WO1996016669A1 - Utilisation du facteur de croissance epidermique humain recombine dans la production d'un medicament contre l'acne - Google Patents
Utilisation du facteur de croissance epidermique humain recombine dans la production d'un medicament contre l'acne Download PDFInfo
- Publication number
- WO1996016669A1 WO1996016669A1 PCT/NL1995/000392 NL9500392W WO9616669A1 WO 1996016669 A1 WO1996016669 A1 WO 1996016669A1 NL 9500392 W NL9500392 W NL 9500392W WO 9616669 A1 WO9616669 A1 WO 9616669A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- egf
- growth factor
- epidermal growth
- manufacture
- medicament
- Prior art date
Links
- 102000009024 Epidermal Growth Factor Human genes 0.000 title claims abstract description 46
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 title claims abstract description 46
- 101800003838 Epidermal growth factor Proteins 0.000 title claims abstract description 42
- 229940116977 epidermal growth factor Drugs 0.000 title claims abstract description 42
- 206010000496 acne Diseases 0.000 title claims abstract description 28
- 208000002874 Acne Vulgaris Diseases 0.000 title claims abstract description 19
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 9
- 239000003814 drug Substances 0.000 title claims abstract description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 12
- 239000006071 cream Substances 0.000 claims abstract description 10
- 230000002500 effect on skin Effects 0.000 claims abstract description 10
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 6
- 239000002674 ointment Substances 0.000 claims abstract description 4
- 238000011282 treatment Methods 0.000 claims description 13
- 230000000699 topical effect Effects 0.000 claims description 7
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 230000002757 inflammatory effect Effects 0.000 description 9
- 230000003902 lesion Effects 0.000 description 9
- 230000003325 follicular Effects 0.000 description 8
- 230000006872 improvement Effects 0.000 description 8
- 102000005962 receptors Human genes 0.000 description 8
- 108020003175 receptors Proteins 0.000 description 8
- 210000004027 cell Anatomy 0.000 description 7
- 239000000902 placebo Substances 0.000 description 7
- 229940068196 placebo Drugs 0.000 description 7
- 108060006698 EGF receptor Proteins 0.000 description 6
- 102000001301 EGF receptor Human genes 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 208000035475 disorder Diseases 0.000 description 5
- 210000003491 skin Anatomy 0.000 description 5
- 206010037888 Rash pustular Diseases 0.000 description 4
- 235000001014 amino acid Nutrition 0.000 description 4
- 150000001413 amino acids Chemical class 0.000 description 4
- 230000004069 differentiation Effects 0.000 description 4
- 210000002615 epidermis Anatomy 0.000 description 4
- 239000003102 growth factor Substances 0.000 description 4
- 208000029561 pustule Diseases 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 201000010099 disease Diseases 0.000 description 3
- 210000000981 epithelium Anatomy 0.000 description 3
- 210000002950 fibroblast Anatomy 0.000 description 3
- 230000028709 inflammatory response Effects 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 210000000440 neutrophil Anatomy 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 241000186427 Cutibacterium acnes Species 0.000 description 2
- 102000018386 EGF Family of Proteins Human genes 0.000 description 2
- 108010066486 EGF Family of Proteins Proteins 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 108010025020 Nerve Growth Factor Proteins 0.000 description 2
- 102000007072 Nerve Growth Factors Human genes 0.000 description 2
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 2
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 2
- 206010052428 Wound Diseases 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 208000031513 cyst Diseases 0.000 description 2
- 230000001086 cytosolic effect Effects 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 235000021588 free fatty acids Nutrition 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 230000035876 healing Effects 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 230000003780 keratinization Effects 0.000 description 2
- 210000002510 keratinocyte Anatomy 0.000 description 2
- 230000010311 mammalian development Effects 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
- 244000005706 microflora Species 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 229940055019 propionibacterium acne 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
- GHMLBKRAJCXXBS-UHFFFAOYSA-N resorcinol Chemical compound OC1=CC=CC(O)=C1 GHMLBKRAJCXXBS-UHFFFAOYSA-N 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 210000001732 sebaceous gland Anatomy 0.000 description 2
- 210000004927 skin cell Anatomy 0.000 description 2
- 208000017520 skin disease Diseases 0.000 description 2
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 2
- 239000002562 thickening agent Substances 0.000 description 2
- 210000001685 thyroid gland Anatomy 0.000 description 2
- 230000037314 wound repair Effects 0.000 description 2
- NMWKYTGJWUAZPZ-WWHBDHEGSA-N (4S)-4-[[(4R,7S,10S,16S,19S,25S,28S,31R)-31-[[(2S)-2-[[(1R,6R,9S,12S,18S,21S,24S,27S,30S,33S,36S,39S,42R,47R,53S,56S,59S,62S,65S,68S,71S,76S,79S,85S)-47-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-3-methylbutanoyl]amino]-3-hydroxypropanoyl]amino]-3-(1H-imidazol-4-yl)propanoyl]amino]-3-phenylpropanoyl]amino]-4-oxobutanoyl]amino]-3-carboxypropanoyl]amino]-18-(4-aminobutyl)-27,68-bis(3-amino-3-oxopropyl)-36,71,76-tribenzyl-39-(3-carbamimidamidopropyl)-24-(2-carboxyethyl)-21,56-bis(carboxymethyl)-65,85-bis[(1R)-1-hydroxyethyl]-59-(hydroxymethyl)-62,79-bis(1H-imidazol-4-ylmethyl)-9-methyl-33-(2-methylpropyl)-8,11,17,20,23,26,29,32,35,38,41,48,54,57,60,63,66,69,72,74,77,80,83,86-tetracosaoxo-30-propan-2-yl-3,4,44,45-tetrathia-7,10,16,19,22,25,28,31,34,37,40,49,55,58,61,64,67,70,73,75,78,81,84,87-tetracosazatetracyclo[40.31.14.012,16.049,53]heptaoctacontane-6-carbonyl]amino]-3-methylbutanoyl]amino]-7-(3-carbamimidamidopropyl)-25-(hydroxymethyl)-19-[(4-hydroxyphenyl)methyl]-28-(1H-imidazol-4-ylmethyl)-10-methyl-6,9,12,15,18,21,24,27,30-nonaoxo-16-propan-2-yl-1,2-dithia-5,8,11,14,17,20,23,26,29-nonazacyclodotriacontane-4-carbonyl]amino]-5-[[(2S)-1-[[(2S)-1-[[(2S)-3-carboxy-1-[[(2S)-1-[[(2S)-1-[[(1S)-1-carboxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl]amino]-5-oxopentanoic acid Chemical compound CC(C)C[C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](Cc1c[nH]cn1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H]1CSSC[C@H](NC(=O)[C@@H](NC(=O)[C@@H]2CSSC[C@@H]3NC(=O)[C@H](Cc4ccccc4)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](Cc4c[nH]cn4)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H]4CCCN4C(=O)[C@H](CSSC[C@H](NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](Cc4c[nH]cn4)NC(=O)[C@H](Cc4ccccc4)NC3=O)[C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](Cc3ccccc3)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N3CCC[C@H]3C(=O)N[C@@H](C)C(=O)N2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2c[nH]cn2)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@@H](N)C(C)C)C(C)C)[C@@H](C)O)C(C)C)C(=O)N[C@@H](Cc2c[nH]cn2)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](Cc2ccc(O)cc2)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1)C(=O)N[C@@H](C)C(O)=O NMWKYTGJWUAZPZ-WWHBDHEGSA-N 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 239000004342 Benzoyl peroxide Substances 0.000 description 1
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 208000032544 Cicatrix Diseases 0.000 description 1
- 206010011732 Cyst Diseases 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 101500025419 Homo sapiens Epidermal growth factor Proteins 0.000 description 1
- 101000851181 Homo sapiens Epidermal growth factor receptor Proteins 0.000 description 1
- 208000025500 Hutchinson-Gilford progeria syndrome Diseases 0.000 description 1
- 206010020649 Hyperkeratosis Diseases 0.000 description 1
- 102000004882 Lipase Human genes 0.000 description 1
- 108090001060 Lipase Proteins 0.000 description 1
- 239000004367 Lipase Substances 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 101000851196 Mus musculus Pro-epidermal growth factor Proteins 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 108700020796 Oncogene Proteins 0.000 description 1
- 206010033733 Papule Diseases 0.000 description 1
- 208000007932 Progeria Diseases 0.000 description 1
- 108700020978 Proto-Oncogene Proteins 0.000 description 1
- 102000052575 Proto-Oncogene Human genes 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 206010043183 Teething Diseases 0.000 description 1
- 102000006747 Transforming Growth Factor alpha Human genes 0.000 description 1
- 101800004564 Transforming growth factor alpha Proteins 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 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 1
- 210000004381 amniotic fluid Anatomy 0.000 description 1
- 230000001548 androgenic effect Effects 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 230000035578 autophosphorylation Effects 0.000 description 1
- 235000019400 benzoyl peroxide Nutrition 0.000 description 1
- 229960003328 benzoyl peroxide Drugs 0.000 description 1
- 230000027455 binding Effects 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000003399 chemotactic effect Effects 0.000 description 1
- 210000000399 corneal endothelial cell Anatomy 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 230000006710 cytostatic response Effects 0.000 description 1
- 210000004207 dermis Anatomy 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 230000008556 epithelial cell proliferation Effects 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 210000002219 extraembryonic membrane Anatomy 0.000 description 1
- 210000000744 eyelid Anatomy 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 230000004761 fibrosis Effects 0.000 description 1
- 210000001061 forehead Anatomy 0.000 description 1
- 230000014509 gene expression Effects 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 210000000224 granular leucocyte Anatomy 0.000 description 1
- 210000004209 hair Anatomy 0.000 description 1
- 210000003780 hair follicle Anatomy 0.000 description 1
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 1
- 210000003494 hepatocyte Anatomy 0.000 description 1
- 230000003054 hormonal effect Effects 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 229940116978 human epidermal growth factor Drugs 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 235000019421 lipase Nutrition 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 230000007040 lung development Effects 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 210000005075 mammary gland Anatomy 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 239000003226 mitogen Substances 0.000 description 1
- 230000000394 mitotic effect Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 210000005087 mononuclear cell Anatomy 0.000 description 1
- 210000000663 muscle cell Anatomy 0.000 description 1
- 210000001087 myotubule Anatomy 0.000 description 1
- GVUGOAYIVIDWIO-UFWWTJHBSA-N nepidermin Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CS)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CS)NC(=O)[C@H](C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C(C)C)C(C)C)C1=CC=C(O)C=C1 GVUGOAYIVIDWIO-UFWWTJHBSA-N 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 231100000915 pathological change Toxicity 0.000 description 1
- 230000036285 pathological change Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 210000002826 placenta Anatomy 0.000 description 1
- 210000005152 placental membrane Anatomy 0.000 description 1
- 210000004180 plasmocyte Anatomy 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000001185 psoriatic effect Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 229930002330 retinoic acid Natural products 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 210000003079 salivary gland Anatomy 0.000 description 1
- 231100000241 scar Toxicity 0.000 description 1
- 230000037387 scars Effects 0.000 description 1
- 210000000582 semen Anatomy 0.000 description 1
- 230000009759 skin aging Effects 0.000 description 1
- 206010040882 skin lesion Diseases 0.000 description 1
- 231100000444 skin lesion Toxicity 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000036346 tooth eruption Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 229960001727 tretinoin Drugs 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- 235000002374 tyrosine Nutrition 0.000 description 1
- 150000003668 tyrosines Chemical group 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
-
- 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
- A61K38/18—Growth factors; Growth regulators
- A61K38/1808—Epidermal growth factor [EGF] urogastrone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/80—Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
- A61K2800/86—Products or compounds obtained by genetic engineering
Definitions
- This invention is related with Medicine boughs, specifi ⁇ cally with the use of human recombinant Epidermal Growth Factor in the manufacture of a medicament for topically treating acne and acneiform dermal disorders.
- Acne is a chronic skin disease, with psychological and esthetic implications, that affects 90% of adolescents. It is characterized by a polymorphous lesion syndrome caused principally by the interaction of predisposing hormonal and genetic factors which act on the sebaceous apparatus. It generally affects the face, neck and upper part of the arms and trunk. The most affected areas on the face are the cheeks, forehead, nose and chin.
- Free intrafollicular fatty acids are mainly the result of the hydrolysis of sebaceous triglycerides by the follicular microflora, especially Propionibacterium acnes, since it is the only one with a lipase capable of hydrolyzing them.
- This microbe also has other functions that lead to the production of a variety of extracellular products which intervene in the inflammatory response.
- the inflammatory process can be modulated by the variable response of the host, particularly by the neutrophils that play a very important role, since they represent more than 90% of the leukocyte population.
- all treatments currently in use are aimed at lowering the inflammatory response by modulating the response of the host and of the aforementioned factors that intervene in this process.
- a blackhead contains keratinized sebaceous cells and some micro ⁇ organisms.
- the follicular papules caused by acne are characterized by a perifollicular lymphocyte infiltrate.
- the intrafollicular pustules which mostly contain neutrophils, usually form after the wall of the follicle has been ruptured.
- the nodules occur at the site of follicular rupture, where the sebaceous free fatty acids, bacteria and keratinized cells have escaped from the follicle towards the dermis.
- the perifollicular infiltrate can form a.cyst containing numerous neutrophils, in addition to plasma cells, mononuclear cells and giant cells which react to foreign bodies.
- the inflammatory infiltrate is replaced by a fibrosis and the epidermis of the follicular wall can extend around and encapsulate part of the inflammatory mass.
- the EGF is a single chain polypeptide with 53 amino acids, an isoelectric point of 4.6 and a molecular weight of 6,045 daltons. It contains 6 cysteine residues that form disulfide bonds, giving rise to 3 peptide loops which give the molecule its characteristic stability (Carpenter G, Cohen S. Epidermal Growth Factor. Ann Rev Biochem 1979, 48; 193-216; Savage Cr, Jr, Hash JH, Cohen S. Epidermal Growth Factor. J Biol Chem 1973; 248: 7669-7672).
- EGF EGF was isolated by Cohen and Carpenter from human urine, with use of an antibody to mouse EGF (Cohen S, Carpenter G. Human Epidermal Growth Factor, Isolation and Chemical and Biological Properties, Proc Natl Acad Sci USA 1975; 72: 1317- 1321). Since then, its presence has been reported in many human body fluids such as sera, salive, calostrum, amniotic fluid and semen (Carpenter G, Cohen S. Epidermal Growth Factor. Ann Rev
- EGF is a powerful mitogenic agent for a great variety of cells, including the keratinocytes, conjunctive and pharyngeal tissues, corneal endothelial cells, smooth muscle cells in the vessels, condrocytes, hepatocytes, cells from the thyroid follicle and the mammary glands (Carpenter G, Cohen S. Epidermal Growth Factor. Ann Rev Biochem 1979; 48: 193-216; Buckley A, Davidson JM, toneth CG, Wolt TB, Woodward SC. Sustained release of Epidermal Growth Factor accelerates wound repair.
- EGF epidermal growth factor
- the action of EGF is exerted by binding to a specific receptor on the cell membrane.
- the presence of this receptor has been reported in many human cell lines with exception of the hematopoietic cells.
- the receptors are also found in relative abundance in the brain, thyroid, lungs, skin, placenta and fetal membranes (Carpenter G, Cohen S. Epidermal Growth Factor. Ann Rev Biochem 1979; 48: 193-216; O'Keefe E, Hollenberg MD, Cuatrecasas P. EGF characteristics of specific binding in membranes from liver, placenta and other tissues. Arch Biochem Biophys 1974;164: 51-52; Gospodarowicz D. Epidermal and nerve growth factors in mammalian development.
- EGF epithelial restoration role
- salivary glands The ancestral instinct in animals to lick their wounds and skin lesions have been associated to the epithelial restoration role of EGF, based on the high concentration of this protein in the salivary glands.
- EGF's unusual capacity to stimulate teething and opening of the eyelids was due to its ability to stimulate the migration, maturation and keratini- zation of the epidermis (Carpenter G, Cohen S. Epidermal Growth Factor. Ann Rev Biochem 1979; 48: 193-216).
- EGF and its receptor have been detected in a variety of skin cells.
- Keratinocytes cells in the ducts of the sudoriferous glands, hair follicles, myoepithelial cells, smooth muscle epithelium, and muscle cells responsible for the raising of hairs, all contain a large number of receptors (Martin P, Hopkinson-Woolley J, McCluskey J Growth factors and cutaneous wound repair. Proc Growth Factor Res 1992, 4: 25-44).
- Another interesting aspect is the fact that as differentiation or keratinization of the epithelial cells increases, the number of expressed EGF receptors decreases.
- EGF induces mitotic activity in the cells of the epidermis, sebaceous glands and dermal fibroblasts.
- EGF receptors decreases in the skin cells of patients suffering from progeria and other forms of early skin involution.
- Other studies have reported disorders in the functional capacity of the intra-cytoplasmic domain of the EGF receptor in patients with psoriasis (Elder JT, Fisher GJ, Lindquist PB, Bennett GL, Pittelkow MR, Coffey RJ, Jr Ellingsworth L, Derynck R, Voorhees JJ. Overexpression of transforming growth factor alpha in psoriatic epideris. Science 1989, 243; 811-813).
- the present invention relates to the use of EGF in the manufacture of a composition for topically treating acne and acneiform dermal disorders.
- a preferred embodiment of the invention is the use of human recombinant Epidermal Growth Factor (EGF) in the manufacture of a pharmaceutical composition for topically treating acne and/or acneiform dermal disorders by applying to the skin a cream or ointment containing this active principle.
- EGF Epidermal Growth Factor
- the invention also provides a pharmaceutical composition useful for treatment of acne and/or acneiform dermal disorders comprising between 2-50 ⁇ g/g of EGF, preferably approximately
- EGF effect in the improvement of active acne was showed in a double blind clinical trial.
- a EGF cream was compared with placebo.
- the concentration of EGF in the cream was 10 ⁇ g/g and the other components were stearic acid as thickener, anhydrous potassium carbonate as emulsifier and thickener, methylparaben and propylparaben for antimicrobial preservation, glycerine as humidifier and purifier water as solvent.
- Pacient 1 grade 6 at the beginning, and 3.5 at the end.
- Pacient 2 grade 5.5 at the beginning, and 3.5 at the end.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Gastroenterology & Hepatology (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Medicinal Chemistry (AREA)
- Immunology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical & Material Sciences (AREA)
- Zoology (AREA)
- Dermatology (AREA)
- Birds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
Abstract
L'invention concerne l'utilisation du facteur de croissance épidermique (EGF) dans la production d'un médicament destiné à traiter l'acné et des dermatoses acnéiformes. L'EGF utilisé peut être l'EGF humain recombiné. L'invention concerne également des compositions pharmaceutiques permettant le traitement topique de l'acné et de dermatoses acnéiformes par application sur la peau d'une crème ou d'un onguent contenant ledit principe actif.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CU1994136A CU22613A1 (es) | 1994-11-25 | 1994-11-25 | Uso de factor de crecimiento epidérmico para el tratamiento del acne |
| CU136/94 | 1994-11-25 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1996016669A1 true WO1996016669A1 (fr) | 1996-06-06 |
Family
ID=46093359
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/NL1995/000392 WO1996016669A1 (fr) | 1994-11-25 | 1995-11-17 | Utilisation du facteur de croissance epidermique humain recombine dans la production d'un medicament contre l'acne |
Country Status (3)
| Country | Link |
|---|---|
| AR (1) | AR002002A1 (fr) |
| CU (1) | CU22613A1 (fr) |
| WO (1) | WO1996016669A1 (fr) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2015182905A1 (fr) * | 2014-05-29 | 2015-12-03 | Daewoong Pharmaceutical Co., Ltd. | Composition pharmaceutique destinée à la prévention ou au traitement d'éruptions cutanées |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0140998A1 (fr) * | 1983-11-02 | 1985-05-15 | Nihon Chemical Research Kabushiki Kaisha | Préparations ophtalmiques |
| WO1991002533A1 (fr) * | 1989-08-16 | 1991-03-07 | Levin Robert H | Composition topiques contenant du lycd et d'autres ingredients medicaux actifs au niveau topique |
| CN1083371A (zh) * | 1993-01-03 | 1994-03-09 | 周至惠 | 痤疮、毛囊炎、皮疹特别护理剂 |
-
1994
- 1994-11-25 CU CU1994136A patent/CU22613A1/es unknown
-
1995
- 1995-11-17 WO PCT/NL1995/000392 patent/WO1996016669A1/fr active Application Filing
- 1995-11-24 AR ARP950100314A patent/AR002002A1/es unknown
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0140998A1 (fr) * | 1983-11-02 | 1985-05-15 | Nihon Chemical Research Kabushiki Kaisha | Préparations ophtalmiques |
| WO1991002533A1 (fr) * | 1989-08-16 | 1991-03-07 | Levin Robert H | Composition topiques contenant du lycd et d'autres ingredients medicaux actifs au niveau topique |
| CN1083371A (zh) * | 1993-01-03 | 1994-03-09 | 周至惠 | 痤疮、毛囊炎、皮疹特别护理剂 |
Non-Patent Citations (2)
| Title |
|---|
| DATABASE INVESTEXT; FILE SERVER STN IN KARLSRUHE, ACCESION NUMBER 89:314028 SACCO, G.R. ET AL: BIOPHARMACEUTICALS -INDUSTRY REPORT, 1989 * |
| DATABASE WPI Section Ch Week 9524, Derwent World Patents Index; Class B04, AN 95-179722 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2015182905A1 (fr) * | 2014-05-29 | 2015-12-03 | Daewoong Pharmaceutical Co., Ltd. | Composition pharmaceutique destinée à la prévention ou au traitement d'éruptions cutanées |
| CN106659768A (zh) * | 2014-05-29 | 2017-05-10 | 株式会社大熊制药 | 用于预防或治疗皮疹的药物组合物 |
Also Published As
| Publication number | Publication date |
|---|---|
| AR002002A1 (es) | 1998-01-07 |
| CU22613A1 (es) | 2000-02-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US5814605A (en) | Therapeutic uses of keratinocyte growth factor | |
| KR101830926B1 (ko) | 피부 노화를 방지 및/또는 개선하기 위해 사용되는 pedf-유도 폴리펩티드의 용도 | |
| EP0492614B1 (fr) | Accélérateur de la croissance de épithéliocytes | |
| JPS63502985A (ja) | 角膜基質創傷の治療のための組成物 | |
| JP5913117B2 (ja) | 孵化液酵素およびその使用 | |
| CN112533676A (zh) | 用于抑制cgrp的神经毒素 | |
| KR101033135B1 (ko) | 상처 치유용 조성물 및 그의 용도 | |
| EP0619370A1 (fr) | Facteur de croissance des kératinocytes pour son utilisation dans une méthode de traitement thérapeutique du corps humain ou animal | |
| JP2013516460A (ja) | スキンケアにおける安定化された植物由来の成長因子の使用方法 | |
| JP5762670B2 (ja) | Ｌｏｐａｐをベースとする医薬組成物およびその使用 | |
| AU2013353957B2 (en) | Protein slurp-1 for use in the treatment of ocular diseases | |
| WO1996016669A1 (fr) | Utilisation du facteur de croissance epidermique humain recombine dans la production d'un medicament contre l'acne | |
| CN113651870B (zh) | 一种促进创伤后组织修复与再生的小分子修饰短肽及其应用 | |
| Guy et al. | Isolation and maintenance of the human pilosebaceous duct: 13‐cis retinoic acid acts directly on the duct in vitro | |
| Schlemm et al. | Medicinal yeast extracts | |
| WO2020037714A1 (fr) | Application de protéines mutantes trail dans la préparation de médicaments pour le traitement de l'acné et préparation associée | |
| CN114929192B (zh) | 包含改善皮肤外观和再生的新型肽的用于局部施用的美容制剂 | |
| WO1995007710A1 (fr) | Remede pour le soin de plaies | |
| JP7462023B2 (ja) | 温度安定性を向上させたｆｇｆ７ポリペプチドおよびその用途 | |
| Lei et al. | The cyclization of human salivary Histatin 1 via click chemistry for skin wound healing | |
| CN119264244A (zh) | 一种面部抗衰老的胶原蛋白肽、组合物及其应用 | |
| IL120696A (en) | Component b as cicatrizant | |
| CN115991758A (zh) | 一种促进糖尿病创面愈合的珍珠粉多肽及其应用 | |
| CN118556067A (zh) | 肽以及包含所述肽的药物和美容组合物 | |
| Ferlauto Jr | Topical delivery of recombinant human epidermal growth factor to a wounded skin model |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| AK | Designated states |
Kind code of ref document: A1 Designated state(s): BR CA MX RU UA |
|
| AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): AT BE CH DE DK ES FR GB GR IE IT LU MC NL PT SE |
|
| 121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
| 122 | Ep: pct application non-entry in european phase | ||
| NENP | Non-entry into the national phase |
Ref country code: CA |