CN101371820B - 含氨甲喋呤增效剂的抗癌缓释剂 - Google Patents
含氨甲喋呤增效剂的抗癌缓释剂 Download PDFInfo
- Publication number
- CN101371820B CN101371820B CN2008103001123A CN200810300112A CN101371820B CN 101371820 B CN101371820 B CN 101371820B CN 2008103001123 A CN2008103001123 A CN 2008103001123A CN 200810300112 A CN200810300112 A CN 200810300112A CN 101371820 B CN101371820 B CN 101371820B
- Authority
- CN
- China
- Prior art keywords
- release
- tumor
- slow
- injection
- methotrexate
- 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
- 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 title claims abstract description 142
- 229960000485 methotrexate Drugs 0.000 title claims abstract description 142
- 230000001093 anti-cancer Effects 0.000 title claims abstract description 47
- 238000013268 sustained release Methods 0.000 title claims description 61
- 239000012730 sustained-release form Substances 0.000 title claims description 61
- 230000003389 potentiating effect Effects 0.000 title 1
- 239000007924 injection Substances 0.000 claims abstract description 127
- 238000002347 injection Methods 0.000 claims abstract description 127
- 239000002904 solvent Substances 0.000 claims abstract description 62
- 239000004005 microsphere Substances 0.000 claims abstract description 45
- CXMXRPHRNRROMY-UHFFFAOYSA-N sebacic acid Chemical compound OC(=O)CCCCCCCCC(O)=O CXMXRPHRNRROMY-UHFFFAOYSA-N 0.000 claims abstract description 20
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical group [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims abstract description 12
- 239000001768 carboxy methyl cellulose Substances 0.000 claims abstract description 12
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims abstract description 12
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims abstract description 12
- JVYNJRBSXBYXQB-UHFFFAOYSA-N 4-[3-(4-carboxyphenoxy)propoxy]benzoic acid;decanedioic acid Chemical compound OC(=O)CCCCCCCCC(O)=O.C1=CC(C(=O)O)=CC=C1OCCCOC1=CC=C(C(O)=O)C=C1 JVYNJRBSXBYXQB-UHFFFAOYSA-N 0.000 claims abstract description 11
- 229950004403 polifeprosan Drugs 0.000 claims abstract description 11
- 229920000305 Nylon 6,10 Polymers 0.000 claims abstract description 10
- AAKJLRGGTJKAMG-UHFFFAOYSA-N erlotinib Chemical compound C=12C=C(OCCOC)C(OCCOC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 AAKJLRGGTJKAMG-UHFFFAOYSA-N 0.000 claims description 23
- 239000003795 chemical substances by application Substances 0.000 claims description 21
- 229960001433 erlotinib Drugs 0.000 claims description 20
- 239000005551 L01XE03 - Erlotinib Substances 0.000 claims description 19
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 13
- 239000000463 material Substances 0.000 claims description 12
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims description 9
- 239000000600 sorbitol Substances 0.000 claims description 9
- OFJWFSNDPCAWDK-UHFFFAOYSA-N 2-phenylbutyric acid Chemical compound CCC(C(O)=O)C1=CC=CC=C1 OFJWFSNDPCAWDK-UHFFFAOYSA-N 0.000 claims description 8
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 6
- 229920000053 polysorbate 80 Polymers 0.000 claims description 6
- 239000003005 anticarcinogenic agent Substances 0.000 claims description 5
- 206010028980 Neoplasm Diseases 0.000 abstract description 106
- 239000003814 drug Substances 0.000 abstract description 95
- 229940079593 drug Drugs 0.000 abstract description 55
- 239000007943 implant Substances 0.000 abstract description 31
- 229920001577 copolymer Polymers 0.000 abstract description 29
- 238000011282 treatment Methods 0.000 abstract description 26
- 239000004626 polylactic acid Substances 0.000 abstract description 25
- 239000000203 mixture Substances 0.000 abstract description 23
- 239000000375 suspending agent Substances 0.000 abstract description 21
- 229920000747 poly(lactic acid) Polymers 0.000 abstract description 20
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 abstract description 15
- 230000000694 effects Effects 0.000 abstract description 15
- 229920000954 Polyglycolide Polymers 0.000 abstract description 10
- 239000002246 antineoplastic agent Substances 0.000 abstract description 10
- 239000000546 pharmaceutical excipient Substances 0.000 abstract description 10
- 239000004633 polyglycolic acid Substances 0.000 abstract description 10
- 229940041181 antineoplastic drug Drugs 0.000 abstract description 9
- 239000005038 ethylene vinyl acetate Substances 0.000 abstract description 9
- 229920001200 poly(ethylene-vinyl acetate) Polymers 0.000 abstract description 9
- 238000001959 radiotherapy Methods 0.000 abstract description 4
- 229940088597 hormone Drugs 0.000 abstract description 3
- 239000005556 hormone Substances 0.000 abstract description 3
- 239000012747 synergistic agent Substances 0.000 abstract 3
- 239000004480 active ingredient Substances 0.000 abstract 2
- 239000004037 angiogenesis inhibitor Substances 0.000 abstract 1
- 229940044683 chemotherapy drug Drugs 0.000 abstract 1
- 238000009472 formulation Methods 0.000 abstract 1
- 231100000057 systemic toxicity Toxicity 0.000 abstract 1
- 238000000034 method Methods 0.000 description 41
- 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 32
- 229960002932 anastrozole Drugs 0.000 description 30
- YBBLVLTVTVSKRW-UHFFFAOYSA-N anastrozole Chemical compound N#CC(C)(C)C1=CC(C(C)(C#N)C)=CC(CN2N=CN=C2)=C1 YBBLVLTVTVSKRW-UHFFFAOYSA-N 0.000 description 29
- -1 chrondroitin Polymers 0.000 description 29
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 26
- 238000012360 testing method Methods 0.000 description 26
- 210000004881 tumor cell Anatomy 0.000 description 24
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 23
- 238000002360 preparation method Methods 0.000 description 23
- 150000003431 steroids Chemical group 0.000 description 18
- 239000005411 L01XE02 - Gefitinib Substances 0.000 description 17
- 239000002147 L01XE04 - Sunitinib Substances 0.000 description 17
- XNRVGTHNYCNCFF-UHFFFAOYSA-N Lapatinib ditosylate monohydrate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1.CC1=CC=C(S(O)(=O)=O)C=C1.O1C(CNCCS(=O)(=O)C)=CC=C1C1=CC=C(N=CN=C2NC=3C=C(Cl)C(OCC=4C=C(F)C=CC=4)=CC=3)C2=C1 XNRVGTHNYCNCFF-UHFFFAOYSA-N 0.000 description 17
- XGALLCVXEZPNRQ-UHFFFAOYSA-N gefitinib Chemical compound C=12C=C(OCCCN3CCOCC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 XGALLCVXEZPNRQ-UHFFFAOYSA-N 0.000 description 17
- 229960002584 gefitinib Drugs 0.000 description 17
- YLMAHDNUQAMNNX-UHFFFAOYSA-N imatinib methanesulfonate Chemical compound CS(O)(=O)=O.C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 YLMAHDNUQAMNNX-UHFFFAOYSA-N 0.000 description 17
- UEJJHQNACJXSKW-UHFFFAOYSA-N 2-(2,6-dioxopiperidin-3-yl)-1H-isoindole-1,3(2H)-dione Chemical compound O=C1C2=CC=CC=C2C(=O)N1C1CCC(=O)NC1=O UEJJHQNACJXSKW-UHFFFAOYSA-N 0.000 description 16
- 108010000817 Leuprolide Proteins 0.000 description 16
- 229960004338 leuprorelin Drugs 0.000 description 16
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 16
- LBWFXVZLPYTWQI-IPOVEDGCSA-N n-[2-(diethylamino)ethyl]-5-[(z)-(5-fluoro-2-oxo-1h-indol-3-ylidene)methyl]-2,4-dimethyl-1h-pyrrole-3-carboxamide;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.CCN(CC)CCNC(=O)C1=C(C)NC(\C=C/2C3=CC(F)=CC=C3NC\2=O)=C1C LBWFXVZLPYTWQI-IPOVEDGCSA-N 0.000 description 16
- WVUNYSQLFKLYNI-AATRIKPKSA-N pelitinib Chemical compound C=12C=C(NC(=O)\C=C\CN(C)C)C(OCC)=CC2=NC=C(C#N)C=1NC1=CC=C(F)C(Cl)=C1 WVUNYSQLFKLYNI-AATRIKPKSA-N 0.000 description 16
- WUWDLXZGHZSWQZ-WQLSENKSSA-N semaxanib Chemical compound N1C(C)=CC(C)=C1\C=C/1C2=CC=CC=C2NC\1=O WUWDLXZGHZSWQZ-WQLSENKSSA-N 0.000 description 16
- 229940034785 sutent Drugs 0.000 description 16
- 229960001603 tamoxifen Drugs 0.000 description 16
- 229960003433 thalidomide Drugs 0.000 description 16
- SGOOQMRIPALTEL-UHFFFAOYSA-N 4-hydroxy-N,1-dimethyl-2-oxo-N-phenyl-3-quinolinecarboxamide Chemical compound OC=1C2=CC=CC=C2N(C)C(=O)C=1C(=O)N(C)C1=CC=CC=C1 SGOOQMRIPALTEL-UHFFFAOYSA-N 0.000 description 15
- 102400000068 Angiostatin Human genes 0.000 description 15
- 108010079709 Angiostatins Proteins 0.000 description 15
- MLDQJTXFUGDVEO-UHFFFAOYSA-N BAY-43-9006 Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=CC(NC(=O)NC=3C=C(C(Cl)=CC=3)C(F)(F)F)=CC=2)=C1 MLDQJTXFUGDVEO-UHFFFAOYSA-N 0.000 description 15
- ZBNZXTGUTAYRHI-UHFFFAOYSA-N Dasatinib Chemical compound C=1C(N2CCN(CCO)CC2)=NC(C)=NC=1NC(S1)=NC=C1C(=O)NC1=C(C)C=CC=C1Cl ZBNZXTGUTAYRHI-UHFFFAOYSA-N 0.000 description 15
- 102400001047 Endostatin Human genes 0.000 description 15
- 108010079505 Endostatins Proteins 0.000 description 15
- 239000005511 L01XE05 - Sorafenib Substances 0.000 description 15
- FZCSTZYAHCUGEM-UHFFFAOYSA-N aspergillomarasmine B Natural products OC(=O)CNC(C(O)=O)CNC(C(O)=O)CC(O)=O FZCSTZYAHCUGEM-UHFFFAOYSA-N 0.000 description 15
- 229940120638 avastin Drugs 0.000 description 15
- 229960002448 dasatinib Drugs 0.000 description 15
- 230000002401 inhibitory effect Effects 0.000 description 15
- GFIJNRVAKGFPGQ-LIJARHBVSA-N leuprolide Chemical compound CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=CC=C(O)C=C1 GFIJNRVAKGFPGQ-LIJARHBVSA-N 0.000 description 15
- 239000011859 microparticle Substances 0.000 description 15
- 229960003522 roquinimex Drugs 0.000 description 15
- 229960003787 sorafenib Drugs 0.000 description 15
- XFCLJVABOIYOMF-QPLCGJKRSA-N toremifene Chemical compound C1=CC(OCCN(C)C)=CC=C1C(\C=1C=CC=CC=1)=C(\CCCl)C1=CC=CC=C1 XFCLJVABOIYOMF-QPLCGJKRSA-N 0.000 description 15
- BFYIZQONLCFLEV-DAELLWKTSA-N Aromasine Chemical compound O=C1C=C[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CC(=C)C2=C1 BFYIZQONLCFLEV-DAELLWKTSA-N 0.000 description 14
- 108010069236 Goserelin Proteins 0.000 description 14
- 239000002136 L01XE07 - Lapatinib Substances 0.000 description 14
- 108010050144 Triptorelin Pamoate Proteins 0.000 description 14
- 229960000255 exemestane Drugs 0.000 description 14
- 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 14
- 239000003205 fragrance Substances 0.000 description 14
- 229960002913 goserelin Drugs 0.000 description 14
- 229950002248 idoxifene Drugs 0.000 description 14
- 229960003685 imatinib mesylate Drugs 0.000 description 14
- 229960004891 lapatinib Drugs 0.000 description 14
- 229920001606 poly(lactic acid-co-glycolic acid) Polymers 0.000 description 14
- 229960004622 raloxifene Drugs 0.000 description 14
- GZUITABIAKMVPG-UHFFFAOYSA-N raloxifene Chemical compound C1=CC(O)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(O)C=C2S1 GZUITABIAKMVPG-UHFFFAOYSA-N 0.000 description 14
- 239000000725 suspension Substances 0.000 description 14
- 229960005026 toremifene Drugs 0.000 description 14
- 229960004824 triptorelin Drugs 0.000 description 14
- 241000196324 Embryophyta Species 0.000 description 13
- BLCLNMBMMGCOAS-URPVMXJPSA-N Goserelin Chemical compound C([C@@H](C(=O)N[C@H](COC(C)(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1[C@@H](CCC1)C(=O)NNC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 BLCLNMBMMGCOAS-URPVMXJPSA-N 0.000 description 13
- JJKOTMDDZAJTGQ-DQSJHHFOSA-N Idoxifene Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN2CCCC2)=CC=1)/C1=CC=C(I)C=C1 JJKOTMDDZAJTGQ-DQSJHHFOSA-N 0.000 description 13
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 13
- 229960003437 aminoglutethimide Drugs 0.000 description 13
- ROBVIMPUHSLWNV-UHFFFAOYSA-N aminoglutethimide Chemical compound C=1C=C(N)C=CC=1C1(CC)CCC(=O)NC1=O ROBVIMPUHSLWNV-UHFFFAOYSA-N 0.000 description 13
- 229910021529 ammonia Inorganic materials 0.000 description 13
- WNRZHQBJSXRYJK-UHFFFAOYSA-N carboxyamidotriazole Chemical compound NC1=C(C(=O)N)N=NN1CC(C=C1Cl)=CC(Cl)=C1C(=O)C1=CC=C(Cl)C=C1 WNRZHQBJSXRYJK-UHFFFAOYSA-N 0.000 description 13
- 229960004616 medroxyprogesterone Drugs 0.000 description 13
- 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 13
- 229920000642 polymer Polymers 0.000 description 13
- VXKHXGOKWPXYNA-PGBVPBMZSA-N triptorelin Chemical compound C([C@@H](C(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)NCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 VXKHXGOKWPXYNA-PGBVPBMZSA-N 0.000 description 13
- 230000004614 tumor growth Effects 0.000 description 13
- NECZZOFFLFZNHL-XVGZVFJZSA-N (2s)-2-amino-5-[[(2r)-3-[2-[bis[bis(2-chloroethyl)amino]-oxidophosphaniumyl]oxyethylsulfonyl]-1-[[(r)-carboxy(phenyl)methyl]amino]-1-oxopropan-2-yl]amino]-5-oxopentanoic acid;hydron;chloride Chemical compound Cl.ClCCN(CCCl)P(=O)(N(CCCl)CCCl)OCCS(=O)(=O)C[C@H](NC(=O)CC[C@H](N)C(O)=O)C(=O)N[C@@H](C(O)=O)C1=CC=CC=C1 NECZZOFFLFZNHL-XVGZVFJZSA-N 0.000 description 12
- FVVPWVFWOOMXEZ-ZIADKAODSA-N 4-[(z)-1-[4-[2-(dimethylamino)ethoxy]phenyl]-2-(4-propan-2-ylphenyl)but-1-enyl]phenol Chemical compound C=1C=C(C(C)C)C=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=C(O)C=C1 FVVPWVFWOOMXEZ-ZIADKAODSA-N 0.000 description 12
- 108700011582 TER 286 Proteins 0.000 description 12
- 230000012010 growth Effects 0.000 description 12
- 229950008642 miproxifene Drugs 0.000 description 12
- 229960001972 panitumumab Drugs 0.000 description 12
- 150000001336 alkenes Chemical class 0.000 description 11
- 229950000772 canfosfamide Drugs 0.000 description 11
- GKIRPKYJQBWNGO-OCEACIFDSA-N clomifene Chemical compound C1=CC(OCCN(CC)CC)=CC=C1C(\C=1C=CC=CC=1)=C(\Cl)C1=CC=CC=C1 GKIRPKYJQBWNGO-OCEACIFDSA-N 0.000 description 11
- 229960003608 clomifene Drugs 0.000 description 11
- 229960003881 letrozole Drugs 0.000 description 11
- HPJKCIUCZWXJDR-UHFFFAOYSA-N letrozole Chemical compound C1=CC(C#N)=CC=C1C(N1N=CN=C1)C1=CC=C(C#N)C=C1 HPJKCIUCZWXJDR-UHFFFAOYSA-N 0.000 description 11
- 229960001786 megestrol Drugs 0.000 description 11
- 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 11
- LKJPYSCBVHEWIU-KRWDZBQOSA-N (R)-bicalutamide Chemical compound C([C@@](O)(C)C(=O)NC=1C=C(C(C#N)=CC=1)C(F)(F)F)S(=O)(=O)C1=CC=C(F)C=C1 LKJPYSCBVHEWIU-KRWDZBQOSA-N 0.000 description 10
- TXUZVZSFRXZGTL-QPLCGJKRSA-N afimoxifene Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=C(O)C=C1 TXUZVZSFRXZGTL-QPLCGJKRSA-N 0.000 description 10
- 229960000997 bicalutamide Drugs 0.000 description 10
- 238000002156 mixing Methods 0.000 description 10
- 239000002689 soil Substances 0.000 description 10
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 9
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 9
- 238000001694 spray drying Methods 0.000 description 9
- 238000007920 subcutaneous administration Methods 0.000 description 9
- 230000001225 therapeutic effect Effects 0.000 description 9
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 8
- 229930195725 Mannitol Natural products 0.000 description 8
- 241000699670 Mus sp. Species 0.000 description 8
- 239000004615 ingredient Substances 0.000 description 8
- 239000000594 mannitol Substances 0.000 description 8
- 235000010355 mannitol Nutrition 0.000 description 8
- 230000001629 suppression Effects 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 206010006187 Breast cancer Diseases 0.000 description 7
- 208000026310 Breast neoplasm Diseases 0.000 description 7
- 230000037396 body weight Effects 0.000 description 7
- 238000011275 oncology therapy Methods 0.000 description 7
- 150000003839 salts Chemical class 0.000 description 7
- 238000010254 subcutaneous injection Methods 0.000 description 7
- 239000007929 subcutaneous injection Substances 0.000 description 7
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 6
- 230000005764 inhibitory process Effects 0.000 description 6
- 239000000693 micelle Substances 0.000 description 6
- 210000004204 blood vessel Anatomy 0.000 description 5
- 201000008275 breast carcinoma Diseases 0.000 description 5
- 201000011510 cancer Diseases 0.000 description 5
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 5
- 239000008187 granular material Substances 0.000 description 5
- 238000002513 implantation Methods 0.000 description 5
- 239000003094 microcapsule Substances 0.000 description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 5
- 231100000331 toxic Toxicity 0.000 description 5
- 230000002588 toxic effect Effects 0.000 description 5
- YCOYDOIWSSHVCK-UHFFFAOYSA-N vatalanib Chemical compound C1=CC(Cl)=CC=C1NC(C1=CC=CC=C11)=NN=C1CC1=CC=NC=C1 YCOYDOIWSSHVCK-UHFFFAOYSA-N 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- 229920002732 Polyanhydride Polymers 0.000 description 4
- 229920001400 block copolymer Polymers 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- 238000007334 copolymerization reaction Methods 0.000 description 4
- 229960000935 dehydrated alcohol Drugs 0.000 description 4
- 238000009792 diffusion process Methods 0.000 description 4
- 238000011978 dissolution method Methods 0.000 description 4
- 239000012153 distilled water Substances 0.000 description 4
- 239000000499 gel Substances 0.000 description 4
- 229960004275 glycolic acid Drugs 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 229920002521 macromolecule Polymers 0.000 description 4
- 230000035479 physiological effects, processes and functions Effects 0.000 description 4
- WINHZLLDWRZWRT-ATVHPVEESA-N sunitinib Chemical compound CCN(CC)CCNC(=O)C1=C(C)NC(\C=C/2C3=CC(F)=CC=C3NC\2=O)=C1C WINHZLLDWRZWRT-ATVHPVEESA-N 0.000 description 4
- 239000004094 surface-active agent Substances 0.000 description 4
- 230000000699 topical effect Effects 0.000 description 4
- 210000003462 vein Anatomy 0.000 description 4
- 239000008215 water for injection Substances 0.000 description 4
- VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 description 3
- PGXWBZJYJBAVKD-UHFFFAOYSA-N 3-amino-1,3-oxazol-2-one Chemical compound NN1C=COC1=O PGXWBZJYJBAVKD-UHFFFAOYSA-N 0.000 description 3
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 3
- 229920002101 Chitin Polymers 0.000 description 3
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 3
- 229920002125 Sokalan® Polymers 0.000 description 3
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 3
- YADZBEISHVCBSJ-UHFFFAOYSA-N [I].OCC(O)CO Chemical compound [I].OCC(O)CO YADZBEISHVCBSJ-UHFFFAOYSA-N 0.000 description 3
- 239000002671 adjuvant Substances 0.000 description 3
- 229960001631 carbomer Drugs 0.000 description 3
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 3
- 229960004316 cisplatin Drugs 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- AMTWCFIAVKBGOD-UHFFFAOYSA-N dioxosilane;methoxy-dimethyl-trimethylsilyloxysilane Chemical compound O=[Si]=O.CO[Si](C)(C)O[Si](C)(C)C AMTWCFIAVKBGOD-UHFFFAOYSA-N 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 229960005309 estradiol Drugs 0.000 description 3
- 229930182833 estradiol Natural products 0.000 description 3
- 238000007710 freezing Methods 0.000 description 3
- 230000008014 freezing Effects 0.000 description 3
- JYGFTBXVXVMTGB-UHFFFAOYSA-N indolin-2-one Chemical class C1=CC=C2NC(=O)CC2=C1 JYGFTBXVXVMTGB-UHFFFAOYSA-N 0.000 description 3
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 3
- 210000003716 mesoderm Anatomy 0.000 description 3
- UDGSVBYJWHOHNN-UHFFFAOYSA-N n',n'-diethylethane-1,2-diamine Chemical compound CCN(CC)CCN UDGSVBYJWHOHNN-UHFFFAOYSA-N 0.000 description 3
- 239000013642 negative control Substances 0.000 description 3
- 229920001542 oligosaccharide Polymers 0.000 description 3
- 150000002482 oligosaccharides Chemical class 0.000 description 3
- 235000010603 pastilles Nutrition 0.000 description 3
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 3
- 208000023958 prostate neoplasm Diseases 0.000 description 3
- DRYRBWIFRVMRPV-UHFFFAOYSA-N quinazolin-4-amine Chemical compound C1=CC=C2C(N)=NC=NC2=C1 DRYRBWIFRVMRPV-UHFFFAOYSA-N 0.000 description 3
- 229940083037 simethicone Drugs 0.000 description 3
- 238000011125 single therapy Methods 0.000 description 3
- 159000000000 sodium salts Chemical class 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000001356 surgical procedure Methods 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 231100000419 toxicity Toxicity 0.000 description 3
- 230000001988 toxicity Effects 0.000 description 3
- 229950000578 vatalanib Drugs 0.000 description 3
- 239000000811 xylitol Substances 0.000 description 3
- 235000010447 xylitol Nutrition 0.000 description 3
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 3
- 229960002675 xylitol Drugs 0.000 description 3
- DNXHEGUUPJUMQT-UHFFFAOYSA-N (+)-estrone Natural products OC1=CC=C2C3CCC(C)(C(CC4)=O)C4C3CCC2=C1 DNXHEGUUPJUMQT-UHFFFAOYSA-N 0.000 description 2
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 2
- NIBFJPXGNVPNHK-UHFFFAOYSA-N 2,2-difluoro-1,3-benzodioxole-4-carbaldehyde Chemical group C1=CC(C=O)=C2OC(F)(F)OC2=C1 NIBFJPXGNVPNHK-UHFFFAOYSA-N 0.000 description 2
- HBZHNVUMFPGVHW-UHFFFAOYSA-N 2-chloro-1h-indole Chemical compound C1=CC=C2NC(Cl)=CC2=C1 HBZHNVUMFPGVHW-UHFFFAOYSA-N 0.000 description 2
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 2
- SWINWPBPEKHUOD-UHFFFAOYSA-N 2-hydroxyestron Natural products OC1=C(O)C=C2C3CCC(C)(C(CC4)=O)C4C3CCC2=C1 SWINWPBPEKHUOD-UHFFFAOYSA-N 0.000 description 2
- SWINWPBPEKHUOD-JPVZDGGYSA-N 2-hydroxyestrone Chemical compound OC1=C(O)C=C2[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1 SWINWPBPEKHUOD-JPVZDGGYSA-N 0.000 description 2
- DODQJNMQWMSYGS-QPLCGJKRSA-N 4-[(z)-1-[4-[2-(dimethylamino)ethoxy]phenyl]-1-phenylbut-1-en-2-yl]phenol Chemical compound C=1C=C(O)C=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 DODQJNMQWMSYGS-QPLCGJKRSA-N 0.000 description 2
- XRYJULCDUUATMC-CYBMUJFWSA-N 4-[4-[[(1r)-1-phenylethyl]amino]-7h-pyrrolo[2,3-d]pyrimidin-6-yl]phenol Chemical compound N([C@H](C)C=1C=CC=CC=1)C(C=1C=2)=NC=NC=1NC=2C1=CC=C(O)C=C1 XRYJULCDUUATMC-CYBMUJFWSA-N 0.000 description 2
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
- 208000003174 Brain Neoplasms Diseases 0.000 description 2
- DLGOEMSEDOSKAD-UHFFFAOYSA-N Carmustine Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 description 2
- 108010035532 Collagen Proteins 0.000 description 2
- 102000008186 Collagen Human genes 0.000 description 2
- 206010052804 Drug tolerance Diseases 0.000 description 2
- 206010014759 Endometrial neoplasm Diseases 0.000 description 2
- DNXHEGUUPJUMQT-CBZIJGRNSA-N Estrone Chemical compound OC1=CC=C2[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1 DNXHEGUUPJUMQT-CBZIJGRNSA-N 0.000 description 2
- VWUXBMIQPBEWFH-WCCTWKNTSA-N Fulvestrant Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3[C@H](CCCCCCCCCS(=O)CCCC(F)(F)C(F)(F)F)CC2=C1 VWUXBMIQPBEWFH-WCCTWKNTSA-N 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 241001062009 Indigofera Species 0.000 description 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 2
- IVDYZAAPOLNZKG-KWHRADDSSA-N Mepitiostane Chemical compound O([C@@H]1[C@]2(CC[C@@H]3[C@@]4(C)C[C@H]5S[C@H]5C[C@@H]4CC[C@H]3[C@@H]2CC1)C)C1(OC)CCCC1 IVDYZAAPOLNZKG-KWHRADDSSA-N 0.000 description 2
- MTMZZIPTQITGCY-OLGWUGKESA-N Moxestrol Chemical compound OC1=CC=C2[C@H]3[C@@H](OC)C[C@]4(C)[C@@](C#C)(O)CC[C@H]4[C@@H]3CCC2=C1 MTMZZIPTQITGCY-OLGWUGKESA-N 0.000 description 2
- ABOLPUDOABZSNW-UHFFFAOYSA-N N1CCNCC1.CC1=C(C=C(C(=O)O)C=C1)C(=O)O Chemical compound N1CCNCC1.CC1=C(C=C(C(=O)O)C=C1)C(=O)O ABOLPUDOABZSNW-UHFFFAOYSA-N 0.000 description 2
- 208000034530 PLAA-associated neurodevelopmental disease Diseases 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 2
- KJQFBVYMGADDTQ-UHFFFAOYSA-N S-butyl-DL-homocysteine (S,R)-sulfoximine Chemical compound CCCCS(=N)(=O)CCC(N)C(O)=O KJQFBVYMGADDTQ-UHFFFAOYSA-N 0.000 description 2
- XPLJEFSRINKZLC-ATVHPVEESA-N SU11652 Chemical compound CCN(CC)CCNC(=O)C1=C(C)NC(\C=C/2C3=CC(Cl)=CC=C3NC\2=O)=C1C XPLJEFSRINKZLC-ATVHPVEESA-N 0.000 description 2
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 2
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 2
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 229920005576 aliphatic polyanhydride Polymers 0.000 description 2
- GGFOZRQCNXQCLO-UHFFFAOYSA-N aniline;methanesulfonic acid Chemical compound CS(O)(=O)=O.NC1=CC=CC=C1 GGFOZRQCNXQCLO-UHFFFAOYSA-N 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 239000011805 ball Substances 0.000 description 2
- JLYXXMFPNIAWKQ-CDRYSYESSA-N beta-hexachlorocyclohexane Chemical compound Cl[C@H]1[C@H](Cl)[C@@H](Cl)[C@H](Cl)[C@@H](Cl)[C@@H]1Cl JLYXXMFPNIAWKQ-CDRYSYESSA-N 0.000 description 2
- 230000017531 blood circulation Effects 0.000 description 2
- 210000001124 body fluid Anatomy 0.000 description 2
- 239000010839 body fluid Substances 0.000 description 2
- 229960005243 carmustine Drugs 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000002512 chemotherapy Methods 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 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 2
- 229960000452 diethylstilbestrol Drugs 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 238000004945 emulsification Methods 0.000 description 2
- 201000003914 endometrial carcinoma Diseases 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- YJGVMLPVUAXIQN-UHFFFAOYSA-N epipodophyllotoxin Natural products COC1=C(OC)C(OC)=CC(C2C3=CC=4OCOC=4C=C3C(O)C3C2C(OC3)=O)=C1 YJGVMLPVUAXIQN-UHFFFAOYSA-N 0.000 description 2
- 229960003399 estrone Drugs 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 229960002074 flutamide Drugs 0.000 description 2
- VZCCETWTMQHEPK-UHFFFAOYSA-N gamma-Linolensaeure Natural products CCCCCC=CCC=CCC=CCCCCC(O)=O VZCCETWTMQHEPK-UHFFFAOYSA-N 0.000 description 2
- VZCCETWTMQHEPK-QNEBEIHSSA-N gamma-linolenic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/CCCCC(O)=O VZCCETWTMQHEPK-QNEBEIHSSA-N 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 229920002674 hyaluronan Polymers 0.000 description 2
- 229960003160 hyaluronic acid Drugs 0.000 description 2
- 230000002209 hydrophobic effect Effects 0.000 description 2
- 229960002411 imatinib Drugs 0.000 description 2
- 150000002460 imidazoles Chemical class 0.000 description 2
- 230000008595 infiltration Effects 0.000 description 2
- 238000001764 infiltration Methods 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- 239000002075 main ingredient Substances 0.000 description 2
- 229950009246 mepitiostane Drugs 0.000 description 2
- 229940098779 methanesulfonic acid Drugs 0.000 description 2
- 239000004530 micro-emulsion Substances 0.000 description 2
- 239000011806 microball Substances 0.000 description 2
- 239000004531 microgranule Substances 0.000 description 2
- 229960001241 moxestrol Drugs 0.000 description 2
- 239000002077 nanosphere Substances 0.000 description 2
- 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 235000015097 nutrients Nutrition 0.000 description 2
- 238000007500 overflow downdraw method Methods 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- YJGVMLPVUAXIQN-XVVDYKMHSA-N podophyllotoxin Chemical compound 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-XVVDYKMHSA-N 0.000 description 2
- 229960001237 podophyllotoxin Drugs 0.000 description 2
- YVCVYCSAAZQOJI-UHFFFAOYSA-N podophyllotoxin Natural products COC1=C(O)C(OC)=CC(C2C3=CC=4OCOC=4C=C3C(O)C3C2C(OC3)=O)=C1 YVCVYCSAAZQOJI-UHFFFAOYSA-N 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 201000001514 prostate carcinoma Diseases 0.000 description 2
- 150000003233 pyrroles Chemical class 0.000 description 2
- VHXNKPBCCMUMSW-FQEVSTJZSA-N rubitecan Chemical compound C1=CC([N+]([O-])=O)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VHXNKPBCCMUMSW-FQEVSTJZSA-N 0.000 description 2
- 229950009213 rubitecan Drugs 0.000 description 2
- 229910052710 silicon Inorganic materials 0.000 description 2
- 239000010703 silicon Substances 0.000 description 2
- 239000003271 steroid hormone antagonist Substances 0.000 description 2
- QNUKRWAIZMBVCU-WCIBSUBMSA-N su9516 Chemical compound C12=CC(OC)=CC=C2NC(=O)\C1=C/C1=CN=CN1 QNUKRWAIZMBVCU-WCIBSUBMSA-N 0.000 description 2
- 150000005846 sugar alcohols Polymers 0.000 description 2
- 210000001685 thyroid gland Anatomy 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- MBMQEIFVQACCCH-QBODLPLBSA-N zearalenone Chemical compound O=C1O[C@@H](C)CCCC(=O)CCC\C=C\C2=CC(O)=CC(O)=C21 MBMQEIFVQACCCH-QBODLPLBSA-N 0.000 description 2
- JLYXXMFPNIAWKQ-UHFFFAOYSA-N γ Benzene hexachloride Chemical compound ClC1C(Cl)C(Cl)C(Cl)C(Cl)C1Cl JLYXXMFPNIAWKQ-UHFFFAOYSA-N 0.000 description 2
- PROQIPRRNZUXQM-UHFFFAOYSA-N (16alpha,17betaOH)-Estra-1,3,5(10)-triene-3,16,17-triol Natural products OC1=CC=C2C3CCC(C)(C(C(O)C4)O)C4C3CCC2=C1 PROQIPRRNZUXQM-UHFFFAOYSA-N 0.000 description 1
- UAKWLVYMKBWHMX-RVDMUPIBSA-N (3e)-3-[[4-(dimethylamino)phenyl]methylidene]-1h-indol-2-one Chemical compound C1=CC(N(C)C)=CC=C1\C=C\1C2=CC=CC=C2NC/1=O UAKWLVYMKBWHMX-RVDMUPIBSA-N 0.000 description 1
- JGSMCYNBVCGIHC-QPEQYQDCSA-N (3z)-3-[(4-hydroxyphenyl)methylidene]-5,6-dimethoxy-1h-indol-2-one Chemical compound C1=2C=C(OC)C(OC)=CC=2NC(=O)\C1=C/C1=CC=C(O)C=C1 JGSMCYNBVCGIHC-QPEQYQDCSA-N 0.000 description 1
- VFCXONOPGCDDBQ-AQTBWJFISA-N (3z)-3-[[4-(dimethylamino)naphthalen-1-yl]methylidene]-1h-indol-2-one Chemical compound C12=CC=CC=C2C(N(C)C)=CC=C1\C=C/1C2=CC=CC=C2NC\1=O VFCXONOPGCDDBQ-AQTBWJFISA-N 0.000 description 1
- SSSSRRYHIQUOCO-UHFFFAOYSA-N 1-(2-chloro-1H-indol-3-yl)-3-methylideneindol-2-one Chemical compound ClC=1NC2=CC=CC=C2C=1N1C(C(C2=CC=CC=C12)=C)=O SSSSRRYHIQUOCO-UHFFFAOYSA-N 0.000 description 1
- HOVXQHXPLKLENE-UHFFFAOYSA-N 1-methylidene-1,3-thiazole Chemical compound C=S1C=CN=C1 HOVXQHXPLKLENE-UHFFFAOYSA-N 0.000 description 1
- 229930182834 17alpha-Estradiol Natural products 0.000 description 1
- VOXZDWNPVJITMN-SFFUCWETSA-N 17α-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-SFFUCWETSA-N 0.000 description 1
- 150000000304 17α-estradiols Chemical class 0.000 description 1
- XKZQKPRCPNGNFR-UHFFFAOYSA-N 2-(3-hydroxyphenyl)phenol Chemical compound OC1=CC=CC(C=2C(=CC=CC=2)O)=C1 XKZQKPRCPNGNFR-UHFFFAOYSA-N 0.000 description 1
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
- IJWBZNNZKGKTEK-UHFFFAOYSA-N 3,3-dichloro-5-(4-methylpiperidin-1-yl)sulfonyl-1h-indol-2-one Chemical compound C1CC(C)CCN1S(=O)(=O)C1=CC=C(NC(=O)C2(Cl)Cl)C2=C1 IJWBZNNZKGKTEK-UHFFFAOYSA-N 0.000 description 1
- KFGPDFWWTNSMLP-UHFFFAOYSA-N 3-(1h-indol-2-ylmethylidene)-1h-indol-2-one Chemical class C1=CC=C2NC(C=C3C4=CC=CC=C4NC3=O)=CC2=C1 KFGPDFWWTNSMLP-UHFFFAOYSA-N 0.000 description 1
- OLVLWYDPBIVIHG-UHFFFAOYSA-N 3-(dipyridin-2-ylmethyl)-1-phenyl-3H-indol-2-one Chemical compound N1=C(C=CC=C1)C(C1C(N(C2=CC=CC=C12)C1=CC=CC=C1)=O)C1=NC=CC=C1 OLVLWYDPBIVIHG-UHFFFAOYSA-N 0.000 description 1
- BAFCXYQTVDGPAM-UHFFFAOYSA-N 3-[(5-chloropyridin-3-yl)methylidene]-1H-indol-2-one Chemical compound ClC=1C=C(C=NC=1)C=C1C(NC2=CC=CC=C12)=O BAFCXYQTVDGPAM-UHFFFAOYSA-N 0.000 description 1
- VFCXONOPGCDDBQ-UHFFFAOYSA-N 3-[[4-(dimethylamino)-1-naphthalenyl]methylidene]-1H-indol-2-one Chemical compound C12=CC=CC=C2C(N(C)C)=CC=C1C=C1C2=CC=CC=C2NC1=O VFCXONOPGCDDBQ-UHFFFAOYSA-N 0.000 description 1
- KUEYYIJXBRWZIB-UHFFFAOYSA-N 3-[bis(4-methoxyphenyl)methylidene]-1H-indol-2-one Chemical compound C1=CC(OC)=CC=C1C(C=1C=CC(OC)=CC=1)=C1C2=CC=CC=C2NC1=O KUEYYIJXBRWZIB-UHFFFAOYSA-N 0.000 description 1
- 125000006284 3-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(F)=C1[H])C([H])([H])* 0.000 description 1
- ZNFJBJDODKHWED-QGOAFFKASA-N 4-[4-[(e)-(2-oxo-1h-indol-3-ylidene)methyl]phenyl]piperazine-1-carbaldehyde Chemical compound C1CN(C=O)CCN1C(C=C1)=CC=C1\C=C\1C2=CC=CC=C2NC/1=O ZNFJBJDODKHWED-QGOAFFKASA-N 0.000 description 1
- JOSBKHSFMWFNIR-UHFFFAOYSA-N 4-methylbenzenesulfonic acid;hydrate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1.CC1=CC=C(S(O)(=O)=O)C=C1 JOSBKHSFMWFNIR-UHFFFAOYSA-N 0.000 description 1
- SRSGVKWWVXWSJT-ATVHPVEESA-N 5-[(z)-(5-fluoro-2-oxo-1h-indol-3-ylidene)methyl]-2,4-dimethyl-n-(2-pyrrolidin-1-ylethyl)-1h-pyrrole-3-carboxamide Chemical compound CC=1NC(\C=C/2C3=CC(F)=CC=C3NC\2=O)=C(C)C=1C(=O)NCCN1CCCC1 SRSGVKWWVXWSJT-ATVHPVEESA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 208000018084 Bone neoplasm Diseases 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- YSVIMZFFVMFOJP-UHFFFAOYSA-N COC1=CC=C(C=C1)N1C(C(C2=CC=CC=C12)=C)=O Chemical compound COC1=CC=C(C=C1)N1C(C(C2=CC=CC=C12)=C)=O YSVIMZFFVMFOJP-UHFFFAOYSA-N 0.000 description 1
- SWOXETHHHSUPEJ-FZPKQIFPSA-N COC=1C(=CC2=C([C@H]3CC[C@@]4(C(CC[C@H]4[C@@H]3CC2)O)C)C1)O.COC=1C(=CC2=C([C@H]3CC[C@@]4(C(CC[C@H]4[C@@H]3CC2)O)C)C1)O Chemical compound COC=1C(=CC2=C([C@H]3CC[C@@]4(C(CC[C@H]4[C@@H]3CC2)O)C)C1)O.COC=1C(=CC2=C([C@H]3CC[C@@]4(C(CC[C@H]4[C@@H]3CC2)O)C)C1)O SWOXETHHHSUPEJ-FZPKQIFPSA-N 0.000 description 1
- RRPAPBCRZGEXTR-YBQIQLKBSA-N C[C@@H]1O[C@@H](O[C@@H]2C[C@@]3(C)[C@@H]4CC=C5C(C[C@H](O)C(=O)C5(C)C)[C@]4(C)C(=O)C[C@]3(C)C2C(C)(O)C(=O)\C=C\C(C)(C)O)[C@@H](OC(C)=O)C(=O)[C@H]1O Chemical compound C[C@@H]1O[C@@H](O[C@@H]2C[C@@]3(C)[C@@H]4CC=C5C(C[C@H](O)C(=O)C5(C)C)[C@]4(C)C(=O)C[C@]3(C)C2C(C)(O)C(=O)\C=C\C(C)(C)O)[C@@H](OC(C)=O)C(=O)[C@H]1O RRPAPBCRZGEXTR-YBQIQLKBSA-N 0.000 description 1
- 101100417166 Caenorhabditis elegans rpi-1 gene Proteins 0.000 description 1
- 239000005461 Canertinib Substances 0.000 description 1
- 206010007247 Carbuncle Diseases 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- 201000000274 Carcinosarcoma Diseases 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 208000002699 Digestive System Neoplasms Diseases 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- OBMLHUPNRURLOK-XGRAFVIBSA-N Epitiostanol Chemical compound C1[C@@H]2S[C@@H]2C[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CC[C@H]21 OBMLHUPNRURLOK-XGRAFVIBSA-N 0.000 description 1
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 208000005422 Foreign-Body reaction Diseases 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Natural products OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- BVVFOLSZMQVDKV-KXQIQQEYSA-N ICI-164384 Chemical compound C1C[C@]2(C)[C@@H](O)CC[C@H]2[C@@H]2[C@H](CCCCCCCCCCC(=O)N(C)CCCC)CC3=CC(O)=CC=C3[C@H]21 BVVFOLSZMQVDKV-KXQIQQEYSA-N 0.000 description 1
- 239000005517 L01XE01 - Imatinib Substances 0.000 description 1
- 239000002067 L01XE06 - Dasatinib Substances 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- LKJPYSCBVHEWIU-UHFFFAOYSA-N N-[4-cyano-3-(trifluoromethyl)phenyl]-3-[(4-fluorophenyl)sulfonyl]-2-hydroxy-2-methylpropanamide Chemical compound C=1C=C(C#N)C(C(F)(F)F)=CC=1NC(=O)C(O)(C)CS(=O)(=O)C1=CC=C(F)C=C1 LKJPYSCBVHEWIU-UHFFFAOYSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- DZKZCXUIXLRBSY-UHFFFAOYSA-N Oc1ccc2oc(O)c(-c3ccccc3)c(=O)c2c1O Chemical class Oc1ccc2oc(O)c(-c3ccccc3)c(=O)c2c1O DZKZCXUIXLRBSY-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- 229920001273 Polyhydroxy acid Polymers 0.000 description 1
- UAKWLVYMKBWHMX-UHFFFAOYSA-N SU4312 Chemical compound C1=CC(N(C)C)=CC=C1C=C1C2=CC=CC=C2NC1=O UAKWLVYMKBWHMX-UHFFFAOYSA-N 0.000 description 1
- XLBQNZICMYZIQT-GHXNOFRVSA-N SU5614 Chemical compound N1C(C)=CC(C)=C1\C=C/1C2=CC(Cl)=CC=C2NC\1=O XLBQNZICMYZIQT-GHXNOFRVSA-N 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 206010066901 Treatment failure Diseases 0.000 description 1
- 210000000683 abdominal cavity Anatomy 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 239000003098 androgen Substances 0.000 description 1
- 230000001548 androgenic effect Effects 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- YTKUWDBFDASYHO-UHFFFAOYSA-N bendamustine Chemical compound ClCCN(CCCl)C1=CC=C2N(C)C(CCCC(O)=O)=NC2=C1 YTKUWDBFDASYHO-UHFFFAOYSA-N 0.000 description 1
- 229960002707 bendamustine Drugs 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- OJCKJHHYVUPUSJ-UHFFFAOYSA-N benzamide;methanesulfonic acid Chemical compound CS(O)(=O)=O.NC(=O)C1=CC=CC=C1 OJCKJHHYVUPUSJ-UHFFFAOYSA-N 0.000 description 1
- SOQJPQZCPBDOMF-YCUXZELOSA-N betamethasone benzoate Chemical compound O([C@]1([C@@]2(C)C[C@H](O)[C@]3(F)[C@@]4(C)C=CC(=O)C=C4CC[C@H]3[C@@H]2C[C@@H]1C)C(=O)CO)C(=O)C1=CC=CC=C1 SOQJPQZCPBDOMF-YCUXZELOSA-N 0.000 description 1
- 229960000870 betamethasone benzoate Drugs 0.000 description 1
- 238000006065 biodegradation reaction Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 210000000133 brain stem Anatomy 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- IVFYLRMMHVYGJH-PVPPCFLZSA-N calusterone Chemical compound C1C[C@]2(C)[C@](O)(C)CC[C@H]2[C@@H]2[C@@H](C)CC3=CC(=O)CC[C@]3(C)[C@H]21 IVFYLRMMHVYGJH-PVPPCFLZSA-N 0.000 description 1
- 229950009823 calusterone Drugs 0.000 description 1
- 239000003560 cancer drug Substances 0.000 description 1
- OMZCMEYTWSXEPZ-UHFFFAOYSA-N canertinib Chemical compound C1=C(Cl)C(F)=CC=C1NC1=NC=NC2=CC(OCCCN3CCOCC3)=C(NC(=O)C=C)C=C12 OMZCMEYTWSXEPZ-UHFFFAOYSA-N 0.000 description 1
- 229950002826 canertinib Drugs 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 229920003123 carboxymethyl cellulose sodium Polymers 0.000 description 1
- 210000003679 cervix uteri Anatomy 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 238000011254 conventional chemotherapy Methods 0.000 description 1
- 239000011258 core-shell material Substances 0.000 description 1
- RRPAPBCRZGEXTR-UHFFFAOYSA-N datiscoside Natural products CC(=O)OC1C(=O)C(O)C(C)OC1OC1C(C(C)(O)C(=O)C=CC(C)(C)O)C2(C)CC(=O)C3(C)C(CC(O)C(=O)C4(C)C)C4=CCC3C2(C)C1 RRPAPBCRZGEXTR-UHFFFAOYSA-N 0.000 description 1
- LPRCVLBATUMNBP-UHFFFAOYSA-N decanedioic acid;propane Chemical compound CCC.OC(=O)CCCCCCCCC(O)=O LPRCVLBATUMNBP-UHFFFAOYSA-N 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000000593 degrading effect Effects 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 239000003640 drug residue Substances 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 210000004696 endometrium Anatomy 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 229950002973 epitiostanol Drugs 0.000 description 1
- 210000003238 esophagus Anatomy 0.000 description 1
- 229960001348 estriol Drugs 0.000 description 1
- PROQIPRRNZUXQM-ZXXIGWHRSA-N estriol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H]([C@H](O)C4)O)[C@@H]4[C@@H]3CCC2=C1 PROQIPRRNZUXQM-ZXXIGWHRSA-N 0.000 description 1
- 230000001076 estrogenic effect Effects 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 210000001508 eye Anatomy 0.000 description 1
- 210000000887 face Anatomy 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 235000011194 food seasoning agent Nutrition 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 229960002258 fulvestrant Drugs 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 210000000232 gallbladder Anatomy 0.000 description 1
- 229940098330 gamma linoleic acid Drugs 0.000 description 1
- 235000020664 gamma-linolenic acid Nutrition 0.000 description 1
- 229960002733 gamolenic acid Drugs 0.000 description 1
- 210000001156 gastric mucosa Anatomy 0.000 description 1
- 239000003349 gelling agent Substances 0.000 description 1
- 230000014509 gene expression Effects 0.000 description 1
- 229940045109 genistein Drugs 0.000 description 1
- TZBJGXHYKVUXJN-UHFFFAOYSA-N genistein Natural products C1=CC(O)=CC=C1C1=COC2=CC(O)=CC(O)=C2C1=O TZBJGXHYKVUXJN-UHFFFAOYSA-N 0.000 description 1
- 235000006539 genistein Nutrition 0.000 description 1
- 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 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 125000005638 hydrazono group Chemical group 0.000 description 1
- KTUFNOKKBVMGRW-UHFFFAOYSA-N imatinib Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 KTUFNOKKBVMGRW-UHFFFAOYSA-N 0.000 description 1
- UVNXNSUKKOLFBM-UHFFFAOYSA-N imidazo[2,1-b][1,3,4]thiadiazole Chemical compound N1=CSC2=NC=CN21 UVNXNSUKKOLFBM-UHFFFAOYSA-N 0.000 description 1
- 230000008676 import Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- QNLOWBMKUIXCOW-UHFFFAOYSA-N indol-2-one Chemical compound C1=CC=CC2=NC(=O)C=C21 QNLOWBMKUIXCOW-UHFFFAOYSA-N 0.000 description 1
- 239000012155 injection solvent Substances 0.000 description 1
- 102000006495 integrins Human genes 0.000 description 1
- 108010044426 integrins Proteins 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 229940099584 lactobionate Drugs 0.000 description 1
- JYTUSYBCFIZPBE-AMTLMPIISA-N lactobionic acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O JYTUSYBCFIZPBE-AMTLMPIISA-N 0.000 description 1
- 229960001320 lapatinib ditosylate Drugs 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 201000005296 lung carcinoma Diseases 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 210000001365 lymphatic vessel Anatomy 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 210000005075 mammary gland Anatomy 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000001394 metastastic effect Effects 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- GXHMMDRXHUIUMN-UHFFFAOYSA-N methanesulfonic acid Chemical compound CS(O)(=O)=O.CS(O)(=O)=O GXHMMDRXHUIUMN-UHFFFAOYSA-N 0.000 description 1
- OKSCSVIOPIVWTC-KRWDZBQOSA-N methyl (2s)-2-[[2-[4-[bis(2-chloroethyl)amino]phenyl]acetyl]amino]-3-(1h-imidazol-5-yl)propanoate Chemical compound C([C@@H](C(=O)OC)NC(=O)CC=1C=CC(=CC=1)N(CCCl)CCCl)C1=CN=CN1 OKSCSVIOPIVWTC-KRWDZBQOSA-N 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 210000000214 mouth Anatomy 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- AZBFJBJXUQUQLF-UHFFFAOYSA-N n-(1,5-dimethylpyrrolidin-3-yl)pyrrolidine-1-carboxamide Chemical compound C1N(C)C(C)CC1NC(=O)N1CCCC1 AZBFJBJXUQUQLF-UHFFFAOYSA-N 0.000 description 1
- WXJDWBDGDSXEFA-UHFFFAOYSA-N n-(3-chlorophenyl)-5,6-dimethyl-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C=12C(C)=C(C)NC2=NC=NC=1NC1=CC=CC(Cl)=C1 WXJDWBDGDSXEFA-UHFFFAOYSA-N 0.000 description 1
- 210000001989 nasopharynx Anatomy 0.000 description 1
- 208000018389 neoplasm of cerebral hemisphere Diseases 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 1
- WGNAKZGUSRVWRH-UHFFFAOYSA-N p-cresol sulfate Chemical compound CC1=CC=C(OS(O)(=O)=O)C=C1 WGNAKZGUSRVWRH-UHFFFAOYSA-N 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 201000002528 pancreatic cancer Diseases 0.000 description 1
- 208000004019 papillary adenocarcinoma Diseases 0.000 description 1
- 229950006299 pelitinib Drugs 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 229920001610 polycaprolactone Polymers 0.000 description 1
- 239000004632 polycaprolactone Substances 0.000 description 1
- 239000000186 progesterone Substances 0.000 description 1
- 229960003387 progesterone Drugs 0.000 description 1
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- DSNYFFJTZPIKFZ-UHFFFAOYSA-N propoxybenzene Chemical compound CCCOC1=CC=CC=C1 DSNYFFJTZPIKFZ-UHFFFAOYSA-N 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 238000010298 pulverizing process Methods 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- BKXVVCILCIUCLG-UHFFFAOYSA-N raloxifene hydrochloride Chemical compound [H+].[Cl-].C1=CC(O)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(O)C=C2S1 BKXVVCILCIUCLG-UHFFFAOYSA-N 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 229950003647 semaxanib Drugs 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 229960001796 sunitinib Drugs 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229940120982 tarceva Drugs 0.000 description 1
- 238000002626 targeted therapy Methods 0.000 description 1
- BPEWUONYVDABNZ-DZBHQSCQSA-N testolactone Chemical compound O=C1C=C[C@]2(C)[C@H]3CC[C@](C)(OC(=O)CC4)[C@@H]4[C@@H]3CCC2=C1 BPEWUONYVDABNZ-DZBHQSCQSA-N 0.000 description 1
- 229960005353 testolactone Drugs 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- 210000000115 thoracic cavity Anatomy 0.000 description 1
- MBMQEIFVQACCCH-UHFFFAOYSA-N trans-Zearalenon Natural products O=C1OC(C)CCCC(=O)CCCC=CC2=CC(O)=CC(O)=C21 MBMQEIFVQACCCH-UHFFFAOYSA-N 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 210000003932 urinary bladder Anatomy 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 239000000052 vinegar Substances 0.000 description 1
- 235000021419 vinegar Nutrition 0.000 description 1
- 229920003169 water-soluble polymer Polymers 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
试验组(n) | 给药方式 | 第一天肿瘤内药物含量 | 第三天肿瘤内药物含量 | 第7天肿瘤内药物含量 |
1(3) | 尾静脉注射普通注射剂 | 0.65 | 0.35 | 0.12 |
2(3) | 腹腔注射普通注射剂 | 0.58 | 0.3 | 0.08 |
3(3) | 瘤周注射普通注射剂 | 2.8 | 1.2 | 0.3 |
4(3) | 瘤周注射缓释注射剂 | 10 | 18 | 20 |
5(3) | 瘤周放置缓释植入剂 | 20 | 30 | 32 |
6(3) | 瘤内注射普通注射剂 | 4 | 2 | 1 |
7(3) | 瘤内注射缓释注射剂 | 90 | 80 | 60 |
8(3) | 瘤内放置缓释植入剂 | 94 | 90 | 84 |
试验组(n) | 给药方式 | 肿瘤体积(cm<sup>3</sup>) | P值 |
1(6) | - | 70 | |
2(6) | 尾静脉注射普通注射剂 | 65 | 0.06 |
3(6) | 腹腔注射普通注射剂 | 66 | 0.06 |
4(6) | 瘤周注射普通注射剂 | 58 | 0.03 |
5(6) | 瘤周注射缓释注射剂 | 32 | <0.01 |
6(6) | 瘤周放置缓释植入剂 | 22 | <0.01 |
7(6) | 瘤内注射普通注射剂 | 54 | 0.04 |
8(6) | 瘤内注射缓释注射剂 | 22 | <0.001 |
9(6) | 瘤内放置缓释植入剂 | 16 | <0.001 |
组别 | 氨甲喋呤 | 增效剂 | 肿瘤抑制率(%) | P值 |
1 | + | - | 60 | * |
2 | - | 曲普瑞林 | 46 | * |
3 | - | 戈舍瑞林 | 42 | * |
4 | - | 亮丙瑞林 | 38 | * |
5 | - | 阿那曲唑 | 48 | * |
6 | - | 艾多昔芬 | 36 | * |
7 | + | 曲普瑞林 | 80 | ** |
8 | + | 戈舍瑞林 | 82 | ** |
9 | + | 亮丙瑞林 | 88 | ** |
10 | + | 阿那曲唑 | 88 | ** |
11 | + | 艾多昔芬 | 90 | ** |
瘤细胞 | 氨 | A | B | C | D | E | 氨+A | 氨+B | 氨+C | 氨+D | 氨+E |
CNS | 62 | 50 | 48 | 38 | 58 | 42 | 84 | 78 | 92 | 88 | 86 |
C6 | 64 | 52 | 46 | 36 | 64 | 40 | 90 | 84 | 94 | 84 | 94 |
SA | 58 | 58 | 36 | 42 | 62 | 48 | 86 | 82 | 88 | 92 | 92 |
BC | 54 | 54 | 40 | 42 | 64 | 54 | 84 | 84 | 94 | 84 | 82 |
瘤细胞 | 氨 | A | B | C | D | E | 氨+A | 氨+B | 氨+C | 氨+D | 氨+E |
BA | 58 | 46 | 38 | 48 | 60 | 56 | 82 | 90 | 98 | 92 | 90 |
LH | 60 | 56 | 40 | 52 | 58 | 60 | 92 | 88 | 90 | 88 | 84 |
PAT | 64 | 48 | 46 | 50 | 54 | 68 | 92 | 78 | 92 | 88 | 90 |
试验组(n) | 所受治疗 | 肿瘤抑制率(%) | P值 |
1(6) | 对照 | - | |
2(6) | 氨甲喋呤 | 42 | <0.05 |
3(6) | 甲羟孕酮 | 36 | <0.01 |
4(6) | 托瑞米芬 | 40 | <0.01 |
5(6) | 阿那曲唑 | 44 | <0.01 |
6(6) | 依西美坦 | 46 | <0.01 |
7(6) | 氨甲喋呤+甲羟孕酮 | 86 | <0.001 |
8(6) | 氨甲喋呤+托瑞米芬 | 80 | <0.001 |
9(6) | 氨甲喋呤+阿那曲唑 | 82 | <0.001 |
试验组(n) | 所受治疗 | 肿瘤抑制率(%) | P值 |
10(6) | 氨甲喋呤+依西美坦 | 92 | <0.001 |
试验组(n) | 所受治疗 | 肿瘤抑制率(%) | P值 |
1(6) | 对照 | - | |
2(6) | 氨甲喋呤 | 58 | <0.05 |
3(6) | 吉非替尼 | 50 | <0.01 |
4(6) | 厄洛替尼 | 40 | <0.01 |
5(6) | 拉帕替尼 | 36 | <0.01 |
6(6) | 伏他拉尼 | 36 | <0.01 |
7(6) | 氨甲喋呤+吉非替尼 | 82 | <0.001 |
8(6) | 氨甲喋呤+厄洛替尼 | 84 | <0.001 |
9(6) | 氨甲喋呤+拉帕替尼 | 92 | <0.001 |
10(6) | 氨甲喋呤+伏他拉尼 | 94 | <0.001 |
试验组(n) | 所受治疗 | 肿瘤抑制率(%) | P值 |
1(6) | 对照 | - | |
2(6) | 氨甲喋呤 | 54 | <0.05 |
3(6) | 培立替尼 | 58 | <0.05 |
4(6) | 反应停 | 36 | <0.05 |
5(6) | 雷诺胺 | 46 | <0.05 |
6(6) | 血管抑素 | 36 | <0.01 |
7(6) | 氨甲喋呤+培立替尼 | 80 | <0.01 |
8(6) | 氨甲喋呤+反应停 | 82 | <0.01 |
9(6) | 氨甲喋呤+雷诺胺 | 90 | <0.01 |
10(6) | 氨甲喋呤+血管抑素 | 88 | <0.001 |
试验组(n) | 所受治疗 | 肿瘤抑制率(%) | P值 |
1(6) | 对照 | - | |
2(6) | 氨甲喋呤 | 58 | <0.05 |
3(6) | 内皮抑素 | 40 | <0.01 |
4(6) | 甲磺酸甲磺酸 | 50 | <0.01 |
5(6) | 司马斯尼 | 40 | <0.01 |
试验组(n) | 所受治疗 | 肿瘤抑制率(%) | P值 |
6(6) | 达萨替尼 | 42 | <0.01 |
7(6) | 氨甲喋呤+内皮抑素 | 86 | <0.001 |
8(6) | 氨甲喋呤+甲磺酸甲磺酸 | 88 | <0.001 |
9(6) | 氨甲喋呤+司马斯尼 | 92 | <0.001 |
10(6) | 氨甲喋呤+达萨替尼 | 94 | <0.001 |
试验组(n) | 所受治疗 | 肿瘤抑制率(%) | P值 |
1(6) | 对照 | - | |
2(6) | 氨甲喋呤 | 52 | <0.05 |
3(6) | 阿瓦斯丁 | 48 | <0.01 |
4(6) | 卡那替尼 | 38 | <0.01 |
5(6) | 索拉非尼 | 40 | <0.01 |
6(6) | 苏尼替尼 | 50 | <0.01 |
7(6) | 氨甲喋呤+阿瓦斯丁 | 80 | <0.001 |
8(6) | 氨甲喋呤+卡那替尼 | 78 | <0.001 |
9(6) | 氨甲喋呤+索拉非尼 | 86 | <0.001 |
10(6) | 氨甲喋呤+苏尼替尼 | 90 | <0.001 |
溶媒黏度(cp) | 注射成功次数 | 注射成功率(%) |
10 | 1 | 5 |
50 | 2 | 10 |
100 | 4 | 20 |
200 | 7 | 35 |
300 | 9 | 45 |
400 | 12 | 60 |
500 | 14 | 70 |
550 | 14 | 70 |
600 | 16 | 80 |
650 | 18 | 90 |
Claims (1)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN2008103001123A CN101371820B (zh) | 2006-01-23 | 2006-01-23 | 含氨甲喋呤增效剂的抗癌缓释剂 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN2008103001123A CN101371820B (zh) | 2006-01-23 | 2006-01-23 | 含氨甲喋呤增效剂的抗癌缓释剂 |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CNB2006102000622A Division CN100531717C (zh) | 2006-01-23 | 2006-01-23 | 含氨甲喋呤增效剂的抗癌缓释剂 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN101371820A CN101371820A (zh) | 2009-02-25 |
CN101371820B true CN101371820B (zh) | 2010-06-02 |
Family
ID=40446324
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN2008103001123A Expired - Fee Related CN101371820B (zh) | 2006-01-23 | 2006-01-23 | 含氨甲喋呤增效剂的抗癌缓释剂 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN101371820B (zh) |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1634584A (zh) * | 2004-11-22 | 2005-07-06 | 山东蓝金生物工程有限公司 | 一种含抗代谢类药物的抗癌药物组合物 |
-
2006
- 2006-01-23 CN CN2008103001123A patent/CN101371820B/zh not_active Expired - Fee Related
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1634584A (zh) * | 2004-11-22 | 2005-07-06 | 山东蓝金生物工程有限公司 | 一种含抗代谢类药物的抗癌药物组合物 |
Also Published As
Publication number | Publication date |
---|---|
CN101371820A (zh) | 2009-02-25 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN1969816A (zh) | 一种含埃坡霉素的抗癌缓释剂 | |
CN100464736C (zh) | 同载抗代谢药物及其增效剂的抗癌缓释注射剂 | |
CN1868452A (zh) | 一种含铂类化合物的抗癌缓释注射剂 | |
CN100531717C (zh) | 含氨甲喋呤增效剂的抗癌缓释剂 | |
CN101219113A (zh) | 含苯达莫司汀的复方抗癌缓释注射剂 | |
CN101385698A (zh) | 一种抗癌缓释植入剂 | |
CN101380303A (zh) | 一种同载铂类化合物及其增效剂的抗癌药物缓释注射剂 | |
CN101371820B (zh) | 含氨甲喋呤增效剂的抗癌缓释剂 | |
CN1883452A (zh) | 一种同载血管抑制剂及其增效剂的抗癌缓释剂 | |
CN101234081A (zh) | 一种含血管抑制剂的缓释注射剂 | |
CN101548948A (zh) | 含5-fu增效剂的抗癌药物缓释剂 | |
CN101380296A (zh) | 同载紫杉烷及其增效剂的抗癌药物缓释剂 | |
CN100594886C (zh) | 一种同载新生血管抑制剂和四唑紫罗兰的抗癌缓释剂 | |
CN101219112A (zh) | 一种含苯达莫司汀的复方抗癌缓释注射剂 | |
CN101234083A (zh) | 一种含血管抑制剂反应停的缓释注射剂 | |
CN100486560C (zh) | 一种含血管抑制剂的复方抗癌缓释注射剂 | |
CN1857204A (zh) | 一种同载血管抑制剂及其增效剂的抗癌缓释剂 | |
CN101234082A (zh) | 一种含血管抑制剂伏他拉尼的缓释注射剂 | |
CN101234080A (zh) | 一种含血管抑制剂及其增效剂的缓释注射剂 | |
CN1969828A (zh) | 一种含间质水解剂的抗癌缓释注射剂 | |
CN1846675A (zh) | 含5-fu增效剂的抗癌药物缓释剂 | |
CN100998555A (zh) | 一种含血管抑制剂的抗癌缓释剂 | |
CN101336889A (zh) | 一种同载血管抑制剂及其增效剂的抗癌缓释剂 | |
CN101019829A (zh) | 一种含血管抑制剂的抗癌缓释剂 | |
CN101380304A (zh) | 同载血管抑制剂及其增效剂的抗癌药物缓释注射剂 |
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 | ||
C56 | Change in the name or address of the patentee | ||
CP02 | Change in the address of a patent holder |
Address after: High tech Zone Tianchen road Ji'nan City, Shandong province 250101 No. 1750 Patentee after: Jinan Shuaihua Pharmaceutical Technology Co., Ltd. Address before: 202, room 2, building 19, Pioneer Park, No. 250100 Huaneng Road, Shandong, Ji'nan Patentee before: Jinan Shuaihua Pharmaceutical Technology Co., Ltd. |
|
ASS | Succession or assignment of patent right |
Owner name: SHANDONG LANJIN BIOENGINEERING CO., LTD. Free format text: FORMER OWNER: JINAN SHUAIHUA MEDICINE TECHNOLOGY CO., LTD. Effective date: 20120815 |
|
C41 | Transfer of patent application or patent right or utility model | ||
TR01 | Transfer of patent right |
Effective date of registration: 20120815 Address after: High tech Zone Tianchen road Ji'nan City, Shandong province 250101 No. 1750 Patentee after: Shandong Lanjin Pharmaceuticals Co., Ltd. Address before: High tech Zone Tianchen road Ji'nan City, Shandong province 250101 No. 1750 Patentee before: Jinan Shuaihua Pharmaceutical Technology Co., Ltd. |
|
CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20100602 Termination date: 20170123 |
|
CF01 | Termination of patent right due to non-payment of annual fee |