AU2012329274B2 - Caffeinated compounds and compositions for treatment of amyloid diseases and synucleinopathies - Google Patents

Info

Publication number

AU2012329274B2

AU2012329274B2 AU2012329274A AU2012329274A AU2012329274B2 AU 2012329274 B2 AU2012329274 B2 AU 2012329274B2 AU 2012329274 A AU2012329274 A AU 2012329274A AU 2012329274 A AU2012329274 A AU 2012329274A AU 2012329274 B2 AU2012329274 B2 AU 2012329274B2

Authority

AU

Australia

Prior art keywords

disease

amyloid

compounds

compound

synuclein

Prior art date

2011-10-27

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.)

Ceased

Links

• Espacenet
• Global Dossier
• Discuss

• 150000001875 compounds Chemical class 0.000 title claims abstract description 273
• 206010002022 amyloidosis Diseases 0.000 title claims abstract description 39
• 208000032859 Synucleinopathies Diseases 0.000 title claims abstract description 13
• 238000011282 treatment Methods 0.000 title abstract description 34
• 239000000203 mixture Substances 0.000 title description 62
• 208000018737 Parkinson disease Diseases 0.000 claims abstract description 52
• 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 51
• 102000013455 Amyloid beta-Peptides Human genes 0.000 claims abstract description 29
• 108010090849 Amyloid beta-Peptides Proteins 0.000 claims abstract description 29
• 150000003839 salts Chemical class 0.000 claims abstract description 24
• 102000003802 alpha-Synuclein Human genes 0.000 claims description 83
• 108090000185 alpha-Synuclein Proteins 0.000 claims description 83
• 238000000034 method Methods 0.000 claims description 51
• 230000015572 biosynthetic process Effects 0.000 claims description 42
• 238000009825 accumulation Methods 0.000 claims description 29
• 230000035508 accumulation Effects 0.000 claims description 26
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 21
• 230000002688 persistence Effects 0.000 claims description 20
• 230000008021 deposition Effects 0.000 claims description 19
• 210000004558 lewy body Anatomy 0.000 claims description 17
• 201000002832 Lewy body dementia Diseases 0.000 claims description 15
• 239000008194 pharmaceutical composition Substances 0.000 claims description 14
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 13
• 230000009885 systemic effect Effects 0.000 claims description 12
• 208000001089 Multiple system atrophy Diseases 0.000 claims description 9
• 239000001257 hydrogen Substances 0.000 claims description 9
• 229910052739 hydrogen Inorganic materials 0.000 claims description 9
• 206010067889 Dementia with Lewy bodies Diseases 0.000 claims description 8
• 208000009829 Lewy Body Disease Diseases 0.000 claims description 7
• 238000004519 manufacturing process Methods 0.000 claims description 7
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
• 208000005145 Cerebral amyloid angiopathy Diseases 0.000 claims description 6
• 201000010374 Down Syndrome Diseases 0.000 claims description 6
• 206010044688 Trisomy 21 Diseases 0.000 claims description 6
• 208000023769 AA amyloidosis Diseases 0.000 claims description 5
• 241000124008 Mammalia Species 0.000 claims description 5
• 208000027089 Parkinsonian disease Diseases 0.000 claims description 5
• 206010034010 Parkinsonism Diseases 0.000 claims description 5
• 230000002490 cerebral effect Effects 0.000 claims description 5
• 208000018282 ACys amyloidosis Diseases 0.000 claims description 4
• 206010059245 Angiopathy Diseases 0.000 claims description 4
• 206010012289 Dementia Diseases 0.000 claims description 4
• 208000007487 Familial Cerebral Amyloid Angiopathy Diseases 0.000 claims description 4
• 208000032849 Hereditary cerebral hemorrhage with amyloidosis Diseases 0.000 claims description 4
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
• 239000005022 packaging material Substances 0.000 claims description 4
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
• 208000035474 group of disease Diseases 0.000 claims description 2
• 206010012601 diabetes mellitus Diseases 0.000 claims 1
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 69
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 49
• 238000012360 testing method Methods 0.000 description 48
• -1 cyano, methyl Chemical group 0.000 description 42
• JADVWWSKYZXRGX-UHFFFAOYSA-M thioflavine T Chemical compound [Cl-].C1=CC(N(C)C)=CC=C1C1=[N+](C)C2=CC=C(C)C=C2S1 JADVWWSKYZXRGX-UHFFFAOYSA-M 0.000 description 41
• 210000004556 brain Anatomy 0.000 description 40
• 201000010099 disease Diseases 0.000 description 39
• 210000004027 cell Anatomy 0.000 description 37
• 238000005755 formation reaction Methods 0.000 description 34
• 239000000243 solution Substances 0.000 description 32
• 229940080817 rotenone Drugs 0.000 description 31
• JUVIOZPCNVVQFO-UHFFFAOYSA-N rotenone Natural products O1C2=C3CC(C(C)=C)OC3=CC=C2C(=O)C2C1COC1=C2C=C(OC)C(OC)=C1 JUVIOZPCNVVQFO-UHFFFAOYSA-N 0.000 description 31
• IQFVPQOLBLOTPF-HKXUKFGYSA-L congo red Chemical compound [Na+].[Na+].C1=CC=CC2=C(N)C(/N=N/C3=CC=C(C=C3)C3=CC=C(C=C3)/N=N/C3=C(C4=CC=CC=C4C(=C3)S([O-])(=O)=O)N)=CC(S([O-])(=O)=O)=C21 IQFVPQOLBLOTPF-HKXUKFGYSA-L 0.000 description 30
• 230000005764 inhibitory process Effects 0.000 description 28
• 238000013268 sustained release Methods 0.000 description 28
• 239000012730 sustained-release form Substances 0.000 description 28
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 28
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 27
• 239000003814 drug Substances 0.000 description 24
• 238000004220 aggregation Methods 0.000 description 23
• 230000002829 reductive effect Effects 0.000 description 23
• 230000002776 aggregation Effects 0.000 description 22
• 108090000623 proteins and genes Proteins 0.000 description 22
• 102000004169 proteins and genes Human genes 0.000 description 20
• 238000000151 deposition Methods 0.000 description 19
• 238000011534 incubation Methods 0.000 description 18
• 239000002953 phosphate buffered saline Substances 0.000 description 18
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 17
• 229940079593 drug Drugs 0.000 description 17
• 238000005558 fluorometry Methods 0.000 description 17
• 238000009472 formulation Methods 0.000 description 17
• 239000011541 reaction mixture Substances 0.000 description 17
• 230000000694 effects Effects 0.000 description 16
• 229920000642 polymer Polymers 0.000 description 16
• 238000003556 assay Methods 0.000 description 15
• 238000006243 chemical reaction Methods 0.000 description 15
• 238000000576 coating method Methods 0.000 description 15
• 239000002904 solvent Substances 0.000 description 15
• 230000003941 amyloidogenesis Effects 0.000 description 14
• RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 14
• 239000002502 liposome Substances 0.000 description 14
• 239000000047 product Substances 0.000 description 14
• 239000000725 suspension Substances 0.000 description 13
• LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical compound O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 description 12
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 12
• 239000011248 coating agent Substances 0.000 description 12
• 239000007787 solid Substances 0.000 description 12
• 230000001225 therapeutic effect Effects 0.000 description 12
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
• 239000000741 silica gel Substances 0.000 description 11
• 229910002027 silica gel Inorganic materials 0.000 description 11
• 239000004480 active ingredient Substances 0.000 description 10
• 239000003795 chemical substances by application Substances 0.000 description 10
• 208000035475 disorder Diseases 0.000 description 10
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
• 238000001228 spectrum Methods 0.000 description 10
• 239000000126 substance Substances 0.000 description 10
• 102000036770 Islet Amyloid Polypeptide Human genes 0.000 description 9
• 108010041872 Islet Amyloid Polypeptide Proteins 0.000 description 9
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
• 108050006783 Synuclein Proteins 0.000 description 9
• 238000007792 addition Methods 0.000 description 9
• 239000003153 chemical reaction reagent Substances 0.000 description 9
• 150000002148 esters Chemical class 0.000 description 9
• 230000035772 mutation Effects 0.000 description 9
• 239000003826 tablet Substances 0.000 description 9
• 208000037259 Amyloid Plaque Diseases 0.000 description 8
• 102000019355 Synuclein Human genes 0.000 description 8
• 239000000872 buffer Substances 0.000 description 8
• 238000002983 circular dichroism Methods 0.000 description 8
• 239000003921 oil Substances 0.000 description 8
• 235000019198 oils Nutrition 0.000 description 8
• 210000000056 organ Anatomy 0.000 description 8
• 239000004014 plasticizer Substances 0.000 description 8
• 229920001223 polyethylene glycol Polymers 0.000 description 8
• 239000000843 powder Substances 0.000 description 8
• 238000003786 synthesis reaction Methods 0.000 description 8
• 210000001519 tissue Anatomy 0.000 description 8
• 208000001072 type 2 diabetes mellitus Diseases 0.000 description 8
• 239000003981 vehicle Substances 0.000 description 8
• 229940075420 xanthine Drugs 0.000 description 8
• LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 7
• 229960001948 caffeine Drugs 0.000 description 7
• VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 7
• LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 7
• 235000019441 ethanol Nutrition 0.000 description 7
• 238000000338 in vitro Methods 0.000 description 7
• 239000007788 liquid Substances 0.000 description 7
• 231100000252 nontoxic Toxicity 0.000 description 7
• 230000003000 nontoxic effect Effects 0.000 description 7
• 239000008363 phosphate buffer Substances 0.000 description 7
• 239000013641 positive control Substances 0.000 description 7
• 230000003389 potentiating effect Effects 0.000 description 7
• 239000000651 prodrug Substances 0.000 description 7
• 229940002612 prodrug Drugs 0.000 description 7
• 102200036626 rs104893877 Human genes 0.000 description 7
• 208000024891 symptom Diseases 0.000 description 7
• 206010002023 Amyloidoses Diseases 0.000 description 6
• CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 6
• 230000007082 Aβ accumulation Effects 0.000 description 6
• VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 6
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
• 241001465754 Metazoa Species 0.000 description 6
• 108010071690 Prealbumin Proteins 0.000 description 6
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
• QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
• 229940024606 amino acid Drugs 0.000 description 6
• 239000007900 aqueous suspension Substances 0.000 description 6
• SESFRYSPDFLNCH-UHFFFAOYSA-N benzyl benzoate Chemical compound C=1C=CC=CC=1C(=O)OCC1=CC=CC=C1 SESFRYSPDFLNCH-UHFFFAOYSA-N 0.000 description 6
• 235000014113 dietary fatty acids Nutrition 0.000 description 6
• 238000004090 dissolution Methods 0.000 description 6
• 231100000673 dose–response relationship Toxicity 0.000 description 6
• 239000000194 fatty acid Substances 0.000 description 6
• 229930195729 fatty acid Natural products 0.000 description 6
• 239000000796 flavoring agent Substances 0.000 description 6
• 239000003112 inhibitor Substances 0.000 description 6
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
• 239000000463 material Substances 0.000 description 6
• 238000002360 preparation method Methods 0.000 description 6
• 230000009467 reduction Effects 0.000 description 6
• 238000010186 staining Methods 0.000 description 6
• 239000000375 suspending agent Substances 0.000 description 6
• 239000000080 wetting agent Substances 0.000 description 6
• 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 5
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 5
• 241000699670 Mus sp. Species 0.000 description 5
• 239000002202 Polyethylene glycol Substances 0.000 description 5
• 238000010521 absorption reaction Methods 0.000 description 5
• 235000010443 alginic acid Nutrition 0.000 description 5
• 229920000615 alginic acid Polymers 0.000 description 5
• VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 5
• 150000001413 amino acids Chemical class 0.000 description 5
• 239000007859 condensation product Substances 0.000 description 5
• 239000012153 distilled water Substances 0.000 description 5
• 238000002474 experimental method Methods 0.000 description 5
• 150000004665 fatty acids Chemical class 0.000 description 5
• 230000035557 fibrillogenesis Effects 0.000 description 5
• WVDDGKGOMKODPV-UHFFFAOYSA-N hydroxymethyl benzene Natural products OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 5
• 238000001727 in vivo Methods 0.000 description 5
• 230000001965 increasing effect Effects 0.000 description 5
• 239000007924 injection Substances 0.000 description 5
• 238000002347 injection Methods 0.000 description 5
• 235000010445 lecithin Nutrition 0.000 description 5
• 239000000787 lecithin Substances 0.000 description 5
• 210000002569 neuron Anatomy 0.000 description 5
• 239000004006 olive oil Substances 0.000 description 5
• 239000002245 particle Substances 0.000 description 5
• 230000008506 pathogenesis Effects 0.000 description 5
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 5
• 229910000027 potassium carbonate Inorganic materials 0.000 description 5
• 238000000159 protein binding assay Methods 0.000 description 5
• 239000003765 sweetening agent Substances 0.000 description 5
• PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 4
• VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 4
• 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 4
• 102000001049 Amyloid Human genes 0.000 description 4
• 108010094108 Amyloid Proteins 0.000 description 4
• 102000009091 Amyloidogenic Proteins Human genes 0.000 description 4
• 108010048112 Amyloidogenic Proteins Proteins 0.000 description 4
• 244000105624 Arachis hypogaea Species 0.000 description 4
• 238000002965 ELISA Methods 0.000 description 4
• IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 4
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
• WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 4
• 241000700159 Rattus Species 0.000 description 4
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
• PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
• 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 4
• 229930006000 Sucrose Natural products 0.000 description 4
• 235000010323 ascorbic acid Nutrition 0.000 description 4
• ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 4
• 239000002775 capsule Substances 0.000 description 4
• 239000003085 diluting agent Substances 0.000 description 4
• 239000006185 dispersion Substances 0.000 description 4
• ADEBPBSSDYVVLD-UHFFFAOYSA-N donepezil Chemical compound O=C1C=2C=C(OC)C(OC)=CC=2CC1CC(CC1)CCN1CC1=CC=CC=C1 ADEBPBSSDYVVLD-UHFFFAOYSA-N 0.000 description 4
• 239000000839 emulsion Substances 0.000 description 4
• 230000005284 excitation Effects 0.000 description 4
• 238000003818 flash chromatography Methods 0.000 description 4
• 235000003599 food sweetener Nutrition 0.000 description 4
• 239000008187 granular material Substances 0.000 description 4
• 238000004128 high performance liquid chromatography Methods 0.000 description 4
• 239000007927 intramuscular injection Substances 0.000 description 4
• 238000010255 intramuscular injection Methods 0.000 description 4
• 210000003734 kidney Anatomy 0.000 description 4
• 229940067606 lecithin Drugs 0.000 description 4
• 150000002632 lipids Chemical class 0.000 description 4
• 235000008390 olive oil Nutrition 0.000 description 4
• NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 4
• 230000036961 partial effect Effects 0.000 description 4
• 239000003755 preservative agent Substances 0.000 description 4
• 230000002265 prevention Effects 0.000 description 4
• 230000008569 process Effects 0.000 description 4
• 108090000765 processed proteins & peptides Proteins 0.000 description 4
• 125000006239 protecting group Chemical group 0.000 description 4
• 238000000746 purification Methods 0.000 description 4
• 238000004611 spectroscopical analysis Methods 0.000 description 4
• 239000007858 starting material Substances 0.000 description 4
• 239000005720 sucrose Substances 0.000 description 4
• 230000002459 sustained effect Effects 0.000 description 4
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
• 231100000419 toxicity Toxicity 0.000 description 4
• 230000001988 toxicity Effects 0.000 description 4
• PFWLFWPASULGAN-UHFFFAOYSA-N 7-methylxanthine Chemical compound N1C(=O)NC(=O)C2=C1N=CN2C PFWLFWPASULGAN-UHFFFAOYSA-N 0.000 description 3
• ARLSKSAJKBBXPV-UHFFFAOYSA-N 8-benzyl-3,7-dihydropurine-2,6-dione Chemical compound N1C=2C(=O)NC(=O)NC=2N=C1CC1=CC=CC=C1 ARLSKSAJKBBXPV-UHFFFAOYSA-N 0.000 description 3
• 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 3
• 235000003911 Arachis Nutrition 0.000 description 3
• 241000416162 Astragalus gummifer Species 0.000 description 3
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
• 108010010803 Gelatin Proteins 0.000 description 3
• 244000068988 Glycine max Species 0.000 description 3
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
• 206010028980 Neoplasm Diseases 0.000 description 3
• 208000012902 Nervous system disease Diseases 0.000 description 3
• 229910019142 PO4 Inorganic materials 0.000 description 3
• 229920001615 Tragacanth Polymers 0.000 description 3
• 102000009190 Transthyretin Human genes 0.000 description 3
• 102100029290 Transthyretin Human genes 0.000 description 3
• 239000002253 acid Substances 0.000 description 3
• 239000002671 adjuvant Substances 0.000 description 3
• 239000000783 alginic acid Substances 0.000 description 3
• 229960001126 alginic acid Drugs 0.000 description 3
• 150000004781 alginic acids Chemical class 0.000 description 3
• 125000003342 alkenyl group Chemical group 0.000 description 3
• 125000000217 alkyl group Chemical group 0.000 description 3
• 125000000304 alkynyl group Chemical group 0.000 description 3
• 125000003710 aryl alkyl group Chemical group 0.000 description 3
• 125000003118 aryl group Chemical group 0.000 description 3
• 229960005070 ascorbic acid Drugs 0.000 description 3
• 239000011668 ascorbic acid Substances 0.000 description 3
• 230000008901 benefit Effects 0.000 description 3
• 229920002988 biodegradable polymer Polymers 0.000 description 3
• 239000004621 biodegradable polymer Substances 0.000 description 3
• 210000004369 blood Anatomy 0.000 description 3
• 239000008280 blood Substances 0.000 description 3
• 210000004204 blood vessel Anatomy 0.000 description 3
• 230000037396 body weight Effects 0.000 description 3
• 239000012267 brine Substances 0.000 description 3
• 229910000019 calcium carbonate Inorganic materials 0.000 description 3
• 235000010216 calcium carbonate Nutrition 0.000 description 3
• 239000001506 calcium phosphate Substances 0.000 description 3
• 239000000969 carrier Substances 0.000 description 3
• 238000001142 circular dichroism spectrum Methods 0.000 description 3
• 210000004748 cultured cell Anatomy 0.000 description 3
• 125000000753 cycloalkyl group Chemical group 0.000 description 3
• 239000008367 deionised water Substances 0.000 description 3
• 229910021641 deionized water Inorganic materials 0.000 description 3
• 239000002270 dispersing agent Substances 0.000 description 3
• 239000002552 dosage form Substances 0.000 description 3
• 229940088679 drug related substance Drugs 0.000 description 3
• 239000003995 emulsifying agent Substances 0.000 description 3
• 150000002084 enol ethers Chemical class 0.000 description 3
• 235000013355 food flavoring agent Nutrition 0.000 description 3
• 210000001035 gastrointestinal tract Anatomy 0.000 description 3
• 239000000499 gel Substances 0.000 description 3
• 239000008273 gelatin Substances 0.000 description 3
• 229920000159 gelatin Polymers 0.000 description 3
• 239000007903 gelatin capsule Substances 0.000 description 3
• 235000019322 gelatine Nutrition 0.000 description 3
• 235000011852 gelatine desserts Nutrition 0.000 description 3
• 210000002216 heart Anatomy 0.000 description 3
• 125000004475 heteroaralkyl group Chemical group 0.000 description 3
• 125000001072 heteroaryl group Chemical group 0.000 description 3
• 125000000623 heterocyclic group Chemical group 0.000 description 3
• BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 3
• 150000004677 hydrates Chemical class 0.000 description 3
• 239000007943 implant Substances 0.000 description 3
• 239000003701 inert diluent Substances 0.000 description 3
• 230000002401 inhibitory effect Effects 0.000 description 3
• 238000007912 intraperitoneal administration Methods 0.000 description 3
• 239000008101 lactose Substances 0.000 description 3
• 229940057995 liquid paraffin Drugs 0.000 description 3
• 235000019359 magnesium stearate Nutrition 0.000 description 3
• 238000004949 mass spectrometry Methods 0.000 description 3
• 239000002609 medium Substances 0.000 description 3
• 239000012528 membrane Substances 0.000 description 3
• 239000004005 microsphere Substances 0.000 description 3
• 239000013642 negative control Substances 0.000 description 3
• 230000004770 neurodegeneration Effects 0.000 description 3
• 208000015122 neurodegenerative disease Diseases 0.000 description 3
• 150000007524 organic acids Chemical class 0.000 description 3
• 230000036542 oxidative stress Effects 0.000 description 3
• 210000000496 pancreas Anatomy 0.000 description 3
• 239000010452 phosphate Substances 0.000 description 3
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 3
• 239000006187 pill Substances 0.000 description 3
• 230000036470 plasma concentration Effects 0.000 description 3
• 239000002243 precursor Substances 0.000 description 3
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
• 239000007909 solid dosage form Substances 0.000 description 3
• 239000012453 solvate Substances 0.000 description 3
• 230000008685 targeting Effects 0.000 description 3
• 235000015112 vegetable and seed oil Nutrition 0.000 description 3
• 239000008158 vegetable oil Substances 0.000 description 3
• 238000005406 washing Methods 0.000 description 3
• JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical class OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 2
• RCVDPBFUMYUKPB-UHFFFAOYSA-N (3,4-dimethoxyphenyl)boronic acid Chemical compound COC1=CC=C(B(O)O)C=C1OC RCVDPBFUMYUKPB-UHFFFAOYSA-N 0.000 description 2
• ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 2
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
• NPELZSDJQUNQTG-UHFFFAOYSA-N 1-benzyl-8-(3,4-dimethoxyphenyl)-3,7-dihydropurine-2,6-dione Chemical compound C(C1=CC=CC=C1)N1C(=O)NC=2N=C(NC=2C1=O)C1=CC(=C(C=C1)OC)OC NPELZSDJQUNQTG-UHFFFAOYSA-N 0.000 description 2
• PLRACCBDVIHHLZ-UHFFFAOYSA-N 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine Chemical compound C1N(C)CCC(C=2C=CC=CC=2)=C1 PLRACCBDVIHHLZ-UHFFFAOYSA-N 0.000 description 2
• MVOYJPOZRLFTCP-UHFFFAOYSA-N 1-methyl-7H-xanthine Chemical compound O=C1N(C)C(=O)NC2=C1NC=N2 MVOYJPOZRLFTCP-UHFFFAOYSA-N 0.000 description 2
• YQUVCSBJEUQKSH-UHFFFAOYSA-N 3,4-dihydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C(O)=C1 YQUVCSBJEUQKSH-UHFFFAOYSA-N 0.000 description 2
• GMSNIKWWOQHZGF-UHFFFAOYSA-N 3-methyl-9H-xanthine Chemical compound O=C1NC(=O)N(C)C2=C1N=CN2 GMSNIKWWOQHZGF-UHFFFAOYSA-N 0.000 description 2
• DDAGFZBQVSGXJN-UHFFFAOYSA-N 4-(chloromethyl)-1,2-bis(phenylmethoxy)benzene Chemical compound C=1C=CC=CC=1COC1=CC(CCl)=CC=C1OCC1=CC=CC=C1 DDAGFZBQVSGXJN-UHFFFAOYSA-N 0.000 description 2
• QTEQVEJOXGBDGI-UHFFFAOYSA-N 8-bromo-3-methyl-7h-purine-2,6-dione Chemical compound O=C1NC(=O)N(C)C2=C1NC(Br)=N2 QTEQVEJOXGBDGI-UHFFFAOYSA-N 0.000 description 2
• 244000215068 Acacia senegal Species 0.000 description 2
• 235000006491 Acacia senegal Nutrition 0.000 description 2
• 229940100578 Acetylcholinesterase inhibitor Drugs 0.000 description 2
• 229920001817 Agar Polymers 0.000 description 2
• 239000005995 Aluminium silicate Substances 0.000 description 2
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
• 229920002261 Corn starch Polymers 0.000 description 2
• 208000020406 Creutzfeldt Jacob disease Diseases 0.000 description 2
• 208000003407 Creutzfeldt-Jakob Syndrome Diseases 0.000 description 2
• 208000010859 Creutzfeldt-Jakob disease Diseases 0.000 description 2
• 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 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
• 229940124602 FDA-approved drug Drugs 0.000 description 2
• 206010016207 Familial Mediterranean fever Diseases 0.000 description 2
• 241000206672 Gelidium Species 0.000 description 2
• 208000003736 Gerstmann-Straussler-Scheinker Disease Diseases 0.000 description 2
• 235000010469 Glycine max Nutrition 0.000 description 2
• 229920000084 Gum arabic Polymers 0.000 description 2
• 241000282412 Homo Species 0.000 description 2
• 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 2
• 206010061218 Inflammation Diseases 0.000 description 2
• 240000007472 Leucaena leucocephala Species 0.000 description 2
• 235000010643 Leucaena leucocephala Nutrition 0.000 description 2
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
• 235000019759 Maize starch Nutrition 0.000 description 2
• 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
• 208000034578 Multiple myelomas Diseases 0.000 description 2
• 241000699666 Mus <mouse, genus> Species 0.000 description 2
• 101001135571 Mus musculus Tyrosine-protein phosphatase non-receptor type 2 Proteins 0.000 description 2
• MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 2
• 206010029260 Neuroblastoma Diseases 0.000 description 2
• 208000025966 Neurological disease Diseases 0.000 description 2
• 240000007817 Olea europaea Species 0.000 description 2
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
• 206010035226 Plasma cell myeloma Diseases 0.000 description 2
• 229920003171 Poly (ethylene oxide) Polymers 0.000 description 2
• 239000004698 Polyethylene Substances 0.000 description 2
• 229920002565 Polyethylene Glycol 400 Polymers 0.000 description 2
• 206010036105 Polyneuropathy Diseases 0.000 description 2
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
• 208000024777 Prion disease Diseases 0.000 description 2
• 229920002472 Starch Polymers 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
• 240000008042 Zea mays Species 0.000 description 2
• 235000010489 acacia gum Nutrition 0.000 description 2
• 150000001241 acetals Chemical class 0.000 description 2
• 230000002378 acidificating effect Effects 0.000 description 2
• 150000007513 acids Chemical class 0.000 description 2
• 239000008186 active pharmaceutical agent Substances 0.000 description 2
• 235000010419 agar Nutrition 0.000 description 2
• 235000012211 aluminium silicate Nutrition 0.000 description 2
• MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 description 2
• 238000004458 analytical method Methods 0.000 description 2
• 238000010171 animal model Methods 0.000 description 2
• 239000012736 aqueous medium Substances 0.000 description 2
• 239000003125 aqueous solvent Substances 0.000 description 2
• 239000012300 argon atmosphere Substances 0.000 description 2
• 210000003719 b-lymphocyte Anatomy 0.000 description 2
• 239000000440 bentonite Substances 0.000 description 2
• 235000012216 bentonite Nutrition 0.000 description 2
• 229910000278 bentonite Inorganic materials 0.000 description 2
• SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 2
• 235000019445 benzyl alcohol Nutrition 0.000 description 2
• 239000011230 binding agent Substances 0.000 description 2
• 230000004071 biological effect Effects 0.000 description 2
• 210000005013 brain tissue Anatomy 0.000 description 2
• 235000019437 butane-1,3-diol Nutrition 0.000 description 2
• 229910052791 calcium Inorganic materials 0.000 description 2
• 239000011575 calcium Substances 0.000 description 2
• 229910000389 calcium phosphate Inorganic materials 0.000 description 2
• 235000011010 calcium phosphates Nutrition 0.000 description 2
• 201000011510 cancer Diseases 0.000 description 2
• 150000001722 carbon compounds Chemical class 0.000 description 2
• 239000001768 carboxy methyl cellulose Substances 0.000 description 2
• 208000003295 carpal tunnel syndrome Diseases 0.000 description 2
• 239000004359 castor oil Substances 0.000 description 2
• 238000000423 cell based assay Methods 0.000 description 2
• 238000004113 cell culture Methods 0.000 description 2
• 230000030833 cell death Effects 0.000 description 2
• 210000003169 central nervous system Anatomy 0.000 description 2
• 208000015114 central nervous system disease Diseases 0.000 description 2
• 238000005119 centrifugation Methods 0.000 description 2
• 229960000541 cetyl alcohol Drugs 0.000 description 2
• 230000008859 change Effects 0.000 description 2
• OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
• 239000000544 cholinesterase inhibitor Substances 0.000 description 2
• 208000037976 chronic inflammation Diseases 0.000 description 2
• 230000006020 chronic inflammation Effects 0.000 description 2
• 208000010877 cognitive disease Diseases 0.000 description 2
• 230000007370 cognitive improvement Effects 0.000 description 2
• 239000003086 colorant Substances 0.000 description 2
• 238000012790 confirmation Methods 0.000 description 2
• 238000013270 controlled release Methods 0.000 description 2
• 238000007796 conventional method Methods 0.000 description 2
• 235000012343 cottonseed oil Nutrition 0.000 description 2
• VFLDPWHFBUODDF-FCXRPNKRSA-N curcumin Chemical compound C1=C(O)C(OC)=CC(\C=C\C(=O)CC(=O)\C=C\C=2C=C(OC)C(O)=CC=2)=C1 VFLDPWHFBUODDF-FCXRPNKRSA-N 0.000 description 2
• 230000001086 cytosolic effect Effects 0.000 description 2
• 230000007850 degeneration Effects 0.000 description 2
• 230000001627 detrimental effect Effects 0.000 description 2
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 2
• BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 2
• 229910000397 disodium phosphate Inorganic materials 0.000 description 2
• 235000019800 disodium phosphate Nutrition 0.000 description 2
• 239000003937 drug carrier Substances 0.000 description 2
• 238000012377 drug delivery Methods 0.000 description 2
• 208000025688 early-onset autosomal dominant Alzheimer disease Diseases 0.000 description 2
• 230000001804 emulsifying effect Effects 0.000 description 2
• 238000006345 epimerization reaction Methods 0.000 description 2
• 208000015756 familial Alzheimer disease Diseases 0.000 description 2
• 239000000945 filler Substances 0.000 description 2
• 238000001914 filtration Methods 0.000 description 2
• 239000012634 fragment Substances 0.000 description 2
• 229930182480 glucuronide Natural products 0.000 description 2
• 150000008134 glucuronides Chemical class 0.000 description 2
• YQEMORVAKMFKLG-UHFFFAOYSA-N glycerine monostearate Natural products CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 description 2
• SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 0.000 description 2
• 229940093915 gynecological organic acid Drugs 0.000 description 2
• 238000001631 haemodialysis Methods 0.000 description 2
• 230000036541 health Effects 0.000 description 2
• 150000002373 hemiacetals Chemical class 0.000 description 2
• 230000000322 hemodialysis Effects 0.000 description 2
• 150000002431 hydrogen Chemical group 0.000 description 2
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
• ZUFVXZVXEJHHBN-UHFFFAOYSA-N hydron;1,2,3,4-tetrahydroacridin-9-amine;chloride Chemical compound [Cl-].C1=CC=C2C([NH3+])=C(CCCC3)C3=NC2=C1 ZUFVXZVXEJHHBN-UHFFFAOYSA-N 0.000 description 2
• CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 description 2
• 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 2
• 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 2
• 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 2
• 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 2
• 238000011065 in-situ storage Methods 0.000 description 2
• 239000000411 inducer Substances 0.000 description 2
• 230000001939 inductive effect Effects 0.000 description 2
• 230000004054 inflammatory process Effects 0.000 description 2
• 238000001802 infusion Methods 0.000 description 2
• 239000007972 injectable composition Substances 0.000 description 2
• 239000000543 intermediate Substances 0.000 description 2
• 230000003834 intracellular effect Effects 0.000 description 2
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
• 210000004153 islets of langerhan Anatomy 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
• 206010023497 kuru Diseases 0.000 description 2
• 239000008297 liquid dosage form Substances 0.000 description 2
• 229910052744 lithium Inorganic materials 0.000 description 2
• 230000007774 longterm Effects 0.000 description 2
• 239000000314 lubricant Substances 0.000 description 2
• 229910052749 magnesium Inorganic materials 0.000 description 2
• 239000011777 magnesium Substances 0.000 description 2
• 230000036210 malignancy Effects 0.000 description 2
• 239000011159 matrix material Substances 0.000 description 2
• 239000008108 microcrystalline cellulose Substances 0.000 description 2
• 229940016286 microcrystalline cellulose Drugs 0.000 description 2
• 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
• 239000011859 microparticle Substances 0.000 description 2
• 239000002480 mineral oil Substances 0.000 description 2
• 235000010446 mineral oil Nutrition 0.000 description 2
• 230000004065 mitochondrial dysfunction Effects 0.000 description 2
• 230000004048 modification Effects 0.000 description 2
• 238000012986 modification Methods 0.000 description 2
• 229920005615 natural polymer Polymers 0.000 description 2
• 230000002887 neurotoxic effect Effects 0.000 description 2
• 239000002736 nonionic surfactant Substances 0.000 description 2
• 239000000346 nonvolatile oil Substances 0.000 description 2
• 239000012053 oil suspension Substances 0.000 description 2
• 235000005985 organic acids Nutrition 0.000 description 2
• 238000006053 organic reaction Methods 0.000 description 2
• 150000002905 orthoesters Chemical class 0.000 description 2
• 230000004792 oxidative damage Effects 0.000 description 2
• 239000012188 paraffin wax Substances 0.000 description 2
• 230000001575 pathological effect Effects 0.000 description 2
• 239000008177 pharmaceutical agent Substances 0.000 description 2
• 239000000825 pharmaceutical preparation Substances 0.000 description 2
• 239000002831 pharmacologic agent Substances 0.000 description 2
• 150000003904 phospholipids Chemical class 0.000 description 2
• 229920000573 polyethylene Polymers 0.000 description 2
• 230000007824 polyneuropathy Effects 0.000 description 2
• 229920000136 polysorbate Polymers 0.000 description 2
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
• 229910052700 potassium Inorganic materials 0.000 description 2
• 239000011591 potassium Substances 0.000 description 2
• 239000001103 potassium chloride Substances 0.000 description 2
• 235000011164 potassium chloride Nutrition 0.000 description 2
• 229960004063 propylene glycol Drugs 0.000 description 2
• QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
• 230000000717 retained effect Effects 0.000 description 2
• 239000008159 sesame oil Substances 0.000 description 2
• 235000011803 sesame oil Nutrition 0.000 description 2
• 229910052708 sodium Inorganic materials 0.000 description 2
• 239000011734 sodium Substances 0.000 description 2
• 229910000029 sodium carbonate Inorganic materials 0.000 description 2
• 239000011780 sodium chloride Substances 0.000 description 2
• 239000001488 sodium phosphate Substances 0.000 description 2
• 239000008247 solid mixture Substances 0.000 description 2
• 235000011069 sorbitan monooleate Nutrition 0.000 description 2
• 239000001593 sorbitan monooleate Substances 0.000 description 2
• 229940035049 sorbitan monooleate Drugs 0.000 description 2
• 239000000600 sorbitol Substances 0.000 description 2
• 235000019698 starch Nutrition 0.000 description 2
• UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
• 239000000829 suppository Substances 0.000 description 2
• 229920001059 synthetic polymer Polymers 0.000 description 2
• 239000006188 syrup Substances 0.000 description 2
• 235000020357 syrup Nutrition 0.000 description 2
• 229960001685 tacrine Drugs 0.000 description 2
• DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 2
• 230000004797 therapeutic response Effects 0.000 description 2
• 238000004809 thin layer chromatography Methods 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
• 230000009466 transformation Effects 0.000 description 2
• 238000000844 transformation Methods 0.000 description 2
• 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 2
• 239000001993 wax Substances 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
• WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
• TZCPCKNHXULUIY-RGULYWFUSA-N 1,2-distearoyl-sn-glycero-3-phosphoserine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OC[C@H](N)C(O)=O)OC(=O)CCCCCCCCCCCCCCCCC TZCPCKNHXULUIY-RGULYWFUSA-N 0.000 description 1
• 229940058015 1,3-butylene glycol Drugs 0.000 description 1
• ORILCKUJEPKHAY-UHFFFAOYSA-N 1-benzyl-8-(3,4-dihydroxyphenyl)-3,7-dihydropurine-2,6-dione Chemical compound C(C1=CC=CC=C1)N1C(=O)NC=2N=C(NC=2C1=O)C1=CC(=C(C=C1)O)O ORILCKUJEPKHAY-UHFFFAOYSA-N 0.000 description 1
• 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 1
• LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
• ASNHGEVAWNWCRQ-UHFFFAOYSA-N 4-(hydroxymethyl)oxolane-2,3,4-triol Chemical compound OCC1(O)COC(O)C1O ASNHGEVAWNWCRQ-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
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
• 235000019489 Almond oil Nutrition 0.000 description 1
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
• 244000144725 Amygdalus communis Species 0.000 description 1
• 235000003276 Apios tuberosa Nutrition 0.000 description 1
• 235000010777 Arachis hypogaea Nutrition 0.000 description 1
• 235000010744 Arachis villosulicarpa Nutrition 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
• 241000283690 Bos taurus Species 0.000 description 1
• 241000282472 Canis lupus familiaris Species 0.000 description 1
• 241000283707 Capra Species 0.000 description 1
• CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
• 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
• 206010007509 Cardiac amyloidosis Diseases 0.000 description 1
• 241000700198 Cavia Species 0.000 description 1
• 206010008111 Cerebral haemorrhage Diseases 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
• 208000028698 Cognitive impairment Diseases 0.000 description 1
• FMGYKKMPNATWHP-UHFFFAOYSA-N Cyperquat Chemical compound C1=C[N+](C)=CC=C1C1=CC=CC=C1 FMGYKKMPNATWHP-UHFFFAOYSA-N 0.000 description 1
• 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 1
• RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 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
• 206010061818 Disease progression Diseases 0.000 description 1
• 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 1
• LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
• 208000001976 Endocrine Gland Neoplasms Diseases 0.000 description 1
• 102000004190 Enzymes Human genes 0.000 description 1
• 108090000790 Enzymes Proteins 0.000 description 1
• 241000283086 Equidae Species 0.000 description 1
• 239000001856 Ethyl cellulose Substances 0.000 description 1
• 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 1
• PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
• 241000282326 Felis catus Species 0.000 description 1
• 101000941893 Felis catus Leucine-rich repeat and calponin homology domain-containing protein 1 Proteins 0.000 description 1
• 239000004606 Fillers/Extenders Substances 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
• 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 1
• ZWZWYGMENQVNFU-UHFFFAOYSA-N Glycerophosphorylserin Natural products OC(=O)C(N)COP(O)(=O)OCC(O)CO ZWZWYGMENQVNFU-UHFFFAOYSA-N 0.000 description 1
• AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Polymers OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 1
• 206010019280 Heart failures Diseases 0.000 description 1
• 239000004705 High-molecular-weight polyethylene Substances 0.000 description 1
• 101000834898 Homo sapiens Alpha-synuclein Proteins 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
• WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-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
• 239000004472 Lysine Substances 0.000 description 1
• 239000005913 Maltodextrin Substances 0.000 description 1
• 229920002774 Maltodextrin Polymers 0.000 description 1
• 240000003183 Manihot esculenta Species 0.000 description 1
• 235000016735 Manihot esculenta subsp esculenta Nutrition 0.000 description 1
• 229930195725 Mannitol Natural products 0.000 description 1
• 241000699660 Mus musculus 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
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium on carbon Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
• 229930040373 Paraformaldehyde Natural products 0.000 description 1
• 235000019483 Peanut oil Nutrition 0.000 description 1
• 241001494479 Pecora Species 0.000 description 1
• 229930182555 Penicillin Natural products 0.000 description 1
• JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
• 108091005804 Peptidases Proteins 0.000 description 1
• 102000007079 Peptide Fragments Human genes 0.000 description 1
• 108010033276 Peptide Fragments Proteins 0.000 description 1
• 229920002732 Polyanhydride Polymers 0.000 description 1
• 229920000954 Polyglycolide Polymers 0.000 description 1
• 229920001710 Polyorthoester Polymers 0.000 description 1
• 108010048233 Procalcitonin Proteins 0.000 description 1
• 239000004365 Protease Substances 0.000 description 1
• 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
• 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
• 208000001647 Renal Insufficiency Diseases 0.000 description 1
• 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
• 241000219061 Rheum Species 0.000 description 1
• 235000004443 Ricinus communis Nutrition 0.000 description 1
• 244000000231 Sesamum indicum Species 0.000 description 1
• 235000003434 Sesamum indicum Nutrition 0.000 description 1
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
• DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
• 244000061456 Solanum tuberosum Species 0.000 description 1
• 235000002595 Solanum tuberosum Nutrition 0.000 description 1
• 235000021355 Stearic acid Nutrition 0.000 description 1
• SSZBUIDZHHWXNJ-UHFFFAOYSA-N Stearinsaeure-hexadecylester Natural products CCCCCCCCCCCCCCCCCC(=O)OCCCCCCCCCCCCCCCC SSZBUIDZHHWXNJ-UHFFFAOYSA-N 0.000 description 1
• 238000000692 Student's t-test Methods 0.000 description 1
• 241000282898 Sus scrofa 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
• 229920002494 Zein Polymers 0.000 description 1
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
• 239000001089 [(2R)-oxolan-2-yl]methanol Substances 0.000 description 1
• WERKSKAQRVDLDW-ANOHMWSOSA-N [(2s,3r,4r,5r)-2,3,4,5,6-pentahydroxyhexyl] (z)-octadec-9-enoate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO WERKSKAQRVDLDW-ANOHMWSOSA-N 0.000 description 1
• 230000002159 abnormal effect Effects 0.000 description 1
• 239000002250 absorbent Substances 0.000 description 1
• 230000002745 absorbent Effects 0.000 description 1
• 239000003655 absorption accelerator Substances 0.000 description 1
• 239000003070 absorption delaying agent Substances 0.000 description 1
• 150000001242 acetic acid derivatives Chemical class 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
• 230000009471 action Effects 0.000 description 1
• 239000011149 active material Substances 0.000 description 1
• 239000000654 additive Substances 0.000 description 1
• 230000000996 additive effect Effects 0.000 description 1
• WNLRTRBMVRJNCN-UHFFFAOYSA-L adipate(2-) Chemical compound [O-]C(=O)CCCCC([O-])=O WNLRTRBMVRJNCN-UHFFFAOYSA-L 0.000 description 1
• 239000000443 aerosol Substances 0.000 description 1
• 230000032683 aging Effects 0.000 description 1
• 229940072056 alginate Drugs 0.000 description 1
• 229910052783 alkali metal Inorganic materials 0.000 description 1
• 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
• 150000003973 alkyl amines Chemical class 0.000 description 1
• 125000002947 alkylene group Chemical group 0.000 description 1
• 208000026935 allergic disease Diseases 0.000 description 1
• 239000008168 almond oil Substances 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
• 230000001668 ameliorated effect Effects 0.000 description 1
• 229910021529 ammonia Inorganic materials 0.000 description 1
• 229960000510 ammonia Drugs 0.000 description 1
• 230000006933 amyloid-beta aggregation Effects 0.000 description 1
• 238000000540 analysis of variance Methods 0.000 description 1
• 239000003242 anti bacterial agent Substances 0.000 description 1
• 230000000844 anti-bacterial effect Effects 0.000 description 1
• 239000003429 antifungal agent Substances 0.000 description 1
• 229940121375 antifungal agent Drugs 0.000 description 1
• 239000003963 antioxidant agent Substances 0.000 description 1
• 230000003078 antioxidant effect Effects 0.000 description 1
• 235000006708 antioxidants Nutrition 0.000 description 1
• 210000002376 aorta thoracic Anatomy 0.000 description 1
• 238000013459 approach Methods 0.000 description 1
• 239000007864 aqueous solution Substances 0.000 description 1
• 229910052786 argon Inorganic materials 0.000 description 1
• 229940039856 aricept Drugs 0.000 description 1
• 125000003289 ascorbyl group Chemical class [H]O[C@@]([H])(C([H])([H])O*)[C@@]1([H])OC(=O)C(O*)=C1O* 0.000 description 1
• 229940009098 aspartate Drugs 0.000 description 1
• 229910052788 barium Inorganic materials 0.000 description 1
• DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 description 1
• 239000002585 base Substances 0.000 description 1
• 210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 description 1
• 235000013871 bee wax Nutrition 0.000 description 1
• 239000012166 beeswax Substances 0.000 description 1
• 230000003542 behavioural effect Effects 0.000 description 1
• UPABQMWFWCMOFV-UHFFFAOYSA-N benethamine Chemical compound C=1C=CC=CC=1CNCCC1=CC=CC=C1 UPABQMWFWCMOFV-UHFFFAOYSA-N 0.000 description 1
• JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
• 125000005605 benzo group Chemical group 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
• 229960002903 benzyl benzoate Drugs 0.000 description 1
• KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 1
• 229940073608 benzyl chloride Drugs 0.000 description 1
• WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
• 238000011953 bioanalysis Methods 0.000 description 1
• 238000002306 biochemical method Methods 0.000 description 1
• 230000036765 blood level Effects 0.000 description 1
• 230000036760 body temperature Effects 0.000 description 1
• 125000005620 boronic acid group Chemical class 0.000 description 1
• 239000006172 buffering agent Substances 0.000 description 1
• 244000309464 bull Species 0.000 description 1
• 150000004648 butanoic acid derivatives Chemical class 0.000 description 1
• 230000000981 bystander Effects 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
• 238000004364 calculation method Methods 0.000 description 1
• 238000011088 calibration curve Methods 0.000 description 1
• 239000007894 caplet Substances 0.000 description 1
• 235000011089 carbon dioxide Nutrition 0.000 description 1
• 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
• 150000001735 carboxylic acids Chemical class 0.000 description 1
• 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
• 230000000747 cardiac effect Effects 0.000 description 1
• 238000012754 cardiac puncture Methods 0.000 description 1
• 235000019438 castor oil Nutrition 0.000 description 1
• 239000003054 catalyst Substances 0.000 description 1
• 150000001768 cations Chemical class 0.000 description 1
• 239000006143 cell culture medium Substances 0.000 description 1
• 239000012578 cell culture reagent Substances 0.000 description 1
• 235000010980 cellulose Nutrition 0.000 description 1
• 229920002678 cellulose Polymers 0.000 description 1
• 239000001913 cellulose Substances 0.000 description 1
• 229960004926 chlorobutanol Drugs 0.000 description 1
• VDANGULDQQJODZ-UHFFFAOYSA-N chloroprocaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1Cl VDANGULDQQJODZ-UHFFFAOYSA-N 0.000 description 1
• 229960002023 chloroprocaine Drugs 0.000 description 1
• OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
• 229960001231 choline Drugs 0.000 description 1
• 238000004587 chromatography analysis Methods 0.000 description 1
• 229940001468 citrate Drugs 0.000 description 1
• 150000001860 citric acid derivatives Chemical class 0.000 description 1
• 239000004927 clay Substances 0.000 description 1
• 238000003776 cleavage reaction Methods 0.000 description 1
• 229940110456 cocoa butter Drugs 0.000 description 1
• 235000019868 cocoa butter Nutrition 0.000 description 1
• 239000003240 coconut oil Substances 0.000 description 1
• 235000019864 coconut oil Nutrition 0.000 description 1
• 238000010668 complexation reaction Methods 0.000 description 1
• 229940125904 compound 1 Drugs 0.000 description 1
• 238000007906 compression Methods 0.000 description 1
• 230000006835 compression Effects 0.000 description 1
• 239000000470 constituent Substances 0.000 description 1
• 229920001577 copolymer Polymers 0.000 description 1
• 235000005822 corn Nutrition 0.000 description 1
• 235000005687 corn oil Nutrition 0.000 description 1
• 239000002385 cottonseed oil Substances 0.000 description 1
• 239000013078 crystal Substances 0.000 description 1
• 238000002425 crystallisation Methods 0.000 description 1
• 230000008025 crystallization Effects 0.000 description 1
• 235000012754 curcumin Nutrition 0.000 description 1
• 239000004148 curcumin Substances 0.000 description 1
• 229940109262 curcumin Drugs 0.000 description 1
• 210000000805 cytoplasm Anatomy 0.000 description 1
• 238000002784 cytotoxicity assay Methods 0.000 description 1
• 231100000263 cytotoxicity test Toxicity 0.000 description 1
• 230000006378 damage Effects 0.000 description 1
• 230000034994 death Effects 0.000 description 1
• 230000006735 deficit Effects 0.000 description 1
• 239000003405 delayed action preparation Substances 0.000 description 1
• 230000003111 delayed effect Effects 0.000 description 1
• 208000017004 dementia pugilistica Diseases 0.000 description 1
• 230000001419 dependent effect Effects 0.000 description 1
• 238000001212 derivatisation Methods 0.000 description 1
• 238000013461 design Methods 0.000 description 1
• 238000011161 development Methods 0.000 description 1
• 230000018109 developmental process Effects 0.000 description 1
• 125000005131 dialkylammonium group Chemical group 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
• 235000005911 diet Nutrition 0.000 description 1
• 230000037213 diet Effects 0.000 description 1
• ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
• 229940043237 diethanolamine Drugs 0.000 description 1
• HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
• VFLDPWHFBUODDF-UHFFFAOYSA-N diferuloylmethane Natural products C1=C(O)C(OC)=CC(C=CC(=O)CC(=O)C=CC=2C=C(OC)C(O)=CC=2)=C1 VFLDPWHFBUODDF-UHFFFAOYSA-N 0.000 description 1
• 230000005750 disease progression Effects 0.000 description 1
• 238000004821 distillation Methods 0.000 description 1
• 229960003530 donepezil Drugs 0.000 description 1
• 210000005064 dopaminergic neuron Anatomy 0.000 description 1
• 239000008298 dragée Substances 0.000 description 1
• 230000036267 drug metabolism Effects 0.000 description 1
• 229940126534 drug product Drugs 0.000 description 1
• 238000002651 drug therapy Methods 0.000 description 1
• 238000001035 drying Methods 0.000 description 1
• 208000018620 early-onset Parkinson disease Diseases 0.000 description 1
• 230000027721 electron transport chain Effects 0.000 description 1
• 239000003974 emollient agent Substances 0.000 description 1
• 238000005538 encapsulation Methods 0.000 description 1
• 201000011523 endocrine gland cancer Diseases 0.000 description 1
• 239000002702 enteric coating Substances 0.000 description 1
• 238000009505 enteric coating Methods 0.000 description 1
• 230000002255 enzymatic effect Effects 0.000 description 1
• 229940088598 enzyme Drugs 0.000 description 1
• BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
• 229940093499 ethyl acetate Drugs 0.000 description 1
• 235000019325 ethyl cellulose Nutrition 0.000 description 1
• 229920001249 ethyl cellulose Polymers 0.000 description 1
• 229960004667 ethyl cellulose Drugs 0.000 description 1
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
• LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
• 229940093471 ethyl oleate Drugs 0.000 description 1
• 230000029142 excretion Effects 0.000 description 1
• 239000000706 filtrate Substances 0.000 description 1
• 235000019634 flavors Nutrition 0.000 description 1
• MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 1
• 239000007850 fluorescent dye Substances 0.000 description 1
• VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical class [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
• 230000006870 function Effects 0.000 description 1
• 238000001502 gel electrophoresis Methods 0.000 description 1
• 239000007897 gelcap Substances 0.000 description 1
• 230000002068 genetic effect Effects 0.000 description 1
• 239000011521 glass Substances 0.000 description 1
• 229940050410 gluconate Drugs 0.000 description 1
• 239000008103 glucose Substances 0.000 description 1
• 235000001727 glucose Nutrition 0.000 description 1
• 229930195712 glutamate Natural products 0.000 description 1
• UHUSDOQQWJGJQS-UHFFFAOYSA-N glycerol 1,2-dioctadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(CO)OC(=O)CCCCCCCCCCCCCCCCC UHUSDOQQWJGJQS-UHFFFAOYSA-N 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
• 231100000304 hepatotoxicity Toxicity 0.000 description 1
• IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 1
• FBPFZTCFMRRESA-UHFFFAOYSA-N hexane-1,2,3,4,5,6-hexol Chemical compound OCC(O)C(O)C(O)C(O)CO FBPFZTCFMRRESA-UHFFFAOYSA-N 0.000 description 1
• 210000001320 hippocampus Anatomy 0.000 description 1
• 239000003906 humectant Substances 0.000 description 1
• 150000003840 hydrochlorides Chemical class 0.000 description 1
• 239000000017 hydrogel Substances 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
• 238000010191 image analysis Methods 0.000 description 1
• 239000012535 impurity Substances 0.000 description 1
• 238000000099 in vitro assay Methods 0.000 description 1
• 210000003000 inclusion body Anatomy 0.000 description 1
• 229940102223 injectable solution Drugs 0.000 description 1
• 229940102213 injectable suspension Drugs 0.000 description 1
• 150000007529 inorganic bases Chemical class 0.000 description 1
• 229910052500 inorganic mineral Inorganic materials 0.000 description 1
• 239000007928 intraperitoneal injection Substances 0.000 description 1
• 230000007794 irritation Effects 0.000 description 1
• 238000002955 isolation Methods 0.000 description 1
• QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
• 201000006370 kidney failure Diseases 0.000 description 1
• 150000003893 lactate salts Chemical class 0.000 description 1
• 230000002045 lasting effect Effects 0.000 description 1
• 210000005240 left ventricle Anatomy 0.000 description 1
• 230000003902 lesion Effects 0.000 description 1
• 230000000670 limiting effect Effects 0.000 description 1
• 239000004973 liquid crystal related substance Substances 0.000 description 1
• 239000012280 lithium aluminium hydride Substances 0.000 description 1
• 210000004185 liver Anatomy 0.000 description 1
• 230000007056 liver toxicity Effects 0.000 description 1
• 210000004072 lung Anatomy 0.000 description 1
• 229940057948 magnesium stearate Drugs 0.000 description 1
• 238000012423 maintenance Methods 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
• 150000004701 malic acid derivatives Chemical class 0.000 description 1
• 229940035034 maltodextrin Drugs 0.000 description 1
• 239000000594 mannitol Substances 0.000 description 1
• 235000010355 mannitol Nutrition 0.000 description 1
• 208000023356 medullary thyroid gland carcinoma Diseases 0.000 description 1
• 229960003194 meglumine Drugs 0.000 description 1
• 206010027175 memory impairment Diseases 0.000 description 1
• 230000002503 metabolic effect Effects 0.000 description 1
• 230000004060 metabolic process Effects 0.000 description 1
• 239000002207 metabolite Substances 0.000 description 1
• 229910052751 metal Inorganic materials 0.000 description 1
• 239000002184 metal Substances 0.000 description 1
• 235000020069 metaxa Nutrition 0.000 description 1
• 229920000609 methyl cellulose Polymers 0.000 description 1
• 235000010981 methylcellulose Nutrition 0.000 description 1
• 239000001923 methylcellulose Substances 0.000 description 1
• 239000004530 micro-emulsion Substances 0.000 description 1
• 208000027061 mild cognitive impairment Diseases 0.000 description 1
• 235000010755 mineral Nutrition 0.000 description 1
• 239000011707 mineral Substances 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• 230000007631 mitochondrial deficit Effects 0.000 description 1
• 230000002438 mitochondrial effect Effects 0.000 description 1
• 238000002156 mixing Methods 0.000 description 1
• CQDGTJPVBWZJAZ-UHFFFAOYSA-N monoethyl carbonate Chemical compound CCOC(O)=O CQDGTJPVBWZJAZ-UHFFFAOYSA-N 0.000 description 1
• 230000007659 motor function Effects 0.000 description 1
• 210000005036 nerve Anatomy 0.000 description 1
• 230000001537 neural effect Effects 0.000 description 1
• 230000016273 neuron death Effects 0.000 description 1
• 230000006764 neuronal dysfunction Effects 0.000 description 1
• 230000004112 neuroprotection Effects 0.000 description 1
• 230000000324 neuroprotective effect Effects 0.000 description 1
• 231100000189 neurotoxic Toxicity 0.000 description 1
• 231100000344 non-irritating Toxicity 0.000 description 1
• 239000012457 nonaqueous media Substances 0.000 description 1
• 230000006911 nucleation Effects 0.000 description 1
• 238000010899 nucleation Methods 0.000 description 1
• 230000000474 nursing effect Effects 0.000 description 1
• GYCKQBWUSACYIF-UHFFFAOYSA-N o-hydroxybenzoic acid ethyl ester Natural products CCOC(=O)C1=CC=CC=C1O GYCKQBWUSACYIF-UHFFFAOYSA-N 0.000 description 1
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
• OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
• OIPZNTLJVJGRCI-UHFFFAOYSA-M octadecanoyloxyaluminum;dihydrate Chemical compound O.O.CCCCCCCCCCCCCCCCCC(=O)O[Al] OIPZNTLJVJGRCI-UHFFFAOYSA-M 0.000 description 1
• ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
• 230000004768 organ dysfunction Effects 0.000 description 1
• 150000007530 organic bases Chemical class 0.000 description 1
• 150000002895 organic esters Chemical class 0.000 description 1
• 230000003204 osmotic effect Effects 0.000 description 1
• 238000002638 palliative care Methods 0.000 description 1
• 206010033675 panniculitis Diseases 0.000 description 1
• 229920002866 paraformaldehyde Polymers 0.000 description 1
• 238000007911 parenteral administration Methods 0.000 description 1
• 238000005192 partition Methods 0.000 description 1
• 230000001717 pathogenic effect Effects 0.000 description 1
• 230000007170 pathology Effects 0.000 description 1
• 239000000312 peanut oil Substances 0.000 description 1
• 239000008188 pellet Substances 0.000 description 1
• 229940049954 penicillin Drugs 0.000 description 1
• 239000002304 perfume Substances 0.000 description 1
• 230000010412 perfusion Effects 0.000 description 1
• 210000000578 peripheral nerve Anatomy 0.000 description 1
• 229940124531 pharmaceutical excipient Drugs 0.000 description 1
• 229940127557 pharmaceutical product Drugs 0.000 description 1
• 230000003285 pharmacodynamic effect Effects 0.000 description 1
• 238000001050 pharmacotherapy Methods 0.000 description 1
• 229960003742 phenol Drugs 0.000 description 1
• WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
• WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 1
• 150000008105 phosphatidylcholines Chemical class 0.000 description 1
• 235000011007 phosphoric acid Nutrition 0.000 description 1
• 150000003016 phosphoric acids Chemical class 0.000 description 1
• 230000004962 physiological condition Effects 0.000 description 1
• 229920001200 poly(ethylene-vinyl acetate) Polymers 0.000 description 1
• 239000002861 polymer material Substances 0.000 description 1
• 238000006116 polymerization reaction Methods 0.000 description 1
• 229920005862 polyol Polymers 0.000 description 1
• 150000003077 polyols Chemical class 0.000 description 1
• 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
• 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
• 229920001184 polypeptide Polymers 0.000 description 1
• 229920001282 polysaccharide Polymers 0.000 description 1
• 239000005017 polysaccharide Substances 0.000 description 1
• 150000004804 polysaccharides Chemical class 0.000 description 1
• 229920001296 polysiloxane Polymers 0.000 description 1
• 229920000053 polysorbate 80 Polymers 0.000 description 1
• 238000010149 post-hoc-test Methods 0.000 description 1
• 238000001556 precipitation Methods 0.000 description 1
• 230000002335 preservative effect Effects 0.000 description 1
• 230000003518 presynaptic effect Effects 0.000 description 1
• MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
• 229960004919 procaine Drugs 0.000 description 1
• CWCXERYKLSEGEZ-KDKHKZEGSA-N procalcitonin Chemical compound C([C@@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)NCC(O)=O)[C@@H](C)O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCSC)NC(=O)[C@H]1NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)[C@@H](N)CSSC1)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 CWCXERYKLSEGEZ-KDKHKZEGSA-N 0.000 description 1
• 102000004196 processed proteins & peptides Human genes 0.000 description 1
• 238000012545 processing Methods 0.000 description 1
• 230000002035 prolonged effect Effects 0.000 description 1
• 238000011321 prophylaxis Methods 0.000 description 1
• 150000003856 quaternary ammonium compounds Chemical class 0.000 description 1
• 239000000376 reactant Substances 0.000 description 1
• 210000000664 rectum Anatomy 0.000 description 1
• 239000013643 reference control Substances 0.000 description 1
• 230000004044 response Effects 0.000 description 1
• 230000011506 response to oxidative stress Effects 0.000 description 1
• 239000003340 retarding agent Substances 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
• 235000019204 saccharin Nutrition 0.000 description 1
• 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
• 230000007017 scission Effects 0.000 description 1
• 208000008864 scrapie Diseases 0.000 description 1
• 230000035945 sensitivity Effects 0.000 description 1
• 150000004760 silicates Chemical class 0.000 description 1
• RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
• 235000012239 silicon dioxide Nutrition 0.000 description 1
• 210000003491 skin Anatomy 0.000 description 1
• 239000007974 sodium acetate buffer Substances 0.000 description 1
• 235000010413 sodium alginate Nutrition 0.000 description 1
• 239000000661 sodium alginate Substances 0.000 description 1
• 229940005550 sodium alginate Drugs 0.000 description 1
• 229910001467 sodium calcium phosphate Inorganic materials 0.000 description 1
• 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
• 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
• 239000001509 sodium citrate Substances 0.000 description 1
• NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
• 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
• 235000011008 sodium phosphates Nutrition 0.000 description 1
• 229910052938 sodium sulfate Inorganic materials 0.000 description 1
• 235000011152 sodium sulphate Nutrition 0.000 description 1
• 238000000638 solvent extraction Methods 0.000 description 1
• 239000004334 sorbic acid Substances 0.000 description 1
• 235000010199 sorbic acid Nutrition 0.000 description 1
• 229940075582 sorbic acid Drugs 0.000 description 1
• 239000003549 soybean oil Substances 0.000 description 1
• 235000012424 soybean oil Nutrition 0.000 description 1
• 238000010183 spectrum analysis Methods 0.000 description 1
• 210000000952 spleen Anatomy 0.000 description 1
• 239000003381 stabilizer Substances 0.000 description 1
• 238000010561 standard procedure Methods 0.000 description 1
• 239000008107 starch Substances 0.000 description 1
• 238000007619 statistical method Methods 0.000 description 1
• 239000008117 stearic acid Substances 0.000 description 1
• 239000008223 sterile water Substances 0.000 description 1
• 239000003206 sterilizing agent Substances 0.000 description 1
• 238000003756 stirring Methods 0.000 description 1
• 229960005322 streptomycin Drugs 0.000 description 1
• 239000007929 subcutaneous injection Substances 0.000 description 1
• 238000010254 subcutaneous injection Methods 0.000 description 1
• 210000004304 subcutaneous tissue Anatomy 0.000 description 1
• 238000006467 substitution reaction Methods 0.000 description 1
• 150000003890 succinate salts Chemical class 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
• 150000003455 sulfinic acids Chemical class 0.000 description 1
• 150000003460 sulfonic acids Chemical class 0.000 description 1
• 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
• 239000004094 surface-active agent Substances 0.000 description 1
• YLJREFDVOIBQDA-UHFFFAOYSA-N tacrine Chemical compound C1=CC=C2C(N)=C(CCCC3)C3=NC2=C1 YLJREFDVOIBQDA-UHFFFAOYSA-N 0.000 description 1
• 229960003565 tacrine hydrochloride Drugs 0.000 description 1
• 239000000454 talc Substances 0.000 description 1
• 229910052623 talc Inorganic materials 0.000 description 1
• 235000012222 talc Nutrition 0.000 description 1
• 229940095064 tartrate Drugs 0.000 description 1
• 150000003892 tartrate salts Chemical class 0.000 description 1
• BSYVTEYKTMYBMK-UHFFFAOYSA-N tetrahydrofurfuryl alcohol Chemical compound OCC1CCCO1 BSYVTEYKTMYBMK-UHFFFAOYSA-N 0.000 description 1
• 239000002562 thickening agent Substances 0.000 description 1
• 231100000331 toxic Toxicity 0.000 description 1
• 230000002588 toxic effect Effects 0.000 description 1
• 239000003053 toxin Substances 0.000 description 1
• 231100000765 toxin Toxicity 0.000 description 1
• 235000010487 tragacanth Nutrition 0.000 description 1
• 239000000196 tragacanth Substances 0.000 description 1
• 229940116362 tragacanth Drugs 0.000 description 1
• 238000011830 transgenic mouse model Methods 0.000 description 1
• 230000001052 transient effect Effects 0.000 description 1
• 229910052723 transition metal Inorganic materials 0.000 description 1
• 125000005208 trialkylammonium group Chemical group 0.000 description 1
• YFDSDPIBEUFTMI-UHFFFAOYSA-N tribromoethanol Chemical compound OCC(Br)(Br)Br YFDSDPIBEUFTMI-UHFFFAOYSA-N 0.000 description 1
• 229950004616 tribromoethanol Drugs 0.000 description 1
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
• RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
• NQPDZGIKBAWPEJ-UHFFFAOYSA-M valerate Chemical class CCCCC([O-])=O NQPDZGIKBAWPEJ-UHFFFAOYSA-M 0.000 description 1
• 238000009736 wetting Methods 0.000 description 1
• 239000005019 zein Substances 0.000 description 1
• 229940093612 zein Drugs 0.000 description 1
• 229910052725 zinc Inorganic materials 0.000 description 1
• 239000011701 zinc Substances 0.000 description 1