ZA200507018B - Oleaginous pharmaceutical and cosmetic foam - Google Patents
Oleaginous pharmaceutical and cosmetic foam Download PDFInfo
- Publication number
- ZA200507018B ZA200507018B ZA200507018A ZA200507018A ZA200507018B ZA 200507018 B ZA200507018 B ZA 200507018B ZA 200507018 A ZA200507018 A ZA 200507018A ZA 200507018 A ZA200507018 A ZA 200507018A ZA 200507018 B ZA200507018 B ZA 200507018B
- Authority
- ZA
- South Africa
- Prior art keywords
- agent
- solvent
- active agent
- oleaginous
- composition
- Prior art date
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- 239000008260 cosmetic foam Substances 0.000 title description 2
- 239000008255 pharmaceutical foam Substances 0.000 title description 2
- 239000000203 mixture Substances 0.000 claims description 264
- 239000002904 solvent Substances 0.000 claims description 162
- 239000004094 surface-active agent Substances 0.000 claims description 100
- 239000013543 active substance Substances 0.000 claims description 84
- 230000002209 hydrophobic effect Effects 0.000 claims description 65
- 230000001225 therapeutic effect Effects 0.000 claims description 58
- 239000003921 oil Substances 0.000 claims description 56
- 239000006260 foam Substances 0.000 claims description 47
- 239000007762 w/o emulsion Substances 0.000 claims description 43
- 239000003349 gelling agent Substances 0.000 claims description 41
- 230000003389 potentiating effect Effects 0.000 claims description 39
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 37
- 239000006184 cosolvent Substances 0.000 claims description 37
- 239000002480 mineral oil Substances 0.000 claims description 37
- 235000010446 mineral oil Nutrition 0.000 claims description 37
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 34
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 33
- 239000003795 chemical substances by application Substances 0.000 claims description 29
- -1 oleates Chemical class 0.000 claims description 26
- 239000000839 emulsion Substances 0.000 claims description 25
- 239000000463 material Substances 0.000 claims description 24
- 229920001223 polyethylene glycol Polymers 0.000 claims description 24
- 239000002202 Polyethylene glycol Substances 0.000 claims description 21
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 21
- 239000003974 emollient agent Substances 0.000 claims description 21
- 229920005862 polyol Polymers 0.000 claims description 21
- 150000003077 polyols Chemical class 0.000 claims description 21
- 208000035475 disorder Diseases 0.000 claims description 19
- 239000003814 drug Substances 0.000 claims description 16
- 235000011187 glycerol Nutrition 0.000 claims description 15
- 238000000034 method Methods 0.000 claims description 15
- 229920002545 silicone oil Polymers 0.000 claims description 15
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 14
- 239000002537 cosmetic Substances 0.000 claims description 12
- 239000006268 oleaginous foam Substances 0.000 claims description 12
- 239000003380 propellant Substances 0.000 claims description 12
- 239000004480 active ingredient Substances 0.000 claims description 11
- 229920001296 polysiloxane Polymers 0.000 claims description 11
- 238000011282 treatment Methods 0.000 claims description 11
- SVTBMSDMJJWYQN-UHFFFAOYSA-N 2-methylpentane-2,4-diol Chemical compound CC(O)CC(C)(C)O SVTBMSDMJJWYQN-UHFFFAOYSA-N 0.000 claims description 10
- 229940124597 therapeutic agent Drugs 0.000 claims description 10
- CTPDSKVQLSDPLC-UHFFFAOYSA-N 2-(oxolan-2-ylmethoxy)ethanol Chemical compound OCCOCC1CCCO1 CTPDSKVQLSDPLC-UHFFFAOYSA-N 0.000 claims description 9
- 150000002148 esters Chemical class 0.000 claims description 9
- 229930195733 hydrocarbon Natural products 0.000 claims description 9
- 150000002430 hydrocarbons Chemical class 0.000 claims description 9
- 239000007788 liquid Substances 0.000 claims description 9
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- 150000003904 phospholipids Chemical class 0.000 claims description 8
- MEJYDZQQVZJMPP-ULAWRXDQSA-N (3s,3ar,6r,6ar)-3,6-dimethoxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan Chemical compound CO[C@H]1CO[C@@H]2[C@H](OC)CO[C@@H]21 MEJYDZQQVZJMPP-ULAWRXDQSA-N 0.000 claims description 7
- 239000002253 acid Substances 0.000 claims description 7
- 239000002671 adjuvant Substances 0.000 claims description 7
- 239000012528 membrane Substances 0.000 claims description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- 150000001298 alcohols Chemical class 0.000 claims description 6
- 239000003242 anti bacterial agent Substances 0.000 claims description 6
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 6
- XXJWXESWEXIICW-UHFFFAOYSA-N diethylene glycol monoethyl ether Chemical compound CCOCCOCCO XXJWXESWEXIICW-UHFFFAOYSA-N 0.000 claims description 6
- 239000000194 fatty acid Substances 0.000 claims description 6
- 229930195729 fatty acid Natural products 0.000 claims description 6
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- KLDXJTOLSGUMSJ-JGWLITMVSA-N Isosorbide Chemical class O[C@@H]1CO[C@@H]2[C@@H](O)CO[C@@H]21 KLDXJTOLSGUMSJ-JGWLITMVSA-N 0.000 claims description 5
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 5
- 150000007513 acids Chemical class 0.000 claims description 5
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- 230000005484 gravity Effects 0.000 claims description 5
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- 150000004492 retinoid derivatives Chemical class 0.000 claims description 5
- 239000000126 substance Substances 0.000 claims description 5
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- WDQFELCEOPFLCZ-UHFFFAOYSA-N 1-(2-hydroxyethyl)pyrrolidin-2-one Chemical compound OCCN1CCCC1=O WDQFELCEOPFLCZ-UHFFFAOYSA-N 0.000 claims description 4
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 claims description 4
- 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 claims description 4
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 4
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- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical group [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 claims description 4
- 150000001408 amides Chemical class 0.000 claims description 4
- 229940121375 antifungal agent Drugs 0.000 claims description 4
- CDQSJQSWAWPGKG-UHFFFAOYSA-N butane-1,1-diol Chemical class CCCC(O)O CDQSJQSWAWPGKG-UHFFFAOYSA-N 0.000 claims description 4
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- 229910044991 metal oxide Inorganic materials 0.000 claims description 4
- 150000004706 metal oxides Chemical class 0.000 claims description 4
- YYZUSRORWSJGET-UHFFFAOYSA-N octanoic acid ethyl ester Natural products CCCCCCCC(=O)OCC YYZUSRORWSJGET-UHFFFAOYSA-N 0.000 claims description 4
- 239000002516 radical scavenger Substances 0.000 claims description 4
- 210000000664 rectum Anatomy 0.000 claims description 4
- 201000010153 skin papilloma Diseases 0.000 claims description 4
- 239000003009 skin protective agent Substances 0.000 claims description 4
- 238000005063 solubilization Methods 0.000 claims description 4
- 230000007928 solubilization Effects 0.000 claims description 4
- 150000003462 sulfoxides Chemical class 0.000 claims description 4
- 210000003708 urethra Anatomy 0.000 claims description 4
- 210000001215 vagina Anatomy 0.000 claims description 4
- WJTCHBVEUFDSIK-NWDGAFQWSA-N (2r,5s)-1-benzyl-2,5-dimethylpiperazine Chemical compound C[C@@H]1CN[C@@H](C)CN1CC1=CC=CC=C1 WJTCHBVEUFDSIK-NWDGAFQWSA-N 0.000 claims description 3
- 208000035484 Cellulite Diseases 0.000 claims description 3
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 claims description 3
- 206010049752 Peau d'orange Diseases 0.000 claims description 3
- 230000003444 anaesthetic effect Effects 0.000 claims description 3
- 230000000202 analgesic effect Effects 0.000 claims description 3
- 230000002924 anti-infective effect Effects 0.000 claims description 3
- 239000002260 anti-inflammatory agent Substances 0.000 claims description 3
- 229940121363 anti-inflammatory agent Drugs 0.000 claims description 3
- 230000001028 anti-proliverative effect Effects 0.000 claims description 3
- 230000001153 anti-wrinkle effect Effects 0.000 claims description 3
- 239000000043 antiallergic agent Substances 0.000 claims description 3
- 239000003429 antifungal agent Substances 0.000 claims description 3
- 239000002246 antineoplastic agent Substances 0.000 claims description 3
- 239000003096 antiparasitic agent Substances 0.000 claims description 3
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- 239000003443 antiviral agent Substances 0.000 claims description 3
- 230000003115 biocidal effect Effects 0.000 claims description 3
- 239000003246 corticosteroid Substances 0.000 claims description 3
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 claims description 3
- 229940093471 ethyl oleate Drugs 0.000 claims description 3
- 239000000314 lubricant Substances 0.000 claims description 3
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 claims description 3
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 claims description 3
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 claims description 3
- 238000002428 photodynamic therapy Methods 0.000 claims description 3
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- MINDHVHHQZYEEK-UHFFFAOYSA-N (E)-(2S,3R,4R,5S)-5-[(2S,3S,4S,5S)-2,3-epoxy-5-hydroxy-4-methylhexyl]tetrahydro-3,4-dihydroxy-(beta)-methyl-2H-pyran-2-crotonic acid ester with 9-hydroxynonanoic acid Natural products CC(O)C(C)C1OC1CC1C(O)C(O)C(CC(C)=CC(=O)OCCCCCCCCC(O)=O)OC1 MINDHVHHQZYEEK-UHFFFAOYSA-N 0.000 claims description 2
- ZFFMLCVRJBZUDZ-UHFFFAOYSA-N 2,3-dimethylbutane Chemical group CC(C)C(C)C ZFFMLCVRJBZUDZ-UHFFFAOYSA-N 0.000 claims description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims description 2
- 235000013871 bee wax Nutrition 0.000 claims description 2
- 239000012166 beeswax Substances 0.000 claims description 2
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- 229960003128 mupirocin Drugs 0.000 claims description 2
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- DDHVILIIHBIMQU-YJGQQKNPSA-L mupirocin calcium hydrate Chemical group O.O.[Ca+2].C[C@H](O)[C@H](C)[C@@H]1O[C@H]1C[C@@H]1[C@@H](O)[C@@H](O)[C@H](C\C(C)=C\C(=O)OCCCCCCCCC([O-])=O)OC1.C[C@H](O)[C@H](C)[C@@H]1O[C@H]1C[C@@H]1[C@@H](O)[C@@H](O)[C@H](C\C(C)=C\C(=O)OCCCCCCCCC([O-])=O)OC1 DDHVILIIHBIMQU-YJGQQKNPSA-L 0.000 claims description 2
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- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 claims 4
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- 229930004069 diterpene Natural products 0.000 description 1
- 125000000567 diterpene group Chemical group 0.000 description 1
- 235000020669 docosahexaenoic acid Nutrition 0.000 description 1
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- DFQOCHPHORLRID-UHFFFAOYSA-N dodecyl tetradecanoate Chemical compound CCCCCCCCCCCCCC(=O)OCCCCCCCCCCCC DFQOCHPHORLRID-UHFFFAOYSA-N 0.000 description 1
- 238000004945 emulsification Methods 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- GADGVXXJJXQRSA-UHFFFAOYSA-N ethenyl 8-methylnonanoate Chemical compound CC(C)CCCCCCC(=O)OC=C GADGVXXJJXQRSA-UHFFFAOYSA-N 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
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- 235000008524 evening primrose extract Nutrition 0.000 description 1
- 239000010475 evening primrose oil Substances 0.000 description 1
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- 238000005187 foaming Methods 0.000 description 1
- FOYKKGHVWRFIBD-UHFFFAOYSA-N gamma-tocopherol acetate Natural products CC(=O)OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1 FOYKKGHVWRFIBD-UHFFFAOYSA-N 0.000 description 1
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- 235000019514 herring Nutrition 0.000 description 1
- XAMHKORMKJIEFW-AYTKPMRMSA-N hexadecyl (z,12r)-12-hydroxyoctadec-9-enoate Chemical compound CCCCCCCCCCCCCCCCOC(=O)CCCCCCC\C=C/C[C@H](O)CCCCCC XAMHKORMKJIEFW-AYTKPMRMSA-N 0.000 description 1
- 239000008240 homogeneous mixture Substances 0.000 description 1
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- 229920001477 hydrophilic polymer Polymers 0.000 description 1
- 125000001165 hydrophobic group Chemical group 0.000 description 1
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- 229920013818 hydroxypropyl guar gum Polymers 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- OPEHDFRKFVXKNP-UHFFFAOYSA-N icosyl propanoate Chemical compound CCCCCCCCCCCCCCCCCCCCOC(=O)CC OPEHDFRKFVXKNP-UHFFFAOYSA-N 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000002085 irritant Substances 0.000 description 1
- 231100000021 irritant Toxicity 0.000 description 1
- 229940113096 isoceteth 20 Drugs 0.000 description 1
- 229940100554 isononyl isononanoate Drugs 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229940093629 isopropyl isostearate Drugs 0.000 description 1
- XUGNVMKQXJXZCD-UHFFFAOYSA-N isopropyl palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC(C)C XUGNVMKQXJXZCD-UHFFFAOYSA-N 0.000 description 1
- 229940075495 isopropyl palmitate Drugs 0.000 description 1
- 229960002479 isosorbide Drugs 0.000 description 1
- 229960004125 ketoconazole Drugs 0.000 description 1
- 235000019388 lanolin Nutrition 0.000 description 1
- 229940039717 lanolin Drugs 0.000 description 1
- 229940061515 laureth-4 Drugs 0.000 description 1
- 239000001102 lavandula vera Substances 0.000 description 1
- 235000018219 lavender Nutrition 0.000 description 1
- 235000001510 limonene Nutrition 0.000 description 1
- 229940087305 limonene Drugs 0.000 description 1
- 235000020778 linoleic acid Nutrition 0.000 description 1
- OYHQOLUKZRVURQ-IXWMQOLASA-N linoleic acid Natural products CCCCC\C=C/C\C=C\CCCCCCCC(O)=O OYHQOLUKZRVURQ-IXWMQOLASA-N 0.000 description 1
- 229960004488 linolenic acid Drugs 0.000 description 1
- KQQKGWQCNNTQJW-UHFFFAOYSA-N linolenic acid Natural products CC=CCCC=CCC=CCCCCCCCC(O)=O KQQKGWQCNNTQJW-UHFFFAOYSA-N 0.000 description 1
- 239000000944 linseed oil Substances 0.000 description 1
- 235000021388 linseed oil Nutrition 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
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- 229960001929 meloxicam Drugs 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- VAOCPAMSLUNLGC-UHFFFAOYSA-N metronidazole Chemical compound CC1=NC=C([N+]([O-])=O)N1CCO VAOCPAMSLUNLGC-UHFFFAOYSA-N 0.000 description 1
- 229960000282 metronidazole Drugs 0.000 description 1
- 239000004530 micro-emulsion Substances 0.000 description 1
- 230000003020 moisturizing effect Effects 0.000 description 1
- 229940105132 myristate Drugs 0.000 description 1
- 229940043348 myristyl alcohol Drugs 0.000 description 1
- 229940078812 myristyl myristate Drugs 0.000 description 1
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 1
- 231100000344 non-irritating Toxicity 0.000 description 1
- 239000001702 nutmeg Substances 0.000 description 1
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- 229960002446 octanoic acid Drugs 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 235000020660 omega-3 fatty acid Nutrition 0.000 description 1
- 229940012843 omega-3 fatty acid Drugs 0.000 description 1
- 239000006014 omega-3 oil Substances 0.000 description 1
- 235000020665 omega-6 fatty acid Nutrition 0.000 description 1
- 229940033080 omega-6 fatty acid Drugs 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
- 230000036961 partial effect Effects 0.000 description 1
- 238000005192 partition Methods 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 229940086560 pentaerythrityl tetrastearate Drugs 0.000 description 1
- JLFNLZLINWHATN-UHFFFAOYSA-N pentaethylene glycol Chemical compound OCCOCCOCCOCCOCCO JLFNLZLINWHATN-UHFFFAOYSA-N 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 229940057874 phenyl trimethicone Drugs 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 229960000502 poloxamer Drugs 0.000 description 1
- 229920001983 poloxamer Polymers 0.000 description 1
- 229940068918 polyethylene glycol 400 Drugs 0.000 description 1
- 229940100518 polyglyceryl-4 isostearate Drugs 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229940068965 polysorbates Drugs 0.000 description 1
- 235000020777 polyunsaturated fatty acids Nutrition 0.000 description 1
- 229920002689 polyvinyl acetate Polymers 0.000 description 1
- 239000011118 polyvinyl acetate Substances 0.000 description 1
- 229920000915 polyvinyl chloride Polymers 0.000 description 1
- 239000004800 polyvinyl chloride Substances 0.000 description 1
- 239000005033 polyvinylidene chloride Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 229960003387 progesterone Drugs 0.000 description 1
- 239000000186 progesterone Substances 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- NEOZOXKVMDBOSG-UHFFFAOYSA-N propan-2-yl 16-methylheptadecanoate Chemical compound CC(C)CCCCCCCCCCCCCCC(=O)OC(C)C NEOZOXKVMDBOSG-UHFFFAOYSA-N 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 239000001651 pyrus cydonia seed extract Substances 0.000 description 1
- 229920005604 random copolymer Polymers 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 239000010667 rosehip oil Substances 0.000 description 1
- 235000002020 sage Nutrition 0.000 description 1
- 229940119224 salmon oil Drugs 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 229920005573 silicon-containing polymer Polymers 0.000 description 1
- 230000037384 skin absorption Effects 0.000 description 1
- 231100000274 skin absorption Toxicity 0.000 description 1
- FOSNFLMXYRQNAF-UHFFFAOYSA-M sodium;2-[2-(16-methylheptadecanoyloxy)propanoyloxy]propanoate Chemical compound [Na+].CC(C)CCCCCCCCCCCCCCC(=O)OC(C)C(=O)OC(C)C([O-])=O FOSNFLMXYRQNAF-UHFFFAOYSA-M 0.000 description 1
- IZWPGJFSBABFGL-GMFCBQQYSA-M sodium;2-[methyl-[(z)-octadec-9-enoyl]amino]ethanesulfonate Chemical compound [Na+].CCCCCCCC\C=C/CCCCCCCC(=O)N(C)CCS([O-])(=O)=O IZWPGJFSBABFGL-GMFCBQQYSA-M 0.000 description 1
- HSFQBFMEWSTNOW-UHFFFAOYSA-N sodium;carbanide Chemical group [CH3-].[Na+] HSFQBFMEWSTNOW-UHFFFAOYSA-N 0.000 description 1
- 230000003381 solubilizing effect Effects 0.000 description 1
- 229950006451 sorbitan laurate Drugs 0.000 description 1
- 235000011067 sorbitan monolaureate Nutrition 0.000 description 1
- 229950003429 sorbitan palmitate Drugs 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 229940100459 steareth-20 Drugs 0.000 description 1
- 229940073743 steareth-20 methacrylate Drugs 0.000 description 1
- 235000010965 sucrose esters of fatty acids Nutrition 0.000 description 1
- 239000001959 sucrose esters of fatty acids Substances 0.000 description 1
- 150000003445 sucroses Chemical class 0.000 description 1
- 239000002600 sunflower oil Substances 0.000 description 1
- 229940104261 taurate Drugs 0.000 description 1
- XOAAWQZATWQOTB-UHFFFAOYSA-N taurine Chemical compound NCCS(O)(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-N 0.000 description 1
- 239000010677 tea tree oil Substances 0.000 description 1
- 229940111630 tea tree oil Drugs 0.000 description 1
- 150000003505 terpenes Chemical class 0.000 description 1
- 235000007586 terpenes Nutrition 0.000 description 1
- TUNFSRHWOTWDNC-UHFFFAOYSA-N tetradecanoic acid Chemical compound CCCCCCCCCCCCCC(O)=O TUNFSRHWOTWDNC-UHFFFAOYSA-N 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
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- OGIDPMRJRNCKJF-UHFFFAOYSA-N titanium oxide Inorganic materials [Ti]=O OGIDPMRJRNCKJF-UHFFFAOYSA-N 0.000 description 1
- LINXHFKHZLOLEI-UHFFFAOYSA-N trimethyl-[phenyl-bis(trimethylsilyloxy)silyl]oxysilane Chemical compound C[Si](C)(C)O[Si](O[Si](C)(C)C)(O[Si](C)(C)C)C1=CC=CC=C1 LINXHFKHZLOLEI-UHFFFAOYSA-N 0.000 description 1
- PHYFQTYBJUILEZ-IUPFWZBJSA-N triolein Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC(OC(=O)CCCCCCC\C=C/CCCCCCCC)COC(=O)CCCCCCC\C=C/CCCCCCCC PHYFQTYBJUILEZ-IUPFWZBJSA-N 0.000 description 1
- 229940117972 triolein Drugs 0.000 description 1
- COXJMKGEQAWXNP-UHFFFAOYSA-N tris(14-methylpentadecyl) 2-hydroxypropane-1,2,3-tricarboxylate Chemical compound CC(C)CCCCCCCCCCCCCOC(=O)CC(O)(C(=O)OCCCCCCCCCCCCCC(C)C)CC(=O)OCCCCCCCCCCCCCC(C)C COXJMKGEQAWXNP-UHFFFAOYSA-N 0.000 description 1
- 150000003648 triterpenes Chemical class 0.000 description 1
- 238000009827 uniform distribution Methods 0.000 description 1
- 229940099259 vaseline Drugs 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 239000010497 wheat germ oil Substances 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
Description
OLEAGINOUS PHARMACEUTICAL AND COSMETIC FOAM
{0001} The invention relates to oleaginous foam compositions including cosmetic or therapeutic active agents, and methods of topical treatment using the compositions.
[0002] Certain foam products for topical application of therapeutical agents and cosmetics have been prepared as oil-in-water emulsions. Foams and, in particular, foam compositions having a high oll content are complicated systems that do not form under all circumstances. Slight shifts in foam composition, such as the addition of an active ingredient, may destabilize the foam. It is known in the art that hydrophobic solvents are difficult to formulate into a foam-producing product. Addition of conventional hydrophobic solvents interferes with the foam forming abllity of the surface active agent, and thus, in the few foam products containing high-oil concentrations that have been reported, high surface active agent concentrations are used, which may cause undesirable irritation on one hand, and costly raw material usage on the other hand are used. :
[0003] Oleaginous formulations for the preparation of cosmetic and therapeutic compositions are known in the art.
[0004] US Pat. No. 6,620,773 relates to a foaming oil composition, including a surface active agent mixture and an oil component, the surface active agent mixture containing an anionic or zwitterionic surface active agent, a nonionic surface active agent and at least one ethoxylated alkyl phosphate ester component. The surface active agent mixture ranges from about 15% to about 50% of the total composition, and that of the oil component ranges from about 50% to about 85%.
[0005] US Pat. Nos. 5,700,396 and 5,589,515 disclose a cosmetic emulsion . ~~ composition containing 0.1 to 99 wt% oily component (balance aqueous component).
The oily component includes at least 85% weight % of cis A9-octadecanoic acid or derivatives thereof, which cis A9-octadecanoic acid or derivatives thereof serve as a surface active agent in the formulation.
[0006] US Pat. No. 6,524,594 describes a gelled oil composition containing an emulsifier, a gelling agent, an oil, and a surface active agent for producing a significant amount of foam when applied to the skin in the presence of water. The surface active agent is used in an amount from about 10% to about 20%, and more preferably, from about 15% to about 20%.
[0007] US Pat. No. 6,121,210 discloses foamable, silicone oil compositions and methods of lubricating surfaces with such compositions. The compositions are oil-in- water emulsions comprising silicone oil-in-water emulsion, a liquid propellant and a foam builder comprising a solid, non-ionic lipophilic surface active agent having an HLB value of about 3 to about 8. Foam stabiliziers including long claim fatty alcohols are included.
A propellant is included to create a foamable composition.
[0008] WO91/11991 teaches an essentially non-aqueous and non-olly foamable composition, that can be used for rectal administration of pharmaceuticals, comprising a liquid polar polyol or polyol mixture, a pharmaceutically active ingredient and at least one foam stabilizing and emulsifying surfactant. However, this foam composition is associated with disadvantages and the purposes of the present invention are not attained (see comparative example below).
[0009] In general, the foamable compositions of the art are based on oil-in-water emulsions. Furthermore, they often include a high content level of surface active agents and foaming agents required to form acceptable stable and posses low specific gravity foams. Such surface active agents, and particularly ionic surface active agents, such as anionic surface active agents (e.g. sodium lauryl sulfate (SDS)), may have adverse affects on certain patients, including concentration-dependent skin irritation.
[0010] There remains an unmet need for improved, stable and non-irritating oleaginous foam formulations, intended for dermal and mucosal delivery of pharmaceutical and cosmetic, with unique therapeutic and cosmetic properties.
[0011] The present invention provides stable, oleaginous foam-forming compositions including at least one active agent for dermal and mucosal delivery. The composition is dispensed as a foam providing a stable product that Is pleasant and easy to spread, resulting in high patient compliance. The “oleaginous” composition has the organoleptic character of an oily substance, i.e., an oily feeling, when topically administered to the : skin or mucosal tissue.
[0012] According to one aspect of the present invention, the composition includes:
a. a solvent selected from the group consisting of a hydrophobic solvent, a co- solvent, and mixtures thereof, wherein the solvent is present at a concentration of about 70% to about 96.5% by weight of the total composition; b. a surface-active agent at a concentration of about 0.1% to about 10% by weight of the total composition; c. optionally, a gelling agent at a concentration of about 0.1% to about 5% by weight of the total composition; d. an active agent in a therapeutically effective concentration; and e. a propellant at a concentration of about 3% to about 25% by weight of the total composition.
[0013] Water and optional ingredients are added to complete the total weight to 100%, although the composition may be essentially free of lower alkyl alcohols. In one or more embodiments, the oleaginous composition of the present invention contains less than about 5% of a short chain alcohol having up to 5 carbon atoms in its carbon chain skeleton.
[0014] In one or more embodiments, the oleaginous composition includes water at a concentration less than about 30%, preferably less than about 20%, more preferably less than about 10% by weight.
[0015] In one or more embodiments, the oleaginous composition of the present invention further includes a foam adjuvant.
[0016] In yet other embodiments, the oleaginous composition of the present invention forms a water in ofl emulsion.
[0017] In one or more embodiments, the oleaginous composition of the present invention Includes a hydrophabic solvent having solubility in distilled water at ambient temperature of less than about one gram per 100 ml. The hydrophobic solvent may be a mineral oil, MCT oil, triglyceride oll, silicone oil, a polyunsaturated oil, an unsaturated oil and an essential oil, and mixtures thereof.
[0018] In one or more embodiments, the oleaginous composition includes a co- solvent. In one or more embodiments, the co-solvent is a polyol. In one or more embodiments, the co-solvent is polyethylene glycol derivative, or glycerin. In one or more embodiments, the oleaginous composition of the present invention includes a mixture of at least one hydrophobic solvent and at least one co-solvent. The mixture of at least one hydrophobic solvent and the at least one co-solvent may have a weight ratio of about 1:8 to about 8:1. In one or more embodiments, a mixture of at least one hydrophobic solvent and glycerin is used; and the mixture may have a weight ratio of about 1:4 to about 4:1, or about 1:2 to about 2:1.
[0019] According to one or more embodiments, the oleaginous composition includes at least one solvent having a high solubilization capacity, termed herein a “potent solvent”. In the context of the present invention, a potent solvent is a solvent other than mineral oil and solubilizes a specific active agent substantially better than a hydrocarbon solvent such as mineral oii or petrolatum, for example, 5-fold better than mineral oil or 10-fold better than mineral oil.
[0020] in one or more embodiments, the oleaginous composition of the present invention contains a potent solvent selected from the group consisting of a polyol, polyethylene glycol, propylene glycol, hexylene glycol, butanediols and isomers thereof, glycerol, benzyl alcohol, dimethyl solfoxide (DMSO), ethyl oleate, ethyl caprylate, diisopropyl adipate, dimethylacetamide, N-methylpyrrolidone, N-hydroxyethylpyrrolidone, polyvinylpyrrolidone, isosorbide derivatives, dimethyl isosorbide, glycofurol and ethoxydiglycol (transcutol) and mixtures thereof in any proportion.
[0021] In one or more embodiments, the oleaginous composition includes at least one gelling agent selected from the group consisting of natural polymeric materials, semi-synthetic polymeric materials, synthetic polymeric materials, inorganic gelling agents and mixtures thereof. Yet, in additional embodiments, a gelling agent is not essential.
[0022] The oleaginous composition of the present invention upon extrusion from a pressured container has a specific gravity of about 0.02 gr/mi to about 0.5 g/mL, and is useful for treating, alleviating or preventing a dermatological or mucosal disorder.
[0023] According to a further aspect of the present invention, an oleaginous water-in- oil emulsion is provided. The emulsion can be essentially free of short chain alcohols.
The emulsion includes: a. at least one solvent selected from the group consisting of a hydrophobic solvent, a co-solvent and an emollient at a concentration of about 30% to about 96.5% by weight; b. water; c. at least one non-ionic lipophilic surface acting agent having an HLB value of about 3 to about 10 at a concentration of about 0.1 % to less than about 10% by weight; d. optionally, at least one gelling agent at a concentration of about 0.1% to about 5% by weight. e. at least one active agent at a therapeutically effective concentration; and f. at least one liquefied or compressed gas propellant at a concentration of about 3% to about 25% by weight of the total composition.
[0024] in one or more embodiments, the oleaginous water-in-oil emulsion contains less than about 5% of a short chain alcohol having up to 5 carbon atoms in its carbon chain skeleton. In another embodiment the oleaginous composition further includes a foam adjuvant.
[0025] In one or more embodiments, the oleaginous water-in-oil emulsion contains a hydrophobic solvent and water at a weight ratio of about 1:3 to about 6:1.
[0026] in one or more embodiments, the oleaginous water-in-oil emulsion contains a hydrophobic solvent having solubility in distilled water at ambient temperature of less than about one gram per 100 ml. The hydrophobic solvent may be selected from mineral oil, MCT oil, triglyceride oil, silicone oil, a polyunsaturated oil, an unsaturated oil and an essential oll.
[0027] The oleaginous water-in-oil emulsion may include a potent solvent selected from the group consisting of a hydrophobic solvent other than mineral oil, a co-solvent and an emollient, wherein the potent solvent solubilizes the active agent substantially better than mineral oll solubilizes the active agent, e.g at least 5-fold better or at least 10- fold better than mineral oil solubilizes the active agent.
[0028] In one or more embodiments, the oleaginous water-in-oil emulsion contains a surface-active agent having an HLB value in the range of about 3 to about 10, for promoting the formation of a water-in-oil emulsion.
[0029] In one or more embodiments, the oleaginous water-in-oil emulsions contains at least one gelling agent selected from the group consisting of natural polymeric materials, semi-synthetic polymeric materials, synthetic polymeric materials, inorganic gelling agents and mixtures thereof. Yet, in additional embodiments, a gelling agent is not essential.
[0030] The active agent can be a therapeutic agent or a cosmetic agent. The therapeutic agent is selected for the treatment or prophylaxis of a disorder of the skin, mucosal membrane, ear channel, vagina, penile urethra and rectum. In one embodiment therapeutic agent is selected from the group consisting of an anti-infective,
an antibiotic, an antibacterial agent, an antifungal agent, an antiviral agent, an antiparasitic agent, an antiinflammatory agent, an anesthetic, an analgesic, an antiallergic agent, a corticosteroid, a retinoid, an antiproliferative agent, an anticancer agent, a photodynamic therapy agent, a lubricating agent and mixtures thereof.
[0031] Alternatively, the active agent is an inorganic solid matter, preferably a metal oxide, more preferably titanium oxide and zinc oxide.
[0032] The active agent can also be a cosmetic agent such as a retinoid, an anti- wrinkle agent, a radical scavenger, a self-tanning agent, a skin whitening agent a skin protective agent, an anti-cellulite agent, a massaging oil and an anti-wart agent.
[0033] In another aspect, the present invention provides a method of treating, alleviating or preventing a dermatological or mucosal disease or disorder by administering topically to a subject having the disease or disorder a therapeutically effective amount of the oleaginous compositions or the oleaginous water-in-oil emulsions of the present invention.
[0034] In yet another aspect, the present invention also provides a method of designing a foamable composition, containing at least one active agent that is substantially insoluble in a hydrocarbon solvent including mineral oil. The method includes selecting at least one active agent, and identifying a solvent that solubilizes the active agent substantially better than mineral oil solubilizes the active agent. The method may further include the step of adjusting the type and concentration of surface active agent and gelling agent to provide a foamable composition.
[0035] In one or more embodiments, the potent solvent solubilizes the active agent 5-fold better or even 10-fold better than mineral oil solubilizes the active agent.
[0036] Despite the commonly known fact that hydrophobic solvents, and oils in particular, are difficult to formulate into foam-producing products and that addition of conventional hydrophobic solvents interferes with the foam forming ability of the surface active agent, the present invention has surprisingly discovered stable oleaginous foam compositions. The oleaginous compositions may include at least one active agent for dermal, transdermal and mucosal delivery. The oleaginous compositions are dispensed as a foam providing a stable product that is pleasant and easy to use for high patient and consumer compliance. The at least one active agent may be a therapeutically active agent or a cosmetic agent.
[0037] The term “oleaginous” is defined as “having the nature or qualities of oil”. The terms “oleaginous composition”, “oleaginous foam", “oleaginous emulsion” and "oleaginous foamable composition,” etc. as used herein interchangeably refer to a composition that has the organoleptic character of an oily substance, i.e., oily feeling, when topically administered to a body area, such as the skin or mucosal tissue.
Materials and properties for the oleaginous compositions and emulsions are described.
Although the description that follows may refer to an oleaginous composition, it is understood that the materials are also suitable for use in an oleaginous emulsion, unless otherwise stated.
[0038] Surprisingly, the oleaginous compositions of the present invention require low surface active agent concentrations, e.g., less than 10% by weight and often much less, thus minimizing both undesirable irritation and costly raw material usage. The foamable compositions are light weight, have low density, spread easily and comfortably over large body area, and are thus, very convenient to use and economical.
[0039] The oleaginous compositions of the present invention include at least one solvent selected from the group consisting of a hydrophobic solvent, a co-solvent, an emollient and mixtures thereof, which provides a refatting and skin soothing effect. In one or more embodiments, the composition comprises at least 30% of said at least one solvent. In one or more embodiments, the composition comprises at least 50% of said at least one solvent. In one or more embodiments, the composition comprises at least 65% of said at least one solvent. The selected solvents allow the inclusion of oil-soluble active agents in the formulation. In one or more embodiments, the solvents provide synergistic benefits in combination with the active agent. The compositions may comprise at least one oil soluble active agent.
[0040] In one or more embodiments, the compositions require only low concentrations of a foaming agent in order to generate a stable foam. The reduced surface active agent requirement is advantageous since surface active agents are known to be irritating when in contact with the skin at elevated concentrations. :
[0041] The foamable compositions are easily spreadable, allowing treatment of large areas such as the ams, back, trunk, legs and the breast. Furthermore, due to enhanced flow properties, they spread effectively into folds and wrinkles and absorb into the skin, providing uniform distribution of the active agent without the need of extensive rubbing thus providing an attractive means for the treatment of large body areas. The foamable compositions may be further used for the treatment of body cavities, such as the vagina,
penile urethra, rectum and the ear channel due to their expansion properties. In one of more embodiments the foamable compositions may be further used for transdermal delivery of drugs.
Class A foam composition
[0042] According to one aspect the present invention provides an oleaginous foam composition for topical application including: at least one solvent selected from the group consisting of a hydrophobic solvent, a co-solvent, an emollient and mixtures thereof, at a concentration of about 70% to about 96.5% by weight, at least a non-ionic surface active agent at a concentration of about 0.1% to about 10% by weight and, optionally, having an HLB value of about 9 or less; optionally, at least one gelling agent at a concentration of about 0.1% to about 5% by weight; at least one active agent at a therapeutically effective concentration; and a propellant at a concentration of about 3% to about 25% by weight of the total composition.
[0043] The balance of the composition contains water and additional optional components. The content of the foam composition is presented herein as concentration (percent by weight, % w/w). The foam composition can be a homogeneous mixture or an emulsion.
[0044] Such a composition is placed in a pressurized aerosol container and, upon release from the container, creates a novel therapeutically-beneficial foam product.
[0045] Low water content provides high skin and body tissue lubrication, refatting, regulating residence of an active ingredient in the skin effects and effective skin absorption of a active agents. It is also helps to avoid degradation of water sensitive active agents.
[0046] Thus, In one or more embodiments, the oleaginous composition includes water at a concentration of about 30% or less, or at a concentration less than about 20%, or at a concentration less than about 10% by weight.
[0047] The oleaginous composition is optionally substantially free of short chain alcohols, i.e. comprises less than about 5% by weight of a short chain alcohol having 5 or less carbon atom In Its skeleton, and may further comprise a foam adjuvant.
[0048] According to one embodiment, the oleaginous composition contains a solvent selected from the group consisting of a hydrophobic soivent and an emollient and at least one co-solvent. According to one embodiment, the co-solvent is an organic solvent other than a short chain alcohol, that dissolves in water. Non-limiting examples of such co-solvents include polyols, propylene glycol, glycerol, and other polyhydroxy solvents (polyols). Preferably, the composition includes glycerol as co-solvent. In one embodiment, the composition includes a hydrophobic solvent component and a co- solvent at a weight ratio in the range of about 4:1 and about 1:4, or about 2:1 to 1:2. Ina further embodiment of the present invention, the co-solvent constitutes a continuous phase of the emulsion and a minor portion of water is included in the co-solvent phase.
[0049] Such a composition is placed in an aerosol container and, upon release from the aerosol container, creates a therapeutically-beneficial foam product.
Class B foam composition:
[0050] According to another aspect the present invention provides an oleaginous foam composition may be a water-in-oil emulsion, i.e., an emulsion having one phase including at least one hydrophobic component (oil phase) and one phase which includes water. Due to the fact that the continuous phase of the emulsion is the oil phase, the composition provides an oily feeling, regulating residence of an active ingredient in the skin properties and protective effects. Notably, while it is known that a composition with a continuous oil phase is unlikely to form foam without high amounts of surface active agents, the oleaginous water-in-oil emulsion surprisingly forms a stable foam with low density. In one or more embodiments, there is an overlap between the compositions of
Class A and Class B, the distinction being that Class B compositions are formed as water-in-oil emulsions.
[0051] According to one embodiment, the water-in-oil emulsion composition contains: at least one solvent selected from the group consisting of a hydrophobic solvent, a co-solvent, an emollient and mixtures thereof, at a concentration of about 30% to about 96% by weight, water at a concentration of 1% to about 70% by weight; at least one non-ionic lipophilic surface active agent,for example, having an HLB value of about 3 to about 10, more preferably about 3.5 to about 9 at a concentration of about 0.1% to about 10% by weight, or between about 0.1% and about 5% by weight, or even between about 0.1% and about 2% by weight;
optionally, at least one gelling agent at a concentration of about 0.1% to about 5% by weight; at least one active agent at a therapeutically effective concentration; and a propellant at a concentration of about 3% to about 25% by weight of the total composition, in an aerosol container.
[0052] According to a further embodiment, the ratio between the oil phase and water is between about 1:3 and about 6:1.
[0053] An oleaginous foam emulsion is a composition having at least one solvent selected from the group consisting of a hydrophobic solvent, a co-solvent, an emollient and mixtures thereof in the continuous phase of the composition and is characterized by an oily feeling upon application to a body surface.
[0054] An oleaginous composition or emulsion may provide an enhanced regulating residence of an active ingredient in the skin effect, which may in tum control the drug residence time and skin penetration of an active agent. Furthermore, oleaginous compositions and emulsions provide moisturizing effects, refatting effects, protective effects and lubrication, all of which contribute to the treatment of dermatological disorders. Thus, a composition of this nature, comprising an oleaginous vehicle and an active agent is expected to provide a synergistic therapeutic effect.
Solvents
[0055] The solvent of the composition of the present invention is selected from the group consisting of a hydrophobic solvent, an emollient, a silicone oil, a co-solvent, and a mixture thereof. The solvent occupies at least the continuous phase; however, it may also partition into the discontinuous phase in those instances when the composition is an emulsion.
Hydrophobic solvent
[0056] A “hydrophobic solvent” as used herein includes but is not limited to a material having solubility in distilled water at ambient temperature of less than about 1 gm per 100 mL, or less than about 0.5 gm per 100 mL, or even less than about 0.1 gm per 100 mL. Its liquid at ambient temperature. The identification of a hydrophobic : solvent by its solubility in water is not intended to characterize the solubilization capabilities of the solvent for any specific active agent or any other component of the foamable composition. Rather, such information is provided to aid in the identification of
: materials suitable for use as a hydrophobic solvent in the foamable compositions described herein.
[0057] In one embodiment, the solvent is a hydrophobic solvent such as mineral oil.
Mineral oil (Chemical Abstracts Service Registry number 8012-95-1) is a mixture of aliphatic, naphthalenic, and aromatic liquid hydrocarbons that derive from petroleum.
They are typically liquid; their viscosity is in the range of between about 35 CST and about 100 CST (at 40°C); and their pour point (the lowest temperature at which an oil can be handled without excessive amounts of wax crystals forming so preventing flow) is below 0°C. By contrast, white petrolatum, also termed “Vaseline”, is disadvantageous, due to the waxy nature and semi-solid texture of petrolatum. it is known to leave a waxy and sticky feeling after application and occasionally stain cloths. Thus, white petrolatum as well as other wax-like, semi-solid compounds are undesirable as a hydrophobic solvent according to the present invention.
[0058] According to one embodiment, the oleaginous foam composition of the present invention includes a hydrophobic solvent selected from mineral oil, a triglyceride oil, an ester of a fatty acid, an ester of a dicarboxylic acid, silicone oil, a polyunsaturated oil, an unsaturated oil and an essential oil.
[0059] According to one embodiment, hydrophobic solvents are liquid oils originating from vegetable, marine or animal sources. The hydrophobic solvent may be selected from the group consisting of a saturated or an unsaturated oil. Preferably, the unsaturated oil is selected from the group consisting of an olive oil, a com oil, a soybean oil, a canola ail, a cottonseed oil, a coconut oil, a sesame oil, a sunflower oil, a borage seed oil, an syzigium aromaticum oil, a hempseed oil, a herring oil, a cod-liver oil, a salmon oil, a flaxseed oil, a wheat germ oil, an evening primrose oil and any mixtures thereof, at any proportion.
[0060] One class of hydrophobic solvents includes, but is not limited to, polyunsaturated oils, containing omega-3 and omega-6 fatty acids, which are know to possess therapeutic properties through different modes of action. Examples of such polyunsaturated fatty acids are linoleic and linolenic acid, gamma-linoleic acid (GLA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Thus, in one embodiment of the present invention the hydrophobic solvent includes at least 6% of an oil selected from omega-3 oil, omega-6 oil, and mixtures thereof.
[0061] Another class of hydrophobic solvents is the essential oils, which are considered “therapeutic oils.” Therapeutic oils contain active biologically occurring molecules and, upon topical application, exert & therapeutic effect. Examples of such oils are rosehip oil, which contain retinoids and is known to reduce acne and post-acne scars, and tea tree oil, which possesses anti-microbial activity including antibacterial, antifungal and antiviral properties. Other examples of essential oils are basil, camphor, cardamom, carrot, citronella, clary sage, clove, cypress, frankincense, ginger, grapefruit, hyssop, jasmine, lavender, lemon, mandarin, marjoram, myrrh, neroli, nutmeg, petitgrain, sage, tangerine, vanilla, verbena, as well as any other therapeutically beneficial oil known in the art of herbal medication.
Emollient
[0062] A further class of solvents is “emollients” that have a softening, refatting, or soothing effect, especially when applied to body areas, such as the skin and mucosal surfaces. Emollients are not necessarily hydrophobic, nor are they necessarily solubilizing of the active agent or other components of the foamable compositions described herein. Without derogating the generality of this definition, examples of suitable emollients for use include hexylenegtycol, propylene glycol, isostearic acid derivatives, isopropyl palmitate, isopropyl isostearate, diisopropyl adipate, diisopropyl! dimerate, maleated soybean oil, octyl palmitate, cetyl lactate, cetyl ricinoleate, tocopheryl acetate, acetylated lanolin alcohol, cetyl acetate, phenyl trimethicone, glyceryl oleate, tocopheryl linoleate, wheat germ glycerides, arachidyl propionate, myristyl lactate, decyl oleate, propylene glycol ricinoleate, isopropyl l1anolate, pentaerythrityl tetrastearate, neopentylglycol dicaprylate/dicaprate, isononyl isononanoate, isotridecy isononanoate, myristyl myristate, triisocetyl citrate, octyl dodecanol, sucrose esters of fatty acids, octyl hydroxystearate and mixtures thereof. Examples of other suitable emollients may be found in the Cosmetic Bench Reference, pp. 1.19-1.22 (1996).
Silicone oil
[0063] Silicone oils possess skin protective properties and readily facilitate regulating residence of an active ingredient in the skin regulating residence of an active ingredient in the skin regulating residence of an active ingredient in the skin. Silicone oil may be either a volatile silicon oil or a non-volatile silicone oil. Water-soluble silicones, such as dimethicone copolyol are not included in the definition of silicone olls (as hydrophobic solvents) according to the present invention. In one embodiment, the hydrophobic solvent includes at least 2% (w/w) silicone oll, or at least 5% (w/w) silicone oll.
[0064] Any mixture, in any proportion of hydrophobic solvents as listed herein can be used.
Co-solvent
[0065] A “co-solvent’, in the context of the present invention is an organic solvent, other than a short chain alcohols, typically soluble in both water and oil. Examples of co- solvents, according to the present invention include polyols, sulfoxides, oleates, lactam compounds, esters, amides, alkanoic acids, and alkanols and admixtures thereof.
Exemplary polyols include glycerol (glycerin), propylene glycol, hexylene glycol, diethylene glycol, propylene glycol n-alkanols, terpenes, diterpenes, tri-terpenes, terpen- ols, limonene, terpene-ol, 1-menthol, dioxolane, ethylene glycol, and other glycols.
Exemplary sulfoxides include dimethylsulfoxide (DMSO), dimethylformanide, methyl dodecyl sulfoxide, and dimethylacetamide. Exemplary oleates include monooleates of ethoxylated glycerides (with 8 to 10 ethylene oxide units) and triolein. Exemplary lactam compounds include azone (1 -dodecylazacycloheptan-2-one) and2-(n-nonyl)-1,3- dioxolane. Exemplary esters includeisopropyl myristate/paimitate, ethyl acetate, butyl ~~. acetate, methyl proprionate, capric/caprylic triglycerides, octyimyristate, and dodecyl- myristate. Exemplary amides include acetamide. Other suitable co-solvents include myristyl alcohol, lauryl alcohol, lauric acid, lauryt lactate ketones; various alkanoic acids such as caprylic acid and alkanols, such as dialkylamino acetates.
[0066] According to one embodiment, the co-solvent is a polyethylene glycol (PEG) or a PEG derivative, and mixtures thereof, that are flowable at ambient temperature, including PEG200 (MW about 190-210 kD), PEG300 (MW about 285-315 kD), PEG400 (MW about 380-420 kD), PEG600 (MW about 570-630 kD) and higher MW PEGs such as PEG 4000, PEG 6000 and PEG 10000 and mixtures thereof, provided, however, that sald PEG or mixture of PEGs is flowable at ambient temperature. By “flowable”, as that term implies, the polyethylene glycol may be viscous at ambient temperature. The PEG or PEG mixture can have a viscosity of about 20,000cps at ambient, or less than about 10,000 cps at ambient.
[0067] In one or more embodiments, the solvent is a mixture (e.g., an emulsion) of a hydrophobic solvent and glycerin, as described, for example, in US Pat. No.6,544,530 to
Friedman. The ratio of hydrophobic solvent to glycerin can range from about 1:4 to about 4:1, and more preferably from about 1:2 to about 2:1.
[0068] In several cases, a given solvent can be defined as both emollient and co- solvent. A co-solvent may also be a potent solvent for selected active agents.
Potent solvent
[0069] In one or more embodiments of the present invention, the foamable composition includes a potent solvent, in addition to or in place of one of the hydrophobic solvents, co-solvents and emollients of the composition. A potent solvent is a solvent other than mineral oil that solubilizes a specific active agent substantially better than a hydrocarbon solvent such as mineral oil or petrolatum. For example, a potent solvent solubilizes the active agent 5 fold better than a hydrocarbon solvent; or even solubilizes the active agent 10-fold better than a hydrocarbon solvent. The solubility of a given active agent in the potent solvent relative to its respective solubility in mineral oil is determined in the absence of the composition. That is, the potent solvent alone solubilizes the active agent better than the the mineral oil alone. This is an independent test, irrespective of the composition in which the potent solvent is incorporated.
[0070] In one or more embodiments of the present invention, the composition includes at least one active agent in a therapeutically effective concentration and at least one potent solvent in a sufficient amount to substantially solubilize the at least one active agent in the composition. The term "substantially soluble" means that at least 95% of the active agent has been solubilized, i.e., 5% or less of the active agent is present in a solid state. In one or more embodiments, the concentration of the at ieast one potent solvent is more than about 40% of the at least one solvent of the composition of the present invention; or even more than about 60%.
[0071] Non-limiting examples of pairs of active agent and potent solvent include:
Betamethasone valerate/ glycofurol: Practically insoluble in mineral oil (<0.01%); soluble more than 1% in glycofurol.
Hydrocortisone butyrate/ glycofurol: Practically insoluble in mineral oil (<0.01%); soluble more than 1% in glycofurol.
Metronidazole/dimethyl isosorbide: Practically insoluble in mineral oil (<0.01 %); soluble more than 1% in dimethyl isosorbide.
Ketoconazole/dimethyi isosorbide: Practically insoluble in mineral oil (<0.01%); soluble more than 1% in glycofurol, propylene glycol and dimethyl isosorbide.
Mupirocin/various solvents: Practically insoluble in mineral oil (<0.01 %); soluble more than 1% in glycofurol, hexylene glycol, dimethyl isosorbide, propylene glycol and polyethylene glycol 400 (PEG 400).
Meloxicam, a nonsteroidal anti-inflammatory agent/propylene glycol: Practically insoluble in mineral oil (<0.001%); soluble in propylene glycol: 0.3 mg/mL; and in PEG
400: 3.7 mg/mL.
Progesterone/PEG 400: Practically insoluble in mineral oil (<0.001%}; soluble in
PEG 400: 15.3 mg/mL.
[0072] A non-limiting exemplary list of solvents that can be considered as potent solvents includes polyols, polyethylene glycol (PEG), propylene glycol, hexylene glycol, butanediols and isomers thereof, glycerol, benzyl alcohol, DMSO, ethyl oleate, ethyl caprylate, diisopropyl adipate, dimethylacetamide, N-methylpyrrolidone, N- hydroxyethylpyrrolidone, polyvinyipyrrolidone, isosorbide derivatives, such as dimethyl isosorbide, glycofurol and ethoxydiglycol (transcutol) and mixtures thereof in any proportion.
[0073] In another aspect, the present invention provides a method of designing a stable oleaginous foamable composition by selecting at least one active agent and identifying a solvent that solubilizes the active agent substantially better than mineral oil or petrolatum, for example, solubilizes the active agent 5-fold better or even 10-fold better than a hydrocarbon solvent such as mineral oil or petrolatum. The method may further include adjusting the type and concentration of surface active agent and gelling agent to provide a foamable composition.
[0074] The use of a potent solvent in a foam composition provides an improved method of delivering poorly soluble therapeutic agents to a target area. itis known that low drug solubility resuits in poor bioavailability, leading to decreased effectiveness of treatment. Foam compositions of the present invention, for which the solvent includes a potent solvent, increase the levels of the active agent in solution and thus, provide high delivery and improved therapy.
[0075] Potent solvents, as defined herein, are usually liquid. Formulations comprising potent solvents and active agents are generally disadvantageous as therapeutics, since their usage involves unwanted dripping and inconvenient method of application, resulting in inadequate dosing. The foams described herein are drip-free, provide a superior vehicle for such active agents, and enable convenient usage and accurate effective dosing.
[0076] The solvent of the present invention may include a mixture of the above solvents selected from the group of hydrophobic solvents, silicone oils, emollients co- solvents and potent solvents in any proportion.
Surface-active agents
[0077] Surface-active agents may include an agent useful in forming an emulsion and/or evolving a foam. A surface active agent's hydrophilic/lipophilic balance (HLB) describes the surface active agent's affinity towards water or oil. The HLB scale ranges from about 1 (totally lipophilic) to 45 (totally hydrophlic) and in the case of non-ionic surface active agents from 1 to 20 (totally hydrophlic), with 10 representing an equal balance of of both hydrophilic and lipophilic characteristics. Lipophilic emulsifiers from water-in-oil (W/o) emulsions, hydrophilic surface active agents form oil-in-water (o/w) emulsions. The HLB of a blend of two emulsifiers equals the weight fraction of emulsifier
A times its HLB value, plus the weight fraction of emulsifier B times its HLB value (e.g., a weighted average).
[0078] Without wishing to be bound by any particular theory or mode of operation, hydrophilic surface active agents produce oil-in-water (o/w) microemulsions, whereas lipophilic surface active agents are used to promote emulsification of the aqueous phase into the oil phase. :
[0079] The oleaginous composition of the present invention according to one or more embodiments includes at least one surface active agent or surface active agent, which is intended to both stabilize the formulation and to evolve an acceptable foam.
[0080] A composition having a low concentration of an ionic surface active agent is desirable In terms of safety, since high concentrations of surface active agents are known to evolve skin and mucosal membrane irritation. Unlike certain foamable oleaginous compositions of the art, the total surface active agent employed to obtain foam that is stable, of low specific gravity and has a fine bubble structure is relatively low. Low surface active agent levels, particularly of ionic surface active agents, are helpful in minimizing skin initations. Total surface active agent may be in the range of about 0.1% to less than about 10% of the foamable composition, and is typically less than about 5%, or even less than about 2%. Yet, in one or more embodiments, when the composition comprises a liquid polar polyol or polyol mixture, such as polyethylene glycol, a foam can be produced even without a surface active agent.
[0081] According to one or more embodiments, the surface active agent Is selected from hydrophilic, hydrophobic, and a mixture of hydrophilic and hydrophobic surface active agents. As is well known in the art, the terms "hydrophilic" and *hydrophobic" are relative terms. A combination of surface-active agents is possible.
[0082] According to one or more embodiments, suitable surface active agents for formation of a water-in-oil emulsion have an HLB value of no greater than 10, and for example from about 3 to about 9. Thus, the composition may include a single surface- active agent having an HLB value between 3 and 8, or a mixture of surface-active agents having a weighted average of their HLB values between 3 and 9.
[0083] Suitable water-in-oil surface active agents include, but are not limited to, sorbitan derivatives such as sorbitan laurate and sorbitan palmitate; alkoxylated alcohols such as laureth-4; hydroxylated derivatives of polymeric silicones, such as dimethicone copolyol; alkylated derivatives of hydroxylated polymeric silicones, such as cetyl dimethicone copolyol; glyceryl esters such as polyglyceryl-4 isostearate; beeswax derivatives such as sodium isostearoyl-2-lactylate; lecithin; and mixtures thereof. In conjunction with the oll component being a silicone oil, the preferred emulsifiers are hydroxylated derivatives of polymeric silicones and alkylated derivatives thereof.
[0084] According to one or more embodiments the present invention, the composition comprises at least one non-ionic surface active agent. In one or more embodiments, the composition includes at least one non-ionic surface active agentand at least one Ionic surface active agent selected from the group consisting of an anionic surface active agent, a cationic surface active agent and a zwitterionic surface active agent, at a weight ratio of between about 1:1 and about 20:0.1, or preferably at a weight ratio of about 4:0.1 to about 20:0.1.
[0085] The choice of specific surface active agents should be made keeping in mind the particular hydrophobic therapeutic agent to be used in the composition, and the range of polarity appropriate for the chosen therapeutic agent. With these general principles in mind, a very broad range of surface active agents is suitable.
[0086] Additional non-limiting examples of possible surface active agents include polysorbates, such as polyoxyethylene (20) sorbitan monostearate (Tween 60) and polyoxyethylene (20) sorbitan monooleate (Tween 80); Polyoxyethylene (POE) fatty acid esters, such as Myrj 45, Myrj 49 and Myrj 59; poly(oxyethylene) alkylyi ethers, such as poly(oxyethylene) cetyl ether, poly(oxyethylene) palmityl ether, polyethylene oxide hexadecyl ether, polyethylene glycol cetyl ether, brij 38, brij 52, brij 56 and brij W1; sucrose esters, partial esters of sorbitol and sorbitol anhydrides, such as sorbitan monolaurate and sorbitan monolaurate; fatty alcohols or acids, mono or diglycerides, isoceteth-20, sodium methyl cocoyi taurate, sodium methyl oleoyl taurate, sodium lauryl sulfate, triethanolamine lauryl sulfate and betaines, provided that, in the case of a single surface active agent, the HLB value Is between 3 and 9; and in the case of a mixture of surface-active agents, the weighted average of their HLB values is between 3 and 9.
[0087] In one or more embodiments, the at least one surface active agentis a phospholipid. In a one or more embodiments, the phospholipid is phosphatidyicholine or 1,2-diacyl-sn-glycerol-3-phosphoryicholine, also termed "lecithin, which is a naturally occuring phospholipid which possesses surface active agent properties. Lecithin is the most abundant lipid in the membranes of biological tissues and as such, is considered a non-Irritant. Lethicin is a phospholipid composition very similar in composition to that of human skin. For this reason, it is possible to use lethicin as an emulsifier or a surfact- active agent at levels about 10% by weight. In one or more embodiments, the surface- active agent includes lethicin up to about 10% by weight and the total surfact-active agent (when a mixture of agents is used) can be up to 15% by weight. [oo88] A composition having a low concentration of an ionic surface active agent, or even no ionic surface active agent, is desirable in terms of safety, since high concentrations of surface active agents are known to evolve skin irritation.
Gelling agents
[0089] The composition according to one or more embodiments of the present invention include at least one gelling agent at a concentration of about 0.1% to about 5%. The at least one gelling agent is selected from the group consisting of a natural polymeric material, a semi-synthetic polymeric material, a synthetic polymeric material, an inorganic gelling agent and mixtures thereof. Yet, in one or more embodiments, a foam with favorable properties can be produced even without a gelling agent.
[0080] Exemplary gelling agents that can be used in accordance with one or more embodiments of the present invention include for example, but are not limited to, naturally-occurring polymeric materials such as, locust bean gum, sodium alginate, sodium caseinate, egg albumin, gelatin agar, carrageenin gum sodium alginate, xanthan gum, quince seed extract, tragacanth gum, starch, chemically modified starches and the like, semi-synthetic polymeric materials such as cellulose ethers (e.g. hydroxyethyl cellulose, methyl cellulose, carboxymethyl cellulose, hydroxy propylmethyl cellulose), polyvinyipyrrolidone, polyvinylalcohol, guar gum, hydroxypropyl guar gum, soluble starch, cationic celluloses, cationic guars and the like and synthetic polymeric materials such as carboxyvinyl polymers, polyvinyipyrrolidone, polyvinyl alcohol polyacrylic acid polymers, polymethacrylic acid polymers, polyvinyl acetate polymers, polyvinyl chloride polymers, polyvinylidene chloride polymers and the like. Optionally, mixtures of the above compounds are contemplated.
[0091] It has been surprisingly discovered that certain gelling agents provide foam compositions that produce foams with high foam stability and an appealing organoleptic feel, even in the absence of foam stabilizing agents such as fatty acids and fatty alcohols. The gelling agent is selected from the class of amphiphilic copolymers.
Amphiphilic copolymers include polymers having hydrophobic groups and hydrophilic groups or regions. These materials are referred to alternatively as "polymeric surfactants” because the hydrophilic and hydrophobic regions of the polymers serve to interact with and stabilize hydrophilic and lipophilic components, respectively, of a composition. The copolymer may be a random copolymer, a block copolymer of a graft or comb copolymer. Exemplary amphiphilic copolymers include include di-, tri- or muiti- block copolymer or graft copolymer of a biodegradable polymer.
[0092] The polymeric surfactant may be an acrylate copolymer, in which hydrophobic moieties are chemically linked to hydrophilic polymer or hydrophilic moieties are attached to hydrophobic polymers to produce amphiphilic surtace active and surface stabilizing agent. By way of example, suitable polymeric surfactants include cross linked copolymers of acrylic acid and a hydrophobic comonomer, such as Pemulen TR-1 and ‘
Pemulen TR-2, ETD 2020 and Carbopol 1382 (all, Acrylates/C10-30 alkyl acrylate crosspolymer), Natrosol CS Plus 330 and 430 and Polysurf 67 ( all, cetyl hydroxyethyl cellulose), Aculyn 22 (acrylates /steareth-20 methacrylate copolymer), Aculyn 25 (acrylates! laureth-25 methacrylate copolymer), Aculyn 28 (acrylates /beheneth-25 methacrylate copolymer), Aculyn 46 (PEG-150/stearyl alcohol/SMDI copolymer),
Stabylen 30 (acrylates/vinyl isodecanoate), Structure 2001 (acrylates/steareth-20 itaconate copolymer), Structure 3001 (acrylates/ceteth-20 itaconate copolymer) and
Structure Plus (acrylates/aminoacrylates/C10-30 alkyl PEG 20 itaconate copolymer), where PEG is polyethylene glycol, PPG is polypropylene glycol.
[0093] Other exemplary amphiphilic copolymers include silicone polymers such as amphiphilic silicone polyols or copolyol, for example cetyl dimethicon copolyol and dimethicone copolyol PPG-3 oleyl ether, acetylated starch derivatives, amphiphilic modified starches, and amphiphilic block copolymers of ethylene oxide, propylene oxide and/or propylene glycol (also known as “poloxamer”).
[0094] The gelling agent may include other types of gelling agents, in combination with an amphiphilic copolymer. For example, naturally-occurring thickening agents may be included. Exemplary polymeric materials include locust bean gum, sodium alginate, sodium caseinate, egg albumin, gelatin agar, carrageenin gum sodium alginate, xanthan
Claims (98)
1. An oleaginous foamable therapeutic composition, comprising:
a. a solvent selected from the group consisting of a hydrophobic solvent, a silicone oil, an emollient, a co-solvent, and mixtures thereof, wherein said solvent is present at a concentration of about 70% to about 96.5% by weight of the total composition;
b. a surface-active agent at a concentration of about 0.1% to about 10% by weight of the total composition;
c. a therapeutically effective amount of an active agent;
d. a propellant at a concentration of about 3% to about 25% by weight of the total composition.
2. The oleaginous foamable therapeutic composition of claim 1, further comprising a gelling agent at a concentration of about 0.1% to about 5% by weight of the total composition.
3. An oleaginous foamable therapeutic composition, comprising:
a. a solvent selected from the group consisting of a hydrophobic solvent, a silicone oil, an emollient, a co-solvent, and mixtures thereof, wherein said solvent is present at a concentration of about 70% to about 96.5% by weight of the total composition;
b. a surface-active agent at a concentration of about 0.1% to about 10% by weight of the total composition;
c. a therapeutically effective amount of an active agent;
d. a gelling agent at a concentration of about 0.1% to about 5% by weight of the total composition; 61 Amended sheet: 29 November 2006 ta = ’
e. a propellant at a concentration of about 3% to about 25% by weight of the total composition.
4, The oleaginous foamable therapeutic composition of claim 1 or 3, further comprising a foam adjuvant selected from the group consisting of a fatty alcohol having at least 15 carbon atoms and a fatty acid having at least 16 carbon atoms.
5. The oleaginous foamable therapeutic composition of claim 1 or 3, wherein said solvent comprises a hydrophobic solvent having a degree of solubility of less than about one gram of solvent per 100 ml of distilled water at ambient temperature.
6. The oleaginous foamable therapeutic composition of claim 1 or 3, wherein said solvent comprises a hydrophobic solvent selected from the group consisting of a mineral oil, a triglyceride oil, a silicone oil, a polyunsaturated oil, an unsaturated oil and an essential oil.
7. The oleaginous foamable therapeutic composition of claim 1 or 3, wherein said solvent comprises a mixture of at least one hydrophobic solvent and at least one co- solvent.
8. The oleaginous foamable therapeutic composition of claim 1 or 3, wherein said solvent includes a mixture of a hydrophobic solvent and a co-solvent in a weight ratio of about 1:8 to about 8:1 said hydrophobic solvent to said co-solvent.
9. The oleaginous foamable therapeutic composition of claim 1 or 3, wherein said co-solvent is selected from the group consisting of polyols, sulfoxides, oleates, lactam compounds, esters, amides, alkanoic acids, and alkanols and admixtures thereof.
10. The oleaginous foamable therapeutic composition of claim 7, wherein said mixture forms an emulsion. 62 Amended sheet: 29 November 2006 v -
11. The oleaginous foamable therapeutic composition of claim 7, wherein said co- solvent comprises glycerin.
12. The oleaginous foamable therapeutic composition of claim 11, wherein said mixture of at least one hydrophobic solvent and glycerin comprises a weight ratio of about 1:4 to about 4:1.
13. The oleaginous foamable therapeutic composition of claim 11, wherein said mixture of at least one hydrophobic solvent and glycerin comprises a weight ratio of about 1:2 to about 2:1.
14. The oleaginous foamable therapeutic composition of claims 1, 3 or 7, wherein said co-solvent comprises a polyethylene glycol.
15. The oleaginous foamable therapeutic composition of claim 1 or 3, wherein the said solvent comprises a potent solvent.
16. The oleaginous foamable therapeutic composition of claim 15, wherein said potent solvent solubilizes the active agent at a degree at least 5 times greater than the degree that mineral oil solubilizes the active agent.
17. The oleaginous foamable therapeutic composition of claim 15, wherein said potent solvent solubilizes the active agent at a degree at least 10 times greater than the degree that mineral oil solubilizes the active agent.
18. The oleaginous foamable therapeutic composition of claim 15, wherein said potent solvent is selected from the group consisting of a polyol, polyethylene glycol, propylene glycol, hexylene glycol, butanediols and isomers thereof, glycerol, benzyl alcohol, DMSO, ethyl oleate, ethyl caprylate, diisopropyl! adipate, dimethylacetamide, N-methylpyrrolidone, N-hydroxyethylpyrrolidone, polyvinylpyrrolidone, isosorbide derivatives, dimethyl isosorbide, glycofurol and ethoxydiglycol (transcutol) and mixture thereof in any propostion. 63 Amended sheet: 29 November 2006 y »
19. The oleaginous foamable therapeutic composition of claim 16 or 17, wherein said potent solvent is a polyol and said active active agent is mupirocin.
20. The oleaginous foamable therapeutic composition of claim 19, wherein said polyol is a liquid polyethylene glycol.
21. The oleaginous foamable therapeutic composition of claim 1 or 3, wherein, said surface active agent comprises at least one non-ionic surface active agent.
22. The oleaginous foamable therapeutic composition of claim 21, further comprising an ionic surface-active agent.
23. The oleaginous foamable therapeutic composition of claim 22, wherein said non- ionic surface-active agent and said ionic surface-active agent are present at a weight ratio of about 20:1 to about 1:1 non-ionic surface active agent to ionic surface active agent.
24. The oleaginous foamable therapeutic composition of claim 1 or 3, wherein the concentration of said surface-active agent is less than about 2% of the entire composition.
25. The oleaginous foamable therapeutic composition of claim 1 or 3, wherein the surface-active agent comprises a phospholipid.
26. The oleaginous foamable therapeutic composition of claim 25, wherein the phospholipid comprises phosphatidylcholine.
27. The oleaginous foamable therapeutic composition of claim 2 or 3, wherein said gelling agent is selected from the group consisting of a natural polymeric material, a semi-synthetic polymeric material, a synthetic polymeric material, an inorganic gelling agent and any mixture thereof.
28. The oleaginous foamable therapeutic composition of claim 1 or 3, wherein oleaginous foamable therapeutic composition includes less than about 20% by weight of water. 64 Amended sheet: 29 November 2006
" -
29. The oleaginous foamable therapeutic composition of claim 28, having a specific gravity of about 0.01 gr/ml to about 0.4 gr/mL upon release from said pressurized container,
30. The oleaginous foamable therapeutic composition of claim 1 or 3, wherein said active agent is selected to treat a dermatological or mucosal disorder.
31. The oleaginous foamable therapeutic composition of claim 30, wherein said disorder is selected from the group consisting of a bacterial disorder, a fungal disorder, a viral disorder, a parasitic disorder, an inflammatory disorder, an autoimmune disorder, an allergic disorder, a hormonal disorder, a malignant disorder, a cosmetic abnormality and any combination thereof.
32. The oleaginous foamable therapeutic composition of claim 1 or 3, wherein the active agent is a component of the foamable composition selected from the group consisting of a solvent, a surface-active agent, a gelling agent and a foam adjuvant.
33. The oleaginous foamable therapeutic composition of claim 30, wherein said therapeutic agent is selected from the group consisting of an an anti-infective, an antibiotic, an antibacterial agent, an antifungal agent, an antiviral agent, an antiparasitic agent, an antiinflammatory agent, an immunosuppressive agent, an immunomodulator, an immunoregulating agent, a hormonal agent, vitamin A, a vitamin A derivative, vitamin B, a vitamin B derivative, vitamin C, a vitamin C derivative, vitamin D, a vitamin D derivative, vitamin E, a vitamin E derivative, vitamin F, a vitamin F derivative, vitamin K, a vitamin K derivative, a wound healing agent, a disinfectant, an anesthetic, an analgesic, an antiallergic agent, a corticosteroid, a non-steroidal anti-inflammatory drug, an alpha hydroxy! acid, a beta- hydroxy acid, a protein, a peptide, a neuropeptide, a allergen, an immunogenic substance, a haptene, an oxidizing agent, an antioxidant, a retinoid, an antiproliferative agent, an anticancer agent, a photodynamic therapy agent, an anti- 65 Amended sheet: 29 November 2006 wrinkle agent, a radical scavenger, a self-tanning agent, a skin whitening agent, a skin protective agent, an anti-celluiite agent, a massaging oil and an anti-wart agent, a refatting agent, a lubricating agent and mixtures thereof.
34. The oleaginous foamable therapeutic composition of claim 30, wherein the therapeutic agent is selected for the treatment of a disorder of the skin, mucosal membrane, ear channel, vagina, penile urethra, colon and rectum.
35. The oleaginous foamable therapeutic composition of claim 30, wherein the cosmetic agent is selected from the group consisting of a retinoid, an anti-wrinkle agent, a radical scavenger, a self-tanning agent, a skin whitening agent, a skin protective agent, an anti-cellulite agent, a massaging oil and an anti-wart agent.
36. The oleaginous composition of claim 1 or 3, wherein the therapeutic agent is intended for transdermal delivery.
37. The oleaginous foamable therapeutic composition of claim 1 or 3, wherein the active agent comprises an inorganic solid matter.
38. The oleaginous foamable therapeutic composition of claim 37, wherein the inorganic solid matter comprises a metal oxide selected to form a protective layer on a body surface or a mucosal membrane.
39. A stable oleaginous foamable water-in-oil emulsion, comprising a. a solvent selected from the group consisting of a hydrophobic solvent, a co- solvent and an emollient at a concentration of about 30% to about 96.5% by weight;
b. water;
C. a lipophilic surface-active agent having an HLB value of about 3 to about 10 at a concentration of about 0.1 % to less than about 10% by weight,
d. a therapeutically effective amount of an active agent; and e. a propeliant at a concentration of about 3% to about 25% by weight of the total composition. 66 Amended sheet: 29 November 2006
. 0m
40. The oleaginous foamable water-in-oil emulsion of claim 39, further comprising a gelling agent at a concentration of about 0.1% to about 5% by weight of the total composition.
41. A stable oleaginous foamable water-in-oil emulsion, comprising (a) a solvent selected from the group consisting of a hydrophobic solvent, a co-solvent and an emollient at a concentration of about 30% to about 96.5% by weight; (b) water; : (c) a lipophilic surface-active agent having an HLB value of about 3 to about 10 at a concentration of about 0.1 % to less than about 10% by weight, (d) a gelling agent at a concentration of about 0.1% to about 5% by weight of the total composition (e) a therapeutically effective amount of an active agent; and (fy a propellant at a concentration of about 3% to about 25% by weight of the total composition.
42. The oleaginous foamable water-in-oil emulsion of claim 39 or 41, further comprising a foam adjuvant selected from the group consisting of fatty alcohols having greater than or equal to 15 carbons and fatty acids having greater than or equal to 16 carbons.
43. The oleaginous foamable water-in-oil emulsion of claim 39 or 41, wherein the solvent comprises a hydrophobic solvent having solubility in distilled water at ambient temperature of less than about one gram per 100 mi. 44, The oleaginous foamable water-in-oil emulsion of claim 39 or 41, wherein the hydrophobic solvent is selected from the group consisting of mineral oil, a triglyceride oil, an ester of a fatty acid, an ester of a dicarboxylic acid, a silicone oil, a polyunsaturated oil, an unsaturated oil and an essential oil. 67 Amended sheet: 29 November 2006
« ou
45. The oleaginous foamable water-in-oil emulsion of claim 39 or 41, wherein the hydrophobic solvent and water are present at a weight ratio in the range of about 1:3 to about 6:1.
46. The oleaginous foamable water-in-oil emulsion of claim 39 or 41, wherein the solvent comprises a potent solvent selected from the group consisting of hydrophobic solvents other than mineral oil, wherein the potent solvent solubilizes an active agent substantially better than mineral oil solubilizes the active agent.
47. The oleaginous foamable water-in-oil emulsion of claim 46, wherein the potent solvent solubilizes the active agent at least 5-fold better than mineral oil solubilizes the active agent.
48, The oleaginous foamable water-in-oil emulsion of claim 46, wherein said potent solvent solubilizes the active agent at least 10-fold better than a mineral oil solubilizes the active agent.
49, The oleaginous foamable water-in-oil emulsion of claim 46, wherein the potent solvent is selected from the group consisting of polyols, polyethylene glycols, propylene glycols, hexylene glycols, butanediols and isomers thereof, glycerols, benzyl alcohol, DMSO, ethyl oleates, ethyl caprylates, diisopropyl adipate, dimethylacetamides, N-methylpyrrolidones, N-hydroxyethylpyrrolidones, polyvinylpyrrolidones, an isosorbide derivatives, glycofurols and ethoxydiglycols (transcutotl) and mixtures thereof in any proportion.
50. The oleaginous foamable therapeutic composition of claim 39 or 41, wherein, said surface active agent comptises at least one non-ionic surface active agent.
51. The oleaginous foamable therapeutic composition of claim 50, further comprising an ionic surface-active agent.
52. The oleaginous foamable water-in-oil emulsion of claim 39 or 41, wherein the concentration of the surface-active agent is less than about 2%. 68 Amended sheet: 29 November 2006
~ N »
53. The oleaginous foamable water-in-oil emulsion of claim 50, wherein said surface-active agent is selected from the group consisting of sorbitan derivatives; alkoxylated alcohols; hydroxylated derivatives of polymeric silicones; alkylated derivatives of hydroxylated polymeric silicones; glyceryl esters; beeswax derivatives; lecithin; and mixtures thereof.
54. The oleaginous foamable water-in-oil emulsion of claim 39 or 41, wherein said co-solvent is selected from the group consisting of polyols, sulfoxides, oleates, lactam compounds, esters, amides, alkanoic acids, and alkanols and admixtures thereof.
55. The oleaginous foamable water-in-oil emulsion of claim 40, wherein the gelling agent is selected from the group consisting of natural polymeric materials, semi- synthetic polymeric materials, synthetic polymeric materials, inorganic gelling agents and mixtures thereof.
56. The oleaginous foamable water-in-oil emulsion of claim 55, wherein the inorganic gelling agent comprises silicone dioxide.
57. The oleaginous foamable water-in-oil emulsion of claim 39 or 41, having a specific gravity of about 0.01 gr/mi to about 0.4 gr/mL, upon extrusion from a pressured container.
58. The oleaginous foamable water-in-oil emulsion of claim 39 or 41, wherein the active agent is a component of the foamable composition and is selected from the group consisting of a solvent, a surface-active agent, a gelling agent and a foam adjuvant.
59. The oleaginous foamable water-in-oil emulsion of claim 39 or 41, wherein the active agent is selected from the group consisting of an an anti-infective, an antibiotic, an antibacterial agent, an antifungal agent, an antiviral agent, an 69 Amended sheet: 29 November 2006
/ antiparasitic agent, an antiinflammatory agent, an immunosuppressive agent, an immunomodaulator, an immunoregulating agent, a hormonal agent, vitamin A, a vitamin A derivative, vitamin B, a vitamin B derivative, vitamin C, a vitamin C derivative, vitamin D, a vitamin D derivative, vitamin E, a vitamin E derivative, vitamin F, a vitamin F derivative, vitamin K, a vitamin K derivative, a wound healing agent, a disinfectant, an anesthetic, an analgesic, an antiallergic agent, a corticosteroid, a non-steroidal anti-inflammatory drug, an alpha hydroxy! acid, a beta- hydroxy acid, a protein, a peptide, a neuropeptide, a allergen, an immunogenic substance, a haptene, an oxidizing agent, an antioxidant, a retinoid, an antiproliferative agent, an anticancer agent, a photodynamic therapy agent, an anti- wrinkle agent, a radical scavenger, a self-tanning agent, a skin whitening agent, a skin protective agent, an anti-cellulite agent, a massaging oil and an anti-wart agent, a refatting agent, a lubricating agent and mixtures thereof.
60. The oleaginous foamable water-in-oil emulsion of claim 39 or 41, wherein the therapeutic agent is selected for the treatment of a disorder of the skin, mucosal membrane, ear channel, vagina, penile urethra and rectum.
61. The oleaginous foamable water-in-oil emulsion of claim 60, wherein the etiology of the dermatological or mucosal disorder is bacterial, fungal, viral, parasitic, inflammatory, autoimmune, allergic, hormonal, malignant and combinations thereof.
62. The oleaginous foamable water-in-oil emulsion of claim 39 or 41, wherein active agent is an inorganic solid matter.
63. The oleaginous foamable water-in-oil emulsion of claim 62, wherein the inorganic solid matter is selected to form a protective layer on a body surface, a body cavity or a mucosal membrane. 70 Amended sheet: 29 November 2006 w v's
64. The oleaginous foamable water-in-oil emulsion of claim 63, wherein the inorganic solid matter is selected to treat a skin disorder selected from sensitive skin, diaper rash and diaper dermatitis.
65. An oleaginous foam for treating or preventing diaper rash comprising at least one solvent selected from the group consisting of a hydrophobic solvent, a co-solvent, an emollient and mixtures thereof, at a concentration of about 30% to about 90%; water at a concentration of 1% to about 60%; about 6% to about 20% metal oxide; at least one non-ionic lipophilic surface active agent, having an HLB value of about 3 to about 10, at least one gelling agent at a concentration of about 0.1% to about 5%, a propeliant at a concentration of about 3% to about 25% of the total composition wherein said composition is contained in an aerosol container.
66. The oleaginous foamable water-in-oil emulsion of claim 65, wherein the concentration of said solvent is about 30% to about 70% .
67. The oleaginous foamable water-in-oil emulsion of claim 65, wherein the metal oxide is zinc oxide.
68. The oleaginous foamable water-in-oil emulsion of claim 65, wherein said surface active agent has an HLB value of about 3.5 to about 9.
69. The oleaginous foamable water-in-oil emulsion of claim 65, wherein the concentration of said surface active agent is about 0.1% to about 10%.
70. The oleaginous foamable water-in-oil emulsion of claim 65, wherein the concentration of said surface active agent is about 0.1% to about 5%. 71 Amended sheet: 29 November 2006
~ t' %
71. An oleaginous foamable therapeutic composition comprising at least one active ingredient, at least one potent solvent, wherein the degree of active ingredient solubilization by said potent solvent is greater than the degree of said at least one active agent solubilization by a mineral oil, and a gelling agent.
72. The oleaginous foamable composition of claim 71, wherein the potent solvent comprises a polyol or a mixture of polyols.
73. The oleaginous foamable composition of claim 72, wherein said polyol is flowable at ambient temperature.
74. The oleaginous foamable composition of claim 72, wherein said polyol has a viscosity of less than about 20,000 cps at ambient temperature.
75. The oleaginous foamable composition of claim 72, wherein said polyol has a viscosity of less than about 10,000 cps at ambient temperature.
76. The oleaginous foamable composition of claim 71, where the gelling agent comprises a polysaccharide
77. The oleaginous foamable composition of claim 76, where said polysaccharide is a hydroxypropylcellolose.
78. The oleaginous foamable water-in-oil emulsion of claim 1, 3, 39, 41, 65 and 71 comprising less than about 5% of short chain alcohols having up to 5 carbon atoms in the short chain alcohol carbon chain.
79. An oleaginous foam composition according to any of claims 1 through 78 for use in a method of treating, alleviating or preventing a dermatological, cosmetic or mucosal disorder, comprising administering topically to a subject having said disorder a therapeutically effective amount of said composition. 72 Amended sheet: 29 November 2006
EE
80. A method of designing a foamable composition, comprising at least one active -agent that is substantially insoluble in mineral oil, comprising the steps of:
i. selecting at least one active agent;
il. identifying a potent solvent that solubilizes said at least one active agent substantially better than mineral oil solubilizes said at least one active agent, whereby the active agent is solubilized in the composition; and iii. adjusting the type and concentration of surface active agent and gelling agent, to provide a foamable composition
81. The method of claim 80, wherein the potent solvent solubilizes the active agent 5 fold better than a hydrocarbon solvent solubilizes the active agent.
82. The method of claim 81, wherein the potent soivent soiubilizes the active agent 10 fold better than a hydrocarbon solvent solubilizes the active agent.
83. An oleaginous foamable therapeutic composition, essentially free of alcohol, comprising:
a. a solvent selected from the group consisting of. a hydrophobic solvent, a co- solvent, and mixtures thereof, wherein the solvent is present at a concentration of about 70% to about 96.5% by weight of the total composition;
b. a surface-active agent at a concentration of about 0.1% to about 25% by weight of the total composition, wherein the surface-active agent comprises a phospholipid;
c. a gelling agent at a concentration of about 0.1% to about 5% by weight of the total composition;
d. a therapeutically effective amount of an active agent;
e. a propellant at a concentration of about 3% to about 25% by weight of the total composition.
84. The composition of claim 83, wherein the phospholipid comprises lethicin. 73 Amended sheet: 29 November 2006
- ff 9
85. The oleaginous foamable therapeutic composition of claim 83, wherein, said surface active agent comprises at least one non-ionic surface active agent.
86. The oleaginous foamable therapeutic composition of claim 83, further comprising an ionic surface-active agent.
87. A therapeutic device, comprising a pressurized can, equipped with a metered dose valve and an actuator capable of dispensing a foam, and containing an oleaginous foam composition according to any of claims 1 through 78 and 83 through 86.
88. The device of claim 87, wherein the metered dose valve provides a unit dose of between about 10 yL and about 1000 pL.
89. The device of claim 87, wherein the metered dose valve provides a unit dose of between about 50 uL and about 250 pL.
90. A kit comprising a packaging material and contained therein an oleaginous foamable pharmaceutical composition in a container comprising at least one active ingredient, at least one solvent, a gelling agent, and a propellant, said gelling agent being capable of thickening the composition; said propellant capable of forming a foam upon release of the composition from the container; and said packaging material comprising a label which indicates that said pharmaceutical composition can be used for the treatment of a given superficial disorder, which responds to treatment by said active agent, delivered in an oleaginous vehicle, in a therapeutically effective dose.
91. An oleaginous foamable therapeutic composition according to claim 1 substantially as herein described with reference to any one of the illustrative Examples.
92. An oleaginous foamable therapeutic composition according to claim 3 substantially as herein described with reference to any one of the illustrative Examples. 73a Amended sheet: 29 November 2006 ww 9
93. A stable oleaginous foamable water-in-oil emulsion according to claim 39 substantially as herein described with reference to any one of the illustrative Examples.
94. A stable oleaginous foamable water-in-oil emulsion according to claim 41 substantially as herein described with reference to any one of the illustrative Examples.
95. An oleaginous foam according to claim 65 substantially as herein described with reference to any one of the illustrative Examples.
96. An oleaginous foamable therapeutic composition according to claim 71 substantially as herein described with reference to any one of the illustrative Exampies.
97. A method according to claim 80 substantially as herein described with reference to any one of the illustrative Examples.
98. An oleaginous foamable therapeutic composition according to claim 83 substantially as herein described with reference to any one of the illustrative Examples. 73b Amended sheet: 29 November 2006
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AU (1) | AU2004313285A1 (en) |
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CN102245169A (en) * | 2008-10-15 | 2011-11-16 | 昆诺瓦制药公司 | Salicylic acid composition |
JP5738839B2 (en) * | 2009-04-01 | 2015-06-24 | ウイラ アイピー プロプライエタリー リミテッド | Multiple dose packages, courses of treatment, and methods of treatment for delivering predetermined multiple doses of a drug |
US20140030201A1 (en) * | 2010-12-21 | 2014-01-30 | Rebecca Susan Ginger | A skin lightening composition |
CN105142600A (en) * | 2013-03-15 | 2015-12-09 | 前沿创新有限公司 | Substantially surfactant-free, submicron dispersions of hydrophobic agents containing high levels of water miscible solvent |
JP6674896B2 (en) * | 2014-02-14 | 2020-04-01 | ミッション・ファーマカル・カンパニー | Spray injection equipment |
EP3116473B1 (en) * | 2014-03-11 | 2020-12-30 | Promius Pharma, LLC | Topical corticosteroid compositions |
JP6510177B2 (en) * | 2014-04-01 | 2019-05-08 | ロレアル | Compositions in the form of nano or microemulsions |
JP6537788B2 (en) | 2014-06-25 | 2019-07-03 | ロレアル | Composition in the form of a nanoemulsion or microemulsion or having a lamellar structure |
CN105126180B (en) * | 2015-07-27 | 2018-06-01 | 广西信业生物技术有限公司 | A kind of medical human lubricant and preparation method thereof |
CN105687027A (en) * | 2016-01-26 | 2016-06-22 | 中国科学院生物物理研究所 | Alcohol-free amino acid type rinse-free foam washing solution |
CN105708716A (en) * | 2016-01-28 | 2016-06-29 | 胡发刚 | Novel oil-in-water vitiligo covering preparation |
FR3085849B1 (en) * | 2018-09-17 | 2021-01-01 | Soc Dexploitation De Produits Pour Les Industries Chimiques Seppic | PHARMACEUTICAL COMPOSITION FOR TOPICAL USE CONTAINING AT LEAST ONE ANTI-INFLAMMATORY SUBSTANCE |
CN109394694A (en) * | 2018-09-30 | 2019-03-01 | 北京兴源联合医药科技有限公司 | A kind of water-free foam agent |
FR3090357B1 (en) * | 2018-12-20 | 2022-10-07 | Oreal | Foam aerosol device containing a composition rich in fatty substances |
FR3094636B1 (en) * | 2019-04-05 | 2022-07-29 | Soc Dexploitation De Produits Pour Les Industries Chimiques Seppic | Pharmaceutical composition for topical use comprising at least one local azole antifungal substance |
KR20220162136A (en) * | 2020-03-30 | 2022-12-07 | 산쇼 이야쿠 가부시키가이샤 | Compositions containing menthol |
CN112403140B (en) * | 2020-10-19 | 2022-07-19 | 傅光明 | Smoke-eliminating and dust-removing agent and preparation method thereof |
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