JP2011506446A - 損傷した創傷治癒組成物および治療 - Google Patents
損傷した創傷治癒組成物および治療 Download PDFInfo
- Publication number
- JP2011506446A JP2011506446A JP2010537970A JP2010537970A JP2011506446A JP 2011506446 A JP2011506446 A JP 2011506446A JP 2010537970 A JP2010537970 A JP 2010537970A JP 2010537970 A JP2010537970 A JP 2010537970A JP 2011506446 A JP2011506446 A JP 2011506446A
- Authority
- JP
- Japan
- Prior art keywords
- gap junction
- wound
- connexin
- wounds
- ulcer
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 128
- 238000011282 treatment Methods 0.000 title abstract description 32
- 230000029663 wound healing Effects 0.000 title description 34
- 208000027418 Wounds and injury Diseases 0.000 claims abstract description 291
- 206010052428 Wound Diseases 0.000 claims abstract description 283
- 102000010970 Connexin Human genes 0.000 claims abstract description 280
- 108050001175 Connexin Proteins 0.000 claims abstract description 280
- 210000003976 gap junction Anatomy 0.000 claims abstract description 265
- 238000000034 method Methods 0.000 claims abstract description 153
- 230000001684 chronic effect Effects 0.000 claims abstract description 85
- 108010069241 Connexin 43 Proteins 0.000 claims abstract description 43
- 102000001045 Connexin 43 Human genes 0.000 claims abstract description 43
- 230000035876 healing Effects 0.000 claims abstract description 38
- 150000001875 compounds Chemical class 0.000 claims abstract description 34
- 230000003111 delayed effect Effects 0.000 claims abstract description 31
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 149
- 208000025865 Ulcer Diseases 0.000 claims description 127
- 231100000397 ulcer Toxicity 0.000 claims description 82
- 239000003607 modifier Substances 0.000 claims description 63
- 239000000816 peptidomimetic Substances 0.000 claims description 37
- 239000003795 chemical substances by application Substances 0.000 claims description 36
- 208000004210 Pressure Ulcer Diseases 0.000 claims description 28
- 230000027455 binding Effects 0.000 claims description 28
- 238000009739 binding Methods 0.000 claims description 28
- 208000000558 Varicose Ulcer Diseases 0.000 claims description 20
- 230000000694 effects Effects 0.000 claims description 19
- 241001465754 Metazoa Species 0.000 claims description 18
- 230000036961 partial effect Effects 0.000 claims description 17
- 239000012634 fragment Substances 0.000 claims description 15
- 102000008394 Immunoglobulin Fragments Human genes 0.000 claims description 13
- 108010021625 Immunoglobulin Fragments Proteins 0.000 claims description 13
- 230000026731 phosphorylation Effects 0.000 claims description 13
- 238000006366 phosphorylation reaction Methods 0.000 claims description 13
- 206010011985 Decubitus ulcer Diseases 0.000 claims description 11
- 230000007547 defect Effects 0.000 claims description 9
- 208000008960 Diabetic foot Diseases 0.000 claims description 8
- 230000002085 persistent effect Effects 0.000 claims description 7
- 206010044546 Traumatic ulcer Diseases 0.000 claims description 6
- 239000000427 antigen Substances 0.000 claims description 6
- 102000036639 antigens Human genes 0.000 claims description 6
- 108091007433 antigens Proteins 0.000 claims description 6
- 238000011200 topical administration Methods 0.000 claims description 5
- 239000000411 inducer Substances 0.000 claims description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 68
- 150000001413 amino acids Chemical class 0.000 description 46
- 230000036269 ulceration Effects 0.000 description 45
- 238000009472 formulation Methods 0.000 description 38
- 210000004027 cell Anatomy 0.000 description 30
- 239000000499 gel Substances 0.000 description 28
- 239000003112 inhibitor Substances 0.000 description 27
- 239000003085 diluting agent Substances 0.000 description 26
- 239000003937 drug carrier Substances 0.000 description 25
- 125000003275 alpha amino acid group Chemical group 0.000 description 24
- 210000001519 tissue Anatomy 0.000 description 23
- 230000037396 body weight Effects 0.000 description 21
- 230000006870 function Effects 0.000 description 21
- 208000014674 injury Diseases 0.000 description 21
- 235000018102 proteins Nutrition 0.000 description 21
- 108090000623 proteins and genes Proteins 0.000 description 21
- 102000004169 proteins and genes Human genes 0.000 description 21
- 239000010410 layer Substances 0.000 description 20
- 229920001184 polypeptide Polymers 0.000 description 20
- -1 antibody Substances 0.000 description 18
- 230000001737 promoting effect Effects 0.000 description 18
- 239000000017 hydrogel Substances 0.000 description 17
- 239000011159 matrix material Substances 0.000 description 17
- 239000008194 pharmaceutical composition Substances 0.000 description 17
- 239000000853 adhesive Substances 0.000 description 16
- 230000006378 damage Effects 0.000 description 16
- 239000000463 material Substances 0.000 description 16
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 15
- 102000014914 Carrier Proteins Human genes 0.000 description 14
- 108091008324 binding proteins Proteins 0.000 description 14
- 230000015572 biosynthetic process Effects 0.000 description 14
- 239000000243 solution Substances 0.000 description 14
- 238000012360 testing method Methods 0.000 description 14
- 206010061218 Inflammation Diseases 0.000 description 13
- 230000001070 adhesive effect Effects 0.000 description 13
- 230000004054 inflammatory process Effects 0.000 description 13
- 238000006467 substitution reaction Methods 0.000 description 13
- 102000008186 Collagen Human genes 0.000 description 12
- 108010035532 Collagen Proteins 0.000 description 12
- 229920001436 collagen Polymers 0.000 description 12
- 208000015181 infectious disease Diseases 0.000 description 12
- 210000003491 skin Anatomy 0.000 description 12
- 102100039290 Gap junction gamma-1 protein Human genes 0.000 description 11
- 210000000988 bone and bone Anatomy 0.000 description 11
- 239000006260 foam Substances 0.000 description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- 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 compound 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 description 10
- 206010056340 Diabetic ulcer Diseases 0.000 description 10
- 239000002585 base Substances 0.000 description 10
- 239000007787 solid Substances 0.000 description 10
- MPDGHEJMBKOTSU-YKLVYJNSSA-N 18beta-glycyrrhetic acid Chemical compound C([C@H]1C2=CC(=O)[C@H]34)[C@@](C)(C(O)=O)CC[C@]1(C)CC[C@@]2(C)[C@]4(C)CC[C@@H]1[C@]3(C)CC[C@H](O)C1(C)C MPDGHEJMBKOTSU-YKLVYJNSSA-N 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- 235000010443 alginic acid Nutrition 0.000 description 9
- 229920000615 alginic acid Polymers 0.000 description 9
- 230000008568 cell cell communication Effects 0.000 description 9
- 108010015426 connexin 45 Proteins 0.000 description 9
- 206010012601 diabetes mellitus Diseases 0.000 description 9
- 201000010099 disease Diseases 0.000 description 9
- 210000001723 extracellular space Anatomy 0.000 description 9
- 230000014509 gene expression Effects 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- MJVAVZPDRWSRRC-UHFFFAOYSA-N Menadione Chemical compound C1=CC=C2C(=O)C(C)=CC(=O)C2=C1 MJVAVZPDRWSRRC-UHFFFAOYSA-N 0.000 description 8
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical class CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 8
- 230000008859 change Effects 0.000 description 8
- 239000003814 drug Substances 0.000 description 8
- 210000002683 foot Anatomy 0.000 description 8
- 230000002458 infectious effect Effects 0.000 description 8
- 210000003141 lower extremity Anatomy 0.000 description 8
- 239000002674 ointment Substances 0.000 description 8
- 229920001983 poloxamer Polymers 0.000 description 8
- 208000009954 pyoderma gangrenosum Diseases 0.000 description 8
- 230000002829 reductive effect Effects 0.000 description 8
- 230000002792 vascular Effects 0.000 description 8
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 7
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 7
- 102100030540 Gap junction alpha-5 protein Human genes 0.000 description 7
- 239000002250 absorbent Substances 0.000 description 7
- 230000002745 absorbent Effects 0.000 description 7
- 239000004480 active ingredient Substances 0.000 description 7
- 229940072056 alginate Drugs 0.000 description 7
- 239000000969 carrier Substances 0.000 description 7
- 239000006071 cream Substances 0.000 description 7
- 230000004064 dysfunction Effects 0.000 description 7
- LPEPZBJOKDYZAD-UHFFFAOYSA-N flufenamic acid Chemical compound OC(=O)C1=CC=CC=C1NC1=CC=CC(C(F)(F)F)=C1 LPEPZBJOKDYZAD-UHFFFAOYSA-N 0.000 description 7
- 230000003993 interaction Effects 0.000 description 7
- 230000008569 process Effects 0.000 description 7
- 210000000278 spinal cord Anatomy 0.000 description 7
- 230000001225 therapeutic effect Effects 0.000 description 7
- 230000008733 trauma Effects 0.000 description 7
- 108010069156 Connexin 26 Proteins 0.000 description 6
- 102000055974 Connexin 26 Human genes 0.000 description 6
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 6
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- 206010030113 Oedema Diseases 0.000 description 6
- 206010040943 Skin Ulcer Diseases 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 206010042674 Swelling Diseases 0.000 description 6
- 108010014510 connexin 40 Proteins 0.000 description 6
- 208000035475 disorder Diseases 0.000 description 6
- 239000000975 dye Substances 0.000 description 6
- 239000000839 emulsion Substances 0.000 description 6
- 210000002744 extracellular matrix Anatomy 0.000 description 6
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 6
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 6
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 6
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 6
- 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 6
- 230000003902 lesion Effects 0.000 description 6
- 238000010647 peptide synthesis reaction Methods 0.000 description 6
- 208000033808 peripheral neuropathy Diseases 0.000 description 6
- 230000000865 phosphorylative effect Effects 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 238000013268 sustained release Methods 0.000 description 6
- 239000012730 sustained-release form Substances 0.000 description 6
- 230000008961 swelling Effects 0.000 description 6
- 230000000699 topical effect Effects 0.000 description 6
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Chemical class CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 5
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Chemical class CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 5
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Chemical class CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 5
- 102100039417 Gap junction beta-5 protein Human genes 0.000 description 5
- MPDGHEJMBKOTSU-UHFFFAOYSA-N Glycyrrhetinsaeure Natural products C12C(=O)C=C3C4CC(C)(C(O)=O)CCC4(C)CCC3(C)C1(C)CCC1C2(C)CCC(O)C1(C)C MPDGHEJMBKOTSU-UHFFFAOYSA-N 0.000 description 5
- 241000282412 Homo Species 0.000 description 5
- 206010020565 Hyperaemia Diseases 0.000 description 5
- 241000124008 Mammalia Species 0.000 description 5
- 239000005642 Oleic acid Chemical class 0.000 description 5
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Chemical class CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 5
- 125000000539 amino acid group Chemical group 0.000 description 5
- 230000004888 barrier function Effects 0.000 description 5
- 210000000270 basal cell Anatomy 0.000 description 5
- 238000004422 calculation algorithm Methods 0.000 description 5
- 229910052799 carbon Inorganic materials 0.000 description 5
- 239000001768 carboxy methyl cellulose Substances 0.000 description 5
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 5
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 5
- 230000032823 cell division Effects 0.000 description 5
- 230000004663 cell proliferation Effects 0.000 description 5
- 229920002678 cellulose Polymers 0.000 description 5
- 239000001913 cellulose Substances 0.000 description 5
- 235000010980 cellulose Nutrition 0.000 description 5
- 238000004891 communication Methods 0.000 description 5
- 239000002131 composite material Substances 0.000 description 5
- 108010021208 connexin 31.1 Proteins 0.000 description 5
- 238000001804 debridement Methods 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 239000003995 emulsifying agent Substances 0.000 description 5
- 229960003720 enoxolone Drugs 0.000 description 5
- 210000000416 exudates and transudate Anatomy 0.000 description 5
- 239000012530 fluid Substances 0.000 description 5
- 108010044046 gap 27 peptide Proteins 0.000 description 5
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Chemical class CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 5
- DLBFLQKQABVKGT-UHFFFAOYSA-L lucifer yellow dye Chemical compound [Li+].[Li+].[O-]S(=O)(=O)C1=CC(C(N(C(=O)NN)C2=O)=O)=C3C2=CC(S([O-])(=O)=O)=CC3=C1N DLBFLQKQABVKGT-UHFFFAOYSA-L 0.000 description 5
- 239000012528 membrane Substances 0.000 description 5
- 201000001119 neuropathy Diseases 0.000 description 5
- 230000007823 neuropathy Effects 0.000 description 5
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical class CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 5
- 229920000642 polymer Polymers 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 230000002035 prolonged effect Effects 0.000 description 5
- 239000007790 solid phase Substances 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 230000032258 transport Effects 0.000 description 5
- 230000003156 vasculitic effect Effects 0.000 description 5
- 230000009724 venous congestion Effects 0.000 description 5
- 150000003721 vitamin K derivatives Chemical class 0.000 description 5
- KBPLFHHGFOOTCA-UHFFFAOYSA-N 1-Octanol Chemical compound CCCCCCCCO KBPLFHHGFOOTCA-UHFFFAOYSA-N 0.000 description 4
- BBMCTIGTTCKYKF-UHFFFAOYSA-N 1-heptanol Chemical compound CCCCCCCO BBMCTIGTTCKYKF-UHFFFAOYSA-N 0.000 description 4
- FAJKLRGSIQZGIB-UHFFFAOYSA-N 4-chloro-3-hydroxy-3h-furan-2-one Chemical compound OC1C(=O)OC=C1Cl FAJKLRGSIQZGIB-UHFFFAOYSA-N 0.000 description 4
- 241000282472 Canis lupus familiaris Species 0.000 description 4
- 108010069176 Connexin 30 Proteins 0.000 description 4
- 102000001051 Connexin 30 Human genes 0.000 description 4
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 4
- 108010010803 Gelatin Proteins 0.000 description 4
- 102000005720 Glutathione transferase Human genes 0.000 description 4
- 108010070675 Glutathione transferase Proteins 0.000 description 4
- 239000012981 Hank's balanced salt solution Substances 0.000 description 4
- SBDNJUWAMKYJOX-UHFFFAOYSA-N Meclofenamic Acid Chemical compound CC1=CC=C(Cl)C(NC=2C(=CC=CC=2)C(O)=O)=C1Cl SBDNJUWAMKYJOX-UHFFFAOYSA-N 0.000 description 4
- JZFPYUNJRRFVQU-UHFFFAOYSA-N Niflumic acid Chemical compound OC(=O)C1=CC=CN=C1NC1=CC=CC(C(F)(F)F)=C1 JZFPYUNJRRFVQU-UHFFFAOYSA-N 0.000 description 4
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 4
- LOUPRKONTZGTKE-WZBLMQSHSA-N Quinine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-WZBLMQSHSA-N 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 description 4
- 229940114079 arachidonic acid Drugs 0.000 description 4
- 235000021342 arachidonic acid Nutrition 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- LOUPRKONTZGTKE-UHFFFAOYSA-N cinchonine Natural products C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-UHFFFAOYSA-N 0.000 description 4
- 210000000805 cytoplasm Anatomy 0.000 description 4
- 230000023753 dehiscence Effects 0.000 description 4
- 235000014113 dietary fatty acids Nutrition 0.000 description 4
- 239000008387 emulsifying waxe Substances 0.000 description 4
- 239000000194 fatty acid Substances 0.000 description 4
- 229930195729 fatty acid Natural products 0.000 description 4
- 150000004665 fatty acids Chemical class 0.000 description 4
- 239000000835 fiber Substances 0.000 description 4
- 239000000945 filler Substances 0.000 description 4
- 239000008273 gelatin Substances 0.000 description 4
- 229920000159 gelatin Polymers 0.000 description 4
- 235000019322 gelatine Nutrition 0.000 description 4
- 235000011852 gelatine desserts Nutrition 0.000 description 4
- 239000000416 hydrocolloid Substances 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 230000035992 intercellular communication Effects 0.000 description 4
- 208000028867 ischemia Diseases 0.000 description 4
- 230000000670 limiting effect Effects 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 210000005265 lung cell Anatomy 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 229960003803 meclofenamic acid Drugs 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 230000017074 necrotic cell death Effects 0.000 description 4
- 229960000916 niflumic acid Drugs 0.000 description 4
- 239000012454 non-polar solvent Substances 0.000 description 4
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 4
- 210000001322 periplasm Anatomy 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 239000003755 preservative agent Substances 0.000 description 4
- 230000002265 prevention Effects 0.000 description 4
- XJMOSONTPMZWPB-UHFFFAOYSA-M propidium iodide Chemical compound [I-].[I-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CCC[N+](C)(CC)CC)=C1C1=CC=CC=C1 XJMOSONTPMZWPB-UHFFFAOYSA-M 0.000 description 4
- 230000004850 protein–protein interaction Effects 0.000 description 4
- LOUPRKONTZGTKE-LHHVKLHASA-N quinidine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@H]2[C@@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-LHHVKLHASA-N 0.000 description 4
- 230000001105 regulatory effect Effects 0.000 description 4
- 230000028327 secretion Effects 0.000 description 4
- 150000003384 small molecules Chemical class 0.000 description 4
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 4
- 230000002459 sustained effect Effects 0.000 description 4
- 210000003371 toe Anatomy 0.000 description 4
- 210000002073 venous valve Anatomy 0.000 description 4
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 description 3
- 241000283690 Bos taurus Species 0.000 description 3
- 229920000742 Cotton Polymers 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 102100030525 Gap junction alpha-4 protein Human genes 0.000 description 3
- 102100037260 Gap junction beta-1 protein Human genes 0.000 description 3
- 206010021143 Hypoxia Diseases 0.000 description 3
- 108010076876 Keratins Proteins 0.000 description 3
- 102000011782 Keratins Human genes 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 229920000297 Rayon Polymers 0.000 description 3
- 206010040844 Skin exfoliation Diseases 0.000 description 3
- 229920002125 Sokalan® Polymers 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 230000000692 anti-sense effect Effects 0.000 description 3
- 230000033228 biological regulation Effects 0.000 description 3
- 230000000903 blocking effect Effects 0.000 description 3
- 230000001413 cellular effect Effects 0.000 description 3
- 229960000541 cetyl alcohol Drugs 0.000 description 3
- 238000000576 coating method Methods 0.000 description 3
- 238000007906 compression Methods 0.000 description 3
- 230000006835 compression Effects 0.000 description 3
- 108010015416 connexin 32 Proteins 0.000 description 3
- 108010015408 connexin 37 Proteins 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 230000001186 cumulative effect Effects 0.000 description 3
- 230000008021 deposition Effects 0.000 description 3
- 210000004207 dermis Anatomy 0.000 description 3
- 229960004369 flufenamic acid Drugs 0.000 description 3
- 230000007954 hypoxia Effects 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 238000001802 infusion Methods 0.000 description 3
- 238000005342 ion exchange Methods 0.000 description 3
- 210000003734 kidney Anatomy 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- 239000006210 lotion Substances 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 230000003278 mimic effect Effects 0.000 description 3
- 238000010369 molecular cloning Methods 0.000 description 3
- 230000000926 neurological effect Effects 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 230000003204 osmotic effect Effects 0.000 description 3
- 206010033675 panniculitis Diseases 0.000 description 3
- 239000012188 paraffin wax Substances 0.000 description 3
- 239000002953 phosphate buffered saline Substances 0.000 description 3
- 238000001556 precipitation Methods 0.000 description 3
- 238000000159 protein binding assay Methods 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 239000002964 rayon Substances 0.000 description 3
- 230000008439 repair process Effects 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 230000036573 scar formation Effects 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 238000007920 subcutaneous administration Methods 0.000 description 3
- 210000004304 subcutaneous tissue Anatomy 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 230000008736 traumatic injury Effects 0.000 description 3
- 208000019553 vascular disease Diseases 0.000 description 3
- 239000003981 vehicle Substances 0.000 description 3
- XEEQGYMUWCZPDN-DOMZBBRYSA-N (-)-(11S,2'R)-erythro-mefloquine Chemical compound C([C@@H]1[C@@H](O)C=2C3=CC=CC(=C3N=C(C=2)C(F)(F)F)C(F)(F)F)CCCN1 XEEQGYMUWCZPDN-DOMZBBRYSA-N 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 2
- VAZJLPXFVQHDFB-UHFFFAOYSA-N 1-(diaminomethylidene)-2-hexylguanidine Polymers CCCCCCN=C(N)N=C(N)N VAZJLPXFVQHDFB-UHFFFAOYSA-N 0.000 description 2
- WRGQSWVCFNIUNZ-GDCKJWNLSA-N 1-oleoyl-sn-glycerol 3-phosphate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](O)COP(O)(O)=O WRGQSWVCFNIUNZ-GDCKJWNLSA-N 0.000 description 2
- BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 description 2
- WDEQLMYIIXBHTJ-UHFFFAOYSA-N 4-chloro-3-(chloromethyl)-2-hydroxy-2h-furan-5-one Chemical compound OC1OC(=O)C(Cl)=C1CCl WDEQLMYIIXBHTJ-UHFFFAOYSA-N 0.000 description 2
- 102000029330 CSK Tyrosine-Protein Kinase Human genes 0.000 description 2
- 108010069682 CSK Tyrosine-Protein Kinase Proteins 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- DQFBYFPFKXHELB-UHFFFAOYSA-N Chalcone Natural products C=1C=CC=CC=1C(=O)C=CC1=CC=CC=C1 DQFBYFPFKXHELB-UHFFFAOYSA-N 0.000 description 2
- 235000001258 Cinchona calisaya Nutrition 0.000 description 2
- 101100329834 Danio rerio gja1 gene Proteins 0.000 description 2
- 241000283086 Equidae Species 0.000 description 2
- 206010015150 Erythema Diseases 0.000 description 2
- 206010063560 Excessive granulation tissue Diseases 0.000 description 2
- 241000282326 Felis catus Species 0.000 description 2
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 2
- 229940080349 GPR agonist Drugs 0.000 description 2
- 101710178004 Gap junction gamma-1 protein Proteins 0.000 description 2
- 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 2
- 239000007995 HEPES buffer Substances 0.000 description 2
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 2
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 2
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
- 102000003820 Lipoxygenases Human genes 0.000 description 2
- 108090000128 Lipoxygenases Chemical class 0.000 description 2
- XJGBDJOMWKAZJS-UHFFFAOYSA-N Nafenoic Acid Chemical compound C1=CC(OC(C)(C)C(O)=O)=CC=C1C1C2=CC=CC=C2CCC1 XJGBDJOMWKAZJS-UHFFFAOYSA-N 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- 229920002413 Polyhexanide Polymers 0.000 description 2
- 102000001708 Protein Isoforms Human genes 0.000 description 2
- 108010029485 Protein Isoforms Proteins 0.000 description 2
- 206010067171 Regurgitation Diseases 0.000 description 2
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 2
- 206010040829 Skin discolouration Diseases 0.000 description 2
- IUJDSEJGGMCXSG-UHFFFAOYSA-N Thiopental Chemical compound CCCC(C)C1(CC)C(=O)NC(=S)NC1=O IUJDSEJGGMCXSG-UHFFFAOYSA-N 0.000 description 2
- 229930003448 Vitamin K Natural products 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 238000001042 affinity chromatography Methods 0.000 description 2
- SHGAZHPCJJPHSC-YCNIQYBTSA-N all-trans-retinoic acid Chemical compound OC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-YCNIQYBTSA-N 0.000 description 2
- AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 2
- 238000012870 ammonium sulfate precipitation Methods 0.000 description 2
- LGEQQWMQCRIYKG-DOFZRALJSA-N anandamide Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(=O)NCCO LGEQQWMQCRIYKG-DOFZRALJSA-N 0.000 description 2
- 229940035674 anesthetics Drugs 0.000 description 2
- 230000033115 angiogenesis Effects 0.000 description 2
- 239000003957 anion exchange resin Substances 0.000 description 2
- PYKYMHQGRFAEBM-UHFFFAOYSA-N anthraquinone Natural products CCC(=O)c1c(O)c2C(=O)C3C(C=CC=C3O)C(=O)c2cc1CC(=O)OC PYKYMHQGRFAEBM-UHFFFAOYSA-N 0.000 description 2
- 150000004056 anthraquinones Chemical class 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 230000000890 antigenic effect Effects 0.000 description 2
- LGEQQWMQCRIYKG-UHFFFAOYSA-N arachidonic acid ethanolamide Natural products CCCCCC=CCC=CCC=CCC=CCCCC(=O)NCCO LGEQQWMQCRIYKG-UHFFFAOYSA-N 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 239000011324 bead Substances 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- 239000012620 biological material Substances 0.000 description 2
- 230000001851 biosynthetic effect Effects 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 230000006727 cell loss Effects 0.000 description 2
- 229940082500 cetostearyl alcohol Drugs 0.000 description 2
- 235000005513 chalcones Nutrition 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 238000004140 cleaning Methods 0.000 description 2
- 239000003405 delayed action preparation Substances 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 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 2
- 229960003957 dexamethasone Drugs 0.000 description 2
- 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 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 230000003828 downregulation Effects 0.000 description 2
- 229960004679 doxorubicin Drugs 0.000 description 2
- 150000002066 eicosanoids Chemical class 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 230000001804 emulsifying effect Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 210000002615 epidermis Anatomy 0.000 description 2
- 238000012869 ethanol precipitation Methods 0.000 description 2
- DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 2
- 230000014818 extracellular matrix organization Effects 0.000 description 2
- 239000004744 fabric Substances 0.000 description 2
- ZWJINEZUASEZBH-UHFFFAOYSA-N fenamic acid Chemical compound OC(=O)C1=CC=CC=C1NC1=CC=CC=C1 ZWJINEZUASEZBH-UHFFFAOYSA-N 0.000 description 2
- 210000002950 fibroblast Anatomy 0.000 description 2
- 230000005714 functional activity Effects 0.000 description 2
- 238000002825 functional assay Methods 0.000 description 2
- 238000011990 functional testing Methods 0.000 description 2
- 108020001507 fusion proteins Proteins 0.000 description 2
- JLYXXMFPNIAWKQ-GNIYUCBRSA-N gamma-hexachlorocyclohexane Chemical compound Cl[C@H]1[C@H](Cl)[C@@H](Cl)[C@@H](Cl)[C@H](Cl)[C@H]1Cl JLYXXMFPNIAWKQ-GNIYUCBRSA-N 0.000 description 2
- JLYXXMFPNIAWKQ-UHFFFAOYSA-N gamma-hexachlorocyclohexane Natural products ClC1C(Cl)C(Cl)C(Cl)C(Cl)C1Cl JLYXXMFPNIAWKQ-UHFFFAOYSA-N 0.000 description 2
- 238000002523 gelfiltration Methods 0.000 description 2
- 239000003193 general anesthetic agent Substances 0.000 description 2
- 229940045109 genistein Drugs 0.000 description 2
- TZBJGXHYKVUXJN-UHFFFAOYSA-N genistein Natural products C1=CC(O)=CC=C1C1=COC2=CC(O)=CC(O)=C2C1=O TZBJGXHYKVUXJN-UHFFFAOYSA-N 0.000 description 2
- 235000006539 genistein Nutrition 0.000 description 2
- ZCOLJUOHXJRHDI-CMWLGVBASA-N genistein 7-O-beta-D-glucoside Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=C2C(=O)C(C=3C=CC(O)=CC=3)=COC2=C1 ZCOLJUOHXJRHDI-CMWLGVBASA-N 0.000 description 2
- 150000004676 glycans Chemical class 0.000 description 2
- 210000001126 granulation tissue Anatomy 0.000 description 2
- 239000003102 growth factor Substances 0.000 description 2
- BCQZXOMGPXTTIC-UHFFFAOYSA-N halothane Chemical compound FC(F)(F)C(Cl)Br BCQZXOMGPXTTIC-UHFFFAOYSA-N 0.000 description 2
- 229960003132 halothane Drugs 0.000 description 2
- 230000003054 hormonal effect Effects 0.000 description 2
- 238000009396 hybridization Methods 0.000 description 2
- 229910000040 hydrogen fluoride Inorganic materials 0.000 description 2
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 2
- 230000005847 immunogenicity Effects 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 238000003780 insertion Methods 0.000 description 2
- 230000037431 insertion Effects 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 210000002414 leg Anatomy 0.000 description 2
- 210000000265 leukocyte Anatomy 0.000 description 2
- 229960002809 lindane Drugs 0.000 description 2
- 229920002521 macromolecule Polymers 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 229960001962 mefloquine Drugs 0.000 description 2
- 239000002207 metabolite Substances 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
- 230000005012 migration Effects 0.000 description 2
- 238000013508 migration Methods 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- 230000035772 mutation Effects 0.000 description 2
- 229920001778 nylon Polymers 0.000 description 2
- QNDVLZJODHBUFM-WFXQOWMNSA-N okadaic acid Chemical compound C([C@H](O1)[C@H](C)/C=C/[C@H]2CC[C@@]3(CC[C@H]4O[C@@H](C([C@@H](O)[C@@H]4O3)=C)[C@@H](O)C[C@H](C)[C@@H]3[C@@H](CC[C@@]4(OCCCC4)O3)C)O2)C(C)=C[C@]21O[C@H](C[C@@](C)(O)C(O)=O)CC[C@H]2O QNDVLZJODHBUFM-WFXQOWMNSA-N 0.000 description 2
- VEFJHAYOIAAXEU-UHFFFAOYSA-N okadaic acid Natural products CC(CC(O)C1OC2CCC3(CCC(O3)C=CC(C)C4CC(=CC5(OC(CC(C)(O)C(=O)O)CCC5O)O4)C)OC2C(O)C1C)C6OC7(CCCCO7)CCC6C VEFJHAYOIAAXEU-UHFFFAOYSA-N 0.000 description 2
- FATBGEAMYMYZAF-KTKRTIGZSA-N oleamide Chemical compound CCCCCCCC\C=C/CCCCCCCC(N)=O FATBGEAMYMYZAF-KTKRTIGZSA-N 0.000 description 2
- FATBGEAMYMYZAF-UHFFFAOYSA-N oleicacidamide-heptaglycolether Natural products CCCCCCCCC=CCCCCCCCC(N)=O FATBGEAMYMYZAF-UHFFFAOYSA-N 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000003973 paint Substances 0.000 description 2
- 229920001277 pectin Polymers 0.000 description 2
- 239000001814 pectin Substances 0.000 description 2
- 235000010987 pectin Nutrition 0.000 description 2
- 230000002093 peripheral effect Effects 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- SHUZOJHMOBOZST-UHFFFAOYSA-N phylloquinone Natural products CC(C)CCCCC(C)CCC(C)CCCC(=CCC1=C(C)C(=O)c2ccccc2C1=O)C SHUZOJHMOBOZST-UHFFFAOYSA-N 0.000 description 2
- 230000035479 physiological effects, processes and functions Effects 0.000 description 2
- 239000002798 polar solvent Substances 0.000 description 2
- 239000004584 polyacrylic acid Substances 0.000 description 2
- 229920000728 polyester Polymers 0.000 description 2
- 108091033319 polynucleotide Proteins 0.000 description 2
- 102000040430 polynucleotide Human genes 0.000 description 2
- 239000002157 polynucleotide Substances 0.000 description 2
- 229920001282 polysaccharide Polymers 0.000 description 2
- 239000005017 polysaccharide Substances 0.000 description 2
- 229920001296 polysiloxane Polymers 0.000 description 2
- 235000020777 polyunsaturated fatty acids Nutrition 0.000 description 2
- 229920002635 polyurethane Polymers 0.000 description 2
- 239000004814 polyurethane Substances 0.000 description 2
- 230000002335 preservative effect Effects 0.000 description 2
- 230000000750 progressive effect Effects 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- OLBCVFGFOZPWHH-UHFFFAOYSA-N propofol Chemical compound CC(C)C1=CC=CC(C(C)C)=C1O OLBCVFGFOZPWHH-UHFFFAOYSA-N 0.000 description 2
- 229960004134 propofol Drugs 0.000 description 2
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
- 230000002797 proteolythic effect Effects 0.000 description 2
- 229960001404 quinidine Drugs 0.000 description 2
- 229960000948 quinine Drugs 0.000 description 2
- 230000000284 resting effect Effects 0.000 description 2
- 229930002330 retinoic acid Natural products 0.000 description 2
- 238000004007 reversed phase HPLC Methods 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 230000035807 sensation Effects 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 230000001953 sensory effect Effects 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 239000008247 solid mixture Substances 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 229960001603 tamoxifen Drugs 0.000 description 2
- OULAJFUGPPVRBK-UHFFFAOYSA-N tetratriacontyl alcohol Natural products CCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCO OULAJFUGPPVRBK-UHFFFAOYSA-N 0.000 description 2
- 230000008719 thickening Effects 0.000 description 2
- 229960003279 thiopental Drugs 0.000 description 2
- 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 2
- RZWIIPASKMUIAC-VQTJNVASSA-N thromboxane Chemical compound CCCCCCCC[C@H]1OCCC[C@@H]1CCCCCCC RZWIIPASKMUIAC-VQTJNVASSA-N 0.000 description 2
- 239000012049 topical pharmaceutical composition Substances 0.000 description 2
- DQFBYFPFKXHELB-VAWYXSNFSA-N trans-chalcone Chemical compound C=1C=CC=CC=1C(=O)\C=C\C1=CC=CC=C1 DQFBYFPFKXHELB-VAWYXSNFSA-N 0.000 description 2
- 230000001052 transient effect Effects 0.000 description 2
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 2
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 2
- 235000019168 vitamin K Nutrition 0.000 description 2
- 239000011712 vitamin K Substances 0.000 description 2
- 235000012711 vitamin K3 Nutrition 0.000 description 2
- 239000011652 vitamin K3 Substances 0.000 description 2
- 229940046010 vitamin k Drugs 0.000 description 2
- 229940041603 vitamin k 3 Drugs 0.000 description 2
- 235000012431 wafers Nutrition 0.000 description 2
- 230000003442 weekly effect Effects 0.000 description 2
- 230000010388 wound contraction Effects 0.000 description 2
- MPDGHEJMBKOTSU-PMTKVOBESA-N β-glycyrrhetinic acid Chemical compound C([C@@H]1C2=CC(=O)[C@H]34)[C@@](C)(C(O)=O)CC[C@]1(C)CC[C@@]2(C)[C@]4(C)CC[C@@H]1[C@]3(C)CC[C@H](O)C1(C)C MPDGHEJMBKOTSU-PMTKVOBESA-N 0.000 description 2
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 1
- ALSTYHKOOCGGFT-KTKRTIGZSA-N (9Z)-octadecen-1-ol Chemical compound CCCCCCCC\C=C/CCCCCCCCO ALSTYHKOOCGGFT-KTKRTIGZSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 1
- PZVRZRARFZZBCA-SOFGYWHQSA-N 2',5'-Dihydroxychalcone Chemical compound OC1=CC=C(O)C(C(=O)\C=C\C=2C=CC=CC=2)=C1 PZVRZRARFZZBCA-SOFGYWHQSA-N 0.000 description 1
- BSWWXRFVMJHFBN-UHFFFAOYSA-N 2,4,6-tribromophenol Chemical compound OC1=C(Br)C=C(Br)C=C1Br BSWWXRFVMJHFBN-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
- 229920000936 Agarose Polymers 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 201000004384 Alopecia Diseases 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 206010003694 Atrophy Diseases 0.000 description 1
- 241000271566 Aves Species 0.000 description 1
- 241000193738 Bacillus anthracis Species 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 241001474374 Blennius Species 0.000 description 1
- 206010006797 Burns first degree Diseases 0.000 description 1
- 206010006802 Burns second degree Diseases 0.000 description 1
- 206010006803 Burns third degree Diseases 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- BQENDLAVTKRQMS-SBBGFIFASA-L Carbenoxolone sodium Chemical compound [Na+].[Na+].C([C@H]1C2=CC(=O)[C@H]34)[C@@](C)(C([O-])=O)CC[C@]1(C)CC[C@@]2(C)[C@]4(C)CC[C@@H]1[C@]3(C)CC[C@H](OC(=O)CCC([O-])=O)C1(C)C BQENDLAVTKRQMS-SBBGFIFASA-L 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 108010076119 Caseins Proteins 0.000 description 1
- 206010008342 Cervix carcinoma Diseases 0.000 description 1
- 208000009043 Chemical Burns Diseases 0.000 description 1
- 208000018380 Chemical injury Diseases 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- 208000027932 Collagen disease Diseases 0.000 description 1
- 229920001651 Cyanoacrylate Polymers 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 201000004624 Dermatitis Diseases 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 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 1
- 102000016942 Elastin Human genes 0.000 description 1
- 108010014258 Elastin Proteins 0.000 description 1
- 206010069808 Electrical burn Diseases 0.000 description 1
- 206010073423 Eye ulcer Diseases 0.000 description 1
- 102000009123 Fibrin Human genes 0.000 description 1
- 108010073385 Fibrin Proteins 0.000 description 1
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 1
- 206010061159 Foot deformity Diseases 0.000 description 1
- 101710177922 Gap junction alpha-5 protein Proteins 0.000 description 1
- 206010018691 Granuloma Diseases 0.000 description 1
- 108010027814 HSP72 Heat-Shock Proteins Proteins 0.000 description 1
- 102100040352 Heat shock 70 kDa protein 1A Human genes 0.000 description 1
- 102000001554 Hemoglobins Human genes 0.000 description 1
- 108010054147 Hemoglobins Proteins 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 108010068250 Herpes Simplex Virus Protein Vmw65 Proteins 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 1
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 1
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 1
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 1
- 238000010824 Kaplan-Meier survival analysis Methods 0.000 description 1
- 239000004166 Lanolin Substances 0.000 description 1
- 208000005230 Leg Ulcer Diseases 0.000 description 1
- 208000008771 Lymphadenopathy Diseases 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
- 239000004909 Moisturizer Substances 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 208000031998 Mycobacterium Infections Diseases 0.000 description 1
- 208000031888 Mycoses Diseases 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 206010056872 Palpable purpura Diseases 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 206010033799 Paralysis Diseases 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 239000004264 Petrolatum Substances 0.000 description 1
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 1
- 229920000954 Polyglycolide Polymers 0.000 description 1
- 229920005830 Polyurethane Foam Polymers 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 208000003251 Pruritus Diseases 0.000 description 1
- 206010037549 Purpura Diseases 0.000 description 1
- 241001672981 Purpura Species 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 206010040030 Sensory loss Diseases 0.000 description 1
- 229920005654 Sephadex Polymers 0.000 description 1
- 239000012507 Sephadex™ Substances 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- 241000700584 Simplexvirus Species 0.000 description 1
- 206010072170 Skin wound Diseases 0.000 description 1
- 206010041736 Sporotrichosis Diseases 0.000 description 1
- 208000013201 Stress fracture Diseases 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 239000004830 Super Glue Substances 0.000 description 1
- 208000002847 Surgical Wound Diseases 0.000 description 1
- 206010042880 Syphilis genital Diseases 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- 208000003443 Unconsciousness Diseases 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- 206010046996 Varicose vein Diseases 0.000 description 1
- 206010047115 Vasculitis Diseases 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 230000001594 aberrant effect Effects 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 239000002535 acidifier Substances 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 239000012790 adhesive layer Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 210000004100 adrenal gland Anatomy 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 238000002266 amputation Methods 0.000 description 1
- 239000012491 analyte Substances 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 210000003484 anatomy Anatomy 0.000 description 1
- 210000003423 ankle Anatomy 0.000 description 1
- 230000000181 anti-adherent effect Effects 0.000 description 1
- 230000002924 anti-infective effect Effects 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 230000002788 anti-peptide Effects 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000004872 arterial blood pressure Effects 0.000 description 1
- 230000003143 atherosclerotic effect Effects 0.000 description 1
- 230000000386 athletic effect Effects 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 230000037444 atrophy Effects 0.000 description 1
- CREXVNNSNOKDHW-UHFFFAOYSA-N azaniumylideneazanide Chemical group N[N] CREXVNNSNOKDHW-UHFFFAOYSA-N 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 239000012867 bioactive agent Substances 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 239000000090 biomarker Substances 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- 208000034158 bleeding Diseases 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 210000001217 buttock Anatomy 0.000 description 1
- 230000000981 bystander Effects 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 229960000530 carbenoxolone Drugs 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 125000002843 carboxylic acid group Chemical group 0.000 description 1
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- 239000005018 casein Substances 0.000 description 1
- BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 1
- 235000021240 caseins Nutrition 0.000 description 1
- 241001233037 catfish Species 0.000 description 1
- 230000023402 cell communication Effects 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000005779 cell damage Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 210000002390 cell membrane structure Anatomy 0.000 description 1
- 230000012292 cell migration Effects 0.000 description 1
- 230000010267 cellular communication Effects 0.000 description 1
- 239000007765 cera alba Substances 0.000 description 1
- 239000007766 cera flava Substances 0.000 description 1
- 201000010881 cervical cancer Diseases 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000011098 chromatofocusing Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 238000007596 consolidation process Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 210000004087 cornea Anatomy 0.000 description 1
- 229920006037 cross link polymer Polymers 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 229940008099 dimethicone Drugs 0.000 description 1
- 239000004205 dimethyl polysiloxane Substances 0.000 description 1
- 235000013870 dimethyl polysiloxane Nutrition 0.000 description 1
- 206010013023 diphtheria Diseases 0.000 description 1
- 238000002845 discoloration Methods 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000002222 downregulating effect Effects 0.000 description 1
- 229920002549 elastin Polymers 0.000 description 1
- 239000003974 emollient agent Substances 0.000 description 1
- 210000003989 endothelium vascular Anatomy 0.000 description 1
- JPGQOUSTVILISH-UHFFFAOYSA-N enflurane Chemical compound FC(F)OC(F)(F)C(F)Cl JPGQOUSTVILISH-UHFFFAOYSA-N 0.000 description 1
- 229960000305 enflurane Drugs 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 210000003560 epithelium corneal Anatomy 0.000 description 1
- 231100000321 erythema Toxicity 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 239000002360 explosive Substances 0.000 description 1
- 238000000556 factor analysis Methods 0.000 description 1
- 238000005562 fading Methods 0.000 description 1
- 210000003195 fascia Anatomy 0.000 description 1
- 229950003499 fibrin Drugs 0.000 description 1
- 239000007888 film coating Substances 0.000 description 1
- 238000009501 film coating Methods 0.000 description 1
- 239000000834 fixative Substances 0.000 description 1
- 238000000799 fluorescence microscopy Methods 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 210000000610 foot bone Anatomy 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000003349 gelling agent Substances 0.000 description 1
- 210000004392 genitalia Anatomy 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 239000003292 glue Substances 0.000 description 1
- 229940075529 glyceryl stearate Drugs 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 230000037313 granulation tissue formation Effects 0.000 description 1
- 239000004519 grease Substances 0.000 description 1
- 230000003676 hair loss Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 208000014951 hematologic disease Diseases 0.000 description 1
- 230000002008 hemorrhagic effect Effects 0.000 description 1
- 239000003906 humectant Substances 0.000 description 1
- 229920002674 hyaluronan Polymers 0.000 description 1
- 229960003160 hyaluronic acid Drugs 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 239000008309 hydrophilic cream Substances 0.000 description 1
- 229920001477 hydrophilic polymer Polymers 0.000 description 1
- 238000002169 hydrotherapy Methods 0.000 description 1
- 229920003063 hydroxymethyl cellulose Polymers 0.000 description 1
- 229940031574 hydroxymethyl cellulose Drugs 0.000 description 1
- 230000001631 hypertensive effect Effects 0.000 description 1
- 208000009326 ileitis Diseases 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 238000007373 indentation Methods 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 230000035990 intercellular signaling Effects 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 235000000396 iron Nutrition 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 238000001155 isoelectric focusing Methods 0.000 description 1
- 235000015110 jellies Nutrition 0.000 description 1
- 210000000281 joint capsule Anatomy 0.000 description 1
- 230000003780 keratinization Effects 0.000 description 1
- 235000019388 lanolin Nutrition 0.000 description 1
- 229940039717 lanolin Drugs 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 210000003041 ligament Anatomy 0.000 description 1
- 208000014987 limb edema Diseases 0.000 description 1
- 239000008308 lipophilic cream Substances 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 239000012160 loading buffer Substances 0.000 description 1
- 210000002751 lymph Anatomy 0.000 description 1
- 210000004324 lymphatic system Anatomy 0.000 description 1
- 208000018555 lymphatic system disease Diseases 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- HZVOZRGWRWCICA-UHFFFAOYSA-N methanediyl Chemical compound [CH2] HZVOZRGWRWCICA-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 239000004200 microcrystalline wax Substances 0.000 description 1
- 235000019808 microcrystalline wax Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 230000001333 moisturizer Effects 0.000 description 1
- 229910000403 monosodium phosphate Inorganic materials 0.000 description 1
- 235000019799 monosodium phosphate Nutrition 0.000 description 1
- 208000027531 mycobacterial infectious disease Diseases 0.000 description 1
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 230000002981 neuropathic effect Effects 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- 239000004745 nonwoven fabric Substances 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 229940055577 oleyl alcohol Drugs 0.000 description 1
- XMLQWXUVTXCDDL-UHFFFAOYSA-N oleyl alcohol Natural products CCCCCCC=CCCCCCCCCCCO XMLQWXUVTXCDDL-UHFFFAOYSA-N 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 230000000399 orthopedic effect Effects 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 238000010979 pH adjustment Methods 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 230000003950 pathogenic mechanism Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 239000012466 permeate Substances 0.000 description 1
- 229940066842 petrolatum Drugs 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 238000002823 phage display Methods 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 230000019612 pigmentation Effects 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 229960000502 poloxamer Drugs 0.000 description 1
- 229920001992 poloxamer 407 Polymers 0.000 description 1
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 239000004633 polyglycolic acid Substances 0.000 description 1
- 239000004626 polylactic acid Substances 0.000 description 1
- 229920006254 polymer film Polymers 0.000 description 1
- 229920002503 polyoxyethylene-polyoxypropylene Polymers 0.000 description 1
- 239000011496 polyurethane foam Substances 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 230000006916 protein interaction Effects 0.000 description 1
- 230000009822 protein phosphorylation Effects 0.000 description 1
- 238000010379 pull-down assay Methods 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 208000012802 recumbency Diseases 0.000 description 1
- 239000012925 reference material Substances 0.000 description 1
- 239000004627 regenerated cellulose Substances 0.000 description 1
- 230000014493 regulation of gene expression Effects 0.000 description 1
- 230000010410 reperfusion Effects 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 210000001525 retina Anatomy 0.000 description 1
- RCTGMCJBQGBLKT-PAMTUDGESA-N scarlet red Chemical compound CC1=CC=CC=C1\N=N\C(C=C1C)=CC=C1\N=N\C1=C(O)C=CC2=CC=CC=C12 RCTGMCJBQGBLKT-PAMTUDGESA-N 0.000 description 1
- 229960005369 scarlet red Drugs 0.000 description 1
- 238000006748 scratching Methods 0.000 description 1
- 230000002393 scratching effect Effects 0.000 description 1
- 230000009758 senescence Effects 0.000 description 1
- 208000037974 severe injury Diseases 0.000 description 1
- 230000009528 severe injury Effects 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 230000037370 skin discoloration Effects 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 239000000021 stimulant Substances 0.000 description 1
- 238000011477 surgical intervention Methods 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 210000002435 tendon Anatomy 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 206010043554 thrombocytopenia Diseases 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 230000017423 tissue regeneration Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 230000007306 turnover Effects 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 208000027185 varicose disease Diseases 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
- 239000011240 wet gel Substances 0.000 description 1
- 239000002759 woven fabric Substances 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
Classifications
-
- 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
-
- 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
- C07K14/78—Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin or cold insoluble globulin [CIG]
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- A61K38/39—Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin, cold insoluble globulin [CIG]
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biophysics (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Toxicology (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Biochemistry (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Dermatology (AREA)
- Epidemiology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
Description
以下は、本発明の理解に有用でありうる情報を含む。このことは、本明細書に記載される情報が、本明細書に記載または特許請求されている発明に対する先行技術であるか、もしくはこれに関連していることを認めるものでも、明示的にもしくは暗黙に言及される刊行物もしくは文書が先行技術であることを認めるものでもない。
本明細書で記載および特許請求される発明は、この「簡単な要旨」において説明または記載または言及される属性および実施形態を含むがこれらに限定されない多くの属性および実施形態を有する。それは包括的であることが意図されるものでなく、本明細書で記載および特許請求される発明は、限定ではなくて例示だけを目的として組み入れられているこの「簡単な要旨」に限定されるものでも、「簡単な要旨」において特定される特徴または実施形態により限定されるものでもない。
治癒が遅い創傷、治癒が遅延している創傷、治癒が不完全な創傷、離開創、および慢性創傷を含む、予測される速度で治癒しない創傷は、結果として感染症をもたらすことが多く、切断術または死亡をもたらしうる。創傷治癒においては、ギャップジャンクションを通る細胞間連絡が中枢的な役割を果たす。本明細書で説明されるかまたは言及される化合物を含む特定の化合物の使用により、細胞連絡を遮断するか、阻害するか、または変化させることが可能であり、これにより、治癒が遅い創傷、治癒が遅延している創傷、治癒が不完全な創傷、離開創、および慢性創傷を含む、予測される速度で治癒しない創傷の閉鎖および治癒が促進される。すべての適用について、コネキシン43ギャップジャンクション調節剤が好ましい。
本明細書で用いられる「障害」とは、創傷治癒を促進し、かつ/または瘢痕形成を軽減する薬剤から利益を得る任意の障害、疾患、または状態である。例えば、神経障害性、虚血性、および微小血管性の病態;骨領域全体[尾骨(仙骨)、股関節(転子骨)、臀部(坐骨)、または足のかかと]にわたる圧迫;再灌流による傷害;ならびに弁逆流による病因と関連する状態および関連の状態と関連する創傷関連の異常が含まれる。
本明細書で説明される一部の薬剤は、細胞内へ、また細胞からの分子の輸送を調節するかまたはこれに影響を及ぼす(例えば、遮断するかまたは阻害する)ことが可能である。したがって、本明細書で説明される一部のギャップジャンクション調節剤は、細胞連絡(例えば、細胞間)を調節する。一部のギャップジャンクション調節剤は、細胞質とペリプラズム腔または細胞外腔との間における分子の移送を調節するかまたはこれに影響を及ぼす。このような薬剤は一般に、細胞質と細胞外腔または組織との間における小分子の交換に個別に関与しうるヘミチャネル(コネクソンとも呼ばれる)を標的とする。したがって、本明細書で提供される化合物は、細胞間(ギャップジャンクションを介する)または細胞と細胞外腔もしくは組織との間(ヘミチャネルを介する)における結合を直接的または間接的に低減させることが可能であり、細胞から細胞外腔内への分子の輸送の調節は、本発明の一部の化合物および実施形態の範囲内にある。
ギャップジャンクション調節剤は、ギャップジャンクションおよび/またはヘミチャネルを閉鎖もしくは遮断するか、またはギャップジャンクションを介する細胞間情報伝達を別の形で防止するかもしくは低下させるか、またはヘミチャネルを介する細胞外環境への細胞の情報伝達を別の形で防止するかもしくは低下させる薬剤を含む。これらは、ヘミチャネルまたはギャップジャンクションの活性、機能、または形成を、全体的または部分的に防止するか、低下させるか、または阻害する薬剤または化合物を含む。
本発明のギャップジャンクション調節剤(本明細書で論じられる製剤の形態における場合が典型的)は、本明細書で言及される創傷のいずれかを有する対象など、治療を必要とする対象に投与することができる。こうして、対象の創傷を改善することができる。したがって、ギャップジャンクション調節剤および製剤は、治療による対象の身体の処置に用いることができる。これらは、本明細書で言及される創傷のいずれかを治療する医薬の製造において用いることができる。
一態様において、ギャップジャンクション調節剤は、包帯材またはマトリックスの形態で提供される。一部の実施形態では、本発明のギャップジャンクション調節剤が直接的な適用のための液体組成物、半固体組成物、もしくは固体組成物の形態で提供されるか、あるいは組成物が包帯材ガーゼもしくはマトリックスなどの固体接触層の表面へと適用されるか、またはこの中へと組み込まれる。包帯材組成物は、例えば、流体またはゲルの形態で提供することができる。1または複数のギャップジャンクション調節剤は、局所適用のための従来の医薬賦形剤と組合せて提供することができる。適切な担体は、プルロニックゲル、ポロキサマーゲル、セルロース誘導体(ヒドロキシエチルセルロース、ヒドロキシメチルセルロース、カルボキシメチルセルロース、ヒドロキシプロピルメチルセルロース、およびこれらの混合物を含む)を含有するヒドロゲル;ならびにポリアクリル酸を含有するヒドロゲル(Carbopols)を含む。適切な担体はまた、局所医薬調製物に用いられるクリーム/軟膏、例えば、セトマクロゴール乳化軟膏に基づくクリームも含む。上記の担体は、アルギン酸塩(増粘剤または刺激剤として)、ベンジルアルコールなどの防腐剤、リン酸水素二ナトリウム/リン酸二水素ナトリウムなどのpH調整のための緩衝液、塩化ナトリウムなどの浸透圧を調整するための薬剤、およびEDTAなどの安定化剤を含みうる。
本発明は、ギャップジャンクション調節化合物(ペプチド模倣剤を含む)を含む医薬組成物に関する。組成物は、例えば、慢性創傷、また本明細書で説明される他の創傷を含む、治癒が遅延しているかまたは困難な創傷の治癒を増強または促進するのに有用である。同様に、他の組織損傷の場合、本発明の方法および組成物は、創傷治癒過程の促進および炎症の軽減の両方において有効である。したがって、本発明の製剤および組成物は、慢性創傷および治癒の遅い創傷、ならびに本明細書で説明される他の創傷の治療において明らかな利益をもたらす。
本発明は、各種の疾患、障害、および創傷を全体的または部分的に治療および/または予防する方法を含み、例えば、予測される速度で治癒しない創傷を治療する方法を含む。これらは、治癒が遅延しているかまたは困難な創傷(治癒が遅延しているかまたは不完全な創傷を含む)、および慢性創傷を含む。予測される速度で治癒しない創傷の例は、糖尿病性潰瘍、血管炎性潰瘍、動脈性潰瘍、静脈性潰瘍、静脈鬱血性潰瘍、熱傷潰瘍、感染性潰瘍、外傷誘導性潰瘍、褥瘡、および褥瘡性潰瘍を含む。予測される速度で治癒しない他の創傷は、離開創を含む。
一態様において、本発明は、予測される速度で治癒しない創傷を治療するためのキットを提供する。
ペプチドの親和性結合アッセイ
プルダウンアッセイを使用してタンパク質−ペプチド相互作用を確認することができる。このアッセイでは、試験ギャップジャンクション調節剤(例えば、ペプチド)を、セルロース、アガロースまたはニッケルビーズへの付着を介してタンパク質結合パートナーを捕捉および「プルダウン」するために使用されるタンパク質反応性または融合タグすなわち、GST(グルタチオン−S−トランスフェラーゼ)でタグ付けする。SDS−PAGEローディングバッファーまたは代替として競合的な分析物の溶出を利用した複合体の溶出に続いて、SDS−PAGEゲル上に流してウェスタン解析検出法を使用することによって、複合体を可視化する。当技術分野において公知の結合アッセイを行う方法は、それぞれその全体が参照により本明細書に組み込まれる、Protein−Protein Interactions:A Molecular Cloning Manual、Cold Spring Harbor Laboratory Press、37〜57頁(2002年)のEinarson, M.B. and Orlinick, J.R.、「Identification of Protein−Protein Interactions with Glutathione S−Transferase Fusion Proteins」;Molecular Cloning:A Laboratory Manual、第3版、Cold Spring Harbor Laboratory Press、18.55〜18.59頁(2001年)のEinarson, M.B.、「Detection of Protein−Protein Interactions Using the GST Fusion Protein Pulldown Technique」;およびProtein−Protein Interactions, Methods and Applications, Methods in Molecular Biology、261号、Fu, H.編、Humana Press、Totowa、N.J.、175〜186頁(2004年)のVikis, H.G. and Guan, K.L.、「Glutathione−S−Transferase−Fusion Based Assays for Studying Protein−Protein Interactions」において記述されている。
機能アッセイ
機能アッセイを使用して、試験ギャップジャンクション調節ペプチド模倣体がギャップジャンクションまたはヘミチャネルの穴を遮断できるかどうかを判定することができる。HeLaヒト子宮頸癌細胞株を、Cx43、Cx45、または対象とする別の特定のコネキシンで安定にトランスフェクトする。細胞を、コネキシンヘミチャネルを活性化することが示されている(Braet, K.ら、「Pharmacological sensitivity of ATP release triggered by photoliberation of inositol−1,4,5−trisphosphate and zero extracellular calcium in brain endothelial cells」、Journal of Cellular Physiology、197巻(2号):205〜213頁(2003年);DeVries, S.H. and E.A. Schwartz、「Hemi−gap−junction channels in solitary horizontal cells of the catfish retina」、Journal of Physiology 445:201〜230頁(1992年);およびLi, H.ら、「Properties and regulation of gap junctional hemichannels in the plasma membranes of cultured cells」、Journal of Cell Biology 134巻(4号):1019〜1030頁(1996年)を参照されたい)無カルシウム溶液(1mMのEGTAを含有するHBSS−HEPES)中でインキュベートする。細胞を、1mMのEGTAおよび2mMのヨウ化プロピジウムを含有するHBSS−HEPES溶液中で30分間インキュベートする。ヨウ化プロピジウムは、膜不透過性であるが、その低分子量のためにギャップジャンクション/ヘミチャネルから入ることができる蛍光色素である。ヨウ化プロピジウムの取り込みは、蛍光顕微鏡検査法を使用して測定される。細胞をペプチド模倣体の存在下でヨウ化プロピジウムとインキュベートし、これらが色素取り込みを妨害することができるかどうかを判定する。
ペプチド模倣体の設計および試験
ペプチド模倣体は、コネクソン連結過程に関与すると考えられている(Footeら、J Cell Biol 140巻(5号):1187〜97頁、(1998年))コネキシン43細胞外ループ領域と同じアミノ酸配列を有するように設計することができる。いくつかのペプチドは、増強された機能阻害を示しうるアルファヘリックス膜貫通サブユニットの外側部分にマッチするアミノ酸を含む。これらのペプチドのすべてが、細胞外ループ領域におけるコネキシン配列の保存のために必ずしもコネキシン特異的というわけではない。
「Formulations Comprising Antisense Nucleotides to Connexins」という表題のBecker, D. and Green. C.のWO2000/44409の実施例1に記述されている系を使用して、培養された脊髄分節に対する試験ペプチドの効果を検査し、これらの腫脹を阻止する能力を試験する。
本明細書に開示されている方法および組成物を使用して、慢性創傷(例えば、血管性潰瘍)を有するヒト対象を治療する。
本明細書に開示されている方法および組成物を使用して、慢性静脈脚潰瘍を有するヒト対象を治療する。
以下を使用して、糖尿病性および別の慢性潰瘍の治癒速度の促進における、例示的な製剤の逐次投与の治療効果を判定する。
抗コネキシン剤は、好都合には、本発明の方法による投与に適する形態に処方される。
Claims (43)
- 慢性創傷を有する対象を治療する方法であって、有効量のコネキシン43ギャップジャンクション調節剤を含む組成物の前記創傷への投与を含む方法。
- 前記慢性創傷が褥瘡である、請求項1に記載の方法。
- 前記慢性創傷が褥瘡性潰瘍である、請求項1に記載の方法。
- 前記慢性創傷が動脈性潰瘍である、請求項1に記載の方法。
- 前記慢性創傷が静脈性潰瘍である、請求項1に記載の方法。
- 前記慢性創傷が静脈鬱血性潰瘍である、請求項1に記載の方法。
- 前記慢性創傷が糖尿病性足部潰瘍である、請求項1に記載の方法。
- 前記慢性創傷が外傷性潰瘍である、請求項1に記載の方法。
- 前記慢性創傷が熱傷潰瘍である、請求項1に記載の方法。
- 予測される速度で治癒しない創傷を有する対象を治療する方法であって、有効量のコネキシン43ギャップジャンクション調節剤の前記創傷への投与を含む方法。
- 前記創傷が、治癒が遅延している創傷または治癒が不完全な創傷である、請求項10に記載の方法。
- 離開創を有する対象を治療する方法であって、有効量のコネキシン43ギャップジャンクション調節剤を含む組成物の前記創傷への投与を含む方法。
- 前記ギャップジャンクション調節剤が、ギャップジャンクションを通る分子の流動を全体的または部分的に妨害または低減する、請求項1、10、または12のいずれかに記載の方法。
- 前記ギャップジャンクション調節剤が、ヘミチャネルを通る分子の流動を全体的または部分的に妨害または低減する、請求項1、10、または12のいずれかに記載の方法。
- 前記ギャップジャンクション調節剤が、ギャップジャンクションを全体的または部分的に閉鎖する、請求項1、10、または12のいずれかに記載の方法。
- 前記ギャップジャンクション調節剤が、ヘミチャネルを全体的または部分的に閉鎖する、請求項1、10、または12のいずれかに記載の方法。
- 前記ギャップジャンクション調節剤が、ギャップジャンクションを全体的または部分的に遮断する、請求項1、10、または12のいずれかに記載の方法。
- 前記ギャップジャンクション調節剤が、ヘミチャネルを全体的または部分的に遮断する、請求項1、10、または12のいずれかに記載の方法。
- 前記ギャップジャンクション調節剤が、ギャップジャンクションの全体的または部分的な閉鎖を誘導する、請求項1、10、または12のいずれかに記載の方法。
- 前記ギャップジャンクション調節剤が、ヘミチャネルの全体的または部分的な閉鎖を誘導する、請求項1、10、または12のいずれかに記載の方法。
- 前記ギャップジャンクション調節剤が、ギャップジャンクションの開口を全体的または部分的に低減または妨害する、請求項1、10、または12のいずれかに記載の方法。
- 前記ギャップジャンクション調節剤が、ヘミチャネルの開口を全体的または部分的に低減または妨害する、請求項1、10、または12のいずれかに記載の方法。
- 前記ギャップジャンクション調節剤が、ギャップジャンクションの活性または機能を妨害または低減する、請求項1、10、または12のいずれかに記載の方法。
- 前記ギャップジャンクション調節剤が、ヘミチャネルの活性または機能を妨害または低減する、請求項1、10、または12のいずれかに記載の方法。
- 前記ギャップジャンクション調節剤がペプチド化合物である、請求項1、10、または12のいずれかに記載の方法。
- 前記ペプチド化合物がペプチド模倣剤である、請求項25に記載の方法。
- 前記ギャップジャンクション調節剤が、抗体または抗体の抗原結合フラグメントである、請求項25に記載の方法。
- 前記抗体がモノクローナル抗体である、請求項27に記載の方法。
- 前記抗原結合フラグメントが、F(v)、Fab、Fab’、またはF(ab’)2抗コネキシン43抗体フラグメントである、請求項27に記載の方法。
- 前記抗体が、キメラ抗体またはヒト化抗体である、請求項27に記載の方法。
- 前記抗体フラグメントが、キメラ抗体フラグメントまたはヒト化抗体フラグメントである、請求項27に記載の方法。
- 前記ギャップジャンクション調節剤が、ギャップジャンクションリン酸化誘導剤である、請求項1、10、または12のいずれかに記載の方法。
- 前記ギャップジャンクション調節剤が、局所投与用に処方される、請求項1、10、または12のいずれかに記載の方法。
- 前記ギャップジャンクション調節剤が、ゲルとして処方される、請求項1、10、または12のいずれかに記載の方法。
- 前記対象がヒトである、請求項1、10、または12のいずれかに記載の方法。
- 前記対象が非ヒト動物である、請求項1、10、または12のいずれかに記載の方法。
- 前記非ヒト動物が競技動物である、請求項36に記載の方法。
- 前記競技動物がウマである、請求項37に記載の方法。
- 前記競技動物がイヌである、請求項37に記載の方法。
- 前記非ヒト動物がペット動物である、請求項36に記載の方法。
- 前記ペット動物がイヌである、請求項40に記載の方法。
- 前記ペット動物がネコである、請求項40に記載の方法。
- 前記慢性創傷が持続性上皮欠損である、請求項1に記載の方法。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US732307P | 2007-12-11 | 2007-12-11 | |
PCT/US2008/013655 WO2009075881A2 (en) | 2007-12-11 | 2008-12-11 | Impaired wound healing compositions and treatments |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2014176870A Division JP2014231521A (ja) | 2007-12-11 | 2014-09-01 | 損傷した創傷治癒組成物および治療 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2011506446A true JP2011506446A (ja) | 2011-03-03 |
JP2011506446A5 JP2011506446A5 (ja) | 2012-02-02 |
Family
ID=40626890
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2010537970A Pending JP2011506446A (ja) | 2007-12-11 | 2008-12-11 | 損傷した創傷治癒組成物および治療 |
JP2014176870A Pending JP2014231521A (ja) | 2007-12-11 | 2014-09-01 | 損傷した創傷治癒組成物および治療 |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2014176870A Pending JP2014231521A (ja) | 2007-12-11 | 2014-09-01 | 損傷した創傷治癒組成物および治療 |
Country Status (8)
Country | Link |
---|---|
US (1) | US20110300130A1 (ja) |
EP (2) | EP2245061A2 (ja) |
JP (2) | JP2011506446A (ja) |
CN (2) | CN107080845A (ja) |
AU (1) | AU2008335717A1 (ja) |
CA (1) | CA2709151A1 (ja) |
WO (1) | WO2009075881A2 (ja) |
ZA (1) | ZA201004999B (ja) |
Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2015513549A (ja) * | 2012-03-01 | 2015-05-14 | ファーストストリング・リサーチ・インコーポレイテッドFirststring Research,Inc. | アルファコネキシンc末端(act)ペプチド含有局所用ゲル剤 |
JP2015515282A (ja) * | 2012-04-25 | 2015-05-28 | エムユーエスシー ファウンデーション フォー リサーチ ディベロップメント | 創傷治癒および組織修復のための組成物および方法 |
JP2019504829A (ja) * | 2016-01-27 | 2019-02-21 | 上海科技大学Shanghai Tech University | コネキシン26特異的阻害性の完全ヒト抗体 |
JP2020531455A (ja) * | 2017-08-15 | 2020-11-05 | セル セラピー アンド テクノロジー,エス.エー. デーイー シー.ヴィ. | 慢性皮膚損傷の治療のための抗微生物剤とピルフェニドンとを含有する局所用半固体組成物 |
US11766426B2 (en) | 2012-03-28 | 2023-09-26 | Excalibur Pharmaceuticals, Inc. | Semi-solid topical composition containing pirfenidone and modified diallyl disulfide oxide (M-DDO) for eliminating or preventing acne |
US11779574B2 (en) | 2007-08-14 | 2023-10-10 | Excalibur Pharmaceuticals, Inc. | Gel containing pirfenidone |
Families Citing this family (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR20080031154A (ko) | 2005-02-03 | 2008-04-08 | 코다 테라퓨틱스 (엔지) 리미티드 | 항-코넥신 화합물 및 그의 용도 |
US8063023B2 (en) | 2006-12-11 | 2011-11-22 | Coda Therapeuctics, Inc. | Impaired wound healing compositions and treatments |
WO2009075882A2 (en) * | 2007-12-11 | 2009-06-18 | Coda Therapeutics, Inc. | Impaired wound healing compositions and treatments |
WO2009085268A2 (en) * | 2007-12-21 | 2009-07-09 | Coda Therapeutics, Inc. | Use of anti-connexin peptides, alone or in combination with anti-connexin polynucleotides, for the treatment of surgical adhesions |
US8975237B2 (en) | 2007-12-21 | 2015-03-10 | Coda Therapeutics, Inc. | Treatment of fibrotic conditions |
PT2536422E (pt) * | 2011-02-02 | 2014-07-18 | Univ Southern California | Métodos para o tratamento de úlceras do pé diabético |
US9156896B2 (en) | 2013-03-15 | 2015-10-13 | Coda Therapeutics, Inc. | Wound healing compositions and treatments |
CA2941140A1 (en) * | 2014-03-14 | 2015-09-17 | Coda Therapeutics | Treatment of resistant lesions |
EP3183346A4 (en) | 2014-08-22 | 2018-10-24 | Auckland Uniservices Limited | Channel modulators |
US11466069B2 (en) | 2017-04-28 | 2022-10-11 | Auckland Uniservices Limited | Methods of treatment and novel constructs |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2006069181A2 (en) * | 2004-12-21 | 2006-06-29 | Musc Foundation For Research Development | Compositions and methods for promoting wound healing and tissue regeneration |
WO2006134494A2 (en) * | 2005-02-03 | 2006-12-21 | Coda Therapeutics Limited | Anti-connexin compounds and therapeutic uses thereof |
Family Cites Families (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5004810A (en) | 1988-09-30 | 1991-04-02 | Schering Corporation | Antiviral oligomers |
US5166195A (en) | 1990-05-11 | 1992-11-24 | Isis Pharmaceuticals, Inc. | Antisense inhibitors of the human immunodeficiency virus phosphorothioate oligonucleotides |
ES2245638T3 (es) | 1999-01-27 | 2006-01-16 | Becker, David, Dr. | Formulaciones que comprenden nucleotidos antisentido para conexinas. |
US7250397B2 (en) | 2000-02-23 | 2007-07-31 | Zealand Pharma A/S | Antiarrhythmic peptides |
US6664230B1 (en) * | 2000-08-24 | 2003-12-16 | The Regents Of The University Of California | Orally administered peptides to ameliorate atherosclerosis |
US20050119211A1 (en) * | 2001-05-18 | 2005-06-02 | Sirna Therapeutics, Inc. | RNA mediated inhibition connexin gene expression using short interfering nucleic acid (siNA) |
EP1435925A2 (en) | 2001-10-17 | 2004-07-14 | University of Wales College of Medicine | Gap junctions and edhf |
KR20040094677A (ko) * | 2002-01-29 | 2004-11-10 | 와이어쓰 | 코넥신 헤미채널 조절을 위한 조성물 및 방법 |
DK1699924T3 (da) * | 2003-12-03 | 2019-10-21 | Ocunexus Therapeutics Inc | Connexin 43-målrettede hæmmende forbindelser og fremgangsmåder til anvendelse deraf i behandling af hornhindetraume |
ITRM20030596A1 (it) * | 2003-12-23 | 2005-06-24 | Sigma Tau Ind Farmaceuti | Uso di inibitori della pentraxina lunga ptx3, per la preparazione di un medicamento per la prevenzione e cura di patologie che rispondono all'inibizione dell'attivita' biologica di detta ptx3. |
CN101965193A (zh) * | 2006-11-15 | 2011-02-02 | 科达治疗公司 | 用于伤口愈合的改进方法和组合物 |
US8063023B2 (en) * | 2006-12-11 | 2011-11-22 | Coda Therapeuctics, Inc. | Impaired wound healing compositions and treatments |
KR20100050443A (ko) * | 2007-05-31 | 2010-05-13 | 안테리오스, 인코퍼레이티드 | 핵산 나노입자 및 이의 용도 |
-
2008
- 2008-12-11 CN CN201710130670.9A patent/CN107080845A/zh active Pending
- 2008-12-11 JP JP2010537970A patent/JP2011506446A/ja active Pending
- 2008-12-11 US US12/747,501 patent/US20110300130A1/en not_active Abandoned
- 2008-12-11 AU AU2008335717A patent/AU2008335717A1/en not_active Abandoned
- 2008-12-11 WO PCT/US2008/013655 patent/WO2009075881A2/en active Application Filing
- 2008-12-11 EP EP08860470A patent/EP2245061A2/en not_active Withdrawn
- 2008-12-11 CN CN2008801265337A patent/CN102105492A/zh active Pending
- 2008-12-11 EP EP13153125.3A patent/EP2628747A1/en not_active Ceased
- 2008-12-11 CA CA2709151A patent/CA2709151A1/en not_active Abandoned
-
2010
- 2010-07-14 ZA ZA2010/04999A patent/ZA201004999B/en unknown
-
2014
- 2014-09-01 JP JP2014176870A patent/JP2014231521A/ja active Pending
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2006069181A2 (en) * | 2004-12-21 | 2006-06-29 | Musc Foundation For Research Development | Compositions and methods for promoting wound healing and tissue regeneration |
WO2006134494A2 (en) * | 2005-02-03 | 2006-12-21 | Coda Therapeutics Limited | Anti-connexin compounds and therapeutic uses thereof |
Non-Patent Citations (2)
Title |
---|
JPN6013024209; C.M.Wang, et al., Diabetes, Nov.2007, 56, pp2809-2817 * |
JPN6013024211; J.M.Brandner, et al., J Invest Dermatol, 2004, 122, pp1310-1320 * |
Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US11779574B2 (en) | 2007-08-14 | 2023-10-10 | Excalibur Pharmaceuticals, Inc. | Gel containing pirfenidone |
JP2015513549A (ja) * | 2012-03-01 | 2015-05-14 | ファーストストリング・リサーチ・インコーポレイテッドFirststring Research,Inc. | アルファコネキシンc末端(act)ペプチド含有局所用ゲル剤 |
US11766426B2 (en) | 2012-03-28 | 2023-09-26 | Excalibur Pharmaceuticals, Inc. | Semi-solid topical composition containing pirfenidone and modified diallyl disulfide oxide (M-DDO) for eliminating or preventing acne |
JP2015515282A (ja) * | 2012-04-25 | 2015-05-28 | エムユーエスシー ファウンデーション フォー リサーチ ディベロップメント | 創傷治癒および組織修復のための組成物および方法 |
JP2019504829A (ja) * | 2016-01-27 | 2019-02-21 | 上海科技大学Shanghai Tech University | コネキシン26特異的阻害性の完全ヒト抗体 |
JP7022690B2 (ja) | 2016-01-27 | 2022-03-03 | 上海科技大学 | コネキシン26特異的阻害性の完全ヒト抗体 |
JP2020531455A (ja) * | 2017-08-15 | 2020-11-05 | セル セラピー アンド テクノロジー,エス.エー. デーイー シー.ヴィ. | 慢性皮膚損傷の治療のための抗微生物剤とピルフェニドンとを含有する局所用半固体組成物 |
US11576905B2 (en) | 2017-08-15 | 2023-02-14 | Excalibur Pharmaceuticals, Inc. | Topical semisolid composition containing an antimicrobial agent and pirfenidone for the treatment of chronic skin damage |
Also Published As
Publication number | Publication date |
---|---|
CN107080845A (zh) | 2017-08-22 |
AU2008335717A1 (en) | 2009-06-18 |
US20110300130A1 (en) | 2011-12-08 |
WO2009075881A3 (en) | 2009-07-30 |
ZA201004999B (en) | 2011-07-27 |
CA2709151A1 (en) | 2009-06-18 |
CN102105492A (zh) | 2011-06-22 |
EP2245061A2 (en) | 2010-11-03 |
WO2009075881A2 (en) | 2009-06-18 |
JP2014231521A (ja) | 2014-12-11 |
EP2628747A1 (en) | 2013-08-21 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP2014231521A (ja) | 損傷した創傷治癒組成物および治療 | |
JP2016135799A (ja) | 損傷した創傷治癒組成物および治療 | |
Reiss et al. | Matrix metalloproteinase-9 delays wound healing in a murine wound model | |
JP5911454B2 (ja) | 減損した創傷治癒の組成物としての抗コネキシンポリヌクレオチド | |
JP2017148075A (ja) | 創傷治癒組成物および治療 | |
JP2015057430A (ja) | 異常瘢痕または過剰瘢痕の治療のための抗コネキシンポリヌクレオチドおよび抗コネキシンペプチドの使用 | |
JP2015520754A (ja) | 創傷治癒のための組合せ治療および組成物 | |
KR20080031405A (ko) | 상피 재생의 촉진 | |
JP2011507862A (ja) | 異常瘢痕または過剰瘢痕の治療のための抗コネキシン43ポリヌクレオチドの使用 | |
JP2014208699A (ja) | 外科的癒着の治療のための、単独のまたは抗コネキシンポリヌクレオチドと組み合わせた抗コネキシンペプチドの使用 | |
JP2015083606A (ja) | 線維症性の状態の治療のための抗コネキシンポリヌクレオチド剤と組み合わせた抗コネキシンポリペプチド剤の使用 | |
US5155038A (en) | Use of thrombospondin to promote wound healing | |
Maggio et al. | A new protocol for the treatment of the chronic venous ulcers of the lower limb | |
CN105209618A (zh) | 改进的伤口愈合组合物和治疗 | |
KR20160018595A (ko) | 다양한 피부 병태의 치료에 유용한 인간 c-x-c 케모카인으로부터 유래된 테트라펩타이드 | |
JP2015513905A (ja) | カドヘリン調節に基づく組成物および処置 | |
US20160244759A1 (en) | Compositions and treatments based on cadherin modulation | |
WO2022081748A1 (en) | Formulation for wound healing | |
AU2017202281A1 (en) | Impaired wound healing compositions and treatments | |
US20110110922A1 (en) | Wound Healing Peptides and Methods of Use Thereof | |
US20220041668A1 (en) | Method of promoting wound healing by inhibiting ccr3 | |
KR20230136597A (ko) | 상처 치료를 위한 조성물들 및 방법들 | |
CA2941140A1 (en) | Treatment of resistant lesions |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Written amendment |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20111209 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20111209 |
|
A521 | Written amendment |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20121128 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20130527 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20130826 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20130902 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20130926 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20131003 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20131025 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20131101 |
|
A521 | Written amendment |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20131127 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20140502 |