CN1139383C - Therapeutic composition based on flavonoids for use in treatment of tumours with cytotoxic agents - Google Patents
Therapeutic composition based on flavonoids for use in treatment of tumours with cytotoxic agents Download PDFInfo
- Publication number
- CN1139383C CN1139383C CNB998095478A CN99809547A CN1139383C CN 1139383 C CN1139383 C CN 1139383C CN B998095478 A CNB998095478 A CN B998095478A CN 99809547 A CN99809547 A CN 99809547A CN 1139383 C CN1139383 C CN 1139383C
- Authority
- CN
- China
- Prior art keywords
- intravenous injection
- transfusion
- day
- osajin
- days
- 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
- 238000011282 treatment Methods 0.000 title claims abstract description 123
- 206010028980 Neoplasm Diseases 0.000 title claims abstract description 78
- 239000000203 mixture Substances 0.000 title abstract description 5
- 229940127089 cytotoxic agent Drugs 0.000 title abstract description 3
- 239000002254 cytotoxic agent Substances 0.000 title abstract description 3
- 231100000599 cytotoxic agent Toxicity 0.000 title abstract 2
- 230000001225 therapeutic effect Effects 0.000 title description 5
- 229930003935 flavonoid Natural products 0.000 title 1
- 150000002215 flavonoids Chemical class 0.000 title 1
- 235000017173 flavonoids Nutrition 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 40
- 230000000694 effects Effects 0.000 claims abstract description 19
- -1 chromone compound Chemical class 0.000 claims abstract description 6
- DCTLJGWMHPGCOS-UHFFFAOYSA-N Osajin Chemical compound C1=2C=CC(C)(C)OC=2C(CC=C(C)C)=C(O)C(C2=O)=C1OC=C2C1=CC=C(O)C=C1 DCTLJGWMHPGCOS-UHFFFAOYSA-N 0.000 claims description 148
- OUZCFMSJGDEXRT-UHFFFAOYSA-N Scandinone Natural products O=C1C=2C(OC)=C(CC=C(C)C)C=3OC(C)(C)C=CC=3C=2OC=C1C1=CC=C(O)C=C1 OUZCFMSJGDEXRT-UHFFFAOYSA-N 0.000 claims description 148
- 230000004087 circulation Effects 0.000 claims description 119
- 239000003153 chemical reaction reagent Substances 0.000 claims description 41
- 229940045109 genistein Drugs 0.000 claims description 41
- TZBJGXHYKVUXJN-UHFFFAOYSA-N genistein Natural products C1=CC(O)=CC=C1C1=COC2=CC(O)=CC(O)=C2C1=O TZBJGXHYKVUXJN-UHFFFAOYSA-N 0.000 claims description 40
- 235000006539 genistein Nutrition 0.000 claims description 40
- ZCOLJUOHXJRHDI-CMWLGVBASA-N genistein 7-O-beta-D-glucoside Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=C2C(=O)C(C=3C=CC(O)=CC=3)=COC2=C1 ZCOLJUOHXJRHDI-CMWLGVBASA-N 0.000 claims description 40
- 238000002512 chemotherapy Methods 0.000 claims description 35
- 231100000167 toxic agent Toxicity 0.000 claims description 32
- 239000003440 toxic substance Substances 0.000 claims description 32
- 230000003203 everyday effect Effects 0.000 claims description 22
- 239000003814 drug Substances 0.000 claims description 11
- 208000032839 leukemia Diseases 0.000 claims description 10
- OTAFHZMPRISVEM-UHFFFAOYSA-N chromone Chemical compound C1=CC=C2C(=O)C=COC2=C1 OTAFHZMPRISVEM-UHFFFAOYSA-N 0.000 claims description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- GOMNOOKGLZYEJT-UHFFFAOYSA-N isoflavone Chemical compound C=1OC2=CC=CC=C2C(=O)C=1C1=CC=CC=C1 GOMNOOKGLZYEJT-UHFFFAOYSA-N 0.000 claims description 6
- CJWQYWQDLBZGPD-UHFFFAOYSA-N isoflavone Natural products C1=C(OC)C(OC)=CC(OC)=C1C1=COC2=C(C=CC(C)(C)O3)C3=C(OC)C=C2C1=O CJWQYWQDLBZGPD-UHFFFAOYSA-N 0.000 claims description 6
- 235000008696 isoflavones Nutrition 0.000 claims description 6
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 5
- 238000001802 infusion Methods 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 125000001424 substituent group Chemical group 0.000 claims description 3
- 229930191576 Biochanin Natural products 0.000 claims 1
- WUADCCWRTIWANL-UHFFFAOYSA-N biochanin A Chemical compound C1=CC(OC)=CC=C1C1=COC2=CC(O)=CC(O)=C2C1=O WUADCCWRTIWANL-UHFFFAOYSA-N 0.000 claims 1
- 239000002552 dosage form Substances 0.000 claims 1
- 230000035755 proliferation Effects 0.000 abstract description 3
- 229930013032 isoflavonoid Natural products 0.000 abstract description 2
- 150000003817 isoflavonoid derivatives Chemical class 0.000 abstract description 2
- 235000012891 isoflavonoids Nutrition 0.000 abstract description 2
- 230000003021 clonogenic effect Effects 0.000 abstract 1
- 238000010253 intravenous injection Methods 0.000 description 382
- 238000002347 injection Methods 0.000 description 124
- 239000007924 injection Substances 0.000 description 124
- 238000013459 approach Methods 0.000 description 109
- 210000004027 cell Anatomy 0.000 description 95
- 229960004528 vincristine Drugs 0.000 description 56
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 56
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 56
- 229960004397 cyclophosphamide Drugs 0.000 description 50
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 49
- NWXMGUDVXFXRIG-WESIUVDSSA-N (4s,4as,5as,6s,12ar)-4-(dimethylamino)-1,6,10,11,12a-pentahydroxy-6-methyl-3,12-dioxo-4,4a,5,5a-tetrahydrotetracene-2-carboxamide Chemical compound C1=CC=C2[C@](O)(C)[C@H]3C[C@H]4[C@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]4(O)C(=O)C3=C(O)C2=C1O NWXMGUDVXFXRIG-WESIUVDSSA-N 0.000 description 43
- 229930195573 Amycin Natural products 0.000 description 43
- UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 description 35
- 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 33
- 229960000485 methotrexate Drugs 0.000 description 31
- 201000011510 cancer Diseases 0.000 description 30
- 241000699670 Mus sp. Species 0.000 description 29
- VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 description 29
- 229960005420 etoposide Drugs 0.000 description 29
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 27
- 229960002949 fluorouracil Drugs 0.000 description 27
- 230000003442 weekly effect Effects 0.000 description 25
- 210000004369 blood Anatomy 0.000 description 24
- 239000008280 blood Substances 0.000 description 24
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 22
- 229960004618 prednisone Drugs 0.000 description 22
- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 20
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 20
- 229960004316 cisplatin Drugs 0.000 description 20
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 20
- 229960000975 daunorubicin Drugs 0.000 description 20
- 238000002474 experimental method Methods 0.000 description 14
- 230000004083 survival effect Effects 0.000 description 13
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 13
- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 12
- 229960001561 bleomycin Drugs 0.000 description 12
- 238000000034 method Methods 0.000 description 12
- 229960003048 vinblastine Drugs 0.000 description 12
- 108010006654 Bleomycin Proteins 0.000 description 11
- RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Natural products CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 description 11
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 11
- 206010006187 Breast cancer Diseases 0.000 description 10
- 208000026310 Breast neoplasm Diseases 0.000 description 10
- DLGOEMSEDOSKAD-UHFFFAOYSA-N Carmustine Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 description 10
- 206010025323 Lymphomas Diseases 0.000 description 10
- 241000699666 Mus <mouse, genus> Species 0.000 description 10
- NRGONRDRXCPMIC-GDKBPFBDSA-N N1C=2C(=O)NC(N)=NC=2NCC1CNC1=CC=C(C(=O)N[C@@H](CC(C=O)C(O)=O)C(O)=O)C=C1 Chemical compound N1C=2C(=O)NC(N)=NC=2NCC1CNC1=CC=C(C(=O)N[C@@H](CC(C=O)C(O)=O)C(O)=O)C=C1 NRGONRDRXCPMIC-GDKBPFBDSA-N 0.000 description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 10
- 230000012010 growth Effects 0.000 description 10
- 239000001963 growth medium Substances 0.000 description 10
- 102000004190 Enzymes Human genes 0.000 description 9
- 108090000790 Enzymes Proteins 0.000 description 9
- HOMGKSMUEGBAAB-UHFFFAOYSA-N ifosfamide Chemical compound ClCCNP1(=O)OCCCN1CCCl HOMGKSMUEGBAAB-UHFFFAOYSA-N 0.000 description 9
- 229960001101 ifosfamide Drugs 0.000 description 9
- 238000010255 intramuscular injection Methods 0.000 description 9
- 239000007927 intramuscular injection Substances 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- 210000004881 tumor cell Anatomy 0.000 description 9
- FDKXTQMXEQVLRF-ZHACJKMWSA-N (E)-dacarbazine Chemical compound CN(C)\N=N\c1[nH]cnc1C(N)=O FDKXTQMXEQVLRF-ZHACJKMWSA-N 0.000 description 8
- 229930012538 Paclitaxel Natural products 0.000 description 8
- NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 description 8
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 8
- 230000000259 anti-tumor effect Effects 0.000 description 8
- 238000009104 chemotherapy regimen Methods 0.000 description 8
- JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 description 8
- 229960004630 chlorambucil Drugs 0.000 description 8
- 201000010099 disease Diseases 0.000 description 8
- SGDBTWWWUNNDEQ-LBPRGKRZSA-N melphalan Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N(CCCl)CCCl)C=C1 SGDBTWWWUNNDEQ-LBPRGKRZSA-N 0.000 description 8
- 229960001924 melphalan Drugs 0.000 description 8
- KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 description 8
- 229960001592 paclitaxel Drugs 0.000 description 8
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 8
- 229920001817 Agar Polymers 0.000 description 7
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 7
- 239000008272 agar Substances 0.000 description 7
- HAWPXGHAZFHHAD-UHFFFAOYSA-N mechlorethamine Chemical compound ClCCN(C)CCCl HAWPXGHAZFHHAD-UHFFFAOYSA-N 0.000 description 7
- 229960004961 mechlorethamine Drugs 0.000 description 7
- 229960001156 mitoxantrone Drugs 0.000 description 7
- HBUBKKRHXORPQB-FJFJXFQQSA-N (2R,3S,4S,5R)-2-(6-amino-2-fluoro-9-purinyl)-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C1=NC=2C(N)=NC(F)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]1O HBUBKKRHXORPQB-FJFJXFQQSA-N 0.000 description 6
- WYWHKKSPHMUBEB-UHFFFAOYSA-N 6-Mercaptoguanine Natural products N1C(N)=NC(=S)C2=C1N=CN2 WYWHKKSPHMUBEB-UHFFFAOYSA-N 0.000 description 6
- 206010027336 Menstruation delayed Diseases 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 201000008275 breast carcinoma Diseases 0.000 description 6
- 229960005243 carmustine Drugs 0.000 description 6
- 229960003901 dacarbazine Drugs 0.000 description 6
- 229940065639 etoposide 100 mg Drugs 0.000 description 6
- 238000011156 evaluation Methods 0.000 description 6
- 238000001990 intravenous administration Methods 0.000 description 6
- 238000012423 maintenance Methods 0.000 description 6
- 210000000130 stem cell Anatomy 0.000 description 6
- 229960003087 tioguanine Drugs 0.000 description 6
- MNRILEROXIRVNJ-UHFFFAOYSA-N tioguanine Chemical compound N1C(N)=NC(=S)C2=NC=N[C]21 MNRILEROXIRVNJ-UHFFFAOYSA-N 0.000 description 6
- PTOAARAWEBMLNO-KVQBGUIXSA-N Cladribine Chemical compound C1=NC=2C(N)=NC(Cl)=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)O1 PTOAARAWEBMLNO-KVQBGUIXSA-N 0.000 description 5
- 108010092160 Dactinomycin Proteins 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 description 5
- 238000010322 bone marrow transplantation Methods 0.000 description 5
- 229960002436 cladribine Drugs 0.000 description 5
- 238000007596 consolidation process Methods 0.000 description 5
- 229940108612 cyclophosphamide 1000 mg Drugs 0.000 description 5
- 229960000640 dactinomycin Drugs 0.000 description 5
- 238000003745 diagnosis Methods 0.000 description 5
- 229960003668 docetaxel Drugs 0.000 description 5
- 229960005277 gemcitabine Drugs 0.000 description 5
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 description 5
- 230000001939 inductive effect Effects 0.000 description 5
- 238000010254 subcutaneous injection Methods 0.000 description 5
- 239000007929 subcutaneous injection Substances 0.000 description 5
- AOJJSUZBOXZQNB-VTZDEGQISA-N 4'-epidoxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-VTZDEGQISA-N 0.000 description 4
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 4
- HTIJFSOGRVMCQR-UHFFFAOYSA-N Epirubicin Natural products COc1cccc2C(=O)c3c(O)c4CC(O)(CC(OC5CC(N)C(=O)C(C)O5)c4c(O)c3C(=O)c12)C(=O)CO HTIJFSOGRVMCQR-UHFFFAOYSA-N 0.000 description 4
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 4
- RJURFGZVJUQBHK-IIXSONLDSA-N actinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-IIXSONLDSA-N 0.000 description 4
- 230000001154 acute effect Effects 0.000 description 4
- 239000002246 antineoplastic agent Substances 0.000 description 4
- 229960002092 busulfan Drugs 0.000 description 4
- 229960001904 epirubicin Drugs 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 229960004768 irinotecan Drugs 0.000 description 4
- UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 description 4
- 229960004635 mesna Drugs 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 229960001603 tamoxifen Drugs 0.000 description 4
- 229930192474 thiophene Natural products 0.000 description 4
- 238000012546 transfer Methods 0.000 description 4
- 230000004614 tumor growth Effects 0.000 description 4
- IGMMTYZWNUSEEU-UHFFFAOYSA-N 3-(2-chloroethyl)-1-cyclohexyl-1-nitrosourea Chemical compound ClCCNC(=O)N(N=O)C1CCCCC1 IGMMTYZWNUSEEU-UHFFFAOYSA-N 0.000 description 3
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 3
- 201000009030 Carcinoma Diseases 0.000 description 3
- 206010009944 Colon cancer Diseases 0.000 description 3
- 229940123780 DNA topoisomerase I inhibitor Drugs 0.000 description 3
- XDXDZDZNSLXDNA-TZNDIEGXSA-N Idarubicin Chemical compound C1[C@H](N)[C@H](O)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2C[C@@](O)(C(C)=O)C1 XDXDZDZNSLXDNA-TZNDIEGXSA-N 0.000 description 3
- XDXDZDZNSLXDNA-UHFFFAOYSA-N Idarubicin Natural products C1C(N)C(O)C(C)OC1OC1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2CC(O)(C(C)=O)C1 XDXDZDZNSLXDNA-UHFFFAOYSA-N 0.000 description 3
- XOGTZOOQQBDUSI-UHFFFAOYSA-M Mesna Chemical compound [Na+].[O-]S(=O)(=O)CCS XOGTZOOQQBDUSI-UHFFFAOYSA-M 0.000 description 3
- 241001597008 Nomeidae Species 0.000 description 3
- 206010061535 Ovarian neoplasm Diseases 0.000 description 3
- 239000000365 Topoisomerase I Inhibitor Substances 0.000 description 3
- 229930013930 alkaloid Natural products 0.000 description 3
- 229960000473 altretamine Drugs 0.000 description 3
- 150000001454 anthracenes Chemical class 0.000 description 3
- 230000001093 anti-cancer Effects 0.000 description 3
- 229940041181 antineoplastic drug Drugs 0.000 description 3
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 3
- 238000003776 cleavage reaction Methods 0.000 description 3
- 238000011443 conventional therapy Methods 0.000 description 3
- 230000001472 cytotoxic effect Effects 0.000 description 3
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 3
- 229960003957 dexamethasone Drugs 0.000 description 3
- 229960001842 estramustine Drugs 0.000 description 3
- UUVWYPNAQBNQJQ-UHFFFAOYSA-N hexamethylmelamine Chemical compound CN(C)C1=NC(N(C)C)=NC(N(C)C)=N1 UUVWYPNAQBNQJQ-UHFFFAOYSA-N 0.000 description 3
- 229960000908 idarubicin Drugs 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 206010061289 metastatic neoplasm Diseases 0.000 description 3
- 229940086322 navelbine Drugs 0.000 description 3
- 230000003287 optical effect Effects 0.000 description 3
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical group [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 3
- CPTBDICYNRMXFX-UHFFFAOYSA-N procarbazine Chemical compound CNNCC1=CC=C(C(=O)NC(C)C)C=C1 CPTBDICYNRMXFX-UHFFFAOYSA-N 0.000 description 3
- 229960000624 procarbazine Drugs 0.000 description 3
- 201000001514 prostate carcinoma Diseases 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 229940117820 purinethol Drugs 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 230000007017 scission Effects 0.000 description 3
- NRUKOCRGYNPUPR-QBPJDGROSA-N teniposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@@H](OC[C@H]4O3)C=3SC=CC=3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 NRUKOCRGYNPUPR-QBPJDGROSA-N 0.000 description 3
- 229960001278 teniposide Drugs 0.000 description 3
- CILBMBUYJCWATM-PYGJLNRPSA-N vinorelbine ditartrate Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O.OC(=O)[C@H](O)[C@@H](O)C(O)=O.C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC([C@]23[C@H]([C@@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC CILBMBUYJCWATM-PYGJLNRPSA-N 0.000 description 3
- NDMPLJNOPCLANR-UHFFFAOYSA-N 3,4-dihydroxy-15-(4-hydroxy-18-methoxycarbonyl-5,18-seco-ibogamin-18-yl)-16-methoxy-1-methyl-6,7-didehydro-aspidospermidine-3-carboxylic acid methyl ester Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 NDMPLJNOPCLANR-UHFFFAOYSA-N 0.000 description 2
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 2
- 206010005003 Bladder cancer Diseases 0.000 description 2
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 2
- 102000006992 Interferon-alpha Human genes 0.000 description 2
- 108010047761 Interferon-alpha Proteins 0.000 description 2
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 2
- 206010027480 Metastatic malignant melanoma Diseases 0.000 description 2
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 2
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 2
- 239000012980 RPMI-1640 medium Substances 0.000 description 2
- 206010038389 Renal cancer Diseases 0.000 description 2
- 208000006265 Renal cell carcinoma Diseases 0.000 description 2
- 206010039491 Sarcoma Diseases 0.000 description 2
- 208000005718 Stomach Neoplasms Diseases 0.000 description 2
- IVTVGDXNLFLDRM-HNNXBMFYSA-N Tomudex Chemical compound C=1C=C2NC(C)=NC(=O)C2=CC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)S1 IVTVGDXNLFLDRM-HNNXBMFYSA-N 0.000 description 2
- 206010066901 Treatment failure Diseases 0.000 description 2
- 108090000704 Tubulin Proteins 0.000 description 2
- 102000004243 Tubulin Human genes 0.000 description 2
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 2
- DZBUGLKDJFMEHC-UHFFFAOYSA-N acridine Chemical compound C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 description 2
- 150000003797 alkaloid derivatives Chemical class 0.000 description 2
- 230000002152 alkylating effect Effects 0.000 description 2
- 239000000051 antiandrogen Substances 0.000 description 2
- 229940100197 antimetabolite Drugs 0.000 description 2
- 239000002256 antimetabolite Substances 0.000 description 2
- 229940045719 antineoplastic alkylating agent nitrosoureas Drugs 0.000 description 2
- 239000004305 biphenyl Substances 0.000 description 2
- 210000001185 bone marrow Anatomy 0.000 description 2
- 230000031709 bromination Effects 0.000 description 2
- 238000005893 bromination reaction Methods 0.000 description 2
- 239000001569 carbon dioxide Substances 0.000 description 2
- 229910002092 carbon dioxide Inorganic materials 0.000 description 2
- 229960004562 carboplatin Drugs 0.000 description 2
- 190000008236 carboplatin Chemical compound 0.000 description 2
- 230000032823 cell division Effects 0.000 description 2
- 229940105443 cisplatin 50 mg Drugs 0.000 description 2
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 2
- 230000003013 cytotoxicity Effects 0.000 description 2
- 231100000135 cytotoxicity Toxicity 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- FRPJXPJMRWBBIH-RBRWEJTLSA-N estramustine Chemical compound ClCCN(CCCl)C(=O)OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 FRPJXPJMRWBBIH-RBRWEJTLSA-N 0.000 description 2
- 230000002349 favourable effect Effects 0.000 description 2
- HKQYGTCOTHHOMP-UHFFFAOYSA-N formononetin Chemical compound C1=CC(OC)=CC=C1C1=COC2=CC(O)=CC=C2C1=O HKQYGTCOTHHOMP-UHFFFAOYSA-N 0.000 description 2
- 206010017758 gastric cancer Diseases 0.000 description 2
- 229940045276 gemcitabine 1000 mg Drugs 0.000 description 2
- 201000010536 head and neck cancer Diseases 0.000 description 2
- 208000014829 head and neck neoplasm Diseases 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 230000002503 metabolic effect Effects 0.000 description 2
- 208000021039 metastatic melanoma Diseases 0.000 description 2
- 239000007758 minimum essential medium Substances 0.000 description 2
- CFCUWKMKBJTWLW-BKHRDMLASA-N mithramycin Chemical compound O([C@@H]1C[C@@H](O[C@H](C)[C@H]1O)OC=1C=C2C=C3C[C@H]([C@@H](C(=O)C3=C(O)C2=C(O)C=1C)O[C@@H]1O[C@H](C)[C@@H](O)[C@H](O[C@@H]2O[C@H](C)[C@H](O)[C@H](O[C@@H]3O[C@H](C)[C@@H](O)[C@@](C)(O)C3)C2)C1)[C@H](OC)C(=O)[C@@H](O)[C@@H](C)O)[C@H]1C[C@@H](O)[C@H](O)[C@@H](C)O1 CFCUWKMKBJTWLW-BKHRDMLASA-N 0.000 description 2
- 230000004899 motility Effects 0.000 description 2
- 229960003171 plicamycin Drugs 0.000 description 2
- 238000001959 radiotherapy Methods 0.000 description 2
- 229960004432 raltitrexed Drugs 0.000 description 2
- 201000010174 renal carcinoma Diseases 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 150000003431 steroids Chemical class 0.000 description 2
- 201000011549 stomach cancer Diseases 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 210000001550 testis Anatomy 0.000 description 2
- 125000003831 tetrazolyl group Chemical group 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 231100000588 tumorigenic Toxicity 0.000 description 2
- 230000000381 tumorigenic effect Effects 0.000 description 2
- 201000005112 urinary bladder cancer Diseases 0.000 description 2
- 229960004355 vindesine Drugs 0.000 description 2
- UGGWPQSBPIFKDZ-KOTLKJBCSA-N vindesine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(N)=O)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1N=C1[C]2C=CC=C1 UGGWPQSBPIFKDZ-KOTLKJBCSA-N 0.000 description 2
- YJGVMLPVUAXIQN-LGWHJFRWSA-N (5s,5ar,8ar,9r)-5-hydroxy-9-(3,4,5-trimethoxyphenyl)-5a,6,8a,9-tetrahydro-5h-[2]benzofuro[5,6-f][1,3]benzodioxol-8-one Chemical class COC1=C(OC)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O)[C@@H]3[C@@H]2C(OC3)=O)=C1 YJGVMLPVUAXIQN-LGWHJFRWSA-N 0.000 description 1
- GPVGDGBVGWUGAL-UHFFFAOYSA-N 1-cyclohexyl-1-nitrosourea Chemical compound NC(=O)N(N=O)C1CCCCC1 GPVGDGBVGWUGAL-UHFFFAOYSA-N 0.000 description 1
- BOMZMNZEXMAQQW-UHFFFAOYSA-N 2,5,11-trimethyl-6h-pyrido[4,3-b]carbazol-2-ium-9-ol;acetate Chemical compound CC([O-])=O.C[N+]1=CC=C2C(C)=C(NC=3C4=CC(O)=CC=3)C4=C(C)C2=C1 BOMZMNZEXMAQQW-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- GFWBKUDRXMQSFD-FJXQXJEOSA-M 3-aminopropanoyl-[(1s)-1-carboxy-2-(1h-imidazol-5-yl)ethyl]azanide;zinc Chemical compound [Zn].NCCC(=O)[N-][C@H](C(O)=O)CC1=CN=CN1 GFWBKUDRXMQSFD-FJXQXJEOSA-M 0.000 description 1
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- YFVNYAXYZNDLIY-UHFFFAOYSA-N 7-hydroxy-3-(3,4,5-trihydroxyphenyl)chromen-4-one Chemical compound C=1C(O)=CC=C(C2=O)C=1OC=C2C1=CC(O)=C(O)C(O)=C1 YFVNYAXYZNDLIY-UHFFFAOYSA-N 0.000 description 1
- 206010000830 Acute leukaemia Diseases 0.000 description 1
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 1
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 1
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 1
- 208000003200 Adenoma Diseases 0.000 description 1
- 206010001233 Adenoma benign Diseases 0.000 description 1
- 101100005765 Arabidopsis thaliana CDF1 gene Proteins 0.000 description 1
- 101100007579 Arabidopsis thaliana CPP1 gene Proteins 0.000 description 1
- 206010003571 Astrocytoma Diseases 0.000 description 1
- 241000972773 Aulopiformes Species 0.000 description 1
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 1
- 208000019838 Blood disease Diseases 0.000 description 1
- 208000031648 Body Weight Changes Diseases 0.000 description 1
- 206010055113 Breast cancer metastatic Diseases 0.000 description 1
- 208000011691 Burkitt lymphomas Diseases 0.000 description 1
- GAGWJHPBXLXJQN-UORFTKCHSA-N Capecitabine Chemical compound C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](C)O1 GAGWJHPBXLXJQN-UORFTKCHSA-N 0.000 description 1
- GAGWJHPBXLXJQN-UHFFFAOYSA-N Capecitabine Natural products C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1C1C(O)C(O)C(C)O1 GAGWJHPBXLXJQN-UHFFFAOYSA-N 0.000 description 1
- 208000017897 Carcinoma of esophagus Diseases 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 241000208328 Catharanthus Species 0.000 description 1
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 1
- ZQZFYGIXNQKOAV-OCEACIFDSA-N Droloxifene Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=C(O)C=CC=1)\C1=CC=C(OCCN(C)C)C=C1 ZQZFYGIXNQKOAV-OCEACIFDSA-N 0.000 description 1
- 208000006168 Ewing Sarcoma Diseases 0.000 description 1
- 239000001828 Gelatine Substances 0.000 description 1
- 206010064571 Gene mutation Diseases 0.000 description 1
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 1
- 229930182566 Gentamicin Natural products 0.000 description 1
- 102000003964 Histone deacetylase Human genes 0.000 description 1
- 108090000353 Histone deacetylase Proteins 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- 229930182816 L-glutamine Natural products 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 102000029749 Microtubule Human genes 0.000 description 1
- 108091022875 Microtubule Proteins 0.000 description 1
- 208000034578 Multiple myelomas Diseases 0.000 description 1
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 1
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 1
- 208000002454 Nasopharyngeal Carcinoma Diseases 0.000 description 1
- 206010061306 Nasopharyngeal cancer Diseases 0.000 description 1
- 208000008636 Neoplastic Processes Diseases 0.000 description 1
- 206010029260 Neuroblastoma Diseases 0.000 description 1
- 208000009277 Neuroectodermal Tumors Diseases 0.000 description 1
- 206010052399 Neuroendocrine tumour Diseases 0.000 description 1
- 206010029350 Neurotoxicity Diseases 0.000 description 1
- 206010030155 Oesophageal carcinoma Diseases 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 208000009565 Pharyngeal Neoplasms Diseases 0.000 description 1
- 206010034811 Pharyngeal cancer Diseases 0.000 description 1
- KMSKQZKKOZQFFG-HSUXVGOQSA-N Pirarubicin Chemical compound O([C@H]1[C@@H](N)C[C@@H](O[C@H]1C)O[C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1CCCCO1 KMSKQZKKOZQFFG-HSUXVGOQSA-N 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 1
- 208000001647 Renal Insufficiency Diseases 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 208000021712 Soft tissue sarcoma Diseases 0.000 description 1
- ZSJLQEPLLKMAKR-UHFFFAOYSA-N Streptozotocin Natural products O=NN(C)C(=O)NC1C(O)OC(CO)C(O)C1O ZSJLQEPLLKMAKR-UHFFFAOYSA-N 0.000 description 1
- 229940123237 Taxane Drugs 0.000 description 1
- 108010022394 Threonine synthase Proteins 0.000 description 1
- 102000005497 Thymidylate Synthase Human genes 0.000 description 1
- GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 1
- 102000007537 Type II DNA Topoisomerases Human genes 0.000 description 1
- 108010046308 Type II DNA Topoisomerases Proteins 0.000 description 1
- 206010057362 Underdose Diseases 0.000 description 1
- 208000033559 Waldenström macroglobulinemia Diseases 0.000 description 1
- 208000008383 Wilms tumor Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- USZYSDMBJDPRIF-SVEJIMAYSA-N aclacinomycin A Chemical compound O([C@H]1[C@@H](O)C[C@@H](O[C@H]1C)O[C@H]1[C@H](C[C@@H](O[C@H]1C)O[C@H]1C[C@]([C@@H](C2=CC=3C(=O)C4=CC=CC(O)=C4C(=O)C=3C(O)=C21)C(=O)OC)(O)CC)N(C)C)[C@H]1CCC(=O)[C@H](C)O1 USZYSDMBJDPRIF-SVEJIMAYSA-N 0.000 description 1
- 229960004176 aclarubicin Drugs 0.000 description 1
- 230000000735 allogeneic effect Effects 0.000 description 1
- 238000011316 allogeneic transplantation Methods 0.000 description 1
- ROBVIMPUHSLWNV-UHFFFAOYSA-N aminoglutethimide Chemical compound C=1C=C(N)C=CC=1C1(CC)CCC(=O)NC1=O ROBVIMPUHSLWNV-UHFFFAOYSA-N 0.000 description 1
- 229960003437 aminoglutethimide Drugs 0.000 description 1
- 230000003388 anti-hormonal effect Effects 0.000 description 1
- 230000001399 anti-metabolic effect Effects 0.000 description 1
- 230000000340 anti-metabolite Effects 0.000 description 1
- 238000011319 anticancer therapy Methods 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- 210000001109 blastomere Anatomy 0.000 description 1
- 230000004579 body weight change Effects 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 210000000621 bronchi Anatomy 0.000 description 1
- 208000003362 bronchogenic carcinoma Diseases 0.000 description 1
- 201000005295 bronchus carcinoma Diseases 0.000 description 1
- VSJKWCGYPAHWDS-FQEVSTJZSA-N camptothecin Chemical compound C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-FQEVSTJZSA-N 0.000 description 1
- 208000035269 cancer or benign tumor Diseases 0.000 description 1
- 229960004117 capecitabine Drugs 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 231100000153 central nervous system (CNS) toxicity Toxicity 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 229940084982 cyclophosphamide 25 mg Drugs 0.000 description 1
- 229940084983 cyclophosphamide 50 mg Drugs 0.000 description 1
- 229940108608 cyclophosphamide 500 mg Drugs 0.000 description 1
- DUSHUSLJJMDGTE-ZJPMUUANSA-N cyproterone Chemical compound C1=C(Cl)C2=CC(=O)[C@@H]3C[C@@H]3[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(=O)C)(O)[C@@]1(C)CC2 DUSHUSLJJMDGTE-ZJPMUUANSA-N 0.000 description 1
- 229960003843 cyproterone Drugs 0.000 description 1
- 229940034086 dacarbazine 200 mg Drugs 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000009849 deactivation Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- CFCUWKMKBJTWLW-UHFFFAOYSA-N deoliosyl-3C-alpha-L-digitoxosyl-MTM Natural products CC=1C(O)=C2C(O)=C3C(=O)C(OC4OC(C)C(O)C(OC5OC(C)C(O)C(OC6OC(C)C(O)C(C)(O)C6)C5)C4)C(C(OC)C(=O)C(O)C(C)O)CC3=CC2=CC=1OC(OC(C)C1O)CC1OC1CC(O)C(O)C(C)O1 CFCUWKMKBJTWLW-UHFFFAOYSA-N 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 229940097957 dexamethasone 2 mg Drugs 0.000 description 1
- 229940084971 dexamethasone 6 mg Drugs 0.000 description 1
- RGLYKWWBQGJZGM-ISLYRVAYSA-N diethylstilbestrol Chemical compound C=1C=C(O)C=CC=1C(/CC)=C(\CC)C1=CC=C(O)C=C1 RGLYKWWBQGJZGM-ISLYRVAYSA-N 0.000 description 1
- 229960000452 diethylstilbestrol Drugs 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 229960004679 doxorubicin Drugs 0.000 description 1
- 229950004203 droloxifene Drugs 0.000 description 1
- 238000004043 dyeing Methods 0.000 description 1
- 229950000549 elliptinium acetate Drugs 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 239000002786 epipodophyllotoxin derivative Substances 0.000 description 1
- 201000005619 esophageal carcinoma Diseases 0.000 description 1
- 229940011871 estrogen Drugs 0.000 description 1
- 239000000262 estrogen Substances 0.000 description 1
- 239000000328 estrogen antagonist Substances 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 229960000961 floxuridine Drugs 0.000 description 1
- ODKNJVUHOIMIIZ-RRKCRQDMSA-N floxuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(F)=C1 ODKNJVUHOIMIIZ-RRKCRQDMSA-N 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 229960002074 flutamide Drugs 0.000 description 1
- MKXKFYHWDHIYRV-UHFFFAOYSA-N flutamide Chemical compound CC(C)C(=O)NC1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 MKXKFYHWDHIYRV-UHFFFAOYSA-N 0.000 description 1
- RIKPNWPEMPODJD-UHFFFAOYSA-N formononetin Natural products C1=CC(OC)=CC=C1C1=COC2=CC=CC=C2C1=O RIKPNWPEMPODJD-UHFFFAOYSA-N 0.000 description 1
- YAKWPXVTIGTRJH-UHFFFAOYSA-N fotemustine Chemical compound CCOP(=O)(OCC)C(C)NC(=O)N(CCCl)N=O YAKWPXVTIGTRJH-UHFFFAOYSA-N 0.000 description 1
- 229960004783 fotemustine Drugs 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 238000001415 gene therapy Methods 0.000 description 1
- 208000005017 glioblastoma Diseases 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 235000015220 hamburgers Nutrition 0.000 description 1
- 208000014951 hematologic disease Diseases 0.000 description 1
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 1
- 210000003677 hemocyte Anatomy 0.000 description 1
- 229940000351 hemocyte Drugs 0.000 description 1
- 229940082156 hydroxyurea 500 mg Drugs 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 238000009169 immunotherapy Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 239000000138 intercalating agent Substances 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 208000022013 kidney Wilms tumor Diseases 0.000 description 1
- 201000006370 kidney failure Diseases 0.000 description 1
- 229960001614 levamisole Drugs 0.000 description 1
- 229940080464 levamisole 50 mg Drugs 0.000 description 1
- 230000000527 lymphocytic effect Effects 0.000 description 1
- 201000000564 macroglobulinemia Diseases 0.000 description 1
- 230000007257 malfunction Effects 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
- 210000005075 mammary gland Anatomy 0.000 description 1
- 231100000682 maximum tolerated dose Toxicity 0.000 description 1
- 238000011177 media preparation Methods 0.000 description 1
- 229960004616 medroxyprogesterone Drugs 0.000 description 1
- FRQMUZJSZHZSGN-HBNHAYAOSA-N medroxyprogesterone Chemical compound C([C@@]12C)CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2CC[C@]2(C)[C@@](O)(C(C)=O)CC[C@H]21 FRQMUZJSZHZSGN-HBNHAYAOSA-N 0.000 description 1
- 229960001786 megestrol Drugs 0.000 description 1
- RQZAXGRLVPAYTJ-GQFGMJRRSA-N megestrol acetate Chemical compound C1=C(C)C2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(C)=O)(OC(=O)C)[C@@]1(C)CC2 RQZAXGRLVPAYTJ-GQFGMJRRSA-N 0.000 description 1
- 230000001394 metastastic effect Effects 0.000 description 1
- 208000011645 metastatic carcinoma Diseases 0.000 description 1
- 229940021348 methotrexate 10 mg Drugs 0.000 description 1
- 210000004688 microtubule Anatomy 0.000 description 1
- PQLXHQMOHUQAKB-UHFFFAOYSA-N miltefosine Chemical compound CCCCCCCCCCCCCCCCOP([O-])(=O)OCC[N+](C)(C)C PQLXHQMOHUQAKB-UHFFFAOYSA-N 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 229960003539 mitoguazone Drugs 0.000 description 1
- MXWHMTNPTTVWDM-NXOFHUPFSA-N mitoguazone Chemical compound NC(N)=N\N=C(/C)\C=N\N=C(N)N MXWHMTNPTTVWDM-NXOFHUPFSA-N 0.000 description 1
- 230000011278 mitosis Effects 0.000 description 1
- 230000000394 mitotic effect Effects 0.000 description 1
- 238000004264 monolayer culture Methods 0.000 description 1
- 230000036457 multidrug resistance Effects 0.000 description 1
- 210000001167 myeloblast Anatomy 0.000 description 1
- 208000025113 myeloid leukemia Diseases 0.000 description 1
- 201000011216 nasopharynx carcinoma Diseases 0.000 description 1
- 230000001613 neoplastic effect Effects 0.000 description 1
- 201000008026 nephroblastoma Diseases 0.000 description 1
- 208000016065 neuroendocrine neoplasm Diseases 0.000 description 1
- 201000011519 neuroendocrine tumor Diseases 0.000 description 1
- XWXYUMMDTVBTOU-UHFFFAOYSA-N nilutamide Chemical compound O=C1C(C)(C)NC(=O)N1C1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 XWXYUMMDTVBTOU-UHFFFAOYSA-N 0.000 description 1
- 229960002653 nilutamide Drugs 0.000 description 1
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000002777 nucleoside Substances 0.000 description 1
- 150000003833 nucleoside derivatives Chemical class 0.000 description 1
- 201000008968 osteosarcoma Diseases 0.000 description 1
- 229960001756 oxaliplatin Drugs 0.000 description 1
- DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 238000003359 percent control normalization Methods 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 230000000505 pernicious effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229960000952 pipobroman Drugs 0.000 description 1
- 229960001221 pirarubicin Drugs 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000000583 progesterone congener Substances 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 229940056457 promace Drugs 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 201000009410 rhabdomyosarcoma Diseases 0.000 description 1
- 235000019515 salmon Nutrition 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 238000011519 second-line treatment Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- INIBXSLTWQVIHS-ASACRTLUSA-O stanford v protocol Chemical compound ClCCN(C)CCCl.O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1.O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1.COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3C(O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1.C([C@H](C[C@]1(C(=O)OC)C=2C(=C3C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)=CC=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21.C([C@H](C[C@]1(C(=O)OC)C=2C(=C3C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C=O)=CC=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21.N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)C(O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1NC=NC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C INIBXSLTWQVIHS-ASACRTLUSA-O 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000005728 strengthening Methods 0.000 description 1
- 229940041022 streptomycins Drugs 0.000 description 1
- 229960001052 streptozocin Drugs 0.000 description 1
- ZSJLQEPLLKMAKR-GKHCUFPYSA-N streptozocin Chemical compound O=NN(C)C(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O ZSJLQEPLLKMAKR-GKHCUFPYSA-N 0.000 description 1
- 230000000153 supplemental effect Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 208000029387 trophoblastic neoplasm Diseases 0.000 description 1
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 1
- 229940035893 uracil Drugs 0.000 description 1
- 208000012991 uterine carcinoma Diseases 0.000 description 1
- GBABOYUKABKIAF-IELIFDKJSA-N vinorelbine Chemical compound C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC([C@]23[C@H]([C@@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC GBABOYUKABKIAF-IELIFDKJSA-N 0.000 description 1
- 229960002066 vinorelbine Drugs 0.000 description 1
- 229960000641 zorubicin Drugs 0.000 description 1
- FBTUMDXHSRTGRV-ALTNURHMSA-N zorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(\C)=N\NC(=O)C=1C=CC=CC=1)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 FBTUMDXHSRTGRV-ALTNURHMSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Abstract
The invention concerns a composition having an activity on the proliferation of clonogenic cells in tumours and comprising a therapeutically efficient amount of an isoflavonoid or an analogous chromone compound, in particular a compound selected among the compounds of formula(I)wherein: R1, R2, R3, R4, R5 and R6 are as defined in Claim 2. Said composition is designed for use in the treatment of tumours with cytotoxic agents.
Description
The present invention relates to isoflavonoid in the purposes aspect cell toxicant reagent treatment cancer.
Cancer belongs to the vivo gene disorder, and during this period, the gene malfunction proceeds to pernicious transformation along with the forming process of tumor by damage pre-cancer and is on the rise, and consequently carcinoma becomes metastatic and normal pair cell cytotoxic drug and produces resistance.
Although particularly made great efforts with the clinical research people by experiment in all developed countries, yet the mortality rate that is caused by various cancers (solid tumor and leukemia) is still high as can't to make us accepting.In a lot of countries, cancer is the second largest cause of the death that is only second to cardiovascular disease.
With regard to the cancer of new diagnosis, the distribution of solid tumor and leukemia (bone marrow, blood, lymphsystem) shows that in the 10 routine cancers 9 examples being arranged is solid tumors.Opposite with the viewed situation of hemooncology (hemocyte treatment for cancer success rate is 40% to 90%), the solid tumor that has only minority late period or diffusion is to chemotherapy side effect.This is the partly cause that the american cancer general mortality rate raises in the period of 1973 to 1992.
Lamentedly, can't determine that this trend can only be reversed owing to new antitumor drug occurs on existing chemotherapeutics basis, taxanes (taxoid) (taxol and the docetaxel) (W.P.McGuire etc. of new antitumor drug as disturbing microtubule to form, Am.Intern.Med., 1989), derive from the topoisomerase I inhibitor (the holder pool is for bearing and irinotecan) of camptothecine, Vinorelbine (deriving from the new alkaloids of Herba Catharanthi Rosei), gemcitabine (new cell toxicant antimetabolite), raltitrexed (thymidylate synthetase inhibitor) and Miltex (first representative compounds of alkyl-lysophosphatide class).These treatments are added in the medicine such as amycin, cisplatin, vincristine, methotrexate and 5-fluorouracil that its specific activity is known as first-line treatment or second line treatment.
One of problem in anticancer chemotherapy at present the most difficult is because a lot of colonies of malignant cell show strong resistance to existing cell toxicant material.Usually, this problem causes by the existence of multi-resistance medicine gene or by the frequency of gene mutation in the tumor of some type.Therefore, treatment for cancer requires to adopt new method, and common method of treatment is replenished, and resists expansion of tumor quantity and inhomogeneities and " cell toxicant multi-drug resistance " better and produces.
In these new methods, some has shown effect.Inducing apoptosis, inhibition tumor-blood-vessel growth and transfer come to this, and more needn't mention gene therapy or immunotherapy.
The inventor all becomes interested to various researchs.The purpose that reaches is to make the colony of tumor cell more responsive so that reach double benefit to the standard anticancer therapy:
1) strengthen cytotoxic activity and also therefore increase effect, and
2) by reducing the frequency of occurrences and the order of severity that dosage reduces some side effect greatly, this may cause the increase of antitumous effect subsequently.
This imagination comes from by having low anti-tumor activity or even lacking that this is active but can cause the discovery of the innovation mechanism that material that the cytotoxic activity of known antitumor drug significantly increases brings.This new mechanism may make in these material incentive tumors the clone form the gathering of cell, therefore makes tumor more responsive or suppress the propagation that the clone forms cell to the conventional therapy that is undertaken by cell toxicant reagent, therefore helps the degeneration of tumor.
Therefore, the present invention relates to that the propagation of tumor clone formation cell is had the purposes of active chemical compound in the treatment of cancer of being undertaken by at least a anti-tumor agent comprising salmosin that is selected from cell toxicant reagent, this chemical compound is selected from the similar compound of osajin and chromone, and following formula: compound particularly:
Wherein:
R
1, R
2, R
3And R
4Be independently from each other H, OH, C
1-C
4Alkoxyl, R wherein
7Be C
1-C
4Alkyl-OCOR
7Group, substituent R
1, R
2, R
3Or R
4In at least one be not H, and R
2And R
3Can form methylene-dioxy together,
R
5Be selected from H, OH, C
1-C
4Alkoxyl, O-glucityl and cyclohexyl,
R
6Be selected from cyclohexyl, phenyl and be selected from H, OH and C
1-C
4The group of alkoxyl replaces 1 to 3 time phenyl,
And
Two keys of expression or singly-bound.
The preferred type of formula I chemical compound is R wherein
6Be selected from phenyl, 4-hydroxy phenyl and 4-(C
1-C
4Alkoxyl) chemical compound of phenyl.
These cell toxicant reagent can its routine dose use and in the case its effect be enhanced, at first be to improve under the situation of patient to the toleration of treatment perhaps in required purpose, then consider the enhancing of its antitumous effect, use with lower dosage.
Theme of the present invention comprises that also the generation by disturbing the clone to form cell has active compositions to the propagation that clone in the tumor forms cell, this interference or by stimulating proliferation and assembling, perhaps realize by suppressing propagation, said composition contains the osajin for the treatment of effective dose or the similar compound of chromone type, and particularly is selected from following formula: compound:
Wherein:
R
1, R
2, R
3And R
4Be independently from each other H, OH, C
1-C
4Alkoxyl, R wherein
7Be C
1-C
4Alkyl-OCOR
7Group, substituent R
1, R
2, R
3Or R
4In at least one be not H, and R
2And R
3Can form methylene-dioxy together,
R
5Be selected from H, OH, C
1-C
4Alkoxyl, O-glucityl and cyclohexyl,
R
6Be selected from cyclohexyl, phenyl and be selected from H, OH and C
1-C
4The group of alkoxyl replaces 1 to 3 time phenyl,
And
Two keys of expression or singly-bound.
The invention still further relates to osajin, particularly above-mentioned formula I chemical compound is used for the formation that tumor clone during by the treatment of at least a cell toxicant reagent forms cell produced and disturbs the purposes aspect the medicine that (by bringing out or suppressing) act in preparation.
When carrying out cancer chemotherapy with cell toxicant reagent, osajin, particularly the chemical compound of formula I can be administered once when chemotherapy begins or administration (for example 5 to 7 days) in some days when these treatment beginnings, and according to chemotherapy regimen, (for example 2 to 5 days) administration during beginning of each treatment cycle in each course of treatment.
Osajin, particularly formula I chemical compound with 5 to 50mg/kg/ days or 200 to 2000mg/m
2The dosage in/sky is favourable by transfusion (general 1 to 3 hour) administration.
For the formation that the clone is formed cell produces maximum effect, the administration of osajin should make the tissue concentration that is obtained reach imaginabale peak.
In the therapeutic scheme of the acute stage of the course of treatment, preferred intravenous route, use:
-be used for by tube for transfusion and with the flow velocity recommended by the direct administration of venous transfusion promptly with transfusion (bag, bottle etc.);
-be used for dissolving lyophilized products again in order to venous transfusion by pharmacy solution well known by persons skilled in the art;
-for keeping treatment, when chemotherapy helps the oral administration of cell toxicant reagent, can also comprise oral route.For this reason, can use oral freeze-dried thing (oral or through tongue absorb), promptly release or slow releasing tablet, oral administration solution, suspensoid, granule, gelatine capsule etc.
The chemical compound of numerical expression (I) is the derivant of the chemical compound or the natural origin chemical compound of natural origin mostly.For example, can mention:
-genistein,
-biochanin,
-Daidezin,
-formononetin,
-7-acetyl group formononetin,
—glycetein，
-orobol or 5,7,3 ', 4 '-the tetrahydroxy isoflavone,
-irizolone or 6,7-methylene-dioxy-4 '-hydroxy-isoflavone,
-irigenine or 3 ', 5,7-trihydroxy-4 ', 5 ', 6-methoxyl group isoflavone,
-tectorigenin or 4 ', 5,7-trihydroxy-6-methoxyl group isoflavone,
-2-hydroxyl-8-methoxyl group-2, the 3-isoflavanone,
-4 ', 7-dihydroxy-5-methoxyl group isoflavone.
Operable other osajin is described in Natural ProductReports by Donnelly etc., and 1995,321, maybe can be by the method preparation of describing in this document.
Cell toxicant reagent can be selected from:
I) intercalating agent, particularly Doxorubicin (amycin), daunorubicin, epirubicin, idarubicin, zorubicin, aclarubicin, pirarubicin, acridine, mitoxantrone, actinomycin D, elliptinium acetate;
Ii) alkylating reagent is selected from platinum derivatives (cisplatin, carboplatin, oxaliplatin etc.);
Iii) be selected from the chemical compound of the alkylating reagent of other type:
-cyclophosphamide, ifosfamide, chlormethine, melphalan, chlorambucil, estramustine,
-busulfan, ametycin,
-nitrosoureas: BCNU (carmustine), CCNU (chlorethyl cyclohexyl nitrosourea), Fotemustine, streptozotocin,
-triazines or derivant, procarbazine, dacarbazine,
-pipobroman,
-ethylenimine class: altretamine, thiophene replace group,
Iv) be selected from the chemical compound of other type antimetabolic reagent:
-anti-folic acid class: methotrexate, raltitrexed,
-anti-pyrimidine reagent: 5-fluorouracil (5-FU), cytosine arabinoside (Ara-C),
-hydroxyurea,
-anti-purine reagent: purinethol, thioguanine, spray Si Tating, cladribine,
-cell toxicant nucleoside synthesizes derivant: gemcitabine,
V) be selected from other type tubulin had the chemical compound of the reagent of affinity,
-catharanthus alkaloid, it destroys mitotic spindle: vincristine, vinblastine, vindesine, navelbine,
The reagent that takes off poly-effect of-blocking-up mitosis spindle: taxol, docetaxel,
-by suppressing the reagent that topoisomerase II causes dna cleavage: etoposide, teniposide,
-cause the topoisomerase I inhibitor of dna cleavage: the holder pool for may, irinotecan,
Vi) dna cleavage or fragment reagent, as bleomycin,
Vii) following compounds it-: plicamycin, altheine enzyme, mitoguazone, dacarbazine,
Viii) anticancer progestogen: medroxyprogesterone, megestrol,
Ix) anticancer estrogen: diethylstilbestrol; Fostestrol four sodium,
X) estrogen antagonist reagent: tamoxifen, droloxifene, Lei Luoxifen, aminoglutethimide,
Xi) steroid class androgen antagonist reagent (coming from Cyproterone) or non-steroid class androgen antagonist reagent (flutamide, nilutamide).
Specifically, the chemical compound of formula I can combine with all treatments of implementing by the main cell toxicant reagent that is used for the comprehensive chemotherapy of solid tumor, these cell toxicant reagent just like:
-amycin,
-alkylating reagent: oxa-phosphoramide types (oxazophorines) (cyclophosphamide, ifosfamide, chlorambucil, melphalan),
-nitroso ureas,
-ametycin,
-antimetabolite such as methotrexate, 5-FU, Ara-C, capecitabine,
The reagent of-interference tubulin: catharanthus alkaloid (vincristine, vinblastine, vindesine, navelbine), taxoids (taxol, docetaxel), epipodophyllotoxin derivatives (etoposide, teniposide),
-bleomycin,
-topoisomerase I inhibitor: holder pool for may, irinotecan.
Similarly, formula I chemical compound can combine with the treatment of the main cell toxicant reagent that is used for the treatment of leukemia:
-Hokdkin disease: cyclophosphamide, chlormethine, chlorambucil, melphalan, ifosfamide, etoposide, amycin, daunorubicin;
-acute leukemia: methotrexate, Ismipur, cytosine arabinoside, vincristine, vinblastine, amycin, daunorubicin, altheine enzyme;
-Fei Hejiejinshi malignant lymphoma: chlormethine, chlorambucil, cyclophosphamide, melphalan, ifosfamide, methotrexate, cytosine arabinoside, vincristine, vinblastine, etoposide, amycin, daunorubicin, carmustine, chlorethyl cyclohexyl nitrosourea, cisplatin;
-chronic lymphatic leukemia: chlormethine, chlorambucil, cyclophosphamide, melphalan, ifosfamide.
Provide the The pharmacological results that shows the gained effect below.
1-form the interaction (stimulate or suppress and breed) that cell produces (clone and form experiment) with the clone
This experiment is by (Science, 1977 such as Hamburger; 197,461-463) and Salmon etc. (New England J.Med., 298,1321-1327) describe.If cell has propagation and produces the ability of cell colony, then this cell is considered to clone formation property." people's tumor stem cell " comes from the oncocyte that constitutes known cancer.These tumor stem cells are relevant, also relevant with the formation of metastatic tumor with the observed recurrence of possibility after the primary tumor excision.In tumor or tumor cell line, these clones form stem cell and other cell of tumor or the difference of tumor cell line and are under the situation that does not have any solid carrier, and they still keep the ability of breeding.
In this experiment, tumor cell culture is on the semi-solid carrier that agar is formed.Have only the cell that does not need solid carrier (promptly to be called the height tumorigenic cell of " set independent cell ", to see M.I.Dawson etc., Cancer Res.1995; 55; 4446-4451; Also be called the clone according to " growth of clone's property " and form cell) could on such agar base carrier, grow.Specifically, in such culture medium, fail to survive with the normal cell such as the fibroblast of " set mode " growth (term according to M.I.Dawson is " a set dependent cells ").In the tumor cell colony of on such carrier, cultivating, just these clones form cells (with the cell division of unlimited number of times, and its propagation be called by M.I.Dawson " set independence [clone's property] growth) can grow.The percentage rate that these clones form cell in tumor or cell line is 0.1% to 0.001%.Non-clone forms cell (with the cell division of limited number of times) and does not grow in this experiment, the solid carrier of growth because they need be rely, it must take place with " set mode ", and (" set dependency [set] growth " sees M.I.Dawson etc., Cancer Res.1995; 55:4446-51).
By for example cultivate mammalian tumor cell on the semisolid culturemedium that is called " soft agar " is MCF7 and MXT and knot rectum cell line HT-29) detection formula (I) chemical compound is to the influence that growth produced of the cell colony that obtains.In such culture medium, have only by M.I.Dawson the clone who is called " set independence (clone's property) cell " to form cell and just survive and grow.These cells are tumorigenic degree with the witness of " non-set " form growth.The inhibition that wherein has a large amount of clones to form plastidogenetic gross tumor volume growth is just become the evidence that cytotoxicity is enhanced.
On the contrary, this experiment can show that also certain chemical compound can suppress generation/propagation that the clone forms cell, therefore makes this tumor be not easy to grow and so reduces the quantity of tumor cell.
The tumor cell line that is studied is incubated in 25 square centimeters the Falcon ware culture medium.Separate fully each other with their trypsinized and with cell then.With the percentage rate that detects survivaling cell behind the trypan blue staining.Preparation concentration is 5 * 10 in 0.3% agar solution
4To 15 * 10
4The cell suspending liquid of cells/ml (according to cell type).Then, 200 these suspensions of μ l are inoculated in the Petri culture dish that diameter is 35mm, wherein are placed the basal layer that 3ml is made up of 0.5% agar solution.200 μ l cell suspending liquids are covered with the upper strata that 1.8ml is made up of 0.3% agar solution successively.Then, these culture dishs are placed the incubator of 37 ℃, 5% carbon dioxide and humidity 70% up to handling constantly.After inoculation, handled in about 1 to 2 hour.With the prepared at concentrations test compound higher 100 times, and 50 these Treatment Solution of μ l are placed on the top-layer agar of corresponding culture dish than desired concn.In this experiment, the ultimate density of tested product is 10
-5, 10
-7With 10
-9M.Then, these culture dishs were deposited in incubator 21 days.At the 21st day, handled 3 hours down at 37 ℃ by MTT (3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl bromination tetrazolium is with the RPMI 1640 medium preparation) solution that adds 100 μ l 1mg/ml on the upper strata.After this, by in each culture dish, adding 2ml formalin cell colony is fixed.After fixing 24 hours, formalin is evaporated, and detect the number of staining cell colony with inverted microscope, the dyeing colony is made up of the metabolic activity cell, and its surface area is greater than 100 μ m
2
Clone's average that the clone that each experiment condition is measured down forms cell in be made as 100% collating condition down the clone of counting clone's average of forming cell be that the percentage rate of benchmark is represented.Be that these numerical value that the percent of benchmark is represented come together in Table I in the collating condition.
Table I
| Cell line | Genistein (mol.l -1) | ||
| 10 -5 | 10 -7 | 10 -9 | |
| MCF7 | 66.9±2.9 ** | 74.2±4.7 * | 89.2±0.9NS |
| HT-29 | 118.2±2.8 ** | 108.9±2.3 * | 104.6±2.5NS |
| MXT | 71±2.5 ** | 118.5±2.2 ** | 117.5±2.2 ** |
The result who sums up in-the table 1 represents the standard error (SEM) based on the meansigma methods ± meansigma methods of at least 6 groups,
-collating condition=100%
—(NS：p＞0.05；
*：p＜0.05；
**：p＜0.01；
***：p＜0.001)。
Based on the cell line of being studied, genistein can:
-(concentration is 10 to collect tumor
-5M and 10
-7The cell line HT-29 of M and concentration are 10
-7M and 10
-9The MXT of M) clone in forms cell, and that is to say that the colony number of comparing these cells with gained result under the collating condition significantly increases, thereby make them more responsive the conventional therapy that carries out with cell toxicant reagent, or
-(MCF7 cell, concentration are 10 directly to suppress these propagation of cloning the formation cells
-5M and 10
-7M).
2-non-clone is formed the cytotoxic activity of cell: " MTT experiment "
Non-clone is formed the influence of cell by means of MTT colorimetric experimental evaluation formula (I) chemical compound.
The MTT experiment principle is blue product first based on passing through metabolic activity survivaling cell mitochondrion reduction yellow product MTT (3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl bromination tetrazolium).The amount of gained first is directly proportional with survivaling cell amount in the culture hole (one or more).This amount is detected by spectrophotography.
At 37 ℃, stop in the culture dish these cell lines to be kept with the form of monolayer culture thing in the sealing that contains MEM 25 MM Hepes (minimum essential medium) culture medium.This culture medium is suitable for the growth of multiple mammal diploid or primary cell.Then, in this culture medium, add:
-5%FCS (hyclone), this serum be 56 ℃ of following deactivation complements 1 hour,
-0.6mg/ml L-glutamine,
-200UI/ml penicillin,
-200 μ g/ml streptomycins,
-0.1mg/ml gentamycin.
12 kinds of used human cancer cell lines derive from American Type Culture Collection (ATCC, Rockville, MD, USA).These 12 kinds of cells are:
-U-373MG (ATCC coding: HTB-17) and U-87MG (ATCC encodes: HTB-14), they are two kinds of glioblastomas,
-SW1088 (the ATCC coding: HTB-12), it is an astrocytoma,
-A549 (ATCC coding: CCL-185) and A-427 (ATCC encodes: HTB-53), they are two kinds of nonsmall-cell lung cancers,
-HTC-15 (ATCC coding: CCL-225) and LoVo (ATCC encodes: CCL-229), they are two kinds of colorectal cancers,
-T-47D (ATCC coding: HTB-133) and MCF7 (ATCC encodes: HTB-22), they are two kinds of breast carcinoma,
-J82 (ATCC coding: HTB-1) and T24 (ATCC encodes: HTB-4), they are two kinds of bladder cancer,
(the ATCC coding: CRL-1435), it is a carcinoma of prostate to-PC-3.
With regard to experiment, the 100 μ l cell suspending liquids that will contain 20000 to 50000 (according to using cell type) cells/ml culture medium are inoculated in the flat porous plate in 96 holes and under 37 ℃, cultivate in the atmosphere that contains 5% carbon dioxide and humidity 70%.Cultivating after 24 hours, is 10 with containing concentration
-5To 10
-10The different test compounds of M or the 100 μ l fresh cultures that are used for dissolving the solvent (collating condition) of tested product are replaced this culture medium.After cultivating 72 hours under these conditions, the MTT yellow solution 100 μ l that are dissolved among the RPMI 1640 in order to 1mg/ml concentration replace this culture medium.Under 37 ℃, again microwell plate was cultivated 3 hours centrifugal 10 minutes then with 400g.Remove yellow MTT solution and the blue first crystallization that forms in the cell is dissolved among the 100 μ lDMSO.Then, this micro plate was shaken 5 minutes.Cell owing to still survival when experiment finishes is converted into blue-colored that blue first causes with yellow product MTT, detect at wavelength 570nm and 630nm with Dynatech Immunoassay System instrument by spectrophotography, these two wavelength correspond respectively to maximum absorption wavelength and the background noise of first .With the computed in software average optical density value in the spectrophotometer with respect to the standard deviation (Std.Dev.) and the standard error (SEM) of this meansigma methods.
As limiting examples, as osajin it-the result of genistein average optical density value that 5 kinds of tumor cell line U-87MG, J82, HCT-15, T-47D and A549 are obtained, to represent, see Table II with respect to the percent of the average optical density value that detects under the collating condition (being made as 100%).
Table II
| Cell line | Genistein (mol.l -1) | |||||
| 10 -5 | 10 -6 | 10 -7 | 10 -8 | 10 -9 | 10 -10 | |
| U-87MG | 83.8±35 ** | 98.1±4.4NS | 94.3±3.7NS | 100.1±6.6NS | 98.2±3.5NS | 108.6±2.3 * |
| J82 | 87.0±1.0 *** | 99.3±1.1NS | 101.6±0.8NS | 101.8±1.8NS | 102.8±7.5NS | 104.2±1.5NS |
| HCT-15 | 96.8±5.3NS | 100.9±6.0NS | 97.5±5.2NS | 89.2±3.5 * | 89.4±4.0 * | 90.5±3.3 * |
| T-47D | 92.3±2.2 * | 98.9±3.3NS | 95.1±1.6NS | 97.8±3.0NS | 100.0±3.4NS | 102.4±1.7NS |
| A-549 | 81.4±4.8 ** | 105.0±4.1NS | 101.6±5.4NS | 106.0±3.2NS | 108.9±2.1 * | 103.6±3.9NS |
The standard error of-xx ± yy=meansigma methods ± meansigma methods
-collating condition=100%
—(NS：p＞0.05；
*：p＜0.05；
**：p＜0.01；
***：p＜0.001)。
Genistein presents low anti-tumor activity.In the case, this non-toxic products only just causes the whole cell inhibition of proliferation to these cell lines when concentration is 10-5M, and this inhibition is no more than 20%.Under other tested concentration, only show some secondary efficacy.
Determining of 3-maximum tolerated dose (MTD):
B6D2F1/Jico mice with 4 to 6 ages in week carries out the evaluation of maximum tolerated dose.To carry out the administration of these chemical compounds by 2.5 to 160mg/kg cumulative dosage intraperitoneal.MTD value (representing with mg/kg) is determined by the observation to animal dis motility rate in behind the tested product of single administration 14 days.The also body weight change of monitor animal during this period.When MTD value during, the MTD value is defaulted as 160mg/kg greater than 160mg/kg.
Genistein MTD default value is 160mg/kg.This result shows that this osajin product does not show any direct toxicity and also can use with high tissue concentration and high dose.
-with the bonded anti-tumor in vivo activity of cell toxicant reagent
This experiment is carried out in drag under the condition that has or do not exist cell toxicant reagent such as cyclophosphamide, etoposide, amycin or vincristine:
The mouse breast cancer MXT (HS-MXT) of-hormone-sensitive,
-lymphoma P388.
When detecting the MTD value of product, its anti-tumor in vivo activity to mouse breast cancer HS-MXT and lymphoma P388 model obtains characterizing under dose Zn-MT D/2, MTD/4 and MTD/8 numerical value.Selecting and using under the situation of this dosage and cell toxicant reagent combined treatment, this dosage all presents best anti-tumor activity to these various models.
In all following embodiment, no matter what (breast carcinoma HS-MXT or lymphoma P388) model is, collating condition is one group of 9 mice, and continuous 5 weeks also contain the normal saline of the solvent that is used for dissolving used not cotype (I) chemical compound with the frequency administration 0.2ml of 5 times weekly (Monday, Tuesday, Wednesday, Thursday and Fridays).
In these experiments, detect following parameters:
I)-survival rate of mice
This survival rate is calculated with the form of the ratio of T/C:
T=(by treatment group median mice survival natural law)+[(the median mice of being treated-prior to being treated the mice number of median dead mouse)/(by the day dead mouse number of treatment median dead mouse)]
C=(matched group median mice survival natural law)+[(the median mice of being treated-prior to being treated the mice number of median dead mouse)/(the day dead mouse number of median control mice death)]
This ratio represents to be treated the ratio of median mice mean survival time and control group mice median mice mean survival time in the group.Therefore, when index T/C surpassed 130%, chemical compound caused significantly (P＜0.05) increase of animal dis motility rate.On the contrary, when this T/C value less than 70% the time, it has toxic action.
Ii)-surf zone (Monday and Friday) that tumor growth is transplanted HS-MXT or P 388 tumors by twice inspection weekly determines tumor growth.This surf zone passes through the product of two maximum perpendicular axis values of tumor is calculated.Check these numerical value with slide gauge.
4.1. mouse breast cancer (HS-MXT)
MXT (HS-MXT) the mouse breast cancer model of transplanting the hormone-sensitive of the B6D2F1/Jico mice of giving for 4 to 6 ages in week derives from lactiferous ducts (Watson C. etc., the Cancer Res.1977 of mammary gland; 37:3344-48).
The experimental result that provides as an example individually or use genistein to obtain with the cell toxicant agent combination.
Treatment 1
Individually dosed genistein.The 7th day (D after transplanting
7) continuous 4 weeks inject this product for the first time with the frequency of injecting 5 times (Monday, Tuesday, Wednesday, Thursday and Fridays) weekly and with the dosage of 20mg/kg.
Treatment 2
Individually dosed cyclophosphamide (CPA).The 14th day (D after transplanting
14) continuous 3 weeks are with the frequency of 3 times weekly (Monday, Wednesday and Fridays) and carry out the injection first time of this product with the dosage of 10mg/kg.
Treatment 3
Individually dosed vincristine (VCR).The 14th day (D after transplanting
14) continuous 3 weeks are with the frequency of 3 times weekly (Monday, Wednesday and Fridays) and carry out the injection first time of this product with the dosage of 0.63mg/kg.
Treatment 4
Individually dosed etoposide (ETO).The 14th day (D after transplanting
14) continuous 3 weeks are with the frequency of 3 times weekly (Monday, Wednesday and Fridays) and carry out the injection first time of this product with the dosage of 10mg/kg.
Treatment 5
Genistein and cyclophosphamide co-administered.In the case, the 7th day (D7) continuous 4 weeks are carried out the injection first time of genistein with the frequency of injecting 5 times (Monday, Tuesday, Wednesday, Thursday and Fridays) weekly and with the dosage of 20mg/kg after transplanting, and after transplanting the 14th day (D
14) continuous 3 weeks are with the frequency of 3 times weekly (Monday, Wednesday and Fridays) and carry out the injection first time of cyclophosphamide with the dosage of 10mg/kg.
Treatment 6
Genistein and vincristine co-administered.In the case, the 7th day (D after transplanting
7) continuous 4 weeks carry out the injection first time of genistein with the frequency of injecting 5 times (Monday, Tuesday, Wednesday, Thursday and Fridays) weekly and with the dosage of 20mg/kg, and after transplanting the 14th day (D
14) continuous 3 weeks are with the frequency of 3 times weekly (Monday, Wednesday and Fridays) and carry out the injection first time of vincristine with the dosage of 0.63mg/kg.
Treatment 7
Genistein and etoposide co-administered.In the case, the 7th day (D after transplanting
7) continuous 4 weeks carry out the injection first time of genistein with the frequency of injecting 5 times (Monday, Tuesday, Wednesday, Thursday and Fridays) weekly and with the dosage of 20mg/kg, and after transplanting the 14th day (D
14) continuous 3 weeks are with the frequency of 3 times weekly (Monday, Wednesday and Fridays) and carry out the injection first time of etoposide with the dosage of 10mg/kg.
The time-to-live that obtains by genistein the results are shown in Table III:
Table III
| Treatment | T/C (representing) with % |
| 1 (genistein) | 100 |
| 2(CPA) | 107 |
| 3(VCR) | 105 |
| 4(ETO) | 116 |
| 5 (genistein+CPA) | 131 |
| 6 (genistein+VCR) | 135 |
| 7 (genistein+ETO) | 131 |
These results show genistein and cell toxicant reagent: cyclophosphamide, vincristine or etoposide co-administered, for the mean survival time of median mice in the control group mice, significantly increased the mean survival time of median mice in each treatment group mice.The increase of the mean survival time of the median mice during in addition, the mice for the treatment of with these co-administered modes is organized is longer significantly than what use the treatment of genistein or these cell toxicant reagent to bring separately.
The research of tumor growth has also disclosed following result.In the infra Table IV, after tumour transplatation the 28th day, promptly after the 15th the genistein administration or the 6th time of different cell toxicant reagent separately or with after genistein combines administration, compare with collating condition, the reduction (-) or the increase (+) of different treatment 1,2,3,4,5, the 6 and 7 HS-MXT tumor areas that cause are represented with percentage rate.After transplanting the 28th day, 89% control animal (promptly having 8 in 9 animals) still survived.
Table IV
| Treatment | Tumor area (representing) with % |
| 1 (genistein) | +2.6 |
| 2(CPA) | -25 |
| 3(VCR) | -32 |
| 4(ETO) | -22 |
| 5 (genistein+CPA) | -20 |
| 6 (genistein+VCR) | -45 |
| 7 (genistein+ETO) | -41 |
These results show, genistein and cell toxicant reagent: the co-administered of vincristine and etoposide is compared to cause that more the HS-MXT tumor growth significantly slows down with using genistein (not having corresponding clinical effectiveness) or back two kinds of cell toxicant reagent separately.
4.2. lymphoma P388:
At the 0th day (D
0), go into right flank for the CDF1 mouse subcutaneous transplanting in 4 to 6 ages in week P 388 tumor biopsies (deriving from the tumor storehouse of keeping in the laboratory).In order to make condition approach clinical practice, we wait until and transplant the 5th day (D in back
5) the ability begin treatment.Its reason is, this time after date, tangible the arriving of subcutaneous P 388 tumors.
For example, it is as follows to obtain experimental result by genistein independent or that be used in combination with vincristine.
Treatment 1
Individually dosed genistein.The 5th day (D after transplanting
5) continuous 5 weeks inject this product for the first time with the frequency of injecting 5 times (Monday, Tuesday, Wednesday, Thursday and Fridays) weekly and with the dosage of 40mg/kg.
Treatment 2
Individually dosed vincristine (VCR).The 5th day (D after transplanting
5) continuous 3 weeks are with the frequency of 3 times weekly (Monday, Wednesday and Fridays) and carry out the injection first time of this product with the dosage of 0.63mg/kg.
Treatment 3
Co-administered genistein and vincristine.In the case, the 5th day (D after transplanting
5) continuous 5 weeks inject genistein for the first time, the 5th day (D after transplanting with the frequency of injecting 5 times (Monday, Tuesday, Wednesday, Thursday and Fridays) weekly and with the dosage of 40mg/kg
5) continuous 3 weeks are with the frequency of 3 times weekly (Monday, Wednesday and Fridays) and carry out the injection first time of vincristine with the dosage of 0.63mg/kg.
The mice time-to-live that above-mentioned treatment 1,2 and 3 obtains the results are shown in Table V:
Table V
| Treatment | T/C (representing) with % |
| 1 (genistein) | 125 |
| 2(VCR) | 122 |
| 3 (genistein+VCR) | 169 |
These results show genistein and vincristine co-administered, for the mean survival time of median mice in the control group mice, have increased the mean survival time of median mice in each treatment group mice very significantly.In addition, the median mice mean survival time in the co-administered treatment group mice is longer than the mean survival time of respectively organizing the median mice in the mice of independent use genistein or vincristine treatment very significantly.
As follows by the mode example that in single or comprehensive chemotherapy regimen, uses formula I chemical compound that cell toxicant reagent carries out.
A. solid tumor
1/ pulmonary carcinoma
1.1. non-small cell tumor (late period):
-for the scheme (T.Le Chevalier etc., the J.Clin.Oncol.1994 that recommend; 12:360-367), add the venous transfusion of genistein or another kind of osajin:
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1、D 8、D 15、 D 22、D 29And D 36 |
| navelbine | 30mg/m 2/ day | Intravenous injection | D 1、D 8、D 15、 D 22、D 29And D 36 |
| Cisplatin | 120mg/m 2 | Intravenous injection | D 1And D 29 |
Repeat this course of treatment 8 times.
1.2. small cell tumor (late period):
-for the scheme CAV or VAC (B.J.Roth etc., the J.Clin.Oncol.1992 that recommend; 10:282-291), increase the osajin transfusion:
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1 |
| Cyclophosphamide | 1000mg/m 2Bolus injection | Intravenous injection | D 1 |
| Amycin | 40 to 50mg/m 2Bolus injection | Intravenous injection | D 1 |
| Vincristine | 1 to 1.4mg/m 2Bolus injection (maximum 2mg) | Intravenous injection | D 1 |
Per 21 days of this course of treatment repeated 6 times.
-for the Pt-E scheme (B.J.Roth etc., the J.Clin.Oncol.1992 that recommend; 10:282-291), increase the genistein transfusion:
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 5 |
| Cisplatin | 20mg/m 2/ day transfusion 20 to 60 minutes | Intravenous injection | D 1-D 5 |
| Etoposide | 80mg/m 2/ day transfusion 60 minutes | Intravenous injection | D 1-D 5 |
Repeat each circulation every 21 days and comprise 6 circulations each course of treatment.
1.3. local late period of non-small cell bronchus or metastatic carcinoma:
Single chemotherapy:
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1、D 8、D 15, then 1 the week/rest |
| Gemcitabine | 1000mg/m 2/ day transfusion 0.5 hour | Intravenous injection | D 1、D 8、D 15, then 1 the week/rest |
Can comprise that this 4 all circulation repeats this course of treatment.
Gemcitabine/cisplatin combination:
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 5、D 8-D 15 |
| Gemcitabine | 1000mg/m 2/ day transfusion 0.5 hour | Intravenous injection | D 1、D 8、D 15 |
| Cisplatin | 20mg/m 2/ day transfusion 20-60 minute | Intravenous injection | D 1 |
Comprise this course of treatment and repeated this circulation every 21 days.
2/ breast carcinoma
CMF scheme (G.Bonnadonna etc., the N.Engl.J.Med. of the auxiliary treatment of-conduct operation back breast carcinoma; 1976; 294:405-410):
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 14 |
| Cyclophosphamide | 100mg/m 2/ day | Oral | D 1-D 14 |
| Methotrexate | 40mg/m 2Bolus injection | Intravenous injection | D 1And D 8 |
| 5-FU | 600mg/m 2 | Intravenous injection | D 1And D 8 |
Repeat each circulation every 28 days, and comprise 6 circulations this course of treatment.
-AC scheme (B.Fisher etc., J.Clin.Oncol.; 1990; 8:1483-1496), as auxiliary therapy:
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1 |
| Amycin | 60mg/m 2Bolus injection | Intravenous injection | D 1 |
| Cyclophosphamide | 600mg/m 2Bolus injection | Intravenous injection | D 1 |
Repeat each circulation every 21 days, and comprise 4 circulations this course of treatment.
The breast carcinoma of-transfer:
-the FAC scheme (A.U.Buzdar etc., Cancer 1981; 47:2537-2542) and various changing form, increase the transfusion of osajin according to following (non-limiting) scheme:
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 5And D 8-D 12Or D 1-D 5 |
| 5-FU | 500mg/m 2/ day bolus injection | Intravenous injection | D 1And D 8Or D 1- D 2 |
| Amycin | 50mg/m 2Bolus injection | Intravenous injection | D 1Or D 1And D 2 |
| Cyclophosphamide | 500mg/m 2 | Bolus injection intravenous injection or oral | D 1D 1 |
Every repeating each circulation 3 weeks till new progress appears in this disease of diagnosis.
-CAF scheme (G.Falkson etc., Cancer 1985; 56:219-224):
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 14 |
| Cyclophosphamide | 100mg/m 2/ day | Oral | D 1-D 14 |
| Amycin | 30mg/m 2Bolus injection | Intravenous injection | D 1And D 8 |
| 5-FU | 500mg/m 2Bolus injection | Intravenous injection | D 1And D 8 |
Repeated each circulation till new progress appears in this disease of diagnosis every 28 days.
-CMF scheme:
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 5And D 8-D 12 |
| Cyclophosphamide | 600mg/m 2/ day bolus injection | Intravenous injection | D 1And D 8 |
| Methotrexate | 40mg/m 2/ day bolus injection | Intravenous injection | D 1And D 8 |
| 5-FU | 600mg/m 2/ day bolus injection | Intravenous injection | D 1And D 8 |
Repeat this circulation every 3 to 5 weeks, and comprise 6 circulations each course of treatment.
-CMF-VP scheme:
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 5，D 8-D 12， D 15-D 19，D 22-D 26 |
| Cyclophosphamide | 2 to 2.5mg/kg/ days | Oral | Every day |
| Methotrexate | 25 to 50mg/m 2/ day | Intravenous injection | D 1，D 8，D 15，D 22 |
| 5-FU | 300 to 500mg/m 2/ day | Intravenous injection | D 1，D 8，D 15，D 22 |
| Vincristine | 0.6 to 1.2mg/m 2/ day | Intravenous injection | D 1，D 8，D 15，D 22 |
| Prednisone | 30mg/m 2/ day | Oral | By D 1To D 10 |
Repeat this course of treatment every 4 weeks.
-FEC scheme:
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 5And D 8-D 12 |
| 5-FU | 600mg/m 2/ day | Intravenous injection | D 1And D 8 |
| Epirubicin | 50mg/m 2 | Intravenous injection | D 1 |
| Cyclophosphamide | 600mg/m 2 | Intravenous injection | D 1 |
Repeat this course of treatment every 3 weeks.
-in MMC-VBC scheme (C.Brambilla etc., Tumori, 1989; 75:141-144):
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 5And D 15-D 19 |
| Ametycin | 10mg/m 2Bolus injection | Intravenous injection | D 1 |
| Vinblastine | 50mg/m 2/ day bolus injection | Intravenous injection | D 1And D 15 |
Repeated this course of treatment till progress appears in this disease of diagnosis every 28 days.
-at NFL scheme (S.E.Jones etc., J.Clin.Oncol.1991; 9:1736-1739):
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 5 |
| Mitoxantrone | 10mg/m 2Bolus injection | Intravenous injection | D 1 |
| 5-FU | 1000mg/m 2Infused 24 hours | Intravenous injection | D 1-D 3 |
| Formyl tetrahydrofolic acid | 100mg/m 2Bolus injection | Intravenous injection | D 1 |
Comprise two circulations this course of treatment, be spaced apart 21 days, need then to estimate.
When using taxoid, also can treat the breast carcinoma of transfer in conjunction with the transfusion of osajin, for example:
-in may having drug-fast treatment, adopt paclitaxel (F.A.Holmes etc., J.Natl Cancer Inst.1991 to the anthracene nucleus class with the form that shifts; 83:1797-1805):
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 5 |
| paclitaxel | 175mg/m 2Infused 3 to 24 hours | Intravenous injection | D 1 |
Repeated this circulation till new development appears in this disease of diagnosis every 21 days.
-local late period or metastatic breast cancer develops immunity to drugs after cytotoxicity chemotherapy (comprising the anthracene nucleus class) or recurs or recur during auxiliary treatment, uses docetaxel:
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 5 |
| docetaxel | 100mg/m 2Or 60-100mg/m 2Infuse 1 hour (or 24 hours) | Intravenous injection | D 1 |
Repeat this circulation every 21 days, comprise 2 circulations per course of treatment or till progress appears in this disease.
-in strengthening dosage, in conjunction with self medullary cell and autologous peripheral blood stemcell transplant, Zhi Liao consolidation phase in the early stage, for example:
-CPB scheme (W.P.Peters etc., J.Clin.Oncol.1993; 11:132-1143), wherein at D
-1, D
0And D
1It carries out the stem cell intravenous infusion:
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D -6-D -1 |
| Cyclophosphamide | 1875mg/m 2Infused 1 hour | Intravenous injection | D -6-D -4 |
| Cisplatin | 55mg/m 2/ day continuous transfusion 24 hours | Intravenous injection | D -6-D -4 |
| Carmustine (BCNU) | 600mg/m 2/ day transfusion 2 hours | Intravenous injection | D -3 |
-CTCb scheme (K.Antman etc., J.Clin.Oncol.1992; 10:102-110),
Wherein at D
0It carries out the intravenous infusion of stem cell:
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D -7-D -1 |
| Cyclophosphamide | 1500mg/m 224 hours (4 dosage) of continuous transfusion | Intravenous injection | D -7-D -3 |
| Thiophene is for group | 125mg/m 224 hours (4 dosage) of continuous transfusion | Intravenous injection | D -7-D -3 |
| Carboplatin | 200mg/m 224 hours (4 dosage) of continuous transfusion | Intravenous injection | D -7-D -3 |
-CTM scheme (L.E.Damon etc., J.Clin.Oncol.1989; 7:560-571 and I.C.Henderson etc., J.Cellular Biochem.1994 (Suppl 18B): 95), wherein at D
0It carries out the intravenous infusion of hematopoietic stem cell:
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D -6-D -1 |
| Cyclophosphamide | 1500mg/m 2/ day transfusion 1 hour | Intravenous injection | D -6-D -3 |
| Thiophene is for group | 150mg/m 2/ day transfusion 2 hours | Intravenous injection | D -6-D -3 |
| Mitoxantrone | 10-15mg/m 2Infused 1 hour | Intravenous injection | D -6-D -3 |
3/ gynecological cancer
3.1. ovarian cancer:
-treatment ovarian tumor, particularly shift:
I) PAC scheme (G.A.Omura etc., J.Clin.Oncol.1989; 7:457-465): carry out the transfusion of osajin according to following scheme:
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 5 |
| Cisplatin | 50mg/m 2(or 40-90mg/m 2) infused 1 to 2 hour | Intravenous injection | D 1 |
| Amycin | 50mg/m 2(or 30 to 50mg/m for bolus injection 2) | Intravenous injection | D 1 |
| Cyclophosphamide | 1000mg/m 2Infusing, (or 200 to 600mg/m in 1 to 2 hour 2) | Intravenous injection | D 1 |
Repeat this circulation every 21 to 28 days, and comprise 8 circulations this course of treatment.
Ii) altretamine scheme is according to (Gynecol.Oncol.1990 such as A.Marietta; 36:93-96):
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 5，D 8-D 12 |
| Altretamine | 200mg/m 2/ day, be divided into 4 dosage | Oral | D 1-D 15 |
Comprise two circulations this course of treatment, be spaced apart 28 days.
Iii) Paclitaxel scheme: can be to (Ann.Intern.Med.1989 such as W.P.McGuire; 111:273-279) add osajin in the paclitaxel scheme of Miao Shuing:
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 3 |
| paclitaxel | 135mg/m 2Infused 3 hours or 24 hours | Intravenous injection | D 1 |
Comprise two such circulations this course of treatment, be spaced apart 28 days (estimating at last).
-treatment transitivity and obstinate ovarian tumor, can add osajin in the secondary scheme of bearing to replacing based on the holder pool:
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 5 |
| The holder pool is for bearing | 1.5mg/m 2/ day transfusion 0.5 hour | Intravenous injection | D 1-D 5 |
According to (J.Clin.Oncol.1996 such as A.P.Kudelka; 14:1552-1557), comprise two circulations this course of treatment, be spaced apart 21 days (estimating at last).
3.2 trophoblastic tumor:
-for the low patient of onset risk, can be with osajin in conjunction with (Semin.Surg.Oncol.1987 such as H.Takamizawa; 3:36-44) the scheme of Miao Shuing:
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 5 |
| Methotrexate (MTX) | 20mg/ days | Intramuscular injection | D 1-D 5 |
| D actinomycin D (DACT) | 0.5mg/ it bolus injection | Intravenous injection | D 1-D 5 |
(MTX-DATC scheme).
3.3 uterus carcinoma:
-can also combine with CAV (or VAC) scheme according to following scheme osajin:
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 3 |
| Cyclophosphamide | 750-1200mg/m 2Transfusion | Intravenous injection | D 1 |
| Amycin | 45-50mg/m 2Transfusion | Intravenous injection | D 1 |
| Vincristine | 1.4mg/m 2 | Intravenous injection | D 1 |
Comprise this course of treatment and repeated this circulation every 21 days.
-in the FAP scheme:
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 5 |
| 5-fluorouracil (5-FU) | 600mg/m 2/ day | Intravenous injection | D 1，D 8 |
| Amycin | 30mg/m 2 | Intravenous injection | D 1 |
| Cisplatin | 75mg/m 2 | Intravenous injection | D 1 |
Comprise this course of treatment and repeated this circulation every 21 or 28 days.
4/ carcinoma of testis and carcinoma of prostate
-osajin can also combine with the carcinoma of testis scheme:
The BEP scheme:
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 5 |
| Bleomycin | 30mg/m 2Transfusion | Intravenous injection | D 1 |
| Etoposide | 100mg/m 2/ day transfusion | Intravenous injection | D 1-D 5 |
| Cisplatin | 20mg/m 2/ day | Intravenous injection | D 1-D 5 |
Comprise 3 circulations this course of treatment, frequency is circulation in per 21 days 1.
5/ bladder cancer
-osajin also can combine with CISCA2 (being also referred to as PAC) scheme:
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 5 |
| Cisplatin | 50mg/m 2 | Intravenous injection | D 1 |
| Cyclophosphamide | 60mg/m 2Transfusion | Intravenous injection | D 1 |
| Amycin | 75mg/m 2Transfusion | Intravenous injection | D 1 |
This circulation repeated every 3 weeks.
-MVAC scheme is (according to C.N.Sternberg etc., J.Urol.1988; 139:461-469):
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 3，D 15-D 18，D 22- D 25 |
| Methotrexate | 30mg/m 2Bolus injection | Intravenous injection | D 1，D 15，D 22 |
| Vincristine | 3mg/m 2 | Intravenous injection | D 2Or D 2，D 15，D 22 |
| Amycin | 30mg/m 2Bolus injection | Intravenous injection | D 2 |
| Cisplatin | 70-100mg/m 2Infused 1 hour | Intravenous injection | D 1Or D 2 |
Repeat this circulation, minimum 2 circulations every 4 to 5 weeks.
6/ rhinopharyngeal neoplasm/head and neck cancer
-osajin can combine with the comprehensive chemotherapy regimen that is used for these treatments of cancer:
6.1 nasopharyngeal carcinoma:
-ABVD scheme:
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 3，D 8-D 10Or D 15-D 17 |
| Amycin | 30mg/m 2/ day | Intravenous injection | D 1And D 8Or D 15 |
| Bleomycin | 10mg/m 2/ day | Intravenous injection | D 1And D 8Or D 15 |
| Vinblastine | 6mg/m 2/ day | Intravenous injection | D 1And D 8Or D 15 |
| Dacarbazine | 200mg/mu/ days | Intravenous injection | D 1And D 8Or D 15 |
Comprise 1 to 6 circulation this course of treatment, repetition rate is per 4 week 1 circulations.
6.2 the head and neck cancer that shifts:
-in Pt-FU scheme (for example, for pharyngeal cancer): according to (the New of DVAL seminar
Engl.J.M.1991; Method 324:1685-1690):
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 5 |
| Cisplatin | 100mg/m 2Infused 1 hour | Intravenous injection | D 1 |
| 5-fluorouracil (5-FU) | 1000mg/m 2/ sky is transfusion continuously | Intravenous injection | D 1-D 5 |
Comprise 2 circulations this course of treatment, frequency is per 3 week 1 circulation.
7/ soft tissue sarcoma
-osajin is introduced in scheme such as the CYVADIC scheme:
-(Cancer 1984 according to H.M.Pinedo etc.; 53:1825):
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 5，D 8-D 10Or D 15-D 17 |
| Cyclophosphamide (Cy) | 500mg/m 2Bolus injection | Intravenous injection | D 2 |
| Vincristine (V) | 1.5mg/m 2/ day bolus injection | Intravenous injection | D 1，D 8，D 15 |
| Amycin (A) | 50mg/m 2Bolus injection | Intravenous injection | D 2 |
| Dacarbazine (DIC) | 250mg/m 2/ day transfusion 15 minutes | Intravenous injection | D 1-D 5 |
Comprise this course of treatment and per 4 weeks repeat this circulation, carry out 2 circulations earlier.
The 8/ anti-hormone carcinoma of prostate that shifts
-VBL-estramustine scheme, according to (J.Clin.Oncol.1992:10:1754-1761) such as G.R.Hudis:
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 3，D 8-D 10， D 15-D 17，D 22-D 24， D 29-D 31，D 36-D 38 |
| Vinblastine | 4mg/m 2/ day bolus injection | Intravenous injection | D 1，D 8，D 15，D 22， D 29，D 36 |
| Estramustine | 200mg/m 2, 3 times on the 1st (600mg/m 2/ day) | Oral | Every day in six weeks |
This treatment circulation continued for 6 weeks, was the interval in 2 weeks thereupon.
9/ blastocyte cancer
I) for the favourable tumor of prognosis:
-Pt-E scheme is according to (J.Clin.Oncol.1988 such as G.J.Bosl; 6:1231-1238):
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 5 |
| Cisplatin (Pt) | 20mg/m 2/ day transfusion 20 to 60 minutes | Intravenous injection | D 1-D 5 |
| Etoposide (E) | 100mg/m 2/ day transfusion 1 hour | Intravenous injection | D 1-D 5 |
Comprise 4 circulations this course of treatment, frequency is 1 circulation in per 21 or 28 days.
Ii) for the tumor that shifts
-PEB scheme is according to (N.Eng.J.Med.1987 such as S.D.Williams; 316:1435-1440):
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 3，D 9-D 11， D 16-D 18 |
| Cisplatin (P) | 20mg/m 2/ day transfusion 20 to 60 minutes | Intravenous injection | D 1-D 5 |
| Etoposide (E) | 100mg/m 2/ day transfusion 1 hour | Intravenous injection | D 2，D 9，D 16 |
| Bleomycin (B) | 30U (or mg)/sky bolus injection | Intravenous injection | D 1-D 5 |
Comprise 4 circulations this course of treatment, frequency is circulation in per 21 days.
10/ renal carcinoma
The renal carcinoma of-transfer: osajin can be incorporated into (Cancer1993 such as M.J.Wilkinson; 71:3601-3604) in the scheme of Miao Shuing:
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 5，D 8-D 15 |
| Floxuridine | 0.075mg/kg/ it is transfusion continuously | Intravenous injection | D 1-D 14 |
Comprise 2 circulations this course of treatment, be spaced apart 28 days.
-nephroblastoma: osajin is introduced the DAVE scheme:
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 3，D 8-D 10 |
| Actinomycin D | 0.6mg/m 2/ day | Intravenous injection | D 1，D 8 |
| Amycin | 30mg/m 2/ day | Intravenous injection | D 1，D 8 |
| Cyclophosphamide | 200mg/m 2/ day transfusion 1 hour | Intravenous injection | D 1，D 8 |
Per 3 to 4 Mondays of a circulation.
11/ alimentary tract cancer
11.1 esophageal carcinoma
-osajin can be introduced the FAP scheme, according to:
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 3，D 8-D 10 |
| 5-fluorouracil (5-FU) | 600mg/m 2 | Intravenous injection | D 1，D 8 |
| Amycin | 30mg/m 2 | Intravenous injection | D 1 |
| Cisplatin | 75mg/m 2 | Intravenous injection | D 1 |
Repeat this circulation every 3 to 4 weeks.
11.2 gastric cancer
-late and/or in the gastric cancer that shifts:
-EAP scheme is (according to P.Preusser etc., J.Clin.Oncol.1989; 7:1310):
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 5，D 8-D 10 |
| Etoposide | 120mg/m 2/ day transfusion 1 hour | Intravenous injection | D 3，D 4，D 5Or D 4-D 6 |
| Amycin | 20mg/m 2/ day bolus injection | Intravenous injection | D 1，D 7 |
| Cisplatin | 40mg/m 2/ day transfusion 1 hour | Intravenous injection | D 2，D 8 |
1 circulation in per 28 days.
-FAMtx scheme: according to (J.Clin.Oncol.1991 such as J.A.Wils; 89:827):
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 3 |
| Fluorouracil (5-FU) (F) | After the methotrexate administration 1 hour, 1500mg/m 2Bolus injection | Intravenous injection | D 1 |
| Amycin (A) | 30mg/m 2Bolus injection | Intravenous injection | D 15 |
| Methotrexate (Mtx) | 1500mg/m 2Infused 30 minutes | Intravenous injection | D 1 |
Comprise two circulations this course of treatment earlier, be 28 days interval.
-in some patient's body, this scheme or its version (replacing amycin with epirubicin) can use according to following manner:
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 3 |
| Fluorouracil (5-FU) | 1500mg/m 2 | Intravenous injection | D 1 |
| Amycin (A) or epirubicin (E) | 30mg/m 2Bolus injection 60mg/m 2Bolus injection | The intravenous injection intravenous injection | D 1＝FAMTx D 1＝FEMTx |
| Methotrexate (before 5-FU, infusing) | 1500mg/m 2 | Intravenous injection | D 1 |
| Formyl tetrahydrofolic acid | 15mg/m 2/ day | Oral | D 2-D 4 |
12/ colorectal cancer
-osajin can be introduced the FU-levamisole supplemental treatment regimens of colorectal cancer (according to C.G.Moertel etc., N.Eng.J.Med.1990; 322:352):
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 5，D 29-D 31 |
| 5-fluorouracil | 450mg/m 2/ day bolus injection | Intravenous injection | D 1-D 5 |
| 5-fluorouracil | 450mg/m 2Bolus injection | Intravenous injection | D 29 |
| Levamisole | 50mg, every day three times | Oral | 3 days/week, every other week |
Inductive phase D
1-D
5After, repeat weekly in 52 weeks with the treatment of 5-FU bolus injection; On the same day of 5-FU bolus injection, then, repeat the osajin treatment with identical frequency subsequently 2 days.
-in order to treat the colorectal cancer that treatment has resistance and takes place to shift for 5-uracil (5-FU):
-according to (J.Clin.Oncol.1996 such as M.L.Rothenberg; 14:1128-1135):
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 3，D 8-D 10， D 15-D 17，D 22-D 24 |
| Irinotecan | 125mg/m 2/ day | Intravenous injection | D 1，D 8，D 15，D 22 |
Comprise two circulations this course of treatment, be 42 days interval.
13/ Kaposi
-osajin can combine with two kinds of schemes that use is formulated as the anthracene nucleus class of liposome form:
I) (J.Clin.Oncol.1995 such as P.S.Gill; 13:996-1003) and C.A.Presant etc. (Lancet 1993; 341:1242-1243) the scheme of Miao Shuing:
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 3And D 15-D 17 |
| Daunorubicin liposome | 20mg/m 2/ day transfusion 1 hour | Intravenous injection | D 1，D 15 |
Before evaluation effect, comprise that with 28 days be multiple two circulations at interval this course of treatment.
Ii) (J.Clin.Oncol.1995 such as M.Harrison; Scheme 13:914-920):
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 3 |
| Evacet | 20mg/m 2Infused 30 minutes | Intravenous injection | D 1 |
Before evaluation effect, comprise that with 28 days be multiple two circulations at interval this course of treatment.
14/ metastatic melanoma
-osajin can also be participated in the association scheme of treatment metastatic malignant melanoma:
-DTIC/TAM scheme: according to (N.Eng.J.Med.1992 such as G.Cocconi; 327516), comprise multiple 4 circulations this course of treatment, frequency is circulation in per 21 days 1, according to following scheme:
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 5 |
| Dacarbazine (DTIC) | 250mg/m 2/ day transfusion [if center conduit, 15 to 30 minutes] or [if periphery transfusion 250ml then 30 minutes] | Intravenous injection | D 1-D 5 |
| Tamoxifen (TAM) | 20mg/m 2/ day | Oral | D 1-D 5 |
Comprise 4 circulations this course of treatment, frequency is 1 circulation in per 21 days.
15/ neuroendocrine tumor
-osajin can (Cancer 1991 with C.G.Moertel etc.; 68:227) the scheme combination of Miao Shuing:
-Pt-F scheme:
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 3 |
| Etoposide | 130mg/m 2/ day transfusion 1 hour | Intravenous injection | D 1-D 3 |
| Cisplatin | 45mg/m 2/ day transfusion 1 hour | Intravenous injection | D 2，D 3 |
Multiple two circulations that comprise per 28 days this course of treatment.
16/ cancer of pancreas
-late period the pancreas adenoma: osajin can be treated with gemcitabine and be combined, according to (Proc.Am.Soc.Clin.Oncol.1995 such as M.Moore; Scheme 14:473):
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 3，D 8-D 10，D 15， D 22，D 29，D 36，D 43， D 57 |
| Gemcitabine | 100mg/m 2Infused 0.5 hour | Intravenous injection | D 1，D 8，D 15，D 22，D 29， D 36，D 43，D 57, in then weekly continuous 3 weeks, then stopped for 1 week, and estimate |
B. neoplastic hematologic disorder
1/ acute one-tenth human leukemia
1.1. acute lymphoblastic leukemia
1.1.1.Linker scheme
Osajin can add the Linker scheme to, promptly induces chemotherapy and consolidates that (see C.A.Linker etc., Blood 1987 in the chemotherapy; 69:1242-1248 and C.A.Linker etc., Blood1991; 78:2814-2822), according to following scheme:
I) induce chemotherapy:
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 5，D 8-D 12， D 15-D 19 |
| Daunorubicin | Every 24 hours bolus injection 50mg/m 2(30mg/m in the patient's body more than 50 years old 2) | Intravenous injection | D 1，D 2，D 3 |
| Vincristine | The 2mg bolus injection | Intravenous injection | D 1，D 8，D 15，D 22 |
| Prednisone | 60mg/m 2/ day | Oral | D 1-D 28 |
| The altheine enzyme | 6000U/m 2 | Intramuscular injection | D 17-D 28 |
Ii) consolidate chemotherapy (option A):
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 5，D 8-D 12 |
| Daunorubicin | Every 24 hours bolus injection 50mg/m 2 | Intravenous injection | D 1，D 2 |
| Vincristine | The 2mg bolus injection | Intravenous injection | D 1，D 8 |
| Prednisone | 60mg/m 2/ day, be divided into 3 dosage | Oral | D 1-D 14 |
| The altheine enzyme | 12000U/m 2 | Intramuscular injection | D 2，D 4，D 7，D 9And D 14 |
Consolidate chemotherapy A and comprise 4 successive circulations, as mentioned above=circulation 1,3,5 and 7.
Iii) consolidate chemotherapy (option b and C):
This scheme is described below, corresponding to consolidating circulation 2,4,6 and 8 (option bs) and 9 (scheme C), by descriptions such as C.A.Linker:
Option b:
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 5，D 8-D 12 |
| Ara-C | 300mg/m 2Infused 2 hours | Intravenous injection | D 1，D 4，D 8，D 11 |
| Teniposide | 165mg/m 2Infuse 2 hours (4 circulations) | Intravenous injection | D 1，D 4，D 8，D 11 |
Scheme C:
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 5 |
| Methotrexate | 690mg/m 2Transfusion is 42 hours continuously | Intravenous injection | D 1-D 2 |
| Formyl tetrahydrofolic acid | 15mg/m 2Per 6 hours | Oral | D 2-D 5 |
1.1.2.Hoelzer scheme
Product required for protection can be added in the cell toxicant reagent of this comprehensive chemotherapy regimen (D.Hoelzer etc., Blood 1984,64:38-47; D.Hoelzer etc., Blood 1988; 71:123-131), according to following scheme:
I) induce chemotherapy/stage 1:
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 5，D 8-D 12， D 15-D 19 |
| Daunorubicin | 25mg/m 2 | Intravenous injection | D 1，D 8，D 15，D 22 |
| Vincristine | 1.5mg/m 2(maximum 2mg) | Intravenous injection | D 1，D 8，D 15，D 22 |
| Prednisone | 60mg/m 2 | Oral | D 1-D 28 |
| The altheine enzyme | 5000U/m 2(maximum 2mg) | Intramuscular injection | D 1-D 14 |
Ii) induce chemotherapy/stage 2:
Induce the stage 2 of chemotherapy followingly to carry out:
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 29-D 33，D 36-D 40， D 43-D 47 |
| Cyclophosphamide | 650mg/m 2(maximum 1000mg) | Intravenous injection | D 29，D 43，D 57 |
| Cytosine arabinoside | 75mg/m 2/ day transfusion 1 hour | Intravenous injection | D 31-D 34，D 38-D 41， D 45-D 48，D 52-D 55 |
| Purinethol | 60mg/m 2 | Oral | D 29-D 57 |
| Methotrexate | 10mg/m 2/ day (maximum 15mg) | Intravenous injection | D 31，D 38，D 45，D 52 |
Iii) induce again chemotherapy/stage 1:
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 5，D 8-D 12， D 15-D 19，D 22-D 26 |
| Amycin | 25mg/m 2/ day | Intravenous injection | D 1，D 8，D 15，D 22 |
| Dexamethasone | 10mg/m 2/ day | Oral | D 1-D 28 |
| Vincristine | 1.5mg/m 2/ day (maximum 2mg) | Oral | D 1，D 8，D 15And D 22 |
Iv) induce again chemotherapy/stage 2:
Induce the stage 2 of chemotherapy followingly to carry out:
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 31-D 35，D 38-D 42 |
| Cyclophosphamide | 650mg/m 2(maximum 1000mg) | Intravenous injection | D 29 |
| Cytosine arabinoside | 75mg/m 2 | Intravenous injection | D 31-D 34，D 38-D 41 |
| Thioguanine | 60mg/m 2 | Oral | D 29-D 42 |
1.2. acute myeloid leukemia:
1.2.1. the adult's at any age treatment
According to following scheme, osajin can be added in the past by (Blood, 1991 such as R.O.Dilleman; 78:2520-2526), (Leukemia 1990 for Z.A.Arlin etc.; 4:177-183) and P.H.Wiernik etc. (Blood 1992; 79:313-319) describe in the therapeutic process that utilizes the enforcement of standard dose cytosine arabinoside:
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 12 |
| Cytosine arabinoside | 100-200mg/m 2/ sky is transfusion continuously | Intravenous injection | D 1-D 7 |
| Daunorubicin or mitoxantrone or idarubicin | 45mg/m 2/ day bolus injection is (if the age is not less than 60 years old then 30mg/m 2/ day) 12mg/m 2Every day bolus injection 13mg/m 2Every day bolus injection | Intravenous injection intravenous injection intravenous injection | D 1-D 3Or D 8-D 10D 1- D3 D 1-D 3 |
1.2.2. the age is less than 60 years old adult's treatment
I) induce chemotherapy:
This induces circulation to comprise according to following scheme administration high dose cytosine arabinoside:
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 10 |
| AFa-C (cytosine arabinoside) | 2000mg/m 2/ day transfusion in per 12 hours 2 hours | Intravenous injection | D 1-D 6 |
| Daunorubicin or cytosine arabinoside | 60mg/m 2/ day 24 hours 3000mg/m of continuous transfusion 2/ day transfusion in per 12 hours 1 hour | The intravenous injection intravenous injection | D 4-D 6 D 1-D 6 |
| Daunorubicin | 45mg/m 2Per 24 hours bolus injections | Intravenous injection | D 7-D 9 |
(in order to reduce central nervous system's toxicity, under the situation of renal insufficiency, adjust cytosine arabinoside dosage to kreatinin and clean up), (Leukemia 1994 according to L.E.Damon etc.; 8:535-541), (Blood 1991 for G.L.Phillips etc.; 77:1492-1435) and (J.Clin.Oncol.1997 such as G.Smith; 15:833-839).
Ii) consolidate chemotherapy:
Following circulation will repeat 8 times, frequency be per 4 to 6 week 1 circulation (according to R.J.Mayer etc., N.Engl J.Med.1994; 331:896-903):
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 5 |
| Cytosine arabinoside is cytosine arabinoside then | 3000mg/m 2Every 3 hours (4 circulations) per 12 hours 100mg/m of transfusion in 12 hours 2/ day | The intravenous injection subcutaneous injection | D 1，D 3，D 5D 1-D 5 |
| Daunorubicin | 45mg/m 2Bolus injection (4 circulations) | Intravenous injection | D 1 |
Iii) consolidate chemotherapy (using HDAC):
Following circulation will repeat twice, and (Blood 1991 according to G.L.Phillips etc.; 77:1429-1435); (J.Clin.Oncol.1989 such as S.N.Wolff; 7:1260-1267); (N.Engl J.Med.1994 such as R.J.Mayer; 331:896-903) carry out.
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 10 |
| Cytosine arabinoside | 3000mg/m 2Transfusion in per 12 hours 1 hour | Intravenous injection | D 1-D 6 |
| Daunorubicin | 30-45mg/m 2/ day bolus injection is once a day | Intravenous injection | D 7-D 9 |
1.2.3.60 above adult's of year treatment
The material that requires to protect can be added to following the consolidation in the chemotherapy regimen:
I) (Blood 1991 according to R.O.Dilman etc.; 78:2520-2526), (Leukemia 1990 for Z.A.Arlin etc.; 4:177-183), (Blood 1992 for P.H.Wiernik etc.; 79:313-319):
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 6 |
| Cytosine arabinoside | 100-200mg/m 2Transfusion is 24 hours continuously | Intravenous injection | D 1-D 5 |
| Daunorubicin or mitoxantrone or idarubicin | 30-45mg/m 2/ day bolus injection 12mg/m 2/ day bolus injection 12mg/m 2/ day bolus injection | Intravenous injection intravenous injection intravenous injection | D 1，D 2D 1，D 2D 1，D 2 |
Ii) according to (N.Engl.J.Med.194 such as R.J.Mayer; 331:896-903):
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 6 |
| Cytosine arabinoside is cytosine arabinoside then | 100mg/m 224 hours (4 circulations) per 12 hours 100mg/m continuously infuse 2 | The intravenous injection subcutaneous injection | D 1-D 5 D 1，D 5 |
| Daunorubicin | 45mg/m 2/ day bolus injection (4 circulations) | Intravenous injection | D 1 |
Iii) (Blood 1993 according to C.A.Linker etc.; 81:311-318), (Blood 1993 for N.Chao etc.; 81:319-323) and (N.Eng.J.Med.1986 such as A.M.Yeager; 315:145-147):
This scheme comprises that autologous bone marrow transplantation is (at D
0It carries out):
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D -7-D -2 |
| Busulfan | 1mg/kg every day four times (totally 16 dosage) | Oral | D -7-D -4 |
| Etoposide | 60mg/m 2/ day transfusion 10 hours | Intravenous injection | D -3 |
Or
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D -9-D -1 |
| Busulfan | 1mg/kg every day four times | Oral | D -9-D -6 |
| Cyclophosphamide | 50mg/m 2/ day transfusion 1 hour | Intravenous injection | D -5-D -2 |
Iv) be harmonious under the situation of allogeneic bone marrow transplantation with HLA, according to:
P.J.Tutscha etc., Blood 1987; 70:1382-1388,
F.R.Applebaum etc., Ann.Int.Med.1984; 101:581-588:
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D -7-D -1 |
| Busulfan | 1mg/kg every day four times (totally 16 dosage) | Oral | D -7-D -4 |
| Cyclophosphamide | 60mg/m 2/ day transfusion 1 hour | Intravenous injection | D -3-D -2 |
2/ chronic one-tenth human leukemia
2.1 chronic granulocytic leukemia
In the myeloblast phase, osajin can be added to by (N.Engl.J.Med.1986 such as C.A.Koller; In the HU-Mith treatment of 315:1433-1438) describing:
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 5，D 8-D 12， D 15-D 19，D 22-D 26 |
| Hydroxyurea | 500mg/ days | Oral | Every day |
| Mithramycin | Transfusion in 25 μ g/kg/ days 2-4 hour | Intravenous injection | Every days in 3 weeks, weekly 3 times then |
2.2. chronic lymphocytic leukemia
2.2.1 FCG-CLL scheme
Osajin can join E.Kimby etc., and (Leuk.Lymphoma 1991; 5 (suppl.) 93-96) and FCGCLL (Blood 1990; 75:1422-1425) in " pulsed chlorambucil " cooperative programs of Miao Shuing:
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 5，D -8-D 12， D 15-D 22 |
| Chlorambucil or chlorambucil and prednisone | 0.1mg/kg/ they per 14 days 0.4mg/kg/ days 75mg/ days | Oral oral | D once a day 1 D 1-D 3 |
2.2.2 NSC-118218-CdA scheme
According to (J.Clin.Oncol.1991 such as H.G.Chun; 9:175-188), (Blood 1989 for M.J.Keating etc.; 74:19-25/J.Clin.Oncol.1991; 9:44-49) and (J.Clin.Oncol.1995 such as A.Saven; 13:570-574):
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 8(every month once, 6 to 12 circulations) |
| NSC-118218 or cladibrine (cladibrine) | 25-30mg/m 2/ day transfusion 30 minutes [6 to 12 circulations of per 4 weeks] infused continuously in 0.09mg/kg/ days [1 circulation in per 28 to 35 days, 1 to 9 circulation (intermediate value: 4 circulations)] | The intravenous injection intravenous injection | D 1-D 5D 1-D 7 |
3/ lymphocytic hyperplasia disease
3.1 Hokdkin disease
Osajin can join in the polyvoltine treatment scheme of conventional therapy He Jiejin lymphomas:
3.1.1 AVDB scheme
According to (Cancer Clin.Trials 1979 such as G.Bonnadonna; 2:217-226) and (N.Engl.J.Med.1993 such as G.P.Canellos; 327:1478-1484):
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 3，D 15-D 18 |
| Amycin (A) | 25mg/m 2Bolus injection | Intravenous injection | D 1，D 15 |
| Bleomycin (B) | 10U/m 2Bolus injection | Intravenous injection | D 1，D 15 |
| Vinblastine (V) | 6mg/m 2Bolus injection | Intravenous injection | D 1，D 15 |
| Dacarbazine (D) | 375mg/m 2Bolus injection | Intravenous injection | D 1，D 15 |
Comprise 6 to 8 circulations this course of treatment, frequency is 1 circulation in per 28 days.
3.1.2 MOPP/ABVD scheme
According to (Ann.Intern.Med.1986 such as G.Bonnadonna; 104:739-746) and (N.Engl.J.Med.1993 such as G.P.CaneUos; 327:1478-1484):
The MOPP scheme should hocket with the ABVD scheme (referring to 3.1.1) in per 28 days, and comprised 6 circulations this course of treatment:
The MOPP scheme:
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 3，D 8-D 11And D 14-D 17 |
| Chlormethine (M) | 6mg/m 2Bolus injection | Intravenous injection | D 1，D 8 |
| Vincristine (O) | 1.4mg/m 2Bolus injection (no maximum) | Intravenous injection | D 1，D 8 |
| Procarbazine (P) | 100mg/m 2/ day | Oral | D 1-D 14 |
| Prednisone (P) | 40mg/m 2/ day | Oral | D 1-D 14 |
3.1.3 Stanford V scheme
According to (J.Clin.Oncol.1995 such as N.L.Bartlett; 13:1080-1088):
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 5，D 8-D 12， D 15-D 19，D 22-D 26 |
| Amycin | 25mg/m 2 | Intravenous injection | D 1，D 15 |
| Vinblastine | 6mg/m 2Bolus injection (if the age is not less than 50 years old the circulation 3 in 4mg/m 2) | Intravenous injection | D 1，D 15 |
| Chlormethine (M) | 6mg/m 2Bolus injection | Intravenous injection | D 1 |
| Vincristine | 1.4mg/m 2Bolus injection (maximal dose: 2mg) [if the age is not less than 50 years old the circulation 3 in 1mg/m 2] | Intravenous injection | D 1，D 22 |
| Bleomycin | 5U/m 2 | Intravenous injection | D 8，D 22 |
| Etoposide | 60mg/m 2 | Oral | D 15，D 16 |
| Prednisone (P) | 40mg/m 2/ day | Oral | (1-9 week) once in a week |
Comprise 3 circulations this course of treatment, frequency 1 circulation in per 28 days.
3.1.4 EVA scheme
According to (Proc.Am.Soc.Clin.Oncol.1991 such as G.P.Canellos; 10:273):
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 5 |
| Etoposide (E) | 100mg/m 2Infused 2 hours | Oral | D 1，D 2，D 3 |
| Vinblastine (V) | 6mg/m 2Bolus injection | Intravenous injection | D 1 |
| Amycin | 50mg/m 2Bolus injection | Intravenous injection | D 1 |
Comprise 6 circulations this course of treatment, frequency is 1 circulation in per 28 days.
3.1.5 B-CAVe scheme
According to (Ann.Intern.Med.1984 such as W.G.Harker; 101:440-446):
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 3 |
| Bleomycin (B) | 5U/m 2Bolus injection | Intravenous injection | D 1 |
| Chlorethyl cyclohexyl nitrosourea (CCnu) | 100mg/m 2 | Oral | D 1 |
| Amycin | 60mg/m 2Bolus injection | Intravenous injection | D 1 |
| Vinblastine (Ve) | 5mg/m 2Bolus injection | Intravenous injection | D 1 |
Comprise 8 circulations this course of treatment, frequency is 1 circulation in per 28 days.
3.2. non_hodgkin lymphoma
3.2.1. deterioration degree is low
I)-the CVP scheme
-according to (Ann.Intern.Med.1972 such as C.M.Bagley; 76:227-234) and C.S.Portlock etc. (Blood 1976; 47:747-756):
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 5 |
| Cyclophosphamide (c) | 300-400mg/m 2/ day | Oral | D 1，D 5 |
| Vincristine (V) | 1.4mg/m 2Bolus injection (maximum 2mg) | Intravenous injection | D 1 |
| Prednisone (P) | 100mg/m 2/ day | Oral | D 1-D 5 |
This circulates and was repeated in per 21 days till the maximum reaction.
Ii)-the I-COPA scheme
-according to (N.Eng.J.Med.1992 such as R.V.Smalley; 327:1336-1341)
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 5 |
| Cyclophosphamide (C) | 600mg/m 2/ day | Intravenous injection | Dx |
| Vincristine (O) | 1.2mg/m 2Bolus injection (maximum 2mg) | Intravenous injection | D 1 |
| Prednisone (P) | 100mg/m 2/ day | Intravenous injection | D 1-D 5 |
| Amycin (A) | 50mg/m 2Bolus injection | Intravenous injection | D 1 |
| Interferon-alpha (I) | 6MU/m 2 | Intramuscular injection | D 22-D 26 |
Comprise 8 to 10 circulations this course of treatment, frequency is circulation in per 28 days.
Iii)-NSC-118218-CdA scheme
-(Blood 1994 according to P.Solol-Celigny etc.; 84 (Supp.1): 383a), (Blood 1994 for H.Hoeschster etc.; 84 (Supp.1): 564a) and A.C.Kay (J.Clin.Oncol.1992; 10:371-377)
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 7 |
| NSC-118218 or NSC-118218 and cyclophosphamide | 25mg/m 2/ day 0.5 hour 20mg/m of transfusion 2/ day 600-1000mg/m 2/ day | Intravenous injection intravenous injection intravenous injection | D 1-D 5 D 1-D 5 D 1 |
| Or cladribine | 0.1mg/m 2/ day transfusion 24 hours | Intravenous injection | D 1-D 7 |
For NSC-118218, each circulation repeated every 28 days, for cladribine, repeated each circulation every 35 days.
3.2.2. moderate worsens
I)-CHOP or CNOP scheme
-(Cancer 1976 according to EM McKelvey etc.; 38:1484-1493), (J.Clin.Oncol.1984 such as J.O.Armitage; 2:898-902), (Ann.OncoL.1992 such as S.Paulovsky; 3:205-209)
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 5 |
| Cyclophosphamide (C) | 750mg/m 2/ day | Intravenous injection | D 1 |
| Amycin (H) | 50mg/m 2Bolus injection | Intravenous injection | D 1 |
| Vincristine (O) | 1.4mg/m 2Bolus injection (maximum: 2mg) | Intravenous injection | D 1 |
| Prednisone (P) | 100mg/m 2/ day (dosage every day) | Oral | D 1-D 5 |
For the CHOP scheme
For the patient of age above 60 years old, mitoxantrone (n) can be used for replacing the amycin (dosage: 12mg/m of (CNOP scheme)
2, with every circulation D
1It intravenous bolus injection mode).
Comprise 6 to 8 circulations the course of treatment of CHOP or CNOP scheme, frequency is 1 circulation in per 21 days.
Ii)-the MACOP-B scheme
-according to (Ann.Intern.Med.1985 such as P.Klimo; 102:596-602) and (J.Clin.Oncol.1994 such as I.A.Cooper; 12:769-778)
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 5，D 8-D 12， D 15-D 22，D 29-D 33， D 43-D 47，D 57-D 61， D 71-D 75 |
| Methotrexate (M) | 100mg/m 2Bolus injection, 300mg/m then 2Infused 4 hours | Intravenous injection | D 8，D 36，D 64 |
| Formyl tetrahydrofolic acid | 15mg every day 4 times | Oral | D 9，D 37，D 65 |
| Amycin (A) | 50mg/m 2Bolus injection | Intravenous injection | D 1，D 15，D 29，D 43， D 57，D 71 |
| Cyclophosphamide (c) | 350mg/m 2Bolus injection | Intravenous injection | D 1，D 5，D 29，D 43， D 57，D 71 |
| Vincristine (O) | 1.4mg/m 2Bolus injection (maximum: 2mg) | Intravenous injection | D 8，D 22，D 36，D 50， D 64，D 78 |
| Prednisone (P) | 75mg/ days | Oral | Every day in 12 weeks |
| Bleomycin (B) | 10U/m 2Bolus injection | Intravenous injection | D 22，D 50，D 78 |
12 weeks of this therapeutic scheme continuity and corresponding to 1 circulation.
Iii)-the VACOP-B scheme
According to J.M.Connors etc. (Proc.Am.Soc.Clin.Oncol.1990,9:254):
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 5，D 8-D 12，D 15- D 22，D 29-D 34，D 43-D 47， D 57-D 61，D 71-D 75 |
| Etoposide (V) | 50mg/m 2 | Intravenous injection | D 15，D 43，D 71 |
| Etoposide | 100mg/m 2 | Oral | D 16，D 17，D 44，D 45， D 72，D 73 |
| Amycin (A) | 50mg/m 2/ day bolus injection | Intravenous injection | D 1，D 15，D 29，D 43， D 57，D 71 |
| Cyclophosphamide (c) | 350mg/m 2Bolus injection | Intravenous injection | D 8，D 22，D 36，D 50， D 64，D 78 |
| Vincristine (O) | 1.2mg/m 2Bolus injection | Intravenous injection | D 8，D 22，D 36，D 50， D 64，D 78 |
| Prednisone (P) | 45mg/m 2/ day | Oral | Every day 1 time in 1 week, every days 4 times in 11 weeks after this |
Each circulation continued for 12 weeks.
Iv)-the m-BACOD/M-BACOD scheme
-according to (Ann.Int.Med.1986 such as M.A.Shipp; 140:757-765) and (J.Clin.Oncol.1983 such as A.T.Skarin; 1:91-98)
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 5，D 8- D 12，D 15-D 19 |
| Methotrexate (m) or (M) | 200mg/m 24 hours 3000mg/m infuse 2Infused 4 hours | The intravenous injection intravenous injection | D 8，D 15Or D 15 |
| Formyl tetrahydrofolic acid | 10mg/m 2Every day 4 times (totally 6 dosage) | Oral | D 9，D 16Or D 16 |
| Bleomycin (B) | 4U/m 2Bolus injection | Intravenous injection | D 1 |
| Amycin (A) | 45mg/m 2Bolus injection | Intravenous injection | D 1 |
| Cyclophosphamide (C) | 600mg/m 2Bolus injection | Intravenous injection | D 1 |
| Vincristine (O) | 1mg/m 2Bolus injection | Intravenous injection | D 1 |
| Dexamethasone (D) | 6mg/m 2/ day | Oral | D 3-D 5 |
Comprise 10 circulations this course of treatment, frequency is 1 circulation in per 21 days.
V)-the ProMACE/CytaBOM scheme
-according to (J.Clin.Oncol.1991 such as D.L.Longo; 9:25-38):
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 5， D 8-D 12 |
| Cyclophosphamide (C) | 650mg/m 2Infused 0.5 hour | Intravenous injection | D 1 |
| Amycin (A) | 25mg/m 2Bolus injection | Intravenous injection | D 1 |
| Etoposide | 120mg/m 2Infused 1 hour | Intravenous injection | D 1 |
| Prednisone (P) | 60mg/ days | Oral | D 1-D 14 |
| Cytosine arabinoside | 300mg/m 2Bolus injection | Intravenous injection | D 8 |
| Bleomycin (B) | 5U/m 2Bolus injection | Intravenous injection | D 8 |
| Vincristine (O) | 1.4mg/m 2Bolus injection | Intravenous injection | D 8 |
| Methotrexate | 120mg/m 2Bolus injection | Intravenous injection | D 8 |
| Formyl tetrahydrofolic acid | 25mg/m 2Every day 4 times (totally 4 dosage) | Oral | D 9 |
Comprise 6 to 8 circulations this course of treatment, frequency is 1 circulation in per 14 days.
3.2.3. low or moderate worsens
I)-the ESHAP rescuing scheme
-under the situation of recurrence or first-line treatment failure, according to (J.Clin.Oncol.1994 such as W.S.Velasquez; 12:1169-1176)
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 5 |
| Etoposide (E) | 40mg/m 2Infused 2 hours | Intravenous injection | D 1-D 4 |
| Methyllprednisolone (S) | Transfusion in 500mg/ days 15 minutes | Intravenous injection | D 1，D 4 |
| Cytosine arabinoside (HA) | 2000mg/m 2Infused 3 hours | Intravenous injection | D 5 |
| Cisplatin (P) | 25mg/m 2/ day bolus injection was infused 24 hours continuously | Intravenous injection | D 1-D 4 |
Comprise 6 circulations this course of treatment, frequency is 1 circulation in per 28 days.
Ii)-the MINE rescuing scheme
-under the situation of recurrence or first-line treatment failure, according to (Semin.Oncol.1990 such as F.Cabanillas; 17 (Suppl.10): 28-33)
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 5 |
| Ifosfamide (I) | 1330mg/m 2Infused 1 hour | Intravenous injection | D 1-D 3 |
| Mesna (M) | 1330mg/m 2Ifosfamide transfusion, after each dosage ifosfamide administration 4 and 8 hours, 266mg/m 2Bolus injection | Intravenous injection | D 1-D 3 |
| Mitoxantrone (M) | 8mg/m 2Infused 15 minutes | Intravenous injection | D 1 |
| Etoposide (E) | 65mg/m 2/ day transfusion 1 hour | Intravenous injection | D 1-D 3 |
This circulation repeated every 21 days.
3.3. non_hodgkin lymphoma: Burkitt lymphomas, minicell lymphoma, lymphoblast lymphoma
3.3.1.Magrath scheme
-product required for protection can combine with the Magrath scheme according to following scheme:
I)-circulation 1
-(Blood 1984 according to I.T.Magrath etc.; 63:1102-1111)
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 5，D 8-D 12 |
| Cytosine arabinoside | 30mg/m 2 | In the sheath | D 1，D 2，D 3，D 7 |
| Cyclophosphamide | 1200mg/m 2Bolus injection | Intravenous injection | D 1 |
| Methotrexate | 12.5mg/m 2(maximum: 12.5mg) | In the sheath | D 10 |
| Methotrexate | 300mg/m 2/ day transfusion 1 hour, 60mg/m then 2/ hour transfusion 41 hours | Intravenous injection | D 10-D 11 |
| Formyl tetrahydrofolic acid | 15mg/m 2Bolus injection, every day 4 times (8 successive doses) | Intravenous injection | The methotrexate administration begins beginning in back 42 hours |
Ii)-circulation 2 to 15
-according to (1984, the same) such as I.T.Magrath.
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 3，D 10-D 11 |
| Cytosine arabinoside | 45mg/m 2 | In the sheath | D 1、D 2(circulation 2 and 3), D 1(circulation 4 and 6) |
| Cyclophosphamide (C) | 1200mg/m 2Bolus injection | Intravenous injection | D 1 |
| Amycin | 40mg/m 2Bolus injection | Intravenous injection | D 1 |
| Vincristine | 1.4mg/m 2Bolus injection (maximum: 2mg) | Intravenous injection | D 1 |
| Methotrexate | 12.5mg/m 2(maximum: 12.5mg) | In the sheath | D 3、D 10(circulation 2 and 3), D 10(circulation 4,5,6) |
| Methotrexate | 300mg/m 2Infused 1 hour, then 60mg/m 2Transfusion is 41 hours continuously | Intravenous injection | D 10、D 11(circulation 2 and 6), D 14、D 15(circulation 7-15) |
| Formyl tetrahydrofolic acid | 15mg/m 2Bolus injection, every day 4 times (8 successive doses) | Intravenous injection | The methotrexate administration begins beginning in back 42 hours |
Comprise 14 circulations this course of treatment, frequency is 1 circulation in per 28 days.
3.4 WaldenstromShi macroglobulinemia
3.4.1 CVP scheme
(Blood 1994 according to M.A.Dimopoulous etc.; 83:1452-1459) and C.S.Portlock etc. (Blood 1976; 47:747-756) the CVP scheme of Miao Shuing:
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 5 |
| Cyclophosphamide (C) | 300-400mg/m 2/ day | Oral | D 1-D 5 |
| Vincristine (V) | 1.4mg/m 2/ day bolus injection (maximum: 2mg) | Intravenous injection | D 1 |
| Prednisone (P) | 100mg/m 2/ day | Oral | D 1-D 5 |
Prolong this indefinite duration course of treatment (1 circulation in per 21 days).
3.4.2 NSC-118218-CdA scheme
(Blood 1990 according to H.M.Kantarjian etc.; 75:1928-1931) and (Ann.Intern.Med.1993 such as M.A.Dinopoulous; 118:195-198):
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 5 |
| NSC-118218 | 25-30mg/m 2Infused 0.5 hour | Intravenous injection | D 1-D 5 |
Or
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 7 |
| Cladribine | 0.09mg/m 2/ sky is transfusion continuously | Intravenous injection | D 1-D 7 |
For NSC-118218, comprise 6 to 12 circulations this course of treatment, be 28 days interval, for cladribine, comprises 2 circulations this course of treatment, also be 28 days interval.
3.5 multiple myeloma
3.5.1 MP scheme
(JAMA 1969 according to R.Alexanian etc.; 208:1680-1685), (Br.J.Cancer 1988 for A.Belch etc.; 57:94-99) and (N.Engl.J.Med.1990 such as F.Mandelli; 322:1430-1434):
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 5 |
| Melphalan (M) | 0.25mg/kg/ my god | Oral | D 1-D 4 |
| Prednisone (P) | 100mg/ days | Oral | D 1-D 4 |
Or
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 5 |
| Melphalan (M) | 9mg/m 2/ day | Oral | D 1-D 4 |
| Prednisone (P) | 100mg/ days | Oral | D 1-D 4 |
Comprise at least 12 circulations this course of treatment, per 4 to 6 week 1 circulation.
3.5.2 VAD scheme
According to (N.Engl.J.Med.1984:310:1353-1356) such as B.Barlogie:
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 5 |
| Vincristine (V) | 0.4mg/ it was infused 24 hours continuously | Intravenous injection | D 1-D 4 |
| Amycin (A) | 9mg/m 2/ day continuous transfusion 24 hours | Intravenous injection | D 1-D 4 |
| Dexamethasone (D) | 40mg/ days | Intravenous injection | D 1-D 4，D 9-D 12，D 17-D 20 |
3.5.3 MP-interferon-alpha scheme
(Blood 1993 according to O.Osterborg etc.; 81:1428-1434):
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 5 |
| Melphalan (M) | 0.25mg/kg/ my god | Oral | D 1-D 4 |
| Prednisone (P) | 2mg/kg/ days | Oral | D 1-D 4 |
| Interferon-alpha | 7MU/m 2/ day | Subcutaneous injection | D 1-D 5And D 22-D 26 |
Comprise that this circulation infinitely repeats this course of treatment, frequency is 1 circulation in per 42 days.
3.5.4 VCAP or VBAP scheme
According to (J.Clin.Oncol.1983 such as S.E.Salmon; 1:453-461):
The VCAP scheme:
| Dosage | Approach | Natural law | |
| Osajin | 200-2000mg/m 2/ sky or transfusion in 5-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 5 |
| Vincristine (V) | 1mg/m 2Bolus injection (maximum: 1.5mg) | Intravenous injection | D 1 |
| Amycin (A) | 30mg/m 2Bolus injection | Intravenous injection | D 1 |
| Prednisone (P) | 60mg/m 2/ day | Oral | D 1-D 4 |
| Cyclophosphamide (C) | 125mg/m 2 | Oral | D 1-D 4 |
The VBAP scheme: replace cyclophosphamide with carmustine (BCNU), all the other are identical:
| Dosage | Approach | Natural law | |
| Carmustine | 30mg/m 2Infused 1 hour | Intravenous injection | D 1 |
C. tumor-pediatric oncology of suffering from of child
Osajin also can join in the comprehensive chemotherapy regimen of department of pediatrics treatment so that improve antitumous effect, simultaneously by the clone being formed the collection of cell and transferring the order of severity with the probability reduction side effect that reduces active dose.
1/Ewing sarcoma/constitutional neuroectodermal tumors
Osajin can be introduced VCR-Doxo-CY-Ifos-Mesha-E scheme (E.D.Berger etc., J.Clin.Oncol.1990; 8:1514-1524; W.H.Meyer etc., J.Clin.Oncol.1992; 10:1737-1742):
| Dosage | Approach | Natural law | |
| Osajin | 100-200mg/m 2/ sky or transfusion in 2-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 5，D 8-D 11， D 15-D 18，D 22-D 27 |
| Vincristine | 2mg/m 2Bolus injection (maximal dose: 2mg) | Intravenous injection | D 1，D 8，D 15，D 43 |
| Amycin | 30mg/m 2/ day transfusion 24 hours | Intravenous injection | D 1-D 3，D 43-D 45 |
| Cyclophosphamide | 2.2g/m 2Infused 0.5 hour | Intravenous injection | D 1，D 43 |
| Ifosfamide | 1800mg/m 2/ day transfusion 1 hour | Intravenous injection | D 22-D 26，D 63-D 67 |
| Mesna | 360mg/m 2Infused 15 minutes, frequency is per 3 hours 5 dosage | Intravenous injection | With cyclophosphamide and ifosfamide administration |
| Etoposide | 100mg/m 2Infused 1 hour | Intravenous injection | D 22-D 26，D 63-D 67 |
According to sarcoma originally seriousness and response amplitude, comprise 6 to 10 such circulations this course of treatment.
2/ acute department of pediatrics lymphoblast leukemia
2.1. the chemotherapy of inducing (D
1-D
30My god)
Osajin can join (P.S.Gaynon etc., J.Clin.Oncol., 1993,11,2234-2242 in the scheme of recommendation; J.Pullen etc., J.Clin.Oncol., 1993,11:2234-2242; J.Pullen etc., J.Clin.Oncol., 1993,11:839-849; V.J.Land etc., J.Clin.Oncol., 1994,12:1939-1945):
| Dosage | Approach | Natural law | |
| Osajin | 100-200mg/m 2/ sky or transfusion in 2-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 5And D 22-D 27And D 1，D 8，D 15And D 22 |
| Vincristine | 1.5mg/m 2Bolus injection (the about 2mg of maximal dose) | Intravenous injection | D 1，D 8，D 15，D 22 |
| The altheine enzyme | 6000IU/m 2 | Intramuscular injection | In 3 weeks 3 times weekly |
| Prednisone | 60mg/m 2, every day 3 dosage | Oral | D 1-D 28 |
| Daunorubicin | 25mg/m 2/ day transfusion 15 minutes | Intravenous injection | D 1，D 8，D 15And D 22 |
| Methotrexate | According to the age | In the sheath | D 15，D 28 |
| Cytosine arabinoside | According to the age | In the sheath | D 1 |
According to the result of bone marrow examination, the 28th day of therapeutic scheme to the consolidation transition.
2.2. consolidation/maintenance chemotherapy
Osajin can be introduced Concept of Maintenance (P.S.Gaynon etc., J.Clin.Oncol., 1993,11,2234-2242; J.Pullen etc., J.Clin.Oncol., 1993,11:839-849; V.J.Land etc., J.Clin.Oncol., 1994,12:1939-1945), according to following scheme:
| Dosage | Approach | Natural law | |
| Osajin | 100-200mg/m 2/ sky or transfusion in 2-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 5，D 15-D 20And D 94- D 99，D 101-D 106，D 108- D 113，D 122-D 127 |
| Cyclophosphamide | 1000mg/m 2Infused 0.5 hour | Intravenous injection | D 1，D 15，D 122 |
| The altheine enzyme | 6000U/m 2 | Intramuscular injection | At D 97To D 122Between 3 times weekly |
| Cytosine arabinoside | 75mg/m 2/ day transfusion 15 minutes | Intravenous injection/subcutaneous injection | By D 2、D 9、D 16、D 23、 D 123、D 14 days series of beginning |
| Amycin | 25mg/m 2/ day transfusion 15 minutes | Intravenous injection | D 94，D 101，D 108 |
| Purinethol | 60mg/m 2/ day | Oral | D 1-D 91，D 143To the treatment end |
| Methotrexate | 20mg/m 2/ day | Oral | At D 36To D 72And D 143To the treatment end, weekly |
| Prednisone | 40mg/m 2/ day (being divided into 3 dosage every day) | Oral | At D 143To treatment finish every month continuous 5 days |
| Thioguanine | 60mg/m 2/ day | Oral | D 122-D 135 |
| Vincristine | 1.5mg/m 2Bolus injection (maximal dose: 2mg) | Intravenous injection | D 94，D 101，D 108, then at D 143Finish every month once to treating |
| Methotrexate | According to the age | In the sheath | D 1，D 8，D 15，D 22，D 123， D 130, then at D 143Finish 3 months once to treating |
3/ acute department of pediatrics myelocytic leukemia
Osajin can join according to following scheme and induce and consolidate/Concept of Maintenance in:
3.1. the chemotherapy of inducing
According to Y.Ravindranath etc., J.Clin.Oncol.1991,9:572-580; M.E.Nesbit etc., J.Clin.Oncol.1994,12:127-135; R.J.Wells etc., J.Clin.Oncol.1994,12:2367-2377:
| Dosage | Approach | Natural law | |
| Osajin | 100-200mg/m 2/ sky or transfusion in 2-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 5，D 10-D 13 |
| Cytosine arabinoside | According to the age | In the sheath | D 1 |
| Daunorubicin | 20mg/m 2/ day transfusion 24 hours | Intravenous injection | D 1-D 4，D 10-D 13 |
| Cytosine arabinoside | 200mg/m 2/ day transfusion 24 hours | Intravenous injection | D 1-D 4，D 10-D 13 |
| Thioguanine | 100mg/m 2/ day, be divided into two dosage every day | Oral | D 1-D 4，D 10-D 13 |
| Etoposide | 100mg/m 2/ day transfusion 24 hours | Intravenous injection | D 1-D 4，D 10-D 13 |
| Dexamethasone | 6mg/m 2, be divided into 3 dosage every day | Intravenous injection/oral | D 1-D 4，D 10-D 13 |
This circulation is from D
28Begin repetition.
3.2. consolidation/maintenance chemotherapy
According to Y.Ravidranath etc., J.Clin.Oncol.1991,9:572-580; M.E.Nesbit etc., J.Clin.Oncol.1994,12:127-135; R.J.Wells etc., J.Clin.Oncol.1994,12:2367-2377:
| Dosage | Approach | Natural law | |
| Cytosine arabinoside | According to the age | In the sheath | D 1，D 28，D 56 |
| Osajin | 100-200mg/m 2/ sky or transfusion in 2-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 5，D 8-D 13， D 28-D 33，D 56-D 61， D 89-D 94 |
| Cytosine arabinoside | 3000mg/m 2Transfusion in per 12 hours 3 hours | Intravenous injection | D 1-D 2, and D 8-D 9 |
| L-N enzyme | The cytosine arabinoside medication is 6000IU/m after 3 hours 2 | Intramuscular injection | D 2，D 9 |
| Vincristine | 1.5mg/m 2Bolus injection (maximal dose: 2mg) | Intravenous injection | D 28，D 56 |
| Thioguanine | 75mg/m 2/ day | Oral | D 28-D 84 |
| Cytosine arabinoside | 25mg/m 2/ day bolus injection | Intravenous injection | D 28-D 31，D 56-D 59 |
| Cyclophosphamide | 75mg/m 2/ day transfusion 0.5 hour | Intravenous injection | D 28-D 31，D 56-D 59 |
| Cytosine arabinoside | 25mg/m 2/ day bolus injection | Subcutaneous injection/intravenous injection | D 89-D 93 |
| Thioguanine | 50mg/m 2/ day | Oral | D 89-D 93 |
| Etoposide | 100mg/m 2/ day transfusion 1 hour | Intravenous injection | D 89，D 92 |
| Dexamethasone | 2mg/m 2/ day | Oral | D 89-D 92 |
| Daunorubicin | 30mg/m 2Infused 15 minutes | Intravenous injection | D 89 |
4/ department of pediatrics Hokdkin disease
According to descriptions such as E.A.Gehan, osajin can join that (Cancer 1990 in the MOPP-ABVD scheme; 65:1429-1437), (J.Clin.Oncol.1994 such as S.P.Hunger; 12:2160-2166) and (J.Clin.Oncol.1993 such as M.M.Hudson; 11:100-108):
| Dosage | Approach | Natural law | |
| Osajin | 100-200mg/m 2/ sky or transfusion in 2-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 5And D 8-D 12 |
| Chlormethine (M) | 6mg/m 2Bolus injection | Intravenous injection | D 1，D 8 |
| Vincristine (O) | 1.5mg/m 2Bolus injection (maximum 2mg) | Intravenous injection | D 1，D 8 |
| Procarbazine (P) | 100mg/m 2/ day | Oral | D 1-D 14 |
| Prednisone (P) | 40mg/m 2/ day (being divided into 3 dosage every day) | Oral | D 1-D 14 |
| Amycin (A) | 25mg/m 2/ day transfusion 15 minutes | Intravenous injection | D 29，D 43 |
| Bleomycin (B) | 10U/m 2Infused 15 minutes | Intravenous injection | D 29，D 43 |
| Vinblastine (V) | 6mg/m 2Bolus injection (maximum 2mg) | Intravenous injection | D 29，D 43 |
| Dacarbazine (D) | 375mg/m 2Infused 15 minutes | Intravenous injection | D 29，D 43 |
This circulation should repeat 6 times with 1 circulation frequency of per 8 weeks, comprises 6 circulations this course of treatment.
If carry out autologous bone marrow transplantation (autograft), can (wherein allotransplantation be at D according to following scheme
0It takes place) (Blood 1993 to use R.Chopra etc.; 81:1137-1145), (J.Clin.Oncol.1990 such as C.Wheeler; 8:648-656) and R.J.Jones etc. (J.Clin.Oncol.1990,8:527-537) described CVB method is carried out:
| Dosage | Approach | Natural law | |
| Osajin | 100-200mg/m 2/ sky or transfusion in 2-50mg/kg/ days 1 hour | Intravenous injection | D -7，D -1 |
| Cyclophosphamide | 1800mg/m 2/ day, transfusion in 1 hour 2 times | Intravenous injection | D -7，D -6，D -5，D -4 |
| Carmustine (BCNU) | 112mg/m 2/ day transfusion 0.5 hour | Intravenous injection | D -7，D -6，D -5，D -4 |
| Etoposide | 500mg/m 2/ day, transfusion in 1 hour 2 times | Intravenous injection | D -7，D -6，D -5，D -4 |
5/ department of pediatrics lymphoblast lymphoma
Osajin also can with induce chemotherapy regimen (A.T.Meadows etc., J.Clin.Oncol.1989,7:92-99; C.Patte etc., Med.Ped.Oncol.1992,20:105-113 and A.Reiter etc., J.Clin.Oncol.1995,13:359-372) and the combination of maintenance chemotherapy scheme:
5.1 the chemotherapy of inducing
| Dosage | Approach | Natural law | |
| Osajin | 100-200mg/m 2/ sky or transfusion in 2-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 5，D 17-D 22， D 24-D 29 |
| Cyclophosphamide | 1200mg/m 2Infused 0.5 hour | Intravenous injection | D 1 |
| Cytosine arabinoside | According to the age | In the sheath | D 1 |
| Vincristine | 1.5mg/m 2Bolus injection (maximum 2mg) | Intravenous injection | D 3，D 10，D 17，D 24 |
| Prednisone | 60mg/m 2/ day, be divided into 3 dosage every day | Oral | D 3-D 28 |
| Daunorubicin | 60mg/m 2Infused 15 minutes | Intravenous injection | D 17 |
| L-N enzyme | 6000U/m 2/ day transfusion 15 minutes | Intramuscular injection | D 17-D 35, 3 times weekly |
| Methotrexate | According to the age | In the sheath | D 17，D -31 |
5.2 maintenance chemotherapy:
According to following scheme:
| Dosage | Approach | Natural law | |
| Osajin | 100-200mg/m 2/ sky or transfusion in 2-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 5，D 15- D 20，D 29-D 34 |
| Cyclophosphamide | 1000mg/m 2Infused 0.5 hour | Intravenous injection | D 1 |
| Vincristine | 1.5mg/m 2Bolus injection (maximum 2mg) | Oral | D 1，D 5(from circulating 2 to 10) |
| Methotrexate | 300mg/m 2/ day (60% transfusion 15 minutes and 40% transfusion 4 hours) | Intravenous injection | D 15 |
| Formyl tetrahydrofolic acid | 10mg/m 2/ per 4 hours | Oral | D 16 |
| Daunorubicin | 30mg/m 2Infused 0.5 hour | Intravenous injection | D 29 |
| Methotrexate | According to the age | In the sheath | D 1，D 8，D 15(circulation 1) once (circulated 2 to 10) in every month then |
Comprise 10 circulations this course of treatment.
6/ department of pediatrics neuroblastoma
Adopt (J.Clin.Oncol.1992 such as R.P.Castleberry; 10:1299-1304), (J.Clin.Oncol.1993 such as A.Garaventa; 11:1770-1779) and (J.Clin.Oncol.1992 such as D.C.West; 11:84-90) the comprehensive chemotherapy regimen Doxo-E-Cy-Pt of Tui Jianing:
| Dosage | Approach | Natural law | |
| Osajin | 100-200mg/m 2/ sky or transfusion in 2-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 5，D 28-D 35， D 58-D 65 |
| Amycin | 25mg/m 2/ day transfusion 15 minutes | Intravenous injection | D 2，D 30，D 58 |
| Etoposide | 100mg/m 2Infused 1 hour | Oral/nasal is interior, stomach | D 2，D 5，D 30，D 33， D 58，D 61 |
| Cyclophosphamide | 1000mg/m 2Infused 0.5 hour | Intravenous injection | D 3，D 4，D 31，D 32， D 59，D 60 |
| Cisplatin | 60mg/m 2Infused 6 hours | Intravenous injection | D 1，D 28，D 56 |
Carry out evaluation to therapeutic response after 9 weeks so that determine whether to take excision, radiotherapy or new chemotherapy.
7/ department of pediatrics osteosarcoma
Osajin can join as (J.Clin.Oncol.1990 such as M.Hudson; 8:1988-1997), P.A.Meyers (J.Clin.Oncol.1992; 10:5-15) and (J.Clin.Oncol.1992 such as V.H.C.Bramwell; 10:1579-1591) in the Doxo-Pt-Mtx-Lcv scheme of Miao Shuing:
| Dosage | Approach | Natural law | |
| Osajin | 100-200mg/m 2/ sky or transfusion in 2-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 5，D 21- D 26，D 28-D 33 |
| Amycin | 25mg/m 2/ day transfusion 24 hours | Intravenous injection | D 1-D 3 |
| Cisplatin | 120mg/m 2Infused 6 hours | Intravenous injection | D 1 |
| Methotrexate | 12mg/m 2/ day transfusion 1 hour | Intravenous injection | D 21，D 28 |
| Formyl tetrahydrofolic acid | Per 6 hours 100mg/m 2 | Oral | D 22，D 29 |
8/ department of pediatrics rhabdomyosarcoma
The Vcr-Dact-CY-Mesna scheme (H.Maurer etc., Cancer 1993; 71:1904-1922 and L.R.Mandell etc., Oncology 1993; 7:71-83) can comprise the intravenous fluids of osajin, scheme is as follows:
| Dosage | Approach | Natural law | |
| Osajin | 100-200mg/m 2/ sky or transfusion in 2-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 5，D 8-D 12， D 22-D 27，D 43-D 47 |
| Vincristine | 1.5mg/m 2/ day bolus injection (maximum 2mg) | Intravenous injection | D 1，D 8，D 15， D 22，D 29，D 36， D 43D 50And D 57 |
| Actinomycin D | 0.015mg/kg bolus injection (every day maximal dose: 0.5mg) | Intravenous injection | D 1-D 5，D 22-D 27， D 43-D 47 |
| Cyclophosphamide | 2.2g/m 2Infused 1 hour | Intravenous injection | D 1，D 22，D 43 |
| Mesna | 360mg/m 2Infused per 3 hours 5 dosage 1 hour | Intravenous injection | D 1，D 22，D 43 |
Treatment the 9th weekend evaluation effect with decision treatment (operation, radiotherapy continue chemotherapy) subsequently.
The intravital WilmShi tumor of 9/ child
In (Cancer, 1989 such as G.J.D ' Angio; 64:349-360) and (J.Clin.Oncol.1993 such as D.M.Green; 11:91-95) in the Vcr-Dact scheme of Miao Shuing:
| Dosage | Approach | Natural law | |
| Osajin | 100-200mg/m 2/ sky or transfusion in 2-50mg/kg/ days 1 hour | Intravenous injection | D 1-D 5，D 8-D 12, then weekly |
| Vincristine | 2mg/m 2Bolus injection (maximal dose: 2mg) | Intravenous injection | D 7, then weekly |
| Actinomycin D | 0.045mg/kg bolus injection (P≤30kg), 1.35mg/m 2(P＞30kg), (maximal dose: 3mg) | Intravenous injection | D 1, per then 3 weeks |
This scheme begins behind excision.
Under autologous bone marrow transplantation (autograft) situation, according to (Med.Pediatr.Oncol.1994 such as A.Garaventar; 22:11-14), the E-Thio-Cy scheme can be amended as follows:
| Dosage | Approach | Natural law | |
| Osajin | 100-200mg/m 2/ sky or transfusion in 2-50mg/kg/ days 1 hour | Intravenous injection | D -8-D -1 |
| Etoposide | 1800mg/m 2(infusing 24 hours) | Intravenous injection | D -8 |
| Thiophene is for group | 300mg/m 2/ day transfusion 2 hours | Intravenous injection | D -7，D -6，D -5 |
| Cyclophosphamide | Transfusion in 50mg/kg/ days 1 hour | Intravenous injection | D -4，D -3，D -2，D -1 |
Bone marrow transplantation is at D
0It carries out.
Claims (9)
1. the similar compound of osajin or chromone type is used for disturbing between by at least a cell toxicant reagent treatment tumor stage tumor clone to form purposes aspect the medicine that cell generates in preparation, and the similar compound of wherein said osajin or chromone type is for being selected from the chemical compound of formula (I):
Wherein:
R
1, R
2, R
3And R
4Be independently from each other H, OH, C
1-C
4Alkoxyl, R wherein
7Be C
1-C
4Alkyl-OCOR
7Group, substituent R
1, R
2, R
3Or R
4In at least one be not H, and R
2And R
3Can form methylene-dioxy together,
R
5Be selected from H, OH, C
1-C
4Alkoxyl and O-glucityl,
R
6Be selected from cyclohexyl, phenyl and be selected from H, OH and C
1-C
4The group of alkoxyl replaces 1 to 3 time phenyl,
And
Two keys of expression or singly-bound.
2. the purposes of claim 1, the analog of osajin or chromone type increases the activity of cell toxicant reagent in the wherein said medicine.
3. claim 1 or 2 purposes, its Chinese style I chemical compound is selected from genistein, Daidezin and biochanin.
4. the administration during at the chemotherapy initial time with in each chemotherapy circulation beginning of claim 1 or 2 purposes, wherein said medicine.
5. claim 1 or 2 purposes, dosage every day of the similar compound of osajin or chromone type is 5-50mg/kg in the wherein said medicine.
6. claim 1 or 2 purposes, dosage every day of the similar compound of osajin or chromone type is 200-2000mg/m in the wherein said medicine
2
7. claim 1 or 2 purposes, wherein said medicine is infusion or oral administered dosage form.
8. claim 1 or 2 purposes, the similar compound of wherein said isoflavone or chromone type is linked together with the cell toxicant reagent that is used for the comprehensive chemotherapy of solid tumor.
9. claim 1 or 2 purposes, the similar compound of wherein said isoflavone or chromone type is linked together with the cell toxicant reagent that is used for the treatment of leukemia.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR98/09059 | 1998-07-15 | ||
| FR9809059A FR2781154B1 (en) | 1998-07-15 | 1998-07-15 | THERAPEUTIC COMPOSITION BASED ON ISOFLAVONOIDS FOR USE IN THE TREATMENT OF TUMORS WITH CYTOTOXIC AGENTS |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1312712A CN1312712A (en) | 2001-09-12 |
| CN1139383C true CN1139383C (en) | 2004-02-25 |
Family
ID=9528649
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB998095478A Expired - Fee Related CN1139383C (en) | 1998-07-15 | 1999-07-13 | Therapeutic composition based on flavonoids for use in treatment of tumours with cytotoxic agents |
Country Status (11)
| Country | Link |
|---|---|
| EP (1) | EP1096929A1 (en) |
| JP (1) | JP2002520357A (en) |
| KR (1) | KR20020006510A (en) |
| CN (1) | CN1139383C (en) |
| AU (1) | AU761417B2 (en) |
| BR (1) | BR9912817A (en) |
| CA (1) | CA2337256A1 (en) |
| EA (1) | EA200100141A1 (en) |
| FR (1) | FR2781154B1 (en) |
| IL (1) | IL140580A0 (en) |
| WO (1) | WO2000003707A1 (en) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6146668A (en) | 1997-04-28 | 2000-11-14 | Novogen, Inc. | Preparation of isoflavones from legumes |
| AUPP260798A0 (en) | 1998-03-26 | 1998-04-23 | Novogen Research Pty Ltd | Treatment of medical related conditions with isoflavone containing extracts of clover |
| AUPQ266199A0 (en) * | 1999-09-06 | 1999-09-30 | Novogen Research Pty Ltd | Compositions and therapeutic methods involving isoflavones and analogues thereof |
| PL205635B1 (en) * | 2001-04-09 | 2010-05-31 | Inst Farmaceutyczny | Novel derivatives of genistein and pharmacological agents containing such derivatives |
| DE60313754T2 (en) * | 2002-03-06 | 2008-01-24 | The Medical Research and Education Trust, San Diego | BOTANICAL EXTRACT WITH ANTICIPATIVE ACTIVITY INCLUDING ISOLIQUIRITIGENIN |
| AU2002951833A0 (en) | 2002-10-02 | 2002-10-24 | Novogen Research Pty Ltd | Compositions and therapeutic methods invloving platinum complexes |
| DE10337863A1 (en) * | 2003-08-18 | 2005-03-17 | Merck Patent Gmbh | Use of chromene-4-one derivatives |
| CA2590048C (en) | 2007-05-23 | 2013-07-16 | Institut National De La Recherche Scientifique | Cytosine nucleoside analogs and isoflavones and uses thereof |
| CN106265669A (en) * | 2016-08-04 | 2017-01-04 | 大连理工大学 | Daidzein and the drug regimen of 10 hydroxy camptothecins and application thereof |
| CN113842387A (en) * | 2021-11-19 | 2021-12-28 | 大连理工大学盘锦产业技术研究院 | Pharmaceutical composition of 10-hydroxycamptothecin and biochanin A and application thereof |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0617304B2 (en) * | 1982-09-09 | 1994-03-09 | 理化学研究所 | Anti-cancer drug |
| US5506211A (en) * | 1994-05-09 | 1996-04-09 | The Uab Research Foundation | Genistein for use in inhibiting osteroclasts |
| US5824702A (en) * | 1996-06-07 | 1998-10-20 | Mount Sinai School Of Medicine Of The City University Of New York | Genistein as a preventive against ultraviolet induced skin photodamage and cancer |
| AUPO203996A0 (en) * | 1996-08-30 | 1996-09-26 | Novogen Research Pty Ltd | Therapeutic uses |
| JP2829387B2 (en) * | 1996-09-13 | 1998-11-25 | 農林水産省四国農業試験場長 | Composition for promoting lipolysis in fat cells |
| GB9621757D0 (en) * | 1996-10-18 | 1996-12-11 | Ciba Geigy Ag | Phenyl-substituted bicyclic heterocyclyl derivatives and their use |
| US5733926A (en) * | 1996-12-13 | 1998-03-31 | Gorbach; Sherwood L. | Isoflavonoids for treatment and prevention of alzheimer dementia and reduced cognitive functions |
-
1998
- 1998-07-15 FR FR9809059A patent/FR2781154B1/en not_active Expired - Fee Related
-
1999
- 1999-07-13 CA CA002337256A patent/CA2337256A1/en not_active Abandoned
- 1999-07-13 WO PCT/FR1999/001715 patent/WO2000003707A1/en not_active Application Discontinuation
- 1999-07-13 EA EA200100141A patent/EA200100141A1/en unknown
- 1999-07-13 BR BR9912817-9A patent/BR9912817A/en not_active IP Right Cessation
- 1999-07-13 EP EP99929481A patent/EP1096929A1/en not_active Withdrawn
- 1999-07-13 CN CNB998095478A patent/CN1139383C/en not_active Expired - Fee Related
- 1999-07-13 KR KR1020017000477A patent/KR20020006510A/en not_active Application Discontinuation
- 1999-07-13 IL IL14058099A patent/IL140580A0/en unknown
- 1999-07-13 JP JP2000559842A patent/JP2002520357A/en active Pending
- 1999-07-13 AU AU46282/99A patent/AU761417B2/en not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| JP2002520357A (en) | 2002-07-09 |
| FR2781154B1 (en) | 2001-09-07 |
| BR9912817A (en) | 2001-05-08 |
| CN1312712A (en) | 2001-09-12 |
| EP1096929A1 (en) | 2001-05-09 |
| KR20020006510A (en) | 2002-01-19 |
| IL140580A0 (en) | 2002-02-10 |
| FR2781154A1 (en) | 2000-01-21 |
| WO2000003707A1 (en) | 2000-01-27 |
| AU4628299A (en) | 2000-02-07 |
| CA2337256A1 (en) | 2000-01-27 |
| EA200100141A1 (en) | 2001-06-25 |
| AU761417B2 (en) | 2003-06-05 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1195740C (en) | Pharmaceutical compositions comprising 2-quinolones | |
| CN1027265C (en) | Water soluble camptothecin analogs | |
| CN1139383C (en) | Therapeutic composition based on flavonoids for use in treatment of tumours with cytotoxic agents | |
| CN1249753A (en) | Farnesyl transferase inhibiting 1,8-annelated quinolinone derivs. substd. with N- or C-linked imidazoles | |
| CN1897971A (en) | Cd40 antibody formulation and methods | |
| CN1192149A (en) | Methods of reducing toxicity of chemotherapeutic and antiviral agents with acylated pyrimidine nucleosides | |
| CN1788086A (en) | Antisense oligonucleotides (ODN) against smad7 and uses in medical field thereof | |
| CN1103431A (en) | Determination of lymph nodes enriched in tumor reactive... | |
| CN1018640B (en) | Process for the preparation of compounds for the induction of in vivo and in vitro production of cytokines | |
| CN1180374A (en) | Method of preparing undifferentiated cell | |
| CN1711266A (en) | Pyrimido compounds having antiproliferative activity | |
| CN1139384C (en) | Therapeutic composition based on flavonoids for use in the treatment of tumours with cytotoxic agents | |
| CN1711094A (en) | Combination product of inhibitor of the SRC family of non-receptor tyrosine kinases and gemcitabine | |
| CN1703229A (en) | Compositions and methods for treatment of prostate and other cancers | |
| CN1812986A (en) | Furazanobenzimidazoles | |
| CN1547613A (en) | Method of estimating the risk of expression of adverse drug reaction caused by the administration of a compound, which is either metabolized per se by UGT1A1 enzyme or whose metabolic intermediate is | |
| CN1224388C (en) | Modified prodrug forms of ap/amp | |
| CN1711099A (en) | Extract with anti-tumor and anti-poisonous activity | |
| CN1649612A (en) | Induction method for cell differentiation | |
| CN1220490C (en) | Method for inducing death of neoplastic cells using piperazine oxirane derivatives | |
| CN1942189A (en) | Use of 5,10-methylene tetrahydrofolate for the treatment of cancer | |
| CN1617755A (en) | Fpt inhibitor and use of other anti-tumor agent in combination in preparing anticancer drug | |
| CN1144586C (en) | 2-(1-hydroxyethyl)-5-hydroxynaphtho{2,3-B}furan-4, 9-dione and antitumor agents comprising this compound | |
| CN1542019A (en) | Anti human non-Hodgkin's lymphoma chimeric antibody and its derivative and application | |
| CN1917877A (en) | Combination of a farnesyl tranferase inhibitor with an antihormonal agent for the treatment of breast cancer |
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 | ||
| C19 | Lapse of patent right due to non-payment of the annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |