WO2022157307A1 - Hyaluronic acid as antimicrobial agent for use on the skin - Google Patents
Hyaluronic acid as antimicrobial agent for use on the skin Download PDFInfo
- Publication number
- WO2022157307A1 WO2022157307A1 PCT/EP2022/051342 EP2022051342W WO2022157307A1 WO 2022157307 A1 WO2022157307 A1 WO 2022157307A1 EP 2022051342 W EP2022051342 W EP 2022051342W WO 2022157307 A1 WO2022157307 A1 WO 2022157307A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- globosa
- skin
- hyaluronic acid
- colony counts
- acnes
- Prior art date
Links
- 229920002674 hyaluronan Polymers 0.000 title claims abstract description 49
- 239000004599 antimicrobial Substances 0.000 title claims abstract description 10
- 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 title claims description 45
- 229960003160 hyaluronic acid Drugs 0.000 title claims description 44
- 230000000699 topical effect Effects 0.000 claims abstract description 10
- 210000003491 skin Anatomy 0.000 claims description 61
- 239000000203 mixture Substances 0.000 claims description 54
- 244000005700 microbiome Species 0.000 claims description 39
- 241000186427 Cutibacterium acnes Species 0.000 claims description 35
- 239000002537 cosmetic Substances 0.000 claims description 35
- 241000191963 Staphylococcus epidermidis Species 0.000 claims description 28
- 238000011534 incubation Methods 0.000 claims description 28
- 244000005714 skin microbiome Species 0.000 claims description 26
- 210000004209 hair Anatomy 0.000 claims description 25
- 210000004761 scalp Anatomy 0.000 claims description 24
- 241001147736 Staphylococcus capitis Species 0.000 claims description 21
- 241000192087 Staphylococcus hominis Species 0.000 claims description 21
- 238000011081 inoculation Methods 0.000 claims description 21
- 230000000845 anti-microbial effect Effects 0.000 claims description 20
- 238000000034 method Methods 0.000 claims description 12
- 210000002615 epidermis Anatomy 0.000 claims description 9
- 241000736262 Microbiota Species 0.000 claims description 7
- 230000003247 decreasing effect Effects 0.000 claims description 7
- 230000036074 healthy skin Effects 0.000 claims description 7
- 239000006210 lotion Substances 0.000 claims description 7
- 239000003921 oil Substances 0.000 claims description 7
- 239000000499 gel Substances 0.000 claims description 6
- 230000008859 change Effects 0.000 claims description 5
- 230000001225 therapeutic effect Effects 0.000 claims description 5
- 239000006071 cream Substances 0.000 claims description 4
- 239000002453 shampoo Substances 0.000 claims description 4
- 235000015961 tonic Nutrition 0.000 claims description 3
- 230000001256 tonic effect Effects 0.000 claims description 3
- 102100030621 Carboxypeptidase A4 Human genes 0.000 claims description 2
- 101000772572 Homo sapiens Carboxypeptidase A4 Proteins 0.000 claims description 2
- 239000008266 hair spray Substances 0.000 claims description 2
- 230000001172 regenerating effect Effects 0.000 claims description 2
- 229960000716 tonics Drugs 0.000 claims description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 2
- 244000036483 Rhodamnia cinerea Species 0.000 claims 11
- 244000079889 Cymbidium pendulum Species 0.000 claims 6
- 241000155310 Stenophylax mitis Species 0.000 claims 6
- 208000020154 Acnes Diseases 0.000 claims 2
- 241000555676 Malassezia Species 0.000 abstract description 8
- 241001291474 Malassezia globosa Species 0.000 description 41
- 238000002360 preparation method Methods 0.000 description 19
- 241001313296 Corynebacterium simulans Species 0.000 description 15
- 241001134658 Streptococcus mitis Species 0.000 description 15
- 239000000839 emulsion Substances 0.000 description 9
- 208000027244 Dysbiosis Diseases 0.000 description 7
- 230000007140 dysbiosis Effects 0.000 description 7
- 150000001875 compounds Chemical class 0.000 description 6
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 5
- 230000009286 beneficial effect Effects 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 150000002016 disaccharides Chemical class 0.000 description 4
- 239000004615 ingredient Substances 0.000 description 4
- 229960003966 nicotinamide Drugs 0.000 description 4
- 235000005152 nicotinamide Nutrition 0.000 description 4
- 239000011570 nicotinamide Substances 0.000 description 4
- 235000016709 nutrition Nutrition 0.000 description 4
- 230000008591 skin barrier function Effects 0.000 description 4
- 241000894007 species Species 0.000 description 4
- 241000233866 Fungi Species 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 101100537098 Mus musculus Alyref gene Proteins 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 230000002411 adverse Effects 0.000 description 3
- 101150095908 apex1 gene Proteins 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 230000002349 favourable effect Effects 0.000 description 3
- 230000000813 microbial effect Effects 0.000 description 3
- 230000003020 moisturizing effect Effects 0.000 description 3
- 229920001542 oligosaccharide Polymers 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- ZFTFOHBYVDOAMH-XNOIKFDKSA-N (2r,3s,4s,5r)-5-[[(2r,3s,4s,5r)-5-[[(2r,3s,4s,5r)-3,4-dihydroxy-2,5-bis(hydroxymethyl)oxolan-2-yl]oxymethyl]-3,4-dihydroxy-2-(hydroxymethyl)oxolan-2-yl]oxymethyl]-2-(hydroxymethyl)oxolane-2,3,4-triol Chemical class O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)OC[C@@H]1[C@@H](O)[C@H](O)[C@](CO)(OC[C@@H]2[C@H]([C@H](O)[C@@](O)(CO)O2)O)O1 ZFTFOHBYVDOAMH-XNOIKFDKSA-N 0.000 description 2
- 208000001840 Dandruff Diseases 0.000 description 2
- 229920002670 Fructan Polymers 0.000 description 2
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- OVRNDRQMDRJTHS-UHFFFAOYSA-N N-acelyl-D-glucosamine Natural products CC(=O)NC1C(O)OC(CO)C(O)C1O OVRNDRQMDRJTHS-UHFFFAOYSA-N 0.000 description 2
- OVRNDRQMDRJTHS-FMDGEEDCSA-N N-acetyl-beta-D-glucosamine Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-FMDGEEDCSA-N 0.000 description 2
- AEMOLEFTQBMNLQ-WAXACMCWSA-N alpha-D-glucuronic acid Chemical compound O[C@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-WAXACMCWSA-N 0.000 description 2
- 230000003712 anti-aging effect Effects 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 235000014633 carbohydrates Nutrition 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 235000021255 galacto-oligosaccharides Nutrition 0.000 description 2
- 150000003271 galactooligosaccharides Chemical class 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 238000012423 maintenance Methods 0.000 description 2
- 150000002772 monosaccharides Chemical class 0.000 description 2
- 229950006780 n-acetylglucosamine Drugs 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 150000002482 oligosaccharides Chemical class 0.000 description 2
- 239000002953 phosphate buffered saline Substances 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 229940094944 saccharide isomerate Drugs 0.000 description 2
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 2
- 159000000000 sodium salts Chemical class 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 239000002562 thickening agent Substances 0.000 description 2
- 239000011782 vitamin Substances 0.000 description 2
- 229940088594 vitamin Drugs 0.000 description 2
- 235000013343 vitamin Nutrition 0.000 description 2
- 229930003231 vitamin Natural products 0.000 description 2
- 230000003313 weakening effect Effects 0.000 description 2
- KIUKXJAPPMFGSW-YXBJCWEESA-N (2s,4s,5r,6s)-6-[(2s,3r,5s,6r)-3-acetamido-2-[(3s,4r,5r,6r)-6-[(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]1C(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(O[C@@H]3[C@@H]([C@@H](O)C(O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)C(C(O)=O)O1 KIUKXJAPPMFGSW-YXBJCWEESA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- SERLAGPUMNYUCK-DCUALPFSSA-N 1-O-alpha-D-glucopyranosyl-D-mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O SERLAGPUMNYUCK-DCUALPFSSA-N 0.000 description 1
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 229920002498 Beta-glucan Polymers 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 239000004386 Erythritol Substances 0.000 description 1
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 229920001202 Inulin Polymers 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 241001291477 Malassezia restricta Species 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 239000004909 Moisturizer Substances 0.000 description 1
- MBLBDJOUHNCFQT-LXGUWJNJSA-N N-acetylglucosamine Natural products CC(=O)N[C@@H](C=O)[C@@H](O)[C@H](O)[C@H](O)CO MBLBDJOUHNCFQT-LXGUWJNJSA-N 0.000 description 1
- 229920000294 Resistant starch Polymers 0.000 description 1
- 206010040914 Skin reaction Diseases 0.000 description 1
- 229920002385 Sodium hyaluronate Polymers 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 230000002009 allergenic effect Effects 0.000 description 1
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 230000003656 anti-hair-loss Effects 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 230000003796 beauty Effects 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose 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-QUYVBRFLSA-N 0.000 description 1
- -1 carbohydrate compounds Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 238000003501 co-culture Methods 0.000 description 1
- 230000001332 colony forming effect Effects 0.000 description 1
- 101150088639 csm4 gene Proteins 0.000 description 1
- 239000007854 depigmenting agent Substances 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000000428 dust Substances 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 235000019414 erythritol Nutrition 0.000 description 1
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 description 1
- 229940009714 erythritol Drugs 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 230000001815 facial effect Effects 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 229930182830 galactose Natural products 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 210000003780 hair follicle Anatomy 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 239000000017 hydrogel Substances 0.000 description 1
- 150000001261 hydroxy acids Chemical class 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 239000002085 irritant Substances 0.000 description 1
- 231100000021 irritant Toxicity 0.000 description 1
- 239000000905 isomalt Substances 0.000 description 1
- 235000010439 isomalt Nutrition 0.000 description 1
- HPIGCVXMBGOWTF-UHFFFAOYSA-N isomaltol Natural products CC(=O)C=1OC=CC=1O HPIGCVXMBGOWTF-UHFFFAOYSA-N 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 239000000845 maltitol Substances 0.000 description 1
- 235000010449 maltitol Nutrition 0.000 description 1
- VQHSOMBJVWLPSR-WUJBLJFYSA-N maltitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-WUJBLJFYSA-N 0.000 description 1
- 229940035436 maltitol Drugs 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 239000004530 micro-emulsion Substances 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 230000001333 moisturizer Effects 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 238000000569 multi-angle light scattering Methods 0.000 description 1
- 239000007908 nanoemulsion Substances 0.000 description 1
- 235000014593 oils and fats Nutrition 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 235000013406 prebiotics Nutrition 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 229940055019 propionibacterium acne Drugs 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 235000021254 resistant starch Nutrition 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 210000001732 sebaceous gland Anatomy 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 230000036559 skin health Effects 0.000 description 1
- 230000035483 skin reaction Effects 0.000 description 1
- 231100000430 skin reaction Toxicity 0.000 description 1
- 229940010747 sodium hyaluronate Drugs 0.000 description 1
- YWIVKILSMZOHHF-QJZPQSOGSA-N sodium;(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- Chemical compound [Na+].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 YWIVKILSMZOHHF-QJZPQSOGSA-N 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 229960002920 sorbitol Drugs 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/726—Glycosaminoglycans, i.e. mucopolysaccharides
- A61K31/728—Hyaluronic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/73—Polysaccharides
- A61K8/735—Mucopolysaccharides, e.g. hyaluronic acid; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/08—Antiseborrheics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/10—Anti-acne agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
- A61Q17/005—Antimicrobial preparations
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/007—Preparations for dry skin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q5/00—Preparations for care of the hair
- A61Q5/006—Antidandruff preparations
Definitions
- the present invention relates to the topical use of certain hyaluronic acids as selective antimicrobial agent.
- Said hyaluronic acids are furthermore suitable to disproportionally high reduce the share of Malassezia species in the presence of and in relation to other microbes such in particular of the microbes of sebaceous skin.
- Skin is the outermost protective covering of living beings and is the largest organ in the body.
- One of the main functions of the skin is to form a physical barrier (commonly called the skin barrier) that protects the body from external factors.
- skin prevents entry of harmful or potentially harmful chemicals and/ or microbes such as e.g. bacteria, fungi and viruses, into the body thereby preventing adverse effects that may be caused thereof.
- Malassezia species are microbes generally contained in the skin microbiome. As the fungus requires fat and oils to grow, it is most commonly found in areas with many sebaceous glands, i.e. on the scalp, face and upper parts of the body and particular prominent in sebaceous skin.
- Malassezia globosa Malassezia globosa (M. globosa) is known to be one of the major root causes of dandruff. It has been established that around 50% of people’s bodies have a negative reaction to the presence of this fungus.
- Said dysbiosis can be mitigated by using antimicrobial compounds that reduce the growth of undesired microbes to a greater extent than the one of desired microbes, which effect is also known microbiome balancing.
- ingredients which can selectively decrease the share of M. globosa in the skin preferably in the scalp microbiome of a person in need thereof to maintain a healthy skin microbiome.
- Preferably already known and well tolerated cosmetic compounds are used for said purpose.
- hyaluronic acids which are widely used in cosmetic compositions for hydration of skin, exhibit a selective antimicrobial activity against common microbes of sebaceous skin. Furthermore, and even more surprisingly, said antimicrobial activity is characterized by affecting disproportionally high the growth of M. globosa.
- said hyaluronic acids are suitable to selectively reduce the share of M. globosa in a microbiome, such as in particular in the microbiome of sebaceous skin while, at the same time, maintaining a favourable ratio or P. acnes to S. epidermis of >1 .
- Said selective antimicrobial effect can accordingly be used to maintain skin healthy, i.e. used in beauty routines for youthful and healthy skin and thus be non-therapeutic, i.e. cosmetic.
- the present invention relates to a topical non-therapeutic (i.e. cosmetic) use of hyaluronic acid having a molecular weight selected in the range of 10 to 75 kDa as antimicrobial agent, such as preferably as a selective antimicrobial agent against P. acnes, S. epidermis, S. hominis, S. capitis, S. mitis, C. simulans and M. globose, in particular when applied to sebaceous skin and/ or to the scalp.
- antimicrobial agent such as preferably as a selective antimicrobial agent against P. acnes, S. epidermis, S. hominis, S. capitis, S. mitis, C. simulans and M. globose, in particular when applied to sebaceous skin and/ or to the scalp.
- the selective antimicrobial effect as defined herein can be used for microbiome balancing when applied to the skin, in particular for microbiome balancing of the microbes of sebaceous skin, such as most in particular for microbiome balancing of the microbes of the scalp.
- the present invention also relates to the use of hyaluronic acid according to the present invention for maintaining the balance of a healthy skin microbiome comprising M. globosa in the presence of at least one, preferably two or more, most preferably all microbes selected from the group of S. epidermidis, P. acnes, S. hominis, S. capitis, S. mitis, and C. simulans when applied in the skin, such as in particular in the skin microbiome of sebaceous skin and/ or of the scalp.
- said skin microbiome comprises concomitantly at least M. globosa, P. acnesand S. epidermidis.
- Said antimicrobial effect can accordingly be used to prevent and/ or treat dysbiosis of a skin microbiota associated with increased levels of Malassezia species such as in particular with M. globosa, most preferably of the scalp microbiome, such as a scalp microbiome exhibiting concomitantly a ratio of P. acnes to S. epidermis of > 1.
- the invention also relates to the hyaluronic acid according to the present invention for use in counteracting the weakening of the skin barrier caused by a disbalance of the skin microbiome as well as in preventing or reducing the penetration of exogeneous molecules and/or microorganisms following such a weakening such as in particular S. aureus.
- said disbalance is associated with increased levels of Malassezia species such as in particular M. globosa in said skin microbiome.
- the present invention also relates to the hyaluronic acid according to the present invention for use in a method of prophylactically treating skin dysbiosis in a subject, wherein said skin dysbiosis is characterized by increased levels of Malassezia species such as preferably M. globosa and wherein said hyaluronic acid has antimicrobial effects (selectively) decreasing the skin levels (shares) of said Malassezia species such as preferably M. globosa while maintaining a ratio of P. acnes to S. epidermis of more than 1 .
- Malassezia species such as preferably M. globosa
- said hyaluronic acid has antimicrobial effects (selectively) decreasing the skin levels (shares) of said Malassezia species such as preferably M. globosa while maintaining a ratio of P. acnes to S. epidermis of more than 1 .
- the present invention relates to a method of decreasing skin relative abundance of non-beneficial skin microorganisms, the method comprising the step of administering a topical composition comprising a hyaluronic acid according to the present invention, wherein the level of the one or more non- beneficial microbial species in the skin of the subject is lower relative to the level of said microbial species in the skin of a subject administered a topical composition lacking the hyaluronic acid.
- said microorganisms respectively microbial species are selected from Malassezia, most preferably the microorganism (microbial species) is M. globosa.
- the antimicrobial effect of the hyaluronic acid according to the present invention is in particular characterized by reducing the share (and growth) of M. globosa in the respective skin microbiome, preferably in the presence of at least one, preferably all microbes selected from the group consisting of S. epidermidis, P. acnes, S. hominis, S. capitis, S. mitis and C. simulans. Most preferably in all embodiments of the present invention concomitantly the ratio of P. acnes to S. epidermidis in said skin microbiome is maintained >1 .
- the antimicrobial effect of the hyaluronic acid according to the present invention is characterized by reducing the growth M. globosa, S. epidermidis, P. acnes, S. hominis, S. capitis, S. mitis and C. simulans in a skin microbiome, while, however the share of M. globosa is disproportionally high decreased and concomitantly the ratio of P. acnes to S. epidermidis is maintained to be >1. This is particularly favourable for the scalp microbiome.
- the overall population of the microbes in the skin microbiome is reduced, preferably, however, by no more than -100%, most preferably by no more than -75%, such as in particular by no more than -65% after incubation at 37°C for4h, as this will maintain a healthy and balanced skin microbiome.
- the ratio of P. acnes to S. epidermidis in the respective microbiome before and after the use according to the present invention is equal and/ or higher than 1 , and equal and/ or lower than 3, preferably equal and/ or lower than 2, most preferably equal and/ or lower than 1.5. More preferably the ratio is selected in the range from 1 to 2, even more preferably in the range from 1 to 1 .5, most preferably in the range from 1.1 to 2, such as in the range from 1 .1 to 1.5.
- antimicrobial agent refers to a compound which reduces, suppresses or inhibits the growth of microorganisms such as in particular of at least M. Globosa, S. epidermidis, P. acnes, S. hominis, S. capitis, S. mitis and C. simulans.
- the antimicrobial agent according to the present invention reduces, suppresses or inhibits the growth of all of M. Globosa, S. epidermidis, P. acnes, S. hominis, S. capitis, S. mitis and C. simulans, more preferably however by no more than -100%, most preferably by no more than -75%, such as in particular by no more than -65% after incubation at 37°C for 4h.
- topical refers to a direct application to skin.
- (skin) microbiome or microbes of sebaceous skin refers to a microbiome which comprises especially two or more, preferably all of Propionibacterium acnes (P. acnes), Staphylococcus epidermidis (S. epidermidis), Staphylococcus hominis (S. hominis), Staphylococcus capitis (S. capitis), Streptococcus mitis (S. mitis), Corynebacterium simulans (C. simulans) and Malassezia globosa (M. globosa) species.
- the skin microbiome is characterized in that the ratio of P. acnes to S. Epidermis before the use/ treatment according to the present invention is > 1 , as it is the case in a healthy scalp as outlined above.
- microbiome balancing refers to maintaining the skin in healthy and infection free condition. Microbiome balancing is generally achieved by selectively reducing the share of at least one genus of harmful microbes and/ or increasing the share of one or more good microbes in a microbiome in need thereof. Said balancing also encompasses maintaining a favorable ratio of certain microbes with regard to each other, which ratio however may be different for different skin regions. Preferably, in all embodiments of the present invention the term microbiome balancing means selectively reducing the share of M. globosa while maintaining a ratio of P. acnes to S. Epidermis ⁇ 1 .
- the microbiome balancing according to the present invention is preferably characterised by not significantly altering the shares of the individual microbes in a skin microbiome after incubation after at 37C for 4h, except for the intended ones, here M. globosa and optionally S. epidermidis and P. acnes.
- the overall colony count in a skin microbiome should not be reduced more than 100%, preferably, not more than 75% as compared to just before the treatment.
- the microbiome balancing according to the present invention is a balancing of M. globosa in the presence of at least one, preferably in the presence of two or more, most preferably in the presence of all microbes selected from the group consisting of Staphylococcus hominis (S. hominis), Staphylococcus capitis (S. capitis), Streptococcus mitis (S. mitis), Corynebacterium simulans (C. simulans) and Malassezia globosa (M. globosa).
- S. hominis Staphylococcus hominis
- S. capitis Staphylococcus capitis
- Streptococcus mitis S. mitis
- Corynebacterium simulans C. simulans
- Malassezia globosa M. globosa
- share refers to the share of each (individual) microbe with regard to the total number of microbes in a microbial co-culture in % (i.e. with regard to at least two, preferably all sebaceous skin microbes as defined herein). Said share is calculated using the colony count of the respective (individual) microbe divided by the sum of the colony counts of all microbes of the respective microbiota * 100%.
- skin as used in this document, is meant to include the external surface of mammals, especially humans and includes the skin and the scalp. Preferred skin in all embodiments of the present invention is, however, facial and body skin such as most preferably the scalp.
- prevention refers to lessening the risk of developing a dysbiosis associated with an increased number in Malessazia species such as M. globosa and consequently any diseases associated therewith and/ or the administration to people in risk of developing a dysbiosis associated with an increased number in Malessazia species such as M. globosa.
- the exogenous molecules can be in particular irritant substances (hygiene products, solvents, etc.) or allergenic substances (perfumes, house dust, microbial agents).
- hyaluronic acid covers the basic unit of hyaluronic acid which includes the smallest fraction of hyaluronic acid comprising a disaccharide dimer, namely D-glucuronic acid and N-acetylglucosamine as well as linear polymers of said disaccharides, which are composed of D-glucuronic acid and N-acetyl-D-glucosamine, linked via alternating (3-(1 ⁇ 4) and (3-(1 ⁇ 3) glycosidic bonds.
- hyaluronic acid as used herein also comprises hydrolysed hyaluronic acid, hyaluronic acid salts, and in particular the alkali metals such as the sodium salt and the potassium salt, most preferably the sodium salts.
- alkali metals such as the sodium salt and the potassium salt, most preferably the sodium salts.
- Such salts are known as sodium hyaluronate.
- hyaluronic acid having a molecular weight selected in the range of 15 to 70 kDa, more preferably in the range of 20 to 65 kDa, such as in particular in the range of 25 to 60 kDa or even 30 to 60 kDa is used.
- hyaluronic acid in all embodiments of the present invention is hydrolysed hyaluronic acid (CAS 9004-61-9), which is e.g. commercially available from DSM Nutritional Products Ltd under the tradename HYA-ACTTM XS (37-56 kDa), from Givaudan under the tradename Primahyal 50 (MW 20 - 50kDa) and from Evonik under the tradename Hyacare 50 (MW 50 kDa).
- the molecular weight of the hyaluronic acid according to the present invention is determined by GPC-MALLS, 0.5 g/l in 0.2 mol/L NaCI.
- the antimicrobial effect respectively the microbiome balancing according to the present invention is most preferably characterized by reducing the growth and decreasing the share of M. globosa, in the concomitant presence of at least one, preferably all microbes selected from the groups consisting of S. hominis, S. capitis, S. mitis, C. simulans and M. globosa. Even more preferably, the ratio of P. acnes to S. epidermidis is maintained to be >1.
- the antimicrobial effect is most preferably characterized in that the change in the individual share of M. globosa in the concomitant presence of at least one microbe M(i) selected from the group consisting of S. epidermidis P. acnes, S. hominis, S. capitis, S. mitis, and C. simulans, preferably in the presence of all microbes M(i) is
- r CMG0 CMG 0 /(CMG 0 + CPA 0 + CSEo +CSH 0 +CSC 0 +CSM 0 +CCS 0 ) and wherein and the individual share of M.
- r cMG4 CMG 4 / CMG 4 + CPA 4 + CSE 4 +CSH 4 +CSC 4 +CSM 4 +CCS 4 ) and and wherein in said definition CPA 0 represents the colony counts of P. acnes directly after inoculation;
- CSEo represents the colony counts of S. epidermidis directly after inoculation
- CSHo represents the colony counts of S. hominis directly after inoculation
- CSH 0 represents the colony counts of S. capitis directly after inoculation
- CSMo represents the colony counts of S. mitis directly after inoculation
- CCSo represents the colony counts of C. simulans directly after inoculation
- CMG 0 represents the colony counts of M. globosa directly after inoculation
- CPA4 represents the colony counts of P. acnes after 4 hours of incubation
- CSE 4 represents the colony counts of S. epidermidis after 4 hours of incubation
- CSH4 represents the colony counts of S. hominis after 4 hours of incubation
- CSC 4 represents the colony counts of S. capitis after 4 hours of incubation
- CSM4 represents the colony counts of S. mitis after 4 hours of incubation
- CCS 4 represents the colony counts of C. simulans after 4 hours of incubation
- CMG 4 represents the colony counts of M. globosa after 4 hours of incubation; wherein the incubation is at 37°C.
- said change in the individual share of M. globosa is
- CM (i)0 represents the colony counts of the respective microbe M(i) directly after inoculation
- CM ( i)4 represents the colony counts of the respective microbe M(i) after 4 hours of incubation wherein the incubation is at 37°C.
- the share of P. acnes is positively affected by the uses and methods according to the invention and is
- the present invention also relates to the use of the hyaluronic acid according to the present invention with all the definitions and preferences as given herein as an antimicrobial agent for M. globosa, S. epidermidis, P. acnes, S. hominis, S. capitis, S. mitis, and C. simulans in the concomitant presence of each other wherein however, the share of M. globosa is reduced while the ratio of S. epidermidis and P. acnes is maintained to be >1 .
- the hyaluronic acid according to the present invention or a composition comprising said hyaluronic acid, respectively is in one advantageous embodiment applied on healthy skin and maintains or improves the aesthetic aspect of said skin; in said embodiments of the present invention, it is well understood that all uses and methods are cosmetic and non-therapeutical.
- the present invention relates to a non-therapeutical, cosmetic method of maintaining a healthy skin microbiome in particular of sebaceous skin and/ or the scalp, said method comprising the step of topically applying a cosmetic composition comprising a hyaluronic acid with all the definitions and preferences as given herein and optionally appreciating the effect. It is well understood that all definitions and preferences as outlined herein also apply to the method.
- the hyaluronic acid is preferably applied to the skin incorporated into a cosmetic or dermatological composition.
- the amount of the hyaluronic acid in the cosmetic composition is preferably selected in the range from 0.001 to 6.0 wt.-%, preferably from 0.01 to 5.0 wt.-%, most preferably from 0.1 to 3.0 wt.-%, based on the total weight of the cosmetic composition. Further suitable ranges encompass 0.5 to 3 wt.-% or 1 to 2.5 wt.-%.
- cosmetic composition refers to cosmetic compositions as defined under the heading "Kosmetika” in Römpp Lexikon Chemie, 10th edition 1997, Georg Thieme Verlag Stuttgart, New York as well as to cosmetic compositions as disclosed in A. Domsch, "Cosmetic Compositions", Verlag fur chemische Industrie (ed. H. Ziolkowsky), 4 th edition, 1992.
- compositions according to the present invention are in particular compositions intended to be topically applied to mammalian keratinous tissue such as in particular to human skin or the human scalp.
- the cosmetic or dermatological composition may be a leave-on or a rinse off cosmetic composition, and includes any product applied to a human body primarily for improving appearance, cleansing, odor control or general aesthetics.
- the cosmetic or dermatological composition of the present invention are rinse-off compositions such as in particular shampoos.
- compositions according to the present invention preferably further comprise a physiologically acceptable medium, that is to say a medium compatible with keratinous substances, such as the skin, mucosa, and keratinous fibers.
- physiologically acceptable medium is a cosmetically respectively dermatologically acceptable carrier.
- cosmetically respectively dermatologically acceptable carrier refers to all carriers and/or excipients and/or diluents conventionally used in cosmetic compositions or dermatological or pharmaceutical compositions.
- the cosmetic or dermatological composition may comprise further ingredients.
- Such ingredients are particularly surfactants, emulsifiers, thickeners, and oils.
- surfactants, emulsifiers, thickeners, and oils are well known to a person skilled in the art.
- the cosmetic or dermatological compositions according to the invention are in the form of a suspension or dispersion in solvents or fatty substances, or alternatively in the form of an emulsion or micro emulsion (in particular of O/W- or W/O- type), PIT-emulsion, nano emulsion, multiple emulsion (e. g. O/W/O- or W/O/W-type), pickering emulsion, hydrogel, lipogel, one- or multiphase solution or vesicular dispersion.
- the cosmetic or dermatological compositions in accordance with the invention can be in the form of a liquid, lotion, a thickened lotion, a gel, a cream, a milk, an ointment or a paste.
- the cosmetic or dermatological compositions according to the invention generally have a pH in the range from 3-10, preferably in the range from pH of 3-8, most preferred in the range from pH 3.5-7.5.
- the pH is adjusted by methods known to a person skilled in the art, e.g. by using an acid such as a hydroxy acid including glycolic acid, lactic acid, malic acid, citric acid and tartaric acid or a base such as e.g. sodium or potassium hydroxide or ammonium hydroxide as well as mixtures thereof.
- the cosmetic or dermatological compositions according to the present invention are in particular skin care preparations, functional preparations and/or hair care preparations such as most in particularly skin or hair care preparations.
- Examples of skin care preparations are, in particular, light protective preparations (sun care preparations), anti-ageing preparations, preparations for the treatment of photoageing, body oils, body lotions, body gels, treatment creams, skin protection ointments, moisturizing preparations such as moisturizing gels or moisturizing sprays, face and/or body moisturizers, as well as skin lightening preparations.
- light protective preparations unsun care preparations
- anti-ageing preparations preparations for the treatment of photoageing
- body oils body lotions, body gels, treatment creams, skin protection ointments
- moisturizing preparations such as moisturizing gels or moisturizing sprays
- face and/or body moisturizers as well as skin lightening preparations.
- Examples of functional preparations are cosmetic compositions containing active ingredients such as hormone preparations, vitamin preparations, vegetable extract preparations, anti-ageing preparations, and/or antimicrobial (antibacterial or antifungal) preparations without being limited thereto.
- hair care preparations which are suitable according to the invention and which may be mentioned are shampoos, hair conditioners (also referred to as hair rinses), hairdressing compositions, hair tonics, hair regenerating compositions, hair lotions, water wave lotions, hair sprays, hair creams, hair gels, hair oils, hair pomades or hair brilliantines. Accordingly, these are always preparations which are applied to the hair and the scalp for a shorter or longer time depending on the actual purpose for which they are used.
- the cosmetic or dermatological compositions according to the present invention are emulsions and/or gels. Even more preferably, the cosmetic or dermatological compositions are emulsions which contain an oily phase and an aqueous phase such as in particular O/W, W/O, Si/W, W/Si, O/W/O, W/O/W multiple or a pickering emulsions.
- the amount of the oily phase (i.e. the phase containing all oils and fats including the polar oils) present in such emulsions is preferably at least 10 wt.-%, such as in the range from 10 to 60 wt.-%, preferably in the range from 15 to 50 wt.-%, most preferably in the range from 15 to 40 wt.-%, based on the total weight of the cosmetic or dermatological composition.
- the amount of the aqueous phase present in such emulsions is preferably at least 20 wt.-%, such as in the range from 20 to 90 wt.-%, preferably in the range from 30 to 80 wt.-%, most preferably in the range from 30 to 70 wt.-%, based on the total weight of the cosmetic or dermatological composition.
- the hyaluronic acid according to the present invention may have a particular beneficial effect on the skin microbiome, when combined with further skin active ingredients.
- Particularly preferred skin active ingredients according to the present invention are plant-derived carbohydrate compounds such as monosaccharides, disaccharides, oligosaccharides or polysaccharides, preferably fructans and galactans, as well as saccharide isomerates and polyols, particularly glycerol, sugar alcohols e.g. maltitol, sorbitol, xylitol, erythritol and isomalt, vitamins such as niacinamide and peptides, such as tripeptides such as in particular SYN®-HYCAN from DSM Nutritional Products Ltd as well as mixtures thereof.
- plant-derived carbohydrate compounds such as monosaccharides, disaccharides, oligosaccharides or polysaccharides, preferably fructans and galactans, as well as saccharide isomerates and polyols, particularly glycerol, sugar alcohols e.g. maltitol, sorbitol, x
- Saccharide isomerate is for example commercially available under trade name Pentavitin® from DSM Nutritional Products AG, Switzerland.
- Niacinamide is for example commercially available under trade name Niacinamid PC from DSM Nutritional Products AG, Switzerland.
- Examples of monosaccharide include glucose, fructose, galactose and mixtures thereof.
- Examples of disaccharides include sucrose, maltose, lactose and mixtures thereof.
- oligosaccharides include fructo-oligosaccharides, gluco-oligosaccharide and mixtures thereof.
- Fructans are a category of carbohydrate consisting of fructooligosaccharides (FOS) and inulins, while galactans consist of galactooligosaccharides (GOS). Further preferred prebiotics are resistant starch, pectin, beta-glucans, and xylooligosaccharides.
- niacinamide is niacinamide
- compositions comprising the hyaluronic acid according to the present invention and at least one skin active ingredient, preferably saccharide isomerate and/or niacinamide, as described above are used to balance the microbiome of human skin and/or hair, particularly of the scalp or the scalp hair, with all the definitions and preferences as given herein.
- skin active ingredient preferably saccharide isomerate and/or niacinamide
- Assay 5 mL of TSB (Tryptic Say Broth) to which 500 pL of 1 wt.-% of the respective hyaluronic acid [(1) HYA-ACTTM XS (HA-XS): MW: 37-56KDa; (Ref1) HYA-ACTTM S HA-S) MW: 200-400 KDa] in PBS (Phosphate-buffered saline) have been added. Then these solutions have been inoculated by 500 pL of the respective calibrated mixture of the microbes (calibrated microbe mixture, which after inoculation mimics the microbiome of sebaceous skin) as outlined below.
- Table 2 shows the counts of colony (CFU/ml) and shares of the respective microbes at to and after t 4 , i.e. 4 hours of incubation at 37°C. All shares have been rounded.
- the hyaluronic acid according to the present invention overall excerpts an antimicrobial effect on the microbes of sebaceous skin.
- Figure 1 furthermore illustrates the share (i.e. distribution) of the respective microbe of sebaceous skin (i.e. r cM(i)0 respectively r cM(i)4 ) for the results (1) directly after inoculation (to) (figure 1a), respectively after 4 hours of incubation (t 4 ) (figure 1b) at 37°C by means of a pie diagram, illustrating the (selective) decrease in the share of M. globosa in the skin microbiome of sebaceous skin, and a concomitant increase in the share of P. acnes.
- Results 2 :
- Table 2 shows the counts of colony (CFU/ml) of the respective microbes after 4 hours of incubation at 37°C of (1) and (Ref1) versus the control.
- the hyaluronic acid according to the present invention leads to a less pronounced decrease in the ratio of P. acnes over S. epidermidis over time compared to the control or the references.
- Table 3 shows the counts of colony (CFU/ml) of the respective microbes after 4 hours of incubation @ 37°C. All shares have been rounded.
- hyaluronic acid having a MW of 200-400 KDa excerpts no antimicrobial effect on the microbes of sebaceous skin.
- Figure 2 furthermore illustrates the share (i.e. distribution) of the respective microbe of sebaceous skin (i.e. r cM(i)0 respectively r cM(i)4 ) for the results (Ref1) directly after inoculation (to) (figure 2a), respectively after 4 hours of incubation (t 4 ) (figure 2b) at 37°C by means of a pie diagram, illustrating no effect on the share of M. globosa in the skin microbiome of sebaceous skin by the treatment with the reference hyaluronic acid.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Dermatology (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Molecular Biology (AREA)
- Birds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention relates to the topical use of certain hyaluronic acids as selective antimicrobial agent suitable to reduce the share of Malassezia species in the presence of other microbes.
Description
HYALURONIC ACID AS ANTIMICROBIAL AGENT FOR USE ON THE SKIN
The present invention relates to the topical use of certain hyaluronic acids as selective antimicrobial agent. Said hyaluronic acids are furthermore suitable to disproportionally high reduce the share of Malassezia species in the presence of and in relation to other microbes such in particular of the microbes of sebaceous skin.
Skin is the outermost protective covering of living beings and is the largest organ in the body. One of the main functions of the skin is to form a physical barrier (commonly called the skin barrier) that protects the body from external factors. For example, skin prevents entry of harmful or potentially harmful chemicals and/ or microbes such as e.g. bacteria, fungi and viruses, into the body thereby preventing adverse effects that may be caused thereof.
It is well known that the surface of the skin is colonized by a great variety of microorganisms which form the skin microbiome (often also called skin microbiota). Resident microbiota are found in the upper parts of the epidermidis and congregated in and around the hair follicle. It is well established that the composition of these microbe communities are crucial for the maintenance of skin health and an overpopulation of certain species within these communities may lead to adverse skin effects.
Malassezia species are microbes generally contained in the skin microbiome. As the fungus requires fat and oils to grow, it is most commonly found in areas with many sebaceous glands, i.e. on the scalp, face and upper parts of the body and particular prominent in sebaceous skin. Next to Malassezia restricta, Malassezia globosa (M. globosa) is known to be one of the major root causes of dandruff. It has been established that around 50% of people’s bodies have a negative reaction to the presence of this fungus.
Furthermore, it has recently been reported that the ratio of P. acnes to S. epidermidis was higher in healthy scalp compared to the dandruff scalp, which corroborates with previous scalp microbiome studies carried out on French, Chinese, and Brazilian population (Clavaud et al., 2013; Wang et al., 2015; Xu et al., 2016).
A reduction or elimination of unwanted microbes on the skin such as M. globosa can be affected by application of topical compositions comprising one or more antimicrobial compounds. However, many antimicrobial compounds do not work in a selective manner. Thus, said compounds generally do not selectively act only against the unwanted microbe(s) but often also lead to the removal of the beneficial ones, which in turn may lead to dysbiosis and thus a weakened skin barrier and resulting adverse skin reactions which is not desired.
Said dysbiosis, however can be mitigated by using antimicrobial compounds that reduce the growth of undesired microbes to a greater extent than the one of desired microbes, which effect is also known microbiome balancing.
Thus, there is an ongoing need of ingredients, which can selectively decrease the share of M. globosa in the skin preferably in the scalp microbiome of a person in need thereof to maintain a healthy skin microbiome. Preferably already known and well tolerated cosmetic compounds are used for said purpose.
Surprisingly, it has now been found that certain hyaluronic acids, which are widely used in cosmetic compositions for hydration of skin, exhibit a selective antimicrobial activity against common microbes of sebaceous skin. Furthermore, and even more surprisingly, said antimicrobial activity is characterized by affecting disproportionally high the growth of M. globosa. Thus, said hyaluronic acids are suitable to selectively reduce the share of M. globosa in a microbiome, such as in particular in the microbiome of sebaceous skin while, at the same time, maintaining a favourable ratio or P. acnes to S. epidermis of >1 .
Said selective antimicrobial effect can accordingly be used to maintain skin healthy, i.e. used in beauty routines for youthful and healthy skin and thus be non-therapeutic, i.e. cosmetic.
Thus, in a first aspect the present invention relates to a topical non-therapeutic (i.e. cosmetic) use of hyaluronic acid having a molecular weight selected in the range of 10 to 75 kDa as antimicrobial agent, such as preferably as a selective antimicrobial agent against P. acnes, S. epidermis, S. hominis, S. capitis, S. mitis, C. simulans and M. globose, in particular when applied to sebaceous skin and/ or to the scalp.
The selective antimicrobial effect as defined herein can be used for microbiome balancing when applied to the skin, in particular for microbiome balancing of the microbes of sebaceous skin, such as most in particular for microbiome balancing of the microbes of the scalp. This in particular as a ratio of P. acnes to S. epidermis is maintained >1 while concomitantly reducing M. globosa, which is beneficial for the skin microbiota of the scalp as discussed above.
Thus, the present invention also relates to the use of hyaluronic acid according to the present invention for maintaining the balance of a healthy skin microbiome comprising M. globosa in the presence of at least one, preferably two or more, most preferably all microbes selected from the group of S. epidermidis, P. acnes, S. hominis, S. capitis, S. mitis, and C. simulans when applied in the skin, such as in particular in the skin microbiome of sebaceous skin and/ or of the scalp. Most preferably said skin microbiome comprises concomitantly at least M. globosa, P. acnesand S. epidermidis.
Said antimicrobial effect can accordingly be used to prevent and/ or treat dysbiosis of a skin microbiota associated with increased levels of Malassezia species such as in particular with M. globosa, most preferably of the scalp microbiome, such as a scalp microbiome exhibiting concomitantly a ratio of P. acnes to S. epidermis of > 1.
As an overall balanced microbiome leads to the maintenance of an intact skin barrier, the invention also relates to the hyaluronic acid according to the present invention for use in counteracting the weakening of the skin barrier caused by a disbalance of the skin microbiome as well as in preventing or reducing the penetration of exogeneous molecules and/or microorganisms following such a weakening such as in particular S. aureus. In particular said disbalance is associated with increased levels of Malassezia species such as in particular M. globosa in said skin microbiome.
In a particular advantageous embodiment, the present invention also relates to the hyaluronic acid according to the present invention for use in a method of prophylactically treating skin dysbiosis in a subject, wherein said skin dysbiosis is characterized by increased levels of Malassezia species such as preferably M. globosa and wherein said hyaluronic acid has antimicrobial effects (selectively) decreasing the skin levels (shares) of said Malassezia species such as preferably M. globosa while maintaining a ratio of P. acnes to S. epidermis of more than 1 .
In a further particular embodiment, the present invention relates to a method of decreasing skin relative abundance of non-beneficial skin microorganisms, the method comprising the step of administering a topical composition comprising a hyaluronic acid according to the present invention, wherein the level of the one or more non- beneficial microbial species in the skin of the subject is lower relative to the level of said microbial species in the skin of a subject administered a topical composition lacking the hyaluronic acid. Preferably said microorganisms respectively microbial species are selected from Malassezia, most preferably the microorganism (microbial species) is M. globosa.
In all embodiments of the present invention, the antimicrobial effect of the hyaluronic acid according to the present invention is in particular characterized by reducing the share (and growth) of M. globosa in the respective skin microbiome, preferably in the presence of at least one, preferably all microbes selected from the group consisting of S. epidermidis, P. acnes, S. hominis, S. capitis, S. mitis and C. simulans. Most preferably in all embodiments of the present invention concomitantly the ratio of P. acnes to S. epidermidis in said skin microbiome is maintained >1 .
More advantageously, the antimicrobial effect of the hyaluronic acid according to the present invention is characterized by reducing the growth M. globosa, S. epidermidis, P. acnes, S. hominis, S. capitis, S. mitis and C. simulans in a skin microbiome, while, however the share of M. globosa is disproportionally high decreased and concomitantly the ratio of P. acnes to S. epidermidis is maintained to be >1. This is particularly favourable for the scalp microbiome.
In all embodiments of the present invention, the overall population of the microbes in the skin microbiome is reduced, preferably, however, by no more than -100%, most preferably by no more than -75%, such as in particular by no more than -65% after incubation at 37°C for4h, as this will maintain a healthy and balanced skin microbiome.
Preferably, in all embodiments of the present invention the ratio of P. acnes to S. epidermidis in the respective microbiome before and after the use according to the present invention is equal and/ or higher than 1 , and equal and/ or lower than 3, preferably equal and/ or lower than 2, most preferably equal and/ or lower than 1.5. More preferably the ratio is selected in the range from 1 to 2, even more preferably in
the range from 1 to 1 .5, most preferably in the range from 1.1 to 2, such as in the range from 1 .1 to 1.5.
For sake of clarity, some terms as used in the present document are defined as follows:
The term ‘antimicrobial agent’ as used herein refers to a compound which reduces, suppresses or inhibits the growth of microorganisms such as in particular of at least M. Globosa, S. epidermidis, P. acnes, S. hominis, S. capitis, S. mitis and C. simulans. Preferably, in all embodiments of the present invention, the antimicrobial agent according to the present invention reduces, suppresses or inhibits the growth of all of M. Globosa, S. epidermidis, P. acnes, S. hominis, S. capitis, S. mitis and C. simulans, more preferably however by no more than -100%, most preferably by no more than -75%, such as in particular by no more than -65% after incubation at 37°C for 4h.
The term ‘preparation’ or ‘formulation’ is used in this document as equivalent to the term ’composition’.
The term ‘topical’ as used refers to a direct application to skin.
The term ‘(skin) microbiome or microbes of sebaceous skin’ as used herein refers to a microbiome which comprises especially two or more, preferably all of Propionibacterium acnes (P. acnes), Staphylococcus epidermidis (S. epidermidis), Staphylococcus hominis (S. hominis), Staphylococcus capitis (S. capitis), Streptococcus mitis (S. mitis), Corynebacterium simulans (C. simulans) and Malassezia globosa (M. globosa) species. Even more preferably, in all embodiments of the present invention, the skin microbiome is characterized in that the ratio of P. acnes to S. Epidermis before the use/ treatment according to the present invention is > 1 , as it is the case in a healthy scalp as outlined above.
The term ‘microbiome balancing’ as used herein refers to maintaining the skin in healthy and infection free condition. Microbiome balancing is generally achieved by selectively reducing the share of at least one genus of harmful microbes and/ or increasing the share of one or more good microbes in a microbiome in need thereof. Said balancing also encompasses maintaining a favorable ratio of certain microbes with regard to each other, which ratio however may be different for different skin regions. Preferably, in all embodiments of the present invention the term microbiome
balancing means selectively reducing the share of M. globosa while maintaining a ratio of P. acnes to S. Epidermis ≥ 1 .
Furthermore, the microbiome balancing according to the present invention is preferably characterised by not significantly altering the shares of the individual microbes in a skin microbiome after incubation after at 37C for 4h, except for the intended ones, here M. globosa and optionally S. epidermidis and P. acnes. To maintain a balanced microbiome, the overall colony count in a skin microbiome should not be reduced more than 100%, preferably, not more than 75% as compared to just before the treatment.
It is well understood that a microbiome balancing always takes place in the mutual presence of at least two microbes of a microbiome. Preferably, the microbiome balancing according to the present invention is a balancing of M. globosa in the presence of at least one, preferably in the presence of two or more, most preferably in the presence of all microbes selected from the group consisting of Staphylococcus hominis (S. hominis), Staphylococcus capitis (S. capitis), Streptococcus mitis (S. mitis), Corynebacterium simulans (C. simulans) and Malassezia globosa (M. globosa).
The term ‘share' as used herein refers to the share of each (individual) microbe with regard to the total number of microbes in a microbial co-culture in % (i.e. with regard to at least two, preferably all sebaceous skin microbes as defined herein). Said share is calculated using the colony count of the respective (individual) microbe divided by the sum of the colony counts of all microbes of the respective microbiota * 100%.
Any 'count(s)’ or ‘colony count(s)’ of microbe(s) is given in this document as colony- forming unit (cfu) per millilitre.
The antimicrobial effect respectively the microbiome balancing according to the present invention is assessed after incubation at 37°C for 4h compared to t=0 h (i.e. directly after inoculation) as outlined in the examples.
The term ‘skin’ as used in this document, is meant to include the external surface of mammals, especially humans and includes the skin and the scalp. Preferred skin in all embodiments of the present invention is, however, facial and body skin such as most preferably the scalp.
The term ‘prevention’ as used herein refers to lessening the risk of developing a dysbiosis associated with an increased number in Malessazia species such as M. globosa and consequently any diseases associated therewith and/ or the administration to people in risk of developing a dysbiosis associated with an increased number in Malessazia species such as M. globosa.
The exogenous molecules can be in particular irritant substances (hygiene products, solvents, etc.) or allergenic substances (perfumes, house dust, microbial agents).
The term ‘hyaluronic acid’ as used herein covers the basic unit of hyaluronic acid which includes the smallest fraction of hyaluronic acid comprising a disaccharide dimer, namely D-glucuronic acid and N-acetylglucosamine as well as linear polymers of said disaccharides, which are composed of D-glucuronic acid and N-acetyl-D-glucosamine, linked via alternating (3-(1 → 4) and (3-(1 → 3) glycosidic bonds.
The term ‘hyaluronic acid’ as used herein also comprises hydrolysed hyaluronic acid, hyaluronic acid salts, and in particular the alkali metals such as the sodium salt and the potassium salt, most preferably the sodium salts. Such salts are known as sodium hyaluronate.
Preferably, in all embodiments of the present invention hyaluronic acid having a molecular weight selected in the range of 15 to 70 kDa, more preferably in the range of 20 to 65 kDa, such as in particular in the range of 25 to 60 kDa or even 30 to 60 kDa is used.
The preferred form of hyaluronic acid in all embodiments of the present invention is hydrolysed hyaluronic acid (CAS 9004-61-9), which is e.g. commercially available from DSM Nutritional Products Ltd under the tradename HYA-ACT™ XS (37-56 kDa), from Givaudan under the tradename Primahyal 50 (MW 20 - 50kDa) and from Evonik under the tradename Hyacare 50 (MW 50 kDa).
The molecular weight of the hyaluronic acid according to the present invention is determined by GPC-MALLS, 0.5 g/l in 0.2 mol/L NaCI.
In all embodiments of the present invention the antimicrobial effect respectively the microbiome balancing according to the present invention is most preferably characterized by reducing the growth and decreasing the share of M. globosa, in the concomitant presence of at least one, preferably all microbes selected from the groups consisting of S. hominis, S. capitis, S. mitis, C. simulans and M. globosa. Even more preferably, the ratio of P. acnes to S. epidermidis is maintained to be >1.
In all embodiments of the present invention the antimicrobial effect is most preferably characterized in that the change in the individual share of M. globosa in the concomitant presence of at least one microbe M(i) selected from the group consisting of S. epidermidis P. acnes, S. hominis, S. capitis, S. mitis, and C. simulans, preferably in the presence of all microbes M(i) is
-25% > ((rCMG4 / r cMG0)-1)*100 > -100% and wherein the individual share of M. globosa in the total number of microbes directly after inoculations is defined as rcMG0= CMG0/(CMG0+ CPA0+ CSEo +CSH0+CSC0+CSM0+CCS0) and wherein and the individual share of M. globosa in the total number of microbes after 4 hours of incubation at 37°C are defined as rcMG4 = CMG4/ CMG4+ CPA4+ CSE4 +CSH4+CSC4+CSM4+CCS4) and and wherein in said definition CPA0 represents the colony counts of P. acnes directly after inoculation;
CSEo represents the colony counts of S. epidermidis directly after inoculation
CSHo represents the colony counts of S. hominis directly after inoculation; CSH0 represents the colony counts of S. capitis directly after inoculation;
CSMo represents the colony counts of S. mitis directly after inoculation;
CCSo represents the colony counts of C. simulans directly after inoculation;
CMG0 represents the colony counts of M. globosa directly after inoculation; and
CPA4 represents the colony counts of P. acnes after 4 hours of incubation;
CSE4 represents the colony counts of S. epidermidis after 4 hours of incubation;
CSH4 represents the colony counts of S. hominis after 4 hours of incubation;
CSC4 represents the colony counts of S. capitis after 4 hours of incubation;
CSM4 represents the colony counts of S. mitis after 4 hours of incubation;
CCS4 represents the colony counts of C. simulans after 4 hours of incubation;
CMG4 represents the colony counts of M. globosa after 4 hours of incubation;
wherein the incubation is at 37°C.
Preferably, said change in the individual share of M. globosa is
-30% > ((rCMG4 I rCMG0)-1)*100 > -75%
Even more preferably, said change in the individual share of M. globosa is
-35% > ((rCMG4 I rCMG0)-1)*100 > -60%.
It is furthermore preferred that the concomitant change in the respective individual share of each of the microbes M(i) is
+ 150% > ((rCM(i)4 I rCM(i)0 -1)*100 > -100%, preferably
+ 125% > ((rCM(i)4 I rCM(i)0 -1)*100 -75%, most preferably
+ 120% > rCM(i)4 I rCM(i)0 -1)*100 > -70%, and wherein rCM(i)0 = CM(i)0/(CPA0+CSE0+CSH0+CSH0+CSMo+CCS0+CMG0), and rCM(i)4 = CM(i4)/ (CPA4+ CSE4+ CSH4+ CSC4+CSM4+ CCS4+ CMG4) ,
CM(i)0 represents the colony counts of the respective microbe M(i) directly after inoculation; and
CM(i)4 represents the colony counts of the respective microbe M(i) after 4 hours of incubation wherein the incubation is at 37°C.
In all embodiments of the present invention, it is furthermore preferred that the share of S. epidermidis is positively affected by the uses and methods according to the invention and is
+ 150% > ((rCM(i)4 I rCM(i)0 -1)*100 > 0%, preferably
+ 125% > ((rCM(i)4 I rCM(i)0 -1)*100 > +25%, most preferably
+ 120% > (( rCM(i)4 / rCM(i)0 -1)*100 > +50%.
In all embodiments of the present invention, it is furthermore preferred that the share of P. acnes is positively affected by the uses and methods according to the invention and is
+50% > ((rCM(i)4 / rCM(i)0 -1)*100 > 0%, preferably
+25% > ((rCM(i)4 / rCM(ii0) -1)*100 > +5%, most preferably
+20% > ((rCM(i)4 I rCM(i)0 -1)*100 > +10%.
Furthermore, as the growth of all microbes M(i) is decreased by the application of the hyaluronic acid according to the present invention overtime, the present invention also relates to the use of the hyaluronic acid according to the present invention with all the definitions and preferences as given herein as an antimicrobial agent for M. globosa, S. epidermidis, P. acnes, S. hominis, S. capitis, S. mitis, and C. simulans in the concomitant presence of each other wherein however, the share of M. globosa is reduced while the ratio of S. epidermidis and P. acnes is maintained to be >1 .
It is important that the balancing of microbial growth allows the skin to remain in a healthy state. Hence, the hyaluronic acid according to the present invention or a composition comprising said hyaluronic acid, respectively, is in one advantageous embodiment applied on healthy skin and maintains or improves the aesthetic aspect of said skin; in said embodiments of the present invention, it is well understood that all uses and methods are cosmetic and non-therapeutical.
Thus, in a further aspect, the present invention relates to a non-therapeutical, cosmetic method of maintaining a healthy skin microbiome in particular of sebaceous skin and/ or the scalp, said method comprising the step of topically applying a cosmetic composition comprising a hyaluronic acid with all the definitions and preferences as given herein and optionally appreciating the effect. It is well understood that all definitions and preferences as outlined herein also apply to the method.
In all embodiments of the present invention, the hyaluronic acid is preferably applied to the skin incorporated into a cosmetic or dermatological composition.
The amount of the hyaluronic acid in the cosmetic composition is preferably selected in the range from 0.001 to 6.0 wt.-%, preferably from 0.01 to 5.0 wt.-%, most preferably from 0.1 to 3.0 wt.-%, based on the total weight of the cosmetic composition. Further suitable ranges encompass 0.5 to 3 wt.-% or 1 to 2.5 wt.-%.
The term ‘cosmetic composition’ as used in the present application refers to cosmetic compositions as defined under the heading "Kosmetika" in Römpp Lexikon Chemie, 10th edition 1997, Georg Thieme Verlag Stuttgart, New York as well as to cosmetic
compositions as disclosed in A. Domsch, "Cosmetic Compositions", Verlag fur chemische Industrie (ed. H. Ziolkowsky), 4th edition, 1992.
The cosmetic or dermatological compositions according to the present invention are in particular compositions intended to be topically applied to mammalian keratinous tissue such as in particular to human skin or the human scalp.
The cosmetic or dermatological composition may be a leave-on or a rinse off cosmetic composition, and includes any product applied to a human body primarily for improving appearance, cleansing, odor control or general aesthetics. Preferably the cosmetic or dermatological composition of the present invention are rinse-off compositions such as in particular shampoos.
The cosmetic or dermatological compositions according to the present invention preferably further comprise a physiologically acceptable medium, that is to say a medium compatible with keratinous substances, such as the skin, mucosa, and keratinous fibers. In particular the physiologically acceptable medium is a cosmetically respectively dermatologically acceptable carrier.
The term cosmetically respectively dermatologically acceptable carrier refers to all carriers and/or excipients and/or diluents conventionally used in cosmetic compositions or dermatological or pharmaceutical compositions.
The cosmetic or dermatological composition may comprise further ingredients. Such ingredients are particularly surfactants, emulsifiers, thickeners, and oils. Such suitable surfactants, emulsifiers, thickeners, and oils are well known to a person skilled in the art.
Preferably, the cosmetic or dermatological compositions according to the invention are in the form of a suspension or dispersion in solvents or fatty substances, or alternatively in the form of an emulsion or micro emulsion (in particular of O/W- or W/O- type), PIT-emulsion, nano emulsion, multiple emulsion (e. g. O/W/O- or W/O/W-type), pickering emulsion, hydrogel, lipogel, one- or multiphase solution or vesicular dispersion.
The cosmetic or dermatological compositions in accordance with the invention can be in the form of a liquid, lotion, a thickened lotion, a gel, a cream, a milk, an ointment or a paste.
The cosmetic or dermatological compositions according to the invention generally have a pH in the range from 3-10, preferably in the range from pH of 3-8, most preferred in the range from pH 3.5-7.5. The pH is adjusted by methods known to a person skilled in the art, e.g. by using an acid such as a hydroxy acid including glycolic acid, lactic acid, malic acid, citric acid and tartaric acid or a base such as e.g. sodium or potassium hydroxide or ammonium hydroxide as well as mixtures thereof.
The cosmetic or dermatological compositions according to the present invention are in particular skin care preparations, functional preparations and/or hair care preparations such as most in particularly skin or hair care preparations.
Examples of skin care preparations are, in particular, light protective preparations (sun care preparations), anti-ageing preparations, preparations for the treatment of photoageing, body oils, body lotions, body gels, treatment creams, skin protection ointments, moisturizing preparations such as moisturizing gels or moisturizing sprays, face and/or body moisturizers, as well as skin lightening preparations.
Examples of functional preparations are cosmetic compositions containing active ingredients such as hormone preparations, vitamin preparations, vegetable extract preparations, anti-ageing preparations, and/or antimicrobial (antibacterial or antifungal) preparations without being limited thereto.
Examples of hair care preparations which are suitable according to the invention and which may be mentioned are shampoos, hair conditioners (also referred to as hair rinses), hairdressing compositions, hair tonics, hair regenerating compositions, hair lotions, water wave lotions, hair sprays, hair creams, hair gels, hair oils, hair pomades or hair brilliantines. Accordingly, these are always preparations which are applied to the hair and the scalp for a shorter or longer time depending on the actual purpose for which they are used.
In a preferred embodiment, the cosmetic or dermatological compositions according to the present invention are emulsions and/or gels. Even more preferably, the cosmetic
or dermatological compositions are emulsions which contain an oily phase and an aqueous phase such as in particular O/W, W/O, Si/W, W/Si, O/W/O, W/O/W multiple or a pickering emulsions.
The amount of the oily phase (i.e. the phase containing all oils and fats including the polar oils) present in such emulsions is preferably at least 10 wt.-%, such as in the range from 10 to 60 wt.-%, preferably in the range from 15 to 50 wt.-%, most preferably in the range from 15 to 40 wt.-%, based on the total weight of the cosmetic or dermatological composition.
The amount of the aqueous phase present in such emulsions is preferably at least 20 wt.-%, such as in the range from 20 to 90 wt.-%, preferably in the range from 30 to 80 wt.-%, most preferably in the range from 30 to 70 wt.-%, based on the total weight of the cosmetic or dermatological composition.
Particularly important is that the hyaluronic acid according to the present invention may have a particular beneficial effect on the skin microbiome, when combined with further skin active ingredients.
Particularly preferred skin active ingredients according to the present invention are plant-derived carbohydrate compounds such as monosaccharides, disaccharides, oligosaccharides or polysaccharides, preferably fructans and galactans, as well as saccharide isomerates and polyols, particularly glycerol, sugar alcohols e.g. maltitol, sorbitol, xylitol, erythritol and isomalt, vitamins such as niacinamide and peptides, such as tripeptides such as in particular SYN®-HYCAN from DSM Nutritional Products Ltd as well as mixtures thereof.
Saccharide isomerate is for example commercially available under trade name Pentavitin® from DSM Nutritional Products AG, Switzerland.
Niacinamide is for example commercially available under trade name Niacinamid PC from DSM Nutritional Products AG, Switzerland.
Examples of monosaccharide include glucose, fructose, galactose and mixtures thereof.
Examples of disaccharides include sucrose, maltose, lactose and mixtures thereof.
Examples of oligosaccharides include fructo-oligosaccharides, gluco-oligosaccharide and mixtures thereof.
Fructans are a category of carbohydrate consisting of fructooligosaccharides (FOS) and inulins, while galactans consist of galactooligosaccharides (GOS). Further preferred prebiotics are resistant starch, pectin, beta-glucans, and xylooligosaccharides.
Further suitable ingredients to be combined with the hyaluronic acid of the present invention in the uses and methods according to the present invention is niacinamide.
Hence, it is preferred that a composition comprising the hyaluronic acid according to the present invention and at least one skin active ingredient, preferably saccharide isomerate and/or niacinamide, as described above are used to balance the microbiome of human skin and/or hair, particularly of the scalp or the scalp hair, with all the definitions and preferences as given herein.
The following examples are provided to further illustrate the compositions and effects of the present invention. These examples are illustrative only and are not intended to limit the scope of the invention in any way.
Experimental series 1: Antimicrobial effect
Assay: 5 mL of TSB (Tryptic Say Broth) to which 500 pL of 1 wt.-% of the respective hyaluronic acid [(1) HYA-ACT™ XS (HA-XS): MW: 37-56KDa; (Ref1) HYA-ACT™ S HA-S) MW: 200-400 KDa] in PBS (Phosphate-buffered saline) have been added. Then these solutions have been inoculated by 500 pL of the respective calibrated mixture of the microbes (calibrated microbe mixture, which after inoculation mimics the microbiome of sebaceous skin) as outlined below. Directly after inoculation (colony count to) and/or after 4 hours of incubation at 37°C, 100pL have been taken and plated on an Agar gel petri dish. The microbes have then been counted based on the colony specific morphology and/or size. The results are presented below.
‘average of 4 samples
Results 1:
Table 2 shows the counts of colony (CFU/ml) and shares of the respective microbes at to and after t4, i.e. 4 hours of incubation at 37°C. All shares have been rounded.
Table 1
As can be retrieved from Table 1 , the hyaluronic acid according to the present invention overall excerpts an antimicrobial effect on the microbes of sebaceous skin.
Figure 1 furthermore illustrates the share (i.e. distribution) of the respective microbe of sebaceous skin (i.e. rcM(i)0 respectively rcM(i)4) for the results (1) directly after inoculation (to) (figure 1a), respectively after 4 hours of incubation (t4) (figure 1b) at 37°C by means of a pie diagram, illustrating the (selective) decrease in the share of M. globosa in the skin microbiome of sebaceous skin, and a concomitant increase in the share of P. acnes.
Results 2:
Table 2 shows the counts of colony (CFU/ml) of the respective microbes after 4 hours of incubation at 37°C of (1) and (Ref1) versus the control. Table 2
As can be retrieved from Table 2, the hyaluronic acid according to the present invention leads to a less pronounced decrease in the ratio of P. acnes over S. epidermidis over time compared to the control or the references.
Results 3: (Reference)
Table 3 shows the counts of colony (CFU/ml) of the respective microbes after 4 hours of incubation @ 37°C. All shares have been rounded.
Table 3
As can be retrieved from Table 3, hyaluronic acid having a MW of 200-400 KDa excerpts no antimicrobial effect on the microbes of sebaceous skin.
Figure 2 furthermore illustrates the share (i.e. distribution) of the respective microbe of sebaceous skin (i.e. rcM(i)0 respectively rcM(i)4) for the results (Ref1) directly after inoculation (to) (figure 2a), respectively after 4 hours of incubation (t4) (figure 2b) at 37°C by means of a pie diagram, illustrating no effect on the share of M. globosa in the skin microbiome of sebaceous skin by the treatment with the reference hyaluronic acid.
Formulation examples
1. IN & OUT Serum
2. Hand sanitizer
3. “ANTI-HAIR LOSS TONIC”
4. “SCALP PEELING”
5. “SHAMPOO”
Claims
1 . A cosmetic, topical non-therapeutic use of hyaluronic acid having a molecular weight selected in the range of 10 to 75 kDa as an antimicrobial agent to reduce the growth of at least one, preferably all of P. acnes, S. epidermis, S. hominis, S. capitis, S. mitis, C. simulans and M. globosa.
2. The use according to claim 1 , wherein the antimicrobial effect of the hyaluronic acid is characterized by decreasing the share of M. globosa in a skin microbiome comprising M. globosa and at least one, preferably all of P acnes, S. epidermis, S. hominis, S. capitis, S. mitis, C. simulans and M. globosa.
3. The use according to claim 1 and/or 2, wherein the ratio of P acnes to S. epidermidis in the skin microbiome before and after the use is > 1.
4. The use according to anyone of the preceding claims, wherein the skin is the scalp.
5. The use according to anyone or more of the preceding claims for maintaining a healthy skin microbiome.
6. The use according to anyone or more of the preceding claims, wherein the antimicrobial effect of the hyaluronic acid is characterized in that the change in the individual share of M. globosa in the concomitant presence of at least one, preferably all the microbes M(i) consisting of the group of S. epidermidis, P. acnes, S. hominis, S. capitis, S. mitis, C. simulans and M. globosa is
-25% > ((rCMG4 / rCMG0)-1)*100 > -100% and wherein rCMG0 = CMG0/(CMG0+ CPA0+ CSE0 +CSH0+CSC0+CSM0+CCS0) and rCMG4 = CMG4/(CMG4+ CPA4+ CSE4 +CSH4+CSC4+CSM4+CCS4) and wherein CPA0 represents the colony counts of P. acnes directly after inoculation;
CSE0 represents the colony counts of S. epidermidis directly after inoculation CSH0 represents the colony counts of S. hominis directly after inoculation; CSH0 represents the colony counts of S. capitis directly after inoculation;
CSM0 represents the colony counts of S. mitis directly after inoculation;
CCS0 represents the colony counts of C. simulans directly after inoculation; CMG0 represents the colony counts of M. globosa directly after inoculation;
and
CPA4 represents the colony counts of P. acnes after 4 hours of incubation;
CSE4 represents the colony counts of S. epidermidis after 4 hours of incubation;
CSH4 represents the colony counts of S. hominis after 4 hours of incubation; CSC4 represents the colony counts of S. capitis after 4 hours of incubation;
CSM4 represents the colony counts of S. mitis after 4 hours of incubation;
CCS4 represents the colony counts of C. simulans after 4 hours of incubation; CMG4 represents the colony counts of M. globosa after 4 hours of incubation; wherein the incubation is at 37°C.
7. The use according to anyone or more of the preceding claims, wherein the hyaluronic acid is hydrolyzed hyaluronic acid.
8. The use according to anyone or more of the preceding claims, wherein the hyaluronic acid has a molecular weight selected in the range from 15 to 70 kDa, preferably in the range from 20 to 65 kDa, most preferably in the range from 25 to 60 kDa.
9. The use according to anyone or more of the preceding claims, wherein the use is in form of a cosmetic or dermatological composition.
10. The use according to claim 9, wherein the amount of the hyaluronic acid in the cosmetic or dermatological composition is selected in the range from 0.001 to 6.0 wt.-%, preferably from 0.01 to 5.0 wt.-%, most preferably from 0.1 to 3.0 wt.-%, based on the total weight of the cosmetic composition.
11 . The use according to claim 9 and/ or 10, wherein the composition is a shampoo, a hair conditioner, a hairdressing composition, hair tonics, hair regenerating compositions, hair lotions, water wave lotions, hair sprays, hair creams, hair gels, hair oils, hair pomades or hair brilliantines.
12. Non-therapeutic cosmetic use of a topical composition comprising a hyaluronic acid having a molecular weight selected in the range of 10 to 75 KDa for maintaining the balance of a healthy skin microbiome comprising M. globosa in the presence of at least one, preferably two or more, most preferably all
microbes selected from the group of S. epidermidis, P. acnes, S. hominis, S. capitis, S. mitis and C. simulans. The use according to claim 12, wherein the skin microbiome is the skin microbiome of the scalp. The use according to claim 12 and/ or 13, wherein the microbiome balancing is characterized by decreasing the share of M. globosa while maintaining the ratio of P. acnes to S. epidermidis ≥ 1 . A method of balancing microbiota of skin, preferably the scalp comprising a step of applying thereto a hyaluronic acid having a molecular weight selected in the range of 10 to 75 KDa in a topical composition, where balancing means selectively reducing the share of M. globosa in said microbiota, while maintaining the ratio of P. acnes to S. epidermidis ≥ 1 .
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP21152933.4 | 2021-01-22 | ||
| EP21152933 | 2021-01-22 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2022157307A1 true WO2022157307A1 (en) | 2022-07-28 |
Family
ID=74205732
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/EP2022/051342 WO2022157307A1 (en) | 2021-01-22 | 2022-01-21 | Hyaluronic acid as antimicrobial agent for use on the skin |
Country Status (1)
| Country | Link |
|---|---|
| WO (1) | WO2022157307A1 (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009124266A2 (en) * | 2008-04-04 | 2009-10-08 | University Of Utah Research Foundation | Alkylated sem-synthetic glycosaminoglycosan ethers, and methods for making and using thereof |
| KR20160141487A (en) * | 2015-06-01 | 2016-12-09 | 서울과학기술대학교 산학협력단 | pH sensitive Hydroxyethyl Cellulose-Hyaluronic Acid Complex Hydrogel and Method of Preparing the Same |
| WO2020245797A1 (en) * | 2019-06-05 | 2020-12-10 | Lac2biome S.r.l. | Compositions comprising a bacterial strain lactobacillus paracasei and hyaluronic acid and the use thereof for the treatment of the skin |
-
2022
- 2022-01-21 WO PCT/EP2022/051342 patent/WO2022157307A1/en active Application Filing
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009124266A2 (en) * | 2008-04-04 | 2009-10-08 | University Of Utah Research Foundation | Alkylated sem-synthetic glycosaminoglycosan ethers, and methods for making and using thereof |
| KR20160141487A (en) * | 2015-06-01 | 2016-12-09 | 서울과학기술대학교 산학협력단 | pH sensitive Hydroxyethyl Cellulose-Hyaluronic Acid Complex Hydrogel and Method of Preparing the Same |
| WO2020245797A1 (en) * | 2019-06-05 | 2020-12-10 | Lac2biome S.r.l. | Compositions comprising a bacterial strain lactobacillus paracasei and hyaluronic acid and the use thereof for the treatment of the skin |
Non-Patent Citations (5)
| Title |
|---|
| "Rompp Lexikon Chemie", 1997, GEORG THIEME VERLAG |
| A. DOMSCH: "Cosmetic Compositions", 1992, VERLAG FUR CHEMISCHE INDUSTRIE |
| PIRNAZAR PAYMAN ET AL: "Bacteriostatic effects of hyaluronic acid", JOURNAL OF PERIODONTOLOGY, AMERICAN ACADEMY OF PERIODONTOLOGY, US, vol. 70, no. 4, 1 April 1999 (1999-04-01), pages 370 - 374, XP008162701, ISSN: 0022-3492, DOI: 10.1902/JOP.1999.70.4.370 * |
| PUVIANI MARIO ET AL: "Effects of a cream containing 5% hyaluronic acid mixed with a bacterial-wall-derived glycoprotein, glycyrretinic acid, piroctone olamine and climbazole on signs, symptoms and skin bacterial microbiota in subjects with seborrheic dermatitis of the face", CLINICAL, COSMETIC AND INVESTIGATIONAL DERMATOLOGY, vol. Volume 12, 1 January 2019 (2019-01-01), pages 285 - 293, XP055812737, Retrieved from the Internet <URL:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6525831/pdf/ccid-12-285.pdf> DOI: 10.2147/CCID.S205904 * |
| TODD SCHLESINGER ET AL: "Efficacy and Safety of a Low-Molecular Weight Hyaluronic Acid Topical Gel in the Treatment of Facial Seborrheic Dermatitis", THE JOURNAL OF CLINICAL AND AESTHETIC DERMATOLOGY, 1 October 2012 (2012-10-01), pages 20 - 23, XP055351197, Retrieved from the Internet <URL:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3486775/pdf/jcad_5_10_20.pdf> [retrieved on 20170302] * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JPH10513165A (en) | Anti-adhesive active ingredient | |
| JP7286907B2 (en) | topical composition | |
| US20110262558A1 (en) | Composition For Skin Sanitization And Protection And Method Of Its Use | |
| US20230301885A1 (en) | Novel use | |
| US10792258B2 (en) | Antiseptic, antiseborrheic and exfoliating composition to remove or prevent acne | |
| US20140271881A1 (en) | Antiseptic composition | |
| EP3723714B1 (en) | Propanediol monoacetate mononitrate | |
| US8486459B2 (en) | Bulbine frutescens extract | |
| WO2022157307A1 (en) | Hyaluronic acid as antimicrobial agent for use on the skin | |
| WO2022157314A1 (en) | Hyaluronic acid for use on the skin | |
| US11324680B2 (en) | Topical compositions | |
| KR102630903B1 (en) | New uses | |
| US10933002B2 (en) | Preservation booster | |
| JP7187740B2 (en) | new use | |
| EP4104814A1 (en) | Novel use of vitamin b12 | |
| WO2019007791A1 (en) | Topical compositions | |
| JP7475873B2 (en) | Defensin expression promoter | |
| KR20090071529A (en) | Cosmetic composition comprising vitamin k1 or vitamin k3 for anti-bacterial and anti-fungal bio-activity | |
| JP2017534689A (en) | Methods for the prevention and treatment of acne | |
| CN117835960A (en) | Composition of ascorbic acid and human milk oligosaccharide |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 22702208 Country of ref document: EP Kind code of ref document: A1 |
|
| NENP | Non-entry into the national phase |
Ref country code: DE |
|
| 122 | Ep: pct application non-entry in european phase |
Ref document number: 22702208 Country of ref document: EP Kind code of ref document: A1 |