ZA200406361B

ZA200406361B - Pharmaceutical formulation of iressa comprising a watersoluble cellulose derivative.

Pharmaceutical formulation of iressa comprising a watersoluble cellulose derivative. Download PDF

Info

Publication number: ZA200406361B
Authority: ZA; South Africa
Prior art keywords: agent; water; cellulose ether; soluble cellulose; ester
Prior art date: 2002-02-26

Application number

ZA200406361A

Other languages

English (en)

Inventor

Paul Richard Gellert

Marcel De Matas

Michael Davis Parker

Original Assignee

Astrazeneca Ab

Priority date

2002-02-26

Filing date

2004-08-11

Publication date

2005-11-30

2004-08-11 Application filed by Astrazeneca Ab filed Critical Astrazeneca Ab

2005-11-30 Publication of ZA200406361B publication Critical patent/ZA200406361B/en

Links

229920002678 cellulose Polymers 0.000 title claims description 60
239000008194 pharmaceutical composition Substances 0.000 title claims description 49
239000001913 cellulose Substances 0.000 title claims description 24
XGALLCVXEZPNRQ-UHFFFAOYSA-N gefitinib Chemical compound C=12C=C(OCCCN3CCOCC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 XGALLCVXEZPNRQ-UHFFFAOYSA-N 0.000 title claims description 11
239000005411 L01XE02 - Gefitinib Substances 0.000 title description 4
229940084651 iressa Drugs 0.000 title description 3
239000003795 chemical substances by application Substances 0.000 claims description 264
229920003086 cellulose ether Polymers 0.000 claims description 182
239000000203 mixture Substances 0.000 claims description 141
235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 94
229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 94
239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 94
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 claims description 91
150000002148 esters Chemical class 0.000 claims description 90
239000000243 solution Substances 0.000 claims description 55
238000001556 precipitation Methods 0.000 claims description 47
-1 alkyl sulphate Chemical compound 0.000 claims description 44
239000000080 wetting agent Substances 0.000 claims description 37
229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 35
235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 35
239000001863 hydroxypropyl cellulose Substances 0.000 claims description 34
238000000034 method Methods 0.000 claims description 32
239000007888 film coating Substances 0.000 claims description 25
238000009501 film coating Methods 0.000 claims description 25
239000001768 carboxy methyl cellulose Substances 0.000 claims description 24
235000010980 cellulose Nutrition 0.000 claims description 23
229920000609 methyl cellulose Polymers 0.000 claims description 23
235000010981 methylcellulose Nutrition 0.000 claims description 23
239000001923 methylcellulose Substances 0.000 claims description 23
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 claims description 22
150000003839 salts Chemical class 0.000 claims description 22
239000003826 tablet Substances 0.000 claims description 20
229920000663 Hydroxyethyl cellulose Polymers 0.000 claims description 19
235000019447 hydroxyethyl cellulose Nutrition 0.000 claims description 19
239000004354 Hydroxyethyl cellulose Substances 0.000 claims description 18
238000000576 coating method Methods 0.000 claims description 17
239000007884 disintegrant Substances 0.000 claims description 17
238000011282 treatment Methods 0.000 claims description 17
239000011230 binding agent Substances 0.000 claims description 16
210000001035 gastrointestinal tract Anatomy 0.000 claims description 16
239000011248 coating agent Substances 0.000 claims description 15
239000007864 aqueous solution Substances 0.000 claims description 14
239000000945 filler Substances 0.000 claims description 14
229920002134 Carboxymethyl cellulose Polymers 0.000 claims description 13
235000010948 carboxy methyl cellulose Nutrition 0.000 claims description 13
239000008112 carboxymethyl-cellulose Substances 0.000 claims description 13
229940105329 carboxymethylcellulose Drugs 0.000 claims description 13
239000008187 granular material Substances 0.000 claims description 13
239000000314 lubricant Substances 0.000 claims description 13
WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims description 12
229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 12
235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 12
229920000168 Microcrystalline cellulose Polymers 0.000 claims description 11
235000019813 microcrystalline cellulose Nutrition 0.000 claims description 11
239000008108 microcrystalline cellulose Substances 0.000 claims description 11
229940016286 microcrystalline cellulose Drugs 0.000 claims description 11
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims description 11
229920001027 sodium carboxymethylcellulose Polymers 0.000 claims description 11
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 claims description 10
229910052783 alkali metal Inorganic materials 0.000 claims description 9
239000003945 anionic surfactant Substances 0.000 claims description 9
230000002401 inhibitory effect Effects 0.000 claims description 9
238000004519 manufacturing process Methods 0.000 claims description 9
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 8
239000003093 cationic surfactant Substances 0.000 claims description 8
239000004014 plasticizer Substances 0.000 claims description 8
229940069328 povidone Drugs 0.000 claims description 8
229910021653 sulphate ion Inorganic materials 0.000 claims description 8
229920002785 Croscarmellose sodium Polymers 0.000 claims description 7
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 claims description 7
IYKJEILNJZQJPU-UHFFFAOYSA-N acetic acid;butanedioic acid Chemical compound CC(O)=O.OC(=O)CCC(O)=O IYKJEILNJZQJPU-UHFFFAOYSA-N 0.000 claims description 7
150000001340 alkali metals Chemical group 0.000 claims description 7
229960001681 croscarmellose sodium Drugs 0.000 claims description 7
235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 claims description 7
239000008101 lactose Substances 0.000 claims description 7
230000036470 plasma concentration Effects 0.000 claims description 7
239000011734 sodium Substances 0.000 claims description 7
229910052708 sodium Inorganic materials 0.000 claims description 7
239000007787 solid Substances 0.000 claims description 7
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 claims description 6
239000006185 dispersion Substances 0.000 claims description 6
239000008188 pellet Substances 0.000 claims description 6
XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 claims description 6
239000003086 colorant Substances 0.000 claims description 5
239000003605 opacifier Substances 0.000 claims description 5
125000005591 trimellitate group Chemical group 0.000 claims description 5
229920003123 carboxymethyl cellulose sodium Polymers 0.000 claims description 4
229940063834 carboxymethylcellulose sodium Drugs 0.000 claims description 4
125000002091 cationic group Chemical group 0.000 claims description 4
125000004185 ester group Chemical group 0.000 claims description 4
239000001267 polyvinylpyrrolidone Substances 0.000 claims description 4
239000000126 substance Substances 0.000 claims description 4
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 claims description 3
229930195725 Mannitol Natural products 0.000 claims description 3
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 3
229960000913 crospovidone Drugs 0.000 claims description 3
QQVIHTHCMHWDBS-UHFFFAOYSA-L isophthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC(C([O-])=O)=C1 QQVIHTHCMHWDBS-UHFFFAOYSA-L 0.000 claims description 3
239000000594 mannitol Substances 0.000 claims description 3
235000010355 mannitol Nutrition 0.000 claims description 3
229920000523 polyvinylpolypyrrolidone Polymers 0.000 claims description 3
235000013809 polyvinylpolypyrrolidone Nutrition 0.000 claims description 3
238000002360 preparation method Methods 0.000 claims description 3
229920003109 sodium starch glycolate Polymers 0.000 claims description 3
239000008109 sodium starch glycolate Substances 0.000 claims description 3
229940079832 sodium starch glycolate Drugs 0.000 claims description 3
KKEYFWRCBNTPAC-UHFFFAOYSA-L terephthalate(2-) Chemical compound [O-]C(=O)C1=CC=C(C([O-])=O)C=C1 KKEYFWRCBNTPAC-UHFFFAOYSA-L 0.000 claims description 3
229940084030 carboxymethylcellulose calcium Drugs 0.000 claims description 2
SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Natural products CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 claims 1
229940071676 hydroxypropylcellulose Drugs 0.000 description 31
235000002639 sodium chloride Nutrition 0.000 description 21
230000002378 acidificating effect Effects 0.000 description 20
239000000546 pharmaceutical excipient Substances 0.000 description 20
GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 18
230000000052 comparative effect Effects 0.000 description 18
239000003814 drug Substances 0.000 description 18
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 16
239000013068 control sample Substances 0.000 description 16
238000009472 formulation Methods 0.000 description 16
UQSXHKLRYXJYBZ-UHFFFAOYSA-N iron oxide Inorganic materials [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 description 16
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
206010028980 Neoplasm Diseases 0.000 description 14
DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 14
230000000694 effects Effects 0.000 description 14
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 14
235000019333 sodium laurylsulphate Nutrition 0.000 description 14
238000006467 substitution reaction Methods 0.000 description 14
229960000686 benzalkonium chloride Drugs 0.000 description 11
CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 11
229940079593 drug Drugs 0.000 description 11
229920001223 polyethylene glycol Polymers 0.000 description 11
210000002784 stomach Anatomy 0.000 description 11
238000010521 absorption reaction Methods 0.000 description 10
238000004090 dissolution Methods 0.000 description 10
238000002156 mixing Methods 0.000 description 10
229920000642 polymer Polymers 0.000 description 10
102000001301 EGF receptor Human genes 0.000 description 9
108060006698 EGF receptor Proteins 0.000 description 9
239000002775 capsule Substances 0.000 description 9
125000002887 hydroxy group Chemical group [H]O* 0.000 description 9
239000004408 titanium dioxide Substances 0.000 description 9
WSVLPVUVIUVCRA-KPKNDVKVSA-N Alpha-lactose monohydrate Chemical compound O.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 WSVLPVUVIUVCRA-KPKNDVKVSA-N 0.000 description 8
239000004141 Sodium laurylsulphate Substances 0.000 description 8
239000002253 acid Substances 0.000 description 8
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 8
239000012738 dissolution medium Substances 0.000 description 8
210000000936 intestine Anatomy 0.000 description 8
229960001021 lactose monohydrate Drugs 0.000 description 8
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 8
239000002202 Polyethylene glycol Substances 0.000 description 7
125000000217 alkyl group Chemical group 0.000 description 7
230000001028 anti-proliverative effect Effects 0.000 description 7
239000007963 capsule composition Substances 0.000 description 7
239000012458 free base Substances 0.000 description 7
235000019359 magnesium stearate Nutrition 0.000 description 7
239000002609 medium Substances 0.000 description 7
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
229920002472 Starch Polymers 0.000 description 6
239000002552 dosage form Substances 0.000 description 6
150000004820 halides Chemical class 0.000 description 6
150000007524 organic acids Chemical class 0.000 description 6
NDLPOXTZKUMGOV-UHFFFAOYSA-N oxo(oxoferriooxy)iron hydrate Chemical compound O.O=[Fe]O[Fe]=O NDLPOXTZKUMGOV-UHFFFAOYSA-N 0.000 description 6
230000009467 reduction Effects 0.000 description 6
235000015424 sodium Nutrition 0.000 description 6
235000019698 starch Nutrition 0.000 description 6
239000000454 talc Substances 0.000 description 6
235000012222 talc Nutrition 0.000 description 6
229910052623 talc Inorganic materials 0.000 description 6
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
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 5
125000003545 alkoxy group Chemical group 0.000 description 5
125000000129 anionic group Chemical group 0.000 description 5
201000011510 cancer Diseases 0.000 description 5
150000001875 compounds Chemical class 0.000 description 5
201000010099 disease Diseases 0.000 description 5
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
238000004128 high performance liquid chromatography Methods 0.000 description 5
235000013980 iron oxide Nutrition 0.000 description 5
229960001375 lactose Drugs 0.000 description 5
229940124531 pharmaceutical excipient Drugs 0.000 description 5
238000005550 wet granulation Methods 0.000 description 5
239000001856 Ethyl cellulose Substances 0.000 description 4
241001465754 Metazoa Species 0.000 description 4
239000004359 castor oil Substances 0.000 description 4
235000019438 castor oil Nutrition 0.000 description 4
238000007906 compression Methods 0.000 description 4
230000006835 compression Effects 0.000 description 4
239000012141 concentrate Substances 0.000 description 4
229910003460 diamond Inorganic materials 0.000 description 4
239000010432 diamond Substances 0.000 description 4
238000007922 dissolution test Methods 0.000 description 4
235000019325 ethyl cellulose Nutrition 0.000 description 4
229920001249 ethyl cellulose Polymers 0.000 description 4
239000010408 film Substances 0.000 description 4
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 description 4
229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 description 4
229910052751 metal Inorganic materials 0.000 description 4
239000002184 metal Substances 0.000 description 4
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
239000000843 powder Substances 0.000 description 4
150000003856 quaternary ammonium compounds Chemical class 0.000 description 4
239000000523 sample Substances 0.000 description 4
ARCGXLSVLAOJQL-UHFFFAOYSA-N trimellitic acid Chemical compound OC(=O)C1=CC=C(C(O)=O)C(C(O)=O)=C1 ARCGXLSVLAOJQL-UHFFFAOYSA-N 0.000 description 4
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
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 3
229920000881 Modified starch 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
GAMPNQJDUFQVQO-UHFFFAOYSA-N acetic acid;phthalic acid Chemical compound CC(O)=O.OC(=O)C1=CC=CC=C1C(O)=O GAMPNQJDUFQVQO-UHFFFAOYSA-N 0.000 description 3
125000005211 alkyl trimethyl ammonium group Chemical group 0.000 description 3
125000004432 carbon atom Chemical group C* 0.000 description 3
150000007942 carboxylates Chemical class 0.000 description 3
229920002301 cellulose acetate Polymers 0.000 description 3
230000008859 change Effects 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
230000001419 dependent effect Effects 0.000 description 3
235000014113 dietary fatty acids Nutrition 0.000 description 3
150000002170 ethers Chemical class 0.000 description 3
239000000194 fatty acid Substances 0.000 description 3
229930195729 fatty acid Natural products 0.000 description 3
239000007941 film coated tablet Substances 0.000 description 3
229920003132 hydroxypropyl methylcellulose phthalate Polymers 0.000 description 3
229940031704 hydroxypropyl methylcellulose phthalate Drugs 0.000 description 3
238000001727 in vivo Methods 0.000 description 3
230000005764 inhibitory process Effects 0.000 description 3
TWNIBLMWSKIRAT-VFUOTHLCSA-N levoglucosan Chemical group O[C@@H]1[C@@H](O)[C@H](O)[C@H]2CO[C@@H]1O2 TWNIBLMWSKIRAT-VFUOTHLCSA-N 0.000 description 3
230000001404 mediated effect Effects 0.000 description 3
XNGIFLGASWRNHJ-UHFFFAOYSA-N o-dicarboxybenzene Natural products OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 description 3
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159000000000 sodium salts Chemical class 0.000 description 3
239000007909 solid dosage form Substances 0.000 description 3
235000000346 sugar Nutrition 0.000 description 3
239000007916 tablet composition Substances 0.000 description 3
229920003169 water-soluble polymer Polymers 0.000 description 3
HSINOMROUCMIEA-FGVHQWLLSA-N (2s,4r)-4-[(3r,5s,6r,7r,8s,9s,10s,13r,14s,17r)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoic acid Chemical class C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 HSINOMROUCMIEA-FGVHQWLLSA-N 0.000 description 2
206010004446 Benign prostatic hyperplasia Diseases 0.000 description 2
FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
201000009030 Carcinoma Diseases 0.000 description 2
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241000124008 Mammalia Species 0.000 description 2
208000004403 Prostatic Hyperplasia Diseases 0.000 description 2
201000004681 Psoriasis Diseases 0.000 description 2
206010039491 Sarcoma Diseases 0.000 description 2
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KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
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 2
208000024770 Thyroid neoplasm Diseases 0.000 description 2
240000008042 Zea mays Species 0.000 description 2
235000002017 Zea mays subsp mays Nutrition 0.000 description 2
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229920000615 alginic acid Polymers 0.000 description 2
125000005210 alkyl ammonium group Chemical group 0.000 description 2
230000001093 anti-cancer Effects 0.000 description 2
239000003125 aqueous solvent Substances 0.000 description 2
125000003118 aryl group Chemical group 0.000 description 2
JXLHNMVSKXFWAO-UHFFFAOYSA-N azane;7-fluoro-2,1,3-benzoxadiazole-4-sulfonic acid Chemical compound N.OS(=O)(=O)C1=CC=C(F)C2=NON=C12 JXLHNMVSKXFWAO-UHFFFAOYSA-N 0.000 description 2
150000007514 bases Chemical class 0.000 description 2
229960001716 benzalkonium Drugs 0.000 description 2
KKEYFWRCBNTPAC-UHFFFAOYSA-N benzene-dicarboxylic acid Natural products OC(=O)C1=CC=C(C(O)=O)C=C1 KKEYFWRCBNTPAC-UHFFFAOYSA-N 0.000 description 2
239000003613 bile acid Substances 0.000 description 2
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210000004556 brain Anatomy 0.000 description 2
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235000001465 calcium Nutrition 0.000 description 2
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150000001735 carboxylic acids Chemical class 0.000 description 2
125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 2
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KXGVEGMKQFWNSR-LLQZFEROSA-N deoxycholic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 KXGVEGMKQFWNSR-LLQZFEROSA-N 0.000 description 2
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