ES2898024T3 - Gemcitabina oral metronómica para terapia contra el cáncer - Google Patents
Gemcitabina oral metronómica para terapia contra el cáncer Download PDFInfo
- Publication number
- ES2898024T3 ES2898024T3 ES17805885T ES17805885T ES2898024T3 ES 2898024 T3 ES2898024 T3 ES 2898024T3 ES 17805885 T ES17805885 T ES 17805885T ES 17805885 T ES17805885 T ES 17805885T ES 2898024 T3 ES2898024 T3 ES 2898024T3
- Authority
- ES
- Spain
- Prior art keywords
- gem
- amount
- formulation
- mice
- group
- 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.)
- Active
Links
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 title claims abstract description 275
- 229960005277 gemcitabine Drugs 0.000 title claims abstract description 273
- 238000011275 oncology therapy Methods 0.000 title description 3
- 239000000203 mixture Substances 0.000 claims abstract description 118
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 90
- 231100000682 maximum tolerated dose Toxicity 0.000 claims abstract description 73
- 238000009472 formulation Methods 0.000 claims abstract description 60
- 239000004094 surface-active agent Substances 0.000 claims abstract description 60
- 239000002904 solvent Substances 0.000 claims abstract description 38
- 239000003814 drug Substances 0.000 claims abstract description 34
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 31
- 229940079593 drug Drugs 0.000 claims abstract description 29
- 150000003839 salts Chemical class 0.000 claims abstract description 25
- 239000012052 hydrophilic carrier Substances 0.000 claims abstract description 24
- 230000037406 food intake Effects 0.000 claims abstract description 13
- 230000001747 exhibiting effect Effects 0.000 claims abstract description 6
- 230000002459 sustained effect Effects 0.000 claims abstract 2
- 238000011282 treatment Methods 0.000 claims description 44
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 43
- DNIAPMSPPWPWGF-UHFFFAOYSA-N monopropylene glycol Natural products CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 34
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 27
- 229920001223 polyethylene glycol Polymers 0.000 claims description 24
- 239000002202 Polyethylene glycol Substances 0.000 claims description 22
- 229920000136 polysorbate Polymers 0.000 claims description 19
- 229950008882 polysorbate Drugs 0.000 claims description 18
- 125000002811 oleoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])/C([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 claims description 16
- 235000013772 propylene glycol Nutrition 0.000 claims description 14
- 241000894007 species Species 0.000 claims description 14
- 239000002775 capsule Substances 0.000 claims description 12
- 230000037396 body weight Effects 0.000 claims description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 9
- 241000282412 Homo Species 0.000 claims description 8
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 8
- 239000002552 dosage form Substances 0.000 claims description 8
- 210000000496 pancreas Anatomy 0.000 claims description 6
- -1 polyoxyethylene Polymers 0.000 claims description 5
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 claims description 4
- GHHURQMJLARIDK-UHFFFAOYSA-N 2-hydroxypropyl octanoate Chemical compound CCCCCCCC(=O)OCC(C)O GHHURQMJLARIDK-UHFFFAOYSA-N 0.000 claims description 4
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 4
- AOBORMOPSGHCAX-UHFFFAOYSA-N Tocophersolan Chemical compound OCCOC(=O)CCC(=O)OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C AOBORMOPSGHCAX-UHFFFAOYSA-N 0.000 claims description 4
- 210000000481 breast Anatomy 0.000 claims description 4
- 210000003932 urinary bladder Anatomy 0.000 claims description 4
- 210000000013 bile duct Anatomy 0.000 claims description 3
- 239000004359 castor oil Substances 0.000 claims description 3
- 235000019438 castor oil Nutrition 0.000 claims description 3
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 claims description 3
- WECGLUPZRHILCT-GSNKCQISSA-N 1-linoleoyl-sn-glycerol Chemical compound CCCCC\C=C/C\C=C/CCCCCCCC(=O)OC[C@@H](O)CO WECGLUPZRHILCT-GSNKCQISSA-N 0.000 claims description 2
- 239000000263 2,3-dihydroxypropyl (Z)-octadec-9-enoate Substances 0.000 claims description 2
- BHIZVZJETFVJMJ-UHFFFAOYSA-N 2-hydroxypropyl dodecanoate Chemical compound CCCCCCCCCCCC(=O)OCC(C)O BHIZVZJETFVJMJ-UHFFFAOYSA-N 0.000 claims description 2
- RZRNAYUHWVFMIP-GDCKJWNLSA-N 3-oleoyl-sn-glycerol Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@H](O)CO RZRNAYUHWVFMIP-GDCKJWNLSA-N 0.000 claims description 2
- 150000005215 alkyl ethers Chemical class 0.000 claims description 2
- XXJWXESWEXIICW-UHFFFAOYSA-N diethylene glycol monoethyl ether Chemical compound CCOCCOCCO XXJWXESWEXIICW-UHFFFAOYSA-N 0.000 claims description 2
- 229940075557 diethylene glycol monoethyl ether Drugs 0.000 claims description 2
- LLRANSBEYQZKFY-UHFFFAOYSA-N dodecanoic acid;propane-1,2-diol Chemical compound CC(O)CO.CCCCCCCCCCCC(O)=O LLRANSBEYQZKFY-UHFFFAOYSA-N 0.000 claims description 2
- 125000000400 lauroyl group Chemical group O=C([*])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])C([H])([H])[H] 0.000 claims description 2
- 125000002669 linoleoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])/C([H])=C([H])\C([H])([H])/C([H])=C([H])\C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- RZRNAYUHWVFMIP-UHFFFAOYSA-N monoelaidin Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC(O)CO RZRNAYUHWVFMIP-UHFFFAOYSA-N 0.000 claims description 2
- 229940049964 oleate Drugs 0.000 claims description 2
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 claims description 2
- 229920001983 poloxamer Polymers 0.000 claims description 2
- 229940026235 propylene glycol monolaurate Drugs 0.000 claims description 2
- 239000007901 soft capsule Substances 0.000 claims description 2
- 125000003696 stearoyl group Chemical group O=C([*])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])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- RUOJZAUFBMNUDX-UHFFFAOYSA-N propylene carbonate Chemical compound CC1COC(=O)O1 RUOJZAUFBMNUDX-UHFFFAOYSA-N 0.000 claims 2
- 210000005265 lung cell Anatomy 0.000 claims 1
- 150000003626 triacylglycerols Chemical class 0.000 claims 1
- 230000001939 inductive effect Effects 0.000 abstract description 6
- 241000699670 Mus sp. Species 0.000 description 143
- 239000000243 solution Substances 0.000 description 23
- 230000004614 tumor growth Effects 0.000 description 23
- 238000002560 therapeutic procedure Methods 0.000 description 22
- 238000002347 injection Methods 0.000 description 17
- 239000007924 injection Substances 0.000 description 17
- 230000000259 anti-tumor effect Effects 0.000 description 16
- 230000006023 anti-tumor response Effects 0.000 description 16
- 208000006990 cholangiocarcinoma Diseases 0.000 description 16
- 229940090044 injection Drugs 0.000 description 16
- 230000004083 survival effect Effects 0.000 description 16
- 239000003981 vehicle Substances 0.000 description 15
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 14
- 210000004027 cell Anatomy 0.000 description 14
- 229960002949 fluorouracil Drugs 0.000 description 14
- 238000000034 method Methods 0.000 description 14
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 12
- 241001465754 Metazoa Species 0.000 description 11
- 201000011510 cancer Diseases 0.000 description 11
- 235000011187 glycerol Nutrition 0.000 description 10
- 238000009097 single-agent therapy Methods 0.000 description 10
- 239000002246 antineoplastic agent Substances 0.000 description 9
- 231100000371 dose-limiting toxicity Toxicity 0.000 description 9
- 201000002528 pancreatic cancer Diseases 0.000 description 9
- 230000000694 effects Effects 0.000 description 8
- 238000001727 in vivo Methods 0.000 description 8
- 238000002156 mixing Methods 0.000 description 8
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 7
- 208000008443 pancreatic carcinoma Diseases 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- 239000012458 free base Substances 0.000 description 6
- 210000001035 gastrointestinal tract Anatomy 0.000 description 6
- 230000002035 prolonged effect Effects 0.000 description 6
- 230000001225 therapeutic effect Effects 0.000 description 6
- 239000000839 emulsion Substances 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 238000003860 storage Methods 0.000 description 5
- 238000011729 BALB/c nude mouse Methods 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 239000012736 aqueous medium Substances 0.000 description 4
- 230000001186 cumulative effect Effects 0.000 description 4
- 239000012153 distilled water Substances 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 229920000314 poly p-methyl styrene Polymers 0.000 description 4
- 229940002612 prodrug Drugs 0.000 description 4
- 239000000651 prodrug Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 238000011269 treatment regimen Methods 0.000 description 4
- 230000003442 weekly effect Effects 0.000 description 4
- 238000012447 xenograft mouse model Methods 0.000 description 4
- 206010006187 Breast cancer Diseases 0.000 description 3
- 208000026310 Breast neoplasm Diseases 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 238000013019 agitation Methods 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 238000002512 chemotherapy Methods 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 230000002354 daily effect Effects 0.000 description 3
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 3
- 238000001647 drug administration Methods 0.000 description 3
- 230000001965 increasing effect Effects 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- JLFNLZLINWHATN-UHFFFAOYSA-N pentaethylene glycol Chemical compound OCCOCCOCCOCCOCCO JLFNLZLINWHATN-UHFFFAOYSA-N 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 229940124597 therapeutic agent Drugs 0.000 description 3
- 230000005748 tumor development Effects 0.000 description 3
- 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 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 241000699660 Mus musculus Species 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 239000008367 deionised water Substances 0.000 description 2
- 229910021641 deionized water Inorganic materials 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 238000012377 drug delivery Methods 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 229940020967 gemzar Drugs 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 239000007928 intraperitoneal injection Substances 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 2
- 238000011580 nude mouse model Methods 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 238000011519 second-line treatment Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 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
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical compound OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 1
- OIQOAYVCKAHSEJ-UHFFFAOYSA-N 2-[2,3-bis(2-hydroxyethoxy)propoxy]ethanol;hexadecanoic acid;octadecanoic acid Chemical compound OCCOCC(OCCO)COCCO.CCCCCCCCCCCCCCCC(O)=O.CCCCCCCCCCCCCCCCCC(O)=O OIQOAYVCKAHSEJ-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 206010004593 Bile duct cancer Diseases 0.000 description 1
- 229940045513 CTLA4 antagonist Drugs 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- 241000581364 Clinitrachus argentatus Species 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 239000008118 PEG 6000 Substances 0.000 description 1
- 229920000604 Polyethylene Glycol 200 Polymers 0.000 description 1
- 229920002556 Polyethylene Glycol 300 Polymers 0.000 description 1
- 229920002560 Polyethylene Glycol 3000 Polymers 0.000 description 1
- 229920001030 Polyethylene Glycol 4000 Polymers 0.000 description 1
- 229920002582 Polyethylene Glycol 600 Polymers 0.000 description 1
- 229920002584 Polyethylene Glycol 6000 Polymers 0.000 description 1
- 229920002594 Polyethylene Glycol 8000 Polymers 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 229940123237 Taxane Drugs 0.000 description 1
- 206010070863 Toxicity to various agents Diseases 0.000 description 1
- 239000003463 adsorbent Substances 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 239000003945 anionic surfactant Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 208000026900 bile duct neoplasm Diseases 0.000 description 1
- 210000003445 biliary tract Anatomy 0.000 description 1
- 201000009036 biliary tract cancer Diseases 0.000 description 1
- 208000020790 biliary tract neoplasm Diseases 0.000 description 1
- 229960000074 biopharmaceutical Drugs 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 239000003093 cationic surfactant Substances 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 229940044683 chemotherapy drug Drugs 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 239000007931 coated granule Substances 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000003684 drug solvent Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000002702 enteric coating Substances 0.000 description 1
- 238000009505 enteric coating Methods 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 238000010579 first pass effect Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 210000001156 gastric mucosa Anatomy 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 239000012456 homogeneous solution Substances 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 238000011221 initial treatment Methods 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 230000002601 intratumoral effect Effects 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 239000006194 liquid suspension Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 208000037841 lung tumor Diseases 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
- 239000011976 maleic acid Substances 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 229940057917 medium chain triglycerides Drugs 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000009826 neoplastic cell growth Effects 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 238000011457 non-pharmacological treatment Methods 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 229940126701 oral medication Drugs 0.000 description 1
- 239000008203 oral pharmaceutical composition Substances 0.000 description 1
- 229940100688 oral solution Drugs 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 238000005191 phase separation Methods 0.000 description 1
- 150000003057 platinum Chemical class 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229920002523 polyethylene Glycol 1000 Polymers 0.000 description 1
- 229940113116 polyethylene glycol 1000 Drugs 0.000 description 1
- 230000003334 potential effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000002203 pretreatment Methods 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- 229940107700 pyruvic acid Drugs 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 238000011127 radiochemotherapy Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000002271 resection Methods 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 238000011125 single therapy Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 1
- 239000000080 wetting agent Substances 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
-
- 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
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
- A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
- A61K31/7068—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
-
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
-
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- 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
- A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
-
- 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
- A61K9/4808—Preparations in capsules, e.g. of gelatin, of chocolate characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release
-
- 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
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4858—Organic compounds
-
- 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
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4866—Organic macromolecular compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Dispersion Chemistry (AREA)
- Nutrition Science (AREA)
- Physiology (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biochemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201662344660P | 2016-06-02 | 2016-06-02 | |
| PCT/CN2017/086942 WO2017206940A1 (en) | 2016-06-02 | 2017-06-02 | Metronomic oral gemcitabine for cancer therapy |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2898024T3 true ES2898024T3 (es) | 2022-03-03 |
Family
ID=60479058
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES17805885T Active ES2898024T3 (es) | 2016-06-02 | 2017-06-02 | Gemcitabina oral metronómica para terapia contra el cáncer |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US10835548B2 (https=) |
| EP (1) | EP3463298B1 (https=) |
| JP (2) | JP2019517490A (https=) |
| KR (1) | KR102383824B1 (https=) |
| CN (2) | CN114224865A (https=) |
| AU (1) | AU2017273495B2 (https=) |
| CA (1) | CA3026144A1 (https=) |
| ES (1) | ES2898024T3 (https=) |
| TW (1) | TWI814703B (https=) |
| WO (1) | WO2017206940A1 (https=) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2020247912A1 (en) * | 2019-06-06 | 2020-12-10 | Board Of Regents, The University Of Texas System | Lipid nanoparticles containing pharmaceutical and/or nutraceutical agents and methods thereof |
| CN120478381A (zh) * | 2025-07-02 | 2025-08-15 | 华中科技大学同济医学院附属同济医院 | Azd1152和吉西他滨在制备治疗胆管癌药物中的用途 |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SI1853250T1 (sl) | 2005-02-18 | 2012-01-31 | Abraxis Bioscience Llc | Kombinacije in reĹľimi dajanja terapevtskih sredstev in kombinirana terapija |
| US8735394B2 (en) | 2005-02-18 | 2014-05-27 | Abraxis Bioscience, Llc | Combinations and modes of administration of therapeutic agents and combination therapy |
| HUE047352T2 (hu) | 2008-09-23 | 2020-04-28 | Nektar Therapeutics | Eljárás ütemezett beadásra kamptotecin elõgyógyszerekkel (például PEG-ironotekánnal) |
| WO2010039039A1 (en) * | 2008-10-03 | 2010-04-08 | Clavis Pharma Asa | Oral formulations of gemcitabine derivatives |
| US20100273730A1 (en) * | 2009-04-27 | 2010-10-28 | Innopharmax, Inc. | Self-emulsifying pharmaceutical compositions of hydrophilic drugs and preparation thereof |
| CN101926779A (zh) * | 2010-08-19 | 2010-12-29 | 苏州特瑞药业有限公司 | 一种吉西他滨固体脂质纳米粒及其制备方法与用途 |
| KR20140079831A (ko) * | 2011-10-18 | 2014-06-27 | 아지노모토 가부시키가이샤 | 췌장암 및／또는 담도암 치료약 |
| WO2015153820A1 (en) * | 2014-04-02 | 2015-10-08 | Felder Mitchell S | Ctla-4 blockade with metronomic chemotherapy for the treatment of cancer |
-
2017
- 2017-06-02 KR KR1020187038225A patent/KR102383824B1/ko active Active
- 2017-06-02 EP EP17805885.5A patent/EP3463298B1/en active Active
- 2017-06-02 CA CA3026144A patent/CA3026144A1/en active Pending
- 2017-06-02 US US15/612,116 patent/US10835548B2/en active Active
- 2017-06-02 ES ES17805885T patent/ES2898024T3/es active Active
- 2017-06-02 CN CN202210080120.1A patent/CN114224865A/zh active Pending
- 2017-06-02 CN CN201780033938.5A patent/CN109310631A/zh active Pending
- 2017-06-02 WO PCT/CN2017/086942 patent/WO2017206940A1/en not_active Ceased
- 2017-06-02 AU AU2017273495A patent/AU2017273495B2/en active Active
- 2017-06-02 JP JP2018562559A patent/JP2019517490A/ja active Pending
- 2017-06-02 TW TW106118362A patent/TWI814703B/zh active
-
2022
- 2022-04-04 JP JP2022062568A patent/JP2022088622A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| CN114224865A (zh) | 2022-03-25 |
| AU2017273495B2 (en) | 2023-01-12 |
| JP2019517490A (ja) | 2019-06-24 |
| KR20190015420A (ko) | 2019-02-13 |
| US20170348341A1 (en) | 2017-12-07 |
| WO2017206940A1 (en) | 2017-12-07 |
| AU2017273495A1 (en) | 2018-12-20 |
| EP3463298B1 (en) | 2021-09-01 |
| TW201808309A (zh) | 2018-03-16 |
| TWI814703B (zh) | 2023-09-11 |
| EP3463298A4 (en) | 2020-01-01 |
| CA3026144A1 (en) | 2017-12-07 |
| US10835548B2 (en) | 2020-11-17 |
| CN109310631A (zh) | 2019-02-05 |
| KR102383824B1 (ko) | 2022-04-06 |
| EP3463298A1 (en) | 2019-04-10 |
| JP2022088622A (ja) | 2022-06-14 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2831037T3 (es) | Composición farmacéutica oral automicroemulsionante de fármacos hidrófilos y método de preparación | |
| ES2283756T3 (es) | Sistemas autoemulsionantes de administracion de farmaco para taxoides. | |
| CA2626579A1 (en) | Formulation comprising a drug of low water solubility and method of use thereof | |
| ES2909741T3 (es) | Tratamiento del cáncer | |
| CN105338977A (zh) | 艾日布林和乐伐替尼作为治疗癌症的联合疗法的用途 | |
| JP2021523169A (ja) | ビスフルオロアルキル−１，４−ベンゾジアゼピノン化合物を含む組み合わせ組成物およびその使用方法 | |
| ES3012841T3 (en) | Compositions, methods, systems and/or kits for preventing and/or treating neoplasms | |
| JP2021523189A (ja) | ビスフルオロアルキル−１，４−ベンゾジアゼピノン化合物を含む組成物およびその使用方法 | |
| TWI880897B (zh) | 腫瘤內注射調配物 | |
| JP2022088622A (ja) | がん療法のためのメトロノミック経口ゲムシタビン | |
| ES2551125T3 (es) | Composición antifúngica | |
| US20160128988A1 (en) | Combinations for the treatment of cancer comprising a mps-1 kinase inhibitor and a mitotic inhibitor | |
| US10080807B2 (en) | Combination chemotherapy comprising a liposomal prodrug of mitomycin C | |
| JP2021523190A (ja) | 腺様嚢胞癌を治療するためのビスフルオロアルキル−１，４−ベンゾジアゼピノン化合物を含む組成物 | |
| PL211114B1 (pl) | Zastosowanie pochodnej epotilonowej w leczeniu choroby nowotworowej | |
| CN103442708B (zh) | 治疗性处理 | |
| US20060205795A1 (en) | Cancer treatment with epothilones |