JP6273272B2 - 炎症性皮膚障害の治療 - Google Patents
炎症性皮膚障害の治療 Download PDFInfo
- Publication number
- JP6273272B2 JP6273272B2 JP2015518732A JP2015518732A JP6273272B2 JP 6273272 B2 JP6273272 B2 JP 6273272B2 JP 2015518732 A JP2015518732 A JP 2015518732A JP 2015518732 A JP2015518732 A JP 2015518732A JP 6273272 B2 JP6273272 B2 JP 6273272B2
- Authority
- JP
- Japan
- Prior art keywords
- apc
- skin
- psoriasis
- area
- keratinocytes
- 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.)
- Active
Links
- 208000017520 skin disease Diseases 0.000 title claims description 24
- 238000011282 treatment Methods 0.000 title description 58
- 230000002757 inflammatory effect Effects 0.000 title description 21
- 210000002510 keratinocyte Anatomy 0.000 claims description 90
- 210000003491 skin Anatomy 0.000 claims description 82
- 201000004681 Psoriasis Diseases 0.000 claims description 78
- 238000000034 method Methods 0.000 claims description 59
- 239000000203 mixture Substances 0.000 claims description 46
- 101800004937 Protein C Proteins 0.000 claims description 41
- 101800001700 Saposin-D Proteins 0.000 claims description 41
- 229960000856 protein c Drugs 0.000 claims description 41
- 230000003463 hyperproliferative effect Effects 0.000 claims description 31
- 230000006907 apoptotic process Effects 0.000 claims description 30
- 208000002874 Acne Vulgaris Diseases 0.000 claims description 28
- 206010000496 acne Diseases 0.000 claims description 28
- 239000003814 drug Substances 0.000 claims description 19
- 238000009472 formulation Methods 0.000 claims description 19
- 239000000499 gel Substances 0.000 claims description 14
- 230000012010 growth Effects 0.000 claims description 11
- 201000004624 Dermatitis Diseases 0.000 claims description 9
- 206010061218 Inflammation Diseases 0.000 claims description 9
- 206010037575 Pustular psoriasis Diseases 0.000 claims description 9
- 230000004054 inflammatory process Effects 0.000 claims description 9
- 238000004519 manufacturing process Methods 0.000 claims description 9
- 239000007921 spray Substances 0.000 claims description 9
- 230000009885 systemic effect Effects 0.000 claims description 8
- 230000002062 proliferating effect Effects 0.000 claims description 7
- 239000002674 ointment Substances 0.000 claims description 6
- 238000010254 subcutaneous injection Methods 0.000 claims description 5
- 239000007929 subcutaneous injection Substances 0.000 claims description 5
- 230000008569 process Effects 0.000 claims description 4
- 230000004888 barrier function Effects 0.000 claims description 3
- 230000001771 impaired effect Effects 0.000 claims description 3
- 239000006210 lotion Substances 0.000 claims description 3
- 206010012455 Dermatitis exfoliative Diseases 0.000 claims description 2
- 201000011152 Pemphigus Diseases 0.000 claims description 2
- 206010047642 Vitiligo Diseases 0.000 claims description 2
- 239000006071 cream Substances 0.000 claims description 2
- 201000001976 pemphigus vulgaris Diseases 0.000 claims description 2
- 102100036546 Salivary acidic proline-rich phosphoprotein 1/2 Human genes 0.000 claims 3
- 208000007514 Herpes zoster Diseases 0.000 claims 1
- 239000002260 anti-inflammatory agent Substances 0.000 claims 1
- 229940124599 anti-inflammatory drug Drugs 0.000 claims 1
- 230000029411 keratinocyte apoptotic process Effects 0.000 claims 1
- 210000004027 cell Anatomy 0.000 description 62
- 102000017975 Protein C Human genes 0.000 description 38
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 34
- 230000001640 apoptogenic effect Effects 0.000 description 18
- 201000010099 disease Diseases 0.000 description 18
- 230000000694 effects Effects 0.000 description 18
- 230000035755 proliferation Effects 0.000 description 18
- 206010012438 Dermatitis atopic Diseases 0.000 description 16
- 201000008937 atopic dermatitis Diseases 0.000 description 16
- 208000035475 disorder Diseases 0.000 description 15
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 14
- 108010009900 Endothelial Protein C Receptor Proteins 0.000 description 13
- 102100030024 Endothelial protein C receptor Human genes 0.000 description 13
- 230000002424 anti-apoptotic effect Effects 0.000 description 13
- 230000003110 anti-inflammatory effect Effects 0.000 description 12
- 230000004663 cell proliferation Effects 0.000 description 12
- 150000001875 compounds Chemical class 0.000 description 12
- 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 12
- 229940079593 drug Drugs 0.000 description 11
- 230000001965 increasing effect Effects 0.000 description 11
- 239000007924 injection Substances 0.000 description 11
- 238000002347 injection Methods 0.000 description 11
- 239000000902 placebo Substances 0.000 description 11
- 229940068196 placebo Drugs 0.000 description 11
- 235000002639 sodium chloride Nutrition 0.000 description 11
- 238000002560 therapeutic procedure Methods 0.000 description 11
- 108090000190 Thrombin Proteins 0.000 description 10
- 210000004969 inflammatory cell Anatomy 0.000 description 10
- 230000003902 lesion Effects 0.000 description 10
- 230000004044 response Effects 0.000 description 10
- 101000924577 Homo sapiens Adenomatous polyposis coli protein Proteins 0.000 description 9
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 9
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 9
- 239000003795 chemical substances by application Substances 0.000 description 9
- 230000001684 chronic effect Effects 0.000 description 9
- 229960004072 thrombin Drugs 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 8
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 8
- 210000001519 tissue Anatomy 0.000 description 8
- 230000000699 topical effect Effects 0.000 description 8
- 238000000134 MTT assay Methods 0.000 description 7
- 231100000002 MTT assay Toxicity 0.000 description 7
- 108020004459 Small interfering RNA Proteins 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- 239000004615 ingredient Substances 0.000 description 7
- 238000002156 mixing Methods 0.000 description 7
- 238000001126 phototherapy Methods 0.000 description 7
- 108090000623 proteins and genes Proteins 0.000 description 7
- 239000011780 sodium chloride Substances 0.000 description 7
- 102100034540 Adenomatous polyposis coli protein Human genes 0.000 description 6
- 102000004127 Cytokines Human genes 0.000 description 6
- 108090000695 Cytokines Proteins 0.000 description 6
- 238000002965 ELISA Methods 0.000 description 6
- 102000003992 Peroxidases Human genes 0.000 description 6
- 230000004913 activation Effects 0.000 description 6
- 238000003556 assay Methods 0.000 description 6
- 230000006870 function Effects 0.000 description 6
- 238000011065 in-situ storage Methods 0.000 description 6
- 208000015181 infectious disease Diseases 0.000 description 6
- 108040007629 peroxidase activity proteins Proteins 0.000 description 6
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 230000001225 therapeutic effect Effects 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 5
- 230000002411 adverse Effects 0.000 description 5
- 238000001574 biopsy Methods 0.000 description 5
- CBGUOGMQLZIXBE-XGQKBEPLSA-N clobetasol propionate 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)CCl)(OC(=O)CC)[C@@]1(C)C[C@@H]2O CBGUOGMQLZIXBE-XGQKBEPLSA-N 0.000 description 5
- 238000001514 detection method Methods 0.000 description 5
- 108010008250 drotrecogin alfa activated Proteins 0.000 description 5
- 238000000338 in vitro Methods 0.000 description 5
- 238000001802 infusion Methods 0.000 description 5
- 210000000440 neutrophil Anatomy 0.000 description 5
- 230000001185 psoriatic effect Effects 0.000 description 5
- 239000001509 sodium citrate Substances 0.000 description 5
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 5
- 230000004936 stimulating effect Effects 0.000 description 5
- 210000000434 stratum corneum Anatomy 0.000 description 5
- 238000007920 subcutaneous administration Methods 0.000 description 5
- 230000004083 survival effect Effects 0.000 description 5
- 208000024891 symptom Diseases 0.000 description 5
- 238000012384 transportation and delivery Methods 0.000 description 5
- 208000023275 Autoimmune disease Diseases 0.000 description 4
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 4
- 206010020649 Hyperkeratosis Diseases 0.000 description 4
- 108050003558 Interleukin-17 Proteins 0.000 description 4
- 102000013691 Interleukin-17 Human genes 0.000 description 4
- 108090001005 Interleukin-6 Proteins 0.000 description 4
- 102000004889 Interleukin-6 Human genes 0.000 description 4
- 229920002125 Sokalan® Polymers 0.000 description 4
- 229930006000 Sucrose Natural products 0.000 description 4
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 4
- 238000012288 TUNEL assay Methods 0.000 description 4
- 208000025865 Ulcer Diseases 0.000 description 4
- 208000010668 atopic eczema Diseases 0.000 description 4
- 239000003124 biologic agent Substances 0.000 description 4
- 230000030833 cell death Effects 0.000 description 4
- 239000003246 corticosteroid Substances 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 210000002950 fibroblast Anatomy 0.000 description 4
- 239000006260 foam Substances 0.000 description 4
- 235000011187 glycerol Nutrition 0.000 description 4
- 229920000642 polymer Polymers 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 238000007388 punch biopsy Methods 0.000 description 4
- 208000009954 pyoderma gangrenosum Diseases 0.000 description 4
- 239000000758 substrate Substances 0.000 description 4
- 239000005720 sucrose Substances 0.000 description 4
- 238000001262 western blot Methods 0.000 description 4
- FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 description 3
- WOVKYSAHUYNSMH-RRKCRQDMSA-N 5-bromodeoxyuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(Br)=C1 WOVKYSAHUYNSMH-RRKCRQDMSA-N 0.000 description 3
- 206010000349 Acanthosis Diseases 0.000 description 3
- 102000004121 Annexin A5 Human genes 0.000 description 3
- 108090000672 Annexin A5 Proteins 0.000 description 3
- 108090000397 Caspase 3 Proteins 0.000 description 3
- 102100029855 Caspase-3 Human genes 0.000 description 3
- 102000011727 Caspases Human genes 0.000 description 3
- 108010076667 Caspases Proteins 0.000 description 3
- AHCYMLUZIRLXAA-SHYZEUOFSA-N Deoxyuridine 5'-triphosphate Chemical group O1[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)C[C@@H]1N1C(=O)NC(=O)C=C1 AHCYMLUZIRLXAA-SHYZEUOFSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 102000011782 Keratins Human genes 0.000 description 3
- 108010076876 Keratins Proteins 0.000 description 3
- 108010057466 NF-kappa B Proteins 0.000 description 3
- 102000003945 NF-kappa B Human genes 0.000 description 3
- 206010037888 Rash pustular Diseases 0.000 description 3
- 108020004511 Recombinant DNA Proteins 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 210000001744 T-lymphocyte Anatomy 0.000 description 3
- 229930003316 Vitamin D Natural products 0.000 description 3
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 description 3
- 239000012190 activator Substances 0.000 description 3
- 230000022131 cell cycle Effects 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 229960004703 clobetasol propionate Drugs 0.000 description 3
- 230000001276 controlling effect Effects 0.000 description 3
- 229960001334 corticosteroids Drugs 0.000 description 3
- 238000002651 drug therapy Methods 0.000 description 3
- 102000055691 human APC Human genes 0.000 description 3
- 206010020718 hyperplasia Diseases 0.000 description 3
- 230000006872 improvement Effects 0.000 description 3
- 230000001939 inductive effect Effects 0.000 description 3
- 208000027866 inflammatory disease Diseases 0.000 description 3
- 229960000598 infliximab Drugs 0.000 description 3
- 230000000394 mitotic effect Effects 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 208000029561 pustule Diseases 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- 229960004889 salicylic acid Drugs 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 230000003068 static effect Effects 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 229940046728 tumor necrosis factor alpha inhibitor Drugs 0.000 description 3
- 231100000397 ulcer Toxicity 0.000 description 3
- 239000003981 vehicle Substances 0.000 description 3
- 235000019166 vitamin D Nutrition 0.000 description 3
- 239000011710 vitamin D Substances 0.000 description 3
- 150000003710 vitamin D derivatives Chemical class 0.000 description 3
- 229940046008 vitamin d Drugs 0.000 description 3
- 239000000080 wetting agent Substances 0.000 description 3
- LXAHHHIGZXPRKQ-UHFFFAOYSA-N 5-fluoro-2-methylpyridine Chemical compound CC1=CC=C(F)C=N1 LXAHHHIGZXPRKQ-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- 206010000503 Acne cystic Diseases 0.000 description 2
- 102100026886 Beta-defensin 104 Human genes 0.000 description 2
- 102100037355 Chromosome alignment-maintaining phosphoprotein 1 Human genes 0.000 description 2
- 102100033215 DNA nucleotidylexotransferase Human genes 0.000 description 2
- 108010008286 DNA nucleotidylexotransferase Proteins 0.000 description 2
- 102000010911 Enzyme Precursors Human genes 0.000 description 2
- 108010062466 Enzyme Precursors Proteins 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 108010008165 Etanercept Proteins 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical group CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 108010061932 Factor VIIIa Proteins 0.000 description 2
- 108010074105 Factor Va Proteins 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- 108010054964 H-hexahydrotyrosyl-alanyl-arginine-4-nitroanilide Proteins 0.000 description 2
- 206010019233 Headaches Diseases 0.000 description 2
- 208000032843 Hemorrhage Diseases 0.000 description 2
- 101000912243 Homo sapiens Beta-defensin 104 Proteins 0.000 description 2
- 101000884714 Homo sapiens Beta-defensin 4A Proteins 0.000 description 2
- 206010020751 Hypersensitivity Diseases 0.000 description 2
- 102000014150 Interferons Human genes 0.000 description 2
- 108010050904 Interferons Proteins 0.000 description 2
- 102000000589 Interleukin-1 Human genes 0.000 description 2
- 108010002352 Interleukin-1 Proteins 0.000 description 2
- 102000015696 Interleukins Human genes 0.000 description 2
- 108010063738 Interleukins Proteins 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 208000001126 Keratosis Diseases 0.000 description 2
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 2
- 102000002274 Matrix Metalloproteinases Human genes 0.000 description 2
- 108010000684 Matrix Metalloproteinases Proteins 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 206010067482 No adverse event Diseases 0.000 description 2
- 206010030113 Oedema Diseases 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- 238000011579 SCID mouse model Methods 0.000 description 2
- 206010040047 Sepsis Diseases 0.000 description 2
- 208000000453 Skin Neoplasms Diseases 0.000 description 2
- 238000000692 Student's t-test Methods 0.000 description 2
- 108010079274 Thrombomodulin Proteins 0.000 description 2
- 102100026966 Thrombomodulin Human genes 0.000 description 2
- 229920004890 Triton X-100 Polymers 0.000 description 2
- 239000013504 Triton X-100 Substances 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
- 108010042591 activated protein C receptor Proteins 0.000 description 2
- 229960002964 adalimumab Drugs 0.000 description 2
- 230000007815 allergy Effects 0.000 description 2
- 239000003146 anticoagulant agent Substances 0.000 description 2
- 229940127219 anticoagulant drug Drugs 0.000 description 2
- 229940030999 antipsoriatics Drugs 0.000 description 2
- 210000001099 axilla Anatomy 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 229960000074 biopharmaceutical Drugs 0.000 description 2
- 208000034158 bleeding Diseases 0.000 description 2
- 230000000740 bleeding effect Effects 0.000 description 2
- 210000001772 blood platelet Anatomy 0.000 description 2
- 239000004067 bulking agent Substances 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 230000003833 cell viability Effects 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 239000003593 chromogenic compound Substances 0.000 description 2
- 230000035602 clotting Effects 0.000 description 2
- 210000004207 dermis Anatomy 0.000 description 2
- 230000004069 differentiation Effects 0.000 description 2
- 230000010339 dilation Effects 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 230000002500 effect on skin Effects 0.000 description 2
- 229940088598 enzyme Drugs 0.000 description 2
- 210000005175 epidermal keratinocyte Anatomy 0.000 description 2
- 210000002615 epidermis Anatomy 0.000 description 2
- 229960000403 etanercept Drugs 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 230000003090 exacerbative effect Effects 0.000 description 2
- 230000007717 exclusion Effects 0.000 description 2
- 206010016256 fatigue Diseases 0.000 description 2
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 2
- 239000003862 glucocorticoid Substances 0.000 description 2
- 210000004013 groin Anatomy 0.000 description 2
- 231100000869 headache Toxicity 0.000 description 2
- 238000010562 histological examination Methods 0.000 description 2
- 230000002055 immunohistochemical effect Effects 0.000 description 2
- 238000012744 immunostaining Methods 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 238000010348 incorporation Methods 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 229940079322 interferon Drugs 0.000 description 2
- 230000016507 interphase Effects 0.000 description 2
- 230000007794 irritation Effects 0.000 description 2
- 238000002372 labelling Methods 0.000 description 2
- 210000000265 leukocyte Anatomy 0.000 description 2
- RLSSMJSEOOYNOY-UHFFFAOYSA-N m-cresol Chemical compound CC1=CC=CC(O)=C1 RLSSMJSEOOYNOY-UHFFFAOYSA-N 0.000 description 2
- 230000003211 malignant effect Effects 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 229960000485 methotrexate Drugs 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
- 238000000386 microscopy Methods 0.000 description 2
- VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 2
- 230000003472 neutralizing effect Effects 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 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
- 230000001823 pruritic effect Effects 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 2
- 230000010076 replication Effects 0.000 description 2
- 210000004761 scalp Anatomy 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 230000019491 signal transduction Effects 0.000 description 2
- 238000007390 skin biopsy Methods 0.000 description 2
- 201000000849 skin cancer Diseases 0.000 description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
- 239000008354 sodium chloride injection Substances 0.000 description 2
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 2
- 238000005507 spraying Methods 0.000 description 2
- 238000007619 statistical method Methods 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 229940037128 systemic glucocorticoids Drugs 0.000 description 2
- 238000009121 systemic therapy Methods 0.000 description 2
- 238000012353 t test Methods 0.000 description 2
- 230000017423 tissue regeneration Effects 0.000 description 2
- 230000009261 transgenic effect Effects 0.000 description 2
- 239000002451 tumor necrosis factor inhibitor Substances 0.000 description 2
- 208000027930 type IV hypersensitivity disease Diseases 0.000 description 2
- 239000002435 venom Substances 0.000 description 2
- 210000001048 venom Anatomy 0.000 description 2
- 231100000611 venom Toxicity 0.000 description 2
- 230000003442 weekly effect Effects 0.000 description 2
- 230000029663 wound healing Effects 0.000 description 2
- 239000000230 xanthan gum Substances 0.000 description 2
- 229920001285 xanthan gum Polymers 0.000 description 2
- 229940082509 xanthan gum Drugs 0.000 description 2
- 235000010493 xanthan gum Nutrition 0.000 description 2
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 1
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 1
- HMLGSIZOMSVISS-ONJSNURVSA-N (7r)-7-[[(2z)-2-(2-amino-1,3-thiazol-4-yl)-2-(2,2-dimethylpropanoyloxymethoxyimino)acetyl]amino]-3-ethenyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound N([C@@H]1C(N2C(=C(C=C)CSC21)C(O)=O)=O)C(=O)\C(=N/OCOC(=O)C(C)(C)C)C1=CSC(N)=N1 HMLGSIZOMSVISS-ONJSNURVSA-N 0.000 description 1
- BDKLKNJTMLIAFE-UHFFFAOYSA-N 2-(3-fluorophenyl)-1,3-oxazole-4-carbaldehyde Chemical compound FC1=CC=CC(C=2OC=C(C=O)N=2)=C1 BDKLKNJTMLIAFE-UHFFFAOYSA-N 0.000 description 1
- OSCJHTSDLYVCQC-UHFFFAOYSA-N 2-ethylhexyl 4-[[4-[4-(tert-butylcarbamoyl)anilino]-6-[4-(2-ethylhexoxycarbonyl)anilino]-1,3,5-triazin-2-yl]amino]benzoate Chemical compound C1=CC(C(=O)OCC(CC)CCCC)=CC=C1NC1=NC(NC=2C=CC(=CC=2)C(=O)NC(C)(C)C)=NC(NC=2C=CC(=CC=2)C(=O)OCC(CC)CCCC)=N1 OSCJHTSDLYVCQC-UHFFFAOYSA-N 0.000 description 1
- QCDWFXQBSFUVSP-UHFFFAOYSA-N 2-phenoxyethanol Chemical compound OCCOC1=CC=CC=C1 QCDWFXQBSFUVSP-UHFFFAOYSA-N 0.000 description 1
- NCZPCONIKBICGS-UHFFFAOYSA-N 3-(2-ethylhexoxy)propane-1,2-diol Chemical compound CCCCC(CC)COCC(O)CO NCZPCONIKBICGS-UHFFFAOYSA-N 0.000 description 1
- MJZJYWCQPMNPRM-UHFFFAOYSA-N 6,6-dimethyl-1-[3-(2,4,5-trichlorophenoxy)propoxy]-1,6-dihydro-1,3,5-triazine-2,4-diamine Chemical compound CC1(C)N=C(N)N=C(N)N1OCCCOC1=CC(Cl)=C(Cl)C=C1Cl MJZJYWCQPMNPRM-UHFFFAOYSA-N 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 102000000412 Annexin Human genes 0.000 description 1
- 108050008874 Annexin Proteins 0.000 description 1
- 206010003645 Atopy Diseases 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 102100026548 Caspase-8 Human genes 0.000 description 1
- 108090000538 Caspase-8 Proteins 0.000 description 1
- 102100026550 Caspase-9 Human genes 0.000 description 1
- 108090000566 Caspase-9 Proteins 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
- 102000002029 Claudin Human genes 0.000 description 1
- 108050009302 Claudin Proteins 0.000 description 1
- 241000223205 Coccidioides immitis Species 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 1
- 108010036949 Cyclosporine Proteins 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 230000006820 DNA synthesis Effects 0.000 description 1
- 101710088194 Dehydrogenase Proteins 0.000 description 1
- 239000003109 Disodium ethylene diamine tetraacetate Substances 0.000 description 1
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 description 1
- 108060006698 EGF receptor Proteins 0.000 description 1
- 102000001301 EGF receptor Human genes 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 206010015548 Euthanasia Diseases 0.000 description 1
- 208000010201 Exanthema Diseases 0.000 description 1
- 108010074860 Factor Xa Proteins 0.000 description 1
- 108010088842 Fibrinolysin Proteins 0.000 description 1
- 206010017533 Fungal infection Diseases 0.000 description 1
- 206010020144 Histoplasmosis disseminated Diseases 0.000 description 1
- 101000971171 Homo sapiens Apoptosis regulator Bcl-2 Proteins 0.000 description 1
- 101000896157 Homo sapiens Baculoviral IAP repeat-containing protein 2 Proteins 0.000 description 1
- 101500025568 Homo sapiens Saposin-D Proteins 0.000 description 1
- 208000037147 Hypercalcaemia Diseases 0.000 description 1
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 1
- 102000051628 Interleukin-1 receptor antagonist Human genes 0.000 description 1
- 108700021006 Interleukin-1 receptor antagonist Proteins 0.000 description 1
- 102000003814 Interleukin-10 Human genes 0.000 description 1
- 108090000174 Interleukin-10 Proteins 0.000 description 1
- 102100030703 Interleukin-22 Human genes 0.000 description 1
- 108090001007 Interleukin-8 Proteins 0.000 description 1
- 102000004890 Interleukin-8 Human genes 0.000 description 1
- 102000012411 Intermediate Filament Proteins Human genes 0.000 description 1
- 108010061998 Intermediate Filament Proteins Proteins 0.000 description 1
- 108010040082 Junctional Adhesion Molecule A Proteins 0.000 description 1
- 102100022304 Junctional adhesion molecule A Human genes 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- 102000019149 MAP kinase activity proteins Human genes 0.000 description 1
- 108040008097 MAP kinase activity proteins Proteins 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 241000187479 Mycobacterium tuberculosis Species 0.000 description 1
- 208000031888 Mycoses Diseases 0.000 description 1
- 201000009053 Neurodermatitis Diseases 0.000 description 1
- 102000003940 Occludin Human genes 0.000 description 1
- 108090000304 Occludin Proteins 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 108010077971 Plasminogen Inactivators Proteins 0.000 description 1
- 102000010752 Plasminogen Inactivators Human genes 0.000 description 1
- 101710111620 Protein C activator Proteins 0.000 description 1
- 229940096437 Protein S Drugs 0.000 description 1
- 102000029301 Protein S Human genes 0.000 description 1
- 108010066124 Protein S Proteins 0.000 description 1
- 208000003251 Pruritus Diseases 0.000 description 1
- MUPFEKGTMRGPLJ-RMMQSMQOSA-N Raffinose Natural products O(C[C@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](O[C@@]2(CO)[C@H](O)[C@@H](O)[C@@H](CO)O2)O1)[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 MUPFEKGTMRGPLJ-RMMQSMQOSA-N 0.000 description 1
- 108010022999 Serine Proteases Proteins 0.000 description 1
- 102000012479 Serine Proteases Human genes 0.000 description 1
- 102100023230 Serine/threonine-protein kinase MAK Human genes 0.000 description 1
- 206010040799 Skin atrophy Diseases 0.000 description 1
- 206010040880 Skin irritation Diseases 0.000 description 1
- 206010067723 Skin plaque Diseases 0.000 description 1
- 229930182558 Sterol Natural products 0.000 description 1
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 102100040247 Tumor necrosis factor Human genes 0.000 description 1
- 206010053613 Type IV hypersensitivity reaction Diseases 0.000 description 1
- MUPFEKGTMRGPLJ-UHFFFAOYSA-N UNPD196149 Natural products OC1C(O)C(CO)OC1(CO)OC1C(O)C(O)C(O)C(COC2C(C(O)C(O)C(CO)O2)O)O1 MUPFEKGTMRGPLJ-UHFFFAOYSA-N 0.000 description 1
- 206010047139 Vasoconstriction Diseases 0.000 description 1
- 206010052428 Wound Diseases 0.000 description 1
- 102000044820 Zonula Occludens-1 Human genes 0.000 description 1
- 108700007340 Zonula Occludens-1 Proteins 0.000 description 1
- 229960003697 abatacept Drugs 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 208000036981 active tuberculosis Diseases 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 1
- 230000003024 amidolytic effect Effects 0.000 description 1
- 229960004238 anakinra Drugs 0.000 description 1
- 238000000540 analysis of variance Methods 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000003255 anti-acne Effects 0.000 description 1
- 230000001567 anti-fibrinolytic effect Effects 0.000 description 1
- -1 anti-inflammatory Substances 0.000 description 1
- 238000011861 anti-inflammatory therapy Methods 0.000 description 1
- 238000003782 apoptosis assay Methods 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000002917 arthritic effect Effects 0.000 description 1
- 238000000889 atomisation Methods 0.000 description 1
- 210000000270 basal cell Anatomy 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000002146 bilateral effect Effects 0.000 description 1
- 238000001815 biotherapy Methods 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 235000015115 caffè latte Nutrition 0.000 description 1
- 229960002882 calcipotriol Drugs 0.000 description 1
- LWQQLNNNIPYSNX-UROSTWAQSA-N calcipotriol Chemical compound C1([C@H](O)/C=C/[C@@H](C)[C@@H]2[C@]3(CCCC(/[C@@H]3CC2)=C\C=C\2C([C@@H](O)C[C@H](O)C/2)=C)C)CC1 LWQQLNNNIPYSNX-UROSTWAQSA-N 0.000 description 1
- 229960005084 calcitriol Drugs 0.000 description 1
- 235000020964 calcitriol Nutrition 0.000 description 1
- 239000011612 calcitriol Substances 0.000 description 1
- GMRQFYUYWCNGIN-NKMMMXOESA-N calcitriol Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@@H](CCCC(C)(C)O)C)=C\C=C1\C[C@@H](O)C[C@H](O)C1=C GMRQFYUYWCNGIN-NKMMMXOESA-N 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 229960001631 carbomer Drugs 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 230000012820 cell cycle checkpoint Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 238000001516 cell proliferation assay Methods 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 230000006020 chronic inflammation Effects 0.000 description 1
- 229960001265 ciclosporin Drugs 0.000 description 1
- 229960002842 clobetasol Drugs 0.000 description 1
- 201000003486 coccidioidomycosis Diseases 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 229930182912 cyclosporin Natural products 0.000 description 1
- 230000016396 cytokine production Effects 0.000 description 1
- POZRVZJJTULAOH-LHZXLZLDSA-N danazol Chemical compound C1[C@]2(C)[C@H]3CC[C@](C)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=CC2=C1C=NO2 POZRVZJJTULAOH-LHZXLZLDSA-N 0.000 description 1
- 229960000766 danazol Drugs 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
- 235000019301 disodium ethylene diamine tetraacetate Nutrition 0.000 description 1
- QQQMUBLXDAFBRH-UHFFFAOYSA-N dodecyl 2-hydroxypropanoate Chemical compound CCCCCCCCCCCCOC(=O)C(C)O QQQMUBLXDAFBRH-UHFFFAOYSA-N 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 239000013583 drug formulation Substances 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 210000003038 endothelium Anatomy 0.000 description 1
- 210000001339 epidermal cell Anatomy 0.000 description 1
- 230000000058 esterolytic effect Effects 0.000 description 1
- 235000019441 ethanol Nutrition 0.000 description 1
- 229940100524 ethylhexylglycerin Drugs 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 201000005884 exanthem Diseases 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 210000003414 extremity Anatomy 0.000 description 1
- 230000020764 fibrinolysis Effects 0.000 description 1
- 239000003527 fibrinolytic agent Substances 0.000 description 1
- 238000000684 flow cytometry Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 1
- 210000003953 foreskin Anatomy 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 210000001654 germ layer Anatomy 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000002489 hematologic effect Effects 0.000 description 1
- 230000013632 homeostatic process Effects 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 229940100689 human protein c Drugs 0.000 description 1
- 239000003906 humectant Substances 0.000 description 1
- 230000000148 hypercalcaemia Effects 0.000 description 1
- 208000030915 hypercalcemia disease Diseases 0.000 description 1
- 230000002390 hyperplastic effect Effects 0.000 description 1
- 238000010191 image analysis Methods 0.000 description 1
- 230000005965 immune activity Effects 0.000 description 1
- 238000003125 immunofluorescent labeling Methods 0.000 description 1
- 238000003364 immunohistochemistry Methods 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 230000000415 inactivating effect Effects 0.000 description 1
- 239000005414 inactive ingredient Substances 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 108010074108 interleukin-21 Proteins 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 239000002085 irritant Substances 0.000 description 1
- 230000007803 itching Effects 0.000 description 1
- 229960005435 ixekizumab Drugs 0.000 description 1
- 210000001503 joint Anatomy 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 238000002690 local anesthesia Methods 0.000 description 1
- 239000003589 local anesthetic agent Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000008176 lyophilized powder Substances 0.000 description 1
- 229960005337 lysine hydrochloride Drugs 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 238000007726 management method Methods 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 229940031722 methyl gluceth-20 Drugs 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
- 229960002216 methylparaben Drugs 0.000 description 1
- HPNSFSBZBAHARI-UHFFFAOYSA-N micophenolic acid Natural products OC1=C(CC=C(C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-UHFFFAOYSA-N 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 230000002438 mitochondrial effect Effects 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 229960000951 mycophenolic acid Drugs 0.000 description 1
- HPNSFSBZBAHARI-RUDMXATFSA-N mycophenolic acid Chemical compound OC1=C(C\C=C(/C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-RUDMXATFSA-N 0.000 description 1
- 230000035407 negative regulation of cell proliferation Effects 0.000 description 1
- 230000009826 neoplastic cell growth Effects 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 230000000474 nursing effect Effects 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 229960005323 phenoxyethanol Drugs 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
- 230000036470 plasma concentration Effects 0.000 description 1
- 229940012957 plasmin Drugs 0.000 description 1
- 239000002797 plasminogen activator inhibitor Substances 0.000 description 1
- 239000008389 polyethoxylated castor oil Substances 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 238000004393 prognosis Methods 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
- 230000017854 proteolysis Effects 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 238000013309 psoriasis mouse model Methods 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- MUPFEKGTMRGPLJ-ZQSKZDJDSA-N raffinose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO[C@@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O2)O)O1 MUPFEKGTMRGPLJ-ZQSKZDJDSA-N 0.000 description 1
- 206010037844 rash Diseases 0.000 description 1
- 238000003753 real-time PCR Methods 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 229940116176 remicade Drugs 0.000 description 1
- 239000006254 rheological additive Substances 0.000 description 1
- 229960004641 rituximab Drugs 0.000 description 1
- 102220264540 rs143494120 Human genes 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 208000037851 severe atopic dermatitis Diseases 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 230000037380 skin damage Effects 0.000 description 1
- 206010040882 skin lesion Diseases 0.000 description 1
- 231100000444 skin lesion Toxicity 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 108010026668 snake venom protein C activator Proteins 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 229940087562 sodium acetate trihydrate Drugs 0.000 description 1
- 229960002668 sodium chloride Drugs 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 239000008227 sterile water for injection Substances 0.000 description 1
- 150000003432 sterols Chemical class 0.000 description 1
- 235000003702 sterols Nutrition 0.000 description 1
- 238000011421 subcutaneous treatment Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 210000001258 synovial membrane Anatomy 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 238000012385 systemic delivery Methods 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 229940042129 topical gel Drugs 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- PIEPQKCYPFFYMG-UHFFFAOYSA-N tris acetate Chemical compound CC(O)=O.OCC(N)(CO)CO PIEPQKCYPFFYMG-UHFFFAOYSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 229960001322 trypsin Drugs 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 201000008827 tuberculosis Diseases 0.000 description 1
- 239000002452 tumor necrosis factor alpha inhibitor Substances 0.000 description 1
- 230000005951 type IV hypersensitivity Effects 0.000 description 1
- 230000036269 ulceration Effects 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 229960003824 ustekinumab Drugs 0.000 description 1
- 230000025033 vasoconstriction Effects 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 239000002821 viper venom Substances 0.000 description 1
- 239000011534 wash buffer Substances 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
- A61K38/482—Serine endopeptidases (3.4.21)
- A61K38/4866—Protein C (3.4.21.69)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- 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
- A61P17/10—Anti-acne agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y304/00—Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
- C12Y304/21—Serine endopeptidases (3.4.21)
- C12Y304/21069—Protein C activated (3.4.21.69)
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Immunology (AREA)
- Dermatology (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Pulmonology (AREA)
- Transplantation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU2012902874 | 2012-07-04 | ||
| AU2012902874A AU2012902874A0 (en) | 2012-07-04 | Treatment of inflammatory skin disorders | |
| PCT/AU2013/000729 WO2014005183A1 (en) | 2012-07-04 | 2013-07-04 | Treatment of inflammatory skin disorders |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2015521632A JP2015521632A (ja) | 2015-07-30 |
| JP2015521632A5 JP2015521632A5 (enExample) | 2016-08-25 |
| JP6273272B2 true JP6273272B2 (ja) | 2018-01-31 |
Family
ID=49881162
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2015518732A Active JP6273272B2 (ja) | 2012-07-04 | 2013-07-04 | 炎症性皮膚障害の治療 |
Country Status (12)
| Country | Link |
|---|---|
| US (3) | US20150150954A1 (enExample) |
| EP (1) | EP2869833B1 (enExample) |
| JP (1) | JP6273272B2 (enExample) |
| KR (1) | KR102068010B1 (enExample) |
| CN (1) | CN104394883B (enExample) |
| AU (1) | AU2013286812B2 (enExample) |
| BR (1) | BR112015000051A2 (enExample) |
| CA (1) | CA2877745C (enExample) |
| ES (1) | ES2676422T3 (enExample) |
| IN (1) | IN2014DN11181A (enExample) |
| RU (1) | RU2662564C2 (enExample) |
| WO (1) | WO2014005183A1 (enExample) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104394883B (zh) * | 2012-07-04 | 2017-05-31 | 悉尼大学 | 炎性皮肤病症的治疗 |
| EP3137102B1 (en) * | 2014-04-16 | 2021-07-14 | ZZ Biotech LLC | Apc for use in the treatment of abnormal cutaneous scarring |
| US20170035862A1 (en) * | 2014-04-16 | 2017-02-09 | Zz Biotech Llc | Use of APC analogue for wound healing |
| CN108779115B (zh) | 2016-10-14 | 2021-02-26 | 江苏恒瑞医药股份有限公司 | 五元杂芳环并桥环类衍生物、其制备方法及其在医药上的应用 |
| US12453743B2 (en) | 2018-05-30 | 2025-10-28 | Direct Biologics, Llc | Mesenchymal stem cell (MSC) growth factor and extracellular vesicle preparation in frozen or powdered form and methods of use |
| US20210268062A1 (en) * | 2018-06-28 | 2021-09-02 | Novapep Pty Ltd | Inflammatory skin disorder treatment |
| CN109337974B (zh) * | 2018-12-14 | 2022-01-25 | 北京蛋白质组研究中心 | 一种检测银屑病的诊断标志物的试剂及其应用 |
| US20220079990A1 (en) * | 2018-12-26 | 2022-03-17 | Direct Biologics Llc | Methods and compositions for treating skin and hair disorders |
| RU2704322C1 (ru) * | 2019-06-11 | 2019-10-28 | Федеральное государственное автономное образовательное учреждение высшего образования "Белгородский государственный национальный исследовательский университет" (НИУ "БелГУ") | Крем с секретомом мультипотентных мезенхимальных стромальных клеток для коррекции псориазиформного воспаления в эксперименте |
| EP3999083A4 (en) | 2019-07-18 | 2023-07-26 | Direct Biologics LLC | Preparations comprising mesenchymal stem cells and cannabinoids and methods of their use |
Family Cites Families (42)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4775624A (en) | 1985-02-08 | 1988-10-04 | Eli Lilly And Company | Vectors and compounds for expression of human protein C |
| US4959318A (en) | 1985-06-27 | 1990-09-25 | Zymogenetics, Inc. | Expression of protein C |
| US5516650A (en) | 1985-06-27 | 1996-05-14 | Zymogenetics, Inc. | Production of activated protein C |
| EP0380508A4 (en) | 1987-05-18 | 1991-04-03 | Integrated Genetics, Inc. | Improved protein c molecules and method for making and activating same |
| US5084274A (en) | 1987-11-17 | 1992-01-28 | Scripps Clinic And Research Foundation | Inhibition of arterial thrombotic occlusion or thromboembolism |
| US4981952A (en) | 1988-10-04 | 1991-01-01 | Eli Lilly And Company | Method for the purification of vitamin K-dependent proteins |
| US5093117A (en) | 1989-01-24 | 1992-03-03 | Baxter International Inc. | Compositions and method for the treatment or prophylaxis of sepsis or septic shock |
| AT402260B (de) | 1990-08-16 | 1997-03-25 | Immuno Ag | Protein c-hältige pharmazeutische präparation |
| US5571786A (en) | 1990-08-16 | 1996-11-05 | Immuno Aktiengesellschaft | Use of protein C or the activation peptide of protein C for preparing a pharmaceutical preparation |
| AT397615B (de) | 1991-05-14 | 1994-05-25 | Immuno Ag | Arzneimittel enthaltend protein c |
| WO1993009807A1 (en) | 1991-11-18 | 1993-05-27 | The Scripps Research Institute | Methods of inhibiting thrombosis via elevation of circulating endogenous activated protein c levels |
| MY110664A (en) | 1992-05-21 | 1999-01-30 | Lilly Co Eli | Protein c derivatives |
| DE4239150A1 (de) | 1992-11-20 | 1994-05-26 | Thomae Gmbh Dr K | O-Acyl-4-phenyl-cyclohexanole, deren Salze, diese Verbindungen enthaltende Arzneimittel und deren Verwendung sowie Verfahren zu ihrer Herstellung |
| JP3043558B2 (ja) | 1993-10-29 | 2000-05-22 | 財団法人化学及血清療法研究所 | ヒト活性化プロテインｃ調製物及びその製法 |
| AU2467395A (en) | 1994-05-04 | 1995-11-29 | Board Of Trustees Of The University Of Arkansas, The | Novel ophthalmologic uses of protein c |
| PL195642B1 (pl) | 1997-04-28 | 2007-10-31 | Lilly Co Eli | Sposób przetwarzania wodnego roztworu aktywowanego białka C |
| HUP0001237A3 (en) | 1997-10-20 | 2002-01-28 | Lilly Co Eli | Methods for treating vascular disorders |
| WO2001056532A2 (en) | 2000-02-04 | 2001-08-09 | The Scripps Research Institute | Neuroprotective, antithrombotic and anti-inflammatory uses of activated protein c (apc) |
| AU2001232799A1 (en) | 2000-02-11 | 2001-08-20 | Eli Lilly And Company | Protein c derivatives |
| ES2242740T3 (es) * | 2000-03-28 | 2005-11-16 | Eli Lilly And Company | Proteina c activada para el tratamiento de pancreatitis. |
| AU1038802A (en) | 2000-10-18 | 2002-04-29 | Maxygen Aps | Protein c or activated protein c-like molecules |
| ES2384099T3 (es) * | 2001-06-13 | 2012-06-29 | The University Of Sydney | Proteína C para cicatrización de heridas |
| WO2004041296A2 (en) * | 2002-11-06 | 2004-05-21 | Novo Nordisk A/S | Pharmaceutical composition comprising a tissue factor antagonist and protein c polypeptides |
| EP1477166B1 (de) | 2003-04-28 | 2006-08-23 | Biofrontera Bioscience GmbH | Verwendung von Riluzole kombiniert mit geeigneten Hilfs-und Zusatzstoffen zur Behandlung von Krankheiten, die durch eine Hyperproliferation von Keratinozyten gekennzeichnet sind, insbesondere Neurodermitis und Psoriasis |
| US9192657B2 (en) | 2003-07-08 | 2015-11-24 | The Scripps Research Institute | Activated protein C variants with normal cytoprotective activity but reduced anticoagulant activity |
| WO2005007820A2 (en) | 2003-07-08 | 2005-01-27 | The Scripps Research Institute | Activated protein c variants with normal cytoprotective activity but reduced anticoagulant activity |
| EP1688161A1 (en) * | 2004-11-02 | 2006-08-09 | Switch Biotech Aktiengesellschaft | Use of pirlindole for the treatment of diseases which are characterized by proliferation of t-lymphocytes and/or hyperproliferation of keratinocytes in particular atopic dermatitis and psoriasis |
| US20080293631A1 (en) * | 2005-01-07 | 2008-11-27 | Christopher John Jackson | Treatment for Autoimmune and Inflammatory Conditions |
| US20070224150A1 (en) * | 2005-03-24 | 2007-09-27 | Yongji Chung | Growth factor for hair and skin treatment |
| CN101262880A (zh) | 2005-06-24 | 2008-09-10 | 德拉格雷丘尔公司 | 在影响呼吸道的炎症病状中气道施用组织因子途径抑制物 |
| AU2006278504B2 (en) * | 2005-08-04 | 2013-01-17 | Sirtris Pharmaceuticals, Inc. | Imidazopyridine derivatives as sirtuin modulating agents |
| GR1005700B (el) * | 2006-09-01 | 2007-10-22 | (40%) ����� �������� | Τροπος αντιμετωπισης της 1ης φασης του εγκαυματοσσε μη σηπτικους ασθενεις με συνεχη ενδοφλεβια χορηγηση ενεργοποιημενης πρωτεινης-c για 48 ωρες με στοχο τη μειωση της τελικης εγκαυματικης βλαβης καιαυξηση της ταχυτητας επουλωσης κατα τα πρωτα επτα μετεγκαυματικα 24ωρα |
| CA2668187A1 (en) | 2006-10-31 | 2008-06-19 | The Scripps Research Institute | Dosing regimen of activated protein c and variants having reduced anticoagulant activity |
| GB0724231D0 (en) | 2007-12-12 | 2008-01-30 | Renono Ltd | Methods for inhibiting scarring |
| ES2316312B1 (es) * | 2008-06-20 | 2010-02-08 | Ignacio Umbert Millet | Composicion farmaceutica dermatologica para el tratamiento de patologias de inflamacion de la piel, tales como por ejemplo dermatitis, dermatitis atopica, vitiligo, alopecia areata, acne, psoriasis y prurito,y combinaciones de las mismas. |
| EP2157176A1 (en) * | 2008-08-20 | 2010-02-24 | The Provost, Fellows And Scholars Of The College Of The Holy And Undivided Trinity Of Queen Elizabeth Near Dublin | Protein C Variants |
| WO2010113146A1 (en) * | 2009-04-01 | 2010-10-07 | The Medical Research, Infrastructure, And Health Services Fund Of The Tel Aviv Medical Center | A method of regulating proliferation and differentiation of keratinocyes |
| CN101912450A (zh) * | 2010-09-01 | 2010-12-15 | 吴业刚 | 一种治疗脚气皮炎的中西药组合物及其制备方法 |
| CN104394883B (zh) * | 2012-07-04 | 2017-05-31 | 悉尼大学 | 炎性皮肤病症的治疗 |
| EP3137102B1 (en) * | 2014-04-16 | 2021-07-14 | ZZ Biotech LLC | Apc for use in the treatment of abnormal cutaneous scarring |
| US20170035862A1 (en) * | 2014-04-16 | 2017-02-09 | Zz Biotech Llc | Use of APC analogue for wound healing |
| US20210268062A1 (en) * | 2018-06-28 | 2021-09-02 | Novapep Pty Ltd | Inflammatory skin disorder treatment |
-
2013
- 2013-07-04 CN CN201380034024.2A patent/CN104394883B/zh active Active
- 2013-07-04 AU AU2013286812A patent/AU2013286812B2/en active Active
- 2013-07-04 ES ES13812528.1T patent/ES2676422T3/es active Active
- 2013-07-04 US US14/409,215 patent/US20150150954A1/en not_active Abandoned
- 2013-07-04 KR KR1020157002889A patent/KR102068010B1/ko active Active
- 2013-07-04 RU RU2015103510A patent/RU2662564C2/ru active
- 2013-07-04 CA CA2877745A patent/CA2877745C/en active Active
- 2013-07-04 EP EP13812528.1A patent/EP2869833B1/en active Active
- 2013-07-04 IN IN11181DEN2014 patent/IN2014DN11181A/en unknown
- 2013-07-04 JP JP2015518732A patent/JP6273272B2/ja active Active
- 2013-07-04 WO PCT/AU2013/000729 patent/WO2014005183A1/en not_active Ceased
- 2013-07-04 BR BR112015000051A patent/BR112015000051A2/pt not_active Application Discontinuation
-
2016
- 2016-11-30 US US15/365,567 patent/US20170080062A1/en not_active Abandoned
-
2020
- 2020-05-21 US US16/880,243 patent/US11617785B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| EP2869833A4 (en) | 2015-11-18 |
| US20200276281A1 (en) | 2020-09-03 |
| EP2869833A1 (en) | 2015-05-13 |
| CN104394883B (zh) | 2017-05-31 |
| US11617785B2 (en) | 2023-04-04 |
| RU2662564C2 (ru) | 2018-07-26 |
| US20150150954A1 (en) | 2015-06-04 |
| JP2015521632A (ja) | 2015-07-30 |
| KR20150036351A (ko) | 2015-04-07 |
| BR112015000051A2 (pt) | 2017-06-27 |
| CA2877745C (en) | 2021-11-30 |
| EP2869833B1 (en) | 2018-04-04 |
| WO2014005183A1 (en) | 2014-01-09 |
| AU2013286812A1 (en) | 2015-01-22 |
| CA2877745A1 (en) | 2014-01-09 |
| IN2014DN11181A (enExample) | 2015-10-02 |
| HK1204573A1 (en) | 2015-11-27 |
| RU2015103510A (ru) | 2016-08-27 |
| AU2013286812B2 (en) | 2017-04-20 |
| US20170080062A1 (en) | 2017-03-23 |
| KR102068010B1 (ko) | 2020-01-20 |
| ES2676422T3 (es) | 2018-07-19 |
| CN104394883A (zh) | 2015-03-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP6273272B2 (ja) | 炎症性皮膚障害の治療 | |
| Cheng et al. | Mesenchymal stem cells attenuate blood-brain barrier leakage after cerebral ischemia in mice | |
| Wells et al. | An adverse role for matrix metalloproteinase 12 after spinal cord injury in mice | |
| AU679165B2 (en) | Treatment of inflammation | |
| CN1961958B (zh) | 改善伤口愈合的方法 | |
| Roda et al. | Infliximab therapy for Netherton syndrome: a case report | |
| Ren et al. | Calcium-sensing receptor on neutrophil promotes myocardial apoptosis and fibrosis after acute myocardial infarction via NLRP3 inflammasome activation | |
| US5190917A (en) | Treatment of psoriasis | |
| Veeravalli | Implications of MMP-12 in the pathophysiology of ischaemic stroke | |
| JP2020023519A (ja) | 異常な皮膚瘢痕化の治療 | |
| Hashizume et al. | Desirable effect of combination therapy with high molecular weight hyaluronate and NSAIDs on MMP production | |
| Sotiriou et al. | Etanercept for the treatment of hidradenitis suppurativa | |
| Dev et al. | Therapeutic potential of matrix metalloprotease inhibitors in neuropathic pain | |
| Jackson et al. | New therapeutic applications for the anticoagulant, activated protein C | |
| HK1204573B (en) | Treatment of inflammatory skin disorders | |
| JPH0565492B2 (enExample) | ||
| WO2022002160A1 (zh) | Pcsk9抑制剂在制备治疗多种疾病产品中的应用 | |
| JP2002522396A (ja) | 乾癬治療用プロテアーゼ阻害因子 | |
| Cole | Dermatologic Therapies | |
| Bubna et al. | Brodalumab: Looking beyond psoriasis | |
| Ponnampalam et al. | Mediators of blood-brain barrier disruption and potential therapeutic interventions for protection of the barrier following focal ischemia | |
| Jackson et al. | Activated protein C to treat chronic wounds | |
| Marzano et al. | Follicular Neutrophilic Inflammation (Hidradenitis Suppurativa) | |
| Alexander | Retinoid and Pentoxifylline-Induced Modulation of Human Melanoma Cell Metastasis | |
| HK1235306B (zh) | 治疗异常皮肤瘢痕形成 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20160407 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20160705 |
|
| A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20170123 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20170131 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20170428 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20170428 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20170808 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20171017 |
|
| A711 | Notification of change in applicant |
Free format text: JAPANESE INTERMEDIATE CODE: A711 Effective date: 20171017 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20171017 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20171128 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20171208 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20171220 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20180105 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 6273272 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |