JP2019526531A - ミトコンドリア生物の活性化による血小板産生刺激 - Google Patents
ミトコンドリア生物の活性化による血小板産生刺激 Download PDFInfo
- Publication number
- JP2019526531A JP2019526531A JP2018567647A JP2018567647A JP2019526531A JP 2019526531 A JP2019526531 A JP 2019526531A JP 2018567647 A JP2018567647 A JP 2018567647A JP 2018567647 A JP2018567647 A JP 2018567647A JP 2019526531 A JP2019526531 A JP 2019526531A
- Authority
- JP
- Japan
- Prior art keywords
- lll
- platelet
- mitochondrial
- drug
- cells
- 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.)
- Granted
Links
- 230000004913 activation Effects 0.000 title claims description 5
- 238000004519 manufacturing process Methods 0.000 title abstract description 46
- 230000002438 mitochondrial effect Effects 0.000 title description 38
- 230000000638 stimulation Effects 0.000 title description 6
- 239000003814 drug Substances 0.000 claims abstract description 86
- 229940079593 drug Drugs 0.000 claims abstract description 84
- 230000008437 mitochondrial biogenesis Effects 0.000 claims abstract description 66
- 206010043554 thrombocytopenia Diseases 0.000 claims abstract description 53
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 51
- 238000000034 method Methods 0.000 claims abstract description 34
- 230000004936 stimulating effect Effects 0.000 claims abstract description 15
- 238000000338 in vitro Methods 0.000 claims abstract description 7
- 238000002560 therapeutic procedure Methods 0.000 claims abstract description 7
- 210000003593 megakaryocyte Anatomy 0.000 claims description 163
- 239000012190 activator Substances 0.000 claims description 18
- 229960000516 bezafibrate Drugs 0.000 claims description 18
- IIBYAHWJQTYFKB-UHFFFAOYSA-N bezafibrate Chemical compound C1=CC(OC(C)(C)C(O)=O)=CC=C1CCNC(=O)C1=CC=C(Cl)C=C1 IIBYAHWJQTYFKB-UHFFFAOYSA-N 0.000 claims description 18
- 239000002243 precursor Substances 0.000 claims description 18
- 229940124577 antithrombocytopenic agent Drugs 0.000 claims description 9
- 102000014156 AMP-Activated Protein Kinases Human genes 0.000 claims description 8
- 108010011376 AMP-Activated Protein Kinases Proteins 0.000 claims description 8
- 239000003795 chemical substances by application Substances 0.000 claims description 8
- 239000003937 drug carrier Substances 0.000 claims description 8
- QNVSXXGDAPORNA-UHFFFAOYSA-N Resveratrol Natural products OC1=CC=CC(C=CC=2C=C(O)C(O)=CC=2)=C1 QNVSXXGDAPORNA-UHFFFAOYSA-N 0.000 claims description 7
- LUKBXSAWLPMMSZ-OWOJBTEDSA-N Trans-resveratrol Chemical compound C1=CC(O)=CC=C1\C=C\C1=CC(O)=CC(O)=C1 LUKBXSAWLPMMSZ-OWOJBTEDSA-N 0.000 claims description 7
- 235000021283 resveratrol Nutrition 0.000 claims description 7
- 229940016667 resveratrol Drugs 0.000 claims description 7
- IASPBORHOMBZMY-UHFFFAOYSA-N srt1720 Chemical compound C=1N=C2C=CC=CC2=NC=1C(=O)NC1=CC=CC=C1C(N=C1SC=2)=CN1C=2CN1CCNCC1 IASPBORHOMBZMY-UHFFFAOYSA-N 0.000 claims description 7
- YASAKCUCGLMORW-UHFFFAOYSA-N Rosiglitazone Chemical compound C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O YASAKCUCGLMORW-UHFFFAOYSA-N 0.000 claims description 6
- HYAFETHFCAUJAY-UHFFFAOYSA-N pioglitazone Chemical compound N1=CC(CC)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 HYAFETHFCAUJAY-UHFFFAOYSA-N 0.000 claims description 6
- RTRQQBHATOEIAF-UHFFFAOYSA-N AICA riboside Natural products NC1=C(C(=O)N)N=CN1C1C(O)C(O)C(CO)O1 RTRQQBHATOEIAF-UHFFFAOYSA-N 0.000 claims description 5
- RTRQQBHATOEIAF-UUOKFMHZSA-N acadesine Chemical compound NC1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 RTRQQBHATOEIAF-UUOKFMHZSA-N 0.000 claims description 5
- REFJWTPEDVJJIY-UHFFFAOYSA-N Quercetin Chemical compound C=1C(O)=CC(O)=C(C(C=2O)=O)C=1OC=2C1=CC=C(O)C(O)=C1 REFJWTPEDVJJIY-UHFFFAOYSA-N 0.000 claims description 4
- XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 claims description 4
- 229960003105 metformin Drugs 0.000 claims description 4
- 238000001126 phototherapy Methods 0.000 claims description 4
- 102000004631 Calcineurin Human genes 0.000 claims description 3
- 108010042955 Calcineurin Proteins 0.000 claims description 3
- 102000004646 Calcium-Calmodulin-Dependent Protein Kinase Type 4 Human genes 0.000 claims description 3
- 108010003613 Calcium-Calmodulin-Dependent Protein Kinase Type 4 Proteins 0.000 claims description 3
- 108091027981 Response element Proteins 0.000 claims description 3
- 229960002297 fenofibrate Drugs 0.000 claims description 3
- YMTINGFKWWXKFG-UHFFFAOYSA-N fenofibrate Chemical compound C1=CC(OC(C)(C)C(=O)OC(C)C)=CC=C1C(=O)C1=CC=C(Cl)C=C1 YMTINGFKWWXKFG-UHFFFAOYSA-N 0.000 claims description 3
- 102000002574 p38 Mitogen-Activated Protein Kinases Human genes 0.000 claims description 3
- 108010068338 p38 Mitogen-Activated Protein Kinases Proteins 0.000 claims description 3
- 229960005095 pioglitazone Drugs 0.000 claims description 3
- 229960004586 rosiglitazone Drugs 0.000 claims description 3
- MUFSINOSQBMSLE-JOCHJYFZSA-N srt2183 Chemical compound C1[C@H](O)CCN1CC1=CSC2=NC(C=3C(=CC=CC=3)NC(=O)C=3C=C4C=CC=CC4=CC=3)=CN12 MUFSINOSQBMSLE-JOCHJYFZSA-N 0.000 claims description 3
- ZVOLCUVKHLEPEV-UHFFFAOYSA-N Quercetagetin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=C(O)C(O)=C(O)C=C2O1 ZVOLCUVKHLEPEV-UHFFFAOYSA-N 0.000 claims description 2
- HWTZYBCRDDUBJY-UHFFFAOYSA-N Rhynchosin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=CC(O)=C(O)C=C2O1 HWTZYBCRDDUBJY-UHFFFAOYSA-N 0.000 claims description 2
- MWDZOUNAPSSOEL-UHFFFAOYSA-N kaempferol Natural products OC1=C(C(=O)c2cc(O)cc(O)c2O1)c3ccc(O)cc3 MWDZOUNAPSSOEL-UHFFFAOYSA-N 0.000 claims description 2
- 210000005074 megakaryoblast Anatomy 0.000 claims description 2
- 239000003614 peroxisome proliferator Substances 0.000 claims description 2
- 229960001285 quercetin Drugs 0.000 claims description 2
- 235000005875 quercetin Nutrition 0.000 claims description 2
- SBEWVVLMFLTQFE-UHFFFAOYSA-N srt1460 Chemical compound COC1=C(OC)C(OC)=CC(C(=O)NC=2C(=CC=CC=2)C=2N=C3SC=C(CN4CCNCC4)N3C=2)=C1 SBEWVVLMFLTQFE-UHFFFAOYSA-N 0.000 claims description 2
- 102000000344 Sirtuin 1 Human genes 0.000 claims 1
- 108010041191 Sirtuin 1 Proteins 0.000 claims 1
- 210000004027 cell Anatomy 0.000 description 70
- 241000699670 Mus sp. Species 0.000 description 53
- 210000001185 bone marrow Anatomy 0.000 description 32
- 230000001965 increasing effect Effects 0.000 description 31
