CA2939655A1 - Modulateurs de caspase 6 - Google Patents

Modulateurs de caspase 6 Download PDF

Info

Publication number: CA2939655A1
Authority: CA; Canada
Prior art keywords: treatment; caspase; neurological disease; pharmaceutical composition; disease
Prior art date: 2014-02-14
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

Application number

CA2939655A

Other languages

English (en)

Inventor

Medhi Mike Khankischpur

Olga PETINA

Detlef Geffken

Dagmar ERNHOEFER

Michael Hayden

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

University of British Columbia

Universitaet Hamburg

Original Assignee

University of British Columbia

Universitaet Hamburg

Priority date (The priority date 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 date listed.)

2014-02-14

Filing date

2015-02-14

Publication date

2016-02-11

2015-02-14 Application filed by University of British Columbia, Universitaet Hamburg filed Critical University of British Columbia

2016-02-11 Publication of CA2939655A1 publication Critical patent/CA2939655A1/fr

Status Abandoned legal-status Critical Current

Links

102000004018 Caspase 6 Human genes 0.000 title claims description 70
108090000425 Caspase 6 Proteins 0.000 title claims description 70
239000000203 mixture Substances 0.000 claims abstract description 70
208000012902 Nervous system disease Diseases 0.000 claims abstract description 26
208000025966 Neurological disease Diseases 0.000 claims abstract description 26
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 21
238000002347 injection Methods 0.000 claims abstract description 9
239000007924 injection Substances 0.000 claims abstract description 9
238000001802 infusion Methods 0.000 claims abstract description 6
238000010254 subcutaneous injection Methods 0.000 claims abstract description 4
238000010255 intramuscular injection Methods 0.000 claims abstract description 3
239000007927 intramuscular injection Substances 0.000 claims abstract description 3
238000010253 intravenous injection Methods 0.000 claims abstract description 3
238000011200 topical administration Methods 0.000 claims abstract 2
210000004027 cell Anatomy 0.000 claims description 39
238000000034 method Methods 0.000 claims description 34
150000003839 salts Chemical class 0.000 claims description 26
239000013543 active substance Substances 0.000 claims description 19
239000003814 drug Substances 0.000 claims description 19
229940079593 drug Drugs 0.000 claims description 17
208000023105 Huntington disease Diseases 0.000 claims description 15
208000024827 Alzheimer disease Diseases 0.000 claims description 13
239000000651 prodrug Substances 0.000 claims description 13
229940002612 prodrug Drugs 0.000 claims description 13
210000003169 central nervous system Anatomy 0.000 claims description 12
239000000546 pharmaceutical excipient Substances 0.000 claims description 7
208000010877 cognitive disease Diseases 0.000 claims description 6
201000010099 disease Diseases 0.000 claims description 6
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 6
ASUTZQLVASHGKV-JDFRZJQESA-N galanthamine Chemical compound O1C(=C23)C(OC)=CC=C2CN(C)CC[C@]23[C@@H]1C[C@@H](O)C=C2 ASUTZQLVASHGKV-JDFRZJQESA-N 0.000 claims description 6
208000000044 Amnesia Diseases 0.000 claims description 5
206010012289 Dementia Diseases 0.000 claims description 5
208000026139 Memory disease Diseases 0.000 claims description 5
125000003118 aryl group Chemical group 0.000 claims description 5
230000006984 memory degeneration Effects 0.000 claims description 5
208000023060 memory loss Diseases 0.000 claims description 5
108020004999 messenger RNA Proteins 0.000 claims description 5
208000027061 mild cognitive impairment Diseases 0.000 claims description 5
208000024891 symptom Diseases 0.000 claims description 5
125000002877 alkyl aryl group Chemical group 0.000 claims description 4
229910052736 halogen Inorganic materials 0.000 claims description 4
150000002367 halogens Chemical class 0.000 claims description 4
230000002401 inhibitory effect Effects 0.000 claims description 4
MKJIEFSOBYUXJB-UHFFFAOYSA-N 9,10-dimethoxy-3-isobutyl-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-one Chemical compound C1CN2CC(CC(C)C)C(=O)CC2C2=C1C=C(OC)C(OC)=C2 MKJIEFSOBYUXJB-UHFFFAOYSA-N 0.000 claims description 3
101150043003 Htt gene Proteins 0.000 claims description 3
WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 claims description 3
WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 claims description 3
XSVMFMHYUFZWBK-NSHDSACASA-N Rivastigmine Chemical compound CCN(C)C(=O)OC1=CC=CC([C@H](C)N(C)C)=C1 XSVMFMHYUFZWBK-NSHDSACASA-N 0.000 claims description 3
XWAIAVWHZJNZQQ-UHFFFAOYSA-N donepezil hydrochloride Chemical compound [H+].[Cl-].O=C1C=2C=C(OC)C(OC)=CC=2CC1CC(CC1)CCN1CC1=CC=CC=C1 XWAIAVWHZJNZQQ-UHFFFAOYSA-N 0.000 claims description 3
229960003135 donepezil hydrochloride Drugs 0.000 claims description 3
229960003980 galantamine Drugs 0.000 claims description 3
ASUTZQLVASHGKV-UHFFFAOYSA-N galanthamine hydrochloride Natural products O1C(=C23)C(OC)=CC=C2CN(C)CCC23C1CC(O)C=C2 ASUTZQLVASHGKV-UHFFFAOYSA-N 0.000 claims description 3
238000007913 intrathecal administration Methods 0.000 claims description 3
LDDHMLJTFXJGPI-UHFFFAOYSA-N memantine hydrochloride Chemical compound Cl.C1C(C2)CC3(C)CC1(C)CC2(N)C3 LDDHMLJTFXJGPI-UHFFFAOYSA-N 0.000 claims description 3
229960000967 memantine hydrochloride Drugs 0.000 claims description 3
210000003061 neural cell Anatomy 0.000 claims description 3
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
RUOKEQAAGRXIBM-GFCCVEGCSA-N rasagiline Chemical compound C1=CC=C2[C@H](NCC#C)CCC2=C1 RUOKEQAAGRXIBM-GFCCVEGCSA-N 0.000 claims description 3
229960000245 rasagiline Drugs 0.000 claims description 3
229960004136 rivastigmine Drugs 0.000 claims description 3
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 2
KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 claims description 2
125000003342 alkenyl group Chemical group 0.000 claims description 2
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
229910052701 rubidium Inorganic materials 0.000 claims description 2
125000005213 alkyl heteroaryl group Chemical group 0.000 claims 1
229940123098 caspase 6 inhibitor Drugs 0.000 abstract description 7
150000001875 compounds Chemical class 0.000 description 73
-1 sodium chloride Chemical class 0.000 description 50
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 33
239000012634 fragment Substances 0.000 description 31
238000003776 cleavage reaction Methods 0.000 description 30
230000007017 scission Effects 0.000 description 30
235000002639 sodium chloride Nutrition 0.000 description 22
238000005481 NMR spectroscopy Methods 0.000 description 20
239000003795 chemical substances by application Substances 0.000 description 20
238000001262 western blot Methods 0.000 description 19
150000001413 amino acids Chemical class 0.000 description 18
229920000642 polymer Polymers 0.000 description 17
235000018102 proteins Nutrition 0.000 description 16
108090000623 proteins and genes Proteins 0.000 description 16
102000004169 proteins and genes Human genes 0.000 description 16
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 15
235000001014 amino acid Nutrition 0.000 description 15
239000013592 cell lysate Substances 0.000 description 15
239000013078 crystal Substances 0.000 description 15
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 15
238000002866 fluorescence resonance energy transfer Methods 0.000 description 14
239000003921 oil Substances 0.000 description 14
235000019198 oils Nutrition 0.000 description 14
238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 13
230000001537 neural effect Effects 0.000 description 13
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 12
210000004556 brain Anatomy 0.000 description 12
229940127255 pan-caspase inhibitor Drugs 0.000 description 12
239000002253 acid Substances 0.000 description 11
230000000694 effects Effects 0.000 description 11
239000000796 flavoring agent Substances 0.000 description 11
238000009472 formulation Methods 0.000 description 11
150000002632 lipids Chemical class 0.000 description 11
229920001223 polyethylene glycol Polymers 0.000 description 11
229920001577 copolymer Polymers 0.000 description 10
230000003834 intracellular effect Effects 0.000 description 10
101000741087 Homo sapiens Caspase-6 Proteins 0.000 description 9
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 9
239000003599 detergent Substances 0.000 description 9
235000019634 flavors Nutrition 0.000 description 9
230000014509 gene expression Effects 0.000 description 9
102000048544 human CASP6 Human genes 0.000 description 9
239000002502 liposome Substances 0.000 description 9
150000003904 phospholipids Chemical class 0.000 description 9
HJZZEVFDPBDIDQ-UHFFFAOYSA-N 3-phenylprop-2-ynamide Chemical compound NC(=O)C#CC1=CC=CC=C1 HJZZEVFDPBDIDQ-UHFFFAOYSA-N 0.000 description 8
102000011727 Caspases Human genes 0.000 description 8
108010076667 Caspases Proteins 0.000 description 8
230000004913 activation Effects 0.000 description 8
HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 8
231100000673 dose–response relationship Toxicity 0.000 description 8
230000001965 increasing effect Effects 0.000 description 8
239000003112 inhibitor Substances 0.000 description 8
230000004770 neurodegeneration Effects 0.000 description 8
239000002245 particle Substances 0.000 description 8
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 8
229920000036 polyvinylpyrrolidone Polymers 0.000 description 8
239000000243 solution Substances 0.000 description 8
239000004094 surface-active agent Substances 0.000 description 8
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
102000006835 Lamins Human genes 0.000 description 7
108010047294 Lamins Proteins 0.000 description 7
VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 7
241000699670 Mus sp. Species 0.000 description 7
239000011324 bead Substances 0.000 description 7
239000000872 buffer Substances 0.000 description 7
210000005053 lamin Anatomy 0.000 description 7
239000007788 liquid Substances 0.000 description 7
239000006166 lysate Substances 0.000 description 7
210000002569 neuron Anatomy 0.000 description 7
239000004014 plasticizer Substances 0.000 description 7
108090000765 processed proteins & peptides Proteins 0.000 description 7
239000002904 solvent Substances 0.000 description 7
230000001225 therapeutic effect Effects 0.000 description 7
239000001993 wax Substances 0.000 description 7
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 6
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
229920003134 Eudragit® polymer Polymers 0.000 description 6
229920002153 Hydroxypropyl cellulose Polymers 0.000 description 6
TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 6
HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 description 6
239000004480 active ingredient Substances 0.000 description 6
235000010443 alginic acid Nutrition 0.000 description 6
229920000615 alginic acid Polymers 0.000 description 6
125000000217 alkyl group Chemical group 0.000 description 6
238000003556 assay Methods 0.000 description 6
239000011230 binding agent Substances 0.000 description 6
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
238000001514 detection method Methods 0.000 description 6
238000010790 dilution Methods 0.000 description 6
239000012895 dilution Substances 0.000 description 6
235000011187 glycerol Nutrition 0.000 description 6
235000010977 hydroxypropyl cellulose Nutrition 0.000 description 6
239000001863 hydroxypropyl cellulose Substances 0.000 description 6
238000011534 incubation Methods 0.000 description 6
239000012139 lysis buffer Substances 0.000 description 6
239000000463 material Substances 0.000 description 6
239000013642 negative control Substances 0.000 description 6
239000000047 product Substances 0.000 description 6
230000009467 reduction Effects 0.000 description 6
239000011780 sodium chloride Substances 0.000 description 6
239000000725 suspension Substances 0.000 description 6
238000001890 transfection Methods 0.000 description 6
230000035899 viability Effects 0.000 description 6
VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 5
KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 description 5
102000008201 Lamin Type A Human genes 0.000 description 5
108010021099 Lamin Type A Proteins 0.000 description 5
229920000881 Modified starch Polymers 0.000 description 5
WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 5
DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 5
238000010521 absorption reaction Methods 0.000 description 5
239000011575 calcium Substances 0.000 description 5
VSJKWCGYPAHWDS-FQEVSTJZSA-N camptothecin Chemical compound C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-FQEVSTJZSA-N 0.000 description 5
229940127093 camptothecin Drugs 0.000 description 5
235000010980 cellulose Nutrition 0.000 description 5
229920002678 cellulose Polymers 0.000 description 5
239000001913 cellulose Substances 0.000 description 5
235000012000 cholesterol Nutrition 0.000 description 5
235000014113 dietary fatty acids Nutrition 0.000 description 5
VSJKWCGYPAHWDS-UHFFFAOYSA-N dl-camptothecin Natural products C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)C5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-UHFFFAOYSA-N 0.000 description 5
LYCAIKOWRPUZTN-UHFFFAOYSA-N ethylene glycol Natural products OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 5
231100000318 excitotoxic Toxicity 0.000 description 5
230000003492 excitotoxic effect Effects 0.000 description 5
239000000194 fatty acid Substances 0.000 description 5
229930195729 fatty acid Natural products 0.000 description 5
239000000499 gel Substances 0.000 description 5
230000003993 interaction Effects 0.000 description 5
239000000314 lubricant Substances 0.000 description 5
239000002105 nanoparticle Substances 0.000 description 5
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical class CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 5
239000001267 polyvinylpyrrolidone Substances 0.000 description 5
238000002360 preparation method Methods 0.000 description 5
102000004196 processed proteins & peptides Human genes 0.000 description 5
235000019333 sodium laurylsulphate Nutrition 0.000 description 5
239000007787 solid Substances 0.000 description 5
239000006228 supernatant Substances 0.000 description 5
239000003826 tablet Substances 0.000 description 5
GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 4
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 4
NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 4
101710137189 Amyloid-beta A4 protein Proteins 0.000 description 4
101710151993 Amyloid-beta precursor protein Proteins 0.000 description 4
102100022704 Amyloid-beta precursor protein Human genes 0.000 description 4
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
241000416162 Astragalus gummifer Species 0.000 description 4
229920000858 Cyclodextrin Polymers 0.000 description 4
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 4
229920003171 Poly (ethylene oxide) Polymers 0.000 description 4
239000002202 Polyethylene glycol Substances 0.000 description 4
229940124158 Protease/peptidase inhibitor Drugs 0.000 description 4
108091006629 SLC13A2 Proteins 0.000 description 4
229920002125 Sokalan® Polymers 0.000 description 4
229920001615 Tragacanth Polymers 0.000 description 4
GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 4
150000007513 acids Chemical class 0.000 description 4
DZHSAHHDTRWUTF-SIQRNXPUSA-N amyloid-beta polypeptide 42 Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O)[C@@H](C)CC)C(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C(C)C)C1=CC=CC=C1 DZHSAHHDTRWUTF-SIQRNXPUSA-N 0.000 description 4
235000013871 bee wax Nutrition 0.000 description 4
239000012166 beeswax Substances 0.000 description 4
230000015572 biosynthetic process Effects 0.000 description 4
OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 4
230000007816 cleavage of lamin Effects 0.000 description 4
239000003086 colorant Substances 0.000 description 4
239000003431 cross linking reagent Substances 0.000 description 4
230000003111 delayed effect Effects 0.000 description 4
239000007884 disintegrant Substances 0.000 description 4
239000003623 enhancer Substances 0.000 description 4
235000003599 food sweetener Nutrition 0.000 description 4
235000004554 glutamine Nutrition 0.000 description 4
230000002209 hydrophobic effect Effects 0.000 description 4
238000000338 in vitro Methods 0.000 description 4
239000010410 layer Substances 0.000 description 4
239000002609 medium Substances 0.000 description 4
208000015122 neurodegenerative disease Diseases 0.000 description 4
JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 4
239000000137 peptide hydrolase inhibitor Substances 0.000 description 4
229920001184 polypeptide Polymers 0.000 description 4
229910052700 potassium Inorganic materials 0.000 description 4
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 4
239000003765 sweetening agent Substances 0.000 description 4
URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 description 4
IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 3
238000005160 1H NMR spectroscopy Methods 0.000 description 3
JNMOSHIXQDVFGD-UHFFFAOYSA-N 3-(2-chlorophenyl)prop-2-ynamide Chemical compound NC(=O)C#CC1=CC=CC=C1Cl JNMOSHIXQDVFGD-UHFFFAOYSA-N 0.000 description 3
FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 3
WRDABNWSWOHGMS-UHFFFAOYSA-N AEBSF hydrochloride Chemical compound Cl.NCCC1=CC=C(S(F)(=O)=O)C=C1 WRDABNWSWOHGMS-UHFFFAOYSA-N 0.000 description 3
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
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 3
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 3
238000002965 ELISA Methods 0.000 description 3
108010010803 Gelatin Proteins 0.000 description 3
101001030705 Homo sapiens Huntingtin Proteins 0.000 description 3
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 3
KXGQENXQQUVFSI-UHFFFAOYSA-N OC(=O)C(C)C(=O)NC(=O)C#CC1=CC=CC=C1 Chemical compound OC(=O)C(C)C(=O)NC(=O)C#CC1=CC=CC=C1 KXGQENXQQUVFSI-UHFFFAOYSA-N 0.000 description 3
229920002845 Poly(methacrylic acid) Polymers 0.000 description 3
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
229920002472 Starch Polymers 0.000 description 3
235000021355 Stearic acid Nutrition 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
239000007983 Tris buffer Substances 0.000 description 3
DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 3
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
229920013820 alkyl cellulose Polymers 0.000 description 3
QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 3
239000003963 antioxidant agent Substances 0.000 description 3
235000006708 antioxidants Nutrition 0.000 description 3
229910052791 calcium Inorganic materials 0.000 description 3
229960005069 calcium Drugs 0.000 description 3
239000004203 carnauba wax Substances 0.000 description 3
235000013869 carnauba wax Nutrition 0.000 description 3
125000002091 cationic group Chemical group 0.000 description 3
239000002738 chelating agent Substances 0.000 description 3
239000003153 chemical reaction reagent Substances 0.000 description 3
238000000576 coating method Methods 0.000 description 3
238000013270 controlled release Methods 0.000 description 3
230000001054 cortical effect Effects 0.000 description 3
229940097362 cyclodextrins Drugs 0.000 description 3
MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 3
239000006185 dispersion Substances 0.000 description 3
239000000975 dye Substances 0.000 description 3
239000000839 emulsion Substances 0.000 description 3
235000019441 ethanol Nutrition 0.000 description 3
GDCRSXZBSIRSFR-UHFFFAOYSA-N ethyl prop-2-enoate;2-methylprop-2-enoic acid Chemical compound CC(=C)C(O)=O.CCOC(=O)C=C GDCRSXZBSIRSFR-UHFFFAOYSA-N 0.000 description 3
150000004665 fatty acids Chemical class 0.000 description 3
230000006870 function Effects 0.000 description 3
229920000159 gelatin Polymers 0.000 description 3
239000008273 gelatin Substances 0.000 description 3
235000019322 gelatine Nutrition 0.000 description 3
235000011852 gelatine desserts Nutrition 0.000 description 3
ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 3
102000054185 human HTT Human genes 0.000 description 3
235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 3
229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 3
239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 3
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 3
150000003949 imides Chemical class 0.000 description 3
230000005764 inhibitory process Effects 0.000 description 3
229910052749 magnesium Inorganic materials 0.000 description 3
229910001629 magnesium chloride Inorganic materials 0.000 description 3
229920000609 methyl cellulose Polymers 0.000 description 3
239000001923 methylcellulose Substances 0.000 description 3
235000010981 methylcellulose Nutrition 0.000 description 3
239000000693 micelle Substances 0.000 description 3
239000004005 microsphere Substances 0.000 description 3
235000019426 modified starch Nutrition 0.000 description 3
231100000252 nontoxic Toxicity 0.000 description 3
230000003000 nontoxic effect Effects 0.000 description 3
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 3
235000010987 pectin Nutrition 0.000 description 3
239000001814 pectin Substances 0.000 description 3
229920001277 pectin Polymers 0.000 description 3
229960000502 poloxamer Drugs 0.000 description 3
229920001983 poloxamer Polymers 0.000 description 3
229920000728 polyester Polymers 0.000 description 3
229920001451 polypropylene glycol Polymers 0.000 description 3
229920000136 polysorbate Polymers 0.000 description 3
239000011591 potassium Substances 0.000 description 3
229940069328 povidone Drugs 0.000 description 3
239000003755 preservative agent Substances 0.000 description 3
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
230000008569 process Effects 0.000 description 3
238000012545 processing Methods 0.000 description 3
235000013772 propylene glycol Nutrition 0.000 description 3
229960004063 propylene glycol Drugs 0.000 description 3
238000010992 reflux Methods 0.000 description 3
150000003384 small molecules Chemical class 0.000 description 3
235000010413 sodium alginate Nutrition 0.000 description 3
239000000661 sodium alginate Substances 0.000 description 3
229940005550 sodium alginate Drugs 0.000 description 3
239000000600 sorbitol Substances 0.000 description 3
235000019698 starch Nutrition 0.000 description 3
239000008117 stearic acid Substances 0.000 description 3
239000000758 substrate Substances 0.000 description 3
238000013268 sustained release Methods 0.000 description 3
230000000699 topical effect Effects 0.000 description 3
231100000419 toxicity Toxicity 0.000 description 3
230000001988 toxicity Effects 0.000 description 3
235000010487 tragacanth Nutrition 0.000 description 3
239000000196 tragacanth Substances 0.000 description 3
229940116362 tragacanth Drugs 0.000 description 3
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 3
239000000080 wetting agent Substances 0.000 description 3
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 2
ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 2
CZLAYBBZHRVSPT-UHFFFAOYSA-N 1,3-oxazin-6-one Chemical class O=C1C=CN=CO1 CZLAYBBZHRVSPT-UHFFFAOYSA-N 0.000 description 2
JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical compound OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 description 2
PBDAIWZGBTWPKK-UHFFFAOYSA-N 3-(4-bromophenyl)prop-2-ynamide Chemical compound NC(=O)C#CC1=CC=C(Br)C=C1 PBDAIWZGBTWPKK-UHFFFAOYSA-N 0.000 description 2
NCOLGLKJDBTXEB-UHFFFAOYSA-N 3-(4-chlorophenyl)prop-2-ynamide Chemical compound NC(=O)C#CC1=CC=C(Cl)C=C1 NCOLGLKJDBTXEB-UHFFFAOYSA-N 0.000 description 2
VWFHGJNGWZLBEF-UHFFFAOYSA-N 3-(4-nitrophenyl)prop-2-ynamide Chemical compound NC(=O)C#CC1=CC=C([N+]([O-])=O)C=C1 VWFHGJNGWZLBEF-UHFFFAOYSA-N 0.000 description 2
UMCMPZBLKLEWAF-BCTGSCMUSA-N 3-[(3-cholamidopropyl)dimethylammonio]propane-1-sulfonate Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCC[N+](C)(C)CCCS([O-])(=O)=O)C)[C@@]2(C)[C@@H](O)C1 UMCMPZBLKLEWAF-BCTGSCMUSA-N 0.000 description 2
OFISGXWFFIBNCO-UHFFFAOYSA-N 4-hydroxy-1,3-oxazin-6-one Chemical class OC1=CC(=O)OC=N1 OFISGXWFFIBNCO-UHFFFAOYSA-N 0.000 description 2
244000215068 Acacia senegal Species 0.000 description 2
102000007469 Actins Human genes 0.000 description 2
108010085238 Actins Proteins 0.000 description 2
229920001817 Agar Polymers 0.000 description 2
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
241000167854 Bourreria succulenta Species 0.000 description 2
108091003079 Bovine Serum Albumin Proteins 0.000 description 2
239000004322 Butylated hydroxytoluene Substances 0.000 description 2
NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 2
WNAWOIOGJYVKRK-UHFFFAOYSA-N C=1C=CC=CC=1C#CC(=O)NC(=O)CC1=CC=CC=C1 Chemical compound C=1C=CC=CC=1C#CC(=O)NC(=O)CC1=CC=CC=C1 WNAWOIOGJYVKRK-UHFFFAOYSA-N 0.000 description 2
102000003952 Caspase 3 Human genes 0.000 description 2
108090000397 Caspase 3 Proteins 0.000 description 2
229920002261 Corn starch Polymers 0.000 description 2
229920002785 Croscarmellose sodium Polymers 0.000 description 2
244000007835 Cyamopsis tetragonoloba Species 0.000 description 2
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 2
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
239000006144 Dulbecco’s modiﬁed Eagle's medium Substances 0.000 description 2
KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
102000004190 Enzymes Human genes 0.000 description 2
108090000790 Enzymes Proteins 0.000 description 2
229920003139 Eudragit® L 100 Polymers 0.000 description 2
229920003135 Eudragit® L 100-55 Polymers 0.000 description 2
229920003141 Eudragit® S 100 Polymers 0.000 description 2
238000011771 FVB mouse Methods 0.000 description 2
229920000084 Gum arabic Polymers 0.000 description 2
229920000569 Gum karaya Polymers 0.000 description 2
HVLSXIKZNLPZJJ-TXZCQADKSA-N HA peptide Chemical group C([C@@H](C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](C)C(O)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=C(O)C=C1 HVLSXIKZNLPZJJ-TXZCQADKSA-N 0.000 description 2
239000007995 HEPES buffer Substances 0.000 description 2
229920000663 Hydroxyethyl cellulose Polymers 0.000 description 2
239000004354 Hydroxyethyl cellulose Substances 0.000 description 2
229920001479 Hydroxyethyl methyl cellulose Polymers 0.000 description 2
ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Chemical compound CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 2
OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 description 2
BAPJBEWLBFYGME-UHFFFAOYSA-N Methyl acrylate Chemical compound COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 description 2
229920000168 Microcrystalline cellulose Polymers 0.000 description 2
229930182555 Penicillin Natural products 0.000 description 2
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 2
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
229920000148 Polycarbophil calcium Polymers 0.000 description 2
239000004372 Polyvinyl alcohol Substances 0.000 description 2
WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
ZTHYODDOHIVTJV-UHFFFAOYSA-N Propyl gallate Chemical compound CCCOC(=O)C1=CC(O)=C(O)C(O)=C1 ZTHYODDOHIVTJV-UHFFFAOYSA-N 0.000 description 2
229920001800 Shellac Polymers 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
238000000692 Student's t-test Methods 0.000 description 2
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 2
229930006000 Sucrose Natural products 0.000 description 2
ULUAUXLGCMPNKK-UHFFFAOYSA-N Sulfobutanedioic acid Chemical class OC(=O)CC(C(O)=O)S(O)(=O)=O ULUAUXLGCMPNKK-UHFFFAOYSA-N 0.000 description 2
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
ZFOZVQLOBQUTQQ-UHFFFAOYSA-N Tributyl citrate Chemical compound CCCCOC(=O)CC(O)(C(=O)OCCCC)CC(=O)OCCCC ZFOZVQLOBQUTQQ-UHFFFAOYSA-N 0.000 description 2
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
229930003427 Vitamin E Natural products 0.000 description 2
235000009754 Vitis X bourquina Nutrition 0.000 description 2
235000012333 Vitis X labruscana Nutrition 0.000 description 2
240000006365 Vitis vinifera Species 0.000 description 2
235000014787 Vitis vinifera Nutrition 0.000 description 2
238000002835 absorbance Methods 0.000 description 2
239000002250 absorbent Substances 0.000 description 2
230000002745 absorbent Effects 0.000 description 2
235000010489 acacia gum Nutrition 0.000 description 2
150000008065 acid anhydrides Chemical class 0.000 description 2
239000008186 active pharmaceutical agent Substances 0.000 description 2
239000008272 agar Substances 0.000 description 2
235000010419 agar Nutrition 0.000 description 2
229910052783 alkali metal Inorganic materials 0.000 description 2
150000001336 alkenes Chemical class 0.000 description 2
229940061720 alpha hydroxy acid Drugs 0.000 description 2
150000001280 alpha hydroxy acids Chemical class 0.000 description 2
150000001412 amines Chemical class 0.000 description 2
235000011114 ammonium hydroxide Nutrition 0.000 description 2
230000006907 apoptotic process Effects 0.000 description 2
239000007864 aqueous solution Substances 0.000 description 2
230000003376 axonal effect Effects 0.000 description 2
239000000440 bentonite Substances 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
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
239000003833 bile salt Substances 0.000 description 2
229940093761 bile salts Drugs 0.000 description 2
239000000227 bioadhesive Substances 0.000 description 2
230000008499 blood brain barrier function Effects 0.000 description 2
210000001218 blood-brain barrier Anatomy 0.000 description 2
210000000133 brain stem Anatomy 0.000 description 2
210000005013 brain tissue Anatomy 0.000 description 2
239000006172 buffering agent Substances 0.000 description 2
235000010354 butylated hydroxytoluene Nutrition 0.000 description 2
229940095259 butylated hydroxytoluene Drugs 0.000 description 2
210000004899 c-terminal region Anatomy 0.000 description 2
235000011132 calcium sulphate Nutrition 0.000 description 2
239000002775 capsule Substances 0.000 description 2
229960001631 carbomer Drugs 0.000 description 2
238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 2
229940084030 carboxymethylcellulose calcium Drugs 0.000 description 2
238000005119 centrifugation Methods 0.000 description 2
238000006243 chemical reaction Methods 0.000 description 2
235000019693 cherries Nutrition 0.000 description 2
239000007958 cherry flavor Substances 0.000 description 2
OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
229940125773 compound 10 Drugs 0.000 description 2
239000008120 corn starch Substances 0.000 description 2
210000003618 cortical neuron Anatomy 0.000 description 2
229960001681 croscarmellose sodium Drugs 0.000 description 2
229960000913 crospovidone Drugs 0.000 description 2
235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 2
210000004748 cultured cell Anatomy 0.000 description 2
238000006114 decarboxylation reaction Methods 0.000 description 2
230000007850 degeneration Effects 0.000 description 2
238000010217 densitometric analysis Methods 0.000 description 2
ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 2
239000002612 dispersion medium Substances 0.000 description 2
239000003937 drug carrier Substances 0.000 description 2
238000012377 drug delivery Methods 0.000 description 2
235000013399 edible fruits Nutrition 0.000 description 2
238000010828 elution Methods 0.000 description 2
LZCLXQDLBQLTDK-UHFFFAOYSA-N ethyl 2-hydroxypropanoate Chemical compound CCOC(=O)C(C)O LZCLXQDLBQLTDK-UHFFFAOYSA-N 0.000 description 2
230000005284 excitation Effects 0.000 description 2
239000012091 fetal bovine serum Substances 0.000 description 2
235000013355 food flavoring agent Nutrition 0.000 description 2
WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 2
239000007789 gas Substances 0.000 description 2
210000001035 gastrointestinal tract Anatomy 0.000 description 2
229940075507 glyceryl monostearate Drugs 0.000 description 2
235000013773 glyceryl triacetate Nutrition 0.000 description 2
239000001087 glyceryl triacetate Substances 0.000 description 2
150000002334 glycols Chemical class 0.000 description 2
229920000591 gum Polymers 0.000 description 2
230000007062 hydrolysis Effects 0.000 description 2
238000006460 hydrolysis reaction Methods 0.000 description 2
229920001477 hydrophilic polymer Polymers 0.000 description 2
229920013821 hydroxy alkyl cellulose Polymers 0.000 description 2
235000019447 hydroxyethyl cellulose Nutrition 0.000 description 2
229920003063 hydroxymethyl cellulose Polymers 0.000 description 2
229940031574 hydroxymethyl cellulose Drugs 0.000 description 2
238000003384 imaging method Methods 0.000 description 2
230000006872 improvement Effects 0.000 description 2
150000007529 inorganic bases Chemical class 0.000 description 2
238000000185 intracerebroventricular administration Methods 0.000 description 2
238000001990 intravenous administration Methods 0.000 description 2
ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 2
235000010494 karaya gum Nutrition 0.000 description 2
KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
239000011777 magnesium Substances 0.000 description 2
229910052943 magnesium sulfate Inorganic materials 0.000 description 2
235000019341 magnesium sulphate Nutrition 0.000 description 2
229960001855 mannitol Drugs 0.000 description 2
238000004519 manufacturing process Methods 0.000 description 2
239000011159 matrix material Substances 0.000 description 2
230000001404 mediated effect Effects 0.000 description 2
239000012528 membrane Substances 0.000 description 2
239000004530 micro-emulsion Substances 0.000 description 2
229940016286 microcrystalline cellulose Drugs 0.000 description 2
239000008108 microcrystalline cellulose Substances 0.000 description 2
235000019813 microcrystalline cellulose Nutrition 0.000 description 2
239000004200 microcrystalline wax Substances 0.000 description 2
235000019808 microcrystalline wax Nutrition 0.000 description 2
239000001788 mono and diglycerides of fatty acids Substances 0.000 description 2
239000002077 nanosphere Substances 0.000 description 2
230000006764 neuronal dysfunction Effects 0.000 description 2
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 2
239000006186 oral dosage form Substances 0.000 description 2
150000007524 organic acids Chemical class 0.000 description 2
150000007530 organic bases Chemical class 0.000 description 2
239000012044 organic layer Substances 0.000 description 2
239000003960 organic solvent Substances 0.000 description 2
239000002357 osmotic agent Substances 0.000 description 2
230000003647 oxidation Effects 0.000 description 2
238000007254 oxidation reaction Methods 0.000 description 2
229940049954 penicillin Drugs 0.000 description 2
230000035699 permeability Effects 0.000 description 2
239000000825 pharmaceutical preparation Substances 0.000 description 2
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 2
229920003229 poly(methyl methacrylate) Polymers 0.000 description 2
229920002401 polyacrylamide Polymers 0.000 description 2
229920000058 polyacrylate Polymers 0.000 description 2
229950005134 polycarbophil Drugs 0.000 description 2
229920000155 polyglutamine Polymers 0.000 description 2
108010040003 polyglutamine Proteins 0.000 description 2
229920005862 polyol Polymers 0.000 description 2
150000003077 polyols Chemical class 0.000 description 2
235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 2
229920001282 polysaccharide Polymers 0.000 description 2
239000005017 polysaccharide Substances 0.000 description 2
150000004804 polysaccharides Chemical class 0.000 description 2
229940068968 polysorbate 80 Drugs 0.000 description 2
229920000053 polysorbate 80 Polymers 0.000 description 2
229920002451 polyvinyl alcohol Polymers 0.000 description 2
235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 2
229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 2
239000011148 porous material Substances 0.000 description 2
239000013641 positive control Substances 0.000 description 2
229920001592 potato starch Polymers 0.000 description 2
239000000843 powder Substances 0.000 description 2
230000006337 proteolytic cleavage Effects 0.000 description 2
150000003242 quaternary ammonium salts Chemical class 0.000 description 2
210000002966 serum Anatomy 0.000 description 2
239000004208 shellac Substances 0.000 description 2
229940113147 shellac Drugs 0.000 description 2
ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 2
235000013874 shellac Nutrition 0.000 description 2
239000000344 soap Substances 0.000 description 2
239000001632 sodium acetate Substances 0.000 description 2
235000017281 sodium acetate Nutrition 0.000 description 2
229920003109 sodium starch glycolate Polymers 0.000 description 2
239000008109 sodium starch glycolate Substances 0.000 description 2
229940079832 sodium starch glycolate Drugs 0.000 description 2
GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 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
239000003549 soybean oil Substances 0.000 description 2
235000012424 soybean oil Nutrition 0.000 description 2
229960005322 streptomycin Drugs 0.000 description 2
KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
239000005720 sucrose Substances 0.000 description 2
235000000346 sugar Nutrition 0.000 description 2
150000008163 sugars Chemical class 0.000 description 2
230000002459 sustained effect Effects 0.000 description 2
239000012730 sustained-release form Substances 0.000 description 2
230000008961 swelling Effects 0.000 description 2
238000003786 synthesis reaction Methods 0.000 description 2
239000006188 syrup Substances 0.000 description 2
235000020357 syrup Nutrition 0.000 description 2
239000000454 talc Substances 0.000 description 2
229910052623 talc Inorganic materials 0.000 description 2
235000012222 talc Nutrition 0.000 description 2
239000011975 tartaric acid Substances 0.000 description 2
235000002906 tartaric acid Nutrition 0.000 description 2
238000012360 testing method Methods 0.000 description 2
210000001519 tissue Anatomy 0.000 description 2
231100000331 toxic Toxicity 0.000 description 2
230000002588 toxic effect Effects 0.000 description 2
229960002622 triacetin Drugs 0.000 description 2
210000003901 trigeminal nerve Anatomy 0.000 description 2
PIEPQKCYPFFYMG-UHFFFAOYSA-N tris acetate Chemical compound CC(O)=O.OCC(N)(CO)CO PIEPQKCYPFFYMG-UHFFFAOYSA-N 0.000 description 2
229960004418 trolamine Drugs 0.000 description 2
235000019165 vitamin E Nutrition 0.000 description 2
229940046009 vitamin E Drugs 0.000 description 2
239000011709 vitamin E Substances 0.000 description 2
229920003169 water-soluble polymer Polymers 0.000 description 2
229920001285 xanthan gum Polymers 0.000 description 2
FTLYMKDSHNWQKD-UHFFFAOYSA-N (2,4,5-trichlorophenyl)boronic acid Chemical compound OB(O)C1=CC(Cl)=C(Cl)C=C1Cl FTLYMKDSHNWQKD-UHFFFAOYSA-N 0.000 description 1
JQWAHKMIYCERGA-UHFFFAOYSA-N (2-nonanoyloxy-3-octadeca-9,12-dienoyloxypropoxy)-[2-(trimethylazaniumyl)ethyl]phosphinate Chemical compound CCCCCCCCC(=O)OC(COP([O-])(=O)CC[N+](C)(C)C)COC(=O)CCCCCCCC=CCC=CCCCCC JQWAHKMIYCERGA-UHFFFAOYSA-N 0.000 description 1
ASWBNKHCZGQVJV-UHFFFAOYSA-N (3-hexadecanoyloxy-2-hydroxypropyl) 2-(trimethylazaniumyl)ethyl phosphate Chemical compound CCCCCCCCCCCCCCCC(=O)OCC(O)COP([O-])(=O)OCC[N+](C)(C)C ASWBNKHCZGQVJV-UHFFFAOYSA-N 0.000 description 1
PXLGUMVBFSDYGK-UHFFFAOYSA-N (4-nitrophenyl)-(4-phenylphenyl)methanone Chemical compound C1=CC([N+](=O)[O-])=CC=C1C(=O)C1=CC=C(C=2C=CC=CC=2)C=C1 PXLGUMVBFSDYGK-UHFFFAOYSA-N 0.000 description 1
KILNVBDSWZSGLL-KXQOOQHDSA-N 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCCCC KILNVBDSWZSGLL-KXQOOQHDSA-N 0.000 description 1
SLKDGVPOSSLUAI-PGUFJCEWSA-N 1,2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine zwitterion Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OCCN)OC(=O)CCCCCCCCCCCCCCC SLKDGVPOSSLUAI-PGUFJCEWSA-N 0.000 description 1
PORPENFLTBBHSG-MGBGTMOVSA-N 1,2-dihexadecanoyl-sn-glycerol-3-phosphate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(O)=O)OC(=O)CCCCCCCCCCCCCCC PORPENFLTBBHSG-MGBGTMOVSA-N 0.000 description 1
NRJAVPSFFCBXDT-HUESYALOSA-N 1,2-distearoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCCCCCC NRJAVPSFFCBXDT-HUESYALOSA-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
PWMWNFMRSKOCEY-UHFFFAOYSA-N 1-Phenyl-1,2-ethanediol Chemical compound OCC(O)C1=CC=CC=C1 PWMWNFMRSKOCEY-UHFFFAOYSA-N 0.000 description 1
OKMWKBLSFKFYGZ-UHFFFAOYSA-N 1-behenoylglycerol Chemical compound CCCCCCCCCCCCCCCCCCCCCC(=O)OCC(O)CO OKMWKBLSFKFYGZ-UHFFFAOYSA-N 0.000 description 1
JOLQKTGDSGKSKJ-UHFFFAOYSA-N 1-ethoxypropan-2-ol Chemical compound CCOCC(C)O JOLQKTGDSGKSKJ-UHFFFAOYSA-N 0.000 description 1
JLPULHDHAOZNQI-ZTIMHPMXSA-N 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/C\C=C/CCCCC JLPULHDHAOZNQI-ZTIMHPMXSA-N 0.000 description 1
239000000263 2,3-dihydroxypropyl (Z)-octadec-9-enoate Substances 0.000 description 1
SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 1
FLPJVCMIKUWSDR-UHFFFAOYSA-N 2-(4-formylphenoxy)acetamide Chemical compound NC(=O)COC1=CC=C(C=O)C=C1 FLPJVCMIKUWSDR-UHFFFAOYSA-N 0.000 description 1
HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 1
UZSGWJQJDLCCFN-UHFFFAOYSA-N 2-acetylbenzonitrile Chemical compound CC(=O)C1=CC=CC=C1C#N UZSGWJQJDLCCFN-UHFFFAOYSA-N 0.000 description 1
OMQSILQQILEWFZ-UHFFFAOYSA-N 2-benzylpropanedioyl dichloride Chemical compound ClC(=O)C(C(Cl)=O)CC1=CC=CC=C1 OMQSILQQILEWFZ-UHFFFAOYSA-N 0.000 description 1
VKNASXZDGZNEDA-UHFFFAOYSA-N 2-cyanoethyl 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)OCCC#N VKNASXZDGZNEDA-UHFFFAOYSA-N 0.000 description 1
ZNQVEEAIQZEUHB-UHFFFAOYSA-N 2-ethoxyethanol Chemical compound CCOCCO ZNQVEEAIQZEUHB-UHFFFAOYSA-N 0.000 description 1
SFPNZPQIIAJXGL-UHFFFAOYSA-N 2-ethoxyethyl 2-methylprop-2-enoate Chemical class CCOCCOC(=O)C(C)=C SFPNZPQIIAJXGL-UHFFFAOYSA-N 0.000 description 1
ZFEKANLLFQEKED-UHFFFAOYSA-N 2-propan-2-yloxypropan-1-ol Chemical compound CC(C)OC(C)CO ZFEKANLLFQEKED-UHFFFAOYSA-N 0.000 description 1
KGWNRZLPXLBMPS-UHFFFAOYSA-N 2h-1,3-oxazine Chemical compound C1OC=CC=N1 KGWNRZLPXLBMPS-UHFFFAOYSA-N 0.000 description 1
MIDXCONKKJTLDX-UHFFFAOYSA-N 3,5-dimethylcyclopentane-1,2-dione Chemical compound CC1CC(C)C(=O)C1=O MIDXCONKKJTLDX-UHFFFAOYSA-N 0.000 description 1
RZRNAYUHWVFMIP-GDCKJWNLSA-N 3-oleoyl-sn-glycerol Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@H](O)CO RZRNAYUHWVFMIP-GDCKJWNLSA-N 0.000 description 1
ZDTNHRWWURISAA-UHFFFAOYSA-N 4',5'-dibromo-3',6'-dihydroxyspiro[2-benzofuran-3,9'-xanthene]-1-one Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C(Br)=C1OC1=C(Br)C(O)=CC=C21 ZDTNHRWWURISAA-UHFFFAOYSA-N 0.000 description 1
VQSUOQUUGBKIKX-UHFFFAOYSA-N 5-oxopent-4-enoyl chloride Chemical class ClC(=O)CCC=C=O VQSUOQUUGBKIKX-UHFFFAOYSA-N 0.000 description 1
GJCOSYZMQJWQCA-UHFFFAOYSA-N 9H-xanthene Chemical compound C1=CC=C2CC3=CC=CC=C3OC2=C1 GJCOSYZMQJWQCA-UHFFFAOYSA-N 0.000 description 1
235000006491 Acacia senegal Nutrition 0.000 description 1
QZCLKYGREBVARF-UHFFFAOYSA-N Acetyl tributyl citrate Chemical compound CCCCOC(=O)CC(C(=O)OCCCC)(OC(C)=O)CC(=O)OCCCC QZCLKYGREBVARF-UHFFFAOYSA-N 0.000 description 1
108091005508 Acid proteases Proteins 0.000 description 1
HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 1
NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 1
229920002126 Acrylic acid copolymer Polymers 0.000 description 1
229920000936 Agarose Polymers 0.000 description 1
235000019489 Almond oil Nutrition 0.000 description 1
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 1
WSVLPVUVIUVCRA-KPKNDVKVSA-N Alpha-lactose monohydrate Chemical compound O.O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O WSVLPVUVIUVCRA-KPKNDVKVSA-N 0.000 description 1
238000010173 Alzheimer-disease mouse model Methods 0.000 description 1
ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 1
244000144725 Amygdalus communis Species 0.000 description 1
244000144730 Amygdalus persica Species 0.000 description 1
208000037259 Amyloid Plaque Diseases 0.000 description 1
244000099147 Ananas comosus Species 0.000 description 1
235000007119 Ananas comosus Nutrition 0.000 description 1
108010011485 Aspartame Proteins 0.000 description 1
235000016068 Berberis vulgaris Nutrition 0.000 description 1
241000335053 Beta vulgaris Species 0.000 description 1
COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
MRABAEUHTLLEML-UHFFFAOYSA-N Butyl lactate Chemical compound CCCCOC(=O)C(C)O MRABAEUHTLLEML-UHFFFAOYSA-N 0.000 description 1
240000004160 Capsicum annuum Species 0.000 description 1
235000008534 Capsicum annuum var annuum Nutrition 0.000 description 1
229920000623 Cellulose acetate phthalate Polymers 0.000 description 1
235000013912 Ceratonia siliqua Nutrition 0.000 description 1
240000008886 Ceratonia siliqua Species 0.000 description 1
229920001661 Chitosan Polymers 0.000 description 1
206010008748 Chorea Diseases 0.000 description 1
244000037364 Cinnamomum aromaticum Species 0.000 description 1
235000014489 Cinnamomum aromaticum Nutrition 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
241000207199 Citrus Species 0.000 description 1
235000008733 Citrus aurantifolia Nutrition 0.000 description 1
235000005979 Citrus limon Nutrition 0.000 description 1
235000019499 Citrus oil Nutrition 0.000 description 1
244000131522 Citrus pyriformis Species 0.000 description 1
240000000560 Citrus x paradisi Species 0.000 description 1
IKIYFCXIRNJNPE-UHFFFAOYSA-N ClC(=O)CC(Cl)=O.ClC(=O)CCC=C=O Chemical compound ClC(=O)CC(Cl)=O.ClC(=O)CCC=C=O IKIYFCXIRNJNPE-UHFFFAOYSA-N 0.000 description 1
235000003392 Curcuma domestica Nutrition 0.000 description 1
244000008991 Curcuma longa Species 0.000 description 1
IELOKBJPULMYRW-NJQVLOCASA-N D-alpha-Tocopheryl Acid Succinate Chemical compound OC(=O)CCC(=O)OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C IELOKBJPULMYRW-NJQVLOCASA-N 0.000 description 1
ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 1
PYGXAGIECVVIOZ-UHFFFAOYSA-N Dibutyl decanedioate Chemical compound CCCCOC(=O)CCCCCCCCC(=O)OCCCC PYGXAGIECVVIOZ-UHFFFAOYSA-N 0.000 description 1
KLFKZIQAIPDJCW-HTIIIDOHSA-N Dipalmitoylphosphatidylserine Chemical compound CCCCCCCCCCCCCCCC(=O)OCC(COP(O)(=O)OC[C@H](N)C(O)=O)OC(=O)CCCCCCCCCCCCCCC KLFKZIQAIPDJCW-HTIIIDOHSA-N 0.000 description 1
241000196324 Embryophyta 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
244000004281 Eucalyptus maculata Species 0.000 description 1
229920003143 Eudragit® FS 30 D Polymers 0.000 description 1
229920003138 Eudragit® L 30 D-55 Polymers 0.000 description 1
229920003153 Eudragit® NE polymer Polymers 0.000 description 1
101710134671 Executioner caspase Proteins 0.000 description 1
235000016623 Fragaria vesca Nutrition 0.000 description 1
240000009088 Fragaria x ananassa Species 0.000 description 1
235000011363 Fragaria x ananassa Nutrition 0.000 description 1
229930091371 Fructose Natural products 0.000 description 1
RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
239000005715 Fructose Substances 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
JZNWSCPGTDBMEW-UHFFFAOYSA-N Glycerophosphorylethanolamin Natural products NCCOP(O)(=O)OCC(O)CO JZNWSCPGTDBMEW-UHFFFAOYSA-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-M Glycolate Chemical compound OCC([O-])=O AEMRFAOFKBGASW-UHFFFAOYSA-M 0.000 description 1
229920002907 Guar gum Polymers 0.000 description 1
235000019487 Hazelnut oil Nutrition 0.000 description 1
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
239000011786 L-ascorbyl-6-palmitate Substances 0.000 description 1
QAQJMLQRFWZOBN-LAUBAEHRSA-N L-ascorbyl-6-palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](O)[C@H]1OC(=O)C(O)=C1O QAQJMLQRFWZOBN-LAUBAEHRSA-N 0.000 description 1
JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
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 1
239000000232 Lipid Bilayer Substances 0.000 description 1
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
229920000161 Locust bean gum Polymers 0.000 description 1
241000220225 Malus Species 0.000 description 1
235000011430 Malus pumila Nutrition 0.000 description 1
235000015103 Malus silvestris Nutrition 0.000 description 1
229930195725 Mannitol Natural products 0.000 description 1
239000004368 Modified starch Substances 0.000 description 1
241001529936 Murinae Species 0.000 description 1
101001030698 Mus musculus Huntingtin Proteins 0.000 description 1
235000009421 Myristica fragrans Nutrition 0.000 description 1
244000270834 Myristica fragrans Species 0.000 description 1
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 1
208000034530 PLAA-associated neurodevelopmental disease Diseases 0.000 description 1
235000019483 Peanut oil Nutrition 0.000 description 1
239000004698 Polyethylene Substances 0.000 description 1
229920000954 Polyglycolide Polymers 0.000 description 1
239000004743 Polypropylene Substances 0.000 description 1
235000009827 Prunus armeniaca Nutrition 0.000 description 1
244000018633 Prunus armeniaca Species 0.000 description 1
235000003893 Prunus dulcis var amara Nutrition 0.000 description 1
235000006040 Prunus persica var persica Nutrition 0.000 description 1
235000014443 Pyrus communis Nutrition 0.000 description 1
240000001987 Pyrus communis Species 0.000 description 1
239000012083 RIPA buffer Substances 0.000 description 1
MUPFEKGTMRGPLJ-RMMQSMQOSA-N Raffinose Natural products O(C[C@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](O[C@@]2(CO)[C@H](O)[C@@H](O)[C@@H](CO)O2)O1)[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 MUPFEKGTMRGPLJ-RMMQSMQOSA-N 0.000 description 1
240000007651 Rubus glaucus Species 0.000 description 1
235000011034 Rubus glaucus Nutrition 0.000 description 1
235000009122 Rubus idaeus Nutrition 0.000 description 1
235000019485 Safflower oil 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
UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
BCKXLBQYZLBQEK-KVVVOXFISA-M Sodium oleate Chemical compound [Na+].CCCCCCCC\C=C/CCCCCCCC([O-])=O BCKXLBQYZLBQEK-KVVVOXFISA-M 0.000 description 1
241000934878 Sterculia Species 0.000 description 1
235000015125 Sterculia urens Nutrition 0.000 description 1
240000001058 Sterculia urens Species 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical class OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 description 1
235000019486 Sunflower oil Nutrition 0.000 description 1
102000000591 Tight Junction Proteins Human genes 0.000 description 1
108010002321 Tight Junction Proteins Proteins 0.000 description 1
235000011941 Tilia x europaea Nutrition 0.000 description 1
DOOTYTYQINUNNV-UHFFFAOYSA-N Triethyl citrate Chemical compound CCOC(=O)CC(O)(C(=O)OCC)CC(=O)OCC DOOTYTYQINUNNV-UHFFFAOYSA-N 0.000 description 1
238000010162 Tukey test Methods 0.000 description 1
MUPFEKGTMRGPLJ-UHFFFAOYSA-N UNPD196149 Natural products OC1C(O)C(CO)OC1(CO)OC1C(O)C(O)C(O)C(COC2C(C(O)C(O)C(CO)O2)O)O1 MUPFEKGTMRGPLJ-UHFFFAOYSA-N 0.000 description 1
235000009499 Vanilla fragrans Nutrition 0.000 description 1
244000263375 Vanilla tahitensis Species 0.000 description 1
235000012036 Vanilla tahitensis Nutrition 0.000 description 1
229930003268 Vitamin C Natural products 0.000 description 1
235000019498 Walnut oil 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
ATBOMIWRCZXYSZ-XZBBILGWSA-N [1-[2,3-dihydroxypropoxy(hydroxy)phosphoryl]oxy-3-hexadecanoyloxypropan-2-yl] (9e,12e)-octadeca-9,12-dienoate Chemical compound CCCCCCCCCCCCCCCC(=O)OCC(COP(O)(=O)OCC(O)CO)OC(=O)CCCCCCC\C=C\C\C=C\CCCCC ATBOMIWRCZXYSZ-XZBBILGWSA-N 0.000 description 1
230000005856 abnormality Effects 0.000 description 1
239000000205 acacia gum Substances 0.000 description 1
238000009825 accumulation Methods 0.000 description 1
OLXZMPJAKGJEDK-JVUUZWNBSA-N acetic acid (Z)-but-2-enedioic acid Chemical compound CC(O)=O.OC(=O)\C=C/C(O)=O.OC(=O)\C=C/C(O)=O.OC(=O)\C=C/C(O)=O OLXZMPJAKGJEDK-JVUUZWNBSA-N 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
229920006243 acrylic copolymer Polymers 0.000 description 1
229920006397 acrylic thermoplastic Polymers 0.000 description 1
230000002776 aggregation Effects 0.000 description 1
238000004220 aggregation Methods 0.000 description 1
150000001298 alcohols Chemical class 0.000 description 1
239000003513 alkali Substances 0.000 description 1
230000003113 alkalizing effect Effects 0.000 description 1
OENHQHLEOONYIE-UKMVMLAPSA-N all-trans beta-carotene Natural products CC=1CCCC(C)(C)C=1/C=C/C(/C)=C/C=C/C(/C)=C/C=C/C=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C OENHQHLEOONYIE-UKMVMLAPSA-N 0.000 description 1
230000003281 allosteric effect Effects 0.000 description 1
239000008168 almond oil Substances 0.000 description 1
AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 1
VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 1
229910052782 aluminium Inorganic materials 0.000 description 1
XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
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
150000001408 amides Chemical class 0.000 description 1
229920003144 amino alkyl methacrylate copolymer Polymers 0.000 description 1
235000010407 ammonium alginate Nutrition 0.000 description 1
239000000728 ammonium alginate Substances 0.000 description 1
KPGABFJTMYCRHJ-YZOKENDUSA-N ammonium alginate Chemical compound [NH4+].[NH4+].O1[C@@H](C([O-])=O)[C@@H](OC)[C@H](O)[C@H](O)[C@@H]1O[C@@H]1[C@@H](C([O-])=O)O[C@@H](O)[C@@H](O)[C@H]1O KPGABFJTMYCRHJ-YZOKENDUSA-N 0.000 description 1
239000001099 ammonium carbonate Substances 0.000 description 1
235000012501 ammonium carbonate Nutrition 0.000 description 1
238000005915 ammonolysis reaction Methods 0.000 description 1
230000003321 amplification Effects 0.000 description 1
238000000540 analysis of variance Methods 0.000 description 1
238000004458 analytical method Methods 0.000 description 1
238000010171 animal model Methods 0.000 description 1
229920006318 anionic polymer Polymers 0.000 description 1
239000010617 anise oil Substances 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
230000003078 antioxidant effect Effects 0.000 description 1
235000010323 ascorbic acid Nutrition 0.000 description 1
239000011668 ascorbic acid Substances 0.000 description 1
229960005070 ascorbic acid Drugs 0.000 description 1
235000010385 ascorbyl palmitate Nutrition 0.000 description 1
IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
239000000605 aspartame Substances 0.000 description 1
235000010357 aspartame Nutrition 0.000 description 1
229960003438 aspartame Drugs 0.000 description 1
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
208000021018 autosomal dominant inheritance Diseases 0.000 description 1
235000021302 avocado oil Nutrition 0.000 description 1
239000008163 avocado oil Substances 0.000 description 1
210000003050 axon Anatomy 0.000 description 1
239000002585 base Substances 0.000 description 1
OGBUMNBNEWYMNJ-UHFFFAOYSA-N batilol Chemical class CCCCCCCCCCCCCCCCCCOCC(O)CO OGBUMNBNEWYMNJ-UHFFFAOYSA-N 0.000 description 1
239000010620 bay oil Substances 0.000 description 1
230000006736 behavioral deficit Effects 0.000 description 1
230000003542 behavioural effect Effects 0.000 description 1
230000008901 benefit Effects 0.000 description 1
229960000686 benzalkonium chloride Drugs 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
229960001950 benzethonium chloride Drugs 0.000 description 1
UREZNYTWGJKWBI-UHFFFAOYSA-M benzethonium chloride Chemical compound [Cl-].C1=CC(C(C)(C)CC(C)(C)C)=CC=C1OCCOCC[N+](C)(C)CC1=CC=CC=C1 UREZNYTWGJKWBI-UHFFFAOYSA-M 0.000 description 1
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
150000001277 beta hydroxy acids Chemical class 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
235000013734 beta-carotene Nutrition 0.000 description 1
239000011648 beta-carotene Substances 0.000 description 1
TUPZEYHYWIEDIH-WAIFQNFQSA-N beta-carotene Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CCCC1(C)C)C=CC=C(/C)C=CC2=CCCCC2(C)C TUPZEYHYWIEDIH-WAIFQNFQSA-N 0.000 description 1
229960002747 betacarotene Drugs 0.000 description 1
210000004369 blood Anatomy 0.000 description 1
239000008280 blood Substances 0.000 description 1
238000009835 boiling Methods 0.000 description 1
229910021538 borax Inorganic materials 0.000 description 1
KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
239000004327 boric acid Substances 0.000 description 1
235000010338 boric acid Nutrition 0.000 description 1
239000008372 bubblegum flavor Substances 0.000 description 1
239000007853 buffer solution Substances 0.000 description 1
BMRWNKZVCUKKSR-UHFFFAOYSA-N butane-1,2-diol Chemical compound CCC(O)CO BMRWNKZVCUKKSR-UHFFFAOYSA-N 0.000 description 1
OWBTYPJTUOEWEK-UHFFFAOYSA-N butane-2,3-diol Chemical compound CC(O)C(C)O OWBTYPJTUOEWEK-UHFFFAOYSA-N 0.000 description 1
239000001191 butyl (2R)-2-hydroxypropanoate Substances 0.000 description 1
235000019282 butylated hydroxyanisole Nutrition 0.000 description 1
239000006227 byproduct Substances 0.000 description 1
NKWPZUCBCARRDP-UHFFFAOYSA-L calcium bicarbonate Chemical compound [Ca+2].OC([O-])=O.OC([O-])=O NKWPZUCBCARRDP-UHFFFAOYSA-L 0.000 description 1
229910000020 calcium bicarbonate Inorganic materials 0.000 description 1
AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
239000000920 calcium hydroxide Substances 0.000 description 1
229910001861 calcium hydroxide Inorganic materials 0.000 description 1
235000011116 calcium hydroxide Nutrition 0.000 description 1
MKJXYGKVIBWPFZ-UHFFFAOYSA-L calcium lactate Chemical compound [Ca+2].CC(O)C([O-])=O.CC(O)C([O-])=O MKJXYGKVIBWPFZ-UHFFFAOYSA-L 0.000 description 1
239000001527 calcium lactate Substances 0.000 description 1
235000011086 calcium lactate Nutrition 0.000 description 1
229960002401 calcium lactate Drugs 0.000 description 1
239000001506 calcium phosphate Substances 0.000 description 1
229910000389 calcium phosphate Inorganic materials 0.000 description 1
235000011010 calcium phosphates Nutrition 0.000 description 1
CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
235000013539 calcium stearate Nutrition 0.000 description 1
239000008116 calcium stearate Substances 0.000 description 1
239000001511 capsicum annuum Substances 0.000 description 1
235000013736 caramel Nutrition 0.000 description 1
239000004202 carbamide Substances 0.000 description 1
239000001768 carboxy methyl cellulose Substances 0.000 description 1
229940096529 carboxypolymethylene Drugs 0.000 description 1
235000012730 carminic acid Nutrition 0.000 description 1
239000004359 castor oil Substances 0.000 description 1
235000019438 castor oil Nutrition 0.000 description 1
229940119201 cedar leaf oil Drugs 0.000 description 1
239000006143 cell culture medium Substances 0.000 description 1
230000030833 cell death Effects 0.000 description 1
230000024245 cell differentiation Effects 0.000 description 1
230000006037 cell lysis Effects 0.000 description 1
230000003833 cell viability Effects 0.000 description 1
210000004671 cell-free system Anatomy 0.000 description 1
238000012054 celltiter-glo Methods 0.000 description 1
230000005754 cellular signaling Effects 0.000 description 1
229920002301 cellulose acetate Polymers 0.000 description 1
229920006217 cellulose acetate butyrate Polymers 0.000 description 1
229940081734 cellulose acetate phthalate Drugs 0.000 description 1
229920003086 cellulose ether Polymers 0.000 description 1
229940074979 cetyl palmitate Drugs 0.000 description 1
229960001927 cetylpyridinium chloride Drugs 0.000 description 1
YMKDRGPMQRFJGP-UHFFFAOYSA-M cetylpyridinium chloride Chemical compound [Cl-].CCCCCCCCCCCCCCCC[N+]1=CC=CC=C1 YMKDRGPMQRFJGP-UHFFFAOYSA-M 0.000 description 1
230000008859 change Effects 0.000 description 1
OIQPTROHQCGFEF-UHFFFAOYSA-L chembl1371409 Chemical compound [Na+].[Na+].OC1=CC=C2C=C(S([O-])(=O)=O)C=CC2=C1N=NC1=CC=C(S([O-])(=O)=O)C=C1 OIQPTROHQCGFEF-UHFFFAOYSA-L 0.000 description 1
229940045110 chitosan Drugs 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
150000001841 cholesterols Chemical class 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
208000012601 choreatic disease Diseases 0.000 description 1
239000010630 cinnamon oil Substances 0.000 description 1
235000020971 citrus fruits Nutrition 0.000 description 1
239000010500 citrus oil Substances 0.000 description 1
238000003759 clinical diagnosis Methods 0.000 description 1
239000010634 clove oil Substances 0.000 description 1
238000000975 co-precipitation Methods 0.000 description 1
239000011247 coating layer Substances 0.000 description 1
230000006999 cognitive decline Effects 0.000 description 1
230000001149 cognitive effect Effects 0.000 description 1
239000000084 colloidal system Substances 0.000 description 1
229940116283 combination glucose Drugs 0.000 description 1
238000002648 combination therapy Methods 0.000 description 1
235000012343 cottonseed oil Nutrition 0.000 description 1
239000002385 cottonseed oil Substances 0.000 description 1
235000003373 curcuma longa Nutrition 0.000 description 1
WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 description 1
HCAJEUSONLESMK-UHFFFAOYSA-N cyclohexylsulfamic acid Chemical compound OS(=O)(=O)NC1CCCCC1 HCAJEUSONLESMK-UHFFFAOYSA-N 0.000 description 1
229940075482 d & c green 5 Drugs 0.000 description 1
229940090962 d&c orange no. 5 Drugs 0.000 description 1
229940099418 d- alpha-tocopherol succinate Drugs 0.000 description 1
230000007423 decrease Effects 0.000 description 1
230000003247 decreasing effect Effects 0.000 description 1
230000006735 deficit Effects 0.000 description 1
238000012217 deletion Methods 0.000 description 1
230000037430 deletion Effects 0.000 description 1
229940009976 deoxycholate Drugs 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
230000006866 deterioration Effects 0.000 description 1
239000008121 dextrose Substances 0.000 description 1
RNPXCFINMKSQPQ-UHFFFAOYSA-N dicetyl hydrogen phosphate Chemical compound CCCCCCCCCCCCCCCCOP(O)(=O)OCCCCCCCCCCCCCCCC RNPXCFINMKSQPQ-UHFFFAOYSA-N 0.000 description 1
229940093541 dicetylphosphate Drugs 0.000 description 1
229940043237 diethanolamine Drugs 0.000 description 1
XXJWXESWEXIICW-UHFFFAOYSA-N diethylene glycol monoethyl ether Chemical compound CCOCCOCCO XXJWXESWEXIICW-UHFFFAOYSA-N 0.000 description 1
229940075557 diethylene glycol monoethyl ether Drugs 0.000 description 1
150000004683 dihydrates Chemical class 0.000 description 1
UGMCXQCYOVCMTB-UHFFFAOYSA-K dihydroxy(stearato)aluminium Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[Al](O)O UGMCXQCYOVCMTB-UHFFFAOYSA-K 0.000 description 1
239000003085 diluting agent Substances 0.000 description 1
239000013024 dilution buffer Substances 0.000 description 1
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
ZGSPNIOCEDOHGS-UHFFFAOYSA-L disodium [3-[2,3-di(octadeca-9,12-dienoyloxy)propoxy-oxidophosphoryl]oxy-2-hydroxypropyl] 2,3-di(octadeca-9,12-dienoyloxy)propyl phosphate Chemical compound [Na+].[Na+].CCCCCC=CCC=CCCCCCCCC(=O)OCC(OC(=O)CCCCCCCC=CCC=CCCCCC)COP([O-])(=O)OCC(O)COP([O-])(=O)OCC(OC(=O)CCCCCCCC=CCC=CCCCCC)COC(=O)CCCCCCCC=CCC=CCCCCC ZGSPNIOCEDOHGS-UHFFFAOYSA-L 0.000 description 1
FPAYXBWMYIMERV-UHFFFAOYSA-L disodium;5-methyl-2-[[4-(4-methyl-2-sulfonatoanilino)-9,10-dioxoanthracen-1-yl]amino]benzenesulfonate Chemical compound [Na+].[Na+].[O-]S(=O)(=O)C1=CC(C)=CC=C1NC(C=1C(=O)C2=CC=CC=C2C(=O)C=11)=CC=C1NC1=CC=C(C)C=C1S([O-])(=O)=O FPAYXBWMYIMERV-UHFFFAOYSA-L 0.000 description 1
238000004821 distillation Methods 0.000 description 1
238000007876 drug discovery Methods 0.000 description 1
230000001804 emulsifying effect Effects 0.000 description 1
230000002708 enhancing effect Effects 0.000 description 1
239000002702 enteric coating Substances 0.000 description 1
238000009505 enteric coating Methods 0.000 description 1
IINNWAYUJNWZRM-UHFFFAOYSA-L erythrosin B Chemical compound [Na+].[Na+].[O-]C(=O)C1=CC=CC=C1C1=C2C=C(I)C(=O)C(I)=C2OC2=C(I)C([O-])=C(I)C=C21 IINNWAYUJNWZRM-UHFFFAOYSA-L 0.000 description 1
235000012732 erythrosine Nutrition 0.000 description 1
229940011411 erythrosine Drugs 0.000 description 1
239000004174 erythrosine Substances 0.000 description 1
239000000686 essence Substances 0.000 description 1
230000032050 esterification Effects 0.000 description 1
238000005886 esterification reaction Methods 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
ZANNOFHADGWOLI-UHFFFAOYSA-N ethyl 2-hydroxyacetate Chemical compound CCOC(=O)CO ZANNOFHADGWOLI-UHFFFAOYSA-N 0.000 description 1
ACJOYTKWHPEIHW-UHFFFAOYSA-N ethyl 3-phenylprop-2-ynoate Chemical compound CCOC(=O)C#CC1=CC=CC=C1 ACJOYTKWHPEIHW-UHFFFAOYSA-N 0.000 description 1
MVPICKVDHDWCJQ-UHFFFAOYSA-N ethyl 3-pyrrolidin-1-ylpropanoate Chemical compound CCOC(=O)CCN1CCCC1 MVPICKVDHDWCJQ-UHFFFAOYSA-N 0.000 description 1
235000019325 ethyl cellulose Nutrition 0.000 description 1
229920001249 ethyl cellulose Polymers 0.000 description 1
125000004494 ethyl ester group Chemical group 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
229940116333 ethyl lactate Drugs 0.000 description 1
229940012017 ethylenediamine Drugs 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
239000000284 extract Substances 0.000 description 1
150000002194 fatty esters Chemical class 0.000 description 1
230000002349 favourable effect Effects 0.000 description 1
229940051147 fd&c yellow no. 6 Drugs 0.000 description 1
239000000706 filtrate Substances 0.000 description 1
239000012467 final product Substances 0.000 description 1
239000003205 fragrance Substances 0.000 description 1
125000000524 functional group Chemical group 0.000 description 1
238000007306 functionalization reaction Methods 0.000 description 1
UPBDXRPQPOWRKR-UHFFFAOYSA-N furan-2,5-dione;methoxyethene Chemical compound COC=C.O=C1OC(=O)C=C1 UPBDXRPQPOWRKR-UHFFFAOYSA-N 0.000 description 1
210000005095 gastrointestinal system Anatomy 0.000 description 1
230000009477 glass transition Effects 0.000 description 1
150000002309 glutamines Chemical class 0.000 description 1
229960005150 glycerol Drugs 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
125000005908 glyceryl ester group Chemical group 0.000 description 1
125000003976 glyceryl group Chemical group [H]C([*])([H])C(O[H])([H])C(O[H])([H])[H] 0.000 description 1
FETSQPAGYOVAQU-UHFFFAOYSA-N glyceryl palmitostearate Chemical compound OCC(O)CO.CCCCCCCCCCCCCCCC(O)=O.CCCCCCCCCCCCCCCCCC(O)=O FETSQPAGYOVAQU-UHFFFAOYSA-N 0.000 description 1
229940046813 glyceryl palmitostearate Drugs 0.000 description 1
229940075529 glyceryl stearate Drugs 0.000 description 1
238000005469 granulation Methods 0.000 description 1
230000003179 granulation Effects 0.000 description 1
235000013761 grape skin extract Nutrition 0.000 description 1
238000000227 grinding Methods 0.000 description 1
235000010417 guar gum Nutrition 0.000 description 1
239000000665 guar gum Substances 0.000 description 1
229960002154 guar gum Drugs 0.000 description 1
229940093915 gynecological organic acid Drugs 0.000 description 1
239000010468 hazelnut oil Substances 0.000 description 1
101150113725 hd gene Proteins 0.000 description 1
238000003505 heat denaturation Methods 0.000 description 1
125000000623 heterocyclic group Chemical group 0.000 description 1
PXDJXZJSCPSGGI-UHFFFAOYSA-N hexadecanoic acid hexadecyl ester Natural products CCCCCCCCCCCCCCCCOC(=O)CCCCCCCCCCCCCCC PXDJXZJSCPSGGI-UHFFFAOYSA-N 0.000 description 1
239000008172 hydrogenated vegetable oil Substances 0.000 description 1
230000003301 hydrolyzing effect Effects 0.000 description 1
229920001600 hydrophobic polymer Polymers 0.000 description 1
WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
125000002768 hydroxyalkyl group Chemical group 0.000 description 1
229920003132 hydroxypropyl methylcellulose phthalate Polymers 0.000 description 1
229940031704 hydroxypropyl methylcellulose phthalate Drugs 0.000 description 1
229920000639 hydroxypropylmethylcellulose acetate succinate Polymers 0.000 description 1
239000012729 immediate-release (IR) formulation Substances 0.000 description 1
230000028993 immune response Effects 0.000 description 1
238000003119 immunoblot Methods 0.000 description 1
238000001114 immunoprecipitation Methods 0.000 description 1
230000001771 impaired effect Effects 0.000 description 1
238000010874 in vitro model Methods 0.000 description 1
238000001727 in vivo Methods 0.000 description 1
KHLVKKOJDHCJMG-QDBORUFSSA-L indigo carmine Chemical compound [Na+].[Na+].N/1C2=CC=C(S([O-])(=O)=O)C=C2C(=O)C\1=C1/NC2=CC=C(S(=O)(=O)[O-])C=C2C1=O KHLVKKOJDHCJMG-QDBORUFSSA-L 0.000 description 1
235000012738 indigotine Nutrition 0.000 description 1
239000004179 indigotine Substances 0.000 description 1
229940060367 inert ingredients Drugs 0.000 description 1
150000002484 inorganic compounds Chemical class 0.000 description 1
229910010272 inorganic material Inorganic materials 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
238000007912 intraperitoneal administration Methods 0.000 description 1
UQSXHKLRYXJYBZ-UHFFFAOYSA-N iron oxide Inorganic materials [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 description 1
230000000302 ischemic effect Effects 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
239000007951 isotonicity adjuster Substances 0.000 description 1
235000015110 jellies Nutrition 0.000 description 1
239000008274 jelly Substances 0.000 description 1
239000000231 karaya gum Substances 0.000 description 1
229940039371 karaya gum Drugs 0.000 description 1
239000008101 lactose Substances 0.000 description 1
229960001375 lactose Drugs 0.000 description 1
150000002605 large molecules Chemical class 0.000 description 1
230000013016 learning Effects 0.000 description 1
239000004571 lime Substances 0.000 description 1
239000008206 lipophilic material Substances 0.000 description 1
239000012669 liquid formulation Substances 0.000 description 1
229910052744 lithium Inorganic materials 0.000 description 1
INHCSSUBVCNVSK-UHFFFAOYSA-L lithium sulfate Inorganic materials [Li+].[Li+].[O-]S([O-])(=O)=O INHCSSUBVCNVSK-UHFFFAOYSA-L 0.000 description 1
238000011068 loading method Methods 0.000 description 1
235000010420 locust bean gum Nutrition 0.000 description 1
239000000711 locust bean gum Substances 0.000 description 1
239000006210 lotion Substances 0.000 description 1
229920002521 macromolecule Polymers 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Substances [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 1
238000002595 magnetic resonance imaging Methods 0.000 description 1
210000004962 mammalian cell Anatomy 0.000 description 1
235000010355 mannitol Nutrition 0.000 description 1
239000000594 mannitol Substances 0.000 description 1
238000001819 mass spectrum Methods 0.000 description 1
238000005259 measurement Methods 0.000 description 1
229960003194 meglumine Drugs 0.000 description 1
230000008384 membrane barrier Effects 0.000 description 1
230000015654 memory Effects 0.000 description 1
239000001525 mentha piperita l. herb oil Substances 0.000 description 1
150000002734 metacrylic acid derivatives Chemical class 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
150000002739 metals Chemical class 0.000 description 1
229920003145 methacrylic acid copolymer Polymers 0.000 description 1
125000005395 methacrylic acid group Chemical group 0.000 description 1
IQSHMXAZFHORGY-UHFFFAOYSA-N methyl prop-2-enoate;2-methylprop-2-enoic acid Chemical compound COC(=O)C=C.CC(=C)C(O)=O IQSHMXAZFHORGY-UHFFFAOYSA-N 0.000 description 1
OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 1
244000005700 microbiome Species 0.000 description 1
239000011785 micronutrient Substances 0.000 description 1
235000013369 micronutrients Nutrition 0.000 description 1
239000011859 microparticle Substances 0.000 description 1
230000003278 mimic effect Effects 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
230000004048 modification Effects 0.000 description 1
238000012986 modification Methods 0.000 description 1
239000003607 modifier Substances 0.000 description 1
RZRNAYUHWVFMIP-UHFFFAOYSA-N monoelaidin Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC(O)CO RZRNAYUHWVFMIP-UHFFFAOYSA-N 0.000 description 1
235000019799 monosodium phosphate Nutrition 0.000 description 1
PJUIMOJAAPLTRJ-UHFFFAOYSA-N monothioglycerol Chemical compound OCC(O)CS PJUIMOJAAPLTRJ-UHFFFAOYSA-N 0.000 description 1
210000000337 motor cortex Anatomy 0.000 description 1
230000035772 mutation Effects 0.000 description 1
DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 description 1
229920001206 natural gum Polymers 0.000 description 1
210000001577 neostriatum Anatomy 0.000 description 1
210000002682 neurofibrillary tangle Anatomy 0.000 description 1
230000002981 neuropathic effect Effects 0.000 description 1
230000007171 neuropathology Effects 0.000 description 1
210000002511 neuropil thread Anatomy 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
150000002829 nitrogen Chemical class 0.000 description 1
229910052757 nitrogen Inorganic materials 0.000 description 1
229910000069 nitrogen hydride Inorganic materials 0.000 description 1
238000003199 nucleic acid amplification method Methods 0.000 description 1
239000001702 nutmeg Substances 0.000 description 1
GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 1
210000000956 olfactory bulb Anatomy 0.000 description 1
210000000196 olfactory nerve Anatomy 0.000 description 1
239000004006 olive oil Substances 0.000 description 1
235000008390 olive oil Nutrition 0.000 description 1
238000005580 one pot reaction Methods 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
150000002894 organic compounds Chemical class 0.000 description 1
230000002018 overexpression Effects 0.000 description 1
NDLPOXTZKUMGOV-UHFFFAOYSA-N oxo(oxoferriooxy)iron hydrate Chemical compound O.O=[Fe]O[Fe]=O NDLPOXTZKUMGOV-UHFFFAOYSA-N 0.000 description 1
239000001301 oxygen Substances 0.000 description 1
229910052760 oxygen Inorganic materials 0.000 description 1
102000006271 p21-Activated Kinases Human genes 0.000 description 1
108010058266 p21-Activated Kinases Proteins 0.000 description 1
239000012188 paraffin wax Substances 0.000 description 1
235000019809 paraffin wax Nutrition 0.000 description 1
230000008506 pathogenesis Effects 0.000 description 1
230000001717 pathogenic effect Effects 0.000 description 1
238000010827 pathological analysis Methods 0.000 description 1
230000007310 pathophysiology Effects 0.000 description 1
239000000312 peanut oil Substances 0.000 description 1
229960000292 pectin Drugs 0.000 description 1
239000008188 pellet Substances 0.000 description 1
230000035515 penetration Effects 0.000 description 1
235000019371 penicillin G benzathine Nutrition 0.000 description 1
235000019477 peppermint oil Nutrition 0.000 description 1
235000019271 petrolatum Nutrition 0.000 description 1
239000008177 pharmaceutical agent Substances 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
229940067107 phenylethyl alcohol Drugs 0.000 description 1
PDTFCHSETJBPTR-UHFFFAOYSA-N phenylmercuric nitrate Chemical compound [O-][N+](=O)O[Hg]C1=CC=CC=C1 PDTFCHSETJBPTR-UHFFFAOYSA-N 0.000 description 1
150000008104 phosphatidylethanolamines Chemical class 0.000 description 1
150000003905 phosphatidylinositols Chemical class 0.000 description 1
239000006187 pill Substances 0.000 description 1
239000010773 plant oil Substances 0.000 description 1
229920001993 poloxamer 188 Polymers 0.000 description 1
229940044519 poloxamer 188 Drugs 0.000 description 1
229920000747 poly(lactic acid) Polymers 0.000 description 1
229920001606 poly(lactic acid-co-glycolic acid) Polymers 0.000 description 1
229920002627 poly(phosphazenes) Polymers 0.000 description 1
239000004584 polyacrylic acid Substances 0.000 description 1
229920000768 polyamine Polymers 0.000 description 1
229920001610 polycaprolactone Polymers 0.000 description 1
239000004632 polycaprolactone Substances 0.000 description 1
229920000573 polyethylene Polymers 0.000 description 1
239000004626 polylactic acid Substances 0.000 description 1
229920000193 polymethacrylate Polymers 0.000 description 1
239000004926 polymethyl methacrylate Substances 0.000 description 1
229920001155 polypropylene Polymers 0.000 description 1
229940100467 polyvinyl acetate phthalate Drugs 0.000 description 1
239000001103 potassium chloride Substances 0.000 description 1
235000011164 potassium chloride Nutrition 0.000 description 1
GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 1
235000011118 potassium hydroxide Nutrition 0.000 description 1
OQZCJRJRGMMSGK-UHFFFAOYSA-M potassium metaphosphate Chemical compound [K+].[O-]P(=O)=O OQZCJRJRGMMSGK-UHFFFAOYSA-M 0.000 description 1
229940099402 potassium metaphosphate Drugs 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
230000000750 progressive effect Effects 0.000 description 1
235000019260 propionic acid Nutrition 0.000 description 1
239000000473 propyl gallate Substances 0.000 description 1
235000010388 propyl gallate Nutrition 0.000 description 1
229940075579 propyl gallate Drugs 0.000 description 1
230000002797 proteolythic effect Effects 0.000 description 1
238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
238000000746 purification Methods 0.000 description 1
238000011002 quantification Methods 0.000 description 1
238000003077 quantum chemistry computational method Methods 0.000 description 1
150000003254 radicals Chemical class 0.000 description 1
MUPFEKGTMRGPLJ-ZQSKZDJDSA-N raffinose 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[C@@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O2)O)O1 MUPFEKGTMRGPLJ-ZQSKZDJDSA-N 0.000 description 1
238000007142 ring opening reaction Methods 0.000 description 1
XWGJFPHUCFXLBL-UHFFFAOYSA-M rongalite Chemical compound [Na+].OCS([O-])=O XWGJFPHUCFXLBL-UHFFFAOYSA-M 0.000 description 1
229940085605 saccharin sodium Drugs 0.000 description 1
235000005713 safflower oil Nutrition 0.000 description 1
239000003813 safflower oil Substances 0.000 description 1
235000002020 sage Nutrition 0.000 description 1
239000000523 sample Substances 0.000 description 1
239000012723 sample buffer Substances 0.000 description 1
HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
238000007790 scraping Methods 0.000 description 1
239000008159 sesame oil Substances 0.000 description 1
235000011803 sesame oil Nutrition 0.000 description 1
230000011664 signaling Effects 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000011734 sodium Substances 0.000 description 1
LLELVHKMCSBMCX-UHFFFAOYSA-M sodium 1-[(4-chloro-5-methyl-2-sulfophenyl)diazenyl]naphthalen-2-olate Chemical compound [Na+].Cc1cc(N=Nc2c(O)ccc3ccccc23)c(cc1Cl)S([O-])(=O)=O LLELVHKMCSBMCX-UHFFFAOYSA-M 0.000 description 1
235000010378 sodium ascorbate Nutrition 0.000 description 1
PPASLZSBLFJQEF-RKJRWTFHSA-M sodium ascorbate Substances [Na+].OC[C@@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RKJRWTFHSA-M 0.000 description 1
229960005055 sodium ascorbate Drugs 0.000 description 1
WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
235000010234 sodium benzoate Nutrition 0.000 description 1
239000004299 sodium benzoate Substances 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
235000017550 sodium carbonate Nutrition 0.000 description 1
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
NRHMKIHPTBHXPF-TUJRSCDTSA-M sodium cholate Chemical compound [Na+].C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC([O-])=O)C)[C@@]2(C)[C@@H](O)C1 NRHMKIHPTBHXPF-TUJRSCDTSA-M 0.000 description 1
AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
235000011121 sodium hydroxide Nutrition 0.000 description 1
229940001584 sodium metabisulfite Drugs 0.000 description 1
235000010262 sodium metabisulphite Nutrition 0.000 description 1
RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical class [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
229910000162 sodium phosphate Inorganic materials 0.000 description 1
229940080313 sodium starch Drugs 0.000 description 1
229940045902 sodium stearyl fumarate Drugs 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
235000010265 sodium sulphite Nutrition 0.000 description 1
235000010339 sodium tetraborate Nutrition 0.000 description 1
PPASLZSBLFJQEF-RXSVEWSESA-M sodium-L-ascorbate Chemical compound [Na+].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RXSVEWSESA-M 0.000 description 1
239000007909 solid dosage form Substances 0.000 description 1
239000012265 solid product Substances 0.000 description 1
238000000527 sonication Methods 0.000 description 1
229940083466 soybean lecithin Drugs 0.000 description 1
239000012798 spherical particle Substances 0.000 description 1
230000002269 spontaneous effect Effects 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
239000008107 starch Substances 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
239000007929 subcutaneous injection Substances 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
239000001384 succinic acid Substances 0.000 description 1
235000011149 sulphuric acid Nutrition 0.000 description 1
239000002600 sunflower oil Substances 0.000 description 1
230000003956 synaptic plasticity Effects 0.000 description 1
230000005062 synaptic transmission Effects 0.000 description 1
239000000271 synthetic detergent Substances 0.000 description 1
238000010189 synthetic method Methods 0.000 description 1
238000007910 systemic administration Methods 0.000 description 1
230000008685 targeting Effects 0.000 description 1
RBTVSNLYYIMMKS-UHFFFAOYSA-N tert-butyl 3-aminoazetidine-1-carboxylate;hydrochloride Chemical compound Cl.CC(C)(C)OC(=O)N1CC(N)C1 RBTVSNLYYIMMKS-UHFFFAOYSA-N 0.000 description 1
ISXSCDLOGDJUNJ-UHFFFAOYSA-N tert-butyl prop-2-enoate Chemical compound CC(C)(C)OC(=O)C=C ISXSCDLOGDJUNJ-UHFFFAOYSA-N 0.000 description 1
UWHCKJMYHZGTIT-UHFFFAOYSA-N tetraethylene glycol Chemical compound OCCOCCOCCOCCO UWHCKJMYHZGTIT-UHFFFAOYSA-N 0.000 description 1
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
239000002562 thickening agent Substances 0.000 description 1
RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
229940033663 thimerosal Drugs 0.000 description 1
239000001789 thuja occidentalis l. leaf oil Substances 0.000 description 1
239000010678 thyme oil Substances 0.000 description 1
210000001578 tight junction Anatomy 0.000 description 1
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 1
WEAPVABOECTMGR-UHFFFAOYSA-N triethyl 2-acetyloxypropane-1,2,3-tricarboxylate Chemical compound CCOC(=O)CC(C(=O)OCC)(OC(C)=O)CC(=O)OCC WEAPVABOECTMGR-UHFFFAOYSA-N 0.000 description 1
239000001069 triethyl citrate Substances 0.000 description 1
VMYFZRTXGLUXMZ-UHFFFAOYSA-N triethyl citrate Natural products CCOC(=O)C(O)(C(=O)OCC)C(=O)OCC VMYFZRTXGLUXMZ-UHFFFAOYSA-N 0.000 description 1
235000013769 triethyl citrate Nutrition 0.000 description 1
ZIBGPFATKBEMQZ-UHFFFAOYSA-N triethylene glycol Chemical compound OCCOCCOCCO ZIBGPFATKBEMQZ-UHFFFAOYSA-N 0.000 description 1
BSVBQGMMJUBVOD-UHFFFAOYSA-N trisodium borate Chemical compound [Na+].[Na+].[Na+].[O-]B([O-])[O-] BSVBQGMMJUBVOD-UHFFFAOYSA-N 0.000 description 1
HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 description 1
GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
230000001228 trophic effect Effects 0.000 description 1
235000013976 turmeric Nutrition 0.000 description 1
238000007492 two-way ANOVA Methods 0.000 description 1
235000015112 vegetable and seed oil Nutrition 0.000 description 1
239000008158 vegetable oil Substances 0.000 description 1
239000003981 vehicle Substances 0.000 description 1
229940117958 vinyl acetate Drugs 0.000 description 1
235000019154 vitamin C Nutrition 0.000 description 1
239000011718 vitamin C Substances 0.000 description 1
239000008170 walnut oil Substances 0.000 description 1
239000009637 wintergreen oil Substances 0.000 description 1
235000010493 xanthan gum Nutrition 0.000 description 1
239000000230 xanthan gum Substances 0.000 description 1
229940082509 xanthan gum Drugs 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
OENHQHLEOONYIE-JLTXGRSLSA-N β-Carotene Chemical compound CC=1CCCC(C)(C)C=1\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C OENHQHLEOONYIE-JLTXGRSLSA-N 0.000 description 1

Classifications

- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C251/00—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton
- C07C251/02—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton containing imino groups
- C07C251/28—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton containing imino groups having nitrogen atoms of imino groups acylated

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Organic Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Epidemiology (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Neurosurgery (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Psychology (AREA)
Hospice & Palliative Care (AREA)
Psychiatry (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

CA2939655A 2014-02-14 2015-02-14 Modulateurs de caspase 6 Abandoned CA2939655A1 (fr)

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date	Title
US61/939,922		2014-02-14
US201462033401P	2014-08-05	2014-08-05
US62/033,401		2014-08-05
PCT/IB2015/000144 WO2016020732A1 (fr)	2014-08-05	2015-02-14	Modulateurs de caspase 6

Publications (1)

Publication Number	Publication Date
CA2939655A1 true CA2939655A1 (fr)	2016-02-11

Family

ID=55263221

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA2939655A Abandoned CA2939655A1 (fr)	2014-02-14	2015-02-14	Modulateurs de caspase 6

Country Status (6)

Country	Link
EP (1)	EP3129027A4 (fr)
JP (1)	JP2018522812A (fr)
AU (1)	AU2015298491A1 (fr)
CA (1)	CA2939655A1 (fr)
DE (1)	DE112015001269T5 (fr)
WO (1)	WO2016020732A1 (fr)

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP3265445B1 (fr)	2015-03-06	2021-05-05	Pharmakea, Inc.	Inhibiteurs de la lysyl oxydase-like 2 et utilisations desdits inhibiteurs
AU2016229268B2 (en)	2015-03-06	2020-09-10	Pharmakea, Inc.	Fluorinated lysyl oxidase-like 2 inhibitors and uses thereof
CA3013917A1 (fr)	2016-02-09	2017-08-17	Pharmakea, Inc.	Inhibiteurs quinolinone de la lysyl oxydase-like 2 et utilisations desdits inhibiteurs
CA3036064A1 (fr)	2016-09-07	2018-03-15	Pharmakea, Inc.	Formes cristallines d'un inhibiteur de lysyl oxydase de type 2 et leurs procedes de fabrication
WO2018048942A1 (fr)	2016-09-07	2018-03-15	Pharmakea, Inc.	Utilisations d'un inhibiteur d'homologue 2 de lysyl-oxydase
BR112022009881A2 (pt) *	2019-11-22	2022-10-11	Univ California	Inibidores de caspase 6 e usos dos mesmos

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP0818439B1 (fr) *	1996-07-02	1999-10-13	Nisshin Flour Milling Co., Ltd.	Dérivés d'imides
EP2102189B1 (fr) *	2006-12-15	2015-07-29	Bristol-Myers Squibb Company	Analogues d'arylpropionamide, d'arylacrylamide, d'arylpropynamide ou d'arylméthylurée en tant qu'inhibiteurs du facteur xia
WO2010017408A1 (fr) *	2008-08-06	2010-02-11	The Buck Institute For Age Research	Inhibiteurs de caspase, et leurs utilisations

2015
- 2015-02-14 WO PCT/IB2015/000144 patent/WO2016020732A1/fr not_active Ceased
- 2015-02-14 DE DE112015001269.9T patent/DE112015001269T5/de not_active Withdrawn
- 2015-02-14 JP JP2016552512A patent/JP2018522812A/ja active Pending
- 2015-02-14 AU AU2015298491A patent/AU2015298491A1/en not_active Abandoned
- 2015-02-14 CA CA2939655A patent/CA2939655A1/fr not_active Abandoned
- 2015-02-14 EP EP15829650.9A patent/EP3129027A4/fr not_active Withdrawn

Also Published As

Publication number	Publication date
WO2016020732A1 (fr)	2016-02-11
DE112015001269T5 (de)	2017-06-08
AU2015298491A1 (en)	2016-09-01
JP2018522812A (ja)	2018-08-16
EP3129027A1 (fr)	2017-02-15
EP3129027A4 (fr)	2017-06-21

Legal Events

Date	Code	Title	Description
2020-04-11	FZDE	Dead	Effective date: 20200214

Publication	Publication Date	Title
CA2939655A1 (fr)	2016-02-11	Modulateurs de caspase 6
AU2017201599B2 (en)	2018-11-08	APP SPECIFIC BACE INHIBITORS (ASBIs) AND USES THEREOF
EP2420235A1 (fr)	2012-02-22	Procédés et polythérapies pour traiter la maladie d'Alzheimer
CN102046151A (zh)	2011-05-04	靶向内质网的脂质体
JP6595345B2 (ja)	2019-10-23	コンフォメーション病におけるβタンパク質凝集の新規の分子モジュレーターとしての化学シャペロニン
JP2023057082A (ja)	2023-04-20	ゲムカベン、薬学的に許容されるその塩、その組成物、およびその使用方法
CN116867488A (zh)	2023-10-10	用于治疗干性老年性黄斑变性（amd）的组合物
US9974767B2 (en)	2018-05-22	Statins in the treatment of muscular dystrophies and myopathies
CA3154596A1 (fr)	2021-05-14	Compositions solides comprenant un inhibiteur de pcsk9 et un sel d'acide n-(8-(2-hydroxybenzoyl)amino) caprylique
JP2019503356A (ja)	2019-02-07	エンドソーマルｇタンパク質共役受容体のトリパータイト・モジュレーター
EP2403859A2 (fr)	2012-01-11	Pince moléculaire pour le traitement d'amyloses
US20190192524A1 (en)	2019-06-27	Modulators of Caspase-6
JP6314135B2 (ja)	2018-04-18	ｉｎ−ｖｉｖｏで神経変性疾患（特にアルツハイマー病）に活性なリポソーム
RU2410376C2 (ru)	2011-01-27	Противовоспалительные агенты
CA3144618A1 (fr)	2021-02-11	Compositions solides comprenant un derive d'egf(a) et un sel d'acide n-(8-(2-hydroxybenzoyl) amino)caprylique
EP1931394A2 (fr)	2008-06-18	Inhibiteurs de l'interaction du domaine apoe4 et methodes d'utilisation
Imbimbo et al.	2009	Semagacestat, a gamma-secretase inhibitor for the potential treatment of Alzheimer’s disease
KR20210093900A (ko)	2021-07-28	젬카빈, 이의 약학적으로 허용가능한 염, 이의 조성물 및 이의 사용 방법
IL295452A (en)	2022-10-01	Use of cyclosporine analogues for treating fibrosis
HUE034353T2 (en)	2018-02-28	Preparation containing a benzothiazolone compound
WO2017222042A1 (fr)	2017-12-28	Composition pharmaceutique ophtalmique
PT1551412E (pt)	2011-08-22	COMPOSIÇÕES FARMACjUTICAS PARA O TRATAMENTO DE DOENÇAS ASSOCIADAS ÀS NEUROTROFINAS
Gado et al.	2025	Physicochemical properties for potential Alzheimer’s disease drugs
KR20230159546A (ko)	2023-11-21	신경학적 질환을 치료하기 위한 조성물 및 방법
US20080227806A1 (en)	2008-09-18	Novel Drugs for Dementia