JP6772142B2 - サリチル酸化合物の組成物 - Google Patents
サリチル酸化合物の組成物 Download PDFInfo
- Publication number
- JP6772142B2 JP6772142B2 JP2017534735A JP2017534735A JP6772142B2 JP 6772142 B2 JP6772142 B2 JP 6772142B2 JP 2017534735 A JP2017534735 A JP 2017534735A JP 2017534735 A JP2017534735 A JP 2017534735A JP 6772142 B2 JP6772142 B2 JP 6772142B2
- Authority
- JP
- Japan
- Prior art keywords
- aspirin
- composition according
- salicylic acid
- administration
- composition
- Prior art date
- 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.)
- Active
Links
- 239000000203 mixture Substances 0.000 title claims description 250
- YGSDEFSMJLZEOE-UHFFFAOYSA-N Salicylic acid Natural products OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 title claims description 141
- -1 salicylic acid compound Chemical class 0.000 title claims description 134
- 229960004889 salicylic acid Drugs 0.000 title claims description 98
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 title claims description 97
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 claims description 287
- 229960001138 acetylsalicylic acid Drugs 0.000 claims description 283
- URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 claims description 127
- 229960002622 triacetin Drugs 0.000 claims description 101
- 239000007788 liquid Substances 0.000 claims description 100
- 235000019204 saccharin Nutrition 0.000 claims description 82
- 229940081974 saccharin Drugs 0.000 claims description 82
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 claims description 82
- 206010028980 Neoplasm Diseases 0.000 claims description 64
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 claims description 57
- 238000000034 method Methods 0.000 claims description 52
- 150000001875 compounds Chemical class 0.000 claims description 42
- 239000000796 flavoring agent Substances 0.000 claims description 42
- 201000011510 cancer Diseases 0.000 claims description 40
- 235000013355 food flavoring agent Nutrition 0.000 claims description 39
- 206010018338 Glioma Diseases 0.000 claims description 28
- 208000032612 Glial tumor Diseases 0.000 claims description 25
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 18
- 238000001990 intravenous administration Methods 0.000 claims description 17
- 238000002156 mixing Methods 0.000 claims description 16
- 208000026106 cerebrovascular disease Diseases 0.000 claims description 14
- 208000031225 myocardial ischemia Diseases 0.000 claims description 14
- 238000002560 therapeutic procedure Methods 0.000 claims description 14
- 239000002775 capsule Substances 0.000 claims description 13
- 208000006011 Stroke Diseases 0.000 claims description 11
- 206010002383 Angina Pectoris Diseases 0.000 claims description 10
- 206010019280 Heart failures Diseases 0.000 claims description 10
- 239000001525 mentha piperita l. herb oil Substances 0.000 claims description 9
- 235000019477 peppermint oil Nutrition 0.000 claims description 9
- 201000006474 Brain Ischemia Diseases 0.000 claims description 8
- 208000003174 Brain Neoplasms Diseases 0.000 claims description 8
- 206010008120 Cerebral ischaemia Diseases 0.000 claims description 8
- 208000032109 Transient ischaemic attack Diseases 0.000 claims description 8
- 206010008118 cerebral infarction Diseases 0.000 claims description 8
- 208000029078 coronary artery disease Diseases 0.000 claims description 8
- 201000010875 transient cerebral ischemia Diseases 0.000 claims description 8
- 206010061218 Inflammation Diseases 0.000 claims description 7
- 230000004054 inflammatory process Effects 0.000 claims description 7
- 238000001361 intraarterial administration Methods 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 208000011200 Kawasaki disease Diseases 0.000 claims description 6
- 208000002193 Pain Diseases 0.000 claims description 6
- 208000001725 mucocutaneous lymph node syndrome Diseases 0.000 claims description 6
- 230000036407 pain Effects 0.000 claims description 6
- 201000006306 Cor pulmonale Diseases 0.000 claims description 5
- 208000004186 Pulmonary Heart Disease Diseases 0.000 claims description 5
- 206010037660 Pyrexia Diseases 0.000 claims description 5
- 238000007911 parenteral administration Methods 0.000 claims description 5
- 206010017993 Gastrointestinal neoplasms Diseases 0.000 claims description 4
- 201000004810 Vascular dementia Diseases 0.000 claims description 4
- 201000007455 central nervous system cancer Diseases 0.000 claims description 4
- 208000002330 Congenital Heart Defects Diseases 0.000 claims description 3
- 206010024119 Left ventricular failure Diseases 0.000 claims description 3
- 206010039163 Right ventricular failure Diseases 0.000 claims description 3
- 208000028831 congenital heart disease Diseases 0.000 claims description 3
- 208000005017 glioblastoma Diseases 0.000 description 47
- 210000004027 cell Anatomy 0.000 description 46
- 230000000694 effects Effects 0.000 description 41
- 239000003814 drug Substances 0.000 description 36
- 150000002314 glycerols Chemical class 0.000 description 28
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 27
- 235000013773 glyceryl triacetate Nutrition 0.000 description 27
- 239000001087 glyceryl triacetate Substances 0.000 description 26
- 239000002245 particle Substances 0.000 description 26
- 230000002496 gastric effect Effects 0.000 description 23
- 241000282414 Homo sapiens Species 0.000 description 21
- 229940079593 drug Drugs 0.000 description 21
- 238000009472 formulation Methods 0.000 description 21
- 239000000243 solution Substances 0.000 description 20
- 125000000217 alkyl group Chemical group 0.000 description 19
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 18
- 125000003342 alkenyl group Chemical group 0.000 description 18
- 125000000304 alkynyl group Chemical group 0.000 description 18
- 239000007924 injection Substances 0.000 description 18
- 238000002347 injection Methods 0.000 description 18
- 241000700159 Rattus Species 0.000 description 16
- 238000000354 decomposition reaction Methods 0.000 description 16
- BPEGJWRSRHCHSN-UHFFFAOYSA-N Temozolomide Chemical compound O=C1N(C)N=NC2=C(C(N)=O)N=CN21 BPEGJWRSRHCHSN-UHFFFAOYSA-N 0.000 description 15
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 15
- 229960004964 temozolomide Drugs 0.000 description 15
- 201000010099 disease Diseases 0.000 description 14
- 210000001156 gastric mucosa Anatomy 0.000 description 14
- 239000002904 solvent Substances 0.000 description 14
- 208000035475 disorder Diseases 0.000 description 13
- 230000002265 prevention Effects 0.000 description 13
- 150000003839 salts Chemical group 0.000 description 13
- 230000001225 therapeutic effect Effects 0.000 description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- 108060000903 Beta-catenin Proteins 0.000 description 12
- 102000015735 Beta-catenin Human genes 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- 230000000259 anti-tumor effect Effects 0.000 description 12
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 12
- 230000006378 damage Effects 0.000 description 11
- 235000002899 Mentha suaveolens Nutrition 0.000 description 10
- 239000002246 antineoplastic agent Substances 0.000 description 10
- 230000015572 biosynthetic process Effects 0.000 description 10
- 238000000338 in vitro Methods 0.000 description 10
- 238000002360 preparation method Methods 0.000 description 10
- 230000002829 reductive effect Effects 0.000 description 10
- WVYADZUPLLSGPU-UHFFFAOYSA-N salsalate Chemical compound OC(=O)C1=CC=CC=C1OC(=O)C1=CC=CC=C1O WVYADZUPLLSGPU-UHFFFAOYSA-N 0.000 description 10
- 238000012360 testing method Methods 0.000 description 10
- 108700012439 CA9 Proteins 0.000 description 9
- 102100024423 Carbonic anhydrase 9 Human genes 0.000 description 9
- 235000006679 Mentha X verticillata Nutrition 0.000 description 9
- 235000001636 Mentha x rotundifolia Nutrition 0.000 description 9
- 239000002253 acid Substances 0.000 description 9
- 230000009471 action Effects 0.000 description 9
- 239000003795 chemical substances by application Substances 0.000 description 9
- XEYBRNLFEZDVAW-ARSRFYASSA-N dinoprostone Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O XEYBRNLFEZDVAW-ARSRFYASSA-N 0.000 description 9
- 235000011187 glycerol Nutrition 0.000 description 9
- 238000001727 in vivo Methods 0.000 description 9
- 239000003921 oil Substances 0.000 description 9
- 235000019198 oils Nutrition 0.000 description 9
- 239000008194 pharmaceutical composition Substances 0.000 description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 9
- 239000000126 substance Substances 0.000 description 9
- 230000002195 synergetic effect Effects 0.000 description 9
- 230000009885 systemic effect Effects 0.000 description 9
- 206010009944 Colon cancer Diseases 0.000 description 8
- 229960002986 dinoprostone Drugs 0.000 description 8
- 208000010125 myocardial infarction Diseases 0.000 description 8
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 8
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 8
- 239000000546 pharmaceutical excipient Substances 0.000 description 8
- XEYBRNLFEZDVAW-UHFFFAOYSA-N prostaglandin E2 Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CC=CCCCC(O)=O XEYBRNLFEZDVAW-UHFFFAOYSA-N 0.000 description 8
- 229940124597 therapeutic agent Drugs 0.000 description 8
- 210000001519 tissue Anatomy 0.000 description 8
- 239000000443 aerosol Substances 0.000 description 7
- 239000003963 antioxidant agent Substances 0.000 description 7
- 235000006708 antioxidants Nutrition 0.000 description 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 7
- 150000001768 cations Chemical class 0.000 description 7
- 239000004927 clay Substances 0.000 description 7
- 206010020871 hypertrophic cardiomyopathy Diseases 0.000 description 7
- 230000001965 increasing effect Effects 0.000 description 7
- 239000004615 ingredient Substances 0.000 description 7
- 230000009467 reduction Effects 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- 239000003826 tablet Substances 0.000 description 7
- 230000002103 transcriptional effect Effects 0.000 description 7
- RMWVZGDJPAKBDE-UHFFFAOYSA-N 2-acetyloxy-4-(trifluoromethyl)benzoic acid Chemical compound CC(=O)OC1=CC(C(F)(F)F)=CC=C1C(O)=O RMWVZGDJPAKBDE-UHFFFAOYSA-N 0.000 description 6
- 102000004889 Interleukin-6 Human genes 0.000 description 6
- 108090001005 Interleukin-6 Proteins 0.000 description 6
- 210000004369 blood Anatomy 0.000 description 6
- 239000008280 blood Substances 0.000 description 6
- 210000004556 brain Anatomy 0.000 description 6
- 239000000969 carrier Substances 0.000 description 6
- 230000000052 comparative effect Effects 0.000 description 6
- HUPFGZXOMWLGNK-UHFFFAOYSA-N diflunisal Chemical compound C1=C(O)C(C(=O)O)=CC(C=2C(=CC(F)=CC=2)F)=C1 HUPFGZXOMWLGNK-UHFFFAOYSA-N 0.000 description 6
- 239000002552 dosage form Substances 0.000 description 6
- 239000000499 gel Substances 0.000 description 6
- 230000014509 gene expression Effects 0.000 description 6
- 229960000905 indomethacin Drugs 0.000 description 6
- 229940100601 interleukin-6 Drugs 0.000 description 6
- 230000001404 mediated effect Effects 0.000 description 6
- 230000035755 proliferation Effects 0.000 description 6
- 230000003442 weekly effect Effects 0.000 description 6
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 5
- 208000031229 Cardiomyopathies Diseases 0.000 description 5
- 201000010915 Glioblastoma multiforme Diseases 0.000 description 5
- 208000000172 Medulloblastoma Diseases 0.000 description 5
- 201000007981 Reye syndrome Diseases 0.000 description 5
- 208000027418 Wounds and injury Diseases 0.000 description 5
- 238000010521 absorption reaction Methods 0.000 description 5
- 239000002671 adjuvant Substances 0.000 description 5
- 229910001413 alkali metal ion Inorganic materials 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 206010003119 arrhythmia Diseases 0.000 description 5
- 238000001574 biopsy Methods 0.000 description 5
- 230000008499 blood brain barrier function Effects 0.000 description 5
- 210000001218 blood-brain barrier Anatomy 0.000 description 5
- 230000015556 catabolic process Effects 0.000 description 5
- 230000030833 cell death Effects 0.000 description 5
- 229940127089 cytotoxic agent Drugs 0.000 description 5
- 238000006731 degradation reaction Methods 0.000 description 5
- 238000011161 development Methods 0.000 description 5
- 230000002526 effect on cardiovascular system Effects 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 235000003599 food sweetener Nutrition 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 208000014674 injury Diseases 0.000 description 5
- 208000028867 ischemia Diseases 0.000 description 5
- 230000007774 longterm Effects 0.000 description 5
- 230000003389 potentiating effect Effects 0.000 description 5
- 239000000651 prodrug Substances 0.000 description 5
- 229940002612 prodrug Drugs 0.000 description 5
- 238000011160 research Methods 0.000 description 5
- 239000012453 solvate Substances 0.000 description 5
- 239000003765 sweetening agent Substances 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- 231100000419 toxicity Toxicity 0.000 description 5
- 230000001988 toxicity Effects 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 4
- 206010014498 Embolic stroke Diseases 0.000 description 4
- 208000012671 Gastrointestinal haemorrhages Diseases 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- 206010021143 Hypoxia Diseases 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 102100038280 Prostaglandin G/H synthase 2 Human genes 0.000 description 4
- 108050003267 Prostaglandin G/H synthase 2 Proteins 0.000 description 4
- 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 4
- 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 4
- 108010016283 TCF Transcription Factors Proteins 0.000 description 4
- 102000000479 TCF Transcription Factors Human genes 0.000 description 4
- 208000007536 Thrombosis Diseases 0.000 description 4
- 206010043647 Thrombotic Stroke Diseases 0.000 description 4
- 235000011054 acetic acid Nutrition 0.000 description 4
- 229910001420 alkaline earth metal ion Inorganic materials 0.000 description 4
- 230000001093 anti-cancer Effects 0.000 description 4
- 230000001754 anti-pyretic effect Effects 0.000 description 4
- 239000002221 antipyretic Substances 0.000 description 4
- 230000006793 arrhythmia Effects 0.000 description 4
- 239000008122 artificial sweetener Substances 0.000 description 4
- 235000021311 artificial sweeteners Nutrition 0.000 description 4
- 210000001130 astrocyte Anatomy 0.000 description 4
- 230000000973 chemotherapeutic effect Effects 0.000 description 4
- 229960000616 diflunisal Drugs 0.000 description 4
- 230000007705 epithelial mesenchymal transition Effects 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 230000037406 food intake Effects 0.000 description 4
- 208000030304 gastrointestinal bleeding Diseases 0.000 description 4
- 230000012010 growth Effects 0.000 description 4
- 125000001072 heteroaryl group Chemical group 0.000 description 4
- 239000012535 impurity Substances 0.000 description 4
- 239000003112 inhibitor Substances 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 229960000953 salsalate Drugs 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 210000002784 stomach Anatomy 0.000 description 4
- 230000009469 supplementation Effects 0.000 description 4
- 230000004083 survival effect Effects 0.000 description 4
- 125000001425 triazolyl group Chemical group 0.000 description 4
- 229960002268 triflusal Drugs 0.000 description 4
- 230000035899 viability Effects 0.000 description 4
- 206010007559 Cardiac failure congestive Diseases 0.000 description 3
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 3
- 206010064147 Gastrointestinal inflammation Diseases 0.000 description 3
- 229930194542 Keto Natural products 0.000 description 3
- 206010025323 Lymphomas Diseases 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 3
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 3
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 3
- 239000000853 adhesive Substances 0.000 description 3
- 230000002411 adverse Effects 0.000 description 3
- 230000000202 analgesic effect Effects 0.000 description 3
- 230000033115 angiogenesis Effects 0.000 description 3
- 229940127218 antiplatelet drug Drugs 0.000 description 3
- 230000006907 apoptotic process Effects 0.000 description 3
- 235000010323 ascorbic acid Nutrition 0.000 description 3
- 239000011668 ascorbic acid Substances 0.000 description 3
- 229960005070 ascorbic acid Drugs 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 210000004204 blood vessel Anatomy 0.000 description 3
- 230000010261 cell growth Effects 0.000 description 3
- 230000004663 cell proliferation Effects 0.000 description 3
- 210000003169 central nervous system Anatomy 0.000 description 3
- 238000012512 characterization method Methods 0.000 description 3
- 230000001684 chronic effect Effects 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 208000029742 colonic neoplasm Diseases 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 238000009792 diffusion process Methods 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 125000005303 dithiazolyl group Chemical group S1SNC(=C1)* 0.000 description 3
- 238000009510 drug design Methods 0.000 description 3
- 150000002085 enols Chemical class 0.000 description 3
- 235000019634 flavors Nutrition 0.000 description 3
- 125000002541 furyl group Chemical group 0.000 description 3
- 210000001035 gastrointestinal tract Anatomy 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- 230000009036 growth inhibition Effects 0.000 description 3
- 210000002216 heart Anatomy 0.000 description 3
- 230000007954 hypoxia Effects 0.000 description 3
- 238000001802 infusion Methods 0.000 description 3
- 230000001788 irregular Effects 0.000 description 3
- 125000000468 ketone group Chemical group 0.000 description 3
- 150000002611 lead compounds Chemical class 0.000 description 3
- 230000003902 lesion Effects 0.000 description 3
- 230000000873 masking effect Effects 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 201000001441 melanoma Diseases 0.000 description 3
- 239000001683 mentha spicata herb oil Substances 0.000 description 3
- 230000002503 metabolic effect Effects 0.000 description 3
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 3
- 210000000214 mouth Anatomy 0.000 description 3
- 206010061311 nervous system neoplasm Diseases 0.000 description 3
- 125000001715 oxadiazolyl group Chemical group 0.000 description 3
- 230000007170 pathology Effects 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 150000003180 prostaglandins Chemical class 0.000 description 3
- 230000002685 pulmonary effect Effects 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 125000002112 pyrrolidino group Chemical group [*]N1C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 3
- 150000003902 salicylic acid esters Chemical class 0.000 description 3
- 230000019491 signal transduction Effects 0.000 description 3
- 230000011664 signaling Effects 0.000 description 3
- 235000019721 spearmint oil Nutrition 0.000 description 3
- 239000007921 spray Substances 0.000 description 3
- 210000004500 stellate cell Anatomy 0.000 description 3
- 230000004936 stimulating effect Effects 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 125000001113 thiadiazolyl group Chemical group 0.000 description 3
- 210000000115 thoracic cavity Anatomy 0.000 description 3
- 229910001428 transition metal ion Inorganic materials 0.000 description 3
- 210000004881 tumor cell Anatomy 0.000 description 3
- GHOKWGTUZJEAQD-ZETCQYMHSA-N (D)-(+)-Pantothenic acid Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-ZETCQYMHSA-N 0.000 description 2
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 2
- KMZHZAAOEWVPSE-UHFFFAOYSA-N 2,3-dihydroxypropyl acetate Chemical compound CC(=O)OCC(O)CO KMZHZAAOEWVPSE-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- 208000004476 Acute Coronary Syndrome Diseases 0.000 description 2
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 2
- 206010006187 Breast cancer Diseases 0.000 description 2
- 208000026310 Breast neoplasm Diseases 0.000 description 2
- 235000004936 Bromus mango Nutrition 0.000 description 2
- 239000004322 Butylated hydroxytoluene Substances 0.000 description 2
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 2
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 208000020446 Cardiac disease Diseases 0.000 description 2
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- 206010012289 Dementia Diseases 0.000 description 2
- 208000003037 Diastolic Heart Failure Diseases 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- 206010014967 Ependymoma Diseases 0.000 description 2
- 206010053155 Epigastric discomfort Diseases 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 208000012895 Gastric disease Diseases 0.000 description 2
- 208000018522 Gastrointestinal disease Diseases 0.000 description 2
- 206010061172 Gastrointestinal injury Diseases 0.000 description 2
- UXDDRFCJKNROTO-UHFFFAOYSA-N Glycerol 1,2-diacetate Chemical compound CC(=O)OCC(CO)OC(C)=O UXDDRFCJKNROTO-UHFFFAOYSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 208000034507 Haematemesis Diseases 0.000 description 2
- 206010061996 Heart valve stenosis Diseases 0.000 description 2
- 208000017604 Hodgkin disease Diseases 0.000 description 2
- 208000010747 Hodgkins lymphoma Diseases 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- QIGBRXMKCJKVMJ-UHFFFAOYSA-N Hydroquinone Chemical compound OC1=CC=C(O)C=C1 QIGBRXMKCJKVMJ-UHFFFAOYSA-N 0.000 description 2
- 206010020751 Hypersensitivity Diseases 0.000 description 2
- 102100022875 Hypoxia-inducible factor 1-alpha Human genes 0.000 description 2
- 208000005016 Intestinal Neoplasms Diseases 0.000 description 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 2
- 235000014826 Mangifera indica Nutrition 0.000 description 2
- 240000007228 Mangifera indica Species 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 201000003793 Myelodysplastic syndrome Diseases 0.000 description 2
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 2
- CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 description 2
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 2
- 201000010133 Oligodendroglioma Diseases 0.000 description 2
- 206010033128 Ovarian cancer Diseases 0.000 description 2
- 206010061535 Ovarian neoplasm Diseases 0.000 description 2
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 206010060862 Prostate cancer Diseases 0.000 description 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 2
- 206010039491 Sarcoma Diseases 0.000 description 2
- 235000009184 Spondias indica Nutrition 0.000 description 2
- 208000007107 Stomach Ulcer Diseases 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 208000031673 T-Cell Cutaneous Lymphoma Diseases 0.000 description 2
- BGNXCDMCOKJUMV-UHFFFAOYSA-N Tert-Butylhydroquinone Chemical compound CC(C)(C)C1=CC(O)=CC=C1O BGNXCDMCOKJUMV-UHFFFAOYSA-N 0.000 description 2
- 102000040945 Transcription factor Human genes 0.000 description 2
- 108091023040 Transcription factor Proteins 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 230000010398 acute inflammatory response Effects 0.000 description 2
- 230000006978 adaptation Effects 0.000 description 2
- 230000001070 adhesive effect Effects 0.000 description 2
- 238000009098 adjuvant therapy Methods 0.000 description 2
- 125000005907 alkyl ester group Chemical group 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 150000001409 amidines Chemical class 0.000 description 2
- 125000000129 anionic group Chemical group 0.000 description 2
- 239000002260 anti-inflammatory agent Substances 0.000 description 2
- 229940121363 anti-inflammatory agent Drugs 0.000 description 2
- 229940124599 anti-inflammatory drug Drugs 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- 230000003078 antioxidant effect Effects 0.000 description 2
- 229940125716 antipyretic agent Drugs 0.000 description 2
- 206010002906 aortic stenosis Diseases 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- 201000007983 brain glioma Diseases 0.000 description 2
- HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 2
- 235000010354 butylated hydroxytoluene Nutrition 0.000 description 2
- 229940095259 butylated hydroxytoluene Drugs 0.000 description 2
- 229910001424 calcium ion Inorganic materials 0.000 description 2
- KRALOLGXHLZTCW-UHFFFAOYSA-L calcium;2-acetyloxybenzoate Chemical compound [Ca+2].CC(=O)OC1=CC=CC=C1C([O-])=O.CC(=O)OC1=CC=CC=C1C([O-])=O KRALOLGXHLZTCW-UHFFFAOYSA-L 0.000 description 2
- 125000002091 cationic group Chemical group 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 230000003833 cell viability Effects 0.000 description 2
- 238000002648 combination therapy Methods 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 235000008504 concentrate Nutrition 0.000 description 2
- 201000007241 cutaneous T cell lymphoma Diseases 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- 230000003111 delayed effect Effects 0.000 description 2
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- 230000029087 digestion Effects 0.000 description 2
- 208000010643 digestive system disease Diseases 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 125000005879 dioxolanyl group Chemical group 0.000 description 2
- 239000002270 dispersing agent Substances 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 125000005411 dithiolanyl group Chemical group S1SC(CC1)* 0.000 description 2
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 2
- 230000002183 duodenal effect Effects 0.000 description 2
- 235000013399 edible fruits Nutrition 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 230000002550 fecal effect Effects 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 201000005917 gastric ulcer Diseases 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 229940093915 gynecological organic acid Drugs 0.000 description 2
- 230000009931 harmful effect Effects 0.000 description 2
- 208000014829 head and neck neoplasm Diseases 0.000 description 2
- 208000019622 heart disease Diseases 0.000 description 2
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 2
- 208000029824 high grade glioma Diseases 0.000 description 2
- 125000002883 imidazolyl group Chemical group 0.000 description 2
- 239000012729 immediate-release (IR) formulation Substances 0.000 description 2
- 238000002513 implantation Methods 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 230000008595 infiltration Effects 0.000 description 2
- 238000001764 infiltration Methods 0.000 description 2
- 230000010354 integration Effects 0.000 description 2
- 201000002313 intestinal cancer Diseases 0.000 description 2
- 125000001786 isothiazolyl group Chemical group 0.000 description 2
- 125000000842 isoxazolyl group Chemical group 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 208000032839 leukemia Diseases 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 201000005202 lung cancer Diseases 0.000 description 2
- 208000020816 lung neoplasm Diseases 0.000 description 2
- 210000002751 lymph Anatomy 0.000 description 2
- 208000003747 lymphoid leukemia Diseases 0.000 description 2
- 201000011614 malignant glioma Diseases 0.000 description 2
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 2
- 230000001394 metastastic effect Effects 0.000 description 2
- 206010061289 metastatic neoplasm Diseases 0.000 description 2
- 150000002772 monosaccharides Chemical group 0.000 description 2
- 201000005962 mycosis fungoides Diseases 0.000 description 2
- 208000025113 myeloid leukemia Diseases 0.000 description 2
- 210000000754 myometrium Anatomy 0.000 description 2
- 229960002009 naproxen Drugs 0.000 description 2
- CMWTZPSULFXXJA-VIFPVBQESA-M naproxen(1-) Chemical compound C1=C([C@H](C)C([O-])=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-M 0.000 description 2
- 239000007923 nasal drop Substances 0.000 description 2
- 229940100662 nasal drops Drugs 0.000 description 2
- 239000007922 nasal spray Substances 0.000 description 2
- 230000001338 necrotic effect Effects 0.000 description 2
- 210000005170 neoplastic cell Anatomy 0.000 description 2
- 230000001613 neoplastic effect Effects 0.000 description 2
- 210000005036 nerve Anatomy 0.000 description 2
- 208000007538 neurilemmoma Diseases 0.000 description 2
- 210000004498 neuroglial cell Anatomy 0.000 description 2
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 230000002018 overexpression Effects 0.000 description 2
- 125000002971 oxazolyl group Chemical group 0.000 description 2
- 201000002528 pancreatic cancer Diseases 0.000 description 2
- 208000008443 pancreatic carcinoma Diseases 0.000 description 2
- 239000003961 penetration enhancing agent Substances 0.000 description 2
- 210000001428 peripheral nervous system Anatomy 0.000 description 2
- 210000004303 peritoneum Anatomy 0.000 description 2
- 229940124531 pharmaceutical excipient Drugs 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 230000026731 phosphorylation Effects 0.000 description 2
- 238000006366 phosphorylation reaction Methods 0.000 description 2
- 239000000419 plant extract Substances 0.000 description 2
- 208000025638 primary cutaneous T-cell non-Hodgkin lymphoma Diseases 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- 125000003226 pyrazolyl group Chemical group 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 229960001860 salicylate Drugs 0.000 description 2
- 230000009863 secondary prevention Effects 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910001415 sodium ion Inorganic materials 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 238000001256 steam distillation Methods 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- 238000013268 sustained release Methods 0.000 description 2
- 239000012730 sustained-release form Substances 0.000 description 2
- 239000004250 tert-Butylhydroquinone Substances 0.000 description 2
- 235000019281 tert-butylhydroquinone Nutrition 0.000 description 2
- 210000001550 testis Anatomy 0.000 description 2
- 229940126585 therapeutic drug Drugs 0.000 description 2
- 125000000335 thiazolyl group Chemical group 0.000 description 2
- RZWIIPASKMUIAC-VQTJNVASSA-N thromboxane Chemical compound CCCCCCCC[C@H]1OCCC[C@@H]1CCCCCCC RZWIIPASKMUIAC-VQTJNVASSA-N 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 238000013520 translational research Methods 0.000 description 2
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 2
- 230000004614 tumor growth Effects 0.000 description 2
- 210000005102 tumor initiating cell Anatomy 0.000 description 2
- 238000005292 vacuum distillation Methods 0.000 description 2
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 2
- 230000002792 vascular Effects 0.000 description 2
- VMQCQYRHANDJBP-IUYQGCFVSA-N (3s)-3-amino-4-[[(2r)-1-amino-3-hydroxy-1-oxopropan-2-yl]amino]-4-oxobutanoic acid Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](CO)C(N)=O VMQCQYRHANDJBP-IUYQGCFVSA-N 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- UWYVPFMHMJIBHE-OWOJBTEDSA-N (e)-2-hydroxybut-2-enedioic acid Chemical compound OC(=O)\C=C(\O)C(O)=O UWYVPFMHMJIBHE-OWOJBTEDSA-N 0.000 description 1
- DDMOUSALMHHKOS-UHFFFAOYSA-N 1,2-dichloro-1,1,2,2-tetrafluoroethane Chemical compound FC(F)(Cl)C(F)(F)Cl DDMOUSALMHHKOS-UHFFFAOYSA-N 0.000 description 1
- TUSDEZXZIZRFGC-UHFFFAOYSA-N 1-O-galloyl-3,6-(R)-HHDP-beta-D-glucose Natural products OC1C(O2)COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC1C(O)C2OC(=O)C1=CC(O)=C(O)C(O)=C1 TUSDEZXZIZRFGC-UHFFFAOYSA-N 0.000 description 1
- KJCVRFUGPWSIIH-UHFFFAOYSA-N 1-naphthol Chemical compound C1=CC=C2C(O)=CC=CC2=C1 KJCVRFUGPWSIIH-UHFFFAOYSA-N 0.000 description 1
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 1
- LODHFNUFVRVKTH-ZHACJKMWSA-N 2-hydroxy-n'-[(e)-3-phenylprop-2-enoyl]benzohydrazide Chemical compound OC1=CC=CC=C1C(=O)NNC(=O)\C=C\C1=CC=CC=C1 LODHFNUFVRVKTH-ZHACJKMWSA-N 0.000 description 1
- VHBSECWYEFJRNV-UHFFFAOYSA-N 2-hydroxybenzoic acid Chemical group OC(=O)C1=CC=CC=C1O.OC(=O)C1=CC=CC=C1O VHBSECWYEFJRNV-UHFFFAOYSA-N 0.000 description 1
- GJJVAFUKOBZPCB-UHFFFAOYSA-N 2-methyl-2-(4,8,12-trimethyltrideca-3,7,11-trienyl)-3,4-dihydrochromen-6-ol Chemical compound OC1=CC=C2OC(CCC=C(C)CCC=C(C)CCC=C(C)C)(C)CCC2=C1 GJJVAFUKOBZPCB-UHFFFAOYSA-N 0.000 description 1
- WLJVXDMOQOGPHL-PPJXEINESA-N 2-phenylacetic acid Chemical compound O[14C](=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-PPJXEINESA-N 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- ZVSFJFKWWCMRGH-UHFFFAOYSA-N 3-acetyl-3,4-dihydroxy-4-(hydroxymethyl)hexane-2,5-dione 2,3-diacetyloxypropyl acetate Chemical compound CC(OCC(OC(C)=O)COC(C)=O)=O.C(C)(=O)C(C(O)(C(C)=O)C(C)=O)(O)CO ZVSFJFKWWCMRGH-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- UOQHWNPVNXSDDO-UHFFFAOYSA-N 3-bromoimidazo[1,2-a]pyridine-6-carbonitrile Chemical compound C1=CC(C#N)=CN2C(Br)=CN=C21 UOQHWNPVNXSDDO-UHFFFAOYSA-N 0.000 description 1
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 1
- LIANOBXIDJHRSH-UHFFFAOYSA-N 4-acetyloxy-3-(acetyloxymethyl)butanoic acid Chemical compound CC(=O)OCC(CC(O)=O)COC(C)=O LIANOBXIDJHRSH-UHFFFAOYSA-N 0.000 description 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- WBZFUFAFFUEMEI-UHFFFAOYSA-M Acesulfame k Chemical compound [K+].CC1=CC(=O)[N-]S(=O)(=O)O1 WBZFUFAFFUEMEI-UHFFFAOYSA-M 0.000 description 1
- 235000009434 Actinidia chinensis Nutrition 0.000 description 1
- 235000009436 Actinidia deliciosa Nutrition 0.000 description 1
- 241001116389 Aloe Species 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 235000007119 Ananas comosus Nutrition 0.000 description 1
- 244000099147 Ananas comosus Species 0.000 description 1
- 244000061520 Angelica archangelica Species 0.000 description 1
- 102100021569 Apoptosis regulator Bcl-2 Human genes 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 206010003225 Arteriospasm coronary Diseases 0.000 description 1
- YZQCXOFQZKCETR-UWVGGRQHSA-N Asp-Phe Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 YZQCXOFQZKCETR-UWVGGRQHSA-N 0.000 description 1
- 108010011485 Aspartame Proteins 0.000 description 1
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 102100031680 Beta-catenin-interacting protein 1 Human genes 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- 206010005949 Bone cancer Diseases 0.000 description 1
- 208000018084 Bone neoplasm Diseases 0.000 description 1
- 101100294106 Caenorhabditis elegans nhr-3 gene Proteins 0.000 description 1
- 235000005881 Calendula officinalis Nutrition 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 206010007558 Cardiac failure chronic Diseases 0.000 description 1
- 240000003538 Chamaemelum nobile Species 0.000 description 1
- 235000007866 Chamaemelum nobile Nutrition 0.000 description 1
- GHOKWGTUZJEAQD-UHFFFAOYSA-N Chick antidermatitis factor Natural products OCC(C)(C)C(O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-UHFFFAOYSA-N 0.000 description 1
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 1
- 244000223760 Cinnamomum zeylanicum Species 0.000 description 1
- 235000005979 Citrus limon Nutrition 0.000 description 1
- 244000131522 Citrus pyriformis Species 0.000 description 1
- 240000000560 Citrus x paradisi Species 0.000 description 1
- ACTIUHUUMQJHFO-UHFFFAOYSA-N Coenzym Q10 Natural products COC1=C(OC)C(=O)C(CC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)C)=C(C)C1=O ACTIUHUUMQJHFO-UHFFFAOYSA-N 0.000 description 1
- 208000003890 Coronary Vasospasm Diseases 0.000 description 1
- 206010011086 Coronary artery occlusion Diseases 0.000 description 1
- 241000195493 Cryptophyta Species 0.000 description 1
- 102000016736 Cyclin Human genes 0.000 description 1
- 108050006400 Cyclin Proteins 0.000 description 1
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 235000002767 Daucus carota Nutrition 0.000 description 1
- 244000000626 Daucus carota Species 0.000 description 1
- 208000019505 Deglutition disease Diseases 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 241000522213 Dichilus lebeckioides Species 0.000 description 1
- 239000004338 Dichlorodifluoromethane Substances 0.000 description 1
- XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
- 102100037024 E3 ubiquitin-protein ligase XIAP Human genes 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 206010014561 Emphysema Diseases 0.000 description 1
- 206010014733 Endometrial cancer Diseases 0.000 description 1
- 206010014759 Endometrial neoplasm Diseases 0.000 description 1
- 241000792859 Enema Species 0.000 description 1
- 208000000461 Esophageal Neoplasms Diseases 0.000 description 1
- 239000004258 Ethoxyquin Substances 0.000 description 1
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 239000001263 FEMA 3042 Substances 0.000 description 1
- 240000009088 Fragaria x ananassa Species 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- 208000007882 Gastritis Diseases 0.000 description 1
- 241001071795 Gentiana Species 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
- 235000001287 Guettarda speciosa Nutrition 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 235000005206 Hibiscus Nutrition 0.000 description 1
- 235000007185 Hibiscus lunariifolius Nutrition 0.000 description 1
- 244000284380 Hibiscus rosa sinensis Species 0.000 description 1
- 208000021519 Hodgkin lymphoma Diseases 0.000 description 1
- 101000971171 Homo sapiens Apoptosis regulator Bcl-2 Proteins 0.000 description 1
- 101000993469 Homo sapiens Beta-catenin-interacting protein 1 Proteins 0.000 description 1
- 101001046870 Homo sapiens Hypoxia-inducible factor 1-alpha Proteins 0.000 description 1
- 235000008694 Humulus lupulus Nutrition 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 108050009527 Hypoxia-inducible factor-1 alpha Proteins 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
- 206010062016 Immunosuppression Diseases 0.000 description 1
- 102000013691 Interleukin-17 Human genes 0.000 description 1
- 108050003558 Interleukin-17 Proteins 0.000 description 1
- 240000007049 Juglans regia Species 0.000 description 1
- 235000009496 Juglans regia Nutrition 0.000 description 1
- 208000007766 Kaposi sarcoma Diseases 0.000 description 1
- 208000008839 Kidney Neoplasms Diseases 0.000 description 1
- QAQJMLQRFWZOBN-LAUBAEHRSA-N L-ascorbyl-6-palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](O)[C@H]1OC(=O)C(O)=C1O QAQJMLQRFWZOBN-LAUBAEHRSA-N 0.000 description 1
- 235000000072 L-ascorbyl-6-palmitate Nutrition 0.000 description 1
- 239000011786 L-ascorbyl-6-palmitate Substances 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 241000207923 Lamiaceae Species 0.000 description 1
- 239000005639 Lauric acid Substances 0.000 description 1
- 244000165082 Lavanda vera Species 0.000 description 1
- 235000010663 Lavandula angustifolia Nutrition 0.000 description 1
- 208000028018 Lymphocytic leukaemia Diseases 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
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- 244000070406 Malus silvestris Species 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 235000007232 Matricaria chamomilla Nutrition 0.000 description 1
- 208000005410 Mediastinal Neoplasms Diseases 0.000 description 1
- 235000010654 Melissa officinalis Nutrition 0.000 description 1
- 244000062730 Melissa officinalis Species 0.000 description 1
- 235000012629 Mentha aquatica Nutrition 0.000 description 1
- 244000173610 Mentha aquatica Species 0.000 description 1
- 235000014749 Mentha crispa Nutrition 0.000 description 1
- 244000246386 Mentha pulegium Species 0.000 description 1
- 235000016257 Mentha pulegium Nutrition 0.000 description 1
- 244000078639 Mentha spicata Species 0.000 description 1
- 244000182807 Mentha suaveolens Species 0.000 description 1
- 235000004357 Mentha x piperita Nutrition 0.000 description 1
- IAOZJIPTCAWIRG-UHFFFAOYSA-N Methyl alpha-aspartylphenylalaninate Chemical compound OC(=O)CC(N)C(=O)NC(C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-UHFFFAOYSA-N 0.000 description 1
- 229920000715 Mucilage Polymers 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 240000005561 Musa balbisiana Species 0.000 description 1
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 1
- MMOXZBCLCQITDF-UHFFFAOYSA-N N,N-diethyl-m-toluamide Chemical compound CCN(CC)C(=O)C1=CC=CC(C)=C1 MMOXZBCLCQITDF-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
- 229910002651 NO3 Inorganic materials 0.000 description 1
- 208000001894 Nasopharyngeal Neoplasms Diseases 0.000 description 1
- 206010061306 Nasopharyngeal cancer Diseases 0.000 description 1
- 206010028851 Necrosis Diseases 0.000 description 1
- 108700019961 Neoplasm Genes Proteins 0.000 description 1
- 102000048850 Neoplasm Genes Human genes 0.000 description 1
- 201000004404 Neurofibroma Diseases 0.000 description 1
- 208000009905 Neurofibromatoses Diseases 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 description 1
- 206010067482 No adverse event Diseases 0.000 description 1
- 206010030155 Oesophageal carcinoma Diseases 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 235000021314 Palmitic acid Nutrition 0.000 description 1
- 235000000370 Passiflora edulis Nutrition 0.000 description 1
- 244000288157 Passiflora edulis Species 0.000 description 1
- 208000031481 Pathologic Constriction Diseases 0.000 description 1
- LRBQNJMCXXYXIU-PPKXGCFTSA-N Penta-digallate-beta-D-glucose Natural products OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@@H]2[C@H]([C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-PPKXGCFTSA-N 0.000 description 1
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 241000220324 Pyrus Species 0.000 description 1
- LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 description 1
- 235000016976 Quercus macrolepis Nutrition 0.000 description 1
- 208000015634 Rectal Neoplasms Diseases 0.000 description 1
- 206010038389 Renal cancer Diseases 0.000 description 1
- 208000006265 Renal cell carcinoma Diseases 0.000 description 1
- 240000007651 Rubus glaucus Species 0.000 description 1
- 241000124033 Salix Species 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 208000000453 Skin Neoplasms Diseases 0.000 description 1
- 206010041067 Small cell lung cancer Diseases 0.000 description 1
- FKNQFGJONOIPTF-UHFFFAOYSA-N Sodium cation Chemical group [Na+] FKNQFGJONOIPTF-UHFFFAOYSA-N 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- 241000271567 Struthioniformes Species 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 239000004376 Sucralose Substances 0.000 description 1
- 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 1
- 229930006000 Sucrose Natural products 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical compound OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 description 1
- 206010042674 Swelling Diseases 0.000 description 1
- 208000008253 Systolic Heart Failure Diseases 0.000 description 1
- 240000000785 Tagetes erecta Species 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 244000269722 Thea sinensis Species 0.000 description 1
- 208000024770 Thyroid neoplasm Diseases 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- 208000008385 Urogenital Neoplasms Diseases 0.000 description 1
- 235000017537 Vaccinium myrtillus Nutrition 0.000 description 1
- 244000078534 Vaccinium myrtillus Species 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 241000219094 Vitaceae Species 0.000 description 1
- 229930003427 Vitamin E Natural products 0.000 description 1
- 108700031544 X-Linked Inhibitor of Apoptosis Proteins 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- 235000006886 Zingiber officinale Nutrition 0.000 description 1
- 244000273928 Zingiber officinale Species 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 208000009956 adenocarcinoma Diseases 0.000 description 1
- 210000004100 adrenal gland Anatomy 0.000 description 1
- 201000005188 adrenal gland cancer Diseases 0.000 description 1
- 208000024447 adrenal gland neoplasm Diseases 0.000 description 1
- 208000030002 adult glioblastoma Diseases 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 235000011399 aloe vera Nutrition 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 150000001449 anionic compounds Chemical class 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 230000002429 anti-coagulating effect Effects 0.000 description 1
- 230000000702 anti-platelet effect Effects 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 230000006502 antiplatelets effects Effects 0.000 description 1
- 210000000436 anus Anatomy 0.000 description 1
- 238000003782 apoptosis assay Methods 0.000 description 1
- 235000021016 apples Nutrition 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 239000000605 aspartame Substances 0.000 description 1
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
- 235000010357 aspartame Nutrition 0.000 description 1
- 229960003438 aspartame Drugs 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 238000011914 asymmetric synthesis Methods 0.000 description 1
- 235000021015 bananas Nutrition 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 235000010233 benzoic acid Nutrition 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
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- 201000009036 biliary tract cancer Diseases 0.000 description 1
- 208000020790 biliary tract neoplasm Diseases 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 239000000090 biomarker Substances 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 210000005101 blood-brain tumor barrier Anatomy 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 235000019282 butylated hydroxyanisole Nutrition 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 230000005907 cancer growth Effects 0.000 description 1
- 208000035269 cancer or benign tumor Diseases 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 229960004424 carbon dioxide Drugs 0.000 description 1
- SKOLWUPSYHWYAM-UHFFFAOYSA-N carbonodithioic O,S-acid Chemical compound SC(S)=O SKOLWUPSYHWYAM-UHFFFAOYSA-N 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 150000001767 cationic compounds Chemical class 0.000 description 1
- 210000004534 cecum Anatomy 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 208000025997 central nervous system neoplasm Diseases 0.000 description 1
- 210000004720 cerebrum Anatomy 0.000 description 1
- 210000003679 cervix uteri Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 235000010675 chips/crisps Nutrition 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 235000017803 cinnamon Nutrition 0.000 description 1
- 235000017471 coenzyme Q10 Nutrition 0.000 description 1
- ACTIUHUUMQJHFO-UPTCCGCDSA-N coenzyme Q10 Chemical compound COC1=C(OC)C(=O)C(C\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CCC=C(C)C)=C(C)C1=O ACTIUHUUMQJHFO-UPTCCGCDSA-N 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 201000011634 coronary artery vasospasm Diseases 0.000 description 1
- 210000004351 coronary vessel Anatomy 0.000 description 1
- 239000006184 cosolvent Substances 0.000 description 1
- 208000035250 cutaneous malignant susceptibility to 1 melanoma Diseases 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 125000005331 diazinyl group Chemical group N1=NC(=CC=C1)* 0.000 description 1
- 235000019404 dichlorodifluoromethane Nutrition 0.000 description 1
- 229940042935 dichlorodifluoromethane Drugs 0.000 description 1
- 229940087091 dichlorotetrafluoroethane Drugs 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 229960001673 diethyltoluamide Drugs 0.000 description 1
- 150000004683 dihydrates Chemical class 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 231100000676 disease causative agent Toxicity 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 235000011869 dried fruits Nutrition 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 210000001198 duodenum Anatomy 0.000 description 1
- 229960001484 edetic acid Drugs 0.000 description 1
- 239000007938 effervescent tablet Substances 0.000 description 1
- 150000002081 enamines Chemical class 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 239000007920 enema Substances 0.000 description 1
- 229940095399 enema Drugs 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 201000004101 esophageal cancer Diseases 0.000 description 1
- 210000003238 esophagus Anatomy 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- AFAXGSQYZLGZPG-UHFFFAOYSA-N ethanedisulfonic acid Chemical compound OS(=O)(=O)CCS(O)(=O)=O AFAXGSQYZLGZPG-UHFFFAOYSA-N 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- 235000019285 ethoxyquin Nutrition 0.000 description 1
- DECIPOUIJURFOJ-UHFFFAOYSA-N ethoxyquin Chemical compound N1C(C)(C)C=C(C)C2=CC(OCC)=CC=C21 DECIPOUIJURFOJ-UHFFFAOYSA-N 0.000 description 1
- 229940093500 ethoxyquin Drugs 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 201000010255 female reproductive organ cancer Diseases 0.000 description 1
- 206010016629 fibroma Diseases 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 235000013373 food additive Nutrition 0.000 description 1
- 239000002778 food additive Substances 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 239000008369 fruit flavor Substances 0.000 description 1
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 201000006585 gastric adenocarcinoma Diseases 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 230000007160 gastrointestinal dysfunction Effects 0.000 description 1
- 235000021474 generally recognized As safe (food) Nutrition 0.000 description 1
- 235000021473 generally recognized as safe (food ingredients) Nutrition 0.000 description 1
- 235000008397 ginger Nutrition 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 239000000174 gluconic acid Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 230000034659 glycolysis Effects 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 235000021021 grapes Nutrition 0.000 description 1
- 235000020688 green tea extract Nutrition 0.000 description 1
- 229940094952 green tea extract Drugs 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 210000005003 heart tissue Anatomy 0.000 description 1
- 210000002443 helper t lymphocyte Anatomy 0.000 description 1
- 230000002489 hematologic effect Effects 0.000 description 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 235000001050 hortel pimenta Nutrition 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
- 230000001146 hypoxic effect Effects 0.000 description 1
- 150000003949 imides Chemical class 0.000 description 1
- 150000002466 imines Chemical class 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 238000010874 in vitro model Methods 0.000 description 1
- 230000006882 induction of apoptosis Effects 0.000 description 1
- 238000002664 inhalation therapy Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 229910001412 inorganic anion Inorganic materials 0.000 description 1
- 229910001411 inorganic cation Inorganic materials 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 230000017306 interleukin-6 production Effects 0.000 description 1
- 239000007925 intracardiac injection Substances 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 230000000622 irritating effect Effects 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000000155 isotopic effect Effects 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 201000010982 kidney cancer Diseases 0.000 description 1
- 210000004561 lacrimal apparatus Anatomy 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 229940099563 lactobionic acid Drugs 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 210000002429 large intestine Anatomy 0.000 description 1
- 239000001102 lavandula vera Substances 0.000 description 1
- 235000018219 lavender Nutrition 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 201000009020 malignant peripheral nerve sheath tumor Diseases 0.000 description 1
- 208000026037 malignant tumor of neck Diseases 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 231100000682 maximum tolerated dose Toxicity 0.000 description 1
- 201000000349 mediastinal cancer Diseases 0.000 description 1
- 210000001370 mediastinum Anatomy 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 210000000713 mesentery Anatomy 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 238000001000 micrograph Methods 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 208000019266 moderate heart failure Diseases 0.000 description 1
- 150000004682 monohydrates Chemical class 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 239000002324 mouth wash Substances 0.000 description 1
- 210000000066 myeloid cell Anatomy 0.000 description 1
- 201000000050 myeloid neoplasm Diseases 0.000 description 1
- LNOPIUAQISRISI-UHFFFAOYSA-N n'-hydroxy-2-propan-2-ylsulfonylethanimidamide Chemical compound CC(C)S(=O)(=O)CC(N)=NO LNOPIUAQISRISI-UHFFFAOYSA-N 0.000 description 1
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 1
- GTWJETSWSUWSEJ-UHFFFAOYSA-N n-benzylaniline Chemical compound C=1C=CC=CC=1CNC1=CC=CC=C1 GTWJETSWSUWSEJ-UHFFFAOYSA-N 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229940097496 nasal spray Drugs 0.000 description 1
- 210000001989 nasopharynx Anatomy 0.000 description 1
- 235000021096 natural sweeteners Nutrition 0.000 description 1
- 239000006199 nebulizer Substances 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 201000011682 nervous system cancer Diseases 0.000 description 1
- 210000001178 neural stem cell Anatomy 0.000 description 1
- 201000004931 neurofibromatosis Diseases 0.000 description 1
- 208000029974 neurofibrosarcoma Diseases 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000000018 nitroso group Chemical group N(=O)* 0.000 description 1
- 239000011356 non-aqueous organic solvent Substances 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 235000021313 oleic acid Nutrition 0.000 description 1
- 230000000174 oncolytic effect Effects 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000010661 oregano oil Substances 0.000 description 1
- 229940111617 oregano oil Drugs 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 150000002891 organic anions Chemical class 0.000 description 1
- 150000002892 organic cations Chemical class 0.000 description 1
- 201000008968 osteosarcoma Diseases 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 150000002923 oximes Chemical class 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 229940055726 pantothenic acid Drugs 0.000 description 1
- 235000019161 pantothenic acid Nutrition 0.000 description 1
- 239000011713 pantothenic acid Substances 0.000 description 1
- RUVINXPYWBROJD-UHFFFAOYSA-N para-methoxyphenyl Natural products COC1=CC=C(C=CC)C=C1 RUVINXPYWBROJD-UHFFFAOYSA-N 0.000 description 1
- 230000003076 paracrine Effects 0.000 description 1
- 235000016236 parenteral nutrition Nutrition 0.000 description 1
- 210000003681 parotid gland Anatomy 0.000 description 1
- 238000010951 particle size reduction Methods 0.000 description 1
- 235000021017 pears Nutrition 0.000 description 1
- 230000000149 penetrating effect Effects 0.000 description 1
- 210000003668 pericyte Anatomy 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 239000000106 platelet aggregation inhibitor Substances 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 229940071643 prefilled syringe Drugs 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000005522 programmed cell death Effects 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 208000002815 pulmonary hypertension Diseases 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 235000021013 raspberries Nutrition 0.000 description 1
- 206010038038 rectal cancer Diseases 0.000 description 1
- 201000001275 rectum cancer Diseases 0.000 description 1
- 235000020095 red wine Nutrition 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 208000015347 renal cell adenocarcinoma Diseases 0.000 description 1
- 210000003660 reticulum Anatomy 0.000 description 1
- 230000000250 revascularization Effects 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 239000010668 rosemary oil Substances 0.000 description 1
- 229940058206 rosemary oil Drugs 0.000 description 1
- 239000010670 sage oil Substances 0.000 description 1
- 210000003079 salivary gland Anatomy 0.000 description 1
- 206010039667 schwannoma Diseases 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 230000028327 secretion Effects 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
- 229920002545 silicone oil Polymers 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 201000000849 skin cancer Diseases 0.000 description 1
- 208000000587 small cell lung carcinoma Diseases 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 239000000344 soap Substances 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000011272 standard treatment Methods 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 230000036262 stenosis Effects 0.000 description 1
- 208000037804 stenosis Diseases 0.000 description 1
- 239000002294 steroidal antiinflammatory agent Substances 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 235000021012 strawberries Nutrition 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- BAQAVOSOZGMPRM-QBMZZYIRSA-N sucralose Chemical compound O[C@@H]1[C@@H](O)[C@@H](Cl)[C@@H](CO)O[C@@H]1O[C@@]1(CCl)[C@@H](O)[C@H](O)[C@@H](CCl)O1 BAQAVOSOZGMPRM-QBMZZYIRSA-N 0.000 description 1
- 235000019408 sucralose Nutrition 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 230000009747 swallowing Effects 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- LRBQNJMCXXYXIU-NRMVVENXSA-N tannic acid Chemical compound OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@@H]2[C@H]([C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-NRMVVENXSA-N 0.000 description 1
- 235000015523 tannic acid Nutrition 0.000 description 1
- 229940033123 tannic acid Drugs 0.000 description 1
- 229920002258 tannic acid Polymers 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000013616 tea Nutrition 0.000 description 1
- ISIJQEHRDSCQIU-UHFFFAOYSA-N tert-butyl 2,7-diazaspiro[4.5]decane-7-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC11CNCC1 ISIJQEHRDSCQIU-UHFFFAOYSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 125000005247 tetrazinyl group Chemical group N1=NN=NC(=C1)* 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 125000004305 thiazinyl group Chemical group S1NC(=CC=C1)* 0.000 description 1
- 201000002510 thyroid cancer Diseases 0.000 description 1
- 210000001685 thyroid gland Anatomy 0.000 description 1
- 229930003799 tocopherol Natural products 0.000 description 1
- 239000011732 tocopherol Substances 0.000 description 1
- 235000019149 tocopherols Nutrition 0.000 description 1
- 229930003802 tocotrienol Natural products 0.000 description 1
- 239000011731 tocotrienol Substances 0.000 description 1
- 235000019148 tocotrienols Nutrition 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 210000003437 trachea Anatomy 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 108091006106 transcriptional activators Proteins 0.000 description 1
- 238000005809 transesterification reaction Methods 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 229940029284 trichlorofluoromethane Drugs 0.000 description 1
- 150000004684 trihydrates Chemical class 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 210000004873 upper jaw Anatomy 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 210000003932 urinary bladder Anatomy 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 208000037964 urogenital cancer Diseases 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 229940120293 vaginal suppository Drugs 0.000 description 1
- 239000006216 vaginal suppository Substances 0.000 description 1
- 229940005605 valeric acid Drugs 0.000 description 1
- 230000009723 vascular congestion Effects 0.000 description 1
- 208000019553 vascular disease Diseases 0.000 description 1
- 230000006444 vascular growth Effects 0.000 description 1
- 230000000982 vasogenic effect Effects 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 230000002861 ventricular Effects 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 235000020234 walnut Nutrition 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
- QUEDXNHFTDJVIY-UHFFFAOYSA-N γ-tocopherol Chemical class OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1 QUEDXNHFTDJVIY-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/60—Salicylic acid; Derivatives thereof
- A61K31/612—Salicylic acid; Derivatives thereof having the hydroxy group in position 2 esterified, e.g. salicylsulfuric acid
- A61K31/616—Salicylic acid; Derivatives thereof having the hydroxy group in position 2 esterified, e.g. salicylsulfuric acid by carboxylic acids, e.g. acetylsalicylic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/20—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
- A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/02—Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/06—Antiarrhythmics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Physiology (AREA)
- Nutrition Science (AREA)
- Zoology (AREA)
- Hospice & Palliative Care (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Psychiatry (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Description
(a)グリセリン誘導体にサリチル酸化合物およびサッカリン化合物を加える工程;
(b)任意で香味剤を加える工程;ならびに
(b)完全に溶解するまで混合する工程
を含んでいてもよい。
前記混合は、液状組成物を超音波処理することによって行ってもよい。
1.アスピリン、トリアセチルグリセリン、サッカリンおよび任意で香味剤を含む安定な液状組成物。
2.アスピリンの濃度が0.5〜3%であり、かつ/またはトリアセチルグリセリンの濃度が94〜99%である、項1に記載の組成物。
3.サッカリンの濃度が0.1〜3%である、項1または項2に記載の組成物。
4.香味剤がハッカ油を含むか、またはハッカ油からなる、先行する項のいずれか1つに記載の組成物。
5.アスピリン、トリアセチルグリセリン、サッカリンおよび任意で香味剤からなる、先行する項のいずれか1つに記載の組成物。
6.トリアセチルグリセリンが、活性白土を通した濾過によって得られる、先行する項のいずれか1つに記載の組成物。
7.25℃におけるアスピリンの分解率が、0.04%/日未満および/または0.006mg/g/日未満である、先行する項のいずれか1つに記載の組成物。
8.25℃におけるアスピリンの分解率が、0.02%/日未満および/または0.004mg/g/日未満である、項7に記載の組成物。
9.粒子が含まれていないか、かつ/またはアスピリンが完全に溶解している、先行する項のいずれか1つに記載の組成物。
10.経口使用に適している、先行する項のいずれか1つに記載の組成物。
11.先行する項のいずれか1つに記載の組成物を含む包装品であって、該組成物が該包装に密封されている包装品。
12.ボトル、ピペット、注射器、バイアル、分包、スティック分包および液体用ゲルカプセルからなる群から選択される、項11に記載の包装品。
13.アスピリンの摂取方法であって、アスピリン、トリアセチルグリセリン、サッカリンおよび任意で香味剤を含む安定な液状組成物を経口投与することを含む方法。
14.鎮痛薬、解熱薬、抗炎症薬および/または抗血小板薬として経口投与により使用するための、アスピリン、トリアセチルグリセリン、サッカリンおよび任意で香味剤を含む安定な液状組成物。
15.安定なアスピリン溶液を製造するための、トリアセチルグリセリン、サッカリンおよび任意で香味剤を含むか、またはこれらからなる組成物の使用。
本明細書において「サリチル酸化合物」は、式(I):
式中、
R1は、負電荷か、または
−H、
−RA、
−OH、−ORA、−CF3、−OCF3、
−COH、−CORA、−COOH、−COORA、
−NH2、−NHRA、−NRA 2および−NRB 2
からなる群から独立して選択され;
R2は、
−H、
−RA、
−OH、−ORA、−CF3、−OCF3、
−COH、−CORA、−COOH、−COORA、
−NH2、−NHRA、−NRA 2、−NRB 2および
−Q
からなる群から独立して選択され;
R3〜R6は、
−H、
−F、−Cl、−Br、−I、
−RA、
−OH、−ORA、−CF3、−OCF3、
−CN、−NO2、
−COH、−CORA、−COOH、−COORA、
−NH2、−NHRA、−NRA 2、−NRB 2、
−SO3H、−S(O)RAおよび−S(O2)RA
からなる群からそれぞれ独立して選択され;
Qは、
Pは、−H、直鎖または分岐鎖のC1〜4アルキル、アルケニルまたはアルキニルおよび−CORAから独立して選択され;
−RAは、
直鎖または分岐鎖のC1〜4アルキル、アルケニルまたはアルキニル、
1つ以上の−RD基で置換されていてもよいフェニル、
1つ以上の−RD基で置換されていてもよいベンジル、
−COOH、−COORC、−C(O)RC、−NH2、−NHRCおよび−NRC 2
からなる群から独立して選択され;
−RDは、
直鎖または分岐鎖のC1〜4アルキル、アルケニルまたはアルキニル、
−F、−Cl、−Br、−I、
−OH、−ORC、−CF3、−OCF3、
−CN、−NO2、
−COH、−CORC、−COOH、−COORC、
−NH2、−NHRC、−NRC 2、−NRB 2、
−S(O)RCおよび−S(O2)RC
から独立して選択され;
−RCは、直鎖または分岐鎖のC1〜4アルキル、アルケニルまたはアルキニルから独立して選択され;
−NRB 2は、直鎖または分岐鎖のC1〜4アルキル、アルケニルまたはアルキニル、フェニルおよびベンジルから選択される1つ以上の基で置換されていてもよい、アゼチジノ、イミダゾリジノ、ピラゾリジノ、ピロリジノ、ピペリジノ、ピペラジノ、N−C1〜4アルキル−ピペラジノ、モルホリノ、アゼピノおよびジアゼピノからなる群から独立して選択され;
[C+]は、任意で存在するカウンターカチオンであり、アルカリ金属イオン、アルカリ土類金属イオン、遷移金属イオン、Al3+、アンモニウムイオン、置換されたアンモニウムイオンおよびNO2 +からなる群から選択される。
いくつかの実施形態において、R1は、負電荷か、または
−H、
−RA、
−COH、−CORA、−COOH、−COORA、
−NH2、−NHRA、−NRA 2および−NRB 2
からなる群から独立して選択される。
−H、
直鎖もしくは分岐鎖のC1〜4アルキル、アルケニルもしくはアルキニル、
1つ以上の−RD基で置換されていてもよいフェニル、
1つ以上の−RD基で置換されていてもよいベンジル、および
−C(O)RC
からなる群から独立して選択される。
いくつかの実施形態において、R2は、
−H、
−RA、
−COH、−CORA、−COOH、−COORAおよび
−Q
からなる群から独立して選択される。
いくつかの実施形態において、R3〜R6は、
−H、
−F、−Cl、−Br、
−CN、−NO2、
−RA、
−OH、−ORA、−CF3および−OCF3
からそれぞれ独立して選択される。
−H、
−F、−Cl、
−RA、
−OH、−ORAおよび−CF3
からそれぞれ独立して選択される。
−H、
1つ以上の−RD基で置換されていてもよいフェニル、および
−CF3
からそれぞれ独立して選択される。
本明細書において「グリセリン誘導体」は、式(II):
式中、
R7〜R9は、
−H、
−RA、
−COH、−CORA、−COOH、−COORA、
−NH2、−NHRA、−NRA 2、−NRB 2、
−S(O)RAおよび−S(O2)RA
からなる群からそれぞれ独立して選択され;
−RAは、
直鎖または分岐鎖のC1〜4アルキル、アルケニルまたはアルキニル、
1つ以上の−RD基で置換されていてもよいフェニル、
1つ以上の−RD基で置換されていてもよいベンジル、
−COOH、−COORC、−C(O)RC、−NH2、−NHRCおよび−NRC 2
からなる群から独立して選択され;
−RDは、
直鎖または分岐鎖のC1〜4アルキル、アルケニルまたはアルキニル、
−F、−Cl、−Br、−I、
−OH、−ORC、−CF3、−OCF3、
−CN、−NO2、
−COH、−CORC、−COOH、−COORC、
−NH2、−NHRC、−NRC 2、−NRB 2、
−S(O)RCおよび−S(O2)RC
から独立して選択され;
−RCは、直鎖または分岐鎖のC1〜4アルキル、アルケニルまたはアルキニルから独立して選択され;
−NRB 2は、直鎖または分岐鎖のC1〜4アルキル、アルケニルまたはアルキニル、フェニルおよびベンジルから選択される1つ以上の基で置換されていてもよい、アゼチジノ、イミダゾリジノ、ピラゾリジノ、ピロリジノ、ピペリジノ、ピペラジノ、N−C1〜4アルキル−ピペラジノ、モルホリノ、アゼピノおよびジアゼピノからなる群から独立して選択される。
いくつかの実施形態において、R7〜R9は、−Hおよび−RAからなる群からそれぞれ独立して選択される。
本明細書において「サッカリン化合物」は、式(III):
式中、
R10〜R13は、
−H、
−F、−Cl、−Br、−I、
−RA、
−OH、−ORA、−CF3、−OCF3、
−CN、−NO2、
−COH、−CORA、−COOH、−COORA、
−NH2、−NHRA、−NRA 2、−NRB 2、
−SO3H、−S(O)RA、−S(O2)RAおよび
−W
からなる群からそれぞれ独立して選択され;
Xは、
−N−、−NHおよび−NRA
からなる群から独立して選択され;
Yは、S(O2)から独立して選択され;
−RAは、
直鎖または分岐鎖のC1〜4アルキル、アルケニルまたはアルキニル、
1つ以上の−RD基で置換されていてもよいフェニル、
1つ以上の−RD基で置換されていてもよいベンジル、
−COOH、−COORC、−C(O)RC、−NH2、−NHRCおよび−NRC 2
からなる群から独立して選択され;
−RDは、
直鎖または分岐鎖のC1〜4アルキル、アルケニルまたはアルキニル、
−F、−Cl、−Br、−I、
−OH、−ORC、−CF3、−OCF3、
−CN、−NO2、
−COH、−CORC、−COOH、−COORC、
−NH2、−NHRC、−NRC 2、−NRB 2、
−S(O)RCおよび−S(O2)RC
から独立して選択され;
−RCは、直鎖または分岐鎖のC1〜4アルキル、アルケニルまたはアルキニルから独立して選択され;
−NRB 2は、直鎖または分岐鎖のC1〜4アルキル、アルケニルまたはアルキニル、フェニルおよびベンジルから選択される1つ以上の基で置換されていてもよい、アゼチジノ、イミダゾリジノ、ピラゾリジノ、ピロリジノ、ピペリジノ、ピペラジノ、N−C1〜4アルキル−ピペラジノ、モルホリノ、アゼピノおよびジアゼピノからなる群から独立して選択され;
−Wは、
LAは、5員または6員のヘテロ芳香族基から独立して選択され、LBは、5員または6員の単糖部分から独立して選択され;
[C+]は、任意で存在するカウンターカチオンであり、アルカリ金属イオン、アルカリ土類金属イオン、遷移金属イオン、Al3+、アンモニウムイオン、置換されたアンモニウムイオン、およびNO2 +からなる群から選択される。
いくつかの実施形態において、Xは、N−およびNHから独立して選択される。
いくつかの実施形態において、R10〜R13は、
−H、
−F、−Cl、−Br、
−RA、
−OH、−ORA、−CF3、−OCF3、
−CN、−NO2、
−COH、−CORA、−COOH、−COORA、
−NH2、−NHRA、−NRA 2、−NRB 2および
−W
からそれぞれ独立して選択される。
−H、
−F、−Cl、−Br、
−RA、
−OH、−ORA、−CF3、−OCF3および
−W
からそれぞれ独立して選択される。
−H、
−F、−Cl、
−RA、
−OH、−ORAおよび
−W
からそれぞれ独立して選択される。
−H、
−F、−Cl、
直鎖または分岐鎖のC1〜4アルキル、アルケニルまたはアルキニル、
−OHおよび
−W
からそれぞれ独立して選択される。
−H、
−F、−Cl、
直鎖または分岐鎖のC1〜4アルキル、アルケニルまたはアルキニル、および
−OH
からそれぞれ独立して選択される。
いくつかの実施形態において、LAは、イミダゾリル、ピラゾリル、オキサゾリル、イソオキサゾリル、チアゾリル、イソチアゾリル、ジオキソラニル、ジチオラニル、トリアゾリル、フラニル、オキサジアゾリル、チアジアゾリル、ジチアゾリル、テトラゾリル、ピリジニル、ピラニル、チオピラニル、ジアジニル、オキサジニル、チアジニル、ジオキシニル、ジチイニル、トリアジニルおよびテトラジニルから独立して選択される5員または6員のヘテロ芳香族基である。
で表されるトリアゾリル部分のうちの1つから独立して選択される5員のヘテロ芳香族基である。
いくつかの実施形態において、LBは、リボフラニル、グルコピラニル、ガラクトピラニル、マンノピラニルおよびアロピラニルから独立して選択される。
式中、[Cn+]は、アルカリ金属イオン、アルカリ土類金属イオン、遷移金属イオン、Al3+、アンモニウムイオン、置換されたアンモニウムイオンおよびNO2 +からなる群から選択されるカウンターカチオンであり、より好ましくはナトリウムイオンまたはカルシウムイオンである。
上述の化合物のいくつかは、幾何異性体、光学異性体、鏡像異性体、ジアステレオ異性体、エピ異性体、アトロプ異性体、立体異性体、互変異性体、配座異性体、アノマー異性体のうちの1つ以上の特定の異性体として存在していてもよく、このような異性体としては、シス体およびトランス体;E体およびZ体;c体、t体およびr体;エンド体およびエキソ体;R体、S体およびメソ体;D体およびL体;d体およびl体;(+)体および(−)体;ケト体、エノール体およびエノラート体;syn体およびanti体;シンクリナル体およびアンチクリナル体;α体およびβ体;アキシアル体およびエカトリアル体;舟型、椅子型、ねじれ型、封筒型および半舟型;ならびにこれらの組み合わせが挙げられるが、これらに限定されない。以下、これらをまとめて「異性体」(または「異性形態」)と呼ぶ。
上述したように、サリチル酸化合物および/またはサッカリン化合物は塩として提供される場合がある。したがって、本明細書において「サリチル酸化合物」および「サッカリン化合物」は、それらの塩も含む。
特定の化合物の溶媒和物を調製、精製、および/または処理することが簡便または望ましい場合がある。本明細書において「溶媒和物」という用語は従来の意味で使用され、溶質(たとえば化合物、化合物の塩)と溶媒の複合体を指す。溶媒が水である場合、溶媒和物は簡便に水和物、たとえば一水和物、二水和物、三水和物などと呼ぶこともできる。
特定の化合物、特にサリチル酸化合物をプロドラッグの形態で調製、精製、および/または処理することが簡便または望ましい場合がある。本明細書において「プロドラッグ」は、(たとえばインビボにおいて)代謝されて、所望の活性化合物に変化する化合物を指す。プロドラッグは通常、不活性であるか、あるいは所望の活性化合物よりも活性が低いが、処理、投与または代謝特性の点において有利な場合がある。
本発明の液状組成物は、医薬組成物または医薬品として製剤化されることが好ましい。
本明細書に記載の液状組成物は、たとえば、サリチル酸化合物(たとえばアスピリン)で治療が行われることが知られている疾患または障害や、サリチル酸化合物(たとえばアスピリン)で治療できることが知られている疾患または障害などの、疾患または障害の治療または予防に有用である。
治療の対象となる対象は、動物であってもヒトであってもよい。対象は哺乳動物であることが好ましく、ヒトであることがより好ましい。対象は非ヒト哺乳動物であってもよいが、ヒトであることがより好ましい。対象は雄性であっても雌性であってもよい。対象は患者であってもよい。対象は、心血管疾患、脳血管疾患またはがんであると診断された個体であってもよく、心血管疾患、脳血管疾患またはがんを有している疑いがある個体であってもよい。いくつかの実施形態において、対象は成人すなわち18歳以上であってもよい。いくつかの実施形態において、対象は、小児、たとえば18歳未満、16歳未満または12歳未満の対象であってもよい。
サリチル酸化合物を含む前記液状医薬組成物は、全身投与/末梢投与または局所投与(すなわち所望の作用部位への投与)などの、任意の簡便な投与経路によって対象に投与してもよい。
当業者であれば、サリチル酸化合物を含む前記組成物の適切な投薬量は、患者によって異なりうることを容易に理解するであろう。最適な投薬量の決定にあたっては、通常、リスクまたは有害な副作用と治療ベネフィットの大きさのバランスを取る必要がある。投薬量の選択は様々な要因に左右され、このような要因としては、たとえば、特定のサリチル酸化合物の活性、投与経路、投与時間、サリチル酸化合物の排泄速度、治療期間、サリチル酸化合物と併用されるその他の薬物、化合物および/または物質、病態の重症度、ならびに患者の生物種、性別、年齢、体重、状態、全体的な健康状態および既往歴が挙げられるが、これらに限定されない。サリチル酸化合物の量および投与経路は、最終的には医師、獣医師または臨床医の判断によって決定されるが、投薬量は、通常、実質的に有毒または有害な副作用を起こさずに所望の効果を奏する局所濃度が作用部位において得られるように選択される。
本発明の一態様は、キットであって、(a)たとえば、好ましくは適切な容器に入れられ、かつ/または適切な包装がなされて提供される、本明細書に記載の液状組成物;および(b)使用説明書、たとえば該組成物の投与方法が記載された説明書を含むキットに関する。
アスピリンは、サリチル酸と酢酸に加水分解される。組成物試料中のアスピリンおよびサリチル酸の濃度を、最も短期間の場合で少なくとも200日間にわたって、好ましくは最大300日間にわたって測定した。密封したガラスバイアルに組成物を入れ、バイアルを25℃のオーブンに保管し、アスピリンおよびサリチル酸の濃度を毎週測定した。ガラスバイアルを開封し、試料を一部取り出して毎週試験を行い、窒素でパージしてから再度ガラスバイアルを密封した。UV検出器を備えた高速液体クロマトグラフィーを使用した。以下の条件を使用した。
・移動相:1%酢酸水溶液:メタノール=40%:60%
・カラム:アジレントZorbax Eclipse XBD-C18、4.6mm×150mm、粒子径5μm
・カラムヒーター:25℃
・試料の濃度:0.02gの試料を移動相で10mlに調製
・注入量:40μl
・流速:1ml/分
・検出:280nmのUV
組成物中のアスピリンの安定性は、(i)(最初のアスピリン濃度に基づいた)1日あたりの平均アスピリン分解率(%)、または(ii)(最初のアスピリン濃度に基づいた)組成物1gに対する1日あたりの平均アスピリン分解率(%)として算出されたアスピリン分解率により定義する。
食用グレードのトリアセチルグリセリン(たとえばシグマ アルドリッチ社製)を40%(w/v)エタノールと混合し、活性白土の固定層を通して濾過した。次いで、減圧蒸留を行い、さらに蒸気蒸留を行うことによって溶媒を除去し、トリアセチルグリセリン中のエタノール濃度を1ppm未満とした。
アスピリン2.5wt%(たとえばシグマ アルドリッチ社製)、トリアセチルグリセリン96.5wt%(実施例1で製造したもの)およびサッカリン1wt%(たとえばシグマ アルドリッチ社製)を混合して組成物を調製した。上記適切な割合で混合した当該成分を超音波攪拌することによって、完全に溶解させた。顕微鏡観察によって、溶液中に粒子が存在しないことを確認した。組成物中のアスピリンの安定性を、上述した方法に従って毎週測定した。277日後のアスピリンの分解量は、最初のアスピリン量の6.9%であった。これは分解率0.025%/日に相当する。
スペアミント油0.15wt%(たとえばQuinessence社製)を組成物にさらに加えた(これに応じてトリアセチルグリセリンの量を0.15wt%減らした(すなわち96.35wt%とした))こと以外は同様にして、実施例2の操作を繰り返した。246日後のアスピリンの分解量は、最初のアスピリン量の5.7%であった。これは分解率0.023%/日に相当する。
アスピリン2.5wt%(たとえばシグマ アルドリッチ社製)、トリアセチルグリセリン96.5wt%(実施例1で製造したもの)およびサッカリン1wt%(たとえばシグマ アルドリッチ社製)を混合して組成物を調製した。上記適切な割合で混合した当該成分を超音波攪拌することによって、完全に溶解させた。顕微鏡観察によって、溶液中に粒子が存在しないことを確認した。組成物中のアスピリンの安定性を、上述した方法に従って毎週測定した。
標準化したサリチル酸量(%)=(サリチル酸の量(%))/(アスピリンの量(%)+サリチル酸の量(%))
実施例2の方法に準じて、アスピリン、トリアセチルグリセリンおよびサッカリンからなる様々な組成物を調製した。5種の組成物を調製し、アスピリンの濃度をそれぞれ2.5wt%、3.0wt%、3.5wt%、4.0wt%および4.5wt%とした。各組成物は、アスピリン以外に、サッカリン1wt%および残部としてのトリアセチルグリセリンを含んでいた。
アスピリン10wt%(たとえばシグマ アルドリッチ社製)およびグリセリン+20EO(20モル当量のエチレンオキシドでエトキシ化したグリセリン)90wt%を混合して組成物を調製した。上記適切な割合で混合した当該成分を超音波攪拌することによって、完全に溶解させた。顕微鏡観察によって、溶液中に粒子が存在しないことを確認した。組成物中のアスピリンの安定性を、上述した方法に従って毎週測定した。
アスピリン10wt%(たとえばシグマ アルドリッチ社製)、サッカリン1%(たとえばシグマ アルドリッチ社製)およびグリセリン+20EO 89wt%を混合して組成物を調製した。上記適切な割合で混合した当該成分を超音波攪拌することによって、完全に溶解させた。顕微鏡観察によって、溶液中に粒子が存在しないことを確認した。組成物中のアスピリンの安定性を、上述した方法に従って毎週測定した。
序論
現在市場に出回っている溶解性アスピリンは、実際は分散剤であり、液体中に粒子が残っており、これが胃粘膜に付着して胃の副作用を引き起こす。つまり、「溶解性」という分類は正確ではない。分散剤の代替となるアスピリン製剤は、急速に水中分散する散剤である。これまで、真の意味で安定に長期保存可能な液体アセチルサリチル酸(ASA)製剤の製造には成功していない。本明細書に記載されている他に類を見ない液体ASA(この実施例においては「液体アスピリン」と呼ぶ)は、消化管副作用が有意に低減されたものであると期待される。
様々な神経膠腫細胞株(C6、A172、U87、U373、U251など)が樹立されている。これらの細胞株は、世界中の研究室において長年にわたり培養/継代されていることから、異質性が高く、元の初代培養/初期の継代培養とは徐々に違いが見られるようになり、特に、これらの細胞株が得られた生検試料とは大きく異なっている。
以下の文献は、引用により本明細書に組み込まれる。
1. Lan et al. “Antitumor effect of aspirin in glioblastoma cells by modulation of β-catenin/T-cell factor-mediated transcriptional activity”, J Neurosurg, 2011, Vol. 115, pp. 780-788;
2. M. W. Brown, ‘Characterisation Of The Effects Of Chronic Aspirin Treatment On The Viability And Proliferation Of Stage 4 Glioblastoma Cells’, Diffusion: the UCLan Journal of Undergraduate Research, Vol. 6, Issue 2, December 2013;
3. Aas et al., ‘Growth inhibition of rat glioma cells in vitro and in vivo by aspirin’, Journal of Neuro-Oncology, 1995, Vol. 24, Issue 2, pp. 171-180;
4. Ning et al., ‘Overexpression of S100A9 in human glioma and in-vitro inhibition by aspirin’, European Journal of Cancer Prevention, 2013, Vol. 22, Issue 6, pp. 585-595;
5. Hwang et al., ‘Effect of aspirin and indomethacin on prostaglandin E2 synthesis in C6 glioma cells’, Kaohsiung J Med Sci, 2004, Vol. 20, pp. 1-5;
6. Okada et al., ‘Integration of epidemiology, immunobiology, and translational research for brain tumors’, Ann N Y Acad Sci, 2013, Vol. 1284, pp. 17-23;
7. Rothwell et al., ‘Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials’, Lancet, 2011, Vol. 377, pp. 31-41;
8. K. D. Rainsford, ‘Aspirin and Related Drugs’, 2004 (book);
9. Douthwaite and Lintott, ‘Gastroscopic observations of the gastric mucosa after use of aspirin’, Lancet, 1938, Vol. 232, pp. 1222-1225;
10. Hurst and Lintott, ‘Aspirin as a cause of hematemesis’, Guy’s Hosp Rep, 1939, p. 173;
11. D. J. Levy ‘An aspirin tablet and gastric ulcer’, N Engl J Med, 2000, Vol. 343, No. 12, p. 863 (photograph);
12. Rainsford et al. ‘Electronmicroscopic observations on the effects of orally administered aspirin and aspirin-bicarbonate mixtures on the development of gastric mucosal damage in the rat’, Gut, 1975, Vol. 16(7), pp. 514-527;
13. Jaiswal et al. IUPHAR 9th Int. Conference of Pharmacology, 1984;
14. Liversage et al. ‘Drug particle size reduction for decreasing gastric irritation and enhanced absorption of Naproxen in rats’, Int J Pharm, 1995, Vol. 125(2), pp. 309-313;
15. Gyory et al. ‘Effect of particle size on aspirin-induced gastrointestinal bleeding’, Lancet, Vol. 292, No. 7563, pp. 300-302;
16. M. I. Grossman et al. ‘Fecal Blood Loss Produced By Oral And Intravenous Administration Of Various Salicylates’, Gastroenterology, 1961, Vol. 40, pp. 383-388;
17. Kevin et al., ‘Acute effect of systemic aspirin on gastric mucosa in man’, Digestive Diseases and Sciences, 1980, Vol. 25, Issue 2, pp 97-99;
18. Cooke et al., ‘Failure of intravenous aspirin to increase gastrointestinal blood loss’, British medical journal, 1969; Vol. 3(5666), pp. 330-332;
19. Wallace et al., ‘Adaptation of rat gastric mucosa to aspirin requires mucosal contact’ Am J Physiol, 1995, Vol. 268, G134-8;
20. Cryer et al. ‘Effects of low dose daily aspirin therapy on gastric, duodenal and rectal prostaglandin levels and on mucosal injury in healthy humans’, Gastroenterology, 1999, Vol. 117, pp. 17-25;
21. Lichtenberger et al., ‘Where is the evidence that cyclooxygenase inhibition is the primary cause of nonsteroidal anti-inflammatory drug (NSAID)-induced gastrointestinal injury? Topical injury revisited’, Biochemical Pharmacology, 2001, Vol. 61, pp. 631-637;
22. Ligumsky M et al., ‘Aspirin can inhibit gastric mucosal cyclo-oxygenase without causing lesions in the rat’, Gastroenterology, 1983, Vol. 84, pp 756-61;
23. Zhao et al., ‘Clinical Research Feasibility of intravenous administration of aspirin in acute coronary syndrome’, Journal of Geriatric Cardiology, 2008, Vol. 5 No. 4, pp. 212-216;
24. Mashita et al., ‘Oral but not parenteral aspirin upregulates COX-2 expression in rat stomachs: a relationship between COX-2 expression and PG deficiency’, Digestion, 2006, Vol. 73(2-3), pp. 124-32;
25. Hall, SL; Lorenc, T (1 February 2010). "Secondary prevention of coronary artery disease". American family physician 81 (3): 289-96;
26. Fengming Lan et al., Antitumor effect of aspirin in glioblastoma cells by modulation of β-catenin/T-cell factor-mediated transcriptional activity. J Neurosurg 115:780-788, 2011;
27. Morris et al., Effects of Low-Dose Aspirin on Acute Inflammatory Responses in Humans. The Journal of Immunology. 2009; 183:2089-2096;
28. Gasic GI, et al. Lancet. 1972;2:932-937;
29. Tsen et al., Triacetin-based acetate supplementation as a chemotherapeutic adjuvant therapy in glioma. Int J Cancer. 2014 March 15; 134(6):1300-1310;
30. Long et al., ‘Acetate Supplementation Induces Growth Arrest of NG2/PDGFRa-Positive Oligodendroglioma-Derived Tumor-Initiating Cells’, PLoS One, 2013, e80714;
31. Mahon et al., Saccharin: a lead compound for structure-based drug design of carbonic anhydrase IX inhibitors. Bioorg Med Chem 2015 Feb 15;23(4):849-54;
32. Proescholdt et al. (‘Function of carbonic anhydrase IX in glioblastoma multiforme’, Neuro Oncol, 2012, Vol. 14, pp. 1357-1366;
33. Buck ML et al., ‘Use of Aspirin in children with cardiac disease’, Pediatr Pharm, 2007, Vol. 13(1);
34. Garcia Albeniz. X et al., ‘Aspirin for the prevention of colorectal cancer’, Best Pract Res Clin Gastroenterol, 2011 Aug, Vol. 25(0), pp. 461-472.
