DE60026826T2 - Alterungsschutztetrapeptid, dieses enthaltende pharmazeutische zusammensetzungen und seine verwendung - Google Patents
Alterungsschutztetrapeptid, dieses enthaltende pharmazeutische zusammensetzungen und seine verwendung Download PDFInfo
- Publication number
- DE60026826T2 DE60026826T2 DE60026826T DE60026826T DE60026826T2 DE 60026826 T2 DE60026826 T2 DE 60026826T2 DE 60026826 T DE60026826 T DE 60026826T DE 60026826 T DE60026826 T DE 60026826T DE 60026826 T2 DE60026826 T2 DE 60026826T2
- Authority
- DE
- Germany
- Prior art keywords
- tetrapeptide
- glu
- asp
- ala
- gly
- 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.)
- Expired - Lifetime
Links
- 230000032683 aging Effects 0.000 title description 27
- 239000008194 pharmaceutical composition Substances 0.000 title 1
- 239000000126 substance Substances 0.000 claims abstract description 37
- 230000002398 geroprotective effect Effects 0.000 claims abstract description 23
- 150000003839 salts Chemical class 0.000 claims abstract description 23
- 239000003814 drug Substances 0.000 claims abstract description 20
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 7
- 239000011734 sodium Substances 0.000 claims abstract description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims abstract description 6
- 206010063493 Premature ageing Diseases 0.000 claims abstract description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 6
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims abstract description 5
- 125000003277 amino group Chemical group 0.000 claims abstract description 5
- 239000011575 calcium Substances 0.000 claims abstract description 5
- 239000011777 magnesium Substances 0.000 claims abstract description 5
- 230000002265 prevention Effects 0.000 claims abstract description 5
- 239000011701 zinc Substances 0.000 claims abstract description 5
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims abstract description 4
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims abstract description 4
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims abstract description 4
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims abstract description 4
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims abstract description 4
- 229910052791 calcium Inorganic materials 0.000 claims abstract description 4
- 229910052744 lithium Inorganic materials 0.000 claims abstract description 4
- 229910052749 magnesium Inorganic materials 0.000 claims abstract description 4
- 239000011591 potassium Substances 0.000 claims abstract description 4
- 229910052700 potassium Inorganic materials 0.000 claims abstract description 4
- 229910052708 sodium Inorganic materials 0.000 claims abstract description 4
- ZMANZCXQSJIPKH-UHFFFAOYSA-O triethylammonium ion Chemical compound CC[NH+](CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-O 0.000 claims abstract description 4
- 229910052725 zinc Inorganic materials 0.000 claims abstract description 4
- 230000000694 effects Effects 0.000 claims description 24
- 239000000203 mixture Substances 0.000 claims description 22
- DRLFMBDRBRZALE-UHFFFAOYSA-N melatonin Chemical compound COC1=CC=C2NC=C(CCNC(C)=O)C2=C1 DRLFMBDRBRZALE-UHFFFAOYSA-N 0.000 claims description 19
- YJPIGAIKUZMOQA-UHFFFAOYSA-N Melatonin Natural products COC1=CC=C2N(C(C)=O)C=C(CCN)C2=C1 YJPIGAIKUZMOQA-UHFFFAOYSA-N 0.000 claims description 17
- 229960003987 melatonin Drugs 0.000 claims description 17
- -1 lipid peroxide Chemical class 0.000 claims description 11
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 claims description 6
- 229960001138 acetylsalicylic acid Drugs 0.000 claims description 6
- 208000032038 Premature aging Diseases 0.000 claims description 5
- 208000006673 asthma Diseases 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 230000003647 oxidation Effects 0.000 claims description 5
- 238000007254 oxidation reaction Methods 0.000 claims description 5
- 208000030603 inherited susceptibility to asthma Diseases 0.000 claims description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 2
- 238000007911 parenteral administration Methods 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 27
- 230000000144 pharmacologic effect Effects 0.000 abstract description 21
- 230000001225 therapeutic effect Effects 0.000 abstract description 8
- 150000001875 compounds Chemical class 0.000 abstract description 6
- 230000037396 body weight Effects 0.000 abstract description 5
- 230000000069 prophylactic effect Effects 0.000 abstract description 5
- 241000255601 Drosophila melanogaster Species 0.000 description 26
- 241001465754 Metazoa Species 0.000 description 24
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
- 238000002474 experimental method Methods 0.000 description 20
- 239000000243 solution Substances 0.000 description 19
- 238000012360 testing method Methods 0.000 description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 16
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 16
- 241000255925 Diptera Species 0.000 description 13
- 230000003064 anti-oxidating effect Effects 0.000 description 13
- 229940079593 drug Drugs 0.000 description 13
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 12
- 230000007123 defense Effects 0.000 description 12
- 102000016938 Catalase Human genes 0.000 description 11
- 230000015572 biosynthetic process Effects 0.000 description 11
- 239000000047 product Substances 0.000 description 11
- 238000003786 synthesis reaction Methods 0.000 description 11
- 108010053835 Catalase Proteins 0.000 description 10
- 241000699670 Mus sp. Species 0.000 description 10
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- 230000008569 process Effects 0.000 description 9
- 230000007423 decrease Effects 0.000 description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 8
- 239000001963 growth medium Substances 0.000 description 8
- 210000000056 organ Anatomy 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 8
- 150000003254 radicals Chemical class 0.000 description 8
- 210000001519 tissue Anatomy 0.000 description 8
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 7
- 230000003078 antioxidant effect Effects 0.000 description 7
- 108090000765 processed proteins & peptides Proteins 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- 241000700159 Rattus Species 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 230000002354 daily effect Effects 0.000 description 6
- 238000011835 investigation Methods 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 6
- 239000011780 sodium chloride Substances 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 238000004809 thin layer chromatography Methods 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 5
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 5
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 5
- 238000010171 animal model Methods 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 238000009826 distribution Methods 0.000 description 5
- GDCAGMMIHUVEEM-JTQLQIEISA-N (3S)-3-amino-4-oxo-4-[(2-oxo-2-phenylmethoxyethyl)amino]butanoic acid Chemical compound C(C1=CC=CC=C1)OC(CNC([C@@H](N)CC(=O)O)=O)=O GDCAGMMIHUVEEM-JTQLQIEISA-N 0.000 description 4
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 4
- VGALFAWDSNRXJK-VIFPVBQESA-N L-aspartic acid beta-benzyl ester Chemical compound OC(=O)[C@@H](N)CC(=O)OCC1=CC=CC=C1 VGALFAWDSNRXJK-VIFPVBQESA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 229940009098 aspartate Drugs 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 230000018109 developmental process Effects 0.000 description 4
- 230000006870 function Effects 0.000 description 4
- 230000014509 gene expression Effects 0.000 description 4
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 4
- 230000006872 improvement Effects 0.000 description 4
- 210000004072 lung Anatomy 0.000 description 4
- 210000000607 neurosecretory system Anatomy 0.000 description 4
- 231100000419 toxicity Toxicity 0.000 description 4
- 230000001988 toxicity Effects 0.000 description 4
- ABBVWCVRIDCTCX-DKWTVANSSA-N (2s)-2-aminobutanedioic acid;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)[C@@H](N)CC(O)=O ABBVWCVRIDCTCX-DKWTVANSSA-N 0.000 description 3
- QQEILXDLZRLTME-UHFFFAOYSA-N 6-sulfatoxymelatonin Chemical compound C1=C(OS(O)(=O)=O)C(OC)=CC2=C1NC=C2CCNC(C)=O QQEILXDLZRLTME-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 102000019197 Superoxide Dismutase Human genes 0.000 description 3
- 108010012715 Superoxide dismutase Proteins 0.000 description 3
- RMZZTJOADJVCIO-UHFFFAOYSA-N acetic acid;acetonitrile;hydrate Chemical compound O.CC#N.CC(O)=O RMZZTJOADJVCIO-UHFFFAOYSA-N 0.000 description 3
- 230000006399 behavior Effects 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 210000002745 epiphysis Anatomy 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 230000035558 fertility Effects 0.000 description 3
- 239000012467 final product Substances 0.000 description 3
- 239000012737 fresh medium Substances 0.000 description 3
- 229940125384 geroprotector Drugs 0.000 description 3
- 125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 description 3
- 230000036541 health Effects 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000007918 intramuscular administration Methods 0.000 description 3
- 150000002500 ions Chemical class 0.000 description 3
- 238000012417 linear regression Methods 0.000 description 3
- 210000004185 liver Anatomy 0.000 description 3
- 230000004060 metabolic process Effects 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- 230000000877 morphologic effect Effects 0.000 description 3
- 239000000825 pharmaceutical preparation Substances 0.000 description 3
- 238000012545 processing Methods 0.000 description 3
- 230000002035 prolonged effect Effects 0.000 description 3
- 230000029058 respiratory gaseous exchange Effects 0.000 description 3
- 229940076279 serotonin Drugs 0.000 description 3
- 210000002784 stomach Anatomy 0.000 description 3
- 230000004083 survival effect Effects 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 238000011287 therapeutic dose Methods 0.000 description 3
- 210000002700 urine Anatomy 0.000 description 3
- JMDKBDALNFZTOV-JQWIXIFHSA-N (2s)-2-[[(2s)-2-(phenylmethoxycarbonylamino)propanoyl]amino]pentanedioic acid Chemical compound OC(=O)CC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)OCC1=CC=CC=C1 JMDKBDALNFZTOV-JQWIXIFHSA-N 0.000 description 2
- GRFNBEZIAWKNCO-UHFFFAOYSA-N 3-pyridinol Chemical compound OC1=CC=CN=C1 GRFNBEZIAWKNCO-UHFFFAOYSA-N 0.000 description 2
- 238000011735 C3H mouse Methods 0.000 description 2
- QRYRORQUOLYVBU-VBKZILBWSA-N Carnosic acid Natural products CC([C@@H]1CC2)(C)CCC[C@]1(C(O)=O)C1=C2C=C(C(C)C)C(O)=C1O QRYRORQUOLYVBU-VBKZILBWSA-N 0.000 description 2
- 108010087806 Carnosine Proteins 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- RDPOETHPAQEGDP-ACZMJKKPSA-N Glu-Asp-Ala Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(O)=O RDPOETHPAQEGDP-ACZMJKKPSA-N 0.000 description 2
- 108010024636 Glutathione Proteins 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 2
- XUMBMVFBXHLACL-UHFFFAOYSA-N Melanin Chemical compound O=C1C(=O)C(C2=CNC3=C(C(C(=O)C4=C32)=O)C)=C2C4=CNC2=C1C XUMBMVFBXHLACL-UHFFFAOYSA-N 0.000 description 2
- CQOVPNPJLQNMDC-UHFFFAOYSA-N N-beta-alanyl-L-histidine Natural products NCCC(=O)NC(C(O)=O)CC1=CN=CN1 CQOVPNPJLQNMDC-UHFFFAOYSA-N 0.000 description 2
- 208000037273 Pathologic Processes Diseases 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 229940024606 amino acid Drugs 0.000 description 2
- 235000001014 amino acid Nutrition 0.000 description 2
- 150000001413 amino acids Chemical group 0.000 description 2
- 239000000924 antiasthmatic agent Substances 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- TXHIDIHEXDFONW-UHFFFAOYSA-N benzene;propan-2-one Chemical compound CC(C)=O.C1=CC=CC=C1 TXHIDIHEXDFONW-UHFFFAOYSA-N 0.000 description 2
- HFACYLZERDEVSX-UHFFFAOYSA-N benzidine Chemical compound C1=CC(N)=CC=C1C1=CC=C(N)C=C1 HFACYLZERDEVSX-UHFFFAOYSA-N 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 235000010354 butylated hydroxytoluene Nutrition 0.000 description 2
- 210000000748 cardiovascular system Anatomy 0.000 description 2
- CQOVPNPJLQNMDC-ZETCQYMHSA-N carnosine Chemical compound [NH3+]CCC(=O)N[C@H](C([O-])=O)CC1=CNC=N1 CQOVPNPJLQNMDC-ZETCQYMHSA-N 0.000 description 2
- 229940044199 carnosine Drugs 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 230000007665 chronic toxicity Effects 0.000 description 2
- 231100000160 chronic toxicity Toxicity 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 230000037213 diet Effects 0.000 description 2
- 235000015872 dietary supplement Nutrition 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- JPGDYIGSCHWQCC-UHFFFAOYSA-N emoxypine Chemical compound CCC1=NC(C)=CC=C1O JPGDYIGSCHWQCC-UHFFFAOYSA-N 0.000 description 2
- 230000029142 excretion Effects 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 230000002496 gastric effect Effects 0.000 description 2
- 108010080575 glutamyl-aspartyl-alanine Proteins 0.000 description 2
- 229960003180 glutathione Drugs 0.000 description 2
- 230000003806 hair structure Effects 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- HWYHZTIRURJOHG-UHFFFAOYSA-N luminol Chemical compound O=C1NNC(=O)C2=C1C(N)=CC=C2 HWYHZTIRURJOHG-UHFFFAOYSA-N 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 238000000386 microscopy Methods 0.000 description 2
- 230000009965 odorless effect Effects 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 230000036542 oxidative stress Effects 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 210000000496 pancreas Anatomy 0.000 description 2
- 239000012188 paraffin wax Substances 0.000 description 2
- 231100000915 pathological change Toxicity 0.000 description 2
- 230000036285 pathological change Effects 0.000 description 2
- 230000009054 pathological process Effects 0.000 description 2
- 210000005259 peripheral blood Anatomy 0.000 description 2
- 239000011886 peripheral blood Substances 0.000 description 2
- KWYUFKZDYYNOTN-UHFFFAOYSA-M potassium hydroxide Substances [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 230000001850 reproductive effect Effects 0.000 description 2
- 230000004202 respiratory function Effects 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 231100000456 subacute toxicity Toxicity 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 239000011782 vitamin Substances 0.000 description 2
- 235000013343 vitamin Nutrition 0.000 description 2
- 229930003231 vitamin Natural products 0.000 description 2
- 229940088594 vitamin Drugs 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- PFTAWBLQPZVEMU-DZGCQCFKSA-N (+)-catechin Chemical compound C1([C@H]2OC3=CC(O)=CC(O)=C3C[C@@H]2O)=CC=C(O)C(O)=C1 PFTAWBLQPZVEMU-DZGCQCFKSA-N 0.000 description 1
- XIXKMSRXBYUXOF-ABLWVSNPSA-N (4s)-2-benzyl-4-[(2-methylpropan-2-yl)oxycarbonylamino]pentanedioic acid Chemical compound CC(C)(C)OC(=O)N[C@H](C(O)=O)CC(C(O)=O)CC1=CC=CC=C1 XIXKMSRXBYUXOF-ABLWVSNPSA-N 0.000 description 1
- HGHOBRRUMWJWCU-FXQIFTODSA-N (4s)-4-[[(2s)-2-aminopropanoyl]amino]-5-[[(2s)-3-carboxy-1-(carboxymethylamino)-1-oxopropan-2-yl]amino]-5-oxopentanoic acid Chemical compound C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)NCC(O)=O HGHOBRRUMWJWCU-FXQIFTODSA-N 0.000 description 1
- RBCOYOYDYNXAFA-UHFFFAOYSA-L (5-hydroxy-4,6-dimethylpyridin-3-yl)methyl phosphate Chemical compound CC1=NC=C(COP([O-])([O-])=O)C(C)=C1O RBCOYOYDYNXAFA-UHFFFAOYSA-L 0.000 description 1
- ADFXKUOMJKEIND-UHFFFAOYSA-N 1,3-dicyclohexylurea Chemical compound C1CCCCC1NC(=O)NC1CCCCC1 ADFXKUOMJKEIND-UHFFFAOYSA-N 0.000 description 1
- YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 1
- KIUYPHAMDKDICO-WHFBIAKZSA-N Ala-Asp-Gly Chemical compound C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)NCC(O)=O KIUYPHAMDKDICO-WHFBIAKZSA-N 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- 125000006847 BOC protecting group Chemical group 0.000 description 1
- 108030002440 Catalase peroxidases Proteins 0.000 description 1
- 206010010774 Constipation Diseases 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- 241000255581 Drosophila <fruit fly, genus> Species 0.000 description 1
- 101100187357 Drosophila melanogaster not gene Proteins 0.000 description 1
- 206010013975 Dyspnoeas Diseases 0.000 description 1
- 208000009701 Embryo Loss Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 239000004258 Ethoxyquin Substances 0.000 description 1
- 208000007882 Gastritis Diseases 0.000 description 1
- 102000006587 Glutathione peroxidase Human genes 0.000 description 1
- 108700016172 Glutathione peroxidases Proteins 0.000 description 1
- 241000288140 Gruiformes Species 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 206010020915 Hypervitaminosis Diseases 0.000 description 1
- 206010062767 Hypophysitis Diseases 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- 125000002842 L-seryl group Chemical group O=C([*])[C@](N([H])[H])([H])C([H])([H])O[H] 0.000 description 1
- 241001599018 Melanogaster Species 0.000 description 1
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 102000003992 Peroxidases Human genes 0.000 description 1
- 206010036790 Productive cough Diseases 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 208000037656 Respiratory Sounds Diseases 0.000 description 1
- 102000005686 Serum Globulins Human genes 0.000 description 1
- 108010045362 Serum Globulins Proteins 0.000 description 1
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- COQLPRJCUIATTQ-UHFFFAOYSA-N Uranyl acetate Chemical compound O.O.O=[U]=O.CC(O)=O.CC(O)=O COQLPRJCUIATTQ-UHFFFAOYSA-N 0.000 description 1
- AOZUYISQWWJMJC-UHFFFAOYSA-N acetic acid;methanol;hydrate Chemical compound O.OC.CC(O)=O AOZUYISQWWJMJC-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 230000007172 age related pathology Effects 0.000 description 1
- 108010084217 alanyl-glutamyl-aspartyl-glycine Proteins 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 230000003712 anti-aging effect Effects 0.000 description 1
- 230000001088 anti-asthma Effects 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 230000006851 antioxidant defense Effects 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 210000000709 aorta Anatomy 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 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
- 230000005540 biological transmission Effects 0.000 description 1
- HOQPTLCRWVZIQZ-UHFFFAOYSA-H bis[[2-(5-hydroxy-4,7-dioxo-1,3,2$l^{2}-dioxaplumbepan-5-yl)acetyl]oxy]lead Chemical compound [Pb+2].[Pb+2].[Pb+2].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HOQPTLCRWVZIQZ-UHFFFAOYSA-H 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 210000000621 bronchi Anatomy 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- ADRVNXBAWSRFAJ-UHFFFAOYSA-N catechin Natural products OC1Cc2cc(O)cc(O)c2OC1c3ccc(O)c(O)c3 ADRVNXBAWSRFAJ-UHFFFAOYSA-N 0.000 description 1
- 235000005487 catechin Nutrition 0.000 description 1
- 150000001767 cationic compounds Chemical class 0.000 description 1
- 230000005779 cell damage Effects 0.000 description 1
- 230000019522 cellular metabolic process Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 208000023652 chronic gastritis Diseases 0.000 description 1
- 229950001002 cianidanol Drugs 0.000 description 1
- 230000007012 clinical effect Effects 0.000 description 1
- 230000002259 coagulatory effect Effects 0.000 description 1
- 230000001447 compensatory effect Effects 0.000 description 1
- 238000004590 computer program Methods 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- KJOZJSGOIJQCGA-UHFFFAOYSA-N dichloromethane;2,2,2-trifluoroacetic acid Chemical compound ClCCl.OC(=O)C(F)(F)F KJOZJSGOIJQCGA-UHFFFAOYSA-N 0.000 description 1
- 208000036526 difference of sexual differentiation Diseases 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000004043 dyeing Methods 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 230000008011 embryonic death Effects 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 235000019285 ethoxyquin Nutrition 0.000 description 1
- DECIPOUIJURFOJ-UHFFFAOYSA-N ethoxyquin Chemical compound N1C(C)(C)C=C(C)C2=CC(OCC)=CC=C21 DECIPOUIJURFOJ-UHFFFAOYSA-N 0.000 description 1
- 229940093500 ethoxyquin Drugs 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 230000005713 exacerbation Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 210000004700 fetal blood Anatomy 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 239000003862 glucocorticoid Substances 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 230000003648 hair appearance Effects 0.000 description 1
- 230000012447 hatching Effects 0.000 description 1
- 210000003128 head Anatomy 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- 230000002489 hematologic effect Effects 0.000 description 1
- 230000001744 histochemical effect Effects 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 238000013115 immunohistochemical detection Methods 0.000 description 1
- 230000002055 immunohistochemical effect Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 229910001411 inorganic cation Inorganic materials 0.000 description 1
- 206010022437 insomnia Diseases 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 229940040145 liniment Drugs 0.000 description 1
- 239000000865 liniment Substances 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 230000003908 liver function Effects 0.000 description 1
- 230000008774 maternal effect Effects 0.000 description 1
- 230000013011 mating Effects 0.000 description 1
- 229940126601 medicinal product Drugs 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 238000013425 morphometry Methods 0.000 description 1
- 230000037023 motor activity Effects 0.000 description 1
- 229940126619 mouse monoclonal antibody Drugs 0.000 description 1
- 230000003387 muscular Effects 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 230000003533 narcotic effect Effects 0.000 description 1
- 229940105631 nembutal Drugs 0.000 description 1
- 235000019645 odor Nutrition 0.000 description 1
- 150000002892 organic cations Chemical class 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 230000017448 oviposition Effects 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000036407 pain Effects 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000007310 pathophysiology Effects 0.000 description 1
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 239000008196 pharmacological composition Substances 0.000 description 1
- 230000037081 physical activity Effects 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 210000004560 pineal gland Anatomy 0.000 description 1
- 210000003635 pituitary gland Anatomy 0.000 description 1
- 238000007747 plating Methods 0.000 description 1
- 229920000729 poly(L-lysine) polymer Polymers 0.000 description 1
- 230000002028 premature Effects 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 206010037833 rales Diseases 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000000611 regression analysis Methods 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 210000004761 scalp Anatomy 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 230000037075 skin appearance Effects 0.000 description 1
- 208000019116 sleep disease Diseases 0.000 description 1
- 230000035943 smell Effects 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 208000024794 sputum Diseases 0.000 description 1
- 210000003802 sputum Anatomy 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 230000003637 steroidlike Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000011477 surgical intervention Methods 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 229940037128 systemic glucocorticoids Drugs 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 210000000115 thoracic cavity Anatomy 0.000 description 1
- 210000001685 thyroid gland Anatomy 0.000 description 1
- 235000010384 tocopherol Nutrition 0.000 description 1
- 229960001295 tocopherol Drugs 0.000 description 1
- 229930003799 tocopherol Natural products 0.000 description 1
- 239000011732 tocopherol Substances 0.000 description 1
- 231100000816 toxic dose Toxicity 0.000 description 1
- 231100000820 toxicity test Toxicity 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 235000019155 vitamin A Nutrition 0.000 description 1
- 239000011719 vitamin A Substances 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/10—Tetrapeptides
- C07K5/1002—Tetrapeptides with the first amino acid being neutral
- C07K5/1005—Tetrapeptides with the first amino acid being neutral and aliphatic
- C07K5/1008—Tetrapeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atoms, i.e. Gly, Ala
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- 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
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/06—Free radical scavengers or antioxidants
-
- 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
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Pulmonology (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Genetics & Genomics (AREA)
- Obesity (AREA)
- Cardiology (AREA)
- Toxicology (AREA)
- Hematology (AREA)
- Heart & Thoracic Surgery (AREA)
- Diabetes (AREA)
- Physical Education & Sports Medicine (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| RU99108841/14A RU2157233C1 (ru) | 1999-05-11 | 1999-05-11 | Тетрапептид, обладающий геропротекторной активностью, фармакологическое средство на его основе и способ его применения |
| RU99108841 | 1999-05-11 | ||
| PCT/RU2000/000012 WO2000068255A2 (en) | 1999-05-11 | 2000-01-20 | Tetrapeptide revealing geroprotective effect, pharmacological substance on its basis, and the method of its application |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE60026826D1 DE60026826D1 (de) | 2006-05-11 |
| DE60026826T2 true DE60026826T2 (de) | 2007-04-12 |
Family
ID=20219149
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE60026826T Expired - Lifetime DE60026826T2 (de) | 1999-05-11 | 2000-01-20 | Alterungsschutztetrapeptid, dieses enthaltende pharmazeutische zusammensetzungen und seine verwendung |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US6727227B1 (https=) |
| EP (1) | EP1179008B1 (https=) |
| JP (1) | JP3902406B2 (https=) |
| AT (1) | ATE321068T1 (https=) |
| AU (1) | AU769847C (https=) |
| CA (1) | CA2373128C (https=) |
| DE (1) | DE60026826T2 (https=) |
| ES (1) | ES2259998T3 (https=) |
| IL (2) | IL146432A0 (https=) |
| RU (1) | RU2157233C1 (https=) |
| WO (1) | WO2000068255A2 (https=) |
Families Citing this family (41)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20050227925A1 (en) * | 2004-04-08 | 2005-10-13 | Robbert Benner | Compositions capable of reducing elevated blood urea concentration |
| US6921751B1 (en) * | 1998-05-20 | 2005-07-26 | Erasmus Universiteit Rotterdam | Immunoregulator |
| US20030220258A1 (en) * | 2001-12-21 | 2003-11-27 | Robbert Benner | Treatment of ischemic events |
| US20040202645A1 (en) * | 2003-04-08 | 2004-10-14 | Khan Nisar Ahmed | Administration of gene-regulatory peptides |
| EP1138692A1 (en) | 2000-03-29 | 2001-10-04 | Erasmus Universiteit Rotterdam | Fragments of human chorionic gonadotropin (hcg) as immunoregulator |
| US8680059B2 (en) * | 1998-05-20 | 2014-03-25 | Biotempt B.V. | Oligopeptide acetate and formulations thereof |
| US6844315B2 (en) * | 1998-05-20 | 2005-01-18 | Erasmus Universiteit Rotterdam | Immunoregulator |
| US7175679B2 (en) * | 2001-03-29 | 2007-02-13 | Biotempt B.V. | Oligopeptide treatment of NF-κB mediated inflammation |
| USRE43279E1 (en) | 2000-03-29 | 2012-03-27 | Biotemp B.V. | Compositions capable of reducing elevated blood urea concentration |
| US7576174B2 (en) * | 2000-03-29 | 2009-08-18 | Biotempt B.V. | Compositions capable of reducing elevated blood urea concentration |
| EP1300418A1 (en) * | 2001-10-04 | 2003-04-09 | Erasmus Universiteit Rotterdam | Gene regulation by oligopeptides |
| US7358330B2 (en) * | 2001-03-29 | 2008-04-15 | Biotempt B.V. | Immunoregulatory compositions |
| RU2161501C1 (ru) * | 2000-06-29 | 2001-01-10 | Санкт-Петербургская Общественная Организация "Санкт-Петербургский Институт Биорегуляции И Геронтологии Сзо Рамн" | Способ получения пептидов, обладающих тканеспецифической активностью, и фармацевтические композиции на их основе |
| WO2002090380A1 (en) * | 2001-04-17 | 2002-11-14 | Sankt-Peterburgskaya Obschestvennaya Organizatsiya 'institut Bioregulyatsii I Gerontologii Czo Ramn' | Tetrapeptide stimulating the retinal function and the method of its application |
| US7501391B2 (en) | 2001-12-21 | 2009-03-10 | Biotempt B.V. | Treatment of transplant survival |
| US7786084B2 (en) * | 2001-12-21 | 2010-08-31 | Biotempt B.V. | Treatment of burns |
| US20040013661A1 (en) * | 2001-12-21 | 2004-01-22 | Gert Wensvoort | Stratification |
| US20030224995A1 (en) * | 2001-12-21 | 2003-12-04 | Khan Nisar Ahmed | Treatment of burns |
| US7560433B2 (en) * | 2001-12-21 | 2009-07-14 | Biotempt B.V. | Treatment of multiple sclerosis (MS) |
| US20080318871A1 (en) * | 2001-12-21 | 2008-12-25 | Khan Nisar A | Treatment of neurological disorders |
| US20030220257A1 (en) * | 2001-12-21 | 2003-11-27 | Robbert Benner | Treatment of trauma |
| US20030220261A1 (en) * | 2001-12-21 | 2003-11-27 | Khan Nisar Ahmed | Treatment of iatrogenic disease |
| US20080242837A1 (en) * | 2001-12-21 | 2008-10-02 | Khan Nisar A | Peptide compositions |
| US7517529B2 (en) * | 2003-04-08 | 2009-04-14 | Biotempt B.V. | Treatment of type I diabetes |
| RU2257910C1 (ru) * | 2003-12-25 | 2005-08-10 | Институт физиологически активных веществ Российской Академии Наук (ИФАВ РАН) | Растительные экстракты, обладающие геропротекторной активностью и средство на их основе |
| RU2257909C1 (ru) * | 2003-12-25 | 2005-08-10 | Институт физиологически активных веществ Российской Академии Наук (ИФАВ РАН) | Концентрат побегов черники и композиции на его основе, обладающие геропротекторной активностью |
| US20090227505A1 (en) * | 2004-01-07 | 2009-09-10 | Biotempt B.V. | Methods and uses for protein breakdown products |
| RU2255756C1 (ru) * | 2004-06-22 | 2005-07-10 | Санкт-Петербургская Общественная Организация "Санкт-Петербургский Институт Биорегуляции И Геронтологии Сзо Рамн" | Пептидное соединение, восстанавливающее функцию миокарда |
| RU2255757C1 (ru) * | 2004-06-22 | 2005-07-10 | Санкт-Петербургская Общественная Организация "Санкт-Петербургский Институт Биорегуляции И Геронтологии Сзо Рамн" | Пептидное соединение, восстанавливающее функцию органов дыхания |
| RU2297215C2 (ru) * | 2005-02-21 | 2007-04-20 | Государственное образовательное учреждение высшего профессионального образования "Рязанский государственный медицинский университет им. акад. И.П. Павлова" МЗ РФ | Антиоксидантное средство для лечения катаракты |
| JP4846799B2 (ja) * | 2005-07-05 | 2011-12-28 | バイオテンプト ベー．フェー． | 腫瘍の治療 |
| EP1864692A1 (en) * | 2006-06-07 | 2007-12-12 | Biotempt B.V. | Use of peptides for the control of radiation injury |
| RU2295970C1 (ru) * | 2006-05-23 | 2007-03-27 | Общество С Ограниченной Ответственностью "Сиа Пептайдс" | Пептид, повышающий резистентность капилляров, фармацевтическая композиция на его основе и способ ее применения |
| RU2304444C1 (ru) * | 2006-05-23 | 2007-08-20 | Общество С Ограниченной Ответственностью "Сиа Пептайдс" | Пептид, обладающий стресспротекторным действием, фармацевтическая композиция на его основе и способ ее применения |
| RU2301074C1 (ru) * | 2006-05-30 | 2007-06-20 | Общество С Ограниченной Ответственностью "Сиа Пептайдс" | Пептид, обладающий иммуногеропротекторным действием, фармацевтическая композиция на его основе и способ ее применения |
| RU2301678C1 (ru) * | 2006-05-30 | 2007-06-27 | Общество С Ограниченной Ответственностью "Сиа Пептайдс" | Пептид, стимулирующий регенерацию нейронов центральной нервной системы, фармацевтическая композиция на его основе и способ ее применения |
| DK2120991T3 (da) * | 2007-02-12 | 2014-04-28 | Biotempt Bv | Behandling af traumatisk blødning med korte oligopeptider |
| RU2464816C1 (ru) * | 2011-04-14 | 2012-10-27 | Общество с ограниченной ответственностью "Вилави" | Композиция биологически активных веществ, обладающая геропротекторной активностью, и способ комплексной коррекции возрастных изменений гормонального баланса, функций эпифиза и антиоксидантного статуса, включающий введение указанной композиции |
| JP7137745B2 (ja) * | 2015-05-22 | 2022-09-15 | ズィ・エイツー・ミルク・カンパニー・リミテッド | ベータカゼインａ２および抗酸化能 |
| CA3175267A1 (en) * | 2020-04-15 | 2021-10-21 | Anton MALYSHEV | Synthetic peptides for modulating the metabotropic glutamate receptor 5 |
| KR102841388B1 (ko) * | 2022-08-30 | 2025-08-01 | 주식회사 제이포셀 | 항노화 펩타이드 및 황기 추출물을 포함하는 항노화 화장료 조성물 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH078273A (ja) * | 1993-06-14 | 1995-01-13 | Kurabo Ind Ltd | 接着性動物細胞の無血清培養法 |
| JPH0851980A (ja) * | 1994-08-11 | 1996-02-27 | Asahi Glass Co Ltd | 合成遺伝子およびこれを用いた癌転移阻害活性を有するペプチドの製造方法 |
| RU2099078C1 (ru) * | 1994-12-08 | 1997-12-20 | Акционерное общество закрытого типа "КОМКОН" | Средство, обладающее антистрессовым, стресспротекторным, ноотропным, антиалкогольным и антинаркотическим действием, способы профилактики и лечения с его использованием |
| RU2112512C1 (ru) * | 1995-09-22 | 1998-06-10 | Иванов Евгений Васильевич | Биологичеcки активная пищевая добавка "глутапирон", обладающая антиканцерогенным и геропротекторным действием |
| GB2348426B (en) * | 1997-04-03 | 2001-06-27 | California Inst Of Techn | Enzyme-mediated modification of fibrin for tissue engineering |
-
1999
- 1999-05-11 RU RU99108841/14A patent/RU2157233C1/ru not_active IP Right Cessation
-
2000
- 2000-01-20 AU AU27034/00A patent/AU769847C/en not_active Ceased
- 2000-01-20 WO PCT/RU2000/000012 patent/WO2000068255A2/en not_active Ceased
- 2000-01-20 IL IL14643200A patent/IL146432A0/xx active IP Right Grant
- 2000-01-20 DE DE60026826T patent/DE60026826T2/de not_active Expired - Lifetime
- 2000-01-20 US US09/959,852 patent/US6727227B1/en not_active Expired - Fee Related
- 2000-01-20 JP JP2000616229A patent/JP3902406B2/ja not_active Expired - Fee Related
- 2000-01-20 CA CA002373128A patent/CA2373128C/en not_active Expired - Fee Related
- 2000-01-20 AT AT00905499T patent/ATE321068T1/de active
- 2000-01-20 EP EP00905499A patent/EP1179008B1/en not_active Expired - Lifetime
- 2000-01-20 ES ES00905499T patent/ES2259998T3/es not_active Expired - Lifetime
-
2001
- 2001-11-11 IL IL146432A patent/IL146432A/en not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| JP2003526622A (ja) | 2003-09-09 |
| ATE321068T1 (de) | 2006-04-15 |
| ES2259998T3 (es) | 2006-11-01 |
| EP1179008A2 (en) | 2002-02-13 |
| AU2703400A (en) | 2000-11-21 |
| CA2373128A1 (en) | 2000-11-16 |
| DE60026826D1 (de) | 2006-05-11 |
| IL146432A0 (en) | 2002-07-25 |
| WO2000068255A2 (en) | 2000-11-16 |
| CA2373128C (en) | 2007-03-13 |
| RU2157233C1 (ru) | 2000-10-10 |
| EP1179008B1 (en) | 2006-03-22 |
| WO2000068255A3 (en) | 2001-06-14 |
| JP3902406B2 (ja) | 2007-04-04 |
| AU769847C (en) | 2005-02-17 |
| AU769847B2 (en) | 2004-02-05 |
| IL146432A (en) | 2007-06-03 |
| US6727227B1 (en) | 2004-04-27 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE60026826T2 (de) | Alterungsschutztetrapeptid, dieses enthaltende pharmazeutische zusammensetzungen und seine verwendung | |
| Bills | Physiology of the sterols, including vitamin D | |
| DE69909794T2 (de) | Verwendung eines dipeptids für wiederherstellungsprozesse | |
| DE69636343T2 (de) | Verwendung von glu-trp dipeptiden zur herstellung eines arzneimittels zur behandlung von verschiedenen gefässneubildung-assozierten erkrankungen | |
| DE3100974C2 (https=) | ||
| DE3784905T2 (de) | Gamma-l-glutamyl-l-cysteinethylester und arzneimittel, die dieses als aktives mittel enthalten. | |
| DE69819488T2 (de) | Verwendung von glp-2 agonisten zur verbesserung der wirkung des oberen gastrointestinaltraktes | |
| DE69534061T2 (de) | Ein peptid, ein verfahren zu seiner darstellung und ein auf ihm basierende pharmazeutische zubereitung | |
| DE69331465T2 (de) | Intravenöse lösung, die den protein - und wasserverlust im körper reduziert | |
| DE69413090T2 (de) | Verwendung von 5-Amino-Phthaloylhydrazid als antihypoxisches und defensives Mittel | |
| DE69001722T2 (de) | Entzuendungshemmende und/oder antiallergische zusammensetzung, die glutathionderivate enthaelt. | |
| EP0474597A2 (de) | Arachidonsäurestoffwechselhemmende Diphenylverbindungen und ihre Verwendung in pharmazeutischen Zusammensetzungen | |
| DE2559989C3 (de) | Polymere und Verfahren zu ihrer Herstellung | |
| RU2054002C1 (ru) | Изоникотиноилгидразоны, проявляющие противотуберкулезную активность | |
| DE60105042T2 (de) | Tetrapeptid zur stimulation der funktionellen aktivität von hepatozyten und seine therapeutische anwendung | |
| DE1493561B2 (de) | Peptid mit Antischockwirkung und Verfahren zu seiner Herstellung | |
| DE69001004T2 (de) | Zusammensetzung gegen leberkrankheiten. | |
| EP2237782A1 (de) | Verwendung von tetrahydropyrimidinen | |
| DE69838303T2 (de) | Derivate hydroxyprolin | |
| DE602004011843T2 (de) | Die myocardfunktion wiederherstellende peptidsubstanz | |
| DE2234832A1 (de) | Verfahren zur herstellung von litoralon | |
| DE69202594T2 (de) | Zusammensetzung gegen Katarakt. | |
| DE602004011842T2 (de) | Die funktion der atmungsorgane wiederherstellende peptidsubstanz | |
| RU2177802C1 (ru) | Тетрапептид, регулирующий функции предстательной железы, фармакологическое средство на его основе и способ его применения | |
| Pantanowitz et al. | Noxious toads and frogs of South Africa |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8364 | No opposition during term of opposition |