DE3247836C2 - - Google Patents
Info
- Publication number
- DE3247836C2 DE3247836C2 DE3247836A DE3247836A DE3247836C2 DE 3247836 C2 DE3247836 C2 DE 3247836C2 DE 3247836 A DE3247836 A DE 3247836A DE 3247836 A DE3247836 A DE 3247836A DE 3247836 C2 DE3247836 C2 DE 3247836C2
- Authority
- DE
- Germany
- Prior art keywords
- lactone
- hydroxyvitamin
- dihydroxyvitamin
- vitamin
- serum
- 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.)
- Expired - Lifetime
Links
- 239000011575 calcium Substances 0.000 claims description 53
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 51
- 229910052791 calcium Inorganic materials 0.000 claims description 51
- 210000002966 serum Anatomy 0.000 claims description 42
- IJNDMZIDDKVXHR-MYEQSZOMSA-N 25-Hydroxyvitamin D3-26,23-lactone Chemical compound C([C@@H](C)[C@@H]1[C@]2(CCCC(/[C@@H]2CC1)=C\C=C/1C(CC[C@@H](O)C\1)=C)C)[C@@H]1C[C@@](C)(O)C(=O)O1 IJNDMZIDDKVXHR-MYEQSZOMSA-N 0.000 claims description 23
- 239000003814 drug Substances 0.000 claims description 19
- WMYIVSWWSRCZFA-RWVJFQLJSA-N 1,25-Dihydroxyvitamin D3-26,23-lactone Chemical compound C([C@@H](C)[C@@H]1[C@]2(CCCC(/[C@@H]2CC1)=C\C=C\1C([C@@H](O)C[C@H](O)C/1)=C)C)[C@H]1C[C@@](C)(O)C(=O)O1 WMYIVSWWSRCZFA-RWVJFQLJSA-N 0.000 claims description 15
- 241001465754 Metazoa Species 0.000 claims description 9
- 229940079593 drug Drugs 0.000 claims description 8
- 150000002596 lactones Chemical class 0.000 claims description 7
- 229940088594 vitamin Drugs 0.000 claims description 6
- 229930003231 vitamin Natural products 0.000 claims description 6
- 235000013343 vitamin Nutrition 0.000 claims description 6
- 239000011782 vitamin Substances 0.000 claims description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 241000700159 Rattus Species 0.000 description 26
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 description 19
- 235000005282 vitamin D3 Nutrition 0.000 description 15
- 239000011647 vitamin D3 Substances 0.000 description 15
- QYSXJUFSXHHAJI-YRZJJWOYSA-N vitamin D3 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C\C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-YRZJJWOYSA-N 0.000 description 15
- 229940021056 vitamin d3 Drugs 0.000 description 15
- GMRQFYUYWCNGIN-NKMMMXOESA-N calcitriol Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@@H](CCCC(C)(C)O)C)=C\C=C1\C[C@@H](O)C[C@H](O)C1=C GMRQFYUYWCNGIN-NKMMMXOESA-N 0.000 description 14
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 14
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 13
- 235000020964 calcitriol Nutrition 0.000 description 12
- 239000011612 calcitriol Substances 0.000 description 12
- 230000000968 intestinal effect Effects 0.000 description 12
- GMRQFYUYWCNGIN-UHFFFAOYSA-N 1,25-Dihydroxy-vitamin D3' Natural products C1CCC2(C)C(C(CCCC(C)(C)O)C)CCC2C1=CC=C1CC(O)CC(O)C1=C GMRQFYUYWCNGIN-UHFFFAOYSA-N 0.000 description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- 150000001875 compounds Chemical class 0.000 description 9
- 239000000203 mixture Substances 0.000 description 9
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
- 229920004890 Triton X-100 Polymers 0.000 description 8
- 239000013504 Triton X-100 Substances 0.000 description 8
- DBDDUVJJIVBQPI-WWBRWCDLSA-N 4-hydroxy-6-[2-[(4e)-4-[(2z)-2-(5-hydroxy-2-methylidenecyclohexylidene)ethylidene]-7a-methyl-2,3,3a,5,6,7-hexahydro-1h-inden-1-yl]propyl]-4-methyldioxan-3-one Chemical compound C1CC2\C(=C\C=C\3C(CCC(O)C/3)=C)CCCC2(C)C1C(C)CC1CC(C)(O)C(=O)OO1 DBDDUVJJIVBQPI-WWBRWCDLSA-N 0.000 description 7
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
- 238000004128 high performance liquid chromatography Methods 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- 229920005654 Sephadex Polymers 0.000 description 6
- 239000012507 Sephadex™ Substances 0.000 description 6
- OFHCOWSQAMBJIW-AVJTYSNKSA-N alfacalcidol Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C\C=C1\C[C@@H](O)C[C@H](O)C1=C OFHCOWSQAMBJIW-AVJTYSNKSA-N 0.000 description 6
- 210000004369 blood Anatomy 0.000 description 6
- 239000008280 blood Substances 0.000 description 6
- 239000002207 metabolite Substances 0.000 description 6
- -1 Aldehyde compound Chemical class 0.000 description 5
- 241000287828 Gallus gallus Species 0.000 description 5
- 208000037147 Hypercalcaemia Diseases 0.000 description 5
- 241000282887 Suidae Species 0.000 description 5
- 235000013330 chicken meat Nutrition 0.000 description 5
- 239000007903 gelatin capsule Substances 0.000 description 5
- 230000000148 hypercalcaemia Effects 0.000 description 5
- 208000030915 hypercalcemia disease Diseases 0.000 description 5
- JWUBBDSIWDLEOM-UHFFFAOYSA-N 25-Hydroxycholecalciferol Natural products C1CCC2(C)C(C(CCCC(C)(C)O)C)CCC2C1=CC=C1CC(O)CCC1=C JWUBBDSIWDLEOM-UHFFFAOYSA-N 0.000 description 4
- JWUBBDSIWDLEOM-DCHLRESJSA-N 25-Hydroxyvitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@@H](CCCC(C)(C)O)C)=C/C=C1\C[C@@H](O)CCC1=C JWUBBDSIWDLEOM-DCHLRESJSA-N 0.000 description 4
- JWUBBDSIWDLEOM-NQZHSCJISA-N 25-hydroxy-3 epi cholecalciferol Chemical compound C1([C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@@H](CCCC(C)(C)O)C)=CC=C1C[C@H](O)CCC1=C JWUBBDSIWDLEOM-NQZHSCJISA-N 0.000 description 4
- 241000282472 Canis lupus familiaris Species 0.000 description 4
- 229920000858 Cyclodextrin Polymers 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 229930003316 Vitamin D Natural products 0.000 description 4
- 238000010521 absorption reaction Methods 0.000 description 4
- 230000004071 biological effect Effects 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 230000007812 deficiency Effects 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000001990 intravenous administration Methods 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 230000000144 pharmacologic effect Effects 0.000 description 4
- 235000019166 vitamin D Nutrition 0.000 description 4
- 239000011710 vitamin D Substances 0.000 description 4
- 150000003710 vitamin D derivatives Chemical class 0.000 description 4
- 229940046008 vitamin d Drugs 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 238000004891 communication Methods 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- GDSRMADSINPKSL-HSEONFRVSA-N gamma-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO GDSRMADSINPKSL-HSEONFRVSA-N 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 238000007918 intramuscular administration Methods 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 210000002700 urine Anatomy 0.000 description 3
- 150000003722 vitamin derivatives Chemical class 0.000 description 3
- BJYLYJCXYAMOFT-RRXOBRNQSA-N (1r,3s,5z)-5-[(2e)-2-[(1r,3as,7ar)-1-[(2r)-5-hydroxy-6-methylheptan-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1h-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCC(O)C(C)C)=C\C=C1\C[C@@H](O)C[C@H](O)C1=C BJYLYJCXYAMOFT-RRXOBRNQSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- QIGBRXMKCJKVMJ-UHFFFAOYSA-N Hydroquinone Chemical compound OC1=CC=C(O)C=C1 QIGBRXMKCJKVMJ-UHFFFAOYSA-N 0.000 description 2
- 241000700157 Rattus norvegicus Species 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 210000000702 aorta abdominal Anatomy 0.000 description 2
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 description 2
- 229960004853 betadex Drugs 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 239000002026 chloroform extract Substances 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 230000037213 diet Effects 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- NUVBSKCKDOMJSU-UHFFFAOYSA-N ethylparaben Chemical compound CCOC(=O)C1=CC=C(O)C=C1 NUVBSKCKDOMJSU-UHFFFAOYSA-N 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 229940080345 gamma-cyclodextrin Drugs 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000004811 liquid chromatography Methods 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 238000001819 mass spectrum Methods 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 230000002110 toxicologic effect Effects 0.000 description 2
- 231100000027 toxicology Toxicity 0.000 description 2
- OILXMJHPFNGGTO-UHFFFAOYSA-N (22E)-(24xi)-24-methylcholesta-5,22-dien-3beta-ol Natural products C1C=C2CC(O)CCC2(C)C2C1C1CCC(C(C)C=CC(C)C(C)C)C1(C)CC2 OILXMJHPFNGGTO-UHFFFAOYSA-N 0.000 description 1
- RQOCXCFLRBRBCS-UHFFFAOYSA-N (22E)-cholesta-5,7,22-trien-3beta-ol Natural products C1C(O)CCC2(C)C(CCC3(C(C(C)C=CCC(C)C)CCC33)C)C3=CC=C21 RQOCXCFLRBRBCS-UHFFFAOYSA-N 0.000 description 1
- FCKJYANJHNLEEP-XRWYNYHCSA-N (24R)-24,25-dihydroxycalciol Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@@H](CC[C@@H](O)C(C)(C)O)C)=C\C=C1\C[C@@H](O)CCC1=C FCKJYANJHNLEEP-XRWYNYHCSA-N 0.000 description 1
- VILCJCGEZXAXTO-UHFFFAOYSA-N 2,2,2-tetramine Chemical compound NCCNCCNCCN VILCJCGEZXAXTO-UHFFFAOYSA-N 0.000 description 1
- CPBJMKMKNCRKQB-UHFFFAOYSA-N 3,3-bis(4-hydroxy-3-methylphenyl)-2-benzofuran-1-one Chemical compound C1=C(O)C(C)=CC(C2(C3=CC=CC=C3C(=O)O2)C=2C=C(C)C(O)=CC=2)=C1 CPBJMKMKNCRKQB-UHFFFAOYSA-N 0.000 description 1
- OQMZNAMGEHIHNN-UHFFFAOYSA-N 7-Dehydrostigmasterol Natural products C1C(O)CCC2(C)C(CCC3(C(C(C)C=CC(CC)C(C)C)CCC33)C)C3=CC=C21 OQMZNAMGEHIHNN-UHFFFAOYSA-N 0.000 description 1
- 241000251468 Actinopterygii Species 0.000 description 1
- 235000019489 Almond oil Nutrition 0.000 description 1
- 229920001450 Alpha-Cyclodextrin Polymers 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
- 244000144725 Amygdalus communis Species 0.000 description 1
- 208000009137 Behcet syndrome Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 239000004255 Butylated hydroxyanisole Substances 0.000 description 1
- 102000055006 Calcitonin Human genes 0.000 description 1
- 108060001064 Calcitonin Proteins 0.000 description 1
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 244000060011 Cocos nucifera Species 0.000 description 1
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical class [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- DNVPQKQSNYMLRS-NXVQYWJNSA-N Ergosterol Natural products CC(C)[C@@H](C)C=C[C@H](C)[C@H]1CC[C@H]2C3=CC=C4C[C@@H](O)CC[C@]4(C)[C@@H]3CC[C@]12C DNVPQKQSNYMLRS-NXVQYWJNSA-N 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 239000004606 Fillers/Extenders Substances 0.000 description 1
- 238000001157 Fourier transform infrared spectrum Methods 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 201000002980 Hyperparathyroidism Diseases 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
- 240000007817 Olea europaea Species 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 206010047626 Vitamin D Deficiency Diseases 0.000 description 1
- MECHNRXZTMCUDQ-UHFFFAOYSA-N Vitamin D2 Natural products C1CCC2(C)C(C(C)C=CC(C)C(C)C)CCC2C1=CC=C1CC(O)CCC1=C MECHNRXZTMCUDQ-UHFFFAOYSA-N 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 238000000862 absorption spectrum Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 229960002535 alfacalcidol Drugs 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 239000008168 almond oil Substances 0.000 description 1
- HFHDHCJBZVLPGP-RWMJIURBSA-N alpha-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO HFHDHCJBZVLPGP-RWMJIURBSA-N 0.000 description 1
- 229940043377 alpha-cyclodextrin Drugs 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 230000027455 binding Effects 0.000 description 1
- 238000009739 binding Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 239000006189 buccal tablet Substances 0.000 description 1
- 235000019282 butylated hydroxyanisole Nutrition 0.000 description 1
- CZBZUDVBLSSABA-UHFFFAOYSA-N butylated hydroxyanisole Chemical compound COC1=CC=C(O)C(C(C)(C)C)=C1.COC1=CC=C(O)C=C1C(C)(C)C CZBZUDVBLSSABA-UHFFFAOYSA-N 0.000 description 1
- 229940043253 butylated hydroxyanisole Drugs 0.000 description 1
- BBBFJLBPOGFECG-VJVYQDLKSA-N calcitonin Chemical compound N([C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(N)=O)C(C)C)C(=O)[C@@H]1CSSC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1 BBBFJLBPOGFECG-VJVYQDLKSA-N 0.000 description 1
- 229960004015 calcitonin Drugs 0.000 description 1
- 229960005084 calcitriol Drugs 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- 150000001793 charged compounds Chemical class 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 239000003240 coconut oil Substances 0.000 description 1
- 235000019864 coconut oil Nutrition 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 239000002285 corn oil Substances 0.000 description 1
- 235000005687 corn oil Nutrition 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 239000002385 cottonseed oil Substances 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 125000000422 delta-lactone group Chemical group 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 229960002061 ergocalciferol Drugs 0.000 description 1
- DNVPQKQSNYMLRS-APGDWVJJSA-N ergosterol Chemical compound C1[C@@H](O)CC[C@]2(C)[C@@H](CC[C@@]3([C@@H]([C@H](C)/C=C/[C@H](C)C(C)C)CC[C@H]33)C)C3=CC=C21 DNVPQKQSNYMLRS-APGDWVJJSA-N 0.000 description 1
- 150000002137 ergosterols Chemical class 0.000 description 1
- 150000002148 esters Chemical class 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
- 235000010228 ethyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004403 ethyl p-hydroxybenzoate Substances 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 239000010685 fatty oil Substances 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 235000019688 fish Nutrition 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
- 235000011187 glycerol Nutrition 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229960004337 hydroquinone Drugs 0.000 description 1
- 238000005805 hydroxylation reaction Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229940126601 medicinal product Drugs 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 208000005368 osteomalacia Diseases 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 230000027425 release of sequestered calcium ion into cytosol Effects 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000007940 sugar coated tablet Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 229960001124 trientine Drugs 0.000 description 1
- 238000000870 ultraviolet spectroscopy Methods 0.000 description 1
- 238000002211 ultraviolet spectrum Methods 0.000 description 1
- 230000000450 urinary calcium excretion Effects 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 235000001892 vitamin D2 Nutrition 0.000 description 1
- 239000011653 vitamin D2 Substances 0.000 description 1
- MECHNRXZTMCUDQ-RKHKHRCZSA-N vitamin D2 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)/C=C/[C@H](C)C(C)C)=C\C=C1\C[C@@H](O)CCC1=C MECHNRXZTMCUDQ-RKHKHRCZSA-N 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/26—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D307/30—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D307/32—Oxygen atoms
- C07D307/33—Oxygen atoms in position 2, the oxygen atom being in its keto or unsubstituted enol form
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D319/00—Heterocyclic compounds containing six-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D319/02—1,2-Dioxanes; Hydrogenated 1,2-dioxanes
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP21310881A JPS58118515A (ja) | 1981-12-29 | 1981-12-29 | ２５‐ヒドロキシビタミンｄ↓３―２６，２３‐ラクトンを含有する血清カルシュウム低下剤 |
| JP21310981A JPS58118516A (ja) | 1981-12-29 | 1981-12-29 | １α，２５−ジヒドロキシビタミンＤ↓３−２６，２３−ラクトンを含有するカルシユウム調節剤 |
| JP17526582A JPS5965014A (ja) | 1982-10-07 | 1982-10-07 | ２５−ヒドロキシビタミンｄ↓３−２６，２３−パ−オキシラクトンを活性成分とするカルシユウム調節剤 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE3247836A1 DE3247836A1 (de) | 1983-07-07 |
| DE3247836C2 true DE3247836C2 (US06826419-20041130-M00005.png) | 1991-08-08 |
Family
ID=27324078
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19823247836 Granted DE3247836A1 (de) | 1981-12-29 | 1982-12-23 | Arzneimittel und verwendung derselben zur steuerung der serumcalciumkonzentration bei warmbluetern |
Country Status (4)
| Country | Link |
|---|---|
| US (1) | US4511564A (US06826419-20041130-M00005.png) |
| CH (1) | CH652929A5 (US06826419-20041130-M00005.png) |
| DE (1) | DE3247836A1 (US06826419-20041130-M00005.png) |
| FR (1) | FR2518881B1 (US06826419-20041130-M00005.png) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4921838A (en) * | 1987-06-16 | 1990-05-01 | Trustees Of Boston University | Angiogenic and blood perfusion inducing properties of amphiphilic compounds |
| DE69403541T2 (de) * | 1993-02-05 | 1997-09-25 | Teijin Ltd | Lacton-Verbindung und Verfahren zu ihrer Herstellung |
| US5373004A (en) * | 1993-11-24 | 1994-12-13 | Wisconsin Alumni Research Foundation | 26,28-methylene-1α, 25-dihydroxyvitamin D2 compounds |
| DE10035513A1 (de) * | 2000-07-21 | 2002-01-31 | Beiersdorf Ag | Wirkstoffkombinationen bzw. Addukte aus Cyclodextrinen und mindestens einem Chinon und/oder mindestens einem Hydrochinon und Verwendung solcher Wirkstoffkombinationen in kosmetischen Zubereitungen |
| US7129230B2 (en) * | 2001-03-12 | 2006-10-31 | Nestec S.A. | Method and product for treating cancer in pets |
| US6635757B1 (en) * | 2001-09-14 | 2003-10-21 | Vittal Mallya Scientific Research Foundation | Process for preparing cyclodextrin inclusion complex |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4223131A (en) * | 1979-01-26 | 1980-09-16 | Wisconsin Alumni Research Foundation | 25-Hydroxycholecalciferol-26,23-lactone |
| US4307231A (en) * | 1980-07-18 | 1981-12-22 | Wisconsin Alumni Research Foundation | Vitamin D-lactone derivative and process for preparing same |
| US4336193A (en) * | 1980-08-04 | 1982-06-22 | Wisconsin Alumni Research Foundation | Process for preparing vitamin D-lactones |
-
1982
- 1982-12-23 DE DE19823247836 patent/DE3247836A1/de active Granted
- 1982-12-29 FR FR8222038A patent/FR2518881B1/fr not_active Expired
- 1982-12-29 CH CH7617/82A patent/CH652929A5/de not_active IP Right Cessation
- 1982-12-29 US US06/454,309 patent/US4511564A/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| DE3247836A1 (de) | 1983-07-07 |
| CH652929A5 (de) | 1985-12-13 |
| US4511564A (en) | 1985-04-16 |
| FR2518881B1 (fr) | 1986-02-21 |
| FR2518881A1 (fr) | 1983-07-01 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE60105035T2 (de) | 1alpha-hydroxy-2-methylene-19-nor-homopregnacalciferol und seine therapeutische verwendungen | |
| DE60127964T2 (de) | Verwendung von 2-alpha-methyl-19-nor-20(s)-1-alpha,25-dihydroxyvitamin als knochenersatz | |
| DE4439888A1 (de) | Ultramikroemulsionen aus spontan dispergierbaren Konzentraten mit antitumoral wirksamen Xanthophyll-Estern | |
| DE69411981T2 (de) | Haarregenerierendes Mittel | |
| DE69627354T2 (de) | Verwendung von calendula-glykosiden zur behandlung der psoriasis | |
| WO2000015206A2 (de) | Tryptophanylester und deren n-acyl-derivate zur prävention und therapie von erkrankungen, die durch oxidationsprozesse verursacht oder verstärkt werden | |
| DE3537656C2 (US06826419-20041130-M00005.png) | ||
| DE3490215C2 (US06826419-20041130-M00005.png) | ||
| DE3013632A1 (de) | Mittel und seine verwendung zur regulierung des knochenmetabolismus | |
| DE3511609C2 (US06826419-20041130-M00005.png) | ||
| DE3310556C2 (US06826419-20041130-M00005.png) | ||
| DE3323585A1 (de) | Komposition zur reduktion der sebumsekretion | |
| DE69028320T2 (de) | Illudin-analoge, verwendet als antitumormittel | |
| DE3247836C2 (US06826419-20041130-M00005.png) | ||
| DE3883208T2 (de) | Mittel zur behandlung von keratose. | |
| CH653995A5 (de) | 2beta-fluorcholecalciferole. | |
| DE4028945A1 (de) | Kawa-kawa-extrakt, verfahren zu seiner herstellung und seine verwendung | |
| DE2325070A1 (de) | Pharmazeutische zubereitungen zur prophylaxe und zur behandlung von kapillarvenoesen erkrankungen | |
| DE2451933C2 (US06826419-20041130-M00005.png) | ||
| EP0086476B1 (de) | Verwendung von Cholecalciferolderivaten | |
| DE2843901A1 (de) | Mittel, enthaltend all-e- oder 13-z-7, 8-dehydro-retinsaeure | |
| DE2623486A1 (de) | 3.5.5-trimethylhexanoyl-ferrocen und verfahren zu seiner herstellung | |
| EP0002219B1 (de) | Arzneimittel mit schwefelhaltigen Estern und Verfahren zu ihrer Herstellung | |
| DE3511236C2 (US06826419-20041130-M00005.png) | ||
| EP0094644B1 (de) | Verwendung eines Cholecalciferolderivates |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8128 | New person/name/address of the agent |
Representative=s name: HENKEL, G., DR.PHIL. FEILER, L., DR.RER.NAT. HAENZ |
|
| 8110 | Request for examination paragraph 44 | ||
| 8125 | Change of the main classification |
Ipc: A61K 31/59 |
|
| D2 | Grant after examination | ||
| 8364 | No opposition during term of opposition | ||
| 8339 | Ceased/non-payment of the annual fee |