CA2539215A1 - Agents de contraste pour imagerie diagnostique presentant une retention prolongee dans le sang - Google Patents

Info

Publication number

CA2539215A1

CA2539215A1 CA002539215A CA2539215A CA2539215A1 CA 2539215 A1 CA2539215 A1 CA 2539215A1 CA 002539215 A CA002539215 A CA 002539215A CA 2539215 A CA2539215 A CA 2539215A CA 2539215 A1 CA2539215 A1 CA 2539215A1

Authority

CA

Canada

Prior art keywords

contrast agent

agent according

moiety

ppbm

plasma

Prior art date

1995-02-01

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

• Espacenet
• Global Dossier
• CIPO
• Discuss

• 239000002872 contrast media Substances 0.000 title claims abstract description 165
• 210000004369 blood Anatomy 0.000 title claims abstract description 76
• 239000008280 blood Substances 0.000 title claims abstract description 76
• 238000002059 diagnostic imaging Methods 0.000 title claims abstract description 30
• 230000014759 maintenance of location Effects 0.000 title abstract description 10
• 239000003795 chemical substances by application Substances 0.000 claims abstract description 66
• 150000001875 compounds Chemical class 0.000 claims abstract description 40
• 108010017384 Blood Proteins Proteins 0.000 claims abstract description 39
• 102000004506 Blood Proteins Human genes 0.000 claims abstract description 39
• 238000000034 method Methods 0.000 claims abstract description 33
• 239000000203 mixture Substances 0.000 claims abstract description 31
• 238000003384 imaging method Methods 0.000 claims description 41
• 150000002148 esters Chemical class 0.000 claims description 40
• 102000004169 proteins and genes Human genes 0.000 claims description 29
• 108090000623 proteins and genes Proteins 0.000 claims description 29
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 26
• 239000013522 chelant Substances 0.000 claims description 26
• 150000003839 salts Chemical class 0.000 claims description 26
• 238000002595 magnetic resonance imaging Methods 0.000 claims description 22
• 239000003446 ligand Substances 0.000 claims description 21
• 229910021645 metal ion Inorganic materials 0.000 claims description 21
• 230000036470 plasma concentration Effects 0.000 claims description 20
• 229910052751 metal Inorganic materials 0.000 claims description 18
• 239000002184 metal Substances 0.000 claims description 18
• 108090000765 processed proteins & peptides Proteins 0.000 claims description 18
• 239000000126 substance Substances 0.000 claims description 18
• 229910052688 Gadolinium Inorganic materials 0.000 claims description 17
• MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical class CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 claims description 17
• 229910019142 PO4 Inorganic materials 0.000 claims description 17
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 16
• 239000010452 phosphate Substances 0.000 claims description 16
• UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 claims description 16
• 229910052760 oxygen Inorganic materials 0.000 claims description 15
• 125000004432 carbon atom Chemical group C* 0.000 claims description 14
• 229910052717 sulfur Inorganic materials 0.000 claims description 14
• 230000002209 hydrophobic effect Effects 0.000 claims description 13
• 239000002245 particle Substances 0.000 claims description 13
• 229910052721 tungsten Inorganic materials 0.000 claims description 13
• 125000003118 aryl group Chemical group 0.000 claims description 12
• 229910052698 phosphorus Inorganic materials 0.000 claims description 12
• 239000004202 carbamide Substances 0.000 claims description 10
• 238000002474 experimental method Methods 0.000 claims description 10
• 229910052750 molybdenum Inorganic materials 0.000 claims description 10
• 230000005298 paramagnetic effect Effects 0.000 claims description 10
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 9
• BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims description 9
• 150000001241 acetals Chemical class 0.000 claims description 9
• 125000001931 aliphatic group Chemical group 0.000 claims description 9
• 150000001412 amines Chemical class 0.000 claims description 9
• 239000007864 aqueous solution Substances 0.000 claims description 9
• 239000002738 chelating agent Substances 0.000 claims description 9
• 125000005647 linker group Chemical group 0.000 claims description 9
• 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 claims description 9
• 125000001424 substituent group Chemical group 0.000 claims description 9
• 150000003457 sulfones Chemical class 0.000 claims description 9
• 229910052742 iron Inorganic materials 0.000 claims description 8
• 229920000642 polymer Polymers 0.000 claims description 8
• 239000012217 radiopharmaceutical Substances 0.000 claims description 7
• 229940121896 radiopharmaceutical Drugs 0.000 claims description 7
• 230000002799 radiopharmaceutical effect Effects 0.000 claims description 7
• 229940124530 sulfonamide Drugs 0.000 claims description 7
• 125000002015 acyclic group Chemical group 0.000 claims description 6
• 125000004122 cyclic group Chemical group 0.000 claims description 6
• 239000002502 liposome Substances 0.000 claims description 6
• 230000036961 partial effect Effects 0.000 claims description 6
• 150000003456 sulfonamides Chemical class 0.000 claims description 6
• 102000008100 Human Serum Albumin Human genes 0.000 claims description 5
• 108091006905 Human Serum Albumin Proteins 0.000 claims description 5
• 125000000539 amino acid group Chemical group 0.000 claims description 5
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
• 229910052757 nitrogen Inorganic materials 0.000 claims description 5
• 230000008685 targeting Effects 0.000 claims description 5
• 239000003981 vehicle Substances 0.000 claims description 5
• 239000002671 adjuvant Substances 0.000 claims description 4
• 239000003937 drug carrier Substances 0.000 claims description 4
• 229910052739 hydrogen Inorganic materials 0.000 claims description 4
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 3
• JPVYNHNXODAKFH-UHFFFAOYSA-N Cu2+ Chemical compound [Cu+2] JPVYNHNXODAKFH-UHFFFAOYSA-N 0.000 claims description 3
• VTLYFUHAOXGGBS-UHFFFAOYSA-N Fe3+ Chemical compound [Fe+3] VTLYFUHAOXGGBS-UHFFFAOYSA-N 0.000 claims description 3
• 239000011575 calcium Substances 0.000 claims description 3
• 229910052791 calcium Inorganic materials 0.000 claims description 3
• BFGKITSFLPAWGI-UHFFFAOYSA-N chromium(3+) Chemical compound [Cr+3] BFGKITSFLPAWGI-UHFFFAOYSA-N 0.000 claims description 3
• 238000012285 ultrasound imaging Methods 0.000 claims description 3
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 2
• WAEMQWOKJMHJLA-UHFFFAOYSA-N Manganese(2+) Chemical compound [Mn+2] WAEMQWOKJMHJLA-UHFFFAOYSA-N 0.000 claims description 2
• 239000007789 gas Substances 0.000 claims description 2
• 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 2
• MMIPFLVOWGHZQD-UHFFFAOYSA-N manganese(3+) Chemical compound [Mn+3] MMIPFLVOWGHZQD-UHFFFAOYSA-N 0.000 claims description 2
• 238000002156 mixing Methods 0.000 claims description 2
• 102000004196 processed proteins & peptides Human genes 0.000 claims description 2
• 230000002285 radioactive effect Effects 0.000 claims description 2
• 239000011734 sodium Substances 0.000 claims description 2
• 229910052708 sodium Inorganic materials 0.000 claims description 2
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 10
• 238000002405 diagnostic procedure Methods 0.000 claims 6
• 239000013110 organic ligand Substances 0.000 claims 2
• GKLVYJBZJHMRIY-OUBTZVSYSA-N Technetium-99 Chemical compound [99Tc] GKLVYJBZJHMRIY-OUBTZVSYSA-N 0.000 claims 1
• 229940056501 technetium 99m Drugs 0.000 claims 1
• 239000008194 pharmaceutical composition Substances 0.000 abstract description 14
• 230000002829 reductive effect Effects 0.000 abstract description 10
• 150000003384 small molecules Chemical class 0.000 abstract description 7
• 238000013459 approach Methods 0.000 abstract description 3
• 150000002605 large molecules Chemical class 0.000 abstract description 2
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 48
• 239000000243 solution Substances 0.000 description 30
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 29
• 229910001868 water Inorganic materials 0.000 description 22
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical group CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 18
• -1 O-O- O Chemical class 0.000 description 17
• UIWYJDYFSGRHKR-UHFFFAOYSA-N gadolinium atom Chemical compound [Gd] UIWYJDYFSGRHKR-UHFFFAOYSA-N 0.000 description 14
• 206010028980 Neoplasm Diseases 0.000 description 13
• 239000008367 deionised water Substances 0.000 description 13
• 229910021641 deionized water Inorganic materials 0.000 description 13
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 13
• 235000021317 phosphate Nutrition 0.000 description 13
• 150000008300 phosphoramidites Chemical class 0.000 description 12
• 239000002904 solvent Substances 0.000 description 12
• 230000001965 increasing effect Effects 0.000 description 11
• 210000001519 tissue Anatomy 0.000 description 11
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
• CMIHHWBVHJVIGI-UHFFFAOYSA-N gadolinium(iii) oxide Chemical compound [O-2].[O-2].[O-2].[Gd+3].[Gd+3] CMIHHWBVHJVIGI-UHFFFAOYSA-N 0.000 description 10
• 230000029142 excretion Effects 0.000 description 9
• IZOOGPBRAOKZFK-UHFFFAOYSA-K gadopentetate Chemical compound [Gd+3].OC(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O IZOOGPBRAOKZFK-UHFFFAOYSA-K 0.000 description 9
• 231100000419 toxicity Toxicity 0.000 description 9
• 230000001988 toxicity Effects 0.000 description 9
• 238000009472 formulation Methods 0.000 description 8
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 8
• 239000000047 product Substances 0.000 description 8
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 7
• 125000000217 alkyl group Chemical group 0.000 description 7
• 238000002347 injection Methods 0.000 description 7
• 239000007924 injection Substances 0.000 description 7
• 230000005291 magnetic effect Effects 0.000 description 7
• 238000002360 preparation method Methods 0.000 description 7
• 239000007787 solid Substances 0.000 description 7
• WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
• 241000700159 Rattus Species 0.000 description 6
• 230000015572 biosynthetic process Effects 0.000 description 6
• 230000007423 decrease Effects 0.000 description 6
• 229940075613 gadolinium oxide Drugs 0.000 description 6
• 229910001938 gadolinium oxide Inorganic materials 0.000 description 6
• 210000003494 hepatocyte Anatomy 0.000 description 6
• 239000011780 sodium chloride Substances 0.000 description 6
• 238000012360 testing method Methods 0.000 description 6
• 238000002604 ultrasonography Methods 0.000 description 6
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
• 210000004204 blood vessel Anatomy 0.000 description 5
• 239000000969 carrier Substances 0.000 description 5
• 210000004027 cell Anatomy 0.000 description 5
• 239000012043 crude product Substances 0.000 description 5
• 150000002500 ions Chemical class 0.000 description 5
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
• 239000003921 oil Substances 0.000 description 5
• 235000019198 oils Nutrition 0.000 description 5
• 229920001223 polyethylene glycol Polymers 0.000 description 5
• 238000010898 silica gel chromatography Methods 0.000 description 5
• 239000000725 suspension Substances 0.000 description 5
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
• 238000005481 NMR spectroscopy Methods 0.000 description 4
• 239000002202 Polyethylene glycol Substances 0.000 description 4
• 125000004429 atom Chemical group 0.000 description 4
• 230000008901 benefit Effects 0.000 description 4
• 230000017531 blood circulation Effects 0.000 description 4
• UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 4
• 201000011510 cancer Diseases 0.000 description 4
• 238000006243 chemical reaction Methods 0.000 description 4
• 239000003085 diluting agent Substances 0.000 description 4
• 238000010494 dissociation reaction Methods 0.000 description 4
• 230000005593 dissociations Effects 0.000 description 4
• 239000003814 drug Substances 0.000 description 4
• 239000012216 imaging agent Substances 0.000 description 4
• 239000000463 material Substances 0.000 description 4
• 238000005259 measurement Methods 0.000 description 4
• 210000000056 organ Anatomy 0.000 description 4
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 4
• 238000000746 purification Methods 0.000 description 4
• 230000000699 topical effect Effects 0.000 description 4
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
• 150000001408 amides Chemical class 0.000 description 3
• 238000002583 angiography Methods 0.000 description 3
• 210000003423 ankle Anatomy 0.000 description 3
• 230000037396 body weight Effects 0.000 description 3
• 210000004556 brain Anatomy 0.000 description 3
• 239000000872 buffer Substances 0.000 description 3
• 125000003636 chemical group Chemical group 0.000 description 3
• 238000004587 chromatography analysis Methods 0.000 description 3
• 235000014113 dietary fatty acids Nutrition 0.000 description 3
• 239000002270 dispersing agent Substances 0.000 description 3
• 235000019439 ethyl acetate Nutrition 0.000 description 3
• 239000000194 fatty acid Substances 0.000 description 3
• 229930195729 fatty acid Natural products 0.000 description 3
• 150000004665 fatty acids Chemical class 0.000 description 3
• 238000001914 filtration Methods 0.000 description 3
• 230000006870 function Effects 0.000 description 3
• 238000001727 in vivo Methods 0.000 description 3
• 230000003993 interaction Effects 0.000 description 3
• 210000003734 kidney Anatomy 0.000 description 3
• 230000003902 lesion Effects 0.000 description 3
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 3
• 231100000252 nontoxic Toxicity 0.000 description 3
• 230000003000 nontoxic effect Effects 0.000 description 3
• HFYZWASYNRTDIO-UHFFFAOYSA-N octoxy dihydrogen phosphate Chemical compound CCCCCCCCOOP(O)(O)=O HFYZWASYNRTDIO-UHFFFAOYSA-N 0.000 description 3
• 235000019271 petrolatum Nutrition 0.000 description 3
• 238000012552 review Methods 0.000 description 3
• 239000000741 silica gel Substances 0.000 description 3
• 229910002027 silica gel Inorganic materials 0.000 description 3
• 229960001866 silicon dioxide Drugs 0.000 description 3
• 231100000331 toxic Toxicity 0.000 description 3
• 230000002588 toxic effect Effects 0.000 description 3
• PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
• VMSLCPKYRPDHLN-UHFFFAOYSA-N (R)-Humulone Chemical compound CC(C)CC(=O)C1=C(O)C(CC=C(C)C)=C(O)C(O)(CC=C(C)C)C1=O VMSLCPKYRPDHLN-UHFFFAOYSA-N 0.000 description 2
• KBPLFHHGFOOTCA-UHFFFAOYSA-N 1-Octanol Chemical compound CCCCCCCCO KBPLFHHGFOOTCA-UHFFFAOYSA-N 0.000 description 2
• KJUGUADJHNHALS-UHFFFAOYSA-N 1H-tetrazole Chemical compound C=1N=NNN=1 KJUGUADJHNHALS-UHFFFAOYSA-N 0.000 description 2
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical group CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
• 102000009027 Albumins Human genes 0.000 description 2
• 108010088751 Albumins Proteins 0.000 description 2
• KXDHJXZQYSOELW-UHFFFAOYSA-N Carbamic acid Chemical compound NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 2
• 229920002261 Corn starch Polymers 0.000 description 2
• PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 2
• 102000006395 Globulins Human genes 0.000 description 2
• 108010044091 Globulins Proteins 0.000 description 2
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
• 102000003886 Glycoproteins Human genes 0.000 description 2
• 108090000288 Glycoproteins Proteins 0.000 description 2
• 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 2
• 102000004895 Lipoproteins Human genes 0.000 description 2
• 108090001030 Lipoproteins Proteins 0.000 description 2
• 239000004472 Lysine Substances 0.000 description 2
• 241000124008 Mammalia Species 0.000 description 2
• QPCDCPDFJACHGM-UHFFFAOYSA-N N,N-bis{2-[bis(carboxymethyl)amino]ethyl}glycine Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(=O)O)CCN(CC(O)=O)CC(O)=O QPCDCPDFJACHGM-UHFFFAOYSA-N 0.000 description 2
• 241000283973 Oryctolagus cuniculus Species 0.000 description 2
• 239000004264 Petrolatum Substances 0.000 description 2
• HEMHJVSKTPXQMS-DYCDLGHISA-M Sodium hydroxide-d Chemical compound [Na+].[2H][O-] HEMHJVSKTPXQMS-DYCDLGHISA-M 0.000 description 2
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
• DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 2
• 239000007900 aqueous suspension Substances 0.000 description 2
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
• 239000002585 base Substances 0.000 description 2
• 235000019445 benzyl alcohol Nutrition 0.000 description 2
• 210000000941 bile Anatomy 0.000 description 2
• 239000000090 biomarker Substances 0.000 description 2
• 229910000085 borane Inorganic materials 0.000 description 2
• 150000001649 bromium compounds Chemical class 0.000 description 2
• 239000002775 capsule Substances 0.000 description 2
• 229910052799 carbon Inorganic materials 0.000 description 2
• 230000015556 catabolic process Effects 0.000 description 2
• 239000003153 chemical reaction reagent Substances 0.000 description 2
• 238000004440 column chromatography Methods 0.000 description 2
• 229940039231 contrast media Drugs 0.000 description 2
• 239000008120 corn starch Substances 0.000 description 2
• 230000008878 coupling Effects 0.000 description 2
• 238000010168 coupling process Methods 0.000 description 2
• 238000005859 coupling reaction Methods 0.000 description 2
• 239000013078 crystal Substances 0.000 description 2
• 150000005690 diesters Chemical class 0.000 description 2
• 235000005911 diet Nutrition 0.000 description 2
• 230000037213 diet Effects 0.000 description 2
• ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
• 229940079593 drug Drugs 0.000 description 2
• 230000000694 effects Effects 0.000 description 2
• 230000002708 enhancing effect Effects 0.000 description 2
• CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 2
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
• 235000019000 fluorine Nutrition 0.000 description 2
• 210000001035 gastrointestinal tract Anatomy 0.000 description 2
• 125000005456 glyceride group Chemical group 0.000 description 2
• 210000004013 groin Anatomy 0.000 description 2
• 229910052736 halogen Inorganic materials 0.000 description 2
• 150000002367 halogens Chemical class 0.000 description 2
• 210000002216 heart Anatomy 0.000 description 2
• 238000010438 heat treatment Methods 0.000 description 2
• 238000011065 in-situ storage Methods 0.000 description 2
• 230000002452 interceptive effect Effects 0.000 description 2
• 150000004694 iodide salts Chemical class 0.000 description 2
• 239000008101 lactose Substances 0.000 description 2
• 239000007788 liquid Substances 0.000 description 2
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
• 230000004060 metabolic process Effects 0.000 description 2
• XELZGAJCZANUQH-UHFFFAOYSA-N methyl 1-acetylthieno[3,2-c]pyrazole-5-carboxylate Chemical compound CC(=O)N1N=CC2=C1C=C(C(=O)OC)S2 XELZGAJCZANUQH-UHFFFAOYSA-N 0.000 description 2
• 239000002480 mineral oil Substances 0.000 description 2
• 235000010446 mineral oil Nutrition 0.000 description 2
• 125000000896 monocarboxylic acid group Chemical group 0.000 description 2
• 230000007935 neutral effect Effects 0.000 description 2
• 125000004433 nitrogen atom Chemical group N* 0.000 description 2
• 239000000346 nonvolatile oil Substances 0.000 description 2
• 125000002347 octyl 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])[H] 0.000 description 2
• 239000012044 organic layer Substances 0.000 description 2
• 239000001301 oxygen Substances 0.000 description 2
• 238000005192 partition Methods 0.000 description 2
• 230000010412 perfusion Effects 0.000 description 2
• 229940066842 petrolatum Drugs 0.000 description 2
• 150000004713 phosphodiesters Chemical class 0.000 description 2
• 150000003013 phosphoric acid derivatives Chemical class 0.000 description 2
• 239000003755 preservative agent Substances 0.000 description 2
• 230000002035 prolonged effect Effects 0.000 description 2
• 230000009467 reduction Effects 0.000 description 2
• 230000000717 retained effect Effects 0.000 description 2
• 229920006395 saturated elastomer Polymers 0.000 description 2
• 238000000926 separation method Methods 0.000 description 2
• 210000002966 serum Anatomy 0.000 description 2
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
• 230000003637 steroidlike Effects 0.000 description 2
• 235000001508 sulfur Nutrition 0.000 description 2
• 239000000375 suspending agent Substances 0.000 description 2
• 238000003786 synthesis reaction Methods 0.000 description 2
• 239000003826 tablet Substances 0.000 description 2
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
• 238000004809 thin layer chromatography Methods 0.000 description 2
• 229910021654 trace metal Inorganic materials 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
• 238000012546 transfer Methods 0.000 description 2
• 210000003462 vein Anatomy 0.000 description 2
• 150000003751 zinc Chemical class 0.000 description 2
• LSPHULWDVZXLIL-UHFFFAOYSA-N (+/-)-Camphoric acid Chemical compound CC1(C)C(C(O)=O)CCC1(C)C(O)=O LSPHULWDVZXLIL-UHFFFAOYSA-N 0.000 description 1
• WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
• KVFBEMVPJGNXSD-UHFFFAOYSA-N 1-(4-methoxyphenyl)pentan-1-ol Chemical compound CCCCC(O)C1=CC=C(OC)C=C1 KVFBEMVPJGNXSD-UHFFFAOYSA-N 0.000 description 1
• VFWCMGCRMGJXDK-UHFFFAOYSA-N 1-chlorobutane Chemical compound CCCCCl VFWCMGCRMGJXDK-UHFFFAOYSA-N 0.000 description 1
• VUQPJRPDRDVQMN-UHFFFAOYSA-N 1-chlorooctadecane Chemical class CCCCCCCCCCCCCCCCCCCl VUQPJRPDRDVQMN-UHFFFAOYSA-N 0.000 description 1
• IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
• WNFXODBOMMSELY-UHFFFAOYSA-N 10-Phenyl-1-decanol Chemical compound OCCCCCCCCCCC1=CC=CC=C1 WNFXODBOMMSELY-UHFFFAOYSA-N 0.000 description 1
• 238000005160 1H NMR spectroscopy Methods 0.000 description 1
• CHHHXKFHOYLYRE-UHFFFAOYSA-M 2,4-Hexadienoic acid, potassium salt (1:1), (2E,4E)- Chemical compound [K+].CC=CC=CC([O-])=O CHHHXKFHOYLYRE-UHFFFAOYSA-M 0.000 description 1
• 229940080296 2-naphthalenesulfonate Drugs 0.000 description 1
• LEACJMVNYZDSKR-UHFFFAOYSA-N 2-octyldodecan-1-ol Chemical compound CCCCCCCCCCC(CO)CCCCCCCC LEACJMVNYZDSKR-UHFFFAOYSA-N 0.000 description 1
• WMPPDTMATNBGJN-UHFFFAOYSA-N 2-phenylethylbromide Chemical class BrCCC1=CC=CC=C1 WMPPDTMATNBGJN-UHFFFAOYSA-N 0.000 description 1
• LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
• QWTBDIBOOIAZEF-UHFFFAOYSA-N 3-[chloro-[di(propan-2-yl)amino]phosphanyl]oxypropanenitrile Chemical compound CC(C)N(C(C)C)P(Cl)OCCC#N QWTBDIBOOIAZEF-UHFFFAOYSA-N 0.000 description 1
• ZRPLANDPDWYOMZ-UHFFFAOYSA-N 3-cyclopentylpropionic acid Chemical compound OC(=O)CCC1CCCC1 ZRPLANDPDWYOMZ-UHFFFAOYSA-N 0.000 description 1
• XMIIGOLPHOKFCH-UHFFFAOYSA-M 3-phenylpropionate Chemical compound [O-]C(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-M 0.000 description 1
• 238000004679 31P NMR spectroscopy Methods 0.000 description 1
• CSDQQAQKBAQLLE-UHFFFAOYSA-N 4-(4-chlorophenyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine Chemical compound C1=CC(Cl)=CC=C1C1C(C=CS2)=C2CCN1 CSDQQAQKBAQLLE-UHFFFAOYSA-N 0.000 description 1
• FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
• QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
• 108010056388 Albunex Proteins 0.000 description 1
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
• 239000004475 Arginine Substances 0.000 description 1
• FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
• FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
• 101150041968 CDC13 gene Proteins 0.000 description 1
• 101100508407 Caenorhabditis elegans mua-6 gene Proteins 0.000 description 1
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
• KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
• 229920002307 Dextran 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
• XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical class C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
• 229910052692 Dysprosium Inorganic materials 0.000 description 1
• 241000792859 Enema Species 0.000 description 1
• VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical group C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
• 239000005977 Ethylene Substances 0.000 description 1
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
• 239000004471 Glycine Substances 0.000 description 1
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
• CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
• JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
• 108010052285 Membrane Proteins Proteins 0.000 description 1
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
• ZOKXTWBITQBERF-UHFFFAOYSA-N Molybdenum Chemical compound [Mo] ZOKXTWBITQBERF-UHFFFAOYSA-N 0.000 description 1
• TZCCKCLHNUSAMQ-DUGSHLAESA-N NC(=O)C[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](Cc2ccc(F)cc2)NC(=O)[C@H](Cc3c[nH]c4ccccc34)NC(=O)Cc5cccs5)C(=O)N Chemical compound NC(=O)C[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](Cc2ccc(F)cc2)NC(=O)[C@H](Cc3c[nH]c4ccccc34)NC(=O)Cc5cccs5)C(=O)N TZCCKCLHNUSAMQ-DUGSHLAESA-N 0.000 description 1
• PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
• 240000008881 Oenanthe javanica Species 0.000 description 1
• 239000005642 Oleic acid Substances 0.000 description 1
• ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
• 241000255964 Pieridae Species 0.000 description 1
• 229920001214 Polysorbate 60 Polymers 0.000 description 1
• XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
• 102000007327 Protamines Human genes 0.000 description 1
• 108010007568 Protamines Proteins 0.000 description 1
• 101100480481 Rattus norvegicus Taar7g gene Proteins 0.000 description 1
• HVUMOYIDDBPOLL-XWVZOOPGSA-N Sorbitan monostearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O HVUMOYIDDBPOLL-XWVZOOPGSA-N 0.000 description 1
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
• ZMZDMBWJUHKJPS-UHFFFAOYSA-M Thiocyanate anion Chemical compound [S-]C#N ZMZDMBWJUHKJPS-UHFFFAOYSA-M 0.000 description 1
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 1
• 239000007983 Tris buffer Substances 0.000 description 1
• 229940124532 absorption promoter Drugs 0.000 description 1
• 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 1
• MPRWIVBRDAXEAF-UHFFFAOYSA-N acetyloxy ethaneperoxoate Chemical group CC(=O)OOOC(C)=O MPRWIVBRDAXEAF-UHFFFAOYSA-N 0.000 description 1
• 239000002253 acid Substances 0.000 description 1
• WNLRTRBMVRJNCN-UHFFFAOYSA-L adipate(2-) Chemical compound [O-]C(=O)CCCCC([O-])=O WNLRTRBMVRJNCN-UHFFFAOYSA-L 0.000 description 1
• 229940072056 alginate Drugs 0.000 description 1
• 235000010443 alginic acid Nutrition 0.000 description 1
• 229920000615 alginic acid Polymers 0.000 description 1
• 229910052783 alkali metal Inorganic materials 0.000 description 1
• 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
• 150000001350 alkyl halides Chemical class 0.000 description 1
• AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 1
• PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
• CEGOLXSVJUTHNZ-UHFFFAOYSA-K aluminium tristearate Chemical compound [Al+3].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CEGOLXSVJUTHNZ-UHFFFAOYSA-K 0.000 description 1
• 229940063655 aluminum stearate Drugs 0.000 description 1
• 229940024606 amino acid Drugs 0.000 description 1
• 150000001413 amino acids Chemical class 0.000 description 1
• 238000004458 analytical method Methods 0.000 description 1
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
• 229940009098 aspartate Drugs 0.000 description 1
• 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 1
• CBHOOMGKXCMKIR-UHFFFAOYSA-N azane;methanol Chemical compound N.OC CBHOOMGKXCMKIR-UHFFFAOYSA-N 0.000 description 1
• 235000013871 bee wax Nutrition 0.000 description 1
• 239000012166 beeswax Substances 0.000 description 1
• 230000009286 beneficial effect Effects 0.000 description 1
• 229940077388 benzenesulfonate Drugs 0.000 description 1
• SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
• 229940050390 benzoate Drugs 0.000 description 1
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
• XMIIGOLPHOKFCH-UHFFFAOYSA-N beta-phenylpropanoic acid Natural products OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 1
• 230000008827 biological function Effects 0.000 description 1
• 238000012984 biological imaging Methods 0.000 description 1
• 230000031018 biological processes and functions Effects 0.000 description 1
• 235000010290 biphenyl Nutrition 0.000 description 1
• 239000004305 biphenyl Substances 0.000 description 1
• 125000006267 biphenyl group Chemical group 0.000 description 1
• 229910052797 bismuth Inorganic materials 0.000 description 1
• 230000008499 blood brain barrier function Effects 0.000 description 1
• 230000036770 blood supply Effects 0.000 description 1
• 210000001218 blood-brain barrier Anatomy 0.000 description 1
• 210000001185 bone marrow Anatomy 0.000 description 1
• 239000012267 brine Substances 0.000 description 1
• KDPAWGWELVVRCH-UHFFFAOYSA-M bromoacetate Chemical compound [O-]C(=O)CBr KDPAWGWELVVRCH-UHFFFAOYSA-M 0.000 description 1
• 239000006227 byproduct Substances 0.000 description 1
• MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
• 239000001768 carboxy methyl cellulose Substances 0.000 description 1
• 150000007942 carboxylates Chemical class 0.000 description 1
• 239000004359 castor oil Substances 0.000 description 1
• 235000019438 castor oil Nutrition 0.000 description 1
• 230000004700 cellular uptake Effects 0.000 description 1
• 239000001913 cellulose Substances 0.000 description 1
• 229920002678 cellulose Polymers 0.000 description 1
• 235000010980 cellulose Nutrition 0.000 description 1
• 229940081733 cetearyl alcohol Drugs 0.000 description 1
• 230000005591 charge neutralization Effects 0.000 description 1
• 230000004087 circulation Effects 0.000 description 1
• 230000010405 clearance mechanism Effects 0.000 description 1
• 239000011248 coating agent Substances 0.000 description 1
• 238000000576 coating method Methods 0.000 description 1
• 229940110456 cocoa butter Drugs 0.000 description 1
• 235000019868 cocoa butter Nutrition 0.000 description 1
• 230000001149 cognitive effect Effects 0.000 description 1
• 239000008119 colloidal silica Substances 0.000 description 1
• 239000003086 colorant Substances 0.000 description 1
• 239000012141 concentrate Substances 0.000 description 1
• 239000000470 constituent Substances 0.000 description 1
• 238000001816 cooling Methods 0.000 description 1
• 229910052802 copper Inorganic materials 0.000 description 1
• 239000006071 cream Substances 0.000 description 1
• 239000010779 crude oil Substances 0.000 description 1
• 230000001086 cytosolic effect Effects 0.000 description 1
• 230000003247 decreasing effect Effects 0.000 description 1
• 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 238000011161 development Methods 0.000 description 1
• 238000003745 diagnosis Methods 0.000 description 1
• 150000008050 dialkyl sulfates Chemical class 0.000 description 1
• 238000000502 dialysis Methods 0.000 description 1
• 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
• IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 1
• GXGAKHNRMVGRPK-UHFFFAOYSA-N dimagnesium;dioxido-bis[[oxido(oxo)silyl]oxy]silane Chemical compound [Mg+2].[Mg+2].[O-][Si](=O)O[Si]([O-])([O-])O[Si]([O-])=O GXGAKHNRMVGRPK-UHFFFAOYSA-N 0.000 description 1
• 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
• GAFRWLVTHPVQGK-UHFFFAOYSA-N dipentyl sulfate Chemical class CCCCCOS(=O)(=O)OCCCCC GAFRWLVTHPVQGK-UHFFFAOYSA-N 0.000 description 1
• ZMZIEZHJTIVGGP-UHFFFAOYSA-N diphenylmethanone;potassium Chemical group [K].C=1C=CC=CC=1C(=O)C1=CC=CC=C1 ZMZIEZHJTIVGGP-UHFFFAOYSA-N 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
• 229910000396 dipotassium phosphate Inorganic materials 0.000 description 1
• 235000019797 dipotassium phosphate Nutrition 0.000 description 1
• BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
• 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical compound CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 1
• 229940043264 dodecyl sulfate Drugs 0.000 description 1
• 239000002552 dosage form Substances 0.000 description 1
• 239000000890 drug combination Substances 0.000 description 1
• 239000003792 electrolyte Substances 0.000 description 1
• 230000005670 electromagnetic radiation Effects 0.000 description 1
• 230000008030 elimination Effects 0.000 description 1
• 238000003379 elimination reaction Methods 0.000 description 1
• 239000003995 emulsifying agent Substances 0.000 description 1
• 230000001804 emulsifying effect Effects 0.000 description 1
• 239000008387 emulsifying waxe Substances 0.000 description 1
• 239000007920 enema Substances 0.000 description 1
• 229940095399 enema Drugs 0.000 description 1
• BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
• 238000001704 evaporation Methods 0.000 description 1
• 230000008020 evaporation Effects 0.000 description 1
• 210000001723 extracellular space Anatomy 0.000 description 1
• 235000019197 fats Nutrition 0.000 description 1
• 210000003608 fece Anatomy 0.000 description 1
• 239000000796 flavoring agent Substances 0.000 description 1
• 239000011737 fluorine Substances 0.000 description 1
• 229910052731 fluorine Inorganic materials 0.000 description 1
• 125000001153 fluoro group Chemical group F* 0.000 description 1
• 229910052733 gallium Inorganic materials 0.000 description 1
• 230000001434 glomerular Effects 0.000 description 1
• 230000024924 glomerular filtration Effects 0.000 description 1
• 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 1
• 229910052737 gold Inorganic materials 0.000 description 1
• 150000004820 halides Chemical class 0.000 description 1
• 230000036541 health Effects 0.000 description 1
• 229910001385 heavy metal Inorganic materials 0.000 description 1
• MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 1
• 125000005842 heteroatom Chemical group 0.000 description 1
• FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
• BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical compound [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 description 1
• 239000001257 hydrogen Substances 0.000 description 1
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
• ZMZDMBWJUHKJPS-UHFFFAOYSA-N hydrogen thiocyanate Natural products SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
• 229920001477 hydrophilic polymer Polymers 0.000 description 1
• 230000005661 hydrophobic surface Effects 0.000 description 1
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
• 230000006872 improvement Effects 0.000 description 1
• 238000010348 incorporation Methods 0.000 description 1
• 229910052738 indium Inorganic materials 0.000 description 1
• 238000001802 infusion Methods 0.000 description 1
• 239000004615 ingredient Substances 0.000 description 1
• 229940102223 injectable solution Drugs 0.000 description 1
• 229940102213 injectable suspension Drugs 0.000 description 1
• 238000003780 insertion Methods 0.000 description 1
• 230000037431 insertion Effects 0.000 description 1
• 238000007917 intracranial administration Methods 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 238000007919 intrasynovial administration Methods 0.000 description 1
• 238000007913 intrathecal administration Methods 0.000 description 1
• 238000001990 intravenous administration Methods 0.000 description 1
• 238000002075 inversion recovery Methods 0.000 description 1
• QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
• 239000010410 layer Substances 0.000 description 1
• 229910052745 lead Inorganic materials 0.000 description 1
• 239000000787 lecithin Substances 0.000 description 1
• 235000010445 lecithin Nutrition 0.000 description 1
• 229940067606 lecithin Drugs 0.000 description 1
• 210000002414 leg Anatomy 0.000 description 1
• 231100001231 less toxic Toxicity 0.000 description 1
• 150000002632 lipids Chemical class 0.000 description 1
• 210000004185 liver Anatomy 0.000 description 1
• 210000005229 liver cell Anatomy 0.000 description 1
• 208000019423 liver disease Diseases 0.000 description 1
• 230000007774 longterm Effects 0.000 description 1
• 239000006210 lotion Substances 0.000 description 1
• 239000000314 lubricant Substances 0.000 description 1
• 210000004072 lung Anatomy 0.000 description 1
• 229920002521 macromolecule Polymers 0.000 description 1
• 239000011777 magnesium Substances 0.000 description 1
• 229910052749 magnesium Inorganic materials 0.000 description 1
• 239000000391 magnesium silicate Substances 0.000 description 1
• 235000019359 magnesium stearate Nutrition 0.000 description 1
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
• 229910000386 magnesium trisilicate Inorganic materials 0.000 description 1
• 229940099273 magnesium trisilicate Drugs 0.000 description 1
• 235000019793 magnesium trisilicate 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
• 238000004519 manufacturing process Methods 0.000 description 1
• HYYBABOKPJLUIN-UHFFFAOYSA-N mefenamic acid Chemical compound CC1=CC=CC(NC=2C(=CC=CC=2)C(O)=O)=C1C HYYBABOKPJLUIN-UHFFFAOYSA-N 0.000 description 1
• 230000002503 metabolic effect Effects 0.000 description 1
• 239000002207 metabolite Substances 0.000 description 1
• GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 1
• 150000004702 methyl esters Chemical class 0.000 description 1
• 229940042472 mineral oil Drugs 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• 239000011733 molybdenum Substances 0.000 description 1
• 238000012544 monitoring process Methods 0.000 description 1
• 125000001421 myristyl 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])[H] 0.000 description 1
• RDIVLNOKDXZMJS-UHFFFAOYSA-N n'-(2-aminoethyl)ethane-1,2-diamine;trihydrochloride Chemical compound Cl.Cl.Cl.NCCNCCN RDIVLNOKDXZMJS-UHFFFAOYSA-N 0.000 description 1
• KVBGVZZKJNLNJU-UHFFFAOYSA-M naphthalene-2-sulfonate Chemical compound C1=CC=CC2=CC(S(=O)(=O)[O-])=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-M 0.000 description 1
• 125000004923 naphthylmethyl group Chemical group C1(=CC=CC2=CC=CC=C12)C* 0.000 description 1
• 239000007922 nasal spray Substances 0.000 description 1
• 235000001968 nicotinic acid Nutrition 0.000 description 1
• 239000011664 nicotinic acid Substances 0.000 description 1
• 231100000344 non-irritating Toxicity 0.000 description 1
• 238000012633 nuclear imaging Methods 0.000 description 1
• 238000001208 nuclear magnetic resonance pulse sequence Methods 0.000 description 1
• 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
• GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 1
• 239000002674 ointment Substances 0.000 description 1
• ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
• 239000004006 olive oil Substances 0.000 description 1
• 235000008390 olive oil Nutrition 0.000 description 1
• 230000014207 opsonization Effects 0.000 description 1
• 150000007524 organic acids Chemical class 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 150000007530 organic bases Chemical class 0.000 description 1
• 125000006353 oxyethylene group Chemical group 0.000 description 1
• JRKICGRDRMAZLK-UHFFFAOYSA-L peroxydisulfate Chemical compound [O-]S(=O)(=O)OOS([O-])(=O)=O JRKICGRDRMAZLK-UHFFFAOYSA-L 0.000 description 1
• 239000000546 pharmaceutical excipient Substances 0.000 description 1
• ACVYVLVWPXVTIT-UHFFFAOYSA-M phosphinate Chemical compound [O-][PH2]=O ACVYVLVWPXVTIT-UHFFFAOYSA-M 0.000 description 1
• UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 1
• PTMHPRAIXMAOOB-UHFFFAOYSA-L phosphoramidate Chemical compound NP([O-])([O-])=O PTMHPRAIXMAOOB-UHFFFAOYSA-L 0.000 description 1
• 230000000704 physical effect Effects 0.000 description 1
• 229940075930 picrate Drugs 0.000 description 1
• OXNIZHLAWKMVMX-UHFFFAOYSA-M picrate anion Chemical compound [O-]C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-M 0.000 description 1
• 229950010765 pivalate Drugs 0.000 description 1
• IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
• 229920000058 polyacrylate Polymers 0.000 description 1
• 239000001818 polyoxyethylene sorbitan monostearate Substances 0.000 description 1
• 235000010989 polyoxyethylene sorbitan monostearate Nutrition 0.000 description 1
• 229920001451 polypropylene glycol Polymers 0.000 description 1
• 229940113124 polysorbate 60 Drugs 0.000 description 1
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
• 159000000001 potassium salts Chemical class 0.000 description 1
• 235000010241 potassium sorbate Nutrition 0.000 description 1
• 239000004302 potassium sorbate Substances 0.000 description 1
• 229940069338 potassium sorbate Drugs 0.000 description 1
• 239000002244 precipitate Substances 0.000 description 1
• 230000002335 preservative effect Effects 0.000 description 1
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 235000013772 propylene glycol Nutrition 0.000 description 1
• 229950008679 protamine sulfate Drugs 0.000 description 1
• 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
• 230000005855 radiation Effects 0.000 description 1
• 239000000700 radioactive tracer Substances 0.000 description 1
• 238000001959 radiotherapy Methods 0.000 description 1
• 239000011541 reaction mixture Substances 0.000 description 1
• 229940100618 rectal suppository Drugs 0.000 description 1
• 239000006215 rectal suppository Substances 0.000 description 1
• 210000000664 rectum Anatomy 0.000 description 1
• 230000002441 reversible effect Effects 0.000 description 1
• 229910052702 rhenium Inorganic materials 0.000 description 1
• 238000005070 sampling Methods 0.000 description 1
• 230000035945 sensitivity Effects 0.000 description 1
• 229910052709 silver Inorganic materials 0.000 description 1
• AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
• 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
• 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
• 159000000000 sodium salts Chemical class 0.000 description 1
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
• 239000012265 solid product Substances 0.000 description 1
• 230000003381 solubilizing effect Effects 0.000 description 1
• 235000010199 sorbic acid Nutrition 0.000 description 1
• 239000004334 sorbic acid Substances 0.000 description 1
• 229940075582 sorbic acid Drugs 0.000 description 1
• 239000001587 sorbitan monostearate Substances 0.000 description 1
• 235000011076 sorbitan monostearate Nutrition 0.000 description 1
• 229940035048 sorbitan monostearate Drugs 0.000 description 1
• 238000001228 spectrum Methods 0.000 description 1
• 210000000952 spleen Anatomy 0.000 description 1
• 239000007921 spray Substances 0.000 description 1
• 238000005556 structure-activity relationship Methods 0.000 description 1
• 238000007920 subcutaneous administration 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
• 125000000565 sulfonamide group Chemical group 0.000 description 1
• 239000011593 sulfur Chemical group 0.000 description 1
• 125000004434 sulfur atom Chemical group 0.000 description 1
• 239000000829 suppository Substances 0.000 description 1
• 239000003765 sweetening agent Substances 0.000 description 1
• 230000002195 synergetic effect Effects 0.000 description 1
• 229940095064 tartrate Drugs 0.000 description 1
• CIHOLLKRGTVIJN-UHFFFAOYSA-N tert‐butyl hydroperoxide Chemical compound CC(C)(C)OO CIHOLLKRGTVIJN-UHFFFAOYSA-N 0.000 description 1
• MHXBHWLGRWOABW-UHFFFAOYSA-N tetradecyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCCCCCCCCCCCCCC MHXBHWLGRWOABW-UHFFFAOYSA-N 0.000 description 1
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
• 239000012049 topical pharmaceutical composition Substances 0.000 description 1
• PNYPSKHTTCTAMD-UHFFFAOYSA-K trichlorogadolinium;hexahydrate Chemical compound O.O.O.O.O.O.[Cl-].[Cl-].[Cl-].[Gd+3] PNYPSKHTTCTAMD-UHFFFAOYSA-K 0.000 description 1
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
• WFKWXMTUELFFGS-UHFFFAOYSA-N tungsten Chemical compound [W] WFKWXMTUELFFGS-UHFFFAOYSA-N 0.000 description 1
• 239000010937 tungsten Substances 0.000 description 1
• 238000000108 ultra-filtration Methods 0.000 description 1
• ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical compound CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
• 235000013311 vegetables Nutrition 0.000 description 1
• 239000003643 water by type Substances 0.000 description 1
• 239000001993 wax Substances 0.000 description 1
• 239000000080 wetting agent Substances 0.000 description 1
• 239000003871 white petrolatum Substances 0.000 description 1
• 210000002268 wool Anatomy 0.000 description 1

Cited By (1)