JP2005502672A - サイモシンβ４、類似体、アイソフォームおよびその他の誘導体を用いて心筋障害の発生前、発生中または発生後に発生する炎症、損傷およびその他の変化を治癒または予防する方法 - Google Patents
サイモシンβ４、類似体、アイソフォームおよびその他の誘導体を用いて心筋障害の発生前、発生中または発生後に発生する炎症、損傷およびその他の変化を治癒または予防する方法 Download PDFInfo
- Publication number
- JP2005502672A JP2005502672A JP2003524529A JP2003524529A JP2005502672A JP 2005502672 A JP2005502672 A JP 2005502672A JP 2003524529 A JP2003524529 A JP 2003524529A JP 2003524529 A JP2003524529 A JP 2003524529A JP 2005502672 A JP2005502672 A JP 2005502672A
- Authority
- JP
- Japan
- Prior art keywords
- composition
- thymosin
- polypeptide
- damage
- amino acid
- 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
- 102000001708 Protein Isoforms Human genes 0.000 title claims abstract description 26
- 108010029485 Protein Isoforms Proteins 0.000 title claims abstract description 26
- 230000006378 damage Effects 0.000 title claims abstract description 21
- 102100035000 Thymosin beta-4 Human genes 0.000 title claims abstract description 19
- 108010079996 thymosin beta(4) Proteins 0.000 title claims abstract description 19
- UGPMCIBIHRSCBV-XNBOLLIBSA-N Thymosin beta 4 Chemical compound N([C@@H](CC(O)=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(O)=O)C(=O)[C@@H]1CCCN1C(=O)[C@H](CCCCN)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(C)=O UGPMCIBIHRSCBV-XNBOLLIBSA-N 0.000 title claims abstract description 17
- 208000037891 myocardial injury Diseases 0.000 title claims abstract description 15
- 238000000034 method Methods 0.000 title claims description 26
- 206010061218 Inflammation Diseases 0.000 title abstract description 8
- 230000004054 inflammatory process Effects 0.000 title abstract description 8
- -1 analogs Proteins 0.000 title description 6
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 23
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract description 22
- 230000003110 anti-inflammatory effect Effects 0.000 claims abstract description 14
- 230000002491 angiogenic effect Effects 0.000 claims abstract description 10
- 239000000203 mixture Substances 0.000 claims description 30
- 229920001184 polypeptide Polymers 0.000 claims description 14
- 230000035876 healing Effects 0.000 claims description 12
- 239000000126 substance Substances 0.000 claims description 10
- 230000002265 prevention Effects 0.000 claims description 8
- 230000001737 promoting effect Effects 0.000 claims description 7
- 210000004351 coronary vessel Anatomy 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 238000002560 therapeutic procedure Methods 0.000 claims description 4
- 239000005557 antagonist Substances 0.000 claims description 3
- 210000004899 c-terminal region Anatomy 0.000 claims description 3
- 125000003275 alpha amino acid group Chemical group 0.000 claims 4
- 150000003462 sulfoxides Chemical class 0.000 claims 2
- 230000001023 pro-angiogenic effect Effects 0.000 claims 1
- 208000027418 Wounds and injury Diseases 0.000 abstract description 9
- 208000014674 injury Diseases 0.000 abstract description 9
- 108010085238 Actins Proteins 0.000 description 21
- 102000007469 Actins Human genes 0.000 description 21
- 238000006116 polymerization reaction Methods 0.000 description 16
- 150000001413 amino acids Chemical group 0.000 description 12
- 108090000623 proteins and genes Proteins 0.000 description 10
- 235000018102 proteins Nutrition 0.000 description 9
- 102000004169 proteins and genes Human genes 0.000 description 9
- 230000033115 angiogenesis Effects 0.000 description 7
- 230000000694 effects Effects 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 5
- 230000014509 gene expression Effects 0.000 description 5
- 230000002401 inhibitory effect Effects 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 4
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 4
- 230000002526 effect on cardiovascular system Effects 0.000 description 4
- 210000002216 heart Anatomy 0.000 description 4
- 210000003709 heart valve Anatomy 0.000 description 4
- 208000010125 myocardial infarction Diseases 0.000 description 4
- 239000008194 pharmaceutical composition Substances 0.000 description 4
- 230000009466 transformation Effects 0.000 description 4
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 3
- 108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 3
- 102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 3
- 102000013275 Somatomedins Human genes 0.000 description 3
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 3
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 3
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 3
- 235000001014 amino acid Nutrition 0.000 description 3
- 229940024606 amino acid Drugs 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 230000036770 blood supply Effects 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 239000012634 fragment Substances 0.000 description 3
- 210000005003 heart tissue Anatomy 0.000 description 3
- 230000006698 induction Effects 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 230000002107 myocardial effect Effects 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 3
- QQKKFVXSQXUHPI-NBVRZTHBSA-N Acidissiminol epoxide Chemical compound O1C(C)(C)C1CC(O)C(/C)=C/COC(C=C1)=CC=C1CCNC(=O)C1=CC=CC=C1 QQKKFVXSQXUHPI-NBVRZTHBSA-N 0.000 description 2
- 108010038798 Actin Depolymerizing Factors Proteins 0.000 description 2
- 102000015693 Actin Depolymerizing Factors Human genes 0.000 description 2
- 102000019034 Chemokines Human genes 0.000 description 2
- 108010012236 Chemokines Proteins 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- 108010008286 DNA nucleotidylexotransferase Proteins 0.000 description 2
- 102100033215 DNA nucleotidylexotransferase Human genes 0.000 description 2
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 2
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 2
- 101710138529 Depactin Proteins 0.000 description 2
- 102000004878 Gelsolin Human genes 0.000 description 2
- 108090001064 Gelsolin Proteins 0.000 description 2
- 102000002151 Microfilament Proteins Human genes 0.000 description 2
- 108010040897 Microfilament Proteins Proteins 0.000 description 2
- 102000007079 Peptide Fragments Human genes 0.000 description 2
- 108010033276 Peptide Fragments Proteins 0.000 description 2
- 108050001408 Profilin Proteins 0.000 description 2
- 102000011195 Profilin Human genes 0.000 description 2
- FCHAMFUEENBIDH-UHFFFAOYSA-N Severin Natural products CC1CCC2C(C)C3CCC4(O)C(CC5C4CC(O)C6CC(CCC56C)OC(=O)C)C3CN2C1 FCHAMFUEENBIDH-UHFFFAOYSA-N 0.000 description 2
- 108010078233 Thymalfasin Proteins 0.000 description 2
- 102400000800 Thymosin alpha-1 Human genes 0.000 description 2
- 108010009583 Transforming Growth Factors Proteins 0.000 description 2
- 102000009618 Transforming Growth Factors Human genes 0.000 description 2
- 206010053648 Vascular occlusion Diseases 0.000 description 2
- 102000050760 Vitamin D-binding protein Human genes 0.000 description 2
- 101710179590 Vitamin D-binding protein Proteins 0.000 description 2
- 230000000692 anti-sense effect Effects 0.000 description 2
- 229960000074 biopharmaceutical Drugs 0.000 description 2
- 210000004413 cardiac myocyte Anatomy 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 230000024245 cell differentiation Effects 0.000 description 2
- 239000005482 chemotactic factor Substances 0.000 description 2
- 239000000512 collagen gel Substances 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 230000005786 degenerative changes Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 210000002889 endothelial cell Anatomy 0.000 description 2
- 230000009762 endothelial cell differentiation Effects 0.000 description 2
- 230000010595 endothelial cell migration Effects 0.000 description 2
- 229940087051 fragmin Drugs 0.000 description 2
- 239000003102 growth factor Substances 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 108091033319 polynucleotide Proteins 0.000 description 2
- 102000040430 polynucleotide Human genes 0.000 description 2
- 239000002157 polynucleotide Substances 0.000 description 2
- 230000001568 sexual effect Effects 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- NZVYCXVTEHPMHE-ZSUJOUNUSA-N thymalfasin Chemical compound CC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O NZVYCXVTEHPMHE-ZSUJOUNUSA-N 0.000 description 2
- 229960004231 thymalfasin Drugs 0.000 description 2
- 208000019553 vascular disease Diseases 0.000 description 2
- 208000021331 vascular occlusion disease Diseases 0.000 description 2
- 108090000195 villin Proteins 0.000 description 2
- 101000644420 Aplysia californica Thymosin beta Proteins 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 102000053642 Catalytic RNA Human genes 0.000 description 1
- 108090000994 Catalytic RNA Proteins 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 101150021185 FGF gene Proteins 0.000 description 1
- 102000009123 Fibrin Human genes 0.000 description 1
- 108010073385 Fibrin Proteins 0.000 description 1
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 1
- 102100024785 Fibroblast growth factor 2 Human genes 0.000 description 1
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 description 1
- 108090000385 Fibroblast growth factor 7 Proteins 0.000 description 1
- 108700039691 Genetic Promoter Regions Proteins 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 102000048143 Insulin-Like Growth Factor II Human genes 0.000 description 1
- 108090001117 Insulin-Like Growth Factor II Proteins 0.000 description 1
- 102000000589 Interleukin-1 Human genes 0.000 description 1
- 108010002352 Interleukin-1 Proteins 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 208000021908 Myocardial disease Diseases 0.000 description 1
- 102100037925 Prothymosin alpha Human genes 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 206010057469 Vascular stenosis Diseases 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 239000002870 angiogenesis inducing agent Substances 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 230000023555 blood coagulation Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 230000012292 cell migration Effects 0.000 description 1
- 230000010307 cell transformation Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000003399 chemotactic effect Effects 0.000 description 1
- 230000008473 connective tissue growth Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 230000003412 degenerative effect Effects 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 210000001174 endocardium Anatomy 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 230000009786 epithelial differentiation Effects 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 229950003499 fibrin Drugs 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 239000003630 growth substance Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 210000003361 heart septum Anatomy 0.000 description 1
- 125000001165 hydrophobic group Chemical group 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 230000036244 malformation Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 230000003680 myocardial damage Effects 0.000 description 1
- 208000031225 myocardial ischemia Diseases 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 239000000816 peptidomimetic Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000009805 platelet accumulation Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 108010014750 prothymosin alpha Proteins 0.000 description 1
- 108091092562 ribozyme Proteins 0.000 description 1
- 238000011808 rodent model Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- 208000037816 tissue injury Diseases 0.000 description 1
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 230000004218 vascular function Effects 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- 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
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/2292—Thymosin; Related peptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/26—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against hormones ; against hormone releasing or inhibiting factors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Endocrinology (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Cardiology (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Heart & Thoracic Surgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US31534701P | 2001-08-29 | 2001-08-29 | |
| PCT/US2002/027520 WO2003020215A2 (en) | 2001-08-29 | 2002-08-29 | Methods of treating mycocardial event related coditions with thymosin beta 4 |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2009123032A Division JP2009221211A (ja) | 2001-08-29 | 2009-05-21 | サイモシンβ４、類似体、アイソフォームおよびその他の誘導体の使用 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2005502672A true JP2005502672A (ja) | 2005-01-27 |
| JP2005502672A5 JP2005502672A5 (enExample) | 2006-01-05 |
Family
ID=23223988
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2003524529A Pending JP2005502672A (ja) | 2001-08-29 | 2002-08-29 | サイモシンβ４、類似体、アイソフォームおよびその他の誘導体を用いて心筋障害の発生前、発生中または発生後に発生する炎症、損傷およびその他の変化を治癒または予防する方法 |
| JP2009123032A Ceased JP2009221211A (ja) | 2001-08-29 | 2009-05-21 | サイモシンβ４、類似体、アイソフォームおよびその他の誘導体の使用 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2009123032A Ceased JP2009221211A (ja) | 2001-08-29 | 2009-05-21 | サイモシンβ４、類似体、アイソフォームおよびその他の誘導体の使用 |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US9056087B2 (enExample) |
| EP (1) | EP1427432A4 (enExample) |
| JP (2) | JP2005502672A (enExample) |
| CN (2) | CN101549148A (enExample) |
| AU (1) | AU2002336408B2 (enExample) |
| CA (1) | CA2458883C (enExample) |
| MX (1) | MXPA04001942A (enExample) |
| WO (1) | WO2003020215A2 (enExample) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2009502938A (ja) * | 2005-07-26 | 2009-01-29 | リジェナークス・バイオファーマスーティカルズ・インコーポレイテッド | 鬱血性心不全が原因である組織の劣化、損傷、または破損を処置または予防する方法 |
| JP2011514383A (ja) * | 2008-03-17 | 2011-05-06 | リジェナークス・バイオファーマスーティカルズ・インコーポレイテッド | 改良されたベータチモシンフラグメント |
Families Citing this family (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2266595A3 (en) * | 2002-02-06 | 2011-07-06 | Regenerx Biopharmaceuticals, Inc. | Treatment of infections and other disorders |
| WO2006076254A2 (en) * | 2005-01-11 | 2006-07-20 | Regenerx Biopharmaceuticals, Inc. | Method of treating or preventing respiratory microbial infection of respiratory tissue |
| US20080051348A1 (en) * | 2002-02-06 | 2008-02-28 | Regenerx Biopharmaceuticals, Inc. | Treatment of infections and other disorders |
| CN1852727A (zh) * | 2003-03-31 | 2006-10-25 | 雷金纳克斯生物制药公司 | 递送胸腺素β4、类似物、同工型和其它衍生物的组合物和方法 |
| CA2532542A1 (en) * | 2003-07-18 | 2005-01-27 | Regenerx Biopharmaceuticals, Inc. | Treatment or prevention of damage due to radiation exposure |
| US20090053194A1 (en) * | 2003-12-22 | 2009-02-26 | Regenerx Biopharmaceuticals, Inc. | Method of treating or preventing biological or immunological responses to a reactive chemical or biological or toxic agent |
| WO2005087805A1 (en) * | 2004-03-05 | 2005-09-22 | Regenerx Biopharmaceuticals, Inc. | Treating or preventing extracellular matrix build-up |
| JP2008510732A (ja) * | 2004-08-20 | 2008-04-10 | ザ・ボード・オブ・リージェンツ・オブ・ザ・ユニバーシティ・オブ・テキサス・システム | 心臓組織の損傷を処置、予防、阻害、または緩和する方法 |
| US7531318B2 (en) | 2004-08-20 | 2009-05-12 | Board Of Regents, The University Of Texas System | Screening of agents for activity against ischemic myocardial insults |
| CA2612522A1 (en) * | 2005-06-17 | 2006-12-28 | Regenerx Biopharmaceuticals, Inc. | Lkktet and/or lkktnt peptide compositions and methods |
| WO2007014254A2 (en) * | 2005-07-26 | 2007-02-01 | Regenerx Biopharmaceuticals, Inc. | Method of treating or preventing tissue deterioration, injury or damage due to hypertrophic muscle disease |
| CN100372572C (zh) * | 2005-09-29 | 2008-03-05 | 北京诺思兰德生物技术有限责任公司 | 携带人胸腺素β4基因的重组质粒 |
| US8399412B2 (en) * | 2006-10-06 | 2013-03-19 | Regenerx Biopharmaceuticals, Inc. | Method of treating or preventing tissue deterioration, injury or damage due to periodontal disease or disease of oral mucosa, and/or downregulating NF-kappabeta or supressing NF-kappabeta-mediated actions |
| HUP0600814A3 (en) * | 2006-10-27 | 2009-08-28 | Biostatin Gyogyszerkutato Fejl | Peptides for activation of angiogenesis, pharmaceutical compounds containing same and use of these compounds |
| KR101297037B1 (ko) * | 2010-03-26 | 2013-08-14 | 숙명여자대학교산학협력단 | 혈관신생촉진용 펩타이드 및 이의 용도 |
| BR112013000923A2 (pt) * | 2010-07-14 | 2016-05-17 | Adistem Ltd | método de tratamento de hiv ou aids |
| WO2012044783A2 (en) * | 2010-09-30 | 2012-04-05 | Regenerx Biopharmaceuticals, Inc. | Method of achieving a thymosin beta 4 concentration in a human patient |
| JP6889771B2 (ja) * | 2016-07-18 | 2021-06-18 | リジェンツリー リミテッド ライアビリティ カンパニー | ドライアイ症候群を治療する方法 |
| WO2021225960A2 (en) * | 2020-05-05 | 2021-11-11 | Regenerx Biopharmaceuticals, Inc. | Beta thymosin peptides for treating viral infections |
| CN111821424B (zh) * | 2020-07-21 | 2023-03-31 | 广东海洋大学深圳研究院 | 胸腺素及其衍生物的应用和治疗抑郁症的药物 |
| CN112023027B (zh) * | 2020-07-21 | 2023-03-14 | 广东海洋大学 | 胸腺素或其衍生物的应用和治疗快感缺乏型抑郁症的药物 |
Family Cites Families (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4297276A (en) * | 1979-03-23 | 1981-10-27 | Hoffman-La Roche Inc. | Thymosin beta 3 and beta 4 |
| JPS61500431A (ja) | 1982-12-09 | 1986-03-13 | ビルトン，ジエラルド エル． | 傷治癒に有用な活性化され、安定化された酵素 |
| US4543340A (en) | 1983-04-07 | 1985-09-24 | George Washington University | Radioimmunoassay of thymosin β4 |
| JPH02124815A (ja) | 1987-10-29 | 1990-05-14 | Takeda Chem Ind Ltd | 血管形成促進剤 |
| US5654267A (en) | 1988-12-20 | 1997-08-05 | La Jolla Cancer Research Center | Cooperative combinations of ligands contained within a matrix |
| JPH03178988A (ja) | 1989-09-14 | 1991-08-02 | Takeda Chem Ind Ltd | 生理活性物質ｔａｎ―８８３、その製造法および用途 |
| CN1173991C (zh) | 1992-11-13 | 2004-11-03 | 马克斯普朗克科学促进协会 | 作为血管内皮生长因子受体的f1k-1 |
| EP0725652A1 (en) | 1993-10-07 | 1996-08-14 | The George Washington University Medical Center | METHOD OF TREATING SEPTIC SHOCK USING THYMOSIN $g(b) 4? |
| US5578570A (en) | 1993-10-07 | 1996-11-26 | The George Washington University Medical Center | Method of treating septic shock using thymosin β4 |
| AU3733295A (en) | 1994-10-06 | 1996-05-02 | Alpha 1 Biomedicals, Inc. | Treatment of obstructive airway disease by administering thymosin beta 4, or coadministration of thymosin beta 4 and dnase i |
| US5663071A (en) | 1996-06-17 | 1997-09-02 | Children's Medical Center Corporation | Human thymosin β 15 gene, protein and uses thereof |
| US6013780A (en) * | 1996-09-06 | 2000-01-11 | Technion Research & Development Co. Ltd. | VEGF145 expression vectors |
| GB9806632D0 (en) | 1998-03-28 | 1998-05-27 | Stevenson Robert | Peptide factor |
| JP4301602B2 (ja) | 1998-09-28 | 2009-07-22 | 株式会社マルハニチロ水産 | 血管内皮細胞増殖促進剤 |
| PT1100529E (pt) | 1998-07-30 | 2005-10-31 | Us Gov Health & Human Serv | A timosina beta 4 promove a preparacao de feridas |
| US7560280B2 (en) * | 2000-11-03 | 2009-07-14 | Kourion Therapeutics Gmbh | Human cord blood derived unrestricted somatic stem cells (USSC) |
-
2002
- 2002-08-29 AU AU2002336408A patent/AU2002336408B2/en not_active Ceased
- 2002-08-29 US US10/488,084 patent/US9056087B2/en not_active Expired - Lifetime
- 2002-08-29 CN CNA200910118323XA patent/CN101549148A/zh active Pending
- 2002-08-29 EP EP02773255A patent/EP1427432A4/en not_active Ceased
- 2002-08-29 WO PCT/US2002/027520 patent/WO2003020215A2/en not_active Ceased
- 2002-08-29 MX MXPA04001942A patent/MXPA04001942A/es active IP Right Grant
- 2002-08-29 JP JP2003524529A patent/JP2005502672A/ja active Pending
- 2002-08-29 CA CA2458883A patent/CA2458883C/en not_active Expired - Fee Related
- 2002-08-29 CN CNA028166884A patent/CN1547480A/zh active Pending
-
2009
- 2009-05-21 JP JP2009123032A patent/JP2009221211A/ja not_active Ceased
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2009502938A (ja) * | 2005-07-26 | 2009-01-29 | リジェナークス・バイオファーマスーティカルズ・インコーポレイテッド | 鬱血性心不全が原因である組織の劣化、損傷、または破損を処置または予防する方法 |
| US8093214B2 (en) | 2005-07-26 | 2012-01-10 | Regenerx Biopharmaceuticals, Inc. | Method of treating or preventing tissue deterioration, injury or damage due to congestive heart failure |
| JP2011514383A (ja) * | 2008-03-17 | 2011-05-06 | リジェナークス・バイオファーマスーティカルズ・インコーポレイテッド | 改良されたベータチモシンフラグメント |
Also Published As
| Publication number | Publication date |
|---|---|
| CA2458883A1 (en) | 2003-03-13 |
| EP1427432A4 (en) | 2008-01-23 |
| US9056087B2 (en) | 2015-06-16 |
| CA2458883C (en) | 2017-11-28 |
| JP2009221211A (ja) | 2009-10-01 |
| WO2003020215A2 (en) | 2003-03-13 |
| CN101549148A (zh) | 2009-10-07 |
| WO2003020215A3 (en) | 2004-03-25 |
| CN1547480A (zh) | 2004-11-17 |
| AU2002336408B2 (en) | 2006-12-21 |
| EP1427432A2 (en) | 2004-06-16 |
| MXPA04001942A (es) | 2004-07-23 |
| US20040258680A1 (en) | 2004-12-23 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2009221211A (ja) | サイモシンβ４、類似体、アイソフォームおよびその他の誘導体の使用 | |
| AU2002336408A1 (en) | Methods of healing or preventing inflammation, damage and other changes that occur prior to, during or immediately after a myocardial event with thymosin beta 4, analogues, isoforms and other derivatives | |
| JP2009046502A (ja) | 皮膚状態の改善を促進するための組成物の製造のための、アミノ酸配列ｌｋｋｔｅｔを含む皮膚変性阻害ポリペプチドの使用 | |
| US8716215B2 (en) | Method of treating or preventing tissue deterioration, injury or damage due to a neuro-, muscular- or neuro-muscular-degenerative disease, or restore tissue adversely affected by said disease | |
| US20060246057A1 (en) | Treatment or prevention of damage due to radiation exposure | |
| JP2007521336A5 (enExample) | ||
| JP2007521336A (ja) | 反応性化学物質、生物学的物質、もしくは毒素に対する、生物学的もしくは免疫学的応答を、処理もしくは防止する方法 | |
| AU2002213513A1 (en) | Inhibition or reversal of skin aging by actin-sequestering peptides | |
| JP2004525988A (ja) | サイモシンβ４を用いる表皮水疱症（ＥｐｉｄｅｒｍｏｌｙｓｉｓＢｕｌｌｏｓａ）の治療 | |
| AU2002309842A1 (en) | Treating epidermlyosis bullosa with thymosin beta 4 | |
| US20040067227A1 (en) | Inhibition or reversal of skin aging by actin-sequestering peptides | |
| AU2005222085B2 (en) | Treating or preventing extracellular matrix build-up | |
| HK1136216A (en) | Use of polypeptides for preparing medicines of promoting the transformation of cardiac endothelial cells to mesenchymal cells | |
| KR20080016675A (ko) | 세포 핵-엔터링 조성물 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20050706 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20050706 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20080909 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20081203 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20090127 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20090423 |