CN104208086B - 落新妇苷或其同系物在制备治疗银屑病药物中的应用 - Google Patents
落新妇苷或其同系物在制备治疗银屑病药物中的应用 Download PDFInfo
- Publication number
- CN104208086B CN104208086B CN201310217584.3A CN201310217584A CN104208086B CN 104208086 B CN104208086 B CN 104208086B CN 201310217584 A CN201310217584 A CN 201310217584A CN 104208086 B CN104208086 B CN 104208086B
- Authority
- CN
- China
- Prior art keywords
- astilbin
- homolog
- preparation
- drugs
- application
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- ZROGCCBNZBKLEL-FHXNIQKESA-N Astilbin Natural products O([C@H]1[C@@H](c2cc(O)c(O)cc2)Oc2c(c(O)cc(O)c2)C1=O)[C@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@H](C)O1 ZROGCCBNZBKLEL-FHXNIQKESA-N 0.000 title claims abstract description 53
- ZROGCCBNZBKLEL-MPRHSVQHSA-N astilbin Chemical compound O[C@@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@H]1O[C@H]1C(=O)C2=C(O)C=C(O)C=C2O[C@@H]1C1=CC=C(O)C(O)=C1 ZROGCCBNZBKLEL-MPRHSVQHSA-N 0.000 title claims abstract description 49
- 201000004681 Psoriasis Diseases 0.000 title claims abstract description 14
- 239000003814 drug Substances 0.000 title claims abstract description 13
- 238000002360 preparation method Methods 0.000 title abstract description 12
- 229940079593 drug Drugs 0.000 title abstract 3
- 239000000839 emulsion Substances 0.000 claims description 6
- 239000007924 injection Substances 0.000 claims description 4
- 238000002347 injection Methods 0.000 claims description 4
- 239000000829 suppository Substances 0.000 claims description 4
- 239000002775 capsule Substances 0.000 claims description 3
- 239000003182 parenteral nutrition solution Substances 0.000 claims description 3
- 239000008187 granular material Substances 0.000 claims description 2
- 239000007788 liquid Substances 0.000 claims description 2
- 239000002674 ointment Substances 0.000 claims description 2
- 239000013543 active substance Substances 0.000 claims 1
- 239000006196 drop Substances 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 9
- 241001465754 Metazoa Species 0.000 abstract description 3
- 238000002474 experimental method Methods 0.000 abstract description 2
- 230000007774 longterm Effects 0.000 abstract description 2
- 231100000331 toxic Toxicity 0.000 abstract description 2
- 230000002588 toxic effect Effects 0.000 abstract description 2
- 230000000073 effect on psoriasis Effects 0.000 abstract 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
- 238000000034 method Methods 0.000 description 12
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 8
- 239000012071 phase Substances 0.000 description 8
- 210000003491 skin Anatomy 0.000 description 8
- 239000011159 matrix material Substances 0.000 description 7
- 241000605422 Asparagus asparagoides Species 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- ZROGCCBNZBKLEL-AEGLVIMLSA-N Isoastibin Natural products O([C@@H]1[C@H](c2cc(O)c(O)cc2)Oc2c(c(O)cc(O)c2)C1=O)[C@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@H](C)O1 ZROGCCBNZBKLEL-AEGLVIMLSA-N 0.000 description 5
- 229920002472 Starch Polymers 0.000 description 5
- ZROGCCBNZBKLEL-MFSALPCASA-N neoastilbin Chemical compound O[C@@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@H]1O[C@@H]1C(=O)C2=C(O)C=C(O)C=C2O[C@H]1C1=CC=C(O)C(O)=C1 ZROGCCBNZBKLEL-MFSALPCASA-N 0.000 description 5
- ZROGCCBNZBKLEL-RMPKKLJSSA-N neoastilbin Natural products C[C@@H]1O[C@H](O[C@H]2[C@@H](Oc3cc(O)cc(O)c3C2=O)c2ccc(O)c(O)c2)[C@H](O)[C@H](O)[C@H]1O ZROGCCBNZBKLEL-RMPKKLJSSA-N 0.000 description 5
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 5
- 229920000053 polysorbate 80 Polymers 0.000 description 5
- 239000008107 starch Substances 0.000 description 5
- 229940032147 starch Drugs 0.000 description 5
- 235000019698 starch Nutrition 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- VQUPQWGKORWZII-WDPYGAQVSA-N (2r,3r)-5,7-dihydroxy-2-(4-hydroxyphenyl)-3-[(2s,3r,4r,5r,6s)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxy-2,3-dihydrochromen-4-one Chemical compound O[C@@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@H]1O[C@H]1C(=O)C2=C(O)C=C(O)C=C2O[C@@H]1C1=CC=C(O)C=C1 VQUPQWGKORWZII-WDPYGAQVSA-N 0.000 description 4
- 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 4
- -1 anthraline Chemical compound 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 239000012467 final product Substances 0.000 description 4
- 235000011187 glycerol Nutrition 0.000 description 4
- 229960000485 methotrexate Drugs 0.000 description 4
- 239000008215 water for injection Substances 0.000 description 4
- 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 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 239000012153 distilled water Substances 0.000 description 3
- 229930182470 glycoside Natural products 0.000 description 3
- 150000002338 glycosides Chemical class 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 239000003018 immunosuppressive agent Substances 0.000 description 3
- 235000010445 lecithin Nutrition 0.000 description 3
- 239000000787 lecithin Substances 0.000 description 3
- 229940067606 lecithin Drugs 0.000 description 3
- 239000004530 micro-emulsion Substances 0.000 description 3
- 239000006187 pill Substances 0.000 description 3
- 229920001983 poloxamer Polymers 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 239000004094 surface-active agent Substances 0.000 description 3
- DKVBOUDTNWVDEP-NJCHZNEYSA-N teicoplanin aglycone Chemical compound N([C@H](C(N[C@@H](C1=CC(O)=CC(O)=C1C=1C(O)=CC=C2C=1)C(O)=O)=O)[C@H](O)C1=CC=C(C(=C1)Cl)OC=1C=C3C=C(C=1O)OC1=CC=C(C=C1Cl)C[C@H](C(=O)N1)NC([C@H](N)C=4C=C(O5)C(O)=CC=4)=O)C(=O)[C@@H]2NC(=O)[C@@H]3NC(=O)[C@@H]1C1=CC5=CC(O)=C1 DKVBOUDTNWVDEP-NJCHZNEYSA-N 0.000 description 3
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 2
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 2
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 2
- 241000123982 Astilbe chinensis Species 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- QCDFBFJGMNKBDO-UHFFFAOYSA-N Clioquinol Chemical compound C1=CN=C2C(O)=C(I)C=C(Cl)C2=C1 QCDFBFJGMNKBDO-UHFFFAOYSA-N 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- 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 2
- VQUPQWGKORWZII-UHFFFAOYSA-N Neoisoengelitin Natural products OC1C(O)C(O)C(C)OC1OC1C(=O)C2=C(O)C=C(O)C=C2OC1C1=CC=C(O)C=C1 VQUPQWGKORWZII-UHFFFAOYSA-N 0.000 description 2
- 239000005642 Oleic acid Substances 0.000 description 2
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 2
- 208000004880 Polyuria Diseases 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
- GAMYVSCDDLXAQW-AOIWZFSPSA-N Thermopsosid Natural products O(C)c1c(O)ccc(C=2Oc3c(c(O)cc(O[C@H]4[C@H](O)[C@@H](O)[C@H](O)[C@H](CO)O4)c3)C(=O)C=2)c1 GAMYVSCDDLXAQW-AOIWZFSPSA-N 0.000 description 2
- 238000013019 agitation Methods 0.000 description 2
- 230000000202 analgesic effect Effects 0.000 description 2
- 210000000481 breast Anatomy 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 210000003022 colostrum Anatomy 0.000 description 2
- 235000021277 colostrum Nutrition 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 230000035619 diuresis Effects 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 210000005069 ears Anatomy 0.000 description 2
- 210000002969 egg yolk Anatomy 0.000 description 2
- 229930003944 flavone Natural products 0.000 description 2
- 150000002212 flavone derivatives Chemical class 0.000 description 2
- 235000011949 flavones Nutrition 0.000 description 2
- 229930182478 glucoside Natural products 0.000 description 2
- 150000008131 glucosides Chemical class 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 229940095990 inderal Drugs 0.000 description 2
- 230000000053 inderal effect Effects 0.000 description 2
- 238000009413 insulation Methods 0.000 description 2
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 239000007908 nanoemulsion Substances 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 2
- 150000003904 phospholipids Chemical class 0.000 description 2
- 231100000614 poison Toxicity 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol Chemical compound C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 235000012424 soybean oil Nutrition 0.000 description 2
- 239000003549 soybean oil Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- VHBFFQKBGNRLFZ-UHFFFAOYSA-N vitamin p Natural products O1C2=CC=CC=C2C(=O)C=C1C1=CC=CC=C1 VHBFFQKBGNRLFZ-UHFFFAOYSA-N 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
- HNAGHMKIPMKKBB-UHFFFAOYSA-N 1-benzylpyrrolidine-3-carboxamide Chemical compound C1C(C(=O)N)CCN1CC1=CC=CC=C1 HNAGHMKIPMKKBB-UHFFFAOYSA-N 0.000 description 1
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 1
- SODWJACROGQSMM-UHFFFAOYSA-N 5,6,7,8-tetrahydronaphthalen-1-amine Chemical compound C1CCCC2=C1C=CC=C2N SODWJACROGQSMM-UHFFFAOYSA-N 0.000 description 1
- 206010000349 Acanthosis Diseases 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 102000016912 Aldehyde Reductase Human genes 0.000 description 1
- 108010053754 Aldehyde reductase Proteins 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
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 241000272525 Anas platyrhynchos Species 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- 206010015150 Erythema Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 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
- 206010020649 Hyperkeratosis Diseases 0.000 description 1
- 206010048865 Hypoacusis Diseases 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- RCEAADKTGXTDOA-UHFFFAOYSA-N OS(O)(=O)=O.CCCCCCCCCCCC[Na] Chemical compound OS(O)(=O)=O.CCCCCCCCCCCC[Na] RCEAADKTGXTDOA-UHFFFAOYSA-N 0.000 description 1
- 208000005775 Parakeratosis Diseases 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 208000003251 Pruritus Diseases 0.000 description 1
- 206010061926 Purulence Diseases 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
- 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
- 241000362909 Smilax <beetle> Species 0.000 description 1
- 241001404789 Smilax glabra Species 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 229930006000 Sucrose Natural products 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
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- OGQICQVSFDPSEI-UHFFFAOYSA-N Zorac Chemical compound N1=CC(C(=O)OCC)=CC=C1C#CC1=CC=C(SCCC2(C)C)C2=C1 OGQICQVSFDPSEI-UHFFFAOYSA-N 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- NUZWLKWWNNJHPT-UHFFFAOYSA-N anthralin Chemical compound C1C2=CC=CC(O)=C2C(=O)C2=C1C=CC=C2O NUZWLKWWNNJHPT-UHFFFAOYSA-N 0.000 description 1
- 230000000118 anti-neoplastic effect Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 210000004204 blood vessel Anatomy 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
- OBNCKNCVKJNDBV-UHFFFAOYSA-N butanoic acid ethyl ester Natural products CCCC(=O)OCC OBNCKNCVKJNDBV-UHFFFAOYSA-N 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 229960003563 calcium carbonate Drugs 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 235000013539 calcium stearate Nutrition 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
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- RNFNDJAIBTYOQL-UHFFFAOYSA-N chloral hydrate Chemical compound OC(O)C(Cl)(Cl)Cl RNFNDJAIBTYOQL-UHFFFAOYSA-N 0.000 description 1
- 229960002327 chloral hydrate Drugs 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 239000011280 coal tar Substances 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 238000001246 colloidal dispersion Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 229960000913 crospovidone Drugs 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 239000003085 diluting agent Substances 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
- 239000007884 disintegrant Substances 0.000 description 1
- VKNSMISEHWURHF-BUFQOAPZSA-L disodium;(e)-2-octadecanoylbut-2-enedioate Chemical compound [Na+].[Na+].CCCCCCCCCCCCCCCCCC(=O)C(\C([O-])=O)=C/C([O-])=O VKNSMISEHWURHF-BUFQOAPZSA-L 0.000 description 1
- 208000035475 disorder Diseases 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
- 230000004064 dysfunction Effects 0.000 description 1
- 229960003645 econazole nitrate Drugs 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- 231100000321 erythema Toxicity 0.000 description 1
- 229960001617 ethyl hydroxybenzoate Drugs 0.000 description 1
- NUVBSKCKDOMJSU-UHFFFAOYSA-N ethylparaben Chemical compound CCOC(=O)C1=CC=C(O)C=C1 NUVBSKCKDOMJSU-UHFFFAOYSA-N 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 229930003935 flavonoid Natural products 0.000 description 1
- 150000002215 flavonoids Chemical class 0.000 description 1
- 235000017173 flavonoids Nutrition 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 230000010354 integration Effects 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
- 229960001375 lactose Drugs 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 238000005461 lubrication Methods 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 210000001595 mastoid Anatomy 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 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
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- GYCKQBWUSACYIF-UHFFFAOYSA-N o-hydroxybenzoic acid ethyl ester Natural products CCOC(=O)C1=CC=CC=C1O GYCKQBWUSACYIF-UHFFFAOYSA-N 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 230000010494 opalescence Effects 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 238000005220 pharmaceutical analysis Methods 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000002574 poison Substances 0.000 description 1
- 229920001993 poloxamer 188 Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229940093430 polyethylene glycol 1500 Drugs 0.000 description 1
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 238000013138 pruning Methods 0.000 description 1
- 230000001185 psoriatic effect Effects 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 229960001285 quercetin Drugs 0.000 description 1
- 235000005875 quercetin Nutrition 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 150000004492 retinoid derivatives Chemical class 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 229940080313 sodium starch Drugs 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 210000000498 stratum granulosum Anatomy 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 229960004793 sucrose Drugs 0.000 description 1
- 229960000565 tazarotene Drugs 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 229940126680 traditional chinese medicines Drugs 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 238000002137 ultrasound extraction Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明公开了落新妇苷或其同系物在制备治疗银屑病药物中的应用。动物试验证明，所述落新妇苷或其同系物等对银屑病具有显著的疗效，可以用于制备治疗银屑病的药物。落新妇苷或其同系物无毒副作用，即使长期服用，也无明显不良反应，具有较大的临床应用价值。
Description
技术领域
本发明涉及落新妇苷及其同系物的新用途。
背景技术
银屑病（Psoriasis）俗称牛皮癣，是一种常见的慢性、复发性、且与免疫相关的疾病。临床表现为在浸润性红斑基础上，被覆多层银白色磷屑。与其他疾病不同的是尽管大约80％的患者仅具有瘙痒症状，但由于皮损外观不雅，导致银屑病患者感受到严重的心理压力，自卑，失落，甚至自杀倾向，极大的影响了患者的生存质量。现代医学认为本病的原因在于免疫系统功能障碍，其治疗普遍应用（内服或外用）免疫抑制剂，以及可改善皮损症状的皮质激素或煤焦油等药物，如蒽林、钙泊三醇，他扎罗汀，皮损下注射皮质激素或内服迪银片，维甲酸类、抗肿瘤药等方法，尽管短期缓解症状效果尚可，但长期应用都具有严重的毒副作用，临床仍缺乏疗效好、副作用小的治疗药物。
发明内容
本发明的目的是公开一种落新妇苷落新妇苷及其同系物在制备治疗银屑病药物中的应用，以克服现有技术存在的上述缺陷，满足临床应用的需要。
所述落新妇苷，花旗松素-3-O-α-L-吡喃鼠李糖苷，英文名Astilbin，分子式C21H22O11，分子量450.408，CAS号：
落新妇苷（astilbin），2R，3R）-花旗松素-3-O-α-L-吡喃鼠李糖苷，是1950年由Kozo Hayashi和Kazuhiko Ouchi首次从植物落新妇中提取得到的化合物，据文献报道，落新妇苷具有多种显著的生物学活性，包括抑制辅酶A还原酶，抑制醛糖还原酶，保护肝脏，镇痛，抗水肿等。近年又来有报道称落新妇苷有显著的选择性免疫抑制作用，且它的选择性作用与以往的免疫抑制剂相比具有明显优势，因此可以作为一种新的免疫抑制剂用于免疫相关疾病的治疗。
落新妇苷的提取方法，可参见周军,曲佳,寿国香,吕曙华在HPLC法测定土茯苓中落新妇苷和黄杞苷[1]文献中报道的方法，用甲醇超声提取60min。提取完全，含量高。相关的理化性能以及检测方法，可参见土茯苓药材中落新妇苷和总黄酮的含量测定方法研究[2]文献的报道方法，利用HPLC方法测定落新妇苷的含量。
[1]周军,曲佳,寿国香,吕曙华的HPLC法测定土茯苓中落新妇苷和黄杞苷。中国药品标准，2009,10（5）：372-374.
[2]方圆，王雪彦，晁若冰.土茯苓药材中落新妇苷和总黄酮的含量测定.药物分析杂志.2010,30(9):1738-1741.
动物试验证明，所述落新妇苷及体内可代谢成其苷元（花旗松素）的同类物质，包括异落新妇苷、新落新妇苷等对银屑病具有显著的疗效，可 以用于制备治疗银屑病的药物。可通过口服、外搽、注射或腔道途径施加于需要治疗的患者，剂量一般为0.1-5g/天；
本发明还包括一种用于治疗银屑病的药物，包括治疗有效量的落新妇苷及体内可代谢成其苷元（花旗松素）的同类物质，包括异落新妇苷、新落新妇苷等和医药上可接受的载体，所述载体如：如稀释剂、赋形剂（比如水）等，填充剂如淀粉、蔗糖、乳糖、微晶纤维素等，粘合剂如纤维素衍生物、明胶和聚乙烯吡咯烷酮等，润湿剂如甘油等，表面活性剂如十六烷醇等，崩解剂如碳酸钙、交聚维酮、羟基乙酸淀粉钠等，润滑剂如滑石粉、硬脂酰富马酸钠、硬脂酸钙和镁等。
可采用本领域公知的方法，将治疗有效量的落新妇苷或其苷元花旗松素、类似结构异落新妇苷、新落新妇苷等与一种或多种药学上可接受的载体相混合，制备成常规的固体制剂如片剂、粉剂、颗粒剂、胶囊、滴丸、软胶囊、口服液、注射液、针剂、乳剂（含微乳、亚微乳）、软膏、栓剂、贴剂、巴布剂等，其中活性成分的含量为0.1%～99.5%（重量比）。
落新妇苷及其同系物无毒副作用，即使长期服用，也无明显不良反应，具有较大的临床应用价值。
具体实施方式
实施例中，所采用的落新妇苷，来源于百合科植物光叶菝契SmilaxglabraRoxb.的干燥根茎土茯苓。土茯苓中含落新妇苷、异落新妇苷、槲皮素、土茯苓苷等黄酮类物质,其中以落新妇苷含量较高。落新妇苷具有的利尿、镇痛作用与土茯苓的除湿、解毒等功效密切相关[3],可以作为土 茯苓药材质量控制的指标成分。
[3]吴丽明，张敏.土茯苓中落新妇苷的利尿和镇痛作用，中药材.1995,18(2):627.
实施例1
落新妇苷对心得安诱导银屑病模型的影响：
1、健康成年白化豚鼠18只，4-5周龄，初始体重250-300g，雄性，对豚鼠编号，称重并记录。按随机数字表法分组，取3只豚鼠作为空白对照组，其余15只作为造模组。
2、用棉棒将5%盐酸心得安乳剂均匀涂抹豚鼠双耳背皮肤，用乳膏基质按照上述方法外涂进行造模，空白对照组涂抹空白基质，所有动物用量均为每次0.2ml/耳，涂抹均匀，使耳背上覆上薄薄一层，每日3次，每次间隔3h。每天观察豚鼠的体重变化以及状态。当造模一周后，观察豚鼠基本出现红肿甚至皮损现象，造模基本成功。
3、造模成功后，将造模组分为落新妇苷组、甲氨蝶呤组两个组，每组13只。落新妇苷外涂，甲氨蝶呤内服（临床剂量折算）每天上午造模2次，下午给药1次。给药后，观察各组之间豚鼠的状态以及与模型组之间的比较。给药10天后，取材。
4、取材。将豚鼠用20%水合氯醛麻醉（0.34ml/100g），等到豚鼠死后，剪下豚鼠的双耳，放入装有10%甲醛溶液的药瓶中，盖好，送检切片，Baker评分。结果见表1。
表1：落新妇苷对豚鼠心得安银屑病模型的影响
Baker法积分评估的标准如下：
(1)角质层中见有Munro小脓疡计2.0分；
(2)过度角化计0.5分；角化不全计1.0分。
(3)表皮层中见有颗粒层变薄或消失计1.0分；
(4)棘层肥厚计1.0分；
(5)皮突延长、基底层迂曲起伏，根据轻、中、重程度分别计0.5、1.0、1.5分；
(6)真皮层见有单一核及多形核细胞浸润，根据轻、中、重程度分别计0.5、1.0、2.0分；
(7)乳突突出明显计0.5分；
(8)真皮浅层毛细血管扩张计0.5分。
实施例2
粉剂：
落新妇苷 5g
乳糖 150g
吐温-80 15g
制备方法：
将落新妇苷与其他组合混合，冷冻干燥，即可获得粉剂。
纳米乳剂：
落新妇苷 10g
卵磷脂 5g
普朗尼克 10g
吐温-80 2g
甘油 25g
制备方法：
称取处方量的甘油、吐温-80,搅拌分散于适量蒸馏水中。另取卵磷脂、普朗尼克F-68适量,搅拌下依次加入到水相溶液中。待卵磷脂与普朗克尼F-68分散完全后,将落新妇苷加入到水相中,同时磁力搅拌，使完全溶解。超声6min,即得落新妇苷初乳。在搅拌下向初乳中加入蒸馏水至一定量,再超声6min。将此胶体分散系用高压匀质机于130MPa循环3次,即可得到乳光明显的落新妇苷纳米乳剂。
胶囊剂：
花旗松素 1g
淀粉 4g
制备方法：
花旗松素与淀粉混匀，装胶囊，即得。
微乳剂：
落新妇苷 16.5g
蒸馏水 18ml
吐温80 30g
正丁酸乙酯和乙醇 90ml
制备方法：
将各种试剂混合搅拌均匀，即可得到透明均一的微乳液。
滴丸；
异落新妇苷 10g
基质（聚乙二醇1500～20000、羧甲基淀粉钠） 90g
制备方法：
以落新妇苷为原料，按照一定的比例，加入表面活性剂聚乙二醇、羧甲基淀粉钠等基质混合均匀，将混合物料加热至熔融，搅拌均匀，置入专用的滴丸机，以适当的速度，滴入冷凝剂中而成。
乳膏剂：
新落新妇苷 5g
O/W型乳膏基质
制备方法：
取将新落新妇苷加入含羟苯乙酯、三乙醇胺、十二烷基硫酸钠、甘油等制成的水相，将硬脂酸、单硬脂酸甘油酯、白凡士林制成水包油型(O/W)乳膏基质，按等量递加法与乳膏基质混合均匀，分装，即得。
亚微乳剂：
落新妇苷 2.0g
大豆油 2.0g
精制蛋黄磷脂 1.2g
油酸 0.04g
泊洛沙姆188 0.8g
注射用水适量
制备方法：
处方比例称取落新妇苷、注射用大豆油、精制蛋黄磷脂、油酸于烧杯，置6O℃水浴中搅拌混合均匀，制备澄清稳定的油相，于60℃保温备用。再按处方比例称取泊洛沙姆188，加热搅拌分散均匀，制得水相，于60℃保温备用。然后将油相滴加到水相中，置高剪切分散乳化机中，混合制成粗乳剂，加入注射用水使成全量。再将粗乳剂经二步高压均质机匀化，调节pH至7．5～8.0，灌封于安瓿，按设定温度和时间灭菌即得。
注射液：
落新妇苷 5g
葡萄糖 125g
吐温-80 15g
注射用水适量
制备方法：
将各成分溶解混合，加入表面活性剂，加入注射用水搅拌，即得。
栓剂：
硝酸益康唑 50g
落新妇苷 200ml
冰片 3g
基质（可可豆脂、半合成脂肪酸酯）适量
制备方法：
将基质水浴加热至熔化，加入药物，药物与基质应充分混匀，注入栓模（已涂润滑剂）冷却至完全凝固，削去溢出部分，脱模。制得乳黄色至浅黄棕色鸭舌型栓剂，有特臭。
Claims (2)
1.落新妇苷作为唯一活性成分在制备治疗银屑病药物中的应用。
2.根据权利要求1所述的应用，其特征在于，所说的药物为片剂、粉剂、颗粒剂、胶囊、滴丸、口服液、注射液、针剂、乳剂、软膏、栓剂、贴剂或巴布剂。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310217584.3A CN104208086B (zh) | 2013-06-04 | 2013-06-04 | 落新妇苷或其同系物在制备治疗银屑病药物中的应用 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310217584.3A CN104208086B (zh) | 2013-06-04 | 2013-06-04 | 落新妇苷或其同系物在制备治疗银屑病药物中的应用 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104208086A CN104208086A (zh) | 2014-12-17 |
| CN104208086B true CN104208086B (zh) | 2017-05-24 |
Family
ID=52090260
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310217584.3A Expired - Fee Related CN104208086B (zh) | 2013-06-04 | 2013-06-04 | 落新妇苷或其同系物在制备治疗银屑病药物中的应用 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104208086B (zh) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112730674B (zh) * | 2020-12-23 | 2022-10-04 | 广西壮族自治区食品药品检验所 | 一种罗汉茶的质量检测方法 |
| CN113813277A (zh) * | 2021-10-19 | 2021-12-21 | 广州白云山敬修堂药业股份有限公司 | 一种包含落新妇苷和/或其异构体的组合物在制备治疗银屑病的药物中的用途 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU767241B2 (en) * | 1998-09-14 | 2003-11-06 | Qiang Xu | Immunosuppressive agents |
| CN101152200B (zh) * | 2006-09-27 | 2011-09-14 | 山东绿叶天然药物研究开发有限公司 | 落新妇苷在制备治疗或预防急慢性肾功能衰竭及肾纤维化的药物中的应用 |
-
2013
- 2013-06-04 CN CN201310217584.3A patent/CN104208086B/zh not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CN104208086A (zh) | 2014-12-17 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN100998650A (zh) | 肉桂在治疗糖尿病上的用途及产品和其制备方法 | |
| CN102631405A (zh) | 一种复方芹菜素纳米乳抗高血压药物 | |
| CN104940930A (zh) | 一种治疗儿童癫痫药物口服乳剂及其制备方法 | |
| EP2512444B1 (en) | Mixtures of plants in spagyric mother tincture for dry cough in babies | |
| EP2974733B1 (de) | Kombination von Baldrianwurzelextrakt und Lavendelöl zur Verwendung zur Behandlung von Schlafstörungen | |
| CN104208086B (zh) | 落新妇苷或其同系物在制备治疗银屑病药物中的应用 | |
| CN101708241A (zh) | 一种祛湿止痒药物组合物 | |
| CN102657841A (zh) | 一种生姜酚类提取物制剂及其制备方法 | |
| TWI662965B (zh) | 含有肉蓯蓉及銀杏萃取物之有助提升個體記憶之組成物 | |
| CN104173907A (zh) | 莪术油在制备治疗银屑病药物中的应用 | |
| JP7034927B2 (ja) | 耽羅笹抽出物を含む女性更年期症状の改善用組成物 | |
| CN101933919B (zh) | 棕矢车菊素的用途 | |
| CN103893593A (zh) | 具有清热解毒、抗炎和增强免疫力作用的药物组合物 | |
| CN104223073A (zh) | 一种助眠的食品、保健品或药物组合物 | |
| CN100509017C (zh) | 治疗胆道感染的药物及其制备方法 | |
| US11484562B2 (en) | Composition for preventing or treating obesity comprising natural mixture extracts | |
| CN106822095A (zh) | 一种防治脂肪肝和肥胖的药物及其在制药中的应用 | |
| JP6510017B1 (ja) | 神経細胞死抑制剤及び神経細胞死抑制用食品組成物 | |
| CN105148069A (zh) | 一种药食两用水溶性珍珠粉组合物及其制备方法与应用 | |
| US9789081B2 (en) | Compositions for improving safety of pharmacological formulations | |
| CN104605344A (zh) | 一种增强免疫力的保健食品及其制备方法 | |
| CN104223066A (zh) | 一种改善睡眠的中药组合物 | |
| KR101307726B1 (ko) | 백지추출물을 유효성분을 함유하는 약물 중독 및 금단증상의 예방 및 치료용 조성물 | |
| KR20130139676A (ko) | 클로로겐산 또는 이의 유도체를 유효성분으로 함유하는 진정, 수면 및 항경련용 약학적 조성물 | |
| JP7452777B2 (ja) | 生活の質改善又は維持用組成物 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20170524 |