AU2016337370A1 - Liposome composition co-encapsulating doxorubicin and a prodrug of mitomycin C - Google Patents
Liposome composition co-encapsulating doxorubicin and a prodrug of mitomycin C Download PDFInfo
- Publication number
- AU2016337370A1 AU2016337370A1 AU2016337370A AU2016337370A AU2016337370A1 AU 2016337370 A1 AU2016337370 A1 AU 2016337370A1 AU 2016337370 A AU2016337370 A AU 2016337370A AU 2016337370 A AU2016337370 A AU 2016337370A AU 2016337370 A1 AU2016337370 A1 AU 2016337370A1
- Authority
- AU
- Australia
- Prior art keywords
- mitomycin
- liposomes
- doxorubicin
- prodrug
- pct
- 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.)
- Abandoned
Links
- 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 title claims abstract description 776
- 229960004857 mitomycin Drugs 0.000 title claims abstract description 395
- 239000002502 liposome Substances 0.000 title claims abstract description 339
- 229940002612 prodrug Drugs 0.000 title claims abstract description 313
- 239000000651 prodrug Substances 0.000 title claims abstract description 313
- 239000000203 mixture Substances 0.000 title claims abstract description 97
- 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 title claims description 634
- 229960004679 doxorubicin Drugs 0.000 title claims description 316
- 239000003814 drug Substances 0.000 claims abstract description 27
- 229940079593 drug Drugs 0.000 claims abstract description 25
- 229940045799 anthracyclines and related substance Drugs 0.000 claims abstract description 12
- 150000002632 lipids Chemical class 0.000 claims abstract description 11
- 206010028980 Neoplasm Diseases 0.000 claims description 55
- 229940062527 alendronate Drugs 0.000 claims description 31
- OGSPWJRAVKPPFI-UHFFFAOYSA-N Alendronic Acid Chemical compound NCCCC(O)(P(O)(O)=O)P(O)(O)=O OGSPWJRAVKPPFI-UHFFFAOYSA-N 0.000 claims description 24
- 150000003863 ammonium salts Chemical class 0.000 claims description 20
- 238000000034 method Methods 0.000 claims description 19
- 206010005003 Bladder cancer Diseases 0.000 claims description 16
- 238000001727 in vivo Methods 0.000 claims description 15
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 14
- 238000002347 injection Methods 0.000 claims description 14
- 239000007924 injection Substances 0.000 claims description 14
- 201000005112 urinary bladder cancer Diseases 0.000 claims description 14
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 11
- 206010033128 Ovarian cancer Diseases 0.000 claims description 11
- 206010017758 gastric cancer Diseases 0.000 claims description 10
- -1 neridonate Chemical compound 0.000 claims description 10
- 239000000232 Lipid Bilayer Substances 0.000 claims description 8
- 208000035269 cancer or benign tumor Diseases 0.000 claims description 7
- 208000026310 Breast neoplasm Diseases 0.000 claims description 6
- 150000003904 phospholipids Chemical class 0.000 claims description 6
- 229940122361 Bisphosphonate Drugs 0.000 claims description 5
- 206010006187 Breast cancer Diseases 0.000 claims description 5
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 5
- 150000004663 bisphosphonates Chemical class 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 4
- MNQYNQBOVCBZIQ-JQOFMKNESA-A sucralfate Chemical compound O[Al](O)OS(=O)(=O)O[C@@H]1[C@@H](OS(=O)(=O)O[Al](O)O)[C@H](OS(=O)(=O)O[Al](O)O)[C@@H](COS(=O)(=O)O[Al](O)O)O[C@H]1O[C@@]1(COS(=O)(=O)O[Al](O)O)[C@@H](OS(=O)(=O)O[Al](O)O)[C@H](OS(=O)(=O)O[Al](O)O)[C@@H](OS(=O)(=O)O[Al](O)O)O1 MNQYNQBOVCBZIQ-JQOFMKNESA-A 0.000 claims description 4
- 229960004291 sucralfate Drugs 0.000 claims description 4
- 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 claims description 3
- 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 claims description 3
- 206010009944 Colon cancer Diseases 0.000 claims description 3
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 3
- 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 claims description 3
- 208000000461 Esophageal Neoplasms Diseases 0.000 claims description 3
- MPBVHIBUJCELCL-UHFFFAOYSA-N Ibandronate Chemical compound CCCCCN(C)CCC(O)(P(O)(O)=O)P(O)(O)=O MPBVHIBUJCELCL-UHFFFAOYSA-N 0.000 claims 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 claims 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 claims description 3
- 229910019142 PO4 Inorganic materials 0.000 claims description 3
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 3
- IIDJRNMFWXDHID-UHFFFAOYSA-N Risedronic acid Chemical compound OP(=O)(O)C(P(O)(O)=O)(O)CC1=CC=CN=C1 IIDJRNMFWXDHID-UHFFFAOYSA-N 0.000 claims description 3
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 3
- UGEPSJNLORCRBO-UHFFFAOYSA-N [3-(dimethylamino)-1-hydroxy-1-phosphonopropyl]phosphonic acid Chemical compound CN(C)CCC(O)(P(O)(O)=O)P(O)(O)=O UGEPSJNLORCRBO-UHFFFAOYSA-N 0.000 claims description 3
- 229960000975 daunorubicin Drugs 0.000 claims description 3
- 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 claims description 3
- 229960000633 dextran sulfate Drugs 0.000 claims description 3
- 229960001904 epirubicin Drugs 0.000 claims description 3
- 229930182480 glucuronide Natural products 0.000 claims description 3
- 150000008134 glucuronides Chemical class 0.000 claims description 3
- 229940015872 ibandronate Drugs 0.000 claims description 3
- 229960000908 idarubicin Drugs 0.000 claims description 3
- 238000001361 intraarterial administration Methods 0.000 claims description 3
- 238000007912 intraperitoneal administration Methods 0.000 claims description 3
- 238000007913 intrathecal administration Methods 0.000 claims description 3
- 230000002601 intratumoral effect Effects 0.000 claims description 3
- 238000001990 intravenous administration Methods 0.000 claims description 3
- WRUUGTRCQOWXEG-UHFFFAOYSA-N pamidronate Chemical compound NCCC(O)(P(O)(O)=O)P(O)(O)=O WRUUGTRCQOWXEG-UHFFFAOYSA-N 0.000 claims description 3
- 229940046231 pamidronate Drugs 0.000 claims description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 3
- 239000010452 phosphate Substances 0.000 claims description 3
- 229940089617 risedronate Drugs 0.000 claims description 3
- XRASPMIURGNCCH-UHFFFAOYSA-N zoledronic acid Chemical compound OP(=O)(O)C(P(O)(O)=O)(O)CN1C=CN=C1 XRASPMIURGNCCH-UHFFFAOYSA-N 0.000 claims description 3
- 229960004276 zoledronic acid Drugs 0.000 claims description 3
- 208000003174 Brain Neoplasms Diseases 0.000 claims description 2
- 206010030155 Oesophageal carcinoma Diseases 0.000 claims description 2
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 2
- 201000004101 esophageal cancer Diseases 0.000 claims description 2
- 201000010536 head and neck cancer Diseases 0.000 claims description 2
- 208000014829 head and neck neoplasm Diseases 0.000 claims description 2
- 201000005202 lung cancer Diseases 0.000 claims description 2
- 208000020816 lung neoplasm Diseases 0.000 claims description 2
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 2
- 201000002528 pancreatic cancer Diseases 0.000 claims description 2
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 2
- 201000011549 stomach cancer Diseases 0.000 claims description 2
- MMPOTNFPDMJTRR-UHFFFAOYSA-N OOOOOOOOOOO Chemical compound OOOOOOOOOOO MMPOTNFPDMJTRR-UHFFFAOYSA-N 0.000 claims 1
- 239000008346 aqueous phase Substances 0.000 abstract description 2
- 210000004027 cell Anatomy 0.000 description 112
- 238000011534 incubation Methods 0.000 description 33
- 241000699670 Mus sp. Species 0.000 description 32
- 231100000135 cytotoxicity Toxicity 0.000 description 30
- 230000003013 cytotoxicity Effects 0.000 description 30
- LIHIIWJRSSLKKX-YCTALCSSSA-N C1=CC(SSCC(COC(=O)CCCCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCCCC)=CC=C1COC(=O)N1[C@@H]2[C@]3(OC)[C@H](COC(N)=O)C(C(=O)C(N)=C(C)C4=O)=C4N3C[C@@H]21 Chemical compound C1=CC(SSCC(COC(=O)CCCCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCCCC)=CC=C1COC(=O)N1[C@@H]2[C@]3(OC)[C@H](COC(N)=O)C(C(=O)C(N)=C(C)C4=O)=C4N3C[C@@H]21 LIHIIWJRSSLKKX-YCTALCSSSA-N 0.000 description 28
- 239000010432 diamond Substances 0.000 description 28
- 238000011282 treatment Methods 0.000 description 26
- 238000009472 formulation Methods 0.000 description 24
- 230000012010 growth Effects 0.000 description 23
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 22
- 238000000338 in vitro Methods 0.000 description 18
- 210000002381 plasma Anatomy 0.000 description 18
- 238000012360 testing method Methods 0.000 description 15
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 14
- 239000003795 chemical substances by application Substances 0.000 description 14
- 239000002202 Polyethylene glycol Substances 0.000 description 13
- 229940044197 ammonium sulfate Drugs 0.000 description 13
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 13
- 235000011130 ammonium sulphate Nutrition 0.000 description 13
- 229920001223 polyethylene glycol Polymers 0.000 description 13
- 238000003776 cleavage reaction Methods 0.000 description 12
- 230000007017 scission Effects 0.000 description 12
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 11
- 201000009030 Carcinoma Diseases 0.000 description 11
- 201000005296 lung carcinoma Diseases 0.000 description 9
- 230000001225 therapeutic effect Effects 0.000 description 9
- 239000011248 coating agent Substances 0.000 description 8
- 238000000576 coating method Methods 0.000 description 8
- 208000010749 gastric carcinoma Diseases 0.000 description 8
- 210000004072 lung Anatomy 0.000 description 8
- 201000000498 stomach carcinoma Diseases 0.000 description 8
- 230000004083 survival effect Effects 0.000 description 8
- 230000002195 synergetic effect Effects 0.000 description 8
- 230000004614 tumor growth Effects 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 7
- 201000011510 cancer Diseases 0.000 description 7
- 210000004185 liver Anatomy 0.000 description 7
- 230000009826 neoplastic cell growth Effects 0.000 description 7
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 238000011068 loading method Methods 0.000 description 6
- 210000000952 spleen Anatomy 0.000 description 6
- 102000004506 Blood Proteins Human genes 0.000 description 5
- 108010017384 Blood Proteins Proteins 0.000 description 5
- 241000699666 Mus <mouse, genus> Species 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 239000003638 chemical reducing agent Substances 0.000 description 5
- 230000002209 hydrophobic effect Effects 0.000 description 5
- 210000003734 kidney Anatomy 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- 230000008901 benefit Effects 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 230000001472 cytotoxic effect Effects 0.000 description 4
- 231100000263 cytotoxicity test Toxicity 0.000 description 4
- 239000003480 eluent Substances 0.000 description 4
- 238000000605 extraction Methods 0.000 description 4
- 238000005755 formation reaction Methods 0.000 description 4
- 206010061289 metastatic neoplasm Diseases 0.000 description 4
- 150000003839 salts Chemical class 0.000 description 4
- 239000003981 vehicle Substances 0.000 description 4
- 229920002684 Sepharose Polymers 0.000 description 3
- 238000002835 absorbance Methods 0.000 description 3
- 239000002246 antineoplastic agent Substances 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 210000000481 breast Anatomy 0.000 description 3
- 230000010261 cell growth Effects 0.000 description 3
- 210000001072 colon Anatomy 0.000 description 3
- 231100000433 cytotoxic Toxicity 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 238000011081 inoculation Methods 0.000 description 3
- 239000010410 layer Substances 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 235000018102 proteins Nutrition 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 231100000331 toxic Toxicity 0.000 description 3
- 230000002588 toxic effect Effects 0.000 description 3
- 230000001988 toxicity Effects 0.000 description 3
- 231100000419 toxicity Toxicity 0.000 description 3
