CN116350620A - Application of puerarin in preparing medicine for preventing or treating autoimmune demyelinating diseases - Google Patents
Application of puerarin in preparing medicine for preventing or treating autoimmune demyelinating diseases Download PDFInfo
- Publication number
- CN116350620A CN116350620A CN202111625337.8A CN202111625337A CN116350620A CN 116350620 A CN116350620 A CN 116350620A CN 202111625337 A CN202111625337 A CN 202111625337A CN 116350620 A CN116350620 A CN 116350620A
- Authority
- CN
- China
- Prior art keywords
- puerarin
- multiple sclerosis
- diseases
- mice
- autoimmune
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- RXUWDKBZZLIASQ-UHFFFAOYSA-N Puerarin Natural products OCC1OC(Oc2c(O)cc(O)c3C(=O)C(=COc23)c4ccc(O)cc4)C(O)C(O)C1O RXUWDKBZZLIASQ-UHFFFAOYSA-N 0.000 title claims abstract description 73
- HKEAFJYKMMKDOR-VPRICQMDSA-N puerarin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1C1=C(O)C=CC(C2=O)=C1OC=C2C1=CC=C(O)C=C1 HKEAFJYKMMKDOR-VPRICQMDSA-N 0.000 title claims abstract description 73
- 208000016192 Demyelinating disease Diseases 0.000 title claims abstract description 37
- 239000003814 drug Substances 0.000 title claims abstract description 37
- 230000001363 autoimmune Effects 0.000 title claims abstract description 22
- 229940079593 drug Drugs 0.000 claims abstract description 17
- 239000000725 suspension Substances 0.000 claims description 18
- 201000006417 multiple sclerosis Diseases 0.000 claims description 16
- 239000008194 pharmaceutical composition Substances 0.000 claims description 14
- 238000011282 treatment Methods 0.000 claims description 13
- 210000003169 central nervous system Anatomy 0.000 claims description 10
- 239000004480 active ingredient Substances 0.000 claims description 7
- -1 controlled release Substances 0.000 claims description 7
- 239000000203 mixture Substances 0.000 claims description 7
- 239000000243 solution Substances 0.000 claims description 7
- 208000023275 Autoimmune disease Diseases 0.000 claims description 6
- 229920002472 Starch Polymers 0.000 claims description 6
- 239000002775 capsule Substances 0.000 claims description 6
- 208000007118 chronic progressive multiple sclerosis Diseases 0.000 claims description 6
- 208000033808 peripheral neuropathy Diseases 0.000 claims description 6
- 230000000750 progressive effect Effects 0.000 claims description 6
- 239000008107 starch Substances 0.000 claims description 6
- 235000019698 starch Nutrition 0.000 claims description 6
- 230000003210 demyelinating effect Effects 0.000 claims description 5
- 239000002552 dosage form Substances 0.000 claims description 5
- 230000002757 inflammatory effect Effects 0.000 claims description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- 239000000843 powder Substances 0.000 claims description 5
- 210000004885 white matter Anatomy 0.000 claims description 5
- 229920001353 Dextrin Polymers 0.000 claims description 4
- 239000004375 Dextrin Substances 0.000 claims description 4
- 235000019425 dextrin Nutrition 0.000 claims description 4
- 239000000839 emulsion Substances 0.000 claims description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 4
- 239000011734 sodium Substances 0.000 claims description 4
- 208000030939 Chronic inflammatory demyelinating polyneuropathy Diseases 0.000 claims description 3
- 208000029067 Neuromyelitis optica spectrum disease Diseases 0.000 claims description 3
- 206010034620 Peripheral sensory neuropathy Diseases 0.000 claims description 3
- 208000002552 acute disseminated encephalomyelitis Diseases 0.000 claims description 3
- 230000001154 acute effect Effects 0.000 claims description 3
- 201000005795 chronic inflammatory demyelinating polyneuritis Diseases 0.000 claims description 3
- 206010061811 demyelinating polyneuropathy Diseases 0.000 claims description 3
- 238000009472 formulation Methods 0.000 claims description 3
- 239000008176 lyophilized powder Substances 0.000 claims description 3
- 201000001119 neuropathy Diseases 0.000 claims description 3
- 230000007823 neuropathy Effects 0.000 claims description 3
- 210000001428 peripheral nervous system Anatomy 0.000 claims description 3
- 239000006187 pill Substances 0.000 claims description 3
- 230000002265 prevention Effects 0.000 claims description 3
- 201000005572 sensory peripheral neuropathy Diseases 0.000 claims description 3
- 229910052708 sodium Inorganic materials 0.000 claims description 3
- 235000015424 sodium Nutrition 0.000 claims description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 2
- 206010067063 Progressive relapsing multiple sclerosis Diseases 0.000 claims description 2
- 208000007400 Relapsing-Remitting Multiple Sclerosis Diseases 0.000 claims description 2
- 238000013270 controlled release Methods 0.000 claims description 2
- 206010014599 encephalitis Diseases 0.000 claims description 2
- 235000019359 magnesium stearate Nutrition 0.000 claims description 2
- 230000003228 microsomal effect Effects 0.000 claims description 2
- 206010063401 primary progressive multiple sclerosis Diseases 0.000 claims description 2
- 201000008628 secondary progressive multiple sclerosis Diseases 0.000 claims description 2
- 238000013268 sustained release Methods 0.000 claims description 2
- 239000012730 sustained-release form Substances 0.000 claims description 2
- 239000000454 talc Substances 0.000 claims description 2
- 229910052623 talc Inorganic materials 0.000 claims description 2
- 208000009174 transverse myelitis Diseases 0.000 claims description 2
- 206010003694 Atrophy Diseases 0.000 claims 2
- 230000037444 atrophy Effects 0.000 claims 2
- 239000003937 drug carrier Substances 0.000 claims 1
- 210000002082 fibula Anatomy 0.000 claims 1
- 239000000463 material Substances 0.000 claims 1
- 230000001953 sensory effect Effects 0.000 claims 1
- 241000699670 Mus sp. Species 0.000 abstract description 41
- 210000000278 spinal cord Anatomy 0.000 abstract description 23
- 201000010099 disease Diseases 0.000 abstract description 21
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 21
- 206010012305 Demyelination Diseases 0.000 abstract description 13
- 230000008595 infiltration Effects 0.000 abstract description 13
- 238000001764 infiltration Methods 0.000 abstract description 13
- 238000002360 preparation method Methods 0.000 abstract description 11
- 208000032116 Autoimmune Experimental Encephalomyelitis Diseases 0.000 abstract description 9
- 208000012997 experimental autoimmune encephalomyelitis Diseases 0.000 abstract description 8
- 210000004969 inflammatory cell Anatomy 0.000 abstract description 8
- 230000001225 therapeutic effect Effects 0.000 abstract description 4
- 206010061818 Disease progression Diseases 0.000 abstract description 2
- 230000005750 disease progression Effects 0.000 abstract description 2
- 230000036285 pathological change Effects 0.000 abstract 1
- 231100000915 pathological change Toxicity 0.000 abstract 1
- 201000002491 encephalomyelitis Diseases 0.000 description 40
- 230000000694 effects Effects 0.000 description 33
- 238000002474 experimental method Methods 0.000 description 23
- 150000001875 compounds Chemical class 0.000 description 15
- 241001465754 Metazoa Species 0.000 description 13
- 238000000034 method Methods 0.000 description 12
- 210000003141 lower extremity Anatomy 0.000 description 11
- 230000037396 body weight Effects 0.000 description 8
- 239000003826 tablet Substances 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 206010033799 Paralysis Diseases 0.000 description 6
- 210000004369 blood Anatomy 0.000 description 6
- 239000008280 blood Substances 0.000 description 6
- 210000004185 liver Anatomy 0.000 description 6
- 241000699666 Mus <mouse, genus> Species 0.000 description 5
- 235000010575 Pueraria lobata Nutrition 0.000 description 5
- 241000219781 Pueraria montana var. lobata Species 0.000 description 5
- 210000004556 brain Anatomy 0.000 description 5
- 239000003085 diluting agent Substances 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 238000010172 mouse model Methods 0.000 description 5
- 230000002829 reductive effect Effects 0.000 description 5
- 229940032147 starch Drugs 0.000 description 5
- 238000011740 C57BL/6 mouse Methods 0.000 description 4
- 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 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- 229930040373 Paraformaldehyde Natural products 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical group [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 238000010171 animal model Methods 0.000 description 4
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 4
- 230000008499 blood brain barrier function Effects 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 239000008103 glucose Substances 0.000 description 4
- 229960001031 glucose Drugs 0.000 description 4
- 229920002866 paraformaldehyde Polymers 0.000 description 4
- 238000010186 staining Methods 0.000 description 4
- 208000024827 Alzheimer disease Diseases 0.000 description 3
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 3
- 229930195725 Mannitol Natural products 0.000 description 3
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 3
- 108010083674 Myelin Proteins Proteins 0.000 description 3
- 102000006386 Myelin Proteins Human genes 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000011230 binding agent Substances 0.000 description 3
- 210000001218 blood-brain barrier Anatomy 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 210000003414 extremity Anatomy 0.000 description 3
- 239000003889 eye drop Substances 0.000 description 3
- 238000005194 fractionation Methods 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 239000007902 hard capsule Substances 0.000 description 3
- 230000003902 lesion Effects 0.000 description 3
- 239000000594 mannitol Substances 0.000 description 3
- 235000010355 mannitol Nutrition 0.000 description 3
- 229960001855 mannitol Drugs 0.000 description 3
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 3
- 239000008108 microcrystalline cellulose Substances 0.000 description 3
- 229940016286 microcrystalline cellulose Drugs 0.000 description 3
- 210000005012 myelin Anatomy 0.000 description 3
- 230000001575 pathological effect Effects 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 239000002002 slurry Substances 0.000 description 3
- 239000007901 soft capsule Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 239000000080 wetting agent Substances 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- 208000024806 Brain atrophy Diseases 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- 241000220485 Fabaceae Species 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- 208000003926 Myelitis Diseases 0.000 description 2
- 208000001132 Osteoporosis Diseases 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 206010039966 Senile dementia Diseases 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 210000001744 T-lymphocyte Anatomy 0.000 description 2
- 206010072731 White matter lesion Diseases 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
- 230000000202 analgesic effect Effects 0.000 description 2
- 210000003719 b-lymphocyte Anatomy 0.000 description 2
- 230000036772 blood pressure Effects 0.000 description 2
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 239000000084 colloidal system Substances 0.000 description 2
- 239000006184 cosolvent Substances 0.000 description 2
- 230000000916 dilatatory effect Effects 0.000 description 2
- 239000007884 disintegrant Substances 0.000 description 2
- 230000002526 effect on cardiovascular system Effects 0.000 description 2
- 239000002662 enteric coated tablet Substances 0.000 description 2
- ASUTZQLVASHGKV-JDFRZJQESA-N galanthamine Chemical compound O1C(=C23)C(OC)=CC=C2CN(C)CC[C@]23[C@@H]1C[C@@H](O)C=C2 ASUTZQLVASHGKV-JDFRZJQESA-N 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 210000002865 immune cell Anatomy 0.000 description 2
- 230000036039 immunity Effects 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 208000023589 ischemic disease Diseases 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 210000002540 macrophage Anatomy 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 201000000585 muscular atrophy Diseases 0.000 description 2
- 230000002107 myocardial effect Effects 0.000 description 2
- 210000005036 nerve Anatomy 0.000 description 2
- 208000008795 neuromyelitis optica Diseases 0.000 description 2
- 210000002569 neuron Anatomy 0.000 description 2
- 210000001328 optic nerve Anatomy 0.000 description 2
- 230000003204 osmotic effect Effects 0.000 description 2
- 239000012188 paraffin wax Substances 0.000 description 2
- 230000008506 pathogenesis Effects 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 230000002516 postimmunization Effects 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 239000008299 semisolid dosage form Substances 0.000 description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000007909 solid dosage form Substances 0.000 description 2
- 235000010356 sorbitol Nutrition 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 229960002920 sorbitol Drugs 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- YFDSDPIBEUFTMI-UHFFFAOYSA-N tribromoethanol Chemical compound OCC(Br)(Br)Br YFDSDPIBEUFTMI-UHFFFAOYSA-N 0.000 description 2
- 229950004616 tribromoethanol Drugs 0.000 description 2
- 210000001364 upper extremity Anatomy 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 230000002087 whitening effect Effects 0.000 description 2
- DTGKSKDOIYIVQL-WEDXCCLWSA-N (+)-borneol Chemical compound C1C[C@@]2(C)[C@@H](O)C[C@@H]1C2(C)C DTGKSKDOIYIVQL-WEDXCCLWSA-N 0.000 description 1
- REPVLJRCJUVQFA-UHFFFAOYSA-N (-)-isopinocampheol Natural products C1C(O)C(C)C2C(C)(C)C1C2 REPVLJRCJUVQFA-UHFFFAOYSA-N 0.000 description 1
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- VEORPZCZECFIRK-UHFFFAOYSA-N 3,3',5,5'-tetrabromobisphenol A Chemical compound C=1C(Br)=C(O)C(Br)=CC=1C(C)(C)C1=CC(Br)=C(O)C(Br)=C1 VEORPZCZECFIRK-UHFFFAOYSA-N 0.000 description 1
- HPOIPOPJGBKXIR-UHFFFAOYSA-N 3,6-dimethoxy-10-methyl-galantham-1-ene Natural products O1C(C(=CC=2)OC)=C3C=2CN(C)CCC23C1CC(OC)C=C2 HPOIPOPJGBKXIR-UHFFFAOYSA-N 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 239000004925 Acrylic resin Substances 0.000 description 1
- 229920000178 Acrylic resin Polymers 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 102000013455 Amyloid beta-Peptides Human genes 0.000 description 1
- 108010090849 Amyloid beta-Peptides Proteins 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 208000010693 Charcot-Marie-Tooth Disease Diseases 0.000 description 1
- 201000008992 Charcot-Marie-Tooth disease type 1B Diseases 0.000 description 1
- LPCKPBWOSNVCEL-UHFFFAOYSA-N Chlidanthine Natural products O1C(C(=CC=2)O)=C3C=2CN(C)CCC23C1CC(OC)C=C2 LPCKPBWOSNVCEL-UHFFFAOYSA-N 0.000 description 1
- 208000032544 Cicatrix Diseases 0.000 description 1
- 229920002785 Croscarmellose sodium Polymers 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 201000009273 Endometriosis Diseases 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 208000035895 Guillain-Barré syndrome Diseases 0.000 description 1
- 208000006411 Hereditary Sensory and Motor Neuropathy Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 206010049567 Miller Fisher syndrome Diseases 0.000 description 1
- 208000010428 Muscle Weakness Diseases 0.000 description 1
- 206010028372 Muscular weakness Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 102100040460 P2X purinoceptor 3 Human genes 0.000 description 1
- 101710189970 P2X purinoceptor 3 Proteins 0.000 description 1
- 108010081690 Pertussis Toxin Proteins 0.000 description 1
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 206010064911 Pulmonary arterial hypertension Diseases 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 206010037714 Quadriplegia Diseases 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 206010063837 Reperfusion injury Diseases 0.000 description 1
- 206010039424 Salivary hypersecretion Diseases 0.000 description 1
- 206010039984 Senile osteoporosis Diseases 0.000 description 1
- 206010040026 Sensory disturbance Diseases 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 210000000662 T-lymphocyte subset Anatomy 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- DFBIRQPKNDILPW-CIVMWXNOSA-N Triptolide Chemical compound O=C1OCC([C@@H]2C3)=C1CC[C@]2(C)[C@]12O[C@H]1[C@@H]1O[C@]1(C(C)C)[C@@H](O)[C@]21[C@H]3O1 DFBIRQPKNDILPW-CIVMWXNOSA-N 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 230000000879 anti-atherosclerotic effect Effects 0.000 description 1
- 210000001130 astrocyte Anatomy 0.000 description 1
- 210000003050 axon Anatomy 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 230000037182 bone density Effects 0.000 description 1
- 229940116229 borneol Drugs 0.000 description 1
- CKDOCTFBFTVPSN-UHFFFAOYSA-N borneol Natural products C1CC2(C)C(C)CC1C2(C)C CKDOCTFBFTVPSN-UHFFFAOYSA-N 0.000 description 1
- 208000029028 brain injury Diseases 0.000 description 1
- 239000006189 buccal tablet Substances 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
- 229940095672 calcium sulfate Drugs 0.000 description 1
- 235000011132 calcium sulphate Nutrition 0.000 description 1
- 229960001631 carbomer Drugs 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 210000003710 cerebral cortex Anatomy 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000007910 chewable tablet Substances 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 208000010877 cognitive disease Diseases 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 210000004351 coronary vessel Anatomy 0.000 description 1
- 239000001767 crosslinked sodium carboxy methyl cellulose Substances 0.000 description 1
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000005786 degenerative changes Effects 0.000 description 1
- 239000003405 delayed action preparation Substances 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 238000001784 detoxification Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 235000019700 dicalcium phosphate Nutrition 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 description 1
- 239000007919 dispersible tablet Substances 0.000 description 1
- DTGKSKDOIYIVQL-UHFFFAOYSA-N dl-isoborneol Natural products C1CC2(C)C(O)CC1C2(C)C DTGKSKDOIYIVQL-UHFFFAOYSA-N 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 239000007938 effervescent tablet Substances 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 206010016256 fatigue Diseases 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000010408 film Substances 0.000 description 1
- 239000007941 film coated tablet Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 210000003194 forelimb Anatomy 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 229960003980 galantamine Drugs 0.000 description 1
- BGLNUNCBNALFOZ-WMLDXEAASA-N galanthamine Natural products COc1ccc2CCCC[C@@]34C=CCC[C@@H]3Oc1c24 BGLNUNCBNALFOZ-WMLDXEAASA-N 0.000 description 1
- ASUTZQLVASHGKV-UHFFFAOYSA-N galanthamine hydrochloride Natural products O1C(=C23)C(OC)=CC=C2CN(C)CCC23C1CC(O)C=C2 ASUTZQLVASHGKV-UHFFFAOYSA-N 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 210000004884 grey matter Anatomy 0.000 description 1
- 210000002443 helper t lymphocyte Anatomy 0.000 description 1
- 208000021995 hereditary motor and sensory neuropathy Diseases 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 239000002955 immunomodulating agent Substances 0.000 description 1
- 229940121354 immunomodulator Drugs 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 229940047124 interferons Drugs 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 208000012947 ischemia reperfusion injury Diseases 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- CJWQYWQDLBZGPD-UHFFFAOYSA-N isoflavone Natural products C1=C(OC)C(OC)=CC(OC)=C1C1=COC2=C(C=CC(C)(C)O3)C3=C(OC)C=C2C1=O CJWQYWQDLBZGPD-UHFFFAOYSA-N 0.000 description 1
- 229930012930 isoflavone derivative Natural products 0.000 description 1
- 150000002515 isoflavone derivatives Chemical class 0.000 description 1
- 235000008696 isoflavones Nutrition 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229960001375 lactose Drugs 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 229940040145 liniment Drugs 0.000 description 1
- 239000000865 liniment Substances 0.000 description 1
- 230000003859 lipid peroxidation Effects 0.000 description 1
- 239000008297 liquid dosage form Substances 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 238000011866 long-term treatment Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 description 1
- IYVSXSLYJLAZAT-NOLJZWGESA-N lycoramine Natural products CN1CC[C@@]23CC[C@H](O)C[C@@H]2Oc4cccc(C1)c34 IYVSXSLYJLAZAT-NOLJZWGESA-N 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 210000000274 microglia Anatomy 0.000 description 1
- 239000011859 microparticle Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 201000005545 motor peripheral neuropathy Diseases 0.000 description 1
- 230000023105 myelination Effects 0.000 description 1
- 239000007923 nasal drop Substances 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 210000004940 nucleus Anatomy 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 210000004248 oligodendroglia Anatomy 0.000 description 1
- 239000006191 orally-disintegrating tablet Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000036284 oxygen consumption Effects 0.000 description 1
- 208000027753 pain disease Diseases 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- 210000004180 plasmocyte Anatomy 0.000 description 1
- 229960000502 poloxamer Drugs 0.000 description 1
- 229920001983 poloxamer Polymers 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 208000026451 salivation Diseases 0.000 description 1
- 231100000241 scar Toxicity 0.000 description 1
- 230000037387 scars Effects 0.000 description 1
- 230000002000 scavenging effect Effects 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229960002668 sodium chloride Drugs 0.000 description 1
- DAJSVUQLFFJUSX-UHFFFAOYSA-M sodium;dodecane-1-sulfonate Chemical compound [Na+].CCCCCCCCCCCCS([O-])(=O)=O DAJSVUQLFFJUSX-UHFFFAOYSA-M 0.000 description 1
- 208000020431 spinal cord injury Diseases 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 229960004793 sucrose Drugs 0.000 description 1
- 239000007940 sugar coated tablet Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 230000035922 thirst Effects 0.000 description 1
- 230000036962 time dependent Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- ODLHGICHYURWBS-LKONHMLTSA-N trappsol cyclo Chemical compound CC(O)COC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)COCC(O)C)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1COCC(C)O ODLHGICHYURWBS-LKONHMLTSA-N 0.000 description 1
- YKUJZZHGTWVWHA-UHFFFAOYSA-N triptolide Natural products COC12CC3OC3(C(C)C)C(O)C14OC4CC5C6=C(CCC25C)C(=O)OC6 YKUJZZHGTWVWHA-UHFFFAOYSA-N 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
-
- 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
- A61K36/488—Pueraria (kudzu)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
-
- 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
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- 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
- A61P37/02—Immunomodulators
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Epidemiology (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Immunology (AREA)
- Neurosurgery (AREA)
- Alternative & Traditional Medicine (AREA)
- Medical Informatics (AREA)
- Botany (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Ophthalmology & Optometry (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention belongs to the technical field of medicines, and discloses application of puerarin in preparation of medicines for preventing, relieving and/or treating autoimmune demyelinating diseases. Puerarin shows a very good therapeutic effect on the experimental autoimmune encephalomyelitis model in mice, and can effectively treat pathological changes and disease progression of diseases. The therapeutic effect is achieved by reducing inflammatory cell infiltration of spinal cord and demyelination of spinal cord.
Description
Technical Field
The invention relates to application of puerarin in preparing a medicine for preventing, relieving and/or treating autoimmune demyelinating diseases, and belongs to the technical field of medicines.
Background
Multiple sclerosis (multiple sclerosis, MS) is a chronic progressive central nervous system (central nervous system, CNS) inflammatory demyelinating disease mediated by immunity. Over 200 tens of thousands of people are affected worldwide, which causes serious harm to human health and a heavy economic burden to society. Multiple sclerosis has a complex pathogenesis and unknown etiology, and is currently incurable, and patients need to receive long-term treatment. Multiple sclerosis is characterized by inflammation and demyelination of brain, spinal cord and optic nerve as major pathological features, and its clinical manifestations are extensive, including muscle weakness, sensory disturbance, cognitive dysfunction and fatigue. The etiology of multiple sclerosis is not clear and may be related to various factors such as genetics, environment, infection, etc. Multiple sclerosis can be divided into four types according to the clinical manifestations of the patient: the recurrence remission is expressed as alternation of recurrence remission, and the disease does not obviously progress; primary progression, i.e. progressive deterioration after onset; secondary progressive, onset with remission of recurrence followed by progressive worsening; the disease is gradually progressed with recurrence after the disease is developed. Currently, clinical therapeutic drugs are mostly aimed at relapsing remitting patients.
Multiple sclerosis is considered an autoimmune disease, mainly caused by the passage of autoreactive immune cells into the CNS through the blood brain barrier. Its early lesions are manifested by infiltration of surrounding immune cells and leakage of the blood brain barrier (blood brain barrier, BBB). Cell infiltration is mainly carried out by macrophages, CD8 + T cell subset, CD4 + T cells, B cells and plasma cells are relatively small in number. The composition of T cells does not change with the progression of the disease, but B cells and plasma cellsThe relative proportion of (2) increases. Microglia and macrophages remain chronically activated throughout the disease process, forming plaques of myelin and oligodendrocyte loss. With the progress of the disease, the brain of the patient has focal white matter lesions, brain and spinal cord injuries are not obvious, but brain atrophy is commonly generated, brain atrophy is accompanied by ventricle enlargement, astrocytes form multiple sclerosis colloid scars in white matter lesions, demyelination can also occur in the gray matter of cerebral cortex, nucleus and spinal cord, but demyelinated areas of white matter can be partially repaired through remyelination; in addition, the disease process affects not only myelin, but also causes degenerative changes in axons and neurons, resulting in irreversible disability in the patient.
Over the past two decades, as people have gained a continual understanding of the pathogenesis of multiple sclerosis, researchers have developed a variety of drugs that address the particular physiological pathways of the disease. Currently, drugs for treating multiple sclerosis are mainly divided into five major categories: immunomodulators, hormones, monoclonal antibodies, interferons and nerve repair agents. The medicines can relieve the disease progression and control the symptoms of patients, but are ineffective in repairing damaged neurons, have no improving effect on the functional disability of the patients, and have serious toxic and side effects after long-term application.
The experimental autoimmune encephalomyelitis (experimentally allergic encephalomyelitis, EAE) model is a classical animal model of multiple sclerosis, and the specific activation of brain helper T cells by myelin autoantigens causes inflammatory infiltration of the central nervous system, demyelination, and the biochemical, immunological and pathological features are very similar to those of multiple sclerosis. In addition, the EAE of rats and mice can be used as an ideal animal model for researching autoimmune demyelinating diseases such as experimental autoimmune encephalomyelitis, optic nerve encephalomyelitis, acute disseminated encephalomyelitis and the like, and is similar to human demyelinating diseases in clinical, pathological, immune, biochemical changes and the like, so that the EAE has wide application.
Pueraria Lobata (Pueraria Lobata) is a dry root of Pueraria Lobata (Pueraria Lobata) of Leguminosae, is a commonly used traditional Chinese medicine, has sweet, pungent and cool nature, and has effects of invigorating spleen and stomach, relieving fever, promoting salivation, quenching thirst, and invigorating yang to arrest diarrhea.
Puerarin (Puerarin) is isoflavone derivative separated from radix Puerariae with crown expanding effect. Is prepared from root of Pueraria lobata Ohwi of Leguminosae. Research by scholars at home and abroad shows that the isoflavone compound has obvious effects in preventing and treating cardiovascular and cerebrovascular diseases, diabetes and the like, such as dilating coronary artery and improving ischemic myocardial metabolism; protecting against cerebral arterial ischemia and ischemia reperfusion injury; lowering blood pressure and dilating blood vessels; lowering blood viscosity, slowing heart rate, and reducing myocardial oxygen consumption; reducing blood sugar and blood lipid, scavenging free radicals and resisting lipid peroxidation; anti-atherosclerosis, improving brain circulation, inhibiting platelet aggregation, etc.; in addition, puerarin has obvious effect on preventing and treating middle-aged and senile osteoporosis, female climacteric syndrome, etc. Modern scientific researches also find that puerarin has various pharmacological effects of protecting liver, regulating immunity, resisting tumor, protecting cardiovascular and cerebrovascular, reducing blood sugar, resisting oxidation, reducing blood sugar, reducing blood lipid, reducing blood pressure, resisting inflammation, improving renal function, increasing bone density, protecting nerve, etc. Is clinically used for treating coronary heart disease, angina, hypertension and the like.
The invention is a new discovery obtained through a great number of animal experimental researches. The novel invention relates to a medicine for treating autoimmune demyelinating diseases. At present, no report is available on the direct or indirect treatment effect of puerarin on autoimmune demyelinating diseases.
To date, a number of patents relate to the use of puerarin. The application of puerarin gel eye drops in preparing medicines for treating ocular fundus ischemic diseases is described in Chinese patent CN 104688672A (publication number). Wherein, the gel eye drop formulation of puerarin can be used as intravenous injection puerarin for treating ocular fundus ischemic diseases. Chinese patent CN 101550133A (publication No.) describes "extraction method of puerarin and use of radix Puerariae in preparation of liver protecting medicine". Animal experiments prove that puerarin has good effects of detoxification and liver protection and can be used as a liver protection medicament. The use of puerarin in the preparation of analgesic drugs is described in chinese patent CN 104940190a (publication No.). The puerarin is used in combination with opioid or compound preparation with opioid, which can prolong the analgesic time, enhance the analgesic effect, and delay or relieve opioid tolerance phenomenon in the treatment course of chronic opioid. Chinese patent No. CN 103520147A (publication No.) describes the use of puerarin or a pharmaceutical composition containing puerarin in the preparation of a medicament for preventing or treating Alzheimer's disease. The pharmaceutical composition comprising puerarin, triptolide, galanthamine and borneol is used for treating senile dementia, so that the toxic and side effects of the medicine can be reduced, and the synergistic treatment effect can be achieved. Puerarin can obviously inhibit the deposition of beta amyloid, has definite curative effect for preventing or treating senile dementia, small side effect and wide medical application prospect. In addition, the pharmacological effects of puerarin are proved from various aspects by the patents such as the application of puerarin in preparing medicines for treating endometriosis (CN 1899295A), the application of puerarin in preparing medicines for treating P2X3 mediated pain/nervous system diseases (CN 101627990A), the application of puerarin and puerarin in preparing medicines for preventing and treating osteoporosis (CN 1321500A), the protective effect of puerarin in TBBPA induced cardiodevelopmental toxicity (CN 103432113A), the application of puerarin in preparing medicines for preventing and/or treating pulmonary arterial hypertension and complications thereof (CN 108567769A) and the like. However, the above studies on the effects of puerarin have not been reported on the treatment of autoimmune demyelinating diseases. Therefore, the application of puerarin in preparing the medicine for preventing, relieving and/or treating autoimmune demyelinating diseases is a new application of the puerarin newly discovered.
Disclosure of Invention
The invention aims to solve the technical problem of providing application of puerarin in preparing a medicine for preventing, relieving and/or treating autoimmune demyelinating diseases.
In order to solve the technical problems of the invention, the invention provides the following technical scheme:
in a first aspect, the invention provides an application of puerarin shown in a formula (I) in preparing a medicament for preventing, relieving and/or treating autoimmune demyelinating diseases,
such autoimmune demyelinating diseases include, but are not limited to, demyelinating autoimmune diseases of the central nervous system (Central nervous system, CNS) such as multiple sclerosis, neuromyelitis optica (Neuromyelitis optica spectrum disorder, NMOSD), acute disseminated encephalomyelitis, white matter encephalitis and transverse myelitis; demyelinating autoimmune diseases affecting the peripheral nervous system such as acute inflammatory demyelinating polyneuropathy (acute inflammatory demyelinating polyneuropathy, AIDP; guillain-Barre syndrome), chronic inflammatory demyelinating polyneuropathy (chronic inflammatory demyelinating polyneuropathy), anti-MAG peripheral neuropathy (anti-MAG peripheral neuropathy), motor and sensory neuropathy (Motor and Sensory Neuropathy, HMSN), hereditary sensorimotor neuropathy (Hereditary Sensorimotor Neuropathy, HSMN), fibular muscular atrophy (Peroneal Muscular Atrophy), progressive neurofibular muscular atrophy (Charcot-Marie-photon Disease), and the like.
The multiple sclerosis includes relapsing remitting multiple sclerosis, primary progressive multiple sclerosis, secondary progressive multiple sclerosis and progressive relapsing multiple sclerosis.
An EAE model was established using female C57BL/6 mice. Detecting the influence of puerarin on animal weight and disease score; and observing the force of the limbs of the animal through a suspension experiment, and observing the treatment condition. The improvement effect of puerarin on inflammatory cell infiltration and myelination in the spinal cord of experimental animals is detected by using H & E staining and LFB staining, and the effect of puerarin in preparing the medicines for preventing, relieving and/or treating autoimmune demyelinating diseases is judged according to the improvement effect.
In a second aspect, the present invention provides an application of a pharmaceutical composition in preparing a medicament for preventing, alleviating and/or treating autoimmune demyelinating diseases, wherein the pharmaceutical composition comprises puerarin shown in formula (I) in an effective dose, and a pharmaceutical excipient,
wherein, the medicine composition contains puerarin as the medicine active ingredient and other active ingredients. The pharmaceutical composition comprises the following dosage forms: solutions, suspensions, lyophilized powders, emulsions, pills, capsules, powders, controlled release, sustained release formulations, and microsomal delivery systems. The medicinal excipient comprises starch, dextrin, sodium polymethyl cellulose, magnesium stearate and talcum powder. The product is selected from medicines and health products.
The invention also relates to the application of the pharmaceutical composition taking puerarin as an active ingredient in the medicines for preventing, relieving and/or treating autoimmune demyelinating diseases. The pharmaceutical compositions may be prepared according to methods well known in the art. Any dosage form suitable for human or animal use may be made by combining the compounds of the invention with one or more pharmaceutically acceptable solid or liquid excipients and/or adjuvants.
The compounds of the present invention or pharmaceutical compositions containing them may be administered in unit dosage form by the enteral or parenteral route, such as oral, intravenous, intramuscular, subcutaneous, nasal, oral mucosal, ocular, pulmonary and respiratory, cutaneous, vaginal, rectal, etc. The dosage form may be a liquid, solid or semi-solid dosage form. The liquid preparation can be solution (including true solution and colloid solution), emulsion (including o/w type, w/o type and multiple emulsion), suspension, injection (including injection solution, powder injection and transfusion), eye drop, nasal drop, lotion, liniment, etc.; the solid dosage forms can be tablets (including common tablets, enteric coated tablets, buccal tablets, dispersible tablets, chewable tablets, effervescent tablets, orally disintegrating tablets), capsules (including hard capsules, soft capsules and enteric coated capsules), granules, powder, micropills, dripping pills, suppositories, films, patches, aerosol (powder) and sprays; the semisolid dosage form may be an ointment, gel, paste, or the like. The compound of the invention can be prepared into common preparations, slow release preparations, controlled release preparations, targeted preparations and various microparticle administration systems.
For the preparation of the compounds of the present invention into tablets, various excipients known in the art may be widely used, including diluents, binders, wetting agents, disintegrants, lubricants, glidants. The diluent can be starch, dextrin, sucrose, glucose, lactose, mannitol, sorbitol, xylitol, microcrystalline cellulose, calcium sulfate, calcium hydrogen phosphate, calcium carbonate, etc.; the wetting agent can be water, ethanol, isopropanol, etc.; the binder may be starch slurry, dextrin, syrup, mel, glucose solution, microcrystalline cellulose, acacia slurry, gelatin slurry, sodium carboxymethyl cellulose, methyl cellulose, hydroxypropyl methylcellulose, ethyl cellulose, acrylic resin, carbomer, polyvinylpyrrolidone, polyethylene glycol, etc.; the disintegrating agent can be dry starch, microcrystalline cellulose, low-substituted hydroxypropyl cellulose, cross-linked polyvinylpyrrolidone, cross-linked sodium carboxymethyl cellulose, sodium carboxymethyl starch, sodium bicarbonate and citric acid, polyoxyethylene sorbitol fatty acid ester, sodium dodecyl sulfonate, etc.; the lubricant and glidant may be talc, silicon dioxide, stearate, tartaric acid, liquid paraffin, polyethylene glycol, and the like. The tablets may be further formulated into coated tablets, such as sugar coated tablets, film coated tablets, enteric coated tablets, or bilayer and multilayer tablets. In order to make the administration unit into a capsule, the compound of the present invention as an active ingredient may be mixed with a diluent, a glidant, and the mixture may be directly placed in a hard capsule or a soft capsule. The active ingredient of the compound can be prepared into particles or pellets by mixing with a diluent, an adhesive and a disintegrating agent, and then placed into hard capsules or soft capsules. The various diluents, binders, wetting agents, disintegrants and glidants used to prepare the tablets of the compounds of the invention may also be used to prepare capsules of the compounds of the invention. For the preparation of the compound of the present invention into injection, water, ethanol, isopropanol, propylene glycol or their mixture may be used as solvent, and appropriate amount of solubilizer, cosolvent, pH regulator and osmotic pressure regulator may be added. The solubilizer or cosolvent can be poloxamer, lecithin, hydroxypropyl-beta-cyclodextrin, etc.; the pH regulator can be phosphate, acetate, hydrochloric acid, sodium hydroxide, etc.; the osmotic pressure regulator can be sodium chloride, mannitol, glucose, phosphate, acetate, etc. For example, mannitol, glucose, etc. can be added as propping agent for preparing lyophilized powder for injection. In addition, colorants, preservatives, fragrances, flavoring agents, or other additives may also be added to the pharmaceutical formulation, if desired. For the purpose of administration, the drug or the pharmaceutical composition of the present invention can be administered by any known administration method to enhance the therapeutic effect.
Beneficial technical effects
1. The compounds of the invention are useful in the prevention, alleviation and/or treatment of autoimmune demyelinating diseases. Besides widening the clinical application field of the compound, the compound also provides medicine selection for the clinical treatment of autoimmune demyelinating diseases.
2. The application of the compound in the medicine for preventing, relieving and/or treating autoimmune demyelinating diseases is disclosed for the first time at present in the world and in the country. See no related papers and patent publications.
3. The compound of the invention can achieve the therapeutic and preventive effects by gastric administration and a small amount of administration. The medicine is safe and reliable. The medicine has obvious advantages when being developed as a medicine.
Drawings
FIG. 1 effects of puerarin on EAE mice body weight. In this experiment, mice in the EAE model group had significantly lower body weight than normal control group after onset. And after the administration, compared with a model group, the body weight of the puerarin treatment group mice in the later administration period is obviously increased.
FIG. 2 effect of puerarin on EAE mouse disease score. In this experiment, the disease score of mice in the EAE model group after onset was significantly higher than that of mice in the normal control group, and the disease score of mice in the puerarin treatment group after administration was significantly lower than that of mice in the EAE model group.
FIG. 3 effect of puerarin on EAE mice suspension time. In this experiment, the suspension time on wire netting was significantly reduced in mice of EAE model group compared to normal control group, while puerarin can prolong the suspension time in model mice. # # P < 0.001vs. normal control group, # P < 0.001vs eae model group.
FIG. 4 effect of puerarin on EAE mice suspension fractionation. # # P < 0.001vs. normal control group, # P < 0.001vs eae model group.
FIG. 5 effect of puerarin on myelitis cell infiltration in EAE mice. In the experiment, compared with a normal control group, the EAE model group mice have obvious infiltration of spinal cord inflammatory cells, and puerarin can obviously reduce the infiltration area of inflammatory cells.
FIG. 6 effect of puerarin on demyelination of the spinal cord of EAE mice. In this experiment, after LFB staining, the spinal cord of mice in EAE model group exhibited demyelination lesions with larger area compared to normal control group. And puerarin can reduce the whitening area of the spinal cord white matter area, so that the demyelination situation is effectively improved. # P <0.01vs. normal control group, # P <0.01vs. eae model group.
Detailed Description
The pharmacological actions of puerarin in the prevention, alleviation and/or treatment of autoimmune demyelinating diseases are further described below in connection with the present invention.
The following examples illustrate the invention in more detail, without any limitation thereof.
Example 1: puerarin effect on improving behaviours of experimental autoimmune encephalomyelitis mice
1.1 establishment of an Experimental autoimmune encephalomyelitis mouse model and dosing Condition
Principle of experiment
MOG for C57BL/6 mice 35-55 An Experimental Autoimmune Encephalomyelitis (EAE) model is induced.
Experimental method
Female C57BL/6 mice, 6-8 weeks old, 18-20g weight, adapted for 3-5 days after feeding, MOG subcutaneous injection 35-55 300 μg and 600ng pertussis toxin were intraperitoneally injected to establish an experimental autoimmune encephalomyelitis animal model (EAE). Normal control group was set, n=10. Animal opening 12 days after modelingInitial disease, limb paralysis with different degrees appears. Mice presenting with quadriplegia were selected as experimental autoimmune encephalomyelitis models.
Female C57BL/6 mice were randomized on day 13 of modeling into 2 groups, EAE control group (n=10) and 100mg/kg puerarin dosing group (n=10). After grouping, the administration was performed by lavage once daily. The normal control group and the EAE model group were given the same volume of 0.5% sodium carboxymethylcellulose (CMC-Na). Puerarin was continuously dosed to day 35 of modeling. Body weight and disease scores were measured daily and animal mortality was recorded. The suspension rating of the animals was determined on days 7, 14, 21, 28 and 35 post immunization, and the suspension time of the animals on wire was determined on day 35.
Experimental results
Animals begin to develop disease on day 12 post immunization, and weight loss and reduced neurological scores occur.
1.2 Puerarin effect on body weight of EAE mice
Experimental method
Body weight is an important indicator of the energy utilization balance and growth of animals. The animal's activity status, hair, etc. were observed and recorded daily in this experiment, and the animal's weight was monitored daily.
Experimental results
In this experiment, mice in the EAE model group had significantly lower body weight than the normal group after onset. And after the administration, compared with a model group, the body weight of the puerarin treatment group mice in the later administration period is obviously increased. The results are shown in FIG. 1.
1.3 Effect of puerarin on EAE mouse disease score
Experimental method
Experimental mice were scored daily after modeling for disease, with the following scoring criteria: 0 point: normal mice; 0.5 point: tail weakness; 1, the method comprises the following steps: complete paralysis of the tail; 1.5 minutes: weakness of a hind limb; 2, the method comprises the following steps: weakness of both hind limbs; 2.5 minutes: paralysis of one hind limb and weakness of the other hind limb; 3, the method comprises the following steps: paralysis of both hind limbs; 3.5 minutes: part of the forelimb is weak; 4, the following steps: partial paralysis of the forelimbs; 4.5 minutes: complete paralysis of the forelimbs; 5, the method comprises the following steps: death.
Experimental results
In this experiment, the disease score of mice in the EAE model group after onset was significantly higher than that of mice in the normal control group, and the disease score of mice in the puerarin treatment group after administration was significantly lower than that of mice in the EAE model group. The results are shown in FIG. 2.
1.4 Effect of puerarin on EAE mouse suspension time
Experimental method
On day 35 after modeling, the drop time of mice from 180 ° wire mesh was determined, time > 120s calculated as 120s, and each mouse was repeated three times.
Experimental results
In this experiment, the suspension time on wire netting was significantly reduced in mice of EAE model group compared to normal control group, while puerarin can prolong the suspension time in model mice. The results are shown in FIG. 3 and Table 1.
TABLE 1 influence of puerarin on MOG-induced EAE mice suspension time
Mean±SEM(n=10)
# # P < 0.001vs. normal control group, # P < 0.001vs eae model group.
1.5 Effect of puerarin on EAE mouse suspension fractionation
Experimental method
On days 7, 14, 21, 28 and 35 after modeling, the front paws of the mice were hung on a balance rope 30cm from the ground, and the limb hanging state of the mice on the balance rope was observed and scored, and the grading standard was as follows: 5, the method comprises the following steps: the rope is grabbed and can be pulled by the hind limb, and the tail is tightly wound around the rope; 4, the following steps: the rope is grabbed and can be pulled by the hind limb, and the tail is lifted but can not be wound; 3, the method comprises the following steps: the rope is grabbed and can be pulled by the hind limb, and the tail sags; 2, the method comprises the following steps: lifting the hind limb, and grasping the rope but not pulling; 1, the method comprises the following steps: lifting the hind limb, but not grasping the rope; 0 point: the hind limb cannot be lifted.
Experimental results
In this experiment, the suspension score was significantly reduced after the onset of mice in the EAE model group compared to the normal control group, whereas the suspension score was significantly increased and time-dependent in the drug-treated group compared to the EAE model group after administration. The results are shown in FIG. 4 and Table 2.
TABLE 2 influence of puerarin on MOG-induced EAE mice suspension fractionation
Mean±SEM(n=10)
# # P < 0.001vs. normal control group, # P < 0.001vs eae model group.
Example 2: effects of puerarin on infiltration and demyelination of myelitis cells in EAE model mice
2.1 Establishment of EAE mouse model and drug administration condition
The experimental principle, experimental method and experimental result are the same as those of example 1.1.
2.2 Effect of puerarin on the infiltration of inflammatory cells in the spinal cord of EAE mice
Experimental method
On day 35 after modeling, 3 mice per group were anesthetized with 4% tribromoethanol. And (3) firstly, irrigating with normal saline, and then irrigating with 4% paraformaldehyde until the liver turns white. Breaking the head, taking the spinal cord waist expansion part, and placing the spinal cord waist expansion part into 4% paraformaldehyde for fixation. Paraffin sections are prepared from the expanded spinal cord and stained with hematoxylin-eosin (H & E), and the inflammatory cell infiltration of spinal cord is observed.
Experimental results
In the experiment, compared with a normal control group, the EAE model group mice have obvious infiltration of spinal cord inflammatory cells, and 100mg/kg puerarin can obviously reduce the infiltration area of inflammatory cells. The results are shown in FIG. 5.
2.3 Effect of puerarin on the demyelination in the spinal cord of EAE mice
Experimental method
On day 35 after modeling, 3 mice per group were anesthetized with 4% tribromoethanol. And (3) firstly, irrigating with normal saline, and then irrigating with 4% paraformaldehyde until the liver turns white. Breaking the head, taking the spinal cord waist expansion part, and placing the spinal cord waist expansion part into 4% paraformaldehyde for fixation. Paraffin sections were prepared for the enlarged portion of the spinal cord, stained with solid blue (LFB), and observed for demyelination in the spinal cord.
Experimental results
In this experiment, after LFB staining, the spinal cord of mice in EAE model group exhibited demyelination lesions with larger area compared to normal control group. And puerarin can reduce the whitening area of the spinal cord white matter area, so that the demyelination situation is effectively improved. The results are shown in FIG. 6 and Table 3.
TABLE 3 effect of puerarin on MOG-induced EAE mice spinal cord demyelination
Mean±SEM(n=3)
# P <0.01vs. normal control group, # P <0.01vs. eae model group.
Claims (8)
2. the use according to claim 1, characterized in that the autoimmune demyelinating diseases include demyelinating autoimmune diseases of the Central Nervous System (CNS) such as multiple sclerosis, neuromyelitis optica spectrum diseases, acute disseminated encephalomyelitis, white matter encephalitis and transverse myelitis; demyelinating autoimmune diseases affecting the peripheral nervous system, chronic inflammatory demyelinating polyneuropathy, anti-MAG peripheral neuropathy, motor and sensory neuropathy, hereditary sensory motor neuropathy, fibula atrophy, progressive neurofibula atrophy.
3. The use according to claim 2, wherein the demyelinating autoimmune disease affecting the peripheral nervous system comprises acute inflammatory demyelinating polyneuropathy.
4. The use according to claim 2, characterized in that the multiple sclerosis comprises relapsing-remitting multiple sclerosis, primary progressive multiple sclerosis, secondary progressive multiple sclerosis and progressive relapsing multiple sclerosis.
5. The application of a pharmaceutical composition in the prevention, alleviation and/or treatment of autoimmune demyelinating diseases is characterized in that the pharmaceutical composition contains puerarin shown in a formula (I) in an effective dose, and optionally pharmaceutically acceptable carriers and/or auxiliary materials;
6. the use according to claim 5, characterized in that the pharmaceutical composition contains, in addition to puerarin as pharmaceutical active ingredient, other active ingredients.
7. The use according to any one of claims 5-6, characterized in that the pharmaceutical composition comprises the following dosage forms: solutions, suspensions, lyophilized powders, emulsions, pills, capsules, powders, controlled release, sustained release formulations, and microsomal delivery systems.
8. The use according to claim 5, characterized in that said pharmaceutically acceptable excipients comprise starch, dextrin, sodium polymethylcellulose, magnesium stearate, talc.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202111625337.8A CN116350620A (en) | 2021-12-28 | 2021-12-28 | Application of puerarin in preparing medicine for preventing or treating autoimmune demyelinating diseases |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202111625337.8A CN116350620A (en) | 2021-12-28 | 2021-12-28 | Application of puerarin in preparing medicine for preventing or treating autoimmune demyelinating diseases |
Publications (1)
Publication Number | Publication Date |
---|---|
CN116350620A true CN116350620A (en) | 2023-06-30 |
Family
ID=86936426
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202111625337.8A Pending CN116350620A (en) | 2021-12-28 | 2021-12-28 | Application of puerarin in preparing medicine for preventing or treating autoimmune demyelinating diseases |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN116350620A (en) |
-
2021
- 2021-12-28 CN CN202111625337.8A patent/CN116350620A/en active Pending
Similar Documents
Publication | Publication Date | Title |
---|---|---|
WO2012027882A1 (en) | Pharmaceutical composition for treating insomnia and preparation method thereof | |
US10383843B2 (en) | Use of total coumarins of cnidium fruit in preparing medicaments for treating psoriasis | |
WO2008031322A1 (en) | Application of acetylcholine esterase inhibitor medication of leonurus extractive as cholinomimetic | |
RU2184562C2 (en) | Ladanum using for treatment of alzheimer's disease | |
US7834056B2 (en) | Pharmaceutical composition for gout | |
CN101033245B (en) | Preparation method and application of pedunculoside | |
KR100860703B1 (en) | Use of l-butylphthalide in the manufacture of medicaments for prevention and treatment of cerebral infarct | |
CN101953864B (en) | Cynanchum otophyllum aglycone and medical application of extractive containing same | |
KR100855389B1 (en) | The use of succinate derivative esters for the treatment of dementia | |
JPH08283148A (en) | Depressive symptom improver | |
CN116350620A (en) | Application of puerarin in preparing medicine for preventing or treating autoimmune demyelinating diseases | |
JPH0680577A (en) | Antitussive | |
CN111084771A (en) | Use of puerarin in treating muscular atrophy, myopathy, and musculoskeletal complications | |
WO2004032941A1 (en) | Pharmaceutical compositions containing polydatin or its salts and their application | |
US7645461B2 (en) | Method of treating cerebral ischemia with hydrogenation products of frankincense extracts | |
WO2021063391A1 (en) | Cornu gorais keratin, preparation method therefor, pharmaceutical composition thereof and use thereof | |
CN112972462B (en) | Application of panobinostat in preparation of medicine for preventing, relieving and/or treating multiple sclerosis | |
CA2100777C (en) | Pharmaceutical composition containing granisetron and dexamethasone | |
CN116650482A (en) | Application of 3-TYP in preparation of medicine for treating autoimmune demyelinating diseases | |
CN112972448B (en) | Application of belicastat in preparing medicine for preventing, relieving and/or treating multiple sclerosis | |
JPH06128165A (en) | Cerebral function-improving agent | |
EP4205734A1 (en) | Application of ?-asarone in preparation of medicine for preventing or treating hemorrhagic stroke | |
CN114272300B (en) | Pharmaceutical composition for improving cerebral ischemia and application thereof | |
KR100201585B1 (en) | Vasodilator composition | |
CN105381170B (en) | A kind of Chinese medicine treating apoplexy disease and preparation technology thereof |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination |