CA2668262A1 - Dipterinyl calcium pentahydrate (dcp) and therapeutic methods based thereon - Google Patents
Dipterinyl calcium pentahydrate (dcp) and therapeutic methods based thereon Download PDFInfo
- Publication number
- CA2668262A1 CA2668262A1 CA002668262A CA2668262A CA2668262A1 CA 2668262 A1 CA2668262 A1 CA 2668262A1 CA 002668262 A CA002668262 A CA 002668262A CA 2668262 A CA2668262 A CA 2668262A CA 2668262 A1 CA2668262 A1 CA 2668262A1
- Authority
- CA
- Canada
- Prior art keywords
- dcp
- administering
- effective amount
- subject
- modulating
- 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
- IGBSGKOLQRKFIU-UHFFFAOYSA-N O.O.O.O.O.[Ca] Chemical compound O.O.O.O.O.[Ca] IGBSGKOLQRKFIU-UHFFFAOYSA-N 0.000 title claims abstract description 24
- 238000002560 therapeutic procedure Methods 0.000 title claims abstract description 7
- 150000001875 compounds Chemical class 0.000 claims abstract description 28
- 238000000034 method Methods 0.000 claims description 95
- HNXQXTQTPAJEJL-UHFFFAOYSA-N 2-aminopteridin-4-ol Chemical compound C1=CN=C2NC(N)=NC(=O)C2=N1 HNXQXTQTPAJEJL-UHFFFAOYSA-N 0.000 claims description 63
- 239000000725 suspension Substances 0.000 claims description 49
- 206010028980 Neoplasm Diseases 0.000 claims description 41
- 206010006187 Breast cancer Diseases 0.000 claims description 30
- 208000026310 Breast neoplasm Diseases 0.000 claims description 30
- 238000004519 manufacturing process Methods 0.000 claims description 27
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 23
- 241001465754 Metazoa Species 0.000 claims description 19
- 201000011510 cancer Diseases 0.000 claims description 16
- 239000000243 solution Substances 0.000 claims description 14
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 claims description 13
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 claims description 13
- 201000010099 disease Diseases 0.000 claims description 13
- 230000000694 effects Effects 0.000 claims description 13
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 12
- 229910021645 metal ion Inorganic materials 0.000 claims description 12
- 230000015556 catabolic process Effects 0.000 claims description 9
- 238000006731 degradation reaction Methods 0.000 claims description 9
- BMQYVXCPAOLZOK-UHFFFAOYSA-N Trihydroxypropylpterisin Natural products OCC(O)C(O)C1=CN=C2NC(N)=NC(=O)C2=N1 BMQYVXCPAOLZOK-UHFFFAOYSA-N 0.000 claims description 8
- BMQYVXCPAOLZOK-XINAWCOVSA-N neopterin Chemical compound OC[C@@H](O)[C@@H](O)C1=CN=C2NC(N)=NC(=O)C2=N1 BMQYVXCPAOLZOK-XINAWCOVSA-N 0.000 claims description 8
- 238000003756 stirring Methods 0.000 claims description 8
- 230000001028 anti-proliverative effect Effects 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 7
- 210000004881 tumor cell Anatomy 0.000 claims description 7
- 239000002244 precipitate Substances 0.000 claims description 5
- 239000007864 aqueous solution Substances 0.000 claims description 4
- 230000002401 inhibitory effect Effects 0.000 claims description 4
- 230000002194 synthesizing effect Effects 0.000 claims description 3
- 206010014733 Endometrial cancer Diseases 0.000 claims description 2
- 206010014759 Endometrial neoplasm Diseases 0.000 claims description 2
- 206010033128 Ovarian cancer Diseases 0.000 claims description 2
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 2
- 238000002512 chemotherapy Methods 0.000 claims 2
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 claims 1
- 206010009944 Colon cancer Diseases 0.000 claims 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims 1
- 208000035473 Communicable disease Diseases 0.000 claims 1
- 208000037845 Cutaneous squamous cell carcinoma Diseases 0.000 claims 1
- 208000003445 Mouth Neoplasms Diseases 0.000 claims 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims 1
- 206010060862 Prostate cancer Diseases 0.000 claims 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims 1
- 208000004337 Salivary Gland Neoplasms Diseases 0.000 claims 1
- 206010061934 Salivary gland cancer Diseases 0.000 claims 1
- 208000005718 Stomach Neoplasms Diseases 0.000 claims 1
- 239000001110 calcium chloride Substances 0.000 claims 1
- 229910001628 calcium chloride Inorganic materials 0.000 claims 1
- 235000011148 calcium chloride Nutrition 0.000 claims 1
- 206010017758 gastric cancer Diseases 0.000 claims 1
- XLYOFNOQVPJJNP-ZSJDYOACSA-N heavy water Substances [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 claims 1
- 238000001794 hormone therapy Methods 0.000 claims 1
- 208000015181 infectious disease Diseases 0.000 claims 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims 1
- 238000002625 monoclonal antibody therapy Methods 0.000 claims 1
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims 1
- 201000002528 pancreatic cancer Diseases 0.000 claims 1
- 208000008443 pancreatic carcinoma Diseases 0.000 claims 1
- 238000001959 radiotherapy Methods 0.000 claims 1
- 201000010106 skin squamous cell carcinoma Diseases 0.000 claims 1
- 210000000130 stem cell Anatomy 0.000 claims 1
- 201000011549 stomach cancer Diseases 0.000 claims 1
- 238000001356 surgical procedure Methods 0.000 claims 1
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims 1
- 239000000203 mixture Substances 0.000 description 23
- -1 Klucel'~') Chemical compound 0.000 description 21
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 15
- 230000000259 anti-tumor effect Effects 0.000 description 13
- 210000004027 cell Anatomy 0.000 description 13
- 238000009472 formulation Methods 0.000 description 13
- 241000699670 Mus sp. Species 0.000 description 12
- 239000011575 calcium Substances 0.000 description 12
- 229960005069 calcium Drugs 0.000 description 12
- 229910052791 calcium Inorganic materials 0.000 description 12
- 238000011580 nude mouse model Methods 0.000 description 12
- 241000699660 Mus musculus Species 0.000 description 11
- 229910001868 water Inorganic materials 0.000 description 11
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- 208000035475 disorder Diseases 0.000 description 10
- 229920002472 Starch Polymers 0.000 description 9
- NAVMQTYZDKMPEU-UHFFFAOYSA-N Targretin Chemical compound CC1=CC(C(CCC2(C)C)(C)C)=C2C=C1C(=C)C1=CC=C(C(O)=O)C=C1 NAVMQTYZDKMPEU-UHFFFAOYSA-N 0.000 description 9
- 229920001223 polyethylene glycol Polymers 0.000 description 9
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 9
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 9
- 235000019698 starch Nutrition 0.000 description 9
- 239000002202 Polyethylene glycol Substances 0.000 description 8
- 229960004679 doxorubicin Drugs 0.000 description 8
- 239000000843 powder Substances 0.000 description 8
- 239000003642 reactive oxygen metabolite Substances 0.000 description 8
- 235000002639 sodium chloride Nutrition 0.000 description 8
- 239000008107 starch Substances 0.000 description 8
- 239000003085 diluting agent Substances 0.000 description 7
- 239000003814 drug Substances 0.000 description 7
- 239000000314 lubricant Substances 0.000 description 7
- 108090000623 proteins and genes Proteins 0.000 description 7
- GLKCOBIIZKYKFN-UHFFFAOYSA-N 2-aminopteridine-4,7-diol Chemical compound N1=CC(O)=NC2=NC(N)=NC(O)=C21 GLKCOBIIZKYKFN-UHFFFAOYSA-N 0.000 description 6
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 6
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 6
- 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
- 229930195725 Mannitol Natural products 0.000 description 6
- 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 6
- 229960002938 bexarotene Drugs 0.000 description 6
- 239000011230 binding agent Substances 0.000 description 6
- 239000001768 carboxy methyl cellulose Substances 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 239000000594 mannitol Substances 0.000 description 6
- 235000010355 mannitol Nutrition 0.000 description 6
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 6
- 230000004614 tumor growth Effects 0.000 description 6
- VURKRJGMSKJIQX-UHFFFAOYSA-N xanthopterin Chemical compound N1C(=O)C=NC2=C1C(=O)N=C(N)N2 VURKRJGMSKJIQX-UHFFFAOYSA-N 0.000 description 6
- 108010010803 Gelatin Proteins 0.000 description 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
- 241000699666 Mus <mouse, genus> Species 0.000 description 5
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 238000000576 coating method Methods 0.000 description 5
- 239000002552 dosage form Substances 0.000 description 5
- 239000008273 gelatin Substances 0.000 description 5
- 229920000159 gelatin Polymers 0.000 description 5
- 229940014259 gelatin Drugs 0.000 description 5
- 235000019322 gelatine Nutrition 0.000 description 5
- 235000011852 gelatine desserts Nutrition 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- 239000001993 wax Substances 0.000 description 5
- LQIAZOCLNBBZQK-UHFFFAOYSA-N 1-(1,2-Diphosphanylethyl)pyrrolidin-2-one Chemical compound PCC(P)N1CCCC1=O LQIAZOCLNBBZQK-UHFFFAOYSA-N 0.000 description 4
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 241000416162 Astragalus gummifer Species 0.000 description 4
- 102000019034 Chemokines Human genes 0.000 description 4
- 108010012236 Chemokines Proteins 0.000 description 4
- 102000004127 Cytokines Human genes 0.000 description 4
- 108090000695 Cytokines Proteins 0.000 description 4
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- 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 4
- 229930012538 Paclitaxel Natural products 0.000 description 4
- 230000005867 T cell response Effects 0.000 description 4
- 229920001615 Tragacanth Polymers 0.000 description 4
- 239000008186 active pharmaceutical agent Substances 0.000 description 4
- 230000000735 allogeneic effect Effects 0.000 description 4
- 235000012216 bentonite Nutrition 0.000 description 4
- 201000008275 breast carcinoma Diseases 0.000 description 4
- 239000001506 calcium phosphate Substances 0.000 description 4
- 239000011248 coating agent Substances 0.000 description 4
- 239000008121 dextrose Substances 0.000 description 4
- 238000009792 diffusion process Methods 0.000 description 4
- 239000003102 growth factor Substances 0.000 description 4
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 4
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 4
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 4
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 4
- 239000012729 immediate-release (IR) formulation Substances 0.000 description 4
- 108091008915 immune receptors Proteins 0.000 description 4
- 102000027596 immune receptors Human genes 0.000 description 4
- 230000006058 immune tolerance Effects 0.000 description 4
- 230000002757 inflammatory effect Effects 0.000 description 4
- 239000008101 lactose Substances 0.000 description 4
- 229960001375 lactose Drugs 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 229920000609 methyl cellulose Polymers 0.000 description 4
- 235000010981 methylcellulose Nutrition 0.000 description 4
- 239000001923 methylcellulose Substances 0.000 description 4
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 4
- 239000007800 oxidant agent Substances 0.000 description 4
- 229960001592 paclitaxel Drugs 0.000 description 4
- 235000020030 perry Nutrition 0.000 description 4
- 229920000053 polysorbate 80 Polymers 0.000 description 4
- 230000000770 proinflammatory effect Effects 0.000 description 4
- 150000003254 radicals Chemical class 0.000 description 4
- 235000010413 sodium alginate Nutrition 0.000 description 4
- 239000000661 sodium alginate Substances 0.000 description 4
- 229940005550 sodium alginate Drugs 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 239000000600 sorbitol Substances 0.000 description 4
- 235000010356 sorbitol Nutrition 0.000 description 4
- 238000010561 standard procedure Methods 0.000 description 4
- 235000000346 sugar Nutrition 0.000 description 4
- 239000000454 talc Substances 0.000 description 4
- 229910052623 talc Inorganic materials 0.000 description 4
- 235000012222 talc Nutrition 0.000 description 4
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 102100021569 Apoptosis regulator Bcl-2 Human genes 0.000 description 3
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 3
- 101000971171 Homo sapiens Apoptosis regulator Bcl-2 Proteins 0.000 description 3
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 3
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 3
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 3
- 240000007472 Leucaena leucocephala Species 0.000 description 3
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 3
- 229920000881 Modified starch Polymers 0.000 description 3
- 102000003945 NF-kappa B Human genes 0.000 description 3
- 108010057466 NF-kappa B Proteins 0.000 description 3
- 229940121908 Retinoid X receptor agonist Drugs 0.000 description 3
- 238000011579 SCID mouse model Methods 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 235000021355 Stearic acid Nutrition 0.000 description 3
- 229930006000 Sucrose Natural products 0.000 description 3
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 3
- 230000001093 anti-cancer Effects 0.000 description 3
- 210000003719 b-lymphocyte Anatomy 0.000 description 3
- 239000000440 bentonite Substances 0.000 description 3
- 229910000278 bentonite Inorganic materials 0.000 description 3
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 3
- 210000000481 breast Anatomy 0.000 description 3
- 229910000019 calcium carbonate Inorganic materials 0.000 description 3
- 229960003563 calcium carbonate Drugs 0.000 description 3
- 235000010216 calcium carbonate Nutrition 0.000 description 3
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 3
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 3
- 239000012876 carrier material Substances 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
- 230000003111 delayed effect Effects 0.000 description 3
- 239000002270 dispersing agent Substances 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- 239000012530 fluid Substances 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 238000011081 inoculation Methods 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 3
- 239000008108 microcrystalline cellulose Substances 0.000 description 3
- 229940016286 microcrystalline cellulose Drugs 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 230000036457 multidrug resistance Effects 0.000 description 3
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 3
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 3
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 3
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 3
- 239000008117 stearic acid Substances 0.000 description 3
- 239000005720 sucrose Substances 0.000 description 3
- 239000004094 surface-active agent Substances 0.000 description 3
- 238000013268 sustained release Methods 0.000 description 3
- 239000012730 sustained-release form Substances 0.000 description 3
- 239000006188 syrup Substances 0.000 description 3
- 235000020357 syrup Nutrition 0.000 description 3
- 238000002626 targeted therapy Methods 0.000 description 3
- 229940099419 targretin Drugs 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 235000010487 tragacanth Nutrition 0.000 description 3
- 239000000196 tragacanth Substances 0.000 description 3
- 229940116362 tragacanth Drugs 0.000 description 3
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 3
- 229920001285 xanthan gum Polymers 0.000 description 3
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- XZIIFPSPUDAGJM-UHFFFAOYSA-N 6-chloro-2-n,2-n-diethylpyrimidine-2,4-diamine Polymers CCN(CC)C1=NC(N)=CC(Cl)=N1 XZIIFPSPUDAGJM-UHFFFAOYSA-N 0.000 description 2
