AU757601B2 - Pharmaceutical composition - Google Patents
Pharmaceutical composition Download PDFInfo
- Publication number
- AU757601B2 AU757601B2 AU33232/99A AU3323299A AU757601B2 AU 757601 B2 AU757601 B2 AU 757601B2 AU 33232/99 A AU33232/99 A AU 33232/99A AU 3323299 A AU3323299 A AU 3323299A AU 757601 B2 AU757601 B2 AU 757601B2
- Authority
- AU
- Australia
- Prior art keywords
- pharmaceutical composition
- minoxidil
- weight
- composition according
- approximately
- 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.)
- Expired
Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 46
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 95
- ZFMITUMMTDLWHR-UHFFFAOYSA-N Minoxidil Chemical compound NC1=[N+]([O-])C(N)=CC(N2CCCCC2)=N1 ZFMITUMMTDLWHR-UHFFFAOYSA-N 0.000 claims description 93
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 89
- 229960003632 minoxidil Drugs 0.000 claims description 89
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 claims description 73
- 239000000203 mixture Substances 0.000 claims description 61
- 235000019441 ethanol Nutrition 0.000 claims description 37
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 34
- 239000002253 acid Substances 0.000 claims description 28
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 26
- 235000019445 benzyl alcohol Nutrition 0.000 claims description 26
- 150000003839 salts Chemical class 0.000 claims description 25
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 21
- IAGROJPXACRRDT-UHFFFAOYSA-N 2-piperidin-1-ylpyrimidine Chemical class C1CCCCN1C1=NC=CC=N1 IAGROJPXACRRDT-UHFFFAOYSA-N 0.000 claims description 19
- 239000006184 cosolvent Substances 0.000 claims description 18
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims description 16
- -1 alkylene glycol Chemical compound 0.000 claims description 14
- 239000002904 solvent Substances 0.000 claims description 14
- 241000195940 Bryophyta Species 0.000 claims description 13
- 235000011929 mousse Nutrition 0.000 claims description 13
- 238000000034 method Methods 0.000 claims description 10
- 201000004384 Alopecia Diseases 0.000 claims description 8
- LYCAIKOWRPUZTN-UHFFFAOYSA-N ethylene glycol Natural products OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 8
- 239000004310 lactic acid Substances 0.000 claims description 8
- 235000014655 lactic acid Nutrition 0.000 claims description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 7
- 230000003676 hair loss Effects 0.000 claims description 6
- 208000024963 hair loss Diseases 0.000 claims description 5
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 claims description 5
- 150000005846 sugar alcohols Polymers 0.000 claims description 5
- 241000282412 Homo Species 0.000 claims description 4
- 125000003118 aryl group Chemical group 0.000 claims description 4
- 210000004761 scalp Anatomy 0.000 claims description 4
- 238000011200 topical administration Methods 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 2
- 239000011707 mineral Substances 0.000 claims description 2
- 150000007524 organic acids Chemical class 0.000 claims description 2
- 235000009917 Crataegus X brevipes Nutrition 0.000 claims 1
- 235000013204 Crataegus X haemacarpa Nutrition 0.000 claims 1
- 235000009685 Crataegus X maligna Nutrition 0.000 claims 1
- 235000009444 Crataegus X rubrocarnea Nutrition 0.000 claims 1
- 235000009486 Crataegus bullatus Nutrition 0.000 claims 1
- 235000017181 Crataegus chrysocarpa Nutrition 0.000 claims 1
- 235000009682 Crataegus limnophila Nutrition 0.000 claims 1
- 235000004423 Crataegus monogyna Nutrition 0.000 claims 1
- 240000000171 Crataegus monogyna Species 0.000 claims 1
- 235000002313 Crataegus paludosa Nutrition 0.000 claims 1
- 235000009840 Crataegus x incaedua Nutrition 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 150000007522 mineralic acids Chemical class 0.000 claims 1
- 238000009472 formulation Methods 0.000 description 19
- 239000000243 solution Substances 0.000 description 16
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 15
- 229920001214 Polysorbate 60 Polymers 0.000 description 14
- 239000001818 polyoxyethylene sorbitan monostearate Substances 0.000 description 14
- 235000010989 polyoxyethylene sorbitan monostearate Nutrition 0.000 description 14
- 229940113124 polysorbate 60 Drugs 0.000 description 14
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 12
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 12
- 230000000699 topical effect Effects 0.000 description 12
- 239000008213 purified water Substances 0.000 description 11
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 9
- 235000011187 glycerol Nutrition 0.000 description 9
- 239000006210 lotion Substances 0.000 description 9
- 239000003380 propellant Substances 0.000 description 9
- 229960000583 acetic acid Drugs 0.000 description 7
- 239000002585 base Substances 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 229960000541 cetyl alcohol Drugs 0.000 description 6
- LQZZUXJYWNFBMV-UHFFFAOYSA-N dodecan-1-ol Chemical compound CCCCCCCCCCCCO LQZZUXJYWNFBMV-UHFFFAOYSA-N 0.000 description 6
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 6
- 239000000499 gel Substances 0.000 description 5
- 239000004615 ingredient Substances 0.000 description 5
- 239000000443 aerosol Substances 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- 239000006260 foam Substances 0.000 description 3
- 239000012362 glacial acetic acid Substances 0.000 description 3
- 239000012047 saturated solution Substances 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
- 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 description 2
- SVTBMSDMJJWYQN-UHFFFAOYSA-N 2-methylpentane-2,4-diol Chemical compound CC(O)CC(C)(C)O SVTBMSDMJJWYQN-UHFFFAOYSA-N 0.000 description 2
