ZA200609596B - Crystalline and amorphous forms of smilagenin - Google Patents
Crystalline and amorphous forms of smilagenin Download PDFInfo
- Publication number
- ZA200609596B ZA200609596B ZA200609596A ZA200609596A ZA200609596B ZA 200609596 B ZA200609596 B ZA 200609596B ZA 200609596 A ZA200609596 A ZA 200609596A ZA 200609596 A ZA200609596 A ZA 200609596A ZA 200609596 B ZA200609596 B ZA 200609596B
- Authority
- ZA
- South Africa
- Prior art keywords
- smilagenin
- crystalline
- crystalline form
- examples
- accompanying drawings
- Prior art date
Links
- GMBQZIIUCVWOCD-UQHLGXRBSA-N (25R)-5beta-spirostan-3beta-ol 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-UQHLGXRBSA-N 0.000 title claims description 427
- RTMWIZOXNKJHRE-UHFFFAOYSA-N Tigogenin Natural products CC1COC2CC(C)(OC12)C3CCC4C5CCC6CC(O)CCC6(C)C5CCC34C RTMWIZOXNKJHRE-UHFFFAOYSA-N 0.000 title claims description 216
- 229950002323 smilagenin Drugs 0.000 title claims description 214
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 92
- 239000000463 material Substances 0.000 claims description 70
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 56
- 238000000034 method Methods 0.000 claims description 42
- 239000012453 solvate Substances 0.000 claims description 32
- 229960004592 isopropanol Drugs 0.000 claims description 31
- 239000000203 mixture Substances 0.000 claims description 30
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 29
- 239000013078 crystal Substances 0.000 claims description 26
- 239000003814 drug Substances 0.000 claims description 16
- -1 Smilagenin monohydrate Chemical class 0.000 claims description 15
- 235000013361 beverage Nutrition 0.000 claims description 14
- 239000007787 solid Substances 0.000 claims description 14
- 230000001149 cognitive effect Effects 0.000 claims description 12
- 238000002425 crystallisation Methods 0.000 claims description 10
- 235000015872 dietary supplement Nutrition 0.000 claims description 9
- 239000003960 organic solvent Substances 0.000 claims description 9
- 238000001556 precipitation Methods 0.000 claims description 9
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims description 8
- 230000008569 process Effects 0.000 claims description 8
- 208000008589 Obesity Diseases 0.000 claims description 7
- 230000002232 neuromuscular Effects 0.000 claims description 7
- 235000020824 obesity Nutrition 0.000 claims description 7
- 230000036571 hydration Effects 0.000 claims description 6
- 238000006703 hydration reaction Methods 0.000 claims description 6
- 230000004770 neurodegeneration Effects 0.000 claims description 6
- 239000003791 organic solvent mixture Substances 0.000 claims description 6
- 239000000651 prodrug Substances 0.000 claims description 6
- 229940002612 prodrug Drugs 0.000 claims description 6
- 239000011149 active material Substances 0.000 claims description 5
- 208000010877 cognitive disease Diseases 0.000 claims description 5
- 239000007788 liquid Substances 0.000 claims description 5
- 239000002002 slurry Substances 0.000 claims description 5
- 238000011282 treatment Methods 0.000 claims description 5
- INLFWQCRAJUDCR-IQVMEADQSA-N (1R,2S,4S,5'S,6R,7S,8R,9S,12S,13S)-5',7,9,13-tetramethylspiro[5-oxapentacyclo[10.8.0.02,9.04,8.013,18]icosane-6,2'-oxane] Chemical compound O([C@@H]1[C@@H]([C@]2(CC[C@@H]3[C@@]4(C)CCCCC4CC[C@H]3[C@@H]2C1)C)[C@@H]1C)[C@]11CC[C@H](C)CO1 INLFWQCRAJUDCR-IQVMEADQSA-N 0.000 claims description 4
- 239000008280 blood Substances 0.000 claims description 4
- 210000004369 blood Anatomy 0.000 claims description 4
- 230000006735 deficit Effects 0.000 claims description 4
- 230000007850 degeneration Effects 0.000 claims description 4
- 206010012601 diabetes mellitus Diseases 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 230000001537 neural effect Effects 0.000 claims description 4
- 208000011580 syndromic disease Diseases 0.000 claims description 4
- 238000010533 azeotropic distillation Methods 0.000 claims description 3
- 230000003637 steroidlike Effects 0.000 claims description 3
- 150000004683 dihydrates Chemical class 0.000 claims description 2
- 229930002600 steroidal saponin Natural products 0.000 claims description 2
- 241001465754 Metazoa Species 0.000 claims 1
- 239000011877 solvent mixture Substances 0.000 claims 1
- 238000000634 powder X-ray diffraction Methods 0.000 description 59
- 239000002904 solvent Substances 0.000 description 21
- 238000000113 differential scanning calorimetry Methods 0.000 description 18
- 238000002844 melting Methods 0.000 description 17
- 230000008018 melting Effects 0.000 description 17
- 238000002411 thermogravimetry Methods 0.000 description 17
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
- 150000001875 compounds Chemical class 0.000 description 12
- 230000001404 mediated effect Effects 0.000 description 11
- 230000009466 transformation Effects 0.000 description 11
- 150000003839 salts Chemical class 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 238000001914 filtration Methods 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- 238000001953 recrystallisation Methods 0.000 description 9
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- 238000002050 diffraction method Methods 0.000 description 8
- 150000004682 monohydrates Chemical class 0.000 description 8
- 238000003109 Karl Fischer titration Methods 0.000 description 7
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- 238000011160 research Methods 0.000 description 6
- 239000002585 base Substances 0.000 description 5
- 230000007704 transition Effects 0.000 description 5
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 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 description 4
- 239000002253 acid Substances 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- 238000000844 transformation Methods 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 239000013543 active substance Substances 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 239000001397 quillaja saponaria molina bark Substances 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 229930182490 saponin Natural products 0.000 description 3
- 235000017709 saponins Nutrition 0.000 description 3
- 238000001179 sorption measurement Methods 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000007416 differential thermogravimetric analysis Methods 0.000 description 2
- WQLVFSAGQJTQCK-UHFFFAOYSA-N diosgenin Natural products CC1C(C2(CCC3C4(C)CCC(O)CC4=CCC3C2C2)C)C2OC11CCC(C)CO1 WQLVFSAGQJTQCK-UHFFFAOYSA-N 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 150000004677 hydrates Chemical class 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 238000010899 nucleation Methods 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 150000002894 organic compounds Chemical class 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 150000007949 saponins Chemical class 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 239000011800 void material Substances 0.000 description 2
- GWYFCOCPABKNJV-UHFFFAOYSA-M 3-Methylbutanoic acid Natural products CC(C)CC([O-])=O GWYFCOCPABKNJV-UHFFFAOYSA-M 0.000 description 1
- 240000004246 Agave americana Species 0.000 description 1
- DHMQDGOQFOQNFH-UHFFFAOYSA-M Aminoacetate Chemical compound NCC([O-])=O DHMQDGOQFOQNFH-UHFFFAOYSA-M 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
- 241000219748 Cyamopsis Species 0.000 description 1
- 235000005903 Dioscorea Nutrition 0.000 description 1
- 244000281702 Dioscorea villosa Species 0.000 description 1
- 235000000504 Dioscorea villosa Nutrition 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 239000001653 FEMA 3120 Substances 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- 241000219823 Medicago Species 0.000 description 1
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 1
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 1
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical class O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 241001092473 Quillaja Species 0.000 description 1
- 235000009001 Quillaja saponaria Nutrition 0.000 description 1
- DWCSNWXARWMZTG-UHFFFAOYSA-N Trigonegenin A Natural products CC1C(C2(CCC3C4(C)CCC(O)C=C4CCC3C2C2)C)C2OC11CCC(C)CO1 DWCSNWXARWMZTG-UHFFFAOYSA-N 0.000 description 1
- 241001532059 Yucca Species 0.000 description 1
- 235000004552 Yucca aloifolia Nutrition 0.000 description 1
- 235000012044 Yucca brevifolia Nutrition 0.000 description 1
- 235000017049 Yucca glauca Nutrition 0.000 description 1
- IPBVNPXQWQGGJP-UHFFFAOYSA-N acetic acid phenyl ester Natural products CC(=O)OC1=CC=CC=C1 IPBVNPXQWQGGJP-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- QNAYBMKLOCPYGJ-UHFFFAOYSA-M alaninate Chemical compound CC(N)C([O-])=O QNAYBMKLOCPYGJ-UHFFFAOYSA-M 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-M argininate Chemical compound [O-]C(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-M 0.000 description 1
- 229940009098 aspartate Drugs 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 229940114081 cinnamate Drugs 0.000 description 1
- 239000002178 crystalline material Substances 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-L cysteinate(2-) Chemical compound [S-]CC(N)C([O-])=O XUJNEKJLAYXESH-UHFFFAOYSA-L 0.000 description 1
- GHVNFZFCNZKVNT-UHFFFAOYSA-N decanoic acid Chemical compound CCCCCCCCCC(O)=O GHVNFZFCNZKVNT-UHFFFAOYSA-N 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 235000004879 dioscorea Nutrition 0.000 description 1
- 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 description 1
- POULHZVOKOAJMA-UHFFFAOYSA-M dodecanoate Chemical compound CCCCCCCCCCCC([O-])=O POULHZVOKOAJMA-UHFFFAOYSA-M 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 229940126534 drug product Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical compound [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-M glutaminate Chemical compound [O-]C(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-M 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-M hexanoate Chemical compound CCCCCC([O-])=O FUZZWVXGSFPDMH-UHFFFAOYSA-M 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- FGKJLKRYENPLQH-UHFFFAOYSA-M isocaproate Chemical compound CC(C)CCC([O-])=O FGKJLKRYENPLQH-UHFFFAOYSA-M 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 238000006317 isomerization reaction Methods 0.000 description 1
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 1
- 229940011051 isopropyl acetate Drugs 0.000 description 1
- 229940070765 laurate Drugs 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-M lysinate Chemical compound NCCCCC(N)C([O-])=O KDXKERNSBIXSRK-UHFFFAOYSA-M 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 150000002688 maleic acid derivatives Chemical class 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- FFEARJCKVFRZRR-UHFFFAOYSA-M methioninate Chemical compound CSCCC(N)C([O-])=O FFEARJCKVFRZRR-UHFFFAOYSA-M 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 229940043265 methyl isobutyl ketone Drugs 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229940105132 myristate Drugs 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 230000006911 nucleation Effects 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- WWZKQHOCKIZLMA-UHFFFAOYSA-M octanoate Chemical compound CCCCCCCC([O-])=O WWZKQHOCKIZLMA-UHFFFAOYSA-M 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- DYUMLJSJISTVPV-UHFFFAOYSA-N phenyl propanoate Chemical compound CCC(=O)OC1=CC=CC=C1 DYUMLJSJISTVPV-UHFFFAOYSA-N 0.000 description 1
- 229940049953 phenylacetate Drugs 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-M phenylalaninate Chemical compound [O-]C(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-M 0.000 description 1
- 125000001557 phthalyl group Chemical group C(=O)(O)C1=C(C(=O)*)C=CC=C1 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-M prolinate Chemical compound [O-]C(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-M 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 239000013557 residual solvent Substances 0.000 description 1
- NWMIYTWHUDFRPL-UHFFFAOYSA-N sapogenin Natural products COC(=O)C1(CO)C(O)CCC2(C)C1CCC3(C)C2CC=C4C5C(C)(O)C(C)CCC5(CCC34C)C(=O)O NWMIYTWHUDFRPL-UHFFFAOYSA-N 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-M serinate Chemical compound OCC(N)C([O-])=O MTCFGRXMJLQNBG-UHFFFAOYSA-M 0.000 description 1
- LVRAKYNQYKVPIK-BSPYNPCNSA-N smilagenin acetate Chemical compound O([C@@H]1[C@@H]([C@]2(CC[C@@H]3[C@@]4(C)CC[C@@H](C[C@H]4CC[C@H]3[C@@H]2C1)OC(C)=O)C)[C@@H]1C)[C@]11CC[C@@H](C)CO1 LVRAKYNQYKVPIK-BSPYNPCNSA-N 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- TUNFSRHWOTWDNC-UHFFFAOYSA-N tetradecanoic acid Chemical compound CCCCCCCCCCCCCC(O)=O TUNFSRHWOTWDNC-UHFFFAOYSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- WBYWAXJHAXSJNI-VOTSOKGWSA-M trans-cinnamate Chemical compound [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-M tryptophanate Chemical compound C1=CC=C2C(CC(N)C([O-])=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-M 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-L tyrosinate(2-) Chemical compound [O-]C(=O)C(N)CC1=CC=C([O-])C=C1 OUYCCCASQSFEME-UHFFFAOYSA-L 0.000 description 1
- 229940070710 valerate Drugs 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-M valinate Chemical compound CC(C)C(N)C([O-])=O KZSNJWFQEVHDMF-UHFFFAOYSA-M 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J71/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton is condensed with a heterocyclic ring
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Neurology (AREA)
- Diabetes (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Obesity (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Hematology (AREA)
- Rheumatology (AREA)
- Psychology (AREA)
- Psychiatry (AREA)
- Child & Adolescent Psychology (AREA)
- Hospice & Palliative Care (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Steroid Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0409567.5A GB0409567D0 (en) | 2004-04-28 | 2004-04-28 | Chemical compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA200609596B true ZA200609596B (en) | 2008-01-30 |
Family
ID=32408243
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200609596A ZA200609596B (en) | 2004-04-28 | 2006-11-17 | Crystalline and amorphous forms of smilagenin |
Country Status (17)
| Country | Link |
|---|---|
| US (2) | US20080004249A1 (ja) |
| EP (2) | EP2402362A2 (ja) |
| JP (1) | JP2007534736A (ja) |
| KR (1) | KR20070028387A (ja) |
| CN (2) | CN102516352A (ja) |
| AU (1) | AU2005238274A1 (ja) |
| BR (1) | BRPI0510458A (ja) |
| CA (1) | CA2564368A1 (ja) |
| GB (1) | GB0409567D0 (ja) |
| IL (1) | IL178870A0 (ja) |
| MX (1) | MXPA06012641A (ja) |
| NO (1) | NO20065485L (ja) |
| RU (1) | RU2006141389A (ja) |
| SG (1) | SG155165A1 (ja) |
| TW (1) | TW200538145A (ja) |
| WO (1) | WO2005105825A2 (ja) |
| ZA (1) | ZA200609596B (ja) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MX2011007842A (es) | 2009-01-24 | 2012-01-12 | Phytopharm Plc | Tratamiento de trastornos mediados por factores neurotroficos. |
| US20130210786A1 (en) | 2010-07-20 | 2013-08-15 | Patrick Alexander Howson | Treatment of l-dopa, dopamine agonist and/or dopamine enhancer induced disorders |
Family Cites Families (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NL292786A (ja) * | 1962-05-15 | |||
| US3169959A (en) * | 1963-07-23 | 1965-02-16 | Intermediates Inc | Method of obtaining smilagenin |
| CA985172A (en) | 1972-10-06 | 1976-03-09 | Dushan M. Dvornik | Compositions and methods for reducing blood cholesterol |
| 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 |
| US4680289A (en) | 1985-06-05 | 1987-07-14 | Progenics, Inc. | Treatment of obesity and diabetes using sapogenins |
| US5017562A (en) * | 1987-02-11 | 1991-05-21 | Regents Of The University Of Minnesota | Crystalline saponin-containing complex |
| KR20070117001A (ko) * | 1998-03-26 | 2007-12-11 | 파이토팜 피엘씨 | 알츠하이머병을 치료하기 위한 스밀라게닌 및안주로게닌-ｄ |
| GB9923076D0 (en) | 1999-09-29 | 1999-12-01 | Phytopharm Plc | Sapogenin derivatives and their use |
| GB9905275D0 (en) | 1999-03-08 | 1999-04-28 | Phytopharm Ltd | Treatment of conditions associated with membrane-bound receptors and their function |
| GB9923078D0 (en) | 1999-09-29 | 1999-12-01 | Phytopharm Plc | Sapogenin derivatives and their use |
| GB9923077D0 (en) | 1999-09-29 | 1999-12-01 | Phytopharm Plc | Sapogenin derivatives and their use |
| GB0000228D0 (en) | 2000-01-06 | 2000-03-01 | Phytopharm Plc | Fluoro substituted sapogenins and their use |
| AT409100B (de) | 2000-07-24 | 2002-05-27 | Evg Entwicklung Verwert Ges | Vorrichtung zum schweissen einer drahtgittermatte |
| GB0107822D0 (en) | 2001-03-28 | 2001-05-23 | Phytopharm Plc | Sapogenin derivatives their synthesis and use methods based upon their use |
| KR20100093621A (ko) | 2002-03-27 | 2010-08-25 | 파이토팜 피엘씨 | 사포게닌 및 그 유도체의 치료 방법 및 용도 |
| US7718792B2 (en) | 2002-10-28 | 2010-05-18 | Phytopharm Plc | Stereospecific reduction of sapogen-3-ones |
-
2004
- 2004-04-28 GB GBGB0409567.5A patent/GB0409567D0/en not_active Ceased
-
2005
- 2005-04-28 EP EP11155898A patent/EP2402362A2/en not_active Withdrawn
- 2005-04-28 SG SG200905023-8A patent/SG155165A1/en unknown
- 2005-04-28 AU AU2005238274A patent/AU2005238274A1/en not_active Abandoned
- 2005-04-28 CN CN2011103029008A patent/CN102516352A/zh active Pending
- 2005-04-28 BR BRPI0510458-0A patent/BRPI0510458A/pt not_active IP Right Cessation
- 2005-04-28 JP JP2007510116A patent/JP2007534736A/ja active Pending
- 2005-04-28 US US11/587,738 patent/US20080004249A1/en not_active Abandoned
- 2005-04-28 CN CNA2005800133676A patent/CN101076539A/zh active Pending
- 2005-04-28 KR KR1020067024949A patent/KR20070028387A/ko not_active Application Discontinuation
- 2005-04-28 WO PCT/GB2005/001635 patent/WO2005105825A2/en active Application Filing
- 2005-04-28 TW TW094113668A patent/TW200538145A/zh unknown
- 2005-04-28 RU RU2006141389/04A patent/RU2006141389A/ru not_active Application Discontinuation
- 2005-04-28 EP EP05738225A patent/EP1742960A2/en not_active Withdrawn
- 2005-04-28 MX MXPA06012641A patent/MXPA06012641A/es unknown
- 2005-04-28 CA CA002564368A patent/CA2564368A1/en not_active Abandoned
-
2006
- 2006-10-26 IL IL178870A patent/IL178870A0/en unknown
- 2006-11-17 ZA ZA200609596A patent/ZA200609596B/en unknown
- 2006-11-28 NO NO20065485A patent/NO20065485L/no not_active Application Discontinuation
-
2011
- 2011-02-22 US US13/032,548 patent/US20110144323A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| EP1742960A2 (en) | 2007-01-17 |
| RU2006141389A (ru) | 2008-06-10 |
| CA2564368A1 (en) | 2005-11-10 |
| CN101076539A (zh) | 2007-11-21 |
| WO2005105825A3 (en) | 2006-02-23 |
| KR20070028387A (ko) | 2007-03-12 |
| US20110144323A1 (en) | 2011-06-16 |
| EP2402362A2 (en) | 2012-01-04 |
| JP2007534736A (ja) | 2007-11-29 |
| WO2005105825A2 (en) | 2005-11-10 |
| NO20065485L (no) | 2007-01-29 |
| GB0409567D0 (en) | 2004-06-02 |
| SG155165A1 (en) | 2009-09-30 |
| IL178870A0 (en) | 2007-03-08 |
| US20080004249A1 (en) | 2008-01-03 |
| AU2005238274A1 (en) | 2005-11-10 |
| CN102516352A (zh) | 2012-06-27 |
| MXPA06012641A (es) | 2006-12-15 |
| TW200538145A (en) | 2005-12-01 |
| BRPI0510458A (pt) | 2007-10-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP3248983B1 (en) | Crystal form a of obeticholic acid and preparation method therefor | |
| US8158780B2 (en) | Processes for the preparation of ciclesonide and its crystal modification | |
| EP3337485B1 (en) | Crystalline forms of ibrutinib | |
| BRPI0618081A2 (pt) | composto, mistura ou composição de formas cristalinas do ácido fusìdico, mistura ou formulação, uso de um composto, método para preparar um composto, e, composição farmacêutica | |
| CA2001938A1 (en) | Estrogen nucleus derivatives for use in the inhibition of sex steroid activity | |
| US20110144323A1 (en) | Amorphous and crystalline forms of smilagenin and its hydrates | |
| EP2262823B1 (en) | Process for the preparation of pregnane derivatives | |
| WO2016127876A1 (zh) | 一种丙酸阿比特龙的晶型及其制备方法 | |
| EP2479183A2 (en) | Polymorphs of sarsasapogenin | |
| IL291468A (en) | A process for the preparation of cortexolone 17alpha-propionate and its new crystalline hydrate | |
| FI56968B (fi) | Foerfarande foer framstaellning av hoegren kristallisk kenodesoxicholsyra | |
| KR900006219B1 (ko) | 2-옥사-또는-아자-프레그난 화합물의 제조방법 | |
| WO2022166774A1 (zh) | 3-羟基-5-孕烷-20-酮衍生物的晶型及其制备方法和用途 | |
| AU2016210812A1 (en) | Crystalline form of S-(4-(3-fluoro-3-methylbutyryloxy)but-2-ynyl)6alpha, 9alpha -difluoro-17alpha,-(furan-2-yl)carbonyloxy-11beta-hydroxy-16alpha-methy1-3-oxoandrosta-1,4-diene-17beta-carbothioate | |
| CA3223165A1 (en) | Novel inhibitors of 17.beta.-hsd7 and uses thereof | |
| EP1630167A1 (en) | Polymorphs of 19-Nor steroid derivatives | |
| JP2021500359A (ja) | 選択的プロゲステロンの受容体モジュレーターの結晶形およびその製造方法 | |
| CN117024503A (zh) | 蟾毒灵磷酸酯衍生物及其药物组合物和制剂及应用 | |
| WO2016142582A1 (en) | Process for the preparation of crystalline salmeterol and its xinafoate salt |