TW201300112A - 組成物及其方法 - Google Patents
組成物及其方法 Download PDFInfo
- Publication number
- TW201300112A TW201300112A TW100129711A TW100129711A TW201300112A TW 201300112 A TW201300112 A TW 201300112A TW 100129711 A TW100129711 A TW 100129711A TW 100129711 A TW100129711 A TW 100129711A TW 201300112 A TW201300112 A TW 201300112A
- Authority
- TW
- Taiwan
- Prior art keywords
- composition
- fenugreek
- saponin
- vetchin
- group
- Prior art date
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 116
- 238000000034 method Methods 0.000 title claims abstract description 51
- 244000250129 Trigonella foenum graecum Species 0.000 claims abstract description 105
- 235000001484 Trigonella foenum graecum Nutrition 0.000 claims abstract description 102
- 235000001019 trigonella foenum-graecum Nutrition 0.000 claims abstract description 102
- 238000011282 treatment Methods 0.000 claims abstract description 41
- 206010039073 rheumatoid arthritis Diseases 0.000 claims abstract description 26
- 206010018364 Glomerulonephritis Diseases 0.000 claims abstract description 24
- 201000000596 systemic lupus erythematosus Diseases 0.000 claims abstract description 24
- 208000024869 Goodpasture syndrome Diseases 0.000 claims abstract description 5
- TVNGRDSDHVARNR-SYQAKRSCSA-N (2R,3R,4S,5S,6R)-2-[(2R)-4-[(1R,2S,4S,6R,7S,8R,9S,12S,13S,15R,16R,18S)-6,15-dihydroxy-7,9,13-trimethyl-16-[(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-[[(2S,3R,4S,5R)-3,4,5-trihydroxyoxan-2-yl]oxymethyl]oxan-2-yl]oxy-5-oxapentacyclo[10.8.0.02,9.04,8.013,18]icosan-6-yl]-2-methylbutoxy]-6-(hydroxymethyl)oxane-3,4,5-triol Chemical compound C[C@H](CC[C@@]1(O)O[C@H]2C[C@H]3[C@@H]4CC[C@H]5C[C@@H](O[C@@H]6O[C@H](CO[C@@H]7OC[C@@H](O)[C@H](O)[C@H]7O)[C@@H](O)[C@H](O)[C@H]6O)[C@H](O)C[C@]5(C)[C@H]4CC[C@]3(C)[C@H]2[C@@H]1C)CO[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O TVNGRDSDHVARNR-SYQAKRSCSA-N 0.000 claims abstract description 3
- OVMFOVNOXASTPA-MCIQUCDDSA-N 5,7-dihydroxy-2-(4-hydroxyphenyl)-8-[(2s,3r,4r,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]-6-[(2s,3r,4s,5r)-3,4,5-trihydroxyoxan-2-yl]chromen-4-one Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1C1=C(O)C([C@H]2[C@@H]([C@@H](O)[C@H](O)CO2)O)=C(O)C2=C1OC(C=1C=CC(O)=CC=1)=CC2=O OVMFOVNOXASTPA-MCIQUCDDSA-N 0.000 claims abstract description 3
- DRLZZQRQMWQRLZ-UHFFFAOYSA-N 6-C-Arabinosyl-8-C-glucosyl apigenin Natural products OCC1OC(C(O)C1O)c2c(O)c(C3OC(CO)C(O)C(O)C3O)c4OC(=CC(=O)c4c2O)c5ccc(O)cc5 DRLZZQRQMWQRLZ-UHFFFAOYSA-N 0.000 claims abstract description 3
- OVMFOVNOXASTPA-UHFFFAOYSA-N Neoisoschaftoside Natural products OC1C(O)C(O)C(CO)OC1C1=C(O)C(C2C(C(O)C(O)CO2)O)=C(O)C2=C1OC(C=1C=CC(O)=CC=1)=CC2=O OVMFOVNOXASTPA-UHFFFAOYSA-N 0.000 claims abstract description 3
- TVNGRDSDHVARNR-UHFFFAOYSA-N trigoneoside Ia Natural products O1C(CO)C(O)C(O)C(O)C1OCC(C)CCC(C(C1C2(C)CCC3C4(C)CC5O)C)(O)OC1CC2C3CCC4CC5OC(C(C(O)C1O)O)OC1COC1OCC(O)C(O)C1O TVNGRDSDHVARNR-UHFFFAOYSA-N 0.000 claims abstract description 3
- 229930182490 saponin Natural products 0.000 claims description 77
- 150000007949 saponins Chemical class 0.000 claims description 77
- 239000001397 quillaja saponaria molina bark Substances 0.000 claims description 71
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 31
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 30
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 27
- 241001465754 Metazoa Species 0.000 claims description 22
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 20
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 19
- 239000000843 powder Substances 0.000 claims description 16
- 208000023275 Autoimmune disease Diseases 0.000 claims description 13
- 239000003795 chemical substances by application Substances 0.000 claims description 11
- 239000002775 capsule Substances 0.000 claims description 10
- 239000000463 material Substances 0.000 claims description 8
- 239000002904 solvent Substances 0.000 claims description 8
- 239000006188 syrup Substances 0.000 claims description 8
- 235000020357 syrup Nutrition 0.000 claims description 8
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 7
- 239000007787 solid Substances 0.000 claims description 7
- 239000011877 solvent mixture Substances 0.000 claims description 7
- 238000001179 sorption measurement Methods 0.000 claims description 7
- 239000008367 deionised water Substances 0.000 claims description 6
- 229910021641 deionized water Inorganic materials 0.000 claims description 6
- 238000001914 filtration Methods 0.000 claims description 6
- 239000011230 binding agent Substances 0.000 claims description 5
- 239000011248 coating agent Substances 0.000 claims description 5
- 239000003086 colorant Substances 0.000 claims description 5
- 239000003995 emulsifying agent Substances 0.000 claims description 5
- 239000000796 flavoring agent Substances 0.000 claims description 5
- 235000013355 food flavoring agent Nutrition 0.000 claims description 5
- 235000003599 food sweetener Nutrition 0.000 claims description 5
- 239000008187 granular material Substances 0.000 claims description 5
- 239000003979 granulating agent Substances 0.000 claims description 5
- 239000000314 lubricant Substances 0.000 claims description 5
- -1 phyotceuticals Substances 0.000 claims description 5
- 239000003755 preservative agent Substances 0.000 claims description 5
- 239000000375 suspending agent Substances 0.000 claims description 5
- 239000003765 sweetening agent Substances 0.000 claims description 5
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 claims description 4
- 239000000443 aerosol Substances 0.000 claims description 4
- 239000007933 dermal patch Substances 0.000 claims description 4
- 239000000839 emulsion Substances 0.000 claims description 4
- 235000013305 food Nutrition 0.000 claims description 4
- 239000002417 nutraceutical Substances 0.000 claims description 4
- 235000021436 nutraceutical agent Nutrition 0.000 claims description 4
- 239000002674 ointment Substances 0.000 claims description 4
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 4
- 239000000725 suspension Substances 0.000 claims description 4
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 claims description 3
- 239000000872 buffer Substances 0.000 claims description 3
- 239000003456 ion exchange resin Substances 0.000 claims description 3
- 229920003303 ion-exchange polymer Polymers 0.000 claims description 3
- 239000004014 plasticizer Substances 0.000 claims description 3
- 239000001917 trigonella foenum graecum l. absolute Substances 0.000 claims description 3
- 238000010306 acid treatment Methods 0.000 claims description 2
- 239000002552 dosage form Substances 0.000 claims description 2
- 206010043561 Thrombocytopenic purpura Diseases 0.000 claims 1
- 201000003710 autoimmune thrombocytopenic purpura Diseases 0.000 abstract description 26
- 235000017709 saponins Nutrition 0.000 description 70
- 238000012360 testing method Methods 0.000 description 46
- 239000000243 solution Substances 0.000 description 40
- 201000010099 disease Diseases 0.000 description 29
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 29
- 206010021245 Idiopathic thrombocytopenic purpura Diseases 0.000 description 25
- 208000031981 Thrombocytopenic Idiopathic Purpura Diseases 0.000 description 24
- 230000000694 effects Effects 0.000 description 14
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 239000003814 drug Substances 0.000 description 12
- 230000006378 damage Effects 0.000 description 11
- 210000000585 glomerular basement membrane Anatomy 0.000 description 11
- 229940079593 drug Drugs 0.000 description 10
- 239000000284 extract Substances 0.000 description 10
- 238000004128 high performance liquid chromatography Methods 0.000 description 9
- 238000005481 NMR spectroscopy Methods 0.000 description 8
- 241000700159 Rattus Species 0.000 description 8
- 239000011347 resin Substances 0.000 description 8
- 229920005989 resin Polymers 0.000 description 8
- 238000004809 thin layer chromatography Methods 0.000 description 8
- 210000002683 foot Anatomy 0.000 description 7
- 210000004072 lung Anatomy 0.000 description 7
- 239000012521 purified sample Substances 0.000 description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- 206010030113 Oedema Diseases 0.000 description 6
- 210000004369 blood Anatomy 0.000 description 6
- 239000008280 blood Substances 0.000 description 6
- 238000005341 cation exchange Methods 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 6
- 150000007955 flavonoid glycosides Chemical class 0.000 description 6
- 230000005764 inhibitory process Effects 0.000 description 6
- 102000004169 proteins and genes Human genes 0.000 description 6
- 108090000623 proteins and genes Proteins 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 239000003826 tablet Substances 0.000 description 6
- 229940024606 amino acid Drugs 0.000 description 5
- 150000001413 amino acids Chemical class 0.000 description 5
- 230000003110 anti-inflammatory effect Effects 0.000 description 5
- 206010003246 arthritis Diseases 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 235000008504 concentrate Nutrition 0.000 description 5
- 239000012141 concentrate Substances 0.000 description 5
- 229930182486 flavonoid glycoside Natural products 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- 230000001575 pathological effect Effects 0.000 description 5
- 230000009467 reduction Effects 0.000 description 5
- 230000002829 reductive effect Effects 0.000 description 5
- 210000002700 urine Anatomy 0.000 description 5
- 102000004127 Cytokines Human genes 0.000 description 4
- 108090000695 Cytokines Proteins 0.000 description 4
- SRBFZHDQGSBBOR-IOVATXLUSA-N D-xylopyranose Chemical compound O[C@@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-IOVATXLUSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- RTMWIZOXNKJHRE-UHFFFAOYSA-N Tigogenin Natural products CC1COC2CC(C)(OC12)C3CCC4C5CCC6CC(O)CCC6(C)C5CCC34C RTMWIZOXNKJHRE-UHFFFAOYSA-N 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 239000007853 buffer solution Substances 0.000 description 4
- 239000003246 corticosteroid Substances 0.000 description 4
- 229960001334 corticosteroids Drugs 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 239000007884 disintegrant Substances 0.000 description 4
- 238000004090 dissolution Methods 0.000 description 4
- 238000000605 extraction Methods 0.000 description 4
- 230000028993 immune response Effects 0.000 description 4
- 230000006872 improvement Effects 0.000 description 4
- 230000001965 increasing effect Effects 0.000 description 4
- 210000003734 kidney Anatomy 0.000 description 4
- 201000006370 kidney failure Diseases 0.000 description 4
- 230000001404 mediated effect Effects 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 208000006820 Arthralgia Diseases 0.000 description 3
- 206010061218 Inflammation Diseases 0.000 description 3
- GMBQZIIUCVWOCD-UQHLGXRBSA-N Isosarsasapogenin Natural products 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 description 3
- 206010037394 Pulmonary haemorrhage Diseases 0.000 description 3
- 208000001647 Renal Insufficiency Diseases 0.000 description 3
- 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 3
- 244000269722 Thea sinensis Species 0.000 description 3
- 230000000202 analgesic effect Effects 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 239000002158 endotoxin Substances 0.000 description 3
- 239000004744 fabric Substances 0.000 description 3
- 210000000548 hind-foot Anatomy 0.000 description 3
- 239000003018 immunosuppressive agent Substances 0.000 description 3
- 230000001939 inductive effect Effects 0.000 description 3
- 230000008595 infiltration Effects 0.000 description 3
- 238000001764 infiltration Methods 0.000 description 3
- 230000004054 inflammatory process Effects 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 229920006008 lipopolysaccharide Polymers 0.000 description 3
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 3
- 235000019796 monopotassium phosphate Nutrition 0.000 description 3
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 3
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 3
- PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 0.000 description 3
- 238000002616 plasmapheresis Methods 0.000 description 3
- 229920001467 poly(styrenesulfonates) Polymers 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 230000001932 seasonal effect Effects 0.000 description 3
- 239000007921 spray Substances 0.000 description 3
- 230000008961 swelling Effects 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 206010043554 thrombocytopenia Diseases 0.000 description 3
- 238000007492 two-way ANOVA Methods 0.000 description 3
- 238000005303 weighing Methods 0.000 description 3
- HMLGSIZOMSVISS-ONJSNURVSA-N (7r)-7-[[(2z)-2-(2-amino-1,3-thiazol-4-yl)-2-(2,2-dimethylpropanoyloxymethoxyimino)acetyl]amino]-3-ethenyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound N([C@@H]1C(N2C(=C(C=C)CSC21)C(O)=O)=O)C(=O)\C(=N/OCOC(=O)C(C)(C)C)C1=CSC(N)=N1 HMLGSIZOMSVISS-ONJSNURVSA-N 0.000 description 2
- 201000004384 Alopecia Diseases 0.000 description 2
- 240000007551 Boswellia serrata Species 0.000 description 2
- 235000012035 Boswellia serrata Nutrition 0.000 description 2
- 241000282994 Cervidae Species 0.000 description 2
- 206010010774 Constipation Diseases 0.000 description 2
- 244000163122 Curcuma domestica Species 0.000 description 2
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 2
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 2
- 108010036949 Cyclosporine Proteins 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- PLAPMLGJVGLZOV-UHFFFAOYSA-N Epi-orientin Natural products OC1C(O)C(O)C(CO)OC1C1=C(O)C=C(O)C2=C1OC(C=1C=C(O)C(O)=CC=1)=CC2=O PLAPMLGJVGLZOV-UHFFFAOYSA-N 0.000 description 2
- FWCXELAAYFYCSR-UHFFFAOYSA-N Episamogenin Natural products CC1C(C2(CCC3C4(C)CC(O)C(O)CC4CCC3C2C2)C)C2OC11CCC(C)CO1 FWCXELAAYFYCSR-UHFFFAOYSA-N 0.000 description 2
- 206010018852 Haematoma Diseases 0.000 description 2
- 102000051628 Interleukin-1 receptor antagonist Human genes 0.000 description 2
- 108700021006 Interleukin-1 receptor antagonist Proteins 0.000 description 2
- 206010023232 Joint swelling Diseases 0.000 description 2
- 240000006240 Linum usitatissimum Species 0.000 description 2
- 235000004431 Linum usitatissimum Nutrition 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- WWNNZCOKKKDOPX-UHFFFAOYSA-N N-methylnicotinate Chemical compound C[N+]1=CC=CC(C([O-])=O)=C1 WWNNZCOKKKDOPX-UHFFFAOYSA-N 0.000 description 2
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 2
- 206010053159 Organ failure Diseases 0.000 description 2
- 235000008184 Piper nigrum Nutrition 0.000 description 2
- 244000203593 Piper nigrum Species 0.000 description 2
- 206010037660 Pyrexia Diseases 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- REFJWTPEDVJJIY-UHFFFAOYSA-N Quercetin Chemical compound C=1C(O)=CC(O)=C(C(C=2O)=O)C=1OC=2C1=CC=C(O)C(O)=C1 REFJWTPEDVJJIY-UHFFFAOYSA-N 0.000 description 2
- JMFSHKGXVSAJFY-UHFFFAOYSA-N Saponaretin Natural products OCC(O)C1OC(Oc2c(O)cc(O)c3C(=O)C=C(Oc23)c4ccc(O)cc4)C(O)C1O JMFSHKGXVSAJFY-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 208000003441 Transfusion reaction Diseases 0.000 description 2
- MOZJVOCOKZLBQB-UHFFFAOYSA-N Vitexin Natural products OCC1OC(Oc2c(O)c(O)cc3C(=O)C=C(Oc23)c4ccc(O)cc4)C(O)C(O)C1O MOZJVOCOKZLBQB-UHFFFAOYSA-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
- JLISZLJGTVNTPC-UBWBUNFISA-N Yuccagenin Natural products C[C@@H]1CC[C@@]2(OC1)O[C@H]3C[C@H]4[C@@H]5CCC6=C[C@@H](O)[C@H](O)C[C@]6(C)[C@H]5CC[C@]4(C)[C@H]3[C@@H]2C JLISZLJGTVNTPC-UBWBUNFISA-N 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 239000003463 adsorbent Substances 0.000 description 2
- 238000013019 agitation Methods 0.000 description 2
- 229930013930 alkaloid Natural products 0.000 description 2
- 229960004238 anakinra Drugs 0.000 description 2
- 230000002456 anti-arthritic effect Effects 0.000 description 2
- 230000000702 anti-platelet effect Effects 0.000 description 2
