WO2022094640A1 - Préparation contenant un constituant aldéhyde pour le traitement de l'onychomycose - Google Patents
Préparation contenant un constituant aldéhyde pour le traitement de l'onychomycose Download PDFInfo
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- WO2022094640A1 WO2022094640A1 PCT/AT2021/060404 AT2021060404W WO2022094640A1 WO 2022094640 A1 WO2022094640 A1 WO 2022094640A1 AT 2021060404 W AT2021060404 W AT 2021060404W WO 2022094640 A1 WO2022094640 A1 WO 2022094640A1
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- weight
- aqueous composition
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- nail
- volatile
- Prior art date
Links
- 238000002360 preparation method Methods 0.000 title claims description 22
- 208000010195 Onychomycosis Diseases 0.000 title claims description 18
- 201000005882 tinea unguium Diseases 0.000 title claims description 7
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 title abstract 2
- 239000000203 mixture Substances 0.000 claims abstract description 43
- 239000006174 pH buffer Substances 0.000 claims abstract description 13
- 239000003638 chemical reducing agent Substances 0.000 claims abstract description 6
- 150000001299 aldehydes Chemical class 0.000 claims description 34
- 238000011282 treatment Methods 0.000 claims description 31
- 239000000126 substance Substances 0.000 claims description 30
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 21
- 239000002904 solvent Substances 0.000 claims description 17
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 13
- 238000001704 evaporation Methods 0.000 claims description 13
- 230000008020 evaporation Effects 0.000 claims description 13
- 239000004094 surface-active agent Substances 0.000 claims description 12
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 claims description 11
- 239000002253 acid Substances 0.000 claims description 11
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 9
- AIJULSRZWUXGPQ-UHFFFAOYSA-N Methylglyoxal Chemical compound CC(=O)C=O AIJULSRZWUXGPQ-UHFFFAOYSA-N 0.000 claims description 8
- 239000007853 buffer solution Substances 0.000 claims description 7
- -1 alkyl ether sulfates Chemical class 0.000 claims description 6
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 6
- LEQAOMBKQFMDFZ-UHFFFAOYSA-N glyoxal Chemical compound O=CC=O LEQAOMBKQFMDFZ-UHFFFAOYSA-N 0.000 claims description 6
- 230000000699 topical effect Effects 0.000 claims description 5
- ZNZYKNKBJPZETN-WELNAUFTSA-N Dialdehyde 11678 Chemical compound N1C2=CC=CC=C2C2=C1[C@H](C[C@H](/C(=C/O)C(=O)OC)[C@@H](C=C)C=O)NCC2 ZNZYKNKBJPZETN-WELNAUFTSA-N 0.000 claims description 4
- 230000003139 buffering effect Effects 0.000 claims description 4
- 150000001875 compounds Chemical class 0.000 claims description 4
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 claims description 4
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 claims description 4
- 150000001241 acetals Chemical class 0.000 claims description 3
- 229940015043 glyoxal Drugs 0.000 claims description 3
- 235000019260 propionic acid Nutrition 0.000 claims description 3
- 150000003242 quaternary ammonium salts Chemical class 0.000 claims description 3
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 2
- 229910019142 PO4 Inorganic materials 0.000 claims description 2
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 claims description 2
- 125000003158 alcohol group Chemical group 0.000 claims description 2
- 125000005600 alkyl phosphonate group Chemical group 0.000 claims description 2
- 150000008051 alkyl sulfates Chemical class 0.000 claims description 2
- 229940045714 alkyl sulfonate alkylating agent Drugs 0.000 claims description 2
- 150000008052 alkyl sulfonates Chemical class 0.000 claims description 2
- 150000007854 aminals Chemical class 0.000 claims description 2
- 150000002373 hemiacetals Chemical class 0.000 claims description 2
- 235000021317 phosphate Nutrition 0.000 claims description 2
- 239000001384 succinic acid Substances 0.000 claims description 2
- 210000000282 nail Anatomy 0.000 description 33
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 29
- 230000000694 effects Effects 0.000 description 19
- 239000013543 active substance Substances 0.000 description 9
- 230000000845 anti-microbial effect Effects 0.000 description 9
- 208000015181 infectious disease Diseases 0.000 description 9
- 206010061217 Infestation Diseases 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 7
- 238000009472 formulation Methods 0.000 description 7
- 230000000843 anti-fungal effect Effects 0.000 description 6
- 229940121375 antifungal agent Drugs 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 239000000872 buffer Substances 0.000 description 5
- 230000035515 penetration Effects 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Natural products CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- 150000001298 alcohols Chemical class 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 239000000645 desinfectant Substances 0.000 description 4
- 239000003205 fragrance Substances 0.000 description 4
- 239000004922 lacquer Substances 0.000 description 4
- 239000007800 oxidant agent Substances 0.000 description 4
- 210000004906 toe nail Anatomy 0.000 description 4
- 241000233866 Fungi Species 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 210000004905 finger nail Anatomy 0.000 description 3
- 230000002538 fungal effect Effects 0.000 description 3
- MWUXSHHQAYIFBG-UHFFFAOYSA-N nitrogen oxide Inorganic materials O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 3
- 150000007524 organic acids Chemical class 0.000 description 3
- 230000008961 swelling Effects 0.000 description 3
- OCAPBUJLXMYKEJ-UHFFFAOYSA-N 1-[biphenyl-4-yl(phenyl)methyl]imidazole Chemical compound C1=NC=CN1C(C=1C=CC(=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 OCAPBUJLXMYKEJ-UHFFFAOYSA-N 0.000 description 2
- 102000011782 Keratins Human genes 0.000 description 2
- 108010076876 Keratins Proteins 0.000 description 2
- 206010034016 Paronychia Diseases 0.000 description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 230000001857 anti-mycotic effect Effects 0.000 description 2
- 239000002543 antimycotic Substances 0.000 description 2
- 229960002206 bifonazole Drugs 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 229960003749 ciclopirox Drugs 0.000 description 2
- SCKYRAXSEDYPSA-UHFFFAOYSA-N ciclopirox Chemical compound ON1C(=O)C=C(C)C=C1C1CCCCC1 SCKYRAXSEDYPSA-UHFFFAOYSA-N 0.000 description 2
- NEHNMFOYXAPHSD-UHFFFAOYSA-N citronellal Chemical compound O=CCC(C)CCC=C(C)C NEHNMFOYXAPHSD-UHFFFAOYSA-N 0.000 description 2
- 229960004022 clotrimazole Drugs 0.000 description 2
- VNFPBHJOKIVQEB-UHFFFAOYSA-N clotrimazole Chemical compound ClC1=CC=CC=C1C(N1C=NC=C1)(C=1C=CC=CC=1)C1=CC=CC=C1 VNFPBHJOKIVQEB-UHFFFAOYSA-N 0.000 description 2
- 230000000249 desinfective effect Effects 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 231100000086 high toxicity Toxicity 0.000 description 2
- 239000000171 lavandula angustifolia l. flower oil Substances 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 230000009257 reactivity Effects 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 239000001632 sodium acetate Substances 0.000 description 2
- 235000017281 sodium acetate Nutrition 0.000 description 2
- KVJHGPAAOUGYJX-UHFFFAOYSA-N 1,1,3,3-tetraethoxypropane Chemical compound CCOC(OCC)CC(OCC)OCC KVJHGPAAOUGYJX-UHFFFAOYSA-N 0.000 description 1
- GFISDBXSWQMOND-UHFFFAOYSA-N 2,5-dimethoxyoxolane Chemical compound COC1CCC(OC)O1 GFISDBXSWQMOND-UHFFFAOYSA-N 0.000 description 1
- VHVPQPYKVGDNFY-DFMJLFEVSA-N 2-[(2r)-butan-2-yl]-4-[4-[4-[4-[[(2r,4s)-2-(2,4-dichlorophenyl)-2-(1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-1,2,4-triazol-3-one Chemical compound O=C1N([C@H](C)CC)N=CN1C1=CC=C(N2CCN(CC2)C=2C=CC(OC[C@@H]3O[C@](CN4N=CN=C4)(OC3)C=3C(=CC(Cl)=CC=3)Cl)=CC=2)C=C1 VHVPQPYKVGDNFY-DFMJLFEVSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- 241001480043 Arthrodermataceae Species 0.000 description 1
- 241000222120 Candida <Saccharomycetales> Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 244000060011 Cocos nucifera Species 0.000 description 1
- 235000013162 Cocos nucifera Nutrition 0.000 description 1
- RUPBZQFQVRMKDG-UHFFFAOYSA-M Didecyldimethylammonium chloride Chemical compound [Cl-].CCCCCCCCCC[N+](C)(C)CCCCCCCCCC RUPBZQFQVRMKDG-UHFFFAOYSA-M 0.000 description 1
- IIUZTXTZRGLYTI-UHFFFAOYSA-N Dihydrogriseofulvin Natural products COC1CC(=O)CC(C)C11C(=O)C(C(OC)=CC(OC)=C2Cl)=C2O1 IIUZTXTZRGLYTI-UHFFFAOYSA-N 0.000 description 1
- 241001480036 Epidermophyton floccosum Species 0.000 description 1
- 206010017533 Fungal infection Diseases 0.000 description 1
- UXWOXTQWVMFRSE-UHFFFAOYSA-N Griseoviridin Natural products O=C1OC(C)CC=C(C(NCC=CC=CC(O)CC(O)C2)=O)SCC1NC(=O)C1=COC2=N1 UXWOXTQWVMFRSE-UHFFFAOYSA-N 0.000 description 1
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical group SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 1
- 208000031888 Mycoses Diseases 0.000 description 1
- DDUHZTYCFQRHIY-UHFFFAOYSA-N Negwer: 6874 Natural products COC1=CC(=O)CC(C)C11C(=O)C(C(OC)=CC(OC)=C2Cl)=C2O1 DDUHZTYCFQRHIY-UHFFFAOYSA-N 0.000 description 1
- 206010073310 Occupational exposures Diseases 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 241000223238 Trichophyton Species 0.000 description 1
- 241000223229 Trichophyton rubrum Species 0.000 description 1
- 239000008351 acetate buffer Substances 0.000 description 1
- 159000000021 acetate salts Chemical class 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 125000003172 aldehyde group Chemical group 0.000 description 1
- 229960003204 amorolfine Drugs 0.000 description 1
- MQHLMHIZUIDKOO-AYHJJNSGSA-N amorolfine Chemical group C1=CC(C(C)(C)CC)=CC=C1CC(C)CN1C[C@@H](C)O[C@@H](C)C1 MQHLMHIZUIDKOO-AYHJJNSGSA-N 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 239000003139 biocide Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 125000003636 chemical group Chemical group 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 235000000983 citronellal Nutrition 0.000 description 1
- 229930003633 citronellal Natural products 0.000 description 1
- 239000012459 cleaning agent Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000037304 dermatophytes Effects 0.000 description 1
- 229960004670 didecyldimethylammonium chloride Drugs 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- NKDDWNXOKDWJAK-UHFFFAOYSA-N dimethoxymethane Chemical compound COCOC NKDDWNXOKDWJAK-UHFFFAOYSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 210000004904 fingernail bed Anatomy 0.000 description 1
- 229960004884 fluconazole Drugs 0.000 description 1
- RFHAOTPXVQNOHP-UHFFFAOYSA-N fluconazole Chemical compound C1=NC=NN1CC(C=1C(=CC(F)=CC=1)F)(O)CN1C=NC=N1 RFHAOTPXVQNOHP-UHFFFAOYSA-N 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 208000033511 fungal infection of the toenail Diseases 0.000 description 1
- 230000000855 fungicidal effect Effects 0.000 description 1
- 239000010647 garlic oil Substances 0.000 description 1
- 230000002070 germicidal effect Effects 0.000 description 1
- DDUHZTYCFQRHIY-RBHXEPJQSA-N griseofulvin Chemical compound COC1=CC(=O)C[C@@H](C)[C@@]11C(=O)C(C(OC)=CC(OC)=C2Cl)=C2O1 DDUHZTYCFQRHIY-RBHXEPJQSA-N 0.000 description 1
- 229960002867 griseofulvin Drugs 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 230000036072 healthy nails Effects 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 229960004130 itraconazole Drugs 0.000 description 1
- 238000013532 laser treatment Methods 0.000 description 1
- 150000002632 lipids Chemical group 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000001525 mentha piperita l. herb oil Substances 0.000 description 1
- 150000002730 mercury Chemical class 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 150000002826 nitrites Chemical class 0.000 description 1
- 231100000675 occupational exposure Toxicity 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000002894 organic compounds Chemical group 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 239000003973 paint Substances 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 235000019477 peppermint oil Nutrition 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- 239000000419 plant extract Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000004848 polyfunctional curative Substances 0.000 description 1
- YBBJKCMMCRQZMA-UHFFFAOYSA-N pyrithione Chemical compound ON1C=CC=CC1=S YBBJKCMMCRQZMA-UHFFFAOYSA-N 0.000 description 1
- 229960002026 pyrithione Drugs 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 230000003319 supportive effect Effects 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000010677 tea tree oil Substances 0.000 description 1
- 229940111630 tea tree oil Drugs 0.000 description 1
- DOMXUEMWDBAQBQ-WEVVVXLNSA-N terbinafine Chemical compound C1=CC=C2C(CN(C\C=C\C#CC(C)(C)C)C)=CC=CC2=C1 DOMXUEMWDBAQBQ-WEVVVXLNSA-N 0.000 description 1
- 229960002722 terbinafine Drugs 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 210000003371 toe Anatomy 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 239000000341 volatile oil Substances 0.000 description 1
- 239000012855 volatile organic compound Substances 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
-
- 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
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
-
- 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
- A61K31/11—Aldehydes
-
- 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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/255—Esters, e.g. nitroglycerine, selenocyanates of sulfoxy acids or sulfur analogues thereof
-
- 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
- A61K31/66—Phosphorus compounds
- A61K31/662—Phosphorus acids or esters thereof having P—C bonds, e.g. foscarnet, trichlorfon
-
- 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
- A61P31/10—Antimycotics
Definitions
- the invention relates to a preparation for use in the treatment of onychomycosis.
- Infection weakens and damages the nail plate, resulting in visual and structural changes. Yellowish, white changes in the nail are observed, which can extend to the nail bed.
- the nail fungus infection is painless, so in many cases, after several unsuccessful attempts at treatment, the infection is accepted as chronic.
- the changed appearance of the toenails leads to personal restrictions for many people, e.g. in the choice of footwear, since the affected toes do not like to be shown visibly.
- impermeable gloves e.g. clean room staff, people in medical professions, etc.
- Treatment of nail fungus infestation depends on the severity of the infestation (intensity of infection, number of nails affected) and can be carried out locally by applying appropriate active substances, by completely removing the nail or systemically by administering appropriate active substances, e.g. in oral form.
- Shift in the biological living conditions in the area of the affected nail areas includes methods using organic acids (e.g. salicylic acid according to US 2011/0160166 A1) achieve a local shift in the pH range and thus change the propagation conditions for the nail fungus so much that further growth is prevented or at least slowed down (US 2014/0142177 A1, WO 2010/019777 A1 ).
- organic acids e.g. salicylic acid according to US 2011/0160166 A1
- fungicidally active substances include substances that have a high toxicity for fungi (bifonazole, clotrimazole, ciclopirox, amorolfm or metal pyrithione according to US 2009/0298805 A1 or formaldehyde according to FR 2 805 745 B1) and, for example, like nail polish can be applied.
- Lavender oil Lavender oil, tea tree oil (US 2006/0251593) and plant extracts are proposed in different preparation forms for the treatment of fungal nail infections.
- Laser treatments Laser light is used to locally remove the affected areas. The affected areas are removed by increasing the temperature.
- the swelling agents are substances containing mercaptan groups, which are able to soften the nail structure by swelling (US Pat. No. 6,123,690 and US Pat. No. 5,696,164).
- oral antimycotics such as griseofulvin, itraconazole, terbinafine (WO 2010/010470 A2) or fluconazole are administered over a longer period of time.
- These treatments require long periods of time because the antifungal agents have to be stored in the nail structure, which can contain the infection.
- the health side effects of this long-term drug administration are considerable.
- the high number of nail fungus infections that still exist today in economically highly developed countries confirms the hitherto inadequate suitability and effect of the proposed solutions, which have a large number of disadvantages.
- fungicidal substances such as bifonazole, clotrimazole, ciclopirox and amorolfm only have a limited effect. This is mainly due to two systematic causes: The substances are high-molecular substances and are insoluble in water. As a result, the preparations are systems with solubilizers or emulsions, which are difficult to penetrate into the branched and deep growth areas in affected nails. A much more critical disadvantage also lies in the increasing resistance of the fungi to known active substances.
- Formulations which contain the sometimes extremely toxic solid substances such as lead or mercury salts are disadvantageous because of the high toxicity of the substances.
- lacquer polymers to strengthen the nail structure has been described in the literature (DE 20 2013 009 976 U1). If antifungal substances are incorporated into the lacquer formulation, an antifungal nail lacquer is produced (DE 20 2013 009 988 U1), with the use of formaldehyde being explicitly excluded in the formulation claimed in DE 20 2013 009 988 U1.
- formaldehyde Due to its high chemical reactivity, formaldehyde has a strong disinfecting effect and is still an important disinfectant in medical cleaning agents today. Chemical resistance of microorganisms to formaldehyde and other aldehydes or aldehyde-releasing substances is not to be expected due to the chemical reactivity and the biocompatibility or the occurrence in the metabolism.
- Formaldehyde is usually used as an aqueous solution (formalin) or in gaseous form.
- AT 516 544 B1 describes a preparation for local treatment, which is an aqueous solution containing an aldehyde component, a surfactant and a water-miscible solvent.
- the special composition ensures deep penetration into the nail and has a particularly good effect against nail fungus.
- the object is therefore to provide a preparation which is suitable for the local treatment of nail fungus and is easy to handle and which enters the affected nail structure.
- the pH buffer system thus has a volatile component.
- the pH of the composition is between 7 and 9 after evaporation of the volatile component.
- the present invention uses the antimicrobial effect of aldehydes or aldehyde-releasing compounds to combat fungal infestation of the toenails or fingernails. By adding a substance that reduces the surface tension, the penetration depth of an aldehyde-containing aqueous solution into the damaged nail areas is increased to such an extent that the unwanted fungal infestation can be completely eliminated.
- aldehyde component includes substances that themselves contain aldehyde groups (such as formaldehyde, propionic acid dialdehyde, succinic acid dialdehyde, glutaraldehyde, glyoxal, methylglyoxal) but also chemical compounds that are capable of splitting off aldehydes. These include, for example, acetals such as dimethylformal, 2,5-dimethoxytetrahydrofuran, 1,1,3,3-tetraethoxypropane, hemiacetals and aminals.
- aldehyde groups such as formaldehyde, propionic acid dialdehyde, succinic acid dialdehyde, glutaraldehyde, glyoxal, methylglyoxal
- acetals such as dimethylformal, 2,5-dimethoxytetrahydrofuran, 1,1,3,3-tetraethoxypropane, hemiacetals and aminals
- the aldehyde component is glutaraldehyde.
- the term surface tension reducing substance includes substances which reduce the surface tension of the composition compared to this composition without the surface tension reducing substance.
- substances that reduce surface tension are, in particular, surfactants, but additives to solvents can also be used to reduce surface tension.
- suitable surfactants are the alkyl sulfates, alkyl sulfonates and alkyl ether sulfates or, for example, the alkyl phosphonates and alkyl phosphates.
- the chemical group of the tenside should be selected in such a way that the function of the tenside is not deactivated by reaction with the aldehyde component.
- the surfactant is selected from the group consisting of quaternary ammonium salts and is preferably itself a biocidally active substance.
- Surfactants are particularly preferably selected from the group of quaternary ammonium salts, for example didecyldimethylammonium chloride or benzyl-Cu-Cis-alkyldimethylammonium chloride, which themselves also have an antimicrobial effect.
- the treatment solution can penetrate sufficiently deep into the very fine growth channels in the affected nail areas. Due to the high penetration depth, a complete treatment of the affected areas is achieved.
- the high disinfecting effect of the aldehydes also allows treatment and elimination of fungal spores.
- the reaction of the aldehydes with the nail keratin results in a superficial sealing of the horn structure and a new infestation is made more difficult by the depot effect.
- a pH buffer system is a mixture of substances whose pH value (concentration of oxonium ions) changes much less when an acid or a base is added than would be the case in an unbuffered system.
- Buffer solutions contain a mixture of a weak acid and its conjugate or corresponding base (or the respective salt) or a weak base and its conjugate or corresponding acid.
- the pH buffer system used in the composition according to the invention is a buffer which adjusts the pH to a maximum of pH 6. This makes the composition storage-stable. The composition therefore has a pH of 6 at most.
- One of the components of the buffering system is a volatile component.
- the pH rises to 7 to 9 by evaporation of the volatile component of the buffer system, preferably an acid of the buffer system.
- the volatile component is therefore preferably an acid, particularly preferably an organic acid.
- this evaporation occurs, for example, following the local application of the composition to the affected nail.
- the increase in pH at the application site results in the local pH being shifted in the direction of the optimal pH for the application.
- glutaraldehyde it is known from the literature that an optimum effect of the antimicrobial effect is observed at a pH value of 7.5-8.5.
- the pH buffering system is to be understood that the pH of the entire composition is in the ideal stabilizing range for the composition, preferably the pH of the composition is at most 6.
- the pH After evaporation of the volatile component of the pH buffer system, the pH begins to rise and reaches a maximum of 7 to 9.
- a buffer system with these properties can easily be determined by the person skilled in the art with knowledge of pKa values and the Henderson-Hasselbalch equation.
- the buffer system comprises acetic acid/acetate.
- buffer systems with other moderately strong acids and their corresponding moderately strong bases and mixtures thereof are also possible.
- formic acid, acetic acid, propionic acid can also be used as the acid and the corresponding salts of these acids or mixtures thereof can be used as the base.
- a volatile, water-miscible solvent is additionally provided.
- the volatility of the solvent supports and improves the reach of all affected areas, as high concentrations of disinfectant can be generated locally, inside the nail.
- solvents are acetone, but also alcohols and polyethylene glycols, it being important to ensure that any acetal/hemiacetal compound that may form can decompose reversibly to form the aldehyde components and the inventive effect of the preparation is therefore not lost.
- the volatile solvent or solvent mixture can also lower the surface tension.
- a possible reaction of the solvent with the aldehyde components is only permissible if the reaction is reversible and the aldehyde component can be released again by reverse reaction during use, so that the effect according to the invention occurs.
- alcohols are used which are also used as biocides, for example 1-propanol, 2-propanol or ethanol.
- the volatile, water-miscible solvent is an alcohol.
- Alcohols can achieve an increase in local concentration when using an aldehyde component with a higher boiling point, e.g. glutaraldehyde.
- suitable alcohols are selected, for example, from the group consisting of 1-propanol, 2-propanol, ethanol or mixtures thereof.
- volatile (be it as a volatile component of the pH buffer system or as a volatile solvent) based on Directive 2004/42 / EC of the European Parliament and of the Council of April 21, 2004 on the limitation of Emissions of volatile organic compounds are understood to mean that the volatile component of the pH buffer system or the volatile solvent is an organic compound that has an initial boiling point of maximum 250 °C at a standard pressure of 1013 mbar having.
- the vapor pressure of this compound is preferably at least 0.1 mbar at 20° C. (to be calculated, for example, using the Clausius-Clapeyron equation).
- composition of the preparation is preferably as follows:
- the individual values refer to the entire composition.
- the amount of surface tension reducing agent is preferably between 0.05 and 10% by weight.
- the surface tension reducing agent is a surfactant, the proportion is preferably 0.05 to 5% by weight, more preferably 0.1 to 3% by weight.
- the pH buffer system is an acetic acid/acetate buffer with 0.02-0.4% by weight acetic acid and 0.03-0.6% by weight acetate salt, preferably sodium acetate.
- Colorants, dyes or fragrances are particularly suitable as "other substances". However, these must be compatible with the function of the aldehyde component and the surface tension reducing component.
- natural or nature-identical fragrances such as citronellal, peppermint oil or lavender oil are used, which also have an antimicrobial effect (ideally 0.1 to 5% by weight).
- the invention relates to a preparation of the aforementioned type as a medicament.
- the invention relates to a preparation of the aforementioned type for the treatment of onychomycosis (nail fungus).
- Topical treatment can be done by applying the preparation to a nail.
- the invention is based on the knowledge of the combination of up to 4 different active substance groups for the treatment of nail fungus:
- aldehyde components e.g. Glutaraldehyde, methylglyoxal, etc. serves as the primary mechanism.
- a substance that reduces surface tension (usually a tenside component) is used to ensure good wetting of the nail and lower surface tension, which is compatible with aldehydes.
- a volatile solvent e.g. isopropanol (which ideally also has an antimicrobial effect) supports the transport of the aldehyde component to the desired location.
- a pH buffer system which shifts the pH value in the nail to the range of 8 - 9 through evaporation, improves the optimal effect of the aldehyde component, while increased stability is achieved during storage due to the lower pH value, e.g. pH 5 to 6 .
- fragrances can also be used which themselves have an antimicrobial effect and thus, in addition to the development of a fresh smell, also support the antifungal function themselves through a germ-killing effect.
- the treatment solution By lowering the surface tension, the treatment solution penetrates very deeply into the dry nail, resulting in a very thorough treatment.
- the preparation is then allowed to dry.
- the alcohol component initially has a germicidal effect, after rapid evaporation an increased concentration of antimicrobial aldehyde, surfactant and fragrance remains.
- the slow evaporation of the volatile organic acid from the buffer leads to a gradual increase in the pH value, and thus to the formation of the optimal effect of the aldehyde component, which can be e.g. glutaraldehyde.
- a composition according to the invention contains the antimicrobial agents glutaraldehyde and 2-propanol.
- the buffer system consists of acetic acid and sodium acetate. 1 to 2 drops of the product are applied to the nail affected by the nail fungus and then allowed to air dry. The evaporation of the acetic acid shifts the pH of the solution into the optimal range of action of the glutaraldehyde.
- the formula has been used on several people with toenail fungus.
- the treatment was carried out three times during the first week, then 2 to 3 times a week during the following month and then 1 to 2 times a month. After just a few weeks of treatment, healthy nails were growing back in the treated areas.
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Abstract
Composition aqueuse contenant un constituant aldéhyde, une substance diminuant la tension superficielle, un système tampon de pH, et un constituant volatil.
Applications Claiming Priority (2)
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ATA50958/2020 | 2020-11-06 | ||
ATA50958/2020A AT524378A1 (de) | 2020-11-06 | 2020-11-06 | Zubereitung |
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WO2022094640A1 true WO2022094640A1 (fr) | 2022-05-12 |
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PCT/AT2021/060404 WO2022094640A1 (fr) | 2020-11-06 | 2021-11-04 | Préparation contenant un constituant aldéhyde pour le traitement de l'onychomycose |
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FR2805745A1 (fr) | 2000-03-01 | 2001-09-07 | Bergerac Nc | Compositions pour vernis a ongles antifongiques et antiseptiques |
US20060251593A1 (en) | 2005-04-07 | 2006-11-09 | Work By Docs, Inc. | Colored nail enamel treatment |
US20090298805A1 (en) | 2008-06-03 | 2009-12-03 | Polson George A | Topical pyrithione compositions and methods for treatment of nail fungus |
WO2010010470A2 (fr) | 2008-07-23 | 2010-01-28 | Tdt, Ltd | Procédé d’administration de formulations antifongiques topiques pour le traitement d’infections fongiques |
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AU2018333058A1 (en) * | 2017-09-15 | 2020-03-12 | Gojo Industries, Inc. | Antimicrobial composition |
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2020
- 2020-11-06 AT ATA50958/2020A patent/AT524378A1/de unknown
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US3382151A (en) | 1964-01-13 | 1968-05-07 | Mavala Sa | Composition for strengthening nails |
US5696164A (en) | 1994-12-22 | 1997-12-09 | Johnson & Johnson Consumer Products, Inc. | Antifungal treatment of nails |
US6123690A (en) | 1998-03-20 | 2000-09-26 | Maersk Medical A/S | Subcutaneous infusion device |
FR2805745A1 (fr) | 2000-03-01 | 2001-09-07 | Bergerac Nc | Compositions pour vernis a ongles antifongiques et antiseptiques |
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US20090298805A1 (en) | 2008-06-03 | 2009-12-03 | Polson George A | Topical pyrithione compositions and methods for treatment of nail fungus |
WO2010010470A2 (fr) | 2008-07-23 | 2010-01-28 | Tdt, Ltd | Procédé d’administration de formulations antifongiques topiques pour le traitement d’infections fongiques |
WO2010014070A1 (fr) | 2008-07-31 | 2010-02-04 | Medtronic, Inc. | Détection d'une aggravation d'insuffisance cardiaque selon des mesures d'impédance |
WO2010019777A1 (fr) | 2008-08-13 | 2010-02-18 | Dermworx Incorporated | Agent anti-infectieux local pour traitement d'infections fongiques de l'ongle |
WO2010125398A2 (fr) | 2009-05-01 | 2010-11-04 | Insense Limited | Traitement d'une infection de surface du corps humain ou animal |
US20140142177A1 (en) | 2009-05-15 | 2014-05-22 | Peter Mladenovich | Topical organic acid salt compositions suitable for treating infections |
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WO2011155887A1 (fr) | 2010-06-07 | 2011-12-15 | Topical Pharma Ab | Kit pour le traitement de l'onychomycose par l'oxyde nitrique |
DE202013009988U1 (de) | 2013-11-04 | 2013-12-12 | Jerg-Hanns Wohnhas | Biologischer antimykotischer Nagellack, Nagellasur, und/oder Nagelhärter |
DE202013009976U1 (de) | 2013-11-04 | 2013-12-12 | Jerg-Hanns Wohnhas | Kosmetischer oder pharmazeutischer Nagellack, Nagellasur, Nagellack-Basis und/ oder Nagelhärter |
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AT516544B1 (de) | 2014-12-02 | 2017-05-15 | Universität Innsbruck | Stoffgemisch und Zubereitung |
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