CA2437592A1 - Malic acid addition salts of terbinafine - Google Patents
Malic acid addition salts of terbinafine Download PDFInfo
- Publication number
- CA2437592A1 CA2437592A1 CA002437592A CA2437592A CA2437592A1 CA 2437592 A1 CA2437592 A1 CA 2437592A1 CA 002437592 A CA002437592 A CA 002437592A CA 2437592 A CA2437592 A CA 2437592A CA 2437592 A1 CA2437592 A1 CA 2437592A1
- Authority
- CA
- Canada
- Prior art keywords
- terbinafine
- compound
- malic acid
- compound according
- formula
- 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.)
- Abandoned
Links
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 title claims abstract description 44
- 150000003839 salts Chemical class 0.000 title claims abstract description 28
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 title claims abstract description 24
- 239000001630 malic acid Substances 0.000 title claims abstract description 11
- 235000011090 malic acid Nutrition 0.000 title claims abstract description 11
- DOMXUEMWDBAQBQ-WEVVVXLNSA-N terbinafine Chemical class C1=CC=C2C(CN(C\C=C\C#CC(C)(C)C)C)=CC=CC2=C1 DOMXUEMWDBAQBQ-WEVVVXLNSA-N 0.000 title description 59
- 229960002722 terbinafine Drugs 0.000 title description 51
- 150000001875 compounds Chemical class 0.000 claims abstract description 66
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 13
- 238000002360 preparation method Methods 0.000 claims abstract description 10
- 229910052739 hydrogen Inorganic materials 0.000 claims description 36
- 239000001257 hydrogen Substances 0.000 claims description 26
- 229940049920 malate Drugs 0.000 claims description 25
- 238000011282 treatment Methods 0.000 claims description 18
- 208000010195 Onychomycosis Diseases 0.000 claims description 16
- 201000005882 tinea unguium Diseases 0.000 claims description 15
- 239000012458 free base Substances 0.000 claims description 12
- 238000000034 method Methods 0.000 claims description 11
- 238000002560 therapeutic procedure Methods 0.000 claims description 11
- 239000003814 drug Substances 0.000 claims description 6
- 239000003085 diluting agent Substances 0.000 claims description 5
- 208000015181 infectious disease Diseases 0.000 claims description 5
- 208000031888 Mycoses Diseases 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 201000010099 disease Diseases 0.000 claims description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 3
- 230000002538 fungal effect Effects 0.000 claims description 3
- 201000009890 sinusitis Diseases 0.000 claims description 3
- 238000009109 curative therapy Methods 0.000 claims description 2
- 230000000069 prophylactic effect Effects 0.000 claims description 2
- 238000011321 prophylaxis Methods 0.000 claims description 2
- 239000011541 reaction mixture Substances 0.000 claims description 2
- 230000001857 anti-mycotic effect Effects 0.000 abstract description 4
- 239000002543 antimycotic Substances 0.000 abstract description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 38
- 239000000203 mixture Substances 0.000 description 26
- 210000000282 nail Anatomy 0.000 description 18
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 14
- 239000013078 crystal Substances 0.000 description 14
- 239000000243 solution Substances 0.000 description 13
- 229940093499 ethyl acetate Drugs 0.000 description 12
- 235000019439 ethyl acetate Nutrition 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
- 230000002411 adverse Effects 0.000 description 11
- 238000009472 formulation Methods 0.000 description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- 241000233866 Fungi Species 0.000 description 9
- 239000002585 base Substances 0.000 description 9
- 238000000634 powder X-ray diffraction Methods 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- 239000000725 suspension Substances 0.000 description 8
- 238000004458 analytical method Methods 0.000 description 7
- 210000004906 toe nail Anatomy 0.000 description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000002775 capsule Substances 0.000 description 6
- 229960000699 terbinafine hydrochloride Drugs 0.000 description 6
- 230000036470 plasma concentration Effects 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 238000002425 crystallisation Methods 0.000 description 4
- 230000035515 penetration Effects 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 210000003491 skin Anatomy 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- BJEPYKJPYRNKOW-UWTATZPHSA-N (R)-malic acid Chemical compound OC(=O)[C@H](O)CC(O)=O BJEPYKJPYRNKOW-UWTATZPHSA-N 0.000 description 3
- 208000030507 AIDS Diseases 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 238000004090 dissolution Methods 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 230000002349 favourable effect Effects 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 239000012729 immediate-release (IR) formulation Substances 0.000 description 3
- 239000004922 lacquer Substances 0.000 description 3
- 238000005567 liquid scintillation counting Methods 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- -1 (E)-N-methyl-6 Chemical compound 0.000 description 2
- 206010060933 Adverse event Diseases 0.000 description 2
- VVJKKWFAADXIJK-UHFFFAOYSA-N Allylamine Chemical class NCC=C VVJKKWFAADXIJK-UHFFFAOYSA-N 0.000 description 2
- 241001480043 Arthrodermataceae Species 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
- 108010001237 Cytochrome P-450 CYP2D6 Proteins 0.000 description 2
- 102100021704 Cytochrome P450 2D6 Human genes 0.000 description 2
- HCYAFALTSJYZDH-UHFFFAOYSA-N Desimpramine Chemical compound C1CC2=CC=CC=C2N(CCCNC)C2=CC=CC=C21 HCYAFALTSJYZDH-UHFFFAOYSA-N 0.000 description 2
- 241001480036 Epidermophyton floccosum Species 0.000 description 2
- 239000001828 Gelatine Substances 0.000 description 2
- 241000725303 Human immunodeficiency virus Species 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- PHVGLTMQBUFIQQ-UHFFFAOYSA-N Nortryptiline Chemical compound C1CC2=CC=CC=C2C(=CCCNC)C2=CC=CC=C21 PHVGLTMQBUFIQQ-UHFFFAOYSA-N 0.000 description 2
- RGCVKNLCSQQDEP-UHFFFAOYSA-N Perphenazine Chemical compound C1CN(CCO)CCN1CCCN1C2=CC(Cl)=CC=C2SC2=CC=CC=C21 RGCVKNLCSQQDEP-UHFFFAOYSA-N 0.000 description 2
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 2
- 241000223238 Trichophyton Species 0.000 description 2
- 241001045770 Trichophyton mentagrophytes Species 0.000 description 2
- 241000223229 Trichophyton rubrum Species 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 2
- BGTOWKSIORTVQH-UHFFFAOYSA-N cyclopentanone Chemical compound O=C1CCCC1 BGTOWKSIORTVQH-UHFFFAOYSA-N 0.000 description 2
- 230000037304 dermatophytes Effects 0.000 description 2
- 229960003914 desipramine Drugs 0.000 description 2
- 206010012601 diabetes mellitus Diseases 0.000 description 2
- 239000007884 disintegrant Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- PJWPNDMDCLXCOM-UHFFFAOYSA-N encainide Chemical compound C1=CC(OC)=CC=C1C(=O)NC1=CC=CC=C1CCC1N(C)CCCC1 PJWPNDMDCLXCOM-UHFFFAOYSA-N 0.000 description 2
- 229960001142 encainide Drugs 0.000 description 2
- 238000011049 filling Methods 0.000 description 2