- 239000003146 anticoagulant agent Substances 0.000 description 2
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 2
- 210000002469 basement membrane Anatomy 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 2
- 230000000975 bioactive effect Effects 0.000 description 2
- 229960000074 biopharmaceutical Drugs 0.000 description 2
- 239000010836 blood and blood product Substances 0.000 description 2
- 229940125691 blood product Drugs 0.000 description 2
- 239000000679 carrageenan Substances 0.000 description 2
- 235000010418 carrageenan Nutrition 0.000 description 2
- 229920001525 carrageenan Polymers 0.000 description 2
- 229940113118 carrageenan Drugs 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 229960001265 ciclosporin Drugs 0.000 description 2
- 229940111134 coxibs Drugs 0.000 description 2
- 235000003373 curcuma longa Nutrition 0.000 description 2
- 239000003255 cyclooxygenase 2 inhibitor Substances 0.000 description 2
- 229960004397 cyclophosphamide Drugs 0.000 description 2
- 229930182912 cyclosporin Natural products 0.000 description 2
- 230000008021 deposition Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 206010012601 diabetes mellitus Diseases 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
- 230000029142 excretion Effects 0.000 description 2
- 238000010812 external standard method Methods 0.000 description 2
- 150000002215 flavonoids Chemical class 0.000 description 2
- 235000004426 flaxseed Nutrition 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- DFNZYFAJQPLJFI-UHFFFAOYSA-N gentianine Chemical compound O=C1OCCC2=C1C=NC=C2C=C DFNZYFAJQPLJFI-UHFFFAOYSA-N 0.000 description 2
- 230000001434 glomerular Effects 0.000 description 2
- 235000009569 green tea Nutrition 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 235000008216 herbs Nutrition 0.000 description 2
- 229940125721 immunosuppressive agent Drugs 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 210000001503 joint Anatomy 0.000 description 2
- 230000003907 kidney function Effects 0.000 description 2
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- XELZGAJCZANUQH-UHFFFAOYSA-N methyl 1-acetylthieno[3,2-c]pyrazole-5-carboxylate Chemical compound CC(=O)N1N=CC2=C1C=C(C(=O)OC)S2 XELZGAJCZANUQH-UHFFFAOYSA-N 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 2
- 230000001766 physiological effect Effects 0.000 description 2
- 230000000770 proinflammatory effect Effects 0.000 description 2
- 239000002464 receptor antagonist Substances 0.000 description 2
- 229940044551 receptor antagonist Drugs 0.000 description 2
- RODXRVNMMDRFIK-UHFFFAOYSA-N scopoletin Chemical compound C1=CC(=O)OC2=C1C=C(OC)C(O)=C2 RODXRVNMMDRFIK-UHFFFAOYSA-N 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 239000002594 sorbent Substances 0.000 description 2
- 238000005507 spraying Methods 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- 208000037918 transfusion-transmitted disease Diseases 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 2
- JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 description 1
- ADHFZEPOBOTKSO-QLTVFDSQSA-N (1R,2S,4R,5'R,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]-3-ol Chemical compound O([C@@H]1[C@@H]([C@]2(CC[C@@H]3[C@@]4(C)CCCCC4CC[C@H]3[C@@H]2C1O)C)[C@@H]1C)[C@]11CC[C@@H](C)CO1 ADHFZEPOBOTKSO-QLTVFDSQSA-N 0.000 description 1
- ORXKASWXOVPKDV-CTGSJARNSA-N (1S,2S,4S,5'S,6R,7S,8R,9S,12S,13R,15R,16R)-5',7,9,13-tetramethylspiro[5-oxapentacyclo[10.8.0.02,9.04,8.013,18]icos-18-ene-6,2'-oxane]-15,16-diol Chemical compound O([C@@H]1[C@@H]([C@]2(CC[C@@H]3[C@@]4(C)C[C@@H](O)[C@H](O)CC4=CC[C@H]3[C@@H]2C1)C)[C@@H]1C)[C@]11CC[C@H](C)CO1 ORXKASWXOVPKDV-CTGSJARNSA-N 0.000 description 1
- MJYQFWSXKFLTAY-OVEQLNGDSA-N (2r,3r)-2,3-bis[(4-hydroxy-3-methoxyphenyl)methyl]butane-1,4-diol;(2r,3r,4s,5s,6r)-6-(hydroxymethyl)oxane-2,3,4,5-tetrol Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O.C1=C(O)C(OC)=CC(C[C@@H](CO)[C@H](CO)CC=2C=C(OC)C(O)=CC=2)=C1 MJYQFWSXKFLTAY-OVEQLNGDSA-N 0.000 description 1
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 1
- ZBMRKNMTMPPMMK-UHFFFAOYSA-N 2-amino-4-[hydroxy(methyl)phosphoryl]butanoic acid;azane Chemical compound [NH4+].CP(O)(=O)CCC(N)C([O-])=O ZBMRKNMTMPPMMK-UHFFFAOYSA-N 0.000 description 1
- ODBRNZZJSYPIDI-UHFFFAOYSA-N 3',4',5,7-tetrahydroxy-6-C-glucopyranosylflavone Natural products OC1C(O)C(O)C(CO)OC1C1=C(O)C=C(OC(=CC2=O)C=3C=C(O)C(O)=CC=3)C2=C1O ODBRNZZJSYPIDI-UHFFFAOYSA-N 0.000 description 1
- CTIHYOZNWNAKHD-UHFFFAOYSA-N 4-methoxybenzaldehyde;sulfuric acid Chemical compound OS(O)(=O)=O.COC1=CC=C(C=O)C=C1 CTIHYOZNWNAKHD-UHFFFAOYSA-N 0.000 description 1
- 240000002234 Allium sativum Species 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 240000007087 Apium graveolens Species 0.000 description 1
- 235000002764 Apium graveolens Nutrition 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 208000027796 Blood pressure disease Diseases 0.000 description 1
- 238000010152 Bonferroni least significant difference Methods 0.000 description 1
- 108010074051 C-Reactive Protein Proteins 0.000 description 1
- 102100032752 C-reactive protein Human genes 0.000 description 1
- 206010048610 Cardiotoxicity Diseases 0.000 description 1
- 206010008479 Chest Pain Diseases 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 244000223760 Cinnamomum zeylanicum Species 0.000 description 1
- 241000189665 Colchicum autumnale Species 0.000 description 1
- 240000003890 Commiphora wightii Species 0.000 description 1
- 235000009852 Cucurbita pepo Nutrition 0.000 description 1
- 240000001980 Cucurbita pepo Species 0.000 description 1
- 235000003392 Curcuma domestica Nutrition 0.000 description 1
- SHZGCJCMOBCMKK-UHFFFAOYSA-N D-mannomethylose Natural products CC1OC(O)C(O)C(O)C1O SHZGCJCMOBCMKK-UHFFFAOYSA-N 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- XEHFSYYAGCUKEN-UHFFFAOYSA-N Dihydroscopoletin Natural products C1CC(=O)OC2=C1C=C(OC)C(O)=C2 XEHFSYYAGCUKEN-UHFFFAOYSA-N 0.000 description 1
- 206010013082 Discomfort Diseases 0.000 description 1
- 108010008165 Etanercept Proteins 0.000 description 1
- 241001553700 Euphorbia lathyris Species 0.000 description 1
- 208000010201 Exanthema Diseases 0.000 description 1
- LFERELMXERXKKQ-KMXXXSRASA-N Fenugreekine Chemical compound NC(=O)C1=CC=CC([C@H]2[C@@H]([C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=N1 LFERELMXERXKKQ-KMXXXSRASA-N 0.000 description 1
- XOXYHGOIRWABTC-UHFFFAOYSA-N Gentisin Natural products C1=C(O)C=C2C(=O)C3=C(O)C=C(OC)C=C3OC2=C1 XOXYHGOIRWABTC-UHFFFAOYSA-N 0.000 description 1
- FWCXELAAYFYCSR-RYKNUXCGSA-N Gitogenin Chemical compound O([C@@H]1[C@@H]([C@]2(CC[C@@H]3[C@@]4(C)C[C@@H](O)[C@H](O)C[C@@H]4CC[C@H]3[C@@H]2C1)C)[C@@H]1C)[C@]11CC[C@@H](C)CO1 FWCXELAAYFYCSR-RYKNUXCGSA-N 0.000 description 1
- ZVWCWPUAQHAINU-UHFFFAOYSA-N Gitogenin Natural products CC1CCC2(CC3OC4C5CCC6CC(O)C(O)CC6(C)C5CCC4(C)C3C2C)OC1 ZVWCWPUAQHAINU-UHFFFAOYSA-N 0.000 description 1
- 206010018378 Glomerulonephritis rapidly progressive Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 201000005569 Gout Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 206010062016 Immunosuppression Diseases 0.000 description 1
- 102000019223 Interleukin-1 receptor Human genes 0.000 description 1
- 108050006617 Interleukin-1 receptor Proteins 0.000 description 1
- 102000004889 Interleukin-6 Human genes 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- 102000010781 Interleukin-6 Receptors Human genes 0.000 description 1
- 108010038501 Interleukin-6 Receptors Proteins 0.000 description 1
- 206010023230 Joint stiffness Diseases 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
- PNNNRSAQSRJVSB-UHFFFAOYSA-N L-rhamnose Natural products CC(O)C(O)C(O)C(O)C=O PNNNRSAQSRJVSB-UHFFFAOYSA-N 0.000 description 1
- PTNJRKBWIYNFSY-UHFFFAOYSA-N Lirinin-O-methyl-ether Natural products COc1ccc-2c(CC3N(C)CCc4cc(OC)c(OC)c-2c34)c1 PTNJRKBWIYNFSY-UHFFFAOYSA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 229920000881 Modified starch Polymers 0.000 description 1
- 208000010428 Muscle Weakness Diseases 0.000 description 1
- 206010028372 Muscular weakness Diseases 0.000 description 1
- 241000186359 Mycobacterium Species 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- FWCXELAAYFYCSR-HJXRQQMRSA-N Neogitogenin Chemical compound O([C@@H]1[C@@H]([C@]2(CC[C@@H]3[C@@]4(C)C[C@@H](O)[C@H](O)C[C@@H]4CC[C@H]3[C@@H]2C1)C)[C@@H]1C)[C@]11CC[C@H](C)CO1 FWCXELAAYFYCSR-HJXRQQMRSA-N 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
- 244000090896 Nigella sativa Species 0.000 description 1
- 235000016698 Nigella sativa Nutrition 0.000 description 1
- 208000001388 Opportunistic Infections Diseases 0.000 description 1
- 208000007117 Oral Ulcer Diseases 0.000 description 1
- RBVAFYCFAFADAG-UHFFFAOYSA-N Orientin Natural products OCC1OC(C(O)c2c(O)cc(O)c3C(=O)C=C(Oc23)c4ccc(O)c(O)c4)C(O)C1O RBVAFYCFAFADAG-UHFFFAOYSA-N 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 239000005662 Paraffin oil Substances 0.000 description 1
- 206010034960 Photophobia Diseases 0.000 description 1
- 206010037549 Purpura Diseases 0.000 description 1
- 241001672981 Purpura Species 0.000 description 1
- ZVOLCUVKHLEPEV-UHFFFAOYSA-N Quercetagetin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=C(O)C(O)=C(O)C=C2O1 ZVOLCUVKHLEPEV-UHFFFAOYSA-N 0.000 description 1
- 208000035977 Rare disease Diseases 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 206010061481 Renal injury Diseases 0.000 description 1
- HWTZYBCRDDUBJY-UHFFFAOYSA-N Rhynchosin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=CC(O)=C(O)C=C2O1 HWTZYBCRDDUBJY-UHFFFAOYSA-N 0.000 description 1
- 244000272264 Saussurea lappa Species 0.000 description 1
- 235000006784 Saussurea lappa Nutrition 0.000 description 1
- 208000031709 Skin Manifestations Diseases 0.000 description 1
- 244000261559 Smilax china Species 0.000 description 1
- 235000000485 Smilax china Nutrition 0.000 description 1
- WJJFWGUVMIUWGG-UHFFFAOYSA-N Stereolensin Natural products OC1C(O)C(O)C(CO)OC1OC1=C(O)C=C(OC(=CC2=O)C=3C=C(O)C(O)=CC=3)C2=C1O WJJFWGUVMIUWGG-UHFFFAOYSA-N 0.000 description 1
- 229930182558 Sterol Natural products 0.000 description 1
- 208000007107 Stomach Ulcer Diseases 0.000 description 1
- 244000045719 Syzygium Species 0.000 description 1
- 235000012096 Syzygium samarangense Nutrition 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 235000006468 Thea sinensis Nutrition 0.000 description 1
- 244000300530 Tragopogon porrifolius Species 0.000 description 1
- 235000012363 Tragopogon porrifolius Nutrition 0.000 description 1
- 241001521901 Tribulus lanuginosus Species 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
- 244000098338 Triticum aestivum Species 0.000 description 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 1
- LQSNPVIQIPKOGP-UHFFFAOYSA-N UNPD159785 Natural products OC1C(O)C(O)C(CO)OC1OC1=C(O)C=C(O)C2=C1OC(C=1C=C(O)C(O)=CC=1)=CC2=O LQSNPVIQIPKOGP-UHFFFAOYSA-N 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 240000004482 Withania somnifera Species 0.000 description 1
- 235000001978 Withania somnifera Nutrition 0.000 description 1
- ORXKASWXOVPKDV-UBWBUNFISA-N Yuccagenin Chemical compound O([C@@H]1[C@@H]([C@]2(CC[C@@H]3[C@@]4(C)C[C@@H](O)[C@H](O)CC4=CC[C@H]3[C@@H]2C1)C)[C@@H]1C)[C@]11CC[C@@H](C)CO1 ORXKASWXOVPKDV-UBWBUNFISA-N 0.000 description 1
- 244000273928 Zingiber officinale Species 0.000 description 1
- 235000006886 Zingiber officinale Nutrition 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000013564 activation of immune response Effects 0.000 description 1
- 229960002964 adalimumab Drugs 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- PNNNRSAQSRJVSB-BXKVDMCESA-N aldehydo-L-rhamnose Chemical compound C[C@H](O)[C@H](O)[C@@H](O)[C@@H](O)C=O PNNNRSAQSRJVSB-BXKVDMCESA-N 0.000 description 1
- 231100000360 alopecia Toxicity 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 235000010208 anthocyanin Nutrition 0.000 description 1
- 229930002877 anthocyanin Natural products 0.000 description 1
- 239000004410 anthocyanin Substances 0.000 description 1
- 150000004636 anthocyanins Chemical class 0.000 description 1
- 230000000181 anti-adherent effect Effects 0.000 description 1
- 230000000049 anti-anxiety effect Effects 0.000 description 1
- 230000006909 anti-apoptosis Effects 0.000 description 1
- 230000003064 anti-oxidating effect Effects 0.000 description 1
- 230000001754 anti-pyretic effect Effects 0.000 description 1
- 230000003208 anti-thyroid effect Effects 0.000 description 1
- 239000003430 antimalarial agent Substances 0.000 description 1
- 229940033495 antimalarials Drugs 0.000 description 1
- 239000003435 antirheumatic agent Substances 0.000 description 1
- 229940043671 antithyroid preparations Drugs 0.000 description 1
- 239000002249 anxiolytic agent Substances 0.000 description 1
- 239000001387 apium graveolens Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 description 1
- 229960002170 azathioprine Drugs 0.000 description 1
- 230000008238 biochemical pathway Effects 0.000 description 1
- 239000003124 biologic agent Substances 0.000 description 1
- 235000013614 black pepper Nutrition 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 238000010322 bone marrow transplantation Methods 0.000 description 1
- 230000005978 brain dysfunction Effects 0.000 description 1
- 239000006189 buccal tablet Substances 0.000 description 1
- 235000004883 caffeic acid Nutrition 0.000 description 1
- 150000001720 carbohydrates Chemical group 0.000 description 1
- 231100000259 cardiotoxicity Toxicity 0.000 description 1
- AMSCMASJCYVAIF-QCVMBYIASA-N carpaine Chemical compound O([C@H]1CC[C@@H](CCCCCCCC(=O)O2)N[C@H]1C)C(=O)CCCCCCC[C@H]1N[C@@H](C)[C@@H]2CC1 AMSCMASJCYVAIF-QCVMBYIASA-N 0.000 description 1
- HXFUVYFNBRBBPM-UHFFFAOYSA-N carpaine Natural products CC1(CCCCCCCC(=O)O1)C2CCCN2 HXFUVYFNBRBBPM-UHFFFAOYSA-N 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 210000000845 cartilage Anatomy 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 235000001368 chlorogenic acid Nutrition 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 235000017803 cinnamon Nutrition 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 201000005637 crescentic glomerulonephritis Diseases 0.000 description 1
- 229960000913 crospovidone Drugs 0.000 description 1
- 108010057085 cytokine receptors Proteins 0.000 description 1
- 102000003675 cytokine receptors Human genes 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000005238 degreasing Methods 0.000 description 1
- 238000000502 dialysis Methods 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
- 208000001848 dysentery Diseases 0.000 description 1
- 201000006549 dyspepsia Diseases 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 229960000403 etanercept Drugs 0.000 description 1
- 201000005884 exanthem Diseases 0.000 description 1
- 206010016256 fatigue Diseases 0.000 description 1
- 235000020765 fenugreek extract Nutrition 0.000 description 1
- 229930003935 flavonoid Natural products 0.000 description 1
- 235000017173 flavonoids Nutrition 0.000 description 1
- 235000004611 garlic Nutrition 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 235000008397 ginger Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229930182478 glucoside Natural products 0.000 description 1
- 150000008131 glucosides Chemical class 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 208000024963 hair loss Diseases 0.000 description 1
- 230000003676 hair loss Effects 0.000 description 1
- 208000007475 hemolytic anemia Diseases 0.000 description 1
- 208000031169 hemorrhagic disease Diseases 0.000 description 1
- 208000014617 hemorrhoid Diseases 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- XXSMGPRMXLTPCZ-UHFFFAOYSA-N hydroxychloroquine Chemical compound ClC1=CC=C2C(NC(C)CCCN(CCO)CC)=CC=NC2=C1 XXSMGPRMXLTPCZ-UHFFFAOYSA-N 0.000 description 1
- 229960004171 hydroxychloroquine Drugs 0.000 description 1
- 208000026278 immune system disease Diseases 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 229960003444 immunosuppressant agent Drugs 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 229960000598 infliximab Drugs 0.000 description 1
- 102000006495 integrins Human genes 0.000 description 1
- 108010044426 integrins Proteins 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 229940008228 intravenous immunoglobulins Drugs 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- ODBRNZZJSYPIDI-VJXVFPJBSA-N isoorientin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1C1=C(O)C=C(OC(=CC2=O)C=3C=C(O)C(O)=CC=3)C2=C1O ODBRNZZJSYPIDI-VJXVFPJBSA-N 0.000 description 1
- UYJGIAWJIRZBNU-UHFFFAOYSA-N isoorientin Natural products OCC1OC(C(O)C(O)C1O)c2cc(O)c(O)c3C(=O)C=C(Oc23)c4ccc(O)c(O)c4 UYJGIAWJIRZBNU-UHFFFAOYSA-N 0.000 description 1
- MYXNWGACZJSMBT-VJXVFPJBSA-N isovitexin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1C1=C(O)C=C(OC(=CC2=O)C=3C=CC(O)=CC=3)C2=C1O MYXNWGACZJSMBT-VJXVFPJBSA-N 0.000 description 1
- OYJCWTROZCNWAA-UHFFFAOYSA-N isovitexin Natural products OCC1OC(C(O)C(O)C1O)c2c(O)cc3CC(=CC(=O)c3c2O)c4ccc(O)cc4 OYJCWTROZCNWAA-UHFFFAOYSA-N 0.000 description 1
- 208000018937 joint inflammation Diseases 0.000 description 1
- MWDZOUNAPSSOEL-UHFFFAOYSA-N kaempferol Natural products OC1=C(C(=O)c2cc(O)cc(O)c2O1)c3ccc(O)cc3 MWDZOUNAPSSOEL-UHFFFAOYSA-N 0.000 description 1
- 208000013469 light sensitivity Diseases 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 229940127554 medical product Drugs 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 229960004866 mycophenolate mofetil Drugs 0.000 description 1
- RTGDFNSFWBGLEC-SYZQJQIISA-N mycophenolate mofetil Chemical compound COC1=C(C)C=2COC(=O)C=2C(O)=C1C\C=C(/C)CCC(=O)OCCN1CCOCC1 RTGDFNSFWBGLEC-SYZQJQIISA-N 0.000 description 1
- PEFNSGRTCBGNAN-UHFFFAOYSA-N nephrocizin Natural products OC1C(O)C(O)C(CO)OC1OC1=CC(O)=C2C(=O)C=C(C=3C=C(O)C(O)=CC=3)OC2=C1 PEFNSGRTCBGNAN-UHFFFAOYSA-N 0.000 description 1
- 239000001711 nigella sativa Substances 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 230000008816 organ damage Effects 0.000 description 1
- PLAPMLGJVGLZOV-VPRICQMDSA-N orientin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1C1=C(O)C=C(O)C2=C1OC(C=1C=C(O)C(O)=CC=1)=CC2=O PLAPMLGJVGLZOV-VPRICQMDSA-N 0.000 description 1
- 230000002746 orthostatic effect Effects 0.000 description 1
- 238000012261 overproduction Methods 0.000 description 1
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 208000028169 periodontal disease Diseases 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 235000013824 polyphenols Nutrition 0.000 description 1
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
- 238000010149 post-hoc-test Methods 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 239000006041 probiotic Substances 0.000 description 1
- 230000000529 probiotic effect Effects 0.000 description 1
- 235000018291 probiotics Nutrition 0.000 description 1
- 208000037821 progressive disease Diseases 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 229960001285 quercetin Drugs 0.000 description 1
- 235000005875 quercetin Nutrition 0.000 description 1
- 206010037844 rash Diseases 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 229960004641 rituximab Drugs 0.000 description 1
- FWYIBGHGBOVPNL-UHFFFAOYSA-N scopoletin Natural products COC=1C=C2C=CC(OC2=C(C1)O)=O FWYIBGHGBOVPNL-UHFFFAOYSA-N 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 206010040882 skin lesion Diseases 0.000 description 1
- 231100000444 skin lesion Toxicity 0.000 description 1
- 229950002323 smilagenin Drugs 0.000 description 1
- 239000000344 soap Substances 0.000 description 1
- AEQFSUDEHCCHBT-UHFFFAOYSA-M sodium valproate Chemical compound [Na+].CCCC(C([O-])=O)CCC AEQFSUDEHCCHBT-UHFFFAOYSA-M 0.000 description 1
- 238000010911 splenectomy Methods 0.000 description 1
- 238000011425 standardization method Methods 0.000 description 1
- 235000003702 sterols Nutrition 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 210000001258 synovial membrane Anatomy 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 229960003989 tocilizumab Drugs 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- NGSWKAQJJWESNS-ZZXKWVIFSA-N trans-4-coumaric acid Chemical class OC(=O)\C=C\C1=CC=C(O)C=C1 NGSWKAQJJWESNS-ZZXKWVIFSA-N 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- HJLDLVBUBSQMEG-UHFFFAOYSA-N trigocoumarin Natural products COC1=CC=C2C(=C(C(OC2=C1OC)=O)CC(=O)OCC)C HJLDLVBUBSQMEG-UHFFFAOYSA-N 0.000 description 1
- 229930184412 trigofoenoside Natural products 0.000 description 1
- 210000005239 tubule Anatomy 0.000 description 1
- 229940046728 tumor necrosis factor alpha inhibitor Drugs 0.000 description 1
- 239000002451 tumor necrosis factor inhibitor Substances 0.000 description 1
- 235000013976 turmeric Nutrition 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 230000002485 urinary effect Effects 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- SGEWCQFRYRRZDC-VPRICQMDSA-N vitexin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1C1=C(O)C=C(O)C2=C1OC(C=1C=CC(O)=CC=1)=CC2=O SGEWCQFRYRRZDC-VPRICQMDSA-N 0.000 description 1
- PZKISQRTNNHUGF-UHFFFAOYSA-N vitexine Natural products OC1C(O)C(O)C(CO)OC1OC1=C(O)C=C(O)C2=C1OC(C=1C=CC(O)=CC=1)=CC2=O PZKISQRTNNHUGF-UHFFFAOYSA-N 0.000 description 1
- SASUFNRGCZMRFD-JCUIILOWSA-N withanolide D Chemical compound C1C(C)=C(C)C(=O)O[C@H]1[C@](C)(O)[C@@H]1[C@@]2(C)CC[C@@H]3[C@@]4(C)C(=O)C=C[C@H](O)[C@@]54O[C@@H]5C[C@H]3[C@@H]2CC1 SASUFNRGCZMRFD-JCUIILOWSA-N 0.000 description 1
- 239000001841 zingiber officinale Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
-
- 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
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Immunology (AREA)
- Epidemiology (AREA)
- Alternative & Traditional Medicine (AREA)
- Molecular Biology (AREA)
- Rheumatology (AREA)
- Mycology (AREA)
- Microbiology (AREA)
- Medical Informatics (AREA)
- Botany (AREA)
- Biotechnology (AREA)
- Dermatology (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Pulmonology (AREA)
- Physical Education & Sports Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Transplantation (AREA)
- Diabetes (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Plant Substances (AREA)
- Medicinal Preparation (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
Abstract
本發明係關於一種包含葫蘆巴新皂苷Ib及巢菜素-1之組成物,其用於治療及管理古巴士德氏病、腎小球性腎炎、類風濕性關節炎、全身性紅斑狼瘡及特發性血小板減少性紫癜。本發明亦關於一種自葫蘆巴獲得該組成物之方法。
Description
本發明係關於包含葫蘆巴新皂苷Ib(Trigoneoside Ib)及巢菜素-1(Vicenin-1)之組成物及獲得該組成物之方法。本發明進一步關於該組成物用於治療及管理自體免疫性病症(諸如古巴士德氏病(Goodpasture's disease)、腎小球性腎炎、類風濕性關節炎、全身性紅斑狼瘡及特發性血小板減少性紫癜)之應用。
自體免疫性病症(諸如古巴士德氏病、腎小球性腎炎、類風濕性關節炎、全身性紅斑狼瘡及特發性血小板減少性紫癜)顯示自體抗體過量產生,從而對細胞、組織、器官等造成嚴重損傷。此等疾病之特徵為對自體抗原喪失身體耐受性,並隨後活化免疫反應,從而造成損傷。遺傳素因及環境因素為此等疾病之主要原因。
古巴士德氏病及腎小球性腎炎之特徵為抗體沿腎小球基膜(GBM)沈積於腎臟中,從而引起毛細血管外腎小球性腎炎。此等疾病通常稱作抗腎小球基膜(抗GBM)病。罹患抗GBM病之患者僅具有10%腎存活機率。古巴士德氏病為每百萬人僅發生一例的罕見疾病。自體抗體介導之腎損傷為古巴士德氏病之主要問題。一些患者亦產生肺出血,然而抗GBM抗體對肺造成之損傷相較於對腎臟之損傷而言並非永久性的且很少會致命。
古巴士德氏病或腎小球性腎炎之現有治療包括自血液去除循環抗GBM抗體之血漿清除術或血漿交換程序。暴露於血液產品之風險、血腫、輸血反應及輸血傳播之疾病為與血漿清除術有關之主要併發症。其他治療選擇包括投予指定用於管理進行性腎衰竭及肺出血之免疫抑制劑(如皮質類固醇(corticosteroids)及環磷醯胺(cyclophosphamide))。此等藥物以非特異性方式抑制免疫反應且提高患者遭受機會性感染之機率。抗GBM病之當前治療途徑不能完全控制該疾病。該疾病發展成末期器官衰竭使死亡風險增加。
類風濕性關節炎(RA)為經由自體抗體介導的影響約1%世界人口的慢性進行性疾病。類似於古巴士德氏病,RA之特徵為對自體抗原喪失身體耐受性,並隨後活化免疫反應,從而造成組織損傷。以滑膜、軟骨及下層骨關節為目標之自體抗體的產生定義RA之發病機制。關節變形造成重度失能及生活品質降低。常見症狀包括關節疼痛、關節僵硬及腫脹、運動失能、肌肉無力、發熱及全身不舒服感。血液中C反應蛋白及類風濕因子之含量增加為RA之診斷指標。RA之現有治療包括改善疾病之抗風濕藥(DMRD)(如羥氯喹(hydroxychloroquine))、免疫抑制劑(如硫唑嘌呤(azathiprine))、皮質類固醇、選擇性COX-2抑制劑、NSAID及用於症狀緩解之止痛劑。長期使用止痛劑、NSAID引起潰瘍且大多數患者具有低耐受性,且選擇性COX-2抑制劑與心臟毒性有關。
免疫抑制劑為治療RA之主要途徑。如先前所述,此等藥物以非特異性方式抑制免疫反應且產生危急生命之併發症。生物藥物(如TNF抑制劑,亦即阿達木單抗(adalimumab)、依那西普(etanercept)、英利昔單抗(infliximab)等;IL-1受體拮抗劑,亦即阿那白滯素(Anakinra);及IL-6受體拮抗劑,亦即妥利珠單抗(tocilizumab))廣泛用於治療RA。此等藥物設計成藉由充當細胞激素受體之拮抗劑來影響引起關節發炎及關節損傷之生物化學路徑。生物製劑之一種主要缺點為在長期使用時患者對此等藥物變得不起反應,且治療功效下降。由於毒性特徵,許多此等藥物僅建議用於不對其他RA治療起反應之患者。
全身性紅斑狼瘡(SLE)為多系統自體免疫性病症,其在臨床上基於如關節疼痛、發熱、疲乏、皮膚病變、光敏感、胸痛、脫髮、口腔腫痛等之特徵進行診斷,由在血液中發現自體抗體及尿液中發現過量血清蛋白質得到證明。腎衰竭為SLE之一種主要併發症。超過50%的SLE患者由於抗體在腎小球中沈積而發生腎衰竭,且需要腎透析或移植。由自體抗體介導之其他併發症包括對肺、心臟之損傷;溶血性貧血;血小板減少;大腦功能障礙等。SLE之現有治療選擇包括NSAID、抗瘧劑、皮質類固醇及甲胺喋呤(methotrexate)以便減輕肌肉骨骼及皮膚表現。根據USFDA,SLE之當前治療途徑具有如疾病控制不完全、發展成末期器官衰竭及致虛弱副作用的問題(Guidance for Industry: Systemic Lupus Erythematosus-Developing Medical Products for Treatment,2010年6月)。
特發性血小板減少性紫癜(ITP)為由血小板大幅減少引起的出血病症。ITP可能由感染、免疫病症(如SLE)、某些藥物、妊娠等引發。儘管ITP發病之確切機制仍不明確,但ITP大體上歸因於由抗血小板抗體對血小板造成之破壞,因為超過50%的ITP患者測出血小板相關抗體呈陽性(Gernsheimer,2009)。ITP之現有治療選擇包括(i)干擾抗體包覆血小板之清除的藥物(如皮質類固醇)及靜脈內免疫球蛋白;(ii)利用藥物(如硫唑嘌呤、環磷醯胺、環孢靈(cyclosporine))進行非特異性T細胞免疫抑制;(iii)干擾抗體合成之黴酚酸嗎啉乙酯(mycophenolate mofetil)及生物藥物(如利妥昔單抗);(iv)脾切除術及清除循環抗血小板抗體的血漿清除術程序;(v)藉由血小板輸注及骨髓移植等增加血小板計數。所有上述治療選擇均具有潛在副作用,諸如抑制免疫力、暴露於血液產品,存在輸血反應及/或輸血傳播之疾病及血腫的風險。
由於自體免疫性病症(諸如古巴士德氏病、腎小球性腎炎、類風濕性關節炎、全身性紅斑狼瘡、特發性血小板減少性紫癜等)之現有治療選擇的缺陷,藥物公司有必要研究及開發具有較低副作用之更有效療法以解決此等危急生命之慢性疾病的問題。
Malireddy S. Reddy等人之美國專利第6080401號描述使用由若干種草藥(其中一種為葫蘆巴(Trigonella foenum-graecum))之混合物連同若干種益生菌製劑之混合物組成的組成物來治療多種疾病,亦即貧血、關節炎、便秘、抑鬱、糖尿病、消化不良、痔瘡、肝炎、高血壓、性無能、超重、牙周病及其組合。
Chaim Lieberman之美國專利第5707631號揭示由葫蘆巴(Trigonella foenum-graecum)、蒲桃果實(Syzygium aromatium fruit)、大蒜球莖(Allium sativum bulb)、肉桂皮(Cinnamon zeylanicum bark)、雲木香根(Saussurea costus root)及續隨子芽(Euphorbia lathyrus bud)組成之草藥組成物的調配物以用於降低膽固醇、治療關節炎、血壓病及阿茲海默氏病(alzheimer's disease)。然而,此專利文獻未揭示可由任一熟習此項技術者根據此專利理解及實施的關於此組成物在關節炎中之任何作用的任何證據。
Chopra等人(2010)最近公開一種用於治療RA之包含葫蘆巴(Trigonella foenum-graecum/Fenugreek)之萃取物以及乳香(Boswellia serrata/Salai Guggul)、亞麻(Linum usitatissimum)(亞麻籽(Flaxseed))、綠茶(Camellia sinensis/Green tea)、薑黃(Curcuma longa/Turmeric)、刺蒺藜(Tribulus terrestris/Gokshur)及黑胡椒(Piper nigrum/Black pepper)之萃取物的多草藥組成物。
Khan等人(2011)在臨床上評估一種用於治療類風濕性關節炎之包含黑種草(Nigella sativa)、睡茄(Withania somnifera)、菝葜(Smilax china)、芹菜(Apium graveolens)、葫蘆巴、薑(Zingiber officinale)及秋水仙(Colchicum autumnale)的草藥組成物。
所有上述先前技術揭示由若干種草藥組成之組成物,而難以確定葫蘆巴是否促成所主張之有益作用。
葫蘆巴最常用於傳統醫學中。葫蘆巴籽之萃取物經研究可用於治療多種疾病,如糖尿病、痛風、胃潰瘍、腹瀉、便秘等。Ahmadiani等人(2001)研究葫蘆巴之消炎及退熱活性。Vyas等人(2008)展示葫蘆巴籽之萃取物具有止痛及消炎活性。此等研究未說明或教示葫蘆巴籽中促成所主張活性之特定組分或化學組成。
葫蘆巴籽由多種化學物質構成,亦即生物鹼,如葫蘆巴鹼(Trigonelline)、龍膽鹼(Gentianine)、番木瓜鹼(Carpaine)、膽鹼(Choline);胺基酸,如4-羥基異白胺酸、組胺酸、離胺酸、精胺酸;類黃酮(Flavonoids)-葉黃酮(Luteolin)、槲皮素(Quercetin)、蔓荊素(Vitexin)、異蔓荊素(Isovitexin)、葒草素(Orientin)、異葒草素(Isoorientin)、巢菜素-1、巢菜素-2;呋喃甾醇皂苷(Furostanol Saponins)-葫蘆巴糖苷C(Triogenelloside C)、葫蘆巴皂苷(Trigofoenoside)、葫蘆巴新皂苷、葫蘆巴素B(Fenugrin B);螺旋甾醇皂苷(Spirostanol Saponins)-葫蘆巴苷(Graecunins)、葫蘆巴肽苷(Fenugreekine);皂苷元(Sapinogen)-薯蕷皂苷元(Diosgenin)、雅姆皂苷元(Yamogenin)、絲蘭皂苷元(Yuccagenin)、利拉皂苷元(Lilagenin)、替告皂苷元(Tigogenin)、新替告皂苷元(Neotigogenin)、芰脫皂苷元(Gitogenin)、新芰脫皂苷元(Neogitogenin)、菝契皂苷元(Sarsasapogenin)、異菝葜皂苷元(Smilagenin);花青苷(Anthocyanins);纖維-膠;其他酚系組分-葫蘆巴香豆精(Trigocoumarin)、東莨菪亭(Scopoletin)、綠原酸(Chlorogenic acids)、咖啡酸(Caffeic acids)及對香豆酸(p-Coumaric acids);脂質;維生素及痕量無機元素。
本發明之主要具體實例為用於治療自體免疫性病症(諸如古巴士德氏病、腎小球性腎炎及類風濕性關節炎)之包含葫蘆巴新皂苷Ib及巢菜素-1之組成物。本發明之新穎性及獨創性在於含有葫蘆巴新皂苷Ib及巢菜素-1之獨特組成物。葫蘆巴新皂苷Ib據報導為存在於葫蘆巴籽中之多種呋喃甾醇皂苷之一。葫蘆巴新皂苷Ib之結構展示於圖1中。Yoshikawa等人(1997)及Murakami等人(2000)對葫蘆巴中所存在之所有葫蘆巴新皂苷進行了特性化,且報導了此等分子之13C NMR、1H NMR及[α]D資料。葫蘆巴新皂苷Ia、Ib及XIb為結構異構體,其分子量為906,且具有類似NMR資料及不同[α]D資料。鑑別特定異構體可使用酸水解進行,其中葫蘆巴新皂苷Ia產生新芰脫皂苷元,葫蘆巴新皂苷Ib產生芰脫皂苷元且葫蘆巴新皂苷XIb產生L-鼠李糖。
多種類黃酮糖苷(亦即蔓荊素、異蔓荊素、葒草素、異葒草素、巢菜素等)存在於葫蘆巴籽中。已研究此等類黃酮之各種生理活性,如抗氧化、抗甲狀腺、抗凋亡、消炎、鎮痛、抗焦慮等。本發明係關於一種類黃酮糖苷巢菜素-1。Wagner等人(1973)報導巢菜素-1存在於葫蘆巴中。巢菜素-1之結構展示於圖2中。含有巢菜素-1之其他植物物種為亞麻、蒜葉婆羅門參(Tragopogon porrifolius)及小麥(Triticum aestivum)。Sato等人(2010)揭示了巢菜素-1之合成方法,且提供合成及天然獲得之巢菜素-1之13C NMR的比較資料。
因此,本發明係關於一種包含葫蘆巴新皂苷Ib及巢菜素-1以及視情況選用之至少一種可接受之賦形劑的組成物;製備包含葫蘆巴新皂苷Ib及巢菜素-1以及視情況選用之至少一種賦形劑之組成物的方法,該方法包含如下操作:a)將葫蘆巴籽製成薄片,b)用溶劑混合物萃取經薄片化葫蘆巴籽,繼而過濾且濃縮,獲得半固體塊,c)溶解該塊,獲得澄清溶液,d)用正丁醇逆流萃取該澄清溶液,獲得包含水層及丁醇層之溶液,e)使水層通過離子交換樹脂及吸附管柱,獲得包含葫蘆巴新皂苷Ib及巢菜素-1之溶離液,f)純化溶離液,獲得自由流動粉末,及g)視情況添加至少一種賦形劑,獲得該組成物;及治療自體免疫性病症之方法,該方法包含向有需要之個體投予包含葫蘆巴新皂苷Ib及巢菜素-1以及視情況選用之至少一種賦形劑之組成物的操作。
本發明係關於一種包含葫蘆巴新皂苷Ib及巢菜素-1以及視情況選用之至少一種賦形劑之組成物。
在本發明之一具體實例中,葫蘆巴新皂苷Ib之濃度在約40%(w/w)至約90%(w/w)範圍內,且巢菜素-1之濃度在約1%(w/w)至約20%(w/w)範圍內。
在本發明之另一具體實例中,葫蘆巴新皂苷Ib及巢菜素-1自植物葫蘆巴獲得。
在本發明之另一具體實例中,賦形劑選自包含以下之群:粒化劑、黏合劑、潤滑劑、崩解劑、甜味劑、著色劑、調味劑、包衣劑、塑化劑、防腐劑、懸浮劑、乳化劑、纖維素物質及滾圓劑或其任何組合。
在本發明之另一具體實例中,組成物調配成選自包含以下之群的劑型:錠劑、膠囊、片劑、口含錠、散劑、糖漿、溶液、氣霧劑、懸浮液、可分散粉末或顆粒、於硬或軟凝膠膠囊中之乳液、糖漿、酏劑、搽劑、軟膏、皮膚貼片、植物藥(phyotceuticals)、營養藥劑(nutraceuticals)及食品。
本發明亦關於一種製備包含葫蘆巴新皂苷Ib及巢菜素-1以及視情況選用之至少一種賦形劑之組成物的方法,該方法包含如下操作:
a. 將葫蘆巴籽製成薄片;
b. 用溶劑混合物萃取經薄片化葫蘆巴籽,繼而過濾且濃縮,獲得半固體塊;
c. 溶解該塊,獲得澄清溶液;
d. 用正丁醇逆流萃取該澄清溶液,獲得包含水層及丁醇層之溶液;
e. 使水層通過離子交換樹脂及吸附管柱,獲得包含葫蘆巴新皂苷Ib及巢菜素-1之溶離液;
f. 純化溶離液,獲得自由流動粉末;及
g. 視情況添加至少一種賦形劑,獲得組成物。
在本發明之一具體實例中,將籽製成尺寸在約1 mm至約5 mm範圍內,更特定言之為2 mm之薄片。
在本發明之另一具體實例中,溶劑混合物包含比率為約1:1至約9:1,更特定言之為4:1之脂族醇及水。
在本發明之另一具體實例中,脂族醇選自包含甲醇、乙醇、丙醇及異丙醇或其任何組合之群。
在本發明之另一具體實例中,將塊溶解於去離子水中。
在本發明之另一具體實例中,進行純化以獲得純度在約90%至約95%範圍內之葫蘆巴新皂苷Ib及純度在約90%至約95%範圍內之巢菜素1。
在本發明之另一具體實例中,純化包含緩衝液處理、繼而醇或酸處理及濃縮以獲得經純化自由流動粉末之步驟。
在本發明之另一具體實例中,濃縮在約40℃至約80℃範圍內,更特定言之約50℃之溫度下進行。
在本發明之另一具體實例中,組成物具有濃度在約40%(w/w)至約90%(w/w)範圍內之葫蘆巴新皂苷Ib及濃度在約1%(w/w)至約20%(w/w)範圍內之巢菜素-1。
在本發明之另一具體實例中,賦形劑選自包含以下之群:粒化劑、黏合劑、潤滑劑、崩解劑、甜味劑、著色劑、調味劑、包衣劑、塑化劑、防腐劑、懸浮劑、乳化劑、纖維素物質及滾圓劑或其任何組合。
本發明亦關於一種治療自體免疫性病症之方法,該方法包含向有需要之個體投予包含葫蘆巴新皂苷Ib及巢菜素-1以及視情況選用之至少一種賦形劑之組成物的操作。
在本發明之一具體實例中,自體免疫性病症選自包含古巴士德氏病、腎小球性腎炎、類風濕性關節炎、全身性紅斑狼瘡及特發性血小板減少性紫癜之群。
在本發明之另一具體實例中,個體為動物或人類。
在本發明之另一具體實例中,組成物以動物中約1 mg/kg至約100 mg/kg及人類中約1 mg/kg至約50 mg/kg範圍內之日劑量投予。
本發明亦關於包含40-90%(w/w)葫蘆巴新皂苷Ib及1-20%(w/w)巢菜素-1之組成物的用途,其用於藉由預防自體抗體介導之器官損傷來治療古巴士德氏病、腎小球性腎炎、類風濕性關節炎、全身性紅斑狼瘡及特發性血小板減少性紫癜。此項技術中尚未知自葫蘆巴籽獲得包含葫蘆巴新皂苷Ib及巢菜素-1之特定組成物的方法。本發明中所揭示方法之獨特之處在於萃取特定言之包含葫蘆巴新皂苷Ib及巢菜素-1之組成物。進行進一步純化,以獲得90-95%純葫蘆巴新皂苷Ib及95%純巢菜素-1以用於組成物之結構特性化及標準化。
在本發明之另一具體實例中,葫蘆巴新皂苷Ib之分子量為906且化學式為C44H74O19。
在本發明之另一具體實例中,巢菜素-1之分子量為564且化學式為C26H28O14。
在本發明之另一具體實例中,該組成物自植物葫蘆巴獲得。
在本發明之另一具體實例中,組成物呈選自包含以下之群之形式:錠劑、膠囊、片劑、口含錠、散劑、糖漿、溶液、氣霧劑、懸浮液、可分散粉末或顆粒、於硬或軟凝膠膠囊中之乳液、糖漿、酏劑、搽劑、軟膏、皮膚貼片、植物藥、營養藥劑及食品。
本發明亦關於一種自葫蘆巴萃取及純化包含葫蘆巴新皂苷Ib及巢菜素-1之組成物的方法,且方法步驟包含以下:
a. 藉由脫脂及移除含氮化合物(如生物鹼、胺基酸)萃取澄清溶液;及
b. 使澄清溶液通過陽離子交換大孔樹脂及吸附管柱以溶離葫蘆巴新皂苷Ib及巢菜素-1;濃縮溶離液且進一步純化。
在本發明之一具體實例中,組成物含有40-90%(w/w)範圍內之葫蘆巴新皂苷Ib及1-20%(w/w)範圍內之巢菜素-1。
在本發明之另一具體實例中,因為葫蘆巴新皂苷Ib及巢菜素-1係自葫蘆巴籽萃取,故暗示該組成物可能包含小比例之來自葫蘆巴籽之含良性分子的纖維素物質,如自HPLC結果可見。(圖3-5)
在本發明之另一具體實例中,步驟(a)中自葫蘆巴萃取澄清溶液由以下步驟組成:
i. 將葫蘆巴籽製成薄片;
ii. 用溶劑萃取薄片狀籽;
iii. 過濾萃取物,得到澄清溶液;
iv. 在真空下濃縮澄清溶液,獲得半固體塊;
v. 溶解濃縮之塊,獲得澄清溶液;
vi. 用正丁醇逆流萃取澄清溶液以移除脂肪物質。
在本發明之一具體實例中,步驟(b)中所用之溶劑為比率在1:1至9:1範圍內且較佳為4:1之水與選自包含甲醇、乙醇、丙醇及異丙醇之群之醇的混合物。
在本發明之另一具體實例中,萃取進行之時間在約8小時至12小時範圍內且較佳為約10小時。
在本發明之另一具體實例中,萃取在約30℃至約40℃範圍內且較佳約35℃之溫度下進行。
在本發明之另一具體實例中,在約45℃至約55℃範圍內且較佳約50℃之溫度下在真空下濃縮萃取物。
在本發明之另一具體實例中,將濃縮之塊溶解於去離子水中。
在本發明之另一具體實例中,包含葫蘆巴新皂苷Ib及巢菜素-1之組成物由步驟(b)中之澄清溶液使用以下步驟獲得:
i. 使澄清水層通過陽離子交換大孔樹脂及吸附管柱以溶離葫蘆巴新皂苷Ib及巢菜素-1;
ii. 濃縮溶離液且噴霧乾燥。
在本發明之另一具體實例中,吸附管柱選自包含酸陽離子交換大孔樹脂、Sephadex LH-20、Dowex Optipore L493或其等效物之群。
在本發明之另一具體實例中,吸附管柱之溶離利用水及乙醇以30:70之初始比率繼而轉變為5:95之比率進行。
在本發明之另一具體實例中,吸附管柱之溶離進行約1小時至約4小時,較佳約2小時。
在本發明之另一具體實例中,濃縮之塊在約110℃至約130℃下,較佳在約120℃下噴霧乾燥。
本發明之另一具體實例係關於葫蘆巴新皂苷Ib之純化方法,且方法步驟包含以下:
i. 將濃縮之溶離液溶解於緩衝液中且過濾不溶物;
ii. 用正丁醇洗滌緩衝溶液;
iii. 濃縮正丁醇溶離份;
iv. 將濃縮之溶離份再溶解於溶劑中;及
v. 使所得溶液通過吸附管柱。
在本發明之另一具體實例中,緩衝溶液選自包含磷酸二氫鉀及鹽酸之群。
在本發明之另一具體實例中,用於再溶解之溶劑為乙醇。
本發明之另一具體實例係關於自包含其他類黃酮糖苷之正丁醇層純化巢菜素-1之方法,且方法步驟包含以下:
i. 在真空下濃縮;
ii. 用緩衝溶液洗滌濃縮物以移除不溶物;
iii.將所得溶液濃縮至一半體積且攪拌;
iv. 過濾以移除不純晶體;及
v. 將不純晶體與溶劑一起回流且過濾,得到95%純巢菜素-1。
在本發明之另一具體實例中,濃縮塊之攪拌進行1小時至48小時,較佳24小時。
在本發明之另一具體實例中,濃縮塊之攪拌在30℃至40℃下,較佳在35℃下進行。
在本發明之另一具體實例中,用於回流之溶劑為比率範圍為1:1之甲醇及二氯甲烷。
本發明亦關於一種製造包含40-90%(w/w)葫蘆巴新皂苷Ib及1-20%(w/w)巢菜素-1以及視情況選用之至少一種賦形劑之組成的醫藥品的方法,及投予有效量之該組成物以治療及管理選自包含古巴士德氏病、腎小球性腎炎、類風濕性關節炎、全身性紅斑狼瘡及特發性血小板減少性紫癜之群之自體免疫性疾病的方法。
本發明亦關於一種治療及管理選自包含古巴士德氏病、腎小球性腎炎、類風濕性關節炎、全身性紅斑狼瘡及特發性血小板減少性紫癜之群之自體免疫性疾病的方法。
在本發明之一具體實例中,個體選自包含動物與人類兩者之群。
本發明進一步藉助於以下實施例闡述。然而,該等實施例不應視為限制本發明之範疇。
實施例1:
將1000 g水分含量低於5%之葫蘆巴籽於輥式刨片機中製成厚度為2 mm之薄片。於包含比率為80:20之乙醇及水的溶劑混合物(8公升)中萃取薄片狀材料,且在40℃下藉由使溶離液再循環通過該層10小時。10小時後,經由200目織物過濾萃取物,得到澄清溶液。在50℃下在真空下將澄清溶液濃縮成半固體塊。將濃縮塊溶解於5公升去離子水中,得到澄清溶液。用正丁醇逆流萃取該澄清水溶液。使澄清水層通過含有200 ml強酸陽離子交換大孔樹脂之管柱2小時。在50℃下濃縮無所有胺基酸、蛋白質、葫蘆巴鹼及其他兩性化合物之澄清管柱流出液體,且在120℃下噴霧乾燥,得到具有約40-46%(w/w)葫蘆巴新皂苷Ib及1-6%(w/w)巢菜素-1之組成的自由流動粉末。組成範圍之變化歸因於季節變化。產量為約60 g。在以下條件下進行HPLC分析:管柱-250 mm長,4.6 mm直徑Kromasil C18 RP 5 μm;移動相-水:乙腈梯度,歷經20分鐘,由75:25開始至65:35;流速-1毫升/分鐘;偵測器波長-210 nm UV。如圖3中所示之HPLC輸出顯示葫蘆巴新皂苷Ib峰在2.2分鐘,且巢菜素-1峰在3.2分鐘。組成藉由外標法(external standardization method)使用獲自實施例4之葫蘆巴新皂苷Ib的經純化樣品及獲自實施例5之巢菜素-1的經純化樣品確定。
實施例2:
將1000 g水分含量低於5%之葫蘆巴籽於輥式刨片機中製成厚度為2 mm之薄片。於包含比率為70:30之異丙醇及水的溶劑混合物(8公升)中萃取薄片狀材料,且在35℃下藉由使溶離液再循環通過該層10小時。10小時後,經由200目織物過濾萃取物,得到澄清溶液。在50℃下在真空下將澄清溶液濃縮成半固體塊。將濃縮塊溶解於5公升去離子水中,得到澄清溶液。用正丁醇逆流萃取該澄清水溶液。使澄清水層通過含有200 ml強酸陽離子交換大孔樹脂之管柱2小時。歷經2小時之時間使無所有胺基酸、蛋白質、葫蘆巴鹼及其他兩性化合物之澄清管柱流出液體再次通過包含Dowex Optipore L493或其等效物之樹脂床,且藉由包含比率為6:3:6:1之甲苯:乙酸乙酯:甲醇:水的薄層層析系統監測吸附過程。如由薄層層析系統所監測,當溶離製程使用95%乙醇時,生物活性化合物開始溶離。收集此等溶離份,篩選,彙集在一起且在55℃下濃縮成55-65%(w/w)葫蘆巴新皂苷Ib及8-12%(w/w)巢菜素-1。組成範圍之變化歸因於季節變化。產量為約15 g。藉由實施例1中所述之方法進行HPLC分析。組成藉由外標法使用獲自實施例4之葫蘆巴新皂苷Ib的經純化樣品及獲自實施例5之巢菜素-1的經純化樣品確定。
實施例3:
將1000 g水分含量低於5%之葫蘆巴籽於輥式刨片機中製成厚度為2 mm之薄片。於包含比率為80:20之乙醇及水的溶劑混合物(8公升)中萃取薄片狀材料,且在35℃下藉由使溶離液再循環通過該層10小時。10小時後,經由200目織物過濾萃取物,得到澄清溶液。在50℃下在真空下將澄清溶液濃縮成半固體塊。將濃縮塊溶解於5公升去離子水中,得到澄清溶液。用正丁醇逆流萃取該澄清水溶液。使澄清水層通過含有200 ml強酸陽離子交換大孔樹脂之管柱2小時。歷經2小時之時間使無所有胺基酸、蛋白質、葫蘆巴鹼及其他兩性化合物之澄清管柱流出液體再次通過包含Dowex Optipore L493或其等效物之樹脂床,且藉由包含比率為6:3:6:1之甲苯:乙酸乙酯:甲醇:水的薄層層析系統監測吸附過程。如由薄層層析系統所監測,當溶離製程使用70:30乙醇:水混合物時,生物活性化合物開始溶離。收集此等溶離份,篩選,彙集在一起且在50℃下濃縮成70-76%(w/w)葫蘆巴新皂苷Ib及15-18%(w/w)巢菜素-1。組成範圍之變化歸因於季節變化。產量為約9 g。藉由實施例1中所述之方法進行HPLC分析,且輸出層析圖展示於圖4中。組成藉由外標法使用獲自實施例4之葫蘆巴新皂苷Ib的經純化樣品及獲自實施例5之巢菜素-1的經純化樣品確定。
葫蘆巴新皂苷Ib及巢菜素-1之純標準物不可自參考標準物供應商獲得。因此,出於組成物之結構闡明及標準化之目的,進行實施例4及實施例5以分別分離葫蘆巴新皂苷Ib及巢菜素-1之經純化樣品。
實施例4:
將實施例1-3之組成物溶解於50 mM磷酸二氫鉀緩衝液(300 ml)中且濾出不溶物。用正丁醇洗滌緩衝溶液三次(75 ml×3)且獨立地濃縮所有三份溶離份。溶離份1、2及3分別展示85%、68%、40%純度之葫蘆巴新皂苷Ib。85%純粉末狀葫蘆巴新皂苷Ib為起始重量之約10%,將其再溶解於乙醇中且通過Sephadex LH-20床(床體積125 ml),收集溶離份且篩選純葫蘆巴新皂苷Ib。濃縮純葫蘆巴新皂苷Ib溶離份,得到約90-95%面積純度,其可用於結構特性化。產率為起始重量之約0.2%的結晶灰白色粉末。藉由實施例1中所述之方法進行HPLC分析,且輸出層析圖展示於圖5中。
熔點為220℃且LCMS分析證實質量為906(M+Na=929)。呋喃甾醇皂苷結構之存在藉由薄層層析(TLC)使用比率為6:3:6:1之甲苯:乙酸乙酯:甲醇:水,繼而噴灑5%茴香醛硫酸且在110℃下加熱15分鐘顯示單個棕綠色斑點證實。CD3OD中之13C NMR分析(100 Mhz):δC(ppm) 44.43(C-1),71.6(C-2),85.8(C-3),34.9(C-4),44.4(C-5),28.4(C-6),30.78(C-7),34.1(C-8),51.7(C-9),36.9(C-10),22.0(C-11),39.6(C-12),41.8(C-13),57.8(C-14),32.8(C-15),82.4(C-16),65.06(C-17),16.9(C-18),12.08(C-19),40.8(C-20),16.3(C-21),114.0(C-22),38.5(C-23),28.9(C-24),34.9(C-25),76.0(C-26),17.6(C-27);葡萄糖-I:102.35(C-1'),75.1(C-2'),79.3(C-3'),73.7(C-4'),77.0(C-5'),70.6(C-6');木糖:104.57(C-1"),76.05(C-2"),78.08(C-3"),72.4(C-4"),67.0(C-5'');葡萄糖-II:103.0(C-1'''),76.5(C-2'''),79.7(C-3'''),72.1(C-4'''),82.43(C-5'''),62.8(C-6''');CD3OD中之1H NMR分析:0.744(19-H3),0.869(18-H3),0.959(27-H3),1.05(5-H),1.51(21-H3),2.06(25-H),2.206(20-H),3.48,4.05(26-H2),3.699(3-H),4.14(2-H),4.04,5.1(6’-H2);[α]D 24(c=0.37,吡啶):-41.9°。
實施例5:
在50℃下使用真空蒸發器將約8000 ml來自實施例1-3之包含其他類黃酮糖苷之正丁醇層濃縮至400 ml。相繼用50 mM磷酸二氫鉀溶液及500 ml 1%鹽酸水溶液洗滌此溶液兩次。在此階段,不溶物以黃色非晶形粉末形式沈降。將上述溶液濃縮至一半體積且在30℃至35℃下攪拌24小時以使更多其他類黃酮糖苷之晶體沈降且過濾。在15℃下於甲醇與二氯甲烷之1:1混合物中回流此等不純晶體3小時且在5℃下過濾,得到95%純巢菜素-1。產量為約1.8 g。
熔點為215℃且伴以分解,且LCMS分析證實質量為564(M+H=565)。類黃酮糖苷結構之存在進一步藉由薄層層析(TLC)使用比率為6:3:6:1之甲苯:乙酸乙酯:甲醇:水,繼而噴灑5%甲醇硫酸且在110℃下加熱15分鐘顯示單個黃色斑點證實。CD3OD中之13C NMR分析(100 Mhz):δC(ppm) 164.57(C-2),103.05(C-3),182.7(C-4),161.4(C-5),108.55(C-6),158.7(C-7),104.1(C-8),155.5(C-9),103.1(C-10),122.0(C-1'),129.2(C-2'),116.45(C-3'),161.6(C-4'),116.29(C-5'),129.1(C-6');木糖:74.6(C-1"),70.5(C-2"),79.3(C-3"),70.7(C-4"),68.9(C-5");葡萄糖:71.76(C-1'''),70.99(C-2'''),79.67(C-3'''),70.05(C-4'''),82.35(C-5'''),61.6(C-6''');DMSO-d6中之1H NMR分析(在25℃下):對應於黃酮質子環之芳族質子-[6.79,6.8;7.936,7.949;6.897,6.951;8.0,8.031],糖質子-6-C-木糖苷在3.09至4.65之間且8-C-葡糖苷在3.29至4.77之間。
實施例6:
在本發明之一具體實例中,將1 g 76%葫蘆巴新皂苷Ib及15%巢菜素-1與14 g 91%葫蘆巴新皂苷Ib及5%巢菜素-1摻合,得到包含15 g 90%葫蘆巴新皂苷Ib及5.7%巢菜素-1之組成物。此實施例展示藉由混合具有變化濃度之葫蘆巴新皂苷Ib及巢菜素-1的不同組成物獲得包含40-90%(w/w)葫蘆巴新皂苷Ib及1-20%(w/w)巢菜素-1之所要組成範圍的方法。熟習此項技術者應瞭解本文獲得之組成物可藉由混合組分葫蘆巴新皂苷Ib及巢菜素-1獲得,該等組分可藉由自植物來源萃取獲得或藉由化學合成該等組分獲得。因此,葫蘆巴並非獲得該組成物之唯一來源。其可藉由混合合成組分葫蘆巴新皂苷Ib及巢菜素-1獲得。
此外,組成物亦可藉由混合如本發明中所述之實施例中獲得之組分葫蘆巴新皂苷Ib及巢菜素-1獲得。
在以下實施例中進一步測試自上述實施例中所說明方法獲得之包含40-90%(w/w)葫蘆巴新皂苷Ib及1-20%(w/w)巢菜素-1的測試組成物的生理活性:
實施例7:在大鼠中誘發之腎小球性腎炎中的活性
腎小球性腎炎為自體免疫性疾病(如古巴士德氏病)中腎衰竭及死亡之主要原因。進行此研究以檢查包含76%(w/w)葫蘆巴新皂苷Ib及15%(w/w)巢菜素-1之測試組成物在抗GBM誘發之新月體性腎小球性腎炎(crescentric glomerulonephritis)之大鼠模型中的作用。
將體重為180-220 g之雄性韋斯大鼠(wistar rat)分組,每組6隻動物。如Chen等人(2004)所說明藉由首先皮下投予含大鼠IgG(5 mg)之傅氏完全佐劑(Freund's complete adjuvant,FCA),繼而5天後靜脈內投予GBM(0.5 ml)誘發腎小球性腎炎。處理組中之動物每天經口接受測試組成物(75 mg/kg)兩次歷時28天。GBM對照組中之動物不接受任何處理。未進行腎小球性腎炎誘發及處理之第三組動物飼養用作正常對照組。在誘發腎小球性腎炎前及完成處理後量測及分析尿液輸出。在第28天,處死動物以對其腎及肺進行組織病理學檢查。
n=5;資料相繼藉由雙因素ANOVA及邦弗朗尼事後檢驗(Bonferroni Post test)進行分析;###:對於各別天,相較於正常對照組,P<0.001;***:對於各別天,相較於GBM對照組,P<0.001。
在第28天,GBM對照組中動物每天排出之尿液蛋白質(毫克/天)增加至基線值之三倍。尿液蛋白質排出增加為腎功能降低之指標。用測試藥物處理使尿液蛋白質排出完全趨於正常,使其維持接近基線值。
病理學分級:重度(+++);中度(++);輕度(+);不存在(--)。
誘發腎小球性腎炎之大鼠的腎組織病理學影像展示於圖6中。用測試組成物處理之動物顯示相較於GBM對照組,不存在腎小管成型物,且腎小球破壞、腎小管腫脹及細胞浸潤顯著較少。因此,藉由用測試組成物處理使病理學病狀顯著減少。
病理學分級:重度(+++);中度(++);輕度(+);不存在(--)。
亦檢查了抗GBM抗體對肺中之肺泡基膜的病理學效應。GBM對照組中動物肺之組織病理學檢查顯示肺泡壁厚度顯著增加,肺泡隔弦長增加以及肺間質增厚,重度發炎(如由淋巴細胞、巨噬細胞及單核細胞浸潤至間質中所證實),及RBC顯著滲出至間質中。用測試組成物處理之動物顯示所有上述病理學病狀顯著減少,表明測試組成物在預防抗體對肺之損傷中具有有益活性。
測試組成物有效降低抗GBM抗體對腎與肺兩者誘發之損傷,從而證實其在特徵為患者罹患腎小球性腎炎與肺出血之古巴士德氏病中具有活性。因此,測試組成物適用於治療抗GBM病,如腎小球性腎炎、古巴士德氏病等。
實施例8:測試組成物之消炎活性
進行此測試以評估包含65%(w/w)葫蘆巴新皂苷Ib及10%(w/w)巢菜素-1之測試組成物抑制由前列腺素引起之發炎的活性。用測試組成物預處理體重為180-220 g之雄性韋斯大鼠。預處理後一小時,向右後爪給予0.1 ml 1%角叉菜膠溶液之次種植注射液(sub-planter injection)。使用器官充滿度測量器(plethysmometer)(UGO Basile 7140)量測誘發之爪水腫。在第3小時時爪水腫之抑制顯示消炎作用。
爪水腫之抑制計算為對照組與測試組成物處理組中爪體積平均值的差異百分比。在2小時及3小時後,測試組成物使由角叉菜膠誘發之爪水腫顯著減少。
n=6;資料相繼藉由雙因素ANOVA及邦弗朗尼事後檢驗分析;對於各別小時,相較於正常對照組,***P<0.001,**P<0.01且*P<0.05。
實施例9:測試組成物之活體外細胞激素抑制作用
脂多醣(LPS)為革蘭氏陰性細菌之組分,其可誘導氧化氮之過量產生,該氧化氮轉而又刺激細胞激素分泌。使用LPS刺激人類周邊血液單核細胞(PBMC)系統以表現IL-1β、IL-6及TNF-α。對測試組成物在抑制此等促發炎性細胞激素之釋放中的活性進行測試。測試組成物對促發炎性細胞激素分泌顯示顯著抑制活性。
實施例10:測試組成物之抗關節炎作用
藉由在大鼠爪中注射傅氏完全佐劑(FCA)且量測未注射爪中的水腫形成及爪體積之抑制百分比來研究抗關節炎活性。
向體重在190-250 g之間的雄性韋斯大鼠的左後爪的次種植區中注射0.1 ml FCA。0.1 ml FCA溶液由懸浮於重石蠟油(Merck)中之6 mg丁酸分枝桿菌(Mycobacterium Butyrium)(Difco)之完全溶離份組成。數小時後產生局部水腫。FCA注射後第13天至第21天用測試化合物進行處理。使用器官充滿度測量器(UGO Basile 7140)記錄未注射後爪之體積。
未注射爪中發炎之抑制百分比量測為FCA對照組與處理動物之平均爪體積之差異。開始用測試組成物處理後5天(第18天)與8天(第21天)均觀察到FCA誘發之關節腫脹顯著減少。測試組成物顯示關節炎幾乎減少80%。
n=6;資料相繼藉由雙因素ANOVA及邦弗朗尼事後檢驗分析;##:對於各別天,相較於正常對照組,P<0.001;***:對於各別天,相較於FCA對照組,P<0.001。
實施例11:類風濕性關節炎患者中測試組成物之軼事研究(Anecdotal Study)
在年齡在45-60歲之間的5位類風濕性關節炎(RA)患者中進行未來性研究。每天向患者投予劑量為500 mg之測試組成物之膠囊兩次歷時1年,且基於由Kumar等人(Rheumatology,第41卷,第1457-1459頁,2002)公開之健康評估問卷(Health Assessment Questionnaire;HAQ)中患者報導之結果分析測試組成物之功效。
分值(0-3):0-無任何困難;1-有一些困難;2-有很大困難;3-不能進行。失能分值計算為所有分值之總和除以12。
表7中提供軼事研究患者在用測試組成物治療開始前及治療1年後之個別健康評估分值。失能分值計算為所有分值之總和除以12。所有患者顯示失能分值得到改良。在研究開始時,4/5患者具有2至3範圍內之重度失能分值。用測試組成物治療12個月後,僅1/5患者仍具有2至3範圍內之重度失能分值。可見日常活動顯著改良且患者對測試組成物具有大於90%之順應性。因此,發現測試組成物為安全的且適用於治療診斷患有類風濕性關節炎之患者。
實施例12:測試組成物之調配物
實施例11中之膠囊藉由將包含76%(w/w)葫蘆巴新皂苷Ib及15%(w/w)巢菜素-1之測試組成物與1.5% w/w微晶纖維素、1% w/w預膠凝化澱粉崩解劑、0.5% w/w交聯聚維酮(crospovidone)及0.5% w/w硬脂酸鎂抗黏著劑摻合進行粒化來製備。將混合之顆粒填充於膠囊中。
含有範圍為40-90%(w/w)葫蘆巴新皂苷Ib及1-20%(w/w)巢菜素-1之測試組成物的類似調配物可藉由添加選自包含以下之清單的賦形劑來製備:粒化劑、黏合劑、潤滑劑、崩解劑、甜味劑、著色劑、調味劑、包衣劑、塑化劑、防腐劑、懸浮劑、乳化劑、滾圓劑及其任何組合。且調配物之類型可選自由以下組成之群:錠劑、膠囊、片劑、口含錠、散劑、糖漿、溶液、氣霧劑、懸浮液、可分散粉末或顆粒、於硬或軟凝膠膠囊中之乳液、糖漿、酏劑、搽劑、軟膏、皮膚貼片、植物藥、營養藥劑及食品。視投藥途徑而定,可使用不同賦形劑/載劑。熟習此項技術者可選擇測試組成物之適合調配物用治療自體免疫性疾病,亦即古巴士德氏病、腎小球性腎炎、類風濕性關節炎、全身性紅斑狼瘡及特發性血小板減少性紫癜。
實施例13:全身性紅斑狼瘡(SLE)患者之軼事研究
於3位診斷患有全身性紅斑狼瘡(SLE)且年齡在35-50歲之間的患者中進行未來性研究歷時6個月的時間。以兩個500 mg膠囊之劑量每天兩次投予如實施例12中所述之測試組成物調配物。藉由追蹤實驗參數及日常活動指數監測測試組成物之活性。
用測試組成物治療顯著改良腎功能、血液參數,且使關節疼痛減輕,減少脫髮、皮疹及口腔潰瘍。此等結果可由患者1之SLE日常活動指數(SLEDAI)分值自治療開始時的20改良為治療結束時的10得到證明。在治療6個月後,對於患者2可見自10至6之類似改良且對於患者3可見自12至8之類似改良。因此,發現測試組成物適用於治療及管理SLE。
實施例14:測試組成物對特發性血小板減少性紫癜(ITP)之活性
檢查Balb-c小鼠以選擇基線血小板計數在生理極限範圍內之小鼠且分成3組。藉由向ITP對照組及測試組成物處理組中之動物腹膜內注射4 μg大鼠抗小鼠整合素(integrin)αIIb抗體誘發特發性血小板減少性紫癜(ITP)。在誘發ITP前1小時,處理組中之動物接受75 mg/kg包含76%(w/w)葫蘆巴新皂苷Ib及15%(w/w)巢菜素-1之測試組成物。正常對照組中之動物既不誘發ITP亦不接受任何處理。誘發ITP後3小時,由所有組中之動物抽取血液以分析血小板計數。
用測試組成物處理之動物在投予抗血小板抗體後顯示血小板減少顯著較低,相較於ITP對照動物中之60%,僅為16.5%。正常對照組動物亦顯示22%之血小板減少。此減少歸因於後續抽取血液以分析血小板計數。
上述實施例證明測試組成物對抗體介導之血小板計數減少有效,且因此適用於治療及管理ITP及/或血小板減少。
圖1展示葫蘆巴新皂苷Ib之結構。
圖2展示巢菜素-1之結構。
圖3展示46%葫蘆巴新皂苷Ib及6%巢菜素-1之HPLC層析圖。
圖4展示76%葫蘆巴新皂苷Ib及15%巢菜素-1之HPLC層析圖。
圖5展示91%葫蘆巴新皂苷Ib及5%巢菜素-1之HPLC層析圖。
圖6展示誘發腎小球性腎炎之大鼠的腎組織病理學影像;(右)GBM對照組;(左)GBM+測試組成物(75 mg/kg)組;(1)尿形成空間,(2)腎小球之破壞;(3)腎小管腫脹;(4)腎小管成型物;(5)細胞浸潤;(6)腎小球炎免疫反應。
Claims (19)
- 一種組成物,其包含葫蘆巴新皂苷Ib(Trigoneoside Ib)及巢菜素-1(Vicenin-1)以及視情況選用之至少一種賦形劑。
- 如申請專利範圍第1項之組成物,其中該葫蘆巴新皂苷Ib之濃度在約40%(w/w)至約90%(w/w)範圍內且巢菜素-1之濃度在約1%(w/w)至約20%(w/w)範圍內。
- 如申請專利範圍第1項之組成物,其中該葫蘆巴新皂苷Ib及該巢菜素-1係自植物葫蘆巴(Trigonella foenum-graecum)獲得。
- 如申請專利範圍第1項之組成物,其中該賦形劑選自包含以下之群:粒化劑、黏合劑、潤滑劑、崩解劑、甜味劑、著色劑、調味劑、包衣劑、塑化劑、防腐劑、懸浮劑、乳化劑、纖維素物質及滾圓劑或其任何組合。
- 如申請專利範圍第1項之組成物,其中該組成物調配成選自包含以下之群的劑型:錠劑、膠囊、片劑、口含錠、散劑、糖漿、溶液、氣霧劑、懸浮液、可分散粉末或顆粒、於硬或軟凝膠膠囊中之乳液、糖漿、酏劑、搽劑、軟膏、皮膚貼片、植物藥(phyotceuticals)、營養藥劑(nutraceuticals)及食品。
- 一種製備包含葫蘆巴新皂苷Ib及巢菜素-1以及視情況選用之至少一種賦形劑之組成物的方法,該方法包含以下操作:a.將葫蘆巴籽製成薄片;b.用溶劑混合物萃取經薄片化葫蘆巴籽,繼而過濾且濃縮,獲得半固體塊;c.溶解該塊,獲得澄清溶液;d.用正丁醇逆流萃取該澄清溶液,獲得包含水層及丁醇層之溶液;e.使該水層通過離子交換樹脂及吸附管柱,獲得包含該葫蘆巴新皂苷Ib及該巢菜素-1之溶離液;f.純化該溶離液,獲得自由流動粉末;及g.視情況添加至少一種賦形劑,獲得該組成物。
- 如申請專利範圍第6項之方法,其中將該等籽製成尺寸在約1 mm至約5 mm範圍內,更特定言之為2 mm之薄片。
- 如申請專利範圍第6項之方法,其中該溶劑混合物包含比率為約1:1至約9:1,更特定言之為4:1之脂族醇及水。
- 如申請專利範圍第8項之方法,其中該脂族醇選自包含甲醇、乙醇、丙醇及異丙醇或其任何組合之群。
- 如申請專利範圍第6項之方法,其中將該塊溶解於去離子水中。
- 如申請專利範圍第6項之方法,其中進行該純化,獲得純度在約90%至約95%範圍內之該葫蘆巴新皂苷Ib及純度在約90%至約95%範圍內之該巢菜素1。
- 如申請專利範圍第6項之方法,其中該純化包含緩衝液處理、繼而醇或酸處理及濃縮以獲得經純化自由流動粉末之步驟。
- 如申請專利範圍第6項之方法,其中該濃縮在約40℃至約80℃範圍內,更特定言之約50℃之溫度下進行。
- 如申請專利範圍第6項之方法,其中該組成物具有濃度在約40%(w/w)至約90%(w/w)範圍內之該葫蘆巴新皂苷Ib及濃度在約1%(w/w)至約20%(w/w)範圍內之該巢菜素-1。
- 如申請專利範圍第6項之方法,其中該賦形劑選自包含以下之群:粒化劑、黏合劑、潤滑劑、崩解劑、甜味劑、著色劑、調味劑、包衣劑、塑化劑、防腐劑、懸浮劑、乳化劑、纖維素物質及滾圓劑或其任何組合。
- 一種用於治療自體免疫性病症的方法,該方法包括將包含葫蘆巴新皂苷Ib及巢菜素-1以及視情況選用之至少一種賦形劑之組成物投予至有需要之個體的操作。
- 如申請專利範圍第16項之方法,其中該自體免疫性病症選自包含古巴士德氏病(Goodpasture's disease)、腎小球性腎炎、類風濕性關節炎、全身性紅斑狼瘡及特發性血小板減少性紫癜之群。
- 如申請專利範圍第16項之方法,其中該個體為動物或人類。
- 如申請專利範圍第16項之方法,其中該組成物以動物中約1 mg/kg至約100 mg/kg及人類中約1 mg/kg至約50 mg/kg範圍內之日劑量投予。
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IN1367MU2011 | 2011-05-02 |
Publications (2)
Publication Number | Publication Date |
---|---|
TW201300112A true TW201300112A (zh) | 2013-01-01 |
TWI449527B TWI449527B (zh) | 2014-08-21 |
Family
ID=47090391
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
TW100129711A TWI449527B (zh) | 2011-05-02 | 2011-08-19 | 組成物及其方法 |
Country Status (11)
Country | Link |
---|---|
US (1) | US8513203B2 (zh) |
EP (1) | EP2704710B1 (zh) |
JP (1) | JP5760145B2 (zh) |
KR (1) | KR101628853B1 (zh) |
CN (1) | CN103517709B (zh) |
AU (1) | AU2011367351B2 (zh) |
BR (1) | BR112013028221B1 (zh) |
CA (1) | CA2833324C (zh) |
ES (1) | ES2664187T3 (zh) |
TW (1) | TWI449527B (zh) |
WO (1) | WO2012150486A1 (zh) |
Families Citing this family (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN104926896A (zh) * | 2015-06-19 | 2015-09-23 | 武汉光谷人福生物医药有限公司 | 从广金钱草中提取分离Vicenin-1的方法和系统 |
US10493088B2 (en) | 2015-09-19 | 2019-12-03 | Indus Biotech Private Limited | Composition of trigofoenoside and flavonoids and methods thereof |
USD870125S1 (en) | 2018-07-31 | 2019-12-17 | Samsung Electronics Co., Ltd. | Display screen or portion thereof with transitional graphical user interface |
CN112299997B (zh) * | 2020-11-20 | 2022-12-20 | 河南大学 | 一种从Nigella sativa种籽中分离提取链状酯类化合物的方法 |
Family Cites Families (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FI955691A (fi) * | 1994-11-28 | 1996-05-29 | Suntory Ltd | Lipoproteiini(a):ta alentava aine, kolesterolia alentava aine ja näitä aineita sisältävät lääkkeet |
US5707631A (en) | 1996-04-30 | 1998-01-13 | Advanced Plant Pharmaceuticals Incorporated | Therapeutic herbal composition |
US6080401A (en) | 1998-11-19 | 2000-06-27 | Reddy; Malireddy S. | Herbal and pharmaceutical drugs enhanced with probiotics |
NL1021288C2 (nl) * | 2002-08-16 | 2004-02-17 | Exenta B V | Kruidenextract, alsmede de toepassing van een dergelijk kruidenextract. |
WO2005058337A1 (fr) * | 2003-12-19 | 2005-06-30 | Jiangxi Yicun Pharmaceutical Co., Ltd | Produits pharmaceutiques issus de la medecine traditionnelle chinoise pour le traitement du cancer du poumon et procede pour preparer lesdits produits |
US20050226948A1 (en) * | 2004-03-02 | 2005-10-13 | Lee Steve S | Methods for enhancing the transport of glucose into muscle |
JP5372358B2 (ja) * | 2007-01-20 | 2013-12-18 | 美智士 谷 | 生体活性治療物質 |
EA018425B1 (ru) * | 2007-04-13 | 2013-07-30 | В-БАЙОТЕК ХОЛДИНГ ЭйПиЭс | Фармацевтический, дезинфицирующий или консервирующий экстракт пажитника сенного (trigonella foenum-graecum), способ его получения и применение экстракта |
WO2010134100A2 (en) * | 2009-05-22 | 2010-11-25 | Bio-Ved Pharmaceuticals, Pvt. Ltd. | A method for extraction of fractions containing pharmacologically active ingredients with less cytotoxicity from one or more plants |
-
2011
- 2011-06-14 US US13/160,347 patent/US8513203B2/en active Active
- 2011-06-15 KR KR1020137031474A patent/KR101628853B1/ko active IP Right Grant
- 2011-06-15 JP JP2014508880A patent/JP5760145B2/ja active Active
- 2011-06-15 EP EP11864742.9A patent/EP2704710B1/en active Active
- 2011-06-15 CA CA2833324A patent/CA2833324C/en active Active
- 2011-06-15 CN CN201180070564.7A patent/CN103517709B/zh active Active
- 2011-06-15 WO PCT/IB2011/052592 patent/WO2012150486A1/en active Application Filing
- 2011-06-15 BR BR112013028221-5A patent/BR112013028221B1/pt active IP Right Grant
- 2011-06-15 ES ES11864742.9T patent/ES2664187T3/es active Active
- 2011-06-15 AU AU2011367351A patent/AU2011367351B2/en active Active
- 2011-08-19 TW TW100129711A patent/TWI449527B/zh active
Also Published As
Publication number | Publication date |
---|---|
TWI449527B (zh) | 2014-08-21 |
KR20140003644A (ko) | 2014-01-09 |
ES2664187T3 (es) | 2018-04-18 |
BR112013028221A2 (pt) | 2017-01-17 |
BR112013028221B1 (pt) | 2022-01-04 |
JP5760145B2 (ja) | 2015-08-05 |
CN103517709A (zh) | 2014-01-15 |
CA2833324A1 (en) | 2012-11-08 |
JP2014518856A (ja) | 2014-08-07 |
KR101628853B1 (ko) | 2016-06-09 |
US20120282332A1 (en) | 2012-11-08 |
EP2704710A1 (en) | 2014-03-12 |
WO2012150486A1 (en) | 2012-11-08 |
CN103517709B (zh) | 2017-05-03 |
EP2704710B1 (en) | 2017-12-27 |
US8513203B2 (en) | 2013-08-20 |
CA2833324C (en) | 2015-06-30 |
AU2011367351B2 (en) | 2015-11-19 |
RU2013153238A (ru) | 2015-06-10 |
AU2011367351A1 (en) | 2013-11-07 |
EP2704710A4 (en) | 2014-11-26 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN103393736B (zh) | 一种用于治疗阿尔茨海默病的药物组合物及其制备方法和用途 | |
Kumar et al. | Effect of Helicteres isora bark extract on blood glucose and hepatic enzymes in experimental diabetes | |
TWI449527B (zh) | 組成物及其方法 | |
Zaki et al. | In vitro antilithiatic activity of the hydro-alcoholic extract of Cinnamomum zeylanicum Blume bark on calcium oxalate crystallization | |
Mworia et al. | Antinociceptive activities of acetone leaf extracts of Carissa Spinarum in mice | |
WO2017148414A1 (zh) | 褐藻多糖及其制备方法和用途 | |
KR101431788B1 (ko) | 신장결석 치료용 중약 조성물 및 그의 제조방법과 이를 이용한 신장결석 치료용 의약 | |
Kayalvizhi et al. | Phytochemical screening and antinephrolithiasis activity of ethanol extract of Aerva lanata on ethylene glycol induced renal stone in rats | |
CN107158050A (zh) | 圆锥绣球总香豆素苷、其制备方法及其组合物与用途 | |
JP2000511166A (ja) | ハルパゴフィタム プロカンベンス及び/又はハルパゴフィタム ゼイヘリ デンスから精製された抽出物、その製造方法及びその使用 | |
Maruthappan et al. | Blood cholesterol lowering effect of adenanthera pavonina seed extract on atherogenic diet induced hyperlipidemia in rats | |
Ingale et al. | Evaluation anti-asthmatic activity of hydroalcoholic extract of Luffa cylindrica leaves | |
RU2575585C2 (ru) | Композиция для лечения аутоиммунных заболеваний и способы, связанные с ней | |
Rao et al. | Evaluation of anti-inflammatory and anti arthritic activity for different extracts of aerial parts of Cassia grandis linn | |
Sharma et al. | In-vitro evaluation of antinephrolithiatic effect of selected medicinal plants (Bryophyllumpinnatum, Durantaerecta, Cynodondactylon, Duchesnea indica, Taraxacum officinalis) | |
Chandrasekar et al. | Evaluation of in vitro antiurolithiatic potential of ethanolic leaf extract of Langerstromia specoisa | |
Sharma et al. | Evaluation of Analgesic and Anti-Inflammatory Activity of Kalanchoe spanthulata Leaves Extract. | |
Tiwari et al. | Nephroprotective role of neeri-kft (a polyherbal formulation) against gentamicin induced nephrotoxicity in experimental rat model: a pre-clinical study | |
KR102048565B1 (ko) | 삼채 및 강황의 혼합 추출물을 포함하는 골관절염 예방 또는 치료용 조성물 | |
Haque | Antinociceptive, anti-inflammatory and central nervous system depressant effects of crude ethanol extract and its aqueous, chloroform and petroleum ether fractions of Dendrophthoe falcata (Linn.) stem | |
KR100558930B1 (ko) | 하르파고피툼프로쿰벤스및/또는하르파고피툼제이헤리덴스로부터얻은정제된추출물,이의제조방법및이의용도 | |
Yasmin et al. | Anti Urolithiatic Activity of Dolichos biflorus by Using Wistar Albino Rats in Ethylene Glycol Induction Method. | |
CN1628747B (zh) | 一种治疗急性热病的药物及其制备方法 | |
Kamil et al. | Pharmacological Evaluation of Aqueous Extract of Plant Formulation Against Sodium Oxalate Induced Urolithiasis in Mice | |
Sharma et al. | Research Article Antiurolithiasis Activity of Bioactivity Guided Fraction of Bergenia ligulata against Ethylene Glycol Induced Renal Calculi in Rat |