CN117018162A - 具有增加端粒酶活性和延长端粒的效果的肽以及组合物 - Google Patents
具有增加端粒酶活性和延长端粒的效果的肽以及组合物 Download PDFInfo
- Publication number
- CN117018162A CN117018162A CN202310707889.6A CN202310707889A CN117018162A CN 117018162 A CN117018162 A CN 117018162A CN 202310707889 A CN202310707889 A CN 202310707889A CN 117018162 A CN117018162 A CN 117018162A
- Authority
- CN
- China
- Prior art keywords
- composition
- disease
- telomerase activity
- peptide
- group
- 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.)
- Pending
Links
- 108010017842 Telomerase Proteins 0.000 title claims abstract description 87
- 230000000694 effects Effects 0.000 title claims abstract description 85
- 108091035539 telomere Proteins 0.000 title claims abstract description 80
- 102000055501 telomere Human genes 0.000 title claims abstract description 80
- 210000003411 telomere Anatomy 0.000 title claims abstract description 79
- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 78
- 239000000203 mixture Substances 0.000 title claims abstract description 67
- 230000001965 increasing effect Effects 0.000 title claims abstract description 23
- 102000004196 processed proteins & peptides Human genes 0.000 title description 27
- 125000003275 alpha amino acid group Chemical group 0.000 claims abstract description 28
- 201000010099 disease Diseases 0.000 claims abstract description 25
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 25
- 230000007423 decrease Effects 0.000 claims abstract description 21
- 239000012634 fragment Substances 0.000 claims abstract description 17
- 208000024891 symptom Diseases 0.000 claims abstract description 17
- 230000006727 cell loss Effects 0.000 claims abstract description 12
- 230000032677 cell aging Effects 0.000 claims abstract description 11
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 21
- 239000002537 cosmetic Substances 0.000 claims description 14
- 239000004480 active ingredient Substances 0.000 claims description 13
- 239000008194 pharmaceutical composition Substances 0.000 claims description 13
- 208000024827 Alzheimer disease Diseases 0.000 claims description 11
- 235000013376 functional food Nutrition 0.000 claims description 11
- 230000036541 health Effects 0.000 claims description 9
- -1 foundation Substances 0.000 claims description 8
- 230000009758 senescence Effects 0.000 claims description 8
- 210000001519 tissue Anatomy 0.000 claims description 8
- 230000030833 cell death Effects 0.000 claims description 7
- 239000006071 cream Substances 0.000 claims description 7
- 239000000843 powder Substances 0.000 claims description 7
- 238000002360 preparation method Methods 0.000 claims description 7
- 210000000653 nervous system Anatomy 0.000 claims description 6
- 239000000839 emulsion Substances 0.000 claims description 5
- 239000008187 granular material Substances 0.000 claims description 5
- 239000003826 tablet Substances 0.000 claims description 5
- 208000026350 Inborn Genetic disease Diseases 0.000 claims description 4
- 206010072170 Skin wound Diseases 0.000 claims description 4
- 235000013361 beverage Nutrition 0.000 claims description 4
- 235000009508 confectionery Nutrition 0.000 claims description 4
- 208000016361 genetic disease Diseases 0.000 claims description 4
- 239000006187 pill Substances 0.000 claims description 4
- 208000014644 Brain disease Diseases 0.000 claims description 3
- 206010008025 Cerebellar ataxia Diseases 0.000 claims description 3
- 208000035473 Communicable disease Diseases 0.000 claims description 3
- 206010012289 Dementia Diseases 0.000 claims description 3
- 208000023105 Huntington disease Diseases 0.000 claims description 3
- 208000018737 Parkinson disease Diseases 0.000 claims description 3
- 201000004681 Psoriasis Diseases 0.000 claims description 3
- 208000010112 Spinocerebellar Degenerations Diseases 0.000 claims description 3
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 3
- 208000007502 anemia Diseases 0.000 claims description 3
- 239000002775 capsule Substances 0.000 claims description 3
- 239000006260 foam Substances 0.000 claims description 3
- 230000003387 muscular Effects 0.000 claims description 3
- 208000027232 peripheral nervous system disease Diseases 0.000 claims description 3
- 208000020431 spinal cord injury Diseases 0.000 claims description 3
- 235000020357 syrup Nutrition 0.000 claims description 3
- 239000006188 syrup Substances 0.000 claims description 3
- 230000003612 virological effect Effects 0.000 claims description 3
- 230000037303 wrinkles Effects 0.000 claims description 3
- 208000005692 Bloom Syndrome Diseases 0.000 claims description 2
- 201000011032 Werner Syndrome Diseases 0.000 claims description 2
- 230000007823 neuropathy Effects 0.000 claims description 2
- 201000001119 neuropathy Diseases 0.000 claims description 2
- 239000002674 ointment Substances 0.000 claims description 2
- 208000033808 peripheral neuropathy Diseases 0.000 claims description 2
- 239000000344 soap Substances 0.000 claims description 2
- 230000000699 topical effect Effects 0.000 claims description 2
- 208000015181 infectious disease Diseases 0.000 claims 1
- 208000027418 Wounds and injury Diseases 0.000 abstract description 2
- 230000005779 cell damage Effects 0.000 abstract description 2
- 208000014674 injury Diseases 0.000 abstract description 2
- 210000004027 cell Anatomy 0.000 description 29
- 108010088535 Pep-1 peptide Proteins 0.000 description 25
- 238000000034 method Methods 0.000 description 23
- 150000001413 amino acids Chemical class 0.000 description 17
- 238000002474 experimental method Methods 0.000 description 13
- 241000699670 Mus sp. Species 0.000 description 12
- 238000010171 animal model Methods 0.000 description 11
- 239000006210 lotion Substances 0.000 description 9
- 108020004414 DNA Proteins 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 8
- 210000000349 chromosome Anatomy 0.000 description 8
- ADEBPBSSDYVVLD-UHFFFAOYSA-N donepezil Chemical compound O=C1C=2C=C(OC)C(OC)=CC=2CC1CC(CC1)CCN1CC1=CC=CC=C1 ADEBPBSSDYVVLD-UHFFFAOYSA-N 0.000 description 8
- 238000009472 formulation Methods 0.000 description 7
- 239000000463 material Substances 0.000 description 7
- 108090000623 proteins and genes Proteins 0.000 description 7
- 230000032683 aging Effects 0.000 description 6
- 230000004770 neurodegeneration Effects 0.000 description 6
- 239000011347 resin Substances 0.000 description 6
- 229920005989 resin Polymers 0.000 description 6
- 230000014509 gene expression Effects 0.000 description 5
- 102000004169 proteins and genes Human genes 0.000 description 5
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 4
- 241000282414 Homo sapiens Species 0.000 description 4
- 241000699660 Mus musculus Species 0.000 description 4
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 210000005013 brain tissue Anatomy 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 229960003530 donepezil Drugs 0.000 description 4
- 235000013305 food Nutrition 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- 238000011830 transgenic mouse model Methods 0.000 description 4
- 208000037051 Chromosomal Instability Diseases 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- 206010028980 Neoplasm Diseases 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 238000004364 calculation method Methods 0.000 description 3
- 230000010094 cellular senescence Effects 0.000 description 3
- 230000008878 coupling Effects 0.000 description 3
- 238000010168 coupling process Methods 0.000 description 3
- 238000005859 coupling reaction Methods 0.000 description 3
- 230000034994 death Effects 0.000 description 3
- 238000010511 deprotection reaction Methods 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 210000002569 neuron Anatomy 0.000 description 3
- 238000010647 peptide synthesis reaction Methods 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 230000010076 replication Effects 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 239000007790 solid phase Substances 0.000 description 3
- 210000001082 somatic cell Anatomy 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- DHBXNPKRAUYBTH-UHFFFAOYSA-N 1,1-ethanedithiol Chemical compound CC(S)S DHBXNPKRAUYBTH-UHFFFAOYSA-N 0.000 description 2
- YLZOPXRUQYQQID-UHFFFAOYSA-N 3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)-1-[4-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]piperazin-1-yl]propan-1-one Chemical compound N1N=NC=2CN(CCC=21)CCC(=O)N1CCN(CC1)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F YLZOPXRUQYQQID-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 102000002812 Heat-Shock Proteins Human genes 0.000 description 2
- 108010004889 Heat-Shock Proteins Proteins 0.000 description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 238000010162 Tukey test Methods 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- 239000002246 antineoplastic agent Substances 0.000 description 2
- 230000003078 antioxidant effect Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 230000007850 degeneration Effects 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003205 fragrance Substances 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 210000003061 neural cell Anatomy 0.000 description 2
- 210000002682 neurofibrillary tangle Anatomy 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 230000002028 premature Effects 0.000 description 2
- 230000002062 proliferating effect Effects 0.000 description 2
- 230000008672 reprogramming Effects 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- ZGYICYBLPGRURT-UHFFFAOYSA-N tri(propan-2-yl)silicon Chemical compound CC(C)[Si](C(C)C)C(C)C ZGYICYBLPGRURT-UHFFFAOYSA-N 0.000 description 2
- 238000012795 verification Methods 0.000 description 2
- 239000011782 vitamin Substances 0.000 description 2
- 235000013343 vitamin Nutrition 0.000 description 2
- 229940088594 vitamin Drugs 0.000 description 2
- 229930003231 vitamin Natural products 0.000 description 2
- REITVGIIZHFVGU-IBGZPJMESA-N (2s)-2-(9h-fluoren-9-ylmethoxycarbonylamino)-3-[(2-methylpropan-2-yl)oxy]propanoic acid Chemical compound C1=CC=C2C(COC(=O)N[C@@H](COC(C)(C)C)C(O)=O)C3=CC=CC=C3C2=C1 REITVGIIZHFVGU-IBGZPJMESA-N 0.000 description 1
- ADOHASQZJSJZBT-SANMLTNESA-N (2s)-2-(9h-fluoren-9-ylmethoxycarbonylamino)-3-[1-[(2-methylpropan-2-yl)oxycarbonyl]indol-3-yl]propanoic acid Chemical compound C12=CC=CC=C2N(C(=O)OC(C)(C)C)C=C1C[C@@H](C(O)=O)NC(=O)OCC1C2=CC=CC=C2C2=CC=CC=C21 ADOHASQZJSJZBT-SANMLTNESA-N 0.000 description 1
- JAUKCFULLJFBFN-VWLOTQADSA-N (2s)-2-(9h-fluoren-9-ylmethoxycarbonylamino)-3-[4-[(2-methylpropan-2-yl)oxy]phenyl]propanoic acid Chemical compound C1=CC(OC(C)(C)C)=CC=C1C[C@@H](C(O)=O)NC(=O)OCC1C2=CC=CC=C2C2=CC=CC=C21 JAUKCFULLJFBFN-VWLOTQADSA-N 0.000 description 1
- KJYAFJQCGPUXJY-UMSFTDKQSA-N (2s)-2-(9h-fluoren-9-ylmethoxycarbonylamino)-4-oxo-4-(tritylamino)butanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)OCC1C2=CC=CC=C2C2=CC=CC=C21)C(=O)NC(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 KJYAFJQCGPUXJY-UMSFTDKQSA-N 0.000 description 1
- OTKXCALUHMPIGM-FQEVSTJZSA-N (2s)-2-(9h-fluoren-9-ylmethoxycarbonylamino)-5-[(2-methylpropan-2-yl)oxy]-5-oxopentanoic acid Chemical compound C1=CC=C2C(COC(=O)N[C@@H](CCC(=O)OC(C)(C)C)C(O)=O)C3=CC=CC=C3C2=C1 OTKXCALUHMPIGM-FQEVSTJZSA-N 0.000 description 1
- WDGICUODAOGOMO-DHUJRADRSA-N (2s)-2-(9h-fluoren-9-ylmethoxycarbonylamino)-5-oxo-5-(tritylamino)pentanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)OCC1C2=CC=CC=C2C2=CC=CC=C21)CC(=O)NC(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 WDGICUODAOGOMO-DHUJRADRSA-N 0.000 description 1
- UMRUUWFGLGNQLI-QFIPXVFZSA-N (2s)-2-(9h-fluoren-9-ylmethoxycarbonylamino)-6-[(2-methylpropan-2-yl)oxycarbonylamino]hexanoic acid Chemical compound C1=CC=C2C(COC(=O)N[C@@H](CCCCNC(=O)OC(C)(C)C)C(O)=O)C3=CC=CC=C3C2=C1 UMRUUWFGLGNQLI-QFIPXVFZSA-N 0.000 description 1
- QWXZOFZKSQXPDC-NSHDSACASA-N (2s)-2-(9h-fluoren-9-ylmethoxycarbonylamino)propanoic acid Chemical compound C1=CC=C2C(COC(=O)N[C@@H](C)C(O)=O)C3=CC=CC=C3C2=C1 QWXZOFZKSQXPDC-NSHDSACASA-N 0.000 description 1
- HNICLNKVURBTKV-NDEPHWFRSA-N (2s)-5-[[amino-[(2,2,4,6,7-pentamethyl-3h-1-benzofuran-5-yl)sulfonylamino]methylidene]amino]-2-(9h-fluoren-9-ylmethoxycarbonylamino)pentanoic acid Chemical compound C12=CC=CC=C2C2=CC=CC=C2C1COC(=O)N[C@H](C(O)=O)CCCN=C(N)NS(=O)(=O)C1=C(C)C(C)=C2OC(C)(C)CC2=C1C HNICLNKVURBTKV-NDEPHWFRSA-N 0.000 description 1
- LZOLWEQBVPVDPR-VLIAUNLRSA-N (2s,3r)-2-(9h-fluoren-9-ylmethoxycarbonylamino)-3-[(2-methylpropan-2-yl)oxy]butanoic acid Chemical compound C1=CC=C2C(COC(=O)N[C@@H]([C@H](OC(C)(C)C)C)C(O)=O)C3=CC=CC=C3C2=C1 LZOLWEQBVPVDPR-VLIAUNLRSA-N 0.000 description 1
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
- HMUNWXXNJPVALC-UHFFFAOYSA-N 1-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)C(CN1CC2=C(CC1)NN=N2)=O HMUNWXXNJPVALC-UHFFFAOYSA-N 0.000 description 1
- LDXJRKWFNNFDSA-UHFFFAOYSA-N 2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)-1-[4-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]piperazin-1-yl]ethanone Chemical compound C1CN(CC2=NNN=C21)CC(=O)N3CCN(CC3)C4=CN=C(N=C4)NCC5=CC(=CC=C5)OC(F)(F)F LDXJRKWFNNFDSA-UHFFFAOYSA-N 0.000 description 1
- 238000011825 3xTg-AD mouse Methods 0.000 description 1
- 208000030507 AIDS Diseases 0.000 description 1
- 102000013455 Amyloid beta-Peptides Human genes 0.000 description 1
- 108010090849 Amyloid beta-Peptides Proteins 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 101100462495 Caenorhabditis elegans rsa-1 gene Proteins 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 208000037088 Chromosome Breakage Diseases 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000655352 Homo sapiens Telomerase reverse transcriptase Proteins 0.000 description 1
- 238000012313 Kruskal-Wallis test Methods 0.000 description 1
- 238000000585 Mann–Whitney U test Methods 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 241000009328 Perro Species 0.000 description 1
- 206010036105 Polyneuropathy Diseases 0.000 description 1
- 206010063493 Premature ageing Diseases 0.000 description 1
- 208000032038 Premature aging Diseases 0.000 description 1
- 208000037340 Rare genetic disease Diseases 0.000 description 1
- 238000002105 Southern blotting Methods 0.000 description 1
- 241000282898 Sus scrofa Species 0.000 description 1
- 102100032938 Telomerase reverse transcriptase Human genes 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- 206010064930 age-related macular degeneration Diseases 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004271 bone marrow stromal cell Anatomy 0.000 description 1
- 238000010322 bone marrow transplantation Methods 0.000 description 1
- 235000008429 bread Nutrition 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- UDSAIICHUKSCKT-UHFFFAOYSA-N bromophenol blue Chemical compound C1=C(Br)C(O)=C(Br)C=C1C1(C=2C=C(Br)C(O)=C(Br)C=2)C2=CC=CC=C2S(=O)(=O)O1 UDSAIICHUKSCKT-UHFFFAOYSA-N 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000000546 chi-square test Methods 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000007822 coupling agent Substances 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- 230000001120 cytoprotective effect Effects 0.000 description 1
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 1
- 235000013365 dairy product Nutrition 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000003412 degenerative effect Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- 229940000406 drug candidate Drugs 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 230000001815 facial effect Effects 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 235000013373 food additive Nutrition 0.000 description 1
- 239000002778 food additive Substances 0.000 description 1
- 235000012041 food component Nutrition 0.000 description 1
- 239000005417 food ingredient Substances 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 235000013402 health food Nutrition 0.000 description 1
- 230000000971 hippocampal effect Effects 0.000 description 1
- 238000009396 hybridization Methods 0.000 description 1
- 238000010191 image analysis Methods 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
- 239000012160 loading buffer Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 208000002780 macular degeneration Diseases 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000003020 moisturizing effect Effects 0.000 description 1
- 230000003961 neuronal insult Effects 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 235000012149 noodles Nutrition 0.000 description 1
- 230000000474 nursing effect Effects 0.000 description 1
- 239000002417 nutraceutical Substances 0.000 description 1
- 235000021436 nutraceutical agent Nutrition 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 238000001543 one-way ANOVA Methods 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 230000002188 osteogenic effect Effects 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 201000002528 pancreatic cancer Diseases 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 230000007824 polyneuropathy Effects 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 208000037821 progressive disease Diseases 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 230000010410 reperfusion Effects 0.000 description 1
- 230000003252 repetitive effect Effects 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 235000011888 snacks Nutrition 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 230000035882 stress Effects 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 235000013616 tea Nutrition 0.000 description 1
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000007492 two-way ANOVA Methods 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/10—Peptides having 12 to 20 amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/45—Transferases (2)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- 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
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- A61P7/06—Antianaemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/02—Preparations for care of the skin for chemically bleaching or whitening the skin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/08—Anti-ageing preparations
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/08—Linear peptides containing only normal peptide links having 12 to 20 amino acids
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/10—Transferases (2.)
- C12N9/12—Transferases (2.) transferring phosphorus containing groups, e.g. kinases (2.7)
- C12N9/1241—Nucleotidyltransferases (2.7.7)
- C12N9/1276—RNA-directed DNA polymerase (2.7.7.49), i.e. reverse transcriptase or telomerase
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y207/00—Transferases transferring phosphorus-containing groups (2.7)
- C12Y207/07—Nucleotidyltransferases (2.7.7)
- C12Y207/07049—RNA-directed DNA polymerase (2.7.7.49), i.e. telomerase or reverse-transcriptase
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/17—Amino acids, peptides or proteins
- A23L33/18—Peptides; Protein hydrolysates
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/322—Foods, ingredients or supplements having a functional effect on health having an effect on the health of the nervous system or on mental function
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q1/00—Make-up preparations; Body powders; Preparations for removing make-up
- A61Q1/02—Preparations containing skin colorants, e.g. pigments
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/10—Washing or bathing preparations
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Dermatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Epidemiology (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Gastroenterology & Hepatology (AREA)
- Immunology (AREA)
- Biochemistry (AREA)
- Mycology (AREA)
- Nutrition Science (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Birds (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Biophysics (AREA)
- Psychology (AREA)
- General Engineering & Computer Science (AREA)
- Gerontology & Geriatric Medicine (AREA)
- Physical Education & Sports Medicine (AREA)
Abstract
本发明涉及具有增加端粒酶活性和延长端粒的效果的肽以及组合物,更具体而言涉及一种用于预防或治疗由端粒酶活性或端粒长度减少引起的疾病或者由细胞损失和衰老引起的症状的组合物,所述组合物包含药学有效量的选自由包含SEQ ID NO:1的氨基酸序列的肽、与该氨基酸序列具有至少80%序列同源性的肽或其片段组成的组中的一种或多种,从而有效预防、缓解和治疗由端粒酶活性降低或端粒长度减少引起的疾病以及由细胞老化或损伤引起的症状。
Description
本申请是分案申请,其原申请的国际申请号是PCT/KR2017/003815,国际申请日是2017年04月07日,中国国家申请号为201780027738.9,进入中国的日期为2018年11月05日,发明名称为“具有增加端粒酶活性和延长端粒的效果的肽以及包含该肽的组合物”。
技术领域
本说明书涉及具有增加端粒酶活性和延长端粒的效果的肽以及包含该肽的组合物,更具体而言涉及包含衍生自端粒酶的肽的组合物,所述肽具有治疗或预防由端粒酶活性降低和端粒损失引起的细胞变性、老化或死亡。
背景技术
已知其中在染色体末端发现的DNA六聚体(TTAGGG)序列重复的端粒具有稳定染色体的功能。反复的细胞复制缩短了染色体的末端,这表明细胞衰老,因此,端粒是各种组织中维持细胞寿命的重要因素,并且用于评估细胞衰老。端粒酶是一种酶蛋白,其催化端粒重复序列在端粒3'末端的添加,并用于恢复由于细胞衰老而丢失的端粒。端粒酶在大多数正常成体细胞中不表达,端粒长度在细胞复制中逐渐减少,并且端粒重复的减少导致细胞衰老。
在特定疾病中,端粒末端异常快速地丢失并导致未成熟细胞的老化或变性。在人的情况下,发现表达人端粒酶(hTERT,人-端粒酶逆转录酶)的细胞绕过正常的细胞衰老途径。当在具有短端粒的老化细胞中诱导端粒酶的表达时,端粒长度增加,并且恢复与较年轻细胞相似的表型。
与癌细胞或特定干细胞不同,体细胞具有很少或没有端粒酶活性,并且当包括端粒在内的一些染色体的末端缩短至一定长度或更短时,细胞停止分裂并进入程序性细胞衰老(细胞死亡)。由于端粒酶活性的增加减少了端粒重复序列的损失,因此预期具有在端粒末端添加端粒重复序列的作用的端粒酶活性的诱导重新启动了处于衰老或死亡阶段的体细胞的复制和分裂,并诱导其中分布有大量衰老或死亡期细胞的受损组织的恢复。
此外,体细胞中端粒酶活性的增加可能有助于:治疗或预防神经退行性疾病(代表性地,阿尔茨海默病),治疗或改善由杀死感染细胞的免疫细胞(细胞毒性T淋巴细胞)过早衰老引发的HIV,伤口愈合如皮肤创伤,和维持移植细胞如骨髓移植。此外,已知端粒酶活性通过作为端粒酶一部分的hTERT的过表达而增加,或通过调节端粒酶组装的蛋白质如热休克蛋白(HSP)的表达而增加。
端粒长度的估计对于理解端粒的生物学和临床意义是重要的。端粒长度是研究染色体稳定性、端粒酶活性和/或表达、增殖能力和细胞衰老过程的有用指标。端粒的临床价值的重要性可以在以下病症中得到证实:Bloom综合征(罕见的遗传性疾病,感染者的染色体断裂频率和重排高),这是一种由癌症、早衰综合征或部分早衰、遗传异常或染色体不稳定引发的疾病;以及Werner综合征(以相对年轻的人中快速出现老化为特征的罕见病症),这是一种与衰老有关的疾病。端粒长度的动态性在某一疾病过程中具有独特的表达模式。因此,它对预测疾病非常有用。
同时,作为开发用于治疗由端粒酶活性和端粒长度减少引起的神经退行性疾病和阿尔茨海默病(这是一种众所周知的神经退行性疾病)的药物的有效性和功效实验中使用的动物模型,采用了小鼠(3xTg-AD小鼠模型):其中三个特定基因(APP,Tau,PS1)被修饰以积累β淀粉样蛋白并诱导神经原纤维缠结(NFT)。其中三个基因被修饰的小鼠随时间显示出包括阿尔茨海默病症状在内的神经元损伤疾病的进展。已知候选药物的有效性和功效可通过观察神经细胞的破坏抑制和再生能力来测量,其中通过向诱导神经细胞损失的动物施用开发的药物并将其与未治疗的对照组进行比较。
已知根据本发明的一方面的肽PEP1是由存在于端粒酶的催化部分中的16个重要氨基酸组成的肽,并且具有抗炎和抗氧化功效。如通过动物实验已经发现,根据本发明的一方面的肽可有效增加端粒酶活性和增加细胞中的端粒长度,预期PEP1可有效预防和治疗由端粒酶活性和端粒长度降低引发的各种疾病。
本说明书提供了一种组合物,其包括衍生自端粒酶的逆转录酶的肽,以增加端粒酶活性和延长端粒。具体地,本说明书提供了包含hTERT衍生肽的组合物,以增加端粒酶活性和延长端粒。更具体而言,本说明书提供了一种组合物,其包含由16个氨基酸(PEP1)组成的hTERT衍生肽,以增加端粒酶活性和延长端粒。
[现有技术文件]
[专利文件]
(专利文件1)WO 2008-149345 A2
[非专利文件]
(非专利文件1)Simonsen,J.L.等,“Telomerase expression extends theproliferative life-span and maintains the osteogenic potential of human bonemarrow stromal cells,”Nat Biotechnol 20(6):592-6(January,2002)
发明内容
技术问题
在这种背景下,本发明人试图开发一种组合物,用于预防和治疗由端粒酶活性和端粒长度降低引起的症状,从而大大增加端粒酶活性并延长端粒而没有副作用,进而完成了本发明。
本说明书的一个目的是提供一种有效、无副作用、增加端粒酶活性和延长端粒长度的肽组合物,以及一种预防、改善和治疗端粒酶活性和端粒长度降低导致的由细胞衰老、损伤和死亡引起的症状的方法。
技术方案
在一方面,本发明提供了一种组合物,所述组合物包含药学有效量的选自以下组的一种或多种,所述组由包含SEQ ID NO:1的氨基酸序列的肽、与该氨基酸序列具有至少80%序列同源性的肽或其片段组成,以增加端粒酶活性或延长端粒长度。在另一方面,本发明提供增加端粒酶活性或延长端粒长度的方法,其包括对受试者施用选自以下组的一种或多种,所述组由包含SEQ ID NO:1的氨基酸序列的肽、与该氨基酸序列具有至少80%序列同源性的肽或其片段组成。
在另一方面,本发明提供选自以下组的一种或多种,所述组由包含SEQ ID NO:1的氨基酸序列的肽、与该氨基酸序列具有至少80%序列同源性的肽或其片段组成,以增加端粒酶活性或延长端粒长度。
在又一方面,本发明提供选自以下组的一种或多种作为增加端粒酶活性或延长端粒长度的非治疗性化妆品的活性成分的应用,所述组由包含SEQ ID NO:1的氨基酸序列的肽、与该氨基酸序列具有至少80%序列同源性的肽或其片段组成。
在又一方面,本发明提供选自以下组的一种或多种在增加端粒酶活性或延长端粒长度的组合物中的应用,所述组由包含SEQ ID NO:1的氨基酸序列的肽、与该氨基酸序列具有至少80%序列同源性的肽或其片段组成。
在又一方面,所述组合物用于预防或治疗由端粒酶活性和端粒长度减少引起的疾病,或由细胞损失和衰老引起的症状。
在又一方面,本发明提供治疗或预防由端粒酶活性或端粒长度减少引起的疾病或者由细胞损失和衰老引起的症状的方法,所述方法包括对对受试者施用选自以下组的一种或多种,所述组由包含SEQ ID NO:1的氨基酸序列的肽、与该氨基酸序列具有至少80%序列同源性的肽或其片段组成。
在又一方面,本发明提供选自由包含SEQ ID NO:1的氨基酸序列的肽、与该氨基酸序列具有至少80%序列同源性的肽或其片段组成的组的一种或多种,其用于治疗或预防由端粒酶活性或端粒长度减少引起的疾病,或由细胞损失和衰老引起的症状。
在又一方面,本发明提供选自以下组的一种或多种作为改善或预防由端粒酶活性或端粒长度减少引起的疾病或者由细胞损失和衰老引起的症状的非治疗性化妆品的活性成分的应用,所述组由包含SEQ ID NO:1的氨基酸序列的肽、与该氨基酸序列具有至少80%序列同源性的肽或其片段组成。
在又一方面,本发明提供选自以下组的一种或多种在改善或预防由端粒酶活性或端粒长度减少引起的疾病或者由细胞损失和衰老引起的症状的组合物中的应用,所述组由包含SEQ ID NO:1的氨基酸序列的肽、与该氨基酸序列具有至少80%序列同源性的肽或其片段组成。
关于根据本发明一方面的组合物,所述疾病是选自神经退行性病症、神经系统的退行性疾病、骨骼系统的退行性疾病、肌肉系统的退行性疾病、病毒感染性疾病和导致细胞加速死亡的遗传性疾病中的一种或多种。
关于根据本发明一方面的组合物,所述神经系统的退行性疾病是选自脑疾病、脊髓损伤、周围神经损伤、周围神经疾病、肌萎缩侧索硬化症、痴呆、亨廷顿病、帕金森病、阿尔茨海默病、脊髓小脑变性和多发性神经病中的任一种。
关于根据本发明一方面的组合物,所述由细胞损失和衰老引起的症状包括选自由皮肤伤口引起的组织损失、皮肤皱纹、贫血、皮肤牛皮癣和皮肤变黑中的一种或多种。
根据本发明的又一方面,提供了包含上述组合物作为活性成分的药物组合物来增加端粒酶活性或延长端粒长度。
关于根据本发明又一方面的药物组合物,所述药物组合物包含以0.1μg/kg至100mg/kg的剂量施用的SEQ ID NO:1的肽。
根据本发明的再一个方面,提供了包含上述组合物作为活性成分的保健功能食品组合物来增加端粒酶活性或延长端粒长度。
关于根据本发明再一方面的保健功能食品组合物,所述组合物制备为选自粉末、颗粒、丸、片剂、胶囊、糖果、糖浆和饮料中的任一种制剂。
根据本发明的另一个方面,提供了包含上述组合物作为活性成分的化妆品组合物来增加端粒酶活性或延长端粒长度。
关于根据本发明另一方面的化妆品组合物,所述化妆品组合物制备为选自由爽肤水乳液、乳霜、粉底、精华素、凝胶、面膜、泡沫洁面乳、肥皂和局部使用的软膏组成的组中的任一种制剂。
有益效果
本说明书的序列为SEQ ID NO:1的肽、与该序列具有至少80%序列同源性的肽或其片段可有效预防和治疗由端粒酶活性异常降低或细胞中端粒长度减少和损失引起的疾病、细胞衰老引起的症状,以及与神经细胞和再生能力丧失相关的疾病,从而预防和治疗这些疾病。
附图说明
图1是显示当诱导神经变性疾病时,通过在遗传操纵的神经退行性疾病实验用动物模型中施用各种浓度(0mg/kg、0.01mg/kg、0.1mg/kg和1mg/kg)的根据本说明书的肽,来比较端粒酶活性的增加的结果的图。
图2是当诱导神经变性疾病时,通过在遗传操纵的神经退行性疾病实验用动物模型中施用各种浓度(0mg/kg、0.01mg/kg、0.1mg/kg和1mg/kg)的根据本说明书的肽,显示出端粒长度增加的染色体电泳图像。
图3是用于测量端粒酶活性的计算相对端粒酶活性(RTA)的计算公式。
图4是显示用于测量端粒酶活性的实验中PCR水平的实验条件的表。
图5是用于测量端粒长度的实验中分析图像的计算公式。
具体实施方式
由于本发明可以具有各种修改和实施方式,因此下面将更详细地描述本发明。然而,本发明不限于特定实施方式,并且应该理解的是本发明包括本发明的技术构思和范围中包括的所有修改、等同物和替代物。为了解释本发明,如果确定相关技术的详细描述可能使本发明的主旨不清,则将省略其详细描述。
端粒是位于染色体每个末端的重复遗传物质,已知其可防止相应染色体的损伤或与不同染色体的结合。随着细胞分裂,端粒逐渐缩短,在一定数量的细胞分裂后变得非常短,细胞最终停止分裂并死亡。另一方面,端粒的延长已知可延长细胞的寿命。端粒酶衍生肽PEP1已被开发为用于包括胰腺癌在内的各种癌症的抗癌剂,并且还鉴定为参与抗炎、抗氧化和细胞渗透,以及细胞中的主要信号传导过程,以及具有抗癌效果。鉴于PEP1的细胞内功能,已经探索了除了将其用作现有抗癌剂之外还使用新适应症的可能性。
本发明人已证实端粒酶衍生肽具有增加端粒酶活性和端粒长度的活性,从而完成了本发明。更具体而言,在本发明的一个方面,通过阿尔茨海默病动物模型实验,证实在对从端粒酶活性或长度减少的阿尔茨海默病动物模型中提取的细胞的实验中通过PEP1增加了端粒酶活性和端粒相关DNA的长度。
在本发明的一个方面,SEQ ID NO:1的肽(PEP1)、SEQ ID NO:1的肽的片段或与所述肽序列具有至少80%序列同源性的肽包括衍生自端粒酶、特别是智人端粒酶的肽。
本文公开的肽可包括具有至少80%、85%、90%、95%、96%、97%、98%或99%序列同源性的肽。另外,本文公开的肽可包括与SEQ ID NO:1的肽或其片段相差1个或更多氨基酸、2个或更多氨基酸、3个或更多氨基酸、4个或更多氨基酸、5个或更多氨基酸、6个或更多氨基酸或7个或更多氨基酸的肽。
在本发明的一个方面,氨基酸变化是改变肽的物理化学性质的性质。例如,可以进行氨基酸变化以改善肽的热稳定性,改变底物特异性,并改变最佳pH。
SEQ ID NO:1中所示的肽显示在下表1中。给出下表1中的“名称”以区分一种肽与另一种肽。在本发明的一个方面,SEQ ID NO:2所示的肽表示人类端粒酶的完整肽。在本发明的另一个方面,SEQ ID NO:1的肽、其片段或与所述肽序列具有至少80%序列同源性的肽包括由端粒酶所含肽的相应位置处存在的肽合成的“合成肽”。SEQ ID NO:2表示端粒酶的全长氨基酸序列。
[表1]
包含本发明一方面的包含SEQ ID NO:1的肽的组合物可有效预防或治疗由端粒酶活性或端粒长度减少引起的疾病或由细胞损失和衰老引起的症状。由端粒酶活性或端粒长度减少引起的疾病包括选自神经退行性病症、神经系统的退行性疾病、骨骼系统的退行性疾病、肌肉系统的退行性疾病、病毒感染性疾病和导致细胞加速死亡的遗传性疾病中的一种或多种。受益于端粒酶活性增加的神经系统的退行性疾病可包括选自脑疾病、脊髓损伤、周围神经损伤、周围神经疾病、肌萎缩侧索硬化症、痴呆、亨廷顿病、帕金森病、阿尔茨海默病、脊髓小脑变性和多发性神经病中的任一种,但本发明不限于此。此外,受益于端粒酶活性增加的疾病状况可包括退行性关节病、动脉粥样硬化、血栓形成、应激诱导的细胞死亡、如心力衰竭或缺血、年龄相关性黄斑变性、艾滋病(AIDS)、伴随导致加速细胞重编程遗的传性疾病发生的组织重编程受损、和其他退行性病况。
根据本发明的一个方面的增加端粒酶活性的组合物可有效促进对由细胞损失和衰老引起的症状的治疗,并且在自由皮肤伤口引起的组织损失、皮肤皱纹、贫血、皮肤牛皮癣和皮肤变黑中的一种或多种症状的治疗中具有优选的效果。
在一方面,本发明提供了药物组合物,其包含含有SEQ ID NO:1的氨基酸序列、与该氨基酸序列具有至少80%序列同源性的肽或其片段作为活性成分来增加端粒酶活性和延长端粒。
本发明一方面的组合物可应用于所有动物,包括:人、狗、鸡、猪、牛、羊、豚鼠和猴。
在一方面,本发明提供了药物组合物,其包含含有SEQ ID NO:1的氨基酸序列、与该氨基酸序列具有至少80%序列同源性的肽或其片段来预防神经细胞的损失和再生神经细胞。本发明一方面的药物组合物可以口服、直肠内、透皮、静脉内、肌肉内、腹膜内、髓内、鞘内或皮下施用。
用于口服施用的剂型可包括但不限于:片剂、丸剂、软胶囊或硬胶囊剂、颗粒剂、粉剂、溶液剂和乳剂。用于肠胃外施用的剂型可包括但不限于注射剂、滴剂、洗剂、软膏、凝胶、霜剂、悬浮液、乳液、栓剂、贴剂或喷雾剂。
本发明一方面的药物组合物在需要时可以包含添加剂,例如稀释剂、赋形剂、润滑剂、粘合剂、崩解剂、缓冲剂、分散剂、表面活性剂、着色剂、调味剂或甜味剂。本发明一方面的药物组合物可以通过现有技术常规方法制备。
本发明示例性实施方式的药物组合物的有效成分可以根据施用对象的年龄、性别、体重、病理状态和严重程度、给药途径或处方者的决定而变化。基于这些因素来决定剂量是处于本领域普通技术人员的水平之内的,并且本发明示例性实施方式的药物组合物的日剂量可以是例如0.01μg/kg/天至10g/kg/天,具体地0.1μg/kg/天至1g/kg/天,更具体地0.5μg/kg/天至100mg/kg/天,并且当效果随剂量而存在差异时可以适当地调整。根据本发明一方面的药物组合物可以每天施用1至3次,但本发明不限于此。
根据本发明一方面的保健功能食品组合物可以制备为选自粉末、颗粒、丸、片剂、胶囊、糖果、糖浆和饮料中的任一种制剂,但本发明不限于此。当根据本发明一方面的保健功能食品组合物用作食品添加剂时,保健功能食品组合物可以原样添加或与不同的食品或食品成分一起使用,因此可以根据常规方法适当地使用。可以添加所述保健功能食品组合物的食品的实例可以包括但不限于肉、面包、糖果、零食、面条、乳制品、维生素复合物、饮品、茶和饮料,并且包括常识中的所有类型的健康食品。
根据本发明一方面的保健功能食品组合物可以作为食品,特别是功能性食品。根据本发明一方面的功能性食品包含在食品生产中常规添加的成分,例如,蛋白质、糖、脂类、营养素和调味料。
本发明的药物组合物或保健功能食品组合物可包含0.1%以上、优选最大约10%、更优选最大约5%、进一步更优选最大1%(w/v)的SEQ ID NO:1的肽。适当浓度的选择取决于诸如优选剂量、频率和递送活性成分的方法等因素。
本发明一方面的化妆品组合物在其制剂上没有特别限制,并且可以具有诸如柔肤水、敛肤水、滋养水、眼霜、滋养霜、按摩霜、洁肤霜、洁肤泡沫、洁肤水、粉、精华素或面膜等制剂。
本发明一方面的化妆品组合物可以根据化妆品组合物的常规制备方法制备为各种制剂。例如,化妆品组合物可以制备为例如含有肽、爽肤水、乳膏和乳液的化妆品和芳香产品,并且可以在用常规液体洁肤水、敛肤水或保湿乳液稀释后使用。另外,化妆品组合物可包括常用的添加剂,如常用于化妆品组合物领域的稳定剂、增溶剂、维生素、颜料或香料。
根据本发明一方面的组合物的制剂没有特别限制,并且可以是例如片剂、颗粒剂、粉剂、液体或固体制剂。每种制剂可以通过混合本领域普通技术人员根据本发明的制剂或其使用目的毫无困难地适当选择的相应领域常用组分以及活性成分来制备,并且这些组分可通过与其它组分同时应用而具有协同效应。
本说明书中使用的术语旨在用于描述具体实施方式而不是限制本发明。前面没有数量的术语不是要限制数量,而是表示存在本文引用的至少一个项目。术语“包含”、“具有”、“包括”和“含有”应该理解为开放式(即“包括但不限于”)。
数值范围的提及取代了范围内各数值的提及,除非另有说明,否则每个数值都如同在本说明书中单独提及那样适用于本说明书。所有范围的端值都包括在范围内,并且可以单独组合。
除非另有说明或在上下文中明确矛盾,否则本说明书中提及的所有方法均可以按照合适的顺序执行。除非包括在权利要求中,否则使用任何一个实施方式和所有实施方式或示例性语言(例如,“诸如”或“如…”)用于更清楚地描述本发明,而不是限制本发明的范围。权利要求之外的本文任何语言不应解释为对本发明的实践必不可少。除非另外定义,否则本文使用的科技术语各自具有本发明所属领域普通技术人员通常理解的含义。
本发明的示例性实施方式包括发明人已知的执行本发明的最佳模式。当阅读以上描述时,示例性实施方式的变化对于本领域技术人员而言将变得清楚。预期发明人适当地使用这样的变化,并通过本说明书中描述的不同方法实施本发明。因此,如专利法允许,本发明包括所附权利要求中提到的本发明要点的等同物和所有修改。此外,除非在上下文中另外明确说明或矛盾,否则具有上述组件的任何组合的所有可能变型均包括在本发明中。尽管通过示例性实施方式描述和示出了本发明,但是本领域技术人员将容易理解,可以在不背离本发明主旨和由所附权利要求限定的范围的情况下,在形式和细节上有各种变化。
下文中,将参考实施例和实验例进一步详细描述本发明的构造和效果。然而,以下实施例和实验例仅供说明本发明以帮助理解本发明,并且本发明的范围不限于此。
[实施例1]
肽的合成
SEQ ID NO:1的肽(下文中称为“PEP 1”)根据固相肽合成的常规已知方法制备。具体地,使用ASP48S(Peptron,Inc.,Daejeon,韩国)通过Fmoc固相肽合成(SPPS)从C-末端将每个氨基酸相互偶联来合成肽。其中C-末端的第一个氨基酸与树脂连接的肽如下使用:
NH2-Lys(Boc)-2-氯-三苯甲基树脂
NH2-Ala-2-氯-三苯甲基树脂
NH2-Arg(Pbf)-2-氯-三苯甲基树脂
在用于合成肽的所有氨基酸成分中,N-末端用Fmoc保护,残基用Trt、Boc、叔丁酯(t-Bu)和可以在酸中除去的2,2,4,6,7-五甲基二氢-苯并呋喃-5-磺酰基(Pbf)保护。氨基酸的实例如下:
Fmoc-Ala-OH、Fmoc-Arg(Pbf)-OH、Fmoc-Glu(OtBu)-OH、Fmoc-Pro-OH、Fmoc-Leu-OH、Fmoc-Ile-OH、Fmoc-Phe-OH、Fmoc-Ser(tBu)-OH、Fmoc-Thr(tBu)-OH、Fmoc-Lys(Boc)-OH、Fmoc-Gln(Trt)-OH、Fmoc-Trp(Boc)-OH、Fmoc-Met-OH、Fmoc-Asn(Trt)-OH、Fmoc-Tyr(tBu)-OH、Fmoc-Ahx-OH、Trt-巯基乙酸。
作为偶联剂,使用2-(1H-苯并三唑-1-基)-1,1,3,3-四甲基脲六氟磷酸盐(HBTU)/N-羟基苯并三唑(HOBt)/4-甲基吗啉(NMM)。使用20%哌啶的DMF溶液进行Fmoc脱保护。为了从树脂中分离合成的肽并除去残基的保护基,使用切割混合物[三氟乙酸(TFA)/三异丙基硅烷(TIS)/乙二硫醇(EDT)/H2O=92.5/2.5/2.5/2.5]。
通过使用其中在与固相支架结合的同时起始氨基酸被氨基酸保护基保护的状态使每个相应氨基酸反应,用溶剂洗涤所得产物,并进行脱保护的重复过程,合成每种肽。从树脂上脱离后,所合成的肽通过HPLC纯化,通过质谱(MS)确认合成,并进行冷冻干燥。
使用高效液相色谱测定,实验中使用的所有肽的纯度为95%或更高。
制备PEP1的具体方法如下。
1)偶联
将用NH2-Lys(Boc)-2-氯-三苯甲基树脂保护的氨基酸(8当量)与溶解在DMF中的偶联试剂HBTU(8当量)/HOBt(8当量)/NMM(16当量)混合,在室温反应2小时,并依次用DMF、MeOH和DMF洗涤。
2)Fmoc脱保护
向所得产物中加入20%哌啶的DMF溶液,在室温反应2次,每次5分钟,然后依次用DMF、MeOH和DMF进行洗涤。
3)重复反应1)和2),以形成肽骨架NH2-E(OtBu)-A-R(Pbf)-P-A-L-L-T(tBu)-S(tBu)-R(Pbf)L-R(Pbf)-F-I-P-K(Boc)-2-氯-三苯甲基树脂。
4)切割:通过向合成完成的肽树脂中添加切割混合物,将肽与树脂分离。
5)冷却后,在得到的混合物中加入二乙醚,使离心获得的肽沉淀。
6)通过制备型HPLC纯化后,通过LC/MS测定分子量并冻干,从而制备粉末。
[实施例2]
实验材料和方法
实施例2-1:实验动物的制备
所有动物相关程序均根据汉阳大学实验动物护理和使用指南进行。在所有实验中,动物受试者的数量和疼痛最小化,并且所有动物使用一次。
此处使用的PEP1根据实施例1中描述的方法制备,并且其他试剂和对照材料是购自Sigma Aldrich的真品。
为了测试PEP1对阿尔茨海默病的治疗效果,阿尔茨海默病转基因小鼠(3XTg-AD)购自Jackson Laboratory。转基因小鼠的遗传特征示于表2中。
[表2]
提供8周龄的转基因小鼠并使其适应环境后,为了增加转基因小鼠的数量,将小鼠以1:2的比例分成雄性和雌性,并在每个笼中繁殖约7至8天然后分离。大约7到8周后确认怀孕的小鼠在一周后分娩并经历哺育期3周。两周后,能够获得成熟小鼠。在驯化和整个实验过程中,在12小时光暗循环中将小鼠圈养在23±2℃的温度和60±10%的相对湿度。
繁殖后为了研究PEP1根据浓度的影响,将实验动物分开,然后如下施用实验材料。作为阳性对照材料,使用多奈哌齐,将实验动物分成5组,每组包括10只小鼠。每组的施用材料和剂量如下。
组1:盐水
组2:0.01mg/kg的PEP1
组3:0.1mg/kg的PEP1
组4:1mg/kg的PEP1
组5:1mg/kg多奈哌齐
PEP1、盐水和多奈哌齐以各浓度从第12个月起每周3次皮下注射2个月,1个月后(15个月龄)小鼠(每组10只小鼠)麻醉,并用0.9%生理盐水对每只小鼠心脏进行再灌注以除去血液。然后,提取大脑,分离成海马区和整个脑区,从而获得脑组织,并用液氮快速冷冻组织。
实施例2-2:端粒酶活性和测量端粒长度的方法
为了证实端粒酶活性和端粒长度随时间的减少,通过实施例2-1的方法从7个月和15个月的诱导阿尔茨海默病的动物模型获得脑组织(表示为AD Tg 7M和AD Tg15M),以测量端粒酶活性和端粒长度。
为了研究PEP1诱导的端粒酶活性,使用TeloTAGGG端粒酶PCR ELISAPLUS(目录号12 013 789 001,Roche Boehringer-Mannheim,IN,美国),将根据实施例2-1的方法制备的整个脑组织粉碎,将200μl冰冷的裂解缓冲液加入到2g至3g组织中,在冰上孵育30分钟,并以16,000x g离心20分钟以分离175μl蛋白。对10μg蛋白质定量,并与反应混合物和内标混合,然后进行PCR(参见图4)。进行杂交,将样品加入到特殊包被的MP模块中进行反应,然后在450nm或690nm使用ELISA读数器测量吸光度。使用计算公式(参见图3)计算相对端粒酶活性(RTA)。
使用TeloTAGGG端粒长度测定法(目录号12 209 136 001,Roche Boehringer-Mannheim,IN,美国)进行端粒长度的测量,将整个脑组织粉碎,然后使用High Pure PCRTemplate制备试剂盒(目录号11 796 828 001,Roche Boehringer-Mannheim,IN,美国)提取DNA,并与1μg至2μg纯化的基因组DNA和Hinf1/Rsa 1酶混合物混合,并在37℃反应2小时。反应后,将反应产物与5μl凝胶电泳上样缓冲液5x混合,并在0.8%琼脂糖凝胶中以5V/cm的速率电泳3小时。当经过反应的凝胶与HCL溶液反应10分钟时,溴酚蓝染色变为黄色。在变性溶液和中和溶液连续反应后,使用20x SSC通过Southern印迹将所得产物转移至尼龙膜至少6至12小时。在Southern转移后,将膜在120℃烘烤20分钟以将DNA固定到膜上,从而使以2x SSC缓冲液洗涤的膜杂交,并且使用图像分析仪(GE Healthcare,ImageQuant LAS4000)通过将曝光时间设定为4小时来进行图像分析(分析式参见图5)。用于成像长度测量的对照DNA(分别表示为对照DNA 1或2)是试剂盒中提供的随机序列DNA。
实施例2-3:统计验证方法
对于所有统计验证,使用SPSS 21统计程序和统计网址(http://vassarstats.net)。以间隔或比例尺度测量的数据表示为平均值±S.E.M.,对于参数分析,在单向或双向ANOVA检验后进行Tukey检验作为后验检验,并且对于非参数统计使用Kruskal-Wallis检验和Mann-Whitney U检验。组间比较采用Tukey检验进行。在名义尺度的情况下,使用卡方分析来比较各组。当p值小于0.05时,差异被认为具有统计学显著性。
[实施例3]
测量端粒酶活性和端粒长度的结果
实施例3-1:测量端粒酶活性的结果
为了确定PEP1是否增加端粒酶活性,通过实施例2-1和2-2的方法测量端粒酶活性。结果,施用PEP1(0.1mg/kg)的组(组3)显示与施用盐水的组(组1)相比增加266%,施用PEP1(1mg/kg)组(组14)与施用盐水的组(组1)相比显示增加370%,并且与施用多奈哌齐(1mg/kg)组(组5)相比显示出统计学显著的增加(参见图1)。另外,与7个月龄的小鼠(AD Tg7M)相比,证实15个月龄的小鼠(AD Tg 15M)的端粒酶活性降低。
实施例3-2:测量端粒长度的结果
为了确认PEP1诱导的端粒酶活性的增加是否对端粒长度的维持或增加具有直接影响,通过实施例2-2的方法进行了测量端粒长度的实验。结果,与端粒酶活性增加的结果相似,端粒长度随PEP1施用浓度而增加(见图2)。可以看出PEP1也增加了端粒长度,从而增加了染色体稳定性和细胞保护作用。另外,确认与7个月龄的小鼠(AD Tg 7M)相比,15个月龄的小鼠(AD Tg 15M)的端粒长度减少。
通过上述实施例,可以看出PEP1在使用动物模型的实验中具有增加端粒酶活性和端粒长度的作用。因此,根据本发明一方面的肽PEP1可以开发为能够预防、改善或治疗由端粒酶活性的异常降低或细胞中端粒长度的减少和丢失引起的疾病以及由细胞衰老引起的症状的材料,并且该材料可用于提供预防和治疗相关疾病的方法。
Claims (11)
1.一种用于预防或治疗由端粒酶活性或端粒长度减少引起的疾病或者由细胞损失和衰老引起的症状的组合物,所述组合物包含药学有效量的选自由包含SEQ ID NO:1的氨基酸序列的肽、与该氨基酸序列具有至少80%序列同源性的肽或其片段组成的组中的一种或多种。
2.如权利要求1所述的组合物,其中,所述疾病包括选自神经退行性病症、神经系统的退行性疾病、骨骼系统的退行性疾病、肌肉系统的退行性疾病、病毒感染性疾病和导致细胞加速死亡的遗传性疾病中的一种或多种。
3.如权利要求2所述的组合物,其中,所述神经系统的退行性疾病是选自脑疾病、脊髓损伤、周围神经损伤、周围神经疾病、肌萎缩侧索硬化症、痴呆、亨廷顿病、帕金森病、阿尔茨海默病、脊髓小脑变性和多发性神经病中的任一种。
4.如权利要求2所述的组合物,其中,所述导致细胞加速死亡的遗传性疾病是选自Bloom综合征和Werner综合征中的任一种。
5.如权利要求1所述的组合物,其中,所述由细胞损失和衰老引起的症状包括选自由皮肤伤口引起的组织损失、皮肤皱纹、贫血、皮肤牛皮癣和皮肤变黑中的一种或多种。
6.一种药物组合物,其包含权利要求1至5中任一项所述的组合物作为增加端粒酶活性或延长端粒长度的活性成分。
7.如权利要求6所述的药物组合物,其包含以0.1μg/kg至100mg/kg的剂量施用的SEQID NO:1的肽。
8.一种保健功能食品组合物,其包含:
权利要求1至5中任一项所述的组合物作为增加端粒酶活性或延长端粒长度的活性成分。
9.如权利要求8所述的保健功能食品组合物,其制备为选自粉末、颗粒、丸、片剂、胶囊、糖果、糖浆和饮料中的任一种制剂。
10.一种化妆品组合物,其包含:
权利要求1至5中任一项所述的组合物作为增加端粒酶活性或延长端粒长度的活性成分。
11.如权利要求10所述的化妆品组合物,其制备为选自由爽肤水、乳液、乳霜、粉底、精华素、凝胶、面膜、泡沫洁面乳、肥皂和局部使用的软膏组成的组中的任一种制剂。
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR10-2016-0042915 | 2016-04-07 | ||
KR20160042915 | 2016-04-07 | ||
PCT/KR2017/003815 WO2017176087A1 (ko) | 2016-04-07 | 2017-04-07 | 텔로머라제 활성 증가 및 텔로미어 연장 효능을 가지는 펩티드 및 이를 포함하는 조성물 |
CN201780027738.9A CN109328068A (zh) | 2016-04-07 | 2017-04-07 | 具有增加端粒酶活性和延长端粒的效果的肽以及包含该肽的组合物 |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201780027738.9A Division CN109328068A (zh) | 2016-04-07 | 2017-04-07 | 具有增加端粒酶活性和延长端粒的效果的肽以及包含该肽的组合物 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN117018162A true CN117018162A (zh) | 2023-11-10 |
Family
ID=60001390
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202310707889.6A Pending CN117018162A (zh) | 2016-04-07 | 2017-04-07 | 具有增加端粒酶活性和延长端粒的效果的肽以及组合物 |
CN201780027738.9A Pending CN109328068A (zh) | 2016-04-07 | 2017-04-07 | 具有增加端粒酶活性和延长端粒的效果的肽以及包含该肽的组合物 |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201780027738.9A Pending CN109328068A (zh) | 2016-04-07 | 2017-04-07 | 具有增加端粒酶活性和延长端粒的效果的肽以及包含该肽的组合物 |
Country Status (7)
Country | Link |
---|---|
US (1) | US10898540B2 (zh) |
EP (2) | EP4272829A3 (zh) |
JP (1) | JP7114481B2 (zh) |
KR (2) | KR20230028596A (zh) |
CN (2) | CN117018162A (zh) |
ES (1) | ES2949697T3 (zh) |
WO (1) | WO2017176087A1 (zh) |
Families Citing this family (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP3085380B1 (en) | 2013-12-17 | 2020-06-17 | Gemvax & Kael Co., Ltd. | Composition for treating prostate cancer |
KR102413243B1 (ko) | 2014-12-23 | 2022-06-27 | 주식회사 젬백스앤카엘 | 안질환 치료 펩티드 및 이를 포함하는 안질환 치료용 조성물 |
ES2799511T3 (es) | 2015-02-27 | 2020-12-18 | Gemvax & Kael Co Ltd | Péptido para prevenir la pérdida de audición, y composición que lo comprende |
KR102638286B1 (ko) | 2015-07-02 | 2024-02-20 | 주식회사 젬백스앤카엘 | 항바이러스 활성 효능을 가지는 펩티드 및 이를 포함하는 조성물 |
CN117018162A (zh) | 2016-04-07 | 2023-11-10 | 珍白斯凯尔有限公司 | 具有增加端粒酶活性和延长端粒的效果的肽以及组合物 |
US20220025352A1 (en) | 2018-10-02 | 2022-01-27 | Stemon Inc. | Method for extending telomere of cell |
CN114364392A (zh) * | 2019-05-02 | 2022-04-15 | 德克萨斯大学系统董事会 | 涉及tert激活疗法的方法和组合物 |
CN114920802B (zh) * | 2022-05-16 | 2023-05-23 | 中国地质大学(武汉) | 调节端粒酶限速蛋白运动的多肽探针及其复合物和方法 |
Family Cites Families (91)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
HU207799B (en) | 1991-07-24 | 1993-06-28 | Beres Export Import Rt | Process for producing pharmaceutical composition for influencing the reticuloendothelial system, for treating chronic pain symptomes of degenerative locomotor disorders or tumors, and for treating mucoviscidosis |
ATE279916T1 (de) | 1996-07-22 | 2004-11-15 | Renovo Ltd | Verwendung von substanzen, die die östrogen wirkung fördern, zur behandlung von wunden |
US6610839B1 (en) | 1997-08-14 | 2003-08-26 | Geron Corporation | Promoter for telomerase reverse transcriptase |
US7585622B1 (en) | 1996-10-01 | 2009-09-08 | Geron Corporation | Increasing the proliferative capacity of cells using telomerase reverse transcriptase |
EP1004313B1 (en) | 1997-05-15 | 2007-05-02 | Chugai Seiyaku Kabushiki Kaisha | Cachexia remedy |
JP2002514928A (ja) | 1997-07-01 | 2002-05-21 | キャンビア バイオシステムス リミティド ライアビリティー カンパニー | 脊椎動物テロメラーゼ遺伝子およびタンパク質ならびにその使用 |
US7030211B1 (en) | 1998-07-08 | 2006-04-18 | Gemvax As | Antigenic peptides derived from telomerase |
US6378526B1 (en) | 1998-08-03 | 2002-04-30 | Insite Vision, Incorporated | Methods of ophthalmic administration |
IL132406A0 (en) | 1998-10-21 | 2001-03-19 | Pfizer Prod Inc | Treatment of bph with cgmp elevators |
US6815426B2 (en) | 2001-02-16 | 2004-11-09 | E. I. Du Pont De Nemours And Company | Angiogenesis-inhibitory tripeptides, compositions and their methods of use |
US6967211B2 (en) | 2001-04-10 | 2005-11-22 | Nippon Shinyaku Co. Ltd. | Remedial agent for chronic articular rheumatism |
SI1425028T1 (sl) | 2001-05-16 | 2010-02-26 | Yeda Res & Dev | Uporaba inhibitorjev za il-18 za zdravljenje ali prepreäśevanje sepse |
AU2002363231A1 (en) | 2001-10-29 | 2003-05-12 | Baylor College Of Medicine | Human telomerase reverse transcriptase as a class-ii restricted tumor-associated antigen |
US7786084B2 (en) | 2001-12-21 | 2010-08-31 | Biotempt B.V. | Treatment of burns |
KR20040107492A (ko) | 2002-04-10 | 2004-12-20 | 어플라이드 리서치 시스템스 에이알에스 홀딩 엔.브이. | 섬유증 질병의 치료 및/또는 예방을 위한오스테오프로테게린의 용도 |
KR20050020987A (ko) | 2002-06-12 | 2005-03-04 | 바이오겐 아이덱 엠에이 인코포레이티드 | 아데노신 수용체 길항제를 사용하여 허혈 재관류 손상을치료하는 방법 |
WO2005000227A2 (en) | 2003-06-06 | 2005-01-06 | Intermune, Inc. | Methods of treating tnf-mediated disorders |
JP4705567B2 (ja) | 2003-06-25 | 2011-06-22 | 株式会社 キャンバス | 免疫調整活性、抗炎症活性、および抗ウイルス活性を有するペプチドおよびペプチド模倣物 |
KR20050040517A (ko) | 2003-10-29 | 2005-05-03 | 주식회사 오리엔트 | 허혈성 질환에 대한 저항성을 나타내는 형질전환 생쥐 |
DE60303854T2 (de) | 2003-11-11 | 2006-08-10 | Mattern, Udo | Nasenformulierung mit kontrollierter Freisetzung von Sexualhormonen |
GB0426146D0 (en) | 2004-11-29 | 2004-12-29 | Bioxell Spa | Therapeutic peptides and method |
WO2006102476A2 (en) | 2005-03-21 | 2006-09-28 | Vicus Therapeutics Spe 1, Llc | Compositions and methods for ameliorating cachexia |
WO2007061029A1 (ja) | 2005-11-25 | 2007-05-31 | Keio University | 前立腺癌治療剤 |
AU2006325030B2 (en) | 2005-12-16 | 2012-07-26 | Cellectis | Cell penetrating peptide conjugates for delivering nucleic acids into cells |
US20100168034A1 (en) | 2006-02-20 | 2010-07-01 | Ewha University-Industry Collaboration Foundation | Peptide having cell membrane penetrating activity |
EP2044108A4 (en) | 2006-07-24 | 2010-06-30 | Forhumantech Co Ltd | PHARMACEUTICAL COMPOSITION FOR THE TREATMENT AND TREATMENT OF ISCHEMIC SUDIDS AND METHOD FOR THEIR ADMINISTRATION |
AU2008211854C1 (en) | 2007-01-29 | 2014-01-23 | Procell Therapeutics Inc. | Novel macromolecule transduction domains and methods for identification and uses thereof |
SI2152663T1 (sl) | 2007-06-04 | 2014-08-29 | Ben Gurion University Of The Negev Research And Development Authority | Tri-arilne spojine in sestavki, ki vsebujejo isto |
CA2691980C (en) | 2007-06-29 | 2022-05-10 | Correlogic Systems, Inc. | Predictive markers for ovarian cancer |
KR20100058541A (ko) | 2007-08-15 | 2010-06-03 | 아뮤닉스 인코포레이티드 | 생물학적 활성 폴리펩티드의 특성을 변경하기 위한 조성물 및 방법 |
US8362209B2 (en) | 2007-08-23 | 2013-01-29 | University Of Medicine And Dentistry Of New Jersey | Telomerase reverse transcriptase variant |
US20090136917A1 (en) | 2007-10-25 | 2009-05-28 | Szalay Aladar A | Systems and methods for viral therapy |
GB2455539B (en) | 2007-12-12 | 2012-01-18 | Cambridge Entpr Ltd | Anti-inflammatory compositions and combinations |
TW200946541A (en) | 2008-03-27 | 2009-11-16 | Idenix Pharmaceuticals Inc | Solid forms of an anti-HIV phosphoindole compound |
CA2727388C (en) | 2008-06-16 | 2017-08-29 | Genovax S.R.L. | Telomerase-derived peptides for use in treatment of cancer |
US8252282B2 (en) | 2008-06-19 | 2012-08-28 | University Of Medicine & Dentistry Of New Jersey | Nuclear telomerase reverse transcriptase variant |
ES2334315B1 (es) | 2008-07-29 | 2011-02-28 | Universitat Pompeu Fabra | Peptidos con capacidad de penetracion celular y sus usos. |
AR072940A1 (es) | 2008-08-20 | 2010-09-29 | Schering Corp | Derivados de piridina y pirimidina sustituidos con etinilo y su uso en el tratamiento de infecciones virales |
KR20110060940A (ko) | 2008-09-22 | 2011-06-08 | 닛신 파마 가부시키가이샤 | 항염증성 펩티드 |
KR101169030B1 (ko) | 2009-01-21 | 2012-07-26 | 애니젠 주식회사 | 신규한 세포막 투과 도메인 및 이를 포함하는 세포내 전달 시스템 |
US20120053134A1 (en) | 2009-05-07 | 2012-03-01 | Jae-Hoon Jung | Pharmaceutical composition for preventing or treating neuronal damage and neurological diseases |
EP2251028A1 (en) | 2009-05-12 | 2010-11-17 | Biocompatibles Uk Ltd. | Treatment of eye diseases using encapsulated cells encoding and secreting an anti-angiogenic factor and/or a neuroprotective factor |
US7928067B2 (en) | 2009-05-14 | 2011-04-19 | Ischemix Llc | Compositions and methods for treating ischemia and ischemia-reperfusion injury |
RU2548807C2 (ru) | 2009-05-20 | 2015-04-20 | Торэй Индастриз, Инк. | Пептиды, проникающие в клетку |
KR20110057049A (ko) | 2009-11-23 | 2011-05-31 | 박의신 | 기능성 전립선염 치료제 |
KR20110062943A (ko) | 2009-12-04 | 2011-06-10 | 주식회사종근당 | 퀴나졸린 유도체를 유효성분으로 하는 전립선 비대증 예방 또는 치료제 |
KR101854926B1 (ko) | 2010-01-11 | 2018-05-04 | 큐알엔에이, 인크. | 성 호르몬 결합 글로불린 (shbg)에 대한 자연 안티센스 전사체의 저해에 의한 성 호르몬 결합 글로불린 (shbg) 관련된 질환의 치료 |
EP2536830B1 (en) | 2010-02-16 | 2019-07-17 | Ultimovacs AS | Polypeptides |
FR2960542B1 (fr) | 2010-05-27 | 2012-08-17 | Esther Suzy Arlette Fellous | Peptide en tant que medicament, en particulier pour le traitement du cancer |
KR101263212B1 (ko) | 2010-05-28 | 2013-05-10 | 성신여자대학교 산학협력단 | 신규한 세포막 투과성 펩타이드 및 그의 용도 |
WO2011150494A1 (en) | 2010-05-30 | 2011-12-08 | The Governing Council Of The University Of Toronto | Mitochondrial penetrating peptides as carriers for anticancer compounds |
KR101388372B1 (ko) | 2010-06-11 | 2014-04-23 | 한국화학연구원 | 청각보호 작용을 하는 신규 화합물 |
KR101348284B1 (ko) | 2010-09-09 | 2014-01-03 | 주식회사 나이벡 | 인간 유래 세포 투과성 펩타이드와 생리활성 펩타이드 결합체 및 그 용도 |
US20120208755A1 (en) | 2011-02-16 | 2012-08-16 | Intarcia Therapeutics, Inc. | Compositions, Devices and Methods of Use Thereof for the Treatment of Cancers |
KR20120121196A (ko) | 2011-04-26 | 2012-11-05 | 주식회사 글루칸 | 관절염 치료제 |
KR101284772B1 (ko) | 2011-05-24 | 2013-07-17 | 정종문 | 항염증, 진통효과를 가지는 기능성 식품 조성물 |
KR20120133661A (ko) | 2011-05-31 | 2012-12-11 | 주식회사 바이오포트코리아 | 아스타잔틴을 포함하는 항염증제 |
KR101288053B1 (ko) | 2011-07-04 | 2013-07-23 | 동국대학교 산학협력단 | 필발 추출물을 유효성분으로 포함하는 내이손상 예방 및 치료용 조성물 |
KR101361445B1 (ko) | 2011-12-26 | 2014-02-12 | 성균관대학교산학협력단 | 펩타이드, 5-플루오로우라실, 및 성숙수지상세포를 포함하는 암 치료용 약학적 조성물 |
SG11201404570WA (en) | 2012-02-10 | 2014-11-27 | Hakushinkouseikai Foundation | Proliferating agent for monocyte, culture medium for proliferating monocyte, method for producing monocyte, method for producing dendritic cell, and method for producing dendritic cell vaccine |
KR102041381B1 (ko) * | 2012-03-12 | 2019-11-27 | 젬백스 에이에스 | 능동적인 면역치료법을 이용한 비-소세포성 폐암의 치료 |
EP2847213B1 (en) * | 2012-05-11 | 2018-01-03 | KAEL-GemVax Co.,Ltd | Anti-inflammatory peptides and composition comprising the same |
US9844584B2 (en) | 2012-05-11 | 2017-12-19 | Gemvax & Kael Co., Ltd. | Composition for preventing or treating sepsis |
KR102578891B1 (ko) | 2012-05-11 | 2023-09-15 | 주식회사 젬백스앤카엘 | 항염증 활성을 갖는 펩티드 및 이를 포함하는 조성물 |
EP2873678B1 (en) | 2012-07-11 | 2024-06-26 | Gemvax & Kael Co.,Ltd | Conjugate comprising a cell-penetrating peptide and compositions comprising same |
US20150125438A1 (en) | 2012-07-20 | 2015-05-07 | Sang Jae Kim | Anti-Inflammatory Peptides and Composition Comprising the Same |
EP2899199B1 (en) | 2012-09-19 | 2019-07-03 | Gemvax & Kael Co., Ltd. | Cell penetrating peptide, conjugate comprising same, and composition comprising conjugate |
WO2014046478A1 (ko) | 2012-09-19 | 2014-03-27 | 주식회사 카엘젬백스 | 세포 투과성 펩티드, 그를 포함한 컨쥬게이트 및 그를 포함한 조성물 |
KR102038487B1 (ko) | 2012-09-19 | 2019-10-30 | 주식회사 젬백스앤카엘 | 텔로머라제 펩티드를 포함하는 항균 또는 항진균용 조성물 |
EP2899201B1 (en) | 2012-09-19 | 2019-09-11 | Gemvax & Kael Co., Ltd. | Cell penetrating peptide, conjugate comprising same, and composition comprising conjugate |
WO2014046983A1 (en) | 2012-09-21 | 2014-03-27 | Intensity Therapeutic | Method of treating cancer |
KR20140104288A (ko) | 2013-02-20 | 2014-08-28 | 주식회사 카엘젬백스 | Tnf-알파 저해제 |
IL240680B2 (en) | 2013-02-22 | 2023-03-01 | Univ Leland Stanford Junior | Nucleic acids encoding telomerase reverse transcriptase, preparations containing them and their uses |
WO2014171792A1 (ko) | 2013-04-19 | 2014-10-23 | 주식회사 카엘젬백스 | 허혈성 손상 치료 및 예방용 조성물 |
KR102077983B1 (ko) * | 2013-05-29 | 2020-02-17 | 주식회사 젬백스앤카엘 | 피부 주름 개선 및 미백용 조성물 |
CA2912557A1 (en) | 2013-06-07 | 2014-12-11 | Gemvax & Kael Co., Ltd. | Biological markers useful in cancer immunotherapy |
ES2808076T3 (es) | 2013-06-21 | 2021-02-25 | Gemvax & Kael Co Ltd | Regulador de la secreción hormonal, composición que lo contiene y procedimiento para controlar la secreción hormonal mediante su uso |
EP3061459B1 (en) | 2013-10-23 | 2019-12-11 | Gemvax & Kael Co., Ltd. | Composition for treating and preventing benign prostatic hyperplasia |
EP2871235A1 (en) * | 2013-11-07 | 2015-05-13 | Centre National de la Recherche Scientifique (CNRS) | New methods to produce active hTERT |
WO2015076621A1 (ko) | 2013-11-22 | 2015-05-28 | 주식회사 카엘젬백스 | 혈관 신생 억제 활성을 가지는 펩티드 및 이를 포함하는 조성물 |
EP3085380B1 (en) | 2013-12-17 | 2020-06-17 | Gemvax & Kael Co., Ltd. | Composition for treating prostate cancer |
WO2015156649A1 (ko) | 2014-04-11 | 2015-10-15 | 주식회사 젬백스앤카엘 | 섬유증 억제 활성을 가지는 펩티드 및 이를 포함하는 조성물 |
ES2962532T3 (es) | 2014-04-30 | 2024-03-19 | Gemvax & Kael Co Ltd | Composición para el trasplante de órganos, tejidos o células, kit y procedimiento de trasplante |
KR102232319B1 (ko) * | 2014-05-09 | 2021-03-26 | 주식회사 젬백스앤카엘 | 텔로머라제 펩티드를 유효성분으로 포함하는 뇌혈관 질환 예방 또는 치료용 조성물 |
KR20160010212A (ko) * | 2014-07-18 | 2016-01-27 | 주식회사 젬백스앤카엘 | 항노화 및 창상 치료용 펩티드 및 이를 포함하는 조성물 |
KR102413243B1 (ko) | 2014-12-23 | 2022-06-27 | 주식회사 젬백스앤카엘 | 안질환 치료 펩티드 및 이를 포함하는 안질환 치료용 조성물 |
ES2799511T3 (es) | 2015-02-27 | 2020-12-18 | Gemvax & Kael Co Ltd | Péptido para prevenir la pérdida de audición, y composición que lo comprende |
KR102638286B1 (ko) | 2015-07-02 | 2024-02-20 | 주식회사 젬백스앤카엘 | 항바이러스 활성 효능을 가지는 펩티드 및 이를 포함하는 조성물 |
EP3372613A4 (en) * | 2015-11-03 | 2019-07-10 | Gemvax & Kael Co., Ltd. | PEPTIDE WITH NERVE DAMAGE PREVENTION AND REGENERATION EFFECT AND COMPOSITION THEREOF |
KR20170054310A (ko) | 2015-11-09 | 2017-05-17 | 주식회사 젬백스앤카엘 | 텔로머라제 유래 펩티드를 포함하는 수지상세포 치료제 및 면역 치료제, 및 이를 사용하는 치료방법 |
CN117018162A (zh) | 2016-04-07 | 2023-11-10 | 珍白斯凯尔有限公司 | 具有增加端粒酶活性和延长端粒的效果的肽以及组合物 |
-
2017
- 2017-04-07 CN CN202310707889.6A patent/CN117018162A/zh active Pending
- 2017-04-07 KR KR1020237005976A patent/KR20230028596A/ko active IP Right Grant
- 2017-04-07 ES ES17779387T patent/ES2949697T3/es active Active
- 2017-04-07 EP EP23177454.8A patent/EP4272829A3/en active Pending
- 2017-04-07 US US16/091,674 patent/US10898540B2/en active Active
- 2017-04-07 KR KR1020187028703A patent/KR20180123512A/ko active Application Filing
- 2017-04-07 EP EP17779387.4A patent/EP3441082B1/en active Active
- 2017-04-07 CN CN201780027738.9A patent/CN109328068A/zh active Pending
- 2017-04-07 WO PCT/KR2017/003815 patent/WO2017176087A1/ko active Application Filing
- 2017-04-07 JP JP2018552817A patent/JP7114481B2/ja active Active
Also Published As
Publication number | Publication date |
---|---|
US20190142894A1 (en) | 2019-05-16 |
KR20180123512A (ko) | 2018-11-16 |
WO2017176087A1 (ko) | 2017-10-12 |
EP4272829A2 (en) | 2023-11-08 |
KR20230028596A (ko) | 2023-02-28 |
US10898540B2 (en) | 2021-01-26 |
JP2019513750A (ja) | 2019-05-30 |
EP3441082C0 (en) | 2023-06-21 |
ES2949697T3 (es) | 2023-10-02 |
EP3441082B1 (en) | 2023-06-21 |
EP4272829A3 (en) | 2024-01-17 |
EP3441082A4 (en) | 2019-12-25 |
EP3441082A1 (en) | 2019-02-13 |
JP7114481B2 (ja) | 2022-08-08 |
CN109328068A (zh) | 2019-02-12 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US10898540B2 (en) | Peptide having effects of increasing telomerase activity and extending telomere, and composition containing same | |
KR101873773B1 (ko) | 류마티즘 관절염 예방 또는 치료 조성물 | |
CN107405380B (zh) | 用于预防听觉损伤的肽及其包含该肽的组合物 | |
US10487113B2 (en) | Peptide having activity to improve skin condition and use thereof | |
CN107667112B (zh) | 新型肽和含有其的组合物 | |
US11872263B2 (en) | AIMP1 protein fragment and hair growth-promoting composition containing same as active ingredient | |
US6180761B1 (en) | Casein from Korean cattle | |
EP3428178A1 (en) | Peptide for preventing or treating inflammatory diseases and use thereof | |
KR101953298B1 (ko) | 우르소데옥시콜산을 함유하는 염증성 질환 또는 척수 손상 예방 또는 치료용 조성물 | |
KR102239075B1 (ko) | IF1 (ATPase inhibitory factor 1)을 유효성분으로 함유하는 근감소증의 예방 또는 치료용 약학 조성물 | |
JP6877924B2 (ja) | 表皮細胞間機能強化剤 | |
KR102499918B1 (ko) | 근위축성 측삭 경화증 치료제 | |
JP2016513645A (ja) | 肥満の処置および体重の制御のための化合物および方法 | |
EP2617432B1 (en) | Brain function enhancement composition and method for enhancing brain function | |
KR20190139910A (ko) | 브라시카세아에 단백질 추출물 및 그의 용도 | |
KR102506076B1 (ko) | 황산아연, 락토바실러스 애시도필러스 및 코엔자임 q를 포함하는 면역질환의 예방 또는 치료용 조성물 | |
KR20190036314A (ko) | 탈모 방지 및 발모 촉진용 조성물 | |
JP6917164B2 (ja) | 小胞体ストレス軽減用組成物及び該組成物を含む食品、医薬品、飼料 | |
CN113853211A (zh) | 包含环(组氨酸-脯氨酸)二肽及甲状旁腺激素的组合物用于预防、改善或治疗骨质流失疾病的用途 | |
JP2015107931A (ja) | グリセルアルデヒド3リン酸脱水素酵素(gapdh)由来ペプチド及びこれを含む抗アレルギー組成物 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination |