GB2598419A - Formulation - Google Patents
Formulation Download PDFInfo
- Publication number
- GB2598419A GB2598419A GB2020461.6A GB202020461A GB2598419A GB 2598419 A GB2598419 A GB 2598419A GB 202020461 A GB202020461 A GB 202020461A GB 2598419 A GB2598419 A GB 2598419A
- Authority
- GB
- United Kingdom
- Prior art keywords
- composition
- weight
- diol
- total
- pmd
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 138
- 238000009472 formulation Methods 0.000 title description 19
- 229930006948 p-menthane-3,8-diol Natural products 0.000 claims abstract description 62
- LMXFTMYMHGYJEI-UHFFFAOYSA-N p-menthane-3,8-diol Chemical compound CC1CCC(C(C)(C)O)C(O)C1 LMXFTMYMHGYJEI-UHFFFAOYSA-N 0.000 claims abstract description 55
- 230000000840 anti-viral effect Effects 0.000 claims abstract description 22
- 239000003995 emulsifying agent Substances 0.000 claims abstract description 20
- 239000002904 solvent Substances 0.000 claims abstract description 20
- -1 ethoxylated sorbitan ester Chemical class 0.000 claims abstract description 11
- 239000004094 surface-active agent Substances 0.000 claims abstract description 8
- 125000005456 glyceride group Chemical group 0.000 claims abstract description 5
- 150000003333 secondary alcohols Chemical class 0.000 claims abstract description 5
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 71
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical group CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 36
- 229960004063 propylene glycol Drugs 0.000 claims description 25
- 235000013772 propylene glycol Nutrition 0.000 claims description 25
- 239000004146 Propane-1,2-diol Substances 0.000 claims description 19
- 239000000839 emulsion Substances 0.000 claims description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 16
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 12
- 229920000053 polysorbate 80 Polymers 0.000 claims description 12
- 150000002148 esters Chemical class 0.000 claims description 11
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 claims description 11
- 229940068968 polysorbate 80 Drugs 0.000 claims description 11
- 125000000374 p-menthane-3,8-diol group Chemical group 0.000 claims description 10
- 239000007921 spray Substances 0.000 claims description 8
- 239000003381 stabilizer Substances 0.000 claims description 3
- 150000003138 primary alcohols Chemical class 0.000 abstract description 3
- 239000000243 solution Substances 0.000 description 21
- 239000013078 crystal Substances 0.000 description 9
- 239000004615 ingredient Substances 0.000 description 9
- 239000000077 insect repellent Substances 0.000 description 8
- 239000012141 concentrate Substances 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- 241000700605 Viruses Species 0.000 description 6
- 239000003921 oil Substances 0.000 description 6
- SASYSVUEVMOWPL-NXVVXOECSA-N decyl oleate Chemical compound CCCCCCCCCCOC(=O)CCCCCCC\C=C/CCCCCCCC SASYSVUEVMOWPL-NXVVXOECSA-N 0.000 description 5
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 239000003443 antiviral agent Substances 0.000 description 4
- DLAHAXOYRFRPFQ-UHFFFAOYSA-N dodecyl benzoate Chemical group CCCCCCCCCCCCOC(=O)C1=CC=CC=C1 DLAHAXOYRFRPFQ-UHFFFAOYSA-N 0.000 description 4
- 229920000136 polysorbate Polymers 0.000 description 4
- 239000003380 propellant Substances 0.000 description 4
- RZRNAYUHWVFMIP-KTKRTIGZSA-N 1-oleoylglycerol Chemical group CCCCCCCC\C=C/CCCCCCCC(=O)OCC(O)CO RZRNAYUHWVFMIP-KTKRTIGZSA-N 0.000 description 3
- 241001678559 COVID-19 virus Species 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 201000003176 Severe Acute Respiratory Syndrome Diseases 0.000 description 3
- PHYFQTYBJUILEZ-UHFFFAOYSA-N Trioleoylglycerol Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC(OC(=O)CCCCCCCC=CCCCCCCCC)COC(=O)CCCCCCCC=CCCCCCCCC PHYFQTYBJUILEZ-UHFFFAOYSA-N 0.000 description 3
- 239000000443 aerosol Substances 0.000 description 3
- PXTQQOLKZBLYDY-UHFFFAOYSA-N bis(2-ethylhexyl) carbonate Chemical compound CCCCC(CC)COC(=O)OCC(CC)CCCC PXTQQOLKZBLYDY-UHFFFAOYSA-N 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 229940068965 polysorbates Drugs 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
- NKEQOUMMGPBKMM-UHFFFAOYSA-N 2-hydroxy-2-[2-(2-hydroxy-3-octadecanoyloxypropoxy)-2-oxoethyl]butanedioic acid Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)COC(=O)CC(O)(C(O)=O)CC(O)=O NKEQOUMMGPBKMM-UHFFFAOYSA-N 0.000 description 2
- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 2
- XZOYHFBNQHPJRQ-UHFFFAOYSA-N 7-methyloctanoic acid Chemical compound CC(C)CCCCCC(O)=O XZOYHFBNQHPJRQ-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 244000165852 Eucalyptus citriodora Species 0.000 description 2
- 235000004722 Eucalyptus citriodora Nutrition 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- FEXQDZTYJVXMOS-UHFFFAOYSA-N Isopropyl benzoate Chemical compound CC(C)OC(=O)C1=CC=CC=C1 FEXQDZTYJVXMOS-UHFFFAOYSA-N 0.000 description 2
- XBLJCYOUYPSETL-UHFFFAOYSA-N Isopropyl citrate Chemical compound CC(C)O.CC(=O)CC(O)(C(O)=O)CC(O)=O XBLJCYOUYPSETL-UHFFFAOYSA-N 0.000 description 2
- 239000002310 Isopropyl citrate Substances 0.000 description 2
- GQPLMRYTRLFLPF-UHFFFAOYSA-N Nitrous Oxide Chemical compound [O-][N+]#N GQPLMRYTRLFLPF-UHFFFAOYSA-N 0.000 description 2
- 229920001214 Polysorbate 60 Polymers 0.000 description 2
- SZYSLWCAWVWFLT-UTGHZIEOSA-N [(2s,3s,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)-2-[(2r,3r,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxolan-2-yl]methyl octadecanoate Chemical compound O([C@@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@]1(COC(=O)CCCCCCCCCCCCCCCCC)O[C@H](CO)[C@@H](O)[C@@H]1O SZYSLWCAWVWFLT-UTGHZIEOSA-N 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000009854 citriodiol Substances 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- SHZIWNPUGXLXDT-UHFFFAOYSA-N ethyl hexanoate Chemical compound CCCCCC(=O)OCC SHZIWNPUGXLXDT-UHFFFAOYSA-N 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
- NNPPMTNAJDCUHE-UHFFFAOYSA-N isobutane Chemical compound CC(C)C NNPPMTNAJDCUHE-UHFFFAOYSA-N 0.000 description 2
- 235000019300 isopropyl citrate Nutrition 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 210000004779 membrane envelope Anatomy 0.000 description 2
- OSORMYZMWHVFOZ-UHFFFAOYSA-N phenethyl benzoate Chemical compound C=1C=CC=CC=1C(=O)OCCC1=CC=CC=C1 OSORMYZMWHVFOZ-UHFFFAOYSA-N 0.000 description 2
- 239000001818 polyoxyethylene sorbitan monostearate Substances 0.000 description 2
- 235000010989 polyoxyethylene sorbitan monostearate Nutrition 0.000 description 2
- 229940113124 polysorbate 60 Drugs 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 description 1
- LMXFTMYMHGYJEI-IWSPIJDZSA-N (1R,2R,5R)-2-(1-hydroxy-1-methylethyl)-5-methylcyclohexanol Chemical compound C[C@@H]1CC[C@@H](C(C)(C)O)[C@H](O)C1 LMXFTMYMHGYJEI-IWSPIJDZSA-N 0.000 description 1
- FFEOEKMMMQFWBO-UHFFFAOYSA-N (4-propan-2-ylcyclohexyl) propanoate Chemical compound CCC(=O)OC1CCC(C(C)C)CC1 FFEOEKMMMQFWBO-UHFFFAOYSA-N 0.000 description 1
- QMMJWQMCMRUYTG-UHFFFAOYSA-N 1,2,4,5-tetrachloro-3-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=C(Cl)C(Cl)=CC(Cl)=C1Cl QMMJWQMCMRUYTG-UHFFFAOYSA-N 0.000 description 1
- OUZJJDFOKSDCHY-UHFFFAOYSA-N 14-methylpentadecyl 12-octadecanoyloxyoctadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC(CCCCCC)CCCCCCCCCCC(=O)OCCCCCCCCCCCCCC(C)C OUZJJDFOKSDCHY-UHFFFAOYSA-N 0.000 description 1
- PHTZMGCAFZLFOL-UHFFFAOYSA-N 14-methylpentadecyl 2-ethylhexanoate Chemical compound CCCCC(CC)C(=O)OCCCCCCCCCCCCCC(C)C PHTZMGCAFZLFOL-UHFFFAOYSA-N 0.000 description 1
- JSOVGYMVTPPEND-UHFFFAOYSA-N 16-methylheptadecyl 2,2-dimethylpropanoate Chemical compound CC(C)CCCCCCCCCCCCCCCOC(=O)C(C)(C)C JSOVGYMVTPPEND-UHFFFAOYSA-N 0.000 description 1
- WGKHLTQBAAWSSR-UHFFFAOYSA-N 16-methylheptadecyl 2-ethylhexanoate Chemical compound CCCCC(CC)C(=O)OCCCCCCCCCCCCCCCC(C)C WGKHLTQBAAWSSR-UHFFFAOYSA-N 0.000 description 1
- ONJJOWWTHJFYOO-UHFFFAOYSA-N 16-methylheptadecyl 3,5,5-trimethylhexanoate Chemical compound CC(C)CCCCCCCCCCCCCCCOC(=O)CC(C)CC(C)(C)C ONJJOWWTHJFYOO-UHFFFAOYSA-N 0.000 description 1
- DGSZGZSCHSQXFV-UHFFFAOYSA-N 2,3-bis(2-ethylhexanoyloxy)propyl 2-ethylhexanoate Chemical compound CCCCC(CC)C(=O)OCC(OC(=O)C(CC)CCCC)COC(=O)C(CC)CCCC DGSZGZSCHSQXFV-UHFFFAOYSA-N 0.000 description 1
- QNESDXMHQYMNGD-UHFFFAOYSA-N 2,3-bis(3,5,5-trimethylhexanoyloxy)propyl 3,5,5-trimethylhexanoate Chemical compound CC(C)(C)CC(C)CC(=O)OCC(OC(=O)CC(C)CC(C)(C)C)COC(=O)CC(C)CC(C)(C)C QNESDXMHQYMNGD-UHFFFAOYSA-N 0.000 description 1
- LVDXDNDMOQYDMZ-UHFFFAOYSA-N 2-[2-(2-phenylmethoxypropoxy)propoxy]propyl tetradecanoate Chemical compound CCCCCCCCCCCCCC(=O)OCC(C)OCC(C)OCC(C)OCc1ccccc1 LVDXDNDMOQYDMZ-UHFFFAOYSA-N 0.000 description 1
- CZVOIAOPRGNENY-UHFFFAOYSA-N 2-butyloctyl 2-hydroxybenzoate Chemical compound CCCCCCC(CCCC)COC(=O)C1=CC=CC=C1O CZVOIAOPRGNENY-UHFFFAOYSA-N 0.000 description 1
- NJMGRJLQRLFQQX-HYXAFXHYSA-N 2-isopropylmaleic acid Chemical compound CC(C)C(\C(O)=O)=C\C(O)=O NJMGRJLQRLFQQX-HYXAFXHYSA-N 0.000 description 1
- ZIIVEKCKOPDBLT-UHFFFAOYSA-N 2-octyldodecyl 2-hydroxypropanoate Chemical compound CCCCCCCCCCC(COC(=O)C(C)O)CCCCCCCC ZIIVEKCKOPDBLT-UHFFFAOYSA-N 0.000 description 1
- HXVCOQUDJKMJQY-UHFFFAOYSA-N 2-octyldodecyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(CCCCCCCC)CCCCCCCCCC HXVCOQUDJKMJQY-UHFFFAOYSA-N 0.000 description 1
- HBTAOSGHCXUEKI-UHFFFAOYSA-N 4-chloro-n,n-dimethyl-3-nitrobenzenesulfonamide Chemical compound CN(C)S(=O)(=O)C1=CC=C(Cl)C([N+]([O-])=O)=C1 HBTAOSGHCXUEKI-UHFFFAOYSA-N 0.000 description 1
- AMEMLELAMQEAIA-UHFFFAOYSA-N 6-(tert-butyl)thieno[3,2-d]pyrimidin-4(3H)-one Chemical compound N1C=NC(=O)C2=C1C=C(C(C)(C)C)S2 AMEMLELAMQEAIA-UHFFFAOYSA-N 0.000 description 1
- BRORPGSJXSLXKN-UHFFFAOYSA-N 6-methylheptyl 3,5,5-trimethylhexanoate Chemical compound CC(C)CCCCCOC(=O)CC(C)CC(C)(C)C BRORPGSJXSLXKN-UHFFFAOYSA-N 0.000 description 1
- FRWDKHJGBUEADF-UHFFFAOYSA-N 8-methylnonyl 2-ethylhexanoate Chemical compound CCCCC(CC)C(=O)OCCCCCCCC(C)C FRWDKHJGBUEADF-UHFFFAOYSA-N 0.000 description 1
- 208000025721 COVID-19 Diseases 0.000 description 1
- 235000005979 Citrus limon Nutrition 0.000 description 1
- 244000131522 Citrus pyriformis Species 0.000 description 1
- 241000711573 Coronaviridae Species 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
- UMVMVEZHMZTUHD-UHFFFAOYSA-N DL-Propylene glycol dibenzoate Chemical compound C=1C=CC=CC=1C(=O)OC(C)COC(=O)C1=CC=CC=C1 UMVMVEZHMZTUHD-UHFFFAOYSA-N 0.000 description 1
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
- 244000166124 Eucalyptus globulus Species 0.000 description 1
- 241000700588 Human alphaherpesvirus 1 Species 0.000 description 1
- DVFZGWDMFKTMFQ-UHFFFAOYSA-N Isopropyl nonanoate Chemical compound CCCCCCCCC(=O)OC(C)C DVFZGWDMFKTMFQ-UHFFFAOYSA-N 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 229920001219 Polysorbate 40 Polymers 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- GCSPRLPXTPMSTL-IBDNADADSA-N [(2s,3r,4s,5s,6r)-2-[(2s,3s,4s,5r)-3,4-dihydroxy-2,5-bis(hydroxymethyl)oxolan-2-yl]-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl] dodecanoate Chemical compound CCCCCCCCCCCC(=O)O[C@@]1([C@]2(CO)[C@H]([C@H](O)[C@@H](CO)O2)O)O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O GCSPRLPXTPMSTL-IBDNADADSA-N 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- HGKOWIQVWAQWDS-UHFFFAOYSA-N bis(16-methylheptadecyl) 2-hydroxybutanedioate Chemical compound CC(C)CCCCCCCCCCCCCCCOC(=O)CC(O)C(=O)OCCCCCCCCCCCCCCCC(C)C HGKOWIQVWAQWDS-UHFFFAOYSA-N 0.000 description 1
- SAOKZLXYCUGLFA-UHFFFAOYSA-N bis(2-ethylhexyl) adipate Chemical compound CCCCC(CC)COC(=O)CCCCC(=O)OCC(CC)CCCC SAOKZLXYCUGLFA-UHFFFAOYSA-N 0.000 description 1
- HOWJQLVNDUGZBI-UHFFFAOYSA-N butane;propane Chemical compound CCC.CCCC HOWJQLVNDUGZBI-UHFFFAOYSA-N 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 229940093528 cetearyl ethylhexanoate Drugs 0.000 description 1
- 229940117860 cetearyl nonanoate Drugs 0.000 description 1
- 229960000541 cetyl alcohol Drugs 0.000 description 1
- 238000001311 chemical methods and process Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- YZFWTZACSRHJQD-UHFFFAOYSA-N ciglitazone Chemical compound C=1C=C(CC2C(NC(=O)S2)=O)C=CC=1OCC1(C)CCCCC1 YZFWTZACSRHJQD-UHFFFAOYSA-N 0.000 description 1
- 229940071160 cocoate Drugs 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- UUHBCYOCNFWRAH-UHFFFAOYSA-N decyl 16-methylheptadecanoate Chemical compound CCCCCCCCCCOC(=O)CCCCCCCCCCCCCCC(C)C UUHBCYOCNFWRAH-UHFFFAOYSA-N 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 229940067572 diethylhexyl adipate Drugs 0.000 description 1
- 229940031578 diisopropyl adipate Drugs 0.000 description 1
- 150000002009 diols Chemical class 0.000 description 1
- SZXQTJUDPRGNJN-UHFFFAOYSA-N dipropylene glycol Chemical compound OCCCOCCCO SZXQTJUDPRGNJN-UHFFFAOYSA-N 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000007046 ethoxylation reaction Methods 0.000 description 1
- ZJCFFCAWTLMEAE-UHFFFAOYSA-N ethyl hexyl carbonate Chemical compound [CH2]COC(=O)OCCCCCC ZJCFFCAWTLMEAE-UHFFFAOYSA-N 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 229940074047 glyceryl cocoate Drugs 0.000 description 1
- 125000005908 glyceryl ester group Chemical group 0.000 description 1
- NKVQUYDKWMXNNW-UHFFFAOYSA-N hexadecyl 2,2-dimethyloctanoate Chemical compound CCCCCCCCCCCCCCCCOC(=O)C(C)(C)CCCCCC NKVQUYDKWMXNNW-UHFFFAOYSA-N 0.000 description 1
- XJNUECKWDBNFJV-UHFFFAOYSA-N hexadecyl 2-ethylhexanoate Chemical compound CCCCCCCCCCCCCCCCOC(=O)C(CC)CCCC XJNUECKWDBNFJV-UHFFFAOYSA-N 0.000 description 1
- HJQLXIPVQPEJRY-UHFFFAOYSA-N hexadecyl 3,5,5-trimethylhexanoate Chemical compound CCCCCCCCCCCCCCCCOC(=O)CC(C)CC(C)(C)C HJQLXIPVQPEJRY-UHFFFAOYSA-N 0.000 description 1
- PMMXXYHTOMKOAZ-UHFFFAOYSA-N hexadecyl 7-methyloctanoate Chemical compound CCCCCCCCCCCCCCCCOC(=O)CCCCCC(C)C PMMXXYHTOMKOAZ-UHFFFAOYSA-N 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 206010022000 influenza Diseases 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 239000001282 iso-butane Substances 0.000 description 1
- 229940117933 isocetyl ethylhexanoate Drugs 0.000 description 1
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 1
- 229940011051 isopropyl acetate Drugs 0.000 description 1
- 229940023733 isopropyl behenate Drugs 0.000 description 1
- 229940033357 isopropyl laurate Drugs 0.000 description 1
- 229940097413 isopropyl maleate Drugs 0.000 description 1
- 229940074928 isopropyl myristate Drugs 0.000 description 1
- 229940089456 isopropyl stearate Drugs 0.000 description 1
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 1
- 239000004816 latex Substances 0.000 description 1
- 229920000126 latex Polymers 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 239000006194 liquid suspension Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229940041616 menthol Drugs 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000003595 mist Substances 0.000 description 1
- 229940078812 myristyl myristate Drugs 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- QNILTEGFHQSKFF-UHFFFAOYSA-N n-propan-2-ylprop-2-enamide Chemical compound CC(C)NC(=O)C=C QNILTEGFHQSKFF-UHFFFAOYSA-N 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000001272 nitrous oxide Substances 0.000 description 1
- VNLRTFSQCPNNIM-UHFFFAOYSA-N octadecyl octanoate Chemical compound CCCCCCCCCCCCCCCCCCOC(=O)CCCCCCC VNLRTFSQCPNNIM-UHFFFAOYSA-N 0.000 description 1
- AEIJTFQOBWATKX-UHFFFAOYSA-N octane-1,2-diol Chemical compound CCCCCCC(O)CO AEIJTFQOBWATKX-UHFFFAOYSA-N 0.000 description 1
- WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 1
- 229940077397 octyldodecyl lactate Drugs 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical class CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 125000000913 palmityl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- 229940098888 phenethyl benzoate Drugs 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-M pivalate Chemical compound CC(C)(C)C([O-])=O IUGYQRQAERSCNH-UHFFFAOYSA-M 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 239000000249 polyoxyethylene sorbitan monopalmitate Substances 0.000 description 1
- 235000010483 polyoxyethylene sorbitan monopalmitate Nutrition 0.000 description 1
- 229950008882 polysorbate Drugs 0.000 description 1
- 229940068977 polysorbate 20 Drugs 0.000 description 1
- 229940101027 polysorbate 40 Drugs 0.000 description 1
- 229940095106 ppg-3 benzyl ether myristate Drugs 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical class CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- PERLTXCUPZSJTA-YTXTXJHMSA-N propan-2-yl (2e,4e)-hexa-2,4-dienoate Chemical compound C\C=C\C=C\C(=O)OC(C)C PERLTXCUPZSJTA-YTXTXJHMSA-N 0.000 description 1
- XEIOPEQGDSYOIH-MURFETPASA-N propan-2-yl (9z,12z)-octadeca-9,12-dienoate Chemical compound CCCCC\C=C/C\C=C/CCCCCCCC(=O)OC(C)C XEIOPEQGDSYOIH-MURFETPASA-N 0.000 description 1
- PZQSQRCNMZGWFT-QXMHVHEDSA-N propan-2-yl (z)-octadec-9-enoate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC(C)C PZQSQRCNMZGWFT-QXMHVHEDSA-N 0.000 description 1
- SDYPTODXHIAHDF-ACQXMXPUSA-N propan-2-yl (z,12r)-12-hydroxyoctadec-9-enoate Chemical compound CCCCCC[C@@H](O)C\C=C/CCCCCCCC(=O)OC(C)C SDYPTODXHIAHDF-ACQXMXPUSA-N 0.000 description 1
- KNVAYBMMCPLDOZ-UHFFFAOYSA-N propan-2-yl 12-hydroxyoctadecanoate Chemical compound CCCCCCC(O)CCCCCCCCCCC(=O)OC(C)C KNVAYBMMCPLDOZ-UHFFFAOYSA-N 0.000 description 1
- IZQHTCYPZWOMFQ-UHFFFAOYSA-N propan-2-yl docosanoate Chemical compound CCCCCCCCCCCCCCCCCCCCCC(=O)OC(C)C IZQHTCYPZWOMFQ-UHFFFAOYSA-N 0.000 description 1
- WLMTYYBAGSMBPQ-UHFFFAOYSA-N propan-2-yl icosanoate Chemical compound CCCCCCCCCCCCCCCCCCCC(=O)OC(C)C WLMTYYBAGSMBPQ-UHFFFAOYSA-N 0.000 description 1
- ZPWFUIUNWDIYCJ-UHFFFAOYSA-N propan-2-yl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC(C)C ZPWFUIUNWDIYCJ-UHFFFAOYSA-N 0.000 description 1
- VSRSQDMWBSKNSF-UHFFFAOYSA-N propan-2-yl pyridine-3-carboxylate Chemical compound CC(C)OC(=O)C1=CC=CN=C1 VSRSQDMWBSKNSF-UHFFFAOYSA-N 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
- 229960001860 salicylate Drugs 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- IJRHDFLHUATAOS-DPMBMXLASA-M sodium ricinoleate Chemical compound [Na+].CCCCCC[C@@H](O)C\C=C/CCCCCCCC([O-])=O IJRHDFLHUATAOS-DPMBMXLASA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- ABTZKZVAJTXGNN-UHFFFAOYSA-N stearyl heptanoate Chemical compound CCCCCCCCCCCCCCCCCCOC(=O)CCCCCC ABTZKZVAJTXGNN-UHFFFAOYSA-N 0.000 description 1
- 229940098758 stearyl heptanoate Drugs 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000000475 sunscreen effect Effects 0.000 description 1
- 239000000516 sunscreening agent Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000012085 test solution Substances 0.000 description 1
- BORJONZPSTVSFP-UHFFFAOYSA-N tetradecyl 2-hydroxypropanoate Chemical compound CCCCCCCCCCCCCCOC(=O)C(C)O BORJONZPSTVSFP-UHFFFAOYSA-N 0.000 description 1
- DZKXJUASMGQEMA-UHFFFAOYSA-N tetradecyl tetradecanoate Chemical compound CCCCCCCCCCCCCCOC(=O)CCCCCCCCCCCCC DZKXJUASMGQEMA-UHFFFAOYSA-N 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- 229940116962 triisononanoin Drugs 0.000 description 1
- FQAZRHVERGEKOS-UHFFFAOYSA-N tripropan-2-yl 2-hydroxypropane-1,2,3-tricarboxylate Chemical compound CC(C)OC(=O)CC(O)(C(=O)OC(C)C)CC(=O)OC(C)C FQAZRHVERGEKOS-UHFFFAOYSA-N 0.000 description 1
- 230000003253 viricidal effect Effects 0.000 description 1
- 239000000341 volatile oil Substances 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
Classifications
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- 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
- A61P31/12—Antivirals
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N31/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic oxygen or sulfur compounds
- A01N31/04—Oxygen or sulfur attached to an aliphatic side-chain of a carbocyclic ring system
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
- A01P1/00—Disinfectants; Antimicrobial compounds or mixtures thereof
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- 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
- A61K31/047—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates having two or more hydroxy groups, e.g. sorbitol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
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- 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
- A61K9/10—Dispersions; Emulsions
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- 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
- A61K9/10—Dispersions; Emulsions
- A61K9/12—Aerosols; Foams
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Abstract
Described herein are compositions including p-Menthane-3,8-diol (PMD) having antiviral properties. The compositions are formulated to be stable and sprayable using one or more solvents selected from short chain primary alcohols and short chain secondary alcohols or combinations thereof as defined therein and either a glyceride-based emulsifier or a non-ionic ethoxylated sorbitan ester surfactant.
Description
Formulation
FIELD OF THE INVENTION
The present invention relates to an antiviral formulation; and more specifically to a stable, sprayable formulation comprising p-Menthane-3,8-diol (PMD).
BACKGROUND TO THE INVENTION
The insect-repellent effect of essential oils from the lemon eucalyptus tree (Corymbia citriodora, formerly known as Eucalyptus citriodora) has been known for some time.
The active ingredient of these oils is PMD (p-Menthane-3,8-diol; also known as menthoglycol, or 2-(2-Hydroxypropan-2-y1)-5-methylcyclohexan-1-01). The structure of PMD is shown below. "OH
OH
Note that PMD may exist in a number of different stereoisomeric forms.
The natural oils may be refined in order to increase the PMD content; the refined oils may be sold under a variety of trade names, including CitridiolTM. It is believed that the natural oils may contain a mixture of different stereoisomers in varying ratios, depending on the source of the oil.
It is also possible to use synthetic PMD; for example, synthetic PMD may be obtained as described by Zimmerman and English in J. A. C. S. 75 (1953) pp 2367-2370. PMD is also a precursor obtained during the synthesis of menthol. The precursor is usually in the form of a specific isomer of PMD.
As well as having insect-repellent properties, PMD is also believed to be useful as an antiviral or viricidal agent. This is described, for example, in US patent 7,872,051, which publication indicates that compositions comprising PMD are effective against influenza Urbani Severe Acute Respiratory Syndrome (Urbani SARS) and HSV-1. The suggestion is also made that, since all these viruses have a lipid envelope, the compositions may also be effective against other viruses having a lipid envelope, including coronaviruses.
This suggestion is also supported by recent work by the UK's Defence Science and Technology Laboratory (Dstl), in which the effectiveness of an off-the-shelf insect repellent formulation containing PMD (Mosi-GuardTm Natural spray) or CitriodiolTm against the SARS-Cov2 virus -responsible for the COVID-19 pandemic -was assessed. The study reported that one minute liquid suspension tests indicated that CitriodiolTm, ethanol, isopropanol and Mosi-guardTM Natural have anti-viral activity against SARS-CoV-2 England-2 isolate if mixed with the virus in the liquid phase; and that SARS-CoV-2 England 2 isolate survival studies on latex as a 'synthetic skin' (which was pre-treated with Mosi-guardTM Natural approximately 1 hour before testing) provided evidence of anti-viral properties against SARS-CoV-2 England-2 isolate. The work is reported at httos://www.gov. uklgovernmentipublicationstexperimental-survivalof-sars-cov-2-on-an-inseci rrepeHent-trealed-surFace--3 (accessed 2 December 2020).
It would be useful to provide formulations comprising PMD suitable for use as antiviral agents. However, off-the-shelf products intended for use as insect repellents, or other CitriodiolTm-containing products such as sunscreens, are generally inappropriate for repurposing as antiviral agents, for reasons including mode of application, consistency, stability, and so on. Furthermore, insect repellent formulations typically have relatively high levels of CitriodiolTM -up to 30% -and may contain additional components. It is therefore an object of the present invention to provide PMD formulations for use as antiviral agents. Particularly preferred formulations are stable and sprayable, to enable easy transport, storage, and application over a wide area.
SUMMARY OF THE INVENTION
The present invention provides a number of embodiments of formulations comprising PMD which are believed to be suitable for use as antiviral agents. The preferred embodiments should be stable, and sprayable (for example, as a mist or a fog) to allow wide coverage. It was found when researching possible formulations that PMD showed a tendency to crystallise, in particular when used at concentrations lower than those which may be found in conventional insect repellents, such that potential formulations required to be modified in order to reduce crystallisation. The skilled person will appreciate that crystallised PMD may interfere with spray delivery mechanisms, so this may be a significant obstacle to practical widespread use as an antiviral.
The antiviral compositions of the invention are intended to be sprayable. Thus, the compositions can be delivered from non-aerosol mechanical pump spray devices or from pressurized aerosol canisters using a propellant or from any other mechanism or method of dispersing compositions. The compositions may be intended for topical application to the skin, and/or for application to surfaces, and/or for misting to fill a volume. A wide range of mechanical pump spray devices and aerosol canister systems are well known to those of ordinary skill in the art. Similarly, a wide range of propellant materials are well known to those skilled in the art. Nonlimiting examples include lower molecular weight hydrocarbons such as propane n-butane and isobutane, nitrogen, carbon dioxide, nitrous oxide, and so forth, as well as compressed or pressurised air.
Mixtures of such propellants can also be used.
Unless otherwise indicated, the concentrations of ingredients specified below are given in terms of the weight of the ingredient based on the weight of the sprayable antiviral composition as a whole but excluding any propellant that might be present.
According to a first aspect of the present invention, there is provided a sprayable antiviral composition, the composition comprising: a) from 0.1% to 25% by weight of the total composition of p-Menthane-3,8-diol (PMD); b) from 5% to 40% by weight of the total composition of one or more solvents selected from short chain (C1-05) primary alcohols and short chain (C3-05) secondary alcohols, and combinations thereof; c) either i) from 0.5% to 10% by weight of the total composition of a glyceride-based emulsifier; or ii) from 10% to 30% by weight of the total composition of a non-ionic ethoxylated sorbitan ester surfactant.
It is to be understood that the term "antiviral", as used herein, means "having the capacity to inhibit or stop the growth and reproduction of viruses", or "having the capacity to destroy or inactivate viruses".
The composition may further optionally comprise: d) from 2% to 10% by weight of a polar ester; and/or e) from 0.1% to 3% of an emulsion stabiliser (non-limiting examples include carbomers, cellulose gun, xanthan gum and microcrystalline cellulose) The balance of the composition may be water, and optional ingredients to improve shelf life and aesthetic properties.
In preferred embodiments, the composition consists essentially of components a) to c), and optionally d) and/or e), and water. That is, no additional components are present. In particular this means the composition can be provided as an oil-free, and (in some embodiments) ethanol-free composition. In other embodiments the composition may consist essentially of components a) to c), and optionally d) and/or e), and water, and further optional ingredients to improve shelf life and aesthetic properties.
The composition may be in the form of an emulsion, when an emulsifier is used, or in the form of a solution, where no emulsifier is used. Preferred embodiments provide the composition as a solution, since this is easier to handle and manipulate, but there may be some circumstances when an emulsion is preferred. In particular, an emulsion may be preferable when the composition is to be formulated on site (for example, to be prepared by the end user or an intermediary), rather than being centrally manufactured and distributed.
The PMD present in the composition may be any single isomer or any combination of one or more isomers. In preferred embodiments, the PMD is at least 90%, 92%, 93%, 94%, 95%, or more of a pure single isomer. However, we believe that the relevant antiviral properties are not dependent on a particular isomer, such that other degrees of purity or mixtures of isomers may be used.
The amount of PMD present in the composition may be from 0.1%-25%, preferably 0.5%-10%, alternatively 1%-9%, preferably 2%-8%, or 3%-7%, or 4%-6%. In preferred embodiments, the composition comprises 5% by weight of PMD.
The solvent may be selected from short chain (C1-05) primary and short chain (C3-05) secondary alcohols, and mixtures thereof. The term alcohols includes diols and polyols. Possible primary alcohols include ethanol or methanol; however, given the potential for abuse of formulations containing these, their use is not preferred. Preferred secondary alcohols are propanols, and particularly preferred are propan-2-ol (also referred to as isopropyl alcohol) and propane-1,2-diol (also referred to as propylene glycol); and indeed these are each particularly preferred in embodiments of the invention. Other alcohols which may be used include On a non-limiting list) ethylene glycol, dipropylene glycol, butylene glycol, and capryl glycol.
The solvent may be present from 5% to 40% by weight of the total weight of the composition. Where a single solvent is present -for example, propan-2-ol or propane1,2-diol -the preferred amount of solvent present is from 5-20% by weight, more preferably 10-20%, yet more preferably 13-18%, and most preferably 15% by weight.
Either of these solvents may be used individually in this amount. Where a mix of solvents is used, then these may be used in any desired ratio, and a preferred amount of solvent is from 20-40% by weight, more preferably 25-35% by weight, and most preferably 30% by weight. One example of a preferred composition includes 25% propan-2-ol and 5% propane-1,2-diol; this is more preferred where the composition is not an emulsion. Hence in a further embodiment, when the solvent is or includes propane-1,2-diol, component c) is not an emulsifier. We have found that propan-2-ol alone is an efficient solvent, but that addition of propane-1,2-diol can help to reduce loss by evaporation and the propensity for the PMD to crystallise and potentially block dispensing of the composition.
The glyceride-based emulsifier, when present, may be present at 0.5-10% by weight; preferably 0.5-5%, more preferably 1.5%-3.5%, and still more preferably 2.5%. Preferred emulsifiers include polyglyceryl-ester emulsifiers or glyceryl esters of fatty acids; one particularly preferred emulsifier is glyceryl oleate citrate, with alternatives being glyceryl stearate citrate or glyceryl cocoate citrate. Commercially-available emulsifiers may be used; for example, that available under the brand "dermofeel0 easymuls plus" from Evonik (which contains glyceryl oleate citrate). Other emulsifiers which may be suitable include: the "Sucrabase" range produced by Alfa Chemicals (comprising caprylic/capric triglycerides, glycerine, sucrose laurate, sucrose stearate); DUB Base Expert+ from Stearinerie Dubois (containing glyceryl stearate citrate, sucrose stearate, polyglycery1-4 cocoate, cetyl alcohol, sodium ricinoleate). Where commercial formulations of emulsifiers are used, it is preferred that these are PEG free.
The non-ionic ethoxylated sorbitan ester surfactant, when present, may be present at 10-30% by weight, preferably 10-20%, more preferably 12.5-17.5%, and most preferably around 15%. Preferred surfactants are polysorbates, in particular polysorbate 80, but in certain embodiments other polysorbates may be used such as polysorbate 20, polysorbate 40, polysorbate 60. Polysorbates are a class of surfactant comprising ethoxylated esters. Polysorbate 80 is a mixture of oleate esters of sorbitol and sorbitol anhydrides, consisting predominantly of the monoester, condensed with approximately 20 moles of ethylene oxide. It is also known as Polyoxyethylene (20) Sorbitan Monooleate. The higher the degree of ethoxylation the more likely it will be a good solubiliser.
In certain embodiments, a polar ester may be present, from 2% to 10% by weight; preferably from 3-9%, from 4-8%, or most preferably 5%. We have found that addition of such an ester may help reduce crystallisation of the PMD. A preferred polar ester is C12-15 alkyl benzoate, but others may be selected; for example, from those commonly used in cosmetics. Examples of other esters which may be useful in the invention include Butyl Stearate, Butyloctyl Salicylate, C12-13 Alkyl Lactate, Cetearyl Ethylhexanoate, Cetearyl Isononanoate, Cetearyl Nonanoate, Cetyl Dimethyloctanoate, Cetyl Ethylhexanoate, Cetyl Isononanoate, Cetyl PaImitate, Decyl Isostearate, Decyl Oleate, Diethyl hexyl Adipate, Diethyl hexyl Carbonate, Diisopropyl Adipate, Diisostearyl Malate, Ethyl Oleate, Ethylhexyl PaImitate, Isocetyl Ethylhexanoate, Isocetyl lsodecanoate, Isocetyl Stearoyl Stearate, Isodecyl Ethylhexanoate, Isodecyl Isononanoate, lsodecyl Neopentanoate, lsononyl Isononanoate, Isopropyl Acetate, Isopropyl Arachidate, Isopropyl Behenate, Isopropyl Benzoate, Isopropyl Citrate, Isopropyl Cyanoacrylate, Isopropyl Cyclohexylpropionate, Isopropyl Hydroxystearate, Isopropyl lsostearate, Isopropyl Laurate, Isopropyl Linoleate, Isopropyl Maleate, Isopropyl Myristate, Isopropyl Nicotinate, Isopropyl Oleate, Isopropyl PaImitate, Isopropyl Pelargonate, Isopropyl Ricinoleate, Isopropyl Sorbate, Isopropyl Stearate, Isopropylacrylamide, lsopropylbenzyl Salicylate, lsosteareth-3 Ethylhexanoate, Isostearyl Ethylhexanoate, Isostearyl Isononanoate, Isostearyl lsostearate, Isostearyl Neopentanoate, lsotridecyl Isononanoate, Myristyl Lactate, Myristyl Myristate, Octyldodecyl Lactate, Octyldodecyl Stearate, Phenethyl Benzoate, PPG 3 Benzyl Ether Myristate, Propylene Glycol Dibenzoate, Stearyl Caprylate, Stearyl Heptanoate, Triethylhexanoin, Triisononanoin, Triisopropyl Citrate, and Triisopropyl Trilinoleate. Particularly preferred examples may include Decyl Oleate, Diethyl hexyl Carbonate, Isopropyl Benzoate, Isopropyl Citrate, Isopropyl Myristate, and Isopropyl PaImitate.
Particularly preferred embodiments of the invention are, first, a sprayable antiviral composition, the composition comprising: a) from 0.5% to 10%, preferably 3-7%, more preferably 5%, by weight of the total composition of p-Menthane-3,8-diol (PMD); b) from 10% to 30%, preferably 15-20%, more preferably 20%, by weight of the total composition of propan-2-ol; c) from 10% to 30%, preferably 10%, by weight of the total composition of polysorbate 80; d) the balance is water.
A second particularly preferred embodiment is a sprayable antiviral composition, the composition comprising: a) from 0.5% to 10%, preferably 3-7%, more preferably 5%, by weight of the total composition of p-Menthane-3,8-diol (PMD); b) 20% by weight of the total composition of propan-2-ol; c) from 10% to 30%, preferably 10%, by weight of the total composition of polysorbate 80; d) 10% by weight of the total composition of propane-1,2-diol; e) the balance is water. 25 An embodiment of the invention provides a sprayable antiviral composition, the composition comprising: a) 5% by weight of the total composition of p-Menthane-3,8-diol (PMD); b) 15-30% by weight of the total composition of propan-2-ol; c) from 10% to 20% by weight of the total composition of polysorbate 80; d) 0-10% by weight of the total composition of propane-1,2-diol; wherein, when propane-1,2-diol is present, the total combined amount of propane-1,2-diol and propan2-ol is 30%; e) the balance is water.
An embodiment of the invention provides a sprayable antiviral composition, the composition comprising: a) 5% by weight of the total composition of p-Menthane-3,8-diol (PMD); b) 10-15% by weight of the total composition of propane-1,2-diol; c) 0-5% by weight of the total composition of a polar ester; d) 1-5% by weight of the total composition of an emulsifier; e) the balance is water.
A further aspect of the invention provides a concentrate which, when diluted with water, yields a sprayable antiviral composition as defined herein. The concentrate cannot be water-free but will preferably contain a minimum amount of water required to provide a stable solution or paste. This can then be diluted as required to yield the composition.
In certain embodiments, we believe that a maximum of 25% by weight of water in the concentrate is preferred.
A still further aspect of the invention provides a spray bottle containing a composition as defined herein.
EXAMPLES
The following examples are intended to illustrate aspects of the invention, and to describe how it may be practiced. They are not intended to limit the scope of the invention.
We aimed to identify ways to solubilise or emulsify PMD into a water-thin solution or emulsion that can be sprayed in a fog. Ideally the ingredients were to be readily available and the formula be suitable for cold-processing, thereby allowing production in many different environments and circumstances (for example, in temporary hospitals, or in remote or underserved areas of the world).
Our research made use of a commercially available PMD solution, from Chemical Process Laboratories, Silverton, South Africa which was specified as being 70-75% active by weight. On analysis, the test sample as received was 71% active. Our objective was to provide an emulsion/solution with 5% active content hence the following examples indicate use of 7.15% PMD solution to give a final 5% active content. Alternative sources of PMD may of course be used, and in particular when scaling up for larger production runs it is possible to commercially obtain PMD Solution with a range of 55% to 75% and up to 95-97% pure PM D in solid form.
The reason for selecting 5% active is to ensure sufficient PMD is present in the applied final product, assuming some inevitable variation in surface skin moisture, inconsistency of application, and so on. However, PMD is believed to provide antiviral effects across a range of concentrations. The insect repellent effect is only seen at much higher concentrations, and hence most existing PMD-containing formulations are geared towards stability at these higher (up to 30%) concentrations.
Formula Development Previous experience with Citriodiol in formulations for insect repellents was expected to be relevant in reaching the goal. However, the formulation process proved to be unexpectedly complex. One particular issue was that a blend of solubilisers that worked when added with Citriodiol at 30% did not work when in the same proportion with PMD Solution at 7.15%. After further consideration of potential formulations, some were prepared but overnight storage at 50 showed crystals developing in most of them; hence these were considered unsuitable.
After further development, four possible solutions were obtained, and were tested at 5C, ambient and 400. After 5 days all were clear at ambient and 400 but three showed different levels of crystal development at 5C. Concurrent with trying to find clear solutions we also looked at various emulsifier possibilities and two were identified that appeared promising. These were also tested for 5 days at the 3 conditions. One emulsion showed signs of instability but the other one remained stable for the full 10 days test period.
Table 1 below shows the components of two test emulsions, and four test solutions, and the results after 10 days storage at the three temperature conditions. One emulsion (F1/7229B) appeared stable after 10 days at 40C and one solution (F1/7743C) showed no sign of crystals after 10 days at 5C. We determined that both propylene glycol (PG) and isopropanol (IPA) show solvent properties for PMD Solution.
Table 1: Tested Samples Emulsions Solutions Ingredients F1/7229 B F1/7229 C F1/7729 A F1/7743 B F1/7743 C F1/7743 D PMD Solution 7.15 7.15 7.15 7.15 7.15 7.15 Propylene Glycol 15.00 10.00 10.00 0 0 20.00 Easymuls Plus* 2.50 0 0 0 0 0 Water 75.35 80.35 42.85 47.85 61.35 56.55 Lysofix Liquid 0 2.5 0 0 0 0 Isopropanol 0 0 30.00 0 15.00 0 Polysorbate -60** 0 0 10.00 0 0 0 Polysorbate 0 0 0 0 16.50 16.30 Butylene Glycol 0 0 0 30.00 0 0 Crodasol WS 0 0 0 15.00 0 0 100% 100% 100% 100% 100% 100% 10-day Storage 5C - Clear Crystals visible V. slight crystals Cloudy Clear Slight crystals crystals? Ambient Stable Stable Clear Clear Clear Clear 40C Stable Unstable Clear Clear Clear Clear Following this investigation and previous screening processes Easymuls plus is the emulsifier of choice. It is Glyceryl Oleate Citrate from Evonik, described as a natural, anionic PEG-free 0/W emulsifier for low-viscous products. It shows excellent cold emulsifying capacities and can stabilise oil contents from 5 % to 30 % without significantly increasing the emulsion viscosity, making it very suitable for a spray application.
Of the many solubilisers tried Polysorbate-80 was the most effective but it was present at quite a high level. We next looked at reducing its level to 10% and adjusting levels of propylene glycol and isopropanol to find the optimum blend when used at 30% in a formulation -see Table 2.
Table 2: To find Optimum Blend of IPA/PG.
Ingredients Blend 1 Blend 2 Blend 3 Blend 4 PMD Solution 7.00 7.00 7.00 7.00 Polysorbate-80 10.00 10.00 10.00 10.00 IPA 30.00 20.00 10.00 0.00 PG 0 10.00 20.00 30.00 Water, deionised 53.00 53.00 53.00 53.00 Storage Results Cloudy when mixed Cloudy when mixed 5C Clear Clear Ambient Clear Clear 40C Clear Clear We were left with one emulsion and three solutions that appeared to fulfil our requirements, they remained stable for a minimum of 10 days and were each sprayed through perfume atomisers without a problem.
We only had one emulsion under test and previous work showed the advantage of using a polar ester to improve stability and inhibit crystal formation. Further samples were prepared using three different esters; C12-15 Alkyl Benzoate, Decyl Oleate and Ethylhexyl Carbonate and these were put under test as before.
There are three solutions; the preference is for F1-7744 B using both PG and IPA. PG will slow evaporation rate and inhibit crystals forming in the spray nozzle after use.
Table 3
Emulsions Solutions Ingredients F1/722 F1/776 4A F1/776 F1/776 F1/774 F1/774 F1/774 9B 4B 4C 3C 4A 4B PMD Solution 7.15 7.15 7.15 7.15 7.15 7.15 7.15 Propylene Glycol 15.00 10.00 10.00 10.00 0 0 10.00 Easymuls 2.50 3.00 3.00 3.00 0 0 0 Plus* C12-15 Alkyl benzoate 0 5.00 0 0 0 0 0 Decyl Oleate 0 0 5.00 0 0 0 0 Diethyl Hexyl Carbonate 0 0 0 5.00 0 0 0 Water 75.35 74.85 74.85 74.85 61.35 52.85 52.85 Isopropanol 0 0 0 0 15.00 30.00 20.00 Polysorbate- 0 0 0 0 16.50 10.00 10.00 100% 100% 100% 100% 100% 100% 100% Experiments have also been carried out on preparing concentrates for emulsions. Examples of concentrates are shown in Table 4 below.
Table 4: Concentrates -to be diluted 40% concentrate /60% water.
Ingredients F1/7764A F1/7764B PMD Solution 17.875 17.875 Propylene Glycol 37.5 37.5 Easymuls Plus* 7.125 7.125 C12-15 Alkyl benzoate 12.50 0 Decyl Oleate 0 12.50 Water 25.00 25.00 100% 100%
Claims (18)
- CLAIMS: 1. A sprayable antiviral composition, the composition comprising: a) from 0.1% to 25% by weight of the total composition of p-Menthane-3,8-diol (PMD); b) from 5% to 40% by weight of the total composition of one or more solvents selected from short chain (C1-05) primary and short chain (C3-05) secondary alcohols, and combinations thereof; c) either i) from 0.5% to 10% by weight of the total composition of a glyceride-based emulsifier; or ii) from 10% to 30% by weight of the total composition of a nonionic ethoxylated sorbitan ester surfactant.
- 2. The composition of claim 1, further comprising: d) from 2% to 10% by weight of a polar ester.
- 3 The composition of claim 1 or 2, further comprising: e) from 0.1% to 3% of an emulsion stabiliser.
- 4. The composition of any preceding claim, consisting essentially of components a) to c) and water, and optionally components d) and/or e).
- 5. The composition of any preceding claim comprising 5% by weight of PMD.
- 6. The composition of any preceding claim wherein the solvent is selected from propan-2-ol and propane-1,2-diol.
- 7. The composition of any preceding claim wherein the solvent comprises from 5% to 20% by weight of the total weight of the composition.
- 8. The composition of any preceding claim wherein a mix of solvents is used, and the mix comprises 25-35% by weight of the total weight of the composition.
- 9. The composition of claim 8 wherein the composition comprises 25% propan-2-ol and 5% propane-1,2-diol, or wherein the composition comprises 20% propan-2-ol and 10% propane-1,2-diol.
- 10. The composition of any preceding claim wherein the solvent is or includes propane-1,2-diol, and component c) is not an emulsifier.
- 11. The composition of any of claims 1-9 wherein the glyceride-based emulsifier is present at 1.5-3.5% by weight.
- 12. The composition of any preceding claim wherein the non-ionic ethoxylated sorbitan ester surfactant is present at 10-20% by weight.
- 13. The composition of any preceding claim wherein the non-ionic ethoxylated sorbitan ester surfactant comprises polysorbate 80.
- 14 A sprayable antiviral composition, the composition comprising: a) from 0.5% to 10%, preferably 3-7%, more preferably 5%, by weight of the total composition of p-Menthane-3,8-diol (PMD); b) from 10% to 30%, preferably 15-20%, more preferably 20%, by weight of the total composition of propan-2-ol; c) from 10% to 30%, preferably 10%, by weight of the total composition of polysorbate 80
- 15. A sprayable antiviral composition; the composition comprising: a) from 0.5% to 10%, preferably 3-7%, more preferably 5%, by weight of the total composition of p-Menthane-3,8-diol (PMD); b) 20% by weight of the total composition of propan-2-ol; c) from 10% to 30%, preferably 10%, by weight of the total composition of polysorbate 80; and d) 10% by weight of the total composition of propane-1,2-diol.
- 16. A sprayable antiviral composition; the composition comprising: a) 5% by weight of the total composition of p-Menthane-3,8-diol (PMD); b) 15-30% by weight of the total composition of propan-2-ol; c) from 10% to 20% by weight of the total composition of polysorbate 80; and d) 0-10% by weight of the total composition of propane-1,2-diol; wherein, when propane-1,2-diol is present, the total combined amount of propane-1,2-diol and propan- 2-ol is 30%.
- 17. A sprayable antiviral composition. the composition comprising: a) 5% by weight of the total composition of p-Menthane-3,8-diol (PMD); b) 10-15% by weight of the total composition of propane-1,2-diol; c) 0-5% by weight of the total composition of a polar ester; d) 1-5% by weight of the total composition of an emulsifier; and.e) 0.1% to 3% by weight of the total composition of an emulsion stabiliser. 15
- 18. A spray bottle containing a composition as defined in any preceding claim.
Priority Applications (7)
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GB2020461.6A GB2598419C (en) | 2020-12-23 | 2020-12-23 | Stable, sprayable antiviral formulation |
GB2108165.8A GB2603220A (en) | 2020-12-23 | 2021-06-08 | Formulation |
EP21844637.5A EP4267106A1 (en) | 2020-12-23 | 2021-12-15 | Formulation comprising p-menthane-3,8-diol |
US18/269,010 US20240050339A1 (en) | 2020-12-23 | 2021-12-15 | Formulation comprising p-menthane-3,8-diol |
CA3203038A CA3203038A1 (en) | 2020-12-23 | 2021-12-15 | Formulation comprising p-menthane-3,8-diol |
PCT/EP2021/086010 WO2022136067A1 (en) | 2020-12-23 | 2021-12-15 | Formulation comprising p-menthane-3,8-diol |
AU2021407343A AU2021407343A1 (en) | 2020-12-23 | 2021-12-15 | Formulation comprising p-menthane-3,8-diol |
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GB2020461.6A GB2598419C (en) | 2020-12-23 | 2020-12-23 | Stable, sprayable antiviral formulation |
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GB2598419A true GB2598419A (en) | 2022-03-02 |
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WO2005087209A1 (en) * | 2004-03-12 | 2005-09-22 | Paul Douglas Clarke | Antiviral composition comprising p-menthane-3, 8-diol |
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GB9917040D0 (en) * | 1999-07-21 | 1999-09-22 | Clarke Paul D | Antiseptic composition |
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WO2005087209A1 (en) * | 2004-03-12 | 2005-09-22 | Paul Douglas Clarke | Antiviral composition comprising p-menthane-3, 8-diol |
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Mintel GNPD Database Redcord ID 6003191 - PMD Outdoor Activity Shield - Farlain Creative Marketing * |
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GB202108165D0 (en) | 2021-07-21 |
GB2598419B (en) | 2022-10-19 |
GB202020461D0 (en) | 2021-02-03 |
GB2598419C (en) | 2022-10-26 |
GB2603220A (en) | 2022-08-03 |
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