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 239000008351 acetate buffer Substances 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 238000007792 addition Methods 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- KVYGGMBOZFWZBQ-UHFFFAOYSA-N benzyl nicotinate Chemical compound C=1C=CN=CC=1C(=O)OCC1=CC=CC=C1 KVYGGMBOZFWZBQ-UHFFFAOYSA-N 0.000 description 2
- FUWUEFKEXZQKKA-UHFFFAOYSA-N beta-thujaplicin Chemical compound CC(C)C=1C=CC=C(O)C(=O)C=1 FUWUEFKEXZQKKA-UHFFFAOYSA-N 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- XSIFPSYPOVKYCO-UHFFFAOYSA-N butyl benzoate Chemical compound CCCCOC(=O)C1=CC=CC=C1 XSIFPSYPOVKYCO-UHFFFAOYSA-N 0.000 description 2
- DOIRQSBPFJWKBE-UHFFFAOYSA-N dibutyl phthalate Chemical compound CCCCOC(=O)C1=CC=CC=C1C(=O)OCCCC DOIRQSBPFJWKBE-UHFFFAOYSA-N 0.000 description 2
- RGXWDWUGBIJHDO-UHFFFAOYSA-N ethyl decanoate Chemical compound CCCCCCCCCC(=O)OCC RGXWDWUGBIJHDO-UHFFFAOYSA-N 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- 150000002430 hydrocarbons Chemical class 0.000 description 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 2
- 229940071676 hydroxypropylcellulose Drugs 0.000 description 2
- 238000011835 investigation Methods 0.000 description 2
- NNPPMTNAJDCUHE-UHFFFAOYSA-N isobutane Chemical compound CC(C)C NNPPMTNAJDCUHE-UHFFFAOYSA-N 0.000 description 2
- 150000003893 lactate salts Chemical class 0.000 description 2
- 230000000149 penetrating effect Effects 0.000 description 2
- 239000002304 perfume Substances 0.000 description 2
- 230000004526 pharmaceutical effect Effects 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- PRAKJMSDJKAYCZ-UHFFFAOYSA-N squalane Chemical compound CC(C)CCCC(C)CCCC(C)CCCCC(C)CCCC(C)CCCC(C)C PRAKJMSDJKAYCZ-UHFFFAOYSA-N 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 description 1
- JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 description 1
- ALSTYHKOOCGGFT-KTKRTIGZSA-N (9Z)-octadecen-1-ol Chemical compound CCCCCCCC\C=C/CCCCCCCCO ALSTYHKOOCGGFT-KTKRTIGZSA-N 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- 229940058015 1,3-butylene glycol Drugs 0.000 description 1
- AXTGDCSMTYGJND-UHFFFAOYSA-N 1-dodecylazepan-2-one Chemical compound CCCCCCCCCCCCN1CCCCCC1=O AXTGDCSMTYGJND-UHFFFAOYSA-N 0.000 description 1
- FRPZMMHWLSIFAZ-UHFFFAOYSA-N 10-undecenoic acid Chemical compound OC(=O)CCCCCCCCC=C FRPZMMHWLSIFAZ-UHFFFAOYSA-N 0.000 description 1
- YDQUROLTIDVHRK-UHFFFAOYSA-N 2-hydroxypropane-1,2,3-tricarboxylic acid;propane-1,2,3-triol Chemical compound OCC(O)CO.OC(=O)CC(O)(C(O)=O)CC(O)=O YDQUROLTIDVHRK-UHFFFAOYSA-N 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- VQAWRQZAAIQXHM-UHFFFAOYSA-N Cepharanthine Natural products O1C(C=C2)=CC=C2CC(C=23)N(C)CCC3=CC=3OCOC=3C=2OC(=CC=23)C(OC)=CC=2CCN(C)C3CC2=CC=C(O)C1=C2 VQAWRQZAAIQXHM-UHFFFAOYSA-N 0.000 description 1
- GHOKWGTUZJEAQD-UHFFFAOYSA-N Chick antidermatitis factor Natural products OCC(C)(C)C(O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-UHFFFAOYSA-N 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 108010036941 Cyclosporins Proteins 0.000 description 1
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 1
- PYGXAGIECVVIOZ-UHFFFAOYSA-N Dibutyl decanedioate Chemical compound CCCCOC(=O)CCCCCCCCC(=O)OCCCC PYGXAGIECVVIOZ-UHFFFAOYSA-N 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- OYHQOLUKZRVURQ-HZJYTTRNSA-N Linoleic acid Chemical compound CCCCC\C=C/C\C=C/CCCCCCCC(O)=O OYHQOLUKZRVURQ-HZJYTTRNSA-N 0.000 description 1
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical class OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- FCKLFGKATYPJPG-SSTBVEFVSA-N Oxendolone Chemical compound C1CC2=CC(=O)CC[C@@H]2[C@@H]2[C@@H]1[C@@H]1C[C@H](CC)[C@H](O)[C@@]1(C)CC2 FCKLFGKATYPJPG-SSTBVEFVSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 229920000604 Polyethylene Glycol 200 Polymers 0.000 description 1
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
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- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- 229930003270 Vitamin B Natural products 0.000 description 1
- 229930003427 Vitamin E Natural products 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 239000006096 absorbing agent Substances 0.000 description 1
- JABXMSSGPHGCII-UHFFFAOYSA-N acetic acid;propane-1,2-diol Chemical compound CC(O)=O.CC(O)CO JABXMSSGPHGCII-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 231100000360 alopecia Toxicity 0.000 description 1
- TUFYVOCKVJOUIR-UHFFFAOYSA-N alpha-Thujaplicin Natural products CC(C)C=1C=CC=CC(=O)C=1O TUFYVOCKVJOUIR-UHFFFAOYSA-N 0.000 description 1
- DTOSIQBPPRVQHS-PDBXOOCHSA-N alpha-linolenic acid Chemical compound CC\C=C/C\C=C/C\C=C/CCCCCCCC(O)=O DTOSIQBPPRVQHS-PDBXOOCHSA-N 0.000 description 1
- 235000020661 alpha-linolenic acid Nutrition 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
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- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 229950004580 benzyl nicotinate Drugs 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
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- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
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- 150000001735 carboxylic acids Chemical class 0.000 description 1
- RZMKWKZIJJNSLQ-UHFFFAOYSA-M carpronium chloride Chemical compound [Cl-].COC(=O)CCC[N+](C)(C)C RZMKWKZIJJNSLQ-UHFFFAOYSA-M 0.000 description 1
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- 238000002425 crystallisation Methods 0.000 description 1
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- 230000007812 deficiency Effects 0.000 description 1
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- 235000014113 dietary fatty acids Nutrition 0.000 description 1
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- 229940012017 ethylenediamine Drugs 0.000 description 1
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- 239000012530 fluid Substances 0.000 description 1
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- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
- 239000003349 gelling agent Substances 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
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- 230000003719 hair strength Effects 0.000 description 1
- ACGUYXCXAPNIKK-UHFFFAOYSA-N hexachlorophene Chemical compound OC1=C(Cl)C=C(Cl)C(Cl)=C1CC1=C(O)C(Cl)=CC(Cl)=C1Cl ACGUYXCXAPNIKK-UHFFFAOYSA-N 0.000 description 1
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- YHSOMIDYWSMROG-UHFFFAOYSA-N nitric acid;propane-1,2-diol Chemical compound O[N+]([O-])=O.CC(O)CO YHSOMIDYWSMROG-UHFFFAOYSA-N 0.000 description 1
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- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
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- 239000004006 olive oil Substances 0.000 description 1
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- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
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- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
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Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
PHARMACEUTICAL COMPOSITION BACKGROUND OF THE INVENTION The present invention relates to a vehicle system for a pharmaceutical composition comprising a piperidinopyrimidine derivative. More particularly minoxidil and to a pharmaceutical composition incorporating the vehicle system.
Minoxidil is a pharmaceutically active ingredient having several indications including use as a hair growth stimulant.
Minoxidil has poor solubility in water and ethanol and pharmaceutical preparations currently marketed only contain a small percentage of minoxidil which is available on the skin of the user for pharmaceutical effect. That is, below minoxidil on the skin.
Numerous formulations comprising minoxidil have been published in the prior art including United States patents 4,139,619,4,820,512,5,104,646, 5,225,189,4,938,953,4,596,812,5,006,332,5,156,836 and 5,643,942. Many of the formulations require (or would require where the amount of minoxidil is greater than a very high percentage (often in the range of 30 to 50%) of propylene glycol or a similar glycol product in order to improve the solubility of minoxidil. Due to the viscosity and tack of propylene glycol, large amounts of propylene glycol or 20 similar agents in a composition are not pharmaceutically or cosmetically elegant and may be unacceptable to the consumer. In addition, high concentrations of propylene glycol may cause local irritation and hypersensitivity upon application to the scalp.
It would accordingly be a significant advance in the art if a composition could be provided which would permit the inclusion of an increased percentage of the active ingredient, but without the disadvantages associated with a high propylene glycol concentration.
Accordingly, it is an object of the present invention to overcome, or at least alleviate, one or more of the difficulties and deficiencies related to the prior art.
These and other objects and features of the present invention will be clear from the following disclosure.
SUMMARY OF THE INVENTION Accordingly, the present invention in a first aspect provides a pharmaceutical composition for topical administration, including, as the pharmaceutically active component:: at least 5% by weight, based on the total weight of the composition of a piperidinopyrimidine derivative or a pharmaceutically acceptable salt thereof; an acid in an amount to substantially completely solubilise the piperidinopyrimidine derivative or a pharmaceutically acceptable salt thereof; a solvent selected from one or both of water and a lower alcohol and, a co-solvent selected from one or more of the group consisting of aromatic and polyhydric alcohols; wherein when the co-solvent includes propylene glycol, it is present in an amount of less than approximately 10% by weight.
Applicants have surprisingly discovered that by adjusting the acid concentration of the composition the solubility of the piperidinopyrimidine derivatives may be significantly increased without the necessity of utilising large amounts of propylene glycol or optionally by excluding propylene glycol altogether. Accordingly the total amount of active in the composition may be significantly increased. In a preferred form, the pharmaceutically active component is present in amounts of approximately 5 to 25% by weight, preferably approximately 5 to 15% by weight, more preferably approximately 7.5 to 12% by weight.
Preferably the piperidinopyrimidine derivative is minoxidil. Preferably the minoxidil is present in the form of a salt. The salt may include acetate, citrate, succinate, benzoate, hydrochloride, sulphate, phosphate or lactate. Preferably an acetate or lactate salt of minoxidil is used. The acetate or lactate salts may exhibit enhanced solubility and improve the ability to incorporate increased amounts of the active component in the composition.
In a preferred form the acid is added in an amount sufficient to provide an WO 99/53923 PCT/AU99/00294 3 apparent pH to the composition of approximately 7.0 or less. The apparent pH of the composition is preferably between approximately 5.0 to 7.0, more preferably between 6.0 to 6.5. Any suitable acid may be used to adjust the pH, including mineral acids, such as hydrochloric acid, sulphuric acid, nitric acid and phosphoric acid, or organic acids such as citric acid, acetic acid, succinic acid, or maleic acid, or mixtures thereof. Acetic acid or lactic acid is preferred.
In a preferred form the acid is present at a level that provides at least 0.01 Normal acid. Alternatively, the acid is present in an amount equal to, or greater than, the amount of the piperidinopyrimidine derivative in Normal amounts.
Preferably the lower alcohol is ethanol. The ratio of water to ethanol is preferably from approximately 9:1 to 1 more preferably approximately 1:1 to 1:3, by volume.
Preferably, the co-solvent includes benzyl alcohol. The benzyl alcohol may be present in amounts of approximately 2.5 to 95% by weight, preferably approximately 5 to 40% by weight, based on the total weight of the pharmaceutical composition.
Alternatively, or in addition the co-solvent may include a polyhydric alcohol, for example a polyol selected from the group consisting of 1,3-butylene glycol, propylene glycol, preferably glycol 200 (PEG 200), polyethylene glycol 400 (PEG 400), hexylene glycol and dipropylene glycol, or glycerol. When propylene glycol is present, it may be present in amounts of approximately 10% by weight or less, preferably approximately 5% by weight, or less.
In compositions comprising 5% of minoxidil or greater, it is preferred to include benzyl alcohol in the composition. The benzyl alcohol may be present in amounts of up to 85% by weight, based on the total weight of the pharmaceutical composition.
In a preferred form the co-solvent system includes water and benzyl alcohol wherein the benzyl alcohol is in an amount of approximately 40 to 100% by weight, based on the total weight of the co-solvent system.
In a preferred form the water is present in an amount no greater than by weight.
In a preferred aspect, the pharmaceutical composition includes approximately 5 to 12% by weight, based on the total weight of the composition, of a minoxidil or a minoxidil acid salt; approximately 88 to 95% by weight of a solvent composition including approximately 10 to 70% by weight of ethanol, approximately 2.5 to 85% by weight of benzyl alcohol; and less than 10% by weight, propylene glycol.
S.i :The final presentation of the composition may be any suitable topical pharmaceutical preparation and may include solutions, lotions, ointments, mousses, foams, sprays, aerosols, shampoos and/or conditioners, gels, creams, pastes, and other preparations known in the art. The composition may also include other ingredients such as preservatives, buffers, stabilisers, propellants and the like.
Preferably the pharmaceutical composition is a mousse composition. The mousse composition may include a suitable propellant, for example hydrocarbons or chlorofluorocarbons. In this embodiment of the invention the addition of the S: 20 propellant to the composition will dilute the amount of the piperidinopyrimidine derivative or pharmaceutically acceptable salt thereof present in the charged composition but will nonetheless leave at least 5% of the derivative or salt thereof available on the skin of the user for pharmaceutical effect.
Alternatively the pharmaceutical composition may be a gel composition.
The gel composition may include a suitable gelling agent, e. g. a cellulose derivative. A hydroxy propyl cellulose, for example that sold under the trade designation Klucel M, has been found to be suitable.
Where an aerosol formulation is used, the aerosol formulation may be a homogeneous, aqueous-alcoholic emulsion system. The aerosol formulation upon actuation produces a stabilized, homogeneous, expandable foam which breaks easily with shear. A composition of this type is sometimes referred to as a In a further preferred aspect, the pharmaceutical composition according to WO 99/53923 PCT/AU99/00294 the present invention may further include an effective amount of a skin penetrating agent.
Suitable skin penetrating agents include alcohols such as dodecanol and oleyl alcohol; amines, such as isopropyl amine, diisopropyl amine, triethyl amine, triethanol amine, diisopropanolamine and ethylene diamine; carboxylic acids, such as oleic acid, linoleic acid and linolenic acid; esters, such as dibutyl sebacate, dibutyl phthalate, butyl benzoate and ethyl caprate; and others, such as Azone, N methyl pyrollidone, bile salts and urea.
All of the compositions herein may be actuated using propellants known per se in the pharmaceutical or cosmetic fields. Such propellants include hydrocarbons such as propane, isobutane or dimethyl ether and chlorofluorocarbons such as P-12, P114, and a 40:60 mixture thereof.
In the pharmaceutical composition according to the present invention, in addition to the above essential components, general purpose components ordinarily used in hair treatment compositions can be formulated, within a range which does not impair the effect of the present invention, including vitamins such as vitamin B.sub.6, vitamin E and derivatives thereof, and biotin; hair generating agents or hair generating aids such as panthothenic acid and derivatives thereof, glycylrrhetic acid and derivatives thereof, nicotinic acid esters such as benzyl nicotinate, cyclosporins, carpronium chloride, cepharanthine, oxendolone, diazoxide, minoxidil, and ethynylesteradiol; antibacterial agents such as hinokitiol, hexachlorophen, phenol, benzalkonium chloride, cetylpyridinium chloride, undecylenic acid, trichlorocarbanilide, and bithionol; refrigerants such as menthol; drugs such as salicylic acid, zinc and derivatives, thereof, and lactic acid and alkyl esters thereof; amino acids such as arginine; oil components such as olive oil, squalane, fluid paraffin, isopropyl myristate, higher fatty acids, and higher alcohols; perfumes; antioxidants; UV-ray absorbers; dyes; humectants; thickeners; perfumes; colour additives and the like.
In a still further aspect of the present invention, there is provided a method for the treatment of hair loss and related indications in humans, which method WO 99/53923 PCT/AU99/00294 6 includes providing a pharmaceutical composition for topical administration, including, as the pharmaceutically active component, at least 5% by weight, based on the total weight of the composition of a piperidinopyrimidine derivative or a pharmaceutically acceptable salt thereof; an acid in an amount to substantially completely solubilise the piperidinopyrimidine derivative or a pharmaceutically acceptable salt thereof; a solvent composition including a solvent selected from water and/or a lower alcohol and a co-solvent selected from one or more of the group consisting of aromatic and polyhydric alcohols; wherein when the co-solvent includes propylene glycol, it is present in an amount of less than approximately 10% by weight; and applying topically to the human scalp a therapeutically or prophylactically effective amount of the pharmaceutical composition.
The hair loss may be related to any of the forms of alopecia including male pattern alopecia. Related indications may include weakening of hair strength, loss of hair colour and the like.
Preferably the pharmaceutically active component includes a minoxidil or a minoxidil salt, more preferably a minoxidil acetate, succinate or citrate salt.
More preferably the pharmaceutical composition includes approximately 5 to 12% by weight, based on the total weight of the composition, of a minoxidil or a minoxidil acid salt; approximately 88 to 95% by weight of a solvent composition including approximately 10 to 70% by weight of ethanol, approximately 2.5 to 85% by weight of benzyl alcohol; and less than 10% by weight, propylene glycol.
The present invention will now be more fully described with reference to the accompanying figures and examples. It should be understood, however, that the WO 99/53923 PCT/AU99/00294 7 description following is illustrative only and should not be taken in any way as a restriction on the generality of the invention described above.
In each of the following examples it was necessary to add an appropriate amount of acid to ensure equivalent acid normality. The standard technique for such an adjustment is to measure the apparent pH of the solution.
In the examples, the apparent pH of each formulation was measured once prepared. The measured taken as the apparent pH due to the high proportion of organic modifiers in the formulations. Typically, 0.5% glacial acetic acid (0.1M) would be used in the formulation, which would equate to a pH of 1.0 in an aqueous system when no other components are contributing to the pH of the solution.
EXAMPLE 1 Topical Minoxidil lotion 5% with no propylene glycol Minoxidil Ethanol Polysorbate 60 Polyoxyethylene lauryl alcohol Acetic Acid Purified Water 5.00% 60.3% 0.4% 1.00% 0.6 to total 100% The apparent pH of the final formulated solution was measured at 6.24.
WO 99/53923 PCT/AU99/00294 8 EXAMPLE 2 Topical Minoxidil mousse 5% for hair treatment Minoxidil Cetyl Alcohol Stearyl Alcohol Ethanol Polysorbate 60 Polyoxyethylene lauryl alcohol Propylene Glycol Propellant P75 Acetic Acid Purified water 5.00% 2.20% 1.00% 51.8 0.4% 1.00% 5.00% 4.30% qs. pH to total 100% EXAMPLE 3 Topical Minoxidil lotion 8% for hair treatment Minoxidil Ethanol Polysorbate 60 Polyoxyethylene lauryl alcohol Nitric Acid Propylene Glycol Benzyl Alcohol Purified Water 8.00% 50.50% 0.4% 1.00% qs. pH 7.30% 5.00% to total 100% WO 99/53923 PCT/AU99/00294 9 EXAMPLE 4 Topical 8% Minoxidil solution Minoxidil Ethanol Crilet 3 Teric 12A4 Glacial Acetic Acid Propylene Glycol Benzyl Alcohol Purified Water 50.5% 0.4% 0.3% to total 100% The apparent pH of the final formulated solution was measured at 6.24.
EXAMPLE Topical Minoxidil lotion 10% for hair treatment Minoxidil Ethanol Polysorbate 60 Polyoxyethylene lauryl alcohol Acetic Acid Propylene Glycol Benzyl Alcohol Purified Water 10.00% 48.0% 0.4% 1.00% qs. pH 10.0% 5.00% to total 100% WO 99/53923 PCT/AU99/00294 EXAMPLE 6 Topical Minoxidil lotion 10% for hair treatment Minoxidil Ethanol Polysorbate 60 Polyoxyethylene lauryl alcohol Acetic Acid Benzyl Alcohol Purified Water 10.00% 47.50% 0.4% 1.00% qs. pH 15.00% to total 100% EXAMPLE 7 Topical 10% Minoxidil solution Minoxidil Ethanol Crillet 3 Teric 12A4 Glacial Acetic Acid Propyiene Glycol Benzyl Alcohol Purified Water Formulation 3a 10.00% 46.80% 0.4% 1.0% 1.0% 10.0% 5.00% to total 100% Formulation 3b 10.00% 44.20% 0.4% 0.3% nil 2.00% to total 100% The apparent pH of the final formulated solutions was measured at 6.0 and for formulations 3a and 3b, respectively.
WO 99/53923 PCT/AU99/00294 11 EXAMPLE 8 Topical Minoxidil lotion 11% for hair treatment Minoxidil Ethanol Polysorbate 60 Polyoxyethylene lauryl alcohol Acetic Acid Benzyl Alcohol Purified Water 11.00% 44.20% 0.4% 1.00% qs. pH 20.00% to total 100% EXAMPLE 9 Topical Minoxidil lotion 12% for hair treatment Minoxidil Ethanol Polysorbate 60 Polyoxyethylene lauryl alcohol Acetic Acid Benzyl Alcohol Purified Water 12.00% 42.7% 0.4% 1.00% qs. pH 20.00% to total 100% WO 99/53923 PCT/AU99/00294 12 EXAMPLE Topical Minoxidil lotion 12% for hair treatment Minoxidil Ethanol Polysorbate 60 Polyoxyethylene lauryl alcohol Acetic Acid Benzyl Alcohol Propylene Glycol Purified Water 12.00% 42.7% 0.4% 1.00% qs. pH 10.00% 10.00% to total 100% EXAMPLE 11 Topical Minoxidil lotion 12% for hair treatment Minoxidil Ethanol Polysorbate 60 Polyoxyethylene lauryl alcohol Acetic Acid Benzyl Alcohol Propylene Glycol Purified Water 12.00% 42.7% 0.4% 1.00% qs. pH 15.00% 5.00% to total 100% There appear to be no obvious gross stability issues associated with any of the formulations. The levels of minoxidil were assayed in formulations 1 and 3a after they had been stored for one and three months at 4°C and 50°C. No measurable loss in potency was observed.
An aqueous gel was prepared by adding 0.75% Klucel M (hydroxypropyl cellulose) to Example 4. The viscosity of the gel was measured at WO 99/53923 PCT/AU99/00294 13 2400 cPoise at 200C.
EXAMPLE 12 Investigations were carried out to determine which of the components present in Example 7 (10% minoxidil solution) were contributing to the solubilisation of minoxidil. The investigation was split into three sections: Effect of Co-solvent Effect of pH Effect of Salt The solubility determination involved preparation of saturated solutions of minoxidil in the media of interest. These solutions were then filtered (0.45 lpm) and analysed against a standard curve by means of direct UV spectroscopy.
Aqueous unbuffered solubility of Minoxidil The aqueous solubility of minoxidil was found to be 2.2 mg/mL.
Effect of Co-solvent The solubility of minoxidil was determined in each of the co-solvents, benzyl alcohol, glycerol, propylene glycol and ethanol. Additionally, the solubility of minoxidil was determined in 10% solutions of each of the co-solvents, ethanol, propylene glycol and glycerol in water. A 4% solution of benzyl alcohol was used since this was found to be the limit of the solubility of benzyl alcohol in water. The following table summarises the results of these studies.
WO 99/53923 PCT/AU99/00294 Sample Minoxidil Solubility (mg/mL) Benzyl alcohol 125.1 Glycerol 47.3 Propylene Glycol 86.9 Ethanol 18.8 Ethanol/Water 3.4 Propylene Glycol/Water 4% Benzyl Alcohol/Water Glycerol/Water 2.7 Analysis indicated that of the systems studied only the use alcohol would result in the desired 10% minoxidil solution.
of pure benzyl Effect of apparent pH Attempts were made to prepare saturated solutions of minoxidil in acetate buffers at apparent pH's 2.5, 3.5, 4.6, 5.0 and 6.0. Saturated solutions were achieved with those pHs above the pKa of minoxidil the results of which are summarised in the following table.
pH Minoxidil Solubility (mg/mL) 4.1 4.6 11.3 It was not possible to determine the solubility limits of minoxidil at pH's below it's pKa, as minoxidil was found to be extremely soluble in acidic media and the buffer used had insufficient capacity to avoid the drift in pH observed with additions of minoxidil to the solution. The maximum minoxidil concentration studied was 22 mg/mL and was found to be completely soluble in pH 2.5 and solutions at this concentration. The following table outlines the maximum solubility that would be expected in an acidic aqueous media knowing the solubility of the base form of minoxidil is 2.2 mg/mL and assuming infinite solubility of the acid form of minoxidil.
pH Minoxidil Solubility (mg/mL) 0 3.622.0 87.6 2.6 220.0 2. 0 876.0 Effect of Salt Minoxidil base was used for these studies with the appropriate salt (acetate or HCI) formed in situ. As discussed above the use of low pH acetate buffers Ssignificantly increased the solubility of minoxidil.
The major factors affecting the solubilisation of minoxidil in an aqueous environment were found to be: The type and proportion of co-solvents present in the formulation The pH of the final formulated solution The amount of minoxidil used 20 The acid form of minoxidil has -been shown to be much more soluble in an aqueous environment. The use of co-solvents has been shown to enhance the solubility of the minoxidil free base. The co-solvents may also enhance the solubility of the acid form. The use of an appropriate salt enhances the solubility of the acid form of minoxidil. Therefore, a combination of these three factors may be used to optimise the solubility of minoxidil in a topical solution based formulation.
All the above examples were stored at room temperature and no crystallisation or precipitation was observed for at least 10 days.
Examples 13 to 17 as set out below are directed to minoxidil compositions formulated as a mousse or foam.
EXAMPLE 13 Minoxidil Mousse Formulations Base Ingredient Formula Minoxidil 4.75% 5.00% Ethanol (SD40B) 53.675% 56.50% Water 31.426% 33.08% Cetyl Alcohol 1.10% 1.15% Stearyl Alcohol 0.50% 0.53% Polysorbate 60 0.40% 0.42% Lactic Acid 1.00% 1.05% Propylene Glycol or Glycerin 2.00% 2.11% Citric Acid 0.10% 0.11% BHT 0.0475% 0.05% Propellant 75 5.00% 0.00% 17 EXAMPLE 14 Minoxidil Mousse Formulations Base Ingredient Formula Minoxidil 4.75% 5.00% Ethanol (SD40B) 53.645% 56.47% Water 31.41% 33.06% Cetyl Alcohol 1.10% 1.15% Stearyl Alcohol 0.50% 0.53% Polysorbate 60 0.40% 0.42% Lactic Acid 1.00% 1.05% S Propylene Glycol or Glycerin 2.00% 2.11% Citric Acid 0.10% 0.11% BHT 0.095% 0.10% Propellant 75 5.00% 0.00% EXAMPLE Minoxidil Mousse Formulations Base Ingredient Formula Minoxidil 4.75% 5.00% Ethanol (SD40B) 53.70% 56.53% Water 31.45% 33.11% Cetyl Alcohol 1.10% 1.15% Stearyl Alcohol 0.50% 0.53% Polysorbate 60 0.40% 0.42% Lactic Acid 1.00% 1.05% Propylene Glycol or Glycerin 2.00% 2.11% Citric Acid 0.10% 0.11% BHT 0.00% 0.00% .iopellant 75 5.00% 0.00% EXAMPLE 16 Minoxidil Mousse Formulations Ingeient Minoxidil 4.75% Ethanol (SID4OB) 53.76% Water 31.49% Cetyl Alcohol 1.10% Stearyl Alcohol 0.50% Polysorbate 60 0.40% Lactic Acid 1.00% Propylene Glycol or Glycerin 2.00% Citric Acid 0.00% BHT 0.00% Propellant 75 5.00% Base Formula 5.00% 56.59% 33.15% 1.15% 0.53% 0.42% 1.05% 2.11% 0.00% 0.00% 0.00% EXAMPLE 17 Minoxidil Mousse Formulations Ingredient Minoxidil Ethanol (SD4OB) Water Cetyl Alcohol Stearyl Alcohol Polysorbate 60 Lactic Acid (90%) Propylene Glycol or Glycerin Citric Acid
BHT
Prorellant 75 4.75% 53.7325% 31 .47% 1.10% 0.50% 0.40% 1.00% 2.00% 0.00% 0.0475% 5.00% Base Formula 5.00% 56.56% 33.13% 1.15% 0.53% 0.42% 1.05% 2.11% 0.00% 0.05% 0.00% 19 Please note all percentages are based upon the total weight of the composition unless otherwise specified.
It will be understood that the invention disclosed and defined in this specification extends to all alternative combinations of two or more of the individual features mentioned or evident from the text or drawings. All of these different combinations constitute various alternative aspects of the invention.
It will also be understood that the term "comprises" (or its grammatical variants) as used in this specification is equivalent to the term "includes" and should not be taken as excluding the presence of other elements or features.
i .i 0• 0@ 0
Claims (30)
1. A pharmaceutical composition for topical administration, including, as the pharmaceutically active component: at least 5% by weight, based on the total weight of the composition of a piperidinopyrimidine derivative or a pharmaceutically acceptable salt thereof; an acid in an amount to substantially completely solubilise the piperidinopyrimidine derivative or a pharmaceutically acceptable salt thereof; a solvent selected from one or both of water and a lower alcohol and, a co-solvent selected from one or more of the group consisting of aromatic and polyhydric alcohols; wherein when the co-solvent includes propylene glycol, it is present in an amount of less than approximately 10% by weight.
2. A pharmaceutical composition according to Claim 1, wherein the acid is added in an amount sufficient to provide an apparent pH to the composition of approximately 7.0 or less.
3. A pharmaceutical composition according to Claim 1 or Claim 2, wherein the piperidinopyrimidine derivative or pharmaceutically acceptable salt thereof is present in an amount of from approximately 5 to 25% by weight, based on the total weight of the pharmaceutical composition.
4. A pharmaceutical composition according to Claim 3, wherein the piperidinopyrimidine derivative or pharmaceutically acceptable salt thereof is present in an amount of approximately 7.5 to 12% by weight, based on the total weight of the pharmaceutical composition.
A pharmaceutical composition according to any one of the preceding claims, wherein the piperidinopyrimidine derivative or pharmaceutically acceptable salt thereof is minoxidil or a salt thereof.
6. A pharmaceutical composition according to Claim 2, wherein the acid provides to the composition an apparent pH in the range of approximately 5.0 to
7. A pharmaceutical composition according to Claim 2, wherein the acid is a mineral or organic acid.
8. A pharmaceutical composition according to Claim 7, wherein the acid includes acetic or lactic acid.
9. A pharmaceutical composition according to any one of the preceding o•. claims, wherein the composition includes water and ethanol in a range of Sapproximately 1: 1 to 1:3 by volume.
S A pharmaceutical composition according to any one of the preceding claims, wherein the co-solvent includes benzyl alcohol.
11. A pharmaceutical composition according to any one of the preceding ll claims, wherein the composition includes water and benzyl alcohol wherein the benzyl alcohol is in an amount of approximately 40 to 100% by weight based on the total weight of the co-solvent system. g. S°
12. A pharmaceutical composition according to any one of the preceding claims, wherein the water is present in an amount no greater than approximately by weight based on the total weight of the co-solvent system.
13. A pharmaceutical composition according to any one of Claims 1 to 9, wherein the co-solvent includes an alkylene glycol.
14. A pharmaceutical composition according to Claim 13, wherein the alkylene glycol is selected from one or more of the group consisting of glycerol, 1,3- J utylene and propylene glycol.
A pharmaceutical composition according to Claim 1, wherein the acid is present at a level that provides at least 0.01 Normal acid.
16. A pharmaceutical composition according to Claim 1, wherein the acid is present in an amount equal to or greater than the amount of the piperidinopyrimidine derivative in Normal amounts.
17. A pharmaceutical composition according to Claim 1, wherein the composition includes water and ethanol in a range of approximately 9: 1 to 1: 9 by volume. 0*
18. A pharmaceutical composition according to Claim 5, wherein the piperidinopyrimidine derivative or pharmaceutically acceptable salt thereof is a minoxidil salt.
19. A pharmaceutical composition according to Claim 18, wherein the minoxidil salt is minoxidil acetate or minoxidil lactate salt.
20. A pharmaceutical composition according to Claim 1, including approximately 5 to 12% by weight, based on the total weight of the composition, of a minoxidil or a minoxidil acid salt; approximately 88 to 95% by weight of a solvent composition including approximately 10 to 70% by weight of ethanol, approximately 2.5 to 85% by weight of benzyl alcohol; and less than 10% by weight, propylene glycol.
21. A pharmaceutical composition according to Claim 1, substantially as hereinbefore described with reference to any one of Examples 1 to 17.
22. A pharmaceutical composition according to any one of Claims 1 to 21, which is formulated as a mousse.
23. A pharmaceutical composition according to Claim 19 which is formulated as a mousse.
24. A method for the treatment of hair loss and related indications in humans, which method includes providing a pharmaceutical composition for topical administration, including: as the pharmaceutically active component at least 5% by weight, based on the total weight of the composition of a piperidinopyrimidine derivative or a pharmaceutically acceptable salt thereof; .i an acid in an amount to substantially completely solubilise the piperidinopyrimidine derivative or a pharmaceutically acceptable salt thereof; a solvent selected from one or both water and a lower alcohol, and 0 a co-solvent selected from one or more of the group consisting of aromatic O and polyhydric alcohols; wherein when the co-solvent includes propylene glycol, it is present in an amount of less than approximately 10% by weight; and applying topically to the human scalp a therapeutically or prophylactically effective amount of the pharmaceutical composition. OO
25. A method according to Claim 24, wherein the piperidinopyrimidine 00 derivative or pharmaceutically acceptable salt thereof is minoxidil or a minoxidil salt. 0
26. A method according to Claim 25, wherein the minoxidil salt is a minoxidil acetate or minoxidil lactate salt.
27. A method according to Claim 24, wherein the pharmaceutical composition includes approximately 5 to 12% by weight, based on the total weight of the composition, of a minoxidil or a minoxidil salt; approximately 88 to 95% by weight of a solvent composition including approximately 10 to 70% by weight of ethanol, approximately 2.5 to 85% by weight of benzyl alcohol; and less than 10% by weight, propylene glycol.
28. A method for the treatment of hair loss and related indications in humans, which method includes applying topically to the human scalp a therapeutically or prophylacticallly effective amount of the pharmaceutical composition according to any one of Claims 1 to 23.
29. A method according to any one of Claims 24 to 28 wherein the pharmaceutical composition is formulated as a mousse.
30. Use of a pharmaceutical composition according to any one of Claims 1 to 23 in the manufacture of a medicament of the treatment of hair loss and related indications in humans. DATED this 1 1 th day of December 2002 SOLTEC RESEARCH PTY LTD WATERMARK PATENT TRADEMARK ATTORNEYS 290 BURWOOD ROAD HAWTHORN VICTORIA 3122 AUSTRALIA P20113AUPC KJS/JMN/APR/dmt
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU33232/99A AU757601B2 (en) | 1998-04-22 | 1999-04-20 | Pharmaceutical composition |
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AUPP3107A AUPP310798A0 (en) | 1998-04-22 | 1998-04-22 | Vehicle system for a composition comprising a piperidinopyrimidine derivative |
| AUPP3107 | 1998-04-22 | ||
| AU33232/99A AU757601B2 (en) | 1998-04-22 | 1999-04-20 | Pharmaceutical composition |
| PCT/AU1999/000294 WO1999053923A1 (en) | 1998-04-22 | 1999-04-20 | Pharmaceutical composition |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU3323299A AU3323299A (en) | 1999-11-08 |
| AU757601B2 true AU757601B2 (en) | 2003-02-27 |
Family
ID=25622412
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU33232/99A Expired AU757601B2 (en) | 1998-04-22 | 1999-04-20 | Pharmaceutical composition |
Country Status (1)
| Country | Link |
|---|---|
| AU (1) | AU757601B2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2001244731B2 (en) * | 2000-04-07 | 2005-02-17 | Taisho Pharmaceutical Co., Ltd. | Hair growth stimulant compositions |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115887313B (en) * | 2022-04-28 | 2025-06-27 | 国润生物科技（深圳）有限公司 | A high-stability whitening and anti-aging atomized liquid and its preparation method |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1983002555A1 (en) * | 1982-01-21 | 1983-08-04 | Us Medical Corp | Prosthesis fixation to bone |
| US4866067A (en) * | 1987-12-07 | 1989-09-12 | Ricerche De Schiena s.n.c del Dr. Michele Giuseppe Di Schiena & C. | 6-piperidino-2,4-diaminopyrimidine-3-oxide salt of 3-carboxypyridine n-oxide and topical, related compositions |
| US5183817A (en) * | 1981-02-17 | 1993-02-02 | Bazzano Gail S | Combinations of retinoids and minoxidil-type compounds for hair growth |
-
1999
- 1999-04-20 AU AU33232/99A patent/AU757601B2/en not_active Expired
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5183817A (en) * | 1981-02-17 | 1993-02-02 | Bazzano Gail S | Combinations of retinoids and minoxidil-type compounds for hair growth |
| WO1983002555A1 (en) * | 1982-01-21 | 1983-08-04 | Us Medical Corp | Prosthesis fixation to bone |
| US4866067A (en) * | 1987-12-07 | 1989-09-12 | Ricerche De Schiena s.n.c del Dr. Michele Giuseppe Di Schiena & C. | 6-piperidino-2,4-diaminopyrimidine-3-oxide salt of 3-carboxypyridine n-oxide and topical, related compositions |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2001244731B2 (en) * | 2000-04-07 | 2005-02-17 | Taisho Pharmaceutical Co., Ltd. | Hair growth stimulant compositions |
Also Published As
| Publication number | Publication date |
|---|---|
| AU3323299A (en) | 1999-11-08 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| NAA1 | Application designating australia and claiming priority from australian document |
Free format text: 199803107 |
|
| TC | Change of applicant's name (sec. 104) |
Owner name: CONNETICS AUSTRALIA PTY LTD Free format text: FORMER NAME: SOLTEC RESEARCH PTY. LTD. |
|
| FGA | Letters patent sealed or granted (standard patent) | ||
| MK14 | Patent ceased section 143(a) (annual fees not paid) or expired |