EP0569532A1 - Improved flexible collodion compositions - Google Patents
Improved flexible collodion compositionsInfo
- Publication number
- EP0569532A1 EP0569532A1 EP19920906146 EP92906146A EP0569532A1 EP 0569532 A1 EP0569532 A1 EP 0569532A1 EP 19920906146 EP19920906146 EP 19920906146 EP 92906146 A EP92906146 A EP 92906146A EP 0569532 A1 EP0569532 A1 EP 0569532A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- composition
- composition according
- acid
- amount
- salicylic acid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 154
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 claims abstract description 121
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 claims abstract description 60
- 229960004889 salicylic acid Drugs 0.000 claims abstract description 60
- LZCLXQDLBQLTDK-UHFFFAOYSA-N ethyl 2-hydroxypropanoate Chemical compound CCOC(=O)C(C)O LZCLXQDLBQLTDK-UHFFFAOYSA-N 0.000 claims abstract description 48
- 229920001577 copolymer Polymers 0.000 claims abstract description 30
- 238000002425 crystallisation Methods 0.000 claims abstract description 29
- 230000008025 crystallization Effects 0.000 claims abstract description 29
- 239000003112 inhibitor Substances 0.000 claims abstract description 25
- 239000003589 local anesthetic agent Substances 0.000 claims abstract description 25
- 229940116333 ethyl lactate Drugs 0.000 claims abstract description 24
- 229920000642 polymer Polymers 0.000 claims abstract description 17
- 239000004359 castor oil Substances 0.000 claims abstract description 14
- 235000019438 castor oil Nutrition 0.000 claims abstract description 14
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 claims abstract description 14
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 claims abstract description 13
- 229920001281 polyalkylene Polymers 0.000 claims abstract description 12
- 229920000728 polyester Polymers 0.000 claims abstract description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 38
- 239000002253 acid Substances 0.000 claims description 27
- 239000003410 keratolytic agent Substances 0.000 claims description 22
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims description 22
- 239000007788 liquid Substances 0.000 claims description 20
- 206010020649 Hyperkeratosis Diseases 0.000 claims description 17
- 239000004310 lactic acid Substances 0.000 claims description 11
- 235000014655 lactic acid Nutrition 0.000 claims description 11
- 239000012530 fluid Substances 0.000 claims description 10
- 150000003839 salts Chemical class 0.000 claims description 10
- 125000000217 alkyl group Chemical group 0.000 claims description 9
- 230000000699 topical effect Effects 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 8
- 150000001720 carbohydrates Chemical class 0.000 claims description 5
- FOCAUTSVDIKZOP-UHFFFAOYSA-N chloroacetic acid Chemical compound OC(=O)CCl FOCAUTSVDIKZOP-UHFFFAOYSA-N 0.000 claims description 5
- 150000002170 ethers Chemical class 0.000 claims description 5
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- SGRCVQDBWHCTIS-UHFFFAOYSA-N 2-nonanoyloxypropyl nonanoate Chemical compound CCCCCCCCC(=O)OCC(C)OC(=O)CCCCCCCC SGRCVQDBWHCTIS-UHFFFAOYSA-N 0.000 claims description 4
- 235000010233 benzoic acid Nutrition 0.000 claims description 4
- 229940106681 chloroacetic acid Drugs 0.000 claims description 4
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 239000013078 crystal Substances 0.000 claims description 3
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims 6
- 239000005711 Benzoic acid Substances 0.000 claims 3
- 238000004519 manufacturing process Methods 0.000 claims 3
- WROUWQQRXUBECT-UHFFFAOYSA-N 2-ethylacrylic acid Chemical compound CCC(=C)C(O)=O WROUWQQRXUBECT-UHFFFAOYSA-N 0.000 claims 1
- 208000001126 Keratosis Diseases 0.000 claims 1
- 125000002947 alkylene group Chemical group 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 abstract description 8
- 239000004926 polymethyl methacrylate Substances 0.000 abstract description 6
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- 235000019441 ethanol Nutrition 0.000 description 16
- 238000003756 stirring Methods 0.000 description 13
- BLFLLBZGZJTVJG-UHFFFAOYSA-N benzocaine Chemical compound CCOC(=O)C1=CC=C(N)C=C1 BLFLLBZGZJTVJG-UHFFFAOYSA-N 0.000 description 12
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- 238000002360 preparation method Methods 0.000 description 9
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- 150000007513 acids Chemical class 0.000 description 8
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- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 6
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- 208000000260 Warts Diseases 0.000 description 6
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- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 6
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- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
- NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 description 5
- 229960004194 lidocaine Drugs 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- 230000001329 hyperkeratotic effect Effects 0.000 description 4
- 230000003902 lesion Effects 0.000 description 4
- 229920001223 polyethylene glycol Polymers 0.000 description 4
- 229960002372 tetracaine Drugs 0.000 description 4
- GKCBAIGFKIBETG-UHFFFAOYSA-N tetracaine Chemical compound CCCCNC1=CC=C(C(=O)OCCN(C)C)C=C1 GKCBAIGFKIBETG-UHFFFAOYSA-N 0.000 description 4
- LEBVLXFERQHONN-UHFFFAOYSA-N 1-butyl-N-(2,6-dimethylphenyl)piperidine-2-carboxamide Chemical compound CCCCN1CCCCC1C(=O)NC1=C(C)C=CC=C1C LEBVLXFERQHONN-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- VTUSIVBDOCDNHS-UHFFFAOYSA-N Etidocaine Chemical compound CCCN(CC)C(CC)C(=O)NC1=C(C)C=CC=C1C VTUSIVBDOCDNHS-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 3
- VQTUBCCKSQIDNK-UHFFFAOYSA-N Isobutene Chemical compound CC(C)=C VQTUBCCKSQIDNK-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid group Chemical group C(C=C)(=O)O NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 3
- 238000013019 agitation Methods 0.000 description 3
- 229960003150 bupivacaine Drugs 0.000 description 3
- VDANGULDQQJODZ-UHFFFAOYSA-N chloroprocaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1Cl VDANGULDQQJODZ-UHFFFAOYSA-N 0.000 description 3
- 229960002023 chloroprocaine Drugs 0.000 description 3
- 229960001747 cinchocaine Drugs 0.000 description 3
- PUFQVTATUTYEAL-UHFFFAOYSA-N cinchocaine Chemical compound C1=CC=CC2=NC(OCCCC)=CC(C(=O)NCCN(CC)CC)=C21 PUFQVTATUTYEAL-UHFFFAOYSA-N 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- SUPCQIBBMFXVTL-UHFFFAOYSA-N ethyl 2-methylprop-2-enoate Chemical compound CCOC(=O)C(C)=C SUPCQIBBMFXVTL-UHFFFAOYSA-N 0.000 description 3
- 229960003976 etidocaine Drugs 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 3
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 3
- 230000001530 keratinolytic effect Effects 0.000 description 3
- 229960000448 lactic acid Drugs 0.000 description 3
- 229960001807 prilocaine Drugs 0.000 description 3
- MVFGUOIZUNYYSO-UHFFFAOYSA-N prilocaine Chemical compound CCCNC(C)C(=O)NC1=CC=CC=C1C MVFGUOIZUNYYSO-UHFFFAOYSA-N 0.000 description 3
- 229960004919 procaine Drugs 0.000 description 3
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- DSSYKIVIOFKYAU-XCBNKYQSSA-N (R)-camphor Chemical compound C1C[C@@]2(C)C(=O)C[C@@H]1C2(C)C DSSYKIVIOFKYAU-XCBNKYQSSA-N 0.000 description 2
- KBPLFHHGFOOTCA-UHFFFAOYSA-N 1-Octanol Chemical compound CCCCCCCCO KBPLFHHGFOOTCA-UHFFFAOYSA-N 0.000 description 2
- XDOFQFKRPWOURC-UHFFFAOYSA-N 16-methylheptadecanoic acid Chemical compound CC(C)CCCCCCCCCCCCCCC(O)=O XDOFQFKRPWOURC-UHFFFAOYSA-N 0.000 description 2
- SJIXRGNQPBQWMK-UHFFFAOYSA-N 2-(diethylamino)ethyl 2-methylprop-2-enoate Chemical compound CCN(CC)CCOC(=O)C(C)=C SJIXRGNQPBQWMK-UHFFFAOYSA-N 0.000 description 2
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 241000723346 Cinnamomum camphora Species 0.000 description 2
- 229940124091 Keratolytic Drugs 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- 239000000020 Nitrocellulose Substances 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 206010040844 Skin exfoliation Diseases 0.000 description 2
- 229920002125 Sokalan® Polymers 0.000 description 2
- 238000005299 abrasion Methods 0.000 description 2
- 229960000583 acetic acid Drugs 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
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- 229930008380 camphor Natural products 0.000 description 2
- 150000001768 cations Chemical class 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- BYEVBITUADOIGY-UHFFFAOYSA-N ethyl nonanoate Chemical compound CCCCCCCCC(=O)OCC BYEVBITUADOIGY-UHFFFAOYSA-N 0.000 description 2
- 230000007794 irritation Effects 0.000 description 2
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 2
- KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 2
- 229960002409 mepivacaine Drugs 0.000 description 2
- INWLQCZOYSRPNW-UHFFFAOYSA-N mepivacaine Chemical compound CN1CCCCC1C(=O)NC1=C(C)C=CC=C1C INWLQCZOYSRPNW-UHFFFAOYSA-N 0.000 description 2
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 2
- 229920001220 nitrocellulos Polymers 0.000 description 2
- FBUKVWPVBMHYJY-UHFFFAOYSA-N nonanoic acid Chemical compound CCCCCCCCC(O)=O FBUKVWPVBMHYJY-UHFFFAOYSA-N 0.000 description 2
- 229920000058 polyacrylate Polymers 0.000 description 2
- NXLOLUFNDSBYTP-UHFFFAOYSA-N retene Chemical compound C1=CC=C2C3=CC=C(C(C)C)C=C3C=CC2=C1C NXLOLUFNDSBYTP-UHFFFAOYSA-N 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- TUSDEZXZIZRFGC-UHFFFAOYSA-N 1-O-galloyl-3,6-(R)-HHDP-beta-D-glucose Natural products OC1C(O2)COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC1C(O)C2OC(=O)C1=CC(O)=C(O)C(O)=C1 TUSDEZXZIZRFGC-UHFFFAOYSA-N 0.000 description 1
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- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- ABEXEQSGABRUHS-UHFFFAOYSA-N 16-methylheptadecyl 16-methylheptadecanoate Chemical compound CC(C)CCCCCCCCCCCCCCCOC(=O)CCCCCCCCCCCCCCC(C)C ABEXEQSGABRUHS-UHFFFAOYSA-N 0.000 description 1
- BDEHGQOUMOLWCN-UHFFFAOYSA-N 16-methylheptadecyl benzoate Chemical compound CC(C)CCCCCCCCCCCCCCCOC(=O)C1=CC=CC=C1 BDEHGQOUMOLWCN-UHFFFAOYSA-N 0.000 description 1
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 1
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- DUAYDERMVQWIJD-UHFFFAOYSA-N 2-n,2-n,6-trimethyl-1,3,5-triazine-2,4-diamine Chemical compound CN(C)C1=NC(C)=NC(N)=N1 DUAYDERMVQWIJD-UHFFFAOYSA-N 0.000 description 1
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- 235000005822 corn Nutrition 0.000 description 1
- LDHQCZJRKDOVOX-NSCUHMNNSA-N crotonic acid Chemical compound C\C=C\C(O)=O LDHQCZJRKDOVOX-NSCUHMNNSA-N 0.000 description 1
- 230000035618 desquamation Effects 0.000 description 1
- 125000004990 dihydroxyalkyl group Chemical group 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- 229940105553 duofilm Drugs 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 229940052296 esters of benzoic acid for local anesthesia Drugs 0.000 description 1
- IAJNXBNRYMEYAZ-UHFFFAOYSA-N ethyl 2-cyano-3,3-diphenylprop-2-enoate Chemical compound C=1C=CC=CC=1C(=C(C#N)C(=O)OCC)C1=CC=CC=C1 IAJNXBNRYMEYAZ-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- LRBQNJMCXXYXIU-QWKBTXIPSA-N gallotannic acid Chemical compound OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@H]2[C@@H]([C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-QWKBTXIPSA-N 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 229940060384 isostearyl isostearate Drugs 0.000 description 1
- 230000035984 keratolysis Effects 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229960005015 local anesthetics Drugs 0.000 description 1
- 238000002803 maceration Methods 0.000 description 1
- 125000005395 methacrylic acid group Chemical group 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- APVPOHHVBBYQAV-UHFFFAOYSA-N n-(4-aminophenyl)sulfonyloctadecanamide Chemical compound CCCCCCCCCCCCCCCCCC(=O)NS(=O)(=O)C1=CC=C(N)C=C1 APVPOHHVBBYQAV-UHFFFAOYSA-N 0.000 description 1
- YKYONYBAUNKHLG-UHFFFAOYSA-N n-Propyl acetate Natural products CCCOC(C)=O YKYONYBAUNKHLG-UHFFFAOYSA-N 0.000 description 1
- 229920000847 nonoxynol Polymers 0.000 description 1
- 229940066429 octoxynol Drugs 0.000 description 1
- 229920002113 octoxynol Polymers 0.000 description 1
- YPMOZWCBANATQH-UHFFFAOYSA-N octyl 7-methyloctanoate Chemical compound CCCCCCCCOC(=O)CCCCCC(C)C YPMOZWCBANATQH-UHFFFAOYSA-N 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 239000004584 polyacrylic acid Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 229940090181 propyl acetate Drugs 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- WBHHMMIMDMUBKC-XLNAKTSKSA-N ricinelaidic acid Chemical compound CCCCCC[C@@H](O)C\C=C\CCCCCCCC(O)=O WBHHMMIMDMUBKC-XLNAKTSKSA-N 0.000 description 1
- 229960003656 ricinoleic acid Drugs 0.000 description 1
- FEUQNCSVHBHROZ-UHFFFAOYSA-N ricinoleic acid Natural products CCCCCCC(O[Si](C)(C)C)CC=CCCCCCCCC(=O)OC FEUQNCSVHBHROZ-UHFFFAOYSA-N 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229940047670 sodium acrylate Drugs 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 125000004079 stearyl 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])C([H])([H])C([H])([H])[H] 0.000 description 1
- 210000000434 stratum corneum Anatomy 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000001797 sucrose acetate isobutyrate Substances 0.000 description 1
- 235000010983 sucrose acetate isobutyrate Nutrition 0.000 description 1
- UVGUPMLLGBCFEJ-SWTLDUCYSA-N sucrose acetate isobutyrate Chemical compound CC(C)C(=O)O[C@H]1[C@H](OC(=O)C(C)C)[C@@H](COC(=O)C(C)C)O[C@@]1(COC(C)=O)O[C@@H]1[C@H](OC(=O)C(C)C)[C@@H](OC(=O)C(C)C)[C@H](OC(=O)C(C)C)[C@@H](COC(C)=O)O1 UVGUPMLLGBCFEJ-SWTLDUCYSA-N 0.000 description 1
- 229940033123 tannic acid Drugs 0.000 description 1
- 235000015523 tannic acid Nutrition 0.000 description 1
- 229920002258 tannic acid Polymers 0.000 description 1
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- LDHQCZJRKDOVOX-UHFFFAOYSA-N trans-crotonic acid Natural products CC=CC(O)=O LDHQCZJRKDOVOX-UHFFFAOYSA-N 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7015—Drug-containing film-forming compositions, e.g. spray-on
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/36—Carboxylic acids; Salts or anhydrides thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/36—Carboxylic acids; Salts or anhydrides thereof
- A61K8/365—Hydroxycarboxylic acids; Ketocarboxylic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/36—Carboxylic acids; Salts or anhydrides thereof
- A61K8/368—Carboxylic acids; Salts or anhydrides thereof with carboxyl groups directly bound to carbon atoms of aromatic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/73—Polysaccharides
- A61K8/731—Cellulose; Quaternized cellulose derivatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/81—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions involving only carbon-to-carbon unsaturated bonds
- A61K8/8105—Compositions of homopolymers or copolymers of unsaturated aliphatic hydrocarbons having only one carbon-to-carbon double bond; Compositions of derivatives of such polymers
- A61K8/8111—Homopolymers or copolymers of aliphatic olefines, e.g. polyethylene, polyisobutene; Compositions of derivatives of such polymers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/81—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions involving only carbon-to-carbon unsaturated bonds
- A61K8/8141—Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by only one carboxyl radical, or of salts, anhydrides, esters, amides, imides or nitriles thereof; Compositions of derivatives of such polymers
- A61K8/8152—Homopolymers or copolymers of esters, e.g. (meth)acrylic acid esters; Compositions of derivatives of such polymers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/20—Chemical, physico-chemical or functional or structural properties of the composition as a whole
- A61K2800/28—Rubbing or scrubbing compositions; Peeling or abrasive compositions; Containing exfoliants
Abstract
Des compositions élastiques filmogènes de collodion peuvent être améliorées par l'inclusion d'un ou de plusieurs polymères topiquement tolérables, dans une quantité suffisante pour augmenter l'élasticité du film formé. Des polymères appropriés incluent les polyalkylènes et les homo- ou copolymères de (méth)acrylate. Des modes préférés de réalisation incluent le copolymère d'isobutylène-butène et/ou le méthacrylate de polyméthyle. Ces compositions peuvent en outre renfermer de l'acide salicylique et un inhibiteur de cristallisation topiquement tolérable, dans une quantité suffisante pour supprimer dans la composition la cristallisation de l'acide salicylique dissous. Les inhibiteurs de cristallisation appropriés comportent au moins un mono- ou polyester et/ou éther. Des formes d'exécution préférées renferment un mélange de lactate d'éthyle et d'huile de ricin, et de lactate d'éthyle seul. Ces compositions renferment de préférence un anesthésique local.Elastic film-forming collodion compositions can be improved by including one or more topically tolerable polymers in an amount sufficient to increase the elasticity of the film formed. Suitable polymers include polyalkylenes and (meth) acrylate homo- or copolymers. Preferred embodiments include the isobutylene-butene copolymer and / or polymethyl methacrylate. These compositions may further contain salicylic acid and a topically tolerable crystallization inhibitor, in an amount sufficient to suppress in the composition the crystallization of dissolved salicylic acid. Suitable crystallization inhibitors include at least one mono- or polyester and / or ether. Preferred embodiments include a mixture of ethyl lactate and castor oil, and ethyl lactate alone. These compositions preferably contain a local anesthetic.
Description
IMPROVED FLEXIBLE COLLODION COMPOSITIONS
The present invention pertains to improved film-forming flexible collodion compositions intended for topical appli¬ cation and related methods.
Both United States Pharmacopoeia (USP) and British Pharmacopoeia (BP) specifications for collodion call for a solution of nitrocellulose in ether and alcohol. Collodion is a solution, typically 4 parts by weight of nitrocellulose dissolved in 75 parts by volume of ethyl ether and 25 parts by volume of ethanol.
Flexible collodion compositions are widely employed in human and veterinary applications. Flexible collodion is generally a pale yellow, syrupy liquid which, when applied to the skin and thus exposed to air, dries forming a color¬ less or nearly colorless flexible, adherent film. Both USP and BP flexible collodions can be used. A useful flexible collodion composition typically consists of collodion with 2% by weight of camphor and 3% by weight of castor oil.
Although flexible collodion itself can be used as a skin protectant, various therapeutic agents often are added, as for example, salicylic acid, tannic acid, cantharides, camphor, and the like.
The present invention relates to improved flexible collodion compositions. One or more topically acceptable polymers can be added to increase the resilience of the film formed by flexible collodion compositions. Optionally and preferably, a local anesthetic can be added to flexible collodion compositions containing a keratolytic agent to alleviate the localized discomfort and irritation often
associated with the application of keratolytic agents to the skin. A topically acceptable crystallization inhibitor can be added to flexible collodion compositions containing salicylic acid. Preferably, combinations of the above can be incorporated into flexible collodion compositions.
Since the therapeutic use of flexible collodion prepa¬ rations depends upon the formation of a protective film, the quality of the film formed is important. The film formed by the flexible collodion composition should be resilient. In other words, the film formed by the flexible collodion composition should be durable and resistant to "rub off" or abrasion, tenacious, flexible (that is, plastic) , and occlusive.
The present invention is based upon the discovery that the addition of one or more topically acceptable polymers increases the resilience of the film formed by the flexible collodion composition.
Typical topically acceptable polymers which can be used are polyalkylenes and (meth)acrylate homo- or copolymers. The use of "meth" as a prefix in parenthesis indicates that the polymer molecule is derived from one or both of acrylic and methacrylic species. Suitable polyalkylenes include homopoly ers and copolymers of butenes, isobutene, isobuty- lene, butadienes, and isoprenes (e.g. Indopol L-50, Indopol H-100) . Among the polyalkylenes, isobutylene- butene copolymer is preferred. Examples of suitable (meth)acrylate homo- or copolymers include polymethyl methacrylate (e.g. Lucite 4F) , polyacrylamide (e.g. Gelamide 250) , polyacrylic acid (e.g. Acrysol A-l) , polyethylacry- late, ethyl methacrylate, ethylene/acrylate copolymer (e.g. A-C Copolymer 540), ethyl-2-cyano-3,3-diphenyl acrylate (e.g. Uvinul N-35) , ethylmethacrylate/abietyl methacrylate/ diethylaminoethyl methacrylate - quaternized with dimethyl
sulf te, ethylmethacrylate/oleyl methacrylate/diethylamino- ethyl methacrylate - quaternized with dimethyl sulfate, sodium aerylate/vinyl alcohol copolymer (e.g. Hydagen F) , acrylic/acrylate copolymer (e.g. Carboset 915) , acrylamide/sodium acrylate copolymer (e.g. Reten 423) , acrylate/acrylamide copolymer (e.g. Ultrahold 8) , acrylates copolymer (e.g. Rhoplex K-3) , and acrylate/ammonium meth¬ acrylate copolymer. Polymethyl methacrylate is a preferred (meth)acrylate polymer.
The amount of topically acceptable polymer added to the flexible collodion composition is at least the minimum amount which is sufficient to increase the resilience of the film formed. Generally, the amount of polymer sufficient to increase the resilience of the film formed is from about 0.05% to about 10.0% by weight of the total composition. While it is recognized that the addition of polymer in amounts greater than 10.0% will still achieve the desired result of increased resilience, a point is reached at which the addition of further amounts of polymer is economically unadvantageous due to the minimal benefit afforded. Gener¬ ally, the amount of polyalkylene added is from 0.05 to 5.0% by weight of the total composition, preferably from 0.1 to 1.0%. The amount of (meth)acrylate homo- or copolymer typically added is from 0.05 to 10.0% by weight of the total composition, preferably from 0.1 to 1.0%.
The resulting flexible collodion composition exhibits an increased resilience in the film formed. The film formed by the resulting composition thus shows increased durability and resistance to "rub-off" or abrasion, increased tenacity, increased flexibility (that is, increased plasticity) , and increased occlusivity. The above attributes imparted by the polymer to the film formed lead to (1) improved compliance, since the film formed is less "sloppy" than the film formed by conventional flexible collodion compositions, and (2)
improved therapeutic efficacy, as the film formed will remain intact where applied for an increased duration and the improved occlusivity will enhance the penetration of any therapeutic agent present in the composition.
One particular area of pharmaceuticals where flexible collodion compositions are employed and thus where the present invention is particularly useful is in the treat¬ ment of hyper eratosis. Hyperkeratosis is characterized by an overgrowth of the horny layer of the skin. Hyperkera- totic conditions include corns, calluses and warts.
Keratolytic agents are used topically in the treatment of hyperkeratosis and act by softening and destroying the stratum corneum layer of the skin, thereby enhancing desqua- mation at the site of application. Salicylic acid is a commonly used keratolytic agent. Other keratolytic agents include ascorbic acid, calcium pantothenate, glacial acetic acid, lactic acid, podophyllum resin, zinc chloride, and mono-, di-, or trichloroacetic acid.
Salicylic acid is keratolytic at about 5% by weight of the total composition. While higher concentrations of salicylic acid can be used, generally no more than 40% by weight of salicylic acid is desirable as higher concentra¬ tions are excessively corrosive or caustic.
Although lactic acid is not traditionally considered to be a keratolytic agent, its use in combination with sali¬ cylic acid or chloroacetic acid softens the skin thereby improving the keratolysis seen with either agent alone. When included, the amount of lactic acid present will be from about 1% to about 20% and preferably, from 5% to 16.5% by weight of composition.
Keratolytic agents are typically applied topically to the hyperkeratotic lesion in a film forming fluid composi¬ tion including flexible collodion. "Fluid" means capable of flowing and thus includes both liquid and gel compositions.
Keratolytic agents generally are formulated in flexible collodion compositions because the film-forming property of the flexible collodion provides two important advantages. First, the application of flexible collodion to a hyperkera¬ totic lesion is far more precise than the application of a runny solution due to the ability of the flexible collodion to rapidly dry and form a film. This property is important as it minimizes the discomfort resulting from inadvertent application of a keratolytic agent to the healthy, normal tissue surrounding the hyperkeratotic lesion. Second, the occlusive film formed by the flexible collodion prevents the evaporation of moisture from the area. The increased reten¬ tion of moisture by the tissues enhances permeation of the keratolytic agent, maceration and sloughing.
Thus in one aspect the present invention is useful in the treatment of hyperkeratosis. A film-forming fluid com¬ position including a keratolytic agent such as salicylic acid, flexible collodion and a topically acceptable polymer according to the present invention in an amount sufficient to increase the resilience of the film formed will exhibit the improved compliance and improved therapeutic efficacy discussed above.
By incorporating a local anesthetic in these composi¬ tions, the present invention alleviates the localized dis¬ comfort and irritation often associated with the application of keratolytics to the skin.
Local anesthetics appropriate for use in the present invention include, but are not limited to, esters of benzoic
acid such as benzocaine, procaine, tetracaine, and chlorop- rocaine, and amides such as bupivacaine, dibucaine, lido- caine, epivacaine, prilocaine, and etidocaine.
The amount of local anesthetic present will be that which is effective in achieving localized anesthesia in the area to which the agent is applied. This is generally from about 0.5% to about 15% or more and preferably is from 1% to 10% by weight of composition. For lidocaine, for example, the effective range is from about 0.5% to about 4%. With benzocaine, the effective range is from about 5% to about 25%.
In another embodiment the present invention comprises a salt, the anion of which is the salicylic acid, lactic acid or chloroacetic acid anion and the cation of which is the protonated form of benzocaine, procaine, tetracaine, chloro- procaine, bupivacaine, dibucaine, lidocaine, mepivacaine, prilocaine, or etidocaine.
The salt can be formed either in situ, i.e. by the contemporaneous application to the skin of an acidic kera- tolytic agent and a basic local anesthetic, or prior to application when these two elements are brought together in a pharmaceutical preparation.
The present invention also includes the method of treating hyperkeratosis which comprises applying to the hyperkeratotic lesions a composition comprising flexible collodion, a therapeutically effective amount of at least one topical keratolytic agent such as salicylic acid, lactic acid, or chloroacetic acid and an anesthetically effective amount of a local anesthetic such as benzocaine, procaine, tetracaine, chloroprocaine, bupivacaine, dibucaine, lido¬ caine, mepivacaine, prilocaine, or etidocaine.
Historically, a problem has been encountered with com¬ positions of salicylic acid and flexible collodion. During normal usage by a patient or consumer, the salicylic acid tends to crystallize out of solution both on the applicator and the mouth of the container. (The terms "crystallize" or "crystallization" refer to the separation of solid from the solution which, for the purposes of this application, is synonymous with precipitation.) The crystallization of the salicylic acid from solution decreases the concentration of salicylic acid in solution which correspondingly decreases the keratolytic activity of the composition. The addition of lactic acid to formulations of salicylic acid in flexible collodion has been found to retard the formation of crystals, thereby yielding formulations acceptable for com- ercialization. Such formulations are marketed under the product names Duofilm®, Wart-Off®, and Tinamed®.
Surprisingly, it has been discovered that a film- forming composition including salicylic acid dissolved in flexible collodion can be improved by the inclusion of a topically acceptable crystallization inhibitor. The crys¬ tallization inhibitor is at least one mono- or polyester and/or ether.
Esters are conventionally defined in terms of an acid portion and an alcohol portion. Typical acids from which the acid portion of the ester-type crystallization inhibitor can be derived include alkanoic acids, hydroxyalkanoic acids, alkenoic acids, or hydroxyalkenoic acids having from two to twenty carbon atoms (straight chain or branched) , and benzoic acids. Examples of suitable alkanoic acids are acetic acid, isobutyric acid, pelargonic acid, isononanoic acid and isostearic acid. Suitable hydroxyalkanoic acids are lactic acid, hydroxybutyric acid, hydroxypentanoic acid, and the like. Suitable alkenoic acids are acrylic acid,
crotonic acid, oleic acid, and the like. An example of a suitable hydrox alkenoic acid is ricinoleic acid.
Typical alcohols from which the alcohol portion of the ester-type crystallization inhibitor can be derived include monohydroxyalkanes, polyhydroxyalkanes, poly(alkanediol)s, and saccharides. Examples of suitable monohydroxyalkanes include ethanol, propanol, butanol, isobutanol, octanol, isostearol and the like. Examples of suitable polyhydrox¬ yalkanes include ethylene glycol, propylene glycol, glycerol, and the like. Suitable pol (alkanediol)s include the polyethylene glycols. Examples of suitable saccharides include the disaccharides, i.e. sucrose, maltose, and lactose.
Examples of suitable mono- or polyester crystallization inhibitors thus include ethyl acetate, ethyl acrylate, ethyl pelargonate, ethyl lactate, propyl acetate, octyl isononanoate, isostearyl isostearate, isobutyl benzoate, isostearyl benzoate, propylene glycol isostearate, propylene glycol dipelargonate, polyethylene glycol dilaurate, castor oil, and sucrose acetate isobutyrate.
The crystallization inhibitor also can include one or more ethers. Ethers can be defined as consisting of a first- group and a second group, the groups being linked through an ethereal oxygen atom.
Suitable first groups are alkyl groups or phenyl groups. Suitable alkyl groups are typically from one to twenty carbon atoms, such as methyl, ethyl, propyl, stearyl, and the like, and can be straight chain or branched. The phenyl groups can be unsubstituted or substituted with alkyl groups, typically of one to ten carbon atoms, which can be straight chain or branched.
Suitable second groups are hydroxyalkyl, polyhy- droxyalkyl, or pol (alkanediol) groups. Typical hydrox¬ yalkyl groups include hydroxyethyl, hydroxypropyl, hydroxy- butyl, and the like. Suitable polyhydroxyalkyl groups include dihydroxyalkyls of one to ten carbon atoms such as dihydroxypropyl, dihydroxybutyl, and the like. Suitable poly(alkanediol)s include the polyethylene glycols.
Examples of suitable ether-type crystallization inhibitors thus include ethoxyethanol, polyethylene glycol stearyl ether, octoxynol, and nonoxynol.
Preferred topically acceptable crystallization inhibitors include propylene glycol dipelargonate, ethyl lactate, and castor oil, either alone or in combination.
Mixtures of ethyl lactate and castor oil or ethyl lactate alone are most preferred.
The amount of topically acceptable crystallization inhibitor utilized is an amount sufficient to suppress the crystallization of dissolved salicylic acid from the flexi¬ ble collodion solution. Generally, the amount of crystal- lization inhibitor sufficient to suppress the crystalliza¬ tion of dissolved salicylic acid from the flexible collodion composition is from about 1.0 to about 60.0% by weight of the total composition. Amounts of crystallization inhibitor greater than 60% will still suppress crystallization. Economic factors, however, outweigh the minimal benefit gained by the addition of further amounts of crystallization inhibitor.
Compositions of the present invention can also include topically acceptable pharmaceutical excipients, such as solvents, diluents, thickeners, etc.
Typical liquid compositions for the topical treatment of hyperkeratosis embodied by the present invention include from 5 to 40% by weight of the total composition of salicylic acid, not less than 50% by weight of the total composition of flexible collodion, and from 15 to 45% by weight of the total composition of ethyl lactate. The amount of salicylic acid is preferably from 15 to 30%, and most preferably about 17% or about 27% by weight of the total composition. Additionally, such liquid compositions typically can include from 1 to 15%, preferably about 3% by weight of the total composition of castor oil. Preferably the compositions also will contain an effective amount, for example from about 0.5% to about 25% by weight of the total composition of a local anesthetic.
Typical gel compositions for the topical treatment of hyperkeratosis embodied by the present invention include from 5 to 40% by weight of the total composition of salicylic acid, from 20 to 60% by weight of the total compo¬ sition of flexible collodion, and from 5 to 25% by weight of the total composition of ethyl lactate. Similar to the liquid compositions, the amount of salicylic acid is prefer¬ ably from 15 to 30%, and most preferably about 17% or about 27% by weight of the total composition. Preferably the compositions also will contain an effective amount, for example from about 0.5% to about 25% by weight of the total composition of a local anesthetic.
The following examples will serve to further typify the nature of this invention. These examples, however, should not be construed as being a limitation on the scope of the invention, which scope is defined solely by the appended claims. The examples are conducted using Flexible Collodion USP. Flexible Collodion BP also can be used.
EXAMPLE 1
A flexible collodion composition is prepared by first adding 15.0 g of ethyl lactate to 64.9 g of flexible collo¬ dion while stirring. Stirring is continued until the mixture is uniform. Next, 3.0 g of castor oil is added, followed by 0.1 g of isobutylene-butene copolymer. Finally, 17.0 g of salicylic acid is slowly dissolved in the mixture while stirring. About 100.0 g of clear pale-yellow liquid is produced.
EXAMPLE 2
While stirring, 45.1 g of ethyl alcohol is added to 21.8 g of flexible collodion. To this mixture, 5.0 g of ethyl lactate is added, followed by 0.1 g of isobutylene- butene copolymer. Once the mixture is uniform, 27.0 g of salicylic acid is slowly added, stirring until completely dissolved. With rapid agitation, 1.0 g of hydroxyethyl cellulose is added and the mixture is allowed to sit overnight. About 100.0 g of clear gel is produced.
EXAMPLE 3
15.0 g of ethyl lactate is added to 64.8 g of flexible collodion, stirring until uniform. To this mixture is added 3.0 g of castor oil. Then 0.1 g of isobutylene-butene copolymer is added. While stirring 17.0 g of salicylic acid is added and dissolved in the mixture. Finally, 0.1 g of polymethyl methacrylate is added to the mixture, yielding 100.0 g of a clear, pale-yellow liquid composition.
EXAMPLE 4
In order to produce 100.0 g of a liquid flexible collo¬ dion composition, 10.0 g of ethyl alcohol and 6.0 g of propylene glycol dipelargonate are stirred, one at a time, into 67.0 g of flexible collodion. When uniform, 17.0 g of salicylic acid is slowly added to the mixture which is stirred until the salicylic acid is completely dissolved. The product is clear and pale-yellow.
EXAMPLE 5
A flexible collodion composition is produced by taking 21.8 g of flexible collodion and adding to it 45.0 g of ethyl alcohol, followed by 5.0 g of ethyl lactate, while stirring. To this mixture, 0.1 g of isobutylene-butene copolymer is added and the mixture is stirred until uniform. Next, 27.0 g of salicylic acid is slowly added while stirring. Once the salicylic acid is completely dissolved, 1.0 g of hydroxyethyl cellulose and 0.1 g of polymethyl methacrylate are added with rapid agitation. After sitting overnight, the mixture yields 100.0 g of a clear gel product.
EXAMPLE 6
The procedure in Example 2 is followed, except the following amounts are used: 32.0 g of ethyl alcohol, 44.9 g of flexible collodion, 5.0 g of ethyl lactate, 0.1 g of isobutylene-butene copolymer, 17.0 g of salicylic acid, and 1.0 g of hydroxyethyl cellulose. The procedure yields 100.0 g of a clear gel composition.
EXAMPLE 7
The procedure in Example 2 is followed, except the following amounts are used: 51.4 g of ethyl alcohol, 25.0 g of flexible collodion, 5.0 g ethyl lactate, 0.1 g of isobutylene-butene copolymer, 17.0 g of salicylic acid, and 1.5 g of hydroxyethyl cellulose. The procedure yields 100.0 g of a clear gel composition.
EXAMPLE 8
A flexible collodion composition is prepared by adding 45.1 g of ethyl alcohol and 5.0 g of ethyl lactate, one at a time, to 21.9 g of flexible collodion while stirring. To this mixture is slowly added 27.0 g of salicylic acid, and the mixture is stirred until the salicylic acid is completely dissolved. Hydroxyethyl cellulose in the amount of 1.0 g is added with rapid agitation and the product is allowed to sit overnight, yielding 100.0 g of a clear gel.
EXAMPLE 9
In order to produce 100.0 g of a flexible collodion composition, 15.0 g of ethyl lactate, followed by 3.0 g of castor oil, are mixed with 65.0 g of flexible collodion.
Then, 17.0 g of salicylic acid is slowly dissolved into this mixture. The product is a clear, pale-yellow liquid.
EXAMPLE 10
The procedure of Example 8 is followed, except the following amounts were used: 51.7 g of ethyl alcohol, 5.0 g of ethyl lactate, 25.0 g of flexible collodion, 17.0 g of salicylic acid, and 1.3 g of hydroxyethyl cellulose. About
100.0 g of clear gel is produced.
EXAMPLE 11
100.0 g of a liquid composition is produced by mixing 16.5 g of ethyl lactate with 66.5 g of flexible collodion, and subsequently dissolving 17.0 g of salicylic acid in this mixture. The final product is clear and pale-yellow in color.
EXAMPLE 12
A flexible collodion composition is prepared by first adding 15.0 g of ethyl lactate to 54.9 g of flexible collo- dion while stirring. Stirring is continued until the mixture is uniform. Next, 3.0 g of castor oil is added, followed by 0.1 g of isobutylene-butene copolymer. Finally, 17.0 g of salicylic acid and 10.0 g of benzocaine are slowly dissolved in the mixture while stirring. About 100.0 g of clear pale-yellow liquid is produced.
EXAMPLE 13
Ingredient % Total Comp.
Flexible Collodion 21.800
Salicylic Acid 17.000 Benzocaine 10.000
Hydroxypropyl Cellulose 1.200
Ethanol (SD alcohol 40B) q.s. to 100.000
The foregoing ingredients are combined in a suitable container and thoroughly mixed to form a uniform prepara- tion. A small amount of the preparation is applied directly to the wart loci. The preparation dries to form a film on the skin.
EXAMPLE 14
Ingredient % Total Comp.
Salicylic Acid 27.000
Flexible Collodion 21.800 Lactic Acid 5.000
Hydroxypropyl Cellulose 1.500
Lidocaine 1.000
Ethanol (SD alcohol 40B) q.s. to 100.000
The foregoing ingredients are combined in a suitable container and thoroughly mixed to form a uniform prepara¬ tion. A small amount of the preparation is applied directly to the wart loci. The preparation dries to form a film.
EXAMPLE 15
Ingredient % Total Comp. Flexible Collodion 24.500
Chloroacetic Acid 17.000
Lactic Acid 5.000
Hydroxypropyl Cellulose 3.000
Lidocaine 2.000 Ethanol (SD alcohol 40B) q.s. to 100.000
The foregoing ingredients are combined in a suitable container and thoroughly mixed to form a uniform prepara¬ tion. A small amount of the preparation is applied directly to the wart loci. The preparation dries to form a film.