- 239000012065 filter cake Substances 0.000 description 2
- 210000004904 fingernail bed Anatomy 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 150000004701 malic acid derivatives Chemical class 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- IUBSYMUCCVWXPE-UHFFFAOYSA-N metoprolol Chemical compound COCCC1=CC=C(OCC(O)CNC(C)C)C=C1 IUBSYMUCCVWXPE-UHFFFAOYSA-N 0.000 description 2
- 229960002237 metoprolol Drugs 0.000 description 2
- 238000000386 microscopy Methods 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 229960001158 nortriptyline Drugs 0.000 description 2
- 238000013148 permeation assay Methods 0.000 description 2
- 229960000762 perphenazine Drugs 0.000 description 2
- 238000009519 pharmacological trial Methods 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- JWHAUXFOSRPERK-UHFFFAOYSA-N propafenone Chemical compound CCCNCC(O)COC1=CC=CC=C1C(=O)CCC1=CC=CC=C1 JWHAUXFOSRPERK-UHFFFAOYSA-N 0.000 description 2
- 229960000203 propafenone Drugs 0.000 description 2
- 239000011369 resultant mixture Substances 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 239000007916 tablet composition Substances 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- 208000004998 Abdominal Pain Diseases 0.000 description 1
- 208000010470 Ageusia Diseases 0.000 description 1
- 201000004384 Alopecia Diseases 0.000 description 1
- 206010002198 Anaphylactic reaction Diseases 0.000 description 1
- 208000006820 Arthralgia Diseases 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 208000007163 Dermatomycoses Diseases 0.000 description 1
- 208000008960 Diabetic foot Diseases 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- IIUZTXTZRGLYTI-UHFFFAOYSA-N Dihydrogriseofulvin Natural products COC1CC(=O)CC(C)C11C(=O)C(C(OC)=CC(OC)=C2Cl)=C2O1 IIUZTXTZRGLYTI-UHFFFAOYSA-N 0.000 description 1
- 206010013911 Dysgeusia Diseases 0.000 description 1
- 206010014935 Enzyme abnormality Diseases 0.000 description 1
- 241001480035 Epidermophyton Species 0.000 description 1
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 1
- 208000010201 Exanthema Diseases 0.000 description 1
- 206010017533 Fungal infection Diseases 0.000 description 1
- 206010017711 Gangrene Diseases 0.000 description 1
- UXWOXTQWVMFRSE-UHFFFAOYSA-N Griseoviridin Natural products O=C1OC(C)CC=C(C(NCC=CC=CC(O)CC(O)C2)=O)SCC1NC(=O)C1=COC2=N1 UXWOXTQWVMFRSE-UHFFFAOYSA-N 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 206010019754 Hepatitis cholestatic Diseases 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 206010062016 Immunosuppression Diseases 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 241001480037 Microsporum Species 0.000 description 1
- 208000000112 Myalgia Diseases 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- DDUHZTYCFQRHIY-UHFFFAOYSA-N Negwer: 6874 Natural products COC1=CC(=O)CC(C)C11C(=O)C(C(OC)=CC(OC)=C2Cl)=C2O1 DDUHZTYCFQRHIY-UHFFFAOYSA-N 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 208000003251 Pruritus Diseases 0.000 description 1
- 206010062237 Renal impairment Diseases 0.000 description 1
- 206010040914 Skin reaction Diseases 0.000 description 1
- 206010042033 Stevens-Johnson syndrome Diseases 0.000 description 1
- 231100000168 Stevens-Johnson syndrome Toxicity 0.000 description 1
- 208000024780 Urticaria Diseases 0.000 description 1
- 206010047571 Visual impairment Diseases 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 235000019666 ageusia Nutrition 0.000 description 1
- 238000002266 amputation Methods 0.000 description 1
- 230000036783 anaphylactic response Effects 0.000 description 1
- 208000003455 anaphylaxis Diseases 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 229940072107 ascorbate Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 229960000074 biopharmaceutical Drugs 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
- 239000007963 capsule composition Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 231100000838 cholestatic hepatitis Toxicity 0.000 description 1
- 208000019425 cirrhosis of liver Diseases 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 229940109239 creatinine Drugs 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 239000004205 dimethyl polysiloxane Substances 0.000 description 1
- 235000013870 dimethyl polysiloxane Nutrition 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 201000006549 dyspepsia Diseases 0.000 description 1
- 201000005884 exanthem Diseases 0.000 description 1
- 206010016256 fatigue Diseases 0.000 description 1
- 210000004905 finger nail Anatomy 0.000 description 1
- 206010016766 flatulence Diseases 0.000 description 1
- WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 1
- 208000024386 fungal infectious disease Diseases 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 229960002867 griseofulvin Drugs 0.000 description 1
- DDUHZTYCFQRHIY-RBHXEPJQSA-N griseofulvin Chemical compound COC1=CC(=O)C[C@@H](C)[C@@]11C(=O)C(C(OC)=CC(OC)=C2Cl)=C2O1 DDUHZTYCFQRHIY-RBHXEPJQSA-N 0.000 description 1
- 210000004209 hair Anatomy 0.000 description 1
- 208000024963 hair loss Diseases 0.000 description 1
- 230000003676 hair loss Effects 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 1
- 229940011051 isopropyl acetate Drugs 0.000 description 1
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 235000012054 meals Nutrition 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 238000003801 milling Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 208000004235 neutropenia Diseases 0.000 description 1
- CXQXSVUQTKDNFP-UHFFFAOYSA-N octamethyltrisiloxane Chemical compound C[Si](C)(C)O[Si](C)(C)O[Si](C)(C)C CXQXSVUQTKDNFP-UHFFFAOYSA-N 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 208000033808 peripheral neuropathy Diseases 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 239000000902 placebo Substances 0.000 description 1
- 229940068196 placebo Drugs 0.000 description 1
- 238000004987 plasma desorption mass spectroscopy Methods 0.000 description 1
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000955 prescription drug Substances 0.000 description 1
- 208000037920 primary disease Diseases 0.000 description 1
- 206010037844 rash Diseases 0.000 description 1
- 210000001525 retina Anatomy 0.000 description 1
- 239000000565 sealant Substances 0.000 description 1
- 229920002379 silicone rubber Polymers 0.000 description 1
- 231100000430 skin reaction Toxicity 0.000 description 1
- 230000035483 skin reaction Effects 0.000 description 1
- 230000000391 smoking effect Effects 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- 238000003892 spreading Methods 0.000 description 1
- 210000000434 stratum corneum Anatomy 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- BWMISRWJRUSYEX-SZKNIZGXSA-N terbinafine hydrochloride Chemical compound Cl.C1=CC=C2C(CN(C\C=C\C#CC(C)(C)C)C)=CC=CC2=C1 BWMISRWJRUSYEX-SZKNIZGXSA-N 0.000 description 1
- 238000011285 therapeutic regimen Methods 0.000 description 1
- 206010043554 thrombocytopenia Diseases 0.000 description 1
- 201000004647 tinea pedis Diseases 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 239000012049 topical pharmaceutical composition Substances 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 230000036642 wellbeing Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
- A61K31/137—Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/16—Otologicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/10—Antimycotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P41/00—Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C211/00—Compounds containing amino groups bound to a carbon skeleton
- C07C211/01—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms
- C07C211/26—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing at least one six-membered aromatic ring
- C07C211/30—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing at least one six-membered aromatic ring the six-membered aromatic ring being part of a condensed ring system formed by two rings
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Emergency Medicine (AREA)
- Epidemiology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Surgery (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Seasonings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0103046.9A GB0103046D0 (en) | 2001-02-07 | 2001-02-07 | Organic Compounds |
| GB0103046.9 | 2001-02-07 | ||
| PCT/EP2002/001249 WO2002070455A1 (en) | 2001-02-07 | 2002-02-06 | Malic acid addition salts of terbinafine |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2437592A1 true CA2437592A1 (en) | 2002-09-12 |
Family
ID=9908301
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002437592A Abandoned CA2437592A1 (en) | 2001-02-07 | 2002-02-06 | Malic acid addition salts of terbinafine |
Country Status (27)
| Country | Link |
|---|---|
| US (2) | US20040147603A1 (enExample) |
| EP (1) | EP1370513B1 (enExample) |
| JP (1) | JP4078206B2 (enExample) |
| KR (2) | KR20080041756A (enExample) |
| CN (1) | CN1216034C (enExample) |
| AT (1) | ATE294154T1 (enExample) |
| AU (1) | AU2002238534C1 (enExample) |
| BR (1) | BR0207077A (enExample) |
| CA (1) | CA2437592A1 (enExample) |
| CZ (1) | CZ20032132A3 (enExample) |
| DE (1) | DE60203890T2 (enExample) |
| DK (1) | DK1370513T3 (enExample) |
| EC (1) | ECSP034713A (enExample) |
| ES (1) | ES2240698T3 (enExample) |
| GB (1) | GB0103046D0 (enExample) |
| HU (1) | HUP0303174A3 (enExample) |
| IL (2) | IL157241A0 (enExample) |
| MX (1) | MXPA03007072A (enExample) |
| NO (1) | NO20033473L (enExample) |
| NZ (1) | NZ527300A (enExample) |
| PL (1) | PL204812B1 (enExample) |
| PT (1) | PT1370513E (enExample) |
| RU (1) | RU2289570C2 (enExample) |
| SI (1) | SI1370513T1 (enExample) |
| SK (1) | SK9992003A3 (enExample) |
| WO (1) | WO2002070455A1 (enExample) |
| ZA (1) | ZA200306029B (enExample) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20050209339A1 (en) * | 2002-07-02 | 2005-09-22 | Ercem Atillasoy | Methods for the treatment of sinusitis |
| GB0503942D0 (en) * | 2005-02-25 | 2005-04-06 | Novartis Ag | Purification process |
| RU2286144C2 (ru) * | 2004-12-02 | 2006-10-27 | Государственное научное учреждение Институт экспериментальной ветеринарии Сибири и Дальнего Востока Сибирского отделения Россельхозакадемии (ГНУ ИЭВСиДВ СО РАСХН) | Способ лечения микроспории кошек |
| WO2007104474A1 (en) * | 2006-03-10 | 2007-09-20 | Novartis Ag | Antifungal compositions comprising (1) a salt of terbinafine with malic acid and (2) malic acid |
| EP2043604A2 (en) | 2006-06-14 | 2009-04-08 | Dr. Reddy's Laboratories Ltd. | Topical compositions |
| RU2350343C1 (ru) * | 2007-08-13 | 2009-03-27 | Государственное научное учреждение Институт экспериментальной ветеринарии Сибири и Дальнего Востока Сибирского отделения Россельхозакадемии (ГНУ ИЭВС и ДВ СО Россельхозакадемии) | Способ лечения микроспории кошек |
| KR101733773B1 (ko) | 2009-01-16 | 2017-05-10 | 엑셀리시스, 인코포레이티드 | Ｎ-（４-｛〔６，７-비스（메틸옥시）퀴놀린-4-일〕옥시｝페닐）-ｎ＇-（４-플루오로페닐）사이클로프로판-1,1-디카르복사미드의 말산염 및 그 결정형 |
| CN106106449A (zh) * | 2016-06-21 | 2016-11-16 | 广西中烟工业有限责任公司 | 特比萘芬制剂及其在提高烟叶角鲨烯含量中的应用 |
Family Cites Families (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3507755A (en) * | 1967-10-17 | 1970-04-21 | Bayer Ag | Process for the purification of acrylonitrile by distillation with side stream withdrawal and decantation |
| US4276125A (en) | 1979-02-02 | 1981-06-30 | Asahi Kasei Kogyo Kabushiki Kaisha | Process for purification of crude olefinically unsaturated nitrile and condenser useful for same process |
| US4269667A (en) | 1979-08-02 | 1981-05-26 | Standard Oil Company | Acrylonitrile purification by extractive distillation |
| ATE10272T1 (de) * | 1979-08-22 | 1984-11-15 | Sandoz Ag | Propenylamine, verfahren zu ihrer herstellung, sie enthaltende pharmazeutische zusammensetzungen und ihre verwendung als arzneimittel. |
| KR850001603B1 (ko) | 1980-12-03 | 1985-10-24 | 아사히 가세이 고오교오 가부시기가이샤 | 불포화 니트릴의 제조법 |
| GB8608335D0 (en) | 1986-04-04 | 1986-05-08 | Pfizer Ltd | Pharmaceutically acceptable salts |
| NZ227042A (en) * | 1987-11-27 | 1991-05-28 | Banyu Pharma Co Ltd | Substituted alkylamine derivatives and pharmaceutical compositions |
| US6005001A (en) | 1991-05-20 | 1999-12-21 | Novartis Ag (Formerly Sandoz Ag) | Pharmaceutical composition |
| HU223343B1 (hu) * | 1991-05-20 | 2004-06-28 | Novartis Ag. | Allil-amin-származékot tartalmazó gyógyászati készítmények és eljárás azok előállítására |
| HU219480B (hu) | 1991-05-23 | 2001-04-28 | Novartis Ag. | Eljárás gombás körömmegbetegségek ellen helyileg alkalmazható, allil-amin-származékot tartalmazó gyógyászati készítmények előállítására |
| US5461068A (en) * | 1993-09-29 | 1995-10-24 | Corwood Laboratories, Inc. | Imidazole derivative tincture and method of manufacture |
| DE4400770C1 (de) * | 1994-01-13 | 1995-02-02 | Lohmann Therapie Syst Lts | Wirkstoffhaltiges Pflaster zur Abgabe von Estradiol mit mindestens einem Penetrationsverstärker, Verfahren zu seiner Herstellung und seine Verwendung |
| NZ280065A (en) * | 1995-09-20 | 1998-04-27 | Apotex Inc | Preparation of n-alkyl-n-(1-naphthylmethyl)alk-2-en-4-ynylamine derivatives |
| CA2285368A1 (en) * | 1997-03-31 | 1998-10-08 | Johnson & Johnson Consumer Companies Inc. | Solvent system for enhanced penetration of pharmaceutical compounds |
| WO1999049895A2 (en) | 1998-03-31 | 1999-10-07 | Johnson And Johnson Consumer Companies, Inc. | Method for increasing the permeability of horny human tissue |
| US6231875B1 (en) | 1998-03-31 | 2001-05-15 | Johnson & Johnson Consumer Companies, Inc. | Acidified composition for topical treatment of nail and skin conditions |
| AU758679B2 (en) * | 1998-07-24 | 2003-03-27 | Seo Hong Yoo | Preparation of aqueous clear solution dosage forms with bile acids |
| JP2000053681A (ja) | 1998-08-10 | 2000-02-22 | Sankyo Co Ltd | 三環性複素環化合物を含有する抗菌剤 |
| ATE245624T1 (de) | 1999-10-22 | 2003-08-15 | Richter Gedeon Vegyeszet | Verfahren zur herstellung substituierter allylamin derivative und deren salze |
| GB0014448D0 (en) | 2000-06-13 | 2000-08-09 | Novartis Ag | Organic compounds |
| JP4899139B2 (ja) | 2000-08-10 | 2012-03-21 | 株式会社ポーラファルマ | 抗真菌医薬組成物 |
| JP4803511B2 (ja) | 2000-08-25 | 2011-10-26 | 株式会社ポーラファルマ | 抗真菌医薬組成物 |
| JP2002068975A (ja) | 2000-08-25 | 2002-03-08 | Pola Chem Ind Inc | 抗真菌医薬組成物 |
-
2001
- 2001-02-07 GB GBGB0103046.9A patent/GB0103046D0/en not_active Ceased
-
2002
- 2002-02-06 PT PT02704689T patent/PT1370513E/pt unknown
- 2002-02-06 SI SI200230146T patent/SI1370513T1/xx unknown
- 2002-02-06 RU RU2003126176/04A patent/RU2289570C2/ru not_active IP Right Cessation
- 2002-02-06 BR BR0207077-4A patent/BR0207077A/pt not_active IP Right Cessation
- 2002-02-06 AT AT02704689T patent/ATE294154T1/de not_active IP Right Cessation
- 2002-02-06 JP JP2002569776A patent/JP4078206B2/ja not_active Expired - Fee Related
- 2002-02-06 MX MXPA03007072A patent/MXPA03007072A/es active IP Right Grant
- 2002-02-06 EP EP02704689A patent/EP1370513B1/en not_active Expired - Lifetime
- 2002-02-06 KR KR1020087010521A patent/KR20080041756A/ko not_active Withdrawn
- 2002-02-06 AU AU2002238534A patent/AU2002238534C1/en not_active Ceased
- 2002-02-06 KR KR1020037010291A patent/KR100859609B1/ko not_active Expired - Fee Related
- 2002-02-06 IL IL15724102A patent/IL157241A0/xx unknown
- 2002-02-06 CA CA002437592A patent/CA2437592A1/en not_active Abandoned
- 2002-02-06 NZ NZ527300A patent/NZ527300A/en unknown
- 2002-02-06 CZ CZ20032132A patent/CZ20032132A3/cs unknown
- 2002-02-06 DE DE60203890T patent/DE60203890T2/de not_active Expired - Lifetime
- 2002-02-06 US US10/470,885 patent/US20040147603A1/en not_active Abandoned
- 2002-02-06 SK SK999-2003A patent/SK9992003A3/sk not_active Application Discontinuation
- 2002-02-06 HU HU0303174A patent/HUP0303174A3/hu unknown
- 2002-02-06 CN CN028046080A patent/CN1216034C/zh not_active Expired - Fee Related
- 2002-02-06 PL PL362554A patent/PL204812B1/pl not_active IP Right Cessation
- 2002-02-06 ES ES02704689T patent/ES2240698T3/es not_active Expired - Lifetime
- 2002-02-06 WO PCT/EP2002/001249 patent/WO2002070455A1/en not_active Ceased
- 2002-02-06 DK DK02704689T patent/DK1370513T3/da active
-
2003
- 2003-08-04 IL IL157241A patent/IL157241A/en not_active IP Right Cessation
- 2003-08-05 NO NO20033473A patent/NO20033473L/no not_active Application Discontinuation
- 2003-08-05 ZA ZA200306029A patent/ZA200306029B/en unknown
- 2003-08-06 EC EC2003004713A patent/ECSP034713A/es unknown
-
2006
- 2006-11-29 US US11/606,268 patent/US7488759B2/en not_active Expired - Fee Related
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US6696496B2 (en) | Low water-soluble venlafaxine salts | |
| US20100190859A1 (en) | Citrate Salt of Rasagiline | |
| US20180071230A1 (en) | Formulations, salts and polymorphs of transnorsertraline and uses thereof | |
| EP1370513B1 (en) | Malic acid addition salts of terbinafine | |
| US20030191347A1 (en) | Venlafaxine base | |
| AU2002238534A1 (en) | Malic acid addition salts of terbinafine | |
| US8022104B2 (en) | Formulations of ladostigil tartrate | |
| US7393977B2 (en) | Dicarboxylic acid salt of sibutramine | |
| CN1295229C (zh) | 紫杉烷衍生物的结晶及其制备方法 | |
| SG188472A1 (en) | Prodrugs of guanfacine | |
| HK1060876B (en) | Malic acid addition salts of terbinafine | |
| EP1846360A1 (en) | A sulphonic acid salt of sibutramine | |
| MXPA01005255A (es) | El uso de ciclobutilalquil aminas sustituidas con arilo para tratar incontinencia urinaria. | |
| US20050013858A1 (en) | Oral pharmaceutical compositions containing terbinafine | |
| CN120865120A (zh) | 一种利鲁唑对甲苯磺酸盐及其制备方法 | |
| CN117756723A (zh) | 一种egfr抑制剂的衍生物及其应用 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |