CA2958820A1 - Targeted delivery of hydrophilic drugs - Google Patents
Targeted delivery of hydrophilic drugs Download PDFInfo
- Publication number
- CA2958820A1 CA2958820A1 CA2958820A CA2958820A CA2958820A1 CA 2958820 A1 CA2958820 A1 CA 2958820A1 CA 2958820 A CA2958820 A CA 2958820A CA 2958820 A CA2958820 A CA 2958820A CA 2958820 A1 CA2958820 A1 CA 2958820A1
- Authority
- CA
- Canada
- Prior art keywords
- alkyl
- straight chain
- sulfonate
- sulfate
- amphiphilic
- 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
- 239000003814 drug Substances 0.000 title claims description 25
- 229940079593 drug Drugs 0.000 title description 23
- 239000000084 colloidal system Substances 0.000 claims abstract description 47
- 238000000034 method Methods 0.000 claims abstract description 47
- 239000000203 mixture Substances 0.000 claims abstract description 45
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 claims abstract description 35
- 239000002245 particle Substances 0.000 claims abstract description 32
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims abstract description 30
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 22
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 22
- 239000007787 solid Substances 0.000 claims abstract description 18
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 7
- 239000000725 suspension Substances 0.000 claims abstract description 7
- 210000001124 body fluid Anatomy 0.000 claims abstract description 6
- 239000010839 body fluid Substances 0.000 claims abstract description 6
- 239000003560 cancer drug Substances 0.000 claims abstract description 5
- 238000004519 manufacturing process Methods 0.000 claims abstract description 5
- 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 claims description 105
- 229960004679 doxorubicin Drugs 0.000 claims description 56
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 54
- -1 sulfonate anion Chemical class 0.000 claims description 53
- 125000000217 alkyl group Chemical group 0.000 claims description 39
- 210000004185 liver Anatomy 0.000 claims description 39
- 239000002246 antineoplastic agent Substances 0.000 claims description 26
- 239000013543 active substance Substances 0.000 claims description 25
- 150000003839 salts Chemical class 0.000 claims description 22
- 229940041181 antineoplastic drug Drugs 0.000 claims description 19
- 229960001156 mitoxantrone Drugs 0.000 claims description 18
- 239000000843 powder Substances 0.000 claims description 18
- 239000000243 solution Substances 0.000 claims description 16
- 229960004768 irinotecan Drugs 0.000 claims description 14
- KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 claims description 14
- 229960002066 vinorelbine Drugs 0.000 claims description 14
- 206010019695 Hepatic neoplasm Diseases 0.000 claims description 13
- 241001465754 Metazoa Species 0.000 claims description 13
- 238000002347 injection Methods 0.000 claims description 13
- 239000007924 injection Substances 0.000 claims description 13
- 125000003277 amino group Chemical group 0.000 claims description 12
- 239000011734 sodium Substances 0.000 claims description 12
- GBABOYUKABKIAF-GHYRFKGUSA-N vinorelbine Chemical compound C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC([C@]23[C@H]([C@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC GBABOYUKABKIAF-GHYRFKGUSA-N 0.000 claims description 12
- 239000003795 chemical substances by application Substances 0.000 claims description 11
- 229910052708 sodium Inorganic materials 0.000 claims description 11
- 230000001225 therapeutic effect Effects 0.000 claims description 11
- 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 10
- 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 10
- 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 10
- 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 10
- 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 10
- XCPGHVQEEXUHNC-UHFFFAOYSA-N amsacrine Chemical compound COC1=CC(NS(C)(=O)=O)=CC=C1NC1=C(C=CC=C2)C2=NC2=CC=CC=C12 XCPGHVQEEXUHNC-UHFFFAOYSA-N 0.000 claims description 10
- 229960001220 amsacrine Drugs 0.000 claims description 10
- 229960000975 daunorubicin Drugs 0.000 claims description 10
- 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 10
- 229960001904 epirubicin Drugs 0.000 claims description 10
- 229960000908 idarubicin Drugs 0.000 claims description 10
- UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical compound C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 claims description 10
- 229960000303 topotecan Drugs 0.000 claims description 10
- 229960004528 vincristine Drugs 0.000 claims description 10
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 claims description 10
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 claims description 10
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 8
- 238000001802 infusion Methods 0.000 claims description 8
- 238000001990 intravenous administration Methods 0.000 claims description 8
- 239000002904 solvent Substances 0.000 claims description 8
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 7
- 239000007864 aqueous solution Substances 0.000 claims description 7
- 150000008052 alkyl sulfonates Chemical class 0.000 claims description 6
- 210000001367 artery Anatomy 0.000 claims description 5
- 239000012530 fluid Substances 0.000 claims description 5
- 229910052700 potassium Inorganic materials 0.000 claims description 5
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 claims description 5
- 210000003462 vein Anatomy 0.000 claims description 5
- 150000007522 mineralic acids Chemical class 0.000 claims description 4
- 150000007524 organic acids Chemical class 0.000 claims description 4
- 210000002767 hepatic artery Anatomy 0.000 claims description 3
- 238000002156 mixing Methods 0.000 claims description 3
- 210000003240 portal vein Anatomy 0.000 claims description 3
- 239000003125 aqueous solvent Substances 0.000 claims description 2
- 239000000872 buffer Substances 0.000 claims description 2
- 201000011510 cancer Diseases 0.000 claims description 2
- 239000003960 organic solvent Substances 0.000 claims description 2
- 230000003836 peripheral circulation Effects 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 claims 4
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims 2
- 125000002704 decyl group Chemical group [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])C([H])([H])C([H])([H])* 0.000 claims 1
- 201000007270 liver cancer Diseases 0.000 abstract description 7
- 208000014018 liver neoplasm Diseases 0.000 abstract description 6
- 239000007900 aqueous suspension Substances 0.000 abstract description 4
- 241000168096 Glareolidae Species 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- 150000003871 sulfonates Chemical class 0.000 description 12
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 11
- 150000001335 aliphatic alkanes Chemical class 0.000 description 10
- 150000008051 alkyl sulfates Chemical class 0.000 description 9
- 210000001519 tissue Anatomy 0.000 description 9
- 239000000463 material Substances 0.000 description 8
- 239000006228 supernatant Substances 0.000 description 8
- 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 7
- 238000009826 distribution Methods 0.000 description 7
- 229960002918 doxorubicin hydrochloride Drugs 0.000 description 7
- GURKHSYORGJETM-WAQYZQTGSA-N irinotecan hydrochloride (anhydrous) Chemical compound Cl.C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 GURKHSYORGJETM-WAQYZQTGSA-N 0.000 description 7
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 6
- 241000283973 Oryctolagus cuniculus Species 0.000 description 6
- 150000001450 anions Chemical class 0.000 description 6
- 210000000056 organ Anatomy 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- 239000008121 dextrose Substances 0.000 description 5
- 238000007429 general method Methods 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 5
- 241000700157 Rattus norvegicus Species 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 239000012736 aqueous medium Substances 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 238000005119 centrifugation Methods 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 210000005228 liver tissue Anatomy 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- 238000005070 sampling Methods 0.000 description 4
- 239000002253 acid Substances 0.000 description 3
- 229940045714 alkyl sulfonate alkylating agent Drugs 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 238000004364 calculation method Methods 0.000 description 3
- 150000001768 cations Chemical class 0.000 description 3
- 230000004087 circulation Effects 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 230000008685 targeting Effects 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 230000000996 additive effect Effects 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 230000000747 cardiac effect Effects 0.000 description 2
- 125000002091 cationic group Chemical group 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000008367 deionised water Substances 0.000 description 2
- 229910021641 deionized water Inorganic materials 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 238000012377 drug delivery Methods 0.000 description 2
- 238000001361 intraarterial administration Methods 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 238000010253 intravenous injection Methods 0.000 description 2
- 238000011835 investigation Methods 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 208000019423 liver disease Diseases 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- 238000004062 sedimentation Methods 0.000 description 2
- 238000007910 systemic administration Methods 0.000 description 2
- 229960002166 vinorelbine tartrate Drugs 0.000 description 2
- GBABOYUKABKIAF-IWWDSPBFSA-N vinorelbinetartrate Chemical compound C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC(C23[C@H]([C@@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC GBABOYUKABKIAF-IWWDSPBFSA-N 0.000 description 2
- 108010088751 Albumins Proteins 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 201000003076 Angiosarcoma Diseases 0.000 description 1
- 206010003827 Autoimmune hepatitis Diseases 0.000 description 1
- 206010048610 Cardiotoxicity Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 208000001258 Hemangiosarcoma Diseases 0.000 description 1
- 206010019728 Hepatitis alcoholic Diseases 0.000 description 1
- 206010019799 Hepatitis viral Diseases 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 239000012891 Ringer solution Substances 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 1
- 229940122803 Vinca alkaloid Drugs 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 208000002353 alcoholic hepatitis Diseases 0.000 description 1
- 239000003945 anionic surfactant Substances 0.000 description 1
- 229940045799 anthracyclines and related substance Drugs 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 230000005784 autoimmunity Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 231100000259 cardiotoxicity Toxicity 0.000 description 1
- 230000010109 chemoembolization Effects 0.000 description 1
- FOCAUTSVDIKZOP-UHFFFAOYSA-N chloroacetic acid Chemical compound OC(=O)CCl FOCAUTSVDIKZOP-UHFFFAOYSA-N 0.000 description 1
- 208000006990 cholangiocarcinoma Diseases 0.000 description 1
- 208000019425 cirrhosis of liver Diseases 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 239000007857 degradation product Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- JEGUKCSWCFPDGT-UHFFFAOYSA-N h2o hydrate Chemical compound O.O JEGUKCSWCFPDGT-UHFFFAOYSA-N 0.000 description 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 229950010538 irinotecan hydrochloride trihydrate Drugs 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 150000003893 lactate salts Chemical class 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 201000010995 liver angiosarcoma Diseases 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 230000006705 mitochondrial oxidative phosphorylation Effects 0.000 description 1
- 210000000107 myocyte Anatomy 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 239000002831 pharmacologic agent Substances 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 239000003642 reactive oxygen metabolite Substances 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 208000011571 secondary malignant neoplasm Diseases 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 230000003746 surface roughness Effects 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000001839 systemic circulation Effects 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- 229960003048 vinblastine Drugs 0.000 description 1
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
- 201000001862 viral hepatitis Diseases 0.000 description 1
- 238000003260 vortexing Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/5123—Organic compounds, e.g. fats, sugars
-
- 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
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
- A61K31/136—Amines having aromatic rings, e.g. ketamine, nortriptyline having the amino group directly attached to the aromatic ring, e.g. benzeneamine
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
-
- 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
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
-
- 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
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Nanotechnology (AREA)
- Physics & Mathematics (AREA)
- Biomedical Technology (AREA)
- Optics & Photonics (AREA)
- Dermatology (AREA)
- Molecular Biology (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE1400427-9 | 2014-09-10 | ||
| SE1400427 | 2014-09-10 | ||
| PCT/SE2015/000055 WO2016039678A1 (en) | 2014-09-10 | 2015-09-09 | Targeted delivery of hydrophilic drugs |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2958820A1 true CA2958820A1 (en) | 2016-03-17 |
Family
ID=55459328
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2958820A Abandoned CA2958820A1 (en) | 2014-09-10 | 2015-09-09 | Targeted delivery of hydrophilic drugs |
Country Status (11)
| Country | Link |
|---|---|
| US (2) | US10034838B2 (enExample) |
| EP (1) | EP3191138B1 (enExample) |
| JP (1) | JP6951971B2 (enExample) |
| KR (1) | KR20170054459A (enExample) |
| CN (1) | CN107073129B (enExample) |
| AU (1) | AU2015316252A1 (enExample) |
| CA (1) | CA2958820A1 (enExample) |
| EA (1) | EA033526B1 (enExample) |
| IL (1) | IL250637A0 (enExample) |
| MX (1) | MX2017003049A (enExample) |
| WO (1) | WO2016039678A1 (enExample) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3426228A1 (en) * | 2016-03-07 | 2019-01-16 | Double Bond Pharmaceutical AB | Targeted delivery of hydrophilic drugs to lung |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1994008599A1 (en) * | 1992-10-14 | 1994-04-28 | The Regents Of The University Of Colorado | Ion-pairing of drugs for improved efficacy and delivery |
| CA2324254C (en) * | 1998-03-18 | 2005-01-04 | University Technology Corporation | Sustained-release composition including amorphous polymer |
| US6613358B2 (en) * | 1998-03-18 | 2003-09-02 | Theodore W. Randolph | Sustained-release composition including amorphous polymer |
| US6384081B2 (en) * | 1998-10-09 | 2002-05-07 | Charles L. Berman | Treatment of diseases of the eye characterized by the formation of metalloproteinase |
| CN101134119A (zh) | 2002-05-24 | 2008-03-05 | 血管技术国际股份公司 | 用于涂覆医用植入物的组合物和方法 |
| US8313760B2 (en) | 2002-05-24 | 2012-11-20 | Angiotech International Ag | Compositions and methods for coating medical implants |
| US20040161466A1 (en) | 2003-02-14 | 2004-08-19 | Biocompatibles Uk Limited | Chemoembolisation |
| GB2415904B (en) | 2005-02-07 | 2006-10-25 | Chiron Corp | Preparing aldesleukin for pharmaceutical use |
| WO2009078756A1 (en) | 2007-12-19 | 2009-06-25 | Ardenia Investments, Ltd. | Drug delivery system for administration of a water soluble, cationic and amphiphilic pharmaceutically active substance |
| WO2009100222A1 (en) | 2008-02-08 | 2009-08-13 | Qps Llc | Non-polymeric compositions for controlled drug delivery |
| CN101327190B (zh) * | 2008-07-29 | 2011-04-27 | 北京大学 | 一种供注射用的抗肿瘤长循环靶向脂质体 |
| KR101576174B1 (ko) * | 2010-07-26 | 2015-12-09 | 르 라보레또레 쎄르비에르 | 간암 요법을 위한 방법 및 조성물 |
| KR101728011B1 (ko) | 2013-01-23 | 2017-04-20 | 재단법인 유타 인하 디디에스 및 신의료기술개발 공동연구소 | 덱스트란 메타크릴레이트 및 생체적합성 음이온성 고분자를 포함하는 생분해성 마이크로 비드 및 이의 제조방법 |
-
2015
- 2015-09-09 KR KR1020177009510A patent/KR20170054459A/ko not_active Withdrawn
- 2015-09-09 AU AU2015316252A patent/AU2015316252A1/en not_active Abandoned
- 2015-09-09 EA EA201790272A patent/EA033526B1/ru not_active IP Right Cessation
- 2015-09-09 US US15/509,875 patent/US10034838B2/en active Active
- 2015-09-09 MX MX2017003049A patent/MX2017003049A/es unknown
- 2015-09-09 CN CN201580048892.5A patent/CN107073129B/zh active Active
- 2015-09-09 CA CA2958820A patent/CA2958820A1/en not_active Abandoned
- 2015-09-09 EP EP15840525.8A patent/EP3191138B1/en active Active
- 2015-09-09 JP JP2017514562A patent/JP6951971B2/ja active Active
- 2015-09-09 WO PCT/SE2015/000055 patent/WO2016039678A1/en not_active Ceased
-
2017
- 2017-02-16 IL IL250637A patent/IL250637A0/en unknown
-
2018
- 2018-07-17 US US16/037,429 patent/US10973772B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| EP3191138A4 (en) | 2018-06-20 |
| IL250637A0 (en) | 2017-04-30 |
| JP2017527593A (ja) | 2017-09-21 |
| JP6951971B2 (ja) | 2021-10-20 |
| EP3191138A1 (en) | 2017-07-19 |
| EP3191138B1 (en) | 2024-05-29 |
| EA033526B1 (ru) | 2019-10-31 |
| US10034838B2 (en) | 2018-07-31 |
| MX2017003049A (es) | 2017-05-23 |
| WO2016039678A1 (en) | 2016-03-17 |
| US20170239192A1 (en) | 2017-08-24 |
| US20190046462A1 (en) | 2019-02-14 |
| KR20170054459A (ko) | 2017-05-17 |
| EP3191138C0 (en) | 2024-05-29 |
| CN107073129A (zh) | 2017-08-18 |
| CN107073129B (zh) | 2021-10-15 |
| AU2015316252A1 (en) | 2017-03-09 |
| US10973772B2 (en) | 2021-04-13 |
| EA201790272A1 (ru) | 2017-07-31 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Yang et al. | Glycyrrhetinic acid-conjugated polymeric prodrug micelles co-delivered with doxorubicin as combination therapy treatment for liver cancer | |
| Baig et al. | Current status of nanomaterial-based treatment for hepatocellular carcinoma | |
| Morsy et al. | Prevention of rat liver fibrosis by selective targeting of hepatic stellate cells using hesperidin carriers | |
| Shen et al. | cRGD-functionalized polymeric magnetic nanoparticles as a dual-drug delivery system for safe targeted cancer therapy | |
| Wang et al. | Cancer nanomedicines stabilized by π-π stacking between heterodimeric prodrugs enable exceptionally high drug loading capacity and safer delivery of drug combinations | |
| KR101578273B1 (ko) | 화학요법적 항종양 약물을 함유하는 나노입자 | |
| Fernandes et al. | Nanostructured lipid carrier co-loaded with doxorubicin and docosahexaenoic acid as a theranostic agent: evaluation of biodistribution and antitumor activity in experimental model | |
| Wang et al. | Supramolecularly engineered phospholipids constructed by nucleobase molecular recognition: upgraded generation of phospholipids for drug delivery | |
| Zhang et al. | Hepatitis B virus preS1-derived lipopeptide functionalized liposomes for targeting of hepatic cells | |
| CN112933046B (zh) | 一种阿霉素前药主动载药脂质体及其制备方法和应用 | |
| Wang et al. | Investigating the crucial roles of aliphatic tails in disulfide bond-linked docetaxel prodrug nanoassemblies | |
| CN102188713A (zh) | 一种肝靶向药物组合物及其制备方法 | |
| CN108779124A (zh) | 金卟啉-peg缀合物及使用方法 | |
| Li et al. | Low density lipoprotein-inspired nanostructured lipid nanoparticles containing pro-doxorubicin to enhance tumor-targeted therapeutic efficiency | |
| Zhu et al. | Exogenous vitamin C boosts the antitumor efficacy of paclitaxel containing reduction-sensitive shell-sheddable micelles in vivo | |
| Xu et al. | A sequentially responsive and structure-transformable nanoparticle with a comprehensively improved ‘CAPIR cascade’for enhanced antitumor effect | |
| CN109381428B (zh) | 用于肿瘤光动力治疗联合免疫治疗的纳米制剂 | |
| Li et al. | Construction and anti-tumor activities of disulfide-linked docetaxel-dihydroartemisinin nanoconjugates | |
| CN114377141A (zh) | 一种药物递送载体及其抗肿瘤应用 | |
| Li et al. | Doxorubicin-loaded dextran-modified goldmag nanoparticles for targeting hepatocellular carcinoma | |
| US10973772B2 (en) | Targeted delivery of hydrophilic drugs | |
| MXPA06010950A (es) | Formulaciones en nano-particulas de compuestos de platino. | |
| CN107233314B (zh) | 一种具有双靶区同时递药效果的复合磷脂热敏脂质体及其制备方法和应用 | |
| KR20190005884A (ko) | 고분자화 약물 함유 약제학적 조성물 | |
| Rong et al. | Polyphenol-based paclitaxel prodrug self-assembled nanoplatform for tumor synergistic therapy |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |
Effective date: 20190910 |