EXAMPLE 16
Ingredient % Total Comp.
Flexible Collodion 66.000
Salicylic Acid 16.500
Lactic Acid 16.500 Tetracaine 1.000
The foregoing ingredients are combined in a suitable container and thoroughly mixed to form a uniform prepara¬ tion. A small amount of the preparation is applied directly to the wart loci. The preparation dries to form a film.
Claims
1. A film-forming flexible collodion composition for topical application, characterized in that it comprises at least one topically acceptable polymer selected from the group consisting of polyalkylenes and (meth)acrylate homo- or copolymers in an amount sufficient to increase the resilience of the film formed.
2. The composition according to claim 1 wherein the poly- alkylene is isobutylene-butene copolymer.
3. The composition according to claim 1 wherein the (meth)acrylate homo- or copolymer is polymethyl ethacry- late.
4. The composition according to claim 1 wherein the amount of polyalkylene is from 0.05 to 5.0% by weight of the total composition.
5. The composition according to claim 4 wherein the amount of polyalkylene is from 0.1 to 1.0% by weight of the total composition.
6. The composition according to claim 1 wherein the amount of (meth)acrylate homo- or copolymer is from 0.05 to 10.0% by weight of the total composition.
7. The composition according to claim 6 wherein the amount of (meth)acrylate homo- or copolymer is from 0.1 to 1.0% by weight of the total composition.
8. The composition according to claim 1 further comprising a therapeutically effective amount of a keratolytic agent.
9. The composition according to claim 8 wherein the kera¬ tolytic agent is salicylic acid or chloroacetic acid.
10. The composition according to claim 9 further comprising lactic acid.
11. The composition according to claim 8 further comprising an anesthetically effective amount of a local anesthetic.
12. The composition according to claim 11 wherein a salt of the local anesthetic and the keratolytic agent is formed.
13. A film-forming fluid composition for use in a medical treatment, which composition comprises a keratolytic agent, flexible collodion, and at least one topically acceptable polymer selected from the group consisting of polyalkylenes and (meth)acrylate homo- or copolymers in an amount sufficient to increase the resiliency in the film formed.
14. The composition for use in a medical treatment according to claim 13 further comprising an anesthetically effec¬ tive amount of a local anesthetic.
15. The composition for use in a medical treatment according to claim 14 wherein a salt of the local anesthetic and the keratolytic agent is formed.
16. A film-forming fluid composition for use in treating hyperkeratosis, which composition comprises a keratolytic agent, flexible collodion, and at least one topically acceptable polymer selected from the group consisting of polyalkylenes and (meth)acrylate homo- or copolymers in an amount sufficient to increase the resiliency in the film formed.
17. The composition for use in treating hyperkeratosis according to claim 16 further comprising an anestheti¬ cally effective amount of a local anesthetic.
18. The composition for use in treating hyperkeratosis according to claim 17 wherein a salt of the local anes¬ thetic and the keratolytic agent is formed.
19. The use in the manufacture of a film-forming fluid composition for treating hyperkeratosis of a keratolytic agent, flexible collodion, and at least one topically acceptable polymer selected from the group consisting of polyalkylenes and (meth)acrylate homo- or copolymers in an amount sufficient to increase the resiliency in the film formed.
20. The use of an anesthetically effective amount of a local anesthetic in the manufacture of a composition for treat¬ ing hyperkeratosis according to claim 19.
21. The use of an anesthetically effective amount of a local anesthetic in the manufacture of a composition for treat¬ ing hyperkeratosis according to claim 19 wherein a salt of the local anesthetic and the keratolytic agent is formed.
22. A film-forming fluid composition for the topical treat¬ ment of hyperkeratosis comprising salicylic acid dissolved in flexible collodion, characterized in that it comprises an amount of a topically acceptable crystal¬ lization inhibitor sufficient to suppress the crystal¬ lization of dissolved salicylic acid from the flexible collodion solution, said crystallization inhibitor being at least one member selected from the group consisting of:
ono- or polyesters, in which the acid portion is derived from an alkanoic acid, hydroxyalkanoic acid, alkenoic acid, hydroxyalkenoic acid or benzoic acid, and the alcohol portion is derived from a monohydroxyalkane, polyhydroxyalkane, poly(alkanediol) or saccharide; and ethers, in which a first group, consisting of alkyl or phenyl which may be unsubstituted or substituted with alkyl, is linked through an ethereal oxygen atom to a hydroxyalkyl, pol (alkanediol) or polyhydroxyalkyl group.
23. The composition according to claim 22 wherein the topically acceptable crystallization inhibitor includes at least one of propylene glycol dipelargonate, ethyl lactate or castor oil.
24. The composition according to claim 23 wherein the topically acceptable crystallization inhibitor is a mixture of ethyl lactate and castor oil.
25. The composition according to claim 23 wherein the topically acceptable crystallization inhibitor is ethyl lactate.
26. The composition according to claim 22 wherein the amount of topically acceptable crystallization inhibitor is from 1.0 to 60.0% by weight of the total composition.
27. The composition according to claim 22 wherein the compo¬ sition is a liquid or gel.
28. The composition according to claim 22 further comprising an anesthetically effective amount of a local anesthetic.
29. The composition according to claim 28 wherein a salt of the local anesthetic and salicylic acid is formed.
30. A liquid composition for the topical treatment of hyper¬ keratosis comprising from 5 to 40% by weight of the total composition of salicylic acid, not less than 50% by weight of the total composition of flexible collodion, and from 15 to 45% by weight of the total composition of ethyl lactate.
31. The liquid composition according to claim 30 further comprising from 1 to 15% by weight of the total compo¬ sition of castor oil.
32. The liquid composition according to claim 31 wherein the amount of castor oil is about 3% by weight of the total composition.
33. The liquid composition according to claim 30 wherein the amount of salicylic acid is from 15 to 30% by weight of the total composition.
34. The liquid composition according to claim 33 wherein the amount of salicylic acid is about 17% by weight of the total composition.
35. The liquid composition according to claim 33 wherein the amount of salicylic acid is about 27% by weight of the total composition.
36. The liquid composition according to claim 30 further comprising an anesthetically effective amount of a local anesthetic.
37. The liquid composition according to claim 36 wherein a salt of the local anesthetic and salicylic acid is formed.
38. A gel composition for the topical treatment of hy¬ perkeratosis comprising from 5 to 40% by weight of the total composition of salicylic acid, from 20 to 60% by weight of the total composition of flexible collodion, and from 5 to 25% by weight of the total composition of ethyl lactate.
39. The gel composition according to claim 38 wherein the amount of salicylic acid is from 15 to 30% by weight of the total composition.
40. The gel composition according to claim 39 wherein the amount of salicylic acid is about 17% by weight of the total composition.
41. The gel composition according to claim 39 wherein the amount of salicylic acid is about 27% by weight of the total composition.
42. The gel composition according to claim 38 further comprising an anesthetically effective amount of a local anesthetic.
43. The gel composition according to claim 42 wherein a salt of the local anesthetic and salicylic acid is formed.
4 . A method of suppressing the crystallization of dissolved salicylic acid from a film-forming fluid composition of salicylic acid dissolved in flexible collodion, which comprises providing an effective amount of a topically acceptable crystallization inhibitor, said crystalliza¬ tion inhibitor being at least one member selected from the group consisting of: mono- or polyesters, in which the acid portion is derived from an alkanoic acid, hydroxyalkanoic acid, alkenoic acid, hydroxyalkenoic acid or benzoic acid, and the alcohol portion is derived from a monohydroxyalkane, polyhydroxyalkane, poly(alkanediol) or saccharide; and ethers, in which a first group.
consisting of alkyl or phenyl which may be unsubstituted or substituted with alkyl, is linked through an ethereal oxygen atom to a hydroxyalkyl, poly(alkanediol) or poly- hydroxyalkyl group.
45. A film-forming fluid composition for the topical treat¬ ment of hyperkeratosis comprising salicylic acid dissolved in flexible collodion, characterized in that it comprises:
(a) an amount of a topically acceptable crystallization inhibitor sufficient to suppress the crystallization of dissolved salicylic acid from the flexible collodion solution, said crystallization inhibitor being at least one member selected from the group consisting of: mono- or polyesters, in which the acid portion is derived from an alkanoic acid, hydroxyalkanoic acid, alkenoic acid, hydroxyalkenoic acid or benzoic acid, and the alcohol portion is derived from a monohydroxyalkane, polyhydroxyalkane, poly(alkanediol) or saccharide; and ethers, in which a first group, consisting of alkyl or phenyl which may be unsubstituted or substituted with alkyl, is linked through an ethereal oxygen atom to a hydroxyalkyl, poly(alkanediol) or polyhydroxyalkyl group; and
(b) at least one topically acceptable polymer selected from the group consisting of polyalkylenes and (meth)- acrylate homo- or copolymers in an amount suffi¬ cient to increase the resilience of the film formed.
46. The film-forming fluid composition according to claim 45 further comprising an anesthetically effective amount of a local anesthetic.
47. The film-forming composition according to claim 46 wherein a salt of the local anesthetic and salicylic acid is formed.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US64969291A | 1991-02-01 | 1991-02-01 | |
| US649692 | 1991-02-01 | ||
| US72482491A | 1991-07-02 | 1991-07-02 | |
| US724824 | 1991-07-02 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| EP0569532A1 true EP0569532A1 (en) | 1993-11-18 |
Family
ID=27095681
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP19920906146 Withdrawn EP0569532A1 (en) | 1991-02-01 | 1992-01-31 | Improved flexible collodion compositions |
Country Status (3)
| Country | Link |
|---|---|
| EP (1) | EP0569532A1 (en) |
| CA (1) | CA2101083C (en) |
| WO (1) | WO1992013529A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SG94818A1 (en) * | 2000-05-31 | 2003-03-18 | Uni Charm Corp | Absorbent article |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9418352D0 (en) * | 1994-09-12 | 1994-11-02 | Bp Chem Int Ltd | Plasticizer composition |
| US6528086B2 (en) * | 1999-09-28 | 2003-03-04 | Zars, Inc. | Methods and apparatus for drug delivery involving phase changing formulations |
| GB0119012D0 (en) * | 2001-08-03 | 2001-09-26 | Strakan Group Plc | Transdermal delivery of drugs |
| US8492366B2 (en) * | 2002-10-07 | 2013-07-23 | Societe L'oreal S.A. | Enhancedly-solubilized beta-hydroxy acids and higher potency skin peels formulated therefrom |
| US8741332B2 (en) | 2004-06-07 | 2014-06-03 | Nuvo Research Inc. | Compositions and methods for dermally treating neuropathic pain |
| US8741333B2 (en) | 2004-06-07 | 2014-06-03 | Nuvo Research Inc. | Compositions and methods for treating dermatitis or psoriasis |
| US8907153B2 (en) | 2004-06-07 | 2014-12-09 | Nuvo Research Inc. | Adhesive peel-forming formulations for dermal delivery of drugs and methods of using the same |
| US9012477B2 (en) | 2009-01-06 | 2015-04-21 | Nuvo Research Inc. | Method of treating neuropathic pain |
| NL2003419C2 (en) * | 2009-09-01 | 2011-03-02 | Shieldmark Zacco | Composition for tropical application, uses thereof, applicator device and kit of parts. |
| BR112012007550B1 (en) * | 2009-10-08 | 2020-01-14 | Bayer Consumer Care Ag | gel composition, products for treating wart, and calluses / calluses, method for treating a skin disease, dispenser for administering a composition for treating a skin disease in an individual, and method for improving topical administration of salicylic acid to an individual. |
| NL2003786C2 (en) * | 2009-11-11 | 2010-07-30 | Medner B V | COMPOSITION FOR TOPICAL APPLICATION, USES THEREOF, APPLICATOR DEVICE AND KIT OF PARTS. |
| US9693976B2 (en) | 2010-01-14 | 2017-07-04 | Crescita Therapeutics Inc. | Solid-forming local anesthetic formulations for pain control |
| NL2016000B1 (en) * | 2015-12-22 | 2017-07-03 | Youmedical B V | Composition for the treatment of keratosis. |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1152222B (en) * | 1961-03-18 | 1963-08-01 | Hoechst Ag | Process for the preparation of durable sprayable solutions of surface anesthetics |
| FR2350833A1 (en) * | 1976-05-13 | 1977-12-09 | Oreal | NEW NAIL POLISH |
| WO1985000288A1 (en) * | 1983-07-14 | 1985-01-31 | Soft Sheen Products, Inc. | Compositions for treating keratosis |
-
1992
- 1992-01-31 CA CA002101083A patent/CA2101083C/en not_active Expired - Lifetime
- 1992-01-31 EP EP19920906146 patent/EP0569532A1/en not_active Withdrawn
- 1992-01-31 WO PCT/US1992/000873 patent/WO1992013529A1/en not_active Application Discontinuation
Non-Patent Citations (1)
| Title |
|---|
| See references of WO9213529A1 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SG94818A1 (en) * | 2000-05-31 | 2003-03-18 | Uni Charm Corp | Absorbent article |
Also Published As
| Publication number | Publication date |
|---|---|
| WO1992013529A1 (en) | 1992-08-20 |
| CA2101083C (en) | 2004-09-14 |
| CA2101083A1 (en) | 1992-08-02 |
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