NO339538B1 - Blanding for behandling av inflammatoriske sykdommer - Google Patents
Blanding for behandling av inflammatoriske sykdommer Download PDFInfo
- Publication number
- NO339538B1 NO339538B1 NO20075660A NO20075660A NO339538B1 NO 339538 B1 NO339538 B1 NO 339538B1 NO 20075660 A NO20075660 A NO 20075660A NO 20075660 A NO20075660 A NO 20075660A NO 339538 B1 NO339538 B1 NO 339538B1
- Authority
- NO
- Norway
- Prior art keywords
- mixture
- use according
- acid
- salts
- inflammatory
- Prior art date
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- 239000000203 mixture Substances 0.000 title claims description 111
- 238000011282 treatment Methods 0.000 title claims description 16
- 208000027866 inflammatory disease Diseases 0.000 title claims description 11
- 150000001875 compounds Chemical class 0.000 claims description 47
- 150000002632 lipids Chemical class 0.000 claims description 46
- 239000002502 liposome Substances 0.000 claims description 43
- 239000004480 active ingredient Substances 0.000 claims description 32
- 150000003904 phospholipids Chemical class 0.000 claims description 32
- 150000003839 salts Chemical class 0.000 claims description 25
- 239000000739 antihistaminic agent Substances 0.000 claims description 22
- 230000003110 anti-inflammatory effect Effects 0.000 claims description 20
- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 claims description 19
- 230000001387 anti-histamine Effects 0.000 claims description 17
- 239000003795 chemical substances by application Substances 0.000 claims description 16
- 229930186217 Glycolipid Natural products 0.000 claims description 14
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 14
- 208000006673 asthma Diseases 0.000 claims description 13
- HVCOBJNICQPDBP-UHFFFAOYSA-N 3-[3-[3,5-dihydroxy-6-methyl-4-(3,4,5-trihydroxy-6-methyloxan-2-yl)oxyoxan-2-yl]oxydecanoyloxy]decanoic acid;hydrate Chemical compound O.OC1C(OC(CC(=O)OC(CCCCCCC)CC(O)=O)CCCCCCC)OC(C)C(O)C1OC1C(O)C(O)C(O)C(C)O1 HVCOBJNICQPDBP-UHFFFAOYSA-N 0.000 claims description 12
- 239000002253 acid Substances 0.000 claims description 11
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- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 7
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- QZXMUPATKGLZAP-DXLAUQRQSA-N [(2S)-1-hexadecanoyloxy-3-[(2R,3R,4S,5R,6R)-3,4,5-trihydroxy-6-[[(2S,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxymethyl]oxan-2-yl]oxypropan-2-yl] (9Z,12Z)-octadeca-9,12-dienoate Chemical compound O[C@@H]1[C@H](O)[C@@H](O)[C@H](OC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCC\C=C/C\C=C/CCCCC)O[C@@H]1CO[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 QZXMUPATKGLZAP-DXLAUQRQSA-N 0.000 claims description 5
- ATBOMIWRCZXYSZ-XZBBILGWSA-N [1-[2,3-dihydroxypropoxy(hydroxy)phosphoryl]oxy-3-hexadecanoyloxypropan-2-yl] (9e,12e)-octadeca-9,12-dienoate Chemical compound CCCCCCCCCCCCCCCC(=O)OCC(COP(O)(=O)OCC(O)CO)OC(=O)CCCCCCC\C=C\C\C=C\CCCCC ATBOMIWRCZXYSZ-XZBBILGWSA-N 0.000 claims description 5
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- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 claims description 5
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 claims description 4
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- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 claims description 4
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- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 claims description 4
- WWUZIQQURGPMPG-KRWOKUGFSA-N sphingosine Chemical compound CCCCCCCCCCCCC\C=C\[C@@H](O)[C@@H](N)CO WWUZIQQURGPMPG-KRWOKUGFSA-N 0.000 claims description 4
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- DSNRWDQKZIEDDB-GCMPNPAFSA-N [(2r)-3-[2,3-dihydroxypropoxy(hydroxy)phosphoryl]oxy-2-[(z)-octadec-9-enoyl]oxypropyl] (z)-octadec-9-enoate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@H](COP(O)(=O)OCC(O)CO)OC(=O)CCCCCCC\C=C/CCCCCCCC DSNRWDQKZIEDDB-GCMPNPAFSA-N 0.000 claims description 3
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- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical group [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 claims description 3
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Description
Oppfinnelsen angår en homogen farmasøytisk blanding for bruk i behandling av inflammatoriske sykdommer.
Bakgrunn
Det fines mange sykdommer/lidelser som har en inflammatorisk natur. Inflammatoriske sykdommer som påvirker befolkningen er astma, inflammatorisk tarmsykdom, reumatoid artritt, slitasjegikt, ri nitt, bindehinnekatarr og dermatitt.
Inflammasjon er også en årsak til smerte. Inflammatorisk smerte kan oppstå av flere årsaker, slik som infeksjon, kirurgi eller trauma. Dessuten er flere sykdommer inkludert kreft og kardiovaskulære sykdommer kjent for å ha inflammatoriske komponenter som gir et bidrag til pasientens symptomatologi.
Astma er en sykdom i luftveiene som inneholder elementer fra både inflammasjon og bronkieforsnevring. Behandlingsregimer for astma er basert på tilstandens alvorlighetsgrad. Milde tilfeller blir enten ikke behandlet eller behandles kun med inhalerte p-agonister som påvirker bronkieinnsnevringselementet, mens pasienter med mer alvorlig astma typisk behandles jevnlig med inhalerte kortikosteroider som i stor grad er antiinflammatorisk av natur. En ny preventiv terapi for astma virker ved å blokkere produksjonen av proinflammatoriske leukotiener og cytokinerved å inhibere enzymet 5-lipoksygenase.
Allergisk og ikke-allergisk rinitt er vanlige lidelser som påvirker omlag 30 % av befolkningen. Rinitt har en betydelig påvirkning på livskvaliteten. Rinitt er faktisk ansett for å påvirke livskvaliteten i større grad enn eksempelvis astma.
Høysnue og permanent allergisk rinitt er kjennetegnet ved nysing, rhinoré, nasal kongestion, pruritus,øyekatarr og faryngitt. I permanent rinitt, er kronisk nasal obstruksjon ofte framtredene og kan utvikles til obstruksjon av eustatisk rør.
Orale eller lokale antihistaminer er førstelinjebehandling, og nasale steroider andrelinjebehandling for rinitt. For de fleste pasientene gir lokale kortikosteroider og langtidsvirkende antihistaminmidler en vesentlig lindring av symptomer. Antihistaminer kan også påvirke ikke-immunologiske (non-lgE)-formidlet overfølsomme reaksjoner slik som ikke-allergisk rinitt, treningsindusert astma, kald urtikaria og ikke-spefikk bronkial hyperreaktivitet.
De viktigste kliniske effekter av antihistaminer inkluderer redusert nysing og rhinoré. Nasal blokkering ser imidlertid ut til å være mindre mottakelig. Lokal administrering av antihistaminer
(slik som azelastin og levocabastin) har fordeler, inkludert rask inntreden av effekt og færre bivirkninger.
Inflammatorisk smerte kan reduseres ved inhibering av enzymet syklooksygenase (COX). COX-enzymet foreligger i to former, en som hovedsakelig uttrykkes i mange celler og vev (COX-1), og en som induseres ved proinflammatoriske stimuli, slik som cytokiner, under en inflammatorisk respons (COX-2).
COX-enzymer metaboliserer arakidonsyre til det ustabile mellomproduktet prostaglandin H2(PGH2). PGH2metaboliseres videre til andre prostaglandiner inkludert PGE2, PGF2a, PGD2, prostasyklin og tromboxan A2. Disse arakidonsyre-metabolittene er kjent for å ha en utstrakt fysiologisk og patofysiologisk aktivitet inkludert proinflammatoriske effekter.
PGE2er særlig kjent for å være en sterk proinflammatorisk bidragsyter, og er også kjent for å indusere feber og smerte. Som en følge av dette har det blitt utviklet en rekke medikamenter med henblikk på å inhibere dannelsen av PGE2, inkludert "NSAIDs" (ikke-steroidale antiinflammatoriske medikamenter) og "coxibs" (selektive COX-2-inhibitorer). Disse medikamentene virker hovedsakelig ved inhibering av COX-1 og/eller COX-1, for derved å redusere dannelsen av PGE2.
Leukotrienene (LTs) dannes fra arakidonsyre ved hjelp av et sett av enzymer som er forskjellig fra de i COX/PGES-alternativet. Nøkkelenzymet i leukotrienbiosyntesen er 5-lipozygenase (5-LO), som i en totrinns reaksjon katalyserer dannelsen av LTA4fra arakidonsyre. Leukotrien A4 kan metaboliseres ytterligere til Leukotrien B4, en reaksjon katalysert av LTA4hydrolase. Cellulær leukotrienbiosyntese er avhengig av 5-lipoksygenase-aktiverende protein (FLAP), et membranbundet protein som binder arakidonsyre og fremmer 5-lipoksygenasereaksjonen. Leukotrien B4er kjent for å være en sterk proinflammatorisk bidragsyter, mens de cystei ny I holdige leukotrienene C4, D4 og E4(CysLTs) er svært effektfulle bronkieforsnevrere og proinflammatoriske bidragsytere som har blitt involvert i patobiologien for astma og inflammasjon. De markedsførte 5-LO-inhibitorer og antagonister for cysteinylholdige leukotrienreseptorer 1 og 2 representerer følgelig do nye klasser anti-inflammatoriske behandlingsmetoder, mens utviklingen av markedsførte FLAP-inhibitorer, leukotrien A4hydrolaseinhibitorer, leukotrien B4reseptorantagonister kan etablere ytterligere nye klasser med anti-inflammatorisk behandling.
Fosfodiesterase type 4 (PDE 4) spiller en viktig rolle i regulering av aktiviteten for celler som er involvert i de inflammatoriske prosessene som finner sted i kronisk obstruktiv lungeforstyrrelse (COPD) og astma. PDE4-inhibitorer representerer en ny klasse medikament som har potensial til å inhibere bronkieforsnevring så vel som inhibere inflammatorisk celleaktivitet (inkludert inhibering av produksjonen av leukotriener).
Liposomer (også kjent som lipide vesikler) er kolloidale partikler som framstilles fra polare lipidmolekyler avledet enten fra naturlige kilder eller kjemisk syntese. Slike sfæriske lukkede strukturer sammensatt av krummede doble lipidlag, brukes typisk til å innkapsle medikamenter, som ofte er cytotoksiske, for å redusere giftighet og/eller øke effekten. Liposom-innkapslede medikamentpreparater er ofte framskaffet i en tørr (for eksempel frysetørket) form, som deretter rekondisjoneres med en vannbasert løsning umiddelbart før administrering. Dette utføres for å minimere muligheten for lekkasje av eksempelvis cytotoksisk medikament til den vannbaserte løsningen og derved redusere liposomets innkapslingseffekt.
Liposomer har også blitt brukt til innkapsling av ulike medikamentforbindelser for tilførsel via den nasale ruten for å fremme biotilgjengelighet eller som et hjelpemiddel. Medikamenter som kan nevnes inkluderer tetanus toksoidvaksine, insulin, desmopressin og difenhydramin-hydroklorid (se Tiirker et al, Review Article: Nasal Route and Drug Delivery Systems, Pharm. World Sei., 2004; 26, 137-142 og litteraturhenvisningene i samme), samt ciprofloxacin, CM3 og salbutamol (se Desai et al, A Facile Method of Delivery of Liposomes by Nebulization, J. Control. Release, 2002; 84, 69-78).
Liposom-innkapslet cetirizin har blitt administrert lokalt for å evaluere perifer antihistaminaktivitet og systemisk absorpsjon i en kaninmodell (Elzainy et al, Cetirizine from Topical Phosphatidylcholine- Hydrogenated Liposomes, The AAPS Journal, 2004; 6, 1-7, se også Drug development and Industrial Pbarma<q>r, 2005; 31, 281-291).
Homogene farmasøytiske blandinger som inneholder cetirizin og et polart lipidliposom er beskrevet i internasjonal patentsøknad WO 2005/107711.
Den lipofile oppførsel av cetirizin i bufret vannbasert fosfatidylcholin-liposomsystemer har også blitt studert (Plemper van Balen G et al., Lipopbilicity bebaviour of the zwitterionic abtibistamine cetirizine in fosfatiidylcboline liposomes/ water systems, Pharm. Res. 2001; 18, 694-701).
Eksempler på andre formuleringer omfatter blant annet liposom-innkapslede aktive bestanddeler er diskutert i US patentskrifter 4,427,649 og 5,569,464, EP patentpublikasjon 0249561, WO patentpublikasjon 00/38681, US patentskrift 4,839,175 og WO patentpublikasjon 98/00111.
Oppfinnelsen
Oppfinnelsen angår en homogen farmasøytisk blanding for bruk i behandlingen av en inflammatorisk lidelse, slik det framgår av patentkrav 1. Ytterligere fordelaktige trekk framgår av de uselvstendige kravene.
En har overraskende nok funnet at irritasjonen som kan være forbundet med (for eksempel nasal) administrering av visse antiinflammatoriske og/eller antihistaminbaserte aktive bestanddeler kan reduseresved bruk av homogene farmasøytiske forbindelser som omfatter slike aktive bestanddeler, et polart lipidliposom og en farmasøytisk akseptabel bærer.
I henhold til oppfinnelsen er det framskaffet en homogen farmasøytisk blanding som er egnet i behandling av en inflammatorisk lidelse som omfatter en antiinflammatorisk og/eller antihistamin aktiv bestanddel, et polart lipidliposom og en farmasøytisk akseptabel vannbasert bærer, forutsatt at den aktive bestanddel ikke er cetirizin, og disse blandingene er i det etterfølgende betegnet som "blandingene ifølge oppfinnelsen".
Fagpersonen vil verdsette at antiinflammatoriske og/eller antihistaminbaserte aktive bestanddeler anvendes i blandinger ifølge oppfinnelsen i en farmakologisk effektiv mengde (se nedenfor). Betegnelsen "farmakologisk effektiv mengde" viser her til en mengde av den antiinflammatoriske og/eller antihistaminbaserte aktive bestanddel, som er i stand til å gi denønskete terapeutiske effekt på en behandlet pasient, hvorvidt administrert alene eller i kombinasjon med andre aktive bestanddeler. En slik effekt kan være objektiv (det vil si målbar ved hjelp av en eller annen form for test eller markør) eller subjektiv (det vil si at subjektet gir en indikasjon på, eller føler, en effekt).
Med "farmasøytiske blandinger" inkluderes her blandinger som er egnet til bruk i direkte administrering til pattedyr, og særlig mennesker. I dette henseende har betegnelsen til hensikt å inkludere formuleringer som bare inkluderer bestanddeler som innen fagområdet er ansett som egnet til administrering til pattedyr, og særlig mennesker. I kontekst av den foreliggende oppfinnelsen, kan betegnelsen også bety at forbindelsene ifølge oppfinnelsen foreligger i en form av en væske som er klar til bruk, direkte fra hylla, og ikke en formulering der medikament er innkapslet inne i liposomer som krever rekondisjonering like før administrering for å unngå lekkasje av medikament fra liposomer til en vannbasert bærer.
Med "homogen" menes her ikke bare blandinger ifølge oppfinnelsen som omfatter liposomer jevnt dispergert i den vannbaserte bæreren, men også at den aktive bestanddel er fordelt i hele blandingen. Dette betyr at medikament, etter framstilling av en blanding som omfattet liposomer og medikament i et vannbasert medium, som ikke er innkapslet i liposom ikke blir fjernet etter liposomdannelse. I tilfellet med visse blandinger ifølge oppfinnelsen kan dette føre til en hovedsakelig lik konsentrasjon av aktiv bestanddel i det relevante vannbaserte mediet, hvorvidt dette mediet er lokalisert inni eller utenfor liposomstrukturene. Med "hovedsakelig lik" menes her at konsentrasjonen kan variere med omlag ± 50 %, slik som omlag ± 40 %, fortrinnsvis omlag ± 30 %, helst omlag ± 20 % og særlig omlag ± 10 % (sammenliknet med konsentrasjoner inne i og utenfor liposomstrukturene) ved romtemperatur og atmosfærisk trykk. Konsentrasjonsprofiler for medikament kan måles med standardteknikker kjent for fagpersonen, slik som<31>P-NMR. Det kan for eksempel anvendes en standard in situ prøveteknikk, eller en teknikk som involverer separasjon av liposomfraksjonen fra den frie vannbaserte bæreren og måling av mengde/konsentrasjon av medikament forbundet med hver fraksjon. Separasjon kan utføres ved sentrifugering, dialyse, ultrafiltrering eller gelfiltrering.
Det er foretrukket at blandingene ifølge oppfinnelsen videre omfatter en farmasøytisk akseptabel buffer med evne til å gi en pH fra omlag 4 (for eksempel 4,0) til omlag 8 (for eksempel 8,0), fortrinnsvis fra omlag pH 5 (for eksempel 5,0) til omlag pH 7 (for eksempel 7,0). Egnede buffere inkluderer de som ikke vil påvirke dannelse av liposomer, slik som fosfat (for eksempel dinatriumfosfat, dikaliumfosfat, natriumdihydrogenfosfat, kalium-dihydrogenfosfat eller fosforsyre pluss base), citrat (for eksempel natriumcitrat eller sitronsyre pluss base), eller acetatbuffer (for eksempel natriumacetat eller etansyre pluss base), som er i stand til å opprettholde en pH innenfor intervallene angitt foran. Det kan brukes buffer i en mengde som er egnet til å gi de ovennevnte effektene, og dette vil verdsettes av fagpersonen uten å avvike fra oppfinnelsen. Egnede mengder ligger eksempelvis i området fra omlag 1 mg/ml til omlag 30 mg/ml.
Betegnelsen "inflammatorisk lidelse" vil av en fagperson bli oppfattet som enhver tilstand kjennetegnet ved en lokal eller systemisk beskyttende respons, som kan framkalles av fysisk trauma, infeksjon, kroniske sykdommer, slik som de omtalt foran, og/eller kjemiske og/eller fysiologiske reaksjoner på eksterne stimuli (for eksempel som en del av en allergisk respons). Enhver slik respons, som kan være vanskelig åødelegge, fortynner eller avsondrer både det skadelige midlet og det skadede vevet, kan fastslås ved eksempelvis varme, hevelse, smerte, rødhet, utvidelse av blodkar og/eller økt blodstrøm, invasjon av det påvirkede området av hvite blodceller, tap av funksjon og/eller ethvert annet symptom kjent for å være forbundet med inflammatoriske tilstander.
Betegnelsen vil følgelig også oppfattes til å inkludere hver inflammatorisk sykdom, lidelse eller tilstand i seg selv, enhver tilstand som har en forbundet inflammatorisk komponent, og/eller enhver tilstand kjennetegnet ved inflammasjon som et symptom, blant annet inkludert akutt, kronisk, ulcerøs, spesifikk, allergisk og nekrotisk inflammasjon, og andre former for inflammasjon som er kjent for fagpersonen. I kontekst av den foreliggende oppfinnelsen, inkluderer følgelig betegnelsen også inflammatorisk smerte, smerte generelt og/eller feber.
Blandinger ifølge oppfinnelsen kan følgelig være nyttige i behandling av astma, kronisk obstruktiv lungesykdom, irritabel tarmsyndrom, inflammatorisk smerte, feber, migrene, hodepine, korsryggsmerte, fibromyalgi, myofacielle sykdommer, virusinfeksjoner (for eksempel influensa, vanlig forkjølelse, herpes zoster, hepatitt C og AIDS), bakterieinfeksjoner, soppinfeksjoner, dysmenorré, forbrenninger, kirurgiske eller dentale prosedyrer, kreft (for eksempel brystkreft, tarmkreft og prostatakreft), hyperprostaglandin E-syndrom, klassisk Barttersyndrom, aterosklerose, gikt, artritt, osteoartritt, barneartritt, reumatoid artritt, ankyloserende spondylitt, Hodgkins sykdom, systemisk lupus erytematosis, vaskulitt, pankreatitt, nyrebetennelse, bursitt, bindehinnekatarr, regnbuehinnebetennelse, skleritt, uveitt, sårheling, dermatitt, eksem, psoriasis, slag, diabetes mellitus, neurodegenerative lidelser slik som Alzheimers sykdom og multippel sklerose, autoimmunsykdommer, allergiske lidelser, rinitt, ulcus, koronar hjertesykdom, sarkoidose og enhver annen sykdom med en inflammatorisk komponent.
Blandinger ifølge oppfinnelsen finner særlig anvendelse i behandling av rinitt, migrene, akutt smerte, kronisk smerte og astma. Betegnelsen "rinitt" skal oppfattes å inkludere enhver irritasjon og/eller inflammasjon i nesen, allergiske som ikke-allergiske, inkludert sesongbetont rinitt (for eksempel forårsaket av utendørs faktorer slik som pollen; høysnue) og/eller vedvarende rinitt (for eksempel forårsaket av husstøvmidd, innendørs mugg osv) samt symptomer på samme.
Betegnelsen "antiinflammatorisk og/eller antihistaminbasert aktiv bestanddel" vil av en fagperson oppfattes å inkludere enhver substans, enten naturlig forekommende eller syntetisk, med antiinflammatoriske og/eller antihistamine egenskaper etter behov. Den antiinflammatoriske klassen av forbindelser omfatter steroidale antiinflammatoriske medikamenter (kortikosteroider) og ikke-steroidale antiinflammatoriske medikamenter (NSAIDs), der sistnevnte omfatter COX-inhibitorer, PDE4-inhibitorer og leukotrienmodifikatorer (for eksempel 5-liposygenase-inhibitorer, inhibitorer for FLAP, LTA4hydrolase-inhibitorer, LTB4reseptorantagonister og CysLT (dvs. CysLTl og CysLT2) reseptorantagonister), mens antihistaminklassen omfatter Ha reseptorantagonister. I kontekst av den foreliggende oppfinnelsen omfatter også betegnelsen "antiinflammatorisk og/eller antihistamin aktiv bestanddel" anti-migreneforbindelser, opioider og analoge til disse. Foretrukne aktive bestanddeler i blandingen ifølge oppfinnelsen omfatter antihistaminbaserte aktive bestanddeler, kortikosteroider og leukotrien-modifikatorer.
Anti-migreneforbindelser som kan nevnes omfatter almotriptan, alpiroprid, dihydroergotamin, eletriptan, ergotamin, matrem, frovatriptan, iprazokhrom, methysergid, naratriptan, pizotifen, rizatriptan, sumatriptan, zolmitriptan og vanlig brukte salter av disse.
Opioider og analoge av samme som kan nevnes inkluderer alfentanil, anileridin, bezitramid, buprenorfin, butorfanol, carfentanil, codein, dextromoramid, dextropropoksyfen, dezocin, diamorfin, dihydrocodein, dipipanon, embutramid, ethoheptazin, etylmorfin, etorphin, fentanyl, hydrocodon, hydromorfon, ketobemidon, levacetylmethadol, levomethadon, levofanol, lofexidin, meptazinol, metadon, morfin, nalbuphin, naltrexon, nikomorfin, opium, oksycodon, oksymorfon, papaveretum, pentazocin, pethidin, fenazocin, fenoperidin, folcodin, piritramid, remifentanil, sufentanil, tilidin, tramadol og vanlig brukte salter av disse.
Steroidale antiinflammatoriske forbindelser som kan nevnes inkluderer alclometason, beclometason, betamethason, budesonid, ciclesonid, clobetasol, clobetason, deflazacort, dexamethason, diflucortolonvalerat, fluocinolonacetonid, fluocinonid, fluocortolon, flupredniden, flurometholon, fluticason, halcinonid, hydrokortison, metylprednisolon, mometason, prednisolon, rimexolon og triamcinolon og vanlig brukte salter av samme. Foretrukne steroidale anti-inflammatoriske forbindelser inkluderer budesonid og fluticason (foreksempel sistnevnte i form av et salt, slik som et propionatsalt).
NSAIDs (inkludert COX-inhibitorer) som kan nevnes inkluderer aceclofenac, acemetacin, acetanilid, alclofenac, alminoprofen, aloxiprin, aminofenazon, aminopropylon, ampiroxicam, amtolmetinguacil, amylsalicylat, aspirin, azapropazon, bendazac, benoxaprofen, benzydamin, beta-aminopropionitril, bornylsalicylat, bromofenac, bufexamac, bumadizon, butibufen, carbasalat, carprofen, celecoxib, clofexamid, clofezon, clonixin, dexketoprofen, diclofenac, diflunisal, dipyron, droxicam, eltenac, epirizol, etodolac, ethenzamid, etylsalicylat, etofenamat, etoricoxib, felbinac, fenbufen, fenoprofen, fentiazac, fepradinol, feprazon, floctafenin, flufenamsyre, flunixin, flunoxaprofen, flurbiprofen, fosfosal, furprofen, glafenin, glucametacin, glykolsalicylat, ibuprofen, ibuproxam, indometacin, ketoprofen, ketorolac, lysinaspirin, mefenamsyre, meloxicam, metylbutenisalicylat, metylsalicylat, nabumeton, naproxen, nedocromil, nifenazon, niflumsyre, nimesulid, oxaprozin, oksyfenbutazon, paracetamol, parecoxib, fenacetin, fenazon, fenylbutazon, picolaminsalicylat, piketoprofen, piroxicam, pranoprofen, proglumetacin, propacetamol, propyfenazon, proquazon, ramifenazon, rofecoxib, salamidetansyre, salicylamid, sa lix, salol, salsalat, natriumkromoglycat, salicylat, thiosalicylat, sulindac, suprofen, suxibuzon, tenidap, tenoxicam, tetridamin, thurfylsalicylat, tiaprofensyre, tiaramid, tinoridin, tolfenamsyre, tolmetin, trisalicylat, trolaminsalicylat, ufenamat, valdecoxib, vedaprofen og zaltoprofen og vanlig brukte salter av disse.
Spesifikke inhibitorer for PDE4 som kan nevnes inkluderer cilomilast, roflumilast, tetomilast, piclamilast, samt
(aa) CP-671305, (+)-2-[4-({[benzo[l,3]dioksol-5-yloksy)-pyridin-3-karbonyl]-amin}-metyl)-3-fluor-fenoksyl-propionsyre,
(bb) SCH351591,N-(3,5-diklor-l-oksido-4-pyridinyl)-8-metoksy-2-(trifluormetyl)-5-quinolinkarboksamid,
(cc) KF 19514, 5-fenyl-3-(3-pyridyl)metyl-3H-imidazo(4,5-c)(l,8)-nafthyridin-4(5H)-on,
(dd) AWD12-281,N-(3,5-diklorpyrid-4-yl)-(l-(4-fluorbenzyl)-5-hydroksy-indol-3-yl)glyoksylsyreamid,
(ee) D 22888, l-etyl-8-metoksy-3-metyl-5-propylimidazo(l,5-a)pyrido(3,2-e)pyrazinon,
(ff) YM976,4-(3-klorfenyl)-l,7-dietylpyrido[2,3-d]pyrinidin-2(lH)-on,
(gg) NVP-ABE171, 4-(8-benzo[l,2,5]oksadiazol-5-yl[l,7]nafthyridin-6-yl)-benzosyre,
(hh) CI-1044,N-(9-amino-4-okso-l-fenyl-3,4,6,7-tetrahydro(l,4)diazepino-(6,7,l-hi)indol-3-yl)nikotinamid),
(ii) SB 207499, c-4-cyano-4-(3-syklopentyloksy-4-metoksyfenyl)-l-sykloheksankarboksylsyre,
(jj) CC-100004, YM-64227, BAY 19-8004 og GRC 3886,
og vanlig brukte salter av disse.
CysLTl og CysLT2 reseptorantagonister som kan nevnes inkluderer abulukast, cinalukast, iralukast, montelukast, pobilukast, pranlukast, sulukast, tomelukast, verlukast, zafirlukast,
(I) BAY-U9773
(II) MK571
og vanlig brukte salter av disse. Foretrukne Cys LT-reseptorantagonister som kan nevnes inkluderer montelukast.
5-lipoksygenaseinhibitorer som kan nevnes inkluderer følgende.
(1) Zileuton (synonymer: A-64077, A BT 077, Zyflo'), beskrevet i eksempelvis EP 0 279 263, US patentskrift 4,873,259, Int. J. Immunopharmacol. 14, 505 (1992), Br. J. Cancer 74, 683 (1996) og Am. J. Resp. Critical Care Med. 157, Part 2,1187 (1998). (2) A-63162, beskrevet i eksempelvis Anticancer Res. 14,1951 (1994). (3) A-72694. (4) A-78773, beskrevet i eksempelvis Curr. Opin. Invest. Drugs 2, 69 (1993).