- 230000000694 effects Effects 0.000 description 30
- 238000011282 treatment Methods 0.000 description 30
- 201000010099 disease Diseases 0.000 description 24
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 24
- 210000003470 mitochondria Anatomy 0.000 description 22
- 230000002407 ATP formation Effects 0.000 description 20
- 241000699666 Mus <mouse, genus> Species 0.000 description 17
- 230000004069 differentiation Effects 0.000 description 15
- 101001123331 Homo sapiens Peroxisome proliferator-activated receptor gamma coactivator 1-alpha Proteins 0.000 description 14
- 102100028960 Peroxisome proliferator-activated receptor gamma coactivator 1-alpha Human genes 0.000 description 14
- 108010041111 Thrombopoietin Proteins 0.000 description 14
- 230000008436 biogenesis Effects 0.000 description 14
- 208000032843 Hemorrhage Diseases 0.000 description 13
- 102000036693 Thrombopoietin Human genes 0.000 description 13
- 208000034158 bleeding Diseases 0.000 description 13
- 230000000740 bleeding effect Effects 0.000 description 13
- 230000001404 mediated effect Effects 0.000 description 13
- 239000000203 mixture Substances 0.000 description 13
- 210000000130 stem cell Anatomy 0.000 description 13
- 101001078143 Homo sapiens Integrin alpha-IIb Proteins 0.000 description 12
- 102100025306 Integrin alpha-IIb Human genes 0.000 description 12
- 208000020584 Polyploidy Diseases 0.000 description 12
- 210000004369 blood Anatomy 0.000 description 12
- 239000008280 blood Substances 0.000 description 12
- 238000001727 in vivo Methods 0.000 description 12
- 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 description 11
- 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 description 11
- 238000002347 injection Methods 0.000 description 11
- 239000007924 injection Substances 0.000 description 11
- 108090000623 proteins and genes Proteins 0.000 description 11
- 210000000689 upper leg Anatomy 0.000 description 11
- 241000282414 Homo sapiens Species 0.000 description 10
- 230000002829 reductive effect Effects 0.000 description 10
- 208000028622 Immune thrombocytopenia Diseases 0.000 description 9
- 208000031981 Thrombocytopenic Idiopathic Purpura Diseases 0.000 description 9
- 201000003710 autoimmune thrombocytopenic purpura Diseases 0.000 description 9
- 238000000684 flow cytometry Methods 0.000 description 9
- 201000003067 thrombocytopenia due to platelet alloimmunization Diseases 0.000 description 9
- -1 SIRT1 Proteins 0.000 description 8
- 238000002474 experimental method Methods 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 7
- 238000010171 animal model Methods 0.000 description 7
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 7
- 239000000546 pharmaceutical excipient Substances 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- MNULEGDCPYONBU-WMBHJXFZSA-N (1r,4s,5e,5'r,6'r,7e,10s,11r,12s,14r,15s,16s,18r,19s,20r,21e,25s,26r,27s,29s)-4-ethyl-11,12,15,19-tetrahydroxy-6'-[(2s)-2-hydroxypropyl]-5',10,12,14,16,18,20,26,29-nonamethylspiro[24,28-dioxabicyclo[23.3.1]nonacosa-5,7,21-triene-27,2'-oxane]-13,17,23-trio Polymers O([C@@H]1CC[C@@H](/C=C/C=C/C[C@H](C)[C@@H](O)[C@](C)(O)C(=O)[C@H](C)[C@@H](O)[C@H](C)C(=O)[C@H](C)[C@@H](O)[C@H](C)/C=C/C(=O)O[C@H]([C@H]2C)[C@H]1C)CC)[C@]12CC[C@@H](C)[C@@H](C[C@H](C)O)O1 MNULEGDCPYONBU-WMBHJXFZSA-N 0.000 description 6
- 108020004414 DNA Proteins 0.000 description 6
- 108020005196 Mitochondrial DNA Proteins 0.000 description 6
- 208000007536 Thrombosis Diseases 0.000 description 6
- 230000037396 body weight Effects 0.000 description 6
- 210000000988 bone and bone Anatomy 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 6
- 210000000805 cytoplasm Anatomy 0.000 description 6
- 230000001419 dependent effect Effects 0.000 description 6
- 210000003743 erythrocyte Anatomy 0.000 description 6
- 210000004185 liver Anatomy 0.000 description 6
- MNULEGDCPYONBU-UHFFFAOYSA-N oligomycin A Natural products CC1C(C2C)OC(=O)C=CC(C)C(O)C(C)C(=O)C(C)C(O)C(C)C(=O)C(C)(O)C(O)C(C)CC=CC=CC(CC)CCC2OC21CCC(C)C(CC(C)O)O2 MNULEGDCPYONBU-UHFFFAOYSA-N 0.000 description 6
- 206010028980 Neoplasm Diseases 0.000 description 5
- 102000003728 Peroxisome Proliferator-Activated Receptors Human genes 0.000 description 5
- 108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 description 5
- 230000006907 apoptotic process Effects 0.000 description 5
- 201000011510 cancer Diseases 0.000 description 5
- 238000011161 development Methods 0.000 description 5
- 230000018109 developmental process Effects 0.000 description 5
- 239000008187 granular material Substances 0.000 description 5
- 230000008811 mitochondrial respiratory chain Effects 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 230000008929 regeneration Effects 0.000 description 5
- 238000011069 regeneration method Methods 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- MNULEGDCPYONBU-UIXCWHRQSA-N (1R,4E,5'S,6S,6'S,7R,8S,10R,11R,12S,14R,15S,16R,18Z,20Z,22R,25S,27R,28S,29R)-22-ethyl-7,11,14,15-tetrahydroxy-6'-[(2R)-2-hydroxypropyl]-5',6,8,10,12,14,16,28,29-nonamethylspiro[2,26-dioxabicyclo[23.3.1]nonacosa-4,18,20-triene-27,2'-oxane]-3,9,13-trione Polymers CC[C@@H]1CC[C@@H]2O[C@]3(CC[C@H](C)[C@H](C[C@@H](C)O)O3)[C@@H](C)[C@H](OC(=O)\C=C\[C@H](C)[C@@H](O)[C@H](C)C(=O)[C@H](C)[C@@H](O)[C@H](C)C(=O)[C@](C)(O)[C@@H](O)[C@H](C)C\C=C/C=C\1)[C@@H]2C MNULEGDCPYONBU-UIXCWHRQSA-N 0.000 description 4
- MNULEGDCPYONBU-CBLVMMTCSA-N (1R,4Z,5'S,6S,6'S,7R,8S,10R,11R,12S,14R,15S,16R,18Z,20Z,22R,25S,27R,28S,29R)-22-ethyl-7,11,14,15-tetrahydroxy-6'-[(2R)-2-hydroxypropyl]-5',6,8,10,12,14,16,28,29-nonamethylspiro[2,26-dioxabicyclo[23.3.1]nonacosa-4,18,20-triene-27,2'-oxane]-3,9,13-trione Polymers CC[C@@H]1CC[C@@H]2O[C@]3(CC[C@H](C)[C@H](C[C@@H](C)O)O3)[C@@H](C)[C@H](OC(=O)\C=C/[C@H](C)[C@@H](O)[C@H](C)C(=O)[C@H](C)[C@@H](O)[C@H](C)C(=O)[C@](C)(O)[C@@H](O)[C@H](C)C\C=C/C=C\1)[C@@H]2C MNULEGDCPYONBU-CBLVMMTCSA-N 0.000 description 4
- MNULEGDCPYONBU-WABYXMGOSA-N (1S,4E,5'R,6R,6'R,7S,8R,10S,11S,12R,14S,15R,16S,18E,22S,25R,27S,28R,29S)-22-ethyl-7,11,14,15-tetrahydroxy-6'-(2-hydroxypropyl)-5',6,8,10,12,14,16,28,29-nonamethylspiro[2,26-dioxabicyclo[23.3.1]nonacosa-4,18,20-triene-27,2'-oxane]-3,9,13-trione Polymers CC[C@H]1CC[C@H]2O[C@@]3(CC[C@@H](C)[C@@H](CC(C)O)O3)[C@H](C)[C@@H](OC(=O)\C=C\[C@@H](C)[C@H](O)[C@@H](C)C(=O)[C@@H](C)[C@H](O)[C@@H](C)C(=O)[C@@](C)(O)[C@H](O)[C@@H](C)C\C=C\C=C1)[C@H]2C MNULEGDCPYONBU-WABYXMGOSA-N 0.000 description 4
- MNULEGDCPYONBU-QECWTJOCSA-N (1r,4s,5e,5'r,6'r,7e,10s,11r,12s,14r,15s,16s,18r,19s,20r,21e,25s,26r,27s,29s)-4-ethyl-11,12,15,19-tetrahydroxy-6'-(2-hydroxypropyl)-5',10,12,14,16,18,20,26,29-nonamethylspiro[24,28-dioxabicyclo[23.3.1]nonacosa-5,7,21-triene-27,2'-oxane]-13,17,23-trione Polymers O([C@@H]1CC[C@@H](/C=C/C=C/C[C@H](C)[C@@H](O)[C@](C)(O)C(=O)[C@H](C)[C@@H](O)[C@H](C)C(=O)[C@H](C)[C@@H](O)[C@H](C)/C=C/C(=O)O[C@H]([C@H]2C)[C@H]1C)CC)[C@]12CC[C@@H](C)[C@@H](CC(C)O)O1 MNULEGDCPYONBU-QECWTJOCSA-N 0.000 description 4
- MNULEGDCPYONBU-BOXGPLBDSA-N (1r,4s,5e,5'r,6'r,7e,10s,11s,12s,14r,15s,16s,18r,19s,20r,21e,25s,26r,27s,29s)-4-ethyl-11,12,15,19-tetrahydroxy-6'-[(2s)-2-hydroxypropyl]-5',10,12,14,16,18,20,26,29-nonamethylspiro[24,28-dioxabicyclo[23.3.1]nonacosa-5,7,21-triene-27,2'-oxane]-13,17,23-trio Polymers O([C@@H]1CC[C@@H](/C=C/C=C/C[C@H](C)[C@H](O)[C@](C)(O)C(=O)[C@H](C)[C@@H](O)[C@H](C)C(=O)[C@H](C)[C@@H](O)[C@H](C)/C=C/C(=O)O[C@H]([C@H]2C)[C@H]1C)CC)[C@]12CC[C@@H](C)[C@@H](C[C@H](C)O)O1 MNULEGDCPYONBU-BOXGPLBDSA-N 0.000 description 4
- MNULEGDCPYONBU-YOKYSHDFSA-N (5'R,10S,11R,12S,14S,15R,16R,18R,19S,20R,26R,29S)-4-ethyl-11,12,15,19-tetrahydroxy-6'-[(2S)-2-hydroxypropyl]-5',10,12,14,16,18,20,26,29-nonamethylspiro[24,28-dioxabicyclo[23.3.1]nonacosa-5,7,21-triene-27,2'-oxane]-13,17,23-trione Polymers C([C@H](C)[C@@H](O)[C@](C)(O)C(=O)[C@@H](C)[C@H](O)[C@@H](C)C(=O)[C@H](C)[C@@H](O)[C@H](C)C=CC(=O)OC([C@H]1C)[C@H]2C)C=CC=CC(CC)CCC2OC21CC[C@@H](C)C(C[C@H](C)O)O2 MNULEGDCPYONBU-YOKYSHDFSA-N 0.000 description 4
- MNULEGDCPYONBU-VVXVDZGXSA-N (5e,5'r,7e,10s,11r,12s,14s,15r,16r,18r,19s,20r,21e,26r,29s)-4-ethyl-11,12,15,19-tetrahydroxy-6'-[(2s)-2-hydroxypropyl]-5',10,12,14,16,18,20,26,29-nonamethylspiro[24,28-dioxabicyclo[23.3.1]nonacosa-5,7,21-triene-27,2'-oxane]-13,17,23-trione Polymers C([C@H](C)[C@@H](O)[C@](C)(O)C(=O)[C@@H](C)[C@H](O)[C@@H](C)C(=O)[C@H](C)[C@@H](O)[C@H](C)/C=C/C(=O)OC([C@H]1C)[C@H]2C)\C=C\C=C\C(CC)CCC2OC21CC[C@@H](C)C(C[C@H](C)O)O2 MNULEGDCPYONBU-VVXVDZGXSA-N 0.000 description 4
- VDABVNMGKGUPEY-UHFFFAOYSA-N 6-carboxyfluorescein succinimidyl ester Chemical compound C=1C(O)=CC=C2C=1OC1=CC(O)=CC=C1C2(C1=C2)OC(=O)C1=CC=C2C(=O)ON1C(=O)CCC1=O VDABVNMGKGUPEY-UHFFFAOYSA-N 0.000 description 4
- MNULEGDCPYONBU-MQLHLVDXSA-N CC[C@@H]1CC[C@@H]2O[C@]3(CC[C@H](C)[C@H](C[C@@H](C)O)O3)[C@@H](C)[C@H](OC(=O)\C=C\[C@H](C)[C@@H](O)[C@H](C)C(=O)[C@H](C)[C@@H](O)[C@H](C)C(=O)[C@](C)(O)[C@@H](O)[C@H](C)C\C=C\C=C\1)C2C Polymers CC[C@@H]1CC[C@@H]2O[C@]3(CC[C@H](C)[C@H](C[C@@H](C)O)O3)[C@@H](C)[C@H](OC(=O)\C=C\[C@H](C)[C@@H](O)[C@H](C)C(=O)[C@H](C)[C@@H](O)[C@H](C)C(=O)[C@](C)(O)[C@@H](O)[C@H](C)C\C=C\C=C\1)C2C MNULEGDCPYONBU-MQLHLVDXSA-N 0.000 description 4
- RZZPDXZPRHQOCG-OJAKKHQRSA-O CDP-choline(1+) Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OCC[N+](C)(C)C)O[C@H]1N1C(=O)N=C(N)C=C1 RZZPDXZPRHQOCG-OJAKKHQRSA-O 0.000 description 4
- 102100031702 Endoplasmic reticulum membrane sensor NFE2L1 Human genes 0.000 description 4
- 101001046529 Homo sapiens Mevalonate kinase Proteins 0.000 description 4
- 101000990990 Homo sapiens Midkine Proteins 0.000 description 4
- 101001046530 Mus musculus Mevalonate kinase Proteins 0.000 description 4
- 101000990991 Mus musculus Midkine Proteins 0.000 description 4
- 108010071380 NF-E2-Related Factor 1 Proteins 0.000 description 4
- 108091093105 Nuclear DNA Proteins 0.000 description 4
- 108010016592 Nuclear Respiratory Factor 1 Proteins 0.000 description 4
- 101150080431 Tfam gene Proteins 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 238000003491 array Methods 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 230000017531 blood circulation Effects 0.000 description 4
- 210000003855 cell nucleus Anatomy 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- 238000002512 chemotherapy Methods 0.000 description 4
- 230000001976 improved effect Effects 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 230000035800 maturation Effects 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- 210000001700 mitochondrial membrane Anatomy 0.000 description 4
- 230000035772 mutation Effects 0.000 description 4
- MNULEGDCPYONBU-AWJDAWNUSA-N oligomycin A Polymers O([C@H]1CC[C@H](/C=C/C=C/C[C@@H](C)[C@H](O)[C@@](C)(O)C(=O)[C@@H](C)[C@H](O)[C@@H](C)C(=O)[C@@H](C)[C@H](O)[C@@H](C)/C=C/C(=O)O[C@@H]([C@@H]2C)[C@@H]1C)CC)[C@@]12CC[C@H](C)[C@H](C[C@@H](C)O)O1 MNULEGDCPYONBU-AWJDAWNUSA-N 0.000 description 4
- 229910052760 oxygen Inorganic materials 0.000 description 4
- 239000001301 oxygen Substances 0.000 description 4
- 230000002265 prevention Effects 0.000 description 4
- 102000005962 receptors Human genes 0.000 description 4
- 108020003175 receptors Proteins 0.000 description 4
- 238000011084 recovery Methods 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- 238000010186 staining Methods 0.000 description 4
- 230000035882 stress Effects 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- PRDFBSVERLRRMY-UHFFFAOYSA-N 2'-(4-ethoxyphenyl)-5-(4-methylpiperazin-1-yl)-2,5'-bibenzimidazole Chemical compound C1=CC(OCC)=CC=C1C1=NC2=CC=C(C=3NC4=CC(=CC=C4N=3)N3CCN(C)CC3)C=C2N1 PRDFBSVERLRRMY-UHFFFAOYSA-N 0.000 description 3
- 102100030497 Cytochrome c Human genes 0.000 description 3
- 108010075031 Cytochromes c Proteins 0.000 description 3
- 101150006098 Dnm1l gene Proteins 0.000 description 3
- 101150075109 FIS1 gene Proteins 0.000 description 3
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 3
- 101000799461 Homo sapiens Thrombopoietin Proteins 0.000 description 3
- 101150103710 MFF gene Proteins 0.000 description 3
- 238000003917 TEM image Methods 0.000 description 3
- 239000000556 agonist Substances 0.000 description 3
- 239000003963 antioxidant agent Substances 0.000 description 3
- 235000006708 antioxidants Nutrition 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical class [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
- 230000009286 beneficial effect Effects 0.000 description 3
- 210000003995 blood forming stem cell Anatomy 0.000 description 3
- 230000010261 cell growth Effects 0.000 description 3
- 230000001186 cumulative effect Effects 0.000 description 3
- 230000001086 cytosolic effect Effects 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 229960002949 fluorouracil Drugs 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 210000000265 leukocyte Anatomy 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 210000004698 lymphocyte Anatomy 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 230000004898 mitochondrial function Effects 0.000 description 3
- 238000010606 normalization Methods 0.000 description 3
- 210000004940 nucleus Anatomy 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 235000019198 oils Nutrition 0.000 description 3
- 239000008194 pharmaceutical composition Substances 0.000 description 3
- 229920005862 polyol Polymers 0.000 description 3
- 150000003077 polyols Chemical class 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- 239000003642 reactive oxygen metabolite Substances 0.000 description 3
- 238000007634 remodeling Methods 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 235000015112 vegetable and seed oil Nutrition 0.000 description 3
- 239000008158 vegetable oil Substances 0.000 description 3
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
- 108090000397 Caspase 3 Proteins 0.000 description 2
- 102100029855 Caspase-3 Human genes 0.000 description 2
- 102000000634 Cytochrome c oxidase subunit IV Human genes 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 101000694103 Homo sapiens Thyroid peroxidase Proteins 0.000 description 2
- JUUBCHWRXWPFFH-UHFFFAOYSA-N Hydroxytyrosol Chemical compound OCCC1=CC=C(O)C(O)=C1 JUUBCHWRXWPFFH-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 102000029749 Microtubule Human genes 0.000 description 2
- 108091022875 Microtubule Proteins 0.000 description 2
- 201000003793 Myelodysplastic syndrome Diseases 0.000 description 2
- 102100030710 NAD-dependent protein deacetylase sirtuin-3, mitochondrial Human genes 0.000 description 2
- 102100036201 Oxygen-dependent coproporphyrinogen-III oxidase, mitochondrial Human genes 0.000 description 2
- 108010015181 PPAR delta Proteins 0.000 description 2
- 238000011529 RT qPCR Methods 0.000 description 2
- 108091005770 SIRT3 Proteins 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 238000000692 Student's t-test Methods 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000002776 aggregation Effects 0.000 description 2
- 238000004220 aggregation Methods 0.000 description 2
- 230000003078 antioxidant effect Effects 0.000 description 2
- 230000005540 biological transmission Effects 0.000 description 2
- 238000004820 blood count Methods 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 229910002091 carbon monoxide Inorganic materials 0.000 description 2
- 230000024245 cell differentiation Effects 0.000 description 2
- 230000003833 cell viability Effects 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 230000003081 coactivator Effects 0.000 description 2
- 230000015271 coagulation Effects 0.000 description 2
- 238000005345 coagulation Methods 0.000 description 2
- 230000001447 compensatory effect Effects 0.000 description 2
- 230000002596 correlated effect Effects 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 239000003599 detergent Substances 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 210000001840 diploid cell Anatomy 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 239000003925 fat Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 210000003714 granulocyte Anatomy 0.000 description 2
- 102000053521 human MDK Human genes 0.000 description 2
- 102000053400 human TPO Human genes 0.000 description 2
- 210000005260 human cell Anatomy 0.000 description 2
- 125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 0.000 description 2
- 230000001771 impaired effect Effects 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 208000032839 leukemia Diseases 0.000 description 2
- 238000009196 low level laser therapy Methods 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 210000004688 microtubule Anatomy 0.000 description 2
- 230000003278 mimic effect Effects 0.000 description 2
- 230000004065 mitochondrial dysfunction Effects 0.000 description 2
- 210000001616 monocyte Anatomy 0.000 description 2
- 238000010172 mouse model Methods 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- 229940105132 myristate Drugs 0.000 description 2
- 238000001543 one-way ANOVA Methods 0.000 description 2
- 230000036542 oxidative stress Effects 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 230000004962 physiological condition Effects 0.000 description 2
- 238000001959 radiotherapy Methods 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 230000002195 synergetic effect Effects 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 230000003582 thrombocytopenic effect Effects 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- 238000002834 transmittance Methods 0.000 description 2
- QGVLYPPODPLXMB-UBTYZVCOSA-N (1aR,1bS,4aR,7aS,7bS,8R,9R,9aS)-4a,7b,9,9a-tetrahydroxy-3-(hydroxymethyl)-1,1,6,8-tetramethyl-1,1a,1b,4,4a,7a,7b,8,9,9a-decahydro-5H-cyclopropa[3,4]benzo[1,2-e]azulen-5-one Chemical compound C1=C(CO)C[C@]2(O)C(=O)C(C)=C[C@H]2[C@@]2(O)[C@H](C)[C@@H](O)[C@@]3(O)C(C)(C)[C@H]3[C@@H]21 QGVLYPPODPLXMB-UBTYZVCOSA-N 0.000 description 1
- OIIMUKXVVLRCAF-UHFFFAOYSA-N 10-(4,5-dimethoxy-2-methyl-3,6-dioxocyclohexa-1,4-dien-1-yl)decyl-triphenylphosphanium Chemical compound O=C1C(OC)=C(OC)C(=O)C(CCCCCCCCCC[P+](C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1C OIIMUKXVVLRCAF-UHFFFAOYSA-N 0.000 description 1
- CVOFKRWYWCSDMA-UHFFFAOYSA-N 2-chloro-n-(2,6-diethylphenyl)-n-(methoxymethyl)acetamide;2,6-dinitro-n,n-dipropyl-4-(trifluoromethyl)aniline Chemical compound CCC1=CC=CC(CC)=C1N(COC)C(=O)CCl.CCCN(CCC)C1=C([N+]([O-])=O)C=C(C(F)(F)F)C=C1[N+]([O-])=O CVOFKRWYWCSDMA-UHFFFAOYSA-N 0.000 description 1
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
- 208000000412 Avitaminosis Diseases 0.000 description 1
- 102000015081 Blood Coagulation Factors Human genes 0.000 description 1
- 108010039209 Blood Coagulation Factors Proteins 0.000 description 1
- 206010065553 Bone marrow failure Diseases 0.000 description 1
- LQZZLIBTPMGYFK-UHFFFAOYSA-N C1=C(C)C(C)=CC=C1N(N=C1C2CC2)C(=O)C1=NNC1=CC=CC(C=2C=C(C=CC=2)C(O)=O)=C1O Chemical compound C1=C(C)C(C)=CC=C1N(N=C1C2CC2)C(=O)C1=NNC1=CC=CC(C=2C=C(C=CC=2)C(O)=O)=C1O LQZZLIBTPMGYFK-UHFFFAOYSA-N 0.000 description 1
- AJSCIDJNLYWXMX-UHFFFAOYSA-N CC1=NN(C=2C=C(F)C(C)=CC=2)C(=O)C1=NNC(C=1O)=CC=CC=1C1=CC=CC(C(O)=O)=C1 Chemical compound CC1=NN(C=2C=C(F)C(C)=CC=2)C(=O)C1=NNC(C=1O)=CC=CC=1C1=CC=CC(C(O)=O)=C1 AJSCIDJNLYWXMX-UHFFFAOYSA-N 0.000 description 1
- NRLTXNINZMOOKV-UHFFFAOYSA-N CC1=NN(C=2C=CC(=CC=2)C(F)(F)F)C(=O)C1=NNC(C=1O)=CC=CC=1C1=CC=CC(C(O)=O)=C1 Chemical compound CC1=NN(C=2C=CC(=CC=2)C(F)(F)F)C(=O)C1=NNC(C=1O)=CC=CC=1C1=CC=CC(C(O)=O)=C1 NRLTXNINZMOOKV-UHFFFAOYSA-N 0.000 description 1
- ZQUGEPIZIXOPNC-UHFFFAOYSA-N CCC1=NN(C=2C=C(C)C(C)=CC=2)C(=O)C1=NNC(C=1O)=CC=CC=1C(C=1)=CC=CC=1C1=NN=NN1 Chemical group CCC1=NN(C=2C=C(C)C(C)=CC=2)C(=O)C1=NNC(C=1O)=CC=CC=1C(C=1)=CC=CC=1C1=NN=NN1 ZQUGEPIZIXOPNC-UHFFFAOYSA-N 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 1
- 102000047934 Caspase-3/7 Human genes 0.000 description 1
- 108700037887 Caspase-3/7 Proteins 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 206010053567 Coagulopathies Diseases 0.000 description 1
- 208000034656 Contusions Diseases 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 108050008072 Cytochrome c oxidase subunit IV Proteins 0.000 description 1
- 108090000365 Cytochrome-c oxidases Proteins 0.000 description 1
- 108010037414 Cytoskeletal Proteins Proteins 0.000 description 1
- 102000010831 Cytoskeletal Proteins Human genes 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 230000004543 DNA replication Effects 0.000 description 1
- 206010013801 Duchenne Muscular Dystrophy Diseases 0.000 description 1
- 108700021058 Dynamin Proteins 0.000 description 1
- 241000792859 Enema Species 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 238000002738 Giemsa staining Methods 0.000 description 1
- 206010018276 Gingival bleeding Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 206010019663 Hepatic failure Diseases 0.000 description 1
- 101100220044 Homo sapiens CD34 gene Proteins 0.000 description 1
- 101001010568 Homo sapiens Interleukin-11 Proteins 0.000 description 1
- 101000588302 Homo sapiens Nuclear factor erythroid 2-related factor 2 Proteins 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 206010021135 Hypovitaminosis Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 102000003812 Interleukin-15 Human genes 0.000 description 1
- 108090000172 Interleukin-15 Proteins 0.000 description 1
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 1
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
- 208000016604 Lyme disease Diseases 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 208000001145 Metabolic Syndrome Diseases 0.000 description 1
- 102100023845 Mitochondrial fission 1 protein Human genes 0.000 description 1
- 101710081788 Mitochondrial fission 1 protein Proteins 0.000 description 1
- 102100025782 Mitochondrial fission factor Human genes 0.000 description 1
- 101710148184 Mitochondrial fission factor Proteins 0.000 description 1
- 102000007474 Multiprotein Complexes Human genes 0.000 description 1
- 108010085220 Multiprotein Complexes Proteins 0.000 description 1
- 101710112216 NAD-dependent histone deacetylase SIR2 Proteins 0.000 description 1
- 108010078702 Nuclear Respiratory Factors Proteins 0.000 description 1
- 102000014967 Nuclear Respiratory Factors Human genes 0.000 description 1
- 102100031701 Nuclear factor erythroid 2-related factor 2 Human genes 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 101710195703 Oxygen-dependent coproporphyrinogen-III oxidase Proteins 0.000 description 1
- 101710200437 Oxygen-dependent coproporphyrinogen-III oxidase, mitochondrial Proteins 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 102000003921 Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha Human genes 0.000 description 1
- 108090000310 Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha Proteins 0.000 description 1
- 241000009328 Perro Species 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 206010037549 Purpura Diseases 0.000 description 1
- 241001672981 Purpura Species 0.000 description 1
- 208000006311 Pyoderma Diseases 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 108700005075 Regulator Genes Proteins 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 102000012152 Securin Human genes 0.000 description 1
- 108010061477 Securin Proteins 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- 108010041218 Sirtuin 3 Proteins 0.000 description 1
- 102000000478 Sirtuin 3 Human genes 0.000 description 1
- 208000004078 Snake Bites Diseases 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
- JLRGJRBPOGGCBT-UHFFFAOYSA-N Tolbutamide Chemical compound CCCCNC(=O)NS(=O)(=O)C1=CC=C(C)C=C1 JLRGJRBPOGGCBT-UHFFFAOYSA-N 0.000 description 1
- 208000030886 Traumatic Brain injury Diseases 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 244000068697 Vitis rotundifolia Species 0.000 description 1
- 235000006359 Vitis rotundifolia var rotundifolia Nutrition 0.000 description 1
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 description 1
- 238000002679 ablation Methods 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 201000004208 acquired thrombocytopenia Diseases 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000000048 adrenergic agonist Substances 0.000 description 1
- 229940126157 adrenergic receptor agonist Drugs 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 229930013930 alkaloid Natural products 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 238000002266 amputation Methods 0.000 description 1
- 230000036592 analgesia Effects 0.000 description 1
- 230000006909 anti-apoptosis Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000000702 anti-platelet effect Effects 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 125000006615 aromatic heterocyclic group Chemical group 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- 230000003416 augmentation Effects 0.000 description 1
- 102000016966 beta-2 Adrenergic Receptors Human genes 0.000 description 1
- 108010014499 beta-2 Adrenergic Receptors Proteins 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
- 230000000975 bioactive effect Effects 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 239000003114 blood coagulation factor Substances 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 210000002449 bone cell Anatomy 0.000 description 1
- 210000002798 bone marrow cell Anatomy 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 229940044683 chemotherapy drug Drugs 0.000 description 1
- 230000004087 circulation Effects 0.000 description 1
- 230000035602 clotting Effects 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 238000004624 confocal microscopy Methods 0.000 description 1
- 230000010485 coping Effects 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 238000010219 correlation analysis Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- VFLDPWHFBUODDF-FCXRPNKRSA-N curcumin Chemical class C1=C(O)C(OC)=CC(\C=C\C(=O)CC(=O)\C=C\C=2C=C(OC)C(O)=CC=2)=C1 VFLDPWHFBUODDF-FCXRPNKRSA-N 0.000 description 1
- 230000021953 cytokinesis Effects 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- NIJJYAXOARWZEE-UHFFFAOYSA-N di-n-propyl-acetic acid Natural products CCCC(C(O)=O)CCC NIJJYAXOARWZEE-UHFFFAOYSA-N 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 230000008482 dysregulation Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000034311 endomitotic cell cycle Effects 0.000 description 1
- 239000007920 enema Substances 0.000 description 1
- 229940079360 enema for constipation Drugs 0.000 description 1
- 208000001780 epistaxis Diseases 0.000 description 1
- 230000031857 establishment of mitochondrion localization Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 108020004067 estrogen-related receptors Proteins 0.000 description 1
- 238000011124 ex vivo culture Methods 0.000 description 1
- 210000003414 extremity Anatomy 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 230000004992 fission Effects 0.000 description 1
- 229930003935 flavonoid Natural products 0.000 description 1
- 235000017173 flavonoids Nutrition 0.000 description 1
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 208000011759 gum bleeding Diseases 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 102000049885 human IL11 Human genes 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- ZFAVADMJZHASIM-UHFFFAOYSA-N hydroxymethyl butanoate Chemical compound CCCC(=O)OCO ZFAVADMJZHASIM-UHFFFAOYSA-N 0.000 description 1
- 229940095066 hydroxytyrosol Drugs 0.000 description 1
- 235000003248 hydroxytyrosol Nutrition 0.000 description 1
- 208000026278 immune system disease Diseases 0.000 description 1
- 238000003318 immunodepletion Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 208000012461 inherited thrombocytopenia Diseases 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 229960002725 isoflurane Drugs 0.000 description 1
- 238000002647 laser therapy Methods 0.000 description 1
- 238000013532 laser treatment Methods 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 208000007903 liver failure Diseases 0.000 description 1
- 231100000835 liver failure Toxicity 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 206010025135 lupus erythematosus Diseases 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 230000006705 mitochondrial oxidative phosphorylation Effects 0.000 description 1
- 230000006540 mitochondrial respiration Effects 0.000 description 1
- 108010045576 mitochondrial transcription factor A Proteins 0.000 description 1
- 230000030544 mitochondrion distribution Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 210000005088 multinucleated cell Anatomy 0.000 description 1
- 210000000663 muscle cell Anatomy 0.000 description 1
- 208000011309 nasal bleeding Diseases 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical class CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- 239000012053 oil suspension Substances 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 238000003305 oral gavage Methods 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000010627 oxidative phosphorylation Effects 0.000 description 1
- 230000036407 pain Effects 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 210000004197 pelvis Anatomy 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 210000002824 peroxisome Anatomy 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- QGVLYPPODPLXMB-QXYKVGAMSA-N phorbol Natural products C[C@@H]1[C@@H](O)[C@]2(O)[C@H]([C@H]3C=C(CO)C[C@@]4(O)[C@H](C=C(C)C4=O)[C@@]13O)C2(C)C QGVLYPPODPLXMB-QXYKVGAMSA-N 0.000 description 1
- XLCISDOVNFLSGO-VONOSFMSSA-N phorbol-12-myristate Chemical compound C([C@]1(O)C(=O)C(C)=C[C@H]1[C@@]1(O)[C@H](C)[C@H]2OC(=O)CCCCCCCCCCCCC)C(CO)=C[C@H]1[C@H]1[C@]2(O)C1(C)C XLCISDOVNFLSGO-VONOSFMSSA-N 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 210000001850 polyploid cell Anatomy 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 230000009862 primary prevention Effects 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 230000004224 protection Effects 0.000 description 1
- 238000001243 protein synthesis Methods 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 238000003762 quantitative reverse transcription PCR Methods 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 238000003753 real-time PCR Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000000611 regression analysis Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 230000004202 respiratory function Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 229910052702 rhenium Inorganic materials 0.000 description 1
- WUAPFZMCVAUBPE-UHFFFAOYSA-N rhenium atom Chemical compound [Re] WUAPFZMCVAUBPE-UHFFFAOYSA-N 0.000 description 1
- 108010017584 romiplostim Proteins 0.000 description 1
- JWHOQZUREKYPBY-UHFFFAOYSA-N rubonic acid Natural products CC1(C)CCC2(CCC3(C)C(=CCC4C5(C)CCC(=O)C(C)(C)C5CC(=O)C34C)C2C1)C(=O)O JWHOQZUREKYPBY-UHFFFAOYSA-N 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 230000009863 secondary prevention Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 201000003624 spinocerebellar ataxia type 1 Diseases 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 238000006467 substitution reaction Methods 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
- 239000000375 suspending agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- TUNFSRHWOTWDNC-UHFFFAOYSA-N tetradecanoic acid Chemical compound CCCCCCCCCCCCCC(O)=O TUNFSRHWOTWDNC-UHFFFAOYSA-N 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 210000002303 tibia Anatomy 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000011820 transgenic animal model Methods 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- 238000004627 transmission electron microscopy Methods 0.000 description 1
- 230000009529 traumatic brain injury Effects 0.000 description 1
- 238000011277 treatment modality Methods 0.000 description 1
- 230000004102 tricarboxylic acid cycle Effects 0.000 description 1
- 210000005239 tubule Anatomy 0.000 description 1
- MSRILKIQRXUYCT-UHFFFAOYSA-M valproate semisodium Chemical compound [Na+].CCCC(C(O)=O)CCC.CCCC(C([O-])=O)CCC MSRILKIQRXUYCT-UHFFFAOYSA-M 0.000 description 1
- 229960000604 valproic acid Drugs 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 208000030401 vitamin deficiency disease Diseases 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
Images
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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/7056—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing five-membered rings with nitrogen as a ring hetero atom
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
-
- 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
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
- A61K31/05—Phenols
-
- 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
- A61K31/13—Amines
- A61K31/155—Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
-
- 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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/216—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
- A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4188—1,3-Diazoles condensed with other heterocyclic ring systems, e.g. biotin, sorbinil
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/429—Thiazoles condensed with heterocyclic ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/498—Pyrazines or piperazines ortho- and peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N5/00—Radiation therapy
- A61N5/06—Radiation therapy using light
- A61N5/0613—Apparatus adapted for a specific treatment
- A61N5/062—Photodynamic therapy, i.e. excitation of an agent
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Molecular Biology (AREA)
- Emergency Medicine (AREA)
- Biomedical Technology (AREA)
- Biophysics (AREA)
- Radiology & Medical Imaging (AREA)
- Pathology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines Containing Plant Substances (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Hydrogenated Pyridines (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Medicinal Preparation (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Saccharide Compounds (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Pyrane Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Steroid Compounds (AREA)
Abstract
Description
本願は2016年6月27日に出願された米国仮特許出願第62/355,027号の権利を主張し、その全ての内容は引用により本明細書に組み込まれる。
血小板生物発生を刺激する
ミトコンドリア生物発生の刺激薬物
抗血小板減少症薬との組み合わせ
薬学的に許容される担体
低レベル光療法
血小板形成を刺激する方法
実施例
実施例1:血小板減少症に用いられる非侵襲的な低レベルレーザー療法
結果
討論
材料及び方法
実施例2:血小板再生のためのミトコンドリア生物発生を促進する薬物
Claims (11)
- ミトコンドリア生物発生を刺激する有効量の薬物を被験者へ投与することにより、前記被験者の体内に血小板の形成を刺激する方法。
- 前記薬物は、p38マイトジェン活性化タンパク質キナーゼ活性化剤、カルモジュリン依存性タンパク質キナーゼIV活性化剤、AMP活性化キナーゼ活性化剤、カルシニューリンA活性化剤、ペルオキシソーム増殖剤応答エレメント活性化剤及びSIRT1活性化剤からなる群より選択される請求項1に記載の方法。
- ミトコンドリア生物発生を刺激する前記薬物は、ベザフィブラート、ロシグリタゾン、ピオグリタゾン、フェノフィブラート、AICAR、メトホルミン、レスベラトロール、SRT1720、SRT2183、SRT1460及びケルセチン、ならびにそれらの誘導体からなる群より選択される請求項1に記載の方法。
- 前記被験者は、血小板減少症を抱えると診断されている請求項1に記載の方法。
- 抗血小板減少症薬を前記被験者へ投与することをさらに含む請求項4に記載の方法。
- 低レベル光(LLL)療法で前記被験者を治療することをさらに含む請求項1に記載の方法。
- 前記薬物は、薬学的に許容される担体とともに投与される請求項1に記載の方法。
- 血小板の形成を刺激する方法であって、
血小板前駆体をミトコンドリア生物発生を刺激する薬物と接触させることを含む方法。 - 前記血小板前駆体は、巨核球又は巨核芽球である請求項8に記載の方法。
- 前記血小板前駆体も低レベル光治療に露出される請求項8に記載の方法。
- 前記血小板前駆体は、インビトロ又はエクスビボである請求項8に記載の方法。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201662355027P | 2016-06-27 | 2016-06-27 | |
PCT/US2017/039389 WO2018005417A1 (en) | 2016-06-27 | 2017-06-27 | Stimulating platelet generation by activating mitochondrial biogenesis |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2019526531A true JP2019526531A (ja) | 2019-09-19 |
JP7104636B2 JP7104636B2 (ja) | 2022-07-21 |
Family
ID=59298542
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2018567647A Active JP7104636B2 (ja) | 2016-06-27 | 2017-06-27 | ミトコンドリア生物の活性化による血小板産生刺激 |
Country Status (8)
Country | Link |
---|---|
US (1) | US10918655B2 (ja) |
EP (1) | EP3474834A1 (ja) |
JP (1) | JP7104636B2 (ja) |
CN (1) | CN110087643B (ja) |
AU (1) | AU2017289071B2 (ja) |
CA (1) | CA3029450C (ja) |
IL (1) | IL263938B2 (ja) |
WO (1) | WO2018005417A1 (ja) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2020092877A1 (en) * | 2018-11-02 | 2020-05-07 | The Children's Hospital Of Philadelphia | Modulation of mitochondrial biogenesis by increase in iron sulfur cluster activity |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2012157586A1 (ja) * | 2011-05-13 | 2012-11-22 | 国立大学法人東京大学 | 多核化巨核球細胞、及び血小板の製造方法 |
WO2016048942A1 (en) * | 2014-09-24 | 2016-03-31 | The General Hospital Corporation Dba Massachusetts General Hospital | Systems and methods for enhancing platelet biogenesis and extending platelet lifespan, in circulation and storage |
Family Cites Families (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CY2010012I2 (el) | 2000-05-25 | 2020-05-29 | Novartis Ag | Μιμητικα θρομβοποιητινης |
US6909030B2 (en) | 2001-10-15 | 2005-06-21 | Cedars-Sinai Medical Center | PTTG knockout rodent as a model to study mechanisms for various physiological phenomena, including diabetes |
US9132162B2 (en) | 2008-07-31 | 2015-09-15 | Shaklee Corporation | Muscadine compositions with anti-oxidant activity |
ES2592210T3 (es) | 2009-04-17 | 2016-11-28 | Dsm Ip Assets B.V. | Combinaciones de hidroxitirosol para mejorar la función mitocondrial y producción de energía |
US9187448B2 (en) | 2011-08-05 | 2015-11-17 | Cardero Therapeutics, Inc. | Flavonoid compounds |
US20140024677A1 (en) | 2012-04-09 | 2014-01-23 | Musc Foundation For Research Development | Methods for inducing mitochondrial biogenesis |
WO2015003254A1 (en) | 2013-07-11 | 2015-01-15 | Exerkine Corporation | Therapeutic method of inducing mitochondrial biogenesis |
CA2918111A1 (en) | 2013-07-14 | 2015-01-22 | Asiros A/S | Novel bioactive alkaloids and alkaloid fractions derivable from ribes species |
EP2868348A1 (en) | 2013-11-04 | 2015-05-06 | Universität Zürich | CO-releasing compounds & formulations thereof useful for inducing mitochondrial biogenesis and tissue repair |
EP3131636A4 (en) | 2014-04-18 | 2018-01-10 | OmniActive Health Technologies Limited | Curcumin compositions and uses thereof |
US20170246470A1 (en) * | 2014-09-24 | 2017-08-31 | The General Hospital Corporation Dba Massachusetts General Hospital | Systems and methods for enhancing platelet biogenesis and extending platelet lifespan with low level light |
CN107847759A (zh) | 2015-06-01 | 2018-03-27 | 代谢科技有限公司 | 用于减少脂肪量的β‑羟基‑β‑甲基丁酸(HMB)的组合物和使用方法 |
-
2017
- 2017-06-27 CN CN201780051087.7A patent/CN110087643B/zh active Active
- 2017-06-27 JP JP2018567647A patent/JP7104636B2/ja active Active
- 2017-06-27 AU AU2017289071A patent/AU2017289071B2/en active Active
- 2017-06-27 EP EP17737430.3A patent/EP3474834A1/en active Pending
- 2017-06-27 US US16/312,709 patent/US10918655B2/en active Active
- 2017-06-27 CA CA3029450A patent/CA3029450C/en active Active
- 2017-06-27 WO PCT/US2017/039389 patent/WO2018005417A1/en unknown
-
2018
- 2018-12-24 IL IL263938A patent/IL263938B2/en unknown
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2012157586A1 (ja) * | 2011-05-13 | 2012-11-22 | 国立大学法人東京大学 | 多核化巨核球細胞、及び血小板の製造方法 |
WO2016048942A1 (en) * | 2014-09-24 | 2016-03-31 | The General Hospital Corporation Dba Massachusetts General Hospital | Systems and methods for enhancing platelet biogenesis and extending platelet lifespan, in circulation and storage |
Non-Patent Citations (5)
Title |
---|
BALON R: "THE EFFECT OF LITHIUM ON PLATELET COUNT", ACTA PSYCHIATR SCAND, vol. 74, JPN5019005812, 1986, pages 474 - 478, XP055400569, ISSN: 0004611336 * |
CHEKALINA SI: "EFFECT OF BERBERINE BISULFATE ON PLATELET HEMOSTASIS IN THROMBOCYTOPENIA PATIENTS", GEMATOL TRANSFUZIOL, vol. VOL:39, NR:5, JPN5019005811, 1994, pages 33 - 35, ISSN: 0004611335 * |
DIABETES (2006 AUG) 55 P.2256-2264, JPN6021021324, ISSN: 0004611337 * |
HALEY RAMSEY: "MITOQUINONE RESTORES PLATELET PRODUCTION IN IRRADIATION-INDUCED THROMBOCYTOPENIA", PLATELETS, vol. VOL:26, NR:5, JPN5019005813, 15 July 2014 (2014-07-15), pages 1 - 16, ISSN: 0004717978 * |
RAM BABU UNDI: "LICL REGULATES MITOCHONDRIAL BIOGENESIS DURING MEGAKARYOCYTE DEVELOPMENT", JOURNAL OF TRACE ELEMENTS IN MEDICINE AND BIOLOGY, vol. 39, JPN5019005814, 2017, US, pages 193 - 201, XP055400557, ISSN: 0004611338, DOI: 10.1016/j.jtemb.2016.10.003 * |
Also Published As
Publication number | Publication date |
---|---|
CN110087643B (zh) | 2022-11-22 |
JP7104636B2 (ja) | 2022-07-21 |
CA3029450C (en) | 2021-07-13 |
EP3474834A1 (en) | 2019-05-01 |
AU2017289071A1 (en) | 2019-01-31 |
US10918655B2 (en) | 2021-02-16 |
AU2017289071B2 (en) | 2019-11-21 |
IL263938B2 (en) | 2023-06-01 |
WO2018005417A1 (en) | 2018-01-04 |
CA3029450A1 (en) | 2018-01-04 |
US20200030353A1 (en) | 2020-01-30 |
IL263938A (en) | 2019-01-31 |
CN110087643A (zh) | 2019-08-02 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Stetler et al. | Preconditioning provides neuroprotection in models of CNS disease: paradigms and clinical significance | |
Streijger et al. | Ketogenic diet improves forelimb motor function after spinal cord injury in rodents | |
Ježek et al. | Distinctions and similarities of cell bioenergetics and the role of mitochondria in hypoxia, cancer, and embryonic development | |
Li et al. | Mn (III) meso-tetrakis-(N-ethylpyridinium-2-yl) porphyrin mitigates total body irradiation-induced long-term bone marrow suppression | |
KR20040032115A (ko) | 조직 및 장기 이식 결과의 개선 및 아폽토시스의 억제에사용되는 일산화탄소 | |
El-Hanoun et al. | Effect of bee venom on reproductive performance and immune response of male rabbits | |
Della-Morte et al. | Post-ischemic activation of protein kinase C epsilon protects the hippocampus from cerebral ischemic injury via alterations in cerebral blood flow | |
JP2019505559A (ja) | 肝臓の再生を向上させるための方法 | |
Blanco et al. | Ischemic preconditioning: a novel target for neuroprotective therapy | |
Suzuki et al. | Ability of NMDA and non-NMDA receptor antagonists to inhibit cerebral ischemic damage in aged rats | |
Zhang et al. | Akt2 knockout alleviates prolonged caloric restriction-induced change in cardiac contractile function through regulation of autophagy | |
CN113795247A (zh) | 用于心脏手术的稳定心脏麻痹液 | |
JP7104636B2 (ja) | ミトコンドリア生物の活性化による血小板産生刺激 | |
Robles et al. | Lead exposure effect on angiotensin II renal vasoconstriction | |
Margolis et al. | The efficacy of dexamethasone and flunixin meglumine in treating endotoxin-induced changes in calves | |
Tang et al. | Virus-mediated decrease of LKB1 activity in the mPFC diminishes stress-induced depressive-like behaviors in mice | |
Huo et al. | Empagliflozin attenuates radiation-induced hematopoietic damage via NOX-4/ROS/p38 pathway | |
JP2022546856A (ja) | 歯周組織由来の多分化能幹細胞を含む肥満または非アルコール性脂肪肝の予防または治療用薬学的組成物 | |
KR102242040B1 (ko) | 줄기세포의 티오레독신 발현을 증진시키는 방법 | |
JP2014189549A (ja) | 海馬神経の新生促進剤 | |
Davis | The effects of in ovo injected Nicotinamide Riboside on avian myogenesis | |
Sulonen | Xylitol toxicosis in dogs: case series study | |
WO2023242599A1 (en) | A benzimidazole compound with antihelminthic activity for use in reversing, arresting or slowing down cellular ageing in a vertebrate subject | |
Pedrosa et al. | Hematology, TransfusionandCellTherapy | |
Vaas | Imaging the effects of the transient middle cerebral artery occlusion filament model on the recruitment of neutrophils with non‐invasive imaging techniques |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20190226 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20200506 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20210611 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20210910 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20211008 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20211231 |
|
C60 | Trial request (containing other claim documents, opposition documents) |
Free format text: JAPANESE INTERMEDIATE CODE: C60 Effective date: 20211231 |
|
A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20220113 |
|
C21 | Notice of transfer of a case for reconsideration by examiners before appeal proceedings |
Free format text: JAPANESE INTERMEDIATE CODE: C21 Effective date: 20220114 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20220302 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20220531 |
|
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: 20220608 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20220708 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 7104636 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |