GB2569682A - Composition - Google Patents
Composition Download PDFInfo
- Publication number
- GB2569682A GB2569682A GB1816988.8A GB201816988A GB2569682A GB 2569682 A GB2569682 A GB 2569682A GB 201816988 A GB201816988 A GB 201816988A GB 2569682 A GB2569682 A GB 2569682A
- Authority
- GB
- United Kingdom
- Prior art keywords
- approximately
- composition
- dressing
- burn
- composition according
- 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.)
- Granted
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 253
- 229910052500 inorganic mineral Inorganic materials 0.000 claims abstract description 57
- 239000011707 mineral Substances 0.000 claims abstract description 57
- 230000000699 topical effect Effects 0.000 claims abstract description 47
- 238000011282 treatment Methods 0.000 claims abstract description 46
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 45
- 230000005855 radiation Effects 0.000 claims abstract description 42
- 239000002562 thickening agent Substances 0.000 claims abstract description 36
- 229920001090 Polyaminopropyl biguanide Polymers 0.000 claims abstract description 26
- 229940093424 polyaminopropyl biguanide Drugs 0.000 claims abstract description 26
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 25
- 230000003750 conditioning effect Effects 0.000 claims abstract description 22
- 239000013535 sea water Substances 0.000 claims abstract description 21
- 239000002904 solvent Substances 0.000 claims abstract description 19
- 239000003755 preservative agent Substances 0.000 claims abstract description 18
- 230000002335 preservative effect Effects 0.000 claims abstract description 17
- QCDWFXQBSFUVSP-UHFFFAOYSA-N 2-phenoxyethanol Chemical compound OCCOC1=CC=CC=C1 QCDWFXQBSFUVSP-UHFFFAOYSA-N 0.000 claims abstract description 15
- AEIJTFQOBWATKX-UHFFFAOYSA-N octane-1,2-diol Chemical compound CCCCCCC(O)CO AEIJTFQOBWATKX-UHFFFAOYSA-N 0.000 claims abstract description 15
- MXOAEAUPQDYUQM-QMMMGPOBSA-N (S)-chlorphenesin Chemical compound OC[C@H](O)COC1=CC=C(Cl)C=C1 MXOAEAUPQDYUQM-QMMMGPOBSA-N 0.000 claims abstract description 14
- 229960003993 chlorphenesin Drugs 0.000 claims abstract description 14
- 229920006037 cross link polymer Polymers 0.000 claims abstract description 14
- 229960005323 phenoxyethanol Drugs 0.000 claims abstract description 14
- 238000011321 prophylaxis Methods 0.000 claims abstract description 14
- FWFUWXVFYKCSQA-UHFFFAOYSA-M sodium;2-methyl-2-(prop-2-enoylamino)propane-1-sulfonate Chemical compound [Na+].[O-]S(=O)(=O)CC(C)(C)NC(=O)C=C FWFUWXVFYKCSQA-UHFFFAOYSA-M 0.000 claims abstract description 14
- 229920002413 Polyhexanide Polymers 0.000 claims description 44
- 239000000463 material Substances 0.000 claims description 41
- ULWHHBHJGPPBCO-UHFFFAOYSA-N propane-1,1-diol Chemical group CCC(O)O ULWHHBHJGPPBCO-UHFFFAOYSA-N 0.000 claims description 23
- 238000000034 method Methods 0.000 claims description 21
- 230000002745 absorbent Effects 0.000 claims description 19
- 239000002250 absorbent Substances 0.000 claims description 19
- 239000011777 magnesium Substances 0.000 claims description 18
- -1 polypropylene Polymers 0.000 claims description 18
- 239000000835 fiber Substances 0.000 claims description 15
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 14
- 229910052749 magnesium Inorganic materials 0.000 claims description 14
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 13
- 239000011734 sodium Substances 0.000 claims description 13
- 229910052708 sodium Inorganic materials 0.000 claims description 13
- 239000011575 calcium Substances 0.000 claims description 11
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 10
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 10
- 229910052791 calcium Inorganic materials 0.000 claims description 10
- 239000008213 purified water Substances 0.000 claims description 9
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 8
- 229910052796 boron Inorganic materials 0.000 claims description 8
- 239000011591 potassium Substances 0.000 claims description 8
- 229910052700 potassium Inorganic materials 0.000 claims description 8
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 claims description 6
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 claims description 6
- 239000010936 titanium Substances 0.000 claims description 6
- GUTLYIVDDKVIGB-OUBTZVSYSA-N Cobalt-60 Chemical compound [60Co] GUTLYIVDDKVIGB-OUBTZVSYSA-N 0.000 claims description 5
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 claims description 5
- 239000011651 chromium Substances 0.000 claims description 5
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 claims description 4
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims description 4
- 239000004743 Polypropylene Substances 0.000 claims description 4
- 229920000297 Rayon Polymers 0.000 claims description 4
- BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical compound [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 claims description 4
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 claims description 4
- 239000004411 aluminium Substances 0.000 claims description 4
- 229910052782 aluminium Inorganic materials 0.000 claims description 4
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 claims description 4
- 229910052788 barium Inorganic materials 0.000 claims description 4
- DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 claims description 4
- 229910052793 cadmium Inorganic materials 0.000 claims description 4
- BDOSMKKIYDKNTQ-UHFFFAOYSA-N cadmium atom Chemical compound [Cd] BDOSMKKIYDKNTQ-UHFFFAOYSA-N 0.000 claims description 4
- 229910052804 chromium Inorganic materials 0.000 claims description 4
- 229910052802 copper Inorganic materials 0.000 claims description 4
- 239000010949 copper Substances 0.000 claims description 4
- 229910052742 iron Inorganic materials 0.000 claims description 4
- 229920001155 polypropylene Polymers 0.000 claims description 4
- 230000002035 prolonged effect Effects 0.000 claims description 4
- 239000002964 rayon Substances 0.000 claims description 4
- 229910052711 selenium Inorganic materials 0.000 claims description 4
- 239000011669 selenium Substances 0.000 claims description 4
- 230000001954 sterilising effect Effects 0.000 claims description 4
- 229910052712 strontium Inorganic materials 0.000 claims description 4
- CIOAGBVUUVVLOB-UHFFFAOYSA-N strontium atom Chemical compound [Sr] CIOAGBVUUVVLOB-UHFFFAOYSA-N 0.000 claims description 4
- 229910052718 tin Inorganic materials 0.000 claims description 4
- 229910052719 titanium Inorganic materials 0.000 claims description 4
- 229910052720 vanadium Inorganic materials 0.000 claims description 4
- LEONUFNNVUYDNQ-UHFFFAOYSA-N vanadium atom Chemical compound [V] LEONUFNNVUYDNQ-UHFFFAOYSA-N 0.000 claims description 4
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 claims description 3
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 3
- 229910052787 antimony Inorganic materials 0.000 claims description 3
- WATWJIUSRGPENY-UHFFFAOYSA-N antimony atom Chemical compound [Sb] WATWJIUSRGPENY-UHFFFAOYSA-N 0.000 claims description 3
- 229910052785 arsenic Inorganic materials 0.000 claims description 3
- RQNWIZPPADIBDY-UHFFFAOYSA-N arsenic atom Chemical compound [As] RQNWIZPPADIBDY-UHFFFAOYSA-N 0.000 claims description 3
- 229910017052 cobalt Inorganic materials 0.000 claims description 3
- 239000010941 cobalt Substances 0.000 claims description 3
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- WPBNNNQJVZRUHP-UHFFFAOYSA-L manganese(2+);methyl n-[[2-(methoxycarbonylcarbamothioylamino)phenyl]carbamothioyl]carbamate;n-[2-(sulfidocarbothioylamino)ethyl]carbamodithioate Chemical compound [Mn+2].[S-]C(=S)NCCNC([S-])=S.COC(=O)NC(=S)NC1=CC=CC=C1NC(=S)NC(=O)OC WPBNNNQJVZRUHP-UHFFFAOYSA-L 0.000 claims description 3
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 claims description 3
- 229910052753 mercury Inorganic materials 0.000 claims description 3
- 229910052759 nickel Inorganic materials 0.000 claims description 3
- 229910052710 silicon Inorganic materials 0.000 claims description 3
- 239000010703 silicon Substances 0.000 claims description 3
- 239000011701 zinc Substances 0.000 claims description 3
- 229910052725 zinc Inorganic materials 0.000 claims description 3
- 230000005484 gravity Effects 0.000 claims description 2
- YPFDHNVEDLHUCE-UHFFFAOYSA-N 1,3-propanediol Substances OCCCO YPFDHNVEDLHUCE-UHFFFAOYSA-N 0.000 abstract description 3
- DNIAPMSPPWPWGF-VKHMYHEASA-N (+)-propylene glycol Chemical group C[C@H](O)CO DNIAPMSPPWPWGF-VKHMYHEASA-N 0.000 abstract description 2
- 229920000166 polytrimethylene carbonate Polymers 0.000 abstract description 2
- 229940035437 1,3-propanediol Drugs 0.000 abstract 1
- 210000003491 skin Anatomy 0.000 description 80
- 108090000623 proteins and genes Proteins 0.000 description 54
- 208000027418 Wounds and injury Diseases 0.000 description 51
- 235000010755 mineral Nutrition 0.000 description 51
- 210000004027 cell Anatomy 0.000 description 35
- 230000006378 damage Effects 0.000 description 33
- 208000014674 injury Diseases 0.000 description 31
- 230000029663 wound healing Effects 0.000 description 25
- 230000014509 gene expression Effects 0.000 description 24
- 210000001519 tissue Anatomy 0.000 description 22
- 206010053615 Thermal burn Diseases 0.000 description 21
- 206010052428 Wound Diseases 0.000 description 20
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 19
- 210000002950 fibroblast Anatomy 0.000 description 17
- 239000000499 gel Substances 0.000 description 17
- 239000004615 ingredient Substances 0.000 description 17
- 239000010410 layer Substances 0.000 description 17
- 239000000126 substance Substances 0.000 description 16
- 230000035876 healing Effects 0.000 description 14
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 13
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 13
- 229920002125 Sokalan® Polymers 0.000 description 13
- 230000008859 change Effects 0.000 description 13
- 238000002474 experimental method Methods 0.000 description 13
- 230000001105 regulatory effect Effects 0.000 description 13
- 210000002744 extracellular matrix Anatomy 0.000 description 12
- 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 11
- 238000011529 RT qPCR Methods 0.000 description 11
- 238000003556 assay Methods 0.000 description 11
- 230000004044 response Effects 0.000 description 11
- 101000935043 Homo sapiens Integrin beta-1 Proteins 0.000 description 9
- 230000001603 reducing effect Effects 0.000 description 9
- 101800003838 Epidermal growth factor Proteins 0.000 description 8
- 102400001368 Epidermal growth factor Human genes 0.000 description 8
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 8
- 101000599951 Homo sapiens Insulin-like growth factor I Proteins 0.000 description 8
- 102100037852 Insulin-like growth factor I Human genes 0.000 description 8
- 102100025304 Integrin beta-1 Human genes 0.000 description 8
- 108010011536 PTEN Phosphohydrolase Proteins 0.000 description 8
- 230000002500 effect on skin Effects 0.000 description 8
- 239000012530 fluid Substances 0.000 description 8
- 230000006870 function Effects 0.000 description 8
- 230000001965 increasing effect Effects 0.000 description 8
- 229960004063 propylene glycol Drugs 0.000 description 8
- 235000013772 propylene glycol Nutrition 0.000 description 8
- 230000037390 scarring Effects 0.000 description 8
- 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 description 8
- 102100032937 CD40 ligand Human genes 0.000 description 7
- 102100033780 Collagen alpha-3(IV) chain Human genes 0.000 description 7
- 101000868215 Homo sapiens CD40 ligand Proteins 0.000 description 7
- 101000710873 Homo sapiens Collagen alpha-3(IV) chain Proteins 0.000 description 7
- 101000746373 Homo sapiens Granulocyte-macrophage colony-stimulating factor Proteins 0.000 description 7
- 101001015064 Homo sapiens Integrin beta-6 Proteins 0.000 description 7
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 7
- 206010061218 Inflammation Diseases 0.000 description 7
- 102100033011 Integrin beta-6 Human genes 0.000 description 7
- 102100032543 Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN Human genes 0.000 description 7
- 108010022233 Plasminogen Activator Inhibitor 1 Proteins 0.000 description 7
- 102100039418 Plasminogen activator inhibitor 1 Human genes 0.000 description 7
- 229940116977 epidermal growth factor Drugs 0.000 description 7
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 7
- 230000004054 inflammatory process Effects 0.000 description 7
- 102100026802 72 kDa type IV collagenase Human genes 0.000 description 6
- 102100036732 Actin, aortic smooth muscle Human genes 0.000 description 6
- 102100021943 C-C motif chemokine 2 Human genes 0.000 description 6
- 102100026540 Cathepsin L2 Human genes 0.000 description 6
- 101000929319 Homo sapiens Actin, aortic smooth muscle Proteins 0.000 description 6
- 101000983577 Homo sapiens Cathepsin L2 Proteins 0.000 description 6
- 101001078158 Homo sapiens Integrin alpha-1 Proteins 0.000 description 6
- 101001078133 Homo sapiens Integrin alpha-2 Proteins 0.000 description 6
- 101000599940 Homo sapiens Interferon gamma Proteins 0.000 description 6
- 101001033249 Homo sapiens Interleukin-1 beta Proteins 0.000 description 6
- 101000990902 Homo sapiens Matrix metalloproteinase-9 Proteins 0.000 description 6
- 102100025323 Integrin alpha-1 Human genes 0.000 description 6
- 102100039065 Interleukin-1 beta Human genes 0.000 description 6
- 102100030417 Matrilysin Human genes 0.000 description 6
- 102100030412 Matrix metalloproteinase-9 Human genes 0.000 description 6
- 102100033762 Proheparin-binding EGF-like growth factor Human genes 0.000 description 6
- 206010063562 Radiation skin injury Diseases 0.000 description 6
- 102100022387 Transforming protein RhoA Human genes 0.000 description 6
- 238000003491 array Methods 0.000 description 6
- 230000003833 cell viability Effects 0.000 description 6
- FOCAHLGSDWHSAH-UHFFFAOYSA-N difluoromethanethione Chemical compound FC(F)=S FOCAHLGSDWHSAH-UHFFFAOYSA-N 0.000 description 6
- 239000003906 humectant Substances 0.000 description 6
- 208000015181 infectious disease Diseases 0.000 description 6
- 210000002510 keratinocyte Anatomy 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 230000002829 reductive effect Effects 0.000 description 6
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 5
- 102100039819 Actin, alpha cardiac muscle 1 Human genes 0.000 description 5
- 229910001369 Brass Inorganic materials 0.000 description 5
- 102100025279 C-X-C motif chemokine 11 Human genes 0.000 description 5
- 102100036150 C-X-C motif chemokine 5 Human genes 0.000 description 5
- 102100031173 CCN family member 4 Human genes 0.000 description 5
- 102100028914 Catenin beta-1 Human genes 0.000 description 5
- 102100025975 Cathepsin G Human genes 0.000 description 5
- 102100024940 Cathepsin K Human genes 0.000 description 5
- 102100029057 Coagulation factor XIII A chain Human genes 0.000 description 5
- 102100031502 Collagen alpha-2(V) chain Human genes 0.000 description 5
- 239000003109 Disodium ethylene diamine tetraacetate Substances 0.000 description 5
- OVBJJZOQPCKUOR-UHFFFAOYSA-L EDTA disodium salt dihydrate Chemical compound O.O.[Na+].[Na+].[O-]C(=O)C[NH+](CC([O-])=O)CC[NH+](CC([O-])=O)CC([O-])=O OVBJJZOQPCKUOR-UHFFFAOYSA-L 0.000 description 5
- 102100031752 Fibrinogen alpha chain Human genes 0.000 description 5
- 102100028412 Fibroblast growth factor 10 Human genes 0.000 description 5
- 102100028071 Fibroblast growth factor 7 Human genes 0.000 description 5
- 102100039619 Granulocyte colony-stimulating factor Human genes 0.000 description 5
- 102100034221 Growth-regulated alpha protein Human genes 0.000 description 5
- 101800001649 Heparin-binding EGF-like growth factor Proteins 0.000 description 5
- 101000959247 Homo sapiens Actin, alpha cardiac muscle 1 Proteins 0.000 description 5
- 101000924552 Homo sapiens Angiopoietin-1 Proteins 0.000 description 5
- 101000947186 Homo sapiens C-X-C motif chemokine 5 Proteins 0.000 description 5
- 101000777560 Homo sapiens CCN family member 4 Proteins 0.000 description 5
- 101000916173 Homo sapiens Catenin beta-1 Proteins 0.000 description 5
- 101000933179 Homo sapiens Cathepsin G Proteins 0.000 description 5
- 101000761509 Homo sapiens Cathepsin K Proteins 0.000 description 5
- 101000918352 Homo sapiens Coagulation factor XIII A chain Proteins 0.000 description 5
- 101000941594 Homo sapiens Collagen alpha-2(V) chain Proteins 0.000 description 5
- 101001060261 Homo sapiens Fibroblast growth factor 7 Proteins 0.000 description 5
- 101000746367 Homo sapiens Granulocyte colony-stimulating factor Proteins 0.000 description 5
- 101001069921 Homo sapiens Growth-regulated alpha protein Proteins 0.000 description 5
- 101000994378 Homo sapiens Integrin alpha-3 Proteins 0.000 description 5
- 101001015004 Homo sapiens Integrin beta-3 Proteins 0.000 description 5
- 101001015059 Homo sapiens Integrin beta-5 Proteins 0.000 description 5
- 101000990912 Homo sapiens Matrilysin Proteins 0.000 description 5
- 101000669513 Homo sapiens Metalloproteinase inhibitor 1 Proteins 0.000 description 5
- 101001052493 Homo sapiens Mitogen-activated protein kinase 1 Proteins 0.000 description 5
- 101000804792 Homo sapiens Protein Wnt-5a Proteins 0.000 description 5
- 101000611183 Homo sapiens Tumor necrosis factor Proteins 0.000 description 5
- 101000803709 Homo sapiens Vitronectin Proteins 0.000 description 5
- 102100025305 Integrin alpha-2 Human genes 0.000 description 5
- 102100032819 Integrin alpha-3 Human genes 0.000 description 5
- 102100033010 Integrin beta-5 Human genes 0.000 description 5
- 102100037850 Interferon gamma Human genes 0.000 description 5
- 102100020873 Interleukin-2 Human genes 0.000 description 5
- 108010002350 Interleukin-2 Proteins 0.000 description 5
- 102000004889 Interleukin-6 Human genes 0.000 description 5
- 108090001005 Interleukin-6 Proteins 0.000 description 5
- 102100037795 Interleukin-6 receptor subunit beta Human genes 0.000 description 5
- 102000000380 Matrix Metalloproteinase 1 Human genes 0.000 description 5
- 102100039364 Metalloproteinase inhibitor 1 Human genes 0.000 description 5
- 102100024193 Mitogen-activated protein kinase 1 Human genes 0.000 description 5
- 102100038124 Plasminogen Human genes 0.000 description 5
- 102100037596 Platelet-derived growth factor subunit A Human genes 0.000 description 5
- 102100038280 Prostaglandin G/H synthase 2 Human genes 0.000 description 5
- 101150111584 RHOA gene Proteins 0.000 description 5
- 102100022122 Ras-related C3 botulinum toxin substrate 1 Human genes 0.000 description 5
- 102100024040 Signal transducer and activator of transcription 3 Human genes 0.000 description 5
- 102100040247 Tumor necrosis factor Human genes 0.000 description 5
- 102100031358 Urokinase-type plasminogen activator Human genes 0.000 description 5
- 102100035140 Vitronectin Human genes 0.000 description 5
- 102000043366 Wnt-5a Human genes 0.000 description 5
- 239000010951 brass Substances 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- 230000007423 decrease Effects 0.000 description 5
- 210000004207 dermis Anatomy 0.000 description 5
- 235000019301 disodium ethylene diamine tetraacetate Nutrition 0.000 description 5
- 210000002615 epidermis Anatomy 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- 239000003102 growth factor Substances 0.000 description 5
- 230000036074 healthy skin Effects 0.000 description 5
- 229920002674 hyaluronan Polymers 0.000 description 5
- 229960003160 hyaluronic acid Drugs 0.000 description 5
- 239000003446 ligand Substances 0.000 description 5
- 108010062302 rac1 GTP Binding Protein Proteins 0.000 description 5
- 238000003753 real-time PCR Methods 0.000 description 5
- 235000002639 sodium chloride Nutrition 0.000 description 5
- 238000004659 sterilization and disinfection Methods 0.000 description 5
- 102100034594 Angiopoietin-1 Human genes 0.000 description 4
- 102100032366 C-C motif chemokine 7 Human genes 0.000 description 4
- 102100039398 C-X-C motif chemokine 2 Human genes 0.000 description 4
- 102100031168 CCN family member 2 Human genes 0.000 description 4
- 102100025805 Cadherin-1 Human genes 0.000 description 4
- 102100022145 Collagen alpha-1(IV) chain Human genes 0.000 description 4
- 102100031501 Collagen alpha-3(V) chain Human genes 0.000 description 4
- 108010037462 Cyclooxygenase 2 Proteins 0.000 description 4
- 102000004127 Cytokines Human genes 0.000 description 4
- 108090000695 Cytokines Proteins 0.000 description 4
- 102100021866 Hepatocyte growth factor Human genes 0.000 description 4
- 101000627872 Homo sapiens 72 kDa type IV collagenase Proteins 0.000 description 4
- 101000858060 Homo sapiens C-X-C motif chemokine 11 Proteins 0.000 description 4
- 101000889128 Homo sapiens C-X-C motif chemokine 2 Proteins 0.000 description 4
- 101000777550 Homo sapiens CCN family member 2 Proteins 0.000 description 4
- 101000901150 Homo sapiens Collagen alpha-1(IV) chain Proteins 0.000 description 4
- 101000941596 Homo sapiens Collagen alpha-3(V) chain Proteins 0.000 description 4
- 101000917237 Homo sapiens Fibroblast growth factor 10 Proteins 0.000 description 4
- 101000898034 Homo sapiens Hepatocyte growth factor Proteins 0.000 description 4
- 101000994375 Homo sapiens Integrin alpha-4 Proteins 0.000 description 4
- 101000994365 Homo sapiens Integrin alpha-6 Proteins 0.000 description 4
- 101001046677 Homo sapiens Integrin alpha-V Proteins 0.000 description 4
- 101001076408 Homo sapiens Interleukin-6 Proteins 0.000 description 4
- 101000599056 Homo sapiens Interleukin-6 receptor subunit beta Proteins 0.000 description 4
- 101001013150 Homo sapiens Interstitial collagenase Proteins 0.000 description 4
- 101000655540 Homo sapiens Protransforming growth factor alpha Proteins 0.000 description 4
- 101000635938 Homo sapiens Transforming growth factor beta-1 proprotein Proteins 0.000 description 4
- 101000760337 Homo sapiens Urokinase plasminogen activator surface receptor Proteins 0.000 description 4
- 101000638886 Homo sapiens Urokinase-type plasminogen activator Proteins 0.000 description 4
- 101000808011 Homo sapiens Vascular endothelial growth factor A Proteins 0.000 description 4
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 4
- 102100032818 Integrin alpha-4 Human genes 0.000 description 4
- 102100032817 Integrin alpha-5 Human genes 0.000 description 4
- 102100022337 Integrin alpha-V Human genes 0.000 description 4
- 102100032999 Integrin beta-3 Human genes 0.000 description 4
- 102000004388 Interleukin-4 Human genes 0.000 description 4
- 108090000978 Interleukin-4 Proteins 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical group [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- 102100032350 Protransforming growth factor alpha Human genes 0.000 description 4
- 108010017324 STAT3 Transcription Factor Proteins 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 102100033663 Transforming growth factor beta receptor type 3 Human genes 0.000 description 4
- 102100030742 Transforming growth factor beta-1 proprotein Human genes 0.000 description 4
- 102100024689 Urokinase plasminogen activator surface receptor Human genes 0.000 description 4
- 102100039037 Vascular endothelial growth factor A Human genes 0.000 description 4
- 239000006096 absorbing agent Substances 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- GUBGYTABKSRVRQ-QRZGKKJRSA-N beta-cellobiose Chemical compound OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QRZGKKJRSA-N 0.000 description 4
- 230000033228 biological regulation Effects 0.000 description 4
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 4
- 210000002808 connective tissue Anatomy 0.000 description 4
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 description 4
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 description 4
- 239000004744 fabric Substances 0.000 description 4
- 238000005469 granulation Methods 0.000 description 4
- 230000003179 granulation Effects 0.000 description 4
- 244000005700 microbiome Species 0.000 description 4
- 238000009343 monoculture Methods 0.000 description 4
- 210000000651 myofibroblast Anatomy 0.000 description 4
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 description 4
- 230000001338 necrotic effect Effects 0.000 description 4
- 108010017843 platelet-derived growth factor A Proteins 0.000 description 4
- 230000002265 prevention Effects 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 238000003860 storage Methods 0.000 description 4
- 210000000434 stratum corneum Anatomy 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 229920001817 Agar Polymers 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- 108091007854 Cdh1/Fizzy-related Proteins 0.000 description 3
- 208000009043 Chemical Burns Diseases 0.000 description 3
- 102100031611 Collagen alpha-1(III) chain Human genes 0.000 description 3
- 102100024203 Collagen alpha-1(XIV) chain Human genes 0.000 description 3
- 102100036213 Collagen alpha-2(I) chain Human genes 0.000 description 3
- CTKXFMQHOOWWEB-UHFFFAOYSA-N Ethylene oxide/propylene oxide copolymer Chemical compound CCCOC(C)COCCO CTKXFMQHOOWWEB-UHFFFAOYSA-N 0.000 description 3
- 102000003974 Fibroblast growth factor 2 Human genes 0.000 description 3
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 description 3
- 206010016654 Fibrosis Diseases 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- 101000797758 Homo sapiens C-C motif chemokine 7 Proteins 0.000 description 3
- 101000993285 Homo sapiens Collagen alpha-1(III) chain Proteins 0.000 description 3
- 101000941708 Homo sapiens Collagen alpha-1(V) chain Proteins 0.000 description 3
- 101000909626 Homo sapiens Collagen alpha-1(XIV) chain Proteins 0.000 description 3
- 101000875067 Homo sapiens Collagen alpha-2(I) chain Proteins 0.000 description 3
- 101000994369 Homo sapiens Integrin alpha-5 Proteins 0.000 description 3
- 101001052490 Homo sapiens Mitogen-activated protein kinase 3 Proteins 0.000 description 3
- 102100032816 Integrin alpha-6 Human genes 0.000 description 3
- 102000003814 Interleukin-10 Human genes 0.000 description 3
- 108090000174 Interleukin-10 Proteins 0.000 description 3
- 102000001776 Matrix metalloproteinase-9 Human genes 0.000 description 3
- 108010015302 Matrix metalloproteinase-9 Proteins 0.000 description 3
- 102100024192 Mitogen-activated protein kinase 3 Human genes 0.000 description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
- 102100033571 Tissue-type plasminogen activator Human genes 0.000 description 3
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 3
- 239000008272 agar Substances 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 230000006907 apoptotic process Effects 0.000 description 3
- 230000009286 beneficial effect Effects 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
- 108010079292 betaglycan Proteins 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 239000000679 carrageenan Substances 0.000 description 3
- 229920001525 carrageenan Polymers 0.000 description 3
- 235000010418 carrageenan Nutrition 0.000 description 3
- 229940113118 carrageenan Drugs 0.000 description 3
- 230000012292 cell migration Effects 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 230000008482 dysregulation Effects 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 230000004761 fibrosis Effects 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 230000028993 immune response Effects 0.000 description 3
- 230000002757 inflammatory effect Effects 0.000 description 3
- 150000002500 ions Chemical class 0.000 description 3
- 239000011159 matrix material Substances 0.000 description 3
- 230000004060 metabolic process Effects 0.000 description 3
- 238000013508 migration Methods 0.000 description 3
- 230000011164 ossification Effects 0.000 description 3
- 229920001993 poloxamer 188 Polymers 0.000 description 3
- 229940044519 poloxamer 188 Drugs 0.000 description 3
- 229920000728 polyester Polymers 0.000 description 3
- NCYDRNOBBHFJHE-UHFFFAOYSA-N propane-1,2-diol;prop-1-ene Chemical group CC=C.CC(O)CO NCYDRNOBBHFJHE-UHFFFAOYSA-N 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 230000008439 repair process Effects 0.000 description 3
- 230000036575 thermal burns Effects 0.000 description 3
- 239000011573 trace mineral Substances 0.000 description 3
- 235000013619 trace mineral Nutrition 0.000 description 3
- 229960004418 trolamine Drugs 0.000 description 3
- 229920001285 xanthan gum Polymers 0.000 description 3
- 239000000230 xanthan gum Substances 0.000 description 3
- 235000010493 xanthan gum Nutrition 0.000 description 3
- 229940082509 xanthan gum Drugs 0.000 description 3
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 3
- VAZJLPXFVQHDFB-UHFFFAOYSA-N 1-(diaminomethylidene)-2-hexylguanidine Polymers CCCCCCN=C(N)N=C(N)N VAZJLPXFVQHDFB-UHFFFAOYSA-N 0.000 description 2
- WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical compound OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 description 2
- CFKMVGJGLGKFKI-UHFFFAOYSA-N 4-chloro-m-cresol Chemical compound CC1=CC(O)=CC=C1Cl CFKMVGJGLGKFKI-UHFFFAOYSA-N 0.000 description 2
- FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 2
- 108091093088 Amplicon Proteins 0.000 description 2
- 102000019034 Chemokines Human genes 0.000 description 2
- 108010012236 Chemokines Proteins 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- 102000008186 Collagen Human genes 0.000 description 2
- 108010035532 Collagen Proteins 0.000 description 2
- 108010042086 Collagen Type IV Proteins 0.000 description 2
- 102000004266 Collagen Type IV Human genes 0.000 description 2
- 102100033601 Collagen alpha-1(I) chain Human genes 0.000 description 2
- 102100031457 Collagen alpha-1(V) chain Human genes 0.000 description 2
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical group CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 101000652736 Homo sapiens Transgelin Proteins 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 2
- 208000013038 Hypocalcemia Diseases 0.000 description 2
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 2
- 102000004218 Insulin-Like Growth Factor I Human genes 0.000 description 2
- 108010016165 Matrix Metalloproteinase 2 Proteins 0.000 description 2
- 108091007960 PI3Ks Proteins 0.000 description 2
- 102000038030 PI3Ks Human genes 0.000 description 2
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 2
- 208000007536 Thrombosis Diseases 0.000 description 2
- 102100031013 Transgelin Human genes 0.000 description 2
- 150000001252 acrylic acid derivatives Chemical class 0.000 description 2
- 239000000853 adhesive Substances 0.000 description 2
- 230000001070 adhesive effect Effects 0.000 description 2
- 230000033115 angiogenesis Effects 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- 230000000845 anti-microbial effect Effects 0.000 description 2
- 230000004888 barrier function Effects 0.000 description 2
- 210000002469 basement membrane Anatomy 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 210000004204 blood vessel Anatomy 0.000 description 2
- 230000021164 cell adhesion Effects 0.000 description 2
- 230000030833 cell death Effects 0.000 description 2
- 230000010261 cell growth Effects 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- 229920001436 collagen Polymers 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 238000011109 contamination Methods 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 238000001804 debridement Methods 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 230000005611 electricity Effects 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 238000010195 expression analysis Methods 0.000 description 2
- 210000004907 gland Anatomy 0.000 description 2
- 239000010931 gold Substances 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 239000000017 hydrogel Substances 0.000 description 2
- 230000000705 hypocalcaemia Effects 0.000 description 2
- 230000002631 hypothermal effect Effects 0.000 description 2
- 210000004969 inflammatory cell Anatomy 0.000 description 2
- 230000028709 inflammatory response Effects 0.000 description 2
- 238000011221 initial treatment Methods 0.000 description 2
- 230000009545 invasion Effects 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- 239000011572 manganese Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 230000005012 migration Effects 0.000 description 2
- NJTGANWAUPEOAX-UHFFFAOYSA-N molport-023-220-454 Chemical compound OCC(O)CO.OCC(O)CO NJTGANWAUPEOAX-UHFFFAOYSA-N 0.000 description 2
- 206010033675 panniculitis Diseases 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 229920003023 plastic Polymers 0.000 description 2
- 239000004033 plastic Substances 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 229920000139 polyethylene terephthalate Polymers 0.000 description 2
- 239000005020 polyethylene terephthalate Substances 0.000 description 2
- 229920001184 polypeptide Polymers 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 230000002250 progressing effect Effects 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 239000010948 rhodium Substances 0.000 description 2
- 231100000241 scar Toxicity 0.000 description 2
- 230000003248 secreting effect Effects 0.000 description 2
- 230000011664 signaling Effects 0.000 description 2
- 210000004927 skin cell Anatomy 0.000 description 2
- 230000037380 skin damage Effects 0.000 description 2
- 229940055689 sodium benzotriazolyl butylphenol sulfonate Drugs 0.000 description 2
- XTXADMXOEMEPAC-UHFFFAOYSA-M sodium;3-(benzotriazol-2-yl)-5-butan-2-yl-4-hydroxybenzenesulfonate Chemical compound [Na+].CCC(C)C1=CC(S([O-])(=O)=O)=CC(N2N=C3C=CC=CC3=N2)=C1O XTXADMXOEMEPAC-UHFFFAOYSA-M 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 230000007480 spreading Effects 0.000 description 2
- 238000003892 spreading Methods 0.000 description 2
- 230000004936 stimulating effect Effects 0.000 description 2
- 210000004304 subcutaneous tissue Anatomy 0.000 description 2
- 239000008399 tap water Substances 0.000 description 2
- 235000020679 tap water Nutrition 0.000 description 2
- AZJYLVAUMGUUBL-UHFFFAOYSA-A u1qj22mc8e Chemical compound [F-].[F-].[F-].[F-].[F-].[F-].[F-].[F-].[F-].[F-].[F-].[F-].[F-].[F-].[F-].[F-].[F-].[F-].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].O=[Si]=O.O=[Si]=O.O=[Si]=O.O1[Si](O2)([O-])O[Si]3([O-])O[Si]1([O-])O[Si]2([O-])O3.O1[Si](O2)([O-])O[Si]3([O-])O[Si]1([O-])O[Si]2([O-])O3.O1[Si](O2)([O-])O[Si]3([O-])O[Si]1([O-])O[Si]2([O-])O3.O1[Si](O2)([O-])O[Si]3([O-])O[Si]1([O-])O[Si]2([O-])O3.O1[Si](O2)([O-])O[Si]3([O-])O[Si]1([O-])O[Si]2([O-])O3.O1[Si](O2)([O-])O[Si]3([O-])O[Si]1([O-])O[Si]2([O-])O3 AZJYLVAUMGUUBL-UHFFFAOYSA-A 0.000 description 2
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 description 1
- JCIIKRHCWVHVFF-UHFFFAOYSA-N 1,2,4-thiadiazol-5-amine;hydrochloride Chemical compound Cl.NC1=NC=NS1 JCIIKRHCWVHVFF-UHFFFAOYSA-N 0.000 description 1
- ANZUDYZHSVGBRF-UHFFFAOYSA-N 3-ethylnonane-1,2,3-triol Chemical compound CCCCCCC(O)(CC)C(O)CO ANZUDYZHSVGBRF-UHFFFAOYSA-N 0.000 description 1
- VOXXWSYKYCBWHO-UHFFFAOYSA-N 3-phenyllactic acid Chemical compound OC(=O)C(O)CC1=CC=CC=C1 VOXXWSYKYCBWHO-UHFFFAOYSA-N 0.000 description 1
- BWRRWBIBNBVHQF-UHFFFAOYSA-N 4-(3-pyridin-2-yl-1,2,4-oxadiazol-5-yl)butanoic acid Chemical compound O1C(CCCC(=O)O)=NC(C=2N=CC=CC=2)=N1 BWRRWBIBNBVHQF-UHFFFAOYSA-N 0.000 description 1
- 229940090248 4-hydroxybenzoic acid Drugs 0.000 description 1
- 102000017304 72kDa type IV collagenases Human genes 0.000 description 1
- 108050005269 72kDa type IV collagenases Proteins 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 102000015735 Beta-catenin Human genes 0.000 description 1
- 108060000903 Beta-catenin Proteins 0.000 description 1
- XNCOSPRUTUOJCJ-UHFFFAOYSA-N Biguanide Chemical compound NC(N)=NC(N)=N XNCOSPRUTUOJCJ-UHFFFAOYSA-N 0.000 description 1
- 229940123208 Biguanide Drugs 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 206010006797 Burns first degree Diseases 0.000 description 1
- 101710155857 C-C motif chemokine 2 Proteins 0.000 description 1
- 101710155834 C-C motif chemokine 7 Proteins 0.000 description 1
- 108700013048 CCL2 Proteins 0.000 description 1
- 102000000905 Cadherin Human genes 0.000 description 1
- 108050007957 Cadherin Proteins 0.000 description 1
- 206010006956 Calcium deficiency Diseases 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 229910052684 Cerium Inorganic materials 0.000 description 1
- LZZYPRNAOMGNLH-UHFFFAOYSA-M Cetrimonium bromide Chemical compound [Br-].CCCCCCCCCCCCCCCC[N+](C)(C)C LZZYPRNAOMGNLH-UHFFFAOYSA-M 0.000 description 1
- 208000018380 Chemical injury Diseases 0.000 description 1
- 102000000018 Chemokine CCL2 Human genes 0.000 description 1
- 108010055124 Chemokine CCL7 Proteins 0.000 description 1
- 102000001304 Chemokine CCL7 Human genes 0.000 description 1
- 108010014419 Chemokine CXCL1 Proteins 0.000 description 1
- 102000016950 Chemokine CXCL1 Human genes 0.000 description 1
- 108010008980 Chemokine CXCL11 Proteins 0.000 description 1
- 102000006577 Chemokine CXCL11 Human genes 0.000 description 1
- 108010014414 Chemokine CXCL2 Proteins 0.000 description 1
- 102000016951 Chemokine CXCL2 Human genes 0.000 description 1
- 108010014421 Chemokine CXCL5 Proteins 0.000 description 1
- 102000016948 Chemokine CXCL5 Human genes 0.000 description 1
- GHXZTYHSJHQHIJ-UHFFFAOYSA-N Chlorhexidine Chemical compound C=1C=C(Cl)C=CC=1NC(N)=NC(N)=NCCCCCCN=C(N)N=C(N)NC1=CC=C(Cl)C=C1 GHXZTYHSJHQHIJ-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 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
- 102000012432 Collagen Type V Human genes 0.000 description 1
- 108010022514 Collagen Type V Proteins 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 241000195493 Cryptophyta Species 0.000 description 1
- IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 description 1
- 101000876610 Dictyostelium discoideum Extracellular signal-regulated kinase 2 Proteins 0.000 description 1
- 102000001301 EGF receptor Human genes 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 229910052691 Erbium Inorganic materials 0.000 description 1
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
- 229910052693 Europium Inorganic materials 0.000 description 1
- 108010071289 Factor XIII Proteins 0.000 description 1
- 206010016334 Feeling hot Diseases 0.000 description 1
- 108010073385 Fibrin Proteins 0.000 description 1
- 102000009123 Fibrin Human genes 0.000 description 1
- 108010049003 Fibrinogen Proteins 0.000 description 1
- 102000008946 Fibrinogen Human genes 0.000 description 1
- 108090001047 Fibroblast growth factor 10 Proteins 0.000 description 1
- 102100024785 Fibroblast growth factor 2 Human genes 0.000 description 1
- 102100037362 Fibronectin Human genes 0.000 description 1
- 108010067306 Fibronectins Proteins 0.000 description 1
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- GYHNNYVSQQEPJS-UHFFFAOYSA-N Gallium Chemical compound [Ga] GYHNNYVSQQEPJS-UHFFFAOYSA-N 0.000 description 1
- 102100033299 Glia-derived nexin Human genes 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 229920002683 Glycosaminoglycan Polymers 0.000 description 1
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
- 229910052689 Holmium Inorganic materials 0.000 description 1
- 101000684275 Homo sapiens ADP-ribosylation factor 3 Proteins 0.000 description 1
- 101100222381 Homo sapiens CXCL11 gene Proteins 0.000 description 1
- 101001052035 Homo sapiens Fibroblast growth factor 2 Proteins 0.000 description 1
- 101000997803 Homo sapiens Glia-derived nexin Proteins 0.000 description 1
- 101000605127 Homo sapiens Prostaglandin G/H synthase 2 Proteins 0.000 description 1
- 101001130437 Homo sapiens Ras-related protein Rap-2b Proteins 0.000 description 1
- 101000826373 Homo sapiens Signal transducer and activator of transcription 3 Proteins 0.000 description 1
- 101000868152 Homo sapiens Son of sevenless homolog 1 Proteins 0.000 description 1
- 101000635804 Homo sapiens Tissue factor Proteins 0.000 description 1
- 101000801481 Homo sapiens Tissue-type plasminogen activator Proteins 0.000 description 1
- 108010042918 Integrin alpha5beta1 Proteins 0.000 description 1
- 102100026019 Interleukin-6 Human genes 0.000 description 1
- 108010085895 Laminin Proteins 0.000 description 1
- 108040008097 MAP kinase activity proteins Proteins 0.000 description 1
- 102000019149 MAP kinase activity proteins Human genes 0.000 description 1
- 102000034655 MIF Human genes 0.000 description 1
- 108060004872 MIF Proteins 0.000 description 1
- 231100000002 MTT assay Toxicity 0.000 description 1
- 238000000134 MTT assay Methods 0.000 description 1
- 102100037791 Macrophage migration inhibitory factor Human genes 0.000 description 1
- 101710119980 Macrophage migration inhibitory factor Proteins 0.000 description 1
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 description 1
- 108090000855 Matrilysin Proteins 0.000 description 1
- 108010016113 Matrix Metalloproteinase 1 Proteins 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 102000044589 Mitogen-Activated Protein Kinase 1 Human genes 0.000 description 1
- 108700027649 Mitogen-Activated Protein Kinase 3 Proteins 0.000 description 1
- 102000046795 Mitogen-Activated Protein Kinase 3 Human genes 0.000 description 1
- 108700015928 Mitogen-activated protein kinase 13 Proteins 0.000 description 1
- 101100286588 Mus musculus Igfl gene Proteins 0.000 description 1
- 241001467460 Myxogastria Species 0.000 description 1
- 206010028851 Necrosis Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 208000001388 Opportunistic Infections Diseases 0.000 description 1
- 206010058667 Oral toxicity Diseases 0.000 description 1
- 102000014160 PTEN Phosphohydrolase Human genes 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 102000010752 Plasminogen Inactivators Human genes 0.000 description 1
- 108010077971 Plasminogen Inactivators Proteins 0.000 description 1
- 102000015795 Platelet Membrane Glycoproteins Human genes 0.000 description 1
- 108010010336 Platelet Membrane Glycoproteins Proteins 0.000 description 1
- 108010040201 Polymyxins Proteins 0.000 description 1
- 208000003251 Pruritus Diseases 0.000 description 1
- 102100031421 Ras-related protein Rap-2b Human genes 0.000 description 1
- 208000001647 Renal Insufficiency Diseases 0.000 description 1
- 102000042463 Rho family Human genes 0.000 description 1
- 108091078243 Rho family Proteins 0.000 description 1
- 108010005113 Serpin E2 Proteins 0.000 description 1
- 102000005821 Serpin E2 Human genes 0.000 description 1
- 206010040867 Skin hypertrophy Diseases 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 208000007107 Stomach Ulcer Diseases 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 101710173511 Tensin homolog Proteins 0.000 description 1
- 229910052771 Terbium Inorganic materials 0.000 description 1
- 102000002262 Thromboplastin Human genes 0.000 description 1
- 108010000499 Thromboplastin Proteins 0.000 description 1
- 229910052775 Thulium Inorganic materials 0.000 description 1
- 102100030859 Tissue factor Human genes 0.000 description 1
- IVOMOUWHDPKRLL-UHFFFAOYSA-N UNPD107823 Natural products O1C2COP(O)(=O)OC2C(O)C1N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-UHFFFAOYSA-N 0.000 description 1
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 102000013814 Wnt Human genes 0.000 description 1
- 108050003627 Wnt Proteins 0.000 description 1
- 229910052769 Ytterbium Inorganic materials 0.000 description 1
- QCWXUUIWCKQGHC-UHFFFAOYSA-N Zirconium Chemical compound [Zr] QCWXUUIWCKQGHC-UHFFFAOYSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 108010029483 alpha 1 Chain Collagen Type I Proteins 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 230000002785 anti-thrombosis Effects 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 229940027983 antiseptic and disinfectant quaternary ammonium compound Drugs 0.000 description 1
- 230000003385 bacteriostatic effect Effects 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- 229960001950 benzethonium chloride Drugs 0.000 description 1
- UREZNYTWGJKWBI-UHFFFAOYSA-M benzethonium chloride Chemical compound [Cl-].C1=CC(C(C)(C)CC(C)(C)C)=CC=C1OCCOCC[N+](C)(C)CC1=CC=CC=C1 UREZNYTWGJKWBI-UHFFFAOYSA-M 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 229960004365 benzoic acid Drugs 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 229960004217 benzyl alcohol Drugs 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- 229910052797 bismuth Inorganic materials 0.000 description 1
- JCXGWMGPZLAOME-UHFFFAOYSA-N bismuth atom Chemical compound [Bi] JCXGWMGPZLAOME-UHFFFAOYSA-N 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 230000003491 cAMP production Effects 0.000 description 1
- 229910052792 caesium Inorganic materials 0.000 description 1
- TVFDJXOCXUVLDH-UHFFFAOYSA-N caesium atom Chemical compound [Cs] TVFDJXOCXUVLDH-UHFFFAOYSA-N 0.000 description 1
- 229960001631 carbomer Drugs 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000004709 cell invasion Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- GWXLDORMOJMVQZ-UHFFFAOYSA-N cerium Chemical compound [Ce] GWXLDORMOJMVQZ-UHFFFAOYSA-N 0.000 description 1
- TVFDJXOCXUVLDH-RNFDNDRNSA-N cesium-137 Chemical compound [137Cs] TVFDJXOCXUVLDH-RNFDNDRNSA-N 0.000 description 1
- 229960002798 cetrimide Drugs 0.000 description 1
- 229960001927 cetylpyridinium chloride Drugs 0.000 description 1
- NFCRBQADEGXVDL-UHFFFAOYSA-M cetylpyridinium chloride monohydrate Chemical compound O.[Cl-].CCCCCCCCCCCCCCCC[N+]1=CC=CC=C1 NFCRBQADEGXVDL-UHFFFAOYSA-M 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 229960003260 chlorhexidine Drugs 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- 229960002242 chlorocresol Drugs 0.000 description 1
- MXOAEAUPQDYUQM-UHFFFAOYSA-N chlorphenesin Chemical compound OCC(O)COC1=CC=C(Cl)C=C1 MXOAEAUPQDYUQM-UHFFFAOYSA-N 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 229940105784 coagulation factor xiii Drugs 0.000 description 1
- 239000003636 conditioned culture medium Substances 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 238000005336 cracking Methods 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 229940095074 cyclic amp Drugs 0.000 description 1
- 210000004292 cytoskeleton Anatomy 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 229960001378 dequalinium chloride Drugs 0.000 description 1
- LTNZEXKYNRNOGT-UHFFFAOYSA-N dequalinium chloride Chemical compound [Cl-].[Cl-].C1=CC=C2[N+](CCCCCCCCCC[N+]3=C4C=CC=CC4=C(N)C=C3C)=C(C)C=C(N)C2=C1 LTNZEXKYNRNOGT-UHFFFAOYSA-N 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 230000005670 electromagnetic radiation Effects 0.000 description 1
- 238000010894 electron beam technology Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 210000001339 epidermal cell Anatomy 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- UYAHIZSMUZPPFV-UHFFFAOYSA-N erbium Chemical compound [Er] UYAHIZSMUZPPFV-UHFFFAOYSA-N 0.000 description 1
- OGPBJKLSAFTDLK-UHFFFAOYSA-N europium atom Chemical compound [Eu] OGPBJKLSAFTDLK-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 229950003499 fibrin Drugs 0.000 description 1
- 229940012952 fibrinogen Drugs 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 230000001408 fungistatic effect Effects 0.000 description 1
- 229910052733 gallium Inorganic materials 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000003349 gelling agent Substances 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 229910052735 hafnium Inorganic materials 0.000 description 1
- VBJZVLUMGGDVMO-UHFFFAOYSA-N hafnium atom Chemical compound [Hf] VBJZVLUMGGDVMO-UHFFFAOYSA-N 0.000 description 1
- 210000003780 hair follicle Anatomy 0.000 description 1
- 230000008821 health effect Effects 0.000 description 1
- 230000017525 heat dissipation Effects 0.000 description 1
- 239000001307 helium Substances 0.000 description 1
- 229910052734 helium Inorganic materials 0.000 description 1
- SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 description 1
- KJZYNXUDTRRSPN-UHFFFAOYSA-N holmium atom Chemical compound [Ho] KJZYNXUDTRRSPN-UHFFFAOYSA-N 0.000 description 1
- 230000013632 homeostatic process Effects 0.000 description 1
- 235000003642 hunger Nutrition 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 229920003111 hydroxyethyl cellulose HHX Polymers 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000010874 in vitro model Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 229910052738 indium Inorganic materials 0.000 description 1
- APFVFJFRJDLVQX-UHFFFAOYSA-N indium atom Chemical compound [In] APFVFJFRJDLVQX-UHFFFAOYSA-N 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000036512 infertility Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000016507 interphase Effects 0.000 description 1
- 210000002011 intestinal secretion Anatomy 0.000 description 1
- 229910052741 iridium Inorganic materials 0.000 description 1
- GKOZUEZYRPOHIO-UHFFFAOYSA-N iridium atom Chemical compound [Ir] GKOZUEZYRPOHIO-UHFFFAOYSA-N 0.000 description 1
- 230000007803 itching Effects 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 201000006370 kidney failure Diseases 0.000 description 1
- 229910052743 krypton Inorganic materials 0.000 description 1
- DNNSSWSSYDEUBZ-UHFFFAOYSA-N krypton atom Chemical compound [Kr] DNNSSWSSYDEUBZ-UHFFFAOYSA-N 0.000 description 1
- 210000001821 langerhans cell Anatomy 0.000 description 1
- 229910052746 lanthanum Inorganic materials 0.000 description 1
- FZLIPJUXYLNCLC-UHFFFAOYSA-N lanthanum atom Chemical compound [La] FZLIPJUXYLNCLC-UHFFFAOYSA-N 0.000 description 1
- 229940094522 laponite Drugs 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- XCOBTUNSZUJCDH-UHFFFAOYSA-B lithium magnesium sodium silicate Chemical compound [Li+].[Li+].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[Na+].[Na+].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].O1[Si](O2)([O-])O[Si]3([O-])O[Si]1([O-])O[Si]2([O-])O3.O1[Si](O2)([O-])O[Si]3([O-])O[Si]1([O-])O[Si]2([O-])O3.O1[Si](O2)([O-])O[Si]3([O-])O[Si]1([O-])O[Si]2([O-])O3.O1[Si](O2)([O-])O[Si]3([O-])O[Si]1([O-])O[Si]2([O-])O3.O1[Si](O2)([O-])O[Si]3([O-])O[Si]1([O-])O[Si]2([O-])O3.O1[Si](O2)([O-])O[Si]3([O-])O[Si]1([O-])O[Si]2([O-])O3 XCOBTUNSZUJCDH-UHFFFAOYSA-B 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 210000004324 lymphatic system Anatomy 0.000 description 1
- 239000000395 magnesium oxide Substances 0.000 description 1
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical class [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 229910052748 manganese Inorganic materials 0.000 description 1
- 108010082117 matrigel Proteins 0.000 description 1
- 238000002493 microarray Methods 0.000 description 1
- 230000003641 microbiacidal effect Effects 0.000 description 1
- 244000005706 microflora Species 0.000 description 1
- PQLXHQMOHUQAKB-UHFFFAOYSA-N miltefosine Chemical compound CCCCCCCCCCCCCCCCOP([O-])(=O)OCC[N+](C)(C)C PQLXHQMOHUQAKB-UHFFFAOYSA-N 0.000 description 1
- 230000002297 mitogenic effect Effects 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 230000004660 morphological change Effects 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- 231100000344 non-irritating Toxicity 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 231100000418 oral toxicity Toxicity 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 229910052762 osmium Inorganic materials 0.000 description 1
- SYQBFIAQOQZEGI-UHFFFAOYSA-N osmium atom Chemical compound [Os] SYQBFIAQOQZEGI-UHFFFAOYSA-N 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 229940124583 pain medication Drugs 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 229940067107 phenylethyl alcohol Drugs 0.000 description 1
- 229940096826 phenylmercuric acetate Drugs 0.000 description 1
- PDTFCHSETJBPTR-UHFFFAOYSA-N phenylmercuric nitrate Chemical compound [O-][N+](=O)O[Hg]C1=CC=CC=C1 PDTFCHSETJBPTR-UHFFFAOYSA-N 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 239000002797 plasminogen activator inhibitor Substances 0.000 description 1
- 239000002985 plastic film Substances 0.000 description 1
- 229920006255 plastic film Polymers 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229920006267 polyester film Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229910001414 potassium ion Inorganic materials 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- OJTDGPLHRSZIAV-UHFFFAOYSA-N propane-1,2-diol Chemical compound CC(O)CO.CC(O)CO OJTDGPLHRSZIAV-UHFFFAOYSA-N 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 150000003856 quaternary ammonium compounds Chemical class 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 229910052702 rhenium Inorganic materials 0.000 description 1
- WUAPFZMCVAUBPE-UHFFFAOYSA-N rhenium atom Chemical compound [Re] WUAPFZMCVAUBPE-UHFFFAOYSA-N 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- 210000003935 rough endoplasmic reticulum Anatomy 0.000 description 1
- 229910052701 rubidium Inorganic materials 0.000 description 1
- IGLNJRXAVVLDKE-UHFFFAOYSA-N rubidium atom Chemical compound [Rb] IGLNJRXAVVLDKE-UHFFFAOYSA-N 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 230000035807 sensation Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 238000007390 skin biopsy Methods 0.000 description 1
- 230000037394 skin elasticity Effects 0.000 description 1
- 239000000344 soap Substances 0.000 description 1
- 229910001415 sodium ion Inorganic materials 0.000 description 1
- 229940104870 sodium magnesium fluorosilicate Drugs 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 229940073743 steareth-20 methacrylate Drugs 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 239000002344 surface layer Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 229920002994 synthetic fiber Polymers 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 229940111630 tea tree oil Drugs 0.000 description 1
- 239000010677 tea tree oil Substances 0.000 description 1
- 229910052714 tellurium Inorganic materials 0.000 description 1
- PORWMNRCUJJQNO-UHFFFAOYSA-N tellurium atom Chemical compound [Te] PORWMNRCUJJQNO-UHFFFAOYSA-N 0.000 description 1
- 210000002435 tendon Anatomy 0.000 description 1
- GZCRRIHWUXGPOV-UHFFFAOYSA-N terbium atom Chemical compound [Tb] GZCRRIHWUXGPOV-UHFFFAOYSA-N 0.000 description 1
- 229910052716 thallium Inorganic materials 0.000 description 1
- BKVIYDNLLOSFOA-UHFFFAOYSA-N thallium Chemical compound [Tl] BKVIYDNLLOSFOA-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 229920001169 thermoplastic Polymers 0.000 description 1
- 239000004416 thermosoftening plastic Substances 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- FRNOGLGSGLTDKL-UHFFFAOYSA-N thulium atom Chemical compound [Tm] FRNOGLGSGLTDKL-UHFFFAOYSA-N 0.000 description 1
- 208000037816 tissue injury Diseases 0.000 description 1
- 239000012049 topical pharmaceutical composition Substances 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- WFKWXMTUELFFGS-UHFFFAOYSA-N tungsten Chemical compound [W] WFKWXMTUELFFGS-UHFFFAOYSA-N 0.000 description 1
- 229910052721 tungsten Inorganic materials 0.000 description 1
- 239000010937 tungsten Substances 0.000 description 1
- 102000009816 urokinase plasminogen activator receptor activity proteins Human genes 0.000 description 1
- 108040001269 urokinase plasminogen activator receptor activity proteins Proteins 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 210000003556 vascular endothelial cell Anatomy 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 229910052724 xenon Inorganic materials 0.000 description 1
- FHNFHKCVQCLJFQ-UHFFFAOYSA-N xenon atom Chemical compound [Xe] FHNFHKCVQCLJFQ-UHFFFAOYSA-N 0.000 description 1
- NAWDYIZEMPQZHO-UHFFFAOYSA-N ytterbium Chemical compound [Yb] NAWDYIZEMPQZHO-UHFFFAOYSA-N 0.000 description 1
- 229910052727 yttrium Inorganic materials 0.000 description 1
- VWQVUPCCIRVNHF-UHFFFAOYSA-N yttrium atom Chemical compound [Y] VWQVUPCCIRVNHF-UHFFFAOYSA-N 0.000 description 1
- 229910052726 zirconium Inorganic materials 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F13/00—Bandages or dressings; Absorbent pads
- A61F13/01—Non-adhesive bandages or dressings
- A61F13/01034—Non-adhesive bandages or dressings characterised by a property
- A61F13/01042—Absorbency
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F13/00—Bandages or dressings; Absorbent pads
- A61F13/00051—Accessories for dressings
- A61F13/00059—Accessories for dressings provided with visual effects, e.g. printed or colored
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F13/00—Bandages or dressings; Absorbent pads
- A61F13/00051—Accessories for dressings
- A61F13/00063—Accessories for dressings comprising medicaments or additives, e.g. odor control, PH control, debriding, antimicrobic
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F13/00—Bandages or dressings; Absorbent pads
- A61F13/01—Non-adhesive bandages or dressings
- A61F13/01034—Non-adhesive bandages or dressings characterised by a property
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F13/00—Bandages or dressings; Absorbent pads
- A61F13/01—Non-adhesive bandages or dressings
- A61F13/01034—Non-adhesive bandages or dressings characterised by a property
- A61F13/01038—Flexibility, stretchability or elasticity
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/02—Medicinal preparations containing materials or reaction products thereof with undetermined constitution from inanimate materials
- A61K35/08—Mineral waters; Sea water
-
- 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
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
-
- 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
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/42—Use of materials characterised by their function or physical properties
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/42—Use of materials characterised by their function or physical properties
- A61L15/46—Deodorants or malodour counteractants, e.g. to inhibit the formation of ammonia or bacteria
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/42—Use of materials characterised by their function or physical properties
- A61L15/60—Liquid-swellable gel-forming materials, e.g. super-absorbents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F13/00—Bandages or dressings; Absorbent pads
- A61F2013/00089—Wound bandages
- A61F2013/00157—Wound bandages for burns or skin transplants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
- A61L2300/204—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials with nitrogen-containing functional groups, e.g. aminoxides, nitriles, guanidines
- A61L2300/206—Biguanides, e.g. chlorohexidine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/404—Biocides, antimicrobial agents, antiseptic agents
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Biomedical Technology (AREA)
- Hematology (AREA)
- Inorganic Chemistry (AREA)
- Materials Engineering (AREA)
- Dermatology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Dispersion Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The present disclosure relates to topical compositions comprising water, solvent, thickener, preservative and conditioning agent wherein the composition has a viscosity in the range 200-6000 cP at 25°C following exposure to gamma radiation. Also disclosed is the use of the said composition in a dressing and the use of compositions and dressings in treatment or prophylaxis of burns. The conditioning agent is a mineral complex derived from seawater. The solvent is preferably 1,3-propane diol. The thickener is preferably an acryloyldimethyl- taurate/VP crosspolymer and the preservative is preferably a mixture of phenoxyethanol, caprylyl glycol, chlorphenesin and a polyaminopropyl biguanide (PHMB). The composition maintains its integrity upon irradiation with gamma radiation, i.e., does not lose viscosity, colour or become denatured.
Description
COMPOSITION
The present invention relates to topical compositions comprising water, solvent, thickener, preservative and conditioning agent wherein the composition has a viscosity approximately in the range 200-6000 cP at 25°C following exposure to gamma radiation, to use of the composition in a dressing and the use of compositions and dressings in treatment or prophylaxis of burns.
BACKGROUND
Approximately 1.4 million people sustain a burn injury each year in the USA alone. Of those, an estimated 54,000 to 180,000 are hospitalised. A burn is a type of injury to skin, or other tissues, caused by heat, cold, electricity, chemicals, friction, or radiation. Most burns are due to heat from hot liquids (scalds), solids or fire.
The skin is comprised of three major tissue layers: the epidermis, dermis and subcutaneous tissue. The epidermis is the outermost layer and has two components, the stratum corneum (comprised of anucleate cornified cells) and the Malpighian layers (viable cells under the stratum corneum). The stratum corneum acts as a barrier to microorganisms and toxins while allowing the body to retain water and electrolytes. The dermis is composed of dense fibroelastic connective tissue containing collagen, elastic fibres and grounds substance (an extracellular gel comprising mucopolysaccharides, salts, water and glycoproteins). The dermis is highly vascular and contains nerve networks and glands. Subcutaneous tissue is primarily areolar and fatty connective tissue and contains glands and hair follicles.
Burns that affect only the outermost skin layers are known as superficial or first-degree burns. They appear red without blisters and pain typically lasts around three days. When the injury extends into some of the underlying skin layer, it is termed a partial-thickness or second-degree burn. Blisters are frequently present and they are often very painful. Healing can require up to eight weeks and scarring may occur. In a full-thickness or third-degree burn, the injury extends to all layers of the skin. Often there is no pain and the burn area is stiff. Healing typically does not occur on its own, requiring skin grafting. A fourth-degree burn additionally involves injury to deeper tissues, such as muscle, tendons, or bone. The burn is often black and frequently leads to loss of the burned part.
When skin is burned, damage to the stratum corneum allows the invasion of microorganisms. The Langerhans cells, which mediate immune response, are also damaged. In severe burn injuries, systemic immune response can be so diminished as to make the patient susceptible to serious infection.
Treatment of burns depends on the severity of the burn. Superficial burns may be managed with little more than simple pain medication, while major burns may require prolonged treatment in specialised burn centres. Early cooling (within 30 minutes of the burn), typically with tap water, reduces burn depth and pain, but care must be taken as over-cooling can result in hypothermia. However, water is frequently not available, either at the site of the injury or in sufficient quantities. Partial-thickness burns may require cleaning with soap and water, followed by dressings. Fullthickness burns usually require surgical treatments, such as skin grafting.
The progression of burn injuries and the body's response to (thermal) burns is summarised in Edlich et al (2017) http://emedicine.medscape.eom/article/1278244-overview#showail
Many of the direct health effects of a burn are secondary to disruption in the normal functioning of the skin. They include disruption of the skin's sensation, ability to prevent water loss through evaporation and ability to control body temperature. Disruption of cell membranes causes cells to lose potassium to the spaces outside the cell and to take up water and sodium.
In large burns (over 30% of the total body surface area), there is a significant inflammatory response. This results in increased leakage of fluid from the capillaries, and subsequent tissue oedema. This causes overall blood volume loss, with the remaining blood suffering significant plasma loss, making the blood more concentrated. Poor blood flow to organs such as the kidneys and gastrointestinal tract may result in renal failure and stomach ulcers.
Wound healing progresses via three overlapping phases: inflammation, granulation and remodelling. Following a cutaneous injury, a blood clot forms and inflammatory cells infiltrate the wound, secreting cytokines and growth factors. During granulation, fibroblasts and other cells differentiate into myofibroblast which deposit extracellular matrix proteins. At the same time, angiogenesis occurs and keratinocytes proliferate and migrate to close the wound. In the remodelling phase apoptosis eliminates myofibroblasts and extraneous blood vessels and the extracellular matrix is remodelled to resemble the original tissue. Dysregulation of the remodelling phase leads to the formation of scar tissue (fibrosis).
The healing of burns progressing in essentially the same manner as all cutaneous injuries. However, the main difference is the amount of necrotic tissue, that is, tissue which is damaged beyond repair that occurs in a burn versus a cut (for example).
It is desirable to save as much of the damaged and inflamed tissue surrounding the necrotic tissue as possible following a burn and in doing so improve and speed up the wound healing ability of surrounding cells to recuperate and form a protective barrier. This allows the healing process to begin faster and improves the healing process.
It is important that any dressing applied to a burn be sterile. Irradiation is a common method of sterilising, typically employing gamma radiation. Sterilisation by gamma irradiation is aimed at reducing the bioburden (that is, the CFUs). Unfortunately, it is not uncommon for a composition or formulation to lose its integrity following irradiation, for example, a composition may become discoloured or less viscous or active ingredients be denatured. It can be a significant challenge to formulate a composition that is resistant to irradiation.
Patent EP0521143 discloses a burn dressing that can be applied to a burn in place of cool water. The dressing comprises a composition comprising tea tree oil and a carrier which is a two-layer nonwoven material. The product is known to be suitable for treatment of both wet and dry burns since they stop the burning process, cool the burned area, relieve pain, prevent further injury and do not contribute to hypothermia or interfere with debridement (removal of damaged tissue or foreign objects from a wound). There are no active ingredients within the composition. The dressing conforms to the uneven burn surface and draws the heat out of a burn by spreading it over the whole gel surface.
Thus, there is a requirement for a composition suitable for application to a burn or a burn dressing that can be applied immediately following a burn injury to cool the burn whilst providing long term benefits to improve wound healing. It is further essential that the composition or dressing be sterile or sterilisable, preferably by means of gamma irradiation.
SUMMARY OF INVENTION
In a first aspect there is provided a topical composition comprising water, solvent, thickener, preservative and conditioning agent wherein the composition has a viscosity approximately in the range 200-6000 cPs at 25°C following exposure to gamma radiation.
The topical composition has particular benefits for the treatment or prophylaxis of burns.
Advantageously, a composition comprising water, solvent, thickener, preservative and conditioning agent is robust during irradiation to sterilise the composition or dressing when the composition is absorbed onto a dressing material. For example, using gamma radiation the composition is substantially unchanged following irradiation. Specifically, the composition following irradiation is a slightly viscous formulation able to sit on the skin following application to a discrete area or to be absorbed onto a dressing material.
In one embodiment there is provided a composition for primary treatment of burns.
Primary treatment as employed herein means treatment immediately following or shortly after a burn, for example within a few seconds to a few hours of the burn, such as within 11,10, 9, 8, 7, 6, 5, 4, 3, 2 or 1 hour or less, particularly within less than 1 hour.
In one embodiment there is provided a composition for moisturising and maintaining the integrity of the affected skin.
In a further aspect there is provided a topical composition according to the disclosure for use as a medicament.
In a further aspect there is provided a topical composition according to the invention for use in the treatment or prophylaxis of burns.
In a yet further aspect there is provided a burn dressing comprising a topical composition according to the invention and a dressing material.
In a further aspect there is provided a method of sterilising a topical composition or a burn dressing according to the invention comprising applying gamma radiation of approximately 25.0 to 44.5 kGy to the composition or dressing.
In a yet further aspect there is provided a composition or a burn dressing according to the disclosure which has been sterilised using the method of the disclosure.
In a further aspect there is provided a kit of parts comprising a composition according to the disclosure and a dressing material.
In a yet further aspect there is provided a method of prophylaxis or treatment of a burn comprising the step of applying a topical composition or a burn dressing according to the invention to skin in need thereof.
The present disclosure for the first time provides a specialised and safe composition or dressing for soothing and promoting healing and regeneration of burn damaged tissue.
BRIEF DESCRIPTION OF THE FIGURES
Figure 1 shows the results of a wound healing assay - Human Primary Dermal Fibroblast data plot Cell index v time.
Figure 2 shows Human Primary Keratinocyte cells cell index v time.
Figure 3a shows RT2 qPCR of fibroblast monoculture comparing cells exposed to WJ24 versus a control (untreated cells).
Figure 3b shows RT2 qPCR of fibroblast monoculture comparing cells exposed to WJ24 at higher concentration versus a control (untreated cells).
Figure 4 shows a representation of the LabSkin system including a cross section through the striated skin. Well insert contains cultured cells in 3D fibrin scaffold.
Figure 5a shows the brass weights that we employed in inflicting thermal burn injury and Figure 5b shows the location of subsequent skin biopsies following burn injury.
Figures 6a and 6b show the damaged (burned) skin 24 hours after burn inflicted.
Figure 7a shows tissue dielectric constant (TDC) as an index of localised skin water content in control model (Figure 7a) and when treated with mineral complex (Figure 7b).
Figure 8a shows wound healing PCR arrays revealing up- and down-regulated genes in 3D skin models in response to thermal burn injury (no treatment) vs healthy skin. Total RNA from 3D skin models were characterised, and the relative expression levels for each gene in the two samples (burn vs healthy skin) are plotted against each other in the Scatter Plot.
Figure 8b shows wound healing PCR arrays revealing up- and down-regulated genes in 3D skin models in response to treatment with NB105-146 (gel formulation without mineral complex) for thermal burn injury. Total RNA from 3D skin models were characterised, and the relative expression levels for each gene in the two samples (treated vs burn (untreated) skin) are plotted against each other in the Scatter Plot.
Figure 8c shows wound healing PCR arrays revealing up- and down-regulated genes in 3D skin models in response to treatment with NB105-142 (gel formulation with mineral complex) for thermal burn injuries. Total RNA from 3D skin models were characterised, and the relative expression levels for each gene in the two samples (treated vs Burn (untreated) skin) are plotted against each other in the Scatter Plot.
DESCRIPTION
Burn as employed herein means an injury to skin, or other tissues, caused by heat, cold, electricity, chemicals, friction, or radiation. Compositions of the present disclosure are particularly beneficial in the treatment and prophylaxis of thermal and radiation burns although they can be employed in the treatment of any burn, including chemical burns.
In one embodiment the composition is suitable for the treatment or prophylaxis of burns, such as thermal or radiation burns, particularly thermal burns.
In one embodiment there is provided a composition for use in the treatment or prophylaxis of burns, such as thermal or radiation burns, particularly thermal burns.
As employed herein thermal burns refers to burns that are not chemical or radiation burns.
In one embodiment there is provided a composition for use in the prophylaxis of radiation burns.
Prophylaxis as employed herein refers to the prevention of condition aimed at stopping the condition developing or progressing, such as a burn or burns.
Treatment as employed herein refers to the reversal of a condition, amelioration or relief of symptoms associated with a condition or prevention of further development/worsening of a condition, such as a burn or burns.
Composition
In one embodiment there is provided a topical composition comprising water, solvent, thickener, preservative and conditioning agent wherein the composition has a viscosity approximately in the range 200-6000 cP at 25°C following exposure to gamma radiation.
Topical composition as employed herein means preparation that is applied to the surface of the body, such as the skin, including but not limited to a cream, foam, ointment, paste, lotion or gel, including a hydrogel.
In one embodiment the topical composition is a fluid or a gel.
Water as employed herein typically refers to purified water that has been cleaned and/or filtered to be suitable for topical application. Water may refer to tap water, purified water, sterile water, halogenated water (especially chlorinated water), and mixtures thereof. As employed herein, water has a heat-absorbing function, aimed at cooling the sensation of heat in the skin following a burn. The water also acts as a solvent. Water as employed herein has the CAS number 7732-18-5 as defined by the chemical abstract service.
In one embodiment the water is purified water. In one embodiment the water is present at approximately 85-95% w/w of the total composition, such as approximately 85.5, 86, 86.5, 87, 87.5, 88, 88.5, 89.5, 90, 90.5, 91, 91.5, 92, 92.5, 93, 93.5, 94 or 94.5% w/w of the total composition, for example approximately 89.45% w/w of the total composition. In one embodiment, the balance of the composition, following addition of other components, is water.
Solvent as employed herein means a substance (a liquid) that dissolves a solute (a chemically distinct liquid, solid or gas), resulting in a solution.
In one embodiment the solvent is present at approximately 5-10% w/w of the total composition, such as approximately 6, 7, 8 or 9% w/w of the total composition, for example approximately 8% w/w of the total composition.
In one embodiment the solvent is propanediol. In one embodiment the propanediol comprises approximately 5-10% w/w of the total composition, such as approximately 6, 7, 8 or 9% w/w of the total composition, for example approximately 8% w/w of the total composition.
Propanediol as employed herein means 1,3-propanediol, a chemical according to formula (I)
HO OH
Propanediol as employed herein has the CAS number 504-63-2.
Thickener or thickening agent as employed herein is an ingredient or ingredients that increase the viscosity of a composition without substantially altering its other properties. Examples of thickening agents include polysaccharides such as gums, starches, in particular corn starch, carbomers, gelling agents and acrylates such as sodium acryloyldimethyltaurate/VP crosspolymer (Aristoflex AVS ®).
In one embodiment the thickener comprises approximately 0.5-1.0% w/w of the total composition, such as approximately 0.55, 0.6, 0.65, 0.7, 0.75, 0.8, 0.85, 0.9 or 0.95% w/w of the total composition, for example approximately 0.8% w/w of the total composition.
In one embodiment the thickener is sodium acryloyldimethyltaurate/VP crosspolymer. Sodium acryloyldimethyltaurate/VP crosspolymer as employed herein has the CAS number 1176663-96-9. In one embodiment the sodium acryloyldimethyltaurate/VP crosspolymer comprises approximately 0.5-1.0% w/w of the total composition, such as approximately 0.55, 0.6, 0.65, 0.7, 0.75, 0.8, 0.85, 0.9 or 0.95% w/w of the total composition, for example approximately 0.8% w/w of the total composition.
Preservative as employed herein refers to a substance that prevents decomposition or contamination either by microorganisms or by chemical change. Typical preservatives suitable for topical compositions include, but are not limited to, phenoxyethanol, ethylhexylglycerine, caprylyl glycol, chlorphenesin, quaternary ammonium compounds, such as benzalkonium chloride, benzethonium chloride, cetrimide, dequalinium chloride, and cetylpyridinium chloride; mercurial agents, such as phenylmercuric nitrate, phenylmercuric acetate, and thimerosal; alcoholic agents, for example, chlorobutanol, phenylethyl alcohol, and benzyl alcohol; antibacterial esters, other examples include, esters of parahydroxybenzoic acid; and other anti-microbial agents such as chlorhexidine, chlorocresol, benzoic acid and polymyxin.
In one embodiment the preservative comprises approximately 0.5-2.0% w/w of the total composition, such as approximately 0.55, 0.6, 0.65, 0.7, 0.75, 0.8, 0.85, 0.9, 0.95, 1.0, 1.05, 1.1, 1.15, 1.2, 1.25, 1.3, 1.35, 1.4, 1.45, 1.5, 1.55, 1.6, 1.65, 1.7, 1.75, 1.8, 1.85, 1.9 or 1.95% w/w of the total composition, for example approximately 1.5% w/w of the total composition.
In one embodiment the composition comprises one or more preservatives from the group consisting: phenoxyethanol and caprylyl glycol and chlorphenesin (commercially known as MikrokilI ®COS) and (PHMB) polyaminopropyl biguanide.
In one embodiment the preservative is phenoxyethanol and caprylyl glycol and chlorphenesin (Mikrokill ®) and (PHMB) polyaminopropyl biguanide.
In one embodiment the phenoxyethanol and caprylyl glycol and chlorphenesin (Mikrokill ®COS) comprises approximately 0.5-1.5% w/w of the total composition, such as approximately 0.55, 0.6,
0.65, 0.7, 0.75, 0.8, 0.85, 0.9, 0.95, 1.0, 1.05, 1.1, 1.15, 1.2, 1.25, 1.3, 1.35, 1.4 or 1.45% w/w of the total composition, for example approximately 1.0% w/w of the total composition.
As employed herein phenoxyethanol & caprylyl glycol & chlorphenesin is the INCI name for Mikrokill ®COS and has the CAS number 122-99-6/1117-86-8/104-29-0.
The composition may comprise approximately 0.25-0.75% (PHMB) polyaminopropyl biguanide, in particular approximately 0.5% (PHMB) polyaminopropyl biguanide.
The composition may comprise approximately 0.05-0.15% (PHMB) polyaminopropyl biguanide, in particular approximately 0.1% (PHMB) polyaminopropyl biguanide.
In one embodiment the (PHMB) polyaminopropyl biguanide comprises approximately 0.25-0.75% w/w of the total composition, such as 0.3, 0.35, 0.4, 0.45, 0.5, 0.55, 0.6, 0.65 or 0.7% w/w of the total composition, for example approximately 0.5% w/w of the total composition. (PHMB) polyaminopropyl biguanide as employed herein has the CAS number 133029-32-0/27083-27-8. polyaminopropyl biguanide is the INCI name. PHMB (polyhexamethylene biguanide) is the chemical name. In one embodiment the (PHMB) polyaminopropyl biguanide is provided as a 20% solution, thus 0.5% of the solution contains 0.1% (PHMB) polyaminopropyl biguanide on a pure basis.
In one embodiment the (PHMB) polyaminopropyl biguanide comprises approximately 0.05-0.15% w/w of the total composition, such as 0.06, 0.07, 0.08, 0.09, 0.1, 0.11, 0.12, 0.13 or 0.14 % w/w of the total composition, for example approximately 0.1% w/w of the total composition. (PHMB) polyaminopropyl biguanide as employed herein has the CAS number 133029-32-0/27083-27-8. polyaminopropyl biguanide is the INCI name. PHMB (polyhexamethylene biguanide) is the chemical name. Typically, the (PHMB) polyaminopropyl biguanide is provided as a 20% solution, thus 0.1% of the solution contains 0.02% (PHMB) polyaminopropyl biguanide on a pure basis.
In one embodiment there is provided a topical composition comprising approximately 1.0% w/w phenoxyethanol and caprylyl glycol and chlorphenesin plus an additional approximately 0.5% w/w (PHMB) polyaminopropyl biguanide (20% solution).
In one embodiment there is provided a topical composition comprising approximately 1.0% w/w phenoxyethanol and caprylyl glycol and chlorphenesin plus an additional approximately 0.1% w/w (PHMB) polyaminopropyl biguanide (20% solution).
Conditioning agent as employed herein means an agent designed to improve the condition of the skin. In some embodiments the conditioning agent is beneficial to wound healing, specifically to burn healing.
In one embodiment the conditioning agent comprises approximately 0.1-1.0% w/w of the total composition, such as approximately 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 0.55, 0.6, 0.65, 0.7, 0.75, 0.8, 0.85, 0.9 or 0.95% w/w of the total composition, for example approximately 0.25% w/w of the total composition.
In some embodiments the conditioning agent is a mineral complex. In one embodiment the mineral complex comprises approximately 0.1-1.0% w/w of the total composition, such as approximately
0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 0.55, 0.6, 0.65, 0.7, 0.75, 0.8, 0.85, 0.9 or 0.95% w/w of the total composition, for example approximately 0.25% w/w of the total composition.
Mineral complex as employed herein refers to a complex of several minerals, typically including, but not limited to magnesium, potassium, sodium, boron, calcium. The conditioning agent/mineral complex is described in further detail below.
Viscosity as employed herein is a measure of a fluid's resistance to flow. It corresponds to a notional thickness of a liquid and is measured in cP (centipoise). Centipoise is a measure of viscosity on the CGS (centimetre gram second) scale. Water has a viscosity of 1 cP at 20°C. Viscosity can be measured using a Brookfield viscometer, such as a Brookfield DV II Pro. Generally, viscosity is measured at room temperature, such as 20 to 25°C, preferably 25°C.
In one embodiment there is provided a topical composition with a viscosity (at approximately 25°C) in the range approximately 100 to 6000 cP, such as approximately 100, 150, 200, 250, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 950, 1000, 1100, 1200, 1300, 1400, 1500, 1600, 1700,
1800, 1900, 2000, 2100, 2200, 2300, 2400, 2500, 2600, 2700, 2800, 2900, 3000, 3100, 3200, 3300,
3400, 3500, 3600, 3700, 3800, 3900, 4000, 4100, 4200, 4300, 4400, 4500, 4600, 4700, 4800, 4900,
5000, 5100, 5200, 5300, 5400, 5500, 5600, 5700, 5800 or 5900 cP, for example approximately 2006000 cP.
In one embodiment the composition has a viscosity in the range 200 to 6000 cP measure using spindle #63 spindle @ 12 RPM.
As employed herein, in relation to the constituents of the composition, all % are % w/w of the total composition.
Exposure to gamma radiation as employed herein means exposure to electromagnetic radiation typically having energy above 100 keV, frequencies above 10 exahertz (or >1019 Hz) and wavelengths less than 10 picometers (10-11 m). Typically, the gamma radiation is employed as irradiation to sterilise the composition or dressing.
In one embodiment the gamma radiation sterilises the composition or dressing. In one embodiment the gamma radiation is bacteriostatic. In one embodiment the gamma radiation is fungistatic. In one embodiment the gamma radiation reduces or eliminates the bioburden of the composition or dressing.
In one embodiment the gamma irradiation is cobalt 60 irradiation.
In one embodiment the gamma radiation is irradiation at approximately 20-50 kGy, such as approximately 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48 or 49 kGy, for example approximately 25-44.5 kGy or 25 kGy or more.
In one embodiment there is provided a composition comprising or consisting approximately: 85-95% purified water, 5-10% solvent, 0.5-1.0% thickener, 0.5-2.0% preservative, 0.1-1.0% conditioning agent wherein each % means % w/w of the total composition.
In one embodiment there is provided a composition consisting essentially of 89.45% purified water, 8% propanediol, 0.8% sodium acryloyldimethyltaurate/VP crosspolymer, 1% phenoxyethanol and caprylyl glycol and chlorphenesin, 0.25% mineral complex and 0.5% (PHMB) polyaminopropyl biguanide (20% solution). In one embodiment the viscosity of the composition is approximately in the range 200 to 6000 cP.
In one embodiment there is provided a composition consisting essentially of 8% propanediol, 0.8% sodium acryloyldimethyltaurate/VP crosspolymer, 1% phenoxyethanol and caprylyl glycol and chlorphenesin, 0.25% mineral complex and 0.1% (PHMB) polyaminopropyl biguanide (20% solution) and purified water to make to 100%, such as approximately 89.85% purified water. In one embodiment the viscosity of the composition is approximately in the range 200 to 6000 cP.
The high water content of the composition enables it to absorb heat from the skin. Whilst not wishing to be bound by theory, the present inventors believe that this helps to reduce the development of burn by reducing the layers of skin cells permeated by the heat associated with burns.
In one embodiment the composition has a specific gravity of approximately 1.000±0.05 at 25°C.
In one embodiment the composition has a pH of approximately 5.5-7.5 at 25°C, such as approximately 5.0, 5.5, 6.5, 6.5 or 7.0, for example approximately 5.0-7.0.
In one embodiment the composition has a pH of approximately 4.0-6.5 at 25°C, such as approximately 4.5, 5.0, 5.5 or 6.0, for example approximately 4.0-6.5.
In one embodiment the topical composition is a fluid.
Fluid as employed herein means a low viscosity topical composition for application to unbroken skin. By contrast, creams and gels, including hydrogels, have a higher viscosity.
Advantageously, a lower viscosity means that the fluid is more easily absorbed by the skin and is easier to spread on the skin because it is less likely to drag the skin surface. This can be particularly useful where the patient is suffering pain or loss of skin integrity at the treatment site.
In one embodiment the composition is cooling.
In one embodiment the composition is anti-inflammatory.
In one embodiment the composition relieves pain.
In one embodiment the composition hydrates the skin.
A critical aspect of the present disclosure is the absorption of heat from the skin by the composition.
Thus, a critical aspect of the present disclosure is the reduction of the loss of skin fluid/moisture and structure by the composition.
In one embodiment there is provided a composition according to the disclosure for use as a medicament.
In one embodiment there is provided a composition according to the disclosure for use in the treatment or prophylaxis of burns. In one embodiment the burn is a thermal burn. In one embodiment the burn is a radiation burn. In one embodiment the burn is a chemical burn.
In one embodiment treatment with the composition relieves pain.
In one embodiment treatment with the composition reduces burning.
In one embodiment treatment with the composition reduces itching.
In one embodiment the composition is antimicrobial. In one embodiment the composition is antibacterial. In one embodiment the composition is antifungal.
As employed herein antimicrobial means that the composition is microbistatic or microbicidal. That is, it hinders the growth of, or kills microbes, including bacteria, fungi, viruses, protozoa, algae, amoebae and slime molds.
In one embodiment the composition increases perfusion. That is, is the passage of fluid through the circulatory system or lymphatic system to the skin, such as the site of the burn.
In one embodiment the composition reduces cell death. Advantageously, reducing cell death reduces the extent and severity of the burn.
In one embodiment the composition reduces scarring. Without wishing to be bound by theory, the inventors believe that the composition reduces dysregulation of tissue remodelling phase of wound healing.
In one embodiment the composition is antithrombotic.
In one embodiment the composition reduces the depth of a burn.
In one embodiment the composition accelerates healing of the burn.
In one embodiment the composition decreases the likelihood of a biofilm forming.
In one embodiment the composition reduces tissue necrosis.
In one embodiment the composition reduces bioburden of the burn.
In one embodiment the composition has substantially no oral toxicity.
In one embodiment there is provided a composition comprising water and one or more ingredients from the list consisting: propanediol, sodium acryloyldimethyltaurate/VP crosspolymer, phenoxyethanol and caprylyl glycol and chlorphenesin, mineral complex and (PHMB) polyaminopropyl biguanide. Optionally the composition has a viscosity in the range 200-6000 cP. Optionally the viscosity of the composition is measured following exposure to gamma radiation.
Conditioning Agent
Conditioning agents may have beneficial properties for wound healing. Without wishing to be bound by theory, it is believed that, following a burn injury, the body withdraws minerals from the skin it considers to be lost (that is, skin that will become necrotic). By replacing those minerals, in a bioavailable form, externally, it is possible to save more of the skin from becoming necrotic and hence lost, thus requiring grafting therapy, or developing scarring.
Thus, in one embodiment the conditioning agent is a mineral complex. In one embodiment the mineral complex comprises bioavailable minerals, such as ion, free ions, elemental, or bound minerals, for example free ions.
Advantageously, it has been found that providing bioavailable minerals to a burn wound helps rebalance the immune response by reducing the inflammatory response.
In one embodiment the mineral complex comprises magnesium, potassium, sodium, boron, calcium and optionally one or more from the group consisting: copper, nickel, silicon, zinc, aluminium, arsenic, barium, cadmium, cobalt, chromium, iron, mercury, manganese, lead, antimony, selenium, tin, strontium, titanium and vanadium.
In one embodiment the mineral complex is sea water extract. As employed herein sea water extract is the INCI name.
As employed herein sea water extract may be harvested from a deep sea source. Typically, the sea water extract is a concentrated solution of deep sea water minerals wherein the amount of sodium and/or chlorine has been reduced and/or substantially eliminated.
In one embodiment the sea water extract is dead sea salt, Cornish sea salt, Maldon sea salt, Himalayan sea salt and the like.
In one embodiment the mineral complex is Epsom salts.
In one embodiment the sea water extract is the INCI and IUPAC name.
In one embodiment the sea water extract is Deep Sea Water provided by Morechem. In one embodiment the sea water extract is Eau de Source Marine SC, Ocaline or Ocaline XP provided by Soliance (Givaudan) or the like.
In one embodiment the conditioning agent is added to the composition in liquid form, such as a concentrate of sea water.
In one embodiment the conditioning agent is added to the composition in dried form. For example, as dried, concentrate of sea water.
In one embodiment the mineral complex does not comprise bound minerals such a magnesium sulphate/oxide/citrate.
In one embodiment the mineral complex comprises free magnesium, such a Mg2+ ions. In one embodiment the major component of the mineral complex is magnesium.
In one embodiment the mineral complex comprises potassium, such as free potassium, such as K+ ions.
In one embodiment the mineral complex comprises sodium, such as free sodium, such as Na+ ions.
In one embodiment the mineral complex comprises boron, such as free boron, such as boron anions or boron cations.
In one embodiment the mineral complex comprises calcium, for example free calcium, such as Ca2+ ions.
A further aspect is the healing of the skin by the mineral complex.
It is known that magnesium depletion and hypocalcaemia (calcium depletion) occur in children and adults with (severe) burns. These losses occur through the burn wound and possibly through abnormal intestinal secretion. Increases in metabolism in burn patients may promote Mg uptake, thereby reducing Mg serum levels. Thus, it is hypothesised that providing magnesium (and calcium) to the site of a burn helps to compensate for the depletion that otherwise occurs. Given that Mg is an important cofactor in cyclic AMP production (which is obviously increased as metabolism increases), depletion of Mg can lead to hindered cAMP production.
Thus, without being bound by theory, it is proposed that providing magnesium at the site of the burn helps improve the wound healing process.
In one embodiment the mineral complex provides bioavailable minerals, such as magnesium.
In one embodiment the mineral complex has substantially no chloride or chlorine.
In one embodiment the sea water extract is Oriel sea water extract (orielmarineextracts.com) provided by Oriel Sea Salt Co.
In one embodiment the sea water extract has a pH of approximately 7 to 8, such as approximately 7.4.
In one embodiment the sea water extract has a density of approximately 40%.
Table 1 shows the components of sea water.
Element | Atomic weight |
Hydrogen H2C3 | 15829 |
Οχναβη H2Q | 15599 |
Sodium Had | 22539 |
Chlerme HaCi | 35,453 |
lOsenasium Me | 24,312 |
Sulfur S | 32.864 |
Potassium K | 39.102 |
Calcium Ca | 20.880 |
Bromine Or | 79.989 |
Helium Ke | 45826 |
Libhiure Li | 6.94 |
Beryllsum Be | 85333 |
Buren B | 10511 |
Carbon C | 12,011 |
nitrogen ion | 14,08? |
Fluorine F | 18,998 |
No ms He | 20.163 |
Al uminium Al | 26.982 |
35iom< si | 28.886 |
Phosphorus P | :30.974 |
Argun Ar | 39.940 |
Guandium So | 44.986 |
Titanium Ti | 47.988 |
Vanadium V | 88.942 |
Chromium Cr | 81596 |
Manganese Mn | 84536 |
Ferrum (Iron) Fe | 55547 |
Cuboil: Ce | 5353:3 |
Nlokel Hi | 53,718 Yxxxxxxxxxxxxxxxxxxxxd |
Copper Co | 68.54 |
Einc En | 65.:37 |
Gallium Sa | 69.32 |
Germenium Ge | 72.89 |
Arsenis As | 74.922 |
Selenium Sa | 7358 |
Krypton Xr | 8353 |
Rubidium Rb | 85.42 |
Strontium Sr | 07,62 |
Yttrium Y | 88,988 |
Zirconium Zr | 91.22 |
Hiohiurn Mb | 92.986 |
ppm | Element | Atomw: | ppm | |
I | weight | ||
..... 118,888 1 Moiybcisnum Msj | 8.09594 | 8,01 | |
533.083 I Puthenium Ru | 181.07 | 8,8888807 : | |
18.888 I Rhodium Rh | 182.985 | ((((((((((((((((((((((((((((y(((: | |
19480 I Palladium Pd | 188.4 | ((((((((((((((((((((((((((((,(((( | |
1.290 1 Argentum (silver) Ag | 187.870 | 0.88828 : | |
984 | Cadmium Cd | 112.4 | 0.80011 : | |
292 I Indium In | 13452 | ((((((((((((((((((((((((((((,<((( | |
4.11 | Stannum (tin.) 5n | 11359 | 8-80881 : | |
87.3 | Anhmany Sb | 181.75 | 3,83033 | |
8.8888872 | Tellurium Te | 127,6 | |
8.178 | ksuh'siS I | 1.66,984 | 0.864 : |
8.8888888 | Xenon Xe | 131,38 | 8,083847 : |
4,453 | Cesium i s | 132.985 | 8580:3 : |
28.8 | Barium Be | 137.34 | <::<<:< : |
155< | Lanthanum La | 138.91 | 0,8880829 : |
X3 | Cerium Ce | 148.12 | 8,8880812 : |
8,88812 | Prae sady mi urn Pr | 148.987 | 8,88380864 : |
8.881 | h'eedymium Nd | 144.84 | 3.06800:28 : |
2/4 | Semerlum Sm | 158.25 | 8,88000845 : |
8.888 | Europium Eu | 15156 | 05080023 : |
8.458 | Gasfossnium Gd | 111.21 | 0.-8000807 : |
<8 >888884 | Terbium Tb | 158,924 | 8.88088814 : |
8,881 | 0 ysprosium Dy | 15250 | 8.88088891 : |
2.8819 | Holmium Ho | 164,938 | 8.88088822 : |
8.8882 | Erbium Er | 1.67,26 | 8.88888837 : |
C.'s^C.'O4 | Thulium Tm | 168,934 | 858003817 : |
8.8834 | Ytterbium Yb | 17:3.04 | 8.68066802 : |
8.88889 | lutebum Lu | 174.97 | 050000016 : |
8.6866 | Hafnium Hf | 178.49 | •<0.800800 |
8.8889 | Tarstaiwn Ta | 188.948 | «3,8300825 |
8.888 | Tungsten W | 13355 | <0.000801 : |
8.08303 | Rhenium Re | 186,2 | 0.-8000804 : |
8.88886 | Osmium Os | 190,2 | 1:1: (: 1: :(((:(^:(((:(^^^^^^^^^^^^^^ |
8.8828 | Iridium Ir | 292,2 | (((((((((((;(((((((((((((((((<(((( |
8.8889 | Platinum Pi | 195,09 | ((((((((((((((((((((((((((((Λ(((( |
8.88821 | Aarum (quid; Au | 196,967 | 8,0838.11 : |
8,128 | Merour? Ho | 288.59 | 0.80015 : |
8.1 | Thallium Ti | 284.37 | (((((((((((((((((((((((((((((.(((I |
8.888818 | Lead Pb | 287.19 | 0.80063 : |
V.' Χλ-ίΟ OcL 6.' | Bismuth bi | 288580 | 0.80062 : |
8,0888.15 | TbesriusS! Th | 28254 | 0.8080864 : |
Lirenium U | 23853 | 8.0833 : | |
Plutonimu Pu | (244) | • |
Table 1
In one embodiment the mineral complex comprises approximately: 66% magnesium, 23.8% potassium, 9.8% sodium, 0.002% boron, 0.0006% calcium, 0.00002% copper, 0.000012% nickel,
0.0000087% silicon and 0.000001% zinc. Wherein approximately is defined to be ±15%. In one embodiment the mineral complex further comprises trace elements. In one embodiment the trace elements include one or more from the group: aluminium, arsenic, barium, cadmium, cobalt, chromium, iron, mercury, manganese, lead, antimony, selenium, tin, strontium, titanium and vanadium. In one embodiment the trace elements may be any element selected from table 1.
In one embodiment the mineral complex comprises one or more minerals according to table 1.
Dressing Material
A burn dressing in accordance with the present disclosure is formed by impregnating a suitable dressing material with the composition of the disclosure.
Dressing material as employed herein means a fabric carrier capable of holding a chosen volume of composition. Preferably the dressing material is a non-woven synthetic material that will hold a substantial quantity of the composition to apply an effective amount of the composition to a burn. The dressing material must be capable of being sterilised, typically by irradiation, such as gamma irradiation and non-irritating to burned skin.
In one embodiment there is provided a burn dressing comprising a topical composition according to the disclosure and a dressing material.
In one embodiment the dressing material comprises thermal bonded, non-woven material.
In one embodiment the dressing material is polyester, PET (polyethylene terephthalate) or the like, such as medical grade non-woven 100% polyester fabric, for example polypropylene or rayon.
Thermal bonded as employed herein means a fabric wherein heat energy is used to stimulate an adhesive, which in turn flows to thermoplastic fibre juncture and interlocks the fibres upon cooling.
Non-woven as employed herein refers to sheet or web structures bonded together by entangling fibre or filaments (and by perforating films) mechanically, thermally or chemically. They are flat, porous sheets that are made directly from separate fibres or from molten plastic or plastic film.
In one embodiment the dressing material comprises super absorbent material, such as super absorbent fibre.
Super absorbent materials have an absorbent capacity of several times their weight. Super absorbent fibres are fibrous form of super absorbent material which can be incorporated into woven or non-woven materials.
In one embodiment the dressing material comprises polypropylene fibre and rayon fibre.
In one embodiment the dressing material comprises super absorbent fibre, polypropylene fibre and rayon fibre.
In one embodiment the dressing material comprises approximately 10-40% super absorbent fibre, such as approximately 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38 or 39% super absorbent fibre, for example approximately 20% super absorbent fibre.
In one embodiment the dressing material has one of more of the properties selected from the group consisting: a weight of approximately 50gsm, a thickness of approximately 0.63mm, a tensile strength of approximately 4.2 N or 24.3 N, an absorbent capacity of approximately 22.7g/g and an absorbent volume of approximately >1150 gsm.
In one embodiment the dressing material is type 2741 fabric as provided by Technical Absorbents.
In one embodiment the dressing has a width of approximately 5cm to 50cm and a length of approximately 5cm to 50cm. Such as approximately 6, 7, 8, 9, 10, 11, 12, 13, 14, 15,16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, or 49 cm width and/or length.
In one embodiment the dressing material holds approximately 15 to 30 grams of composition per gram, such as approximately 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28 or 29 grams of composition per gram, for example approximately 22.7g/g.
In one embodiment the dressing material holds approximately 1000 to 2000 g of composition per square metre of dressing material, such as approximately 1100, 1200,1300,1400, 1500, 1600,1700, 1800 or 1900 g of composition per square metre of dressing material. For example, approximately 1674 g of composition per square metre of dressing material.
In one embodiment the dressing is of shape and dimension suitable for application to the face. In such embodiment the dressing may have slots or holes for the eyes and/or nose and/or mouth.
In one embodiment the dressing material has pockets in which the composition may be placed. For examples, see EP0521143 which is incorporated herein by reference.
Sterilisation
In one embodiment the composition or dressing is sterilised, for example by heat (such as by steam or dry heat), irradiation (such as electron beam or gamma radiation), gas (such as ethylene oxide or formaldehyde) or low temperature oxidative sterilisation (such as vaporised hydrogen peroxide, hydrogen peroxide/ gas plasma).
In one embodiment the composition or dressing is sterilised by gamma irradiation.
In one embodiment the gamma irradiation is cobalt 60 or caesium 137 radiation, particularly cobalt 60 radiation.
In one embodiment the composition or dressing is irradiated to meet 10E6 sterility assurance level (SAL).
In one embodiment the sterilisation method is AAMI11137-2 compliant.
Advantageously, compositions and dressing that have been sterilised employing the method have substantially zero bioburden. That is, they have zero CFUs. Such as no microbe that can replicate or grow.
Packaging
In one embodiment the burn dressing as disclosed herein is packaged into a storage pouch. Advantageously, the storage pouch permits the dressing to remain sterile and be easily transported, for example is a first aid kit or medical kit, such as for use by a paramedic.
Typically, the storage pouch has a three-layer construction of a layer of polyester having a layer of aluminium thereon and a layer of, for example, Scotchpak ® heat sealable polyester film thereof. The three layers are adhered with adhesive.
The compositions, dressings and methods of the present disclosure when employed help maintain skin integrity, minimise the deleterious effects of burns and reduce opportunistic infections that may occur when skin is damaged.
The maintenance of moisture around the burn may also minimise scarring and prevent reduced flexibility in the area of skin damage. This is advantageous because it may reduce pain associated with scar tissue and avoids skin thickening and reduced skin elasticity which, in skin folds, can be problematic.
It is desirable to avoid skin toughness that can arise following damage to the skin because toughened skin is prone to flaking and cracking which in turn can lead to inflammation and infection.
In one embodiment the topical composition or dressing has an anti-inflammatory effect. Advantageously this reduces the pain associated with burns.
In one embodiment the topical composition or dressing protects against a decrease in cell viability. Inflammatory impact is known to reduce cell viability, detectable by MTT assay. In one embodiment the mineral complex in the topical composition increases cell viability relative to untreated cells. In one embodiment this improvement in cell viability or reduced decrease in cell viability is obtained when the topical composition is applied either prophylactically or following burn injury.
In one embodiment damaged cells treated with the topical composition or dressing recover viability more quickly than untreated cells. In one embodiment cell viability is restored more quickly in cells treated with the topical composition or dressing.
In one embodiment there is provided a burn dressing for use in the treatment or prophylaxis of burns. Typically, the burn dressing comprises a composition as disclosed herein absorbed and carried on or in a dressing material as described herein.
Ideally the composition or dressing as described herein is applied to a burn as soon as possible following the burn. Preferably the composition or dressing is applied immediately, such as within a minute of the burn. The composition or dressing may be applied within a few hours of the burn injury.
In some situations, the composition or dressing may be applied following treatment by a medical professional. That is, the composition or dressing may be employed other than as a first aid treatment. For example, the composition or dressing may be employed for prolonged use, for example, to keep a burn wound sterile and/or hydrated. Such use of the composition or dressing supports the skin cells by providing external bioavailable minerals which, it is thought, supports the increased metabolism of the cells.
In one embodiment the composition or dressing is applied once, twice, three or four a day.
In one embodiment the composition or dressing is applied to skin, such as the area of the burn, and left for approximately 10 minutes to 36 hours, for example approximately 20, 30, 40 or 50 minutes or approximately 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12,13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34 or 35 hours. In one embodiment the composition or dressing is applied to a burn for up to approximately 24 hours.
In one embodiment there is provided a composition or dressing for use in treatment of a burn wherein the treatment is prolonged treatment.
In one embodiment there is provided a method of prophylaxis or treatment wherein the composition or dressing is applied to a burn for approximately 24 hours. For example approximately 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 or 36 hours or more.
In one embodiment treatment with the composition or dressing continues for about 2 to 10 weeks following each burn injury, such as 3, 4, 5, 6, 7, 8, or 9 weeks following burn injury.
Typically, the composition or dressing is changed daily and a new composition or dressing according to the disclosure applied to the burn injury.
In one embodiment the composition or dressing provide bioavailable minerals to the skin. In one embodiment the minerals include magnesium. It is believed that bioavailable magnesium helps prevent magnesium depletion which is known to be a complicating factor in burn injuries. In one embodiment the minerals include calcium. It is believed that bioavailable calcium helps prevent hypocalcaemia which is known to be a complication factor in burn injuries.
In one embodiment the composition or dressing promote faster healing of the burn wound. In one embodiment use of the composition or dressing results in reduced scarring.
It is hypothesised that the present composition or dressing, especially the mineral complex, affects the expression of certain genes associated with the healing of wounds, including burns. For example, it is believed that the composition or dressing increases the expression of type IV collagen, alpha 3 subunit. This gene plays a role in forming the structure of the cutaneous basal lamina during wound healing.
Thus, in one embodiment there is provided a composition or dressing as disclosed herein for use in increasing expression of type IV collagen, alpha 3 subunit.
In one embodiment there is provided a composition or dressing as disclosed herein for use in forming the structure of cutaneous basal lamina.
It is believed that the composition or dressing decreases expression of PTEN, a tumour suppressor which is a regulator of PI3K signalling. PTEN and PI3K play a role in cell polarisation and directional cell migration during wound healing.
Thus, in one embodiment there is provided a composition or dressing as disclosed herein for use in decreasing expression of PTEN.lt is believed that the composition or dressing targets beta-catenin which, it is hypothesised, impairs healing. Thus, reducing the amount present at a burn wound site promotes healing.
It is also believed that the composition or dressing down regulates SERPINE1 which plays a role in fibrosis and pathological scarring. Thus, leading to reduced scarring at a burn wound site.
Thus, in one embodiment there is provided a composition or dressing as disclosed herein for use in decreasing expression of SERPINE1.
In one embodiment there is provided a composition or dressing as disclosed herein for use in reducing scarring.
It has been shown that CSF2 is knocked out upon treatment with the presently disclosed composition. Upregulated expression of CSF2 is implicated in the pathogenesis of heterotropic ossification of war wounds and burns. Thus, it is believed that the composition or dressing reduces the likelihood of heterotropic wound or burn ossification.
In one embodiment there is provided a composition or dressing as disclosed herein for use in the prevention or reduction of heterotropic wound or burn ossification.
Treatment of burns with the presently disclosed composition ameliorates the overexpression of IL6, which is implicated in burn inflammation and infection. Thus, it is believed that the composition or dressing reduces burn inflammation and/or infection.
In one embodiment there is provided a composition or dressing as disclosed herein for use in the prevention or reduction of burn inflammation and/or infection.
Epidermal Growth Factor (EGF) increased 24-fold upon treatment of wounds with the presently disclosed composition. Thus, it is believed that the composition or dressing increases EGF expression.
In one embodiment there is provided a composition or dressing as disclosed herein for use in increasing EGF expression.
A 76-fold increase in Insulin Like Growth Factor 1, upon treatment of wounds/burns with the presently disclosed composition. Thus, it is believed that the composition or dressing increases IGF-1 expression.
Growth factors are important in regulating a variety of biological processes including cell growth, proliferation and differentiation. Insulin-like growth factor 1 (IGFl) and related family members play an important role in wound healing by stimulating fibroblast mitogenesis, helping to maintain epidermal homeostasis, and inducing keratinocytes to proliferate, differentiate, migrate, and survive. Treatment of wounds with IGF1 has been shown to accelerate healing by stimulating fibroblast collagen synthesis, in addition to its mitogenic effect on both keratinocytes and fibroblasts.
In one embodiment there is provided a composition or dressing as disclosed herein for use in increasing IGF-1 expression.
Thus, there is provided a composition or dressing for direct application to a burn wound. The dressing can be employed to cover the entire burn. Debridement of the burn is not necessary prior to application of the composition or dressing. The composition rapidly penetrates clothing and wets, cools and soothes a burn. The burn is wet, cooled and soothed, not only on the surface but beneath the surface, thereby reducing progression of the burn. The burn dressing cools by heat transference and helps create an isothermic environment. Additionally, the composition or burn dressing helps reduce contamination of the burn by covering the burn and blocking air-borne microbes. Clothing and skin do not adhere to the burn dressing when it is removed, thereby limiting pain and skin damage when the dressing is removed.
The composition and dressing are non-toxic, water-soluble and retain properties after extended storage. Advantageously, the composition and dressing are easy to use.
In the context of this specification comprising is to be interpreted as including.
Approximately, as used herein, means ±10%.
Aspects of the invention comprising certain elements are also intended to extend to alternative embodiments consisting or consisting essentially of the relevant elements.
Where technically appropriate, embodiments of the invention may be combined.
Embodiments are described herein as comprising certain features/elements. The disclosure also extends to separate embodiments consisting or consisting essentially of said features/elements.
Technical references such as patents and applications are incorporated herein by reference.
Any embodiments specifically and explicitly recited herein may form the basis of a disclaimer either alone or in combination with one or more further embodiments.
The present invention is further described by way of illustration only in the following examples:
EXAMPLES
Example 1
Following several failed attempts to formulate a composition with suitable viscosity and other properties to function as a burn treatment, the Inventors obtained stable compositions which were sent for testing to assess stability under gamma radiation.
OVERVIEW: To incorporate: Polyaminopropyl biguanide (INCI name); Chemical name: Polyhexamethylene Biguanide Hydrochloride (PHMB) and later Oriel sea mineral complex into a gel formula that can withstand the impact of gamma radiation sterilisation.
rounds of formulas were sent out for gamma radiations as outlined below.
Round 1 Summary: Started with our current BD (Burn Dressing) Gel with hyaluronic acid (HA) formula to which various ingredients were added.
The table below shows the key ingredients added to BD gel w/ HA formula to determine their impact on gamma radiation resistance (Experiments A through L). Experiment L containing Carbopol and water only, shows that PHMB @1% (20% solution) is incompatible with Carbopol (thickening agent). The gel curdles. Carbopol is the thickening agent used in BD Gel with HA, the only experiment in round 1 to which PHMB was added.
Experiment | Key ingredients (Round 1) BD and HA plus: | Ingredient INCI/ Name | Function | Discolouration following Y radiation (ΙΙΟ) |
A | Glycerin | Glycerin | Humectant | 1.2 |
B | Propylene glycol | 1,2-Propanediol | Humectant | 1.0 |
C | Tinoguard HS (BASF) | Sodium Benzotriazolyl Butylphenol Sulfonate | UV absorber | 4.0 |
D | Cibafash H Liquid(BASF) | Sodium Benzotriazolyl Butylphenol Sulfonate | UV absorber | 3.5 |
E | Tinoguard TT (BASF) | Penaerythityl Tetra-di-tbutyl Hydroxyhydrocinnamate | UV absorber | 2.5 (slightly hazy) |
F | PHMB | Polyaminoproyl biguanide | Preservative | 3 (off white, hazy) |
G | A,B,C,D,E | See above | See above | 3.5 (off white, hazy) |
H | A,B,C, D,E,F | See above | See above | 1.5 |
1 | microsilver | Not sent for radiation - too dark | ||
J | Control additional ingredients | 1.2 | ||
K | Control - just Carbopol and water, not irradiated | |||
L | Control - just Carbopol, water and trolamine | 6.0 |
Table 2
After gamma results: Discolouration was measured on a scale of 1 (no discolouration) to 10 (intense discolouration) UV absorbers showed some discolouration; propylene glycol showed little or no change following gamma radiation.
Round 2 Summary: Since PHMB was incompatible with Carbopol, new formulas containing various other thickeners were tried. Since propylene glycol, a humectant helped, another humectant (propanediol) was tried. For all the experimental batches made, only the stable formulas were sent out for gamma radiation. Only some of round 2 formulas contain PHMB (20% solution) @0.2%
The base gel employed in experiments is water plus thickener (Natrosol or Laponite for example).
Key Ingredients (Round 2) | Ingredient INCI/Chemical Name | Function |
Natrosol 250 HHX | Pharm hydroxyethylcellulose | Thickening agent |
Propylene glycol | Propylene glycol( 1,2Propanediol) | humectant |
Laponite XL 21 | Sodium Magnesium Fluorosilicate | Thickening agent |
Propanediol | Propanediol (1,3-Propanediol) | Solvent |
Xanthan gum | Xanthan gum | Thickening agent |
Carrageenan | Carrageenan | Thickening agent |
Aculyn 21 | Acrylates/Steareth-20 Methacrylate Copolymer | Thickening agent |
Agar powder | Agar | Thickening agent |
Poloxamer 188 | Poloxamer 188 | Surfactant/Thickening agent |
Glycerin | Glycerin | Humectant |
Table 3
Formulas with xanthan gum carrageenan, aculyn 46 N, poloxamer 188 and agar were unstable/thinned out or discoloured (thickening agents not compatible with PHMB) and therefore gels were not sent out for gamma radiation.
After gamma radiation results: Formulas containing Natrosol 250 HHX completely loss viscosity and became water thin but gel was not discoloured. Formulas with propylene glycol were clear but also had a pinkish hue. Formulas with propanediol remained clear; those with glycerin acquired a yellowish hue
Round 3 Summary: For round 3 experiments, 2 new thickening agents (Sodium Carboxymethyl Cellose and Aristoflex AVS) were tested.
Experiment | Key Ingredients (Round 3) Water plus: | Ingredient INCI/Chemical Name | Function |
A | Sodium Carboxymethyl Cellose and PHMB | Sodium Carboxymethyl Cellose | Thickening agent |
B | A plus propanediol | ||
C | B plus Mikrokill and disodium EDTA | ||
D | A plus disodium EDTA, propylene glycol, Mikrokill | ||
E | Disodium EDTA, propanediol, Mikrokill, PHMB, Carbopol 980, trolamine | ||
F | Disodium EDTA, propanediol, Mikrokill, PHMB, Aristoflex AVS | Sodium Acryloyldimethyltaurate/VP Crosspolymer | Thickening agent |
G | Disodium EDTA, propanediol, Mikrokill, PHMB, Natrosol HHX, Carbopol 980, trolamine |
Table 4
All the formulas in round 3 contained PHMB 0.2% (20% solution). Only stable formulas were sent out for gamma radiation.
After gamma radiation results: Formulas containing sodium carboxymethyl cellose became watery. Although the combination of Carbopol and Natrosol 250 HHX showed some promising results (Exp. G), the best result was EXP.F which contained a combination of propanediol and Aristoflex AVS.
Round 4 Summary: In round 4 experiments, Oriel sea mineral extract was introduced into the formulas. This ingredient lowers the viscosity of the gel. As in Round 3 experiments, PHMB was still used @ 0.2% (20% solution). Experiment F, (Round 3) having the best results from round 3 was the starting point. The level of Aristoflex AVS (thickening agent) was varied to compensate for the viscosity reducing effect of the Oriel sea mineral extract. The levels of propanediol were also varied from 5% to 12% to see what if any effect that had on the gamma radiation results as well on overall product appearance.
Key Ingredients (Round 4) | Ingredient INCI/Chemical Name | Function |
Oriel Sea Mineral Extract | Sea water extract | Skin conditioning agent |
Aristoflex AVS | Sodium Acryloyldimethyltaurate/VP Cross polymer | Thickening agent |
Propylene glycol | Propylene glycol(l,2Propanediol) | Solvent |
Propanediol | Propanediol (1,3-Propanediol) | Solvent |
Carbopol980 | Carbomer | Thickening agent |
Natrosol 250 HHX | Pharm hydroxyethylcellulose | Thickening agent |
Table 5
Only stable formulas were sent out for gamma radiation.
After gamma results: All the experiments containing a combination of Aristoflex AVS, PHMB and propanediol showed good results regardless of the level of propanediol. Compositions with propanediol and Carbopol but without PHMB had good results. Compositions with propanediol/Carbopol/PHMB combination showed a significant decrease in viscosity.
Round 5 Summary: Round 5 experiments involved: (a) optimising the viscosity of the product to work more efficiently with the new absorbent material, (b) Increasing the level of PHMP from 0.2% to 0.5% (20 % solution), (c) Making formulas for preservative challenge without the main preservative Microkill COS but with PHMB along with various levels of propanediol (which has preservative properties). Note: Final formula contains Microkill COS. (d) Optimising the manufacturing process.
Key Ingredients (Round 5) | Ingredient INCI/Chemical Name | Function |
Oriel Sea Mineral Extract | Sea water extract | Skin conditioning agent |
Aristoflex AVS | Sodium Acryloyldimethyltaurate/VP Crosspolymer | Thickening agent |
Propylene glycol | Propylene glycol(l,2- Propanediol) | Solvent |
Propanediol | Propanediol (1,3-Propanediol) | Solvent |
Table 6
In round 5, the final formula was determined from a selection of which were sent out for gamma radiation with acceptable results. All the formulas are similar except for their levels of Aristoflex AVS (thickening agent) varying from 1.0%, 0.9% and 0.8% respectively. A decision was made to go with a formula with 0.8% Aristoflex AVS (final formula), the least viscous formula.
In order to test physical integrity of the composition following gamma radiation, the viscosity at room temperature and 40°C can be tested and compared to a control which was not irradiated.
Example 2
Wound healing progresses via three overlapping phases: inflammation, granulation and tissue remodelling. After cutaneous injury, a blood clot forms, and inflammatory cells infiltrate the wound, secreting cytokines and growth factors to promote the inflammation phase. During the granulation phase, fibroblasts and other cells differentiate into myofibroblasts, which deposit extracellular matrix (ECM) proteins. Simultaneously, angiogenesis occurs, and keratinocytes proliferate and migrate to close the wound. In the final tissue-remodelling phase, apoptosis eliminates myofibroblasts and extraneous blood vessels, and the ECM is remodelled to resemble the original tissue. Dysregulation of this last tissue remodelling phase leads to fibrosis.
In order to monitor this cytotoxicity, behaviour, impact and biofunctionality of the composition in (1) Human Vascular Endothelial Cells, (2) Human Dermal Fibroblasts and (3) Human Dermal Keratinocytes we employed an electrical-impedance based technique that monitors and quantifies in real-time the behaviour of cells, which is also amenable to high throughput. Giaever and Keese first described a technique for measuring fluctuations in impedance based on the principle of population cell growth on a specialized electrode surface. The xCELLigence instrument, established and optimised in the laboratory of Dr Ronan Murphy (Dublin City University), utilises a similar technique to measure changes in electrical impedance. Through preliminary studies and data from working with the 'mineral-complex' active ingredient, we have determined protocols and conditions that are optimal for cell functionality and activation in all three cell types. For this we used a 2.5D model on e-plates. Briefly, as cells attach and spread in a culture dish covered with a gold microelectrode array that covers approximately 80% of the area on the bottom of a well. As cells attach and spread on the electrode surface, it leads to an increase in electrical impedance. The impedance is displayed as a dimensionless parameter termed cell-index, which is directly proportional to the total area of tissueculture well that is covered by cells. Hence, the cell-index can be used to monitor many critical stages of cell behaviour such as wound healing: cell adhesion, spreading, morphological changes, detachment, proliferation, migration, apoptosis and cell density.
The standard wound healing assay was utilised in this study based on changes in electrical impedance at the electrode/cell interphase, as a population of cells migrates an advanced double chamber apparatus know as a CIM plate. Cell migration, fate, function and behaviour lead to large changes in impedance. These changes directly correlate with the wound healing capacity of the three cell types, i.e., migration and tissue/ECM remodelling by cells lead to large changes in cell impedance and vice versa. This advanced wound-healing assay involved a two-chamber system (xCELLigence CIM (cell invasion and migration) plate) to monitor and measure transmigration as well as initial surface layer disruption. This technique provides a two-fold advantage over existing methods of measuring invasion, such as Boyden chamber and matrigel assays: firstly, the Cell-Extra Cellular Matrix interactions and remodelling more closely mimics the in vivo process, and secondly, the data was obtained in real-time and is more easily quantifiable, as opposed to end-point analysis for other methods.
Dermal fibroblasts are cells that lay within the dermis layer of skin and are responsible for generating connective tissue and allowing the skin to recover from injury.Dermal fibroblasts generate and maintain the connective tissue which unites separate cell layers, particularly via the rough endoplasmic reticulum. Crucially, it is these dermal fibroblasts that produce the protein molecules, including laminin and fibronectin, which comprise the extracellular matrix (ECM). Hence, by creating the ECM between the dermis and epidermis, fibroblasts facilitate the epithelial cells of the epidermis to affix the matrix, thereby allowing the epidermal cells to effectively join together to form the top layer of the skin.
In our experiments, dermal fibroblast cells were grown in culture, starving them of magnesium for 24 hours before treating them to WJ24-(NB105-142) & appropriate controls. Cells were seeded onto 0.32cm2 wells of the xCELLigence real-time monitoring system, upon which, a minimal layer of ECM had been permitted to form. Cells were then allowed to adhere to the electrode surface and migrate accordingly. Results are presented In Figures 1 and 2.
Example 3
We employed the Wound Healing RT2 Profiler PCR Array to assess the effect of the composition on gene expression during the process outlined in Example 2. This time both fibroblast monoculture (Example 3a) and our established human LabSkin model (see Duffy Et al, 2017, Cosmetics, 4, 44) was used (Example 3b).
This array contains genes important for each of the three phases of wound healing, including ECM remodelling factors, inflammatory cytokines and chemokines, as well as growth factors and major signalling molecules. Using real-time PCR, you can easily and reliably analyse the expression of a focused panel of genes involved in wound healing, tissue injury and repair with this array. The RT2 Profiler PCR Array System is the most reliable and accurate tool for analysing the expression of a focused panel of genes using SYBR Green-based real-time PCR. It brings together the quantitative performance of real-time PCR and the multiple gene profiling capability of microarrays. Each PCR Array profiles the expression of 84 genes relevant to a specific pathway or disease state- in this case Wound Healing. Expression levels are measured by gene-specific RT2 qPCR Primer Assays optimized for simultaneous use in the PCR Array System. RT2 qPCR Primer Assays are key components in the PCR Array System. Each qPCR assay on the array is uniquely designed for use in SYBR Green real-time PCR analysis. The assay design criteria ensure that each qPCR reaction will generate single, genespecific amplicons and prevent the co-amplification of non-specific products. The qPCR Assays used in PCR Arrays are optimised to work under standard conditions enabling a large number of genes to be assayed simultaneously. This system is specifically designed to meet the unique challenges of profiling pathway-focused sets of genes using real-time PCR. Simultaneous gene expression analyses require similar qPCR efficiencies for accurate comparison among genes. RT2 qPCR Primer Assays are designed with an amplicon size ranging from 100 to 250 bp and with PCR efficiencies uniformly greater than 90%. Overall, more than 10 thermodynamic criteria are included in the design of each RT2 qPCR Primer Assay to ensure the most reliable and accurate results for pathway-based gene expression analysis in the PCR Array System. The array layout is shown in Table 7 below.
Position Ref/Seq Number Symbol Description
A01 NM_001613 ACTA2 Actin, alpha 2, smooth muscle, aorta
A02 NM_005159 ACTC1 Actin, alpha, cardiac muscle 1
A03 NM_001146 ANGPT1 Angiopoietin 1
A04 NM 002982 CCL2 Chemokine (C-C motif) ligand 2
A05 NM_006273 CCL7 Chemokine (C-C motif) ligand 7
A06 NM_000074 CD40LG CD40 ligand
A07 NM_004360 CDH1 Cadherin 1, type 1, E-cadherin (epithelial)
A08 NM_021110 COL14A1 Collagen, type XIV, alpha 1
A09 NM_000088 COL1A1 Collagen, type I, alpha 1
A10 NM_000089 COL1A2 Collagen, type I, alpha 2
All NM_000090 COL3A1 Collagen, type III, alpha 1
A12 NM_001845 COL4A1 Collagen, type IV, alpha 1
B01 NM_000091 COL4A3 Collagen, type IV, alpha 3 (Goodpasture antigen)
B02 NM_000093 COL5A1 Collagen, type V, alpha 1
B03 NM_000393 COL5A2 Collagen, type V, alpha 2
B04 NM_015719 COL5A3 Collagen, type V, alpha 3
B05 NM_000758 CSF2 Colony stimulating factor 2 (granulocyte-macrophage)
B06 NM_000759 CSF3 Colony stimulating factor 3 (granulocyte)
B07 NM_001901 CTGF Connective tissue growth factor
B08 NM_001904 CTNNB1 Catenin (cadherin-associated protein), beta 1, 88kDa
B09 NM_001911 CTSG Cathepsin G
BIO NM_000396 CTSK Cathepsin K
Bll NM_001333 CTSV Cathepsin L2
B12 NM_001511 CXCL1 Chemokine (C-X-C motif) ligand 1 (melanoma growth stimulating activity, alpha)
C01 NM_005409 CXCL11 Chemokine (C-X-C motif) ligand 11
C02 NM_002089 CXCL2 Chemokine (C-X-C motif) ligand 2
C03 NM_002994 CXCL5 Chemokine (C-X-C motif) ligand 5
C04 NM_001963 EGF Epidermal growth factor
C05 NM_005228 EGFR Epidermal growth factor receptor
C06 NM_000129 F13A1 Coagulation factor XIII, Al polypeptide
C07 NM_001993 F3 Coagulation factor III (thromboplastin, tissue factor)
C08 NM_000508 FGA Fibrinogen alpha chain
C09 NM_004465 FGF1O Fibroblast growth factor 10
CIO NM_002006 FGF2 Fibroblast growth factor 2 (basic)
Cll NM_002009 FGF7 Fibroblast growth factor 7
C12 NM_001945 HBEGF Heparin-binding EGF-like growth factor
DOI NM_000601 HGF Hepatocyte growth factor (hepapoietin A; scatter factor)
D02 NM_000619 IFNG Interferon, gamma
D03 NM_000618 IGF1 Insulin-like growth factor 1 (somatomedin C)
D04 NM_000572 IL10 Interleukin 10
D05 NM_000576 IL1B Interleukin 1, beta
D06 NM_000586 IL2 Interleukin 2
D07 NM_000589 IL4 Interleukin 4
D08 NM_000600 IL6 Interleukin 6 (interferon, beta 2)
D09 NM_002184 IL6ST Interleukin 6 signal transducer (gpl30, oncostatin IVI receptor)
DIO NM_181501 ITGA1 Integrin, alpha 1
Dll NM_002203 ITGA2 Integrin, alpha 2 (CD49B, alpha 2 subunit of VLA-2 receptor)
D12 NM_002204 ITGA3 Integrin, alpha 3 (antigen CD49C, alpha 3 subunit of VLA-3 receptor)
E01 NM_000885 ITGA4 Integrin, alpha 4 (antigen CD49D, alpha 4 subunit of VLA-4 receptor)
E02 NM_002205 ITGA5 Integrin, alpha 5 (fibronectin receptor, alpha polypeptide)
E03 NM_000210 ITGA6 Integrin, alpha 6
E04 NM_002210 ITGAV Integrin, alpha V (vitronectin receptor, alpha polypeptide, antigen CD51) E05 NM_002211 ITGB1 Integrin, beta 1 (fibronectin receptor, beta polypeptide, antigen CD29 includes MDF2, MSK12)
E06 NM_000212 ITGB3 Integrin, beta 3 (platelet glycoprotein Illa, antigen CD61)
E07 NM_002213 ITGB5 Integrin, beta 5
E08 NM_000888 ITGB6 Integrin, beta 6
E09 NM_002745 MAPK1 Mitogen-activated protein kinase 1
E10 NM_002746 MAPK3 Mitogen-activated protein kinase 3
Ell NM_002415 MIF Macrophage migration inhibitory factor (glycosylation-inhibiting factor)
E12 NM_002421 MMP1 Matrix metallopeptidase 1 (interstitial collagenase)
F01 NM_004530 MMP2 Matrix metallopeptidase 2 (gelatinase A, 72kDa gelatinase, 72kDa type IV collagenase)
F02 NM_002423 MMP7 Matrix metallopeptidase 7 (matrilysin, uterine)
F03 NM_004994 MMP9 Matrix metallopeptidase 9 (gelatinase B, 92kDa gelatinase, 92kDa type IV collagenase)
F04 NM_002607 PDGFA Platelet-derived growth factor alpha polypeptide
F05 NM_000930 PLAT Plasminogen activator, tissue
F06 NM_002658 PLAU Plasminogen activator, urokinase
F07 NM_002659 PLAUR Plasminogen activator, urokinase receptor
F08 NM_000301 PLG Plasminogen
F09 NM_000314 PTEN Phosphatase and tensin homolog
F10 NM_000963 PTGS2 Prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase)
Fll NM_006908 RAC1 Ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rael)
F12 NM_001664 RHOA Ras homolog gene family, member A
G01 NM_000602 SERPINE1 Serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1
G02 NM_003150 STAT3 Signal transducer and activator of transcription 3 (acute-phase response factor)
G03 NM_003186 TAGLN Transgelin
G04 NM_003236 TGFA Transforming growth factor, alpha
G05 NM_000660 TGFB1 Transforming growth factor, beta 1
G06 NM_003243 TGFBR3 Transforming growth factor, beta receptor III
G07 NM_003254 TIMP1 TIMP metallopeptidase inhibitor 1
G08 NM_000594 TNF Tumor necrosis factor
G09 NM_003376 VEGFA Vascular endothelial growth factor A
GIO NM_000638 VTN Vitronectin
Gil NM_003882 WISP1 WNT1 inducible signaling pathway protein 1
G12 NM_003392 WNT5A Wingless-type MMTV integration site family, member 5A
Table 7
Example 3a
In fibroblast monoculture, 2 genes were found to be upregulated and 22 were downregulated when treated with WJ24 versus the control. Results are shown in Figure 3a and Table 8 below.
Up-Regulated Genes | ||
Position | Gene | Fold Regulation |
B01 | COL4A3 | 19.2929 |
F08 | PLG | 5.579 |
Down-Regulated Genes | ||
Position | Gene Fold Regulation | |
iA02 | ACTC1 | | -11.0809 |
A06 | CD40LG | -14.8254 |
isio | CTSK ] | -4.2871 |
!B11 | CTSV | | -9.5798 |
icoi | CXCL11 | -4.5948 |
iC04 | EGF | -33.8246 |
iC06 | iF13A1 | -92.4115 |
iC07 | F3 I | -7.3107 |
iC09 | FGF10 | | -27.4741 |
iD05 | IL1B | | -4.084 |
iD07 | i!L4 | -15.8895 |
iD10 | ITGA1 I | -5.0281 |
iE05 | ITGB1 ] | -6.2767 |
iE07 | ITGB5 | | -4.8906 |
iE08 | ITGB6 | -16.4498 |
iF09 | PTEN | -8.5742 |
iF11 | RAC1 | -8.6939 |
iF12 | RHOA ] | -6.021 |
iG02 | STAT3 | | -4.5948 |
G10 | VTN | -5.8159 |
!G12 | WNT5A I | -16.2234 |
When the concentration of WJ24 was doubled, it was found that the effect was more pronounced additional or different genes being up or down regulated. 4 genes were upregulated and 47 downregulated. The results are shown in Figure 3b and Table 9 below.
Up-Regulated Genes
Position | Gene | i Fold Regulation |
B01 | COL4A3 | | 9.1896 |
D02 | IFNG | 35.0174 |
iF03 | MMP9 | 17.6305 |
iG08 | TNF | 5.1694 |
Down-Regulated Genes | |||
Position | Gene Symbol | i Fold Regulation | |
A01 | ACTA2 | -7.1602 | |
IA02 | iACTCI | -4.0278 | |
iA03 | iANGPTI | -9.9866 | |
IA04 | ;CCL2 | -5.7358 | |
iA06 | iCD40LG | -10.1261 | |
IA08 | iCOL14A1 | -8.0556 | |
iA10 | iCOL1A2 | -17.5087 | |
IA11 | iCOL3A1 | -5.0281 | |
A12 | iCOL4A1 | -5.579 | |
B02 | iCOLSAI | -4.4383 | |
|B03 | iCOL5A2 | -6.3643 | |
IB06 | iCSF3 | -5.0982 | |
iB07 | iCTGF | -9.0005 | |
iB08 | iCTNNBI | -22.6274 | |
IB10 | CTSK | -24.761 | |
|B11 | iCTSV | -57.68 | |
IB12 | iCXCLI | -4.2871 | |
iC03 | iCXCL5 | -19.6983 | |
C04 | ;EGF | -22.6274 | |
C06 | IF13A1 | -4.3772 | |
IC07 | iF3 | -60.1295 | |
iC09 | FGF10 | -18.7654 | |
IC10 | iFGF2 | -4.8906 | |
iC11 | FGF7 | -8 | |
iC12 | HBEGF | -7.8899 | |
I DOS | IIL1B | -15.455 | |
iD09 | HL6ST | -9.3827 | |
D10 | IITGA1 | -30.0647 | |
E03 | ilTGA6 | -5.4264 | |
IE04 | ilTGAV | -6.8211 | |
I EOS | ITGB1 | -81.5719 | |
iE06 | ilTGB3 | -17.5087 | |
IE07 | ilTGBS | -25.4572 | |
iE08 | ITGB6 | -11.2356 | |
IE09 | ;MAPK1 | -5.6569 | |
ΪΕΪ2 | iMMP1 | -5.3517 | |
IF04 | iPDGFA | -4.1989 | |
iF05 | iPLAT | -30.6965 | |
IF09 | iPTEN | -113.7719 | |
|F11 | iRAC1 | -73.0089 | |
iF12 | RHOA | -30.4844 | |
IG01 | iSERPINEI | -15.1369 | |
iG02 | iSTAT3 | -22.4711 | |
IG03 | iTAGLN | -9.5798 | |
|G10 | iVTN | -51.2685 | |
IG11 | iWISPI | -9.7136 | |
iG12 | WNT5A | -156.498 |
Table 9
Example 3b
Development of in vitro Human 3D Deep-Skin Technology & Application in Burn Research
A highly advanced 3D living skin equivalent model (developed by Dr Ronan Murphy's team at Dublin City University) is unique in providing unrivalled opportunities for non-animal testing and research. The fully differentiated epidermis is supported by a dermal component consisting of fibroblasts in a fibrin matrix. The model also allows micro-organisms to be grown on its surface, mimicking infection or the skin's natural microflora. This configuration ensures we can assess topical formulations with possibly the most comprehensive range of tests available in an in vitro model. A schematic of the system is shown in Figure 4. Culture medium 10 sits below the skin 20 to provide nutrients for growth. The resulting skin is stratified as shown in the cross section 30.
Skin Model Burn Protocol
Custom 3.66g brass weights were milled from brass stock with a surface contact area of 10 mm and a protrusion for handling with tweezers (see Figure 5a). The weights were heated to 100°C on a heating block (Stuart) and temperature checked using an IR thermometer.
Skin models were removed from the 6-well plate and placed onto a plastic surface in a laminar hood to avoid heat dissipation. Brass weights were removed from the heating block using tweezers and immediately placed on the centre of each 2.5cm model for 10 seconds. After 10 seconds, the brass weight was removed and the appropriate treatment was applied.
Each treatment consisted of custom cut 2.5cm gauze disks (Water-jel) soaked in different formulations.
Model skin turned white in the centre following removal of the weight. Figures 6a and 6b show photographs of the models 24 hours after the burn infliction.
All models were biopsied using a 3mm biopsy punch (Miltex) in the centre and at the burn boundary 24 and 48 hours after the burn was inflicted (see Figure 5b), and conditioned media was sampled.
Genes associated with wound (burn) repair are:
Extracellular Matrix & Cell Adhesion:
ECM Components: COL14A1, COL1A1, COL1A2, COL3A1, COL4A1, COL4A3, COL5A1, COL5A2, COL5A3, VTN.
Remodelling Enzymes: CTSG, CTSK, CTSL2, F13A1, F3 (Tissue Factor), FGA (Fibrinogen), MMP1,
MMP2, MMP7, MMP9, PLAT (tPA), PLAU (uPA), PLAUR (uPAR), PLG, SERPINE1 (PAI-1), TIMP1.
Cellular Adhesion: CDH1 (E-cadherin), ITGA1, ITGA2, ITGA3, ITGA4, ITGA5, ITGA6, ITGAV, ITGB1, ITGB3,
ITGB5, ITGB6.
Cytoskeleton: ACTA2 (a-SMA), ACTC1, RAC1, RHOA, TAGLN.
Inflammatory Cytokines & Chemokines: CCL2 (MCP-1), CCL7 (MCP-3), CD40LG (TNFSF5), CXCL1, CXCL11 (ITAC/IP-9), CXCL2, CXCL5 (ENA-78/LIX), IFNG, IL10, IL1B, IL2, IL4, IL6.
Growth Factors: ANGPT1, CSF2 (GM-CSF), CSF3 (GCSF), CTGF, EGF, FGF10, FGF2, FGF7, HBEGF (DTR), HGF, IGF1, MIF, PDGFA, TGFA, TGFB1, TNF, VEGFA
Signal Transduction:
TGFR: TGFB1, TGFBR3, STAT3.
WNT: CTNNB1, WISP1, WNT5A.
Phosphorylation: MAPK1 (ERK2), MAPK3 (ERK1), PTEN.
Receptors: EGFR, IL6ST (GP130).
Other: PTGS2.
Firstly, RT2 qPCR was first employed to compared burned skin to healthy skin to obtain a baseline.
Figure 8a shows up- and down-regulated genes in 3D skin models in response to thermal burn injury (no treatment) vs healthy skin. Total RNA from 3D skin models was characterised, and the relative expression levels for each gene in the two samples (burn vs healthy skin) plotted against each other in the Scatter Plot. Table 10 shows 22 genes that are upregulated in burned skin relative to unburned skin. Table 11 shows 49 genes that are down regulated in thermally injured (burned) skin 10 relative to unburned skin.
Position | Gene | Fold Change | Position | Gene | Fold Change | |
C03 | CXCL5 | 6942.47 | C02 | CXCL2 | 6.45 | |
E06 | ITGB3 | 785.57 | D02 | IFNG | 5.78 | |
C06 | F13A1 | 620.97 | A06 | CD40LG | 5.59 | |
B05 | CSF2 | 503.94 | F02 | MMP7 | 4.78 | |
G08 | TNF | 156.36 | B06 | CSF3 | 4.2 | |
D06 | IL2 | 112.45 | D05 | IL1B | 4.1 | |
C08 | FGA | 105.14 | G07 | TIMP1 | 3.79 | |
C01 | CXCL11 | 45.2 | D07 | IL4 | 3.32 | |
D08 | IL6 | 36.04 | G01 | SERPINE1 | 2.77 | |
F10 | PTGS2 | 12.85 | B12 | CXCL1 | 2.65 | |
A04 | CCL2 | 9.69 | F01 | MMP2 | 2.4 |
Table 10
Position | Gene | Fold Change | Position | Gene | Fold Change | |
A07 | CDH1 | -565.25 | E01 | ITGA4 | -5.22 | |
E08 | ITGB6 | -239.99 | G03 | TAG LN | -5.02 | |
E03 | ITGA6 | -144.31 | F12 | RHOA | -4.91 |
C12 | HBEGF | -122.9 | A03 | ANGPT1 | -4.56 | |
Bll | CTSV | -118.6 | All | C0L3A1 | -4.43 | |
D12 | ITGA3 | -91.25 | A08 | C0L14A1 | -4.25 | |
F06 | PLAU | -30.44 | G06 | TGFBR3 | -4.17 | |
D03 | IGF1 | -27.01 | F08 | PLG | -4.06 | |
F04 | PDGFA | -24.48 | E07 | ITGB5 | -3.96 | |
Dll | ITGA2 | -19.13 | E09 | MAPK1 | -3.95 | |
D04 | IL1O | -17.43 | A10 | C0L1A2 | -3.81 | |
Fll | RAC1 | -16 | B03 | COL5A2 | -3.79 | |
B09 | CTSG | -15.86 | F03 | MMP9 | -3.77 | |
G04 | TGFA | -11.3 | E02 | ITGA5 | -3.76 | |
GIO | VTN | -10.43 | B02 | C0L5A1 | -3.43 | |
B08 | CTNNB1 | -8.7 | E10 | MAPK3 | -3.37 | |
F09 | PTEN | -8.28 | CIO | FGF2 | -3.26 | |
B04 | COL5A3 | -8.16 | A01 | ACTA2 | -2.89 | |
GO2 | STAT3 | -8.12 | C05 | EGFR | -2.83 | |
AO2 | ACTC1 | -7.78 | DIO | ITGA1 | -2.8 | |
E04 | ITGAV | -7.62 | DOI | HGF | -2.44 | |
BO1 | COL4A3 | -6.28 | A05 | CCL7 | -2.3 | |
A12 | COL4A1 | -5.87 | Gil | WISP1 | -2.21 | |
C07 | F3 | -5.42 | B07 | CTGF | -2.18 | |
A09 | CO LI Al | -5.37 |
Table 11
Next, wound healing PCR arrays revealed up- and down-regulated genes in 3D skin models in response to treatment with NB105-146 for thermal burn injury.
Total RNA from 3D skin models were characterised, and the relative expression levels for each gene in the two samples (burn (untreated) vs burned and treated with gel without mineral complex) are 5 plotted against each other in the Scatter Plot. Results are shown in Figure 8b and Tables 12 and 13.
Table 12 shows 12 genes that are up-regulated in response to treatment with NB105-146 relative to thermal burn injured (untreated) skin. Table 13 shows 57 genes that are down-regulated in response to NB105-146 treated versus untreated thermal burn injured skin.
Position | Gene | Fold Change |
C09 | FGF1O | 26.19 |
A06 | CD40LG | 10.89 |
D06 | IL2 | 6.65 |
C04 | EGF | 4.43 |
D03 | IGF1 | 3.62 |
H06 | HGDC | 3.35 |
B09 | CTSG | 3.16 |
E08 | ITGB6 | 2.95 |
C08 | FGA | 2.78 |
D02 | IFNG | 2.63 |
C06 | F13A1 | 2.61 |
B01 | COL4A3 | 2.2 |
Table 12
Position | Gene | Fold Change | Position | Gene | Fold Change | |
G01 | SERPINE1 | -499.23 | G02 | STAT3 | -24.3 | |
F10 | PTGS2 | -246.35 | E09 | MAPK1 | -23.23 | |
B05 | CSF2 | -238.7 | G12 | WNT5A | -21.34 | |
C07 | F3 | -180.08 | BIO | CTSK | -21.29 |
D08 | IL6 | -169.09 | F12 | RHOA | -21.12 | |
B08 | CTNNB1 | -110.64 | A04 | CCL2 | -20.78 | |
E12 | MMP1 | -106.16 | F03 | MMP9 | -17.38 | |
B12 | CXCL1 | -102.5 | Gil | WISP1 | -14.98 | |
C03 | CXCL5 | -99.01 | DIO | ITGA1 | -14.98 | |
G09 | VEGFA | -83.69 | E02 | ITGA5 | -14.58 | |
C02 | CXCL2 | -76.57 | B06 | CSF3 | -13.47 | |
F07 | PLAUR | -64.15 | Cll | FGF7 | -12.97 | |
F02 | MMP7 | -64.13 | F09 | PTEN | -11.23 | |
G07 | TIMP1 | -61.21 | Fll | RAC1 | -11.19 | |
E05 | ITGB1 | -50.11 | B07 | CTGF | -9.55 | |
F01 | MMP2 | -50.02 | A10 | C0L1A2 | -9.38 | |
HOI | ACTB | -47.39 | G03 | TAG LN | -8.99 | |
AO1 | ACTA2 | -45.62 | F06 | PLAU | -8.37 | |
Ell | MIF | -40.95 | E04 | ITGAV | -8.13 | |
D05 | IL1B | -39.86 | H09 | RTC | -7.88 | |
C05 | EGFR | -39.4 | G04 | TGFA | -6.52 | |
H05 | RPLPO | -33.51 | B03 | COL5A2 | -5.72 | |
E07 | ITGB5 | -32.45 | D12 | ITGA3 | -4.66 | |
BO2 | COL5A1 | -29.47 | F04 | PDGFA | -4.24 | |
A12 | COL4A1 | -28.78 | Bll | CTSV | -3.99 | |
F05 | PLAT | -28.73 | A09 | C0L1A1 | -3.94 | |
E1O | MAPK3 | -26.37 | CIO | FGF2 | -3.67 |
G05 | TGFB1 | -25.26 | A03 | ANGPT1 | -3.66 | |
D09 | IL6ST | -24.61 | ||||
Ta | ale 13 |
Finally, wound healing PCR arrays revealed up- and down-regulated genes in 3D skin models in response to treatment with NB105-142 (WJ24) for thermal burn injuries. Total RNA from 3D skin models was characterised, and the relative expression levels for each gene in the two samples (WJ + 5 Oriel vs Burn) were plotted against each other in the Scatter Plot, results are shown in Figure 8c and Tables 14 and 15.
Table 14 shows 38 genes that are up-regulated in response to treatment with NB105-146 relative to thermal burn injured (untreated) skin. Table 15 shows 26 genes that are down-regulated in response to NB105-146 treated versus untreated thermal burn injured skin.
Position | Gene | Fold Change | Position | Gene | Fold Change | |
D03 | IGF1 | 75.98 | C12 | HBEGF | 5.12 | |
B09 | CTSG | 50.93 | E06 | ITGB3 | 5.03 | |
D06 | IL2 | 40.07 | B03 | COL5A2 | 4.97 | |
C09 | FGF10 | 38.70 | A10 | COL1A2 | 4.71 | |
C08 | FGA | 33.71 | G06 | TGFBR3 | 4.67 | |
E08 | ITGB6 | 29.08 | D01 | HGF | 4.52 | |
A07 | CDH1 | 26.53 | H08 | RTC | 4.48 | |
C04 | EGF | 23.98 | D07 | IL4 | 4.44 | |
C06 | F13A1 | 19.38 | A08 | COL14A1 | 4.19 | |
B01 | COL4A3 | 15.06 | F04 | PDGFA | 4.00 | |
D02 | IFNG | 14.21 | E03 | ITGA6 | 3.65 | |
All | COL3A1 | 12.14 | G10 | VTN | 3.16 | |
A02 | ACTC1 | 12.00 | D12 | ITGA3 | 3.02 | |
A09 | CO LI Al | 11.47 | A03 | ANGPT1 | 2.97 | |
F08 | PLG | 8.99 | Bll | CTSV | 2.73 | |
A06 | CD40LG | 7.86 | E01 | ITGA4 | 2.69 |
B04 | COL5A3 | 7.62 | Gil | WISP1 | 2.62 | |
D04 | IL10 | 7.59 | Dll | ITGA2 | 2.50 | |
H09 | RTC | 5.53 | G03 | TAG LN | 2.00 | |
Ta | ale 14 | |||||
Position | Gene | Fold Change | Position | Gene | Fold Change | |
B05 | CSF2 | -10845.5 | Cll | FGF7 | -5.68 | |
G09 | VEGFA | -7722.46 | A04 | CCL2 | -5.3 | |
A05 | CCL7 | -98.27 | A01 | ACTA2 | -4.24 | |
D08 | IL6 | -83.67 | G08 | TNF | -3.56 | |
B06 | CSF3 | -64.95 | D05 | IL1B | -3.24 | |
F10 | PTGS2 | -60.18 | F03 | MMP9 | -3 | |
C02 | CXCL2 | -21.04 | C05 | EGFR | -2.78 | |
B12 | CXCL1 | -12.87 | G07 | TIMP1 | -2.62 | |
E12 | MMP1 | -8.49 | D10 | ITGA1 | -2.29 | |
F02 | MMP7 | -8.01 | D09 | IL6ST | -2.22 | |
C03 | CXCL5 | -7.12 | B08 | CTNNB1 | -2.21 | |
G01 | SERPINE1 | -6.69 | F07 | PLAUR | -2.14 | |
C07 | F3 | -6.02 | E05 | ITGB1 | -2.06 | |
Ta | ale 15 |
Example 4
Tissue dielectric constant of burned skin models was tested at time intervals following exposure to (treatment with) the mineral complex active ingredient (Figure 7b) versus control (treatment with nothing) (Figure 7a).
Claims (30)
1. A topical composition comprising water, solvent, thickener, preservative and conditioning agent wherein the composition has a viscosity approximately in the range 200-6000 cP at 25°C following exposure to gamma radiation.
2. A topical composition according to claim 1 comprising or consisting approximately:
85-95% purified water
5-10% solvent
0.5-1.0% thickener
0.5-2.0% preservative
0.1-1.0% conditioning agent w/w of the composition.
3. A topical composition according to any preceding claim wherein the solvent is propanediol.
4. A topical composition according to claim 3 wherein the propanediol comprises approximately 8% w/w of the composition.
5. A topical composition according to any preceding claim wherein the thickener is sodium acryloyldimethyltaurate/VP crosspolymer.
6. A topical composition according to claim 5 wherein the sodium acryloyldimethyltaurate/VP crosspolymer comprises approximately 0.8% w/w of the composition.
7. A topical composition according to any preceding claim wherein the preservative is one or more selected from the group consisting: phenoxyethanol and caprylyl glycol and chlorphenesin and (PHMB) polyaminopropyl biguanide.
8. A topical composition according to claim 7 comprising approximately 1.0% w/w phenoxyethanol and caprylyl glycol and chlorphenesin plus an additional approximately 0.1% w/w (PHMB) polyaminopropyl biguanide.
9. A topical composition according to any preceding claim wherein the conditioning agent is a mineral complex.
10. A topical composition according to claim 9 wherein the mineral complex comprises approximately 0.25% w/w of the composition.
11. A topical composition according to any preceding claim consisting approximately:
89.85% purified water
8% propanediol
0.8% sodium acryloyldimethyltaurate/VP crosspolymer
1% phenoxyethanol and caprylyl glycol and chlorphenesin
0.25% mineral complex and
0.1% (PHMB) polyaminopropyl biguanide w/w of the composition.
12. A topical composition according to any one of claims 9 to 11 wherein the mineral complex is sea water extract.
13. A topical composition according to any one of claims 9 to 12 wherein the mineral complex comprises magnesium, potassium, sodium, boron, calcium and optionally one or more from the group consisting: copper, nickel, silicon, zinc, aluminium, arsenic, barium, cadmium, cobalt, chromium, iron, mercury, manganese, lead, antimony, selenium, tin, strontium, titanium and vanadium.
14. A topical composition according to any preceding claim wherein the composition has a specific gravity of approximately 1.000 ±0.05 at 25°C.
15. A topical composition according to any preceding claim wherein the composition has a pH approximately in the range 4.0-6.5 at 25°C.
16. A topical composition according to any preceding claim wherein the gamma radiation is irradiation at approximately 25.0 to 44.5 kGy.
17. A topical composition according to any preceding claim wherein the gamma radiation is cobalt 60 irradiation.
18. A topical composition according to any preceding claim for use as a medicament.
19. A topical composition according to any one of claims 1 to 17 for use in the treatment or prophylaxis of burns.
20. The use according to claim 18 or 19 wherein the composition is applied for a prolonged period, for example up to 24 hours.
21. A burn dressing comprising a topical composition according to any one of claims 1 to 17 and a dressing material.
22. A burn dressing according to claim 21 wherein the dressing material comprises thermal bonded, non-woven material.
23. A burn dressing according to claim 21 or 22 wherein the dressing material comprises super absorbent material, such as super absorbent fibre.
24. A burn dressing according to any one of claims 21 to 23 wherein the dressing material comprises polypropylene fibre and rayon fibre.
25. A burn dressing according to any one of claims 22 to 24 wherein the dressing material is approximately 20% super absorbent fibre.
26. A burn dressing according to any one of claims 21 to 25 wherein the dressing material has one of more of the properties selected from the group consisting:
a weight of approximately 50gsm, a thickness of approximately 0.63mm, a tensile strength of approximately 4.2 N or 24.3 N, an absorbent capacity of approximately 22.7g/g and an absorbent volume of approximately >1150 gsm.
27. A method of sterilising a topical composition according to any one of claims 1 to 17 or a burn dressing according to any one of claims 21 to 26 comprising applying gamma radiation of approximately 25.0 to 44.5 kGy to the composition or dressing.
28. A method of sterilising according to claim 27 wherein the gamma radiation is cobalt 60 irradiation.
29. A composition according to any one of claims 1 to 17 or a burn dressing according to any one of claims 21 to 26 which has been sterilised using the method of claim 27 or 28.
30. A kit of parts comprising a composition according to any one of claims 1 to 17 and a dressing material.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GBGB1717224.8A GB201717224D0 (en) | 2017-10-20 | 2017-10-20 | Composition |
GBGB1813442.9A GB201813442D0 (en) | 2018-08-17 | 2018-08-17 | Composition |
Publications (4)
Publication Number | Publication Date |
---|---|
GB201816988D0 GB201816988D0 (en) | 2018-12-05 |
GB2569682A true GB2569682A (en) | 2019-06-26 |
GB2569682A8 GB2569682A8 (en) | 2019-08-21 |
GB2569682B GB2569682B (en) | 2020-06-17 |
Family
ID=60481604
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
GBGB1717224.8A Ceased GB201717224D0 (en) | 2017-10-20 | 2017-10-20 | Composition |
GB1816988.8A Active GB2569682B (en) | 2017-10-20 | 2018-10-18 | Topical composition for use in the treatment of burns |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
GBGB1717224.8A Ceased GB201717224D0 (en) | 2017-10-20 | 2017-10-20 | Composition |
Country Status (1)
Country | Link |
---|---|
GB (2) | GB201717224D0 (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR3130575A1 (en) * | 2021-12-22 | 2023-06-23 | L'oreal | Cosmetic composition comprising propane-1,3-diol, one or more alkaline agents, one or more nonionic surfactants, one or more non-associative anionic acrylic polymers and one or more colorants |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1074245A2 (en) * | 1999-08-06 | 2001-02-07 | Sam Schwartz | Composition using mineral salts for therapeutic treatment |
WO2005007071A2 (en) * | 2003-07-15 | 2005-01-27 | Intercosma Ltd. | Skin formulation |
US20140212513A1 (en) * | 2013-01-29 | 2014-07-31 | Ahava - Dead Sea Laboratories Ltd. | Topical compositions comprising dead sea water and uses thereof |
-
2017
- 2017-10-20 GB GBGB1717224.8A patent/GB201717224D0/en not_active Ceased
-
2018
- 2018-10-18 GB GB1816988.8A patent/GB2569682B/en active Active
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1074245A2 (en) * | 1999-08-06 | 2001-02-07 | Sam Schwartz | Composition using mineral salts for therapeutic treatment |
WO2005007071A2 (en) * | 2003-07-15 | 2005-01-27 | Intercosma Ltd. | Skin formulation |
US20140212513A1 (en) * | 2013-01-29 | 2014-07-31 | Ahava - Dead Sea Laboratories Ltd. | Topical compositions comprising dead sea water and uses thereof |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR3130575A1 (en) * | 2021-12-22 | 2023-06-23 | L'oreal | Cosmetic composition comprising propane-1,3-diol, one or more alkaline agents, one or more nonionic surfactants, one or more non-associative anionic acrylic polymers and one or more colorants |
Also Published As
Publication number | Publication date |
---|---|
GB2569682A8 (en) | 2019-08-21 |
GB201816988D0 (en) | 2018-12-05 |
GB201717224D0 (en) | 2017-12-06 |
GB2569682B (en) | 2020-06-17 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
AU2018352330B2 (en) | Composition | |
Field et al. | Overview of wound healing in a moist environment | |
Zhou et al. | Rational design of intelligent and multifunctional dressing to promote acute/chronic wound healing | |
Whelan et al. | Mechanics of wound healing and importance of vacuum assisted closure® in urology | |
CN113332162B (en) | protamine-PDRN compound, composition and application in preparation of skin care product | |
US20190151496A1 (en) | Novel active ingredient in cicatrization and use thereof | |
Claxton et al. | Healing the diabetic wound and keeping it healed: modalities for the early 21st century | |
US7737130B2 (en) | Pharmaceutical compositions for topical use in treatment of skin or mucous injuries | |
CN111743830A (en) | Acne-removing composition and application thereof | |
CN102274493B (en) | Bleeding-stopping, inflammation-diminishing and pain-relieving nano emulsion for use in minimally invasive beauty treatment therapy and preparation method thereof | |
BR0210994A (en) | Pharmaceutical and diagnostic compounds containing nanoparticles useful for tissue and cell treatment | |
CN111588815A (en) | Acne-removing traditional Chinese medicine composition, application thereof and acne-removing balancing essence containing composition | |
GB2569682A (en) | Composition | |
JP6087917B2 (en) | Use of oligosaccharide compounds for the prevention and treatment of pathological scars | |
JP2019511468A (en) | Compositions and methods for treating chronic wounds | |
US20230338296A1 (en) | Devices and methods for delivery of oxygen to a wound | |
Hao et al. | Dermlin and silver nanoparticles combined antibacterial dressing for skin wound repair | |
Atiyeh et al. | Improved healing of split thickness skin graft donor sites | |
Cameron et al. | Burn wound management: a surgical perspective | |
JP2007197349A (en) | Transdermal absorption type pharmaceutical | |
Ermolov et al. | The use of bioactive wound dressing, stimulating epithelial regeneration of IIIa-degree burn wounds | |
WO2004089406A1 (en) | Topical composition in the form of a gel for treating skin burns | |
Karayel et al. | Antimicrobial wound dressing materials | |
Popli et al. | Current Aspects and Therapies for Wound healing | |
Bari et al. | 7.5. 5 USE OF RADIATION-STERILISED AMNIOTIC MEMBRANE GRAFTS AS TEMPORARY BIOLOGICAL DRESSINGS FOR THE TREATMENT OF LEPROTIC ULCERS |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
REG | Reference to a national code |
Ref country code: HK Ref legal event code: DE Ref document number: 40005766 Country of ref document: HK |