
- 1997-09-03 BR BR9711681A patent/BR9711681A/pt not_active Application Discontinuation
- 1997-09-03 CZ CZ99766A patent/CZ76699A3/cs unknown
- 1997-09-03 CN CN97199492A patent/CN1236299A/zh active Pending
- 1997-09-03 IL IL12864597A patent/IL128645A0/xx unknown
- 1997-09-03 KR KR1019997001860A patent/KR20000068472A/ko not_active Application Discontinuation
- 1997-09-03 AU AU42473/97A patent/AU4247397A/en not_active Abandoned
- 1997-09-03 EP EP97940773A patent/EP0929216A4/en not_active Withdrawn
- 1997-09-04 CO CO97051289A patent/CO5070658A1/es unknown
- 1997-09-04 CO CO97051287A patent/CO4920218A1/es unknown
- 1997-12-11 TW TW086112930A patent/TW411273B/zh active
-
1999
- 1999-03-05 NO NO991097A patent/NO991097D0/no not_active Application Discontinuation
- 1999-03-05 NO NO991096A patent/NO991096L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| TW411273B (en) | 2000-11-11 |
| WO1998009619A1 (en) | 1998-03-12 |
| AR008155A1 (es) | 1999-12-09 |
| PL332278A1 (en) | 1999-08-30 |
| JP2002515047A (ja) | 2002-05-21 |
| TR199900504T2 (xx) | 1999-06-21 |
| WO1998009519A1 (en) | 1998-03-12 |
| KR20000068473A (ko) | 2000-11-25 |
| CO4920218A1 (es) | 2000-05-29 |
| CO5070658A1 (es) | 2001-08-28 |
| NO991097L (no) | 1999-03-05 |
| CN1236299A (zh) | 1999-11-24 |
| NO991097D0 (no) | 1999-03-05 |
| AU4247397A (en) | 1998-03-26 |
| NO991096D0 (no) | 1999-03-05 |
| BR9711676A (pt) | 1999-08-24 |
| EP0927029A4 (en) | 2001-06-13 |
| NO991096L (no) | 1999-03-05 |
| CA2264943A1 (en) | 1998-03-12 |
| EP0929216A4 (en) | 2001-04-04 |
| CN1236313A (zh) | 1999-11-24 |
| EP0927029A1 (en) | 1999-07-07 |
| EP0929216A1 (en) | 1999-07-21 |
| CZ76699A3 (cs) | 1999-08-11 |
| CA2264775A1 (en) | 1998-03-12 |
| IL128645A0 (en) | 2000-01-31 |
| PL332038A1 (en) | 1999-08-16 |
| AU4409797A (en) | 1998-03-26 |
| BR9711681A (pt) | 1999-08-24 |
| KR20000068472A (ko) | 2000-11-25 |
| TR199900506T2 (xx) | 1999-07-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR101141763B1 (ko) | 체중 증가의 치료 및/또는 억제에 사용하는 약학 조성물 | |
| KR0161300B1 (ko) | 뼈 손실 예방에 유용한 벤조티오펜 | |
| Evans et al. | Raloxifene inhibits bone turnover and prevents further cancellous bone loss in adult ovariectomized rats with established osteopenia | |
| RU2132682C1 (ru) | Применение антиэстрогенных соединений, а также фармацевтически приемлемых солей и сольватов для уменьшения концентрации глюкозы в крови и фармацевтический препарат | |
| JPH06234632A (ja) | ベンゾチオフェン類を含有する医薬組成物 | |
| KR20000023633A (ko) | 배합된 약제학적 에스트로겐-안드로겐-프로제스틴 경구 피임약 | |
| HOL et al. | Selective estrogen receptor modulators and postmenopausal women's health | |
| HUT72638A (en) | Pharmaceutical compositions containing benzotiophene derivative for inhibiting bone loss and for lowering serum cholesterol and process for its preparation | |
| JP2001515038A (ja) | エストロゲン依存性疾患および障害の予防または治療方法 | |
| AU2003210757B2 (en) | Method of hormonal therapy | |
| JPH07304661A (ja) | １，１，２−トリフェニルブタ−１−エン誘導体類を使用する子宮内膜炎及び子宮類線維腫疾患の抑制法 | |
| Legha et al. | Nafoxidine–‐an antiestrogen for the treatment of breast cancer | |
| JPH07196500A (ja) | 閉経期後症候群に関連する血管運動症状および併発性心理的障害を抑制するための医薬組成物 | |
| JP2002515484A (ja) | ２−フェニルインドール化合物およびエストロゲン製剤からなる組成物 | |
| Palacios | The future of the new selective estrogen receptor modulators | |
| RU2320339C2 (ru) | Применение анастрозола для лечения женщин в постклимактерическом периоде, которые страдают ранним раком молочной железы | |
| CZ382997A3 (cs) | Použití sloučenin k přípravě farmaceutického prostředku pro minimalizaci účinku ztráty kostní hmoty a farmaceutický prostředek s obsahem těchto sloučenin | |
| JP2002515046A (ja) | 骨粗鬆症を含む閉経後疾患を治療する方法 | |
| Stovall et al. | Tissue-selective estrogen complex bazedoxifene and conjugated estrogens for the treatment of menopausal vasomotor symptoms | |
| JPWO2004035089A1 (ja) | ホルモン依存性癌の治療剤 | |
| Fitzpatrick et al. | Gender-related differences in vascular smooth muscle cell proliferation: Implications for prevention of arteriosclerosis | |
| MXPA99002213A (en) | Method of treating post menopausal diseases, including osteoporosis | |
| Marín et al. | Clinical pharmacology of selective estrogen receptor modulators (SERMs) | |
| CA2223174A1 (en) | Methods for minimizing bone loss | |
| WO1999000019A1 (en) | Methods of treating the symptoms of atrophic vaginitis and altered sexual behavior in postmenopausal women |