JP5411857B2 - 医薬組成物及び関連方法 - Google Patents
医薬組成物及び関連方法 Download PDFInfo
- Publication number
- JP5411857B2 JP5411857B2 JP2010518808A JP2010518808A JP5411857B2 JP 5411857 B2 JP5411857 B2 JP 5411857B2 JP 2010518808 A JP2010518808 A JP 2010518808A JP 2010518808 A JP2010518808 A JP 2010518808A JP 5411857 B2 JP5411857 B2 JP 5411857B2
- Authority
- JP
- Japan
- Prior art keywords
- seq
- insulin
- sequence number
- pharmaceutical composition
- wound
- 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 - Fee Related
Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 81
- 238000000034 method Methods 0.000 title description 64
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims description 319
- 206010052428 Wound Diseases 0.000 claims description 196
- 208000027418 Wounds and injury Diseases 0.000 claims description 196
- 108090001061 Insulin Proteins 0.000 claims description 141
- 102000004877 Insulin Human genes 0.000 claims description 140
- 229940125396 insulin Drugs 0.000 claims description 135
- 239000003112 inhibitor Substances 0.000 claims description 105
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 81
- PBGKTOXHQIOBKM-FHFVDXKLSA-N insulin (human) Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 PBGKTOXHQIOBKM-FHFVDXKLSA-N 0.000 claims description 50
- 239000003937 drug carrier Substances 0.000 claims description 44
- 150000001768 cations Chemical class 0.000 claims description 43
- 239000012190 activator Substances 0.000 claims description 38
- 206010072170 Skin wound Diseases 0.000 claims description 35
- 230000004054 inflammatory process Effects 0.000 claims description 35
- 206010061218 Inflammation Diseases 0.000 claims description 34
- 241001465754 Metazoa Species 0.000 claims description 28
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 25
- COCFEDIXXNGUNL-RFKWWTKHSA-N Insulin glargine Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(=O)NCC(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 COCFEDIXXNGUNL-RFKWWTKHSA-N 0.000 claims description 24
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 23
- 101000976075 Homo sapiens Insulin Proteins 0.000 claims description 22
- 108010057186 Insulin Glargine Proteins 0.000 claims description 22
- 108010065920 Insulin Lispro Proteins 0.000 claims description 21
- 230000001684 chronic effect Effects 0.000 claims description 21
- WNRQPCUGRUFHED-DETKDSODSA-N humalog Chemical compound C([C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CS)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CO)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CS)NC(=O)[C@H](CS)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(O)=O)C1=CC=C(O)C=C1.C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CS)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CS)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 WNRQPCUGRUFHED-DETKDSODSA-N 0.000 claims description 21
- 102000015532 Nicotinamide phosphoribosyltransferase Human genes 0.000 claims description 20
- 108010064862 Nicotinamide phosphoribosyltransferase Proteins 0.000 claims description 19
- 239000004026 insulin derivative Substances 0.000 claims description 18
- 229960002068 insulin lispro Drugs 0.000 claims description 18
- 108010073961 Insulin Aspart Proteins 0.000 claims description 15
- 229960004717 insulin aspart Drugs 0.000 claims description 15
- VOMXSOIBEJBQNF-UTTRGDHVSA-N novorapid Chemical compound C([C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CS)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CO)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CS)NC(=O)[C@H](CS)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(O)=O)C1=CC=C(O)C=C1.C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CS)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CS)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 VOMXSOIBEJBQNF-UTTRGDHVSA-N 0.000 claims description 15
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 14
- 125000000539 amino acid group Chemical group 0.000 claims description 13
- 239000011780 sodium chloride Substances 0.000 claims description 13
- 206010000269 abscess Diseases 0.000 claims description 12
- 229960002869 insulin glargine Drugs 0.000 claims description 12
- 150000003839 salts Chemical class 0.000 claims description 11
- 239000008365 aqueous carrier Substances 0.000 claims description 9
- 206010031252 Osteomyelitis Diseases 0.000 claims description 7
- 230000003179 granulation Effects 0.000 claims description 6
- 238000005469 granulation Methods 0.000 claims description 6
- 206010056340 Diabetic ulcer Diseases 0.000 claims description 5
- 210000004899 c-terminal region Anatomy 0.000 claims description 5
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical group C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims description 4
- 101001011741 Bos taurus Insulin Proteins 0.000 claims description 4
- 108010005991 Pork Regular Insulin Proteins 0.000 claims description 4
- IXIBAKNTJSCKJM-BUBXBXGNSA-N bovine insulin Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)C(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 IXIBAKNTJSCKJM-BUBXBXGNSA-N 0.000 claims description 4
- 208000002847 Surgical Wound Diseases 0.000 claims description 3
- 239000000203 mixture Substances 0.000 description 182
- 101001051777 Homo sapiens Protein kinase C alpha type Proteins 0.000 description 131
- 238000009472 formulation Methods 0.000 description 121
- 102100024924 Protein kinase C alpha type Human genes 0.000 description 113
- 210000004027 cell Anatomy 0.000 description 55
- 238000011282 treatment Methods 0.000 description 53
- 239000011575 calcium Substances 0.000 description 48
- 108090000315 Protein Kinase C Proteins 0.000 description 47
- 102000003923 Protein Kinase C Human genes 0.000 description 46
- 108010029485 Protein Isoforms Proteins 0.000 description 41
- 102000001708 Protein Isoforms Human genes 0.000 description 41
- 210000002510 keratinocyte Anatomy 0.000 description 41
- 230000000694 effects Effects 0.000 description 37
- 230000029663 wound healing Effects 0.000 description 37
- 210000003491 skin Anatomy 0.000 description 36
- 239000011777 magnesium Substances 0.000 description 33
- 239000002609 medium Substances 0.000 description 31
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 27
- 108010090613 Human Regular Insulin Proteins 0.000 description 23
- 102000013266 Human Regular Insulin Human genes 0.000 description 23
- 230000037313 granulation tissue formation Effects 0.000 description 23
- 102000004196 processed proteins & peptides Human genes 0.000 description 23
- 230000002401 inhibitory effect Effects 0.000 description 22
- 230000015572 biosynthetic process Effects 0.000 description 20
- 238000003556 assay Methods 0.000 description 19
- 235000001014 amino acid Nutrition 0.000 description 18
- 239000003814 drug Substances 0.000 description 18
- 229940103471 humulin Drugs 0.000 description 18
- 108090000623 proteins and genes Proteins 0.000 description 18
- 102000004169 proteins and genes Human genes 0.000 description 18
- 241000699670 Mus sp. Species 0.000 description 17
- 238000002474 experimental method Methods 0.000 description 17
- 230000035876 healing Effects 0.000 description 17
- 230000004663 cell proliferation Effects 0.000 description 16
- 229940079593 drug Drugs 0.000 description 16
- 235000018102 proteins Nutrition 0.000 description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 229940024606 amino acid Drugs 0.000 description 15
- 150000001413 amino acids Chemical class 0.000 description 15
- 230000014509 gene expression Effects 0.000 description 15
- 238000000338 in vitro Methods 0.000 description 15
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 14
- 206010012601 diabetes mellitus Diseases 0.000 description 14
- 238000011746 C57BL/6J (JAX™ mouse strain) Methods 0.000 description 13
- 102100022905 Keratin, type II cytoskeletal 1 Human genes 0.000 description 13
- 108010070514 Keratin-1 Proteins 0.000 description 13
- 210000001519 tissue Anatomy 0.000 description 13
- 238000004113 cell culture Methods 0.000 description 12
- 210000000265 leukocyte Anatomy 0.000 description 12
- 239000001103 potassium chloride Substances 0.000 description 12
- 235000011164 potassium chloride Nutrition 0.000 description 12
- 239000000758 substrate Substances 0.000 description 12
- 230000035755 proliferation Effects 0.000 description 11
- 239000011734 sodium Substances 0.000 description 11
- 238000010186 staining Methods 0.000 description 11
- 206010063560 Excessive granulation tissue Diseases 0.000 description 10
- 230000004913 activation Effects 0.000 description 10
- 210000004204 blood vessel Anatomy 0.000 description 10
- 210000003414 extremity Anatomy 0.000 description 10
- 229940060975 lantus Drugs 0.000 description 10
- 230000008569 process Effects 0.000 description 10
- 230000002829 reductive effect Effects 0.000 description 10
- 239000000523 sample Substances 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- 230000004069 differentiation Effects 0.000 description 9
- 210000001126 granulation tissue Anatomy 0.000 description 9
- 239000001963 growth medium Substances 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 8
- 241000282414 Homo sapiens Species 0.000 description 8
- 210000002615 epidermis Anatomy 0.000 description 8
- 239000000499 gel Substances 0.000 description 8
- 230000007246 mechanism Effects 0.000 description 8
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 241000282472 Canis lupus familiaris Species 0.000 description 7
- 102000003746 Insulin Receptor Human genes 0.000 description 7
- 108010001127 Insulin Receptor Proteins 0.000 description 7
- 239000012083 RIPA buffer Substances 0.000 description 7
- 208000025865 Ulcer Diseases 0.000 description 7
- 239000000872 buffer Substances 0.000 description 7
- 210000003743 erythrocyte Anatomy 0.000 description 7
- 230000006870 function Effects 0.000 description 7
- 208000015181 infectious disease Diseases 0.000 description 7
- 230000004048 modification Effects 0.000 description 7
- 238000012986 modification Methods 0.000 description 7
- 230000026731 phosphorylation Effects 0.000 description 7
- 238000006366 phosphorylation reaction Methods 0.000 description 7
- 230000009467 reduction Effects 0.000 description 7
- 238000007447 staining method Methods 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- -1 3-Dimethylaminopropyl Chemical group 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- 201000004624 Dermatitis Diseases 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 239000006145 Eagle's minimal essential medium Substances 0.000 description 6
- 241000283086 Equidae Species 0.000 description 6
- 241000699666 Mus <mouse, genus> Species 0.000 description 6
- 210000000270 basal cell Anatomy 0.000 description 6
- 150000001982 diacylglycerols Chemical class 0.000 description 6
- 239000000839 emulsion Substances 0.000 description 6
- 208000027866 inflammatory disease Diseases 0.000 description 6
- 206010024378 leukocytosis Diseases 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 239000002953 phosphate buffered saline Substances 0.000 description 6
- 238000006467 substitution reaction Methods 0.000 description 6
- 231100000397 ulcer Toxicity 0.000 description 6
- 238000001262 western blot Methods 0.000 description 6
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 5
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 108010044467 Isoenzymes Proteins 0.000 description 5
- 239000011324 bead Substances 0.000 description 5
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 5
- 239000013592 cell lysate Substances 0.000 description 5
- 229940038563 human regular insulin Drugs 0.000 description 5
- 238000001114 immunoprecipitation Methods 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- 238000010348 incorporation Methods 0.000 description 5
- 239000004615 ingredient Substances 0.000 description 5
- 230000001105 regulatory effect Effects 0.000 description 5
- 239000006228 supernatant Substances 0.000 description 5
- 229940104230 thymidine Drugs 0.000 description 5
- 230000000699 topical effect Effects 0.000 description 5
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 5
- 241000701161 unidentified adenovirus Species 0.000 description 5
- 230000000007 visual effect Effects 0.000 description 5
- 108010039627 Aprotinin Proteins 0.000 description 4
- 241000283073 Equus caballus Species 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- 102100040445 Keratin, type I cytoskeletal 14 Human genes 0.000 description 4
- 108010066321 Keratin-14 Proteins 0.000 description 4
- GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 4
- JLVVSXFLKOJNIY-UHFFFAOYSA-N Magnesium ion Chemical compound [Mg+2] JLVVSXFLKOJNIY-UHFFFAOYSA-N 0.000 description 4
- 229910019142 PO4 Inorganic materials 0.000 description 4
- 229960004405 aprotinin Drugs 0.000 description 4
- 210000002469 basement membrane Anatomy 0.000 description 4
- 229910052791 calcium Inorganic materials 0.000 description 4
- 229910001424 calcium ion Inorganic materials 0.000 description 4
- 230000011712 cell development Effects 0.000 description 4
- 210000004207 dermis Anatomy 0.000 description 4
- 229940038661 humalog Drugs 0.000 description 4
- 230000002757 inflammatory effect Effects 0.000 description 4
- ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 4
- 108010052968 leupeptin Proteins 0.000 description 4
- GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 4
- 239000006166 lysate Substances 0.000 description 4
- 229910001425 magnesium ion Inorganic materials 0.000 description 4
- 210000004379 membrane Anatomy 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- BMGQWWVMWDBQGC-IIFHNQTCSA-N midostaurin Chemical compound CN([C@H]1[C@H]([C@]2(C)O[C@@H](N3C4=CC=CC=C4C4=C5C(=O)NCC5=C5C6=CC=CC=C6N2C5=C43)C1)OC)C(=O)C1=CC=CC=C1 BMGQWWVMWDBQGC-IIFHNQTCSA-N 0.000 description 4
- 229940112879 novolog Drugs 0.000 description 4
- 239000002674 ointment Substances 0.000 description 4
- 229950000964 pepstatin Drugs 0.000 description 4
- 108010091212 pepstatin Proteins 0.000 description 4
- FAXGPCHRFPCXOO-LXTPJMTPSA-N pepstatin A Chemical compound OC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)CC(C)C FAXGPCHRFPCXOO-LXTPJMTPSA-N 0.000 description 4
- 239000002644 phorbol ester Substances 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 4
- 239000010452 phosphate Substances 0.000 description 4
- 150000003904 phospholipids Chemical class 0.000 description 4
- 238000011533 pre-incubation Methods 0.000 description 4
- 102000005962 receptors Human genes 0.000 description 4
- 108020003175 receptors Proteins 0.000 description 4
- 230000019491 signal transduction Effects 0.000 description 4
- 239000002002 slurry Substances 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 239000007790 solid phase Substances 0.000 description 4
- 238000010561 standard procedure Methods 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 4
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 3
- 229920000936 Agarose Polymers 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- 208000008960 Diabetic foot Diseases 0.000 description 3
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 3
- 208000003790 Foot Ulcer Diseases 0.000 description 3
- 102000042846 PKC family Human genes 0.000 description 3
- 108091082203 PKC family Proteins 0.000 description 3
- 239000000654 additive Substances 0.000 description 3
- 230000024245 cell differentiation Effects 0.000 description 3
- 238000001516 cell proliferation assay Methods 0.000 description 3
- 238000002737 cell proliferation kit Methods 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 239000006071 cream Substances 0.000 description 3
- 210000004748 cultured cell Anatomy 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 210000000981 epithelium Anatomy 0.000 description 3
- 239000000835 fiber Substances 0.000 description 3
- 210000002950 fibroblast Anatomy 0.000 description 3
- 230000001771 impaired effect Effects 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 150000002500 ions Chemical class 0.000 description 3
- 150000002632 lipids Chemical class 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 229940103453 novolin Drugs 0.000 description 3
- 206010033675 panniculitis Diseases 0.000 description 3
- 238000010647 peptide synthesis reaction Methods 0.000 description 3
- PHEDXBVPIONUQT-RGYGYFBISA-N phorbol 13-acetate 12-myristate Chemical compound C([C@]1(O)C(=O)C(C)=C[C@H]1[C@@]1(O)[C@H](C)[C@H]2OC(=O)CCCCCCCCCCCCC)C(CO)=C[C@H]1[C@H]1[C@]2(OC(C)=O)C1(C)C PHEDXBVPIONUQT-RGYGYFBISA-N 0.000 description 3
- 230000010399 physical interaction Effects 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 229920001184 polypeptide Polymers 0.000 description 3
- 230000002062 proliferating effect Effects 0.000 description 3
- 238000010188 recombinant method Methods 0.000 description 3
- 230000011664 signaling Effects 0.000 description 3
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 230000017423 tissue regeneration Effects 0.000 description 3
- 101710175516 14 kDa zinc-binding protein Proteins 0.000 description 2
- SXGZJKUKBWWHRA-UHFFFAOYSA-N 2-(N-morpholiniumyl)ethanesulfonate Chemical compound [O-]S(=O)(=O)CC[NH+]1CCOCC1 SXGZJKUKBWWHRA-UHFFFAOYSA-N 0.000 description 2
- UJOBWOGCFQCDNV-UHFFFAOYSA-N 9H-carbazole Chemical compound C1=CC=C2C3=CC=CC=C3NC2=C1 UJOBWOGCFQCDNV-UHFFFAOYSA-N 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- 101100181137 Caenorhabditis elegans pkc-3 gene Proteins 0.000 description 2
- 101100269980 Drosophila melanogaster aPKC gene Proteins 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 102100037362 Fibronectin Human genes 0.000 description 2
- 108010067306 Fibronectins Proteins 0.000 description 2
- 108010033040 Histones Proteins 0.000 description 2
- 101000599951 Homo sapiens Insulin-like growth factor I Proteins 0.000 description 2
- 102100037852 Insulin-like growth factor I Human genes 0.000 description 2
- 102000012355 Integrin beta1 Human genes 0.000 description 2
- 108010022222 Integrin beta1 Proteins 0.000 description 2
- NPPQSCRMBWNHMW-UHFFFAOYSA-N Meprobamate Chemical compound NC(=O)OCC(C)(CCC)COC(N)=O NPPQSCRMBWNHMW-UHFFFAOYSA-N 0.000 description 2
- 241000699660 Mus musculus Species 0.000 description 2
- 101000998854 Mus musculus Nicotinamide phosphoribosyltransferase Proteins 0.000 description 2
- 108700043304 PKC-3 Proteins 0.000 description 2
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 2
- 229940123924 Protein kinase C inhibitor Drugs 0.000 description 2
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 2
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 2
- 229920002684 Sepharose Polymers 0.000 description 2
- 206010040943 Skin Ulcer Diseases 0.000 description 2
- ZKHQWZAMYRWXGA-KNYAHOBESA-N [[(2r,3s,4r,5r)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] dihydroxyphosphoryl hydrogen phosphate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)O[32P](O)(O)=O)[C@@H](O)[C@H]1O ZKHQWZAMYRWXGA-KNYAHOBESA-N 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 2
- NMYKBZSMOUFOJV-FJSWQEPZSA-N aprinocarsen Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](COP(O)(=S)O[C@@H]2[C@H](O[C@H](C2)N2C3=C(C(NC(N)=N3)=O)N=C2)COP(O)(=S)O[C@@H]2[C@H](O[C@H](C2)N2C3=C(C(NC(N)=N3)=O)N=C2)COP(O)(=S)O[C@@H]2[C@H](O[C@H](C2)N2C(NC(=O)C(C)=C2)=O)COP(O)(=S)O[C@@H]2[C@H](O[C@H](C2)N2C(N=C(N)C=C2)=O)COP(O)(=S)O[C@@H]2[C@H](O[C@H](C2)N2C3=C(C(NC(N)=N3)=O)N=C2)COP(O)(=S)O[C@@H]2[C@H](O[C@H](C2)N2C(N=C(N)C=C2)=O)COP(O)(=S)O[C@@H]2[C@H](O[C@H](C2)N2C(NC(=O)C(C)=C2)=O)COP(O)(=S)O[C@@H]2[C@H](O[C@H](C2)N2C(N=C(N)C=C2)=O)COP(O)(=S)O[C@@H]2[C@H](O[C@H](C2)N2C(NC(=O)C(C)=C2)=O)COP(O)(=S)O[C@@H]2[C@H](O[C@H](C2)N2C(NC(=O)C(C)=C2)=O)COP(O)(=S)O[C@@H]2[C@H](O[C@H](C2)N2C3=C(C(NC(N)=N3)=O)N=C2)CO)[C@@H](OP(O)(=S)OC[C@@H]2[C@H](C[C@@H](O2)N2C3=C(C(NC(N)=N3)=O)N=C2)OP(O)(=S)OC[C@@H]2[C@H](C[C@@H](O2)N2C3=NC=NC(N)=C3N=C2)OP(O)(=S)OC[C@@H]2[C@H](C[C@@H](O2)N2C3=C(C(NC(N)=N3)=O)N=C2)OP(O)(=S)OC[C@@H]2[C@H](C[C@@H](O2)N2C(NC(=O)C(C)=C2)=O)OP(O)(=S)OC[C@@H]2[C@H](C[C@@H](O2)N2C(NC(=O)C(C)=C2)=O)OP(O)(=S)OC[C@@H]2[C@H](C[C@@H](O2)N2C(NC(=O)C(C)=C2)=O)OP(O)(=S)OC[C@@H]2[C@H](C[C@@H](O2)N2C(N=C(N)C=C2)=O)OP(O)(=S)OC[C@@H]2[C@H](C[C@@H](O2)N2C3=NC=NC(N)=C3N=C2)O)C1 NMYKBZSMOUFOJV-FJSWQEPZSA-N 0.000 description 2
- 238000000376 autoradiography Methods 0.000 description 2
- 230000004888 barrier function Effects 0.000 description 2
- 230000000975 bioactive effect Effects 0.000 description 2
- 229910021538 borax Inorganic materials 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 230000003111 delayed effect Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 2
- 229910000397 disodium phosphate Inorganic materials 0.000 description 2
- 235000019800 disodium phosphate Nutrition 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 238000001378 electrochemiluminescence detection Methods 0.000 description 2
- 210000001339 epidermal cell Anatomy 0.000 description 2
- 230000037305 epidermis formation Effects 0.000 description 2
- YUPQOCKHBKYZMN-UHFFFAOYSA-N ethylaminomethanetriol Chemical compound CCNC(O)(O)O YUPQOCKHBKYZMN-UHFFFAOYSA-N 0.000 description 2
- 239000012091 fetal bovine serum Substances 0.000 description 2
- 239000006260 foam Substances 0.000 description 2
- 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 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 210000000003 hoof Anatomy 0.000 description 2
- 230000002209 hydrophobic effect Effects 0.000 description 2
- 238000003364 immunohistochemistry Methods 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 230000028709 inflammatory response Effects 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 230000003902 lesion Effects 0.000 description 2
- 238000011068 loading method Methods 0.000 description 2
- 230000004807 localization Effects 0.000 description 2
- 239000012139 lysis buffer Substances 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 230000035800 maturation Effects 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 229950010895 midostaurin Drugs 0.000 description 2
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 2
- 235000019796 monopotassium phosphate Nutrition 0.000 description 2
- 229920002113 octoxynol Polymers 0.000 description 2
- 235000019271 petrolatum Nutrition 0.000 description 2
- 239000008363 phosphate buffer Substances 0.000 description 2
- PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 0.000 description 2
- 230000004962 physiological condition Effects 0.000 description 2
- IWZKICVEHNUQTL-UHFFFAOYSA-M potassium hydrogen phthalate Chemical compound [K+].OC(=O)C1=CC=CC=C1C([O-])=O IWZKICVEHNUQTL-UHFFFAOYSA-M 0.000 description 2
- 229910000160 potassium phosphate Inorganic materials 0.000 description 2
- 235000011009 potassium phosphates Nutrition 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 239000003881 protein kinase C inhibitor Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000011535 reaction buffer Substances 0.000 description 2
- 238000003259 recombinant expression Methods 0.000 description 2
- 230000008929 regeneration Effects 0.000 description 2
- 238000011069 regeneration method Methods 0.000 description 2
- 239000004328 sodium tetraborate Substances 0.000 description 2
- 235000010339 sodium tetraborate Nutrition 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 210000004003 subcutaneous fat Anatomy 0.000 description 2
- 210000004304 subcutaneous tissue Anatomy 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 230000002459 sustained effect Effects 0.000 description 2
- 230000026683 transduction Effects 0.000 description 2
- 238000010361 transduction Methods 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 2
- 239000013598 vector Substances 0.000 description 2
- 239000001993 wax Substances 0.000 description 2
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- DSEKYWAQQVUQTP-XEWMWGOFSA-N (2r,4r,4as,6as,6as,6br,8ar,12ar,14as,14bs)-2-hydroxy-4,4a,6a,6b,8a,11,11,14a-octamethyl-2,4,5,6,6a,7,8,9,10,12,12a,13,14,14b-tetradecahydro-1h-picen-3-one Chemical compound C([C@H]1[C@]2(C)CC[C@@]34C)C(C)(C)CC[C@]1(C)CC[C@]2(C)[C@H]4CC[C@@]1(C)[C@H]3C[C@@H](O)C(=O)[C@@H]1C DSEKYWAQQVUQTP-XEWMWGOFSA-N 0.000 description 1
- RISSBZWRJRRXTD-OLBPYZPGSA-N (2s)-2,6-diamino-n-[(1-tridecanoylpiperidin-2-yl)methyl]hexanamide;dihydrochloride Chemical compound Cl.Cl.CCCCCCCCCCCCC(=O)N1CCCCC1CNC(=O)[C@@H](N)CCCCN RISSBZWRJRRXTD-OLBPYZPGSA-N 0.000 description 1
- PORPENFLTBBHSG-MGBGTMOVSA-N 1,2-dihexadecanoyl-sn-glycerol-3-phosphate Chemical group CCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(O)=O)OC(=O)CCCCCCCCCCCCCCC PORPENFLTBBHSG-MGBGTMOVSA-N 0.000 description 1
- TZCPCKNHXULUIY-RGULYWFUSA-N 1,2-distearoyl-sn-glycero-3-phosphoserine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OC[C@H](N)C(O)=O)OC(=O)CCCCCCCCCCCCCCCCC TZCPCKNHXULUIY-RGULYWFUSA-N 0.000 description 1
- HNLXNOZHXNSSPN-UHFFFAOYSA-N 2-[2-[2-[2-[2-[2-[2-[4-(2,4,4-trimethylpentan-2-yl)phenoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethanol Chemical compound CC(C)(C)CC(C)(C)C1=CC=C(OCCOCCOCCOCCOCCOCCOCCO)C=C1 HNLXNOZHXNSSPN-UHFFFAOYSA-N 0.000 description 1
- 125000001731 2-cyanoethyl group Chemical group [H]C([H])(*)C([H])([H])C#N 0.000 description 1
- WHOOZDLAJIKMBZ-UHFFFAOYSA-N 3-[1-[3-(dimethylamino)propyl]indol-3-yl]-4-(1-methylindol-3-yl)pyrrole-2,5-dione Chemical compound C12=CC=CC=C2N(CCCN(C)C)C=C1C1=C(C=2C3=CC=CC=C3N(C)C=2)C(=O)NC1=O WHOOZDLAJIKMBZ-UHFFFAOYSA-N 0.000 description 1
- QMGUOJYZJKLOLH-UHFFFAOYSA-N 3-[1-[3-(dimethylamino)propyl]indol-3-yl]-4-(1h-indol-3-yl)pyrrole-2,5-dione Chemical compound C12=CC=CC=C2N(CCCN(C)C)C=C1C1=C(C=2C3=CC=CC=C3NC=2)C(=O)NC1=O QMGUOJYZJKLOLH-UHFFFAOYSA-N 0.000 description 1
- MWWKMFTXNBHVJT-UHFFFAOYSA-N 4-(4-butoxyphenyl)phenol Chemical compound C1=CC(OCCCC)=CC=C1C1=CC=C(O)C=C1 MWWKMFTXNBHVJT-UHFFFAOYSA-N 0.000 description 1
- GJCOSYZMQJWQCA-UHFFFAOYSA-N 9H-xanthene Chemical compound C1=CC=C2CC3=CC=CC=C3OC2=C1 GJCOSYZMQJWQCA-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 102000014777 Adipokines Human genes 0.000 description 1
- 108010078606 Adipokines Proteins 0.000 description 1
- 108010028091 Albulin Proteins 0.000 description 1
- 240000003291 Armoracia rusticana Species 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 208000035404 Autolysis Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- NOVSBNOTERYJBO-UHFFFAOYSA-N CCCCCC(=O)N.O.Cl.Cl Chemical compound CCCCCC(=O)N.O.Cl.Cl NOVSBNOTERYJBO-UHFFFAOYSA-N 0.000 description 1
- 241000282465 Canis Species 0.000 description 1
- 206010057248 Cell death Diseases 0.000 description 1
- 208000035484 Cellulite Diseases 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 102000010831 Cytoskeletal Proteins Human genes 0.000 description 1
- 108010037414 Cytoskeletal Proteins Proteins 0.000 description 1
- 230000006820 DNA synthesis Effects 0.000 description 1
- 108010092160 Dactinomycin Proteins 0.000 description 1
- 208000002249 Diabetes Complications Diseases 0.000 description 1
- 239000012591 Dulbecco’s Phosphate Buffered Saline Substances 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 230000005526 G1 to G0 transition Effects 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 108010024636 Glutathione Proteins 0.000 description 1
- ZWZWYGMENQVNFU-UHFFFAOYSA-N Glycerophosphorylserin Natural products OC(=O)C(N)COP(O)(=O)OCC(O)CO ZWZWYGMENQVNFU-UHFFFAOYSA-N 0.000 description 1
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Natural products NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- VWVYILCFSYNJHF-UHFFFAOYSA-N Goe 6976 Chemical compound C1=CC=C2N(CCC#N)C3=C4N(C)C5=CC=CC=C5C4=C(C(=O)NC4)C4=C3C2=C1 VWVYILCFSYNJHF-UHFFFAOYSA-N 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 101000998855 Homo sapiens Nicotinamide phosphoribosyltransferase Proteins 0.000 description 1
- 101001059454 Homo sapiens Serine/threonine-protein kinase MARK2 Proteins 0.000 description 1
- 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 description 1
- 108010089308 Insulin Detemir Proteins 0.000 description 1
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 1
- 241000764238 Isis Species 0.000 description 1
- QUOGESRFPZDMMT-UHFFFAOYSA-N L-Homoarginine Natural products OC(=O)C(N)CCCCNC(N)=N QUOGESRFPZDMMT-UHFFFAOYSA-N 0.000 description 1
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-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
- QUOGESRFPZDMMT-YFKPBYRVSA-N L-homoarginine Chemical compound OC(=O)[C@@H](N)CCCCNC(N)=N QUOGESRFPZDMMT-YFKPBYRVSA-N 0.000 description 1
- NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Chemical group 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Chemical group NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 description 1
- 208000002720 Malnutrition Diseases 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- GXCLVBGFBYZDAG-UHFFFAOYSA-N N-[2-(1H-indol-3-yl)ethyl]-N-methylprop-2-en-1-amine Chemical compound CN(CCC1=CNC2=C1C=CC=C2)CC=C GXCLVBGFBYZDAG-UHFFFAOYSA-N 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 1
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 1
- 206010049752 Peau d'orange Diseases 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 239000004264 Petrolatum Substances 0.000 description 1
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
- 102000010995 Pleckstrin homology domains Human genes 0.000 description 1
- 108050001185 Pleckstrin homology domains Proteins 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 108010076181 Proinsulin Proteins 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- 229940124639 Selective inhibitor Drugs 0.000 description 1
- 229920005654 Sephadex Polymers 0.000 description 1
- 239000012507 Sephadex™ Substances 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 102100028904 Serine/threonine-protein kinase MARK2 Human genes 0.000 description 1
- 102000013275 Somatomedins Human genes 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 239000006180 TBST buffer Substances 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 206010062910 Vascular infections Diseases 0.000 description 1
- 206010058042 Wound abscess Diseases 0.000 description 1
- 238000004847 absorption spectroscopy Methods 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 229930183665 actinomycin Natural products 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 210000001789 adipocyte Anatomy 0.000 description 1
- 238000001261 affinity purification Methods 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 230000009435 amidation Effects 0.000 description 1
- 238000007112 amidation reaction Methods 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 238000002266 amputation Methods 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 210000003484 anatomy Anatomy 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 239000010775 animal oil Substances 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 229940112930 apidra Drugs 0.000 description 1
- RCHHVVGSTHAVPF-ZPHPLDECSA-N apidra Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3N=CNC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CNC=N1 RCHHVVGSTHAVPF-ZPHPLDECSA-N 0.000 description 1
- 238000003782 apoptosis assay Methods 0.000 description 1
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N aspartic acid group Chemical group N[C@@H](CC(=O)O)C(=O)O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 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
- 230000004071 biological effect Effects 0.000 description 1
- 238000010170 biological method Methods 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- UDSAIICHUKSCKT-UHFFFAOYSA-N bromophenol blue Chemical compound C1=C(Br)C(O)=C(Br)C=C1C1(C=2C=C(Br)C(O)=C(Br)C=2)C2=CC=CC=C2S(=O)(=O)O1 UDSAIICHUKSCKT-UHFFFAOYSA-N 0.000 description 1
- 230000003139 buffering effect Effects 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 210000004671 cell-free system Anatomy 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 230000036232 cellulite Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 239000003636 conditioned culture medium Substances 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 239000013068 control sample Substances 0.000 description 1
- 238000011443 conventional therapy Methods 0.000 description 1
- 229920001577 copolymer Chemical compound 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 239000013058 crude material Substances 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 239000007857 degradation product Substances 0.000 description 1
- 230000023753 dehiscence Effects 0.000 description 1
- 238000000326 densiometry Methods 0.000 description 1
- 229960003964 deoxycholic acid Drugs 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 210000005175 epidermal keratinocyte Anatomy 0.000 description 1
- 230000008508 epithelial proliferation Effects 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000010408 film Substances 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229960003180 glutathione Drugs 0.000 description 1
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- 210000003780 hair follicle Anatomy 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 230000014726 immortalization of host cell Effects 0.000 description 1
- 239000012133 immunoprecipitate Substances 0.000 description 1
- 125000000814 indol-3-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C([*])C2=C1[H] 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 108700039926 insulin glulisine Proteins 0.000 description 1
- 210000005061 intracellular organelle Anatomy 0.000 description 1
- 102000027411 intracellular receptors Human genes 0.000 description 1
- 108091008582 intracellular receptors Proteins 0.000 description 1
- 230000029774 keratinocyte migration Effects 0.000 description 1
- 229940102988 levemir Drugs 0.000 description 1
- UGOZVNFCFYTPAZ-IOXYNQHNSA-N levemir Chemical compound CCCCCCCCCCCCCC(=O)NCCCC[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H]([C@@H](C)O)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)CNC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@H]1NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=2N=CNC=2)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=2N=CNC=2)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=2C=CC=CC=2)C(C)C)CSSC[C@@H]2NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)C(C)C)CSSC[C@H](NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CO)NC(=O)[C@H]([C@@H](C)O)NC2=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H](CSSC1)C(=O)N[C@@H](CC(N)=O)C(O)=O)CC1=CC=C(O)C=C1 UGOZVNFCFYTPAZ-IOXYNQHNSA-N 0.000 description 1
- 229960004194 lidocaine Drugs 0.000 description 1
- 210000003041 ligament Anatomy 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 239000003589 local anesthetic agent Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 238000002595 magnetic resonance imaging Methods 0.000 description 1
- 230000001071 malnutrition Effects 0.000 description 1
- 235000000824 malnutrition Nutrition 0.000 description 1
- 238000007726 management method Methods 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- SAWVGDJBSPLRRB-UHFFFAOYSA-N methanesulfonic acid;3-[3-[4-(1-methylindol-3-yl)-2,5-dioxopyrrol-3-yl]indol-1-yl]propyl carbamimidothioate Chemical compound CS(O)(=O)=O.C12=CC=CC=C2N(C)C=C1C1=C(C=2C3=CC=CC=C3N(CCCSC(N)=N)C=2)C(=O)NC1=O SAWVGDJBSPLRRB-UHFFFAOYSA-N 0.000 description 1
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 1
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 239000013081 microcrystal Substances 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 230000000394 mitotic effect Effects 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 230000007498 myristoylation Effects 0.000 description 1
- 229920001206 natural gum Polymers 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 201000001119 neuropathy Diseases 0.000 description 1
- 230000007823 neuropathy Effects 0.000 description 1
- 229940053973 novocaine Drugs 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 208000015380 nutritional deficiency disease Diseases 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 231100000590 oncogenic Toxicity 0.000 description 1
- 230000002246 oncogenic effect Effects 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 229960003104 ornithine Drugs 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 239000012186 ozocerite Substances 0.000 description 1
- 230000000242 pagocytic effect Effects 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 239000000813 peptide hormone Substances 0.000 description 1
- 208000033808 peripheral neuropathy Diseases 0.000 description 1
- 229940066842 petrolatum Drugs 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 150000004633 phorbol derivatives Chemical class 0.000 description 1
- 150000003905 phosphatidylinositols Chemical class 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 238000007747 plating Methods 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000004237 preparative chromatography Methods 0.000 description 1
- 108010066381 preproinsulin Proteins 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000005522 programmed cell death Effects 0.000 description 1
- 210000001236 prokaryotic cell Anatomy 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 230000008844 regulatory mechanism Effects 0.000 description 1
- 238000007634 remodeling Methods 0.000 description 1
- 230000008521 reorganization Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 239000012723 sample buffer Substances 0.000 description 1
- 210000001732 sebaceous gland Anatomy 0.000 description 1
- 230000011218 segmentation Effects 0.000 description 1
- 230000028043 self proteolysis Effects 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000002924 silencing RNA Substances 0.000 description 1
- 230000037204 skin physiology Effects 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- FHHPUSMSKHSNKW-SMOYURAASA-M sodium deoxycholate Chemical compound [Na+].C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC([O-])=O)C)[C@@]2(C)[C@@H](O)C1 FHHPUSMSKHSNKW-SMOYURAASA-M 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- HKSZLNNOFSGOKW-FYTWVXJKSA-N staurosporine Chemical class C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1[C@H]1C[C@@H](NC)[C@@H](OC)[C@]4(C)O1 HKSZLNNOFSGOKW-FYTWVXJKSA-N 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 210000005127 stratified epithelium Anatomy 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 210000000106 sweat gland Anatomy 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 229920001059 synthetic polymer Polymers 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 1
- 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 239000003104 tissue culture media Substances 0.000 description 1
- 230000009772 tissue formation Effects 0.000 description 1
- 230000008364 tissue synthesis Effects 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- IHIXIJGXTJIKRB-UHFFFAOYSA-N trisodium vanadate Chemical compound [Na+].[Na+].[Na+].[O-][V]([O-])([O-])=O IHIXIJGXTJIKRB-UHFFFAOYSA-N 0.000 description 1
- 230000036269 ulceration Effects 0.000 description 1
- LSGOVYNHVSXFFJ-UHFFFAOYSA-N vanadate(3-) Chemical compound [O-][V]([O-])([O-])=O LSGOVYNHVSXFFJ-UHFFFAOYSA-N 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 208000019553 vascular disease Diseases 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 230000010388 wound contraction Effects 0.000 description 1
- 239000003357 wound healing promoting agent Substances 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/45—Transferases (2)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61K31/553—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having at least one nitrogen and one oxygen as ring hetero atoms, e.g. loxapine, staurosporine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/08—Peptides having 5 to 11 amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/28—Insulins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Endocrinology (AREA)
- Diabetes (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Molecular Biology (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Dermatology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US96270607P | 2007-07-30 | 2007-07-30 | |
| US60/962,706 | 2007-07-30 | ||
| PCT/IL2008/001049 WO2009016629A2 (en) | 2007-07-30 | 2008-07-30 | Pharmaceutical composition for treating wounds and related methods |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2013044384A Division JP2013144697A (ja) | 2007-07-30 | 2013-03-06 | 医薬組成物 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2010535194A JP2010535194A (ja) | 2010-11-18 |
| JP5411857B2 true JP5411857B2 (ja) | 2014-02-12 |
Family
ID=40305016
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2010518808A Expired - Fee Related JP5411857B2 (ja) | 2007-07-30 | 2008-07-30 | 医薬組成物及び関連方法 |
| JP2013044384A Pending JP2013144697A (ja) | 2007-07-30 | 2013-03-06 | 医薬組成物 |
| JP2013221921A Pending JP2014024862A (ja) | 2007-07-30 | 2013-10-25 | 医薬組成物 |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2013044384A Pending JP2013144697A (ja) | 2007-07-30 | 2013-03-06 | 医薬組成物 |
| JP2013221921A Pending JP2014024862A (ja) | 2007-07-30 | 2013-10-25 | 医薬組成物 |
Country Status (10)
| Country | Link |
|---|---|
| US (3) | US20100310542A1 (https=) |
| EP (2) | EP2653166A3 (https=) |
| JP (3) | JP5411857B2 (https=) |
| KR (2) | KR20100040912A (https=) |
| CN (2) | CN102755649A (https=) |
| AU (1) | AU2008281374B2 (https=) |
| CA (1) | CA2694927A1 (https=) |
| NZ (1) | NZ582556A (https=) |
| RU (2) | RU2502520C2 (https=) |
| WO (1) | WO2009016629A2 (https=) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005013885A2 (en) | 2003-08-07 | 2005-02-17 | Healor Ltd. | Pharmaceutical compositions and methods for accelerating wound healing |
| EP2462944A3 (en) | 2005-08-29 | 2012-09-12 | HealOr Ltd. | Methods and compositions for prevention and treatment of diabetic and aged skin |
| WO2011011808A1 (en) * | 2009-07-30 | 2011-02-03 | Roman Buga | A cosmetic composition comprising sodium chloride in combination with one or more of protein, collagen, gelatin or amino acid |
| WO2011082231A1 (en) * | 2009-12-31 | 2011-07-07 | New York University | Compositions and methods for promoting epithelialization and wound closure |
| JP2013516500A (ja) * | 2010-01-11 | 2013-05-13 | ヒールオア・リミテッド | 炎症性疾患および障害を治療するための方法 |
| EP2944319A1 (en) * | 2010-11-08 | 2015-11-18 | Arava Bio-Tech Ltd. | Buffered ophthalmic compositions and use thereof |
| US10342891B2 (en) * | 2013-09-19 | 2019-07-09 | Medline Industries, Inc. | Wound dressing containing saccharide and collagen |
| CN106456700B (zh) | 2014-01-29 | 2020-02-18 | 斯特拉斯堡大学 | 糖尿病治疗和预防的新靶标 |
| EP3421485A1 (en) | 2017-06-30 | 2019-01-02 | Université de Strasbourg | Peptides for treatment and prevention of hyperglycaemia |
| RU2766292C1 (ru) * | 2021-08-05 | 2022-03-14 | Федеральное государственное унитарное предприятие "Санкт-Петербургский научно-исследовательский институт вакцин и сывороток и предприятие по производству бактерийных препаратов" Федерального медико-биологического агентства (ФГУП СПбНИИВС ФМБА России) | Состав вакцины против covid-19 |
Family Cites Families (87)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3549747A (en) * | 1968-02-20 | 1970-12-22 | Flow Pharma Inc | Contact lens wetting solution and method of using same |
| US3947573A (en) * | 1969-12-01 | 1976-03-30 | Burton, Parsons And Company, Inc. | Opthalmic solution |
| US3856919A (en) * | 1970-06-08 | 1974-12-24 | Burton Parsons Chemicals Inc | Ophthalmic solution |
| US3767788A (en) * | 1970-06-08 | 1973-10-23 | Burton Parsons Chemicals Inc | Ophthalmic solution |
| US3767789A (en) * | 1971-06-21 | 1973-10-23 | Burton Parsons & Co Inc | Method of providing a synthetic mucus in vivo |
| US3907985A (en) * | 1973-07-27 | 1975-09-23 | Burton Parsons And Company Inc | Polystyrene sulfonate containing opthalmic solutions |
| US3987163A (en) * | 1973-07-27 | 1976-10-19 | Burton, Parsons And Company, Inc. | Polystyrene sulfonate containing opthalmic solutions |
| US4029817A (en) * | 1973-09-24 | 1977-06-14 | Allergan Pharmaceuticals | Soft contact lens preserving solutions |
| US3920810A (en) * | 1974-04-23 | 1975-11-18 | Burton Parsons And Company Inc | Polyacrylamide containing ophthalmic solutions |
| US4120949A (en) * | 1977-10-05 | 1978-10-17 | Cooper Laboratories, Inc. | Ophthalmic solution |
| US4131651A (en) * | 1977-10-25 | 1978-12-26 | Barnes-Hind Pharmaceuticals, Inc. | Treatment of dry eye |
| US4409205A (en) * | 1979-03-05 | 1983-10-11 | Cooper Laboratories, Inc. | Ophthalmic solution |
| US4558033A (en) * | 1983-06-06 | 1985-12-10 | Amgen | Potentiation of the effects of insulin by peptides |
| US4673649A (en) * | 1983-07-15 | 1987-06-16 | University Patents, Inc. | Process and defined medium for growth of human epidermal keratinocyte cells |
| EP0223977B1 (en) * | 1985-11-25 | 1990-10-10 | Wako Pure Chemical Industries, Ltd. | Colour developing method in clinical examinations |
| US4801612A (en) * | 1986-07-03 | 1989-01-31 | Regents Of The University Of California | Method of inhibiting inflammatory response |
| US4833257A (en) * | 1986-07-28 | 1989-05-23 | Arizona Board Of Regents | Compositions of matter and methods of using same |
| IL80298A (en) * | 1986-10-14 | 1993-01-31 | Res & Dev Co Ltd | Eye drops |
| JPH0739508B2 (ja) * | 1986-11-11 | 1995-05-01 | 株式会社林原生物化学研究所 | プルラン・ポリエチレングリコ−ル会合物とその製造方法並びに用途 |
| US4808402A (en) * | 1987-05-29 | 1989-02-28 | Northwestern University | Method and compositions for modulating neovascularization |
| US5137734A (en) * | 1989-03-22 | 1992-08-11 | Dana Farber Cancer Institute | Angiogenic monoglycerides |
| US5019400A (en) * | 1989-05-01 | 1991-05-28 | Enzytech, Inc. | Very low temperature casting of controlled release microspheres |
| US5158935A (en) * | 1989-05-12 | 1992-10-27 | Chiron Corporation | Human epidermal growth factor having substitution at position 11 |
| US5723119A (en) * | 1989-07-28 | 1998-03-03 | Schering Corporation | Method for enhancing wound healing/repair with IL-4 |
| US5145679A (en) * | 1989-10-05 | 1992-09-08 | Hinson Joan B | Topical emollient for prevention and treatment of circulatory induced lesions |
| US5981606A (en) * | 1991-03-01 | 1999-11-09 | Warner-Lambert Company | Therapeutic TGF-beta-wound healing compositions and methods for preparing and using same |
| AU668509B2 (en) * | 1991-04-19 | 1996-05-09 | Affinity Biotech, Inc. | Convertible microemulsion formulations |
| HUT67319A (en) * | 1991-08-30 | 1995-03-28 | Life Medical Sciences Inc | Compositions for treating wounds |
| US5591709A (en) * | 1991-08-30 | 1997-01-07 | Life Medical Sciences, Inc. | Compositions and methods for treating wounds |
| WO1993008825A1 (en) * | 1991-11-04 | 1993-05-13 | Zymogenetics, Inc. | Pdgf gel formulation |
| US5922686A (en) * | 1992-03-16 | 1999-07-13 | Isis Pharmaceuticals, Inc. | Oligonucleotide modulation of protein kinase C |
| US6537973B1 (en) * | 1992-03-16 | 2003-03-25 | Isis Pharmaceuticals, Inc. | Oligonucleotide inhibition of protein kinase C |
| DE4208552A1 (de) * | 1992-03-17 | 1993-09-23 | Liedtke Pharmed Gmbh | Topische arzneiformen mit insulin |
| GB9210574D0 (en) * | 1992-05-18 | 1992-07-01 | Ca Nat Research Council | Biotherapeutic cell-coated microspheres for wound/burn and prothesis implant applications |
| CA2125060C (en) * | 1993-07-02 | 1999-03-30 | Henry P. Dabrowski | Ophthalmic solution for artificial tears |
| US6028118A (en) * | 1996-08-08 | 2000-02-22 | Les Laboratoires Aeterna Inc. | Methods of using extracts of shark cartilage |
| JP3414539B2 (ja) * | 1994-05-11 | 2003-06-09 | 有限会社ドット | 経鼻吸収用組成物 |
| US5631245A (en) * | 1995-06-06 | 1997-05-20 | Biodynamics Pharmaceuticals, Inc. | Method for medicating the inflammatory controlling system and adverse inflammatory reactions and for making compounds for treating the pathology of adverse inflammatory reactions |
| GB2304047A (en) * | 1995-08-09 | 1997-03-12 | Univ Manchester | Pharmaceutical compositions containing cytokines |
| DE69722176T2 (de) * | 1996-01-23 | 2004-03-18 | The Board Of Trustees Of The Leland Stanford Junior University, Palo Alto | Verfahren zur suche nach transdominanten effektorpeptiden und rna-molekülen |
| US5869037A (en) * | 1996-06-26 | 1999-02-09 | Cornell Research Foundation, Inc. | Adenoviral-mediated gene transfer to adipocytes |
| JPH10158188A (ja) * | 1996-11-29 | 1998-06-16 | Senju Pharmaceut Co Ltd | 角膜治療用組成物 |
| GB9702943D0 (en) * | 1997-02-13 | 1997-04-02 | Univ Manchester | Wound healing |
| US6274712B1 (en) * | 1997-12-23 | 2001-08-14 | 3-Dimensional Pharmaceuticals, Inc. | Analogs of human basic fibroblast growth factor mutated at one or more of the positions glutamute 89, aspartate 101 or leucine 137 |
| FR2773075B1 (fr) * | 1997-12-31 | 2000-05-05 | Cird Galderma | Utilisation d'activateurs de ppar-gamma en dermatologie |
| EP1044016B1 (en) * | 1998-01-09 | 2005-03-16 | Novo Nordisk A/S | Stabilised insulin compositions |
| US6790207B2 (en) * | 1998-06-04 | 2004-09-14 | Curon Medical, Inc. | Systems and methods for applying a selected treatment agent into contact with tissue to treat disorders of the gastrointestinal tract |
| US6489306B2 (en) * | 1998-02-23 | 2002-12-03 | University Of South Florida | Method of intranasal gene transfer for protection against respiratory infection |
| DE19826628C1 (de) * | 1998-06-17 | 2000-07-20 | Werner Kern | Intranasale Verwendung von Insulin bei Hirnleistungsstörungen |
| US6376467B1 (en) * | 1998-10-09 | 2002-04-23 | The Regents Of The University Of California | Use of inhibitors of protein kinase C epsilon to treat pain |
| WO2000005250A1 (en) * | 1998-07-23 | 2000-02-03 | Yeda Research And Development Co., Ltd | Treatment of autoimmune conditions with copolymer 1 and related copolymers and peptides |
| US6096288A (en) * | 1998-10-12 | 2000-08-01 | Mobil Oil Corporation | Synthesis of the cubic mesoporous molecular sieve MCM-48 |
| WO2000030628A2 (en) * | 1998-11-20 | 2000-06-02 | Genentech, Inc. | Method of inhibiting angiogenesis |
| US7261881B1 (en) * | 1999-05-20 | 2007-08-28 | Yale University | Modulation of angiogenesis and wound healing |
| US6541447B1 (en) * | 1999-09-01 | 2003-04-01 | B & M Healthcare Technologies, Inc. | Wound healing composition and method for use thereof |
| CA2400040A1 (en) * | 2000-02-25 | 2001-08-30 | Immunex Corporation | Integrin antagonists |
| CZ20023174A3 (cs) * | 2000-03-24 | 2003-01-15 | Novartis Ag | Farmaceutické prostředky obsahující antiangiogenní léčivo a fotosenzitivní činidlo |
| JP2003530156A (ja) * | 2000-04-06 | 2003-10-14 | ユニバーシティ ライセンス ホールディングス インコーポレイテッド | 創傷治癒を促進するための組成物および方法 |
| US20100129332A1 (en) * | 2000-07-31 | 2010-05-27 | Tamar Tennenbaum | Methods and pharmaceutical compositions for healing wounds |
| WO2002009639A2 (en) * | 2000-07-31 | 2002-02-07 | Bar Ilan University | Methods and pharmaceutical compositions for healing wounds |
| US20040037828A1 (en) * | 2002-07-09 | 2004-02-26 | Bar-Ilan University | Methods and pharmaceutical compositions for healing wounds |
| US20060258562A1 (en) * | 2000-07-31 | 2006-11-16 | Healor Ltd. | Methods and pharmaceutical compositions for healing wounds |
| GB2369572A (en) * | 2000-11-29 | 2002-06-05 | Raft Trustees Ltd | Wound treatment composition comprising insulin |
| JP2002198443A (ja) * | 2000-12-26 | 2002-07-12 | Nec Corp | 半導体装置及びその製造方法 |
| US20020119914A1 (en) * | 2000-12-26 | 2002-08-29 | Deguang Zhu | New uses of insulin and pancreatin |
| GB0103877D0 (en) * | 2001-02-16 | 2001-04-04 | King S College London | Novel Drug Delivery system |
| DE10109280A1 (de) * | 2001-02-26 | 2002-09-05 | Peter Mayser | Indolderivate mit inhibitorischer Wirkung auf Proteinkinasen |
| KR100404072B1 (ko) * | 2001-03-12 | 2003-11-03 | 주식회사 두산 | 광범위 피부질환 치료용 조성물 |
| US20030091601A1 (en) * | 2001-11-13 | 2003-05-15 | Abat Inc. | Use of topical arginine to enhance wound healing |
| US20030124503A1 (en) * | 2001-12-28 | 2003-07-03 | Olivencia-Yurvati Albert H. | Pyruvate cardioplegia solutions for administration to the heart during cardiopulmonary surgery and methods of use thereof |
| WO2003059396A1 (en) * | 2002-01-11 | 2003-07-24 | Sergei Zolotukhin | Adiponectin gene therapy |
| RU2249467C2 (ru) * | 2002-11-25 | 2005-04-10 | ООО Научно-производственное предприятие "ЭРЛОН", Лтд. | Медицинский материал и изделия на его основе |
| US20040175384A1 (en) * | 2003-12-12 | 2004-09-09 | Mohapatra Shyam S. | Protein kinase C as a target for the treatment of respiratory syncytial virus |
| SE0300207D0 (sv) * | 2003-01-29 | 2003-01-29 | Karolinska Innovations Ab | New use and composition |
| US7190893B2 (en) * | 2003-06-27 | 2007-03-13 | Valeo Electrical Systems, Inc. | Fluid heater with low porosity thermal mass |
| NZ588743A (en) * | 2003-07-15 | 2012-05-25 | Univ Bar Ilan | Use of a protein kinase C (PKC) alpha inhibitor for treating inflammation of the skin |
| WO2005013885A2 (en) * | 2003-08-07 | 2005-02-17 | Healor Ltd. | Pharmaceutical compositions and methods for accelerating wound healing |
| US20050164323A1 (en) * | 2003-12-24 | 2005-07-28 | Wyeth | Methods of treating asthma |
| US7902330B2 (en) * | 2004-02-13 | 2011-03-08 | Albert Einstein College Of Medicine Of Yeshiva University | Protein kinase inhibitors and methods for identifying same |
| US8158586B2 (en) * | 2005-04-11 | 2012-04-17 | Pharmagap Inc. | Inhibitors of protein kinases and uses thereof |
| CA2659961A1 (en) * | 2005-08-05 | 2007-02-15 | Pharmagap Inc. | Targeted protein kinase c inhibitors and uses thereof |
| AU2006280953B2 (en) * | 2005-08-19 | 2013-01-24 | Emisphere Technologies, Inc. | Cyclopropyl compounds and compositions for delivering active agents |
| EP2462944A3 (en) * | 2005-08-29 | 2012-09-12 | HealOr Ltd. | Methods and compositions for prevention and treatment of diabetic and aged skin |
| US20090306045A1 (en) * | 2005-12-22 | 2009-12-10 | Ira Mellman | Inhibition of Glycogen Synthase Kinase and Methods of Treating Autoimmune or Immune Inflammatory Disease |
| US20080292726A1 (en) * | 2007-01-23 | 2008-11-27 | Bernstein Lawrence R | Ophthalmic gallium compositions and methods of their use |
| WO2010029350A1 (en) * | 2008-09-09 | 2010-03-18 | University Of East Anglia | Treatment of fibrotic eye disorders |
| CN102325789A (zh) * | 2009-02-24 | 2012-01-18 | 希尔洛有限公司 | 用于治疗痤疮和其它病症的内脂素治疗药物 |
-
2008
- 2008-07-30 CN CN2012102198145A patent/CN102755649A/zh active Pending
- 2008-07-30 US US12/451,625 patent/US20100310542A1/en not_active Abandoned
- 2008-07-30 JP JP2010518808A patent/JP5411857B2/ja not_active Expired - Fee Related
- 2008-07-30 CN CN2008801012390A patent/CN101835486B/zh not_active Expired - Fee Related
- 2008-07-30 NZ NZ582556A patent/NZ582556A/xx not_active IP Right Cessation
- 2008-07-30 KR KR1020107002645A patent/KR20100040912A/ko not_active Ceased
- 2008-07-30 CA CA2694927A patent/CA2694927A1/en not_active Abandoned
- 2008-07-30 WO PCT/IL2008/001049 patent/WO2009016629A2/en not_active Ceased
- 2008-07-30 KR KR1020127028542A patent/KR20130121678A/ko not_active Ceased
- 2008-07-30 EP EP12007936.3A patent/EP2653166A3/en not_active Withdrawn
- 2008-07-30 RU RU2010106661/15A patent/RU2502520C2/ru not_active IP Right Cessation
- 2008-07-30 EP EP08789725A patent/EP2185184A2/en not_active Withdrawn
- 2008-07-30 AU AU2008281374A patent/AU2008281374B2/en not_active Ceased
-
2013
- 2013-02-15 US US13/768,583 patent/US20130336952A1/en not_active Abandoned
- 2013-02-15 US US13/768,555 patent/US20140227243A1/en not_active Abandoned
- 2013-03-06 JP JP2013044384A patent/JP2013144697A/ja active Pending
- 2013-09-16 RU RU2013142159/15A patent/RU2013142159A/ru not_active Application Discontinuation
- 2013-10-25 JP JP2013221921A patent/JP2014024862A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| WO2009016629A3 (en) | 2009-05-22 |
| EP2653166A2 (en) | 2013-10-23 |
| RU2013142159A (ru) | 2015-03-27 |
| EP2185184A2 (en) | 2010-05-19 |
| EP2653166A3 (en) | 2014-08-27 |
| JP2013144697A (ja) | 2013-07-25 |
| CN101835486B (zh) | 2012-12-12 |
| KR20100040912A (ko) | 2010-04-21 |
| KR20130121678A (ko) | 2013-11-06 |
| JP2010535194A (ja) | 2010-11-18 |
| AU2008281374A1 (en) | 2009-02-05 |
| HK1148467A1 (en) | 2011-09-09 |
| US20130336952A1 (en) | 2013-12-19 |
| RU2010106661A (ru) | 2011-09-10 |
| NZ582556A (en) | 2013-02-22 |
| RU2502520C2 (ru) | 2013-12-27 |
| CN102755649A (zh) | 2012-10-31 |
| CA2694927A1 (en) | 2009-02-05 |
| AU2008281374B2 (en) | 2012-05-31 |
| US20140227243A1 (en) | 2014-08-14 |
| JP2014024862A (ja) | 2014-02-06 |
| US20100310542A1 (en) | 2010-12-09 |
| WO2009016629A2 (en) | 2009-02-05 |
| CN101835486A (zh) | 2010-09-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5411857B2 (ja) | 医薬組成物及び関連方法 | |
| Anderson et al. | Insulin and angiotensin II are additive in stimulating TGF-β1 and matrix mRNAs in mesangial cells | |
| Combs et al. | Adiponectin signaling in the liver | |
| Ansurudeen et al. | Carnosine enhances diabetic wound healing in the db/db mouse model of type 2 diabetes | |
| JP5385321B2 (ja) | 創傷治療のための方法および薬学的組成物 | |
| JP2009506107A (ja) | 糖尿病および皮膚の老化を予防および治療するための方法および組成物 | |
| Mavrommatis et al. | The E-domain region of mechano-growth factor inhibits cellular apoptosis and preserves cardiac function during myocardial infarction | |
| KR20150058363A (ko) | 피부 노화를 방지 및/또는 개선하기 위해 사용되는 pedf-유도 폴리펩티드의 용도 | |
| El-Kebbi et al. | Regulation of glucose transport by pioglitazone in cultured muscle cells | |
| Zorina et al. | Prospects for the use of intranasally administered insulin and insulin-like growth factor-1 in cerebral ischemia | |
| AU2014277568B2 (en) | Anti-fibrogenic compounds, methods and uses thereof | |
| WO2010027802A2 (en) | Methods for treating diabetic wounds | |
| CN116194143A (zh) | 中性粒细胞驱动的炎症性病理的治疗方法 | |
| Lee et al. | Enhanced skin penetration of berberine from proniosome gel attenuates pain and inflammation in a mouse model of osteoarthritis | |
| HK1172249A (en) | Pharmaceutical composition for treating wounds and related methods | |
| CA2823372A1 (en) | Pharmaceutical composition for treating wounds and related methods | |
| Bragado et al. | CCK activates p90rsk in rat pancreatic acini through protein kinase C | |
| HK1148467B (en) | Pharmaceutical composition for treating wounds and related methods | |
| US7157439B2 (en) | HoxD3, HoxA3, and HoxB3 compositions and methods for improved wound healing | |
| US7115582B2 (en) | HoxD3 and HoxA3 compositions and methods for improved wound healing | |
| Gennero et al. | A novel composition for in vitro and in vivo regeneration of skin and connective tissues | |
| Crist et al. | Effects of adenosine receptor antagonism on protein tyrosine phosphatase in rat skeletal muscle | |
| Aoki et al. | Sphingosine-1-Phosphate Facilitates Skin Wound Healing by Increasing Angiogenesis and | |
| US7544670B2 (en) | HoxD3, HoxA3 and HoxB3 compositions and methods for improved wound healing | |
| Sato et al. | DNA Microarray Analysis of Effects of TSH, Iodide, Cytokines, and Therapeutic Agents on Gene Expression in Cultured Human Thyroid Follicles |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20120830 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20120906 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20121206 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20121213 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20130306 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20130523 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20130920 |
|
| A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20131003 |
|
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20131024 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20131108 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| LAPS | Cancellation because of no payment of annual fees |