- 238000009010 Bradford assay Methods 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 229930192392 Mitomycin Natural products 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 238000007792 addition Methods 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- 229940034982 antineoplastic agent Drugs 0.000 description 2
- 201000001531 bladder carcinoma Diseases 0.000 description 2
- 230000017531 blood circulation Effects 0.000 description 2
- 239000011449 brick Substances 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 235000012000 cholesterol Nutrition 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 229910003460 diamond Inorganic materials 0.000 description 2
- 125000004396 dithiobenzyl group Chemical group 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 2
- 210000002216 heart Anatomy 0.000 description 2
- 210000005260 human cell Anatomy 0.000 description 2
- 230000001394 metastastic effect Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 2
- 229920001467 poly(styrenesulfonates) Polymers 0.000 description 2
- 230000002062 proliferating effect Effects 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- WEPNHBQBLCNOBB-FZJVNAOYSA-N sucrose octasulfate Chemical compound OS(=O)(=O)O[C@@H]1[C@H](OS(O)(=O)=O)[C@H](COS(=O)(=O)O)O[C@]1(COS(O)(=O)=O)O[C@@H]1[C@H](OS(O)(=O)=O)[C@@H](OS(O)(=O)=O)[C@@H](OS(O)(=O)=O)[C@@H](COS(O)(=O)=O)O1 WEPNHBQBLCNOBB-FZJVNAOYSA-N 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 208000010570 urinary bladder carcinoma Diseases 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 1
- 238000011725 BALB/c mouse Methods 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- MWWSFMDVAYGXBV-RUELKSSGSA-N Doxorubicin hydrochloride Chemical compound Cl.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 MWWSFMDVAYGXBV-RUELKSSGSA-N 0.000 description 1
- 108010024636 Glutathione Proteins 0.000 description 1
- 101100448208 Human herpesvirus 6B (strain Z29) U69 gene Proteins 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- 241000452413 Sabra Species 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 229930182558 Sterol Natural products 0.000 description 1
- HPZOOQSXPMEJBV-ODCFVKFUSA-N Tirilazad mesylate Chemical compound CS(O)(=O)=O.O=C([C@@H]1[C@@]2(C)CC=C3[C@@]4(C)C=CC(=O)C=C4CC[C@H]3[C@@H]2C[C@H]1C)CN(CC1)CCN1C(N=1)=CC(N2CCCC2)=NC=1N1CCCC1 HPZOOQSXPMEJBV-ODCFVKFUSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 239000003957 anion exchange resin Substances 0.000 description 1
- 230000001028 anti-proliverative effect Effects 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 125000005228 aryl sulfonate group Chemical group 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 230000036952 cancer formation Effects 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000003729 cation exchange resin Substances 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 108091092356 cellular DNA Proteins 0.000 description 1
- 230000007541 cellular toxicity Effects 0.000 description 1
- 210000003679 cervix uteri Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 238000002784 cytotoxicity assay Methods 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 150000001982 diacylglycerols Chemical class 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 229960002918 doxorubicin hydrochloride Drugs 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 210000003238 esophagus Anatomy 0.000 description 1
- 238000001125 extrusion Methods 0.000 description 1
- 239000013020 final formulation Substances 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 238000005227 gel permeation chromatography Methods 0.000 description 1
- 229960003180 glutathione Drugs 0.000 description 1
- 210000003128 head Anatomy 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 230000003463 hyperproliferative effect Effects 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007919 intrasynovial administration Methods 0.000 description 1
- 239000013554 lipid monolayer Substances 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- CXKWCBBOMKCUKX-UHFFFAOYSA-M methylene blue Chemical compound [Cl-].C1=CC(N(C)C)=CC2=[S+]C3=CC(N(C)C)=CC=C3N=C21 CXKWCBBOMKCUKX-UHFFFAOYSA-M 0.000 description 1
- 229960000907 methylthioninium chloride Drugs 0.000 description 1
- 231100000324 minimal toxicity Toxicity 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 210000003739 neck Anatomy 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 239000004417 polycarbonate Substances 0.000 description 1
- 229920000515 polycarbonate Polymers 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 150000003432 sterols Chemical class 0.000 description 1
- 235000003702 sterols Nutrition 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 231100000337 synergistic cytotoxicity Toxicity 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 238000011277 treatment modality Methods 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 230000005740 tumor formation Effects 0.000 description 1
- 238000000825 ultraviolet detection Methods 0.000 description 1
- 239000002691 unilamellar liposome Substances 0.000 description 1
- 210000003932 urinary bladder Anatomy 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
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/407—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
- A61K47/543—Lipids, e.g. triglycerides; Polyamines, e.g. spermine or spermidine
- A61K47/544—Phospholipids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6905—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a colloid or an emulsion
- A61K47/6911—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a colloid or an emulsion the form being a liposome
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Molecular Biology (AREA)
- Dispersion Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Dermatology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oncology (AREA)
- Biophysics (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201562242097P | 2015-10-15 | 2015-10-15 | |
| US62/242,097 | 2015-10-15 | ||
| PCT/US2016/057176 WO2017066667A1 (en) | 2015-10-15 | 2016-10-14 | Liposome composition co-encapsulating doxorubicin and a prodrug of mitomycin c |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU2016337370A1 true AU2016337370A1 (en) | 2018-05-17 |
Family
ID=57209906
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2016337370A Abandoned AU2016337370A1 (en) | 2015-10-15 | 2016-10-14 | Liposome composition co-encapsulating doxorubicin and a prodrug of mitomycin C |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US10617672B2 (enExample) |
| EP (1) | EP3362099A1 (enExample) |
| JP (1) | JP2018530623A (enExample) |
| AU (1) | AU2016337370A1 (enExample) |
| CA (1) | CA3001699A1 (enExample) |
| WO (1) | WO2017066667A1 (enExample) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA3001699A1 (en) | 2015-10-15 | 2017-04-20 | Lipomedix Pharmaceuticals Ltd. | Liposome composition co-encapsulating doxorubicin and a prodrug of mitomycin c |
| US20220073638A1 (en) * | 2018-09-19 | 2022-03-10 | INSERM (Institut National de la Santé et de la Recherche Médicale | Methods and pharmaceutical composition for the treatment of cancers resistant to immune checkpoint therapy |
| CN109260155B (zh) * | 2018-11-05 | 2021-04-06 | 杭州高田生物医药有限公司 | 伊立替康脂质体制剂及其制备与应用 |
| CA3126211A1 (en) * | 2019-01-11 | 2020-07-16 | Lipomedix Pharmaceuticals Ltd. | Liposome composition comprising liposomal prodrug of mitomycin c and method of manufacture |
| JPWO2021225113A1 (enExample) * | 2020-05-08 | 2021-11-11 |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL91664A (en) | 1988-09-28 | 1993-05-13 | Yissum Res Dev Co | Ammonium transmembrane gradient system for efficient loading of liposomes with amphipathic drugs and their controlled release |
| US7303760B2 (en) * | 1999-04-23 | 2007-12-04 | Alza Corporation | Method for treating multi-drug resistant tumors |
| US20050129753A1 (en) | 2003-11-14 | 2005-06-16 | Gabizon Alberto A. | Method for drug loading in liposomes |
| EP2531175A2 (en) | 2010-02-01 | 2012-12-12 | Yissum Research Development Company of the Hebrew University of Jerusalem, Ltd. | Liposomes comprising amphipathic drugs and method for their preparation |
| US10085940B2 (en) | 2011-07-13 | 2018-10-02 | Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd. | Liposomes co-encapsulating a bisphosphonate and an amphipathic agent |
| AU2012284147A1 (en) * | 2011-07-19 | 2014-02-27 | Stc. Unm | Intraperitoneally-administered nanocarriers that release their therapeutic load based on the inflammatory environment of cancers |
| EP2776013B8 (en) * | 2011-11-08 | 2023-08-30 | The Board of Trustees of the University of Arkansas | Methods and compositions for x-ray induced release from ph sensitive liposomes |
| CN103622912B (zh) * | 2013-12-05 | 2016-02-24 | 常州金远药业制造有限公司 | 盐酸多柔比星-多西他赛或紫杉醇脂质体制剂及其制备方法 |
| US9937261B2 (en) | 2014-06-09 | 2018-04-10 | Lipomedix Pharmaceuticals Ltd. | Combination therapy comprising a liposomal prodrug of mitomycin C and radiotherapy |
| CA3001699A1 (en) | 2015-10-15 | 2017-04-20 | Lipomedix Pharmaceuticals Ltd. | Liposome composition co-encapsulating doxorubicin and a prodrug of mitomycin c |
-
2016
- 2016-10-14 CA CA3001699A patent/CA3001699A1/en not_active Abandoned
- 2016-10-14 JP JP2018539238A patent/JP2018530623A/ja active Pending
- 2016-10-14 EP EP16788348.7A patent/EP3362099A1/en not_active Withdrawn
- 2016-10-14 WO PCT/US2016/057176 patent/WO2017066667A1/en not_active Ceased
- 2016-10-14 AU AU2016337370A patent/AU2016337370A1/en not_active Abandoned
- 2016-10-14 US US15/768,526 patent/US10617672B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| US20180296529A1 (en) | 2018-10-18 |
| WO2017066667A1 (en) | 2017-04-20 |
| CA3001699A1 (en) | 2017-04-20 |
| US10617672B2 (en) | 2020-04-14 |
| EP3362099A1 (en) | 2018-08-22 |
| JP2018530623A (ja) | 2018-10-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP3787607B1 (en) | Carotenoid compositions and uses thereof | |
| JP5419716B2 (ja) | オキサリプラチンリポソーム製剤からなる抗腫瘍効果増強剤及び当該リポソーム製剤を含有する抗腫瘍剤 | |
| US10617672B2 (en) | Liposome composition co-encapsulating doxorubicin and a prodrug of mitomycin C | |
| RS20080388A (sr) | Lečenje malignih bolesti | |
| Marzban et al. | Optimizing the therapeutic efficacy of cisplatin PEGylated liposomes via incorporation of different DPPG ratios: In vitro and in vivo studies | |
| WO2014101356A1 (zh) | 一种蟾毒灵脂质体及其制备方法和应用 | |
| CN115605196A (zh) | 用于治疗癌症和癌症耐药性的脂质体制剂 | |
| CN107530283A (zh) | 组合脂质体药物制剂 | |
| EP3861987A1 (en) | Combination medicine comprising drug-encapsulating liposome composition and platinum preparation | |
| WO2022008471A1 (en) | Liposome formulations | |
| US20220347168A1 (en) | Lung targeted anticancer therapies with liposomal annamycin | |
| US20250064784A1 (en) | Liposome composition comprising liposomal prodrug of mitomycin c and methods of treatment | |
| CN114746124A (zh) | 包含活性剂沉淀物的递送系统复合物和使用方法 | |
| US20220296518A1 (en) | Lipid-based nanoparticle delivery system for hydrophilic charged compound | |
| WO2025184543A1 (en) | Compositions and methods for delivery of therapeutic compounds | |
| HK40086650A (zh) | 用於治疗癌症和癌症耐药性的脂质体制剂 | |
| US20230021879A1 (en) | Synthesis of 3 -rna oligonucleotides | |
| CN120225196A (zh) | 含有内含拓扑替康或其盐的脂质体组合物及dna损伤修复抑制剂的组合药物 | |
| HK40084394A (en) | Ethanolamine formulation for treating epithelial ovarian carcinoma | |
| CN116407548A (zh) | 一种蒽环类抗肿瘤药和铂类抗肿瘤药的组合物及其制备方法 | |
| KR20100031320A (ko) | 혈류 내 순환시간 증가를 위한 단백질로 결합된 리포솜 및 이의 제조방법 | |
| KR20110122682A (ko) | 콜레스탄올 유도체의 병용 용도 | |
| Lewi et al. | Liposomal drug carriers | |
| HK1146469B (en) | Agent for enhancing anti-tumor effect comprising oxaliplatin liposome preparation, and anti-tumor agent comprising the liposome preparation |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MK4 | Application lapsed section 142(2)(d) - no continuation fee paid for the application |