CN1220519C - Chinese medicinal composition for treating prostate cancer, its preparation method and its application in the preparation of medicine for treating prostate cancer - Google Patents
Chinese medicinal composition for treating prostate cancer, its preparation method and its application in the preparation of medicine for treating prostate cancer Download PDFInfo
- Publication number
- CN1220519C CN1220519C CN02136655.1A CN02136655A CN1220519C CN 1220519 C CN1220519 C CN 1220519C CN 02136655 A CN02136655 A CN 02136655A CN 1220519 C CN1220519 C CN 1220519C
- Authority
- CN
- China
- Prior art keywords
- obtains
- extraction
- water
- extract
- ethanol
- 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 - Lifetime
Links
- 239000003814 drug Substances 0.000 title claims abstract description 61
- 239000000203 mixture Substances 0.000 title claims abstract description 61
- 238000002360 preparation method Methods 0.000 title claims abstract description 23
- 206010060862 Prostate cancer Diseases 0.000 title abstract description 4
- 208000000236 Prostatic Neoplasms Diseases 0.000 title abstract description 4
- 238000000605 extraction Methods 0.000 claims abstract description 56
- 241000222336 Ganoderma Species 0.000 claims abstract description 26
- 229930013930 alkaloid Natural products 0.000 claims abstract description 23
- 150000003797 alkaloid derivatives Chemical class 0.000 claims abstract description 19
- ZYGHJZDHTFUPRJ-UHFFFAOYSA-N coumarin Chemical compound C1=CC=C2OC(=O)C=CC2=C1 ZYGHJZDHTFUPRJ-UHFFFAOYSA-N 0.000 claims abstract description 19
- 229930003944 flavone Natural products 0.000 claims abstract description 19
- 235000011949 flavones Nutrition 0.000 claims abstract description 19
- CRDNMYFJWFXOCH-YPKPFQOOSA-N (3z)-3-(3-oxo-1h-indol-2-ylidene)-1h-indol-2-one Chemical compound N/1C2=CC=CC=C2C(=O)C\1=C1/C2=CC=CC=C2NC1=O CRDNMYFJWFXOCH-YPKPFQOOSA-N 0.000 claims abstract description 18
- 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 claims abstract description 16
- 150000002212 flavone derivatives Chemical class 0.000 claims abstract description 16
- VHBFFQKBGNRLFZ-UHFFFAOYSA-N vitamin p Natural products O1C2=CC=CC=C2C(=O)C=C1C1=CC=CC=C1 VHBFFQKBGNRLFZ-UHFFFAOYSA-N 0.000 claims abstract description 16
- 241000180649 Panax notoginseng Species 0.000 claims abstract description 14
- 235000003143 Panax notoginseng Nutrition 0.000 claims abstract description 14
- 150000004676 glycans Chemical class 0.000 claims abstract description 12
- 229920001282 polysaccharide Polymers 0.000 claims abstract description 12
- 239000005017 polysaccharide Substances 0.000 claims abstract description 12
- 239000001397 quillaja saponaria molina bark Substances 0.000 claims abstract description 11
- 229930182490 saponin Natural products 0.000 claims abstract description 11
- 150000007949 saponins Chemical class 0.000 claims abstract description 11
- JBQATDIMBVLPRB-UHFFFAOYSA-N isoliquiritigenin Natural products OC1=CC(O)=CC=C1C1OC2=CC(O)=CC=C2C(=O)C1 JBQATDIMBVLPRB-UHFFFAOYSA-N 0.000 claims abstract description 10
- 150000002596 lactones Chemical class 0.000 claims abstract description 10
- CRDNMYFJWFXOCH-BUHFOSPRSA-N Couroupitine B Natural products N\1C2=CC=CC=C2C(=O)C/1=C1/C2=CC=CC=C2NC1=O CRDNMYFJWFXOCH-BUHFOSPRSA-N 0.000 claims abstract description 9
- IPQKDIRUZHOIOM-UHFFFAOYSA-N Oroxin A Natural products OC1C(O)C(O)C(CO)OC1OC(C(=C1O)O)=CC2=C1C(=O)C=C(C=1C=CC=CC=1)O2 IPQKDIRUZHOIOM-UHFFFAOYSA-N 0.000 claims abstract description 9
- IKIIZLYTISPENI-ZFORQUDYSA-N baicalin Chemical compound O1[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1OC(C(=C1O)O)=CC2=C1C(=O)C=C(C=1C=CC=CC=1)O2 IKIIZLYTISPENI-ZFORQUDYSA-N 0.000 claims abstract description 9
- 229960003321 baicalin Drugs 0.000 claims abstract description 9
- AQHDANHUMGXSJZ-UHFFFAOYSA-N baicalin Natural products OC1C(O)C(C(O)CO)OC1OC(C(=C1O)O)=CC2=C1C(=O)C=C(C=1C=CC=CC=1)O2 AQHDANHUMGXSJZ-UHFFFAOYSA-N 0.000 claims abstract description 9
- LPLVUJXQOOQHMX-QWBHMCJMSA-N glycyrrhizinic acid Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@@H]1C([C@H]2[C@]([C@@H]3[C@@]([C@@]4(CC[C@@]5(C)CC[C@@](C)(C[C@H]5C4=CC3=O)C(O)=O)C)(C)CC2)(C)CC1)(C)C)C(O)=O)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O LPLVUJXQOOQHMX-QWBHMCJMSA-N 0.000 claims abstract description 9
- CRDNMYFJWFXOCH-UHFFFAOYSA-N isoindigotin Natural products N1C2=CC=CC=C2C(=O)C1=C1C2=CC=CC=C2NC1=O CRDNMYFJWFXOCH-UHFFFAOYSA-N 0.000 claims abstract description 9
- DXDRHHKMWQZJHT-FPYGCLRLSA-N isoliquiritigenin Chemical compound C1=CC(O)=CC=C1\C=C\C(=O)C1=CC=C(O)C=C1O DXDRHHKMWQZJHT-FPYGCLRLSA-N 0.000 claims abstract description 9
- 235000008718 isoliquiritigenin Nutrition 0.000 claims abstract description 9
- DQJCDTNMLBYVAY-ZXXIYAEKSA-N (2S,5R,10R,13R)-16-{[(2R,3S,4R,5R)-3-{[(2S,3R,4R,5S,6R)-3-acetamido-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy}-5-(ethylamino)-6-hydroxy-2-(hydroxymethyl)oxan-4-yl]oxy}-5-(4-aminobutyl)-10-carbamoyl-2,13-dimethyl-4,7,12,15-tetraoxo-3,6,11,14-tetraazaheptadecan-1-oic acid Chemical compound NCCCC[C@H](C(=O)N[C@@H](C)C(O)=O)NC(=O)CC[C@H](C(N)=O)NC(=O)[C@@H](C)NC(=O)C(C)O[C@@H]1[C@@H](NCC)C(O)O[C@H](CO)[C@H]1O[C@H]1[C@H](NC(C)=O)[C@@H](O)[C@H](O)[C@@H](CO)O1 DQJCDTNMLBYVAY-ZXXIYAEKSA-N 0.000 claims abstract description 7
- 102000002068 Glycopeptides Human genes 0.000 claims abstract description 7
- 108010015899 Glycopeptides Proteins 0.000 claims abstract description 7
- 238000002156 mixing Methods 0.000 claims abstract description 5
- -1 rubescensine A Chemical compound 0.000 claims abstract description 5
- 235000006200 Glycyrrhiza glabra Nutrition 0.000 claims abstract 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 101
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 99
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 89
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 64
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 64
- 239000007788 liquid Substances 0.000 claims description 64
- 239000000284 extract Substances 0.000 claims description 58
- 229960004756 ethanol Drugs 0.000 claims description 40
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 33
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical group CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 31
- 239000000843 powder Substances 0.000 claims description 29
- 239000000243 solution Substances 0.000 claims description 28
- 239000000706 filtrate Substances 0.000 claims description 27
- 238000001556 precipitation Methods 0.000 claims description 25
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 21
- 201000001514 prostate carcinoma Diseases 0.000 claims description 20
- 239000003208 petroleum Substances 0.000 claims description 18
- 238000005406 washing Methods 0.000 claims description 18
- 238000002481 ethanol extraction Methods 0.000 claims description 17
- 239000002994 raw material Substances 0.000 claims description 17
- 241000628997 Flos Species 0.000 claims description 16
- 239000002253 acid Substances 0.000 claims description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 15
- 230000002378 acidificating effect Effects 0.000 claims description 15
- 238000002425 crystallisation Methods 0.000 claims description 14
- 230000008025 crystallization Effects 0.000 claims description 14
- 238000001035 drying Methods 0.000 claims description 13
- 238000003810 ethyl acetate extraction Methods 0.000 claims description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 12
- 241001646826 Isodon rubescens Species 0.000 claims description 12
- 238000001704 evaporation Methods 0.000 claims description 12
- 230000008020 evaporation Effects 0.000 claims description 12
- 238000011282 treatment Methods 0.000 claims description 12
- 239000002244 precipitate Substances 0.000 claims description 10
- 239000003513 alkali Substances 0.000 claims description 9
- 229960000956 coumarin Drugs 0.000 claims description 9
- 235000001671 coumarin Nutrition 0.000 claims description 9
- 238000003756 stirring Methods 0.000 claims description 9
- 241000233866 Fungi Species 0.000 claims description 8
- 239000004378 Glycyrrhizin Substances 0.000 claims description 8
- 238000001914 filtration Methods 0.000 claims description 8
- 239000012530 fluid Substances 0.000 claims description 8
- LPLVUJXQOOQHMX-UHFFFAOYSA-N glycyrrhetinic acid glycoside Natural products C1CC(C2C(C3(CCC4(C)CCC(C)(CC4C3=CC2=O)C(O)=O)C)(C)CC2)(C)C2C(C)(C)C1OC1OC(C(O)=O)C(O)C(O)C1OC1OC(C(O)=O)C(O)C(O)C1O LPLVUJXQOOQHMX-UHFFFAOYSA-N 0.000 claims description 8
- 229960004949 glycyrrhizic acid Drugs 0.000 claims description 8
- UYRUBYNTXSDKQT-UHFFFAOYSA-N glycyrrhizic acid Natural products CC1(C)C(CCC2(C)C1CCC3(C)C2C(=O)C=C4C5CC(C)(CCC5(C)CCC34C)C(=O)O)OC6OC(C(O)C(O)C6OC7OC(O)C(O)C(O)C7C(=O)O)C(=O)O UYRUBYNTXSDKQT-UHFFFAOYSA-N 0.000 claims description 8
- 235000019410 glycyrrhizin Nutrition 0.000 claims description 8
- 239000000401 methanolic extract Substances 0.000 claims description 8
- 239000007864 aqueous solution Substances 0.000 claims description 7
- 239000012141 concentrate Substances 0.000 claims description 7
- 238000004090 dissolution Methods 0.000 claims description 7
- 238000000034 method Methods 0.000 claims description 7
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 6
- 229920001503 Glucan Polymers 0.000 claims description 6
- 239000004952 Polyamide Substances 0.000 claims description 6
- 239000012043 crude product Substances 0.000 claims description 6
- 238000000502 dialysis Methods 0.000 claims description 6
- TWNIBLMWSKIRAT-VFUOTHLCSA-N levoglucosan Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@H]2CO[C@@H]1O2 TWNIBLMWSKIRAT-VFUOTHLCSA-N 0.000 claims description 6
- 229920002647 polyamide Polymers 0.000 claims description 6
- 238000001953 recrystallisation Methods 0.000 claims description 6
- 239000013049 sediment Substances 0.000 claims description 6
- 238000000926 separation method Methods 0.000 claims description 5
- 239000006228 supernatant Substances 0.000 claims description 5
- QQILFGKZUJYXGS-UHFFFAOYSA-N Indigo dye Chemical compound C1=CC=C2C(=O)C(C3=C(C4=CC=CC=C4N3)O)=NC2=C1 QQILFGKZUJYXGS-UHFFFAOYSA-N 0.000 claims description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 4
- 239000003463 adsorbent Substances 0.000 claims description 4
- 238000005119 centrifugation Methods 0.000 claims description 4
- SIHHLZPXQLFPMC-UHFFFAOYSA-N chloroform;methanol;hydrate Chemical compound O.OC.ClC(Cl)Cl SIHHLZPXQLFPMC-UHFFFAOYSA-N 0.000 claims description 4
- 239000008367 deionised water Substances 0.000 claims description 4
- 229910021641 deionized water Inorganic materials 0.000 claims description 4
- MQRJBSHKWOFOGF-UHFFFAOYSA-L disodium;carbonate;hydrate Chemical compound O.[Na+].[Na+].[O-]C([O-])=O MQRJBSHKWOFOGF-UHFFFAOYSA-L 0.000 claims description 4
- 238000010828 elution Methods 0.000 claims description 4
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 claims description 4
- 238000000855 fermentation Methods 0.000 claims description 4
- 230000004151 fermentation Effects 0.000 claims description 4
- 239000006260 foam Substances 0.000 claims description 4
- 238000003808 methanol extraction Methods 0.000 claims description 4
- 239000012452 mother liquor Substances 0.000 claims description 4
- 239000011347 resin Substances 0.000 claims description 4
- 229920005989 resin Polymers 0.000 claims description 4
- 239000000741 silica gel Substances 0.000 claims description 4
- 229910002027 silica gel Inorganic materials 0.000 claims description 4
- 238000010898 silica gel chromatography Methods 0.000 claims description 4
- 229910052708 sodium Inorganic materials 0.000 claims description 4
- 239000011734 sodium Substances 0.000 claims description 4
- 244000004005 Nypa fruticans Species 0.000 claims description 3
- 235000005305 Nypa fruticans Nutrition 0.000 claims description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 3
- 229910021529 ammonia Inorganic materials 0.000 claims description 3
- 230000006837 decompression Effects 0.000 claims description 3
- 238000005202 decontamination Methods 0.000 claims description 3
- 230000003588 decontaminative effect Effects 0.000 claims description 3
- 229960000935 dehydrated alcohol Drugs 0.000 claims description 3
- 238000011026 diafiltration Methods 0.000 claims description 3
- 238000007598 dipping method Methods 0.000 claims description 3
- 150000002213 flavones Chemical class 0.000 claims description 3
- 229930182470 glycoside Natural products 0.000 claims description 3
- 150000002338 glycosides Chemical class 0.000 claims description 3
- 239000012535 impurity Substances 0.000 claims description 3
- 238000002386 leaching Methods 0.000 claims description 3
- 239000000463 material Substances 0.000 claims description 3
- 229910052700 potassium Inorganic materials 0.000 claims description 3
- 239000011591 potassium Substances 0.000 claims description 3
- 238000004064 recycling Methods 0.000 claims description 3
- 238000003809 water extraction Methods 0.000 claims description 3
- GOLORTLGFDVFDW-UHFFFAOYSA-N 3-(1h-benzimidazol-2-yl)-7-(diethylamino)chromen-2-one Chemical compound C1=CC=C2NC(C3=CC4=CC=C(C=C4OC3=O)N(CC)CC)=NC2=C1 GOLORTLGFDVFDW-UHFFFAOYSA-N 0.000 claims description 2
- 238000003811 acetone extraction Methods 0.000 claims description 2
- 239000000872 buffer Substances 0.000 claims description 2
- DZGCGKFAPXFTNM-UHFFFAOYSA-N ethanol;hydron;chloride Chemical compound Cl.CCO DZGCGKFAPXFTNM-UHFFFAOYSA-N 0.000 claims description 2
- 239000008363 phosphate buffer Substances 0.000 claims description 2
- 239000000049 pigment Substances 0.000 claims description 2
- 102000004169 proteins and genes Human genes 0.000 claims description 2
- 108090000623 proteins and genes Proteins 0.000 claims description 2
- 240000004670 Glycyrrhiza echinata Species 0.000 claims 1
- 235000001453 Glycyrrhiza echinata Nutrition 0.000 claims 1
- 235000017382 Glycyrrhiza lepidota Nutrition 0.000 claims 1
- 229940010454 licorice Drugs 0.000 claims 1
- 238000010992 reflux Methods 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 12
- 241000723353 Chrysanthemum Species 0.000 abstract 2
- 235000007516 Chrysanthemum Nutrition 0.000 abstract 2
- PQMOXTJVIYEOQL-UHFFFAOYSA-N Cumarin Natural products CC(C)=CCC1=C(O)C(C(=O)C(C)CC)=C(O)C2=C1OC(=O)C=C2CCC PQMOXTJVIYEOQL-UHFFFAOYSA-N 0.000 abstract 1
- 244000303040 Glycyrrhiza glabra Species 0.000 abstract 1
- 241000334160 Isatis Species 0.000 abstract 1
- 241001183967 Isodon Species 0.000 abstract 1
- FURUXTVZLHCCNA-UHFFFAOYSA-N Liquiritigenin Natural products C1=CC(O)=CC=C1C1OC2=CC(O)=CC=C2C(=O)C1 FURUXTVZLHCCNA-UHFFFAOYSA-N 0.000 abstract 1
- FSOGIJPGPZWNGO-UHFFFAOYSA-N Meomammein Natural products CCC(C)C(=O)C1=C(O)C(CC=C(C)C)=C(O)C2=C1OC(=O)C=C2CCC FSOGIJPGPZWNGO-UHFFFAOYSA-N 0.000 abstract 1
- FURUXTVZLHCCNA-AWEZNQCLSA-N liquiritigenin Chemical compound C1=CC(O)=CC=C1[C@H]1OC2=CC(O)=CC=C2C(=O)C1 FURUXTVZLHCCNA-AWEZNQCLSA-N 0.000 abstract 1
- 235000011477 liquorice Nutrition 0.000 abstract 1
- GSZUGBAEBARHAW-UHFFFAOYSA-N sophoraflavone B Natural products OC1C(O)C(O)C(CO)OC1OC1=CC=C(C=2OC3=CC(O)=CC=C3C(=O)C=2)C=C1 GSZUGBAEBARHAW-UHFFFAOYSA-N 0.000 abstract 1
- 230000001419 dependent effect Effects 0.000 description 6
- 239000003163 gonadal steroid hormone Substances 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- 239000000047 product Substances 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 3
- 241000207929 Scutellaria Species 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- 230000007935 neutral effect Effects 0.000 description 3
- 229960001866 silicon dioxide Drugs 0.000 description 3
- 244000104275 Phoenix dactylifera Species 0.000 description 2
- 235000010659 Phoenix dactylifera Nutrition 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 230000035614 depigmentation Effects 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 229940023462 paste product Drugs 0.000 description 2
- 238000007670 refining Methods 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 229920000018 Callose Polymers 0.000 description 1
- 241000202807 Glycyrrhiza Species 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 241001083505 Punica Species 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 230000002155 anti-virotic effect Effects 0.000 description 1
- 230000036528 appetite Effects 0.000 description 1
- 235000019789 appetite Nutrition 0.000 description 1
- 230000000680 avirulence Effects 0.000 description 1
- 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 1
- 230000004611 cancer cell death Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000007963 capsule composition Substances 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 238000002681 cryosurgery Methods 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000000745 gonadal hormone Substances 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 238000003672 processing method Methods 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 239000000941 radioactive substance Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Landscapes
- Medicines Containing Plant Substances (AREA)
Abstract
The present invention provides a traditional Chinese medicine composition which is prepared from ganoderma, astragali, rabdosia, isatis leaf, chrysanthemum, liquorice and notoginseng. The preparation method of the composition comprises the following steps of mixing extraction and object extraction. The composition uses polysaccharide, lactone, alkaloid, flavone, cumarin and saponin, or ganodermal glycopeptide, baicalin, rubescensine A, indirubin, chrysanthemum flavone, liquiritigenin, isoliquiritigenin and notoginseng saponin as extractive effective components. The traditional Chinese medicine composition can effectively treat prostate cancer, and has the characteristics of small side effect and high effective rate.
Description
(1) technical field
The present invention relates to a kind of Chinese medicine composition for the treatment of carcinoma of prostate, the application in the medicine of preparation treatment carcinoma of prostate of the preparation method of said composition and said composition.
(2) background technology
Carcinoma of prostate be among the male because of the main diseases of cancer mortality therefore, can be divided into two types of sex hormone dependent and non-sex hormone dependent.Usually can only implant or carry out cryosurgery from external irradiation, radioactive substance with laser.For some patient, these treatments just " limited and confine " disease several years.Most patient can be accepted chemotherapy simultaneously, though its energy kill cancer cell, the while is the intravital normal cell of grievous injury also, and its side effect is very big.Give gonadal hormone for the sex hormone dependent carcinoma of prostate and treat, effective percentage is still not ideal enough; For non-sex hormone dependent carcinoma of prostate, still do not have specific drug at present and treat.When patient is diagnosed as the cancer the 3rd or the fourth phase, or during the carcinoma of prostate relapse and metastasis, most patients can only wait for death.Therefore, it is little that people are sought after side effect, treats Therapeutic Method easily, and in other words, people are sought after the novel drugs that side effect is little, curative effect is high, and through present inventor's the discovery that studies for a long period of time, a kind of Chinese medicine can reach these therapeutic purposes.
(3) summary of the invention
An object of the present invention is to provide the Chinese medicine composition of the treatment carcinoma of prostate of a kind of good effect, few side effects;
Another object of the present invention provides the preparation method of described Chinese medicine composition;
A further object of the present invention provides the application of described Chinese medicine composition in the medicine of preparation treatment carcinoma of prostate.
These purposes of the present invention realize by following design: a kind of Chinese medicine composition for the treatment of carcinoma of prostate is characterized in that it is the medicament of being made by the following weight proportion raw material:
Ganoderma 3-4
Radix Scutellariae 1-2
Rabdosia rubescens 1-2
Folium Isatidis 1-2
Flos Chrysanthemi 0.5-1.5
Radix Glycyrrhizae 0.5-1.5
Radix Notoginseng 0.5-1.5
Best raw material weight proportioning is: Ganoderma: Radix Scutellariae: Rabdosia rubescens: Folium Isatidis: Flos Chrysanthemi: Radix Glycyrrhizae: Radix Notoginseng=3: 1.5: 1.2: 1.2: 0.9: 0.9: 0.9.
The best place of production of described Radix Scutellariae is Sichuan, and the optimal acquisition time is autumn; The best place of production of described Radix Notoginseng is Yunnan, and the optimal acquisition time is autumn (before the flowers are in blossom); The best place of production of described Folium Isatidis is south, and the optimal acquisition time is autumn, and the best place of production of described Flos Chrysanthemi is Zhejiang, and the optimal acquisition time is autumn; The best place of production of described Rabdosia rubescens is Henan, and the optimal acquisition time is May; Ganoderma obtains by cultivation/fermentation, the ganoderan that can adopt the Shanghai institute of agricultural sciences to produce, and described ganoderan contains required active component Ganoderma polypeptide and Ganoderma callose; The best place of production of Radix Glycyrrhizae is Gansu, and the optimal acquisition time is autumn.
The present invention also relates to the preparation method of described Chinese medicine composition, comprise mixed extraction preparation method or goal object extraction preparation method, described mixed extraction preparation method comprises:
1) prepare raw material:
With Ganoderma: Radix Scutellariae, Rabdosia rubescens, Folium Isatidis, Flos Chrysanthemi, Radix Glycyrrhizae, Radix Notoginseng are that the ratio of 3-4: 1-2: 1-2: 1-2: 0.5-1.5: 0.5-1.5: 0.5-1.5 is mixed with the weight ratio, preferably with further being processed into Chinese medicine coarse powder or Chinese medicine fluid extract, described processing method is well-known in the art; Described mixture is divided into six equal portions;
2) extract alkaloid:
I) a Chinese medicine mixture that step 1) is obtained obtains acidic ethanol extraction liquid with 0.1% hydrochloride ethanol liquid diafiltration or gradation leaching;
Ii) concentrating under reduced pressure obtains concentrate;
Iii) acid water (pH=4-5) washing in one embodiment, preferably makes this acidic aqueous liquid freeze overnight, filters, and obtains residue, and residue obtains acidic aqueous liquid with acid water (pH=4-5) washing;
Iv) in the acidic aqueous liquid that step I obtains in ii), add ammonia precipitation process, filter and obtain the total alkaloids precipitation; Perhaps
A) in the acidic aqueous liquid that step I obtains in ii), add diluted acid, use chloroform extraction, obtain chloroform layer and water layer to pH=2; Chloroform in the evaporation chloroform layer obtains weak alkaloid;
B) described water layer adds alkali to pH=6-7, uses chloroform extraction, obtains water layer and chloroform layer, and the chloroform in the evaporation chloroform layer obtains strong alkaloid;
C) above-mentioned b) water layer that obtains is adjusted to pH10 with alkali, uses butyl alcohol extraction then, and the butanols in the evaporation butanols layer obtains water miscible alkaloid;
Merge above-mentioned a), b) and the alkaloid that c) obtains, obtain total alkaloids.
Described chloroform, butanols preferably reclaim, and recycle for extraction step.Described alkaloid residue preferably carries out cold drying, crystallization.
3) extract polysaccharide:
95-100 ℃ hot water extraction of a Chinese medicine mixture with step 1) obtains preferably extracted 2 hours, discarded residue, and filtrate was placed after 12 hours, added the ethanol of concentration more than 50%, the centrifugal polysaccharide precipitation that obtains in supernatant;
Described polysaccharide precipitation is preferably refining with ether.
4) extract lactone:
With a Chinese medicine mixture aether backflow that step 1) obtains, remove pigment, preferably by the polyamide column depigmentation, reclaim ether, obtain total lactone;
5) extract Saponin:
A Chinese medicine mixture that step 1) is obtained and petroleum ether backflow 2-4 time, the evaporation petroleum ether obtains the defat coarse powder, uses 95% ethanol extraction, and concentrating under reduced pressure obtains concentrated solution;
A) concentrated solution is used chloroform, ethanol extraction successively, and reclaim under reduced pressure chloroform, ethanol obtain the general glycoside crude product; Perhaps
B) concentrated solution butyl alcohol extraction obtains the butanols layer, and the reclaim under reduced pressure butanols obtains the general glycoside crude product.
6) extract coumarin:
The a Chinese medicine mixture that step 1) is obtained decocts with water 1-2 hour, and the condensed water decocting liquid adds concentrated hydrochloric acid (30%), removes the impurity insoluble matter, places clear liquor, obtains the coarse crystallization of coumarin; It preferably uses washing with acetone after drying, drying adds the water recrystallization, and heating is filtered, and decolouring obtains aqueous solution, obtains the coumarin of faint yellow paste product after the cooling.
7) extract flavone:
A) a Chinese medicine mixture that obtains to step 1) adds the 70-80% alcohol dipping, the ethanol in the decompression recycling ethanol liquid, and the residue water dissolution filters, and obtains water liquid; With ethyl acetate extraction water liquid, the concentrating under reduced pressure acetic acid ethyl fluid obtains total flavones.
With step 2)-7) extract the alkaloid, polysaccharide, lactone, Saponin, coumarin, the flavone mixing that obtain, obtain the Chinese medicine composition of treatment carcinoma of prostate of the present invention.
Described goal object is extracted preparation method and is comprised:
1) extract baicalin:
I) in above-mentioned Radix Scutellariae component, add 10 times of (volume) water gagings and decocted 1-2 hour, filter;
Ii) filtrate is transferred to pH 1-2, kept centrifugation 30-40 minute down at 80-90 ℃ with acid;
Precipitate adds water and stirs, and adds alkali pH regulator is arrived neutrality, adds the doubly ethanol of (volume) amount of 3-5 again, filters;
Iii) in filtrate, add acid pH regulator is arrived 1-2, stir, kept 30-40 minute down, filter at 80-90 ℃;
Iv) the precipitate of gained is distinguished water, 50% washing with alcohol, and reuse 95% washing with alcohol or recrystallization obtain baicalin.
2) extract arasaponin:
I) with the solvable composition of concentration in the methanol extraction Radix Notoginseng root coarse powder below 50%, the concentrating under reduced pressure methanol extract liquid adds doubly (volume) water gaging of 3-5 in residue;
Ii) aqueous solution ether extraction, water layer reuse n-butanol extraction, evaporated under reduced pressure through silica gel column chromatography, is used CHCl
3-MeOH-H
2O obtains arasaponin than 65: 35: 10 eluting.
3) extract rubescensine A
With ether extraction Rabdosia rubescens leaf dried powder, discard residue, reclaim the ether in the ether solution, obtain green and brown color residue; Use the dissolve with methanol residue, decolouring obtains clear and bright methanol solution, and room temperature is placed and spent the night behind the concentrating under reduced pressure, filters methanol mother liquor evaporate to dryness, porphyrize; The neutral Al of reuse preferably
2O
3Absorption is used the ether eluting, crystallization.
4) extract indirubin:
Folium Isatidis is processed into dry Indigo Naturalis through drying, and gradation adds 30% concentrated hydrochloric acid, until no longer producing foam, filters, and water is washed till neutrality with precipitation, drying; Add methanol eddy 2-4 time, obtain methanol extract liquid, filter, reclaim the methanol in the methanol solution, the residue Petroleum ether extraction is removed petroleum ether, residue 3%NaOH solution-treated, and precipitation washes with water to neutrality, obtains indirubin with the ethyl acetate extracting.
5) extract the Flos Chrysanthemi flavone
Pulverize Flos Chrysanthemi, use the 50-70% ethanol extraction, concentrating under reduced pressure, add 90-95% ethanol, precipitation is filtered, concentrated filtrate is to there not being ethanol, the residue water dissolution filters, and filtrate is through macroporous adsorbent resin (DM130), it is colourless to be washed till post with deionized water, reuse 95% ethanol is eluting repeatedly, collects flavone, crystallization.
6) extract glycyrrhizin, isoliquiritigenin
The 90-95% ethanol extraction that Radix Glycyrrhizae is measured with 3-4 times (volume), ethanol liquid is through petroleum ether extraction, and water layer is admixed silica gel, uses MeOH-H
2O is 7: 3 eluting, and concentrate eluant obtains residue;
In residue, add water to dissolving fully, in water liquid, add ethyl acetate extraction, ethyl acetate layer 5%Na
2CO
3The extraction of water liquid is adjusted to pH5-6 with diluted acid with sodium carbonate water liquid, the reuse ethyl acetate extraction, and dry acetic acid ethyl fluid separates through polyamide column, obtains glycyrrhizin and isoliquiritigenin through 10-90% ethanol water gradient elution.
7) make the ganoderan that comprises lucidum glycopeptide and Ganoderma β-D glucosan (have commercially available, the Shanghai institute of agricultural sciences produces) and above-mentioned steps 1)-6) active component that obtains of extraction mixes and obtains product of the present invention.
The also available following method of described lucidum glycopeptide and Ganoderma β-D glucosan is extracted and is obtained:
I.a) pulverize behind the Ganoderma sporophore decontamination, add water 8-10 and doubly soaked 24 hours, be heated to 95-100 ℃ and stirred 8-10 hour down;
B) filter, preferably centrifugal or sheet frame separation and Extraction liquid and medicinal residues obtain filtrate and medicinal residues;
C) in medicinal residues, add water 3-4 and doubly carry out lixiviate, preferably stirred 8 hours down at 95-100 ℃; Repeating step b) and c)
II.a) Ganoderma fermentation liquid (containing fungus ball) is heated to 95-100 ℃, stirred 4 hours;
B) filter preferably centrifugal or sheet frame separation and Extraction liquid and fungus ball;
C) in the medicinal residues that contain fungus ball, add water 3-4 doubly (volume), extracted 2 hours, filter, separation and Extraction liquid and medicinal residues,
D) merge I.b), c) and II.c) in filtrate, be concentrated into the 1/8-1/10 of original volume, add edible ethanol (3-5 doubly), reach about 70% to ethanol, leave standstill alcohol and analysed 24 hours, use the centrifuge sediment separate out, recovered alcohol, dry sediment.Perhaps,
Ganoderma sporophore is carried out Soxhlet extract, with ethyl acetate extraction 4 hours, sucking filtration, the residue that obtains carried out Soxhlet again and extract, and with acetone extraction 4 hours, sucking filtration, the residue of gained was with 90% soak with ethanol 24 hours, and is centrifugal, sucking filtration; Residue with 0.2 mol phosphate buffer (PBS pH=7.0) extracts three times down at 80 ℃, and 4 hours/time, sucking filtration discarded residue, and buffer is removed protein, and is centrifugal,, with the upper strata liquid dialysis of gained, preferably the clear water dialysis is 7 days, distill water dialysis 3 days;
Add a large amount of acetone in non-dialysis liquid, precipitation occurs, abandoning supernatant precipitates and uses washing with acetone 6 times, obtains the powdery solid of required product.
The preparation method of Chinese medicine composition of the present invention further comprises step 8):
A) with described step 1)-7) active component that obtains is crushed to≤200 microns fine powders;
B) pulverize, dry nothing is leaked seed/nipa palm seed (PHOENIX DACTYLIFERA L) or Fructus punicae granati seed/short Semen Granati (PUNICA GRANAT-UN L), with the dehydrated alcohol extraction of 8 times of volumes, preferably extract merging filtrate, concentrating under reduced pressure three times, handle with ethinylation potassium, obtain powder
C) with a), b) material of gained is with 100-200: 1 weight ratio is mixed.
In one embodiment of the invention, with above-mentioned steps c) mixture that obtains incapsulates.
In general, product of the present invention can be mixed with multiple dosage form as required for using, preferably being mixed with capsule formulation carries out oral, described excipient and preparation technique are known in the pharmaceutics field, and those skilled in the art can obtain above-mentioned preparation according to corresponding document and technology of the prior art preparation.
Chinese medicine composition of the present invention has following properties:
1. free radical is eliminated in polyphenoils effect;
2. the erythrocytic quantity of two-ways regulation;
3. the leukocytic quantity of two-ways regulation;
4. avirulence;
5. remarkable antivirus action is arranged;
6. lead to cancer cell death;
7. regulate the central nervous system.
For showing Chinese medicine composition of the present invention to the treatment of prostate cancer effect, now to choose 6 patients and take Chinese medicine composition of the present invention, its effect sees Table 1:
Six patients of table 1 take the effect behind the Chinese medicine composition of the present invention
| Age | Take the preceding PSA of Chinese medicine composition of the present invention | Take the PSA behind the Chinese medicine composition of the present invention |
| 74 | 136.0 | 76 (5 weeks) |
| 73 | 308.0 | 233 (2 weeks) |
| 52 | 40.6 | (9.0 7 week) |
| 73 | 89.0 | (7.12 11 week) |
| 65 | 8.3 | (4.9 2 months) |
| 60 | 37 | 15 (2 months) |
Annotate: PSA is an important indicator of sign carcinoma of prostate, and PSA is high, and explanation suffers from carcinoma of prostate.
As seen, the patient who all suffers from carcinoma of prostate is after taking Chinese medicine composition of the present invention from The above results, and its PSA index descends, and Chinese medicine composition promptly of the present invention has therapeutical effect to carcinoma of prostate.All patients' quality of the life is improved, and appetite increases, and is full of vitality.
In the another clinical trial, the carcinoma of prostate of 36 routine sex hormone dependent is taken behind the Chinese medicine composition of the present invention all effectively.Effective percentage reached 60-70% after the carcinoma of prostate of non-sex hormone dependent was taken Chinese medicine composition of the present invention.This clinical effectiveness surface, the curative effect of product of the present invention obviously surpass medicine commonly used in the prior art field.
(4) specific embodiment
Further set forth the present invention below by embodiment.
Embodiment 1
Take by weighing raw material (kilogram) by following proportioning
Ganoderma 3 Radix Scutellariaes 1 Rabdosia rubescens 1
Folium Isatidis 2 Flos Chrysanthemis 1.5 Radix Glycyrrhizaes 0.5
Radix Notoginseng 0.5
Mix above-mentioned raw materials, grind to form the Chinese medicine coarse powder, described coarse powder is divided into six equal portions for following 1)-6) individual extraction step use;
1) extract alkaloid:
I) with the above-mentioned a Chinese medicine coarse powder that obtains with 0.1% acidic alcohol (95%) liquid diafiltration or gradation leaching, obtain acidic ethanol extraction liquid;
Ii) concentrating under reduced pressure obtains concentrate;
Iii) acid water (pH=4-5) washing in one embodiment, preferably makes this acidic aqueous liquid freeze overnight, filters, and obtains residue, and residue obtains acidic aqueous liquid with acid water (pH=4-5) washing;
Iv) in the acidic aqueous liquid that step I obtains in ii), add ammonia precipitation process, filter and obtain the total alkaloids precipitation; Perhaps
A) in the acidic aqueous liquid that step I obtains in ii), add dilute hydrochloric acid, use chloroform extraction, obtain chloroform layer and water layer to pH=2; Chloroform in the evaporation chloroform layer obtains weak alkaloidal residue;
B) described water layer adds alkali to pH=6, uses chloroform extraction, obtains water layer and chloroform layer, and the chloroform in the evaporation chloroform layer obtains strong alkaloidal residue;
C) above-mentioned b) water layer that obtains is adjusted to pH10 with sodium hydroxide solution, uses butyl alcohol extraction then, and the butanols in the evaporation butanols layer obtains water miscible alkaloid;
Merge above-mentioned a), b) and the alkaloid that c) obtains, obtain total alkaloids.
Reclaim above-mentioned chloroform, butanols, recycle for extraction step.Make the cold drying of described alkaloid residue, crystallization.
2) extract polysaccharide:
Reach 2 hours with the above-mentioned Chinese medicine coarse powder that obtains of 95 ℃ hot water extraction, discard residue, filtrate was placed after 12 hours, added the ethanol of concentration 60% in supernatant, the centrifugal polysaccharide precipitation that obtains;
Described polysaccharide precipitation is refining with ether.
3) extract lactone:
With the above-mentioned Chinese medicine coarse powder aether backflow that obtains, by the polyamide column depigmentation, reclaim ether, obtain total lactone;
4) extract Saponin:
The above-mentioned Chinese medicine coarse powder that obtains is refluxed with petroleum ether, and the evaporation petroleum ether obtains the defat coarse powder, uses 95% ethanol extraction, and concentrating under reduced pressure obtains concentrated solution;
A) concentrated solution is used chloroform, ethanol extraction successively, and reclaim under reduced pressure chloroform, ethanol obtain the Saponin crude product; Perhaps
B) concentrated solution butyl alcohol extraction obtains the butanols layer, and the reclaim under reduced pressure butanols obtains the Saponin crude product.
5) extract coumarin:
The above-mentioned Chinese medicine coarse powder that obtains is decocted with water 1 hour, in the condensed water decocting liquid, add concentrated hydrochloric acid (30%), remove the impurity insoluble matter, place clear liquor, obtain the coarse crystallization of coumarin; With this crystallization of washing with acetone, drying adds the water recrystallization after dry, and heating is filtered, and decolouring obtains aqueous solution, obtains the coumarin of faint yellow paste product after the cooling.
6) extract flavone:
A) in the above-mentioned a Chinese medicine coarse powder that obtains, add 70% alcohol dipping, the ethanol in the decompression recycling ethanol liquid, the residue water dissolution filters, and obtains water liquid; With ethyl acetate extraction water liquid, the concentrating under reduced pressure acetic acid ethyl fluid obtains total flavones.
With step 1)-6) extract the alkaloid, polysaccharide, lactone, Saponin, coumarin and the flavone mixing that obtain, obtain the Chinese medicine composition of treatment carcinoma of prostate of the present invention.
Embodiment 2
1) extract baicalin:
I) in 2 kilograms of Radix Scutellariaes, add 10 times of (volume) water gagings and decocted 1 hour, filter;
Ii) filtrate is transferred to pH 2, kept centrifugation 30 minutes down at 80 ℃ with acid; Precipitate adds water and stirs, and adds alkali pH regulator is arrived neutrality, adds the ethanol of 5 times (volume) amount again, filters;
Iii) in filtrate, add hydrochloric acid,, stir, kept 30 minutes down, filter at 80 ℃ with pH regulator to 2;
Iv) the precipitate of gained is distinguished water, 50% washing with alcohol, and reuse 95% washing with alcohol or recrystallization obtain baicalin.
2) extract arasaponin:
I) with the solvable composition in 1.5 kilograms of Radix Notoginseng roots of methanol extraction coarse powder of 40%, the concentrating under reduced pressure methanol extract liquid adds 5 times of (volume) water gagings in residue;
Ii) aqueous solution ether extraction, water layer reuse n-butanol extraction, evaporated under reduced pressure through silica gel column chromatography, is used CHCl
3-MeOH-H
2O obtains arasaponin than 65: 35: 10 eluting.
3) extract rubescensine A
With 2 kilograms of Rabdosia rubescens leaf dried powders of ether extraction, discard residue, reclaim the ether in the ether solution, obtain green and brown color residue; The dissolve with methanol residue, decolouring obtains clear and bright methanol solution, and room temperature is placed and is spent the night behind the concentrating under reduced pressure, filters methanol mother liquor evaporate to dryness, porphyrize; The neutral Al of reuse
2O
3Absorption is used the ether eluting, crystallization.
4) extract indirubin:
1.5 the kilogram Folium Isatidis is processed into dry Indigo Naturalis through drying, gradation adds 30% concentrated hydrochloric acid, until no longer producing foam, filters, and water is washed till neutrality with precipitation, drying; Add methanol eddy 2-4 time, obtain methanol extract liquid, filter, reclaim the methanol in the methanol solution, the residue Petroleum ether extraction is removed petroleum ether, residue 3%NaOH solution-treated, and precipitation washes with water to neutrality, obtains indirubin with the ethyl acetate extracting.
5) extract the Flos Chrysanthemi flavone
Pulverize 1.5 kilograms of Flos Chrysanthemis, use 50% ethanol extraction, concentrating under reduced pressure adds ethanol, precipitation, filter, concentrated filtrate is not to there being ethanol, and the residue water dissolution filters, and filtrate is through DM 130 macroporous adsorbent resins, it is colourless to be washed till post with deionized water, and reuse 95% ethanol is eluting repeatedly, collects flavone, crystallization.
6) extract glycyrrhizin, isoliquiritigenin
1.5 95% ethanol extraction that the kilogram Radix Glycyrrhizae is measured with 3 times (volume), ethanol liquid is through petroleum ether extraction, and water layer is used MeOH-H through the silicagel column eluting
2O is 7: 3 eluting, and concentrate eluant obtains residue;
In residue, add water to dissolving fully, in water liquid, add ethyl acetate extraction, ethyl acetate layer 5%Na
2CO
3The extraction of water liquid is adjusted to pH5-6 with dilute hydrochloric acid with sodium carbonate water liquid, the reuse ethyl acetate extraction, and dry acetic acid ethyl fluid separates through 60 order polyamide columns, and the ethanol water gradient elution of 10-90% obtains glycyrrhizin and isoliquiritigenin.
7) I.a) pulverize behind the Ganoderma sporophore decontamination, add water and soaked 24 hours for 8 times, be heated to 95 ℃ and stirred 8 hours down;
B) centrifugalize extracting solution and medicinal residues obtain filtrate and medicinal residues;
C) in medicinal residues, add water and carry out lixiviate for 3 times, stirred 8 hours down at 95 ℃; Repeating step b) and c),
II.a) Ganoderma fermentation liquid (containing fungus ball) is heated to 95 ℃, stirred 4 hours;
B centrifugalize extracting solution and fungus ball;
C) in the medicinal residues that contain fungus ball, add 3 times in water (volume), extracted 2 hours, filter, separation and Extraction liquid and medicinal residues,
D) merge I.b), c) and II.c) in filtrate, be concentrated into 1/8 of original volume, add edible ethanol (3-5 doubly), reach about 70% to ethanol, leave standstill alcohol and analysed 24 hours, use the centrifuge sediment separate out, recovered alcohol, dry sediment.
With above-mentioned steps 1)-7) extract the active component obtain and mix and obtain Chinese medicine composition of the present invention (1).
Chinese medicine composition (1) is crushed to≤200 microns fine powders (2);
Pulverize, dry nothing is leaked seed/nipa palm seed (PHOENIX DACTYLIFERA L), with the dehydrated alcohol extraction of 8 times of volumes, preferably extract three times, and merging filtrate, concentrating under reduced pressure is handled with ethinylation potassium, obtains powder (3),
With fine powder (2) and powder (3) with 100-200: 1 weight ratio is mixed, and incapsulates then, obtains the capsule of Chinese medicine composition of the present invention.
Embodiment 3
1) extract baicalin:
I) in 1.5 kilograms of Radix Scutellariaes, add 10 times of (volume) water gagings and decocted 1 hour, filter;
Ii) filtrate is transferred to pH 2, kept 30 minutes centrifugation at 80 ℃ down with dilute hydrochloric acid; Precipitate adds water and stirs, and adds alkali pH regulator is arrived neutrality, adds the ethanol of 3 times (volume) amount again, filters;
Iii) in filtrate, add hydrochloric acid,, stir, kept 30 minutes down, filter at 80 ℃ with pH regulator to 2;
Iv) the precipitate of gained is distinguished water, 50% washing with alcohol, and reuse 95% washing with alcohol or recrystallization obtain baicalin.
2) extract arasaponin:
I) with the solvable composition in 0.9 kilogram of Radix Notoginseng root of methanol extraction coarse powder of 40%, the concentrating under reduced pressure methanol extract liquid adds 5 times of (volume) water gagings in residue;
Ii) aqueous solution ether extraction, water layer reuse n-butanol extraction, evaporated under reduced pressure through silica gel column chromatography, is used CHCl
3-MeOH-H
2O obtains arasaponin than 65: 35: 10 eluting.
3) extract rubescensine A
With 1.2 kilograms of Rabdosia rubescens leaf dried powders of ether extraction, discard residue, reclaim the ether in the ether solution, obtain green and brown color residue; The dissolve with methanol residue, decolouring obtains clear and bright methanol solution, and room temperature is placed and is spent the night behind the concentrating under reduced pressure, filters methanol mother liquor evaporate to dryness, porphyrize; The neutral Al of reuse
2O
3Absorption is used the ether eluting, crystallization.
4) extract indirubin:
1.2 the kilogram Folium Isatidis is processed into dry Indigo Naturalis through drying, gradation adds 30% concentrated hydrochloric acid, until no longer producing foam, filters, and water is washed till neutrality with precipitation, drying; Added methanol eddy 1 hour, and obtained methanol extract liquid, filter, reclaim the methanol in the methanol solution, the residue Petroleum ether extraction is removed petroleum ether, residue 3%NaOH solution-treated, and precipitation washes with water to neutrality, obtains indirubin with the ethyl acetate extracting.
5) extract the Flos Chrysanthemi flavone
Pulverize 0.9 kilogram of Flos Chrysanthemi, use 50% ethanol extraction, concentrating under reduced pressure, add 70% ethanol, precipitation is filtered, concentrated filtrate is to there not being ethanol, the residue water dissolution filters, and filtrate is through the DM130 macroporous adsorbent resin, it is colourless to be washed till post with deionized water, reuse 95% ethanol is eluting repeatedly, collects flavone, crystallization.
6) extract glycyrrhizin, isoliquiritigenin
0.9 95% ethanol extraction that the kilogram Radix Glycyrrhizae is measured with 4 times (volume), ethanol liquid is through petroleum ether extraction, and water layer is admixed silica gel, uses MeOH-H
2O is 7: 3 eluting, and concentrate eluant obtains residue;
In residue, add water to dissolving fully, in water liquid, add ethyl acetate extraction, ethyl acetate layer 5%Na
2CO
3The extraction of water liquid is adjusted to pH5-6 with diluted acid with sodium carbonate water liquid, the reuse ethyl acetate extraction, and dry acetic acid ethyl fluid separates through polyamide column, and 10-90% ethanol water gradient elution obtains glycyrrhizin and isoliquiritigenin.
7) buy ganoderan from the Shanghai institute of agricultural sciences, its consumption is equivalent to 3 kilograms of Ganoderma material quantities, the described ganoderan and above-mentioned steps 1 that comprises lucidum glycopeptide and Ganoderma β-D glucosan that make)-6) extract the active component that obtains and mix, this mixture is ground into fine powder, incapsulate for using.
Claims (6)
1. a Chinese medicine composition for the treatment of carcinoma of prostate is characterized in that, it is made by the following weight proportion raw material:
Ganoderma 3-4
Radix Scutellariae 1-2
Rabdosia rubescens 1-2
Folium Isatidis 1-2
Flos Chrysanthemi 0.5-1.5
Radix Glycyrrhizae 0.5-1.5
Radix Notoginseng 0.5-1.5
2. Chinese medicine composition according to claim 1, wherein the weight proportion of each raw material is:
Ganoderma: Radix Scutellariae: Rabdosia rubescens: Folium Isatidis: Flos Chrysanthemi: Radix Glycyrrhizae: Radix Notoginseng=3: 1.5: 1.2: 1.2: 0.9: 0.9: 0.9
3. the preparation method of Chinese medicine composition as claimed in claim 1 is characterized in that, it comprises mixed extraction preparation method or goal object extraction preparation method, and wherein said mixed extraction preparation method comprises:
1) prepare raw material:
With Ganoderma, Radix Scutellariae, Rabdosia rubescens, Folium Isatidis, Flos Chrysanthemi, Radix Glycyrrhizae, Radix Notoginseng is that the ratio of 3-4: 1-2: 1-2: 1-2: 0.5-1.5: 0.5-1.5: 0.5-1.5 is pulverized mixing with the weight ratio, and described mixture is divided into six equal portions;
2) extract alkaloid:
I) a Chinese medicine mixture that step 1) is obtained obtains acidic ethanol extraction liquid with 0.1% hydrochloride ethanol liquid diafiltration or gradation leaching;
Ii) concentrating under reduced pressure obtains concentrate;
The iii) acid water of pH=4-5 washing is filtered, and obtains residue, and residue obtains acidic aqueous liquid with the acid water washing of pH=4-5;
Iv) in the acidic aqueous liquid that step I obtains in ii), add ammonia precipitation process, filter and obtain the total alkaloids precipitation; Perhaps
A) add diluted acid to pH=2 in the acidic aqueous liquid that step I obtains in ii), use chloroform extraction, obtain chloroform layer and water layer, the chloroform in the evaporation chloroform layer obtains weak alkaloid;
B) described water layer adds alkali to pH=6-7, uses chloroform extraction, obtains water layer and chloroform layer, and the chloroform in the evaporation chloroform layer obtains strong alkaloid;
C) above-mentioned b) water layer that obtains is adjusted to pH=10 with alkali, uses butyl alcohol extraction then, and the butanols in the evaporation butanols layer obtains water miscible alkaloid;
D) merge above-mentioned a), b) and the alkaloid that c) obtains, obtain total alkaloids;
3) extract polysaccharide:
95-100 ℃ hot water extraction of a Chinese medicine mixture with step 1) obtains discards residue, and filtrate was placed after 12 hours, adds the ethanol of concentration more than 50%, the centrifugal polysaccharide precipitation that obtains in supernatant;
4) extract lactone:
With a Chinese medicine mixture aether backflow that step 1) obtains, remove pigment, reclaim ether, obtain total lactone;
5) extract Saponin:
The a Chinese medicine mixture that step 1) is obtained refluxes with petroleum ether, and the evaporation petroleum ether obtains the defat coarse powder, uses the 90-95% ethanol extraction, and concentrating under reduced pressure obtains concentrated solution;
A) concentrated solution is used chloroform, ethanol extraction successively, and reclaim under reduced pressure chloroform, ethanol obtain the general glycoside crude product; Perhaps
B) concentrated solution butyl alcohol extraction, the reclaim under reduced pressure butanols obtains the Saponin crude product;
6) extract coumarin:
The a Chinese medicine mixture that step 1) is obtained decocts with water 1-2 hour, and the condensed water decocting liquid adds concentrated hydrochloric acid, removes the impurity insoluble matter, places clear liquor, obtains the coarse crystallization of coumarin;
7) extract flavone:
The a Chinese medicine mixture that obtains to step 1) adds the 70-80% alcohol dipping, the ethanol in the decompression recycling ethanol liquid, and the residue water dissolution filters, and obtains water liquid; With ethyl acetate extraction water liquid, the concentrating under reduced pressure acetic acid ethyl fluid obtains total flavones;
With step 2)-7) extract the alkaloid, polysaccharide, lactone, Saponin, coumarin, the flavone mixing that obtain, obtain described Chinese medicine composition;
Wherein said goal object is extracted preparation method and is comprised:
1) extract baicalin:
I) in the described Radix Scutellariae raw material of claim 1, add 10-15 times of volume decocting and boiled 1-2 hour, filter;
Ii) filtrate is transferred to pH1-2, kept centrifugation 30-40 minute down at 80-90 ℃ with acid; Precipitate adds water and stirs, and adds alkali pH regulator is arrived neutrality, adds the ethanol of 3-5 times of volume again, filters;
Iii) in filtrate, add acid pH regulator is arrived 1-2, stir, kept 30-40 minute down, filter at 80-90 ℃;
Iv) the precipitate of gained is distinguished water, 50% washing with alcohol, and reuse 95% washing with alcohol or recrystallization obtain baicalin;
2) extract arasaponin:
I) with the solvable composition of concentration in the root coarse powder of the described Radix Notoginseng raw material of methanol extraction claim 1 below 50%, the concentrating under reduced pressure methanol extract liquid adds 3-5 times of volume water gaging in residue;
Ii) aqueous solution ether extraction, water layer reuse n-butanol extraction, evaporated under reduced pressure through silica gel column chromatography, is used CHCl
3-MeOH-H
2O obtains arasaponin than 65: 35: 10 eluting;
3) extract rubescensine A
Leaf dried powder with the described Rabdosia rubescens raw material of ether extraction claim 1 discards residue, reclaims the ether in the ether solution, obtains green and brown color residue; Use the dissolve with methanol residue, decolouring obtains clear and bright methanol solution, and room temperature is placed and spent the night behind the concentrating under reduced pressure, filters methanol mother liquor evaporate to dryness, porphyrize; Use the ether eluting, crystallization;
4) extract indirubin:
The described Folium Isatidis raw material of claim 1 is processed into dry Indigo Naturalis through drying, and gradation adds 30% concentrated hydrochloric acid, until no longer producing foam, filters, and water is washed till neutrality with precipitation, drying; Add methanol eddy 2-4 time, obtain methanol extract liquid, filter, reclaim the methanol in the methanol solution, the residue Petroleum ether extraction is removed petroleum ether, residue 3%NaOH solution-treated, and precipitation washes with water to neutrality, obtains indirubin with the ethyl acetate extracting;
5) extract the Flos Chrysanthemi flavone
Pulverize the described Flos Chrysanthemi raw material of claim 1, use the 50-70% ethanol extraction, concentrating under reduced pressure, add 90-95% ethanol, precipitation is filtered, concentrated filtrate is to there not being ethanol, the residue water dissolution filters, and filtrate is through macroporous adsorbent resin, it is colourless to be washed till post with deionized water, reuse 95% ethanol is eluting repeatedly, collects flavone, crystallization;
6) extract glycyrrhizin, isoliquiritigenin
The described licorice raw material of claim 1 is with the 90-95% ethanol extraction of 3-4 times of volume, and ethanol liquid is through petroleum ether extraction, and water layer is admixed silica gel, uses MeOH-H
27: 3 eluting of O, concentrate eluant obtains residue;
In residue, add water to dissolving fully, in aqueous solution, add ethyl acetate extraction, ethyl acetate layer 5%Na
2CO
3The extraction of water liquid is adjusted to pH=5-6 with diluted acid with sodium carbonate water liquid, the reuse ethyl acetate extraction, and dry acetic acid ethyl fluid separates through polyamide column, obtains glycyrrhizin and isoliquiritigenin with 10-90% ethanol water gradient elution;
7) extract ganoderan:
I.a) pulverize behind the sporophore decontamination with the described Ganoderma raw material of claim 1, add water 8-10 and doubly soaked 24 hours, be heated to 95-100 ℃ and stirred 8-10 hour down;
B) filter, obtain filtrate and medicinal residues;
C) in medicinal residues, add water 3-4 and doubly carry out lixiviate;
II.a) fermentation liquid that contains fungus ball with the described Ganoderma raw material of claim 1 is heated to 95-100 ℃, stirs 4 hours;
B) filter;
C) in the medicinal residues that contain fungus ball, add water 3-4 times volume, extracted 2 hours, filter, separation and Extraction liquid and medicinal residues,
D) merge I.b), c) and II.c) in filtrate, be concentrated into the 1/8-1/10 of original volume, add edible ethanol 3-5 doubly, reach about 70% to ethanol, leave standstill alcohol and analysed 24 hours, use the centrifuge sediment separate out, recovered alcohol, dry sediment; Obtain comprising the ganoderan of lucidum glycopeptide and Ganoderma β-D glucosan; Perhaps,
The sporophore of the described Ganoderma raw material of claim 1 is carried out Soxhlet extract, with ethyl acetate extraction 4 hours, sucking filtration, the residue that obtains carried out Soxhlet again and extract, and with acetone extraction 4 hours, sucking filtration, the residue of gained was with 90% soak with ethanol 24 hours, and is centrifugal, sucking filtration; Residue extracts three times down at 80 ℃ with the phosphate buffer of 0.2 mol pH=7, and 4 hours/time, sucking filtration discarded residue, and buffer is removed protein, and is centrifugal, with the upper strata liquid dialysis of gained,
Add a large amount of acetone in non-dialysis liquid, precipitation occurs, abandoning supernatant precipitates and uses washing with acetone 6 times, obtains comprising the ganoderan of lucidum glycopeptide and Ganoderma β-D glucosan,
The ganoderan and above-mentioned steps 1 that comprise lucidum glycopeptide and Ganoderma β-D glucosan that step 7) is obtained)-6) extract the active component obtain and mix and obtain described Chinese medicine composition.
4. method according to claim 3, it also comprises step 8):
A) with described step 1)-7) active component that obtains is crushed to≤200 microns fine powders;
B) pulverize, dry nothing is leaked seed/nipa palm seed or Fructus punicae granati seed/short Semen Granati, with the dehydrated alcohol extraction of 8 times of volumes, concentrating under reduced pressure, handles with ethinylation potassium, obtains powder;
C) with a), b) material of gained is with 100-200: 1 weight ratio is mixed.
5. method according to claim 4, it also comprises step d): with c) in the mixture that obtains incapsulate.
6. the application of Chinese medicine composition as claimed in claim 1 in the medicine of preparation treatment carcinoma of prostate.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN02136655.1A CN1220519C (en) | 2002-08-26 | 2002-08-26 | Chinese medicinal composition for treating prostate cancer, its preparation method and its application in the preparation of medicine for treating prostate cancer |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN02136655.1A CN1220519C (en) | 2002-08-26 | 2002-08-26 | Chinese medicinal composition for treating prostate cancer, its preparation method and its application in the preparation of medicine for treating prostate cancer |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1478538A CN1478538A (en) | 2004-03-03 |
| CN1220519C true CN1220519C (en) | 2005-09-28 |
Family
ID=34146593
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN02136655.1A Expired - Lifetime CN1220519C (en) | 2002-08-26 | 2002-08-26 | Chinese medicinal composition for treating prostate cancer, its preparation method and its application in the preparation of medicine for treating prostate cancer |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1220519C (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008022505A1 (en) * | 2006-08-18 | 2008-02-28 | Rui Jin Hospital Affiliated To Shanghai Jiao Tong University School Of Medicine | Use of rubescensine a and derivatives thereof in pharmacy |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100446802C (en) * | 2005-12-27 | 2008-12-31 | 武汉哈福科技有限公司 | Natural Medicines to Prevent Tumor Metastasis |
| GB0609386D0 (en) * | 2006-05-11 | 2006-06-21 | Active Botan Ltd | Treating drug resistant cancers |
| CN101991681A (en) * | 2010-11-11 | 2011-03-30 | 北京绿源求证科技发展有限责任公司 | Traditional Chinese medicine for treating benign prostatic hyperplasia |
| CN104435657B (en) * | 2013-11-13 | 2018-01-16 | 程惠华 | A kind of medicine for preventing and treating prostate cancer endocrine therapy side effect and preparation method thereof |
| CN105106307B (en) * | 2015-08-10 | 2020-10-20 | 上海中耀生物科技有限公司 | A kind of traditional Chinese medicine composition for treating prostate cancer, preparation method and application thereof |
| CN106344830A (en) * | 2016-10-10 | 2017-01-25 | 南宁多灵生物科技有限公司 | Traditional Chinese medicine composition for treating prostatic cancer |
-
2002
- 2002-08-26 CN CN02136655.1A patent/CN1220519C/en not_active Expired - Lifetime
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008022505A1 (en) * | 2006-08-18 | 2008-02-28 | Rui Jin Hospital Affiliated To Shanghai Jiao Tong University School Of Medicine | Use of rubescensine a and derivatives thereof in pharmacy |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1478538A (en) | 2004-03-03 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1082904A (en) | Pharmaceutical composition for treating skin diseases | |
| CN1220519C (en) | Chinese medicinal composition for treating prostate cancer, its preparation method and its application in the preparation of medicine for treating prostate cancer | |
| CN1220518C (en) | Chinese medicinal composition for anti-cancer and analgesia, its preparation method and its application in the preparation of product and medicine for treating cancer and analgesia | |
| CN1200723C (en) | White peony and licorice extract and its prepn process | |
| CN1872282A (en) | Active extractive of Foliumnerviliae, preparation method and application | |
| CN1628662A (en) | Medicine with abirritation | |
| CN1268323C (en) | Rhodiola sacra soft capsule and its preparation | |
| CN1212141C (en) | Application of Atractylodes Atractylodes Oil in the Preparation of Drugs for Treating Osteoporosis | |
| CN1511583A (en) | Chinese rose flower extract and preparation method and application thereof | |
| CN100344315C (en) | Medicinal composition for promoting bone fracture healing and its preparing method | |
| CN1720978A (en) | Pulse invigorating injection and method for preparing the same | |
| CN1895302A (en) | Cercopithecoidealin with anti-tumor function, its preparation and use | |
| CN101040999A (en) | Medicine compound for treating snoring and the preparing method and the quality control method | |
| CN1544032A (en) | Anticancer Chinese traditional extracts and preparation process and application thereof | |
| CN1186351C (en) | Total saponin of polygara aureocauda dunn and madication combination as well as its preparing method | |
| CN1857654A (en) | Trachaitis treating preparation and its preparing process | |
| CN1634463A (en) | Medicine for treating diabetes and production method thereof | |
| CN1323700C (en) | Traditional Chinese medicine composition for treating deficiency disease and preparation method and quality standard thereof | |
| CN1244341C (en) | Chinese medicine composition for treating endometriosis and its prepn process | |
| CN1872199A (en) | Composition of Chinese traditional medicine, and preparation method | |
| CN1509729A (en) | Yanning adjuvant | |
| CN1234253A (en) | Health-care drink of nourishing spleen and kidney | |
| CN1586600A (en) | Tibet medicine lamivphlomis root injection preparation and its preparing method | |
| CN1263490C (en) | Yang reinforcing medicine and its preparation method | |
| CN100342878C (en) | Antiphlogistic, antasthmatic and apophlegmatic Chinese medicine |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C41 | Transfer of patent application or patent right or utility model | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20160125 Address after: 200126, room 8, No. 190, Lane 1802, Changli Road, Pudong New Area, Shanghai Patentee after: Yang Qiliang Address before: 201802 No. 4278 South Main Road, Shanghai, 5-150 Patentee before: SHANGHAI ZHONGYAO BIO-TECHNOLOGY Co.,Ltd. |
|
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20190807 Address after: Room 119, Building 333 Cailun Road, China (Shanghai) Free Trade Pilot Area, Pudong New Area, Shanghai, 201203 Patentee after: SHANGHAI ZHONGYAO BIO-TECHNOLOGY Co.,Ltd. Address before: 200126, room 8, No. 190, Lane 1802, Changli Road, Pudong New Area, Shanghai Patentee before: Yang Qiliang |
|
| CX01 | Expiry of patent term | ||
| CX01 | Expiry of patent term |
Granted publication date: 20050928 |