CN1301160A - 用于治疗肌与骨骼脆弱的(选择性)雌激素受体调节剂(serm)和生长激素促分泌剂(ghs)的治疗用联合形式 - Google Patents
用于治疗肌与骨骼脆弱的(选择性)雌激素受体调节剂(serm)和生长激素促分泌剂(ghs)的治疗用联合形式 Download PDFInfo
- Publication number
- CN1301160A CN1301160A CN99806237A CN99806237A CN1301160A CN 1301160 A CN1301160 A CN 1301160A CN 99806237 A CN99806237 A CN 99806237A CN 99806237 A CN99806237 A CN 99806237A CN 1301160 A CN1301160 A CN 1301160A
- Authority
- CN
- China
- Prior art keywords
- chemical compound
- phenyl
- oxo
- bone
- ethyoxyl
- 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
- 208000036119 Frailty Diseases 0.000 title abstract 3
- 206010003549 asthenia Diseases 0.000 title abstract 3
- 230000001225 therapeutic effect Effects 0.000 title description 10
- 229940095743 selective estrogen receptor modulator Drugs 0.000 title description 8
- 239000000333 selective estrogen receptor modulator Substances 0.000 title description 8
- 239000003324 growth hormone secretagogue Substances 0.000 title 2
- 239000002834 estrogen receptor modulator Substances 0.000 title 1
- 238000000034 method Methods 0.000 claims abstract description 66
- 210000000988 bone and bone Anatomy 0.000 claims abstract description 62
- 150000003839 salts Chemical class 0.000 claims abstract description 38
- 208000001132 Osteoporosis Diseases 0.000 claims abstract description 20
- 239000000203 mixture Substances 0.000 claims abstract description 15
- 210000003205 muscle Anatomy 0.000 claims abstract description 13
- 150000001875 compounds Chemical class 0.000 claims description 72
- 239000003814 drug Substances 0.000 claims description 33
- 229910052739 hydrogen Inorganic materials 0.000 claims description 30
- 239000001257 hydrogen Substances 0.000 claims description 30
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 30
- 229940047889 isobutyramide Drugs 0.000 claims description 27
- 241000124008 Mammalia Species 0.000 claims description 22
- 239000008194 pharmaceutical composition Substances 0.000 claims description 18
- 206010065687 Bone loss Diseases 0.000 claims description 10
- 239000002552 dosage form Substances 0.000 claims description 9
- FEWJPZIEWOKRBE-LWMBPPNESA-L D-tartrate(2-) Chemical compound [O-]C(=O)[C@@H](O)[C@H](O)C([O-])=O FEWJPZIEWOKRBE-LWMBPPNESA-L 0.000 claims description 8
- FEWJPZIEWOKRBE-JCYAYHJZSA-L L-tartrate(2-) Chemical compound [O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O FEWJPZIEWOKRBE-JCYAYHJZSA-L 0.000 claims description 7
- 238000002360 preparation method Methods 0.000 claims description 7
- 239000003085 diluting agent Substances 0.000 claims description 5
- 230000035876 healing Effects 0.000 claims description 5
- 238000009940 knitting Methods 0.000 claims description 5
- 201000001245 periodontitis Diseases 0.000 claims description 5
- 230000002708 enhancing effect Effects 0.000 claims description 4
- 230000012010 growth Effects 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 2
- 208000001164 Osteoporotic Fractures Diseases 0.000 abstract description 4
- KVLLHLWBPNCVNR-SKCUWOTOSA-N capromorelin Chemical compound C([C@@]12CN(CCC1=NN(C2=O)C)C(=O)[C@@H](COCC=1C=CC=CC=1)NC(=O)C(C)(C)N)C1=CC=CC=C1 KVLLHLWBPNCVNR-SKCUWOTOSA-N 0.000 abstract 1
- GXESHMAMLJKROZ-IAPPQJPRSA-N lasofoxifene Chemical compound C1([C@@H]2[C@@H](C3=CC=C(C=C3CC2)O)C=2C=CC(OCCN3CCCC3)=CC=2)=CC=CC=C1 GXESHMAMLJKROZ-IAPPQJPRSA-N 0.000 abstract 1
- 102000018997 Growth Hormone Human genes 0.000 description 33
- 108010051696 Growth Hormone Proteins 0.000 description 33
- 239000000122 growth hormone Substances 0.000 description 33
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 21
- 201000010099 disease Diseases 0.000 description 20
- 241000700159 Rattus Species 0.000 description 18
- 239000003826 tablet Substances 0.000 description 14
- 230000000694 effects Effects 0.000 description 13
- 208000010392 Bone Fractures Diseases 0.000 description 11
- 239000002775 capsule Substances 0.000 description 11
- 239000000262 estrogen Substances 0.000 description 11
- 206010017076 Fracture Diseases 0.000 description 10
- 230000037396 body weight Effects 0.000 description 10
- 229940011871 estrogen Drugs 0.000 description 10
- WFKAJVHLWXSISD-UHFFFAOYSA-N isobutyramide Chemical compound CC(C)C(N)=O WFKAJVHLWXSISD-UHFFFAOYSA-N 0.000 description 10
- 230000001009 osteoporotic effect Effects 0.000 description 10
- 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 9
- 230000003203 everyday effect Effects 0.000 description 8
- 210000000689 upper leg Anatomy 0.000 description 8
- -1 vassopressin Chemical compound 0.000 description 8
- 206010062767 Hypophysitis Diseases 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 230000036541 health Effects 0.000 description 6
- 230000001965 increasing effect Effects 0.000 description 6
- 238000011889 obduction Methods 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 5
- 230000008859 change Effects 0.000 description 5
- 210000002468 fat body Anatomy 0.000 description 5
- 229910052500 inorganic mineral Inorganic materials 0.000 description 5
- 239000011707 mineral Substances 0.000 description 5
- 230000002265 prevention Effects 0.000 description 5
- 230000028327 secretion Effects 0.000 description 5
- 230000008901 benefit Effects 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 229920003023 plastic Polymers 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- 238000012546 transfer Methods 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 206010020100 Hip fracture Diseases 0.000 description 3
- 230000002411 adverse Effects 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 230000037182 bone density Effects 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 239000000890 drug combination Substances 0.000 description 3
- 239000011888 foil Substances 0.000 description 3
- 150000002632 lipids Chemical class 0.000 description 3
- 238000012423 maintenance Methods 0.000 description 3
- 230000004060 metabolic process Effects 0.000 description 3
- 239000004033 plastic Substances 0.000 description 3
- 229960004622 raloxifene Drugs 0.000 description 3
- 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 3
- 230000009467 reduction Effects 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 2
- 206010006187 Breast cancer Diseases 0.000 description 2
- 208000026310 Breast neoplasm Diseases 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 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 2
- 206010014759 Endometrial neoplasm Diseases 0.000 description 2
- 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 2
- 102000015779 HDL Lipoproteins Human genes 0.000 description 2
- 108010010234 HDL Lipoproteins Proteins 0.000 description 2
- WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 description 2
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound 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 2
- 239000000556 agonist Substances 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 201000008275 breast carcinoma Diseases 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 229950004203 droloxifene Drugs 0.000 description 2
- 201000003914 endometrial carcinoma Diseases 0.000 description 2
- 210000003016 hypothalamus Anatomy 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 238000011835 investigation Methods 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 230000008520 organization Effects 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 229940077150 progesterone and estrogen Drugs 0.000 description 2
- 239000003488 releasing hormone Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 210000004291 uterus Anatomy 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- ZEMPKEQAKRGZGQ-AAKVHIHISA-N 2,3-bis[[(z)-12-hydroxyoctadec-9-enoyl]oxy]propyl (z)-12-hydroxyoctadec-9-enoate Chemical compound CCCCCCC(O)C\C=C/CCCCCCCC(=O)OCC(OC(=O)CCCCCCC\C=C/CC(O)CCCCCC)COC(=O)CCCCCCC\C=C/CC(O)CCCCCC ZEMPKEQAKRGZGQ-AAKVHIHISA-N 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 229940122361 Bisphosphonate Drugs 0.000 description 1
- 208000020084 Bone disease Diseases 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 208000010859 Creutzfeldt-Jakob disease Diseases 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 102000051325 Glucagon Human genes 0.000 description 1
- 108060003199 Glucagon 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
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 239000004705 High-molecular-weight polyethylene Substances 0.000 description 1
- 208000013016 Hypoglycemia Diseases 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 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
- 238000008214 LDL Cholesterol Methods 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
- 240000003183 Manihot esculenta Species 0.000 description 1
- 235000016735 Manihot esculenta subsp esculenta Nutrition 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- BPQQTUXANYXVAA-UHFFFAOYSA-N Orthosilicate Chemical compound [O-][Si]([O-])([O-])[O-] BPQQTUXANYXVAA-UHFFFAOYSA-N 0.000 description 1
- 102000003982 Parathyroid hormone Human genes 0.000 description 1
- 108090000445 Parathyroid hormone Proteins 0.000 description 1
- IIDJRNMFWXDHID-UHFFFAOYSA-N Risedronic acid Chemical compound OP(=O)(O)C(P(O)(O)=O)(O)CC1=CC=CN=C1 IIDJRNMFWXDHID-UHFFFAOYSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 239000004141 Sodium laurylsulphate Substances 0.000 description 1
- 102000005157 Somatostatin Human genes 0.000 description 1
- 108010056088 Somatostatin Proteins 0.000 description 1
- 229920002472 Starch Polymers 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
- 239000002250 absorbent Substances 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000001785 acacia senegal l. willd gum Substances 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 210000000577 adipose tissue Anatomy 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 239000008135 aqueous vehicle Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 230000003542 behavioural effect Effects 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 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
- 239000011230 binding agent Substances 0.000 description 1
- 150000004663 bisphosphonates Chemical class 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- DEGAKNSWVGKMLS-UHFFFAOYSA-N calcein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC(CN(CC(O)=O)CC(O)=O)=C(O)C=C1OC1=C2C=C(CN(CC(O)=O)CC(=O)O)C(O)=C1 DEGAKNSWVGKMLS-UHFFFAOYSA-N 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 229910000019 calcium carbonate 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
- 201000011510 cancer Diseases 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 210000005056 cell body Anatomy 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000004737 colorimetric analysis Methods 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000002357 endometrial effect Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000000328 estrogen antagonist Substances 0.000 description 1
- 230000001076 estrogenic effect Effects 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 MASNOZXLGMXCHN-ZLPAWPGGSA-N 0.000 description 1
- 229960004666 glucagon Drugs 0.000 description 1
- 239000003862 glucocorticoid Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 210000001624 hip Anatomy 0.000 description 1
- 230000002218 hypoglycaemic effect Effects 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 229960003299 ketamine Drugs 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 210000002414 leg Anatomy 0.000 description 1
- 210000000088 lip Anatomy 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000004973 liquid crystal related substance Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 230000007257 malfunction Effects 0.000 description 1
- 230000009245 menopause Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000002107 myocardial effect Effects 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 238000010606 normalization Methods 0.000 description 1
- 229960002378 oftasceine Drugs 0.000 description 1
- 238000009806 oophorectomy Methods 0.000 description 1
- 230000011164 ossification Effects 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 238000012858 packaging process Methods 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 239000000199 parathyroid hormone Substances 0.000 description 1
- 229960001319 parathyroid hormone Drugs 0.000 description 1
- 239000003182 parenteral nutrition solution Substances 0.000 description 1
- 230000003239 periodontal effect Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 230000007180 physiological regulation Effects 0.000 description 1
- 239000000902 placebo Substances 0.000 description 1
- 229940068196 placebo Drugs 0.000 description 1
- 206010036067 polydipsia Diseases 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 208000001685 postmenopausal osteoporosis Diseases 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 239000000186 progesterone Substances 0.000 description 1
- 229960003387 progesterone Drugs 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 230000010349 pulsation Effects 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
- 238000011084 recovery Methods 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- 230000008521 reorganization Effects 0.000 description 1
- 229940089617 risedronate Drugs 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 210000000582 semen Anatomy 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 230000000391 smoking effect Effects 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- NHXLMOGPVYXJNR-ATOGVRKGSA-N somatostatin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CSSC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N1)[C@@H](C)O)NC(=O)CNC(=O)[C@H](C)N)C(O)=O)=O)[C@H](O)C)C1=CC=CC=C1 NHXLMOGPVYXJNR-ATOGVRKGSA-N 0.000 description 1
- 229960000553 somatostatin Drugs 0.000 description 1
- 210000001875 somatotroph Anatomy 0.000 description 1
- 206010041569 spinal fracture Diseases 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 230000008467 tissue growth Effects 0.000 description 1
- 239000006211 transdermal dosage form Substances 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
- 208000012991 uterine carcinoma Diseases 0.000 description 1
- 238000005303 weighing Methods 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
- A61K31/33—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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Physical Education & Sports Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Rheumatology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US8946998P | 1998-06-16 | 1998-06-16 | |
US60/089,469 | 1998-06-16 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN1301160A true CN1301160A (zh) | 2001-06-27 |
Family
ID=22217825
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN99806237A Pending CN1301160A (zh) | 1998-06-16 | 1999-06-16 | 用于治疗肌与骨骼脆弱的(选择性)雌激素受体调节剂(serm)和生长激素促分泌剂(ghs)的治疗用联合形式 |
Country Status (30)
Country | Link |
---|---|
EP (1) | EP1087764A1 (sk) |
JP (1) | JP2002518326A (sk) |
KR (1) | KR20010052852A (sk) |
CN (1) | CN1301160A (sk) |
AP (1) | AP9901582A0 (sk) |
AR (1) | AR018869A1 (sk) |
AU (1) | AU4054799A (sk) |
BG (1) | BG105041A (sk) |
BR (1) | BR9911324A (sk) |
CA (1) | CA2335134A1 (sk) |
CO (1) | CO5070587A1 (sk) |
EA (1) | EA200001186A1 (sk) |
GT (1) | GT199900087A (sk) |
HN (1) | HN1999000097A (sk) |
HR (1) | HRP20000859A2 (sk) |
HU (1) | HUP0102505A3 (sk) |
ID (1) | ID27599A (sk) |
IL (1) | IL138630A0 (sk) |
IS (1) | IS5691A (sk) |
MA (1) | MA26652A1 (sk) |
NO (1) | NO20006312L (sk) |
OA (1) | OA11505A (sk) |
PA (1) | PA8475901A1 (sk) |
PE (1) | PE20000646A1 (sk) |
PL (1) | PL344981A1 (sk) |
SK (1) | SK18912000A3 (sk) |
TN (1) | TNSN99124A1 (sk) |
TR (1) | TR200003544T2 (sk) |
WO (1) | WO1999065486A1 (sk) |
ZA (1) | ZA993975B (sk) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101111512B (zh) * | 2004-06-18 | 2013-05-01 | 特兰齐姆制药公司 | 生长素释放肽受体的大环调节剂 |
Families Citing this family (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2360103A1 (en) * | 1999-02-08 | 2000-08-17 | Robert Sladek | Non-human transgenic animal whose germ cells and somatic cells contain a knockout mutation in dna encoding orphan nuclear receptor erralpha |
ATE346159T1 (de) | 2000-05-08 | 2006-12-15 | Pfizer Prod Inc | Enzymatische spaltung von selektiven modulatoren des östrogenrezeptors |
AU2001276608A1 (en) | 2000-08-30 | 2002-03-13 | Pfizer Products Inc. | Sustained release formulations for growth hormone secretagogues |
IL145106A0 (en) * | 2000-08-30 | 2002-06-30 | Pfizer Prod Inc | Intermittent administration of a geowth hormone secretagogue |
WO2006024931A2 (en) * | 2004-08-31 | 2006-03-09 | Pfizer Products Inc. | Therapeutic combinations comprising a selective estrogen receptor modulator and a selective androgen receptor modulator |
CU23558A1 (es) | 2006-02-28 | 2010-07-20 | Ct Ingenieria Genetica Biotech | Compuestos análogos a los secretagogos peptidicos de la hormona de crecimiento |
BRPI0807046A2 (pt) | 2007-02-09 | 2015-05-26 | Tranzyme Pharma Inc | Composto, composição farmacêutica, métodos de tratar um distúrbio, uma doença cardiovascular e um paciente que sofre de motilidade gastrointestinal reduzida ou disfuncional e, kit. |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
UA51676C2 (uk) * | 1995-11-02 | 2002-12-16 | Пфайзер Інк. | (-)цис-6(s)-феніл-5(r)[4-(2-піролідин-1-ілетокси)феніл]-5,6,7,8-тетрагідронафталін-2-ол d-тартрат, спосіб його одержання, спосіб лікування захворювань, що піддаються лікуванню агоністами естрогену, та фармацевтична композиція |
TW432073B (en) * | 1995-12-28 | 2001-05-01 | Pfizer | Pyrazolopyridine compounds |
HN1996000101A (es) * | 1996-02-28 | 1997-06-26 | Inc Pfizer | Terapia combinada para la osteoporosis |
-
1999
- 1999-06-15 PA PA19998475901A patent/PA8475901A1/es unknown
- 1999-06-15 AR ARP990102848A patent/AR018869A1/es not_active Application Discontinuation
- 1999-06-15 HN HN1999000097A patent/HN1999000097A/es unknown
- 1999-06-15 PE PE1999000528A patent/PE20000646A1/es not_active Application Discontinuation
- 1999-06-15 AP APAP/P/1999/001582A patent/AP9901582A0/en unknown
- 1999-06-15 ZA ZA9903975A patent/ZA993975B/xx unknown
- 1999-06-16 HU HU0102505A patent/HUP0102505A3/hu unknown
- 1999-06-16 GT GT199900087A patent/GT199900087A/es unknown
- 1999-06-16 KR KR1020007014186A patent/KR20010052852A/ko not_active Application Discontinuation
- 1999-06-16 EA EA200001186A patent/EA200001186A1/ru unknown
- 1999-06-16 PL PL99344981A patent/PL344981A1/xx not_active Application Discontinuation
- 1999-06-16 MA MA25628A patent/MA26652A1/fr unknown
- 1999-06-16 SK SK1891-2000A patent/SK18912000A3/sk unknown
- 1999-06-16 ID IDW20002627A patent/ID27599A/id unknown
- 1999-06-16 WO PCT/IB1999/001117 patent/WO1999065486A1/en not_active Application Discontinuation
- 1999-06-16 AU AU40547/99A patent/AU4054799A/en not_active Abandoned
- 1999-06-16 IL IL13863099A patent/IL138630A0/xx unknown
- 1999-06-16 CO CO99037622A patent/CO5070587A1/es unknown
- 1999-06-16 CN CN99806237A patent/CN1301160A/zh active Pending
- 1999-06-16 BR BR9911324-4A patent/BR9911324A/pt not_active Application Discontinuation
- 1999-06-16 EP EP99923802A patent/EP1087764A1/en not_active Withdrawn
- 1999-06-16 TN TNTNSN99124A patent/TNSN99124A1/fr unknown
- 1999-06-16 JP JP2000554366A patent/JP2002518326A/ja active Pending
- 1999-06-16 CA CA002335134A patent/CA2335134A1/en not_active Abandoned
- 1999-06-16 TR TR2000/03544T patent/TR200003544T2/xx unknown
-
2000
- 2000-10-20 OA OA1200000290A patent/OA11505A/en unknown
- 2000-10-27 IS IS5691A patent/IS5691A/is unknown
- 2000-12-11 BG BG105041A patent/BG105041A/xx unknown
- 2000-12-12 NO NO20006312A patent/NO20006312L/no not_active Application Discontinuation
- 2000-12-14 HR HR20000859A patent/HRP20000859A2/hr not_active Application Discontinuation
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101111512B (zh) * | 2004-06-18 | 2013-05-01 | 特兰齐姆制药公司 | 生长素释放肽受体的大环调节剂 |
Also Published As
Publication number | Publication date |
---|---|
AR018869A1 (es) | 2001-12-12 |
HUP0102505A2 (hu) | 2001-11-28 |
IL138630A0 (en) | 2001-10-31 |
OA11505A (en) | 2004-05-07 |
NO20006312D0 (no) | 2000-12-12 |
ID27599A (id) | 2001-04-12 |
ZA993975B (en) | 2000-12-15 |
HRP20000859A2 (en) | 2001-04-30 |
HN1999000097A (es) | 1999-11-03 |
AU4054799A (en) | 2000-01-05 |
AP9901582A0 (en) | 1999-06-30 |
TR200003544T2 (tr) | 2001-04-20 |
SK18912000A3 (sk) | 2001-10-08 |
PE20000646A1 (es) | 2000-08-05 |
JP2002518326A (ja) | 2002-06-25 |
HUP0102505A3 (en) | 2002-12-28 |
BR9911324A (pt) | 2001-04-03 |
GT199900087A (es) | 2000-12-07 |
BG105041A (en) | 2001-08-31 |
MA26652A1 (fr) | 2004-12-20 |
WO1999065486A1 (en) | 1999-12-23 |
TNSN99124A1 (fr) | 2005-11-10 |
PA8475901A1 (es) | 2000-05-24 |
CO5070587A1 (es) | 2001-08-28 |
KR20010052852A (ko) | 2001-06-25 |
EA200001186A1 (ru) | 2001-06-25 |
PL344981A1 (en) | 2001-11-19 |
NO20006312L (no) | 2000-12-12 |
IS5691A (is) | 2000-10-27 |
CA2335134A1 (en) | 1999-12-23 |
EP1087764A1 (en) | 2001-04-04 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Eastell | Treatment of postmenopausal osteoporosis | |
CN1240387C (zh) | 含有叶酸的药用组合物及其用途和给药系统 | |
CN102133395B (zh) | 骨骼保健物或药物组合物及其应用 | |
JP2007504182A (ja) | 骨の治癒を促進するための組成物および方法 | |
US20040152713A1 (en) | Methods for treating joint pain or improving sleep using an estrogen agonist/antagonist | |
EP0747054B1 (en) | Methods for minimizing bone loss | |
CN1301160A (zh) | 用于治疗肌与骨骼脆弱的(选择性)雌激素受体调节剂(serm)和生长激素促分泌剂(ghs)的治疗用联合形式 | |
CN1305373A (zh) | 含有选择性雌激素受体调节剂和甲状旁腺激素的治疗组合物 | |
Hasling et al. | A comparison of the effects of oestrogen/progestogen, high-dose oral calcium, intermittent cyclic etidronate and an ADFR regime on calcium kinetics and bone mass in postmenopausal women with spinal osteoporosis | |
CN1305378A (zh) | 治疗肌与骨骼的脆性的(选择性)雌激素受体调节剂(serm)和生长激素促分泌素(ghs)的药物组合物 | |
CN102626420B (zh) | 一种含有锶、钙和维生素d的混合制剂 | |
JPH10506638A (ja) | アレンドロネート又はその塩の投与による歯喪失の予防 | |
EP0966968B1 (en) | Therapeutic combinations comprising a selective estrogen receptor modulator and prostaglandin E2 | |
HUT76855A (en) | Use of benzotiophene derivatives for production pharmaceutical compositions useful for bone healing and fracture repair | |
CN1759851A (zh) | 补钙制剂及制备方法 | |
TW201105333A (en) | Agent for preventing non-traumatic vertebral fracture in severe osteoporosis patients which comprises eldecalcitol | |
CZ20004679A3 (cs) | Terapeutické kombinace (selektivních) modulátorů estrogenního receptoru (ŠERM) a prostředků podporujících sekreci růstového hormonu (GHS) pro léčbu muskuloskeletární fragility | |
MXPA99005564A (en) | Therapeutic combinations comprising a selective estrogen receptor modulator and prostaglandin e2 | |
MXPA00012728A (en) | Therapeutic combinations comprising a selective estrogen receptor modulator and parathyroid hormone | |
MXPA00012727A (en) | Therapeutic combinations of (selective) estrogen receptor modulators (serm) and growth hormone secretagogues (ghs) for treating musculoskeletal frailty | |
CZ20004680A3 (cs) | Terapeutické kombinace (selektivních) modulátorů estrogenního receptorů (ŠERM) a prostředků podporujících sekreci růstového hormonu (GHS) pro léčbu muskuloskeletární fragility |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
WD01 | Invention patent application deemed withdrawn after publication | ||
REG | Reference to a national code |
Ref country code: HK Ref legal event code: WD Ref document number: 1036414 Country of ref document: HK |