(5) A-79175 (R-enantiomeren av A 78773), beskrevet i eksempelvis Carcinogenesis 19, 1393
(1998) og J. Med. Chem. 40,1955 (1997).
(6) A-80263. (7) A-81834. (8) A-93178 (9) A-121798, beskrevet i eksempelvis 211th Am. Chem. Soc. Meeting. 211: abstr. 246, 24. mars 1996. (10) Atreleuton (synonymer ABT-761 and A-85761), beskrevet i eksempelvis Exp. Opin. Therap.
Patents 5 127 (1995).
(11) MLN-977 (synonymer LPD-977 og CMI-977), beskrevet i eksempelvis Curr. Opin. Anti-Inflamm. & Immunomod. Invest. Drugs 1, 468 (1999). Denne, samt andre liknende forbindelser er beskrevet i US patentpublikasjon 5,703,093. (12) CMI-947, beskrevet i eksempelvis 215th Am. Chem. Soc. Meeting. 215: abstr. MÉDI 004, 29. mars 1998. Denne, samt andre liknende forbindelser er beskrevet i US patentpublikasjon 5,792,776. (13) CMI-568, beskrevet i eksempelvis 211th Am. Chem. Soc. Meeting. 211: abstr. 205, 24. mars 1996. (14) LDP 392 (synonym CMI 392), beskrevet i eksempelvis Pharmacol. Res. 44, 213 (2001). (15) Linetastin (synonymer: linazolast, TMK 688, YM 257), beskrevet i eksempelvis Int. J. Immunopharmacol. 22,123 (2000). (16) Lonapalen (synonym: RS 43179), beskrevet i eksempelvis Pharm. Res. 9,1145 (1992). (17) LY-221068, beskrevet i eksempelvis Ann. N. Y. Acad. Sei. ( Immunosuppressive and Antiinflammatory Drugs) 696, 415 (1993). (18) LY 269415, beskrevet i eksempelvis Agents and Actions 42, 67 (1994). (19) 5-LO-inhibitorer med histamin Ha reseptorantagonistaktivitet beskrevet i eksempelvis Bioorg. Med. Chem. Lett. 14, 2265 (2004), slik som følgende forbindelse: (20) BF-389 (21) BIL 226 og BIL 357, beskrevet i eksempelvis./. Pharmacol. Exp. Therap. 265,483 (1993). (22) BU 4601A, BU 4601B og BU 4601C, beskrevet i eksempelvist. Antibiotics 46, 705 (1993). (23) BW 755C, beskrevet i eksempelvis / Pharm. Exp. Therap. 277,17 (1996). (24) BW-A4C, beskrevet i eksempelvis Eur. J. Biochem. 267, 3633 (2000). (25) BWB 70C, beskrevet i eksempelvis Br. J. Pharmacol. 108 (Suppl), 186P (1993). (26) CBS 1108. (27) CGS 26529, beskrevet i eksempelvis Inflamm. Res. 44 (Suppl. 2) 147 (1995). (28) CGS 25667, CGS 25997 and CGS 25998, beskrevet i eksempelvist. Med. Chem. 38, 68 (1995). (29) CGS-23885, beskrevet i eksempelvist. Med. Chem. 36, 3580 (1993). (30) CI-986 (31) CT 3 (synonymer: ajumelsyre ("ajumelic"), DMH-11C, HU 239), beskrevet i eksempelvis J. Med. Chem. 35,3153 (1992). (32) CV 6504, beskrevet i eksempelvis 4/7/7. Oncol. 11,1165 (2000).
(33) Darbufelon (synonymer: CI-1004, PD 136095-0073) og analoge av samme, beskrevet i eksempelvis Arthritis and Rheumatism 42 (Suppl.) 404 (1999), ibid 42 (Suppl.) 81 (plus poster)
(1999) og J. Med. Chem. 37, 322 (1994).
(34) Docebenon (synonym AA861) og analoge av samme, beskrevet i eksempelvis Int. Arch. Allergy and Immunol. 100,178 (1993) og Biochim. Biophys. Acta 713,470 (1982). (35) DuP 654, beskrevet i eksempelvist. Med. Chem. 33, 360 (1990). (36) XA 547, beskrevet i eksempelvis BTG International Inc. Company Communication 15. okt 1999, og Bioorg. Med. Chem. 3,1255 (1995). (37) E-3040 (38) E 6080, beskrevet i eksempelvis Res. Commun. Mol. Pathol. Pharmacol. 86, 75 (1994). (39) E6700. (40) Epocarbazolin A, en forbindelse isolert fra Streptomyces anulatus T688-8 og beskrevet i eksempelvist. Antibiotics 46, 25 (1993). (41) ER 34122, beskrevet i eksempelvis Inflamm. Res. 47, 375 (1998). (42) ETH 615, beskrevet i eksempelvis Exp. Dermatol. 2,165 (1993). (43) F 1322, beskrevet i eksempelvis XV International Congress of Allergologi and Clinical Immunology (Suppl 2) 325 (1994).
(44) Flezalastin (synonymer: D 18024, IDB 18024), beskrevet i eksempelvis Allergy (Suppl.) 47, 47
(1992).
(45) Azelastin, beskrevet i eksempelvis Int. Arch. Allergy and Applied Immunol. 90, 285 (1989). (46) FPL 62064, beskrevet i eksempelvis Agents andActions 30, 432 (1990). (47) FR 110302, beskrevet i eksempelvis Am. Rev. Resp. Dis. 145, A614 (1992). (48) HP 977 og P 10294, beskrevet i eksempelvist. Med. Chem. 39, 246 (1996). (49) P-8977 (50) HX-0835, beskrevet i eksempelvis Rinsho lyaku. 11,1577 & 1587 (1995). (51) HX-0836, beskrevet i eksempelvist. Med. Chem. 36 3904 (1993). (52) Følgende forbindelse, beskrevet i Bioorg. Med. Chem. Lett. 6, 93 (1996). (53) Icodulinium (synonymer: CBS 113A, icodulin), beskrevet i eksempelvis Arzneimittel- Forschung ( Drug Research) 39,1242 & 1246 (1989). (54) KC-11404, beskrevet i eksempelvis Eur. Resp. J. 7 (Suppl. 18), 48 (1994). (55) KC-11425 (56) KME4. (57) L 651392, beskrevet i eksempelvis A dv. Prostaglandin, Thromboxane and Leukotriene Res. 17, 554 (1987). (58) L651896. (59) L652343. (60) L653150. (61) L-656224, beskrevet i eksempelvist. Gastroenterol. Hepatol. 11, 922 (1996). (62) L-702539, beskrevet i eksempelvist. Med. Chem. 37,512 (1994). (63) L-670630. (64) L-691816, beskrevet i eksempelvis Curr. Opin. Invest. Drugs 2, 683 (1993). (65) L 699333, beskrevet i eksempelvist. Med. Chem. 38,4538 (1995). (66) L739010. (67) Lagunamycin, beskrevet i eksempelvist. Antibiotics 46, 900 (1993) (68) Licofelon (synonym: ML 3000), beskrevet i eksempelvis Eur. J. Pharm. 453, 131 (2002) and t. Med. Chem. 37,1894 (1994). (69) PD 145246. (70) R 840 (synonym: S 26431). (71) R 68151, beskrevet i eksempelvis Arch. Dermatol. 128, 993 (1992). (72) R 85355, beskrevet i eksempelvis Skin Pharmacol. 9, 307 (1996). (73) REV 5901 (synonymer: PF 5901, Revlon 5901, RG 5901), beskrevet i eksempelvis J. Allergy Clin. Immunol. 91, 214 (1993).
(74) RWJ 63556, beskrevet i eksempelvis 214th Am. Chem. Soc. Nat. Meeting. abstr. MEDI 091
(1997).
(75) S 19812, beskrevet i eksempelvis Mediators of Inflammation 8 (Suppl. 1), 134 & 135 (1999). (76) SC 45662, beskrevet i eksempelvist. Allergy and Clin. Immunol. 89, 208 (1992) (77) SC-41661A (78) SCH 40120. (79) SKF-86002 (80) SKF 104351 and SKF 105809. (81) SKF-107649, beskrevet i eksempelvist. Med. Chem. 39, 5035 (1996). (82) T0757 and T0799), beskrevet i eksempelvis Jap. J. Pharmacol. 66, 363 (1994)
(83) TA 270, beskrevet i eksempelvis Naunyn- Schmiedeberg' s Arch. Pharmacol. 358 (Suppl. 2) 737
(1998).
(84) Tagorizin (synonym: AL 3264), beskrevet i eksempelvis Jap. J. Pharmacol. 65, 19 (1994) og ibid. 64 (Suppl. 1), 312 (1994) (85) Tepoxalin (synonymer: ORF 20485, RWJ 20485), beskrevet i eksempelvis J. Pharmacol. Exp. Therap. 271,1399 (1994). (86) UPA 780, beskrevet i eksempelvis Inflamm. Res. 44 (Suppl. 3), 273 (1995). (87) VUFB 19363. (88) VZ 564, beskrevet i eksempelvis Arzneimittel- Forschung ( Drug Research) 25,155 (1995). (89) Følgende forbindelse, beskrevet i J. Med. Chem. 40, 819 (1997). (90) WAY 120739. (91) WAY 121520, beskrevet i eksempelvis Agents and Actions 39 (Spee. issue Cl) C30 (1993) og Exp. Opin. Invest. Drugs 6, 279 (1997). (92) WAY-126299A, beskrevet i eksempelvis Inflamm. Res. 44 (Suppl. 2), 170 (1995). (93) WAY-125007, beskrevet i eksempelvis WO 04/004773
(94) WHIP 97, beskrevet i eksempelvis 216th Am. Chem. Soc. Nat. Meeting. abstr. MÉDI 363
(1998).
(95) WY 28342, beskrevet i eksempelvist. Med. Chem. 38,1473 (1995). (96) WY 50295 (S-enantiomeren av WY 49232), beskrevet i eksempelvis Eur. J. Pharmacol. 236, 217 (1993).
(97) ZD 2138 (synonym: ICI D 2138), beskrevet i eksempelvis Asthma 95: Theory to Treatment 15
(1995) og Trends in Pharm. Sei. 13, 323 (1992).
(98) ZM 230487 (synonym: ICI 230487), beskrevet i eksempelvis Inpharma 660, 9 (1994). (99) ZD 4007 og ZD 4407, beskrevet i eksempelvis EP 0 623 614.
(100) ZD 7717, beskrevet i eksempelvis EP 0 462 813.
(101) ZM-216800
(102) CJ-12,918, og analoge av samme, beskrevet i eksempelvis Bioorg. Med. Chem. 11, 3879
(2003).
(103) Forbindelser beskrevet som blandede 5-LO / COX-2 inhibitorer i Bioorg. Med. Chem. Lett. 12, 779 (2002), slik som følgende forbindelse.
(104) AKBA (acetyl-ll-keto-p-boswellinsyre), beskrevet i eksempelvis Br. J. Pharmacol. 117, 615
(1996) og Eur. J. Biochem. 256, 364 (1998).
(105) Forbindelser beskrevet som doble 5-LO og COX-inhibitorer i Eur. J. Med. Chem. 22, 147
(1997) og Arzneimittel- Forschung ( Drug Research) 35, 1260 (1985), slik som 2-acetylthiofen-2-thiazolylhydrazon (CBS-1108) og A/-fenylbenzamidrazon.
(106) Boswellin (et ekstrakt fra Boswellia serrata), beskrevet i eksempelvis Fifth Chemical Congress of North America, Abstract 01/1351 (1997) og ibid. Abstract 01/1350 (1997).
(107) 2,4,6-triiodofenol, beskrevet som en 5-LO-inhibitor i eksempelvis US patentpublikasjon 5,985,937.
(108) Nicaraven, beskrevet i eksempelvis Curr. Opin. Invest. Drugs 4, 83 (2003).
(109) Tenidap, beskrevet i eksempelvis EP patentpublikasjon 0 156 603, US patentpublikasjon 4,556,672, Arthritis Rheum. 31, Suppl. S52 (1988) og P. Katz et al., ibid. S52.
(110) Sykliske hydrazider beskrevet som 5-LO-inhibitorer i J. Med. Chem. 39, 3938 (1996), slik som fenidon, l-fenyl-2ft-tetrahydropyridazin-3-on, og l-fenylperhydro-l,2,4-tetrahydropyridazin-3-on.
(111) ICI 207968, beskrevet i eksempelvist. Med. Chem. 34,1028 (1991).
(112) ICI 211965, og andre (metoksyalkyl)thiazoler, beskrevet i eksempelvis J. Med. Chem. 34, 2176 (1991).
(113) 2,3-Dihydro-5-benzofuranoler beskrevet i J. Med. Chem. 32,1006 (1989), slik som følgende forbindelse.
(114) 2,6-Di-tert-butylfenolderivater beskrevet i Bioorg. Med. Chem. 11, 4207 (2003), slik som tebufelon, R-830, og S2474.
(115) 7-te/"f-Butyl-2,3-dihydro-3,3-dimetylbenzofuraner beskrevet som 5-LO/COX-2 inhibitorer i J. Med. Chem. 41,1112 (1998), slik som PGV-20229.
(116) Forbindelser beskrevet som doble 5-LO/COX-inhibitorer i Eur. J. Med. Chem. 35, 1897
(2003), slik som følgende forbindelse.
(117) Helenalin, et seskviterpenlakton ("sesquiterpene lactone") som kan isoleres fra flere plantearter innen familien Asteraceae, beskrevet i for eksempel Biochem. Pharm. 62, 903 (2001).
(118) AS-35,(9-[(4-acetyl-3-hydroksy-2-/?-propylfenoksy)metyl]-3-(lH-tetrazol-5-yl)-4H-pyrido[l,2-cr]pyrimidin-4-on), beskrevet i eksempelvis Int. J. Immunopharmacol. 22, 483 (2000).
(119) Magnolol, beskrevet i eksempelvis Planta Medica 65, 222 (1999).
(120) Honokiol, ekstrahert fra kinesisk urtemedisin, og beskrevet i eksempelvis Arch. Allergy og Immunol. 110, 278 (1996).
(121) Chrysarobin.
(122) E-3040.
(123) Flobufen, beskrevet i eksempelvis Chirality 16,1 (2004).
(124) YPE-01, beskrevet i eksempelvis Eur. J. Pharmacol. 404,375 (2000). (125) BW-A137C
(126) LY-233569
(127) PD-138387
(128) SB-210661
(129) DuP-983
(130) BTS-71321
(131) Piripost, beskrevet i eksempelvis Toxicon. 24,614 (1986).
(132) MK-866, beskrevet i eksempelvis Eur i Pharmacol 205, 259 (1991).
(133) UCB 62045, beskrevet i eksempelvis Chest 123, 371S (2003).
(134) ONO-LP-049, beskrevet i eksempelvist. Immunol. 140, 2361 (1988).
(135) 3323W, L-697198, L-7080780, FR-122788, CMI-206, FPL-64170 og PD-089244
og vanlig brukte salter av samme. Foretrukne 5-lipoksygenaseinhibitorer inkluderer zileuton, eller helst azelastin.
Andre spesifikke 5-LO-inhibitorer som kan nevnes inkluderer de beskrevet i artiklene Prog. Med. Chem., G. P. Ellis og D. K. Luscombe, Elsevier 29,1 (1992) og i J. Med. Chem. 14, 2501 (1992).
Spesifikke inhibitorer for FLAP som kan nevnes inkluderer følgende.
(a) L-674,573, og relaterte FLAP-inhibitorer (for eksempel L-655,238), beskrevet i eksempelvis Mol. Pharmacol. 40, 22 (1991). (b) L-674,636, beskrevet i eksempelvis J. Med. Chem. 38,4538 (1995).
(c)L-689,037, og fotoaffinitetanaloger [<125>l]-669,083 og [<125>l]-691,678, beskrevet i eksempelvis Mol. Pharmacol. 41, 267 (1992). (d) L-705,302, beskrevet i eksempelvis J. Med. Chem. 38,4538 (1995). (e) MK-886 (synonymer: L663536, MK 0886), beskrevet i eksempelvis US patentpublikasjon 5,081,138, Am. Rev. Resp. Dis. 147, 839 (1993), Eur. J. Pharmacol. 267, 275 (1994), The Search for Anti- lnflammatory Drug. 233 (1995) Eds.:V. J. Merluzzi og J. Adams, Boston, Birkhåuser. (f) Forbindelser strukturelt relatert til MK-886, beskrevet i eksempelvis WO patentpublikasjon 93/16069, US patentpublikasjon 5,308,850 og WO patentpublikasjon 94/13293 (g) Quiflapon (synonymer: MK-591, L 686708), beskrevet i eksempelvist. Physiol. Pharmacol. 70, 799 (1992) og J. Lipid Mediators 6, 239 (1993). (h) BAY X 1005, beskrevet i eksempelvis Thorax 52,342 (1997). (i) BAY Y 105, beskrevet i eksempelvis Arthritis and Rheumatism 39, 515 (1996) og Drug & Market Devel. 7,177 (1996).
(j) VML 530 (synonym: A BT 080), beskrevet i eksempelvis Pharmacologist39, 33 (1997)
og vanlig brukte salter av samme.
Inhibitorer for LTA4-hydrolase som kan nevnes inkluderer følgende.
(A) Forbindelser beskrevet som LTA4-hydrolaseinhibitorer i US patentpublikasjon 5,455,271 og WO 94/00420, for eksempel: (B) Forbindelser beskrevet som LTA4-hydrolaseinhibitorer i J. Med. Chem. 36, 211 (1993) og J. Am. Chem. Soc. 114, 6552 (1992), slik som følgende forbindelse. (C) Forbindelser som kan identifiseres ved framgangsmåten ifølge patentkrav 24 i WO 00/50577. (D) Forbindelser beskrevet som LTA4-hydrolaseinhibitorer i US patentpublikasjon 6,506,876, slik
som SC-56938.
(E) Analoge av SC-56938, beskrevet i eksempelvis Bioorg. Med. Chem. Lett. 12, 3383 (2002). (F) Forbindelser beskrevet som LTA4-hydrolaseinhibitorer i US patentpublikasjon 5,719,306, for eksempel: (G) Forbindelser beskrevet som LTA4-hydrolaseinhibitorer i WO 96/11192, slik som:
(H) Forbindelser beskrevet som LTA4-hydrolaseinhibitorer i US patentpublikasjon 6,265,433 og
WO 98/40364, for eksempel:
(I) Forbindelser beskrevet som LTA4-hydrolaseinhibitorer i US patentpublikasjon 6,506,876 og WO 96/10999, slik som: (J) Forbindelser beskrevet som LTA4-hydrolaseinhibitorer i WO patentpublikasjon 98/40370, slik som:
(K) Forbindelser beskrevet som LTA4 hydrolaseinhibitorer i WO 98/40354.
(L)Forbindelser (3-oxiranylbenzosyrer) beskrevet som LTA4-hydrolaseinhibitorer i EP patentpublikasjon 0 360 246, slik som: (M) 20,20,20-Trifluorleukotrien B4-derivater, beskrevet i eksempelvis JP patentpublikasjon 01211549 A2, slik som følgende forbindelse: (N) Forbindelser beskrevet som LTA4hydrolaseinhibitorer i EP patentpublikasjoner 1 165 491 og WO 00/059864, slik som 2-amino-6-(4-benzylfenoksy)heksansyre: (O) Forbindelser beskrevet som LTA4hydrolaseinhibitorer i US patentpublikasjon 6,436,973 og WO 00/017133, slik som (25,3/?)-2-amino-3-(benzyloksy)butan-l-thiol: (P) Forbindelser beskrevet som LTA4hydrolaseinhibitorer i Bioorg. Med. Chem. 3, 969 (1995), slik som: (Q) [4-((jj-Arylalkyl)fenyl]alkansyrer beskrevet som LTA4hydrolaseinhibitorer i DE patentpublikasjon 4121849 Al, slik som: (R) Aralkylthienylalkanoater beskrevet som LTA4hydrolaseinhibitorer i DE patentpublikasjon 4118173 Al, slik som: (S) a)-[(4-Arylalkyl)thien-2-yl]alkanoater beskrevet som LTA4hydrolaseinhibitorer. i DE patentpublikasjon 4118014 Al, slik som: (T) Forbindelser beskrevet som LTA4hydrolaseinhibitorer i J. Med. Chem. 35, 3156 (1992), slik som RP64966:
(U) Forbindelser strukturelt relatert til RP66153 og beskrevet i J. Med. Chem. 35, 3170 (1992).
(V) 2-Hydroksyfenyl-substituerte isoksazoler beskrevet som LTA4hydrolaseinhibitorer i DE patentpublikasjon 4314966 Al, slik som: (W) Bestatin, beskrevet i eksempelvist. Nat. Cancer Institute 95,1053 (2003). (X) SC-22716 (l-[2-(4-fenylfenoksy)etyl]pyrrolidin), beskrevet i eksempelvis J. Med. Chem. 43, 721 (2000). (Y) SC57461A, beskrevet i eksempelvist. Med. Chem. 45, 3482 (2002) og Curr. Pharm. Design 7, 163 (2001).
(Z) Imidazopyridiner og puriner beskrevet som LTA4hydrolaseinhibitorer in Bioorg. Med. Chem. Lett. 13,1137 (2003).
(AA) Captopril, beskrevet i eksempelvis FASEB Journal 16,1648 (2002).
(AB) Hydroksaminsyrederivater beskrevet som LTA4hydrolaseinhibitorer i WO patentpublikasjon 99/40910, slik som: (AC) AB5366, beskrevet i eksempelvis JP 11049675 A2. (AD) SA6541, beskrevet i eksempelvis WO 96/27585, Life Sei. 64, PL51-PL56 (1998) og Eur. J. Pharmacol. 346, 81 (1998). (AE) Forbindelser som inneholder N-merkaptoacylproliner beskrevet som LTA4hydrolaseinhibitorer i JP patentpublikasjon 10265456 A2, slik som: (AF) Amphotericin B, beskrevet i eksempelvis Prostaglandins, Leukotrienes and Essential Fatty Acids 58,105 (1998).
(AG) 14,15-Dehydroleukotrien A4, beskrevet i eksempelvis Biochem. J. 328, 225 (1997).
(AH) 8(5)-amino-2(/?)-metyl-7-oksononansyre, produsert av Streptomyces diastaticus og beskrevet i eksempelvist. NaturalProducts 59, 962 (1996).
(Al) Det hydroksaminsyreholdige peptidtkelatorfan, beskrevet i eksempelvis Bioorg. Med. Chem. Lett. 5, 2517 (1995). (AJ) Aminohydroksaminsyrer beskrevet som inhibitorer for LTA4hydrolase i Bioorg. Med. Chem. 3, 1405 (1995), slik som: (AK) a-Keto-p-aminoestere og thioaminer beskrevet som inhibitorer for LTA4hydrolase i J. Pharmacol. Exp. Therap. 275, 31 (1995). (AL) N-(fenylbutanoyl)leuciner beskrevet som inhibitorer for LTA4hydrolase i JP patentpublikasjon 05310668 A2
og vanlig brukte salter av samme.
Andre spesifikke inhibitorer for LTA4hydrolase som kan nevnes inkluderer de beskrevet i artiklene i Curr. Pharm. Design 7,163 (2001) og i Curr. Med. Chem. 4, 67 (1997).
Antagonister av LTB4-reseptorer (for eksempel BLT1) som kan nevnes inkluderer følgende.
(i) Forbindelser beskrevet som LTB4reseptorantagonister i US patentpublikasjon 6,291,530, slik som (E)-[5-(2-dietylkarbamoyl-l-metylvinyl)-2-(2,6-difluor-benzyloksy)fenoksy]etansyre: (ii) Forbindelser beskrevet som LTB4reseptorantagonister i US patentpublikasjon 2002/0128315, slik som 4-(4-fenylpiperidinylmetyl)benzosyre-4-amidinofenylester av 4-(2-fenylimidazolylmetyl)benzosyre 4-amidinofenylester: (iii) Forbindelser beskrevet som LTB4reseptorantagonister i US patentpublikasjon 2004/0053962, slik som 2-(2-propyl-3-(3-(2-etyl-4-(4-fluorfenyl)-5-hydroksyfenoksy)propoksy)fenoksy)benzosyre: (iv) BIIL, beskrevet i eksempelvis J. Pharmacol. Exp. Therap. 297, 458 (2001) og WO patentpublikasjon 02/055065. (v) CP 105696 og CP 195543, beskrevet i eksempelvist. Pharmacol. Exp. Therap. 285, 946 (1998). (vi) LY 210073 (vii) LY 223982 (synonymer: CGS 23131, SKF 107324). (viii) LY 255283 (synonymer: CGS 23356, LY 177455), beskrevet i eksempelvis Eur. J. Pharmacol. 223, 57 (1992). (ix) LY 292728.
(x)LY 293111 (synonym: VML 295), beskrevet i eksempelvis Drugs of the Future 21, 610 (1996), Clin. Cancer Res. 8, 3232 (2002) og WO patentpublikasjon 01/085166.
(xi) LTB019.
(xii) Moxilubant (synonym: CGS 25019C), beskrevet i eksempelvis Exp. Opin. Therap. Patents 5, 127 (1995).
(xiii) Olopatidin (synonymer: allelock, ALO 4943A, KW 4679, Patanol™), beskrevet i eksempelvis Drugs of the Future 18, 794 (1993).
(xiv) ONO 4057 (synonym: LB 457), beskrevet i eksempelvis Gastroenterology 110 (Suppl.), 110
(1996).
(xv) Ontazolast (synonym: BIRM 270), beskrevet i eksempelvist. Pharm. Exp. Therap. 271, 1418
(1994).
(xvi) PF 10042, beskrevet i eksempelvis Eur. J. Pharmacol. - Enviromental Toxicology and Pharmacology Section 293, 369 (1995). (xvii) RG 14893, beskrevet i eksempelvis Pharmacologist 34, 205 (1992). (xviii) RO 254094, beskrevet i eksempelvis ISSX Proceedings 6, 232 (1994). (xix) RP 66153. (xx) RP 66364. (xxi) RP 69698. (xxii)SB 201146, beskrevet i eksempelvis Thorax 53,137 (1998). (xxiii) SB 201993, beskrevet i eksempelvist. Med. Chem. 36, 2703 (1993). (xxiv) SC 41930, beskrevet i eksempelvist. Pharmacol. Exp. Therap. 269,917 (1994). (xxv)SC 50605. (xxvi) SC 51146. (xxvii) SC 53228, beskrevet i eksempelvis Inflammation Res. 44 (Suppl. 2), 143 (1995). (xxviii) Ticolubant (synonym: SB 209247), beskrevet i eksempelvis Adv. Prostaglandin Thromboxane and Leukotriene Res. 23, 275 (1995). (xxix) U 75302 (synonymer: U 75485, U 77692, U 78489), beskrevet i eksempelvis Adv. Prostaglandin Thromboxane and Leukotriene Res. 23, 275 (1995).
(xxx) VM 301 (synonymer: OAS 1000, pseudopterosin-A-metyleter), beskrevet i eksempelvis Inflammation Res. 44, (Suppl. 3) 268 (1995).
(xxxi) ZD 158252, beskrevet i eksempelvis Inpharma 1094, 9 (1997).
(xxxii) ZK 158252, beskrevet i eksempelvis Inpharma 1094, 9 (1997).
(xxxiii) U-75509, beskrevet i eksempelvis Am. J. Physiol. Heart Circ. Physiol. 2004, Mar 11 [Epub ahead of print].
(xxxiv) CP-105,696, beskrevet i eksempelvis Br. J. Pharmacol. 139, 388 (2003).
(xxxv) LY293111, beskrevet i eksempelvis Clin. Cancer Res. 8, 3232 (2002)
og vanlig brukte salter av samme.
H1histamin reseptorantagonister som kan nevnes inkluderer acrivastin, alimemazin, anatazolin, astemizol, azatadin, azelastin, bamipin, bepotastin, bromazin, bromofeniramin, buclizin, carbinoxamin, klorcyclizin, klorpyramin, klorphenamin, cinnarizin, clemastin, clemizol, clocinizin, cyclizin, cyproheptadin, deptropin, desloratadin, dexchlorpheniramin, dimenhydrinat, dimetinden, dimetotiazin, diphenhydramin, pifenylpyralin, doksylamin, ebastin, embramin, emedastin, epinastin, fexofenadin, flunarizin, homoklorcyclizin, hydroksyzin, isothipendyl, levocarbastin, loratidin, mebhydrolin, meclozin, mepyramin, mequitazin, methdilazin, mizolastin, niaprazin, olopatadin, oxatomid, oksomemazin, phenindamin, pheniramin, fenyltoloxamin, pimethixen, pipinhydrinat, promethazin, propiomazin, quifenadin, ruputadin, setastin, terfenadin, thenyldiamin, thietylperazin, thonzylamin, tolpropamin, trimethobenzamin, tripelennamin, triprolidin og tritoqualin og vanlig brukte salter av samme.
Aktive bestanddeler kan anvendes i kombinasjon.
Det kan brukes ethvert farmasøytisk akseptabelt salt av en antiinflammatorisk og/eller antihistaminbasert aktiv bestanddel, samt den frie baseform av samme i framstilling av blandinger ifølge oppfinnelsen. Foretrukne salter inkluderer acetatsalter, acetonatsalter, aluminiumsalter, ammoniumsalter, argininsalter, bromidsalter, butyratsalter, kalsiumsalter, kloridsalter, kolinsalter, citratsalter, dietanolaminsalter, dietylaminsalter, dipropionatsalter, embonatsalter, etanolaminsalter, etylendiaminsalter, formatsalter, fumaratsalter, fuoratsalter, hydrobromidsalter, hydrokloridsalter, imidazolsalter, laktatsalter, lysinsalter, magnesiumsalter, malatsalter, maleatsalter, malonatsalter, megluminsalter, mesilatsalter, morfolinsalter, nitratsalter, fosfatsalter, piperazinsalter, kaliumsalter, propionatsalter, natriumsalter, succinatsalter, sulfatsalter, tartratsalter, teoclatsalter, pcr/xr-toluensulfatsalter, trietanolaminsalter, trietylaminsalter, valeratsalter, osv. og/eller som beskrevet i " Handbook of Pharmaceutical Salts", Eds. Stahl og Wermuth, Wiley, 2002, kapittel 12.
Mengden av en antiinflammatorisk og/eller antihistaminbasert aktiv bestanddel, eller salt av samme, som kan anvendes i framstilling av forbindelser ifølge oppfinnelsen kan bestemmes av legen, eller av fagpersonen; i relasjon til hva som vil være mest egnet for den individuelle pasient. Dette har en tendens til å variere med den aktive bestanddelens natur, tilstandens alvorlighetsgrad, samt art, alder, vekt, kjønn, nyrefunksjon, leverfunksjon og respons hos den spesifikke pasienten som skal behandles. Det er imidlertid foretrukket at blandingene ifølge oppfinnelsen omfatter et antiinflammatorisk og/eller antihistaminbasert medikament, eller et salt av samme i en mengde fra omlag 0,1 mg/ml til omlag 200 mg/ml beregnet fra den frie baseformen.
Den totale mengden av den aktive bestanddel som kan være tilstede, kan være tilstrekkelig til å gi en daglig dose medikament per enhetsdose som er passende for den aktive bestanddel(ene) som skal anvendes. Dette kan for eksempel være i et område fra omlag 20 u.g til omlag 200 mg. Fagpersonen vil verdsette at blandinger ifølge oppfinnelsen kan doseres en eller flere ganger daglig i en eller flere administreringer for å gi den forannevnte daglige dosen. Foretrukne intervaller varierer fra omlag 0,1 mg/ml til omlag 100 (for eksempel omlag 70) mg/ml, helst fra omlag 0,2 mg/ml til omlag 50 mg/ml.
De ovennevnte dosene er eksempler på et gjennomsnittstilfelle, og det kan naturligvis forekomme individuelle tilfeller der det tilmåles større eller mindre doseintervaller, og slike intervaller anses for å ligge innenfor rammen av den foreliggende oppfinnelsen.
Betegnelsen "liposom" vil av en fagperson oppfattes som å inkludere en struktur som består av en eller flere konsentriske kuler av polare dobbeltsjikt av lipid atskilt av vann eller kammer av vannbasert buffer.
Liposomer kan framstilles med ulike framgangsmåter ved bruk av løsningsmidler, redusert trykk, tofasesystemer, frysetørking, ultralyd osv. beskrevet i eksempelvis Liposome Drug Delivery Systems, Betageri G V et al, Techomic Publishing AG, Basel, Sveits 1993.
Betegnelsen "polart lipid" vil av en fagperson oppfattes til å inkludere ethvert lipid med en polar frontgruppe og to fettsyrerester, som er i stand til å danne liposomer.
Polare lipider, slik som de beskrevet i det etterfølgende, kan ha et naturlig opphav og/eller et syntetisk/halvsyntetisk opphav. Blandinger av naturlige og syntetiske/halvsyntetiske polare lipider kan også anvendes i blandinger ifølge oppfinnelsen.
Polare lipider som kan anvendes i blandinger ifølge oppfinnelsen kan følgelig være basertpå eksempelvis fosfolipider, og særlig fosfatidylkolin (PC), fosfatidylglyserol (PG), fosfatidylinositol (Pl), fosfatidinsyre (PA), fosfatidylserin (PS) samt blandinger av disse.
Fosfolipider som kan anvendes i blandinger ifølge oppfinnelsen omfatter polare og ikke-polare grupper lenket til en kjedeenhet som bærer hydroksylgrupper, slik som glyserol.
Fosfolipider kan også være representert ved den generelle formelen I:
der Ri og R2uavhengig representerer en mettet eller umettet (for eksempel alkenyl), forgrenet eller rettkjedet alkylgruppe med 7 til 23 karbonatomer, fortrinnsvis mellom 11 og 19 karbonatomer; og R3representerer en amid- eller estergruppe, slik som
-CH2-CH(OH)-CH2OH (fosfatidylglyserol),
-CH2-CH2-N(CH3)3(fosfatidylkolin),
-CH2-CH2-NH2 (fosfatidylethanolamin),
-H (fosfatidinsyre), eller
-CH2-CH(NH2)-COOH (fosfatidylserin).
Fosfolipidet kan ha et naturlig opphav. Naturlig forekommende fosfolipider er fortrinnsvis membranlipider avledet fra ulike kilder av både vegetabilsk (for eksempel rapsfrø, solsikke osv., eller fortrinnsvis soyabønne) og animalsk opphav (for eksempel eggeplomme, kumelk osv.). Fosfolipider fra soyabønner, en hovedkilde for vegetabilske fosfolipider, framskaffes normalt fra biproduktene (dvs. lecitiner) i raffinering av rå soyabønneolje ved utkokingsprosessen. Lecitinene prosesseres ytterligere og renses ved bruk av andre fysikalske enhetsoperasjoner, slik som fraksjonering og/eller kromatografi. Andre fosfolipider kan oppnås ved eksempelvis pressing av ulike egnete frø og korn, etterfulgt av løsningsmiddelekstraksjon etterfulgt av ytterligere prosessering som beskrevet foran. Fosfolipider av naturlig opphav som kan nevnes inkluderer for eksempel de som er tilgjengelig under handelsnavnene Lipoid S75, Lipoid S100 og Lipoid S75-3N (Lipoid GmbH, Tyskland), som alle er blandinger av flere ulike fosfolipider som forefinnes i soyabønner.
Fosfolipidet kan alternativt være av syntetisk eller halvsyntetisk opphav (dvs framstilt ved kjemisk syntese). For eksempel kan det brukes en flertrinns kjemisk syntetisk tilnærming for å framskaffe de sentrale fosfolipid-mellomproduktene 1,2-diacylglyserol, fra (s)-l,2-isopropylidenglyserol, der sistnevnte gir glyserolkjeden som er karakteristisk for fosfolipider. 1,2-diacetylerte fosfolipider kan deretter framskaffes når den korresponderende polare frontgruppe festes via kjemisk syntese til mellomproduktet 1,2-diacylglyserol. Opphavet for glyserol og fettsyrene som brukes i de ulike trinnene kan imidlertid være både av naturlig og syntetisk opphav. Syntetiske og/eller halvsyntetiske fosfolipider som kan nevnes inkluderer dilaurylfosfatidylkolin (DLPC), dimyristolfosfatidylkolin (DMPC), dipalmitoylfosfatidylkolin (DPPC), dilaurylfosfatidylglyserol (DLPG), dimyristolfosfatidylglyserol (DMPG), dioleoylfosfatidylkolin (DOPC) og dioleoylfosfatidylglyserol (DOPG).
Det polare lipidet kan alternativt omfatte, eller helst bestå av, et glykolipid. I kontekst av den foreliggende oppfinnelsen, betegner "glykolipid" en forbindelse som inneholder en eller flere monosakkaridrester bundet ved en glykosidbinding til en hydrofob gruppe, slik som en acylglyserol, et sfingoid eller et ceramin (N-acylsfingiod).
Et gykolipid kan være et glykoglyserolipid. I kontekst av den foreliggende oppfinnelsen betegner "glykoglyserolipid" et glykolipid som inneholder en eller flere glyserolrester. I henhold til et foretrukket aspekt ved oppfinnelsen, omfatter eller består glykoglyserolipidet av galaktoglyserolipid, helst en digalaktosyldiacylglyserol med den generelle formelen II:
der Ri og R2er som definert foran.
Glykolipidet kan alternativt være et glykosfingolipid. I kontekst av den foreliggende oppfinnelsen, betegner "glykosfingolipid" et lipid som inneholder minst en monosakkaridrest og enten et sfingoid eller et keramid. Betegnelsen kan slik sett omfatte nøytrale glykofingolipider, slik som mono- og oligoglykosylsfingoider så vel som oligo- og, helst, monoglykosylceramider. Betegnelsen omfatter i tillegg sure glykosfingolipider slik som sialoglykosfingolipider, uronoglykosfingolipider, sulfoglykosfingolipider, fosfoglykosfingolipider, og fosfonoglyko-sfingolipider. Glykosfingolipidet kan være ceramid, monoheksosylceramid, diheksosylceramid, sfingomyelin, lysosfingomyelin, sfingosin, eller en blanding av samme. Glykosfingolipidet er fortrinnsvis sfingomyelin eller produkter avledet fra samme. Sfingomyelininnholdet er fortrinnsvis etablert ved kromatografiske metoder. Sfingomyelin kan være ekstrahert fra melk, fortrinnsvis kumelk, hjerne, eggeplomme eller erytrocytter fra dyreblod, fortrinnsvis sau. For å unngå tvil, omfattes også syntetiske og halvsyntetiske sfingolipider av oppfinnelsen.
Glykolipidet kan alternativt være en glykofosfatidylinositol. I kontekst av den foreliggende oppfinnelsen, betegner "glykofosfatidylinositol" et glykolipid som inneholder sakkarider bundet glykosidalttil inositol-delen avfosfatidylinositoler.
Foretrukne glykolipider inkluderer digalaktosyldiacylglyserol (DGDG).
Det er foretrukket at det polare lipidet er basert på et fosfolipid, og særlig et fosfolipid avledet fra soyabønner (for eksempel Lipoid S100, Lipoid S75 eller Lipoid S75-3N).
Foretrukne polare lipider (slik som fosfolipider) er de som sveller i målbar grad og/eller de som er i stand til å bevirke spontan liposomdannelse.
Dersom det polare (for eksempel fosfo-) lipidet ikke sveller spontant i vann, vil fagpersonen se at det ikke desto mindre er mulig å framskaffe liposomer ved å tilsette et mer polart, svellbart (for eksempel fosfo-) lipid, slik som anionisk (for eksempel fosfo-) lipid (for eksempel fosfatidylglyserol).
Liposomdannelse kan utføres som foran ved omlag 0 °C (for eksempel romtemperatur) dersom faseovergangstemperaturen for acylkjedene (kjedesmelting; gel-til-væske-krystaller) er under vannets frysepunkt.
Uansett hvilken polar lipidsubstans som benyttes (eller kombinasjon av), er egnede totale mengder/konsentrasjoner av lipid(er) som kan anvendes i framstilling av en blanding ifølge oppfinnelsen innenfor området fra omlag 10 mg/ml til omlag 120 mg/ml. Blandinger ifølge oppfinnelsen som kan nevnes inkluderer de der, når det polare lipidet omfatter fosfolipid (i kombinasjon med et annet lipid eller ikke), den totale mengden av fosfolipid(er) i blandingen er fra omlag 10 (for eksempel omlag 17, slik som omlag 20) mg/ml til omlag 120 mg/ml, helst omlag 25 (for eksempel omlag 35) mg/ml til omlag 100 (for eksempel omlag 70, slik som omlag 50, for eksempel omlag 40) mg/ml. Typiske intervaller som kan nevnes inkluderer fra omlag 25 (for eksempel 27) mg/ml til omlag 50 mg/ml (for eksempel 45, eller helst 35 mg/ml). Totalmengden av fosfolipid (når det polare lipidet omfatter fosfolipid) ligger fortrinnsvis i området fra omlag 10 mg til omlag 80 mg (slik som fra omlag 17 (for eksempel 20) mg til omlag 70 (for eksempel 40) mg.
Blandinger ifølge oppfinnelsen kan også omfatte en antioksidant, slik som a-tocoferol, askorbinsyre, butylert hydroksyanisol, butylert hydroksytoluen, sitronsyre, fumarsyre, maleinsyre, monothioglyserol, propionsyre, propylgallat, natriumaskorbat, natriumbisulfitt, natriummetabisulfitt, kaliummetabisulfitt, natriumsulfitt, tartarsyre eller vitamin E. Foretrukne antioksidanter inkluderer butylert hydroksytoluen, a-tokoferol, askorbinsyre og butylert hydroksyanisol.
I henhold til oppfinnelsen kan det brukes et chelaterende middel for å redusere metallionkatalysert oksidasjon av fosfolipid og/eller aktive bestanddeler. Eksempler på nyttige chelaterende midler et etylendiamintetraetansyre (EDTA) og salter av samme (for eksempel natrium- eller kalium-EDTA), etylendiamintrietansyre og dietylentriamin-pentaetansyre (DTPA). Det er også mulig å bruke andre midler som beskytter blandingen ifølge oppfinnelsen, og særlig enhver umettet fettsyrerest som kan være tilstede i samme, mot oksidasjon. Foretrukne chelaterende midler inkluderer EDTA og salter av samme.
Blandingen ifølge oppfinnelsen kan omfatte ett eller flere konserveringsmidler. Eksempler på vanlige konserveringsmidler for flytende farmasøytiske blandinger er benzalkoniumklorid, benzosyre, butylert hydroksyanisol, butylparaben, klorbutanol, etylparaben, metylparaben, propylparaben, fenoksyetanol eller fenyletylalkohol. Foretrukne konserveringsmidler inkluderer benzalkoniumklorid. Andre konserveringsmidler som kan nevnes inkluderer sorbinsyre.
For å holde blandingen ifølge oppfinnelsen på sitt anvendelsessted, kan den også omfatte et viskositetsøkende middel, slik som hydrofile polymerer slik som polyetylenglykol, eller kryssbundet polyvinylpyrrolidon og/eller celullosederivater slik som hydroksypropylmetylcellulose. Viskositetsøkende midler kan også tjene som beskyttende kolloider for å gi en fysikalsk stabilisering av blandingen ifølge oppfinnelsen før administrering. Foretrukne beskyttende kolloider omfatter hydroksypropylmetylcellulose og særlig polyetylenglykol.
Blandinger ifølge oppfinnelsen kan også omfatte smaksstoffer (for eksempel sitron, mentol eller peppermyntepulver) og/eller søtningsstoff (for eksempel neohesperidin).
Blandinger ifølge oppfinnelsen kan også omfatte tonisitetmodifiserende midler, slik som natriumklorid, kaliumklorid, glyserol, glukose, dekstrose, sukrose, mannitol osv.
Valgfrie additiver, inkludert buffermidler, konserveringsmidler, viskositetsøkende midler, antioksidanter, tonisitetmodifiserende midler og chelaterende midler bør velges i lys av deres identitet og mengde som anvendes, og ha i minne at deres negative effekt på liposomstabilitet bør holdes på et minimum. For et gitt middel kan dette verifiseres ved hjelp av enkle forsøk, som er godt innenfor kunnskapsområdet for en fagperson. Passende mengder av slike bestanddeler er imidlertid innenfor området fra omlag 0,01 mg/ml til omlag 10 mg/ml. Det er foretrukket at blandingene ifølge oppfinnelsen inneholder minst ett konserveringsmiddel, antioksidant, chelaterende middel, buffermiddel og/eller viskositetsøkende middel. Passende mengder av noen/alle disse valgfrie additivene inkluderer fra omlag 0,02 til omlag 5 (for eksempel omlag 3) mg/ml (for eksempel fra omlag 0,1 til omlag 2 mg/ml).
Oppfinnelsen anviser også en framgangsmåte for framstilling av blandinger ifølge oppfinnelsen. En har overraskende funnet at liposomer kan framstilles ved direkte svelling av de polare lipidene i et vannbasert medium uten tilsats av noen andre tilsatsstoffer slik som ladede lipider og/eller tensider osv., som normalt er påkrevet.
I henhold til nok et aspekt ved den foreliggende oppfinnelsen er det framskaffet en framgangsmåte for framstilling av en blanding ifølge oppfinnelsen, hvilken framgangsmåte omfatter: (a) å blande (i) et polart lipid eller en blanding av polare lipider som er sve 11 ba re i vannbaserte medier, (ii) en vannfase, og (iii) en antiinflammatorisk og/eller antihistamin aktiv bestanddel; og
(b) å homogenisere blandingen.
Vannbaserte faser som anvendes i trinn (a) foran inkluderer vann, eller vann der noe annet er oppløst (dvs. en vannbasert løsning). Vannbaserte løsninger kan omfatte eksempelvis buffer (se nedenfor). Vannbaserte løsninger kan også omfatte en antiinflammatorisk og/eller antihistaminbasert aktiv bestanddel (dvs. bestanddel (iii) foran), hvorved det polare lipidet, eller blandingen av polare lipider tilsettes til en vannbasert løsning av en antiinflammatorisk og/eller antihistamin aktiv bestanddel i trinn (a) foran.
Trinn (a) i den forannevnte framgangsmåten utføres fortrinnsvis i nærvær av egnet rysting (for eksempel omrøring).
Blandingens pH justeres fortrinnsvis, for eksempel før homogeniseringstrinn (b) foran, til en ønsket verdi innenfor området fra omlag pH 4 (for eksempel 4,0) til omlag pH 8 (for eksempel 8,0), fortrinnsvis fra omlag pH 5 (for eksempel 5,0) til omlag pH 7 (for eksempel 7,0), ved tilsats av ei syre eller en base (for eksempel saltsyre og/eller natriumhydroksid ved en passende konsentrasjon (for eksempel IM)).
Fortrinnsvis tilsettes vann, saltløsning eller bufferløsning, for eksempel før homogeniseringstrinnet (b) foran og/eller etter justering av pH omtalt foran, til blandingen for å oppnå et ønsket sluttvolum.
Løsninger/væsker kan spyles med nitrogen eller argon ved et passende trinn i framgangsmåten foran, alt etter behov.
I kontekst av den foreliggende oppfinnelsen kan en si at et lipid er sve 11 bart i et vannbasert medium dersom det sveller i målbar grad når det plasseres i kontakt med et slikt medium.
Buffere kan fortrinnsvis tilsettes til den vannbaserte løsningen av medikament (og/eller medikament kan tilsettes til en vannbasert bufferløsning) før tilsatsen av lipid.
Dannelsen av liposom ifølge oppfinnelsen kan tilrettelegges ved den spontane svelling av det polare lipidet i vann for å danne en lamellær flytende krystallinsk fase med et maksimalt vanninnhold på omlag 35 vekt % eller mer avhengig av det polare lipidets natur. Avhengig av lipidet eller lipidblandingen som brukes og andre betingelser, kan det oppnås spontan dannelse av liposomer når det tilsettes vann i overskudd til denne lamellære fasen. Dersom det oppnås spontan dannelse, kan dannelsen av liposomer oppnås ved det mekaniske dispergeringstrinnet (dvs. homogeniseringstrinnet (b) i framgangsmåten beskrevet foran) av den lamellære væskekrystallfasen i overskuddsvannet.
Homogeniserings/dispergerings-metodene inkluderer voldsom mekanisk blanding eller høyhastighetshomogenisering, for eksempel ved hjelp av en Ultra Turrax™ (Jankel & Kiihnke, Tyskland). Risting, omrøring og rulling kan også utføres som en del av homogeniseringstrinnet i framgangsmåten beskrevet foran.
Det kan væreønskelig med en homogen størrelsesfordeling av liposomene ifølge oppfinnelsen og kan oppnås ved ekstrudering gjennom et membranfilter, slik som ett framstilt av polykarbonat, med en porestørrelse på omlag 100 nm. Membranfiltere kan skaffes fra Avesting Inc., Canada.
Det kan fortrinnsvis også oppnås en midlere liposomstørrelse og en innsnevret liposomstørrelsesfordeling når liposomdispersjonen underlegges høyttrykks-homogenisering med en egnet homogenisator (Rannie APV, type 7,30 VH, Rannie AS, Danmark), ved et trykk fra eksempelvis omlag 300 bar til omlag 1000 bar, slik som fra omlag 400 bar til omlag 900 bar, for eksempel omlag 500 til omlag 800 bar i et antall sykluser fra omlag 4 til omlag 8 (for eksempel 7, slik som 6).
En har funnet at nærværet av visse aktive bestanddeler kan føres til en reduksjon av liposomstørrelsen. Mindre liposomer er generelt fordelaktig fordi de er mer fysikalsk stabile og lar seg lettere resorberes av slimhinner på grunn av deres høyere forhold mellom overflateareal/volum.
Det er foretrukket at diameteren av liposomer i blandinger ifølge oppfinnelsen er mindre enn omlag 200 nm (for eksempel mellom omlag 40 til omlag 100 nm), målt ved eksempelvis laserdiffraksjon eller dynamisk lysspredning, for eksempel som beskrevet i det etterfølgende.
Framgangsmåten beskrevet foran for framstilling av blandinger ifølge oppfinnelsen krever normalt ingen konvensjonell behandling med organiske løsningsmidler slik som kloroform eller diklormetan. Dersom det brukes to eller flere membranlipider, kan det imidlertid være passende og/eller nødvendig å behandle dem med organisk løsningsmiddel før tilsats av det vannbaserte løsningsmidlet. For eksempel kan lipidene løses opp i et flyktig løsningsmiddel eller løsningsmiddelblanding, slik som kloroform eller kloroform/metanol. Løsningen kan deretter avsettes på overflatene av en rundbunnet kolbe mens løsningsmidlet fjernes ved roterende inndamping under redusert trykk. Et overskuddsvolum av vannbasert buffer som inneholder medikamentet kan deretter tilsettes til den tørre tynne filmen av lipider, som deretter kan tillates å svelle for å danne liposomer. Dersom den aktive bestanddelen er lite løselig i vann og/eller fosfolipid, kan det i andre tilfeller være nødvendig å løse forbindelsen og fosfolipidet i et organisk løsningsmiddel før tilsats til den vannbaserte fasen. Igjen kan organisk løsningsmiddel fjernes (for eksempel under vakuum) før tilsats av vannfasen.
Blandingene ifølge oppfinnelsen er egnet til behandling av enhver indikasjon som den relevante aktive bestanddel er kjent for å være effektiv mot, for eksempel de som er spesielt oppramset for de aktive bestanddelene i Martindale "The Complete Drug Reference", 34. utgave, Royal Pharmaceutical Society (2005).
I henhold til nok et aspekt ved den foreliggende oppfinnelsen, er det framskaffet en framgangsmåte for behandling av en inflammatorisk lidelse (og/eller migrene eller smerte (for eksempel akutt smerte), alt etter omstendighetene) som omfatter administrering av en farmakologisk effektiv mengde av en blanding ifølge oppfinnelsen til en person som lider av eller er utsatt for denne lidelsen.
For å unngå tvil, betyr betegnelsen "behandling" her den terapeutiske behandling, så vel som den symptomatiske behandling, profylaksen, eller diagnosen, av en tilstand.
Selv om blandinger i følge oppfinnelsen kan administreres via enhver kjent rute, inkludert parenteralt, lokalt og/eller peroralt, kan de normalt administreres transmukosalt, og helst nasalt, okulært og pulmonært. For eksempel kan blandinger ifølge oppfinnelsen administreres ved hjelp av nesespray, nesedråper og/ellerøyedråper. Det er også mulig å administrere blandinger av oppfinnelsen i form av fint støv til lungene ved forstøvning. For nasal administrering kan det brukes enhver kjent anordning som er egnet for produksjon av spray av vannbaserte liposomale dispersjoner.
Slike formuleringer kan framstilles i henhold til standard og/eller akseptert farmasøytisk praksis.
Når ordet "omlag" benyttes i den foreliggende beskrivelsen i kontekst av dimensjoner (for eksempel pH-verdier, størrelser, temperaturer, trykk osv.) og mengder (for eksempel mengder, vekt og/eller konsentrasjoner av individuelle bestanddeler i en blanding eller en komponent av en blanding, andeler av medikament i/utenfor de liposomale strukturene, absolutte doser av aktiv bestanddel osv.), skal det bemerkes at slike variabler er omtrentlige og slik sett kan variere med 10 %, for eksempel ± 5 % og fortrinnsvis ±2% (for eksempel ± 1 %) fra de angitte tallverdiene. Blandingene ifølge oppfinnelsen, og framgangsmåten beskrevet foran som kan brukes til framstilling av samme, har de fordeler som er beskrevet foran. Blandinger ifølge oppfinnelsen kan særlig redusere opptreden av ubeleilige bivirkninger (og særlig irritasjon) som ofte observeres med eksempelvis nasalt administrerte formuleringer.
Blandinger ifølge oppfinnelsen er lett å framstille og muliggjør produksjon av liposombaserte formuleringer i en form som er lettvint å bruke, og unngår behovet for rekondisjonering før administrering.
Blandinger ifølge oppfinnelsen kan også ha den fordel at de kan framstilles ved bruk av etablerte farmasøytiske prosesseringsmetoder og ved bruk av materialer som er godkjent for bruk i næringsmidler eller farmasøytiske preparater, eller som har tilsvarende forskriftsmessig status.
Blandinger ifølge oppfinnelsen kan også ha den fordel at de kan være mer effektive enn, være mindre giftige enn, ha lengre virkning enn, være mer virkningsfull enn, produsere færre bivirkninger enn, være lettere absorberbar enn og/eller ha en bedre farmakokinetisk profil enn, og/eller ha andre nyttige farmakologiske, fysikalske eller kjemiske egenskaper framfor farmasøytiske blandinger fra teknikkens stand, enten for bruk i behandling av rinitt eller ikke.
Oppfinnelsen er i det etterfølgende illustrert ved hjelp av eksempler.
Generell prosedyre. For informasjon om vekt og volum vises det til tabellene nedenfor. Det ble laget en bufferløsning ved å løse vannfri sitronsyre og fast natriumhydroksid i 160 ml vann (80 % av det totale satsvolumet) i en 200 ml volumetrisk kolbe. Den innveide mengden aktiv bestanddel tilsettes og løses ved omrøring med en magnetrører. Fosfolipidet veies separat og tilsettes til løsningen. Omrøring fortsettes inntil det er dannet en godt dispergert suspensjon, hvis pH er justert til pH 5,0 ± 0,1 med 1,0 M NaOH og/eller 1,0 M HCI. Volumet av blandingen bringes deretter til et endelig satsvolum på 200 ml. Blandingen overføres til en høytrykkshomogenisator (Rannie APV, type 7.30, Rannie AS, Danmark) og homogeniseres ved 500-800 bar i 5 runder. Alikvoter av blandingen framskaffet på denne måten fjernes fra oppsamlingsbeholderen og overføres til glassampuller.
Prosedyren beskrevet foran ble brukt til å framstille ferdige blandinger som beskrevet i eksempel 1 til 8 nedenfor. Der det passet, ble mengdene av bestanddelene skalert opp etter behov (for eksempel i tilfellet med eksempel 1 til 8, multiplisert med 200). Prosedyren for eksempel 9 er beskrevet separat nedenfor.
Eksempel 1
Eksempel 2
Eksempel 3
Eksempel 4 Eksempel 5
Eksempel 6
Eksempel 7
Eksempel 8
Eksempel 9
Det kommersielt tilgjengelige nasale antihistaminet azelastin (markedsført under handelsnavn slik som Azelvin™, Azosin™, Astelin™, Lastin™ og Rhinolast™) ble formulert ved bruk av mengdene og trinnene beskrevet nedenfor. 1. 160 mL azelastinløsning for nasal administrering (Lastin™) som inneholdt 0,9 mg/mL azelastin ble overført til en 200 ml volumetrisk kolbe. 2. 7 g soyabønne fosfolipid (Lipoid S100; Lipoid GmbH, Tyskland) ble tilsatt, og blandingen fikk svelle over natta.
3. Volumet ble justert til 200 ml ved tilsats av mer azelastinløsning (se trinn 1 foran).
4. pH ble kontrollert.
Løsningen ble homogenisert i 7 sykluser ved 800 bar som beskrevet i den generelle prosedyren foran
Claims (31)
1. Homogen farmasøytisk blanding for bruk i behandlingen av en inflammatorisk lidelse, omfattende en antiinflammatorisk og/eller aktiv antihistaminbestanddelvalgt fra gruppen omfattende azelastin eller et farmasøytisk akseptabelt salt av samme, et steroid valgt fra alclometason, beclometason, budesonid, ciclesonid, clobetasol, clobetason, deflazacort, dexamethason, diflucortolon valerat, fluocinonid, fluocortolon, flupredniden, flurometholon, fluticason, halcinonid, hydrokortison, mometason, prednisolon, rimexolon, triamcinolon og et farmasøytisk akseptabelt salt en eller flere av disse forbindelsene i en farmasøytisk akseptabel vandig bærer, og et polart lipidliposom, forutsatt at den aktive bestanddelen ikke er cetirizin, hvori konsentrasjonen av aktiv bestanddel i den vannbaserte bæreren er hovedsakelig lik, enten lokalisert inne i eller utenfor de liposomale strukturene og varierer med ±20% sammenliknet med konsentrasjoner inne i og på utsiden av de liposomale strukturene ved romtemperatur og atmosfærisk trykk.
2. Blanding for bruk ifølge krav 1 som videre inkluderer en farmasøytisk akseptabel buffer med evne til å forsyne en pH fra pH 4 til pH 8.
3. Blanding for bruk ifølge krav 2, hvori pH-området er pH 5 til pH 7.
4. Blanding for bruk ifølge krav 2 eller krav 3, hvori bufferen er et fosfat, citrat eller acetatbuffer.
5. Blanding for bruk ifølge krav 4, hvori bufferen er dinatriumfosfat, dikaliumfosfat, natriumdihydrogenfosfat, kalium-dihydrogenfosfat, fosforsyre pluss base, natriumcitrat, sitronsyre pluss base, natriumacetat eller etansyre pluss base.
6. Blanding for bruk ifølge et av kravene 2 til 5, hvori mengden buffer er i intervallet fra 1 mg/ml til 30 mg/ml.
7. Blanding for bruk ifølge et av kravene foran, hvori det polare lipidet er fra en naturlig kilde, eller er fra en syntetisk/halv-syntetisk kilde, eller omfatter en blanding av de to.
8. Blanding for bruk ifølge et av kravene foran, hvori det polare lipidet omfatter eller består av et fosfolipid eller em blanding av fosfolipider.
9. Blanding for bruk ifølge krav 8, hvori fosfolipidet omfatter et som er basert på fosfatidylcholin, fosfatidylglyserol, fosfatidylinositol, fosfatididsyre, fosfatidylserin eller en blanding av samme.
10. Blanding for bruk ifølge krav 8 eller 9, hvori fosfolipidet omfatter et som er representert ved den generelle formel I,
hvori RI og R2 uavhengig representerer en mettet eller umettet, forgrenet eller rettkjedet alkylgruppe med mellom 7 og 23 karbonatomer, og R3 representerer et amid eller en ester-bindingsgruppe.
11. Blanding for bruk ifølge krav 10, hvori amid eller ester-bindingsgruppen er -CH2-CH(OH)-CH20H, -CH2-CH2-N(CHs)3, -CH2-CH2-NH2, -H eller -CH2-CH(NH2)-COOH.
12. Blanding for bruk ifølge et av kravene 8 til 11, hvori fosfolipidet omfatter et membranlipid avledet fra soyabønne.
13. Blanding for bruk ifølge et av kravene 8 til 12, hvori fosfolipidet omfatter dilaurylfosfatidylcholin, dimyristolfosfatidylcholin, dipalmitoylfosfatidylcholin, dilaurylfosfatidylglyserol, dimyristolfosfatidylglyserol, dioleoylfosfatidylcholin eller dioleoylfosfatidylglyserol.
14. Blanding for bruk ifølge et av kravene 1 til 7, hvori det polare lipidet omfatter eller består av et glykolipid eller en blanding av glykolipider.
15. Blanding for bruk ifølge krav 14, hvori glykolipidet omfatter et glykoglyserolipid.
16. Blanding for bruk ifølge krav 15, hvori glykoglyserolipidet omfatter et galaktoglyserolipid.
17. Blanding for bruk ifølge krav 15, hvori glykoglyserolipidet omfatter en digalaktosyldiacylglyserol med den generelle formelen II,
hvori RI og R2 er som definert i krav 10.
18. Blanding for bruk ifølge et av kravene 14 til 17, hvori glykolipidet omfatter digalaktosyldiacylglyserol.
19. Blanding for bruk ifølge krav 14, hvori glykolipidet omfatter et glykosfingolipid.
20. Blanding for bruk ifølge krav 19, hvori glykosfingolipidet omfatter et monoglykosylsfingoid, et oligoglykosylsfingoid, et oligoglykosylceramid, et monoglykosylceramid, et sialoglykosfingolipid, et uronoglykosfingolipid, et sulfoglykosfingolipid, et fosfoglykosfingolipid, et fosfonoglykosfingolipid, et ceramid, et monoheksosylceramid, et diheksosylceramid, et sfingomyelin, et lysosfingomyelin, et sfingosin eller en blanding derav.
21. Blanding for bruk ifølge krav 20, hvori glykosphingolipidet omfatter sfingomyelin eller et produkt avledet fra samme.
22. Blanding for bruk ifølge krav 14, hvori glykolipidet omfatter en glykofosfatidylinositol.
23. Blanding for bruk ifølge et av kravene foran, hvori mengden av polar lipidsubstans som anvendes, er i intervallet fra 10 mg/ml til 120 mg/ml.
24. Blanding for bruk ifølge et av kravene 1 til 13 eller 23, hvori mengden fosfolipid i blandingen er fra 17 mg/ml til 70 mg/ml.
25. Blanding for bruk ifølge krav 24, hvori mengden er fra 20 mg/ml til 40 mg/ml.
26. Blanding for bruk ifølge et av kravene foran, som videre omfatter en antioksidant, et chelaterende middel, et konserveringsmiddel eller et viskoisitetsøkende middel.
27. Blanding for bruk ifølge krav 26, hvori antioksidanten er alfa-tocoferol, ascorbinsyre, butylert hydroksyanisol, butylert hydroksytoluen, sitronsyre, fumarsyre, maleinsyre, monothioglyserol, propionsyre, propylgallat, natriumascorbat, natriumbisulfitt, natrium-metabisulfitt, kaliummetabisulfitt, natriumsulfitt, tartarsyre og/eller vitamin E; hvori det chelaterende midlet er etylendiamintetraetansyre (og/eller et salt av samme), etylendiamintrietansyre og/eller dietylentriaminpentaetansyre; hvori konserveringsmidlet er benzalkoniumklorid, benzosyre, butylert hydroksyanisol, butylparaben, klorbutanol, etylparaben, metylparaben, propylparaben, fenoksyetanol og/eller fenyletylalkohol; eller hvori det viskositetsøkende midlet er polyetylenglykol, kryssbundet polyvinylpyrrolidon og/eller hydroksypropylmetylcellulose.
28. Blanding for bruk ifølge et av kravene foran, hvori diameteren av liposomene er mindre enn 200 nm.
29. Blanding for bruk ifølge krav 28, hvori diameteren er mellom 40 nm og 100 nm.
30. Blanding for bruk ifølge et av kravene 1 til 29, hvori blandingen administreres nasalt.
31. Blanding for bruk ifølge et av kravene 1 til 29, hvori den inflammatoriske lidelsen er rhinitt, astma eller inflammatorisk smerte.
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PCT/GB2006/002090 WO2006131737A2 (en) | 2005-06-09 | 2006-06-08 | Method and composition for treating inflammatory disorders |
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EP (1) | EP1888033B1 (no) |
JP (2) | JP5846711B2 (no) |
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AU (1) | AU2006256518B2 (no) |
CA (1) | CA2608631C (no) |
DK (1) | DK1888033T3 (no) |
ES (1) | ES2462541T3 (no) |
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HR (1) | HRP20140406T1 (no) |
IL (1) | IL187480A (no) |
MX (1) | MX2007015577A (no) |
NO (1) | NO339538B1 (no) |
NZ (1) | NZ563373A (no) |
PL (1) | PL1888033T3 (no) |
PT (1) | PT1888033E (no) |
RS (1) | RS53329B (no) |
RU (1) | RU2468797C2 (no) |
SI (1) | SI1888033T1 (no) |
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Families Citing this family (53)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8916546B2 (en) | 2003-08-29 | 2014-12-23 | Therapeutic Research Llc | Materials and methods for treatment and diagnosis of disorders associated with oxidative stress |
US8399666B2 (en) | 2005-11-04 | 2013-03-19 | Panmira Pharmaceuticals, Llc | 5-lipoxygenase-activating protein (FLAP) inhibitors |
US7977359B2 (en) | 2005-11-04 | 2011-07-12 | Amira Pharmaceuticals, Inc. | 5-lipdxygenase-activating protein (FLAP) inhibitors |
GB2431927B (en) | 2005-11-04 | 2010-03-17 | Amira Pharmaceuticals Inc | 5-Lipoxygenase-activating protein (FLAP) inhibitors |
US20070134341A1 (en) * | 2005-11-15 | 2007-06-14 | Kipp James E | Compositions of lipoxygenase inhibitors |
US9101628B2 (en) | 2007-09-18 | 2015-08-11 | The Board Of Trustees Of The Leland Stanford Junior University | Methods and composition of treating a flaviviridae family viral infection |
US9149463B2 (en) | 2007-09-18 | 2015-10-06 | The Board Of Trustees Of The Leland Standford Junior University | Methods and compositions of treating a Flaviviridae family viral infection |
US8940730B2 (en) | 2007-09-18 | 2015-01-27 | The Board Of Trustees Of The Leland Stanford Junior University | Methods and compositions of treating a Flaviviridae family viral infection |
JP5715820B2 (ja) * | 2007-09-18 | 2015-05-13 | スタンフォード ユニバーシティー | フラビウイルス科ファミリーのウイルスへの感染を治療する方法ならびに、フラビウイルス科ファミリーのウイルスへの感染を治療するための組成物 |
EP2244693B1 (de) * | 2008-01-18 | 2012-05-16 | Horst Kief | Mittel zur intraartikulären injektion |
RU2487131C2 (ru) * | 2008-03-14 | 2013-07-10 | Оцука Фармасьютикал Ко., Лтд. | Ингибитор ммр-2 и/или ммр-9 |
WO2010068311A1 (en) | 2008-05-23 | 2010-06-17 | Amira Pharmaceuticals, Inc. | 5-lipoxygenase-activating protein inhibitor |
CA2725535C (en) * | 2008-05-23 | 2016-01-05 | The University Of British Columbia | Modified drugs for use in liposomal nanoparticles |
EP2296711A2 (en) * | 2008-05-29 | 2011-03-23 | MDRNA, Inc. | Multi-arm amines and uses thereof |
EP2949752B1 (en) | 2008-09-22 | 2017-12-20 | RXi Pharmaceuticals Corporation | Reduced size self-delivering rnai compounds |
US8546431B2 (en) | 2008-10-01 | 2013-10-01 | Panmira Pharmaceuticals, Llc | 5-lipoxygenase-activating protein (FLAP) inhibitors |
EP2408449A4 (en) | 2009-03-18 | 2012-08-08 | Univ Leland Stanford Junior | METHODS AND COMPOSITIONS FOR TREATING INFECTION WITH A FLAVIVIRIDAE FAMILY VIRUS |
WO2011044140A1 (en) * | 2009-10-05 | 2011-04-14 | Catabasis Pharmaceuticals, Inc. | Substituted thioacetic acid salicylate derivatives and their uses |
CN102858176A (zh) * | 2010-03-10 | 2013-01-02 | 加林制药公司 | 镇痛化合物、组合物及其应用 |
RU2615143C2 (ru) | 2010-03-24 | 2017-04-04 | Адвирна | Самодоставляющие PHKi соединения уменьшенного размера |
PL2402012T3 (pl) * | 2010-06-30 | 2013-07-31 | J Uriach Y Compania S A | Płynne preparaty fumaranu rupatadyny |
CA2827875A1 (en) | 2011-03-01 | 2012-10-18 | Npharmakon, Llc | Use of n-(4-methoxyphenyl)-1-phenyl-1h-pyrazol-3-amine and related compounds |
US10449193B2 (en) | 2011-06-03 | 2019-10-22 | Signpath Pharma Inc. | Protective effect of DMPC, DMPG, DMPC/DMPG, lysoPG and lysoPC against drugs that cause channelopathies |
US10117881B2 (en) | 2011-06-03 | 2018-11-06 | Signpath Pharma, Inc. | Protective effect of DMPC, DMPG, DMPC/DMPG, LYSOPG and LYSOPC against drugs that cause channelopathies |
US12004868B2 (en) | 2011-06-03 | 2024-06-11 | Signpath Pharma Inc. | Liposomal mitigation of drug-induced inhibition of the cardiac IKr channel |
CA2836904C (en) * | 2011-06-03 | 2019-09-24 | Signpath Pharma Inc. | Liposomal mitigation of drug-induced long qt syndrome and potassium delayed-rectifier current |
US10349884B2 (en) | 2011-06-03 | 2019-07-16 | Sighpath Pharma Inc. | Liposomal mitigation of drug-induced inhibition of the cardiac ikr channel |
US10238602B2 (en) | 2011-06-03 | 2019-03-26 | Signpath Pharma, Inc. | Protective effect of DMPC, DMPG, DMPC/DMPG, LysoPG and LysoPC against drugs that cause channelopathies |
US10532045B2 (en) | 2013-12-18 | 2020-01-14 | Signpath Pharma, Inc. | Liposomal mitigation of drug-induced inhibition of the cardiac IKr channel |
WO2013058527A2 (ko) * | 2011-10-18 | 2013-04-25 | 주식회사 네비팜 | 류코트리엔 길항제와 에피나스틴의 복합제제 |
CA2891090A1 (en) * | 2012-11-09 | 2014-05-15 | Scidose, Llc | Enema composition for treatment of ulcerative colitis having long term stability |
MX365950B (es) | 2013-03-13 | 2019-06-19 | Flatley Discovery Lab Llc | Compuestos de piridazinona y metodos para el tratamiento de la fibrosis quistica. |
ES2540151B1 (es) * | 2013-10-11 | 2016-02-29 | Farmalider S.A. | Composición farmacéutica de ibuprofeno y tramadol para uso oftálmico |
CN106061488B (zh) | 2013-12-02 | 2021-04-09 | 菲奥医药公司 | 癌症的免疫治疗 |
JP2017516813A (ja) | 2014-06-03 | 2017-06-22 | サインパス ファルマ, インク.Signpath Pharma, Inc. | チャネル病を引き起こす薬物に対するdmpc、dmpg、dmpc/dmpg、egpg、lysopg及びlysopcの防御効果 |
JP2016008204A (ja) * | 2014-06-25 | 2016-01-18 | 協和ファーマケミカル株式会社 | 皮膚外用剤 |
IL310969A (en) * | 2015-06-30 | 2024-04-01 | Eiger Group Int Inc | Use of chloroquine and calamizole compounds to treat inflammatory and cancerous conditions |
FR3048883B1 (fr) * | 2016-03-18 | 2020-10-02 | Gaetan Terrasse | Utilisation d'une molecule h4 agoniste pour le traitement de la fibrose pulmonaire idiopathique |
US11806401B2 (en) | 2016-04-27 | 2023-11-07 | Signpath Pharma, Inc. | Prevention of drug-induced atrio-ventricular block |
WO2018089495A1 (en) * | 2016-11-08 | 2018-05-17 | University Of Louisville Research Foundation, Inc. | Encapsulation of phosphodiesterase inhibitors to treat alcoholic liver disease |
US10954307B2 (en) * | 2016-12-22 | 2021-03-23 | Lipidair, Llc | Targeted delivery methods and compositions for antihistamines |
RU2667467C1 (ru) * | 2017-05-17 | 2018-09-19 | Федеральное государственное бюджетное образовательное учреждение высшего образования "Национальный исследовательский Мордовский государственный университет им. Н.П. Огарёва" | Липосомальный препарат дексаметазона в гипертоническом растворе хлорида натрия и способ лечения острого повреждения легких на его основе |
US20200155524A1 (en) | 2018-11-16 | 2020-05-21 | Arcutis, Inc. | Method for reducing side effects from administration of phosphodiesterase-4 inhibitors |
US20210161870A1 (en) | 2017-06-07 | 2021-06-03 | Arcutis Biotherapeutics, Inc. | Roflumilast formulations with an improved pharmacokinetic profile |
US12042487B2 (en) | 2018-11-16 | 2024-07-23 | Arcutis Biotherapeutics, Inc. | Method for reducing side effects from administration of phosphodiesterase-4 inhibitors |
US12011437B1 (en) | 2017-06-07 | 2024-06-18 | Arcutis Biotherapeutics, Inc. | Roflumilast formulations with an improved pharmacokinetic profile |
US11129818B2 (en) | 2017-06-07 | 2021-09-28 | Arcutis Biotherapeutics, Inc. | Topical roflumilast formulation having improved delivery and plasma half life |
AU2019207717B2 (en) | 2018-01-11 | 2024-08-01 | Viropharma Biologics Llc | Stable corticosteroid compositions |
CA3102689C (en) | 2018-06-04 | 2023-08-29 | Arcutis, Inc. | Method and formulation for improving roflumilast skin penetration lag time |
CN112703000B (zh) | 2018-07-23 | 2024-05-31 | 特雷维治疗股份有限公司 | 慢性咳嗽、呼吸急促和呼吸困难的治疗 |
EP3488851A1 (en) | 2018-10-03 | 2019-05-29 | AVM Biotechnology, LLC | Immunoablative therapies |
KR102414285B1 (ko) * | 2020-06-02 | 2022-06-28 | 이화여자대학교 산학협력단 | 플루나리진 또는 이의 약학적으로 허용 가능한 염을 유효성분으로 함유하는 골질환의 예방 또는 치료용 약학적 조성물 |
WO2022175829A1 (en) | 2021-02-17 | 2022-08-25 | Cellix Bio Private Limited | Topical formulations and compositions |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4839175A (en) * | 1986-07-28 | 1989-06-13 | Liposome Technology, Inc. | Liposomes with enhanced retention on mucosal tissue |
Family Cites Families (39)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB1523965A (en) * | 1976-03-19 | 1978-09-06 | Ici Ltd | Pharmaceutical compositions containing steroids |
US4897269A (en) * | 1984-09-24 | 1990-01-30 | Mezei Associates Limited | Administration of drugs with multiphase liposomal delivery system |
EP0249561B1 (en) | 1986-06-12 | 1992-05-13 | The Liposome Company, Inc. | Compositions using liposome-encapsulated non-steroidal anti-inflammatory drugs |
US4962022A (en) * | 1986-09-22 | 1990-10-09 | Becton Dickinson And Company | Storage and use of liposomes |
DE3836892A1 (de) * | 1988-10-29 | 1990-05-03 | Nattermann A & Cie | Parenteral applizierbare, stabile arzneimittelloesungen |
JPH04505616A (ja) * | 1989-05-15 | 1992-10-01 | ザ リポソーム カンパニー,インコーポレイテッド | プロトン勾配によるリポソームへの薬剤の蓄積 |
WO1991006310A1 (en) * | 1989-10-30 | 1991-05-16 | The Liposome Company, Inc. | Liposomal compositions |
US5252319A (en) * | 1990-06-12 | 1993-10-12 | Insite Vision Incorporated | Aminosteroids for ophthalmic use |
US5455271A (en) * | 1992-06-18 | 1995-10-03 | The Scripps Research Institute | Tight-binding inhibitors of leukotriene A4 hydrolase |
JP3383704B2 (ja) * | 1993-04-02 | 2003-03-04 | わかもと製薬株式会社 | 安定なリポソーム水分散液 |
CA2120197A1 (en) * | 1993-04-02 | 1994-10-03 | Kenji Endo | Stable aqueous dispersions containing liposomes |
US5554382A (en) * | 1993-05-28 | 1996-09-10 | Aphios Corporation | Methods and apparatus for making liposomes |
JPH09506084A (ja) * | 1993-11-04 | 1997-06-17 | シエーリング アクチエンゲゼルシヤフト | 荷電リポソームの製造 |
DE4341472A1 (de) * | 1993-12-02 | 1995-06-08 | Schering Ag | Verfahren zur Erhöhung der Stabilität von hydrophile Wirkstoffe enthaltenden Liposomensuspensionen |
DE4420727A1 (de) * | 1994-06-15 | 1995-12-21 | Rovi Gmbh | Hautfreundliche wäßrige Liposomendispersionen, enthaltend alpha-Hydroxycarbonsäuren und/oder alpha-Hydroxyketosäuren in ihrer Salzform |
US5703093A (en) * | 1995-05-31 | 1997-12-30 | Cytomed, Inc. | Compounds and methods for the treatment of cardiovascular, inflammatory and immune disorders |
US5792776A (en) * | 1994-06-27 | 1998-08-11 | Cytomed, Inc., | Compounds and methods for the treatment of cardiovascular, inflammatory and immune disorders |
DE4447770C2 (de) * | 1994-08-20 | 2002-12-19 | Max Delbrueck Centrum | Verfahren zur Herstellung von liposomal verkapseltem Taxol |
DE4432378A1 (de) * | 1994-09-12 | 1996-03-14 | Bayer Ag | Injizierbare liposomale Arzneizubereitungen |
US5589189A (en) * | 1994-09-14 | 1996-12-31 | Nexstar Pharmaceuticals, Inc. | Liposome dispersion |
FR2728166A1 (fr) * | 1994-12-19 | 1996-06-21 | Oreal | Composition topique contenant un antagoniste de substance p |
US5660855A (en) * | 1995-02-10 | 1997-08-26 | California Institute Of Technology | Lipid constructs for targeting to vascular smooth muscle tissue |
EP0831796A1 (en) * | 1995-06-07 | 1998-04-01 | University Of Southern California | Method for reducing or preventing post-surgical adhesion formation using 5-lipoxygenase inhibitors |
US5858397A (en) * | 1995-10-11 | 1999-01-12 | University Of British Columbia | Liposomal formulations of mitoxantrone |
TW497974B (en) * | 1996-07-03 | 2002-08-11 | Res Dev Foundation | High dose liposomal aerosol formulations |
US6515016B2 (en) * | 1996-12-02 | 2003-02-04 | Angiotech Pharmaceuticals, Inc. | Composition and methods of paclitaxel for treating psoriasis |
WO1999000111A1 (en) * | 1997-06-27 | 1999-01-07 | Astra Aktiebolag (Publ) | Proliposome powders for inhalation stabilised by tocopherol |
DE59911149D1 (de) * | 1998-07-24 | 2004-12-30 | Jago Res Ag Muttenz | Medizinische aerosolformulierungen |
CN1320880C (zh) * | 1998-12-23 | 2007-06-13 | 伊迪亚股份公司 | 改进的体内局部无创伤用制剂 |
GR1003359B (el) | 1998-12-24 | 2000-04-10 | �.�. ����������� �.�.�.�. | Λιποσωμιακο νιφλουμικο οξυ - νεο διαδερμικο αντιφλεγμονωδες φαρμακο [κεφαλη ψαροτουφεκου |
GB9930160D0 (en) * | 1999-12-22 | 2000-02-09 | Biovector Solutions Limited | Drug delivery |
AU4239302A (en) * | 2001-06-28 | 2003-01-02 | Pfizer Products Inc. | Benzoic acid substituted benzopyrans for the treatment of atherosclerosis |
GB0118517D0 (en) * | 2001-07-30 | 2001-09-19 | Mitsubishi Tokyo Pharm Inc | Compound |
US20030054030A1 (en) * | 2001-09-13 | 2003-03-20 | Gary Gordon | Method and compositions for the treatment of pruritus |
US20040224012A1 (en) * | 2001-10-05 | 2004-11-11 | Pichit Suvanprakorn | Topical application and methods for administration of active agents using liposome macro-beads |
US20030235610A1 (en) * | 2002-06-21 | 2003-12-25 | Piedmont Pharmaceuticals, Llc | Liposomes containing biologically active compounds |
SE0300207D0 (sv) * | 2003-01-29 | 2003-01-29 | Karolinska Innovations Ab | New use and composition |
GB0317509D0 (en) * | 2003-07-25 | 2003-08-27 | Pfizer Ltd | Nicotinamide derivatives useful as PDE4 inhibitors |
US20050255154A1 (en) | 2004-05-11 | 2005-11-17 | Lena Pereswetoff-Morath | Method and composition for treating rhinitis |
-
2006
- 2006-06-08 JP JP2008515287A patent/JP5846711B2/ja not_active Expired - Fee Related
- 2006-06-08 RU RU2007149239/15A patent/RU2468797C2/ru active
- 2006-06-08 PT PT67441436T patent/PT1888033E/pt unknown
- 2006-06-08 ES ES06744143.6T patent/ES2462541T3/es active Active
- 2006-06-08 US US11/921,850 patent/US20090220583A1/en not_active Abandoned
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- 2006-06-08 DK DK06744143.6T patent/DK1888033T3/da active
- 2006-06-08 KR KR1020077028659A patent/KR20080016621A/ko active Search and Examination
- 2006-06-08 MX MX2007015577A patent/MX2007015577A/es active IP Right Grant
- 2006-06-08 AU AU2006256518A patent/AU2006256518B2/en active Active
- 2006-06-08 WO PCT/GB2006/002090 patent/WO2006131737A2/en active Application Filing
- 2006-06-08 SI SI200631775T patent/SI1888033T1/sl unknown
- 2006-06-08 CA CA2608631A patent/CA2608631C/en active Active
- 2006-06-08 PL PL06744143T patent/PL1888033T3/pl unknown
-
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- 2007-11-07 NO NO20075660A patent/NO339538B1/no unknown
- 2007-11-19 IL IL187480A patent/IL187480A/en active IP Right Grant
-
2008
- 2008-05-09 HK HK08105222.1A patent/HK1111884A1/xx unknown
-
2013
- 2013-06-18 JP JP2013127234A patent/JP2013209423A/ja not_active Ceased
-
2014
- 2014-05-06 HR HRP20140406TT patent/HRP20140406T1/hr unknown
-
2015
- 2015-11-12 US US14/939,911 patent/US20160166508A1/en not_active Abandoned
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4839175A (en) * | 1986-07-28 | 1989-06-13 | Liposome Technology, Inc. | Liposomes with enhanced retention on mucosal tissue |
Also Published As
Publication number | Publication date |
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JP5846711B2 (ja) | 2016-01-20 |
MX2007015577A (es) | 2008-02-25 |
WO2006131737A3 (en) | 2007-03-29 |
RU2007149239A (ru) | 2009-07-20 |
EP1888033A2 (en) | 2008-02-20 |
PT1888033E (pt) | 2014-05-15 |
KR20080016621A (ko) | 2008-02-21 |
JP2008542438A (ja) | 2008-11-27 |
WO2006131737A2 (en) | 2006-12-14 |
PL1888033T3 (pl) | 2014-09-30 |
JP2013209423A (ja) | 2013-10-10 |
EP1888033B1 (en) | 2014-02-19 |
US20090220583A1 (en) | 2009-09-03 |
ES2462541T3 (es) | 2014-05-23 |
HK1111884A1 (en) | 2008-08-22 |
NO20075660L (no) | 2008-02-22 |
CA2608631A1 (en) | 2006-12-14 |
AU2006256518B2 (en) | 2012-03-15 |
US20160166508A1 (en) | 2016-06-16 |
RS53329B (en) | 2014-10-31 |
SI1888033T1 (sl) | 2014-06-30 |
HRP20140406T1 (hr) | 2014-06-06 |
RU2468797C2 (ru) | 2012-12-10 |
DK1888033T3 (da) | 2014-05-26 |
IL187480A0 (en) | 2008-02-09 |
NZ563373A (en) | 2012-06-29 |
AU2006256518A1 (en) | 2006-12-14 |
IL187480A (en) | 2014-02-27 |
CA2608631C (en) | 2014-07-29 |
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