SE466683B - SPIROKETAL STEROID GLYCOSIDES AND / OR ESTARS THEREOF TO USE AS A MEDICINE - Google Patents
SPIROKETAL STEROID GLYCOSIDES AND / OR ESTARS THEREOF TO USE AS A MEDICINEInfo
- Publication number
- SE466683B SE466683B SE7813443A SE7813443A SE466683B SE 466683 B SE466683 B SE 466683B SE 7813443 A SE7813443 A SE 7813443A SE 7813443 A SE7813443 A SE 7813443A SE 466683 B SE466683 B SE 466683B
- Authority
- SE
- Sweden
- Prior art keywords
- glucoside
- spiroketal
- steroid glycosides
- compounds
- glycosides
- Prior art date
Links
- 229930002534 steroid glycoside Natural products 0.000 title claims description 18
- 150000003180 prostaglandins Chemical class 0.000 claims description 17
- 229940094443 oxytocics prostaglandins Drugs 0.000 claims description 14
- 239000002245 particle Substances 0.000 claims description 10
- 239000003814 drug Substances 0.000 claims description 6
- 150000002148 esters Chemical class 0.000 claims description 6
- 229930182478 glucoside Natural products 0.000 claims description 6
- 150000008131 glucosides Chemical class 0.000 claims description 6
- OXLGJTRVVNGJRK-UHFFFAOYSA-N Hecogenin Natural products CC1CCC2(CC3CC4C5CCC6CC(O)CCC6(C)C5CC(=O)C4(C)C3C2C)OC1 OXLGJTRVVNGJRK-UHFFFAOYSA-N 0.000 claims description 5
- UVLDESQWQRMYKD-UHFFFAOYSA-N Neobotogenin Natural products CC1C(C2(C(=O)CC3C4(C)CCC(O)CC4=CCC3C2C2)C)C2OC11CCC(C)CO1 UVLDESQWQRMYKD-UHFFFAOYSA-N 0.000 claims description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 5
- QOLRLLFJMZLYQJ-LOBDNJQFSA-N Hecogenin Chemical compound O([C@@H]1[C@@H]([C@]2(C(=O)C[C@@H]3[C@@]4(C)CC[C@H](O)C[C@@H]4CC[C@H]3[C@@H]2C1)C)[C@@H]1C)[C@]11CC[C@@H](C)CO1 QOLRLLFJMZLYQJ-LOBDNJQFSA-N 0.000 claims description 4
- RTMWIZOXNKJHRE-UHFFFAOYSA-N Tigogenin Natural products CC1COC2CC(C)(OC12)C3CCC4C5CCC6CC(O)CCC6(C)C5CCC34C RTMWIZOXNKJHRE-UHFFFAOYSA-N 0.000 claims description 4
- WQLVFSAGQJTQCK-UHFFFAOYSA-N diosgenin Natural products CC1C(C2(CCC3C4(C)CCC(O)CC4=CCC3C2C2)C)C2OC11CCC(C)CO1 WQLVFSAGQJTQCK-UHFFFAOYSA-N 0.000 claims description 4
- 201000010099 disease Diseases 0.000 claims description 4
- GMBQZIIUCVWOCD-WWASVFFGSA-N Sarsapogenine Chemical compound O([C@@H]1[C@@H]([C@]2(CC[C@@H]3[C@@]4(C)CC[C@H](O)C[C@H]4CC[C@H]3[C@@H]2C1)C)[C@@H]1C)[C@]11CC[C@H](C)CO1 GMBQZIIUCVWOCD-WWASVFFGSA-N 0.000 claims description 3
- DWCSNWXARWMZTG-UHFFFAOYSA-N Trigonegenin A Natural products CC1C(C2(CCC3C4(C)CCC(O)C=C4CCC3C2C2)C)C2OC11CCC(C)CO1 DWCSNWXARWMZTG-UHFFFAOYSA-N 0.000 claims description 3
- WQLVFSAGQJTQCK-VKROHFNGSA-N diosgenin Chemical compound O([C@@H]1[C@@H]([C@]2(CC[C@@H]3[C@@]4(C)CC[C@H](O)CC4=CC[C@H]3[C@@H]2C1)C)[C@@H]1C)[C@]11CC[C@@H](C)CO1 WQLVFSAGQJTQCK-VKROHFNGSA-N 0.000 claims description 3
- 239000013543 active substance Substances 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 description 19
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
- 239000000203 mixture Substances 0.000 description 13
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 239000000243 solution Substances 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- 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 10
- 230000000694 effects Effects 0.000 description 10
- 239000008101 lactose Substances 0.000 description 10
- 238000002360 preparation method Methods 0.000 description 10
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 7
- 241000700159 Rattus Species 0.000 description 7
- 239000008187 granular material Substances 0.000 description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- 239000002775 capsule Substances 0.000 description 6
- 229930182470 glycoside Natural products 0.000 description 6
- 108010010803 Gelatin Proteins 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 229960002986 dinoprostone Drugs 0.000 description 5
- 239000008298 dragée Substances 0.000 description 5
- 239000008273 gelatin Substances 0.000 description 5
- 229920000159 gelatin Polymers 0.000 description 5
- 235000019322 gelatine Nutrition 0.000 description 5
- 235000011852 gelatine desserts Nutrition 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- XEYBRNLFEZDVAW-UHFFFAOYSA-N prostaglandin E2 Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CC=CCCCC(O)=O XEYBRNLFEZDVAW-UHFFFAOYSA-N 0.000 description 5
- 239000002599 prostaglandin synthase inhibitor Substances 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
- 230000009471 action Effects 0.000 description 4
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 4
- 206010003246 arthritis Diseases 0.000 description 4
- 230000037396 body weight Effects 0.000 description 4
- 238000009835 boiling Methods 0.000 description 4
- 239000006071 cream Substances 0.000 description 4
- 150000002338 glycosides Chemical class 0.000 description 4
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 4
- 235000019359 magnesium stearate Nutrition 0.000 description 4
- 239000002002 slurry Substances 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- PXGPLTODNUVGFL-BRIYLRKRSA-N (E,Z)-(1R,2R,3R,5S)-7-(3,5-Dihydroxy-2-((3S)-(3-hydroxy-1-octenyl))cyclopentyl)-5-heptenoic acid Chemical compound CCCCC[C@H](O)C=C[C@H]1[C@H](O)C[C@H](O)[C@@H]1CC=CCCCC(O)=O PXGPLTODNUVGFL-BRIYLRKRSA-N 0.000 description 3
- 229920002261 Corn starch Polymers 0.000 description 3
- 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 3
- 102000003960 Ligases Human genes 0.000 description 3
- 108090000364 Ligases Proteins 0.000 description 3
- 241000220317 Rosa Species 0.000 description 3
- 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 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 239000008120 corn starch Substances 0.000 description 3
- XEYBRNLFEZDVAW-ARSRFYASSA-N dinoprostone Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O XEYBRNLFEZDVAW-ARSRFYASSA-N 0.000 description 3
- WXMARHKAXWRNDM-GAMIEDRGSA-N diosgenin 3-O-beta-D-glucoside Chemical compound O([C@@H]1CC2=CC[C@H]3[C@@H]4C[C@H]5[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@@H]([C@]1(OC[C@H](C)CC1)O5)C)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O WXMARHKAXWRNDM-GAMIEDRGSA-N 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 239000002674 ointment Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- ZXSQEZNORDWBGZ-UHFFFAOYSA-N 1,3-dihydropyrrolo[2,3-b]pyridin-2-one Chemical compound C1=CN=C2NC(=O)CC2=C1 ZXSQEZNORDWBGZ-UHFFFAOYSA-N 0.000 description 2
- 208000031295 Animal disease Diseases 0.000 description 2
- YZXBAPSDXZZRGB-DOFZRALJSA-M Arachidonate Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC([O-])=O YZXBAPSDXZZRGB-DOFZRALJSA-M 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
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
- 206010020751 Hypersensitivity Diseases 0.000 description 2
- 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 2
- 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 2
- 208000025747 Rheumatic disease Diseases 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 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 2
- WQLVFSAGQJTQCK-CAKNJAFZSA-N Yamogenin Chemical compound O([C@@H]1[C@@H]([C@]2(CC[C@@H]3[C@@]4(C)CC[C@H](O)CC4=CC[C@H]3[C@@H]2C1)C)[C@@H]1C)[C@]11CC[C@H](C)CO1 WQLVFSAGQJTQCK-CAKNJAFZSA-N 0.000 description 2
- MJOQJPYNENPSSS-XQHKEYJVSA-N [(3r,4s,5r,6s)-4,5,6-triacetyloxyoxan-3-yl] acetate Chemical compound CC(=O)O[C@@H]1CO[C@@H](OC(C)=O)[C@H](OC(C)=O)[C@H]1OC(C)=O MJOQJPYNENPSSS-XQHKEYJVSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000007815 allergy Effects 0.000 description 2
- 229940114078 arachidonate Drugs 0.000 description 2
- 229940114079 arachidonic acid Drugs 0.000 description 2
- 235000021342 arachidonic acid Nutrition 0.000 description 2
- 208000006673 asthma Diseases 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- -1 glycoside compound Chemical class 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 229960000905 indomethacin Drugs 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 238000011835 investigation Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 150000002772 monosaccharides Chemical group 0.000 description 2
- 230000017074 necrotic cell death Effects 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 229920001592 potato starch Polymers 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 201000003068 rheumatic fever Diseases 0.000 description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 description 2
- LKZMBDSASOBTPN-UHFFFAOYSA-L silver carbonate Substances [Ag].[O-]C([O-])=O LKZMBDSASOBTPN-UHFFFAOYSA-L 0.000 description 2
- 229910001958 silver carbonate Inorganic materials 0.000 description 2
- NDVLTYZPCACLMA-UHFFFAOYSA-N silver oxide Chemical compound [O-2].[Ag+].[Ag+] NDVLTYZPCACLMA-UHFFFAOYSA-N 0.000 description 2
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 2
- 150000003431 steroids Chemical group 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- KZJWDPNRJALLNS-VPUBHVLGSA-N (-)-beta-Sitosterol Natural products O[C@@H]1CC=2[C@@](C)([C@@H]3[C@H]([C@H]4[C@@](C)([C@H]([C@H](CC[C@@H](C(C)C)CC)C)CC4)CC3)CC=2)CC1 KZJWDPNRJALLNS-VPUBHVLGSA-N 0.000 description 1
- CSVWWLUMXNHWSU-UHFFFAOYSA-N (22E)-(24xi)-24-ethyl-5alpha-cholest-22-en-3beta-ol Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(C)C=CC(CC)C(C)C)C1(C)CC2 CSVWWLUMXNHWSU-UHFFFAOYSA-N 0.000 description 1
- WFBHLGOLOWZMBJ-GVYWOMJSSA-N (4r,5s,6r,7r)-1-bromo-4,5,6,7,8-pentahydroxyoctane-2,3-dione Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(=O)C(=O)CBr WFBHLGOLOWZMBJ-GVYWOMJSSA-N 0.000 description 1
- KLEXDBGYSOIREE-UHFFFAOYSA-N 24xi-n-propylcholesterol Natural products C1C=C2CC(O)CCC2(C)C2C1C1CCC(C(C)CCC(CCC)C(C)C)C1(C)CC2 KLEXDBGYSOIREE-UHFFFAOYSA-N 0.000 description 1
- QCVGEOXPDFCNHA-UHFFFAOYSA-N 5,5-dimethyl-2,4-dioxo-1,3-oxazolidine-3-carboxamide Chemical compound CC1(C)OC(=O)N(C(N)=O)C1=O QCVGEOXPDFCNHA-UHFFFAOYSA-N 0.000 description 1
- BSYNRYMUTXBXSQ-FOQJRBATSA-N 59096-14-9 Chemical compound CC(=O)OC1=CC=CC=C1[14C](O)=O BSYNRYMUTXBXSQ-FOQJRBATSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- TWCMVXMQHSVIOJ-UHFFFAOYSA-N Aglycone of yadanzioside D Natural products COC(=O)C12OCC34C(CC5C(=CC(O)C(O)C5(C)C3C(O)C1O)C)OC(=O)C(OC(=O)C)C24 TWCMVXMQHSVIOJ-UHFFFAOYSA-N 0.000 description 1
- PLMKQQMDOMTZGG-UHFFFAOYSA-N Astrantiagenin E-methylester Natural products CC12CCC(O)C(C)(CO)C1CCC1(C)C2CC=C2C3CC(C)(C)CCC3(C(=O)OC)CCC21C PLMKQQMDOMTZGG-UHFFFAOYSA-N 0.000 description 1
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 description 1
- 208000027796 Blood pressure disease Diseases 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- LPZCCMIISIBREI-MTFRKTCUSA-N Citrostadienol Natural products CC=C(CC[C@@H](C)[C@H]1CC[C@H]2C3=CC[C@H]4[C@H](C)[C@@H](O)CC[C@]4(C)[C@H]3CC[C@]12C)C(C)C LPZCCMIISIBREI-MTFRKTCUSA-N 0.000 description 1
- ARVGMISWLZPBCH-UHFFFAOYSA-N Dehydro-beta-sitosterol Natural products C1C(O)CCC2(C)C(CCC3(C(C(C)CCC(CC)C(C)C)CCC33)C)C3=CC=C21 ARVGMISWLZPBCH-UHFFFAOYSA-N 0.000 description 1
- 201000004624 Dermatitis Diseases 0.000 description 1
- 102000002322 Egg Proteins Human genes 0.000 description 1
- 108010000912 Egg Proteins Proteins 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 208000017701 Endocrine disease Diseases 0.000 description 1
- 102000009123 Fibrin Human genes 0.000 description 1
- 108010073385 Fibrin Proteins 0.000 description 1
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 1
- 206010017788 Gastric haemorrhage Diseases 0.000 description 1
- 208000012671 Gastrointestinal haemorrhages Diseases 0.000 description 1
- 201000005569 Gout Diseases 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 238000006945 Knorr synthesis reaction Methods 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- GMBQZIIUCVWOCD-PUHUBZITSA-N Neotigogenin Chemical compound O([C@@H]1[C@@H]([C@]2(CC[C@@H]3[C@@]4(C)CC[C@H](O)C[C@@H]4CC[C@H]3[C@@H]2C1)C)[C@@H]1C)[C@]11CC[C@H](C)CO1 GMBQZIIUCVWOCD-PUHUBZITSA-N 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 208000004403 Prostatic Hyperplasia Diseases 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- QOLRLLFJMZLYQJ-KYRQEAISSA-N Sisalagenin Chemical compound O([C@@H]1[C@@H]([C@]2(C(=O)C[C@@H]3[C@@]4(C)CC[C@H](O)C[C@@H]4CC[C@H]3[C@@H]2C1)C)[C@@H]1C)[C@]11CC[C@H](C)CO1 QOLRLLFJMZLYQJ-KYRQEAISSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 229930182558 Sterol Natural products 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 208000025609 Urogenital disease Diseases 0.000 description 1
- 206010046996 Varicose vein Diseases 0.000 description 1
- 206010000210 abortion Diseases 0.000 description 1
- 231100000176 abortion Toxicity 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- MJVXAPPOFPTTCA-UHFFFAOYSA-N beta-Sistosterol Natural products CCC(CCC(C)C1CCC2C3CC=C4C(C)C(O)CCC4(C)C3CCC12C)C(C)C MJVXAPPOFPTTCA-UHFFFAOYSA-N 0.000 description 1
- LGJMUZUPVCAVPU-UHFFFAOYSA-N beta-Sitostanol Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(C)CCC(CC)C(C)C)C1(C)CC2 LGJMUZUPVCAVPU-UHFFFAOYSA-N 0.000 description 1
- NJKOMDUNNDKEAI-UHFFFAOYSA-N beta-sitosterol Natural products CCC(CCC(C)C1CCC2(C)C3CC=C4CC(O)CCC4C3CCC12C)C(C)C NJKOMDUNNDKEAI-UHFFFAOYSA-N 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 239000013068 control sample Substances 0.000 description 1
- 210000004087 cornea Anatomy 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000002497 edematous effect Effects 0.000 description 1
- 235000014103 egg white Nutrition 0.000 description 1
- 210000000969 egg white Anatomy 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- KAQKFAOMNZTLHT-VVUHWYTRSA-N epoprostenol Chemical compound O1C(=CCCCC(O)=O)C[C@@H]2[C@@H](/C=C/[C@@H](O)CCCCC)[C@H](O)C[C@@H]21 KAQKFAOMNZTLHT-VVUHWYTRSA-N 0.000 description 1
- 229960001123 epoprostenol Drugs 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 150000002191 fatty alcohols Chemical class 0.000 description 1
- 229950003499 fibrin Drugs 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 208000030304 gastrointestinal bleeding Diseases 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 210000004392 genitalia Anatomy 0.000 description 1
- UVLDESQWQRMYKD-MOAZMYQBSA-N gentrogenin Chemical compound O([C@@H]1[C@@H]([C@]2(C(=O)C[C@@H]3[C@@]4(C)CC[C@H](O)CC4=CC[C@H]3[C@@H]2C1)C)[C@@H]1C)[C@]11CC[C@@H](C)CO1 UVLDESQWQRMYKD-MOAZMYQBSA-N 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 208000014617 hemorrhoid Diseases 0.000 description 1
- 229960001340 histamine Drugs 0.000 description 1
- PFOARMALXZGCHY-UHFFFAOYSA-N homoegonol Natural products C1=C(OC)C(OC)=CC=C1C1=CC2=CC(CCCO)=CC(OC)=C2O1 PFOARMALXZGCHY-UHFFFAOYSA-N 0.000 description 1
- 229960001680 ibuprofen Drugs 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000003978 infusion fluid Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 239000006193 liquid solution Substances 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 239000011859 microparticle Substances 0.000 description 1
- 230000004660 morphological change Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 229930182490 saponin Natural products 0.000 description 1
- 150000007949 saponins Chemical class 0.000 description 1
- 235000017709 saponins Nutrition 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 229910001923 silver oxide Inorganic materials 0.000 description 1
- KZJWDPNRJALLNS-VJSFXXLFSA-N sitosterol 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)CC[C@@H](CC)C(C)C)[C@@]1(C)CC2 KZJWDPNRJALLNS-VJSFXXLFSA-N 0.000 description 1
- 235000015500 sitosterol Nutrition 0.000 description 1
- 229950005143 sitosterol Drugs 0.000 description 1
- NLQLSVXGSXCXFE-UHFFFAOYSA-N sitosterol Natural products CC=C(/CCC(C)C1CC2C3=CCC4C(C)C(O)CCC4(C)C3CCC2(C)C1)C(C)C NLQLSVXGSXCXFE-UHFFFAOYSA-N 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000007962 solid dispersion Substances 0.000 description 1
- 239000006104 solid solution Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 235000000891 standard diet Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 150000005856 steroid saponins Chemical class 0.000 description 1
- 235000003702 sterols Nutrition 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- OULAJFUGPPVRBK-UHFFFAOYSA-N tetratriacontan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCO OULAJFUGPPVRBK-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 150000003595 thromboxanes Chemical class 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 208000027185 varicose disease Diseases 0.000 description 1
- 208000019553 vascular disease Diseases 0.000 description 1
- 230000000304 vasodilatating effect Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 239000003871 white petrolatum Substances 0.000 description 1
- 210000002268 wool Anatomy 0.000 description 1
- 150000008498 β-D-glucosides Chemical class 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J17/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, having an oxygen-containing hetero ring not condensed with the cyclopenta(a)hydrophenanthrene skeleton
- C07J17/005—Glycosides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J71/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton is condensed with a heterocyclic ring
- C07J71/0005—Oxygen-containing hetero ring
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
466 683 2 Prostaglandinernas omfattande ämnesomsättningseffekter medger många terapeutiska användningsmöjligheter. Sålunda sättes prostaglandiner in vid behandling av astma och blodomlopps- sjukdomar, eftersom prostaglandiner av E-typ har en kärldila- terande verkan. Å andra sidan sätter prostaglandiner igång värkar och inleder födseln så att de i förekommande fall även kan användas såsom abortmedel. 466 683 2 The extensive metabolic effects of prostaglandins allow for many therapeutic uses. Thus, prostaglandins are used in the treatment of asthma and circulatory diseases, as E-type prostaglandins have a vasodilating effect. On the other hand, prostaglandins cause pain and initiate labor so that they can also be used as abortion products if necessary.
Sedan helt nyligen är det känt att verkningen från några, delvis sedan flera år kända läkemedel med analgetisk och inflammationshämmande aktivitet beror på en hämning av prostaglandinsyntetaser. Detta gäller t ex acetylsalycylsyra, indometacin och ibuprofen. Den starka inhiberande verkan från dessa föreningar förklarar å ena sidan deras verkan mot inflammatoriska symptom men å andra sidan förekomsten av många biverkningar av vilka såsom exempel endast utlösning av magblödningar nämnes.It has been known very recently that the effect of some drugs, partly known for several years with analgesic and anti-inflammatory activity, is due to an inhibition of prostaglandin synthetases. This applies, for example, to acetylsalycylic acid, indomethacin and ibuprofen. The strong inhibitory effect of these compounds explains on the one hand their action against inflammatory symptoms but on the other hand the presence of many side effects of which by way of example only the onset of gastric bleeding is mentioned.
Biosyntesen av prostaglandinerna utgår från membranfosforli- pider, som omvandlas till arachidonsyra och genom syreradika- ler överföres till endoperoxid-prostaglandiner. Från dessa endoperoxid-prostaglandiner bildas de relativt stabila pro- staglandinerna, tromboxanerna samt det förhållandevis in- stabila prostacyklinet. Bildningen av PGE2 och PGF2a från arachidonsyra kan återges med följande formelschema: (fw 3 466 683 Prostaglandinernas och i synnerhet prostaglandinförstegens biologiska halveringstid är mycket kort. Nedbrytningen sker snabbt genom oxidation vid kolatom nr 15 och sedan via den för fettsyrorna typiska ß-oxidationen.The biosynthesis of the prostaglandins is based on membrane phospholipids, which are converted to arachidonic acid and converted to endoperoxide-prostaglandins by acid radicals. From these endoperoxide oxide prostaglandins are formed the relatively stable prostaglandins, thromboxanes and the relatively unstable prostacyclin. The formation of PGE2 and PGF2α from arachidonic acid can be represented by the following formula scheme: (fw 3 466 683 The biological half-life of prostaglandins and in particular prostaglandin precursors is very short.
Det är redan känt att vissa kemiska föreningar är starka prostaglandinsyntetasinhibitorer. Dessa föreningar, såsom t ex indometacin eller acetylsalicytlsyra betraktas som inhibitorer för PGE2-syntetaser och användes därför för be- handling av inflammatoriska symptom av olika ursprung såsom t ex reumatiska sjukdomar och artritåkommor och liknande. Den starkt uttalade inhibitor-verkningen, som inte endast före- faller vara inskränkt till PGE2-syntetaserna leder emellertid _ även till härigenom orsakade icke önskvärda biverkningar, såsom utlösning av mag- och tarmblödningar, andra diffusa blödningar, uppträdande av allergier och eventuellt påverkan av en graviditet.It is already known that some chemical compounds are strong prostaglandin synthetase inhibitors. These compounds, such as indomethacin or acetylsalicylic acid, are considered inhibitors of PGE2 synthetases and are therefore used to treat inflammatory symptoms of various origins such as rheumatic diseases and arthritis and the like. However, the strongly pronounced inhibitory effect, which not only appears to be restricted to the PGE2 synthetases, also leads to undesirable side effects, such as the triggering of gastrointestinal bleeding, other diffuse bleeding, the occurrence of allergies and the possible effect of a pregnancy.
Syftet med föreliggande uppfinning är att åstadkomma ett läkemedel med verkan såsom prostaglandinsyntetasinhibitor utan de kända nackdelarna.The object of the present invention is to provide a medicament having the action of a prostaglandin synthetase inhibitor without the known disadvantages.
Uppfinningen avser därför spiroketalsteroidglykosider och/el- ler estrar därav till användning som läkemedel, och i synner- het spiroketalsteroidglykosider och/eller estrar därav till användning som läkemedel för behandling av sjukdomar, som orsakas av en för hög halt av prostaglandiner.The invention therefore relates to spiroketal steroid glycosides and / or esters thereof for use as medicaments, and in particular to spiroketal steroid glycosides and / or esters thereof for use as medicaments for the treatment of diseases caused by an excess of prostaglandins.
Det har helt överraskande visat sig att spiroketalsteroid- glykosider och estrar därav är verksamma inhibitorer för prostaglandin Ez- och prostaglandin Fza-syntetaser och trots detta inte utlöser några genom påverkan av prostaglandin- halten annars uppträdande biverkningar.It has surprisingly been found that spiroketal steroid glycosides and esters thereof are effective inhibitors of prostaglandin Ez and prostaglandin Fza synthetases and nevertheless do not trigger any by side effects of prostaglandin otherwise occurring side effects.
Såsom spiroketalsteroidglykosider betecknas steroidsaponiner- na, som i det såsom aglykon föreliggande steroidgrundskelet- tet har en vid kolatomerna 16 och 17 ansluten spiroketalgrup- pering. Aglykonerna kan för övrigt vara olika beroende på om 466 685 4 det rör sig om 5-en-steroidsapogeniner eller 5-a-steroidsapo- geniner. Till 5-en-föreningarna hör t ex diosgenin, yamoge- nin, botogenin och correlogenin, under det att såsom typiska exempel på 5-a-föreningarna t ex tigogenin, neotigogenin, hecogenin sisalagenin kan nämnas.Spiroketal steroid glycosides are the steroid saponins which, in the steroid backbone of aglycone, have a spiroketal moiety attached to carbon atoms 16 and 17. The aglycones can also be different depending on whether they are 5-en-steroidal apogenines or 5-α-steroidal apogenins. The 5-ene compounds include, for example, diosgenin, yamogenin, botogenin and correlogenin, while typical examples of the 5-α compounds are, for example, tigogenin, neotigogenin, hecogenin sisalagenin.
I naturen förekommer aglykonerna i saponinerna såsom glykosi- der och innehåller för det mesta 3 eller flera monosackari- denheter i sockerdelen. Av detta skäl är de förhållandevis sockerrika föreningarna någorlunda väl lösliga i vatten och bildar ofta ett tvålliknande skum.In nature, the aglycones in the saponins occur as glycosides and usually contain 3 or more monosaccharide units in the sugar moiety. For this reason, the relatively sugary compounds are relatively readily soluble in water and often form a soap-like foam.
Spiroketalsteroidglykosiderna har följande allmänna formel z-o / vari en dubbelbindning eller en a-väteatom föreligger i 5- ställning, och vari Z betecknar en mono- eller disackarid, i synnerhet glukos, eventuellt förestrad.The spiroketal steroid glycosides have the following general formula z-o / wherein a double bond or an α-hydrogen atom is in the 5-position, and wherein Z represents a mono- or disaccharide, in particular glucose, optionally esterified.
De enligt uppfinningen satsade spiroketalsteroidglykosiderna och estrarna därav kan satsas såsom extrakt från växtmaterial såsom anrikat extrakt eller såsom syntetiskt framställda föreningar. Syntesen sker på i och för sig känt sätt såsom t ex med den kända Königs-Knorr-syntesen för framställning av glykosider med användning av motsvarande aglykoner, ett vid kolatom 1 bromerat sockeracetat och silveroxid och silverkar- bonat.The spiroketal steroid glycosides and esters thereof charged according to the invention can be charged as extracts from plant materials such as enriched extracts or as synthetically produced compounds. The synthesis takes place in a manner known per se, such as with the known Königs-Knorr synthesis for the production of glycosides using the corresponding aglycones, a brominated sugar acetate at carbon atom 1 and silver oxide and silver carbonate.
Spiroketalsteroidglykosiderna bör, p grund av att de ej är lättlösta i vatten ges i en för resorptionen tillräckligt 5 0 466 683 liten partikelstorlek. Det är därför lämpligt att de enligt uppfinningen använda spiroketalsteroidglykosiderna framstäl- les och/eller förberedes och/eller inkorporeras i farmaceu- tiska preparat så att flytande eller fasta lösningar, emul- sioner eller fasta dispersioner bildas, som kan erhållas på i och för sig känt sätt genom adsorption, absorption eller genom malförfarande med eller utan tillsatsmedel. Dessa för- faranden syftar alla till att minska partiklarna och sänka kristalliniteten så att dessa föreligger i form av ytterst små amorfa mono- eller multimolekylära aggregat i stället för i form av kristallina mikropartiklar. De föreningar enligt uppfinningen, som skall administreras, sättes för det mesta in med en partikelstorlek av ca 0,1 mm och företrädesvis 0,06 mm och mindre. Samma gäller, trots deras något bättre vattenlöslighet, för spiroketalsteroidglykosiderna, som även användes med en partikelstorlek av ca 0,1 mm och företrädes- vis 0,06 mm eller mindre.The spirochetal steroid glycosides, because they are not readily soluble in water, should be given in a sufficiently small particle size for resorption. It is therefore convenient that the spiroketal steroid glycosides used according to the invention are prepared and / or prepared and / or incorporated into pharmaceutical preparations so that liquid or solid solutions, emulsions or solid dispersions are formed, which can be obtained in a manner known per se. by adsorption, absorption or by grinding procedure with or without additives. These methods all aim to reduce the particles and lower the crystallinity so that they are in the form of extremely small amorphous mono- or multimolecular aggregates instead of in the form of crystalline microparticles. The compounds of the invention to be administered are usually introduced with a particle size of about 0.1 mm and preferably 0.06 mm and less. The same applies, despite their slightly better water solubility, to the spiroketal steroid glycosides, which are also used with a particle size of about 0.1 mm and preferably 0.06 mm or less.
De föreningar enligt uppfinningen, som skall administreras, ges i en dagsdos om ca 0,03- ca 10 mg. Såsom upprätthållande eller profylaktisk dos ges för det mesta ca 0,45-0,1 mg per dag. Dessa doser kan delas upp i tre enskilda doser eller administreras i en enda dos med fördröjd verkan.The compounds of the invention to be administered are given in a daily dose of about 0.03 to about 10 mg. As a maintenance or prophylactic dose, it is usually given about 0.45-0.1 mg per day. These doses can be divided into three single doses or administered in a single dose with delayed action.
Enligt vad man hittills vet är de föreningar, som skall sättas in enligt uppfinningen, lämpliga för behandling av sådana sjukdomar, vid vilka en nedsättning av PGE2- eller PGF2a-halten erfordras. Det rör sig härvid t ex om 1. sår, i synnerhet i mag-tarmtrakten, 2. endokrina störningar, 3. urogenitalåkommor, i synnerhet godartade prostatahyper- trofier och därigenom orsakade besvär, 4. hjärtåkommor och blodtrycksrubbningar, 5. ödematösa tillstånd, 6. kärlsjukdomar, tromboser, åderbrock och hemorojder, 7. dermatitider och histaminöverskottsreaktioner, 8. inflammatoriska åkommor, 9. reumatiska sjukdomar och artritåkommor, 10. allergier, inklusive astma. 466 685 6 På samma sätt kan de föreningar enligt uppfinningen, som skall administreras, även sättas in för behandling av djurå- kommor. Doserna vid bekämpning av djursjukdomar kan beräknas på känt sätt, dvs på viktsbasis vid en antagen mänsklig genomsnittsvikt av 75 kg.As far as is known, the compounds to be used according to the invention are suitable for the treatment of such diseases in which a reduction of the PGE2 or PGF2a content is required. These are, for example, 1. ulcers, especially in the gastrointestinal tract, 2. endocrine disorders, 3. urogenital disorders, in particular benign prostatic hypertrophies and thereby caused problems, 4. heart disorders and blood pressure disorders, 5. edematous conditions, 6 vascular diseases, thromboses, varicose veins and hemorrhoids, 7. dermatitis and excess histamine reactions, 8. inflammatory disorders, 9. rheumatic diseases and arthritis disorders, 10. allergies, including asthma. 466 685 6 In the same way, the compounds according to the invention which are to be administered can also be used for the treatment of animal diseases. The doses in the control of animal diseases can be calculated in a known manner, ie on a weight basis at an assumed human average weight of 75 kg.
Föreningarna kan på i och för sig känt sätt bearbetas till farmaceutiska specialiteter såsom t ex till pulver, piller och tabletter, kapslar, dragëer, emulsioner, lösningar, injektions- respektive infusionslösningar, salvor och krämer.The compounds can be processed in a manner known per se into pharmaceutical specialties such as, for example, powders, pills and tablets, capsules, dragees, emulsions, solutions, injection or infusion solutions, ointments and creams.
Uppfinningen belyses närmare med följande exempel.The invention is further illustrated by the following examples.
Exempel 1 Framställning av diosgenin 3-ß-D-glukosid. 41,4 g diosgenin och 55,2 g silverkarbonat satsas i kokande toluen och blandningen destilleras under omrörning tills destillatet övergår vattenfritt. Därefter försättes den omrörda kokande lösningen droppvis med en lösning av 82,2 g bromacetylglukos i 100 ml toluen. Blandningen destilleras vidare kontinuerligt för avlägsning av det under reaktionen bildade vattnet. Under denna tid skyddas reaktionskärlet mot ljus. Om så erfordras hålles reaktionsblandningens volym konstant genom tillsats av torr toluen. Efter tillsats av acetobromglukoslösningen destilleras vidare tills destillatet övergår vattenfritt. Reaktionsblandningen kyles därefter och filtreras. Återstoden tvättas med ny varm toluen. De förenade filtraten och tvättvätskorna indunstas till torrhet under sänkt tryck. Återstoden omkristalliseras ur etanol eller hexan. Utbytet av diosgenin-3-B-D-glukosid-tetraacetat utgör 25,5 g eller 34,3 %. 1 g natrium löses i 100 ml absolut etanol. Av denna lösning sättes 15 ml snabbt under omrörning til en lösning av 10 g diosgenin-glukosid-tetraacetat i 600 ml etanol vid 45°C.Example 1 Preparation of diosgenin 3-β-D-glucoside. 41.4 g of diosgenin and 55.2 g of silver carbonate are charged to boiling toluene and the mixture is distilled with stirring until the distillate turns anhydrous. Then the stirred boiling solution is added dropwise with a solution of 82.2 g of bromoacetyl glucose in 100 ml of toluene. The mixture is further distilled continuously to remove the water formed during the reaction. During this time, the reaction vessel is protected from light. If necessary, the volume of the reaction mixture is kept constant by the addition of dry toluene. After addition of the acetobromine glucose solution, it is further distilled until the distillate becomes anhydrous. The reaction mixture is then cooled and filtered. The residue is washed with fresh hot toluene. The combined filtrates and washings are evaporated to dryness under reduced pressure. The residue is recrystallized from ethanol or hexane. The yield of diosgenin-3-β-D-glucoside tetraacetate is 25.5 g or 34.3%. 1 g of sodium is dissolved in 100 ml of absolute ethanol. Of this solution, 15 ml are rapidly added with stirring to a solution of 10 g of diosgenin-glucoside tetraacetate in 600 ml of ethanol at 45 ° C.
Blandningen omröres 1 timme innan 2 liter vatten tilsättes och blandningen omröres därefter återigen 1 timme. Den ut- fällda diosgenin-ß-D-glukosiden filtreras av och tvättas med vatten till neutral reaktion innan den torkas i vakuum 7 g 466 685 12 timmar. Utbytet är 7 g eller 90 %.The mixture is stirred for 1 hour before 2 liters of water are added and the mixture is then stirred again for 1 hour. The precipitated diosgenin-β-D-glucoside is filtered off and washed with water until neutral before being dried in vacuo for 7 g 466 685 12 hours. The yield is 7 g or 90%.
På motsvarande sätt kan även alla övriga nämnda spiroketal- steroidglykosider framställas.Correspondingly, all the other mentioned spiroketal steroid glycosides can also be prepared.
Exempel 2 Framställning av farmaceutiska beredningar. a) Framställning av laktos-majsstärkelse-pulver med en halt av diosgenin-ß-D-glukosid. 15 g diosgenin-ß-D-glukosid löses i 3 liter av en kokande blandning av kloroform och etanol i förhållande 3:1. Lös- ningen sättes därefter till 1 kg laktos med en partikelstor- lek ej överstigande 0,15 mm. Den så bildade uppslamningen indunstas under ständig omrörning till torrhet. Den torkade, impregnerade laktosen sönderdelas åter till den ursprungliga partikelstorleken och blandas slutligen med 9 kg majsstärkel- se och 50 g magnesiumstearat. Denna blandning är utmärkt lämplig för fyllning i kapslar. Varje kapsel kan t ex in- nehålla 100 mg av blandningen, vilket motsvarar en halt av 0,15 mg diosgenin-ß-D-glukosid, 10 mg laktos, 90 mg majsstär- kelse och 0,5 mg magnesiumstearat. b) Framställning av laktosgranulat med en halt av diosgenin- ß-D-glukosid. 5 g diosgenin-ß-D-glukosit löses i 5 liter kokande etanol.Example 2 Preparation of pharmaceutical preparations. a) Preparation of lactose-corn starch powder with a content of diosgenin-β-D-glucoside. 15 g of diosgenin-β-D-glucoside are dissolved in 3 liters of a boiling mixture of chloroform and ethanol in a ratio of 3: 1. The solution is then added to 1 kg of lactose with a particle size not exceeding 0.15 mm. The slurry thus formed is evaporated to dryness with constant stirring. The dried, impregnated lactose is decomposed back to the original particle size and finally mixed with 9 kg of corn starch and 50 g of magnesium stearate. This mixture is excellent for filling into capsules. Each capsule may, for example, contain 100 mg of the mixture, which corresponds to a content of 0.15 mg of diosgenin-β-D-glucoside, 10 mg of lactose, 90 mg of corn starch and 0.5 mg of magnesium stearate. b) Preparation of lactose granules with a content of diosgenin-ß-D-glucoside. 5 g of diosgenin-β-D-glucose are dissolved in 5 liters of boiling ethanol.
Lösningen sättes därefter till 3,32 kg laktos med en parti- kelstorlek ej över 0,15 mm. Uppslamningen indunstas under ständig omrörning till torrhet. Den torra, impregnerade laktosen sönderdelas till den ursprungliga partikelstorleken innan den bearbetas till granulat med en föredragen partikel- storlek av ca 0,7-1,2 mm. Denna granulerade produkt är också speciellt lämplig för vidare bearbetning i kapslar, varvid t ex en kapsel med 100 mg av granulatet innehåller 0,15 mg diosgenin-B-D-glukosid.The solution is then added to 3.32 kg of lactose with a particle size not exceeding 0.15 mm. The slurry is evaporated to constant dryness with constant stirring. The dry, impregnated lactose is decomposed to the original particle size before being processed into granules with a preferred particle size of about 0.7-1.2 mm. This granulated product is also particularly suitable for further processing into capsules, whereby, for example, a capsule with 100 mg of the granulate contains 0.15 mg of diosgenin-B-D-glucoside.
Produkterna under a) och b) kan även framställas med använd- ning av 466 685 8 1. glykosider av de nämnda 3-ß-hydroxispiroketalsteroi- derna och i synnerhet ß-D-glukosiderna av tigogenin och hekogenin. 2. Glukos, askorbinsyra eller talk såsom bärare för glykosiderna eller även användning av andra inerta farmaceutiskt godtagbara bärare. 3. Halten av aktiv glykosidförening i varje kapsel kan inställas på värden mellan 0,01 mg och mer. 4. De under a) och b) nämnda hjälpsubstanserna kan varieras motsvarande de vanliga farmaceutiska fram- ställningsförfarandena. 5. I varje stadium av framställningsförfarandet i a) eller b) kan andra farmaceutiskt aktiva föreningar arbetas in. c) Framställning av tabletter med en halt av diosgenin-ß-D- glukosid. 1,250 g diosgenin-ß-D-glukosid löses i 1 liter kloroform och försättes med 900 g laktos. Uppslamningen torkas under sänkt tryck och ständig omrörning vid rumstemperatur. Därefter försättes blandningen med 2100 g potatisstärkelse och omröres på nytt kraftigt. Den impregnerade laktos-stärkelse-bland- ningen försättes med 2500 ml av en vattenlösning av 250 g gelatin och 5 g glycerin och granuleras på i och för sig känt sätt. Granulatet torkas under sänkt tryck vid rumstemperatur.The products under a) and b) can also be prepared using glycosides of the said 3-β-hydroxypirooketal steroids and in particular the β-D-glucosides of tigogenin and hecogenin. Glucose, ascorbic acid or talc as carriers for the glycosides or also the use of other inert pharmaceutically acceptable carriers. The content of active glycoside compound in each capsule can be adjusted to values between 0.01 mg and more. 4. The excipients mentioned in a) and b) may be varied according to the usual pharmaceutical manufacturing procedures. 5. At any stage of the preparation process in a) or b) other pharmaceutically active compounds may be incorporated. c) Preparation of tablets with a content of diosgenin-β-D-glucoside. 1.250 g of diosgenin-β-D-glucoside are dissolved in 1 liter of chloroform and added with 900 g of lactose. The slurry is dried under reduced pressure and constant stirring at room temperature. Then the mixture is added with 2100 g of potato starch and stirred vigorously again. The impregnated lactose-starch mixture is added to 2500 ml of an aqueous solution of 250 g of gelatin and 5 g of glycerin and granulated in a manner known per se. The granules are dried under reduced pressure at room temperature.
Därefter pressas granulatet på i och för sig känt sätt till tabletter med en totalvikt av 400 mg. Varje tablett innehål- ler således 0,15 mg diosgenin-ß-D-glukosid, 110,56 mg laktos, 257,97 mg potatisstärkelse, 30,31 mg gelatin och 0,61 mg glycerin. d) Framställning av dragëer med en halt av hecogenin-ß-D- glukosid.The granules are then compressed in a manner known per se into tablets with a total weight of 400 mg. Thus, each tablet contains 0.15 mg of diosgenin-β-D-glucoside, 110.56 mg of lactose, 257.97 mg of potato starch, 30.31 mg of gelatin and 0.61 mg of glycerin. d) Preparation of dragees with a content of hecogenin-ß-D-glucoside.
En lösning av 450 mg hecogenin-B-D-glukosid i 2 liter kloro- form försättes med 1850 g laktos och 300 g sackaros. Upp- slamningen torkas vid 30°C under sänkt tryck och granulers därefter på i och för sig känt sätt genom tillsats av 1,6 liter av en vattenhaltig gelatinlösning med en halt av 40 g 9 466 685 gelatin. Granulatet torkas under sänkt tryck vid en tempera- tur av 45°C. Därefter blandas granulatet väl med 10 g magne- siumstearat. Den så framställda blandningen (2200 g) pressas till ca 3000 kärnor, som därefter överdrages med känt dragé- erförfarande med ett eventuellt färgat, tunt dragéeöverdrag.A solution of 450 mg of hecogenin B-D-glucoside in 2 liters of chloroform is added with 1850 g of lactose and 300 g of sucrose. The slurry is dried at 30 ° C under reduced pressure and then granulated in a manner known per se by adding 1.6 liters of an aqueous gelatin solution with a content of 40 g of gelatin. The granules are dried under reduced pressure at a temperature of 45 ° C. Then mix the granules well with 10 g of magnesium stearate. The mixture thus prepared (2200 g) is pressed into about 3000 cores, which are then coated by known dragee method with a possible colored, thin dragee coating.
Varje dragëe innehåller således 0,15 mg hecogenin-ß-D-gluko- sid, 616,67 mg laktos, 100,00 mg sackaros, 13,33 mg gelatin och 3,33 mg magnesiumstearat. e) Framställning av en salva med en halt av hecogenin-ß-D- glukosid. 1 g hecogenin-ß-D-glukosid inarbetas i 90 g emulgerande cetylstearylalkohol. Efter tillsats av 105 g tjockflytande paraffin och 105 g vit vaselin smältes på vattenbad vid 60°C.Thus, each dragee contains 0.15 mg of hecogenin-β-D-glucoside, 616.67 mg of lactose, 100.00 mg of sucrose, 13.33 mg of gelatin and 3.33 mg of magnesium stearate. e) Preparation of an ointment containing hecogenin-ß-D-glucoside content. 1 g of hecogenin-β-D-glucoside is incorporated into 90 g of emulsifying cetylstearyl alcohol. After adding 105 g of viscous paraffin and 105 g of white petroleum jelly, it was melted on a water bath at 60 ° C.
Smältan försättes med 699 g vatten i små satser vid ungefär samma temperatur. Blandningen omröres tills den kallnat, varvid man erhåller en salva med en halt av 0,1 % glukosid. f) Framställning av en kräm med en halt av tigogenin-ß-D- glukosid. 1 g tigogenin-ß-D-glukosid satsas i 500 g ullfettalkohol och värmes på vattenbad vid ca 50°C. Blandningen försättes där- efter med 499 g vatten av ca samma temperatur i små satser.The melt is added with 699 g of water in small batches at approximately the same temperature. The mixture is stirred until it has cooled, whereby an ointment with a content of 0.1% glucoside is obtained. f) Preparation of a cream with a content of tigogenin-ß-D-glucoside. 1 g of tigogenin-β-D-glucoside is charged into 500 g of wool fatty alcohol and heated on a water bath at about 50 ° C. The mixture is then added with 499 g of water of about the same temperature in small batches.
Krämen omröres tills den kallnat, varvid förångad vattenandel tillsättes. Krämen har en halt av 0,1 % glukosid.The cream is stirred until it has cooled, whereby evaporated water is added. The cream has a content of 0.1% glucoside.
Exempel 3 Farmakologisk undersökning av spiroketalsteroidglykosiderna.Example 3 Pharmacological examination of the spiroketal steroid glycosides.
Undersökning av spiroketalsteroidglykosidernas toxicitet.Investigation of the toxicity of spiroketal steroid glycosides.
Vid undersökning av akut toxicitet på råtta, mus, kanin, hund och primat kunde efter oral administrering av t ex sitoste- rol-B-D-glukosid även i doser om 1-2 g/kg kroppsvikt ingen toxisk effekt fastställas. Även vid administrering under en längre tidsperiod av dagliga doser om 100-200 mg/kg kropps- vikt kunde hos dessa djurspecies inga toxiska och inga gikt- liknande åkommor fastställas, så att fördragbarheten måste betecknas som god. 466 683 10 Exempel 4 Föreningarnas verkan som prostaglandinsyntetasinhibitor.When examining acute toxicity in rats, mice, rabbits, dogs and primates, no oral effect could be established after oral administration of, for example, sitosterol B-D glucoside, even at doses of 1-2 g / kg body weight. Even when administered over an extended period of daily doses of 100-200 mg / kg body weight, no toxic and no gout-like conditions could be established in these animal species, so that the tolerability must be described as good. Example 4 Activity of the compounds as prostaglandin synthetase inhibitor.
Föreningarnas verkan såsom prostaglandinsyntetasinhibitor påvisades med metoden enligt A.L.Willis under de försöksbe- Û tingelser, som beskrives t ex i Proceedings of a Workshop hållet under den åttonde europeiska reumatologikongressen i Helsingfors 1975.The action of the compounds as a prostaglandin synthetase inhibitor was demonstrated by the method of A.L. Willis under the experimental conditions described, for example, in the Proceedings of a Workshop held at the Eighth European Rheumatology Congress in Helsinki in 1975.
Silikoniserade kyvetter till en aggregometer användes såsom inkuberingskärl vid en temperatur av 37°C. I inkuberingskär- let försättes en arachidonatlösning snabbt med ett prostag- landinsyntetasenzymsystem, oftast framställt från fårblåsa, och omröres. Till denna lösning i kyvetten sättes därefter med antikoagulantia behandlad blodplätthaltig plasma, som också värmts till 37°C. Ljustransmissionen genom kyvetten bestämmes omedelbart efter tillsatsen. I kontrollproven visar sig efter 45 sekunders inkuberingstid en tydlig topp i blod- plättaggregationen som visar bildningen av prostaglandinerna PGE2 och PGF2a och den därigenom orsakade blodplättaggrega- tionen.Siliconized cuvettes for an aggregometer were used as incubators at a temperature of 37 ° C. In the incubation vessel, an arachidonate solution is rapidly added to a prostaglandin synthetase enzyme system, usually prepared from sheep bladder, and stirred. To this solution in the cuvette is then added anticoagulant-treated platelet-containing plasma, which is also heated to 37 ° C. The light transmission through the cuvette is determined immediately after the addition. In the control samples, after a 45 second incubation period, a clear peak in the platelet aggregation is shown, which shows the formation of the prostaglandins PGE2 and PGF2a and the platelet aggregation caused thereby.
I försöksproven med en tillsats av 0,00001 % sterolglykosider eller spiroketalsteroidglykosider uteblir aggregationen av blodplättarna. Detta visar tydligt att bildningen av pro- staglandinerna via endoperoxidföreningar från arachidonat inhiberas.In the experimental tests with an addition of 0.00001% sterol glycosides or spiroketal steroid glycosides, the aggregation of the platelets is absent. This clearly shows that the formation of prostaglandins via endoperoxide compounds from arachidonate is inhibited.
Exempel 5 Enligt nya rön spelar prostaglandinerna PGE och PGF a samt 2 2 endoperoxidförstegen av dessa föreningar en väsentlig roll vid utlösning av reumatoid artrit. I farmakologiska försök undersöktes därför verkan av de enligt uppfinningen insatta föreningarna såsom prostaglandinsyntetasinhibitorer.Example 5 According to new findings, the prostaglandins PGE and PGF α and the endoperoxide precursors of these compounds play a significant role in triggering rheumatoid arthritis. Therefore, in pharmacological experiments, the effect of the compounds used according to the invention as prostaglandin synthetase inhibitors was investigated.
Vid en jämförelse av artriten efter experimentell ros, t ex på råtta med reumatisk artrit hos människa kan en långtgående överensstämmelse av de enskilda morfologiska förändringarna iakttagas. Undersökningarna skedde enligt anvisningarna av 11 466 683 Schulz et al. Beitr. Path. 154, 1-26, 27-51 (1975). Den rosbetingade artriten hos råttor kan med nästan 100-procentig säkerhet reproduceras genom en engångsinjektion. Vid rosar- trit är alltid mer än 6 leder förändrade, nämligen stora och små extremitetleder med samma karaktär. Vid experimentell ros visar samtliga djur fortfarande efter 3 månader höggradiga proliferativa processer.In a comparison of arthritis after experimental rose, for example in rats with rheumatoid arthritis in humans, a far-reaching agreement of the individual morphological changes can be observed. The investigations were performed according to the instructions of Schulz et al. Beitr. Path. 154, 1-26, 27-51 (1975). The rose-related arthritis in rats can be reproduced with almost 100% certainty by a single injection. In arthritis, more than 6 joints are always altered, namely large and small extremity joints with the same character. In experimental rose, all animals still show high proliferative processes after 3 months.
För undersökning av substanserna användes från den fas, när symptom förekommer, följande parametrar för bedömning av preparatets verkan: Tassvolym Råttartriten kännetecknas kliniskt av ett höggradigt periar- tikulärt ödem hos djur med en kroppsvikt av 150 g redan från tredje dagen och vid en kroppsvikt av 200 g från femte dagen.For the examination of the substances, from that phase, when symptoms occur, the following parameters were used to assess the effect of the preparation: Paw volume Rat arthritis is clinically characterized by a high degree of periarticular edema in animals with a body weight of 150 g from the third day and at a body weight of 200 g from the fifth day.
Njurar (äggviteutsöndring) Genom mikrotromber betingade nefroser kan uppträda hos ca 30-40 % av djuren på sjunde - åttonde dagen. Ögon Inflammationer (grumlingar) i kornea på ungefär åttonde dagen.Kidneys (egg white secretion) Necrosis caused by microtombosis can occur in about 30-40% of the animals on the seventh - eighth day. Eyes Inflammations (clouding) of the cornea at about the eighth day.
Yttre könsorganen, svansspetsen Av tromber betingade nekroser från sjätte - åttonde dagen. êeššâ Mellan sjätte och elfte dagen uppträder fibrinrika tromber i aorta intima hos råttorna. Den största ytutbredningen sker på ca åttonde dagen.External genitals, the tip of the tail Necrosis caused by thrombi from the sixth to the eighth day. êeššâ Between the sixth and eleventh day, fibrin-rich thrombi occur intimately in the rats of the rats. The largest surface area occurs on about the eighth day.
För undersökningen användes Wistar-råttor av hankön med en vikt mellan 150 och 180 g. Djuren hölls i enskilda burar och fick standarddiet för råttor (Ssniff R) och vatten ad libi- tum. 466 683 12 Rumstemperaturen var konstant 22°C, och den relativa luft- fuktigheten mellan 50 och 60 %. Den dagliga belysningstiden utgjorde 12 timmar. Innan testet startade hade djuren en acklimationstid av 10 dagar.For the study, male Wistar rats weighing between 150 and 180 g were used. The animals were kept in individual cages and given the standard diet for rats (Ssniff R) and water ad libitum. 466 683 12 The room temperature was constant 22 ° C, and the relative humidity between 50 and 60%. The daily lighting time was 12 hours. Before the test started, the animals had an acclimation time of 10 days.
Infektionen skedde med rosstam T28. Doseringen utgjorde 2 ml subkutant (ca 100-200 miljoner mikroorganismer). De före- ningar, som skulle undersökas, suspenderas i steril fysiolo- gisk koksaltlösning och gavs i en dosering om 5 mg/kg in- traperitonealt. Behandlingen skedde från infektionsdagen till försökets slut eller tills djuren dog 5 gånger per vecka.The infection occurred with rosstam T28. The dosage was 2 ml subcutaneously (approximately 100-200 million microorganisms). The compounds to be tested are suspended in sterile physiological saline and given at a dose of 5 mg / kg intraperitoneally. The treatment took place from the day of infection until the end of the experiment or until the animals died 5 times a week.
Vid utvärderingen av de karakteristiska aortatromberna er- hölls följande värden: kontrollprov: antal punkter 2,80 hecogeninglukosid: 1,38 diosgeninglukosid: 1,33In the evaluation of the characteristic aortic thrombi, the following values were obtained: control sample: number of points 2.80 hecogenic glucoside: 1.38 diosgenic glucoside: 1.33
Claims (4)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19772759171 DE2759171A1 (en) | 1977-12-31 | 1977-12-31 | MEDICINAL PRODUCTS WITH EFFECT AS PROSTAGLANDIN SYNTHETASE INHIBITOR |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| SE7813443L SE7813443L (en) | 1979-07-01 |
| SE466683B true SE466683B (en) | 1992-03-23 |
Family
ID=6027873
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SE7813443A SE466683B (en) | 1977-12-31 | 1978-12-29 | SPIROKETAL STEROID GLYCOSIDES AND / OR ESTARS THEREOF TO USE AS A MEDICINE |
Country Status (19)
| Country | Link |
|---|---|
| JP (1) | JPS54101436A (en) |
| AR (1) | AR223334A1 (en) |
| AU (1) | AU516933B2 (en) |
| BE (1) | BE873222A (en) |
| CA (1) | CA1113006A (en) |
| CH (1) | CH637829A5 (en) |
| DE (1) | DE2759171A1 (en) |
| DK (1) | DK587778A (en) |
| ES (1) | ES476443A1 (en) |
| FR (1) | FR2425859A1 (en) |
| GB (1) | GB2039217B (en) |
| IL (1) | IL56345A (en) |
| IT (1) | IT1109336B (en) |
| LU (1) | LU80739A1 (en) |
| NL (1) | NL7812656A (en) |
| NZ (1) | NZ189297A (en) |
| PT (1) | PT69012A (en) |
| SE (1) | SE466683B (en) |
| ZA (1) | ZA787399B (en) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2926463A1 (en) * | 1978-07-05 | 1980-01-24 | Roecar Holdings Nv | SPIROKETALINE AND THEIR USE |
| JPS5874619A (en) * | 1981-10-29 | 1983-05-06 | Nippon Shinyaku Co Ltd | Liposome and its preparation |
| CA1209912A (en) | 1982-04-19 | 1986-08-19 | Siegfrid Drewes | Extract of plants of the family of hypoxidaceae for treatment of cancer |
| US4602005A (en) * | 1982-05-17 | 1986-07-22 | Medical Research Foundation Of Oregon | Tigogenin cellobioside for treating hypercholesterolemia and atherosclerosis |
| US4602003A (en) * | 1982-05-17 | 1986-07-22 | Medical Research Foundation Of Oregon | Synthetic compounds to inhibit intestinal absorption of cholesterol in the treatment of hypercholesterolemia |
| DE3401178A1 (en) * | 1984-01-14 | 1985-07-18 | Roecar Holdings (Netherlands Antilles) N.V., Willemstad, Curacao, Niederländische Antillen | USE OF PHYTOSTEROL GLYCOSIDES FOR TREATING INCREASED 5 (6) (ALPHA) EPOXICHOLESTEROL LEVELS |
| DE3416112A1 (en) * | 1984-04-30 | 1985-10-31 | Roecar Holdings (Netherlands Antilles) N.V., Willemstad, Curacao, Niederländische Antillen | USE OF STEROLINES AND SPIROKETALINES AS LIPOXYGENAS REGULATORS |
| DE3829643A1 (en) * | 1988-09-01 | 1990-03-15 | Roecar Holdings Nv | PHYTO AND ZOOSTEROLS AND THEIR DERIVATIVES WITH IMPROVED WATER SOLUBILITY |
| DE3829641A1 (en) * | 1988-09-01 | 1990-03-15 | Roecar Holdings Nv | TRANSDERMAL APPLICABLE PHARMACEUTICAL PREPARATIONS WITH STEROLINES AND / OR SPIROKETALINES |
| DE3829640C1 (en) * | 1988-09-01 | 1990-04-26 | Roecar Holdings (Netherlands Antilles) N.V., Willemstad, Curacao, Niederlaendische Antillen, Nl | |
| US5166194A (en) * | 1988-09-01 | 1992-11-24 | Roecar Holdings | Transdermally applicable pharmaceutical preparations having a pharmaceutically usable glycoside content |
| DE3838716A1 (en) * | 1988-11-15 | 1990-05-17 | Kanoldt Arzneimittel Gmbh | MEDICINAL PRODUCTION OF ESTER DERIVATIVES OF HECOGENINE AND ITS USE FOR THE TREATMENT OF BENIGNER PROSTATE HYPERPLASIA |
| US5502038A (en) * | 1993-06-21 | 1996-03-26 | Medical Research Foundation Of Oregon | Cholesterol sequestrant glycosides that inhibit intestinal cholesterol absorption |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IE35018B1 (en) * | 1970-03-18 | 1975-10-15 | Liebenberg R W | Therapeutic agent |
| US3966918A (en) * | 1973-12-12 | 1976-06-29 | Nippon Shinyaku Co., Ltd. | Method of preparing aqueous solutions of sterol glycosides and their ester derivatives |
| JPS51118817A (en) * | 1975-04-08 | 1976-10-19 | Nippon Shinyaku Co Ltd | A process for preparing absorbable steroid glycoside pharmaceutical |
-
1977
- 1977-12-31 DE DE19772759171 patent/DE2759171A1/en active Granted
-
1978
- 1978-12-28 ZA ZA787399A patent/ZA787399B/en unknown
- 1978-12-28 ES ES476443A patent/ES476443A1/en not_active Expired
- 1978-12-28 AR AR274988A patent/AR223334A1/en active
- 1978-12-29 FR FR7836823A patent/FR2425859A1/en active Granted
- 1978-12-29 IT IT52493/78A patent/IT1109336B/en active
- 1978-12-29 BE BE192687A patent/BE873222A/en not_active IP Right Cessation
- 1978-12-29 LU LU80739A patent/LU80739A1/en unknown
- 1978-12-29 AU AU43024/78A patent/AU516933B2/en not_active Expired
- 1978-12-29 IL IL56345A patent/IL56345A/en not_active IP Right Cessation
- 1978-12-29 PT PT69012A patent/PT69012A/en unknown
- 1978-12-29 CA CA318,817A patent/CA1113006A/en not_active Expired
- 1978-12-29 SE SE7813443A patent/SE466683B/en not_active IP Right Cessation
- 1978-12-29 NL NL7812656A patent/NL7812656A/en not_active Application Discontinuation
- 1978-12-29 GB GB7850259A patent/GB2039217B/en not_active Expired
- 1978-12-29 DK DK587778A patent/DK587778A/en not_active Application Discontinuation
- 1978-12-29 JP JP16443078A patent/JPS54101436A/en active Pending
- 1978-12-29 CH CH1330878A patent/CH637829A5/en not_active IP Right Cessation
-
1979
- 1979-01-04 NZ NZ189297A patent/NZ189297A/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| DE2759171A1 (en) | 1979-07-12 |
| IT7852493A0 (en) | 1978-12-29 |
| SE7813443L (en) | 1979-07-01 |
| CA1113006A (en) | 1981-11-24 |
| NL7812656A (en) | 1979-07-03 |
| IT1109336B (en) | 1985-12-16 |
| ES476443A1 (en) | 1979-10-16 |
| JPS54101436A (en) | 1979-08-10 |
| NZ189297A (en) | 1984-10-19 |
| PT69012A (en) | 1979-01-01 |
| DK587778A (en) | 1979-07-01 |
| BE873222A (en) | 1979-06-29 |
| FR2425859B1 (en) | 1983-04-08 |
| GB2039217B (en) | 1982-08-04 |
| CH637829A5 (en) | 1983-08-31 |
| FR2425859A1 (en) | 1979-12-14 |
| LU80739A1 (en) | 1980-01-22 |
| AU4302478A (en) | 1979-07-05 |
| IL56345A (en) | 1984-11-30 |
| AR223334A1 (en) | 1981-08-14 |
| ZA787399B (en) | 1980-01-30 |
| AU516933B2 (en) | 1981-07-02 |
| GB2039217A (en) | 1980-08-06 |
| IL56345A0 (en) | 1979-03-12 |
| DE2759171C2 (en) | 1990-10-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US4260603A (en) | Sterol glycoside with activity as prostaglandin synthetase inhibitor | |
| EP0058665B1 (en) | Carbohydrate derivatives for inhibiting bacterial adherence | |
| JPS60224697A (en) | Tigogenin serobioside and medicine | |
| SE466683B (en) | SPIROKETAL STEROID GLYCOSIDES AND / OR ESTARS THEREOF TO USE AS A MEDICINE | |
| US4117121A (en) | Method of increasing bile flow and decreasing lipid levels | |
| CA1090702A (en) | Sterolins and their use | |
| US4265886A (en) | Spiroketalins and their applications | |
| JPS6056920A (en) | Reduction of lipid level | |
| JP2022517743A (en) | Acetylsalicylic acid derivatives and their use | |
| KR830000630B1 (en) | Process for preparing spiroketal-steroid glycosides | |
| GB2024624A (en) | Anti inflammatory spiroketalins | |
| JPS5843385B2 (en) | Medicinal ingredients of freshwater clam and its manufacturing method | |
| US4482540A (en) | Method for treating hypercholesterolemia with endomycin | |
| US4039659A (en) | Method for treating hypercholesterolemia with levorin | |
| US3627879A (en) | Method for treating hypercholesterolemia | |
| US3855409A (en) | Method for treating hypercholesterolemia | |
| Wallace | The treatment of the acute attack of gout | |
| US3966910A (en) | Method for treating hypercholesterolemia with mediocidin | |
| US4067966A (en) | Method of treating hypercholesterolemia with antibiotic SCH-16656 | |
| US4292310A (en) | Method of treating hypercholesterolemia with n-acyl amphotericin B | |
| US3714348A (en) | Method for controlling absorption of cholesterol | |
| DE19925810A1 (en) | Use of verapamil and verapamil derivatives for the manufacture of medicinal products with glucuronidase inhibitory activity | |
| US4692334A (en) | Method for treating hypercholesterolemia with cryptocidin | |
| WO2000047594A1 (en) | Novel gymnemic acid derivatives, process for the preparation thereof and use thereof as medicine | |
| US3966911A (en) | Method for treating hypercholesterolemia with N-acetyl candicidin |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| NUG | Patent has lapsed |
Ref document number: 7813443-4 Effective date: 19930709 Format of ref document f/p: F |