- 229920001817 Agar Polymers 0.000 description 2
- 239000005995 Aluminium silicate Substances 0.000 description 2
- 229920000856 Amylose Polymers 0.000 description 2
- GUBGYTABKSRVRQ-DCSYEGIMSA-N Beta-Lactose Chemical compound OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-DCSYEGIMSA-N 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 108010062580 Concanavalin A Proteins 0.000 description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-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
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- 229920000715 Mucilage Polymers 0.000 description 2
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 description 2
- 108091034117 Oligonucleotide Proteins 0.000 description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
- BCKXLBQYZLBQEK-KVVVOXFISA-M Sodium oleate Chemical compound [Na+].CCCCCCCC\C=C/CCCCCCCC([O-])=O BCKXLBQYZLBQEK-KVVVOXFISA-M 0.000 description 2
- NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 description 2
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 2
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 2
- 208000036142 Viral infection Diseases 0.000 description 2
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000000853 adhesive Substances 0.000 description 2
- 235000010419 agar Nutrition 0.000 description 2
- 235000012211 aluminium silicate Nutrition 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 2
- 239000002246 antineoplastic agent Substances 0.000 description 2
- 239000000074 antisense oligonucleotide Substances 0.000 description 2
- 238000012230 antisense oligonucleotides Methods 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 2
- 230000010261 cell growth Effects 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 239000008119 colloidal silica Substances 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 229920001577 copolymer Polymers 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 229940096516 dextrates Drugs 0.000 description 2
- 235000019700 dicalcium phosphate Nutrition 0.000 description 2
- 229940095079 dicalcium phosphate anhydrous Drugs 0.000 description 2
- RBLGLDWTCZMLRW-UHFFFAOYSA-K dicalcium;phosphate;dihydrate Chemical compound O.O.[Ca+2].[Ca+2].[O-]P([O-])([O-])=O RBLGLDWTCZMLRW-UHFFFAOYSA-K 0.000 description 2
- 229960003668 docetaxel Drugs 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 239000002702 enteric coating Substances 0.000 description 2
- 238000009505 enteric coating Methods 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 239000012091 fetal bovine serum Substances 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 238000011049 filling Methods 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 230000002519 immonomodulatory effect Effects 0.000 description 2
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 208000020816 lung neoplasm Diseases 0.000 description 2
- 208000037841 lung tumor Diseases 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 238000003305 oral gavage Methods 0.000 description 2
- LUMKNAVTFCDUIE-VHXPQNKSSA-N ospemifene Chemical compound C1=CC(OCCO)=CC=C1C(\C=1C=CC=CC=1)=C(\CCCl)C1=CC=CC=C1 LUMKNAVTFCDUIE-VHXPQNKSSA-N 0.000 description 2
- 229960003969 ospemifene Drugs 0.000 description 2
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 2
- 229940068968 polysorbate 80 Drugs 0.000 description 2
- 229940069328 povidone Drugs 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 210000002307 prostate Anatomy 0.000 description 2
- 208000023958 prostate neoplasm Diseases 0.000 description 2
- 230000000541 pulsatile effect Effects 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 238000004467 single crystal X-ray diffraction Methods 0.000 description 2
- 238000009491 slugging Methods 0.000 description 2
- 210000000813 small intestine Anatomy 0.000 description 2
- 239000001632 sodium acetate Substances 0.000 description 2
- 235000017281 sodium acetate Nutrition 0.000 description 2
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 2
- 239000004299 sodium benzoate Substances 0.000 description 2
- 235000010234 sodium benzoate Nutrition 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 2
- RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical class [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 150000003431 steroids Chemical class 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 150000008163 sugars Chemical class 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 2
- XFCLJVABOIYOMF-QPLCGJKRSA-N toremifene Chemical compound C1=CC(OCCN(C)C)=CC=C1C(\C=1C=CC=CC=1)=C(\CCCl)C1=CC=CC=C1 XFCLJVABOIYOMF-QPLCGJKRSA-N 0.000 description 2
- 229960005026 toremifene Drugs 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
- 235000019731 tricalcium phosphate Nutrition 0.000 description 2
- 229940078499 tricalcium phosphate Drugs 0.000 description 2
- 229910000391 tricalcium phosphate Inorganic materials 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 230000009385 viral infection Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 230000003442 weekly effect Effects 0.000 description 2
- 235000010493 xanthan gum Nutrition 0.000 description 2
- 239000000230 xanthan gum Substances 0.000 description 2
- 229940082509 xanthan gum Drugs 0.000 description 2
- 239000000811 xylitol Substances 0.000 description 2
- 235000010447 xylitol Nutrition 0.000 description 2
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 2
- 229960002675 xylitol Drugs 0.000 description 2
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 1
- LDVVTQMJQSCDMK-UHFFFAOYSA-N 1,3-dihydroxypropan-2-yl formate Chemical compound OCC(CO)OC=O LDVVTQMJQSCDMK-UHFFFAOYSA-N 0.000 description 1
- OKMWKBLSFKFYGZ-UHFFFAOYSA-N 1-behenoylglycerol Chemical compound CCCCCCCCCCCCCCCCCCCCCC(=O)OCC(O)CO OKMWKBLSFKFYGZ-UHFFFAOYSA-N 0.000 description 1
- PZNPLUBHRSSFHT-RRHRGVEJSA-N 1-hexadecanoyl-2-octadecanoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[C@@H](COP([O-])(=O)OCC[N+](C)(C)C)COC(=O)CCCCCCCCCCCCCCC PZNPLUBHRSSFHT-RRHRGVEJSA-N 0.000 description 1
- RTBFRGCFXZNCOE-UHFFFAOYSA-N 1-methylsulfonylpiperidin-4-one Chemical compound CS(=O)(=O)N1CCC(=O)CC1 RTBFRGCFXZNCOE-UHFFFAOYSA-N 0.000 description 1
- 125000003821 2-(trimethylsilyl)ethoxymethyl group Chemical group [H]C([H])([H])[Si](C([H])([H])[H])(C([H])([H])[H])C([H])([H])C(OC([H])([H])[*])([H])[H] 0.000 description 1
- CQOQDQWUFQDJMK-SSTWWWIQSA-N 2-methoxy-17beta-estradiol Chemical compound C([C@@H]12)C[C@]3(C)[C@@H](O)CC[C@H]3[C@@H]1CCC1=C2C=C(OC)C(O)=C1 CQOQDQWUFQDJMK-SSTWWWIQSA-N 0.000 description 1
- 108010022579 ATP dependent 26S protease Proteins 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 235000006491 Acacia senegal Nutrition 0.000 description 1
- 230000024704 B cell apoptotic process Effects 0.000 description 1
- 208000031648 Body Weight Changes Diseases 0.000 description 1
- 239000001736 Calcium glycerylphosphate Substances 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 102000011632 Caseins Human genes 0.000 description 1
- 108010076119 Caseins Proteins 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 229920001353 Dextrin Polymers 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
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
- 108010075944 Erythropoietin Receptors Proteins 0.000 description 1
- 102100036509 Erythropoietin receptor Human genes 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
- 229940124226 Farnesyltransferase inhibitor Drugs 0.000 description 1
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- 241000237858 Gastropoda Species 0.000 description 1
- 241000206672 Gelidium Species 0.000 description 1
- 102000053187 Glucuronidase Human genes 0.000 description 1
- 108010060309 Glucuronidase Proteins 0.000 description 1
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 1
- 229920002907 Guar gum Polymers 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- SQUHHTBVTRBESD-UHFFFAOYSA-N Hexa-Ac-myo-Inositol Natural products CC(=O)OC1C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C1OC(C)=O SQUHHTBVTRBESD-UHFFFAOYSA-N 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 229920003085 Kollidon® CL Polymers 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- 229930182816 L-glutamine Natural products 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- 241000218652 Larix Species 0.000 description 1
- 235000005590 Larix decidua Nutrition 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 239000005913 Maltodextrin Substances 0.000 description 1
- 229920002774 Maltodextrin Polymers 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 229920003091 Methocel™ Polymers 0.000 description 1
- UBQYURCVBFRUQT-UHFFFAOYSA-N N-benzoyl-Ferrioxamine B Chemical compound CC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCN UBQYURCVBFRUQT-UHFFFAOYSA-N 0.000 description 1
- 108700019961 Neoplasm Genes Proteins 0.000 description 1
- 102000048850 Neoplasm Genes Human genes 0.000 description 1
- BUQLXKSONWUQAC-UHFFFAOYSA-N Parthenolide Natural products CC1C2OC(=O)C(=C)C2CCC(=C/CCC1(C)O)C BUQLXKSONWUQAC-UHFFFAOYSA-N 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 229920001214 Polysorbate 60 Polymers 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- GOOHAUXETOMSMM-UHFFFAOYSA-N Propylene oxide Chemical compound CC1CO1 GOOHAUXETOMSMM-UHFFFAOYSA-N 0.000 description 1
- 108090000708 Proteasome Endopeptidase Complex Proteins 0.000 description 1
- 102000004245 Proteasome Endopeptidase Complex Human genes 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 229920001800 Shellac Polymers 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-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
- HATRDXDCPOXQJX-UHFFFAOYSA-N Thapsigargin Natural products CCCCCCCC(=O)OC1C(OC(O)C(=C/C)C)C(=C2C3OC(=O)C(C)(O)C3(O)C(CC(C)(OC(=O)C)C12)OC(=O)CCC)C HATRDXDCPOXQJX-UHFFFAOYSA-N 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- SNAAJJQQZSMGQD-UHFFFAOYSA-N aluminum magnesium Chemical compound [Mg].[Al] SNAAJJQQZSMGQD-UHFFFAOYSA-N 0.000 description 1
- 238000000540 analysis of variance Methods 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- JFCQEDHGNNZCLN-UHFFFAOYSA-N anhydrous glutaric acid Natural products OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 description 1
- 229960004977 anhydrous lactose Drugs 0.000 description 1
- 239000000420 anogeissus latifolia wall. gum Substances 0.000 description 1
- 230000001833 anti-estrogenic effect Effects 0.000 description 1
- 230000006023 anti-tumor response Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 239000008122 artificial sweetener Substances 0.000 description 1
- 235000021311 artificial sweeteners Nutrition 0.000 description 1
- 125000003785 benzimidazolyl group Chemical class N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 239000003833 bile salt Substances 0.000 description 1
- 229940093761 bile salts Drugs 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000008033 biological extinction Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 230000036765 blood level Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 230000004579 body weight change Effects 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 239000004327 boric acid Substances 0.000 description 1
- 235000010338 boric acid Nutrition 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- LLSDKQJKOVVTOJ-UHFFFAOYSA-L calcium chloride dihydrate Chemical compound O.O.[Cl-].[Cl-].[Ca+2] LLSDKQJKOVVTOJ-UHFFFAOYSA-L 0.000 description 1
- 229940052299 calcium chloride dihydrate Drugs 0.000 description 1
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
- 229940095618 calcium glycerophosphate Drugs 0.000 description 1
- UHHRFSOMMCWGSO-UHFFFAOYSA-L calcium glycerophosphate Chemical compound [Ca+2].OCC(CO)OP([O-])([O-])=O UHHRFSOMMCWGSO-UHFFFAOYSA-L 0.000 description 1
- 235000019299 calcium glycerylphosphate Nutrition 0.000 description 1
- 239000000920 calcium hydroxide Substances 0.000 description 1
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 1
- MKJXYGKVIBWPFZ-UHFFFAOYSA-L calcium lactate Chemical compound [Ca+2].CC(O)C([O-])=O.CC(O)C([O-])=O MKJXYGKVIBWPFZ-UHFFFAOYSA-L 0.000 description 1
- 239000001527 calcium lactate Substances 0.000 description 1
- 235000011086 calcium lactate Nutrition 0.000 description 1
- 229960002401 calcium lactate Drugs 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 235000011132 calcium sulphate Nutrition 0.000 description 1
- UBWYRXFZPXBISJ-UHFFFAOYSA-L calcium;2-hydroxypropanoate;trihydrate Chemical compound O.O.O.[Ca+2].CC(O)C([O-])=O.CC(O)C([O-])=O UBWYRXFZPXBISJ-UHFFFAOYSA-L 0.000 description 1
- ZHZFKLKREFECML-UHFFFAOYSA-L calcium;sulfate;hydrate Chemical compound O.[Ca+2].[O-]S([O-])(=O)=O ZHZFKLKREFECML-UHFFFAOYSA-L 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 229940105329 carboxymethylcellulose Drugs 0.000 description 1
- 238000012754 cardiac puncture Methods 0.000 description 1
- 235000010418 carrageenan Nutrition 0.000 description 1
- 239000000679 carrageenan Substances 0.000 description 1
- 229920001525 carrageenan Polymers 0.000 description 1
- 229940113118 carrageenan Drugs 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000007541 cellular toxicity Effects 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 235000013339 cereals Nutrition 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 229940075614 colloidal silicon dioxide Drugs 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 230000001010 compromised effect Effects 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 229960000913 crospovidone Drugs 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 229940099217 desferal Drugs 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
- 229940038472 dicalcium phosphate Drugs 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 208000010643 digestive system disease Diseases 0.000 description 1
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 1
- 235000019797 dipotassium phosphate Nutrition 0.000 description 1
- 229910000396 dipotassium phosphate Inorganic materials 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 239000013583 drug formulation Substances 0.000 description 1
- 208000028715 ductal breast carcinoma in situ Diseases 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000003628 erosive effect Effects 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical compound [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 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
- 208000018685 gastrointestinal system disease Diseases 0.000 description 1
- 229960005150 glycerol Drugs 0.000 description 1
- 229940049654 glyceryl behenate Drugs 0.000 description 1
- 229940075507 glyceryl monostearate Drugs 0.000 description 1
- 235000010417 guar gum Nutrition 0.000 description 1
- 239000000665 guar gum Substances 0.000 description 1
- 229960002154 guar gum Drugs 0.000 description 1
- 235000019314 gum ghatti Nutrition 0.000 description 1
- 239000010903 husk Substances 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 239000008173 hydrogenated soybean oil Substances 0.000 description 1
- 239000008172 hydrogenated vegetable oil Substances 0.000 description 1
- 229920001477 hydrophilic polymer Polymers 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- CDAISMWEOUEBRE-GPIVLXJGSA-N inositol Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@@H]1O CDAISMWEOUEBRE-GPIVLXJGSA-N 0.000 description 1
- 229960000367 inositol Drugs 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 239000000832 lactitol Substances 0.000 description 1
- 235000010448 lactitol Nutrition 0.000 description 1
- VQHSOMBJVWLPSR-JVCRWLNRSA-N lactitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-JVCRWLNRSA-N 0.000 description 1
- 229960003451 lactitol Drugs 0.000 description 1
- 235000005772 leucine Nutrition 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- HCWCAKKEBCNQJP-UHFFFAOYSA-N magnesium orthosilicate Chemical compound [Mg+2].[Mg+2].[O-][Si]([O-])([O-])[O-] HCWCAKKEBCNQJP-UHFFFAOYSA-N 0.000 description 1
- 239000000391 magnesium silicate Substances 0.000 description 1
- 235000019792 magnesium silicate Nutrition 0.000 description 1
- 229910052919 magnesium silicate Inorganic materials 0.000 description 1
- 229960002366 magnesium silicate Drugs 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 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
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 229940035034 maltodextrin Drugs 0.000 description 1
- 210000005075 mammary gland Anatomy 0.000 description 1
- 239000001525 mentha piperita l. herb oil Substances 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 235000013379 molasses Nutrition 0.000 description 1
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 1
- 235000021096 natural sweeteners Nutrition 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- KTEXNACQROZXEV-PVLRGYAZSA-N parthenolide Chemical compound C1CC(/C)=C/CC[C@@]2(C)O[C@@H]2[C@H]2OC(=O)C(=C)[C@@H]21 KTEXNACQROZXEV-PVLRGYAZSA-N 0.000 description 1
- 229940069510 parthenolide Drugs 0.000 description 1
- 239000011236 particulate material Substances 0.000 description 1
- 235000019477 peppermint oil Nutrition 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229920001983 poloxamer Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229940068965 polysorbates Drugs 0.000 description 1
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
- 229920006316 polyvinylpyrrolidine Polymers 0.000 description 1
- 238000010837 poor prognosis Methods 0.000 description 1
- LWIHDJKSTIGBAC-UHFFFAOYSA-K potassium phosphate Substances [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 1
- 229920003124 powdered cellulose Polymers 0.000 description 1
- 235000019814 powdered cellulose Nutrition 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000000644 propagated effect Effects 0.000 description 1
- 239000011253 protective coating Substances 0.000 description 1
- 239000003528 protein farnesyltransferase inhibitor Substances 0.000 description 1
- 238000009790 rate-determining step (RDS) Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 238000004626 scanning electron microscopy Methods 0.000 description 1
- CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 229930009674 sesquiterpene lactone Natural products 0.000 description 1
- 150000002107 sesquiterpene lactone derivatives Chemical class 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 229920002545 silicone oil Polymers 0.000 description 1
- 235000015424 sodium Nutrition 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229940080237 sodium caseinate Drugs 0.000 description 1
- 229960002668 sodium chloride Drugs 0.000 description 1
- ODFAPIRLUPAQCQ-UHFFFAOYSA-M sodium stearoyl lactylate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC(=O)OC(C)C(=O)OC(C)C([O-])=O ODFAPIRLUPAQCQ-UHFFFAOYSA-M 0.000 description 1
- 229940080352 sodium stearoyl lactylate Drugs 0.000 description 1
- 235000011069 sorbitan monooleate Nutrition 0.000 description 1
- 239000001593 sorbitan monooleate Substances 0.000 description 1
- 229940035049 sorbitan monooleate Drugs 0.000 description 1
- 239000008347 soybean phospholipid Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 125000004079 stearyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])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 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000012385 systemic delivery Methods 0.000 description 1
- 229960001603 tamoxifen Drugs 0.000 description 1
- 239000008399 tap water Substances 0.000 description 1
- 235000020679 tap water Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 238000012549 training Methods 0.000 description 1
- 238000012384 transportation and delivery Methods 0.000 description 1
- 230000002476 tumorcidal effect Effects 0.000 description 1
- 238000002211 ultraviolet spectrum Methods 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 1
- 229930195724 β-lactose Natural products 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D475/00—Heterocyclic compounds containing pteridine ring systems
- C07D475/02—Heterocyclic compounds containing pteridine ring systems with an oxygen atom directly attached in position 4
- C07D475/04—Heterocyclic compounds containing pteridine ring systems with an oxygen atom directly attached in position 4 with a nitrogen atom directly attached in position 2
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US86354706P | 2006-10-30 | 2006-10-30 | |
| US60/863,547 | 2006-10-30 | ||
| PCT/US2007/023012 WO2008054793A2 (en) | 2006-10-30 | 2007-10-30 | Dipterinyl calcium pentahydrate (dcp) and therapeutic methods based thereon |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2668262A1 true CA2668262A1 (en) | 2008-05-08 |
Family
ID=39344907
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002668262A Abandoned CA2668262A1 (en) | 2006-10-30 | 2007-10-30 | Dipterinyl calcium pentahydrate (dcp) and therapeutic methods based thereon |
Country Status (7)
| Country | Link |
|---|---|
| US (2) | US7662820B2 (https=) |
| EP (1) | EP2094715B1 (https=) |
| JP (1) | JP2010508349A (https=) |
| CN (1) | CN101663308A (https=) |
| CA (1) | CA2668262A1 (https=) |
| ES (1) | ES2394227T3 (https=) |
| WO (1) | WO2008054793A2 (https=) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1535616B1 (en) | 2002-08-22 | 2009-05-13 | Dainippon Sumitomo Pharma Co., Ltd. | Remedy for integration dysfunction syndrome |
| KR101113630B1 (ko) | 2003-06-23 | 2012-02-13 | 다이닛본 스미토모 세이야꾸 가부시끼가이샤 | 노인성 치매 치료제 |
| US20070160537A1 (en) * | 2004-02-20 | 2007-07-12 | Takeo Ishiyama | In vivo screening method of therapeutic agent for memory/learning dysfunctions by schizophrenia |
| ES2444695T3 (es) * | 2006-06-23 | 2014-02-26 | Alethia Biotherapeutics Inc. | Polinucleótidos y polipéptidos implicados en el cáncer |
| CN101663308A (zh) * | 2006-10-30 | 2010-03-03 | 桑尔克斯药品公司 | N-甲基色胺钙五水合物(dcp)和基于它的治疗方法 |
| US20120251495A1 (en) * | 2008-01-18 | 2012-10-04 | Phillip Moheno | Pterin based therapies for inflammatory conditions |
| CA2740900C (en) | 2008-11-03 | 2019-09-24 | Alethia Biotherapeutics Inc. | Antibodies that specifically block the biological activity of a tumor antigen |
| US8258139B2 (en) | 2010-11-08 | 2012-09-04 | Dainippon Sumitomo Pharma Co., Ltd. | Method of treatment for mental disorders |
| SI3173427T1 (sl) | 2011-03-31 | 2019-08-30 | ADC Therapeutics SA, | Protitelesa proti antigenu 1, povezanemu z ledvicami, in antigen vezavni fragmenti le-tega |
| KR102102239B1 (ko) | 2012-01-09 | 2020-04-21 | 에이디씨 테라퓨틱스 에스에이 | 유방암을 치료하기 위한 방법 |
| US20150010509A1 (en) * | 2012-01-30 | 2015-01-08 | Sanrx Pharmaceuticals, Inc. | Calcium folate (cafolate) and therapeutic methods based thereon |
| CN104788300B (zh) * | 2014-01-22 | 2017-01-11 | 南京华威医药科技开发有限公司 | 欧司哌米芬多晶型 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2000012137A1 (en) | 1998-09-02 | 2000-03-09 | Allergan Sales, Inc. | Preserved cyclodextrin-containing compositions |
| AU1223400A (en) * | 1998-10-22 | 2000-05-08 | Phillip B. B. Moheno | Novel pterin antineoplastic agents |
| DE19944767A1 (de) * | 1999-09-17 | 2001-03-29 | Vasopharm Biotech Gmbh & Co Kg | N-substituierte 4-Aminopteridine, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
| CN101663308A (zh) * | 2006-10-30 | 2010-03-03 | 桑尔克斯药品公司 | N-甲基色胺钙五水合物(dcp)和基于它的治疗方法 |
-
2007
- 2007-10-30 CN CN200780048992A patent/CN101663308A/zh active Pending
- 2007-10-30 JP JP2009535306A patent/JP2010508349A/ja active Pending
- 2007-10-30 US US11/981,398 patent/US7662820B2/en not_active Expired - Fee Related
- 2007-10-30 WO PCT/US2007/023012 patent/WO2008054793A2/en not_active Ceased
- 2007-10-30 EP EP07867329A patent/EP2094715B1/en not_active Not-in-force
- 2007-10-30 ES ES07867329T patent/ES2394227T3/es active Active
- 2007-10-30 CA CA002668262A patent/CA2668262A1/en not_active Abandoned
-
2009
- 2009-12-21 US US12/643,752 patent/US20100105692A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| WO2008054793A3 (en) | 2008-08-28 |
| CN101663308A (zh) | 2010-03-03 |
| EP2094715B1 (en) | 2012-08-29 |
| EP2094715A2 (en) | 2009-09-02 |
| EP2094715A4 (en) | 2010-04-28 |
| ES2394227T3 (es) | 2013-01-23 |
| WO2008054793A2 (en) | 2008-05-08 |
| US20080166355A1 (en) | 2008-07-10 |
| US20100105692A1 (en) | 2010-04-29 |
| JP2010508349A (ja) | 2010-03-18 |
| US7662820B2 (en) | 2010-02-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP2094715B1 (en) | Dipterinyl calcium pentahydrate (dcp) and therapeutic methods based thereon | |
| KR101633134B1 (ko) | 시티딘 유사체의 경구 제형 및 그의 사용 방법 | |
| TWI641374B (zh) | 含低用量伊立替康鹽酸鹽水合物之抗腫瘤劑 | |
| CN101360495B (zh) | 对癌症病人给药mTOR抑制剂 | |
| TWI818954B (zh) | 三取代之苯并三唑衍生物的使用方法 | |
| US20100266590A1 (en) | Combination therapy | |
| CN121490094A (zh) | 药物在治疗肿瘤疾病中的应用 | |
| WO2017162055A1 (zh) | 环二核苷酸cGAMP-脂质体在抗肿瘤中的应用 | |
| JP2018513130A (ja) | Ｈｓｐ９０阻害ペプチド結合体及びその腫瘍治療における応用 | |
| JPH0617304B2 (ja) | 制癌剤 | |
| EP3527210B1 (en) | Combined composition comprising a benzoheterocyclic compound and an androgen receptor pathway modulator and uses thereof | |
| US20080207644A1 (en) | Therapeutic materials and methods | |
| CN118903175B (zh) | 小分子药物联用在增强低氧条件下nk细胞的代谢、杀伤能力中的应用 | |
| CN116271090B (zh) | 一种具有tlr9激动剂活性的dna纳米笼及其在制备抗肿瘤药物中的应用 | |
| WO1992004028A1 (en) | Antineoplastic effect potentiator and antineoplastic agent | |
| CN102218065B (zh) | 苦豆碱在制药中的新应用 | |
| CN104434948B (zh) | 一种抗胰腺癌的药物组合物及其应用 | |
| CN113993515B (zh) | 使用藏红花酸治疗实体肿瘤的方法 | |
| CN115068474A (zh) | 脱氢卡维丁在制备治疗人肺腺癌药物组合物中的应用 | |
| HK1139952A (en) | Dipterinyl calcium pentahydrate (dcp) and therapeutic methods based thereon | |
| US20220305026A1 (en) | Use of polaprezinc in preparing drug for treating castration-resistant prostate cancer | |
| CN101155600A (zh) | 放射线治疗增强剂 | |
| KR20200093575A (ko) | 종양 전이를 억제하는 방법 | |
| JP2001081047A (ja) | 経口摂取用製剤 | |
| CN118845803A (zh) | 人参皂苷Ra1防治消化道肿瘤的应用 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDC | Correction of dead application (reinstatement) | ||
| FZDE | Dead |
Effective date: 20130507 |