Claims (29)
- サリチル酸化合物、トリアセチルグリセリンおよびサッカリンを含む液状組成物であって、該サリチル酸化合物が、アスピリンおよびトリフルサルからなる群から選択され、該組成物中の前記サリチル酸化合物の含量が0.5〜7重量%であり、前記トリアセチルグリセリンの含量が90〜99重量%である、液状組成物。
- 前記サリチル酸化合物がアスピリンである、請求項1に記載の組成物。
- 前記サリチル酸化合物の含量が1〜5重量%である、請求項1または2に記載の組成物。
- 前記サリチル酸化合物の含量が0.5〜3重量%である、請求項1または2に記載の組成物。
- 前記トリアセチルグリセリンの含量が94〜99重量%である、請求項1〜4のいずれか1項に記載の組成物。
- 前記トリアセチルグリセリンの含量が95〜97.5重量%である、請求項1〜4のいずれか1項に記載の組成物。
- 前記サリチル酸化合物の含量が0.5〜3重量%であり、前記トリアセチルグリセリンの含量が94〜99重量%である、請求項1または2に記載の組成物。
- 前記サッカリンの含量が0.1〜3重量%である、請求項1〜7のいずれか1項に記載の組成物。
- 0〜0.5重量%の水を含む、請求項1〜8のいずれか1項に記載の組成物。
- 香味剤をさらに含む、請求項1〜9のいずれか1項に記載の組成物。
- 前記香味剤がハッカ油である、請求項10に記載の組成物。
- 経口使用に適している、請求項1〜11のいずれか1項に記載の組成物。
- 静脈内投与用または動脈内投与用に製剤化されている、請求項1〜11のいずれか1項に記載の組成物。
- 吸入投与用または吹送投与用に製剤化されている、請求項1〜11のいずれか1項に記載の組成物。
- 請求項1〜14のいずれか1項に記載の液状組成物の調製方法であって、サリチル酸化合物、トリアセチルグリセリンおよびサッカリンを混合することを含み、該サリチル酸化合物が、アスピリンおよびトリフルサルからなる群から選択される、方法。
- 前記サリチル酸化合物がアスピリンである、請求項15に記載の方法。
- 香味剤を混合することをさらに含む、請求項15または16に記載の方法。
- 前記香味剤がハッカ油である、請求項17に記載の方法。
- 請求項1〜14のいずれか1項に記載の組成物を含む包装品であって、該組成物が該包装に密封されている包装品。
- ボトル、ピペット、注射器、バイアル、分包、スティック分包および液体用ゲルカプセルからなる群から選択される、請求項19に記載の包装品。
- 治療方法において使用するための、請求項1〜14のいずれか1項に記載の液状組成物。
- 前記治療方法が、経口投与、直腸投与、経鼻胃投与、非経口投与、静脈内投与、動脈内投与、吸入投与または吹送投与によって前記液状組成物を投与することを含む、請求項21に記載の液状組成物。
- 心血管疾患の治療方法において使用するための、請求項1〜14のいずれか1項に記載の液状組成物。
- 前記心血管疾患が、狭心症;心不全(HF);左室不全または右室不全;肺性心;虚血性心疾患(IHD);心筋症;冠性心疾患;小児の心血管疾患(たとえば川崎病);および先天性心疾患から選択されるものである、請求項23に記載の液状組成物。
- 脳血管疾患の治療方法において使用するための、請求項1〜14のいずれか1項に記載の液状組成物。
- 前記脳血管疾患が、脳卒中、大脳虚血、脳虚血、一過性脳虚血発作(TIA)および血管性認知症から選択されるものである、請求項25に記載の液状組成物。
- がんの治療方法において使用するための、請求項1〜14のいずれか1項に記載の液状組成物。
- 前記がんが、中枢神経系がん、脳がん、消化管がんまたは神経膠腫である、請求項27に記載の液状組成物。
- 疼痛、発熱または炎症の治療方法において使用するための、請求項1〜14のいずれか1項に記載の液状組成物。
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB201423109 | 2014-12-23 | ||
GB1423109.6 | 2014-12-23 | ||
GB1514012.2 | 2015-08-07 | ||
GB1514012.2A GB2533669B (en) | 2014-12-23 | 2015-08-07 | Salicylate compound composition |
PCT/GB2015/054129 WO2016102959A1 (en) | 2014-12-23 | 2015-12-22 | Salicylate compound composition |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2018500369A JP2018500369A (ja) | 2018-01-11 |
JP2018500369A5 JP2018500369A5 (ja) | 2019-02-07 |
JP6772142B2 true JP6772142B2 (ja) | 2020-10-21 |
Family
ID=54200417
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2017534735A Active JP6772142B2 (ja) | 2014-12-23 | 2015-12-22 | サリチル酸化合物の組成物 |
Country Status (11)
Country | Link |
---|---|
US (1) | US11129837B2 (ja) |
EP (1) | EP3236971B1 (ja) |
JP (1) | JP6772142B2 (ja) |
CN (1) | CN107295795B (ja) |
AR (1) | AR103253A1 (ja) |
AU (1) | AU2015370673B2 (ja) |
BR (1) | BR112017013629B1 (ja) |
CA (1) | CA3009583A1 (ja) |
GB (1) | GB2533669B (ja) |
MA (1) | MA41255A (ja) |
WO (1) | WO2016102959A1 (ja) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN115998725A (zh) * | 2022-06-02 | 2023-04-25 | 福建医科大学 | 三醋酸甘油酯在制备治疗痴呆症或增龄性认知功能减退的药物中的用途 |
Family Cites Families (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB873526A (en) * | 1957-08-14 | 1961-07-26 | Upjohn Co | Fluid compositions comprising (acetyl-salicylic acid)-anhydride |
US3316150A (en) * | 1964-02-26 | 1967-04-25 | Faeges Marvin | Stable suspensions of acetyl salicylic acid |
US4375468A (en) * | 1981-07-13 | 1983-03-01 | Verex Laboratories, Inc. | Constant order release aspirin composition and method of treating arthritis |
US4975269A (en) * | 1989-07-31 | 1990-12-04 | Leonard Chavkin | Shelf stable aspirin solutions |
US5110606A (en) * | 1990-11-13 | 1992-05-05 | Affinity Biotech, Inc. | Non-aqueous microemulsions for drug delivery |
JPH1112177A (ja) * | 1997-06-25 | 1999-01-19 | Teikoku Seiyaku Co Ltd | 安定なアスピリン含有外用製剤 |
ES2196574T3 (es) * | 1997-07-15 | 2003-12-16 | Walter Burghart | Procedimiento para la preparacion de soluciones estables de acido acetilsalicilico. |
GB0018322D0 (en) * | 2000-07-27 | 2000-09-13 | Boots Co Plc | Pharmaceutical compositions |
US6669955B2 (en) * | 2001-08-28 | 2003-12-30 | Longwood Pharmaceutical Research, Inc. | Combination dosage form containing individual dosage units of a cholesterol-lowering agent, an inhibitor of the renin-angiotensin system, and aspirin |
JP2005082488A (ja) * | 2003-09-04 | 2005-03-31 | Lion Corp | 口腔用組成物及び異味異臭のマスキング方法 |
TWI394593B (zh) * | 2007-03-30 | 2013-05-01 | Lintec Corp | Methods of making pharmaceuticals for oral administration |
WO2011076401A1 (de) * | 2009-12-23 | 2011-06-30 | Holger Schankin | Acetylsalicylsäure-haltige, im wesentlichen wasserfreie pharmazeutische zusammensetzungen |
CN102218088A (zh) * | 2011-06-08 | 2011-10-19 | 王国玉 | 一种口腔溃疡涂擦液 |
JP2014517046A (ja) | 2011-06-24 | 2014-07-17 | アセンダ ファーマ インコーポレイテッド | エステルプロドラッグの吸収を改善するための方法及び改善された医薬組成物 |
-
2015
- 2015-08-07 GB GB1514012.2A patent/GB2533669B/en active Active
- 2015-12-21 MA MA041255A patent/MA41255A/fr unknown
- 2015-12-22 AU AU2015370673A patent/AU2015370673B2/en not_active Ceased
- 2015-12-22 AR ARP150104264A patent/AR103253A1/es unknown
- 2015-12-22 EP EP15826045.5A patent/EP3236971B1/en active Active
- 2015-12-22 US US15/538,974 patent/US11129837B2/en active Active
- 2015-12-22 BR BR112017013629-5A patent/BR112017013629B1/pt active IP Right Grant
- 2015-12-22 JP JP2017534735A patent/JP6772142B2/ja active Active
- 2015-12-22 CA CA3009583A patent/CA3009583A1/en active Pending
- 2015-12-22 WO PCT/GB2015/054129 patent/WO2016102959A1/en active Application Filing
- 2015-12-22 CN CN201580076406.0A patent/CN107295795B/zh active Active
Also Published As
Publication number | Publication date |
---|---|
CN107295795A (zh) | 2017-10-24 |
AU2015370673B2 (en) | 2021-06-03 |
GB2533669B (en) | 2016-12-14 |
AU2015370673A1 (en) | 2017-08-10 |
CN107295795B (zh) | 2021-10-29 |
CA3009583A1 (en) | 2016-06-30 |
WO2016102959A1 (en) | 2016-06-30 |
BR112017013629A2 (pt) | 2018-03-13 |
AR103253A1 (es) | 2017-04-26 |
GB2533669A (en) | 2016-06-29 |
JP2018500369A (ja) | 2018-01-11 |
US11129837B2 (en) | 2021-09-28 |
MA41255A (fr) | 2017-10-31 |
EP3236971B1 (en) | 2023-08-30 |
EP3236971A1 (en) | 2017-11-01 |
BR112017013629B1 (pt) | 2022-11-29 |
GB201514012D0 (en) | 2015-09-23 |
US20170348332A1 (en) | 2017-12-07 |
EP3236971C0 (en) | 2023-08-30 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
ES2882192T3 (es) | Combinaciones antiinflamatorias sinérgicas de astaxantina con licopeno y ácido carnósico | |
ES2627020T3 (es) | Composición farmacéutica que comprende un inhibidor de HDAC y un esteroide y el uso de la misma | |
KR102403047B1 (ko) | 중추 신경계 장애를 치료하기 위한 벤조에이트 화합물과 탄닌산을 함유하는 조성물 | |
EP2995308B1 (en) | Antihypoxic pharmaceutical composition and application thereof | |
US20130079401A1 (en) | Novel use of isothiocyanates for treating cancer | |
EP1481669A1 (en) | Use of polyhydroxy phenols and polyphenols for modulating p-selectin activity | |
JP2013515690A (ja) | アルテミシニンベースの薬剤と他の化学療法薬の抗癌用組合せ | |
ES2932248T3 (es) | Combinaciones sinérgicas antiinflamatorias que comprenden ácido graso omega-3, licopeno de tomate, luteína y ácido carnósico | |
JP6772142B2 (ja) | サリチル酸化合物の組成物 | |
BR112015005284B1 (pt) | Combinação de compostos derivados do ácido gálico, composição farmacêutica compreendendo a referida combinação e seus usos no tratamento de câncer | |
WO2012075754A1 (zh) | 一种治疗急性淋巴白血病的复方药物组合物 | |
KR102157771B1 (ko) | 다이설피람을 포함하는 항암용 조성물 | |
WO2020062951A1 (zh) | 化合物及其用途 | |
KR20180057590A (ko) | 멜라토닌 유도체를 포함하는 염증성 질환, 알러지 질환 또는 암 질환 예방 또는 치료용 조성물 | |
CN109384759B (zh) | 一种药物化合物及其制备与用途 | |
KR20150080249A (ko) | 프로토베르베린 유도체 또는 이의 약학적으로 허용가능한 염을 유효성분으로 함유하는 nfat5의 활성 관련 질환의 예방 또는 치료용 약학적 조성물 | |
US9198922B2 (en) | Therapeutic composition for treating cancers | |
BR112020009596A2 (pt) | combinações de moduladores duplos de irs/stat3 e anticorpos anti pd-1/pd-l1 para tratar câncer | |
CN117460738A (zh) | 冠状病毒感染的预防和治疗 | |
Delpón | Juan Tamargo, Ricardo Caballero, and | |
CN114159427A (zh) | 一种包含安卓幸醇的组合物用于制备抑制肝癌细胞或肝癌干细胞生长的药物的用途 | |
TWI406658B (zh) | 使用異硫氰酸酯類來治療癌症之方法及用途 | |
FR3121038A1 (fr) | Composition pharmaceutique destinée à inhiber l’infectiosité des virus à bicouche lipidique, à traiter les maladies associées et leurs complications. | |
Dąbrowska-Maś et al. | New approaches to the synthesis of diclofenac choline |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20171106 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20181221 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20181221 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20190904 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20190917 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20191211 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20200317 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20200901 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20200930 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6772142 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |