ZA200005196B - Oxidized Thymosin Beta 4. - Google Patents

Oxidized Thymosin Beta 4. Download PDF

Info

Publication number: ZA200005196B
Authority: ZA; South Africa
Prior art keywords: thymosin; oxidised; salt; active variant; pharmaceutical formulation
Prior art date: 1998-03-28

Application number

ZA200005196A

Other languages

English (en)

Inventor

Robert Duncan Stevenson

Anthony John Lawrence

John Young

Darryl John Cecil Pappin

Original Assignee

Univ Glasgow

Imp Cancer Res Technology

Robert Duncan Stevenson

Priority date (The priority date 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 date listed.)

1998-03-28

Filing date

2000-09-27

Publication date

2002-01-02

2000-09-27 Application filed by Univ Glasgow, Imp Cancer Res Technology, Robert Duncan Stevenson filed Critical Univ Glasgow

2002-01-02 Publication of ZA200005196B publication Critical patent/ZA200005196B/en

Links

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 abstract 3
102100035000 Thymosin beta-4 Human genes 0.000 title abstract 3
108010079996 thymosin beta(4) Proteins 0.000 title abstract 3
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 14
238000002560 therapeutic procedure Methods 0.000 claims abstract description 7
206010040070 Septic Shock Diseases 0.000 claims abstract description 5
201000010099 disease Diseases 0.000 claims abstract description 5
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 5
230000036303 septic shock Effects 0.000 claims abstract description 5
102000007501 Thymosin Human genes 0.000 claims description 111
108010046075 Thymosin Proteins 0.000 claims description 110
LCJVIYPJPCBWKS-NXPQJCNCSA-N thymosin Chemical compound SC[C@@H](N)C(=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(C)C)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(C)C)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)=O LCJVIYPJPCBWKS-NXPQJCNCSA-N 0.000 claims description 110
108090000765 processed proteins & peptides Proteins 0.000 claims description 42
230000000694 effects Effects 0.000 claims description 32
239000000203 mixture Substances 0.000 claims description 31
238000009472 formulation Methods 0.000 claims description 21
238000000034 method Methods 0.000 claims description 18
150000003839 salts Chemical class 0.000 claims description 13
125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 claims description 11
239000003814 drug Substances 0.000 claims description 10
229930182817 methionine Natural products 0.000 claims description 10
FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 claims description 9
150000001413 amino acids Chemical class 0.000 claims description 8
230000004968 inflammatory condition Effects 0.000 claims description 7
230000004054 inflammatory process Effects 0.000 claims description 7
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims description 6
206010061218 Inflammation Diseases 0.000 claims description 6
238000007254 oxidation reaction Methods 0.000 claims description 6
238000004519 manufacturing process Methods 0.000 claims description 5
230000003647 oxidation Effects 0.000 claims description 5
239000003937 drug carrier Substances 0.000 claims description 4
230000002757 inflammatory effect Effects 0.000 claims description 4
QEFRNWWLZKMPFJ-YGVKFDHGSA-N L-methionine S-oxide Chemical compound CS(=O)CC[C@H](N)C(O)=O QEFRNWWLZKMPFJ-YGVKFDHGSA-N 0.000 claims description 3
238000007911 parenteral administration Methods 0.000 claims description 3
230000000699 topical effect Effects 0.000 claims description 3
208000036487 Arthropathies Diseases 0.000 claims description 2
208000023661 Haematological disease Diseases 0.000 claims description 2
208000012659 Joint disease Diseases 0.000 claims description 2
208000018631 connective tissue disease Diseases 0.000 claims description 2
208000015181 infectious disease Diseases 0.000 claims description 2
229910052751 metal Inorganic materials 0.000 claims description 2
239000002184 metal Substances 0.000 claims description 2
208000023504 respiratory system disease Diseases 0.000 claims description 2
208000011580 syndromic disease Diseases 0.000 claims description 2
238000002054 transplantation Methods 0.000 claims description 2
230000003156 vasculitic effect Effects 0.000 claims description 2
239000008177 pharmaceutical agent Substances 0.000 claims 2
208000018522 Gastrointestinal disease Diseases 0.000 claims 1
208000010643 digestive system disease Diseases 0.000 claims 1
238000002651 drug therapy Methods 0.000 claims 1
208000018685 gastrointestinal system disease Diseases 0.000 claims 1
230000028709 inflammatory response Effects 0.000 abstract description 5
239000000546 pharmaceutical excipient Substances 0.000 abstract 1
210000000440 neutrophil Anatomy 0.000 description 60
210000004027 cell Anatomy 0.000 description 58
230000033001 locomotion Effects 0.000 description 37
PRQROPMIIGLWRP-UHFFFAOYSA-N N-formyl-methionyl-leucyl-phenylalanin Chemical compound CSCCC(NC=O)C(=O)NC(CC(C)C)C(=O)NC(C(O)=O)CC1=CC=CC=C1 PRQROPMIIGLWRP-UHFFFAOYSA-N 0.000 description 29
241000282414 Homo sapiens Species 0.000 description 25
150000003431 steroids Chemical class 0.000 description 24
210000001616 monocyte Anatomy 0.000 description 19
102000007469 Actins Human genes 0.000 description 18
108010085238 Actins Proteins 0.000 description 18
238000003556 assay Methods 0.000 description 18
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 17
230000004044 response Effects 0.000 description 16
239000006228 supernatant Substances 0.000 description 16
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
210000002889 endothelial cell Anatomy 0.000 description 15
239000002245 particle Substances 0.000 description 15
230000003110 anti-inflammatory effect Effects 0.000 description 14
150000001875 compounds Chemical class 0.000 description 13
239000000443 aerosol Substances 0.000 description 12
229960003957 dexamethasone Drugs 0.000 description 12
UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 12
238000002360 preparation method Methods 0.000 description 12
241000283690 Bos taurus Species 0.000 description 10
239000004615 ingredient Substances 0.000 description 10
108090001007 Interleukin-8 Proteins 0.000 description 9
102000004890 Interleukin-8 Human genes 0.000 description 9
239000007788 liquid Substances 0.000 description 9
239000012528 membrane Substances 0.000 description 9
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 8
239000004480 active ingredient Substances 0.000 description 8
239000003855 balanced salt solution Substances 0.000 description 8
229920001525 carrageenan Polymers 0.000 description 8
230000035605 chemotaxis Effects 0.000 description 8
238000009826 distribution Methods 0.000 description 8
239000011521 glass Substances 0.000 description 8
239000001963 growth medium Substances 0.000 description 8
230000005012 migration Effects 0.000 description 8
238000013508 migration Methods 0.000 description 8
239000007787 solid Substances 0.000 description 8
239000000243 solution Substances 0.000 description 8
235000010418 carrageenan Nutrition 0.000 description 7
LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 7
230000003137 locomotive effect Effects 0.000 description 7
230000002688 persistence Effects 0.000 description 7
239000002953 phosphate buffered saline Substances 0.000 description 7
238000000746 purification Methods 0.000 description 7
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
235000001014 amino acid Nutrition 0.000 description 6
229940024606 amino acid Drugs 0.000 description 6
239000003921 oil Substances 0.000 description 6
239000012071 phase Substances 0.000 description 6
239000000758 substrate Substances 0.000 description 6
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical group CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 5
239000000556 agonist Substances 0.000 description 5
210000000709 aorta Anatomy 0.000 description 5
230000003399 chemotactic effect Effects 0.000 description 5
238000001360 collision-induced dissociation Methods 0.000 description 5
239000006071 cream Substances 0.000 description 5
239000003995 emulsifying agent Substances 0.000 description 5
239000003925 fat Substances 0.000 description 5
235000019197 fats Nutrition 0.000 description 5
239000003862 glucocorticoid Substances 0.000 description 5
239000000463 material Substances 0.000 description 5
235000018102 proteins Nutrition 0.000 description 5
108090000623 proteins and genes Proteins 0.000 description 5
102000004169 proteins and genes Human genes 0.000 description 5
238000004626 scanning electron microscopy Methods 0.000 description 5
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
108091003079 Bovine Serum Albumin Proteins 0.000 description 4
102000004127 Cytokines Human genes 0.000 description 4
108090000695 Cytokines Proteins 0.000 description 4
ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 4
101100281510 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) met-6 gene Proteins 0.000 description 4
206010030113 Oedema Diseases 0.000 description 4
102100040247 Tumor necrosis factor Human genes 0.000 description 4
238000007792 addition Methods 0.000 description 4
239000000853 adhesive Substances 0.000 description 4
230000001070 adhesive effect Effects 0.000 description 4
238000004458 analytical method Methods 0.000 description 4
230000015572 biosynthetic process Effects 0.000 description 4
229940098773 bovine serum albumin Drugs 0.000 description 4
239000000679 carrageenan Substances 0.000 description 4
229940113118 carrageenan Drugs 0.000 description 4
210000005056 cell body Anatomy 0.000 description 4
238000004624 confocal microscopy Methods 0.000 description 4
238000009792 diffusion process Methods 0.000 description 4
239000012153 distilled water Substances 0.000 description 4
238000010828 elution Methods 0.000 description 4
230000003511 endothelial effect Effects 0.000 description 4
238000004128 high performance liquid chromatography Methods 0.000 description 4
239000002609 medium Substances 0.000 description 4
230000002085 persistent effect Effects 0.000 description 4
230000008569 process Effects 0.000 description 4
102000004196 processed proteins & peptides Human genes 0.000 description 4
230000000770 proinflammatory effect Effects 0.000 description 4
210000002966 serum Anatomy 0.000 description 4
241000894007 species Species 0.000 description 4
238000010186 staining Methods 0.000 description 4
230000004936 stimulating effect Effects 0.000 description 4
239000000725 suspension Substances 0.000 description 4
239000003826 tablet Substances 0.000 description 4
239000013598 vector Substances 0.000 description 4
UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 4
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical class CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
241000283073 Equus caballus Species 0.000 description 3
AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 3
241001465754 Metazoa Species 0.000 description 3
ATTZFSUZZUNHBP-UHFFFAOYSA-N Piperonyl sulfoxide Chemical compound CCCCCCCCS(=O)C(C)CC1=CC=C2OCOC2=C1 ATTZFSUZZUNHBP-UHFFFAOYSA-N 0.000 description 3
102000003923 Protein Kinase C Human genes 0.000 description 3
108090000315 Protein Kinase C Proteins 0.000 description 3
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
229930006000 Sucrose Natural products 0.000 description 3
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 3
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
239000005864 Sulphur Substances 0.000 description 3
208000027418 Wounds and injury Diseases 0.000 description 3
238000010521 absorption reaction Methods 0.000 description 3
210000004369 blood Anatomy 0.000 description 3
239000008280 blood Substances 0.000 description 3
230000037396 body weight Effects 0.000 description 3
244000309466 calf Species 0.000 description 3
239000013553 cell monolayer Substances 0.000 description 3
239000003795 chemical substances by application Substances 0.000 description 3
229960001760 dimethyl sulfoxide Drugs 0.000 description 3
239000002270 dispersing agent Substances 0.000 description 3
239000000839 emulsion Substances 0.000 description 3
239000000796 flavoring agent Substances 0.000 description 3
235000011187 glycerol Nutrition 0.000 description 3
238000001727 in vivo Methods 0.000 description 3
230000002401 inhibitory effect Effects 0.000 description 3
230000005764 inhibitory process Effects 0.000 description 3
230000009545 invasion Effects 0.000 description 3
230000004899 motility Effects 0.000 description 3
230000030505 negative regulation of chemotaxis Effects 0.000 description 3
239000002773 nucleotide Substances 0.000 description 3
125000003729 nucleotide group Chemical group 0.000 description 3
230000001766 physiological effect Effects 0.000 description 3
239000003755 preservative agent Substances 0.000 description 3
239000000047 product Substances 0.000 description 3
238000004007 reversed phase HPLC Methods 0.000 description 3
239000003381 stabilizer Substances 0.000 description 3
230000000638 stimulation Effects 0.000 description 3
239000005720 sucrose Substances 0.000 description 3
239000004094 surface-active agent Substances 0.000 description 3
230000008961 swelling Effects 0.000 description 3
229940037128 systemic glucocorticoids Drugs 0.000 description 3
238000012360 testing method Methods 0.000 description 3
210000001519 tissue Anatomy 0.000 description 3
238000005406 washing Methods 0.000 description 3
PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
238000007809 Boyden Chamber assay Methods 0.000 description 2
OBMZMSLWNNWEJA-XNCRXQDQSA-N C1=CC=2C(C[C@@H]3NC(=O)[C@@H](NC(=O)[C@H](NC(=O)N(CC#CCN(CCCC[C@H](NC(=O)[C@@H](CC4=CC=CC=C4)NC3=O)C(=O)N)CC=C)NC(=O)[C@@H](N)C)CC3=CNC4=C3C=CC=C4)C)=CNC=2C=C1 Chemical compound C1=CC=2C(C[C@@H]3NC(=O)[C@@H](NC(=O)[C@H](NC(=O)N(CC#CCN(CCCC[C@H](NC(=O)[C@@H](CC4=CC=CC=C4)NC3=O)C(=O)N)CC=C)NC(=O)[C@@H](N)C)CC3=CNC4=C3C=CC=C4)C)=CNC=2C=C1 OBMZMSLWNNWEJA-XNCRXQDQSA-N 0.000 description 2
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
201000004624 Dermatitis Diseases 0.000 description 2
108010010803 Gelatin Proteins 0.000 description 2
WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 2
239000007995 HEPES buffer Substances 0.000 description 2
CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 2
WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 2
235000010643 Leucaena leucocephala Nutrition 0.000 description 2
240000007472 Leucaena leucocephala Species 0.000 description 2
ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 2
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
239000004472 Lysine Substances 0.000 description 2
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
241001529936 Murinae Species 0.000 description 2
241000699670 Mus sp. Species 0.000 description 2
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 2
241000283973 Oryctolagus cuniculus Species 0.000 description 2
101710176384 Peptide 1 Proteins 0.000 description 2
KPKZJLCSROULON-QKGLWVMZSA-N Phalloidin Chemical compound N1C(=O)[C@@H]([C@@H](O)C)NC(=O)[C@H](C)NC(=O)[C@H](C[C@@](C)(O)CO)NC(=O)[C@H](C2)NC(=O)[C@H](C)NC(=O)[C@@H]3C[C@H](O)CN3C(=O)[C@@H]1CSC1=C2C2=CC=CC=C2N1 KPKZJLCSROULON-QKGLWVMZSA-N 0.000 description 2
AUNGANRZJHBGPY-SCRDCRAPSA-N Riboflavin Chemical class OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-SCRDCRAPSA-N 0.000 description 2
238000012300 Sequence Analysis Methods 0.000 description 2
MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
229930003270 Vitamin B Natural products 0.000 description 2
230000009471 action Effects 0.000 description 2
230000004913 activation Effects 0.000 description 2
238000013019 agitation Methods 0.000 description 2
239000003963 antioxidant agent Substances 0.000 description 2
235000003704 aspartic acid Nutrition 0.000 description 2
208000006673 asthma Diseases 0.000 description 2
208000010668 atopic eczema Diseases 0.000 description 2
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 2
239000011230 binding agent Substances 0.000 description 2
-1 cachets Substances 0.000 description 2
238000012512 characterization method Methods 0.000 description 2
238000006243 chemical reaction Methods 0.000 description 2
239000003153 chemical reaction reagent Substances 0.000 description 2
230000001684 chronic effect Effects 0.000 description 2
239000003246 corticosteroid Substances 0.000 description 2
229960001334 corticosteroids Drugs 0.000 description 2
125000004122 cyclic group Chemical group 0.000 description 2
239000003085 diluting agent Substances 0.000 description 2
238000006073 displacement reaction Methods 0.000 description 2
231100000673 dose–response relationship Toxicity 0.000 description 2
210000003038 endothelium Anatomy 0.000 description 2
150000002148 esters Chemical class 0.000 description 2
201000001155 extrinsic allergic alveolitis Diseases 0.000 description 2
235000013355 food flavoring agent Nutrition 0.000 description 2
210000002683 foot Anatomy 0.000 description 2
239000008273 gelatin Substances 0.000 description 2
229920000159 gelatin Polymers 0.000 description 2
235000019322 gelatine Nutrition 0.000 description 2
235000011852 gelatine desserts Nutrition 0.000 description 2
238000002523 gelfiltration Methods 0.000 description 2
235000013922 glutamic acid Nutrition 0.000 description 2
239000004220 glutamic acid Substances 0.000 description 2
239000008187 granular material Substances 0.000 description 2
239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 2
235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 2
229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 2
UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 2
208000022098 hypersensitivity pneumonitis Diseases 0.000 description 2
238000000338 in vitro Methods 0.000 description 2
230000006698 induction Effects 0.000 description 2
230000003993 interaction Effects 0.000 description 2
238000001990 intravenous administration Methods 0.000 description 2
150000002500 ions Chemical class 0.000 description 2
229960000310 isoleucine Drugs 0.000 description 2
AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 2
GUBGYTABKSRVRQ-QKKXKWKRSA-N lactose group Chemical group OC1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@@H](O)[C@H](O2)CO)[C@H](O1)CO GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
239000000314 lubricant Substances 0.000 description 2
210000004072 lung Anatomy 0.000 description 2
238000004949 mass spectrometry Methods 0.000 description 2
238000005259 measurement Methods 0.000 description 2
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
230000004048 modification Effects 0.000 description 2
238000012986 modification Methods 0.000 description 2
238000000302 molecular modelling Methods 0.000 description 2
238000000465 moulding Methods 0.000 description 2
230000031990 negative regulation of inflammatory response Effects 0.000 description 2
230000011242 neutrophil chemotaxis Effects 0.000 description 2
229910052757 nitrogen Inorganic materials 0.000 description 2
229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 2
239000003883 ointment base Substances 0.000 description 2
239000012285 osmium tetroxide Substances 0.000 description 2
229910000489 osmium tetroxide Inorganic materials 0.000 description 2
239000008188 pellet Substances 0.000 description 2
VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
YPJUNDFVDDCYIH-UHFFFAOYSA-N perfluorobutyric acid Chemical compound OC(=O)C(F)(F)C(F)(F)C(F)(F)F YPJUNDFVDDCYIH-UHFFFAOYSA-N 0.000 description 2
230000026731 phosphorylation Effects 0.000 description 2
238000006366 phosphorylation reaction Methods 0.000 description 2
HZEBHPIOVYHPMT-UHFFFAOYSA-N polonium atom Chemical compound [Po] HZEBHPIOVYHPMT-UHFFFAOYSA-N 0.000 description 2
229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
229940069328 povidone Drugs 0.000 description 2
239000000843 powder Substances 0.000 description 2
239000013014 purified material Substances 0.000 description 2
230000002829 reductive effect Effects 0.000 description 2
206010039073 rheumatoid arthritis Diseases 0.000 description 2
230000028327 secretion Effects 0.000 description 2
239000011780 sodium chloride Substances 0.000 description 2
239000000600 sorbitol Substances 0.000 description 2
235000010356 sorbitol Nutrition 0.000 description 2
238000004611 spectroscopical analysis Methods 0.000 description 2
238000001228 spectrum Methods 0.000 description 2
239000011550 stock solution Substances 0.000 description 2
150000005846 sugar alcohols Polymers 0.000 description 2
238000000352 supercritical drying Methods 0.000 description 2
230000001629 suppression Effects 0.000 description 2
238000003786 synthesis reaction Methods 0.000 description 2
239000006188 syrup Substances 0.000 description 2
235000020357 syrup Nutrition 0.000 description 2
230000001225 therapeutic effect Effects 0.000 description 2
235000019156 vitamin B Nutrition 0.000 description 2
239000011720 vitamin B Substances 0.000 description 2
WZUVPPKBWHMQCE-XJKSGUPXSA-N (+)-haematoxylin Chemical compound C12=CC(O)=C(O)C=C2C[C@]2(O)[C@H]1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-XJKSGUPXSA-N 0.000 description 1
MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 1
QMMJWQMCMRUYTG-UHFFFAOYSA-N 1,2,4,5-tetrachloro-3-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=C(Cl)C(Cl)=CC(Cl)=C1Cl QMMJWQMCMRUYTG-UHFFFAOYSA-N 0.000 description 1
LGEZTMRIZWCDLW-UHFFFAOYSA-N 14-methylpentadecyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCCCCCCCCCCCCCC(C)C LGEZTMRIZWCDLW-UHFFFAOYSA-N 0.000 description 1
VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 description 1
BDZKYKKRSAWCBP-UHFFFAOYSA-N 2-[1-(2,5-dioxopyrrolidin-1-yl)-2H-pyridin-3-yl]acetic acid Chemical compound C1C(CC(=O)O)=CC=CN1N1C(=O)CCC1=O BDZKYKKRSAWCBP-UHFFFAOYSA-N 0.000 description 1
SFAAOBGYWOUHLU-UHFFFAOYSA-N 2-ethylhexyl hexadecanoate Chemical compound CCCCCCCCCCCCCCCC(=O)OCC(CC)CCCC SFAAOBGYWOUHLU-UHFFFAOYSA-N 0.000 description 1
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
108010088751 Albumins Proteins 0.000 description 1
102000009027 Albumins Human genes 0.000 description 1
208000032671 Allergic granulomatous angiitis Diseases 0.000 description 1
206010001889 Alveolitis Diseases 0.000 description 1
ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 1
229910000013 Ammonium bicarbonate Inorganic materials 0.000 description 1
206010002556 Ankylosing Spondylitis Diseases 0.000 description 1
102000000412 Annexin Human genes 0.000 description 1
108050008874 Annexin Proteins 0.000 description 1
239000004475 Arginine Substances 0.000 description 1
206010003267 Arthritis reactive Diseases 0.000 description 1
DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
CKLJMWTZIZZHCS-UHFFFAOYSA-N Aspartic acid Chemical compound OC(=O)C(N)CC(O)=O CKLJMWTZIZZHCS-UHFFFAOYSA-N 0.000 description 1
241000416162 Astragalus gummifer Species 0.000 description 1
238000011725 BALB/c mouse Methods 0.000 description 1
208000031872 Body Remains Diseases 0.000 description 1
239000004358 Butane-1, 3-diol Substances 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
102000005701 Calcium-Binding Proteins Human genes 0.000 description 1
108010045403 Calcium-Binding Proteins Proteins 0.000 description 1
241000282472 Canis lupus familiaris Species 0.000 description 1
241000283707 Capra Species 0.000 description 1
102000014914 Carrier Proteins Human genes 0.000 description 1
108010078791 Carrier Proteins Proteins 0.000 description 1
208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 1
208000006344 Churg-Strauss Syndrome Diseases 0.000 description 1
235000013162 Cocos nucifera Nutrition 0.000 description 1
244000060011 Cocos nucifera Species 0.000 description 1
206010009900 Colitis ulcerative Diseases 0.000 description 1
208000011231 Crohn disease Diseases 0.000 description 1
229920002785 Croscarmellose sodium Polymers 0.000 description 1
FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
150000008574 D-amino acids Chemical class 0.000 description 1
206010048768 Dermatosis Diseases 0.000 description 1
229920002307 Dextran Polymers 0.000 description 1
102000004190 Enzymes Human genes 0.000 description 1
108090000790 Enzymes Proteins 0.000 description 1
208000018428 Eosinophilic granulomatosis with polyangiitis Diseases 0.000 description 1
241000283086 Equidae Species 0.000 description 1
241000282326 Felis catus Species 0.000 description 1
102000011652 Formyl peptide receptors Human genes 0.000 description 1
108010076288 Formyl peptide receptors Proteins 0.000 description 1
102000030782 GTP binding Human genes 0.000 description 1
108091000058 GTP-Binding Proteins 0.000 description 1
241000295146 Gallionellaceae Species 0.000 description 1
208000007465 Giant cell arteritis Diseases 0.000 description 1
SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
208000009329 Graft vs Host Disease Diseases 0.000 description 1
206010072579 Granulomatosis with polyangiitis Diseases 0.000 description 1
WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Natural products C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 1
241000282412 Homo Species 0.000 description 1
101000658157 Homo sapiens Thymosin beta-4 Proteins 0.000 description 1
206010020751 Hypersensitivity Diseases 0.000 description 1
206010021245 Idiopathic thrombocytopenic purpura Diseases 0.000 description 1
208000004575 Infectious Arthritis Diseases 0.000 description 1
102000014150 Interferons Human genes 0.000 description 1
108010050904 Interferons Proteins 0.000 description 1
108010002386 Interleukin-3 Proteins 0.000 description 1
208000003456 Juvenile Arthritis Diseases 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
DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-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
COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-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
206010024229 Leprosy Diseases 0.000 description 1
108010014691 Lithostathine Proteins 0.000 description 1
102100027361 Lithostathine-1-alpha Human genes 0.000 description 1
206010025323 Lymphomas Diseases 0.000 description 1
101150036121 MARCKS gene Proteins 0.000 description 1
241000124008 Mammalia Species 0.000 description 1
229930195725 Mannitol Natural products 0.000 description 1
208000034578 Multiple myelomas Diseases 0.000 description 1
229940123921 Nitric oxide synthase inhibitor Drugs 0.000 description 1
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
102000016387 Pancreatic elastase Human genes 0.000 description 1
108010067372 Pancreatic elastase Proteins 0.000 description 1
229930040373 Paraformaldehyde Natural products 0.000 description 1
241001494479 Pecora Species 0.000 description 1
108091005804 Peptidases Proteins 0.000 description 1
108010009711 Phalloidine Proteins 0.000 description 1
206010035226 Plasma cell myeloma Diseases 0.000 description 1
208000005384 Pneumocystis Pneumonia Diseases 0.000 description 1
206010073755 Pneumocystis jirovecii pneumonia Diseases 0.000 description 1
239000002202 Polyethylene glycol Substances 0.000 description 1
208000007048 Polymyalgia Rheumatica Diseases 0.000 description 1
229920001214 Polysorbate 60 Polymers 0.000 description 1
241000206607 Porphyra umbilicalis Species 0.000 description 1
239000004365 Protease Substances 0.000 description 1
201000004681 Psoriasis Diseases 0.000 description 1
201000001263 Psoriatic Arthritis Diseases 0.000 description 1
208000036824 Psoriatic arthropathy Diseases 0.000 description 1
241000700159 Rattus Species 0.000 description 1
102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
208000025747 Rheumatic disease Diseases 0.000 description 1
BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical compound [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 description 1
RJFAYQIBOAGBLC-BYPYZUCNSA-N Selenium-L-methionine Chemical compound C[Se]CC[C@H](N)C(O)=O RJFAYQIBOAGBLC-BYPYZUCNSA-N 0.000 description 1
RJFAYQIBOAGBLC-UHFFFAOYSA-N Selenomethionine Natural products C[Se]CCC(N)C(O)=O RJFAYQIBOAGBLC-UHFFFAOYSA-N 0.000 description 1
208000021386 Sjogren Syndrome Diseases 0.000 description 1
DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
239000004141 Sodium laurylsulphate Substances 0.000 description 1
NWGKJDSIEKMTRX-AAZCQSIUSA-N Sorbitan monooleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O NWGKJDSIEKMTRX-AAZCQSIUSA-N 0.000 description 1
241000282887 Suidae Species 0.000 description 1
244000299461 Theobroma cacao Species 0.000 description 1
235000009470 Theobroma cacao Nutrition 0.000 description 1
AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
239000004473 Threonine Substances 0.000 description 1
208000031981 Thrombocytopenic Idiopathic Purpura Diseases 0.000 description 1
229920001615 Tragacanth Polymers 0.000 description 1
206010052779 Transplant rejections Diseases 0.000 description 1
GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 1
102000004142 Trypsin Human genes 0.000 description 1
108090000631 Trypsin Proteins 0.000 description 1
QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
201000006704 Ulcerative Colitis Diseases 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
208000024780 Urticaria 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
230000001133 acceleration Effects 0.000 description 1
230000021736 acetylation Effects 0.000 description 1
238000006640 acetylation reaction Methods 0.000 description 1
239000002253 acid Substances 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
239000011149 active material Substances 0.000 description 1
239000013543 active substance Substances 0.000 description 1
230000001154 acute effect Effects 0.000 description 1
239000000654 additive Substances 0.000 description 1
230000001464 adherent effect Effects 0.000 description 1
210000001552 airway epithelial cell Anatomy 0.000 description 1
235000004279 alanine Nutrition 0.000 description 1
230000001476 alcoholic effect Effects 0.000 description 1
150000001298 alcohols Chemical class 0.000 description 1
125000005907 alkyl ester group Chemical group 0.000 description 1
208000006778 allergic bronchopulmonary aspergillosis Diseases 0.000 description 1
125000000539 amino acid group Chemical group 0.000 description 1
235000012538 ammonium bicarbonate Nutrition 0.000 description 1
239000001099 ammonium carbonate Substances 0.000 description 1
239000002269 analeptic agent Substances 0.000 description 1
239000003957 anion exchange resin Substances 0.000 description 1
239000005557 antagonist Substances 0.000 description 1
230000003466 anti-cipated effect Effects 0.000 description 1
239000008346 aqueous phase Substances 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
229910052786 argon Inorganic materials 0.000 description 1
206010003246 arthritis Diseases 0.000 description 1
235000009582 asparagine Nutrition 0.000 description 1
229960001230 asparagine Drugs 0.000 description 1
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
201000003710 autoimmune thrombocytopenic purpura Diseases 0.000 description 1
238000004166 bioassay Methods 0.000 description 1
210000001124 body fluid Anatomy 0.000 description 1
239000010839 body fluid Substances 0.000 description 1
210000000621 bronchi Anatomy 0.000 description 1
239000000872 buffer Substances 0.000 description 1
239000006172 buffering agent Substances 0.000 description 1
235000019437 butane-1,3-diol Nutrition 0.000 description 1
235000014121 butter Nutrition 0.000 description 1
210000004899 c-terminal region Anatomy 0.000 description 1
239000011575 calcium Substances 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
239000002775 capsule Substances 0.000 description 1
210000000170 cell membrane Anatomy 0.000 description 1
230000001413 cellular effect Effects 0.000 description 1
230000007969 cellular immunity Effects 0.000 description 1
230000036755 cellular response Effects 0.000 description 1
229940082500 cetostearyl alcohol Drugs 0.000 description 1
238000007385 chemical modification Methods 0.000 description 1
201000009323 chronic eosinophilic pneumonia Diseases 0.000 description 1
230000000536 complexating effect Effects 0.000 description 1
239000007891 compressed tablet Substances 0.000 description 1
238000007906 compression Methods 0.000 description 1
230000006835 compression Effects 0.000 description 1
239000012141 concentrate Substances 0.000 description 1
239000000356 contaminant Substances 0.000 description 1
238000011109 contamination Methods 0.000 description 1
238000013270 controlled release Methods 0.000 description 1
239000012050 conventional carrier Substances 0.000 description 1
230000001054 cortical effect Effects 0.000 description 1
239000002537 cosmetic Substances 0.000 description 1
239000001767 crosslinked sodium carboxy methyl cellulose Substances 0.000 description 1
235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
201000009805 cryptogenic organizing pneumonia Diseases 0.000 description 1
239000013078 crystal Substances 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 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
JVHIPYJQMFNCEK-UHFFFAOYSA-N cytochalasin Natural products N1C(=O)C2(C(C=CC(C)CC(C)CC=C3)OC(C)=O)C3C(O)C(=C)C(C)C2C1CC1=CC=CC=C1 JVHIPYJQMFNCEK-UHFFFAOYSA-N 0.000 description 1
ZMAODHOXRBLOQO-UHFFFAOYSA-N cytochalasin-A Natural products N1C(=O)C23OC(=O)C=CC(=O)CCCC(C)CC=CC3C(O)C(=C)C(C)C2C1CC1=CC=CC=C1 ZMAODHOXRBLOQO-UHFFFAOYSA-N 0.000 description 1
230000009089 cytolysis Effects 0.000 description 1
230000003436 cytoskeletal effect Effects 0.000 description 1
210000004292 cytoskeleton Anatomy 0.000 description 1
230000001086 cytosolic effect Effects 0.000 description 1
230000007423 decrease Effects 0.000 description 1
SASYSVUEVMOWPL-NXVVXOECSA-N decyl oleate Chemical compound CCCCCCCCCCOC(=O)CCCCCCC\C=C/CCCCCCCC SASYSVUEVMOWPL-NXVVXOECSA-N 0.000 description 1
230000002939 deleterious effect Effects 0.000 description 1
238000012217 deletion Methods 0.000 description 1
230000037430 deletion Effects 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
238000001212 derivatisation Methods 0.000 description 1
231100000223 dermal penetration Toxicity 0.000 description 1
238000011161 development Methods 0.000 description 1
238000000502 dialysis Methods 0.000 description 1
235000014113 dietary fatty acids Nutrition 0.000 description 1
238000010790 dilution Methods 0.000 description 1
239000012895 dilution Substances 0.000 description 1
230000003292 diminished effect Effects 0.000 description 1
230000026058 directional locomotion Effects 0.000 description 1
239000007884 disintegrant Substances 0.000 description 1
239000002552 dosage form Substances 0.000 description 1
229940079593 drug Drugs 0.000 description 1
238000000635 electron micrograph Methods 0.000 description 1
238000001493 electron microscopy Methods 0.000 description 1
230000001804 emulsifying effect Effects 0.000 description 1
239000008387 emulsifying waxe Substances 0.000 description 1
239000003623 enhancer Substances 0.000 description 1
210000003743 erythrocyte Anatomy 0.000 description 1
230000032050 esterification Effects 0.000 description 1
238000005886 esterification reaction Methods 0.000 description 1
230000007717 exclusion Effects 0.000 description 1
239000000194 fatty acid Substances 0.000 description 1
229930195729 fatty acid Natural products 0.000 description 1
150000004665 fatty acids Chemical class 0.000 description 1
239000012467 final product Substances 0.000 description 1
235000019253 formic acid Nutrition 0.000 description 1
239000012634 fragment Substances 0.000 description 1
238000013467 fragmentation Methods 0.000 description 1
238000006062 fragmentation reaction Methods 0.000 description 1
238000004108 freeze drying Methods 0.000 description 1
239000007789 gas Substances 0.000 description 1
230000002496 gastric effect Effects 0.000 description 1
238000001641 gel filtration chromatography Methods 0.000 description 1
230000014509 gene expression Effects 0.000 description 1
239000003292 glue 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
YQEMORVAKMFKLG-UHFFFAOYSA-N glycerine monostearate Natural products CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 description 1
SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 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
208000024908 graft versus host disease Diseases 0.000 description 1
238000000227 grinding Methods 0.000 description 1
230000035876 healing Effects 0.000 description 1
208000007475 hemolytic anemia Diseases 0.000 description 1
208000006454 hepatitis Diseases 0.000 description 1
231100000283 hepatitis Toxicity 0.000 description 1
UBHWBODXJBSFLH-UHFFFAOYSA-N hexadecan-1-ol;octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO.CCCCCCCCCCCCCCCCCCO UBHWBODXJBSFLH-UHFFFAOYSA-N 0.000 description 1
210000000548 hind-foot Anatomy 0.000 description 1
239000008309 hydrophilic cream Substances 0.000 description 1
125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
238000005286 illumination Methods 0.000 description 1
239000012642 immune effector Substances 0.000 description 1
229940121354 immunomodulator Drugs 0.000 description 1
239000003701 inert diluent Substances 0.000 description 1
230000008595 infiltration Effects 0.000 description 1
238000001764 infiltration Methods 0.000 description 1
208000027866 inflammatory disease Diseases 0.000 description 1
238000001802 infusion Methods 0.000 description 1
239000003112 inhibitor Substances 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
238000003780 insertion Methods 0.000 description 1
230000037431 insertion Effects 0.000 description 1
229940079322 interferon Drugs 0.000 description 1
230000031261 interleukin-10 production Effects 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
238000005342 ion exchange Methods 0.000 description 1
238000004255 ion exchange chromatography Methods 0.000 description 1
229940078545 isocetyl stearate Drugs 0.000 description 1
XUGNVMKQXJXZCD-UHFFFAOYSA-N isopropyl palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC(C)C XUGNVMKQXJXZCD-UHFFFAOYSA-N 0.000 description 1
239000008101 lactose Substances 0.000 description 1
210000000867 larynx Anatomy 0.000 description 1
208000032839 leukemia Diseases 0.000 description 1
150000002632 lipids Chemical class 0.000 description 1
229940057995 liquid paraffin Drugs 0.000 description 1
239000007937 lozenge Substances 0.000 description 1
229910052943 magnesium sulfate Inorganic materials 0.000 description 1
235000019341 magnesium sulphate Nutrition 0.000 description 1
230000014759 maintenance of location Effects 0.000 description 1
201000004792 malaria Diseases 0.000 description 1
239000000594 mannitol Substances 0.000 description 1
235000010355 mannitol Nutrition 0.000 description 1
230000007246 mechanism Effects 0.000 description 1
238000002844 melting Methods 0.000 description 1
230000008018 melting Effects 0.000 description 1
150000002739 metals Chemical class 0.000 description 1
SXTAYKAGBXMACB-UHFFFAOYSA-N methionine S-imide-S-oxide Natural products CS(=N)(=O)CCC(N)C(O)=O SXTAYKAGBXMACB-UHFFFAOYSA-N 0.000 description 1
LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
210000003632 microfilament Anatomy 0.000 description 1
239000002480 mineral oil Substances 0.000 description 1
239000003595 mist Substances 0.000 description 1
108091005601 modified peptides Proteins 0.000 description 1
230000000877 morphologic effect Effects 0.000 description 1
239000004570 mortar (masonry) Substances 0.000 description 1
239000002324 mouth wash Substances 0.000 description 1
210000003928 nasal cavity Anatomy 0.000 description 1
239000006199 nebulizer Substances 0.000 description 1
239000000236 nitric oxide synthase inhibitor Substances 0.000 description 1
239000002674 ointment Substances 0.000 description 1
239000001301 oxygen Substances 0.000 description 1
229910052760 oxygen Inorganic materials 0.000 description 1
230000000242 pagocytic effect Effects 0.000 description 1
239000012188 paraffin wax Substances 0.000 description 1
229920002866 paraformaldehyde Polymers 0.000 description 1
230000036961 partial effect Effects 0.000 description 1
235000010603 pastilles Nutrition 0.000 description 1
230000035515 penetration Effects 0.000 description 1
230000000737 periodic effect Effects 0.000 description 1
210000005259 peripheral blood Anatomy 0.000 description 1
239000011886 peripheral blood Substances 0.000 description 1
210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 1
239000008251 pharmaceutical emulsion Substances 0.000 description 1
238000002135 phase contrast microscopy Methods 0.000 description 1
COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
150000003906 phosphoinositides Chemical class 0.000 description 1
230000035790 physiological processes and functions Effects 0.000 description 1
239000004033 plastic Substances 0.000 description 1
229920003023 plastic Polymers 0.000 description 1
201000000317 pneumocystosis Diseases 0.000 description 1
229910052699 polonium Inorganic materials 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
239000011148 porous material Substances 0.000 description 1
239000013641 positive control Substances 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
230000002335 preservative effect Effects 0.000 description 1
230000007112 pro inflammatory response Effects 0.000 description 1
235000013772 propylene glycol Nutrition 0.000 description 1
210000001243 pseudopodia Anatomy 0.000 description 1
239000002510 pyrogen Substances 0.000 description 1
208000002574 reactive arthritis Diseases 0.000 description 1
230000009467 reduction Effects 0.000 description 1
239000011347 resin Substances 0.000 description 1
229920005989 resin Polymers 0.000 description 1
201000000306 sarcoidosis Diseases 0.000 description 1
239000013049 sediment Substances 0.000 description 1
229910052711 selenium Inorganic materials 0.000 description 1
239000011669 selenium Substances 0.000 description 1
229960002718 selenomethionine Drugs 0.000 description 1
238000000926 separation method Methods 0.000 description 1
201000001223 septic arthritis Diseases 0.000 description 1
125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 1
238000007493 shaping process Methods 0.000 description 1
239000002356 single layer Substances 0.000 description 1
208000017520 skin disease Diseases 0.000 description 1
150000003384 small molecules Chemical class 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
PXLIDIMHPNPGMH-UHFFFAOYSA-N sodium chromate Chemical compound [Na+].[Na+].[O-][Cr]([O-])(=O)=O PXLIDIMHPNPGMH-UHFFFAOYSA-N 0.000 description 1
235000019333 sodium laurylsulphate Nutrition 0.000 description 1
229940080313 sodium starch Drugs 0.000 description 1
239000002904 solvent Substances 0.000 description 1
239000000021 stimulant Substances 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
239000000126 substance Substances 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
239000000829 suppository Substances 0.000 description 1
230000002459 sustained effect Effects 0.000 description 1
230000009897 systematic effect Effects 0.000 description 1
201000000596 systemic lupus erythematosus Diseases 0.000 description 1
239000008399 tap water Substances 0.000 description 1
235000020679 tap water Nutrition 0.000 description 1
229910052714 tellurium Inorganic materials 0.000 description 1
PORWMNRCUJJQNO-UHFFFAOYSA-N tellurium atom Chemical compound [Te] PORWMNRCUJJQNO-UHFFFAOYSA-N 0.000 description 1
JGVWCANSWKRBCS-UHFFFAOYSA-N tetramethylrhodamine thiocyanate Chemical compound [Cl-].C=12C=CC(N(C)C)=CC2=[O+]C2=CC(N(C)C)=CC=C2C=1C1=CC=C(SC#N)C=C1C(O)=O JGVWCANSWKRBCS-UHFFFAOYSA-N 0.000 description 1
OULAJFUGPPVRBK-UHFFFAOYSA-N tetratriacontyl alcohol Natural products CCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCO OULAJFUGPPVRBK-UHFFFAOYSA-N 0.000 description 1
239000002562 thickening agent Substances 0.000 description 1
238000011200 topical administration Methods 0.000 description 1
229940100611 topical cream Drugs 0.000 description 1
229940100615 topical ointment Drugs 0.000 description 1
239000012049 topical pharmaceutical composition Substances 0.000 description 1
239000000196 tragacanth Substances 0.000 description 1
235000010487 tragacanth Nutrition 0.000 description 1
229940116362 tragacanth Drugs 0.000 description 1
GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
239000012588 trypsin Substances 0.000 description 1
201000008827 tuberculosis Diseases 0.000 description 1
OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
210000003606 umbilical vein Anatomy 0.000 description 1
230000003827 upregulation Effects 0.000 description 1
239000004474 valine Substances 0.000 description 1
239000003981 vehicle Substances 0.000 description 1
230000035899 viability Effects 0.000 description 1
239000000341 volatile oil Substances 0.000 description 1
239000008096 xylene Substances 0.000 description 1

Classifications

- 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
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/67—General methods for enhancing the expression
- 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
- 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
- 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
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
- 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
- A61P19/04—Drugs for skeletal disorders for non-specific disorders of the connective tissue
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
- 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
- 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
- A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/575—Hormones
- C07K14/57581—Thymosin; Related peptides
- 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
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Landscapes

Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Chemical & Material Sciences (AREA)
Engineering & Computer Science (AREA)
Organic Chemistry (AREA)
Bioinformatics & Cheminformatics (AREA)
Genetics & Genomics (AREA)
General Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Veterinary Medicine (AREA)
Animal Behavior & Ethology (AREA)
Public Health (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Zoology (AREA)
Chemical Kinetics & Catalysis (AREA)
Biomedical Technology (AREA)
Wood Science & Technology (AREA)
General Engineering & Computer Science (AREA)
Biotechnology (AREA)
Molecular Biology (AREA)
Biochemistry (AREA)
Biophysics (AREA)
Immunology (AREA)
Plant Pathology (AREA)
Microbiology (AREA)
Physics & Mathematics (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Gastroenterology & Hepatology (AREA)
Endocrinology (AREA)
Rheumatology (AREA)
Toxicology (AREA)
Physical Education & Sports Medicine (AREA)
Dermatology (AREA)
Communicable Diseases (AREA)
Heart & Thoracic Surgery (AREA)
Hematology (AREA)
Orthopedic Medicine & Surgery (AREA)
Cardiology (AREA)

ZA200005196A 1998-03-28 2000-09-27 Oxidized Thymosin Beta 4. ZA200005196B (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
GBGB9806632.7A GB9806632D0 (en)	1998-03-28	1998-03-28	Peptide factor

Publications (1)

Publication Number	Publication Date
ZA200005196B true ZA200005196B (en)	2002-01-02

Family

ID=10829414

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
ZA200005196A ZA200005196B (en)	1998-03-28	2000-09-27	Oxidized Thymosin Beta 4.

Country Status (15)

Country	Link
US (3)	US6602519B1 (de)
EP (1)	EP1094833B1 (de)
JP (1)	JP2002509893A (de)
KR (1)	KR20010074461A (de)
CN (2)	CN1178695C (de)
AT (1)	ATE232396T1 (de)
AU (1)	AU766493B2 (de)
CA (1)	CA2325984A1 (de)
DE (1)	DE69905368T2 (de)
ES (1)	ES2192839T3 (de)
GB (1)	GB9806632D0 (de)
IL (1)	IL138665A0 (de)
NZ (1)	NZ507642A (de)
WO (1)	WO1999049883A2 (de)
ZA (1)	ZA200005196B (de)

Families Citing this family (30)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB9806632D0 (en) *	1998-03-28	1998-05-27	Stevenson Robert	Peptide factor
US20070015698A1 (en) *	1998-07-30	2007-01-18	United States Of America As Represented By The Secretary Of Health	Treatment of skin, and wound repair, with thymosin beta 4
US20060100156A1 (en) *	2004-10-01	2006-05-11	Regenerx Biopharmaceuticals, Inc.	Cell nucleus-entering compositions
EP1100529B2 (de) *	1998-07-30	2010-08-25	The Government of the United States of America, as repres. by the Secretary of Health and Human Services, Nat. Inst. of Health	Thymosin beta 4 stimuliert wundheilung
US20040067227A1 (en) *	2001-11-02	2004-04-08	Goldstein Allan L.	Inhibition or reversal of skin aging by actin-sequestering peptides
US20070191275A1 (en) *	1998-07-30	2007-08-16	Regenerx Biopharmaceuticals, Inc.	Method of treating, preventing, inhibiting or reducing damage to cardiac tissue with thymosin beta 4 fragments
EP1328289B1 (de) *	2000-10-20	2008-09-03	Hamburger Stiftung zur Förderung von Wissenschaft und Kultur	Oxidierte proteine und deren biologische und therapeutische aktivität sowie diagnostische verwendung über die hemmung der interaktion zwischen oxidierten proteinen und cd36
JP4224297B2 (ja)	2000-11-02	2009-02-12	リジェナークス・バイオファーマシューティカルズ・インコーポレイテッド	アクチン隔離ペプチドによる皮膚老化の阻害又は反転
JP2005506293A (ja) *	2001-03-15	2005-03-03	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	サイモシンβ４（Ｔβ４）、類似体、アイソホーム、および他の誘導体を用いて眼および周辺組織の疾患を治療するための方法
CN101549148A (zh) *	2001-08-29	2009-10-07	雷根内克斯生物制药有限公司	多肽在制备用于促进心内膜细胞向间质细胞转化的药物中的应用
EP2266595A3 (de) *	2002-02-06	2011-07-06	Regenerx Biopharmaceuticals, Inc.	Behandlung von Infektionen und anderen Erkrankungen
AU2008201749B2 (en) *	2002-02-06	2010-05-13	Regenerx Biopharmaceuticals, Inc.	Treatment of Infections and Other Disorders
US20060264360A1 (en) *	2002-04-12	2006-11-23	Yale University Office Of Cooperstive Research	Anti-inflammatory and wound healing effects of lymphoid thymosin beta-4
US6821524B2 (en) *	2002-06-03	2004-11-23	Jan Marini Skin Research, Inc.	Cosmetic skin care compositions
AU2004229336B2 (en) *	2003-03-31	2008-12-04	Regenerx Biopharmaceuticals, Inc.	Compositions and methods for delivering thymosin beta 4, analogues, isoforms and other derivatives
WO2005027958A1 (en) *	2003-09-19	2005-03-31	Imperial College Innovations Ltd	Thymosin-beta-sulphoxide as an immunosuppressive active agent
CA2550833A1 (en) *	2003-12-22	2005-07-14	Regenerx Biopharmaceuticals, Inc.	Method of treating or preventing biological or immunological responses to a reactive chemical or biological or toxic agent
EP1720904A4 (de) *	2004-03-05	2007-08-22	Regenerx Biopharmaceuticals	Behandlung bzw. prävention des aufbaus einer extrazellulären matrix
WO2006076523A1 (en) *	2005-01-14	2006-07-20	Regenerx Biopharmaceuticals, Inc.	Modified beta thymosin peptides
KR20080018268A (ko)	2005-06-17	2008-02-27	리지너크스 바이오 파마소티컬스, 인코포레이티드	조직 악화, 부상 또는 손상을 치료하거나 또는 예방하기위한 엘케이케이티이티 및/또는 엘케이케이티엔티 조성물들및 그 방법
EP1913013A2 (de) *	2005-07-19	2008-04-23	Grannus Biosciences	Gekürztes oxidiertes thymosin-beta4 und derivate davon
ES2288118B1 (es) *	2006-05-10	2008-11-01	Bcn Peptides, S.A.	Procedimiento para sintetizar timosinas.
CN101297965B (zh) *	2008-06-16	2011-01-05	浙江省中医药研究院	胸腺肽β4在制备防治支气管哮喘药物中的应用
US20100247693A1 (en) *	2009-03-24	2010-09-30	Marini Jan L	Cosmetic formulation to treat rosacea telangiectasia
US8580742B2 (en) *	2010-03-05	2013-11-12	N.V. Perricone Llc	Topical glutathione formulations for menopausal skin
US8609604B2 (en)	2009-12-28	2013-12-17	N.V. Perricone Llc	Methods of improving the appearance of aging skin
US20110160144A1 (en) *	2009-12-28	2011-06-30	Perricone Nicholas V	Topical Acyl Glutathione Formulations
JP5847418B2 (ja)	2011-03-30	2016-01-20	富士フイルム株式会社	細胞接着性タンパク質
US9808654B2 (en)	2013-02-11	2017-11-07	Jan Marini Skin Research	Post procedure skin care gel and methods of use thereof
CN110215513B (zh) *	2018-11-15	2022-02-22	北京诺思兰德生物技术股份有限公司	经修饰的胸腺素β4在治疗放射性肠炎方面的用途

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US388234A (en) *		1888-08-21		Car-brake
US3998798A (en) *	1972-12-22	1976-12-21	The Trustees Of The University Of Pennsylvania	Monellin, a sweet polypeptide derived from fruit of dioscoreophyllum cumminsii
US4297276A (en) *	1979-03-23	1981-10-27	Hoffman-La Roche Inc.	Thymosin beta 3 and beta 4
US4389343A (en) *	1981-12-24	1983-06-21	Hoffmann-La Roche Inc.	Immunopotentiating peptides from thymus
US4388234A (en)	1981-12-28	1983-06-14	Hoffmann-La Roche Inc.	Peptide isolation
US4572798A (en) *	1984-12-06	1986-02-25	Cetus Corporation	Method for promoting disulfide bond formation in recombinant proteins
US5578570A (en) *	1993-10-07	1996-11-26	The George Washington University Medical Center	Method of treating septic shock using thymosin β4
US5593964A (en) *	1993-10-07	1997-01-14	The George Washington University Medical Center	Method of treating septic shock by preventing actin polymerization
US5468729A (en) *	1993-10-26	1995-11-21	Alpha 1 Biomedicals	Method for treatment of autoimmune hepatitis
GB9806632D0 (en) *	1998-03-28	1998-05-27	Stevenson Robert	Peptide factor

1998
- 1998-03-28 GB GBGB9806632.7A patent/GB9806632D0/en not_active Ceased
1999
- 1999-03-29 JP JP2000540846A patent/JP2002509893A/ja active Pending
- 1999-03-29 CA CA002325984A patent/CA2325984A1/en not_active Abandoned
- 1999-03-29 CN CNB998059579A patent/CN1178695C/zh not_active Expired - Fee Related
- 1999-03-29 IL IL13866599A patent/IL138665A0/xx not_active IP Right Cessation
- 1999-03-29 EP EP99913428A patent/EP1094833B1/de not_active Expired - Lifetime
- 1999-03-29 AT AT99913428T patent/ATE232396T1/de not_active IP Right Cessation
- 1999-03-29 AU AU31553/99A patent/AU766493B2/en not_active Ceased
- 1999-03-29 NZ NZ507642A patent/NZ507642A/en unknown
- 1999-03-29 KR KR1020007010794A patent/KR20010074461A/ko not_active Withdrawn
- 1999-03-29 US US09/647,117 patent/US6602519B1/en not_active Expired - Fee Related
- 1999-03-29 WO PCT/GB1999/000833 patent/WO1999049883A2/en not_active Ceased
- 1999-03-29 CN CNA2004100879091A patent/CN1644586A/zh active Pending
- 1999-03-29 ES ES99913428T patent/ES2192839T3/es not_active Expired - Lifetime
- 1999-03-29 DE DE69905368T patent/DE69905368T2/de not_active Expired - Fee Related
2000
- 2000-09-27 ZA ZA200005196A patent/ZA200005196B/en unknown
2003
- 2003-01-09 US US10/339,271 patent/US20040213772A1/en not_active Abandoned
2006
- 2006-06-14 US US11/452,738 patent/US20060229234A1/en not_active Abandoned

Also Published As

Publication number	Publication date
KR20010074461A (ko)	2001-08-04
CN1308543A (zh)	2001-08-15
US6602519B1 (en)	2003-08-05
JP2002509893A (ja)	2002-04-02
IL138665A0 (en)	2001-10-31
DE69905368D1 (en)	2003-03-20
EP1094833A2 (de)	2001-05-02
CN1178695C (zh)	2004-12-08
NZ507642A (en)	2003-10-31
WO1999049883A2 (en)	1999-10-07
ATE232396T1 (de)	2003-02-15
CN1644586A (zh)	2005-07-27
GB9806632D0 (en)	1998-05-27
WO1999049883A3 (en)	2001-02-22
US20040213772A1 (en)	2004-10-28
DE69905368T2 (de)	2003-12-18
CA2325984A1 (en)	1999-10-07
AU3155399A (en)	1999-10-18
US20060229234A1 (en)	2006-10-12
AU766493B2 (en)	2003-10-16
EP1094833B1 (de)	2003-02-12
ES2192839T3 (es)	2003-10-16

Publication	Publication Date	Title
EP1094833B1 (de)	2003-02-12	Oxydiertes thymosin beta 4
Erickson et al.	1984	A six-armed oligomer isolated from cell surface fibronectin preparations
Rovera et al.	1971	Early changes in the synthesis of acidic nuclear proteins in human diploid fibroblasts stimulated to synthesize DNA by changing the medium
JPH0662677B2 (ja)	1994-08-17	アンギオゲニン活性を有する精製蛋白及びその製造方法
Zingg et al.	1982	Biosynthesis of immunoreactive somatostatin by hypothalamic neurons in culture.
Yurewicz et al.	1992	Porcine oocyte zona pellucida Mr 55,000 glycoproteins: Identification of O‐glycosylated domains
JP2983224B2 (ja)	1999-11-29	哺乳動物の１４―β―ｇａ１レクチン類
KR102268955B1 (ko)	2021-06-25	항분비 인자 17
WO2016049881A1 (zh)	2016-04-07	芋螺毒素多肽κ-CPTx-bt104、其制备方法及应用
Paukovits et al.	1977	The Granulocytic Chalone–A Specific Inhibitor of Granulopoiesis: Molecular Weight and Chemical Nature
CA2010660A1 (en)	1990-08-23	Osteogenic growth polypeptides identified from regenerating bone marrow
JPH06501270A (ja)	1994-02-10	ヒト骨由来インスリン様成長因子結合タンパク
AU8756591A (en)	1992-05-26	Cell growth inhibitors
EP1027027B1 (de)	2006-12-20	Verwendung von Amylin, Adrenomedullin und deren Analoga zur Behandlung von Knorpeldefekten
WO1995023214A1 (en)	1995-08-31	Method for stimulating profileration of colon cells using pomc¿76-103?
Merli et al.	1996	An expression system for the single-step production of recombinant human amidated calcitonin
Fortier et al.	1989	Similar molecular requirements for antigen receptor-triggered secretion of interferon and granule enzymes by cytolytic T lymphocytes
DE69202136T2 (de)	1995-11-30	Neuartiges calcitonin, und seine herstellung und verwendung.
US20100215583A1 (en)	2010-08-26	Cell nucleus-entering compositions
WO2016049873A1 (zh)	2016-04-07	芋螺毒素多肽κ-CPTx-btl03、其制备方法及应用
KR20030094262A (ko)	2003-12-11	인간 ｇｈｒｈ-결합 단백질, 헤테로카르핀
WO2016049864A1 (zh)	2016-04-07	芋螺毒素多肽κ-CPTx-btl01、其制备方法及应用
RU2827791C2 (ru)	2024-10-02	Модифицированный эритропоэтин человека
EP1295943B1 (de)	2009-06-03	Polypeptide mit aktivität der stimulierung von neutrophilen
KR20080016675A (ko)	2008-02-21	세포 핵-엔터링 조성물