CA3038519A1 - Uridine nucleoside derivatives, compositions and methods of use - Google Patents

Info

Publication number

CA3038519A1

CA3038519A1 CA3038519A CA3038519A CA3038519A1 CA 3038519 A1 CA3038519 A1 CA 3038519A1 CA 3038519 A CA3038519 A CA 3038519A CA 3038519 A CA3038519 A CA 3038519A CA 3038519 A1 CA3038519 A1 CA 3038519A1

Authority

CA

Canada

Prior art keywords

compound

subject

need

inflammatory

disease

Prior art date

2016-09-26

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Abandoned

Links

• Espacenet
• Global Dossier
• CIPO
• Discuss

• 238000000034 method Methods 0.000 title claims abstract description 184
• 239000000203 mixture Substances 0.000 title claims abstract description 136
• -1 Uridine nucleoside derivatives Chemical class 0.000 title claims abstract description 83
• DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Natural products O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 title abstract description 8
• DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 0.000 title abstract description 6
• DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 title abstract description 6
• 229940045145 uridine Drugs 0.000 title abstract description 6
• 150000001875 compounds Chemical class 0.000 claims abstract description 555
• 230000004968 inflammatory condition Effects 0.000 claims abstract description 98
• 208000002193 Pain Diseases 0.000 claims abstract description 83
• 230000036407 pain Effects 0.000 claims abstract description 73
• 208000010412 Glaucoma Diseases 0.000 claims abstract description 52
• 108010026311 purinoceptor P2Y6 Proteins 0.000 claims abstract description 47
• 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 46
• 230000006378 damage Effects 0.000 claims abstract description 31
• 201000010374 Down Syndrome Diseases 0.000 claims abstract description 26
• 208000018737 Parkinson disease Diseases 0.000 claims abstract description 26
• 208000015122 neurodegenerative disease Diseases 0.000 claims abstract description 20
• 208000014674 injury Diseases 0.000 claims abstract description 18
• 208000027418 Wounds and injury Diseases 0.000 claims abstract description 12
• 230000001537 neural effect Effects 0.000 claims abstract description 10
• 230000003247 decreasing effect Effects 0.000 claims description 96
• 150000003839 salts Chemical class 0.000 claims description 90
• 102000004127 Cytokines Human genes 0.000 claims description 82
• 108090000695 Cytokines Proteins 0.000 claims description 82
• 230000002757 inflammatory effect Effects 0.000 claims description 76
• 238000011282 treatment Methods 0.000 claims description 62
• 239000008194 pharmaceutical composition Substances 0.000 claims description 61
• 230000007423 decrease Effects 0.000 claims description 43
• 206010061218 Inflammation Diseases 0.000 claims description 42
• 230000004054 inflammatory process Effects 0.000 claims description 42
• 102000013462 Interleukin-12 Human genes 0.000 claims description 36
• 108010065805 Interleukin-12 Proteins 0.000 claims description 36
• 125000003118 aryl group Chemical group 0.000 claims description 36
• 125000005842 heteroatom Chemical group 0.000 claims description 29
• 102000003814 Interleukin-10 Human genes 0.000 claims description 27
• 108090000174 Interleukin-10 Proteins 0.000 claims description 27
• 208000010877 cognitive disease Diseases 0.000 claims description 25
• 210000004027 cell Anatomy 0.000 claims description 24
• 102000004388 Interleukin-4 Human genes 0.000 claims description 23
• 108090000978 Interleukin-4 Proteins 0.000 claims description 23
• 208000028698 Cognitive impairment Diseases 0.000 claims description 20
• 201000009273 Endometriosis Diseases 0.000 claims description 20
• 230000004410 intraocular pressure Effects 0.000 claims description 20
• 125000006574 non-aromatic ring group Chemical group 0.000 claims description 20
• 201000004681 Psoriasis Diseases 0.000 claims description 19
• 229910052760 oxygen Inorganic materials 0.000 claims description 19
• 125000001118 alkylidene group Chemical group 0.000 claims description 18
• 230000003920 cognitive function Effects 0.000 claims description 18
• 206010039073 rheumatoid arthritis Diseases 0.000 claims description 18
• 229910052717 sulfur Inorganic materials 0.000 claims description 18
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 18
• 201000006417 multiple sclerosis Diseases 0.000 claims description 16
• 125000001931 aliphatic group Chemical group 0.000 claims description 15
• 230000013629 beta-amyloid clearance Effects 0.000 claims description 15
• 230000002708 enhancing effect Effects 0.000 claims description 15
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 15
• 125000004076 pyridyl group Chemical group 0.000 claims description 15
• 229910052736 halogen Inorganic materials 0.000 claims description 14
• 150000002367 halogens Chemical class 0.000 claims description 14
• 230000001965 increasing effect Effects 0.000 claims description 14
• 208000001640 Fibromyalgia Diseases 0.000 claims description 13
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical group C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 13
• 210000004072 lung Anatomy 0.000 claims description 13
• 230000001404 mediated effect Effects 0.000 claims description 13
• 101100134927 Gallus gallus COR8 gene Proteins 0.000 claims description 12
• 201000001263 Psoriatic Arthritis Diseases 0.000 claims description 12
• 208000036824 Psoriatic arthropathy Diseases 0.000 claims description 12
• 206010009900 Colitis ulcerative Diseases 0.000 claims description 11
• 206010028391 Musculoskeletal Pain Diseases 0.000 claims description 11
• 206010030043 Ocular hypertension Diseases 0.000 claims description 11
• 210000003734 kidney Anatomy 0.000 claims description 11
• 230000027928 long-term synaptic potentiation Effects 0.000 claims description 11
• 230000000770 proinflammatory effect Effects 0.000 claims description 11
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 10
• 208000030886 Traumatic Brain injury Diseases 0.000 claims description 10
• 201000006704 Ulcerative Colitis Diseases 0.000 claims description 10
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 10
• 229910052794 bromium Inorganic materials 0.000 claims description 10
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 10
• 230000009529 traumatic brain injury Effects 0.000 claims description 10
• 208000011231 Crohn disease Diseases 0.000 claims description 9
• 101100134922 Gallus gallus COR5 gene Proteins 0.000 claims description 9
• 230000001363 autoimmune Effects 0.000 claims description 9
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 9
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 9
• 206010012601 diabetes mellitus Diseases 0.000 claims description 9
• 125000000623 heterocyclic group Chemical group 0.000 claims description 9
• 210000004185 liver Anatomy 0.000 claims description 9
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
• 201000001320 Atherosclerosis Diseases 0.000 claims description 8
• 208000023275 Autoimmune disease Diseases 0.000 claims description 8
• 102000003802 alpha-Synuclein Human genes 0.000 claims description 8
• 108090000185 alpha-Synuclein Proteins 0.000 claims description 8
• 230000009286 beneficial effect Effects 0.000 claims description 8
• 229910052799 carbon Inorganic materials 0.000 claims description 8
• 230000000971 hippocampal effect Effects 0.000 claims description 8
• 208000004296 neuralgia Diseases 0.000 claims description 8
• 208000021722 neuropathic pain Diseases 0.000 claims description 8
• 108060008682 Tumor Necrosis Factor Proteins 0.000 claims description 7
• 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 claims description 7
• 238000009825 accumulation Methods 0.000 claims description 7
• 230000036470 plasma concentration Effects 0.000 claims description 7
• 208000011580 syndromic disease Diseases 0.000 claims description 7
• 208000037259 Amyloid Plaque Diseases 0.000 claims description 6
• 208000023105 Huntington disease Diseases 0.000 claims description 6
• 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 6
• 208000028389 Nerve injury Diseases 0.000 claims description 6
• 230000001154 acute effect Effects 0.000 claims description 6
• 230000008764 nerve damage Effects 0.000 claims description 6
• 125000000464 thioxo group Chemical group S=* 0.000 claims description 6
• 102000003816 Interleukin-13 Human genes 0.000 claims description 5
• 108090000176 Interleukin-13 Proteins 0.000 claims description 5
• 102000013691 Interleukin-17 Human genes 0.000 claims description 5
• 108050003558 Interleukin-17 Proteins 0.000 claims description 5
• 102000000704 Interleukin-7 Human genes 0.000 claims description 5
• 108010002586 Interleukin-7 Proteins 0.000 claims description 5
• 102000015696 Interleukins Human genes 0.000 claims description 5
• 108010063738 Interleukins Proteins 0.000 claims description 5
• 206010029240 Neuritis Diseases 0.000 claims description 5
• 208000005298 acute pain Diseases 0.000 claims description 5
• 208000015181 infectious disease Diseases 0.000 claims description 5
• 208000002551 irritable bowel syndrome Diseases 0.000 claims description 5
• 230000013016 learning Effects 0.000 claims description 5
• 230000000626 neurodegenerative effect Effects 0.000 claims description 5
• 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims description 4
• 208000007848 Alcoholism Diseases 0.000 claims description 4
• 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims description 4
• 125000000041 C6-C10 aryl group Chemical group 0.000 claims description 4
• 201000005569 Gout Diseases 0.000 claims description 4
• 206010020751 Hypersensitivity Diseases 0.000 claims description 4
• 206010059176 Juvenile idiopathic arthritis Diseases 0.000 claims description 4
• 201000007930 alcohol dependence Diseases 0.000 claims description 4
• 208000030961 allergic reaction Diseases 0.000 claims description 4
• 210000000653 nervous system Anatomy 0.000 claims description 4
• 125000004043 oxo group Chemical group O=* 0.000 claims description 4
• 230000003956 synaptic plasticity Effects 0.000 claims description 4
• 208000030507 AIDS Diseases 0.000 claims description 3
• 208000003456 Juvenile Arthritis Diseases 0.000 claims description 3
• 239000002671 adjuvant Substances 0.000 claims description 3
• 125000004429 atom Chemical group 0.000 claims description 3
• 238000002512 chemotherapy Methods 0.000 claims description 3
• 210000002808 connective tissue Anatomy 0.000 claims description 3
• 201000002215 juvenile rheumatoid arthritis Diseases 0.000 claims description 3
• 208000030159 metabolic disease Diseases 0.000 claims description 3
• 208000027061 mild cognitive impairment Diseases 0.000 claims description 3
• 201000008482 osteoarthritis Diseases 0.000 claims description 3
• 210000003200 peritoneal cavity Anatomy 0.000 claims description 3
• 230000000699 topical effect Effects 0.000 claims description 3
• 230000002792 vascular Effects 0.000 claims description 3
• 208000000412 Avitaminosis Diseases 0.000 claims description 2
• 208000037157 Azotemia Diseases 0.000 claims description 2
• 206010064147 Gastrointestinal inflammation Diseases 0.000 claims description 2
• 206010019233 Headaches Diseases 0.000 claims description 2
• 208000007514 Herpes zoster Diseases 0.000 claims description 2
• 206010062016 Immunosuppression Diseases 0.000 claims description 2
• 208000009829 Lewy Body Disease Diseases 0.000 claims description 2
• 208000019695 Migraine disease Diseases 0.000 claims description 2
• 208000004983 Phantom Limb Diseases 0.000 claims description 2
• 206010056238 Phantom pain Diseases 0.000 claims description 2
• 206010036376 Postherpetic Neuralgia Diseases 0.000 claims description 2
• 208000004550 Postoperative Pain Diseases 0.000 claims description 2
• 206010040026 Sensory disturbance Diseases 0.000 claims description 2
• 208000028911 Temporomandibular Joint disease Diseases 0.000 claims description 2
• 206010043220 Temporomandibular joint syndrome Diseases 0.000 claims description 2
• 206010045171 Tumour pain Diseases 0.000 claims description 2
• 238000002266 amputation Methods 0.000 claims description 2
• 230000002490 cerebral effect Effects 0.000 claims description 2
• 208000019069 chronic childhood arthritis Diseases 0.000 claims description 2
• 231100000869 headache Toxicity 0.000 claims description 2
• 210000002216 heart Anatomy 0.000 claims description 2
• 208000003532 hypothyroidism Diseases 0.000 claims description 2
• 230000002989 hypothyroidism Effects 0.000 claims description 2
• 230000001506 immunosuppresive effect Effects 0.000 claims description 2
• 239000012678 infectious agent Substances 0.000 claims description 2
• 238000001990 intravenous administration Methods 0.000 claims description 2
• 238000007914 intraventricular administration Methods 0.000 claims description 2
• 230000005906 menstruation Effects 0.000 claims description 2
• 206010027599 migraine Diseases 0.000 claims description 2
• 210000004165 myocardium Anatomy 0.000 claims description 2
• 206010044652 trigeminal neuralgia Diseases 0.000 claims description 2
• 208000009852 uremia Diseases 0.000 claims description 2
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims 5
• MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 claims 3
• 125000006717 (C3-C10) cycloalkenyl group Chemical group 0.000 claims 1
• 201000002832 Lewy body dementia Diseases 0.000 claims 1
• 206010047627 Vitamin deficiencies Diseases 0.000 claims 1
• 230000006999 cognitive decline Effects 0.000 claims 1
• 238000007913 intrathecal administration Methods 0.000 claims 1
• 230000002685 pulmonary effect Effects 0.000 claims 1
• 238000007920 subcutaneous administration Methods 0.000 claims 1
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 57
• 208000035475 disorder Diseases 0.000 abstract description 22
• 239000000556 agonist Substances 0.000 abstract description 19
• 150000003833 nucleoside derivatives Chemical class 0.000 abstract description 4
• 230000000472 traumatic effect Effects 0.000 abstract description 4
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 83
• 235000002639 sodium chloride Nutrition 0.000 description 80
• 239000000243 solution Substances 0.000 description 76
• 208000024891 symptom Diseases 0.000 description 75
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 60
• 229940002612 prodrug Drugs 0.000 description 58
• 239000000651 prodrug Substances 0.000 description 58
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 48
• 230000002829 reductive effect Effects 0.000 description 46
• 241000699670 Mus sp. Species 0.000 description 41
• 239000011541 reaction mixture Substances 0.000 description 39
• 159000000000 sodium salts Chemical class 0.000 description 38
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 36
• 210000002381 plasma Anatomy 0.000 description 35
• 201000010099 disease Diseases 0.000 description 34
• 230000000694 effects Effects 0.000 description 33
• 229910052938 sodium sulfate Inorganic materials 0.000 description 31
• 235000011152 sodium sulphate Nutrition 0.000 description 31
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 31
• 238000005481 NMR spectroscopy Methods 0.000 description 27
• 239000011734 sodium Substances 0.000 description 27
• 239000003795 chemical substances by application Substances 0.000 description 25
• 230000006872 improvement Effects 0.000 description 25
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 24
• 235000015320 potassium carbonate Nutrition 0.000 description 24
• 229910000027 potassium carbonate Inorganic materials 0.000 description 24
• 239000000741 silica gel Substances 0.000 description 23
• 229910002027 silica gel Inorganic materials 0.000 description 23
• 210000001519 tissue Anatomy 0.000 description 23
• 239000007832 Na2SO4 Substances 0.000 description 22
• 239000003814 drug Substances 0.000 description 22
• 210000003169 central nervous system Anatomy 0.000 description 21
• 239000007787 solid Substances 0.000 description 21
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 20
• 230000004770 neurodegeneration Effects 0.000 description 20
• 238000004440 column chromatography Methods 0.000 description 19
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 18
• 239000004698 Polyethylene Substances 0.000 description 18
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 18
• 239000001177 diphosphate Substances 0.000 description 18
• XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 18
• 235000011180 diphosphates Nutrition 0.000 description 18
• 238000004128 high performance liquid chromatography Methods 0.000 description 18
• 238000012360 testing method Methods 0.000 description 18
• HWCKGOZZJDHMNC-UHFFFAOYSA-M tetraethylammonium bromide Chemical compound [Br-].CC[N+](CC)(CC)CC HWCKGOZZJDHMNC-UHFFFAOYSA-M 0.000 description 18
• 210000001508 eye Anatomy 0.000 description 17
• 238000000338 in vitro Methods 0.000 description 17
• 238000001727 in vivo Methods 0.000 description 17
• 239000003937 drug carrier Substances 0.000 description 16
• 230000004406 elevated intraocular pressure Effects 0.000 description 16
• 239000012044 organic layer Substances 0.000 description 16
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 15
• 102100028074 P2Y purinoceptor 6 Human genes 0.000 description 15
• 101710096702 P2Y purinoceptor 6 Proteins 0.000 description 15
• 230000028709 inflammatory response Effects 0.000 description 15
• 238000010898 silica gel chromatography Methods 0.000 description 15
• 210000003491 skin Anatomy 0.000 description 15
• 241001465754 Metazoa Species 0.000 description 14
• 239000005457 ice water Substances 0.000 description 14
• 239000012074 organic phase Substances 0.000 description 14
• 229940079593 drug Drugs 0.000 description 13
• 210000001328 optic nerve Anatomy 0.000 description 13
• 230000009467 reduction Effects 0.000 description 13
• 230000015572 biosynthetic process Effects 0.000 description 12
• 239000012267 brine Substances 0.000 description 12
• 239000003921 oil Substances 0.000 description 12
• 239000011347 resin Substances 0.000 description 12
• 229920005989 resin Polymers 0.000 description 12
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 12
• HLUIWGCMLRIUNQ-UHFFFAOYSA-N tributylazanium;phosphate Chemical compound [O-]P([O-])([O-])=O.CCCC[NH+](CCCC)CCCC.CCCC[NH+](CCCC)CCCC.CCCC[NH+](CCCC)CCCC HLUIWGCMLRIUNQ-UHFFFAOYSA-N 0.000 description 12
• 108010090849 Amyloid beta-Peptides Proteins 0.000 description 11
• 201000002862 Angle-Closure Glaucoma Diseases 0.000 description 11
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 11
• 206010030348 Open-Angle Glaucoma Diseases 0.000 description 11
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 11
• 230000006735 deficit Effects 0.000 description 11
• 230000000302 ischemic effect Effects 0.000 description 11
• 210000001503 joint Anatomy 0.000 description 11
• 210000005036 nerve Anatomy 0.000 description 11
• 235000019198 oils Nutrition 0.000 description 11
• 239000003981 vehicle Substances 0.000 description 11
• 102000013455 Amyloid beta-Peptides Human genes 0.000 description 10
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 10
• 229910052740 iodine Inorganic materials 0.000 description 10
• 239000012279 sodium borohydride Substances 0.000 description 10
• 229910000033 sodium borohydride Inorganic materials 0.000 description 10
• UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 9
• 208000006011 Stroke Diseases 0.000 description 9
• 210000004556 brain Anatomy 0.000 description 9
• 239000001110 calcium chloride Substances 0.000 description 9
• 235000011148 calcium chloride Nutrition 0.000 description 9
• 229910001628 calcium chloride Inorganic materials 0.000 description 9
• 230000001684 chronic effect Effects 0.000 description 9
• 238000002474 experimental method Methods 0.000 description 9
• 208000027866 inflammatory disease Diseases 0.000 description 9
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 9
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 9
• 101150041968 CDC13 gene Proteins 0.000 description 8
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 8
• 238000010171 animal model Methods 0.000 description 8
• 239000008346 aqueous phase Substances 0.000 description 8
• 238000004108 freeze drying Methods 0.000 description 8
• 229910052757 nitrogen Inorganic materials 0.000 description 8
• 210000001428 peripheral nervous system Anatomy 0.000 description 8
• 239000002904 solvent Substances 0.000 description 8
• RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 8
• 208000008035 Back Pain Diseases 0.000 description 7
• 208000030858 Myofascial Pain Syndromes Diseases 0.000 description 7
• FKNQFGJONOIPTF-UHFFFAOYSA-N Sodium cation Chemical compound [Na+] FKNQFGJONOIPTF-UHFFFAOYSA-N 0.000 description 7
• 238000006243 chemical reaction Methods 0.000 description 7
• 239000007924 injection Substances 0.000 description 7
• 238000002347 injection Methods 0.000 description 7
• HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 7
• 238000002953 preparative HPLC Methods 0.000 description 7
• 239000000018 receptor agonist Substances 0.000 description 7
• 229940044601 receptor agonist Drugs 0.000 description 7
• 102000005962 receptors Human genes 0.000 description 7
• 108020003175 receptors Proteins 0.000 description 7
• 229910001415 sodium ion Inorganic materials 0.000 description 7
• 238000003786 synthesis reaction Methods 0.000 description 7
• 230000009885 systemic effect Effects 0.000 description 7
• 238000004679 31P NMR spectroscopy Methods 0.000 description 6
• 201000004569 Blindness Diseases 0.000 description 6
• 229910019142 PO4 Inorganic materials 0.000 description 6
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
• 230000035508 accumulation Effects 0.000 description 6
• 239000002585 base Substances 0.000 description 6
• 230000003750 conditioning effect Effects 0.000 description 6
• 210000003205 muscle Anatomy 0.000 description 6
• 208000033808 peripheral neuropathy Diseases 0.000 description 6
• 235000021317 phosphate Nutrition 0.000 description 6
• 229920001223 polyethylene glycol Polymers 0.000 description 6
• 238000000746 purification Methods 0.000 description 6
• 239000000126 substance Substances 0.000 description 6
• 230000001225 therapeutic effect Effects 0.000 description 6
• 230000008733 trauma Effects 0.000 description 6
• IMFACGCPASFAPR-UHFFFAOYSA-O tributylazanium Chemical compound CCCC[NH+](CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-O 0.000 description 6
• 230000000007 visual effect Effects 0.000 description 6
• UDQTXCHQKHIQMH-KYGLGHNPSA-N (3ar,5s,6s,7r,7ar)-5-(difluoromethyl)-2-(ethylamino)-5,6,7,7a-tetrahydro-3ah-pyrano[3,2-d][1,3]thiazole-6,7-diol Chemical compound S1C(NCC)=N[C@H]2[C@@H]1O[C@H](C(F)F)[C@@H](O)[C@@H]2O UDQTXCHQKHIQMH-KYGLGHNPSA-N 0.000 description 5
• YQOLEILXOBUDMU-KRWDZBQOSA-N (4R)-5-[(6-bromo-3-methyl-2-pyrrolidin-1-ylquinoline-4-carbonyl)amino]-4-(2-chlorophenyl)pentanoic acid Chemical compound CC1=C(C2=C(C=CC(=C2)Br)N=C1N3CCCC3)C(=O)NC[C@H](CCC(=O)O)C4=CC=CC=C4Cl YQOLEILXOBUDMU-KRWDZBQOSA-N 0.000 description 5
• 229940127007 Compound 39 Drugs 0.000 description 5
• 201000004624 Dermatitis Diseases 0.000 description 5
• 206010012735 Diarrhoea Diseases 0.000 description 5
• 206010057249 Phagocytosis Diseases 0.000 description 5
• 241000700159 Rattus Species 0.000 description 5
• 229910006124 SOCl2 Inorganic materials 0.000 description 5
• XCCTYIAWTASOJW-XVFCMESISA-N Uridine-5'-Diphosphate Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(=O)OP(O)(O)=O)O[C@H]1N1C(=O)NC(=O)C=C1 XCCTYIAWTASOJW-XVFCMESISA-N 0.000 description 5
• 238000004458 analytical method Methods 0.000 description 5
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 5
• 125000002619 bicyclic group Chemical group 0.000 description 5
• 229940125936 compound 42 Drugs 0.000 description 5
• 229940125844 compound 46 Drugs 0.000 description 5
• 206010016256 fatigue Diseases 0.000 description 5
• 238000009472 formulation Methods 0.000 description 5
• RENRQMCACQEWFC-UGKGYDQZSA-N lnp023 Chemical compound C1([C@H]2N(CC=3C=4C=CNC=4C(C)=CC=3OC)CC[C@@H](C2)OCC)=CC=C(C(O)=O)C=C1 RENRQMCACQEWFC-UGKGYDQZSA-N 0.000 description 5
• 239000000463 material Substances 0.000 description 5
• 125000002950 monocyclic group Chemical group 0.000 description 5
• 239000012299 nitrogen atmosphere Substances 0.000 description 5
• 239000001301 oxygen Substances 0.000 description 5
• 230000008782 phagocytosis Effects 0.000 description 5
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 5
• 239000010452 phosphate Substances 0.000 description 5
• 230000004044 response Effects 0.000 description 5
• 235000017557 sodium bicarbonate Nutrition 0.000 description 5
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
• 229910000029 sodium carbonate Inorganic materials 0.000 description 5
• 235000017550 sodium carbonate Nutrition 0.000 description 5
• 239000007858 starting material Substances 0.000 description 5
• 235000013616 tea Nutrition 0.000 description 5
• IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 5
• AUFUWRKPQLGTGF-FMKGYKFTSA-N uridine triacetate Chemical compound CC(=O)O[C@@H]1[C@H](OC(C)=O)[C@@H](COC(=O)C)O[C@H]1N1C(=O)NC(=O)C=C1 AUFUWRKPQLGTGF-FMKGYKFTSA-N 0.000 description 5
• ASGMFNBUXDJWJJ-JLCFBVMHSA-N (1R,3R)-3-[[3-bromo-1-[4-(5-methyl-1,3,4-thiadiazol-2-yl)phenyl]pyrazolo[3,4-d]pyrimidin-6-yl]amino]-N,1-dimethylcyclopentane-1-carboxamide Chemical compound BrC1=NN(C2=NC(=NC=C21)N[C@H]1C[C@@](CC1)(C(=O)NC)C)C1=CC=C(C=C1)C=1SC(=NN=1)C ASGMFNBUXDJWJJ-JLCFBVMHSA-N 0.000 description 4
• ABJSOROVZZKJGI-OCYUSGCXSA-N (1r,2r,4r)-2-(4-bromophenyl)-n-[(4-chlorophenyl)-(2-fluoropyridin-4-yl)methyl]-4-morpholin-4-ylcyclohexane-1-carboxamide Chemical compound C1=NC(F)=CC(C(NC(=O)[C@H]2[C@@H](C[C@@H](CC2)N2CCOCC2)C=2C=CC(Br)=CC=2)C=2C=CC(Cl)=CC=2)=C1 ABJSOROVZZKJGI-OCYUSGCXSA-N 0.000 description 4
• IUSARDYWEPUTPN-OZBXUNDUSA-N (2r)-n-[(2s,3r)-4-[[(4s)-6-(2,2-dimethylpropyl)spiro[3,4-dihydropyrano[2,3-b]pyridine-2,1'-cyclobutane]-4-yl]amino]-3-hydroxy-1-[3-(1,3-thiazol-2-yl)phenyl]butan-2-yl]-2-methoxypropanamide Chemical compound C([C@H](NC(=O)[C@@H](C)OC)[C@H](O)CN[C@@H]1C2=CC(CC(C)(C)C)=CN=C2OC2(CCC2)C1)C(C=1)=CC=CC=1C1=NC=CS1 IUSARDYWEPUTPN-OZBXUNDUSA-N 0.000 description 4
• STBLNCCBQMHSRC-BATDWUPUSA-N (2s)-n-[(3s,4s)-5-acetyl-7-cyano-4-methyl-1-[(2-methylnaphthalen-1-yl)methyl]-2-oxo-3,4-dihydro-1,5-benzodiazepin-3-yl]-2-(methylamino)propanamide Chemical compound O=C1[C@@H](NC(=O)[C@H](C)NC)[C@H](C)N(C(C)=O)C2=CC(C#N)=CC=C2N1CC1=C(C)C=CC2=CC=CC=C12 STBLNCCBQMHSRC-BATDWUPUSA-N 0.000 description 4
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
• QOHNRGHTJPFMSL-UHFFFAOYSA-N 1-(3-isothiocyanatophenyl)-3-[4-[(3-isothiocyanatophenyl)carbamothioylamino]butyl]thiourea Chemical compound S=C=NC1=CC=CC(NC(=S)NCCCCNC(=S)NC=2C=C(C=CC=2)N=C=S)=C1 QOHNRGHTJPFMSL-UHFFFAOYSA-N 0.000 description 4
• JJHBEEIDIXTYER-UHFFFAOYSA-N 2-(bromomethyl)-4-phenoxypyridine Chemical compound BrCC1=NC=CC(=C1)OC1=CC=CC=C1 JJHBEEIDIXTYER-UHFFFAOYSA-N 0.000 description 4
• MLGZWVYHIJUAMZ-UHFFFAOYSA-N 2-(bromomethyl)-N-phenylpyridin-4-amine Chemical compound BrCC1=NC=CC(=C1)NC1=CC=CC=C1 MLGZWVYHIJUAMZ-UHFFFAOYSA-N 0.000 description 4
• PYRKKGOKRMZEIT-UHFFFAOYSA-N 2-[6-(2-cyclopropylethoxy)-9-(2-hydroxy-2-methylpropyl)-1h-phenanthro[9,10-d]imidazol-2-yl]-5-fluorobenzene-1,3-dicarbonitrile Chemical compound C1=C2C3=CC(CC(C)(O)C)=CC=C3C=3NC(C=4C(=CC(F)=CC=4C#N)C#N)=NC=3C2=CC=C1OCCC1CC1 PYRKKGOKRMZEIT-UHFFFAOYSA-N 0.000 description 4
• NRTWGZHROYJTNL-UHFFFAOYSA-N 4-benzyl-1-oxidopyridin-1-ium Chemical compound C1=C[N+]([O-])=CC=C1CC1=CC=CC=C1 NRTWGZHROYJTNL-UHFFFAOYSA-N 0.000 description 4
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 4
• 208000000094 Chronic Pain Diseases 0.000 description 4
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
• 208000033962 Fontaine progeroid syndrome Diseases 0.000 description 4
• 241000699666 Mus <mouse, genus> Species 0.000 description 4
• 229910020667 PBr3 Inorganic materials 0.000 description 4
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
• 208000009415 Spinocerebellar Ataxias Diseases 0.000 description 4
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 4
• 229930006000 Sucrose Natural products 0.000 description 4
• 239000002253 acid Substances 0.000 description 4
• 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 4
• 230000006907 apoptotic process Effects 0.000 description 4
• 210000004369 blood Anatomy 0.000 description 4
• 239000008280 blood Substances 0.000 description 4
• 210000004958 brain cell Anatomy 0.000 description 4
• 238000004587 chromatography analysis Methods 0.000 description 4
• 229940125878 compound 36 Drugs 0.000 description 4
• 229940125807 compound 37 Drugs 0.000 description 4
• 229940127573 compound 38 Drugs 0.000 description 4
• 229940126540 compound 41 Drugs 0.000 description 4
• 230000034994 death Effects 0.000 description 4
• 238000003745 diagnosis Methods 0.000 description 4
• 238000000502 dialysis Methods 0.000 description 4
• 230000002526 effect on cardiovascular system Effects 0.000 description 4
• 239000003480 eluent Substances 0.000 description 4
• 230000004438 eyesight Effects 0.000 description 4
• 239000000706 filtrate Substances 0.000 description 4
• 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 4
• 210000001035 gastrointestinal tract Anatomy 0.000 description 4
• 235000011187 glycerol Nutrition 0.000 description 4
• 210000000987 immune system Anatomy 0.000 description 4
• 239000007928 intraperitoneal injection Substances 0.000 description 4
• 239000003456 ion exchange resin Substances 0.000 description 4
• 229920003303 ion-exchange polymer Polymers 0.000 description 4
• 210000004558 lewy body Anatomy 0.000 description 4
• 238000004519 manufacturing process Methods 0.000 description 4
• 206010027175 memory impairment Diseases 0.000 description 4
• BYSRVCQMGFTUBK-UHFFFAOYSA-N methyl 3-phenylbenzoate Chemical compound COC(=O)C1=CC=CC(C=2C=CC=CC=2)=C1 BYSRVCQMGFTUBK-UHFFFAOYSA-N 0.000 description 4
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
• IOMMMLWIABWRKL-WUTDNEBXSA-N nazartinib Chemical compound C1N(C(=O)/C=C/CN(C)C)CCCC[C@H]1N1C2=C(Cl)C=CC=C2N=C1NC(=O)C1=CC=NC(C)=C1 IOMMMLWIABWRKL-WUTDNEBXSA-N 0.000 description 4
• 201000001119 neuropathy Diseases 0.000 description 4
• 239000002777 nucleoside Substances 0.000 description 4
• PIDFDZJZLOTZTM-KHVQSSSXSA-N ombitasvir Chemical compound COC(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@H]1C(=O)NC1=CC=C([C@H]2N([C@@H](CC2)C=2C=CC(NC(=O)[C@H]3N(CCC3)C(=O)[C@@H](NC(=O)OC)C(C)C)=CC=2)C=2C=CC(=CC=2)C(C)(C)C)C=C1 PIDFDZJZLOTZTM-KHVQSSSXSA-N 0.000 description 4
• 210000000056 organ Anatomy 0.000 description 4
• 239000003208 petroleum Substances 0.000 description 4
• 239000000546 pharmaceutical excipient Substances 0.000 description 4
• IPNPIHIZVLFAFP-UHFFFAOYSA-N phosphorus tribromide Chemical compound BrP(Br)Br IPNPIHIZVLFAFP-UHFFFAOYSA-N 0.000 description 4
• 238000011160 research Methods 0.000 description 4
• 239000005720 sucrose Substances 0.000 description 4
• 239000000725 suspension Substances 0.000 description 4
• 238000011830 transgenic mouse model Methods 0.000 description 4
• 235000020334 white tea Nutrition 0.000 description 4
• HUWSZNZAROKDRZ-RRLWZMAJSA-N (3r,4r)-3-azaniumyl-5-[[(2s,3r)-1-[(2s)-2,3-dicarboxypyrrolidin-1-yl]-3-methyl-1-oxopentan-2-yl]amino]-5-oxo-4-sulfanylpentane-1-sulfonate Chemical compound OS(=O)(=O)CC[C@@H](N)[C@@H](S)C(=O)N[C@@H]([C@H](C)CC)C(=O)N1CCC(C(O)=O)[C@H]1C(O)=O HUWSZNZAROKDRZ-RRLWZMAJSA-N 0.000 description 3
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 3
• KQZLRWGGWXJPOS-NLFPWZOASA-N 1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-6-[(4S,5R)-4-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]-5-methylcyclohexen-1-yl]pyrazolo[3,4-b]pyrazine-3-carbonitrile Chemical compound ClC1=C(C=CC(=C1)Cl)[C@@H](C)N1N=C(C=2C1=NC(=CN=2)C1=CC[C@@H]([C@@H](C1)C)N1[C@@H](CCC1)CO)C#N KQZLRWGGWXJPOS-NLFPWZOASA-N 0.000 description 3
• WZZBNLYBHUDSHF-DHLKQENFSA-N 1-[(3s,4s)-4-[8-(2-chloro-4-pyrimidin-2-yloxyphenyl)-7-fluoro-2-methylimidazo[4,5-c]quinolin-1-yl]-3-fluoropiperidin-1-yl]-2-hydroxyethanone Chemical compound CC1=NC2=CN=C3C=C(F)C(C=4C(=CC(OC=5N=CC=CN=5)=CC=4)Cl)=CC3=C2N1[C@H]1CCN(C(=O)CO)C[C@@H]1F WZZBNLYBHUDSHF-DHLKQENFSA-N 0.000 description 3
• NPRYCHLHHVWLQZ-TURQNECASA-N 2-amino-9-[(2R,3S,4S,5R)-4-fluoro-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-7-prop-2-ynylpurin-8-one Chemical compound NC1=NC=C2N(C(N(C2=N1)[C@@H]1O[C@@H]([C@H]([C@H]1O)F)CO)=O)CC#C NPRYCHLHHVWLQZ-TURQNECASA-N 0.000 description 3
• UGHWNQGDHDAXFS-CWJKEVGVSA-N 3-[(4-benzylpyridin-2-yl)methyl]-1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidine-2,4-dione Chemical compound OC[C@H]1O[C@H]([C@H](O)[C@@H]1O)N1C=CC(=O)N(CC2=NC=CC(CC3=CC=CC=C3)=C2)C1=O UGHWNQGDHDAXFS-CWJKEVGVSA-N 0.000 description 3
• BGAJNPLDJJBRHK-UHFFFAOYSA-N 3-[2-[5-(3-chloro-4-propan-2-yloxyphenyl)-1,3,4-thiadiazol-2-yl]-3-methyl-6,7-dihydro-4h-pyrazolo[4,3-c]pyridin-5-yl]propanoic acid Chemical compound C1=C(Cl)C(OC(C)C)=CC=C1C1=NN=C(N2C(=C3CN(CCC(O)=O)CCC3=N2)C)S1 BGAJNPLDJJBRHK-UHFFFAOYSA-N 0.000 description 3
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
• 241000283690 Bos taurus Species 0.000 description 3
• 206010018325 Congenital glaucomas Diseases 0.000 description 3
• 206010012565 Developmental glaucoma Diseases 0.000 description 3
• 208000032131 Diabetic Neuropathies Diseases 0.000 description 3
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
• 108010010803 Gelatin Proteins 0.000 description 3
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
• 240000007472 Leucaena leucocephala Species 0.000 description 3
• 235000010643 Leucaena leucocephala Nutrition 0.000 description 3
• 208000008930 Low Back Pain Diseases 0.000 description 3
• 208000002720 Malnutrition Diseases 0.000 description 3
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
• 241000699660 Mus musculus Species 0.000 description 3
• 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 3
• 206010030113 Oedema Diseases 0.000 description 3
• 102100028045 P2Y purinoceptor 2 Human genes 0.000 description 3
• 101710096700 P2Y purinoceptor 2 Proteins 0.000 description 3
• NFHFRUOZVGFOOS-UHFFFAOYSA-N Pd(PPh3)4 Substances [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 3
• 208000000450 Pelvic Pain Diseases 0.000 description 3
• 206010035664 Pneumonia Diseases 0.000 description 3
• 239000002202 Polyethylene glycol Substances 0.000 description 3
• 206010036105 Polyneuropathy Diseases 0.000 description 3
• 102000002298 Purinergic P2Y Receptors Human genes 0.000 description 3
• 108010000818 Purinergic P2Y Receptors Proteins 0.000 description 3
• 208000005392 Spasm Diseases 0.000 description 3
• LJOOWESTVASNOG-UFJKPHDISA-N [(1s,3r,4ar,7s,8s,8as)-3-hydroxy-8-[2-[(4r)-4-hydroxy-6-oxooxan-2-yl]ethyl]-7-methyl-1,2,3,4,4a,7,8,8a-octahydronaphthalen-1-yl] (2s)-2-methylbutanoate Chemical compound C([C@H]1[C@@H](C)C=C[C@H]2C[C@@H](O)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)CC1C[C@@H](O)CC(=O)O1 LJOOWESTVASNOG-UFJKPHDISA-N 0.000 description 3
• PSLUFJFHTBIXMW-WYEYVKMPSA-N [(3r,4ar,5s,6s,6as,10s,10ar,10bs)-3-ethenyl-10,10b-dihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-6-(2-pyridin-2-ylethylcarbamoyloxy)-5,6,6a,8,9,10-hexahydro-2h-benzo[f]chromen-5-yl] acetate Chemical compound O([C@@H]1[C@@H]([C@]2(O[C@](C)(CC(=O)[C@]2(O)[C@@]2(C)[C@@H](O)CCC(C)(C)[C@@H]21)C=C)C)OC(=O)C)C(=O)NCCC1=CC=CC=N1 PSLUFJFHTBIXMW-WYEYVKMPSA-N 0.000 description 3
• SMNRFWMNPDABKZ-WVALLCKVSA-N [[(2R,3S,4R,5S)-5-(2,6-dioxo-3H-pyridin-3-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [[[(2R,3S,4S,5R,6R)-4-fluoro-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl] hydrogen phosphate Chemical compound OC[C@H]1O[C@H](OP(O)(=O)OP(O)(=O)OP(O)(=O)OP(O)(=O)OC[C@H]2O[C@H]([C@H](O)[C@@H]2O)C2C=CC(=O)NC2=O)[C@H](O)[C@@H](F)[C@@H]1O SMNRFWMNPDABKZ-WVALLCKVSA-N 0.000 description 3
• 238000010521 absorption reaction Methods 0.000 description 3
• 230000009471 action Effects 0.000 description 3
• 230000004913 activation Effects 0.000 description 3
• 238000007792 addition Methods 0.000 description 3
• 210000000577 adipose tissue Anatomy 0.000 description 3
• 230000032683 aging Effects 0.000 description 3
• 125000003342 alkenyl group Chemical group 0.000 description 3
• 206010003246 arthritis Diseases 0.000 description 3
• 210000003403 autonomic nervous system Anatomy 0.000 description 3
• 230000007845 axonopathy Effects 0.000 description 3
• 239000011324 bead Substances 0.000 description 3
• 230000006399 behavior Effects 0.000 description 3
• 230000004071 biological effect Effects 0.000 description 3
• 230000000903 blocking effect Effects 0.000 description 3
• 239000007853 buffer solution Substances 0.000 description 3
• 239000002775 capsule Substances 0.000 description 3
• 125000004432 carbon atom Chemical group C* 0.000 description 3
• 208000015114 central nervous system disease Diseases 0.000 description 3
• 230000008859 change Effects 0.000 description 3
• 229940127204 compound 29 Drugs 0.000 description 3
• 229940125877 compound 31 Drugs 0.000 description 3
• 210000004087 cornea Anatomy 0.000 description 3
• 239000012043 crude product Substances 0.000 description 3
• 125000000392 cycloalkenyl group Chemical group 0.000 description 3
• NXQGGXCHGDYOHB-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloropalladium;iron(2+) Chemical compound [Fe+2].Cl[Pd]Cl.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 NXQGGXCHGDYOHB-UHFFFAOYSA-L 0.000 description 3
• 239000006185 dispersion Substances 0.000 description 3
• 230000004064 dysfunction Effects 0.000 description 3
• 239000003995 emulsifying agent Substances 0.000 description 3
• 239000000839 emulsion Substances 0.000 description 3
• 230000002124 endocrine Effects 0.000 description 3
• 210000004696 endometrium Anatomy 0.000 description 3
• 230000007613 environmental effect Effects 0.000 description 3
• FJIIFNUNDAWHGH-UHFFFAOYSA-N ethyl 2-oxo-2-(phenacylamino)acetate Chemical compound CCOC(=O)C(=O)NCC(=O)C1=CC=CC=C1 FJIIFNUNDAWHGH-UHFFFAOYSA-N 0.000 description 3
• 238000013265 extended release Methods 0.000 description 3
• 238000001914 filtration Methods 0.000 description 3
• 230000006870 function Effects 0.000 description 3
• 239000008273 gelatin Substances 0.000 description 3
• 229920000159 gelatin Polymers 0.000 description 3
• 235000019322 gelatine Nutrition 0.000 description 3
• 235000011852 gelatine desserts Nutrition 0.000 description 3
• 125000001072 heteroaryl group Chemical group 0.000 description 3
• 230000000977 initiatory effect Effects 0.000 description 3
• 229940047122 interleukins Drugs 0.000 description 3
• 230000007154 intracellular accumulation Effects 0.000 description 3
• 239000010410 layer Substances 0.000 description 3
• 239000003446 ligand Substances 0.000 description 3
• 230000033001 locomotion Effects 0.000 description 3
• 238000005259 measurement Methods 0.000 description 3
• 230000010534 mechanism of action Effects 0.000 description 3
• 230000002503 metabolic effect Effects 0.000 description 3
• 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 3
• UPRZUDDGCDKNJK-UHFFFAOYSA-N methyl 4-benzylpyridine-2-carboxylate Chemical compound C1=NC(C(=O)OC)=CC(CC=2C=CC=CC=2)=C1 UPRZUDDGCDKNJK-UHFFFAOYSA-N 0.000 description 3
• 230000002025 microglial effect Effects 0.000 description 3
• 230000017074 necrotic cell death Effects 0.000 description 3
• 230000007823 neuropathy Effects 0.000 description 3
• 239000006187 pill Substances 0.000 description 3
• 125000003386 piperidinyl group Chemical group 0.000 description 3
• 239000000843 powder Substances 0.000 description 3
• 230000002265 prevention Effects 0.000 description 3
• 230000008569 process Effects 0.000 description 3
• 102000004169 proteins and genes Human genes 0.000 description 3
• 108090000623 proteins and genes Proteins 0.000 description 3
• 238000010992 reflux Methods 0.000 description 3
• 229920006395 saturated elastomer Polymers 0.000 description 3
• 230000035945 sensitivity Effects 0.000 description 3
• 210000002027 skeletal muscle Anatomy 0.000 description 3
• 230000003093 somatogenic effect Effects 0.000 description 3
• 230000000638 stimulation Effects 0.000 description 3
• 238000001356 surgical procedure Methods 0.000 description 3
• 239000000375 suspending agent Substances 0.000 description 3
• 239000003826 tablet Substances 0.000 description 3
• CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 3
• 239000003053 toxin Substances 0.000 description 3
• 231100000765 toxin Toxicity 0.000 description 3
• 108700012359 toxins Proteins 0.000 description 3
• 238000011269 treatment regimen Methods 0.000 description 3
• 210000002700 urine Anatomy 0.000 description 3
• 230000004580 weight loss Effects 0.000 description 3
• 239000000080 wetting agent Substances 0.000 description 3
• PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
• JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical compound OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 2
• JSEYDHRHJGYMLT-PNHWDRBUSA-N 1-[(2s,3r,4s,5r)-2-acetyl-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidine-2,4-dione Chemical compound C1=CC(=O)NC(=O)N1[C@]1(C(=O)C)O[C@H](CO)[C@@H](O)[C@H]1O JSEYDHRHJGYMLT-PNHWDRBUSA-N 0.000 description 2
• VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
• IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 2
• MZSAMHOCTRNOIZ-UHFFFAOYSA-N 3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy-N-phenylaniline Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)OC=1C=C(NC2=CC=CC=C2)C=CC=1 MZSAMHOCTRNOIZ-UHFFFAOYSA-N 0.000 description 2
• WBTYJEKADPHWEW-UHFFFAOYSA-N 4-benzylpyridine-2-carbonitrile Chemical compound C1=NC(C#N)=CC(CC=2C=CC=CC=2)=C1 WBTYJEKADPHWEW-UHFFFAOYSA-N 0.000 description 2
• 229920001817 Agar Polymers 0.000 description 2
• 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 2
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
• 206010002556 Ankylosing Spondylitis Diseases 0.000 description 2
• 241000416162 Astragalus gummifer Species 0.000 description 2
• 206010003571 Astrocytoma Diseases 0.000 description 2
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
• 206010003694 Atrophy Diseases 0.000 description 2
• 241000894006 Bacteria Species 0.000 description 2
• KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 2
• 102100036170 C-X-C motif chemokine 9 Human genes 0.000 description 2
• 101710085500 C-X-C motif chemokine 9 Proteins 0.000 description 2
• VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
• 208000030939 Chronic inflammatory demyelinating polyneuropathy Diseases 0.000 description 2
• 206010010774 Constipation Diseases 0.000 description 2
• 206010012289 Dementia Diseases 0.000 description 2
• 201000008163 Dentatorubral pallidoluysian atrophy Diseases 0.000 description 2
• 208000004483 Dyspareunia Diseases 0.000 description 2
• 102000004190 Enzymes Human genes 0.000 description 2
• 108090000790 Enzymes Proteins 0.000 description 2
• 241000233866 Fungi Species 0.000 description 2
• 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 2
• 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 2
• 241000206672 Gelidium Species 0.000 description 2
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
• 229930186217 Glycolipid Natural products 0.000 description 2
• 208000030836 Hashimoto thyroiditis Diseases 0.000 description 2
• 208000032843 Hemorrhage Diseases 0.000 description 2
• 241000282412 Homo Species 0.000 description 2
• 208000004454 Hyperalgesia Diseases 0.000 description 2
• 206010020772 Hypertension Diseases 0.000 description 2
• 206010061216 Infarction Diseases 0.000 description 2
• 206010065390 Inflammatory pain Diseases 0.000 description 2
• 206010053678 Iridocorneal endothelial syndrome Diseases 0.000 description 2
• 208000027747 Kennedy disease Diseases 0.000 description 2
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
• 208000002569 Machado-Joseph Disease Diseases 0.000 description 2
• 208000026139 Memory disease Diseases 0.000 description 2
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
• 208000007101 Muscle Cramp Diseases 0.000 description 2
• 206010052904 Musculoskeletal stiffness Diseases 0.000 description 2
• 206010028813 Nausea Diseases 0.000 description 2
• 208000012902 Nervous system disease Diseases 0.000 description 2
• 208000025966 Neurological disease Diseases 0.000 description 2
• 208000001294 Nociceptive Pain Diseases 0.000 description 2
• 208000008589 Obesity Diseases 0.000 description 2
• 206010061323 Optic neuropathy Diseases 0.000 description 2
• 241000283973 Oryctolagus cuniculus Species 0.000 description 2
• 102100028070 P2Y purinoceptor 4 Human genes 0.000 description 2
• 108050009478 P2Y purinoceptor 4 Proteins 0.000 description 2
• 208000024777 Prion disease Diseases 0.000 description 2
• 208000033063 Progressive myoclonic epilepsy Diseases 0.000 description 2
• 208000001647 Renal Insufficiency Diseases 0.000 description 2
• 241000593989 Scardinius erythrophthalmus Species 0.000 description 2
• 208000036834 Spinocerebellar ataxia type 3 Diseases 0.000 description 2
• 229920002472 Starch Polymers 0.000 description 2
• 229920001615 Tragacanth Polymers 0.000 description 2
• 108700019146 Transgenes Proteins 0.000 description 2
• 208000037280 Trisomy Diseases 0.000 description 2
• 208000025865 Ulcer Diseases 0.000 description 2
• 206010047115 Vasculitis Diseases 0.000 description 2
• 206010047700 Vomiting Diseases 0.000 description 2
• 208000006269 X-Linked Bulbo-Spinal Atrophy Diseases 0.000 description 2
• REAYFGLASQTHKB-UHFFFAOYSA-N [2-[3-(1H-pyrazol-4-yl)phenoxy]-6-(trifluoromethyl)pyridin-4-yl]methanamine Chemical compound N1N=CC(=C1)C=1C=C(OC2=NC(=CC(=C2)CN)C(F)(F)F)C=CC=1 REAYFGLASQTHKB-UHFFFAOYSA-N 0.000 description 2
• 230000002159 abnormal effect Effects 0.000 description 2
• 235000010419 agar Nutrition 0.000 description 2
• 235000010443 alginic acid Nutrition 0.000 description 2
• 229920000615 alginic acid Polymers 0.000 description 2
• 125000000304 alkynyl group Chemical group 0.000 description 2
• 230000001668 ameliorated effect Effects 0.000 description 2
• 239000012491 analyte Substances 0.000 description 2
• 208000007502 anemia Diseases 0.000 description 2
• 239000005557 antagonist Substances 0.000 description 2
• 210000001367 artery Anatomy 0.000 description 2
• 208000010668 atopic eczema Diseases 0.000 description 2
• 230000037444 atrophy Effects 0.000 description 2
• 125000003725 azepanyl group Chemical group 0.000 description 2
• 239000000440 bentonite Substances 0.000 description 2
• 235000012216 bentonite Nutrition 0.000 description 2
• 229910000278 bentonite Inorganic materials 0.000 description 2
• SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 2
• HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
• SESFRYSPDFLNCH-UHFFFAOYSA-N benzyl benzoate Chemical compound C=1C=CC=CC=1C(=O)OCC1=CC=CC=C1 SESFRYSPDFLNCH-UHFFFAOYSA-N 0.000 description 2
• 229960000074 biopharmaceutical Drugs 0.000 description 2
• 230000000740 bleeding effect Effects 0.000 description 2
• 230000008499 blood brain barrier function Effects 0.000 description 2
• 230000017531 blood circulation Effects 0.000 description 2
• 210000001218 blood-brain barrier Anatomy 0.000 description 2
• 210000001124 body fluid Anatomy 0.000 description 2
• 239000010839 body fluid Substances 0.000 description 2
• 239000000872 buffer Substances 0.000 description 2
• 210000001217 buttock Anatomy 0.000 description 2
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 2
• 239000001768 carboxy methyl cellulose Substances 0.000 description 2
• 150000001805 chlorine compounds Chemical class 0.000 description 2
• OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
• 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 2
• 210000000349 chromosome Anatomy 0.000 description 2
• 208000037976 chronic inflammation Diseases 0.000 description 2
• 230000006020 chronic inflammation Effects 0.000 description 2
• 201000005795 chronic inflammatory demyelinating polyneuritis Diseases 0.000 description 2
• 208000022371 chronic pain syndrome Diseases 0.000 description 2
• 239000003086 colorant Substances 0.000 description 2
• 229940000425 combination drug Drugs 0.000 description 2
• 239000003246 corticosteroid Substances 0.000 description 2
• 229960001334 corticosteroids Drugs 0.000 description 2
• 125000004122 cyclic group Chemical group 0.000 description 2
• 125000000753 cycloalkyl group Chemical group 0.000 description 2
• 231100000433 cytotoxic Toxicity 0.000 description 2
• 230000001472 cytotoxic effect Effects 0.000 description 2
• 230000001934 delay Effects 0.000 description 2
• 230000008021 deposition Effects 0.000 description 2
• 235000014113 dietary fatty acids Nutrition 0.000 description 2
• XPPKVPWEQAFLFU-UHFFFAOYSA-N diphosphoric acid Chemical class OP(O)(=O)OP(O)(O)=O XPPKVPWEQAFLFU-UHFFFAOYSA-N 0.000 description 2
• VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
• 206010013990 dysuria Diseases 0.000 description 2
• 230000008030 elimination Effects 0.000 description 2
• 238000003379 elimination reaction Methods 0.000 description 2
• 150000002148 esters Chemical class 0.000 description 2
• 235000019441 ethanol Nutrition 0.000 description 2
• BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 2
• FWBZHFHLKWUNKL-UHFFFAOYSA-N ethyl 5-phenyl-1,3-thiazole-2-carboxylate Chemical compound S1C(C(=O)OCC)=NC=C1C1=CC=CC=C1 FWBZHFHLKWUNKL-UHFFFAOYSA-N 0.000 description 2
• 238000011156 evaluation Methods 0.000 description 2
• 239000000284 extract Substances 0.000 description 2
• 239000003889 eye drop Substances 0.000 description 2
• 229940012356 eye drops Drugs 0.000 description 2
• 210000003195 fascia Anatomy 0.000 description 2
• 239000000194 fatty acid Substances 0.000 description 2
• 229930195729 fatty acid Natural products 0.000 description 2
• 208000037957 feline spongiform encephalopathy Diseases 0.000 description 2
• 239000000945 filler Substances 0.000 description 2
• 239000012530 fluid Substances 0.000 description 2
• 230000037406 food intake Effects 0.000 description 2
• 238000007710 freezing Methods 0.000 description 2
• 230000008014 freezing Effects 0.000 description 2
• 239000008187 granular material Substances 0.000 description 2
• 239000001963 growth medium Substances 0.000 description 2
• 208000035861 hematochezia Diseases 0.000 description 2
• 210000001320 hippocampus Anatomy 0.000 description 2
• 238000003384 imaging method Methods 0.000 description 2
• 208000026278 immune system disease Diseases 0.000 description 2
• 230000001771 impaired effect Effects 0.000 description 2
• 239000003701 inert diluent Substances 0.000 description 2
• 230000007574 infarction Effects 0.000 description 2
• 208000000509 infertility Diseases 0.000 description 2
• 230000036512 infertility Effects 0.000 description 2
• 231100000535 infertility Toxicity 0.000 description 2
• 230000008595 infiltration Effects 0.000 description 2
• 238000001764 infiltration Methods 0.000 description 2
• 238000005342 ion exchange Methods 0.000 description 2
• 208000028867 ischemia Diseases 0.000 description 2
• 201000006370 kidney failure Diseases 0.000 description 2
• 239000008101 lactose Substances 0.000 description 2
• 239000000787 lecithin Substances 0.000 description 2
• 235000010445 lecithin Nutrition 0.000 description 2
• 229940067606 lecithin Drugs 0.000 description 2
• 239000007788 liquid Substances 0.000 description 2
• 239000008297 liquid dosage form Substances 0.000 description 2
• YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 2
• 210000002540 macrophage Anatomy 0.000 description 2
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
• 235000000824 malnutrition Nutrition 0.000 description 2
• 230000001071 malnutrition Effects 0.000 description 2
• 230000003340 mental effect Effects 0.000 description 2
• 229910052751 metal Inorganic materials 0.000 description 2
• 239000002184 metal Substances 0.000 description 2
• 230000004048 modification Effects 0.000 description 2
• 238000012986 modification Methods 0.000 description 2
• 210000001616 monocyte Anatomy 0.000 description 2
• 201000005518 mononeuropathy Diseases 0.000 description 2
• 208000005264 motor neuron disease Diseases 0.000 description 2
• 210000004400 mucous membrane Anatomy 0.000 description 2
• 230000003387 muscular Effects 0.000 description 2
• 230000008693 nausea Effects 0.000 description 2
• 201000008383 nephritis Diseases 0.000 description 2
• 230000000926 neurological effect Effects 0.000 description 2
• 210000002569 neuron Anatomy 0.000 description 2
• 230000002981 neuropathic effect Effects 0.000 description 2
• 231100000252 nontoxic Toxicity 0.000 description 2
• 230000003000 nontoxic effect Effects 0.000 description 2
• 230000004493 normal intraocular pressure Effects 0.000 description 2
• 108020004707 nucleic acids Proteins 0.000 description 2
• 102000039446 nucleic acids Human genes 0.000 description 2
• 150000007523 nucleic acids Chemical class 0.000 description 2
• 208000015380 nutritional deficiency disease Diseases 0.000 description 2
• 235000020824 obesity Nutrition 0.000 description 2
• 239000004006 olive oil Substances 0.000 description 2
• 208000020911 optic nerve disease Diseases 0.000 description 2
• 150000007530 organic bases Chemical class 0.000 description 2
• 238000007911 parenteral administration Methods 0.000 description 2
• 230000007310 pathophysiology Effects 0.000 description 2
• 229910052698 phosphorus Inorganic materials 0.000 description 2
• 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 2
• 125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 description 2
• 108010040003 polyglutamine Proteins 0.000 description 2
• 229920000155 polyglutamine Polymers 0.000 description 2
• 238000003752 polymerase chain reaction Methods 0.000 description 2
• 230000007824 polyneuropathy Effects 0.000 description 2
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
• 238000002360 preparation method Methods 0.000 description 2
• 239000003755 preservative agent Substances 0.000 description 2
• 230000000069 prophylactic effect Effects 0.000 description 2
• 229960004063 propylene glycol Drugs 0.000 description 2
• 239000002719 pyrimidine nucleotide Substances 0.000 description 2
• 150000003230 pyrimidines Chemical class 0.000 description 2
• 230000029058 respiratory gaseous exchange Effects 0.000 description 2
• 230000037390 scarring Effects 0.000 description 2
• 210000002966 serum Anatomy 0.000 description 2
• 230000035939 shock Effects 0.000 description 2
• 208000019116 sleep disease Diseases 0.000 description 2
• 208000022925 sleep disturbance Diseases 0.000 description 2
• 239000011780 sodium chloride Substances 0.000 description 2
• 239000012453 solvate Substances 0.000 description 2
• 235000010199 sorbic acid Nutrition 0.000 description 2
• 229940075582 sorbic acid Drugs 0.000 description 2
• 239000004334 sorbic acid Substances 0.000 description 2
• 210000000278 spinal cord Anatomy 0.000 description 2
• 235000019698 starch Nutrition 0.000 description 2
• 230000035882 stress Effects 0.000 description 2
• 235000000346 sugar Nutrition 0.000 description 2
• 150000008163 sugars Chemical class 0.000 description 2
• 230000009469 supplementation Effects 0.000 description 2
• 239000006188 syrup Substances 0.000 description 2
• 235000020357 syrup Nutrition 0.000 description 2
• 230000000451 tissue damage Effects 0.000 description 2
• 231100000827 tissue damage Toxicity 0.000 description 2
• 231100000331 toxic Toxicity 0.000 description 2
• 230000002588 toxic effect Effects 0.000 description 2
• 235000010487 tragacanth Nutrition 0.000 description 2
• 239000000196 tragacanth Substances 0.000 description 2
• 229940116362 tragacanth Drugs 0.000 description 2
• 238000012549 training Methods 0.000 description 2
• LEIMLDGFXIOXMT-UHFFFAOYSA-N trimethylsilyl cyanide Chemical compound C[Si](C)(C)C#N LEIMLDGFXIOXMT-UHFFFAOYSA-N 0.000 description 2
• 208000001072 type 2 diabetes mellitus Diseases 0.000 description 2
• 231100000397 ulcer Toxicity 0.000 description 2
• 210000000689 upper leg Anatomy 0.000 description 2
• 230000004393 visual impairment Effects 0.000 description 2
• 230000008673 vomiting Effects 0.000 description 2
• HAYKGPXJHWUMOC-UHFFFAOYSA-N (4-piperidin-1-ylpyridin-2-yl)methanol Chemical compound C1=NC(CO)=CC(N2CCCCC2)=C1 HAYKGPXJHWUMOC-UHFFFAOYSA-N 0.000 description 1
• IAAWQWDIYQQVGE-UHFFFAOYSA-N (4-pyridin-2-ylpyridin-2-yl)methanol Chemical compound N1=C(C=CC=C1)C1=CC(=NC=C1)CO IAAWQWDIYQQVGE-UHFFFAOYSA-N 0.000 description 1
• ZWXICIGAZGWICX-UHFFFAOYSA-N (4-pyridin-4-yl-3H-pyridin-4-yl)methanol Chemical compound N1=CCC(C=C1)(C1=CC=NC=C1)CO ZWXICIGAZGWICX-UHFFFAOYSA-N 0.000 description 1
• CFLMVPYEVZXIED-UHFFFAOYSA-N (5-bromofuran-2-yl)methanol Chemical compound OCC1=CC=C(Br)O1 CFLMVPYEVZXIED-UHFFFAOYSA-N 0.000 description 1
• ROICYBLUWUMJFF-RDTXWAMCSA-N (6aR,9R)-N,7-dimethyl-N-propan-2-yl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinoline-9-carboxamide Chemical compound CN(C(=O)[C@H]1CN(C)[C@@H]2CC3=CNC4=CC=CC(C2=C1)=C34)C(C)C ROICYBLUWUMJFF-RDTXWAMCSA-N 0.000 description 1
• LFKXWKGYHQXRQA-FDGPNNRMSA-N (z)-4-hydroxypent-3-en-2-one;iron Chemical compound [Fe].C\C(O)=C\C(C)=O.C\C(O)=C\C(C)=O LFKXWKGYHQXRQA-FDGPNNRMSA-N 0.000 description 1
• 125000004502 1,2,3-oxadiazolyl group Chemical group 0.000 description 1
• 125000004511 1,2,3-thiadiazolyl group Chemical group 0.000 description 1
• 125000001399 1,2,3-triazolyl group Chemical group N1N=NC(=C1)* 0.000 description 1
• 125000004504 1,2,4-oxadiazolyl group Chemical group 0.000 description 1
• 125000004506 1,2,5-oxadiazolyl group Chemical group 0.000 description 1
• 125000004517 1,2,5-thiadiazolyl group Chemical group 0.000 description 1
• 125000004520 1,3,4-thiadiazolyl group Chemical group 0.000 description 1
• 125000003363 1,3,5-triazinyl group Chemical group N1=C(N=CN=C1)* 0.000 description 1
• 229940058015 1,3-butylene glycol Drugs 0.000 description 1
• AICIYIDUYNFPRY-UHFFFAOYSA-N 1,3-dihydro-2H-imidazol-2-one Chemical compound O=C1NC=CN1 AICIYIDUYNFPRY-UHFFFAOYSA-N 0.000 description 1
• HXKKHQJGJAFBHI-UHFFFAOYSA-N 1-aminopropan-2-ol Chemical compound CC(O)CN HXKKHQJGJAFBHI-UHFFFAOYSA-N 0.000 description 1
• 125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 description 1
• 238000005160 1H NMR spectroscopy Methods 0.000 description 1
• YMFWYDYJHRGGPF-UHFFFAOYSA-N 2,3-dibromoprop-1-ene Chemical compound BrCC(Br)=C YMFWYDYJHRGGPF-UHFFFAOYSA-N 0.000 description 1
• YJUFGFXVASPYFQ-UHFFFAOYSA-N 2,3-dihydro-1-benzothiophene Chemical compound C1=CC=C2SCCC2=C1 YJUFGFXVASPYFQ-UHFFFAOYSA-N 0.000 description 1
• CHHHXKFHOYLYRE-UHFFFAOYSA-M 2,4-Hexadienoic acid, potassium salt (1:1), (2E,4E)- Chemical compound [K+].CC=CC=CC([O-])=O CHHHXKFHOYLYRE-UHFFFAOYSA-M 0.000 description 1
• VCUXVXLUOHDHKK-UHFFFAOYSA-N 2-(2-aminopyrimidin-4-yl)-4-(2-chloro-4-methoxyphenyl)-1,3-thiazole-5-carboxamide Chemical compound ClC1=CC(OC)=CC=C1C1=C(C(N)=O)SC(C=2N=C(N)N=CC=2)=N1 VCUXVXLUOHDHKK-UHFFFAOYSA-N 0.000 description 1
• GLITZAQNKBBURP-UHFFFAOYSA-N 2-(bromomethyl)-4-cyclohexylpyridine Chemical compound BrCC1=NC=CC(=C1)C1CCCCC1 GLITZAQNKBBURP-UHFFFAOYSA-N 0.000 description 1
• IMRWILPUOVGIMU-UHFFFAOYSA-N 2-bromopyridine Chemical compound BrC1=CC=CC=N1 IMRWILPUOVGIMU-UHFFFAOYSA-N 0.000 description 1
• 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 1
• JNODDICFTDYODH-UHFFFAOYSA-N 2-hydroxytetrahydrofuran Chemical compound OC1CCCO1 JNODDICFTDYODH-UHFFFAOYSA-N 0.000 description 1
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
• 125000004485 2-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])C1([H])* 0.000 description 1
• 125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 description 1
• 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
• FSUYMKXZLQOFQY-UHFFFAOYSA-N 3,4-dihydro-1,2-benzodithiine Chemical compound C1=CC=C2SSCCC2=C1 FSUYMKXZLQOFQY-UHFFFAOYSA-N 0.000 description 1
• DFRAKBCRUYUFNT-UHFFFAOYSA-N 3,8-dicyclohexyl-2,4,7,9-tetrahydro-[1,3]oxazino[5,6-h][1,3]benzoxazine Chemical compound C1CCCCC1N1CC(C=CC2=C3OCN(C2)C2CCCCC2)=C3OC1 DFRAKBCRUYUFNT-UHFFFAOYSA-N 0.000 description 1
• HVCOBJNICQPDBP-UHFFFAOYSA-N 3-[3-[3,5-dihydroxy-6-methyl-4-(3,4,5-trihydroxy-6-methyloxan-2-yl)oxyoxan-2-yl]oxydecanoyloxy]decanoic acid;hydrate Chemical compound O.OC1C(OC(CC(=O)OC(CCCCCCC)CC(O)=O)CCCCCCC)OC(C)C(O)C1OC1C(O)C(O)C(O)C(C)O1 HVCOBJNICQPDBP-UHFFFAOYSA-N 0.000 description 1
• NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
• 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 1
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
• 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 125000001397 3-pyrrolyl group Chemical group [H]N1C([H])=C([*])C([H])=C1[H] 0.000 description 1
• 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 1
• MRZRJTZGNFPMNY-UHFFFAOYSA-N 4-(7-methoxy-1-methylpyrido[3,4-b]indol-9-yl)butanamide Chemical compound C(=O)(CCCN1C2=C(C3=C1C=C(OC)C=C3)C=CN=C2C)N MRZRJTZGNFPMNY-UHFFFAOYSA-N 0.000 description 1
• DBOLXXRVIFGDTI-UHFFFAOYSA-N 4-benzylpyridine Chemical compound C=1C=NC=CC=1CC1=CC=CC=C1 DBOLXXRVIFGDTI-UHFFFAOYSA-N 0.000 description 1
• FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
• 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
• KDDQRKBRJSGMQE-UHFFFAOYSA-N 4-thiazolyl Chemical group [C]1=CSC=N1 KDDQRKBRJSGMQE-UHFFFAOYSA-N 0.000 description 1
• ZRDAKARAOUNJJT-UHFFFAOYSA-N 5-(bromomethyl)-2-phenyl-1,3-oxazole Chemical compound O1C(CBr)=CN=C1C1=CC=CC=C1 ZRDAKARAOUNJJT-UHFFFAOYSA-N 0.000 description 1
• VKLKXFOZNHEBSW-UHFFFAOYSA-N 5-[[3-[(4-morpholin-4-ylbenzoyl)amino]phenyl]methoxy]pyridine-3-carboxamide Chemical compound O1CCN(CC1)C1=CC=C(C(=O)NC=2C=C(COC=3C=NC=C(C(=O)N)C=3)C=CC=2)C=C1 VKLKXFOZNHEBSW-UHFFFAOYSA-N 0.000 description 1
• MULZWPFQTUDZPD-UHFFFAOYSA-N 5-methyl-2-phenyl-1,3-oxazole Chemical compound O1C(C)=CN=C1C1=CC=CC=C1 MULZWPFQTUDZPD-UHFFFAOYSA-N 0.000 description 1
• YPYPBEGIASEWKA-UHFFFAOYSA-N 5-phenyl-1,3-oxazole Chemical compound O1C=NC=C1C1=CC=CC=C1 YPYPBEGIASEWKA-UHFFFAOYSA-N 0.000 description 1
• GJRAYWVAZQGENN-UHFFFAOYSA-N 5-phenyl-1,3-oxazole-2-carbaldehyde Chemical compound O1C(C=O)=NC=C1C1=CC=CC=C1 GJRAYWVAZQGENN-UHFFFAOYSA-N 0.000 description 1
• CWDWFSXUQODZGW-UHFFFAOYSA-N 5-thiazolyl Chemical group [C]1=CN=CS1 CWDWFSXUQODZGW-UHFFFAOYSA-N 0.000 description 1
• GDUANFXPOZTYKS-UHFFFAOYSA-N 6-bromo-8-[(2,6-difluoro-4-methoxybenzoyl)amino]-4-oxochromene-2-carboxylic acid Chemical compound FC1=CC(OC)=CC(F)=C1C(=O)NC1=CC(Br)=CC2=C1OC(C(O)=O)=CC2=O GDUANFXPOZTYKS-UHFFFAOYSA-N 0.000 description 1
• XASOHFCUIQARJT-UHFFFAOYSA-N 8-methoxy-6-[7-(2-morpholin-4-ylethoxy)imidazo[1,2-a]pyridin-3-yl]-2-(2,2,2-trifluoroethyl)-3,4-dihydroisoquinolin-1-one Chemical compound C(N1C(=O)C2=C(OC)C=C(C=3N4C(=NC=3)C=C(C=C4)OCCN3CCOCC3)C=C2CC1)C(F)(F)F XASOHFCUIQARJT-UHFFFAOYSA-N 0.000 description 1
• 208000004998 Abdominal Pain Diseases 0.000 description 1
• 208000002874 Acne Vulgaris Diseases 0.000 description 1
• 208000009304 Acute Kidney Injury Diseases 0.000 description 1
• 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 1
• 229930024421 Adenine Natural products 0.000 description 1
• GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
• 201000004384 Alopecia Diseases 0.000 description 1
• 239000005995 Aluminium silicate Substances 0.000 description 1
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
• 208000000044 Amnesia Diseases 0.000 description 1
• 206010002383 Angina Pectoris Diseases 0.000 description 1
• 206010059245 Angiopathy Diseases 0.000 description 1
• 235000003276 Apios tuberosa Nutrition 0.000 description 1
• 244000105624 Arachis hypogaea Species 0.000 description 1
• 235000010777 Arachis hypogaea Nutrition 0.000 description 1
• 235000010744 Arachis villosulicarpa Nutrition 0.000 description 1
• 239000004475 Arginine Substances 0.000 description 1
• 102000007371 Ataxin-3 Human genes 0.000 description 1
• 102000007370 Ataxin2 Human genes 0.000 description 1
• 108010032951 Ataxin2 Proteins 0.000 description 1
• 206010069002 Autoimmune pancreatitis Diseases 0.000 description 1
• 206010061666 Autonomic neuropathy Diseases 0.000 description 1
• NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 1
• 208000009137 Behcet syndrome Diseases 0.000 description 1
• 102100022548 Beta-hexosaminidase subunit alpha Human genes 0.000 description 1
• 208000008439 Biliary Liver Cirrhosis Diseases 0.000 description 1
• 208000033222 Biliary cirrhosis primary Diseases 0.000 description 1
• 102000004506 Blood Proteins Human genes 0.000 description 1
• 108010017384 Blood Proteins Proteins 0.000 description 1
• 206010068597 Bulbospinal muscular atrophy congenital Diseases 0.000 description 1
• 206010006811 Bursitis Diseases 0.000 description 1
• COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
• 102100021943 C-C motif chemokine 2 Human genes 0.000 description 1
• 101710155857 C-C motif chemokine 2 Proteins 0.000 description 1
• 102100025248 C-X-C motif chemokine 10 Human genes 0.000 description 1
• 101710098275 C-X-C motif chemokine 10 Proteins 0.000 description 1
• 101100063435 Caenorhabditis elegans din-1 gene Proteins 0.000 description 1
• 241000282465 Canis Species 0.000 description 1
• 241000283707 Capra Species 0.000 description 1
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
• 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
• 206010007247 Carbuncle Diseases 0.000 description 1
• 206010007882 Cellulitis Diseases 0.000 description 1
• 206010064012 Central pain syndrome Diseases 0.000 description 1
• 208000010693 Charcot-Marie-Tooth Disease Diseases 0.000 description 1
• 208000018380 Chemical injury Diseases 0.000 description 1
• 206010008479 Chest Pain Diseases 0.000 description 1
• 206010008609 Cholangitis sclerosing Diseases 0.000 description 1
• 208000033895 Choreoacanthocytosis Diseases 0.000 description 1
• 208000017667 Chronic Disease Diseases 0.000 description 1
• 208000032544 Cicatrix Diseases 0.000 description 1
• 208000015943 Coeliac disease Diseases 0.000 description 1
• 206010010317 Congenital absence of bile ducts Diseases 0.000 description 1
• 206010010741 Conjunctivitis Diseases 0.000 description 1
• 206010010904 Convulsion Diseases 0.000 description 1
• 208000020406 Creutzfeldt Jacob disease Diseases 0.000 description 1
• 208000003407 Creutzfeldt-Jakob Syndrome Diseases 0.000 description 1
• 208000010859 Creutzfeldt-Jakob disease Diseases 0.000 description 1
• 208000014311 Cushing syndrome Diseases 0.000 description 1
• 201000003883 Cystic fibrosis Diseases 0.000 description 1
• 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 1
• FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
• 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 1
• 206010067889 Dementia with Lewy bodies Diseases 0.000 description 1
• 206010012441 Dermatitis bullous Diseases 0.000 description 1
• 206010012442 Dermatitis contact Diseases 0.000 description 1
• 229920002307 Dextran Polymers 0.000 description 1
• 206010012643 Diabetic amyotrophy Diseases 0.000 description 1
• 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
• 208000003556 Dry Eye Syndromes Diseases 0.000 description 1
• 206010013774 Dry eye Diseases 0.000 description 1
• 208000012661 Dyskinesia Diseases 0.000 description 1
• 208000005171 Dysmenorrhea Diseases 0.000 description 1
• 206010013935 Dysmenorrhoea Diseases 0.000 description 1
• 208000000059 Dyspnea Diseases 0.000 description 1
• 206010013975 Dyspnoeas Diseases 0.000 description 1
• LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
• 206010014498 Embolic stroke Diseases 0.000 description 1
• 241000196324 Embryophyta Species 0.000 description 1
• 208000017701 Endocrine disease Diseases 0.000 description 1
• 102100023688 Eotaxin Human genes 0.000 description 1
• 101710139422 Eotaxin Proteins 0.000 description 1
• 206010053177 Epidermolysis Diseases 0.000 description 1
• 206010015150 Erythema Diseases 0.000 description 1
• 208000010201 Exanthema Diseases 0.000 description 1
• 208000009386 Experimental Arthritis Diseases 0.000 description 1
• 241000282324 Felis Species 0.000 description 1
• 241000282326 Felis catus Species 0.000 description 1
• 239000004606 Fillers/Extenders Substances 0.000 description 1
• 206010016717 Fistula Diseases 0.000 description 1
• OUVXYXNWSVIOSJ-UHFFFAOYSA-N Fluo-4 Chemical compound CC1=CC=C(N(CC(O)=O)CC(O)=O)C(OCCOC=2C(=CC=C(C=2)C2=C3C=C(F)C(=O)C=C3OC3=CC(O)=C(F)C=C32)N(CC(O)=O)CC(O)=O)=C1 OUVXYXNWSVIOSJ-UHFFFAOYSA-N 0.000 description 1
• 208000024412 Friedreich ataxia Diseases 0.000 description 1
• 206010018307 Glaucoma and ocular hypertension Diseases 0.000 description 1
• 206010018364 Glomerulonephritis Diseases 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
• 239000004471 Glycine Substances 0.000 description 1
• 208000024869 Goodpasture syndrome Diseases 0.000 description 1
• 206010018634 Gouty Arthritis Diseases 0.000 description 1
• 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 1
• 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 description 1
• 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
• 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 1
• 208000003807 Graves Disease Diseases 0.000 description 1
• 208000015023 Graves' disease Diseases 0.000 description 1
• 208000035895 Guillain-Barré syndrome Diseases 0.000 description 1
• 208000031886 HIV Infections Diseases 0.000 description 1
• 208000037357 HIV infectious disease Diseases 0.000 description 1
• 208000001204 Hashimoto Disease Diseases 0.000 description 1
• 208000016988 Hemorrhagic Stroke Diseases 0.000 description 1
• 239000004705 High-molecular-weight polyethylene Substances 0.000 description 1
• 101000588130 Homo sapiens Microsomal triglyceride transfer protein large subunit Proteins 0.000 description 1
• 101000667092 Homo sapiens Vacuolar protein sorting-associated protein 13A Proteins 0.000 description 1
• 102000008100 Human Serum Albumin Human genes 0.000 description 1
• 108091006905 Human Serum Albumin Proteins 0.000 description 1
• 241000725303 Human immunodeficiency virus Species 0.000 description 1
• 241000713772 Human immunodeficiency virus 1 Species 0.000 description 1
• 208000007157 Hydrophthalmos Diseases 0.000 description 1
• 208000035154 Hyperesthesia Diseases 0.000 description 1
• 206010021135 Hypovitaminosis Diseases 0.000 description 1
• 206010021143 Hypoxia Diseases 0.000 description 1
• 206010021197 Ichthyoses Diseases 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
• 108010002350 Interleukin-2 Proteins 0.000 description 1
• 108010002386 Interleukin-3 Proteins 0.000 description 1
• 108010002616 Interleukin-5 Proteins 0.000 description 1
• 108090001005 Interleukin-6 Proteins 0.000 description 1
• 108010002335 Interleukin-9 Proteins 0.000 description 1
• PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 1
• 206010023126 Jaundice Diseases 0.000 description 1
• 208000012659 Joint disease Diseases 0.000 description 1
• 208000002260 Keloid Diseases 0.000 description 1
• 208000009319 Keratoconjunctivitis Sicca Diseases 0.000 description 1
• 206010024229 Leprosy Diseases 0.000 description 1
• 229910013470 LiC1 Inorganic materials 0.000 description 1
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
• 208000005777 Lupus Nephritis Diseases 0.000 description 1
• 101000577064 Lymnaea stagnalis Molluscan insulin-related peptide 1 Proteins 0.000 description 1
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
• 239000004472 Lysine Substances 0.000 description 1
• 108010046938 Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
• 102000007651 Macrophage Colony-Stimulating Factor Human genes 0.000 description 1
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
• 206010025476 Malabsorption Diseases 0.000 description 1
• 208000004155 Malabsorption Syndromes Diseases 0.000 description 1
• 241000124008 Mammalia Species 0.000 description 1
• 240000003183 Manihot esculenta Species 0.000 description 1
• 235000016735 Manihot esculenta subsp esculenta Nutrition 0.000 description 1
• 229930195725 Mannitol Natural products 0.000 description 1
• 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
• 102100031545 Microsomal triglyceride transfer protein large subunit Human genes 0.000 description 1
• 206010049567 Miller Fisher syndrome Diseases 0.000 description 1
• 101710151803 Mitochondrial intermediate peptidase 2 Proteins 0.000 description 1
• 206010027918 Mononeuropathy multiplex Diseases 0.000 description 1
• 208000026072 Motor neurone disease Diseases 0.000 description 1
• 206010028116 Mucosal inflammation Diseases 0.000 description 1
• 201000010927 Mucositis Diseases 0.000 description 1
• 208000002740 Muscle Rigidity Diseases 0.000 description 1
• 208000009525 Myocarditis Diseases 0.000 description 1
• 101000737895 Mytilus edulis Contraction-inhibiting peptide 1 Proteins 0.000 description 1
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 1
• AVYVHIKSFXVDBG-UHFFFAOYSA-N N-benzyl-N-hydroxy-2,2-dimethylbutanamide Chemical compound C(C1=CC=CC=C1)N(C(C(CC)(C)C)=O)O AVYVHIKSFXVDBG-UHFFFAOYSA-N 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
• 206010052437 Nasal discomfort Diseases 0.000 description 1
• 206010028836 Neck pain Diseases 0.000 description 1
• 206010028851 Necrosis Diseases 0.000 description 1
• 206010028980 Neoplasm Diseases 0.000 description 1
• IPEARMYLWJENPB-UHFFFAOYSA-N OCC1=NC=CC(=C1)C1=CC=NC=C1 Chemical compound OCC1=NC=CC(=C1)C1=CC=NC=C1 IPEARMYLWJENPB-UHFFFAOYSA-N 0.000 description 1
• 206010061876 Obstruction Diseases 0.000 description 1
• 208000022873 Ocular disease Diseases 0.000 description 1
• 208000014723 Oculomotor Nerve disease Diseases 0.000 description 1
• 240000007817 Olea europaea Species 0.000 description 1
• 206010030865 Ophthalmic herpes zoster Diseases 0.000 description 1
• 208000001388 Opportunistic Infections Diseases 0.000 description 1
• 208000001132 Osteoporosis Diseases 0.000 description 1
• 229910003873 O—P—O Inorganic materials 0.000 description 1
• 229930012538 Paclitaxel Natural products 0.000 description 1
• 229930040373 Paraformaldehyde Natural products 0.000 description 1
• 208000031481 Pathologic Constriction Diseases 0.000 description 1
• 229910021120 PdC12 Inorganic materials 0.000 description 1
• 241001494479 Pecora Species 0.000 description 1
• 241000721454 Pemphigus Species 0.000 description 1
• 208000018262 Peripheral vascular disease Diseases 0.000 description 1
• 206010034719 Personality change Diseases 0.000 description 1
• 206010051246 Photodermatosis Diseases 0.000 description 1
• 206010034972 Photosensitivity reaction Diseases 0.000 description 1
• 206010035015 Pigmentary glaucoma Diseases 0.000 description 1
• 240000004760 Pimpinella anisum Species 0.000 description 1
• 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
• 206010062519 Poor quality sleep Diseases 0.000 description 1
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
• 208000012654 Primary biliary cholangitis Diseases 0.000 description 1
• 208000032319 Primary lateral sclerosis Diseases 0.000 description 1
• 241000288906 Primates Species 0.000 description 1
• 206010036774 Proctitis Diseases 0.000 description 1
• 102000007327 Protamines Human genes 0.000 description 1
• 108010007568 Protamines Proteins 0.000 description 1
• YZCKVEUIGOORGS-IGMARMGPSA-N Protium Chemical compound [1H] YZCKVEUIGOORGS-IGMARMGPSA-N 0.000 description 1
• 208000003251 Pruritus Diseases 0.000 description 1
• 208000033626 Renal failure acute Diseases 0.000 description 1
• 206010063837 Reperfusion injury Diseases 0.000 description 1
• 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 1
• 235000004443 Ricinus communis Nutrition 0.000 description 1
• 241000283984 Rodentia Species 0.000 description 1
• 208000021811 Sandhoff disease Diseases 0.000 description 1
• 208000008765 Sciatica Diseases 0.000 description 1
• 206010039705 Scleritis Diseases 0.000 description 1
• 206010039710 Scleroderma Diseases 0.000 description 1
• 206010039793 Seborrhoeic dermatitis Diseases 0.000 description 1
• 206010070834 Sensitisation Diseases 0.000 description 1
• 206010040070 Septic Shock Diseases 0.000 description 1
• 208000007613 Shoulder Pain Diseases 0.000 description 1
• 206010053262 Skin swelling Diseases 0.000 description 1
• DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
• 235000002595 Solanum tuberosum Nutrition 0.000 description 1
• 244000061456 Solanum tuberosum Species 0.000 description 1
• 206010072005 Spinal pain Diseases 0.000 description 1
• 201000003622 Spinocerebellar ataxia type 2 Diseases 0.000 description 1
• 201000003620 Spinocerebellar ataxia type 6 Diseases 0.000 description 1
• 201000002661 Spondylitis Diseases 0.000 description 1
• 206010041955 Stasis dermatitis Diseases 0.000 description 1
• SSZBUIDZHHWXNJ-UHFFFAOYSA-N Stearinsaeure-hexadecylester Natural products CCCCCCCCCCCCCCCCCC(=O)OCCCCCCCCCCCCCCCC SSZBUIDZHHWXNJ-UHFFFAOYSA-N 0.000 description 1
• 208000002847 Surgical Wound Diseases 0.000 description 1
• 208000022292 Tay-Sachs disease Diseases 0.000 description 1
• QIOZLISABUUKJY-UHFFFAOYSA-N Thiobenzamide Chemical compound NC(=S)C1=CC=CC=C1 QIOZLISABUUKJY-UHFFFAOYSA-N 0.000 description 1
• 206010043647 Thrombotic Stroke Diseases 0.000 description 1
• 206010056697 Tissue anoxia Diseases 0.000 description 1
• 206010051446 Transient acantholytic dermatosis Diseases 0.000 description 1
• 206010044565 Tremor Diseases 0.000 description 1
• 206010045178 Tunnel vision Diseases 0.000 description 1
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
• HSCJRCZFDFQWRP-JZMIEXBBSA-N UDP-alpha-D-glucose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OP(O)(=O)OP(O)(=O)OC[C@@H]1[C@@H](O)[C@@H](O)[C@H](N2C(NC(=O)C=C2)=O)O1 HSCJRCZFDFQWRP-JZMIEXBBSA-N 0.000 description 1
• 206010046298 Upper motor neurone lesion Diseases 0.000 description 1
• ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 1
• HSCJRCZFDFQWRP-UHFFFAOYSA-N Uridindiphosphoglukose Natural products OC1C(O)C(O)C(CO)OC1OP(O)(=O)OP(O)(=O)OCC1C(O)C(O)C(N2C(NC(=O)C=C2)=O)O1 HSCJRCZFDFQWRP-UHFFFAOYSA-N 0.000 description 1
• 206010046851 Uveitis Diseases 0.000 description 1
• 102100039114 Vacuolar protein sorting-associated protein 13A Human genes 0.000 description 1
• 208000036142 Viral infection Diseases 0.000 description 1
• 241000700605 Viruses Species 0.000 description 1
• 206010047513 Vision blurred Diseases 0.000 description 1
• 240000008042 Zea mays Species 0.000 description 1
• 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
• 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
• 229920000392 Zymosan Polymers 0.000 description 1
• ABRVLXLNVJHDRQ-UHFFFAOYSA-N [2-pyridin-3-yl-6-(trifluoromethyl)pyridin-4-yl]methanamine Chemical compound FC(C1=CC(=CC(=N1)C=1C=NC=CC=1)CN)(F)F ABRVLXLNVJHDRQ-UHFFFAOYSA-N 0.000 description 1
• SZPWXAOBLNYOHY-UHFFFAOYSA-N [C]1=CC=NC2=CC=CC=C12 Chemical group [C]1=CC=NC2=CC=CC=C12 SZPWXAOBLNYOHY-UHFFFAOYSA-N 0.000 description 1
• PGAVKCOVUIYSFO-UHFFFAOYSA-N [[5-(2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate Chemical compound OC1C(O)C(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)OC1N1C(=O)NC(=O)C=C1 PGAVKCOVUIYSFO-UHFFFAOYSA-N 0.000 description 1
• 210000000683 abdominal cavity Anatomy 0.000 description 1
• 208000020560 abdominal swelling Diseases 0.000 description 1
• 230000001594 aberrant effect Effects 0.000 description 1
• 206010000269 abscess Diseases 0.000 description 1
• 239000002250 absorbent Substances 0.000 description 1
• 230000002745 absorbent Effects 0.000 description 1
• 239000003655 absorption accelerator Substances 0.000 description 1
• DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
• 230000002378 acidificating effect Effects 0.000 description 1
• 206010000496 acne Diseases 0.000 description 1
• 239000004480 active ingredient Substances 0.000 description 1
• 208000038016 acute inflammation Diseases 0.000 description 1
• 230000006022 acute inflammation Effects 0.000 description 1
• 201000011040 acute kidney failure Diseases 0.000 description 1
• 208000012998 acute renal failure Diseases 0.000 description 1
• 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
• 229960000643 adenine Drugs 0.000 description 1
• 210000004404 adrenal cortex Anatomy 0.000 description 1
• 208000011341 adult acute respiratory distress syndrome Diseases 0.000 description 1
• 201000000028 adult respiratory distress syndrome Diseases 0.000 description 1
• 239000000783 alginic acid Substances 0.000 description 1
• 229960001126 alginic acid Drugs 0.000 description 1
• 150000004781 alginic acids Chemical class 0.000 description 1
• 239000003513 alkali Substances 0.000 description 1
• 125000000217 alkyl group Chemical group 0.000 description 1
• 239000013566 allergen Substances 0.000 description 1
• 208000002029 allergic contact dermatitis Diseases 0.000 description 1
• 230000000172 allergic effect Effects 0.000 description 1
• 206010053552 allodynia Diseases 0.000 description 1
• 231100000360 alopecia Toxicity 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
• PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
• 235000012211 aluminium silicate Nutrition 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
• 150000001413 amino acids Chemical class 0.000 description 1
• 235000011114 ammonium hydroxide Nutrition 0.000 description 1
• 150000003863 ammonium salts Chemical class 0.000 description 1
• 230000003444 anaesthetic effect Effects 0.000 description 1
• 239000003242 anti bacterial agent Substances 0.000 description 1
• 230000000844 anti-bacterial effect Effects 0.000 description 1
• 239000003429 antifungal agent Substances 0.000 description 1
• 229940121375 antifungal agent Drugs 0.000 description 1
• 239000003963 antioxidant agent Substances 0.000 description 1
• 210000000436 anus Anatomy 0.000 description 1
• 230000004596 appetite loss Effects 0.000 description 1
• 239000008365 aqueous carrier Substances 0.000 description 1
• 239000007864 aqueous solution Substances 0.000 description 1
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
• 125000006615 aromatic heterocyclic group Chemical group 0.000 description 1
• 230000002917 arthritic effect Effects 0.000 description 1
• 208000006673 asthma Diseases 0.000 description 1
• 230000006472 autoimmune response Effects 0.000 description 1
• 230000008901 benefit Effects 0.000 description 1
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
• 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
• 229960002903 benzyl benzoate Drugs 0.000 description 1
• WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
• 125000002527 bicyclic carbocyclic group Chemical group 0.000 description 1
• 230000002146 bilateral effect Effects 0.000 description 1
• 201000005271 biliary atresia Diseases 0.000 description 1
• 239000011230 binding agent Substances 0.000 description 1
• 239000012620 biological material Substances 0.000 description 1
• 230000033228 biological regulation Effects 0.000 description 1
• SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
• 210000004204 blood vessel Anatomy 0.000 description 1
• 208000027503 bloody stool Diseases 0.000 description 1
• 210000000988 bone and bone Anatomy 0.000 description 1
• GXJABQQUPOEUTA-RDJZCZTQSA-N bortezomib Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)B(O)O)NC(=O)C=1N=CC=NC=1)C1=CC=CC=C1 GXJABQQUPOEUTA-RDJZCZTQSA-N 0.000 description 1
• 229960001467 bortezomib Drugs 0.000 description 1
• 210000003461 brachial plexus Anatomy 0.000 description 1
• 201000006431 brachial plexus neuropathy Diseases 0.000 description 1
• 230000003925 brain function Effects 0.000 description 1
• 201000007293 brain stem infarction Diseases 0.000 description 1
• 238000009395 breeding Methods 0.000 description 1
• 230000001488 breeding effect Effects 0.000 description 1
• 206010006451 bronchitis Diseases 0.000 description 1
• 239000006172 buffering agent Substances 0.000 description 1
• 235000019437 butane-1,3-diol Nutrition 0.000 description 1
• 229910000024 caesium carbonate Inorganic materials 0.000 description 1
• 229910000019 calcium carbonate Inorganic materials 0.000 description 1
• 235000010216 calcium carbonate Nutrition 0.000 description 1
• 239000001506 calcium phosphate Substances 0.000 description 1
• 159000000007 calcium salts Chemical class 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
• 239000008116 calcium stearate Substances 0.000 description 1
• 235000013539 calcium stearate Nutrition 0.000 description 1
• 201000011510 cancer Diseases 0.000 description 1
• 150000001720 carbohydrates Chemical class 0.000 description 1
• 235000014633 carbohydrates Nutrition 0.000 description 1
• 150000001721 carbon Chemical group 0.000 description 1
• 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
• 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
• 210000000748 cardiovascular system Anatomy 0.000 description 1
• 239000000969 carrier Substances 0.000 description 1
• 239000004359 castor oil Substances 0.000 description 1
• 230000015556 catabolic process Effects 0.000 description 1
• 230000003915 cell function Effects 0.000 description 1
• 230000004663 cell proliferation Effects 0.000 description 1
• 230000001413 cellular effect Effects 0.000 description 1
• 239000001913 cellulose Substances 0.000 description 1
• 235000010980 cellulose Nutrition 0.000 description 1
• 229920002678 cellulose Polymers 0.000 description 1
• 201000004559 cerebral degeneration Diseases 0.000 description 1
• 210000001175 cerebrospinal fluid Anatomy 0.000 description 1
• 229960000541 cetyl alcohol Drugs 0.000 description 1
• 208000007287 cheilitis Diseases 0.000 description 1
• 210000000038 chest Anatomy 0.000 description 1
• 229960004926 chlorobutanol Drugs 0.000 description 1
• 235000012000 cholesterol Nutrition 0.000 description 1
• 201000008675 chorea-acanthocytosis Diseases 0.000 description 1
• 230000012085 chronic inflammatory response Effects 0.000 description 1
• 208000020832 chronic kidney disease Diseases 0.000 description 1
• 239000004927 clay Substances 0.000 description 1
• 239000011248 coating agent Substances 0.000 description 1
• 238000000576 coating method Methods 0.000 description 1
• 239000008119 colloidal silica Substances 0.000 description 1
• 210000001072 colon Anatomy 0.000 description 1
• 238000004040 coloring Methods 0.000 description 1
• 238000013270 controlled release Methods 0.000 description 1
• 238000007796 conventional method Methods 0.000 description 1
• 238000001816 cooling Methods 0.000 description 1
• 235000005822 corn Nutrition 0.000 description 1
• 235000012343 cottonseed oil Nutrition 0.000 description 1
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 125000001162 cycloheptenyl group Chemical group C1(=CCCCCC1)* 0.000 description 1
• 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
• JCWIWBWXCVGEAN-UHFFFAOYSA-L cyclopentyl(diphenyl)phosphane;dichloropalladium;iron Chemical compound [Fe].Cl[Pd]Cl.[CH]1[CH][CH][CH][C]1P(C=1C=CC=CC=1)C1=CC=CC=C1.[CH]1[CH][CH][CH][C]1P(C=1C=CC=CC=1)C1=CC=CC=C1 JCWIWBWXCVGEAN-UHFFFAOYSA-L 0.000 description 1
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
• 125000004855 decalinyl group Chemical group C1(CCCC2CCCCC12)* 0.000 description 1
• 230000007812 deficiency Effects 0.000 description 1
• 230000007850 degeneration Effects 0.000 description 1
• 230000003412 degenerative effect Effects 0.000 description 1
• 230000003210 demyelinating effect Effects 0.000 description 1
• 230000001419 dependent effect Effects 0.000 description 1
• 230000006866 deterioration Effects 0.000 description 1
• NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
• 229940038472 dicalcium phosphate Drugs 0.000 description 1
• 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
• 235000019621 digestibility Nutrition 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
• FSBVERYRVPGNGG-UHFFFAOYSA-N dimagnesium dioxido-bis[[oxido(oxo)silyl]oxy]silane hydrate Chemical compound O.[Mg+2].[Mg+2].[O-][Si](=O)O[Si]([O-])([O-])O[Si]([O-])=O FSBVERYRVPGNGG-UHFFFAOYSA-N 0.000 description 1
• 230000003292 diminished effect Effects 0.000 description 1
• ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 1
• 235000019797 dipotassium phosphate Nutrition 0.000 description 1
• 229910000396 dipotassium phosphate Inorganic materials 0.000 description 1
• LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
• 208000037765 diseases and disorders Diseases 0.000 description 1
• BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
• 239000002270 dispersing agent Substances 0.000 description 1
• 208000002173 dizziness Diseases 0.000 description 1
• 229960003638 dopamine Drugs 0.000 description 1
• 231100000673 dose–response relationship Toxicity 0.000 description 1
• 239000008298 dragée Substances 0.000 description 1
• 239000003792 electrolyte Substances 0.000 description 1
• 238000002001 electrophysiology Methods 0.000 description 1
• 230000007831 electrophysiology Effects 0.000 description 1
• 230000004970 emotional disturbance Effects 0.000 description 1
• 230000001804 emulsifying effect Effects 0.000 description 1
• 201000000523 end stage renal failure Diseases 0.000 description 1
• 210000000750 endocrine system Anatomy 0.000 description 1
• 238000005516 engineering process Methods 0.000 description 1
• 210000002615 epidermis Anatomy 0.000 description 1
• 230000003628 erosive effect Effects 0.000 description 1
• ITQFPVUDTFABDH-AATRIKPKSA-N ethyl (e)-3-ethoxyprop-2-enoate Chemical compound CCO\C=C\C(=O)OCC ITQFPVUDTFABDH-AATRIKPKSA-N 0.000 description 1
• OWZFULPEVHKEKS-UHFFFAOYSA-N ethyl 2-chloro-2-oxoacetate Chemical compound CCOC(=O)C(Cl)=O OWZFULPEVHKEKS-UHFFFAOYSA-N 0.000 description 1
• ROKNTXACUCMRQU-UHFFFAOYSA-N ethyl 2-phenyl-1,3-thiazole-5-carboxylate Chemical compound S1C(C(=O)OCC)=CN=C1C1=CC=CC=C1 ROKNTXACUCMRQU-UHFFFAOYSA-N 0.000 description 1
• GWNFQAKCJYEJEW-UHFFFAOYSA-N ethyl 3-[8-[[4-methyl-5-[(3-methyl-4-oxophthalazin-1-yl)methyl]-1,2,4-triazol-3-yl]sulfanyl]octanoylamino]benzoate Chemical compound CCOC(=O)C1=CC(NC(=O)CCCCCCCSC2=NN=C(CC3=NN(C)C(=O)C4=CC=CC=C34)N2C)=CC=C1 GWNFQAKCJYEJEW-UHFFFAOYSA-N 0.000 description 1
• PZNHMXAOMDQLLE-UHFFFAOYSA-N ethyl 5-bromothiophene-2-carboxylate Chemical compound CCOC(=O)C1=CC=C(Br)S1 PZNHMXAOMDQLLE-UHFFFAOYSA-N 0.000 description 1
• UXNYFCYTHBUYNK-UHFFFAOYSA-N ethyl 5-phenylthiophene-2-carboxylate Chemical compound S1C(C(=O)OCC)=CC=C1C1=CC=CC=C1 UXNYFCYTHBUYNK-UHFFFAOYSA-N 0.000 description 1
• 229940093499 ethyl acetate Drugs 0.000 description 1
• LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
• 229940093471 ethyl oleate Drugs 0.000 description 1
• 201000005884 exanthem Diseases 0.000 description 1
• 201000004356 excessive tearing Diseases 0.000 description 1
• 230000005284 excitation Effects 0.000 description 1
• 230000004373 eye development Effects 0.000 description 1
• 150000004665 fatty acids Chemical class 0.000 description 1
• 230000003890 fistula Effects 0.000 description 1
• 238000003818 flash chromatography Methods 0.000 description 1
• 206010016766 flatulence Diseases 0.000 description 1
• 239000000796 flavoring agent Substances 0.000 description 1
• 235000013305 food Nutrition 0.000 description 1
• 239000012458 free base Substances 0.000 description 1
• GIVLTTJNORAZON-HDBOBKCLSA-N ganglioside GM2 (18:0) Chemical compound O[C@@H]1[C@@H](O)[C@H](OC[C@H](NC(=O)CCCCCCCCCCCCCCCCC)[C@H](O)\C=C\CCCCCCCCCCCCC)O[C@H](CO)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@]2(O[C@H]([C@H](NC(C)=O)[C@@H](O)C2)[C@H](O)[C@H](O)CO)C(O)=O)[C@@H](O[C@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](CO)O1 GIVLTTJNORAZON-HDBOBKCLSA-N 0.000 description 1
• 239000007903 gelatin capsule Substances 0.000 description 1
• 238000012252 genetic analysis Methods 0.000 description 1
• 230000002068 genetic effect Effects 0.000 description 1
• 239000008103 glucose Substances 0.000 description 1
• 125000005456 glyceride group Chemical group 0.000 description 1
• YQEMORVAKMFKLG-UHFFFAOYSA-N glycerine monostearate Natural products CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 description 1
• SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 0.000 description 1
• 229960002449 glycine Drugs 0.000 description 1
• 125000005843 halogen group Chemical group 0.000 description 1
• 230000036541 health Effects 0.000 description 1
• 210000005003 heart tissue Anatomy 0.000 description 1
• 208000006454 hepatitis Diseases 0.000 description 1
• 231100000283 hepatitis Toxicity 0.000 description 1
• BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 1
• 208000002557 hidradenitis Diseases 0.000 description 1
• 201000007162 hidradenitis suppurativa Diseases 0.000 description 1
• 239000005556 hormone Substances 0.000 description 1
• 229940088597 hormone Drugs 0.000 description 1
• 210000005260 human cell Anatomy 0.000 description 1
• 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 1
• 239000003906 humectant Substances 0.000 description 1
• XGIHQYAWBCFNPY-AZOCGYLKSA-N hydrabamine Chemical class C([C@@H]12)CC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC[C@@]1(C)CNCCNC[C@@]1(C)[C@@H]2CCC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC1 XGIHQYAWBCFNPY-AZOCGYLKSA-N 0.000 description 1
• 150000004677 hydrates Chemical class 0.000 description 1
• 229910052739 hydrogen Inorganic materials 0.000 description 1
• 239000001257 hydrogen Substances 0.000 description 1
• AFQIYTIJXGTIEY-UHFFFAOYSA-N hydrogen carbonate;triethylazanium Chemical compound OC(O)=O.CCN(CC)CC AFQIYTIJXGTIEY-UHFFFAOYSA-N 0.000 description 1
• 230000001969 hypertrophic effect Effects 0.000 description 1
• 206010021198 ichthyosis Diseases 0.000 description 1
• 210000003405 ileum Anatomy 0.000 description 1
• 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 description 1
• 239000012642 immune effector Substances 0.000 description 1
• 230000000899 immune system response Effects 0.000 description 1
• 238000003364 immunohistochemistry Methods 0.000 description 1
• 229940121354 immunomodulator Drugs 0.000 description 1
• 239000007943 implant Substances 0.000 description 1
• 238000002513 implantation Methods 0.000 description 1
• 235000013666 improved nutrition Nutrition 0.000 description 1
• 238000011503 in vivo imaging Methods 0.000 description 1
• 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
• 125000001041 indolyl group Chemical group 0.000 description 1
• 150000007529 inorganic bases Chemical class 0.000 description 1
• 150000002484 inorganic compounds Chemical class 0.000 description 1
• 229910010272 inorganic material Inorganic materials 0.000 description 1
• 230000003993 interaction Effects 0.000 description 1
• 201000006334 interstitial nephritis Diseases 0.000 description 1
• 208000020658 intracerebral hemorrhage Diseases 0.000 description 1
• 238000007912 intraperitoneal administration Methods 0.000 description 1
• 150000002500 ions Chemical class 0.000 description 1
• 201000004614 iritis Diseases 0.000 description 1
• LZKLAOYSENRNKR-LNTINUHCSA-N iron;(z)-4-oxoniumylidenepent-2-en-2-olate Chemical compound [Fe].C\C(O)=C\C(C)=O.C\C(O)=C\C(C)=O.C\C(O)=C\C(C)=O LZKLAOYSENRNKR-LNTINUHCSA-N 0.000 description 1
• 230000001788 irregular Effects 0.000 description 1
• 208000001875 irritant dermatitis Diseases 0.000 description 1
• 230000007794 irritation Effects 0.000 description 1
• 208000012947 ischemia reperfusion injury Diseases 0.000 description 1
• 229960002725 isoflurane Drugs 0.000 description 1
• 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
• 125000001786 isothiazolyl group Chemical group 0.000 description 1
• 239000007951 isotonicity adjuster Substances 0.000 description 1
• 230000007803 itching Effects 0.000 description 1
• NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
• 210000001117 keloid Anatomy 0.000 description 1
• 238000002372 labelling Methods 0.000 description 1
• 210000002429 large intestine Anatomy 0.000 description 1
• 201000010901 lateral sclerosis Diseases 0.000 description 1
• 201000003723 learning disability Diseases 0.000 description 1
• 210000002414 leg Anatomy 0.000 description 1
• 230000003902 lesion Effects 0.000 description 1
• 210000000265 leukocyte Anatomy 0.000 description 1
• 201000011486 lichen planus Diseases 0.000 description 1
• 150000002632 lipids Chemical class 0.000 description 1
• 229910052744 lithium Inorganic materials 0.000 description 1
• 210000005228 liver tissue Anatomy 0.000 description 1
• 244000144972 livestock Species 0.000 description 1
• 208000019017 loss of appetite Diseases 0.000 description 1
• 235000021266 loss of appetite Nutrition 0.000 description 1
• 210000003141 lower extremity Anatomy 0.000 description 1
• 239000007937 lozenge Substances 0.000 description 1
• 239000000314 lubricant Substances 0.000 description 1
• 210000004705 lumbosacral region Anatomy 0.000 description 1
• 206010025135 lupus erythematosus Diseases 0.000 description 1
• 229920002521 macromolecule Polymers 0.000 description 1
• 239000011777 magnesium Substances 0.000 description 1
• 229910052749 magnesium Inorganic materials 0.000 description 1
• 239000000391 magnesium silicate Substances 0.000 description 1
• 235000019359 magnesium stearate Nutrition 0.000 description 1
• 229910000386 magnesium trisilicate Inorganic materials 0.000 description 1
• 235000019793 magnesium trisilicate Nutrition 0.000 description 1
• 229940099273 magnesium trisilicate Drugs 0.000 description 1
• GFTXWCQFWLOXAT-UHFFFAOYSA-M magnesium;cyclohexane;bromide Chemical compound [Mg+2].[Br-].C1CC[CH-]CC1 GFTXWCQFWLOXAT-UHFFFAOYSA-M 0.000 description 1
• 238000012423 maintenance Methods 0.000 description 1
• 238000007726 management method Methods 0.000 description 1
• 239000000594 mannitol Substances 0.000 description 1
• 235000010355 mannitol Nutrition 0.000 description 1
• 210000003784 masticatory muscle Anatomy 0.000 description 1
• 230000007246 mechanism Effects 0.000 description 1
• 210000004379 membrane Anatomy 0.000 description 1
• 239000012528 membrane Substances 0.000 description 1
• 230000006984 memory degeneration Effects 0.000 description 1
• 230000006386 memory function Effects 0.000 description 1
• 208000023060 memory loss Diseases 0.000 description 1
• 210000004914 menses Anatomy 0.000 description 1
• 230000003924 mental process Effects 0.000 description 1
• 230000004066 metabolic change Effects 0.000 description 1
• 239000002207 metabolite Substances 0.000 description 1
• JEURNBCYNWNADN-UHFFFAOYSA-N methyl 5-bromopyridine-2-carboxylate Chemical compound COC(=O)C1=CC=C(Br)C=N1 JEURNBCYNWNADN-UHFFFAOYSA-N 0.000 description 1
• AQGYGJYEJSHSKE-UHFFFAOYSA-N methyl 5-phenylpyridine-2-carboxylate Chemical compound C1=NC(C(=O)OC)=CC=C1C1=CC=CC=C1 AQGYGJYEJSHSKE-UHFFFAOYSA-N 0.000 description 1
• 239000004530 micro-emulsion Substances 0.000 description 1
• 244000005700 microbiome Species 0.000 description 1
• 229940016286 microcrystalline cellulose Drugs 0.000 description 1
• 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
• 239000008108 microcrystalline cellulose Substances 0.000 description 1
• 230000027939 micturition Effects 0.000 description 1
• 235000013336 milk Nutrition 0.000 description 1
• 239000008267 milk Substances 0.000 description 1
• 210000004080 milk Anatomy 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• 230000037230 mobility Effects 0.000 description 1
• CQDGTJPVBWZJAZ-UHFFFAOYSA-N monoethyl carbonate Chemical compound CCOC(O)=O CQDGTJPVBWZJAZ-UHFFFAOYSA-N 0.000 description 1
• 201000002003 mononeuritis multiplex Diseases 0.000 description 1
• 210000002161 motor neuron Anatomy 0.000 description 1
• 238000010172 mouse model Methods 0.000 description 1
• 210000003097 mucus Anatomy 0.000 description 1
• 230000035772 mutation Effects 0.000 description 1
• YGBMCLDVRUGXOV-UHFFFAOYSA-N n-[6-[6-chloro-5-[(4-fluorophenyl)sulfonylamino]pyridin-3-yl]-1,3-benzothiazol-2-yl]acetamide Chemical compound C1=C2SC(NC(=O)C)=NC2=CC=C1C(C=1)=CN=C(Cl)C=1NS(=O)(=O)C1=CC=C(F)C=C1 YGBMCLDVRUGXOV-UHFFFAOYSA-N 0.000 description 1
• 125000001624 naphthyl group Chemical group 0.000 description 1
• 201000003142 neovascular glaucoma Diseases 0.000 description 1
• 210000004126 nerve fiber Anatomy 0.000 description 1
• 230000007230 neural mechanism Effects 0.000 description 1
• 208000007431 neuroacanthocytosis Diseases 0.000 description 1
• 210000004498 neuroglial cell Anatomy 0.000 description 1
• 239000002581 neurotoxin Substances 0.000 description 1
• 231100000618 neurotoxin Toxicity 0.000 description 1
• 239000002858 neurotransmitter agent Substances 0.000 description 1
• 208000004235 neutropenia Diseases 0.000 description 1
• 230000003040 nociceptive effect Effects 0.000 description 1
• 239000012457 nonaqueous media Substances 0.000 description 1
• 125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 description 1
• 238000010606 normalization Methods 0.000 description 1
• 210000001331 nose Anatomy 0.000 description 1
• 239000002773 nucleotide Substances 0.000 description 1
• 125000003729 nucleotide group Chemical group 0.000 description 1
• 231100000862 numbness Toxicity 0.000 description 1
• 235000018343 nutrient deficiency Nutrition 0.000 description 1
• 235000016709 nutrition Nutrition 0.000 description 1
• 230000035764 nutrition Effects 0.000 description 1
• 235000008390 olive oil Nutrition 0.000 description 1
• 230000003287 optical effect Effects 0.000 description 1
• 150000007524 organic acids Chemical class 0.000 description 1
• 150000002894 organic compounds Chemical class 0.000 description 1
• 150000002895 organic esters Chemical class 0.000 description 1
• 230000027758 ovulation cycle Effects 0.000 description 1
• 229960001592 paclitaxel Drugs 0.000 description 1
• QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
• 239000012188 paraffin wax Substances 0.000 description 1
• 229920002866 paraformaldehyde Polymers 0.000 description 1
• 244000045947 parasite Species 0.000 description 1
• 230000036961 partial effect Effects 0.000 description 1
• 239000002245 particle Substances 0.000 description 1
• 235000010603 pastilles Nutrition 0.000 description 1
• 230000008506 pathogenesis Effects 0.000 description 1
• 230000007170 pathology Effects 0.000 description 1
• 230000037361 pathway Effects 0.000 description 1
• 210000004197 pelvis Anatomy 0.000 description 1
• 230000008447 perception Effects 0.000 description 1
• 239000002304 perfume Substances 0.000 description 1
• 210000003516 pericardium Anatomy 0.000 description 1
• 208000028169 periodontal disease Diseases 0.000 description 1
• 230000002093 peripheral effect Effects 0.000 description 1
• 210000000578 peripheral nerve Anatomy 0.000 description 1
• 208000027232 peripheral nervous system disease Diseases 0.000 description 1
• 230000005043 peripheral vision Effects 0.000 description 1
• 230000008855 peristalsis Effects 0.000 description 1
• 210000003024 peritoneal macrophage Anatomy 0.000 description 1
• 210000004303 peritoneum Anatomy 0.000 description 1
• CVXGFPPAIUELDV-UHFFFAOYSA-N phenacylazanium;chloride Chemical compound [Cl-].[NH3+]CC(=O)C1=CC=CC=C1 CVXGFPPAIUELDV-UHFFFAOYSA-N 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
• 239000002953 phosphate buffered saline Substances 0.000 description 1
• WRMXOVHLRUVREB-UHFFFAOYSA-N phosphono phosphate;tributylazanium Chemical compound OP(O)(=O)OP([O-])([O-])=O.CCCC[NH+](CCCC)CCCC.CCCC[NH+](CCCC)CCCC WRMXOVHLRUVREB-UHFFFAOYSA-N 0.000 description 1
• PTMHPRAIXMAOOB-UHFFFAOYSA-L phosphoramidate Chemical compound NP([O-])([O-])=O PTMHPRAIXMAOOB-UHFFFAOYSA-L 0.000 description 1
• 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
• 230000008845 photoaging Effects 0.000 description 1
• 208000002440 photoallergic dermatitis Diseases 0.000 description 1
• 208000007578 phototoxic dermatitis Diseases 0.000 description 1
• 230000035479 physiological effects, processes and functions Effects 0.000 description 1
• 230000035790 physiological processes and functions Effects 0.000 description 1
• 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 1
• 238000007747 plating Methods 0.000 description 1
• 229920000058 polyacrylate Polymers 0.000 description 1
• 229920000642 polymer Polymers 0.000 description 1
• 208000019629 polyneuritis Diseases 0.000 description 1
• 229920005862 polyol Polymers 0.000 description 1
• 150000003077 polyols Chemical class 0.000 description 1
• 238000011886 postmortem examination Methods 0.000 description 1
• 239000011591 potassium Substances 0.000 description 1
• 229910052700 potassium Inorganic materials 0.000 description 1
• 235000010241 potassium sorbate Nutrition 0.000 description 1
• 239000004302 potassium sorbate Substances 0.000 description 1
• 229940069338 potassium sorbate Drugs 0.000 description 1
• 239000002244 precipitate Substances 0.000 description 1
• 239000002243 precursor Substances 0.000 description 1
• 238000003825 pressing Methods 0.000 description 1
• 208000037920 primary disease Diseases 0.000 description 1
• 201000009395 primary hyperaldosteronism Diseases 0.000 description 1
• 201000000742 primary sclerosing cholangitis Diseases 0.000 description 1
• 108090000765 processed proteins & peptides Proteins 0.000 description 1
• 239000000047 product Substances 0.000 description 1
• 230000002250 progressing effect Effects 0.000 description 1
• 230000000750 progressive effect Effects 0.000 description 1
• 230000035755 proliferation Effects 0.000 description 1
• 230000002035 prolonged effect Effects 0.000 description 1
• VVWRJUBEIPHGQF-MDZDMXLPSA-N propan-2-yl (ne)-n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)\N=N\C(=O)OC(C)C VVWRJUBEIPHGQF-MDZDMXLPSA-N 0.000 description 1
• 235000013772 propylene glycol Nutrition 0.000 description 1
• 229950008679 protamine sulfate Drugs 0.000 description 1
• 230000001107 psychogenic effect Effects 0.000 description 1
• 208000005069 pulmonary fibrosis Diseases 0.000 description 1
• 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
• 125000003373 pyrazinyl group Chemical group 0.000 description 1
• 125000003226 pyrazolyl group Chemical group 0.000 description 1
• 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 description 1
• 125000002098 pyridazinyl group Chemical group 0.000 description 1
• QLULGIRFKAWHOJ-UHFFFAOYSA-N pyridin-4-ylboronic acid Chemical compound OB(O)C1=CC=NC=C1 QLULGIRFKAWHOJ-UHFFFAOYSA-N 0.000 description 1
• 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 1
• 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 1
• 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 1
• 150000003856 quaternary ammonium compounds Chemical class 0.000 description 1
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
• 208000006934 radiodermatitis Diseases 0.000 description 1
• 206010037844 rash Diseases 0.000 description 1
• 239000002464 receptor antagonist Substances 0.000 description 1
• 229940044551 receptor antagonist Drugs 0.000 description 1
• 230000011514 reflex Effects 0.000 description 1
• 230000001850 reproductive effect Effects 0.000 description 1
• 239000003340 retarding agent Substances 0.000 description 1
• 210000001525 retina Anatomy 0.000 description 1
• 210000003994 retinal ganglion cell Anatomy 0.000 description 1
• 230000000250 revascularization Effects 0.000 description 1
• 238000012552 review Methods 0.000 description 1
• PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 description 1
• 230000033764 rhythmic process Effects 0.000 description 1
• 201000004700 rosacea Diseases 0.000 description 1
• 231100000241 scar Toxicity 0.000 description 1
• 230000037387 scars Effects 0.000 description 1
• 210000003497 sciatic nerve Anatomy 0.000 description 1
• 210000003786 sclera Anatomy 0.000 description 1
• 208000010157 sclerosing cholangitis Diseases 0.000 description 1
• 208000008864 scrapie Diseases 0.000 description 1
• 208000008742 seborrheic dermatitis Diseases 0.000 description 1
• 230000035807 sensation Effects 0.000 description 1
• 230000008313 sensitization Effects 0.000 description 1
• 230000001953 sensory effect Effects 0.000 description 1
• 238000013207 serial dilution Methods 0.000 description 1
• 239000008159 sesame oil Substances 0.000 description 1
• 235000011803 sesame oil Nutrition 0.000 description 1
• 238000010008 shearing Methods 0.000 description 1
• 208000013220 shortness of breath Diseases 0.000 description 1
• 150000004760 silicates Chemical class 0.000 description 1
• RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
• 235000012239 silicon dioxide Nutrition 0.000 description 1
• 208000017520 skin disease Diseases 0.000 description 1
• 231100000046 skin rash Toxicity 0.000 description 1
• 230000007958 sleep Effects 0.000 description 1
• 210000002460 smooth muscle Anatomy 0.000 description 1
• 101150114085 soc-2 gene Proteins 0.000 description 1
• 229910052708 sodium Inorganic materials 0.000 description 1
• 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
• 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
• 239000001509 sodium citrate Substances 0.000 description 1
• NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
• 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
• 239000007909 solid dosage form Substances 0.000 description 1
• 239000008247 solid mixture Substances 0.000 description 1
• 230000000392 somatic effect Effects 0.000 description 1
• 230000003238 somatosensory effect Effects 0.000 description 1
• 239000000600 sorbitol Substances 0.000 description 1
• 241000894007 species Species 0.000 description 1
• 201000003624 spinocerebellar ataxia type 1 Diseases 0.000 description 1
• 201000003570 spinocerebellar ataxia type 17 Diseases 0.000 description 1
• 201000003632 spinocerebellar ataxia type 7 Diseases 0.000 description 1
• 239000007921 spray Substances 0.000 description 1
• 239000008107 starch Substances 0.000 description 1
• 230000036262 stenosis Effects 0.000 description 1
• 208000037804 stenosis Diseases 0.000 description 1
• 238000003756 stirring Methods 0.000 description 1
• 238000003860 storage Methods 0.000 description 1
• 125000001424 substituent group Chemical group 0.000 description 1
• 239000000758 substrate Substances 0.000 description 1
• 239000006228 supernatant Substances 0.000 description 1
• 239000004094 surface-active agent Substances 0.000 description 1
• 238000011477 surgical intervention Methods 0.000 description 1
• 230000002459 sustained effect Effects 0.000 description 1
• 239000003765 sweetening agent Substances 0.000 description 1
• 230000008961 swelling Effects 0.000 description 1
• 210000005222 synovial tissue Anatomy 0.000 description 1
• 239000000454 talc Substances 0.000 description 1
• 229910052623 talc Inorganic materials 0.000 description 1
• 235000012222 talc Nutrition 0.000 description 1
• RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
• 210000002435 tendon Anatomy 0.000 description 1
• 125000004192 tetrahydrofuran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
• 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
• 125000003831 tetrazolyl group Chemical group 0.000 description 1
• 229940124597 therapeutic agent Drugs 0.000 description 1
• 238000002560 therapeutic procedure Methods 0.000 description 1
• 239000002562 thickening agent Substances 0.000 description 1
• 210000000115 thoracic cavity Anatomy 0.000 description 1
• 230000001988 toxicity Effects 0.000 description 1
• 231100000419 toxicity Toxicity 0.000 description 1
• 230000009261 transgenic effect Effects 0.000 description 1
• 201000006397 traumatic glaucoma Diseases 0.000 description 1
• 125000001425 triazolyl group Chemical group 0.000 description 1
• ZMANZCXQSJIPKH-UHFFFAOYSA-O triethylammonium ion Chemical compound CC[NH+](CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-O 0.000 description 1
• UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
• UNXRWKVEANCORM-UHFFFAOYSA-N triphosphoric acid Chemical class OP(O)(=O)OP(O)(=O)OP(O)(O)=O UNXRWKVEANCORM-UHFFFAOYSA-N 0.000 description 1
• 238000002604 ultrasonography Methods 0.000 description 1
• 208000019553 vascular disease Diseases 0.000 description 1
• 235000015112 vegetable and seed oil Nutrition 0.000 description 1
• 239000008158 vegetable oil Substances 0.000 description 1
• 235000013311 vegetables Nutrition 0.000 description 1
• OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 1
• 229960004528 vincristine Drugs 0.000 description 1
• OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 1
• 230000009385 viral infection Effects 0.000 description 1
• 230000003612 virological effect Effects 0.000 description 1
• 208000009935 visceral pain Diseases 0.000 description 1
• 230000004304 visual acuity Effects 0.000 description 1
• 208000030401 vitamin deficiency disease Diseases 0.000 description 1
• 208000010484 vulvovaginitis Diseases 0.000 description 1
• 239000001993 wax Substances 0.000 description 1
• 230000004584 weight gain Effects 0.000 description 1
• 235000019786 weight gain Nutrition 0.000 description 1
• 208000016261 weight loss Diseases 0.000 description 1
• 210000002268 wool Anatomy 0.000 description 1
• 230000029663 wound healing Effects 0.000 description 1
• 150000003751 zinc Chemical class 0.000 description 1