HRP20050804A2 - Combination therapy for the treatment of immunoinflammatory disorders - Google Patents
Combination therapy for the treatment of immunoinflammatory disorders Download PDFInfo
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- HRP20050804A2 HRP20050804A2 HR20050804A HRP20050804A HRP20050804A2 HR P20050804 A2 HRP20050804 A2 HR P20050804A2 HR 20050804 A HR20050804 A HR 20050804A HR P20050804 A HRP20050804 A HR P20050804A HR P20050804 A2 HRP20050804 A2 HR P20050804A2
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Abstract
Izum prikazuje metodu tretmana pacijenta kojem jedijagnosticiran imunoupalni poremećaj ili je rizičan na njegov razvitak, a davanjem pacijentu nesteroidnog o imunofilinu ovisnog imunosupresanta (NsIDI), pojačivača NsIDI (NsIDIE) ili analog ili metabolita za tretman ili prevenciju imunoupalnog poremećaja.
Description
Dosadašnje spoznaje
Izum se odnosi na tretman imunopalnih poremećaja.
Imunoupalni poremećaji su katakterizirani neodgovarajućom aktivacijom tjelesnog imunog sustava za obarnu. Umjesto ciljanja izazivača infekcije, imuni odgovori ciljaju i oštećuju vlastita tkiva od tijela ili transplantiranih tkiva. Tkivo ciljano od imunog sustava se razlikuje prema poremećaju. Primjerice, kod multiple skleroze je imuni odgovor upućen na neuronalno tkivo, dok je kod Crohnove bolesti ciljan probavni trakt. Imunoupalni poremećaji pogađaju milijune pojedinaca i uključuju stanja kao što su astma, alergijske intraokularne upalne bolesti, artritis, atopični dermatitis, atopična ekcema, dijabetes, hemolitička anemija, upalne dermatoze, upala crijeva, ili gastointestinalni poremećaji (npr. Crohnova bolest i ulcerativni kolitis), multiple skleroza, miastenija gravis, pruritis/upala, psorijaza, reumatoidni artritis i sistemski eritematozni lupus.
Sadašnji režimi tretmana imunoupalnih poremećaja se tipično oslanjaju na imunsupresivna sredstva. Učinkovitost tih sredstava se može mijenjati i njihova uptreba je često praćena nepoželjhnim nuzefektima. Stoga su poboljšana terapisjka sredstva i metode za tretman imunoupalnih poremećaja potrebna.
Sažetak izuma
Mi smo otkrili da je kombinacija nesteroidnog o imunofilinu ovisnog imunosupresanta (NsIDI) (npr. ciklosporin A) i nesteroidnog o imunofilinu ovisnog pojačivača imunosupresanta (NsIDIE) (npr. selektivni inhibitor prihvata serotonina (SSRI), triciklički antidepresiv, fenoksifenol, antihistamin, fenotiazin ili agonist �-opioidnog receptora) učinkovitiji u smanjivanju izlučivanja proinflamatornih citokina od bilo kojeg sredstva samog. Stoga se kombinacije NsIDI i NsIDIE kao i njihovih strukturnih ili funkcionalnih analoga mogu koristiti u antiupalnoj kombinaciji iz izuma.
U jednom aspektu izum općenito prikazuje pripravak koji sadrži nesteroidni o imunofilinu ovisni imunosupresant i nesteroidni o imunofilinu ovisni pojačivač imunosupresanta (NsIDIE) u količinama koje su zajedno dovoljne za in vivo smanjivanje izlučivanja proinflamatornih citokina ili produkciju ili tretman imunoupalnog poremećaja.
Pripravak može dalje sadržavati nesteroidni protuulani lijek (NSAID), inhibitor COX-2, biologik, antireumatski lijek koji modificira bolest (DMARD), ksantin, antikolinergični spoj, agonist beta receptora, bronhodilatator, nesteroidni inhibitor klacineurina, analog vitamina D, psoralen, retinoid ili 5-aminosalicilnu kiselinu. U nekim cjelinama pripravak je formuliran za topičko ili sistemsko davanje.
Izum također prikazuje metodu smanjivanja izlučivanja ili produkcije proinflamatornog citokina kod pacijenta, a metoda obuhvaća davanje pacijentu pripravak koji sadrži nesteroidni o imunofilinu ovisni imunosupresant (NsIDI) i pojačivač NsIDI (NsIDIE), istovremeno ili u razmaku jedan od drugog do 14 dana, a u količinama dovoljnim da in vivo smanje izlučivanje proinflamatornog citokina ili njegovu produkciju kod pacijenta.
Izum također prikazuje metodu smanjivanja izlučivanja ili produkcije proinflamatornog citokina kod pacijenta. Metoda obuhvaća davanje pacijentu NsIDI i pojačivač NsIDIE, istovremeno ili u razmaku jedan od drugog do 14 dana, a u količinama dovoljnim da in vivo smanje izlučivanje proinflamatornog citokina ili njegovu produkciju kod pacijenta.
Uz ovo izum prikazuje metodu tretmana pacijenta kojem je dijagnosticiran imunoupalni poremećaj ili je na njega rizičan. Metoda obuhvaća davanje pacijentu NsIDI i NsIDIE, istovremeno ili u razmaku jedan od drugog do 14 dana, a u količinama dovoljnim da in vivo smanje izlučivanje proinflamatornog citokina ili njegovu produkciju kod pacijenta.
Izum također prikazuje metodu smanjivanja izlučivanja ili produkcije proinflamatornog citokina ili njegove produkcije u stanici (npr. stanice sisavaca in vivo). Metoda obuhvaća dovođenje u kontakt stanica s NsIDI i NsIDIE, istovremeno ili u razmaku jedan od drugog do 14 dana, a u količinama dovoljnim da in vivo smanje izlučivanje proinflamatornog citokina ili njegovu produkciju u stanici.
Izum također prikazuje komplet koji sadrži NsIDI i NsIDIE, upute za davanje pripravka pacijentu kojem je dijagnosticiran upalni poremećaj ili je rizičan na njega.
Izum također prikazuje komplet koji sadrži pripravak koji sadrži NsIDI i NsIDIE, upute za davanje NsIDI i NsIDIE pacijentu kojem je dijagnosticiran uupalni poremećaj iz je rizičan na njega.
Izum također prikazuje komplet koji sadrži NsIDI, upute za davanje NsIDI i NsIDIE pacijentu kojem je dijagnosticiran uupalni poremećaj iz je rizičan na njega.
Uz ovo, izum također prikazuje komplet koji sadrži NsIDIE i upute za davanje NsIDI i NsIDIE pacijentu kojem je dijagnosticiran uupalni poremećaj iz je rizičan na njega.
Izum prikazuje metodu identifikacije kombinacija spojeva korisnih za sprječavanje izlučivanja proinflamatornih citokina kod pacijenta koji ima potrebu za takvim tretmanom. Metoda obuhvaća (a) dovođenjem u kontakt stanica in vitro sa NsIDI i spojem kandidatom, te (b) određivanje je li kombinacija NsIDI i spoja kandidata smanjuje razine citokina u stanicama krvi stimuliranim da izlučuju citokine, a u odnosu na stanice koje su došle u kontakt sa NsIDI a nisu došle u kontakt sa spojem kandidatom ili stanicama koje su došle u kontakt sa spojem kandidatom ali nisu došle u kontakt sa NsIDI, pri čemu smanjivanje razine citokina identificira kombinaciju kao kombinaciju koja je korisna za tretman pacijenta koji ima portrebu za takvim tretmanom.
U preferiranim cjelinama bilo kojeg od prethodnih aspekata bilo kejeg od prethodnih aspekata, NsIDI je primjerice inhibitor kalcineurina kao što je ciklosporin, takrolimus, askomicin, pimekrolimus ili ISAtx247 ili protein koji vezuje FK506 kao što je rapamicin ili everolimus.
U preferiranim cjelinama bilo kojeg od prethodnih aspekata bilo kejeg od prethodnih aspekata, pojačivač NsIDI (NsIDIE) je primjerice selektivni inhibitor prihvata serotonina (SSRI), triciklički antidepresiv (TCA), fenoksifenol, antihistamin, fenotiazin ili agonist opioidnog receptora.
"Nesteroidni o imunofilinu ovisan imunosupresant" ili "NsIDI" znači nesteroidno sredstvo koje smanjuje produkciju ili izlučivanje proinflamatornog citokina, vezuje imunofilin ili uzrokuje smanjivanje protuupalne reakcije. NsIDI ukjlučuju inhibitore kalcineurina kao što je: ciklosporin, takrolimus, askomicin, pimekrolimus kao i ostala sredstva (peptidi, fragmenti peptida, kemijski modigicirani peptidi ili mimetici peptida) koji inhibiraju fosfonatnu aktivnost kalcineurina. NsIDI također uljučuju repamicin (sirolimus) i everolim, koji se vežu na FK5065-vezujući protein, FKBP-12, blok antigenom induciranu proliferaciju bijelih krvnih zrnaca i izlučivanja citokina.
"Pojačivač nesteroidnog o imunofilinu ovisnog imunosupresanta" ili "NsIDIE" označuje bilo koji spoj koji povećava učinkovitost nesteroidnog o imunofilinu ovisnog imunosupresanta. NsIDIE obuhvaća selektivne inhibitore prihvata serotonina, tricikličke antidepresive, fenoksifenol (npr. triklosan), antihistamine, fenotiazin ili agoniste opioidnog receptora.
"Antihistamin" označuje spoj koji blokira djelovanje histamina. Klase antikisamina jesu ali bez ograničenja etanolamini, etilendiamini, fenotiazin, alkilamini, piperazini i piperidini.
"Selektivni inhibitor prihvata serotonina" "SSRI" označuje bilo koji član klase spojeva koji (i) inhibira prihvat serotonina od neurona u centralnom nervnom sustavu, (ii) ima inhibicijsku konstatnu (Ki) od 10 nM ili manju te (iii) selektivnost prema serotoninu o odnosu nanorpinefedrin (t.j. omjer Ki(norpineferdin) prema Ki(serotonon) je veći od 100). Tipično, SSRI su dani u dozama većim od 10 mg po dana kada se koriste kao antidepresivi. Ovjde su opisani primjeri SSRI za uptrebu u izumu.
"Triciklički antidepresiv" ili "TCA" označuje spoj koji ima formule (I), (II), (III) ili (IV):
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u kojima svaki X neovinso jeste H, Cl, F, Br, I, CH3, CF3, OH, OCH3, CH2CH3 ili OCH2CH3; Y jeste CH2, O, NH, S(O)0-2, (CH2)3, (CH)2, CH2O, CH2NH, CHN ili CH2S; A je razgranati ili nerazgranati zasićeni ili mono-nezasićeni ugljikovodičmi lanac koji ima uključujući između 3 i 6 ugljika; B neovinso jeste H, Cl, F, Br, I, CX3, CH2CH3, OCX3 ili OCX2CX3; te D jeste CH2, O, NH, S(O)0-2.
U preferiranim cjelinama svaki X neovinso jeste H, Cl ili F Y jeste (CH2)2, Z jeste C; A jeste (CH2)3, te svaki B neovisno jeste H. Cl ili F.
Primjeri tricikličkih antidepresiva jesu maprotilin, amoksapin, 8-hidroksiamoksapin, 7-hidroksiamoksapin, loksapin, loksapin sukcinat, loksapin hidroklorid, 8-hidroksilokspain, amitriptilin, klomipramin, doksepin, imipramin, trimipramin, desipramin, notriptilin i protriptilin.
"Kortikosteroid" označuje prirodni ili sintetski steroidni hormon koji se može izvesti od kolesterola i karakteriziran je hidriranom ciklopentanperhidro-fenantrenskim sustavom prstena. Prirodni kortikosteroidi se općenito dobivaju iz nadbubrežnog korteksa. Sintetski kortikosteroidi se mogu halogenirati. Primjeri kortikosteroida su prikazani ovdje.
"Imunomodulator male molekule" označuje nesteroidni ne-NsIDI spoj koji smanjuje produkciju ili izlučivanje proinflamatornog citokina, uzrokuje smanjivanje proinflamatorne reakcije ili na drugi način modulira imuni sustav na o imunofilinu neovisan način. Primjeri malih molekula imunomodulatora su inhibitori p38 kinaze kao što je VX 702 (Vertex Pharmaceutsicals), SCIO 469 (Scios), doramapimod (Boeringer Ingelheim), RO 30201195 (Roche) i SCIO 323 (Scios), inhibitori TACE kao što je DPC 333 (Bristol Myers Squibb), inhibitori ICE kao što je pranalkasan (Vertex Pharmaceuticals) i inhibitori IMPDH kao što jemikofenolat (Roche) i merimepodib (Vertex Pharmaceuticals).
"Niska doza" označuje najmanje 5% manju (npr. najmanje 10%, 20%, 50%, 80%, 90% ili čak 95%) od najniže standardne preporučene doze određenog spoja formuliranog za dani način davanja za tretman bilo koje humane bolesti ili stanja. Primjerice, niska doza kortikosteroida formulirana za davanje inhalacijom će se razlikovati od niske doze kortikosteroida formuliranog za oralno davanje.
"Visoka doza" označuje najmanje 5% (npr. najmanje 10%, 20%, 50%, 100%, 200% ili čak 300%) veću od najviše standardne preporučene doze određenog spoja za tretman humene bolesti ili stanja.
"Srednja doza" označuje dozu između niske doze i visoke doze.
"Tretiranje" označuje davanje ili prepisivanje farmaceutskog pripravka za tretman ili prevenciju imunoupalne bolesti.
"Pacijent" znači bilo koju životinju (npr. čovjeka). Ostale životinje koje mogu biti tretirane upotrebom metoda, pripravaka i kompleta iz izuma jesu: konji, psi, mačke, svinje, koze, zečevi, hrčci, majmuni, zamorci, štakori, miševi, gušteri, zmije, ovce, ribe i ptice. U jednoj cjelini izuma, pacijent je subjekt za ovjde opisan tretman koji nema kliničku depresiju, anksioznost ili panični poremećaj, poremećaj pomanjkanja pažnje, granični poremežaj osobnosti, poremežaj spavanja, glavobolju, premenstrualni sindrom, neregularne otkucaje srca, shizofreniju, Touretteov sindrom ili fobije.
"Dovoljna količina" označuje količinu spoja u kombinaciji iz izuma potrebnu za tretman ili prevenciju imunoupalne bolesti na klinički relevantni način. Dovoljna količina aktivnog spoja korištena za praksu ovog izuma za terapijski tretman stanja uzrokovanih ili koja su doprinijela imunoupalnoj bolesti se razlikuju ovisno o načinu davanja, starosti, tjelesnoj težini i općen zdravlju pacijenta. Konačno će osoba koja prepisuje lijek će odlučiti o pogodnoj količini i režimu doziranja.
"Učinkovitija" označuje da metoda, pripravak ili paket pokazuje veću učinkovitost ili je manje toksičan sigurniji je i pogodniji ili je jeftiniji od druge metode pripravka ili paketa s kojim se uspoređuje. Učinkovitost može mjeriti stručnjak upotrebom standardne metode koja je pogodna za danu indikaciju.
Termin "imunoupalni premećaj" obuhvaća različita stanja uključujući autoimune bolesti, proliferativne kožne bolesti i upalne dermatoze. Imunoupalni poremećaju imaju kao rezultat uništavanje zdravog tkiva upalnim procesom, poremećenu regulaciju imunog sustava i neželjenu proliferaciju stanica. Primjeri imunoupalnih poremećaja su: akne vulgaris, akutni respiratorni distresni sindrom, Addisonova bolest, alergijski rinitis, alergijski intraokularni upalni poremećaji, s ANCA povezan vaskupitis malih žila, ankilozni spondilitis, artritis, astma, eteroskleroza, atopični dermatitis, autoimuna hemolitička anemija, autoimuni hepatitis, Bechetova bolest, Bellova parazliza, bulozni penfigoid, cerebralna ishemija, kronična opstruktivna plućna bolest, Coganov sindrom, kontaktni dermatitis, COPD, Cronova bolest, Cusgingov sindrom, dermatoiozitis, dijabetes melitus, diskoidni eritematozni lupus, eozinofilni fascitis, eritema nodusum, eksfoliativni drmatitis, fibromialgija, fokalni glomeruloskleroza, arterisi velikih stanica, giht, artritis uzrokovan gihtom, bolest odbacivanja transplanta, ekcenma na ruci, Henoch-Schonleinova purpura, herpes gestationis, hirsuitizam, idipatski kerato-skleritis, idiopatska plučna fibroza, idopatska trombocitopensk purpura, upalni crijevni ili gastointestinalni poremećaj, upalna dermatoza, lišaj, lupus nefritis, lumfomatni traheobronhitis, makularna edema, multipla skleroza, miastenija gravis, miozitis, osteoartritis, pankreatitis, pemfigoidna gestatinoza, pemfigus vulgaris, poliarteritis nodoza, reumatična polimialgija, pruritus skrotiuma, pruritis/upala, psorijaza, psorijatički artritis, reumatoidni artritis, relapsirajći polikondritis, rozacea uzrokovana sarkoidozom, rozacea uzrokovana sklerodemom, rozacea uzrokovana Sweerovim sindromom, rozacea uzrokovana sistemskim lupus eritematozom, rozacea uzrokovana utrikarijom, rozacea uzrokovana boli povezanom sa zoster, sarkoidoza, skleroderma, segmentalna glomeruloskleroza, sindrom septičkog šoka, tendinitis ramena ili bursitis, Sjorgenov sindrom, Stillova bolest, udarom inducirana smrt stanica mozga, Sweetova bolest, sistemski eritematozni lupus, sistemska skleroza, Takayasuov srteritis, prolazni arteiritis, toksična epidermalna nekroza, dijabetes tipa-1, ulcerativni kolitis, uveitis, vaskulitis i Wegenerova granulomatoza.
"Nedermalni upalni poremećaj" uključuje primjerice sljedeće: reumatoidni artritis, upalna bolest crijeva i kornična opstruktivna plućna bolest.
"Dermalni upalni poremećaj" ili "upalna dermatoza" uključuje primjerice psorijazu, akutnu febrilnu neurofilnu dermatozu, akcemu (npr. asteatičnu ekcemu, dishidrotičku ekcemu, vezikularno palmoplantarnu ekcemu), balanitis cirkumskripta plazmacelularis, balanopostitis, Bechetova bolest, eritema anusa, multiformna eritema, anusni granulom, lišaj nitidus, lišaj planus, lišaj sklerosus i atropikus, kronični lišaj simpleks, lišaj spinulozus, numularni dermatitis, gangrena piroderme, sarkoidoza, subkornealna pustularna dermatoza, utrikarija i prolazna akantolitička dermatoza.
"Proliferativna bolest kože" označuje benignu ili malignu bolest koja je karakterizirana ubrzanom diobom stanica u epidermu ili dermisu. Primjeri proliferativne bolesti kože su psorijaza, atopični dermatitis, nespecifični dermatitis, primarni irirantni kontaktni dermatitis, alergijski kontktni dermatitis, karcinom bazalnih i skvamoznih stanica kože, lamelarna ihtioza, epidermolitička hiperkeratoza, premalgna keratoza, premaligna keratoza, akne i seborični dermatitis.
Kao što će stručnjak prepoznati, određena bolest, poremećaj ili stanje se može karakterizirati proliferativnom kožnom bolesti i upalnom dermatozom. Primjer takve bolesti je psorijaza.
"Odgođeno oslobađanje" ili "kontrolirano oslobađanje" označuje da se terapijski aktivna komponenta iz formulacije oslobađa kontroliranom brzinom tako da se terapijski pogodna razina u krvi (ali ispod toksične razine) komponente održava u produljenom periodu vremena u rasponu od npr. 12 do oko 24 sata i time omogućuju primjerice obik doze od 12 do 24 sata.
U generičkom opisu spojeva iz izuma, broj atoma određenog tipa u suptituiranoj skupini je općenito dana u rasponu, npr. alkilna skupina koja sadrži od 1 do 7 atoma ugljika ili C1-7alkil. Takvim navodom skupine se ukazuje na određenu skupinu koja može imati svaki cijeli broj atoma u zadanom rasponu. Primjerice alkilna skupina od 1 do 7 atoma ugljika uključuje C1, C2, C3, C4, C5, C6 i C7. C1-7heteroalkil primjerice sadrži 1 do 7 atoma uljika i jedan ili više heteroatoma. Ostali brojevi atoma drugog tipa atoma mogu biti naznačeni na sličan način.
"Acil" označuje kemijski ostatak formule R-C(O)- u kojem je R odabran od C1-7alkil, C2-7alkenil, C2-7alkinil, C2-6heterociklil, C6-12aril, C7-14alkaril, C3-10alkheterociklil, ili C1-7heteroalkil.
"Alkoksi" označuje kemijski supstituent formule -OR u kojem je R odabran od C1-7alkil, C2-7alkenil, C2-7alkinil, C2-6heterociklil, C6-12aril, C7-14alkaril, C3-10alkheterociklil, ili C1-7heteroalkil.
"Ariloksi" označuje kemijski supstituent formule -OR u kojem R jeste C6-12arilna skupina.
"C6-12aril" označuje aromatsku skupinu koja ima sustav prstena koji sadrži ugljikove atome s konjugiranim �-elektronima (npr. fenil). Arilna skupina ima od 6 do 12 atoma ugljika. Arilne skupine mogu uključivati monociklički, biciklički ili triciklički prsten u kojem je poželjno da svaki prsten ima pet ili šest članova. Arilna skpina može biti supstituirana ili nesupstituirana. Primjeri supstituenata uključuju alkill, hidroksi, alkoksi, ariloksi, sulfhidril, alkiltio, ariltio, halogenid, fluoralkil, karboksil, hidroksialkil, karboksialkil, amino, aminoalkil, monosupstituirani nitro, disupstituirani amino i kvaterna amino-skupina.
"Amido" označuje kemijski supstituent formule -NRR', u kojem je sušik dio amidne veze (npr. -C(O)-NRR') te u kojem R i R' svaki neovinsko jesu C1-7alkil, C2-7alkenil, C2-7alkinil, C2-6heterociklil, C6-12aril, C7-14alkaril, C3-10alkheterociklil, te C1-7heteroalkil, ili -NRR' tvori a C2-6 heterociklički prsten, koji je kao što je gore definirano, a sadrži baren jedan atom dušika kao što je među inima piperidino, morfolino i azabiciklo.
"Halogenid" ili "halo" označuje brom, klor, jod ili fluor.
Termin "farmaceutski prihvatljiva sol" predstavlja soli koje su unutar obujma medicinske procjene pogodne za upotrebu u kontatu s humanim tkivom i tkivom nižih životinja, a bez nepoželjne toksičnosti, iritacije, alergijskog odgovora i slični, te ima s razumni omjer koristi/rizik. Farmaceutski prihvatljive soli su dobro poznate u struci. Soli se mogu pripraviti in situ tjekom konačne izolacije i čišćenja ili u zasobnom koraku reakcijom slobodne bazne funcionalne skupine s pogodnom orgnaskom kiselinom. Predstavnici soli nastale adicijom kiseline jesu acetat, adipat, alginat, askorbat, aspartat, benzenesulfonat, benzoat, bisulfat, borat, butirat, kamforat, kamforsulfonat, citrat, ciklopentanepropionat, diglukonat, dodecilsulfat, etansulfonat, fumarat, glukoheptonat, glicerofosfat, hemisulfat, heptonat, heksanoat, hidrobromid, hidroklorid, hidrojodid, 2-hidroksietansulfonat, isotionat, laktobionat, laktat, laurat, lauril-sulfat, malat, maleat, malonat, mezilat, metansulfonat, 2-naftalensulfonat, nikotinat, nitrat, oleat, oksalat, palmitat, palmoat, pektinat, persulfat, 3-fenilpropionat, fosfat, pikrat, pivalat, propionat, stearat, sukcinat, sulfat, tartarat, tiocijanat, toluenesulfonat, undekanoat, valerat i slično. Predstavnici soli alkalijskih metala jesu natrij, litij, kalij, kalcij, magnezij kao i netoksične amonijeve, kvaterne amonijeve soli i aminski kationi uključujući ali bez ograniženja amonijeve, etrametilaminojeve, tetraetilamonijeve, metilamin, dimetilamin, trimetilamin, trietilamin, etilamin i sllično.
Spojevi korisni u izumu uključuju one opisane uključuju one opisane ovdje u bilo kojem njihovom farmaceutski prihvatljivom obliku uključujući izomere kao što su dijastereomeri i enantiomeri, soli, esteri, amidi, tioesteri, solvati i njihovi polimorfi kao i racemične smjese čistih izomera ovdje opisanih spojeva. Primjerice "paroketin" označuje slobodnu bazu kao i bilo koju odgovarajuću farmaceutski prihvatljivu sol (npr. paroksetin maleat, paroksetin hidroklorid semihidrat i paroksetin mezilat).
Ostale karakteristike i prednosti izuma će biti očite iz sljedećeg detaljnog opisa te iz zahtjeva.
Detaljni opis
Izum prikazuje metode, pripravke i komplete za davanje učinkovite količine nesteroidnog o imunofilinu ovisnog imunosupresanta (NsIDI) i nesteroidnog o imunofilinu ovisnog pojačivača imunosupresanta (NsIDIE) npr. selektivnoh inhibitora prihvata serotonina, tricikličkog antidepresiva, fenoksifenol, antihistamin, fenotiazin ili agonist opiodinog receptora.
Izum je detaljnije opisan niže.
Nesteroidni o imunofilinu ovisna imunosupresant
U jednoj cjelini izum prijazuje metode, priprave i komplete koji koriste NsIDI i NsIDIE, a može s kortikosteroidom ili drugim ovdje opisanim sredstvom.
Kod zdravih pojedinaca imuni sustav koristi stanične efektore kao što su B-stanice ili T-stanice, za ciljanje infektivnih mikroba i abnormalnih tipova stanica, dok zdrave stanice ostavljaju netaknute. Kod pojedinaca s autoimunim poremećajem ili koji imaju translantirane organe, aktivirane T-stanice oštećuju zdravo tkivo. Inhibitori kalcineurina (ciklosporini, takrolimus, pimekrolimus) i rapamicin ciljaju mnoge tipove imunoregularoskih stanica uključujući T-stanice i sprječavaju imuni odgovor u transplantiranom organu i autoimuni poremećaj.
Ciklosporini
Ciklosporini su gljivični metaboliti koji sadrže klasu cikličkih oligopeptida koji djeluju kao imunosupresanti. Ciklosporin A i njegov deuterirani analog ISAtx247 su hidrofobni ciklički polipeptidi koji sadrže jedanaest aminokiselina. Ciklosporin A se veže i tvori kompleks s intraceluarnim receptorom ciklofilina. Kompleks ciklosporin/ciklofilina se veže i inhibira kalcineurin, koji je o Ca2+-kalmodulinu ovisna serin-treonin specifilčna fosfotaza. Kalcineurin održava transdukcijski signal potreban za aktivaciju T-stanice (revijalni prikaz u Schreiber et al., Cell 70:365-368, 1991). Ciklosporini i njihovi funkcionalni i strukturni analozi sprječavaju imuni odgovor ovisan o T-stanicama, a inhibicijom antigenom potaknute transdukcije signala. Inhibicija smanjuje ekspresiju proinflamatornih citokina kao što je IL-2.
Mnoge ciklosporine (npr. ciklosporin A, B, C, D, E, F, G, H i I) stvaraju gljivice. Ciklosporin A je komercijalno pristupačan pod trgovačkim nazivom NEORAL od Novartis. Strukturni i funkcionalni analozi uključuju ciklosporine koji imaju jednu ili više fluoriranu aminokiselinu (opisano npr. u U.S. Patent br. 5,227,467); ciklosporine koji imaju modificirane aminokiseline (opisano npr. u U.S. Patent br. 5,122,511 i 4,798,823); te deuterirane ciklosporine kao što je ISAtx247 (opisanu u U.S. Patentnoj publikaciji br. 20020132763). Dodatni analozi ciklosporina su opisani u U.S. Patentima br. 6,136,357, 4,384,996, 5,284,826, te 5,709,797. Analozi ciklosporina uključuju, ali bez ograničenja na njih, D-Sar(�-SMe)3 Val2-DH-Cs (209-825), Allo-Thr-2-Cs, Norvaline-2-Cs, D-Ala (3-acetil-amino)-8-Cs, Thr-2-Cs i D-MeSer-3-Cs, D-Ser(O-CH2CH2-OH)-8-Cs, te D-Ser-8-Cs, koji su opisani u Cruz et al. (Antimicrob. Agents Cbemother. 44:143149,2000).
Mnogi ciklosporini su vrlo hidrofobni i lako se talože u prisutnosti vode (npr. nakon kontakta s tjelesnim tekućinama). Metode koje prikazuju formulacije ciklosporina s poboljšanom bioraspoložljivosti su opisane u U.S. Patentima br. 4,388,307, 6,468,968, 5,051,402, 5,342,625, 5,977,066 i 6,022,852. Mikroemulzijski pripravci ciklosporina su opisani u U.S. Patentima br. 5,866,159, 5,916,589, 5,962,014, 5,962,017, 6,007,840 i 6,024,978.
Ciklosporini mogu biti dani itravenozno ili oralno, ali je oralno davanje preferirano. Da bi se djelovalo na hidrofobnost ciklsporina A, intravenozni ciklosporin A je običnu u vezikulu etanol-polioksietiliranog ricinusovog ulja koji se mora prije davanja razrijediti. Ciklosporin A može biti npr. kao mikroemulzija u tabletama od 25 mg ili 100 mg ili u oralnim otopinama od 100 mg/mL (NEORAL™).
Mada se tipična doza za pacijenta oralnog danog ciklosporina se mijenja prema stanju pacijenta, neke prethodne stadarne preporuke u režima tretamna su ovdje prikazane. Pacijenti koji podliježu transplantaciji organa tipično primaju početnu dozu oralnog ciklosporina A u količinama između 12 i 15 mg/kg/dan. Doza se zatim postupno smanjuje 5% tjedno dok nije dostignuta doza od 7-12 mg/kg/dan, koja se održava. Za intravenozno davanje preferirano je 2-6 mg/kg/dan kod većine pacijenata. Za pacijente kojima je dijagnosticirana Crohnova bolest ili ulcerativni kolitis, općenito se daje doza od 6-8 mg/kg/danu. Za pacijente koji imaju sistemski eritematozni lupus doza je od 2.2-6.0 mg/kg/dan. Za psorijazu i reumatoidni artritis tipična količina doze je od 0.5-4 mg/kg/danu. često su ciklosporini dani u kombinaciji s ostalim imunosupresivnim sredstvoma kao što su glukokortikoidi. Dodatne informacije su prikazane u Tablici 3.
Tablica 3 - NsIDI
[image] Legenda
CsA=ciklosporin A
RA=reumatoidni artritis
UC=ulcerativni kolitis
SLE-sistemski eritematozni lupus
Takrolimus
Takrolimus (PROGRAF, Fujisawa), također poznat kao FK506, je imunosupresivno sredstvo koje je usmjeren na intracelularni signalnu transdukciju T-stanica. Takrolimus se vezuje na intracelularni protein FK506 (FKBP-12) koji nije strukturno povezan s ciklofilinom (Harding et al. Nature 341:758-7601, 1989; Siekienka et al. Nature 341:755-757, 1989; te Soltoff et al., J. Biol. Chem. 267:17472-17477,1992). Kompleks TFKBP/FK506 se vezuje na klacineurin i inhibira kalcineurinsku fosfataznu aktivnost. Ta inhibicija sprječava defosforilaciju nuklearne translokacije NFAT, koja je nuklearna komponenta koja započinje transkripciju gena potrebne za produkciju limfokine (npr. gama interferon IL-2) i aktivaciju T-stanica. Stoga takrolimus inhibira aktivaciju T-stanica.
Takrolimus je makrolidni antibiotik kojeg tvori Streptomyces tsukbaensis. On spječava djelovanje imunog sustava i produljuje preživljavanje transplatiranoh organa. Sada se može dobiti kao oralna formulacija ili za injektiranje. Kapsule traholima sadrže 0.5 mg, 1 mg ili 5 mg bezvodnog traholima unutar želatinzone kapsule. Formulacija za injektiranje sadrži 5 mg bezvodnog tarholima u ricinusovom ulju i alkoholu koja je razrijeđena s 9% natrijevim kloridom ili 5% dektrozom prije injektiranja. Mada je oralno davanje preferirano, pacijenti koji ne mogu primati oralne kapsule primaju traholim za injketiranje. Početna doza treba biti dana ne prije od šest sati nakon transplantacije pod uvjetima kontinuirane infuzije.
Traholim ili analozi traholima su opisani u Tanaka et al., (J. Am. Chem. Soc. 109:5031, 1987), i u U.S. Patentima br. 4,894,366, 4,929,611 i 4,956,352. Spojevi odgovarajući FK506, uključujući FR-900520, FR-900523 i FR-900525 su opisani u U.S. Patentu br. 5;254,562; O-aril, O-alkil, O-alkenil i O-alkini makrolidi su opisani u U.S. Patentima br. 5,250,678, 532,248, 5,693,648; amino-O makrolidi su opisani u U.S. Patentu br. 5,262,533; alkilidenski makrolidi su opisani u U.S. Patentu No. 5,284,840; N-beteroaril, N-alkilheteroaril, N-alkenilheteroaril i N-alkinilheteroarilni makrolidi su opisani u U.S. Patentu No. 5,208,241; aminomacrolidi i njegovi derivati su opisani u U.S. Patent br. 5,208,228; fluormakrolidi su opisani u U.S. Patentu br. 5,189,042; amino-O-alkil, O-alkenil i O- aliklmakrolidi su opisani u U.S. Patent No. 5,162,334; a balomakrolidi su opisani u U.S. Patentu No. 5,143,918.
Mada će se preporučene doze mijenjati prema stanju pacijenta, standardne doze preporučene u prehodnim tretmanima su prikazane niže. Za pacijente kojima je dijagnosticirana Crohnova bolest ili ulcerativni kolitis, općenito se daje doza od 0.1-0.2 mg/kg/danu oralnog takrolimusa. Za pacijente kojima je transplantian organ tipične doze su od 0.1-2 mg/kg/dan oralnog takrolimusa. Pacijenti kojima je tretiran reumatoidni artritis tipično primaju 1-3 mg/danu takrolimus oralno. Za tretman sporijaze pacijentu se oralno daje 0.01-0.15 mg/kg/danu. Atopični dermatitis se može tretirati dva puta dnevno nanošenjem na pogođena mjesta kreme koja ima 0.01-0.1% takrolimusa. Pacijenti koji primaju kapsule takrolimusa tipično prime prvu dozu ne prije nego šest sati nakon transplantacije ili osam ili dvanaest sati nakon prestanka intravenozne infuzije takrolimusa. Druge preporučene doze takrolimusa uključuju 0.005-0.01 mg/kg/dan, 0.01-0.03 mg/kg/dan, 0.03-0.05 mg/kg/dan, 0.05-0.07 mg/kg/dan, 0.07-0.10 mg/kg/dan, 0.10-0.25 mg/kg/dan ili 0.25-0. 5 mg/kg/dan.
Takrolimus je ekstenzivno metaboliziran sa sustavom oksidaze s više funkcija, posebice s sustavim citokroma P-450. Primarni mehanizam metabolizma je demetiliranje i hidroksiliranje. Dok je vjerojatno da različiti metaboliti takrolimusa imaju imunosupresivnu biološku aktivnost, pokazano je da 13-demetilni metabolit ima isto aktivnost kao takrolimus.
Derivati pimekrolimusa i askomicina
Askomicin je bliski strukturni analog FK506 su moćni imunosupresanti. On se veže na FKBP-12 i sprječava aktivnost njegove prolinske rotamaze. Kompleks askiomicin-FKBP inhibira kalcineurin, fosfatazu tipa 2B.
Pimekrolimus (također poznat kao SDZ ASM-981) je 33-epi-klor-derivat askomicina. Prozivodi ga Streptomyces hygroscopicus var. ascomyceitus. Kao i takrolimus, pimekrolimus (ELIDEL™, Novartis) vezuje FKBP-12, inhibira aktivnost kalcineurin fosfata i inhibira aktivaciju T-stanica blokiranjem transkripcije ranog citokina. Tako pimekrolimus inhibira produkciju IL-2 i oslobađanje drugih proinflamatornih citokina.
Strukturni i funkcionalni analozi pimekrolimusa su opisani u U.S. Patenru br. 6,384,073. Pimekrolimus je posebno pogodan za tretman atotičnog dermatitia. Pimekrolimus je sada pristupačan kao 1% krema. Mada će se preporučene doze mijenjati prema stanju pacijenta, neke standardne preporučene doze su prikazane niže. Oralni pimekroplim može biti dan za tretman psorijaze i reumatoidnog artritisa u količinama od 40-60 mg/danu. Za tretman Crohnove bolest ili ulcerativnog kolitisa mogu se dati količine pimekrolimusa od 80-160 mg/danu. Pacijentima koji imaju transplantirani organ se može dati 160-240 mg/dan pimerolimusa. Pacijentima kojima je dijagnosticiran sistemski eritamatozni lupus se može dati pimekrolimus 40-120 mg/dan. Ostale kornse doze pimekrolimusa obuhvaćaju 0.5-5 mg/dan, 5-10 ,g/dan, 10-30 mg/dan, 40-80 mg/dan, 80-120 mg/dan ili čak 120-200 mg/dan.
Rapamicin
Rapamicin (RAPAMUNE® sirolimus, Wyeth) je ciklički lakton produciran od Steptomyces hygroscopicus. Rapamicin je inunosupresivno sredstvo koje inhibita aktivaciju i proliferaciju T-limfocita. Kao i ciklosporini, takrolimus i pimekrolimus, rapamicin tvor kompleks s imunofilinom FKBP-12, ali kompleks rapamycin-FKBP-12 ne inhibira aktivnost kalcineurin fosfata. Kompleks rapamicin-imunofilin se vezuje i inhibira kod sisavaca cilj rapamicina (mTOR), kinazu koja je potrebna za odvijanje staničnog ciklusa. Inihibicija aktivnosti mTOR kinaze blokira proliferaciju T-limfocita i izlučivanje limfokina.
Struktirni i funkcionalni analozi rapamicina uključuju mono- i diacetilirane derivate rapamicina (U.S. Patent br. 4,316,885); u vodi topljiv prolijek rapamicina (U.S. Patent No. 4,650,803); estere karboksilne kiseline (PCT publikacija br. WO 92/05179); karbamate (U.S. Patent br. 5,118,678); amid-estere (U.S. Patent br. 5,118,678); estere biotina (U.S. Patent br. 5,504,091); fluorirane estere (U.S. Patent br. 5,100,883); acetale (U.S. Patent br. 5,151,413); siline etere (U.S. Patent br. 5,120,842); bicikličke derivate (U.S. Patent br. 5,120,725); dimete rapamicina (U.S. Patent br. 5,120,727); O-aril, O-alkil, O-alkenik i O-alkinilne derivate (U.S. Patent br. 5,258,389); i deuterirani rapamicin (U.S. Patent br. 6,503,921). Dodatni analozi rapamicina su opisani u U.S. Patentima br. 5,202,332 and 5,169,851.
Everolim (40-O-(2-hidroksietil)rapamicin; CERTICAIN™; Novartis) je imunosupresivni makrolid koji je strukturno sličan rapamicinu za kojeg je nađeno da je posebno učinkovit u prevenciji akutnog odbijanja trnasplantiranog organa, a kada je dan u kombinaciji s ciklosporinom A.
Rapamicin je sada na raspolaganju za oralno davanje u formulaciji talbete i tekućine. RAPAMUNE™ tekućina sadrži 1 mg/mL rapamicina koji se razrijeđuje u vodi ili soku od naranče prije davanja. Također su na raspolaganju talbete koje sadrže 1 ili 2 mg rapamicina. Rapamicin je preferirano dan jedanput na dan, neposredno nakon transplantacije. Brzo i potpuuno se apsorbira nakon oralnog davanja. Mada se tipinčo pacijentova doza rapamicina mijenja prema stanju pacijenta, neke stadardne preporučene doze su dane niže. Početna doza rapamicina je 6 mg. Zatim se održava tipična doza od 2 mg/dan. Alternativno se može koristiti početna doza od 3 mg, 5 mg, 10 mg, 15 mg, 20 mg ili 25 mg, a održavati doza od 1 mg, 3 mg, 5 mg ili 10 mg dnevno. Ako je težina pacijeta manja od 40 kg, doza rapamicina je tipično podešena zasnovano na površini tijela, općenito se koristi 3 mg/m2/dan početna doza i 1 mg/m2/dan održavana doza.
Peptidni dijelovi
Peptidi, peptidomimetici, fragmenti peptida, bilo prirodni, sintetski ili kemijski modificirani, a koji sprječavaju kalcineurinom održavanu defosforilaciju i nukleoarnu translokaciju NFAT su korisni za upotrebu u praksi izuma. Primjeri peptida koji djeluju kao inhibitori klacineurina inhibicijom aktivacije NFAT transkripcijskog faktora su oisani primjeri u Aramburu et al. Scinece 285:2129-2133, 1999) i Aramburu et al. Mol. Cell 1:627-637, 1998). Kao klasa inhibitora klacineurina, ti spojevi su korisni u metodama iz izuma.
Selektivni inhibitori prihvata serotonina
Metode, pripravci i kopmleti iz izuma koriste selektivni inhibitor prihvata serotonina (SSRI) ili njegov strukturni ili funkcionalni analog u kombinaciji s nesteroidnim o imunofilinu ovisnim imunosupresantu (NsIDI). Pogodni SSRI uključuju ceriklamin (npr. ceriklamin hidroklorid), citalopram (npr. citalopram hidrobromid), klovoksamin, cijanodotiepin, dapoksetin, escitalopram (escitalopram oksalat), femoksetin (npr. femoksetin hidroklorid), fluoksetin (npr. fluoksetin hidroklorid); fluvoksamin (npr. fluvoksamin maleat); ifoksetin; indalpin (npr. indalpin hidroklorid); indeloksazin (npr. indeloksazin hidroklorid); litoksetin; milnacipran (npr. minlacipran hidroklorid); paroksetin (npr., paroksetin hidroklorid bemihidrat; paroksetin-maleat; paroksetin-mezilat); sertralin (npr., sertralin hidroklorid); tametralin hidroklorid; vikvalin i zimeldin (npr. zimeldin hidroklorid).
SSRI su lijekovi koji imhibiraju prihvat 5-hidroksitriptamina (5-HT) u neurone centralnog nervnog sustava. SSRI pokazuju selektivnost prema 5-HT u odnosu na prihvat norepinefrina. Manje je vjeroijatno da triciklički antidepresiv uzrokuje antikolinergični nusefekt i manje je opasan pri predoziranju. SSRI kao što je paroksetin, sertralin, fluoksetin, citalopram, fluvoskamin, nor1-citalopram, venlafaksin, milnacipran, nor2-citalopram, nor-fluoksetin ili nor-sertralin se koriste u tretmanu različitih psihijatrijskih poremećaja uključujući depresiju, poremećaj anksioznoati, napad panike i opsesivno komplsive poremećaj. Ovdje dane suze su standardne preporučene doze za psihijatriske poremećaje. U praksi metoda iz izuma, učinkovite količine mogu biti različite.
Davanje svakog lijeka u kombinaciji može neovisno biti jedan do četiri puta na dan kroz godinu dana, ili čak može biti cijeli život pacijenta. Kronično dugotrajno davanje će biti indicirano u mnogim slučajevima. Tipično će doza pacijenta SSRI varirari prema stanju pacijenta. SSRI se mogu davati oralno, u supozitoriju ili injekcijom. »esto se oralne doze daje jedanput na dan kao tableta ili tekući koncentrat.
Ceriklamin
Ceriklamin ima sljedeću strukturu:
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Strukturni analozi ceriklamina su oni koji imaju formulu:
[image]
kao i farmaceutski prihvaljive soli, pri čemu R1 jeste C1-C4 alkil, a R jeste H ili C1-C4 alkil, R3 jeste H, C1-C4 alkil, C2-C4 alenkil, fenilalkil ili cikloalkilalkil sa 3 do 6 ugljika u prstenu, alkanoil, fenilalkanoil ili cikloalklkarbonil koji ima 3 do 6 ugljika u prstenu ili R2 i R2 tvore zajedno s dušikovim atomom na koji su vezani hetericiklički zasićeni sa 5 do 7 vezanih prestena, kisik i sumpor ili dušik, a taj dušikov heteroatom može nositi C2-4alkil.
Primjeri analoga ceriklamisnke strukture su 2-metil-2-amino-3-(3,4-diklorfenil)-propanol, 2-pentil-2-amino-3-(3,4-diklorfenil)-propanol, 2-metil-2-metilamino-3-(3,4-diklorfenil)-propanol, 2-metil-2-dimetilamino-3-(3,4-diklorfenil)-propanol, te njihove farmaceutski prihvatljive soli.
Citalopram
Citalopram HBr (CELEXATM) je racemični biciklički derivat ftalana označen kao (±)-1-(3-dimetilaminopropil)-1-(4-fluorfenil)-1,3-dihidroizobenzofuran-5-karbonitril HBr. Citalopram podliježe metaboliziranju a glavni metaboliti su nor1-citalopram i nor2-citalopram. Citalpram je dostupan u tabletama od 10 mg, 20 mg i 40 mg za oralno davanje. CELEXATM je oralna otopina koja sadrži citalopram HBr ekvivalenan 2 mg/L citalopram u obliku baze. CELEXATM se tipično daje pri početnoj dozi od 20 mg jedanput na dan, a općenito se doza poeća do 40 mg/dan. Povećanje doze je tipično po 20 mg i razmacima ne manjim od jednog tjedna.
Citalopram ima sljedeću strukturu:
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Strukturni analozi citaloprama imaju formulu:
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kao i farmaceutski prihvaljive soli, pri čemu je svaki R1 i R2 neovisno odabran iz sljedeće skupine: brom, klr, fluor, trifoulrmetil, cijano i R-CO-, pri čemu R jeste C1-C4 alkil.
Primjeri strukturnih analoga citaloprama (koji su stoga strukturni analozi SSRI prema izumu) jesu: 1-(4'-fluorfenil)-1-(3-dimetilaminopropil)-5-bromftalan, 1-(4'-klorfenil)-1-(3-dimetilami-nopropil)-5-klorftalan, 1-(4'-bromfenil)-1-(3-dimetilaminopropil)-5-klorftalan, 1-(4'-fluorfenil)-1-(3-di-metilaminopropil)-5-klorftalan, 1-(4'-klorfenil)-1-(3-dimetilaminopropil)-5-trifluormetil-ftalan, 1-(4'-bromfenil)-1-(3-dimetilaminopropil)-5-trifluormetil-ftalan, 1-(4'-fluorfenil)-1-(3-dimetilaminopropil)-5-trifluormetil-ftalan, 1-(4'-fluorfenil)-1-(3-dimetilaminopropil)-5-fluorftalan, 1-(4'-klorfenil)-1-(3-dimetil-aminopropil)-5- fluorftalan, 1-(4'-klorfenil)-1-(3-dimetilaminopropil)-5-ftalankarbonitril, 1-(4'- fluor-fenil)-1-(3-dimetilaminopropil)-5- ftalankarbonitril, 1-(4'-cijanofenil)-1-(3-dimetilaminopropil)-5- ftalankarbonitril, 1-(4'-cijanofenil)-1-(3-dimetilaminopropil)-5-klorftalan, 1-(4'-cijanofenil)-1-(3-dimetilaminopropil)-5-trifluormetilftalan, 1-(4'-fluorfenil)-1-(3-dimetilaminopropil)-5-ftalankarbonitril, 1-(4'-klorenil)-1-(3-dimetilaminopropil)-5-propionilftalan, 1-(4-(klorfenil)-1-(3-dimetilaminopropil)-5-propionilftalan, te njihove farmaceutski prihvatljive soli.
Klovoksamin
Klovoksamin ima sljedeću strukturu:
[image]
Strukturni analozi klovoksamina su oni koji imaju formulu:
[image]
kao i farmaceutski prihvaljive soli, pri čemu Hal jeste klor, brom ili fluor, a R jeste cijano, metoksi,
etoksi, metoksimetil, etoksimetil, metoksietoksi ili cijenometil.
Primjeri strukturnih analoga klovoksamina su: 4'-klor-5-etoksivalerofenon O-(2-aminoetil)oksim, 4'-klor-5-(2-metoksi-etoksi)valerofenon-O-(2-aminoetil)oksim, 4'-klor-6-metoksikaprofenon-O-(2-aminoetil)-oksim, 4'-klor-6-etoksikaprofenon-O-(2-aminoetil)oksim, 4'-brom-5-(2-metoksietoksi)valerofenon-O-(2-aminoetil)oksim; 4'-brom-5-metoksivalerofenon-O-(2-aminoetil)oksim; 4'-klor-6-cijano-kaprofenon-O-(2-aminoetil)oksim, 4'-klor-5-cijanovalerofenon-O-(2-aminoetil)oksim, 4'-brom-5- cijanovalero-fenon-O-(2aminoetil)oksim, te njihove farmaceutski prihvatljive soli.
Femoksetin
Femoksetin ima sljedeću strukturu:
[image]
Strukturni analozi femoksetina su oni koji imaju formulu:
[image]
u kojoj R1 predstavlja C1-4alkilnu ili C2-4alkinilnu skupinu ili fenilnu skuinu koja može biti supstituirana s C1-4alkil, C1-4alkiltio, C1-4alkosi, brom, klor, fluor, nitro, acilamino, metansulfonil, metilendioksi ili tetrahidronaftil, R2 predstavlja C1-4 alkilnu ili C2-4 alkinilnu skupinu a R3 predstavlja vodik, C1-4alkil, C1-4alkosi, trifluoralkil, hidroksi, brom, klor, fluor, metiltio ili aralkiloksi.
Primjeri strukturnih analoga femoksetina su prikazani u Primjerima 7-67 U.S. Patenta br. 3,912,743, a ovdje s ugrađeni citatom.
Fluoksetin
Fluoksetin hidroklorid ((±)-N-metil-3-fenil-3-[((alfa),(alfa),(alfa)-trifluor-p-tolil)oksi]propilamin hidroklorid) se prodaje kao PROZACTM u tabletama od 10 mg, 20 mg, i 40 mg za oralno davanje. Glavni metabolit fluoksetina je nor-fluoksetin. Fluoksetin hidroklorid se također može davati kao oralna otopina ekvivaletna 20 mg/5 mL fluoksetina. Formulacija s odgođenim oslobađanjem sadrži enteralnu presvalku fluoksetin hidroklorida elvivalentno 90 mg fluoksetina. Doza od 20 mg/danu dana ujutro je tipična preporučena doza. Povećanje doze se može razmatrati nakon nekoliko tjedana kao kliničko poboljšanje nije uočeno. Doze iznad 20 mg/dan se mogu davati jedanput na dan (ujutro) ili dva puta na dan (npr. ujutro i u podne) i ne smiju prelaziti maksimalnu dozu od 80 mg/dan.
Fluoksetin ima sljedeću strukturu:
[image]
Strukturni analozi fluoksetina su oni koji imaju formulu:
[image]
kao i farmaceutski prihvaljive soli, pri čemu svaki R1 je neovisno vodik ili meti, R je naftil ili
[image]
gdje svak R2 i R3 neovisno jeste brom, klor, fluor, trifluormetil, C1-4alkil, C1-3alkosi, ili C3-4alkenil, a svaki n i m je neovisno 0. 1 ili 2. Kada R jeste naftil, može biti �-naftil ili �-naftil.
Primjeri strukturnih analoga fluoksetina jesu: 3-(p-izopropoksifenoksi)-3-fenilpropilamin-metansulfonate, N,N-dimetil 3-(3',4'-dimetoksifenoksi)-3-fenilpropilamin-p-hidroksibenzoat, N,N-dimetil-3-(�-naftoksii)-3-fenilpropilamin-bromide, N,N-dimetil 3-(�-naftoksi)-3-fenil-1-metilpropil-amin-iodide, 3-(2'-metil-4',5'-diklorfenoksi)-3-fenilpropilamin-nitrate, 3-(p-t-butilfenoksi)-3-fenilpro-pilamin-glutarate, N-metil 3-(2'-klor-p-toliloksi)-3-fenil-1-metilpropilamin-laktat, 3-(2',4'-diklorfen-oksi)-3-fenil-2metilpropilamin-citrate, N,N-dimetil 3-(m-anisiloksi)-3-fenil-1-metilpropilamin-maleate, N-metil-3-(p-tolil-oksi)-3-fenilpropilamin-sulfate, N,N-dimetil-3-(2',4'-difluorfenoksi)-3-fenilpropil-amin-2,4dinitrobenzoat, 3-(o-etilfenoksi)-3-fenilpropilamin dihidrogen-fosfat, N-metil 3-(2'-klor-4'-izopropilfenoksi)-3-fenil-2metilpropilamin maleate, N,N-dimetil 3-(2'-alkil-4'-fluorfenoksi)-3-fenil-propilamin-sukcinat, N,N-dimetil-3-(o-izopropoksifenoksi)-3-fenil-propilamin-fenilacetate, N,N-dimetil-3-(o-bromfenoksi)-3-fenil-propilamin-�-fenilpropionate, N-metil-3-(p- iodofenoksi)-3-fenil-propilamin-propiolate, te N-metil-3-(3-n-propilfenoksi)-3-fenil-propilamin-dekanoat.
Fluvoksamin
Fluvoksamin-maleat (LUVOXTM) se kemijski naziva 5-metoksi-4'-(trifluormetil)-valerofenon (E)-O-(2-aminoetil)oskim-maleat. Fluvoksamin-maleat dolazi kao talbeta od 50 mg i 100 mg. Tretman tipično započinje s 50 mg dane jedanput na dan u vrijeme spavanja a zatim se povećava na 100 mg na dan u vrijeme spavanja nakon nekoliko dana, a ovisno o toleranciji. Učinkovita doza je obično između 100 i 200 mg, ali može biti dana do maksimalno 300 mg.
Fluvoksamin ima sljedeću strukturu:
[image]
Strukturni analozi klovoksamina su oni koji imaju formulu:
[image]
kao i farmaceutski prihvaljive soli, pri čemu R jeste cijano, cijanometil, metoksimetil ili etoksimetil.
Indalpin
Indalpin ima sljedeću strukturu:
[image]
Strukturni analozi klovoksamina su oni koji imaju formulu:
[image]
kao i farmaceutski prihvaljive soli, pri čemu svaki R1 je neovisno vodikov atom, C1-C4 alkilna skupina ili aralkilna skupina u kojoj alkil ima od 1 do 2 atoma ugljika, R2 je vodik, C1-4alkil, C1-4alkosi ili C1-4alkiltio, klor, brom, fluor, trifluometil, nitro, hidroksi ili amino, a amino može biti supstituiran jednom ili divjema C1-C4 alkilnim skupinama, acilnom skupinom ili C1-C4 alkilsulfonilnom skupinom, A predstavlja -CO ili -CH2-skupinu a n jeste 0, 1 ili 2.
Primjeri strukturnih analoga indalpina jesu: indolil-3-(piperidinil-4-metil)-ketone, (metoksi-5-indolil-3)(piperidinil-4-metil)-ketone, (klor-5-indolil-3)(piperidinil-4-metil)-ketone; (indolil-3)-1-(piperidinil-4)-3-propanone, indolil-3-piperidinil-4-ketone; (metil-1-indolil-3)(piperidinil-4-metil)-ketone, (benzil-1-indolil-3)(piperidinil-4-metil)-ketone; [(metoksi-5-indolil-3)-2etil]-piperidin, [(metil-1-indolil-3)-2-etil]-4-piperidin, [(indolil-3)-2-etil]-4-piperidin; (indolil-3-metil)-4-piperidin, [(klor-5-indolil-3)-2-etil-4-piperidin, [(indolil-b3)-3-propil]-4piperidin, [(benzil-1-indolil-3)-2-etil]-4-piperidin, te njihove farmaceutski prihvatljive soli.
Indeloksazin
Indeoksazin ima sljedeću strukturu:
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Strukturni analozi klovoksamina su oni koji imaju formulu:
[image]
kao i farmaceutski prihvaljive soli, pri čemu svaki R1 i R3 predstavljaju vodikov atom, C1-C4 alkil ili fenil, R2 je vodik, C1-4alkil, C4-7cikloalkil, fenil ili beznil; jedna od iscrtkanih lijeka označuje jednostruku vezu a druga oznaluje svostruku vezu, ili smjese njihovih taurtomera.
Primjeri strukturnih analoga indeoksazina jesu: 2-(7-indeniloksimetil)-4-izopropilmorfolin; 4-butil-2-(7-indeniloksimetil)morfolin; 2-(7-indeniloksimetil)-4-metilmorfolin; 4-etil-2-(7-indeniloksi-metil)morfolin, 2-(7-indeniloksimetil)-morfolin; 2-(7-indeniloksimetil)-4-propilmorfolin; 4-cikloheksil-2-(7-indeniloksimetil)morfolin; 4-benzil-2-(7-indeniloksimetil)-morfolin; 2-(7-indeniloksimetil)-4-fenilmorfolin; 2-(4-indeniloksimetil)morfolin; 2-(3-metil-7-indeniloksimetil)-morfolin; 4-izopropil-2-(3-metil-7-indeniloksimetil)morfolin; 4-izopropil-2-(3-metil-4-indeniloksimetil)morfolin; 4-izopropil-2-(3-metil-5-indeniloksimetil)morfolin; 4-izopropil-2-(1-metil-3-fenil-6-indeniloksimetil)morfolin; 2-(5-indeniloksimetil)-4- izopropilmorfolin, 2-(6-indeniloksimetil)-4-izopropilmorfolin; te 4-izopropil-2-(3- fenil-6-indeniloksimetil)morfolin te njihove farmaceutski prihvatljive soli.
Milnacipram
Milnacipram (IXELTM, Cypress Bioscience Inc.) ima kemijsku formulu (Z)-1-dietilaminokarbonil-2-aminoetil-1-fenil-ciklopropan)hidroklorat i dolazi u tabletama od 25 mg i 50 mg za oralno davanje. Tipično se daje u dozama od 25 mg jedanput na dan, 25 mg dva puta na dan ili 50 mg dva puta na da a za tretman ozbiljne depresije.
Milnacipram ima sljedeću strukturu:
[image]
Strukturni analozi milnaciprama su oni koji imaju formulu:
[image]
kao i farmaceutski prihvaljive soli, pri čemu svaki R je neovisno vodik, brom, klor, fluor, C1-4alkil, C1-4alkosi, hidroksi, nitro ili amino, svaki R1 i R2 neovisno predstavljaju vodik, C1-4alkil, C6-12aril, C7-14alkilaril, koji može biti supstituiran, preferirano u para položaju s bromom, klorom ili fkuporom ili R1 i R2 zajedno tvore heterociklil koji ima 5 ili 6 članoca sa susjednim dušikovim atomima, R3 i R4 predstavljaju vodik ili C1-4alkilnu skupinu ili R3 i R4 tvore sa susjedni dušikovim atomom heterociklil koji ima 5 ili 6 članova a može sadržavati dodatni heteroatom odabran od dušika, sumpora i kisika.
Primjeri strukturnih analoga milnaciprama jesu: 1-fenil 1-aminokarbonil-2-dimetilamino-metil-ciklopropan, 1-fenil-1-dimetilaminokarbonil-2-dimetilaminometil-ciklopropan, 1-fenil 1-etil-aminokarbonil-2-dimetilaminometil-ciklopropan, 1-fenil-1-dietilaminokarbonil-2-aminometil-ciklo-propan, 1-fenil-2-dimetilaminometil-N-(4'-klorfenil)ciklopropan-karboksamide, 1-fenil-2-dimetil-aminometil-N-(4'-klorbenzil)ciklopropan-karboksamide, 1-fenil-2-dimetilaminometil-N-(2-feniletil)ciklopropan-karboksamide, (3,4-diklor-1-fenil)-2-dimetilaminometil-N,N-dimetilciklopropan-karboksamide, 1-fenil1-pirolidinokarbonil-2-morfolinometil-ciklopropan, 1-p-klorfenil-1-amino-karbonil-2-aminometil-ciklopropan, 1-o-klorfenil-1-aminokarbonil-2-dimetilaminometil-ciklopropan, 1-p-hidroksifenil-1-aminokarbonil-2-dimetilaminometil-ciklopropan, 1-p-nitrofenil-1-dimetilamino-karbonil-2-dimetilaminometil-ciklopropan, 1-p-aminofenil-1-dimetilaminokarbonil-2-dimetilamino-metil ciklopropan, 1-p-tolyl-1-metilaminokarbonil-2-dimetilaminometil-ciklopropan, 1-p-metoksi-fenil-1-aminometilkarbonil-2-aminometil-ciklopropan te njihove farmaceutski prihvatljive soli.
Paroksetin
Paroksetin hidroklorid ((-)-trans-4R-(4'fluorfenil)3S-[3',4'-metildioksifenoksi)metil]piperidin hidroklorid hemihidrat) dolazi kao PAXILTM. Tablete s kontroliranim oslobađanjem sadrže paroksetin hidroklorid ekvivalentan paroksetinu u dozama od 12.5 mg, 25 mg, ili 37.5 mg. Jedan sloj tablete se sastoji od sloja barijere koja se može degradirati a drugi sadrži aktivni materijal u hidrofilnoj matrici. Preporučena početna doza PAXILTM je 25 mg/san. Neki pacijetu ne daju odgovor na dozu od 25 mg/san i može biti pogodno povećanje doze po 12.5 mg/dan, a do maksimalno 62.5 mg/dan. Promjene doza se tipično odvijaju u intervalima od najmanje tjedan dana.
Paroksetin ima sljedeću strukturu:
[image]
Strukturni analozi paroksetina su oni koji imaju formulu:
[image]
kao i farmaceutski prihvaljive soli, pri čemu svaki R1 predstavlja vodik ili C1-4alkilni skupinu, a atom fluora može biti u bilo kojem raspoloživom položaju.
Sertralin
Sertralin ((1S-cis)-4-(3,4-diklorfenil)-1,2,3,4-tetrahidro-N-metil-1-naftalenamin hidroklorid) dolazi kao ZOLOFTTM u tabletama od 25 mg, 50 mg i 100 mg za oralno davanje. Kako setralin podliježe značajnoj metaboličkoj transformaciji u brojne metabolite koji mogu biti terapijski aktivni, a ti metaboliti mogu zamijeniti sertalin u protuupalnoj kombinaciji iz izuma. Metabolizam sertralina obuhvaća primjerice oksidativno N-demetiliranje i nastaje N-dimetilsertralin (nor-sertralin). ZOLOFT se tipično daje u dozi od 50 mg jedanput na dan.
Sertralin ima sljedeću strukturu:
[image]
Strukturni analozi paroksetina su oni koji imaju formulu:
[image]
gdje je R1 odabran iz skupine koji čine vodik i C1-4alkil, R2 je C1-4alkil, X i Y je svaki odabran iz skupine koju čine vodik, fluor, klor, brom, trifluormetil, C1-3alkoksi i cijano, te W jeste trifluormetil i C1-3alkoksi. Preferirano analozi sertalina su izomeri cis-konfiguracije. Termin "cis-izomer" se odnosi na relativni položaj NR1R2 i fenilne skupine na cikloheksanskom prstenu (t.j. oba su smještena s iste strane prstena). Kako su 1- i 4-ugljici asietrično supstituirani, svaki cis-spoj ima dva optički aktivna enatiomerna oblika označenih (prema ugljiku 1) kao cis-(1R) i cis-(1S) enantiomeri.
Posebno su korisni sljedeći spojevi kao (1S)-enantiomerni ili (1S)(1R) racemični oblici, te njihove farmaceutski prihvatljive soli: cis-N-metil-4-(3,4-diklorfenil)-1,2,3,4-tetrahidro-1-naftalen-amin; cis-N-metil-4-(4-bromfenil)-1,2,3,4-tetrahidro-1-naftalenamin; cis-N-metil-4-(4-klorfenil)-1,2,3,4-tetrahidro-1-naftalenamin; cis- N-metil-4-(3-trifluormetil-fenil)-1,2,3,4 tetrahidro-1-nafta-lenamin; cis-N-metil- 4-(3-trifluormetil-4-klorfenil)-1,2,3,4-tetrahidro-1-naftalenamin; cis-N,N-dimetil- 4-(4-klorfenil)-1,2,3,4-tetrahidro-1-naftalenamin; cis-N,N-dimetil-4-(3-trifluormetil-fenil)-1,2,3,4-tetrahidro-1-naftalenamin; te cis-N-metil-4-(4-klorfenil)-7-klor-1,2,3,4-tetrahidro-1-nafta-lenamin. Od interesa je također (1R)-enantiomer cis-N-metil-4-(3,4-diklorfenil)-1,2,3,4-tetrahidro-1-naftalenamin.
Sibutramin hidroklorid monohidrat
Sibutramin hidroklorid monohidrat (MERIDIATM) je sredstvo za oralno davanje za tretman pretilosti. Sibutramin hidroklorid monohidrat je racemična smjesa (+) i (-) enantiomera 1-(4-klorfen-il)-N,N-dietil-(alfa)-(2-metilpropil)-ciklobutanmetanamina monohidrata. Svaka kapsula MERIDIATM sadrži 5 mg, 10 mg ili 15 mg sibutramin hidroklorid monohidrata. Preporučena početna doza MERIDIATM je 10 mg dana jedanput na da sa ili bez hrane. Ako ne dođe do odgovarajućeg gubitka težine, doza se može titrirati nakon četiri tjedna do ukupno 15 mg jedanput na dan. Doza od 5 mg je tipično za pacijente koje ne toleriraju dozu od 10 mg.
Zimeldin
Zimeldin ima sljedeću strukturu:
[image]
Strukturni analozi paroksetina su oni koji imaju formulu:
[image]
kao i njegove farmaceutski prihvaljive soli, pri čemu je piridnska jezgra vezana u ortho-, meta- ili para-položaju na susjedni ugljikov atom a R1 je odabran iz skupine koju čine H, klor, fluor i brom.
Primjeri analoga zimeldina jesu: (E)- i (Z)- 3-(4'-bromfenil-3-(2"pyridyl)dimetilalilamin, 3-(4'-bromfenil)-3-(3"-pyridyl)dimetilalilamin, 3-(4'-bromfenil)-3-(4"-pyridyl)-dimetilalilamin, te njihove farmaceutski prihvatljive soli.
Strukturni analozi bilo kojeg od gronjih SSRI se ovdje smatraju analozima SSRI i stoga se mogu koristiti u metodama, pripravcima i paketima iz izuma.
Metaboliti
Farmakološki aktivni metaboliti bilo kojeg od prethodnih SSRI se također mogu koristiti u metodama, pripravcima i kompletima iz izuma. Primjeri metabolita su didesmetilcitalopram, desmetilcitalopram, desmetilsertralin i norfluoksetin.
Analozi
Funkcionalni analozi SSRI se također mogu koristiti u metodama, pripravcima i kompletima iz izuma. Primjeri funkcionalnih analoga SSRI su prikazani niže. Jedna klasa analoga SSRI su SNRI (selektivni inhibitori prihvata serotonin norpinefrina), a koji uključuju velafaksin i duloksetin.
Venlafaksin
Velafaksin hidroklroid (EFFEXORTM) je antidepresiv za oralno davanje. On je (R/S)-1-[2-(dimetilamino)-1-(4-metoksifenil)etil]cikloheksanol hidroklorid ili (±)-1-[(alfa)-[(dimetil-amino)metil]-p-metoksibenzil]cikloheksanol hidroklorid. Prešane tablete sadrže venlafaksin hidroklorid ekvivalenta 25 mg, 37.5 mg, 50 mg, 75 mg ili 100 mg venlafaksina. Preporučena početna doza venlafaksina je 75 mg/dan, dana u dvije ili tri podijeljene doze skupa s hranom. Ovisno o toleranciji i potrebi za daljnji klinički učinak, doza se može povećati na 150 mg/dan. Ako je poželjno doza se može dalje povećati do 225 mg/dan. Kada se doza poećava, povećanja do 75 mg/danu su tipična u intervalima od ne manje od četiri dana.
Venlafaksin ima sljedeću strukturu:
[image]
Strukturni analozi venlafaksina su oni koji imaju formulu:
[image]
kao i njegove farmaceutski prihvaljive soli, pri čemu A jeste ostatak sljedeće formule:
[image] ili [image]
u kojoj iscrtana linia predstavlja moguće nezasićenje, R1 je vodik ili alkil, R2 je C1-4alkil, formil ili alkanoil, R3 je vodik ili C1-4alkil, R5 i R6 neovisno jesu vodik, hidroksi, C1-4alkil,, C1-4alkoksi, C1-4alkanoiloksi, cijano, nitro, alkilmerkapto, amino, C1-4alkillamino, dialilamino, C1-4alanamido, halogen, trifluormetil ili uzeti zajedno metilendioksi, te n jeste 0, 1, 2, 3, ili 4.
Duloksetin
Duloksetin ima sljedeću strukturu:
[image]
Strukturni analozi duloksetina su spojevi opisani formulom prikazanom u U. S. Patentu br. 4,956,388, a ovdje ugrađen citatom.
Ostali analozi SSRI su: 4-(2-fluorfenil)-6-metil-2-piperazinotioeno-[2,3-d]pirimidin, 1,2,3,4-tetrahidro-N-metil-4-fenil-lnaftilamin hidroklorid; 1,2,3,4-tetrahidro-N-metil-4-fenil-(E)-1-naftilamin hidroklorid; N,N-dimetil-1-fenil-1-ftalanpropilamin hidro-klorid; gama-(4-(trifluormetil)fenoksi)-benzenpropanamin hidroklorid; BP 554; CP 53261; O-des-metilvenlafaksin; WY 45,818; WY 45,88 1; N-(3-fluorpropil)paroksetin; Lu 19005 te SNRI opisani u PCT publikaciji br. WO 04/004734.
Standardne preporučene doze
Standardne preporučene doze nekih SSRI su prikazane niže u Tablici 2. Ostale standardne doze u prikazane npr. u Merck Manual of Diagnosis & Therapy (17, izd. Ed. MH Beers et al., Merck & Co.) te u Physicians' Desk Reference 2003 (57. izd Medical Economics Staff et al., Medical Economics Co., 2002).
Tablica 2
[image]
Triciklički antidepresivi
U sljedećoj cjelini, u metodama, pripravcima i paketima iz izuma koristi se triciklički antidepresiv (TCA) ili njegov strukturni ili funkcionalni analog u kombinaciji s nesterodinim o imunofilinu ovisnim imunodepresivom (NsIDI). Maprolitin (trgovačko ime LUDIOMIL) je sekundarni aminski triciklički antidepresiv koji inhibira prihvat norepinefedrina i strukturno je blizak imipraminu koji je dibenzazepin. Mada su se ovakva sredstva koristila za tretman anksioznosti i depresije, mi ovdje prikazujemo da se povećanjem maprotilina može povećati sposobnost imunosupresivnog sredstva te da je koristan u antiupalnoj kombinaciji iz izuma.
Maprolitin (trgovačko ime LUDIOMIL) i struktrni analozi maprotilina imaju tricikličke molekulske jezgre (vidi formulu (IV), supra). Ti analozi obuhvaćaju druge tricikličke antidepresive (TCA) koji imaju sekundarni amin kao bočne lance (npr. nortriptilin, protriptilin, desipramin) kao i N-demetilirane metabolite TCA koji imaju tercijarni amin kao bočne lance. Preferirani strukturni i funkcionalni analozi obuhvaćaju tricikličke antidepresive koji su selektivni inhibitori prihvata norefinpfrina. Triciklički spojevi koji se mogu koristiti u metodama, pripravcima i paketima iz izuma obuhvaćaju sljedeće: amitriptilin, amoksapin, klomipramin, desipramin, dotiepin, doksepin, imipramin, lofepramin, maprotilin, mianserin, mertazpin, mnortriptilin, oktriptilin, oksaprotilin, protriptilin, trimipramin, 10-(4-metilpiperazin-1-1l)pyrido(4,3-b)(1,4)benzotiazepin; 11-(4-metil-1-piperazinil)-5H-dibenzo(b,e)(1,4)diazepin; 5,10-dihidro-7-klor-10-(2-(morfolino)etil)-11H-dibenzo (b,e)(1,4)diazepin-11-on; 2-(2-(7-hidroksi-4-dibenzo(b,f)(1,4)tiazepin-11-il-1- piperazinil)etoksi) etanol; 2-klor-11-(4-metil-1-piperazinil)-5H-dibenzo(b,e)(1,4)diazepin; 4-(11H-dibenz(b,e)azepin-6-il)piperazin; 8-klor-11-(4-metil-1-piperazinil)-5H-dibenzo(b,e)(1,4)diazepin-2-ol; 8-klor-11-(4-met-il-1-piperazinil)-5H-dibenzo(b,e)(1,4)diazepin monohidroklorid; (Z)-2-butenedioat-5H-dibenzo(b,e)(1,4) diazepin; adinazolam; amineptin; amitriptilinoksid; butriptilin; klotiapin; klozapin; deme ksiptilin; 11-(4-metil-1-piperazinil)-dibenz(b,f)(1,4)oksazepin; 11-(4-metil-1-piperazinil)-2-nitrodi-benz(b,f)(1,4)ok-sazepin; 2-klor-11-(4-metil-1-piperazinil)dibenz(b,f)(1,4)oksazepin monohidro-klorid; dibenzepin; 11-(4-metil-1-piperazinil)-dibenzo(b,f)(1,4)tiazepin; dimetakrin; fluacizin; fluperlapin; imiprainin-N-oksid; iprindol; lofepratnin; melitracen; metapramin; metiapin; metralindol; mianserin; mirtazapin; 8-klor-6-(4-metil-1-piperazinil)-morfantridin; N-acetilamoksapin; nomifensin; norklo-mipramin; norklozapin; noksiptilin; opipramol; oksaprotilin; perlapin; pizotilin; propizepin; kvetiapin; kvinupramin; tianeptin; tomoksetin; flupentiksol; clopentiksol; piflutiksol; klorprothiksen; te tiotiksene. Ostali triciklički spojevi su opisani primjerice u U.S. Patentima br. 2,554,736; 3,046,283; 3,310,553; 3,177,209; 3,205,264; 3,244,748; 3,271,451; 3,272,826; 3,282,942; 3,299,139, 13,312,689; 3,389,139; 3,399,201; 3,409,640; 3,419,547-1 3,438,981; 3,454,554; 3,467,650; 3,505,321; 3,527,766; 3,534,041; 3,539,573; 3,574,852; 3,622,565; 3,637,660; 3,663,696; 3,758,528; 3,922,305; 3,963,779; 3,978,121; 3,981,917; 4,017,542; 4,017,621; 4,020,096; 4,045,560; 4,045,580; 4,048,223; 4,062,848; 4,088,647; 4,128,641; 4,148,919; 4,153,629; 4,224,321; 4,224,344; 4,250,094; 4,284,559; 4,333,935; 4,358,620; 4,548,933; 4,691,040; 4,879,288; 5,238,959; 5,266,570; 5,399,568; 5,464,840; 5,455,246; 5,512,575; 5,550,136; 5,574,173; 5,681,840; 5,688,805; 5,916,889; 6,545,057; te 6,600,065, te fenotiazinski spojevi koji odgovaraju spojevima Formule (1) U.S. Patentnih prijava br. 10/617,424 or 60/504,310.
TCA se općenito koriste u jedinici oralne doze do ekvivalenata od 150 mg imipramina. TCA je metaboliziran putem oksidacije s hepatičnim mikrosomalnim enzimima a zatim konjugacijom s glukuronskom kiselinom. TCA metaboliti mogu biti supstituirani sa sekundarnim aminskim tricikličkim antidepresivima kao što je maprotilin, a u protuupalnoj kombinaciji iz izuma. 10-hidroksi-metaboliti TCA su posebno korisni u metodama iz izuma tako što imaju istu biološku aktivnost kao originalni triciklički antidepresiv ali su manje toksični.
Standardne preporučene doze TCA
Tipično se doza maprotilina za pacijente mijenja prema stanju pacijenta, ali su ovdje prikazane neke standardne preporučene doze. Maprotilin je sada na raspolaganju u tabletama od 25, 50 i 100 mg i može se najčešće dati u dozama od 100-150 mg/dan, mada su standardne preporučene doze od 1-25 mg/dan, 100-150 mg/dan, 150-225 mg.dan ili 225-350 mg/dan. Većina antiepresiva se dobro apsorbira nakon oralnog davanja, mada je intramuskularno davanmje nekih TCA (npr. amitriptilin, klomipramin) također moguće.
Triklosan
U jednoj cjelini metode, pripravci i kompleti iz izuma koriste trilklosan ili drugi fenoksifenili ili njegov strukturni ili funkcionalni analog u kombinaciji s nesteroidnim o imunofilinu ovisnim imunodepsresivom (NsIDI).
Triklosan je klorom supstituirani fenoksifenil koji djeluje kao antibiotik širokog spektra. Mi sada prikazujemo da triklosan također povećava snagu imunodepresivnih sredstava kao što je ciklosporin te je koristan u protuuplanoj kombiaciji iz izuma za tretman inumoupalnog poremećaja, proliferativne bolesti kože, sprječavanje odbijanja transplatiranog organa ili bolesti odbacivanja transplanta. Strukturni analozi triklosana obuhvaćaju klorom supstituirane fenolksifenole kao što je 5-klor-2-(2,4-diklorfenoksi)fenol, heksaklorofen, dikiorofen kao i drugi halogenirani hidroksidifenil-eterski spojevi. Funkcionalni analozi obuhvaćaju klotrimazol kao i različita antimikrobna sredstva kao što je selenijev sulfid, ketokonazol, triklokarbon, cinkov pirition, itrakonazol, asiatska kiselina, hinokitiol, mipironcin, klinacicin hidroklorid, benzoil-peroksid, benzil-peroksid, minociklin, oktopiroks, ciklopiroks, eritromicin, cink, tetraciklin, azelska kiselina i njeni derivati, fenoksi-etanol, etil-acetat, klindamicin, meklociklin. Funkcionalni i strukturni analozi triklosana su također opisani u U.S. Patentima br. 5,043,154, 5,800,803, 6,307,049 i 6,503,903.
Triklosan može postići svoju antibakterijsku aktivnost vezanjem na bakterijski enzim Fab1 i njegovom inhibicijom. Funkcionalni i struktirni analozi triklosama, uključujući antibiotike koji se vezuju na Fab1, mogu također biti korisni u kombinaciji iz izuma.
Standardne preporučene doze triklosana
Mada će se preporučene doze mijenjati prema stanju pacijenta, standardne preporučene doze su ovdje prikazane. Tipično će pacijent primiti 3.24 mg po kg, mada se mogu koristiti količine između 0.5 i 3.24 ili 3.24 i 5.0. Ostale korisne doze triklosana obuhvaćaju 0.5 mg/kg, 1.0 mg/kg, 1.5 mg/kg, 2.0 mg/kg, 2.5 mg/kg, 3.0 mg/kg, 4.0 mg/kg, te 4.5 mg/kg za ljude. Preferirano se triklosan nanosi tipički u formulaciji koja sadrži 0.5 do 3% triklosana. OStale korisne formulacije sadrže 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 7.5% ili 10% triklosana.
Antihistaminici
U sljedećoj cjelini izuma pripravci i kompleti iz izuma koriste antagonist histaminskog receptora (ili njegov analog) i nesteroidni i imnunofilinu ovisan inhibitor za pacijenta koji ima potrebu za takvim tretmanom.
Antihistamini su spojevi koji blokiraju djelovanje histamina. Klase antihistamina jesu:
(1) etanolamini (npr. bromodifenhidramin, karbonoksamin, klemastin, dimenhidrinat, difenhidramin,difenilpiralin i doksilamin),
(2) etilendiamini (npr. feilramin, pirilamin, tripelenamin i triprolidin),
(3) fenotiazini (npr. dietazin, etopropazin, metdilazin, prometiazin, trietilperazin i trimeprazin),
(4) alkilamini (npr. (akrivastin, bromofeinramin, klorfeniramin, despbromfeniramin, desklor-feniramin, pirobutamin i triprolidin),
(5) piperazini (npr. buklizin, cetirizin, klorciklizin, ciklizin, meciklizin, hidroksizin),
(6) piperidini (npr. astemizol, azatadin, ciprohptadin, dessloratidin, feksofenadin, loratadin, ketotofen, olopatadin, fenindiazmin te terfenadin),
(7) atipični antihidtyamini (npr. azelastin, levokabastin, metapirilen i feniltokssamin).
U metodma, pripravcima i paketima iz izuma, mogu se koristiti nesedirajući i sedirajući antihistaminici. Posebno poželjni antihistaminici za upotrebu u metodama, pripravcima i paketima iz izum su nesedirajući antihistamini kao što je loratadin i desloratadin. Također se u metodama, pripravcima i paketima iz izuma mogu koristiti sedirajući antihistaminici. Preferirani sedirajući antihistaminici za upotrebu u metodama, pripravcima i paketima iz izuma jesu azatadin, bromodifenhidramin; klorfeniramin; clemizol; ciproheptadin; dimenhidrinat; difenhidramin; doksilainin; meklizin; prometazin; pirilamin; tietilperazin; te tripelennamin.
Ostali antihistaminici pogodni za upotrebu u metodma, pripravcima i paketima iz izuma jesu akrivastin; ahistan; antazolin; astemizol; azelastin (npr. azelsatin hidroklorid); bamipin; bepotastin; bietanautin; bromfeniramin (npr. bromfeniramin-maleat); karbinoksamin (npr. carbinoksamin-maleate); cetirizin (npr. cetirizin hidroklorid); cetoksime; klorociklizin; kloropiramin; kloroten; klorfenoksamin; cinarizin; klemastin (npr. klemastin-fumarat); klobenzepam; klobenztropin; klocinizin; ciklizin (npr. ciklizin hidroklorid; ciklizin-lactat); (npr. tiazinamium-metilsulfat); tonzilamin hidroklorid; tolpropamin; triprolidin; te tritokvalin.
Ostali antihistamini pogodni za upotrebu u metodama i prirpavcima iz izuma su sljedeći: ahistan, antazolin, astemizol, azlesatin (npr. azlesatin hidroklorid), bamipin, bepotazin, bietanutin, bromfeniramin (npr. bromfeniramin-maleat), karbinoksamin (npr. karbinoksamin-maleat), cetirazin (npr. cetirazin hidroklorid), cetoksamin, klorciklizin, klorpiramin, kloroten, klorfenoksamin, cinarizin, klematsin (npr. klemastin-fumarat), klobenzepam, klobenztropin, klocinizin, ciklizin (npr. ciklizin hidroklorid, ciklizin-laktat), deptropin, deksklofeniramin, deksklorfeiramin-maleat, difenilpiralin, doksepin, ebastin, embrabin, emedastin (npr. emedastin-difumarat), epinastin, etimemazin hidroklorid, feoksfenadin (npr. feksfenadin hidroklorid), histapirodin, hidroksizin (npr. hidroksizin hidroklorid, hidroksizin-pamoat), izoprometazin, izotifendil, levokabastin (npr. levokabastin hidroklorid), mebhidrolin, mequvitazin, metafurilen, metapirilen, metrin, mizolastin, olapatadin (npr. olapatadin hidroklorid), orfenadrin, fenindiazmin (npr. fenindiamin-tartarat), feniramin, feniltoloksamin, p-metildifenhidramin, pirobutamin, setatin, talastin, terfenadin, tienildiamin, tiaznamij (npr. tiazinamijev-metandulfonat), tonzilamin hidroklorid, tolproamin, triprolidin i tritokvalin.
Strukturni analozi antihidstamina se također mogu koristiti prema ovom izumu. Analozi antihistamina obuhvaćaju bez ograničenja sljedeće: 10-piperazinilpropilfenotiazin; 4-(3-(2-klorofenotiazin-10-il)propil)-1-piperazinetanol dihidroklorid; 1-(10-(3-(4-metil-1-piperazinil)propil)-10H-fenotiazin-2-il)-(9Cl)-1-propanon; 3-metoksiciproheptadin; 4-(3-(2-klor-10H-fenotiazin-10-il)-propil)piperazin-1-etanol hidroklorid; 10,11-dihidro-5-(3-(4-etoksikarbonil-4-fenilpiperidino)propil-iden)-5H-dibenzo(a,d)ciklohepten; aceprometazin; acetofenazin; alimemazin (npr. alimemazin hidroklorid); aminopromazin; benzimidazol; butaperazin; karfenazin; klorfenetazin; klortnidazol; cinprazol; desmetilastemizol; desmetilciproheptadin; dietazin (npr. dietazin hidroklorid); etopropazin (npr. etopropazin hidroklorid); 2-(p-bromofenil-(p'-tolil)metoksi)-N,N-dimetil-etilamin hidroklorid; N,N-dimetil-2-(difenilmetoksi)-etilamin metilbromid; EX-10-542A; fenetazin; fuprazol; metil-10-(3-(4-metil-1-piperazinil)propil)fenotiazin-2-iI-ketone; lerisetron; medrilamin; mesoridazin; metilpromazin; N-desmetilprometazin; nilprazol; nortioridazin; perfenazin (npr. perfenazin enantat); 10-(3-dimetil-aminopropil)-2-metilthiofenotiazin; 4-(dibenzo(b,e)tiepin-6(11H)-ilidene)-1-metil-piperidin hidroklorid; proklorperazin; promazin; propiomazin (npr. propiomazin hidroklorid); rotoksamin; rupatadin; Sch 37370; Sch 434; tekastemizol; tiazinamium; tiopropazat; tioridazin (npr. thioridazin hidroklorid); te 3-(10,11-dihidro-5H- dibenzo(a,d)ciklohepten-5-iliden)-tropan.
Ostali spojevi koji su pogodnu za upotrebu u izumu jesu: AD-0261; AHR-5333; alinastin; arpromidin; ATI-19000; bermastin; bilastin; Bron-12; carebastin; klorfenamin; klofurenadin; korsim; DF-1105501; DF-11062; DF-1111301; EL-301; elbanizin; F-7946T; F-9505; HE-90481; HE-90512; hivenil; HSR-609; ikotidin; KAA-276; KY-234; lamiakast; LAS-36509; LAS-36674; levocetirizin; levoprotilin; metoklopramid; NIP-531; noberastin; oksatomid; PR-881-884A; kvisultazin; rokastin; selenotifen; SK&F-94461; SODAS- HC; tagorizin; TAK-427; temelastin; UCB-34742; UCB-35440; VUF-K-8707; Wy-49051; te ZCR-2060.
Daljnji spojevi koji su pogodni za upotrebu u izumu su oni opisani u US Patentima br. 3,956,296; 4,254,129; 4,254,130; 4,282,833; 4,283,408; 4,362,736; 4,394,508; 4,285,957; 4,285,958; 4,440,933; 4,510,309; 4,550,116; 4,692,456; 4,742,175; 4,833,138; 4,908,372; 5,204,249; 5,375,693; 5,578,610; 5,581,011; 5,589,487; 5,663,412; 5,994,549; 6,201,124; te 6,458,958.
Standardne preporučene doze antihistamina
Standardne preporučene doze za neke primjere antihistamina su prikazane u Tablici 3. Ostale standardne doze su prikazane primjerice u Merck Manual of Diagnosis & Therapy (17. iz. NM Beers et al., Merck & Co.) te Physicians' Desk Reference 2003 (57. izd. Medical Economics Staff et al., Medical Economics Co 2002).
Tablica 3
[image]
Primjer antagonista histaminskog receptora: loratidin
Loratidin (CLARITIN) je triciklički piperidin koji djeluje kao selektivni antagonist perifernog histaminskog H1-receptora. Mi ovdje prikazujemo loratidin i njegove strukturne i funkcionalne analoge kao što su piperidini, triciklički piperidini, antagonisti H1-receptora koji su korisni u antiimunoupalnoj kombinaciji iz izuma, a za tretman imunoupalnih poremećaja, odbijanje transplantiranog organa i bolest odbacivanja transplanta.
Strukturne i/ili funkcionalni analozi loratidina jesu drugi antagonisti H1-receptora kao što je AHR-11325, akrivastin, antazolin, astemizol, azatadin, azelastin, bromfeniramin, karebastin, cetirizin, klorfeniramin, klorciklizin, klemastin, ciproheptadin, deskarboetoksiloratadin, deksklor-feniramin, dimenhidrinat, difenilpiralin, difenhidramin, ebastin, feksofenadin, hidroksizin ketotifen, lodoksamid, levokabastin, metdilazin, mekvitazin, oksatomid, feniramin pirilainin, prometazin, pirilamin, setastin, tazifilin, emelastin, terfenadin, trimeprazin , tripelenamin, triprolidin, utrizin, te similar slični spojevi (opisani npr. u U.S. Patentima br. 3,956,296, 4,254,129, 4,254,130, 4,283,408, 4,362,736, 4,394,508, 4,285,957, 4,285,958, 4,440,933, 4,510,309, 4,550,116, 4,692,456, 4,742,175, 4,908,372, 5,204,249, 5,375,693, 5,578,610, 5,581,011, 5,589,487, 5,663,412, 5,994,549, 6,201,124, te 6,458,958).
Loratadin, cetirizin i feksofenadin su druga generacija antagonista H-1 receptora kojima nedostaje sedirajući efekt koji ima prva generacija antagonista H-1 receptora. Piperidinski antagonisti H1-receptora su sljedeći: loratadin, ciproheptadin hidroklorid (PERIACTIN) te fenindiamin tartrat (NOLAHIST). Piperazinski antagonisti H1-receptora su sljedeći: hidroksizin hidroklorid (ATARAKS), hidroksizin pamoate (VISTARIL), ciklizin hidroklorid (NLAREZINE), ciklizin lactate, te meklizin hidroklorid.
Standardne preporučene doze loratidina
Oralne formulacije loratidina obuhvaćaju tablete, lako radgrađujuće tablete i sirupe. Tablete loratidina sadrže 10 mg usitnjenog loratidina. Sirup loratidina sadrži 1 mg/mL uzitnjenog loratidina a lako radgrađujuće tablete sadrže 10 mg usitnjenog loratidina u tabletama koje se brzo raspadaju u ustima. Mada će se preporučena doza mijenjati ovisno o stanju pacijenta, niže su prikazane standardne preporučene doze. Loratidin se tipično daje jedanpu na dan u dozi od 10 mg, mada druge dnevne doze korisne u protuimunouplanoj kombinaciji iz izuma obuhvaćaju 0.01-0.05 mg, 0.05-1 mg, 1-3 mg, 3-5 mg, 5-10 ,g. 10-15 mg. 15-20 mg, 20-30 mg, te 30-40 mg.
Loratidin se brzo apsorbira nakon pralnog davanja. On metabolizira u jetri udeskarboetoksiloratidin pomoću citokroma P450 3A4 u citokroma P450 2D6. Metaboliti loratidina su također korisni u protuimunouplanoj kombinaciji iz izuma.
Fenotiazini
U sljedećoj cjelini, metode, pripravci i paketi iz izuma koriste fenotiazin ili njegov strukturni ili funkcionalni analog u kombinaciji s nesteroidnim o imunofilinu ovisnom imunodepresivom (NsIDI).
Fenotiazini korisni u u metodma, pripravcima i paketima iz izuma obuhvaćaju spojeve koji imaju opću formulu (V):
[image]
(V)
ili odgovarajuću farmaceutski prihvatljivu sol, pri čemu je R2 odabran iz sljedeće skupine: CF3, Cl, F, OCH3, COOCH3, CN, OCF3, COCH2CH3, CO(CH2)2CH3 i SCH2CH3; R9 je odabran iz sljedeće skupine:
[image]
gdje svaki R1, R3, R4, R5, R6, R7 i R8 neovisno jeste H, OH, F, OCF3 ili OCH3, te je W odabran iz sljedeće skupine: [image]
U nekim cjelinama je fenotiazin konjugat fenotiazina s tim da je fenotiazin kovalentno spojen preko spojnice na veliku skupinu koja je veća od 200 daltona ili na nabijenu skupinu koja je manja od 200 daltona. Takvi konjugati zadržavaju svoju protuupalnu aktivnost in vivo i imaju smanjenu aktivnost u centralnom nervonom sustavu u usporedbi sa samim fenotiazinom. Konjugati fenotiazina koji su korisni u metadama, paketima i pripavcima iz izuma su spojevi opće formule (VI).
[image]
(VI)
U Formuli (VI) je R2 odabran iz sljedeće skupine: CF3, halogen, OCH3, COCH3, CN, OCF3, COCH2CH3, CO(CH2)2CH3, S(O)2CH3, S(O)2N(CH3)2 i SCH2CH3, a A1 je odabran iz skupine koja sadrži G1:
[image]
a svaki R1, R3, R4, R5, R6, R7 i R8 neovisno jeste H, OH, F, OCF3 ili OCH3, R32, R33, R34 i R35 je svaki neovisno odabran iz sljedeće skupine: H ili C1-6 alkil, W je odabran iz skupine koju čine: NO,
[image]
te je G1 veza između fenotiazina i sponice L.
Spojnica L je opisana formulom (VII):
G1-(Z1)0-(Y1)u-(Z2)s-(R9)-(Z3)t-(Y2)v-(Z4)p-G4
(VII)
U formuli (VII) G1 je veza između fenotiazina u spojnice, G2 je veza između spojnice i velike skupine ili između spojnice i nabijene skupine, svaki od Z1, Z2, Z3 i Z4 neovisno jesu odabrani od O, S i NR39; R39 je vodik ili C1-6 alkilna skupina; svaki Y1 i Y2 je neovisno odabran od sljedećih: karbonil, tiokarbonil, sulfonil, fosforil ili slične skupine koje tvore kiseline, o, p, s, t, u i v su svaki neovinso 0 ili 1; te je R9 C1-10 alkil, linearni ili razgranati heteroalkil od 1 do 10 atoma, -CH2CH2O)qCH2CH2- u kojem je q cijeli broj od 1 do 4 ili je kemijska veza koja spjaja G1-(Z1)0-(Y1)u-(Z2)s-(R9)-(Z3)t-(Y2)v-(Z4)p-G4.
Velika skupina može biti prirodni polimer ili sintetski polimer. Prirodni polimeri koji se koriste obuhvaćaju bez ograničenja glikoprotein, polipeptide ili polisaharide. Kada je velika skupina prirodni polimer poećljno je da je odabran od sljedećih: alfa-1-kiselina-glikoprotein i hialuronska kiselina. Sintetski polimeri koji se mogu koristiti kao velike skupine obuhvaćaju bez ograničenja polietilenglikol i sintetske N-hxg polpeptide.
Najčešće prepisivani član obitelji fenotiazina je klorpromazin koji ima sljedeću strukturu:
[image]
Klorpromazin je fenotiazin koji se dugo koristio za tretman psihotičkih poremećaja. Fenotiazini obuhvaćaju klorpromazinsku funkcionalnu skupinu i strukturne analoge kao što je acepromazin, klorfenetazin, klorpromazin, ciamemazin, enantat, flufenazin, mepazin, mezordiazin besilat, metotrimetprazin, metoksipromazin, norklorpromazin, perazin, perfenazin, proklorperazin, prome-tazin, propioazin, putaperazin, trietilperazin, tiopropazat, tioridazin, trifkuorperazin ili triflupromazin (ili sol od bilo kojeg gornjeg spoja), te funkcionalne analoge koji djeluju kao dpamin D2 antagonisti (npr. sulfprid, pimozid, spiperon, kleboprid, bupropion i haloperidol).
Klorpromazin je sada dostupan u sljedećim oblicima: tablete, kapsule, supozitoriji, oralni koncentrati i sirupi te formulacije za injekciju.
Kako klorpromazin podliježe značajnoj metabolitskoj transformaciji u brojne metabolite koji mogu biti terapijski aktivni, ti metaboliti mogu supstituirati klorpromazin u protuuplanoj kombinaciji iz izuma. Tijekom metabolizma klorpromazina nastaje primjerice odgovarajući primarmi i sekundarni amin oksidativnim N-demetiliranjem, fenol aromatskom oksidacijom, N-oksidacijom nastaje N-oksid, S-oksidacijom nastaje sulfoksid ili sulfon, oksidativnim deaminiranjem aminopropilnog bočnog lanca nastaje fenotiaznska jezgra, a glukuronidacijom fenolnih hidroksilnih skupina i tercijarne amino skupine nastaje kvaterni amonijev glukuronid.
U drugim primjerima metaboliti klorpromazina korisni u antiupalnoj kombinaciji iz izuma u položajima 3, 7 i 8 fenotiazina mogu neovisno biti supstituirani s hidroksilnim ili metoskilnim dijelom.
Sljedeći fenotiazin je etopropazin (trgovačko ima PARSITAN) i antikolinergični fenotiazn koje se koristi kao antidiskinetik za tretman poremećaja kretanja kao što je Parkinsonova bolest. Etopropazin također ima antihistaminska svojstva. Mi ovdje prikazujemo da etoproazin također poećava sposobnost imunosupresivnog sredstva kao što su ciklosporini. Za razliku od antipsihotičnih fenotiazina koji ima tri ugljikova atoma između položaja 10 centralnog prstena i prvog atoma dušika amino skupine u bočnom lancu na tom položaju, jaki antikolinergični fenitiazini (npr. etopropazin, dietazin) imaju samo dva ugljikova atoma koji odvajaju aminu-skupinu od položaja 10 centralnog prstena.
Strukturni analozi etopropazina obuhvaćaju sljedeće: trifluorperazin dihidroklorid, tioridazin hidroklorid te prometazin hidroklorid. Dodatni strukturni analozi etopropazina obuhvaćaju 10-[2,3-bis(dimetilamino)propil]fenotiazin, 10-[2,3-bis(dimetilamino)propil]fenotiazin hidroklorid, 10-[2-(dime-tilamino)propil]fenotiazin, 10-[2-(dimetilamino)propil]fenotiazin hidroklorid, te 10-[2-(dietilamino)-etil]fenotiazin i njihove smjese (vidi npr. US Patent br. 4,833,138).
Etopropazin djeluje inhibirajući butirilkolinesterazu. Funkcionalni analozi etopropazina obuhvaćaju antikolinergične spojeve kao što je Artane (triheksifenidil), Cogentin (benztropin), biperdin (U.S. Patent br. 5,221,536), karambifen, etopropazin, prociklidin (Kemadrin) tetriheksilfenidil. Antikolinergični fenotiazini su metabolizirani primarno u N-dealkilirane i hidroksilirane metabolite. Metaboliti etopropazina mogu biti umjesto etopropazina u antimuno-upalnoj kombinaciji iz izuma.
Standardne preporučene doze fenotiazina
Tipično se doza klorpromazina za pacijente mijenja prema stanju pacijenta, ali su ovdje prikazane neke standardne preporučene doze. Klorpromazin može biti dan oralno, supozitorijem ili injekcijom. Često se doze daju u intervalima od 4-6 sati tijekom dana. Svaka doze je općenito između 0.25-0.5 mg, 0.5-1.0 mg, 1-5 mg, 0.5-2 mg, 5-10 mg, 10-25 mg, 25-50 mg, 50-75 mg, ili 75-100 mg, . Općenito se daje ukupna doza od 0.25 g, 0.50 g, 0.75 g, 1.0 g, 1.5 g, ili 2.0 g na dan.
Etopropazin koji sada na raspolaganju u tabletama od 10 i 50 mg se obično daje oralno. Početno pacijentima je tipično dana doza od 50 mg etopropazina dva puta na dan. Ostale standardne preporučene doze etopropazina su 1-10 mg/dan, 10-25 mg/dan, 50-100 mg/dan, 100-400 mg/dan, 500-600 mg/dan ili 600-700 mg/dan,
Agonisti �-opoidnog receptora
U sljedećoj cjelini, metode, pripravci i paketi iz izuma koriste agonist �-opoidnog receptora (ili njegov analog) i nesteroidni o imunofilinu ovistan imunodepresiv za pacijetne koji imaju potrebu za takvim tretmanom. Loperamid hidroklorid (IMMODIUM) je agonist �-opoidnog receptora koristan u tretmanu diareja (US Patent br. 3,714,159). Mi ovdje prikazujema da loperamid i analozi loperamida povećavaju snagu imunosupresivnog sredstva i korisni su u tretmanu imunoupalnih poremećaja, pri odbijanju transplatiranog organa ili bolesti odbacivanja transplanta. Loperamid je derivat piperidin butiramida koji se odnosi na meperidin i difenoksilat. On relaskira glatke mišiće i usporuje intarstinalnu pokretljivost. Ostali funkcionalni i/ili sturkturno slični spojevi jesu: meperidin, difenoksilat i odgovarajući propanamini. Dodatni funkcionalni i strukturni analozi loperamida su opisani u US Patentima br. 4,066,654, 4,069,233, 4,072,686, 4, 116,963, 4, 125,531, 4,194,045, 4,824,853, 4,898,873, 5,143,938, 5,236,947, 5,242,944, 5,849,761, te 6,353,004. Funkcionalni analozi lorperamida obhvaćaju peptide i agonsit �-opioidnog receptira malih molekula (opisani u U.S Patentu br. 5,837,809). Takva sredstva su također korisna u protuimunoupalnoj kombinaciji iz izuma. Loperamid se vezuje na opoidne receptore unutar probavnog trakta mijenjajući gastointestinalnu pokretljivost.
Standardne preporučene doze loperamida
Loperamid je sada na raspolaganju u tabletama od 2 mg. Mada će se doza mijenjati prema stanju pacijenta, niže su prikazane standardne preporučene doze. Tipično, doza za odrasle je početno 4 mg a zatim slije sljedeće doza od 2 mg ili 16 mg po danu. Druge korisne doze obuhvaćaju 0.5-1 mg, 1-2 mg, 2-4 mg, 4-8 mg, 8-12 mg ili 12-16 mg.
Kortikosteroidi
Ako je poželjno pripravci i metode iz izuma se mogu koristiti s uobičajenim terapeuticima ukjlučujući kortikosteroide Jedan ili više kortikosteroida se mogu dati u metodi iz izuma ili mogu biti formulirani s nesteroidnim o imunofilinu ovisnim pojačivačem ili njegovim analogom ili metabolitom. Pogodni kortikosteroidi uključuju sljedeće: 11-alfa,17-alfa,21-trihidroksipregn-4-en-3,20-dion, 11-beta,16-alfa,17,21-tetrahidroksipregn-4-en-3,20-dion, 11-beta,16-alfa,17,21-tetrahidroksipregn-1,4-dien-3,20-dion, 11-beta,17-alfa,21-trihidroksi-6-alfa-metilpregn-4-en-3,20-dion, 11-dehidrokortiko-steron, 11-deoksikortizol, 11-hidroksi-1,4-androstadien-3,17-dion, 11-ketotestosteron, 14-hidroksi-androst-4-en-3,6,17-trion, 15,17-dihidroksiprogesteron, 16-metilhidrokortizon, 17,21-dihidroksi-16-alfa-metilpregna-1,4,9(11)-trien-3,20-dion, 17-alfa-hidroksipregn-4-en-3,20-dion, 17-alfa-hid-roksipregnenolon, 17-hidroksi-16-beta-metil-5-beta-pregn-9(11)-ene-3,20-dion, 17-hidroksi-4,6,8(14)-pregnatrien-3,20-dion, 17-hidroksipregna-4,9(11)-dien-3,20-dion, 18-hidroksikortiko-steron, 18-hidroksikortizon, 18-oksokortizol, 21-deoksialdosteron, 21-deoksikortizon, 2-deoksi-ekdison, 2-metilkortizon, 3-dehidroekdison, 4-pregnen-17-alfa,20-beta,21-triol-3,11-dion, 6,17,20-trihidroksipregn-4-en-3-on, 6-alfa-hidroksikortizol, 6-alfa-fluorprednisolon, 6-alfa-metil-prednisolon, 6-alfa-metilprednisolon-21 acetat, 6-alfa-metilprednisolon-21-hemisukcinat natrijeva sol, 6-beta-hidroksikortizol, 6-alfa,9-alfa-difluorprednisolon-21-acetat-17-butirat, 6-hidroksikorti-kosteron, 6-hidroksideksametazon, 6-hidroksiprednisolon, 9-fluorkortizon, alklometazon-dipro-pionat, aldosteron, algeston, alfaderm, amadinon, amcinonid, anageston, androstendion, anekortav-acetat, beklometazon, beklometazon-dipropionat, beklometazon-dipropionat mono-hidrat, betametazon-17-valerat, betametazon natrijev acetat, betametazon natrijev fosfat, betametazon-valerat, bolasteron, budesonid, kalusteron, klormadinon, klorprednison, klorpre-dnisone-acetat, kolesterol, klobetazol, klobetazol-propionat, klobetazon, klokortolon, klokorto-lon-pivalat, klogeston, kloprednol, kortikosteron, kortizol, kortizol-acetat, kortizo-butirat, kortizol-cipionat, kortizol-oktanoat, kortizol natrijev fosfat, kortizol natrijev sukcinat, kortizol-valerat, kortizon, kortizon-acetat, kortodokson, daturaolon, deflazakort, 21-deoksikortizol, dehidroepian-drosteron, delmadinon, deoksikortikosteron, deprodon, descinolon, desonide, dezoksimetazon, deksafen, deksametazon, deksametazone-21-acetat, deksametazone-acetat, deksametazone natrijev fosfat, dicklorison, diflorason, diflorasone-diacetat, diflukortolon, dihidroelatericin a, domoprednat, doksibetazol, ekdison, ecdisteron, endrison, enoksolon, flucinolon, fludrokorti-zon, fludrokortizon-acetat, flugeston, flumetazon, flumetazone-pivalat, flumoksonid, flunisolid, fluocinolon, fluocinolone-acetonide, fluocinonid, 9-fluorkortizon, fluokortolon, fluorhidroksiandro-stenedion, fluormetolon, fluormetolone-acetat, fluoksimesteron, flupredniden, fluprednisolon, flurandrenolid, flutikason, flutikason-propionat, formebolon, formestan, formokortal, gestonoron, gliderinin, halcinonid, hirkanozid, halometazon, halopredon, haloprogesteron, hidrokortiozon-cipionat, hidrokortizon, hidrokortizon-21-butirat, hidrokortizon-aceponat, hidrokortizon-acetat, hidrokortizon-buteprat, hidrokortizon-butirat, hidrokortizon-cipionate, hidrokortizon-hemisukcinat, hidrokortizon-probutat, hidrokortizon natrijev fosfat, hidrokortizon natrijev sukcinat, hidrokortizon valerat, hidroksiprogesteron, inokosteron, izoflupredon, izoflupredon-acetat, izopredniden, meklorison, mekortolon, medrogeston, medroksiprogesteron, medrizon, megestrol, megestrol-acetat, melengestrol, meprednison, methandrostenolon, metilprednisolon, metilprednisolone-aceponat, metilprednisolone-acetat, metilprednisolone-hemisukcinat, metilprednisolone natrijev sukcinat, metiltestosteron, metriboIon, mometazon, mometazon-furoate, mometazonfuroate monohidrat, nison, nomegestrol, norgestomet, norvinisteron, oksimesteron, parametazon, parametazon-acetat, ponasteron, prednisolamat, prednisolon, prednisolon-21-hemisukcinat, prednisolon-acetat, prednisolon-farnezilat, prednisolon-hemisukcinat, prednisolone-21(beta-D-glukuronid), prednisolon-metasulfobenzoat, prednisolone natrijev fosfat, prednisolone-steaglat, prednisonol-tebutat, prednisonol-tetrahidroftalat, prednison, prednival, predniliden, pregne-nolon, procinonid, tralonid, progesteron, promegeston, rapontisteron, rimeksolon, roksibolon, rubrosteron, stizofilin, tiksokortol, topteron, triamcinolon, triamcinolon-acetonide, triamcinolon-acetonide-21-palmitat, triamcinolon-diacetat, triamcinolon-heksacetonid, trimegeston, turkesteron, te vortmanin.
Standardne preporučene doze za različite kombinacije steroid/bolest su prikazane niže u Tablici 4.
Tablica 4 - Standardne preporučene doze kortikosteroida
[image]
Ostale standardne preporučene doze kortikosteroida su prikazane u npr. Merck Manual of Diagnosis & Therapy (17. izd.. MH Beers et al., Merck & Co.) te u Physicians' Desk Reference 2003 (57. izd. Medical Economics Staff et al., Medical Economics Co., 2002). U jednoj cjelini je doza kortikosteroida dana u dozi ekvivalentoj dozi prednisolona, kao što je ovdje definirano. Primjerice, niska doza kortikosteroida se može smatrati kao doza ekvivalentna niskoj dozi prednisolona.
Modulatori steroidnoh receptora
U pripravcima i metodama iz izuma mogu se koristiti modulatori steroidnog receptora (npr. antagonisti i agonisti) kao zamjena ili kao dodatak kortikosteroidu prema metodama, prirpavcima i kompletima iz izuma. Stoga u jednoj cjelini izum prikazuje kombinaciju NsIDI (ili njegovog analoga ili njegovog metabolita) i NsIDIE i modulatora glukokortikoidnog receptora i drugog modulatora sterioidnog receptora, te metode tretmana imunoupalnih poremećaja s njima.
Modulatoru glukokortikoidnog receptora koji se mogu koristiti u metodama, prirpavcima i kompletima iz izuma uključuju spojeve opisane u Patent br. 6,380,207, 6,380,223, 6,448,405, 6,506,766, te 6,570,020, U.S. Patente prijave br. 20030176478, 20030171585, 20030120081, 20030073703,2 002015631, 20020147336, 20020107235, 20020103217, te 20010041802, te PCT publikaciju br. WO 00/66522, a svi su ovdje ugrađeni citatom. Ostali modulatori steroidnih receptora koji se mogu koristiti u metodama, prirpavcima i kompletima iz izuma U.S. Patent br. 6,093,821, 6,121,450, 5,994,544, 5,696,133, 5,696,127, 5,693,647, 5,693,646, 5,688,810, 5,688,808, te 5,696,130, a svi su ovdje ugrađeni citatom.
Ostali spojevi
Ostali spojevi koji se mogu koristiti kao dodatak kombinaciji NsIDI/NsIDIE prema metodama, prirpavcima i kompletima iz izuma jesu: A34-8441 (Karo Bio) ekstrakt adrenala iz korteksa (GlaksoSmithKIine), alsaktid (Aventis), amebukort (Schering AG), amelometazon (Taisho), ATSA (Pfizer), bitolterol (Elan), CBP-2011 (InKine Pharmaceutical), cebaracetam (Novartis) CGP-13774 (Kissei), ciklesonid (Altana), ciklometazon (Avenfis), klobetazon-butirat (GlaksoSmithKline), kloprednol (Hoffmann-La Roche), kolizmicin A (Kirin), kukurbitacin E (NIH), deflazakort (Aventis), deprodon-propionat (SSP), deksametazon-acefurat (Schering-Plough), deksametazon-linoleat (GlaksoSmithKIine), deksametazon-valerat (Abbott), difluprednat (Pfizer), domoprednat (Hoffmann-La Roche), ebiratid (Aventis), etiprednol-dikloacetat (IVAKS), fluazakort (Vicuron), flumoksonid (Hoffinann-La Roche), fluokortin-butil (Schering AG), fluocortolone monohidrat (Schering AG), GR-250495KS (GlaksoSmithKIine), halometazon (Novartis), halopredon (Dainippon), HYC-141 (Fidia), icometazone-enbutat (Hovione), itrocinonide (AstraZeneca), L-6485 (Vicuron), Lipocort (Draksis Health), locickorton (Aventis), meclorizon (Schering-Plough), naflockort (Bristol-Myers Squibb), NCKS-1015 (NicOx), NCKS-1020 (NicOx), NCKS-1022 (NicOx), nicokortonid (Yamanouchi), NIK-236 (Nikken Chemicals), NS-126 (SSP), Org-2766 (Akzo Nobel), Org-6632 (Akzo Nobel), P16CM, propilmesterolone (Schering AG), RGH-1113 (Gedeon Ricbter), rofleponid (AstraZeneca), rofleponide palmitate (AstraZeneca), RPR-106541 (Aventis), RU-26559 (Aventis), Sch-19457 (Schering-Plough), T25 (Matriks Therapeutics), TBI-PAB (Sigma-Tau), ticabesone propionat (Hoffmann-La Roche), tifluadom (Solvay), timobesone (Hoffmann-La Roche), TSC-5 (Takeda), te ZK-73634 (Schering AG).
Terapija
Izum prikazuje metode za sprječavanja izlučivanja proinflamatornih citokina tretmanom imunoupalnog poremećaja, proliferativne bolesti kože, odbijanja tranplantacije organa ili bolest odbacivanja translpanta. Sprječavanje izlučivanja citokina je postignuto davanjem jednog ili više NsIDIE u kombinaciji, a može s jednim ili više NsIDI. Dok primjeri opisuju jedan NsIDIE i jedan NsIDI, podrazumijeva se da je kombinacija više sredstava poželjna. Primjerice, metotreksat, hidroksiklorkin i sulfasalazin su uobičajeno davani za tretman reumatoidnog artritisa. Dodatne terapije su opisane niže.
Kronična opsturktivna bolest pluća
U jednoj cjelini metode, pripravci i kompleti iz izuma su korišteni za tretman kronične opstruktivne bolesti pulća (COPD). Ako je poželjno, mogu se koristiti jedno ili više tipičnih sredstava za tretman COPD kao zamjena ili kao dodatak NsIDI u metodama, pripravicma i kompletima iz izuma. Takva sredstva obuhvaćaju ksantin (npr. teofilin), antikolinergične spojeve (npr. ipratropij, triotropij) te agonsti/bronhodilatator beta receptora (npr. ibutierol-sulfat, bioterol-mezilat, epinefrin, formoterol-fumarat, izoproterenol, levabuterol hidroklorid, metaproterenol-sulfat, pirbuterol-acetat, salmeterol-ksinafonat i terbutalin). Stoga u jednoj cjelini izum prikazuje kombinaciju SSRI (ili njegovog analoga ili njegovog metabolita) i bronhodilatator te metoda tretmana COPD s njima.
Psorijaza
Metode, pripravci i kompleti iz izuma se mogu koristiti za tretman psorijaze. Ako je poželjno, mogu se koristiti jedno ili više antipsorijatičkih sredstava koja se tipično koriste u tretmanu psorijaze, a kao zamjena ili kao dodatak NsIDI u metodama, pripravicma i kompletima iz izuma. Takva sredstva uključuju biologična sredstva (npr. alefacept, infliksamab, adelimumab, efalizumab, etanercept i CDP-870), nesteroidne inhibitore kalcineurina (npr. cilosporin, takrolimus, pimekrolimus i ISAtx247), analoge vitamina D (npr. kalcipotrien, kalcipotriol), psoralene (npr. metoksalen), retinoide (npr. acitretin, tazoreten), DMARD (npr. metotretaksat) i antralin. Stoga u jednoj cjelini izum prikazuje kombinaciju SSRI (ili njegovog analoga ili njegovog metabolita) i sredstva protiv psorijaze, te metoda tretmana psorijaze s njima.
Upalna bolest crijeva
Metode, pripravci i kompleti iz izuma se mogu koristiti za tretman upalne bolesti crijeva. Ako je poželjno, mogu se koristiti jedno ili više sredstava koja se tipično koriste u tretmanu upalne bolesti crijeva, a kao zamjena ili kao dodatak NsIDI u metodama, pripravicma i kompletima iz izuma. Takva sredstva uključuju biologična sredstva (npr. infliksamab, adelimumab i CDP-870), nesteroidne inhibitore kalcineurina (npr. cilosporin, takrolimus, pimekrolimus i ISAtx247), 5-aminosalicilnu kiselinu (npr. mesalamin, sulfasalazin, balzalazid dinatrij ili oksalazin natrij) DMARD (npr. metotretaksat i azatioprin) i alosteron. Stoga u jednoj cjelini izum prikazuje kombinaciju SSRI (ili njegovog analoga ili njegovog metabolita) i bilo kojeg prethodno navedenog sredstva, te metoda tretmana upalne bolesti crijeva s njima.
Reumatoidni artritis
Metode, pripravci i kompleti iz izuma se mogu koristiti za tretman reumatoidnog artritisa. Ako je poželjno, mogu se koristiti jedno ili više sredstava koja se tipično koriste u tretmanu reumatoidnog artritisa, a kao zamjena ili kao dodatak NsIDI u metodama, pripravicma i kompletima iz izuma. Takva sredstva uključuju: NSAID (npr. naproksen natrij, dikIofenak natrij, diklofenac kalij, aspirin, sulindak, diflunisal, piroksikam, indometacin, ibuprofen, nabumeton, kolin magnezijev trisalicilat, natrijev salicilat, salicilna kiselina (salsalat), fenoprofen, flurbiprofen, ketoprofen, meklofenamat natrij, meloksikam, oksaprozin, sulindak, te tolmetin), inhibitore COX-2 (npr. rofekoksib, celekoksib, valdekoksib, te lumirakoksib), biologična sredstva (npr. infliksamab, adelimumab, etanercept i CDP-870), nesteroidni inhibitori kalcinerina (npr. ciklosporin, takrolimus, pimekrolimus i ISAtx247), 5-aminosalicilna kiselina (npr. mesalamin, sulfasalazin, balsalazid dinatrij i olsalazin natrij), DMARDs (npr. metotreksat, leflunomid, minociclin, auranofin, zlatov natrijev thiomalat, aurotioglukosa, azatrioprin), hidroksiklorkin-sulfat i penicilniamin. Stoga u jednoj cjelini izum prikazuje kombinaciju SSRI (ili njegovog analoga ili njegovog metabolita) i bilo kojeg prethodno navedenog sredstva, te metoda tretmana reumatoidnogatrtirisa s njima.
Astma
Metode, pripravci i kompleti iz izuma se mogu koristiti za tretman astme. Ako je poželjno, mogu se koristiti jedno ili više sredstava koja se tipično koriste u tretmanu astme, a kao zamjena ili kao dodatak NsIDI u metodama, pripravicma i kompletima iz izuma. Takva sredstva uključuju modulatora beta 2 agonista/bronhodilatatora/leukotriena (npr. zafirlukast, montelukast, i zileuton), biologična sredstva (npr. omalizumab), antikolinergične spojeve, ksantin, efedrin, guaifenesin, kromolin natrij, nedoromolin natrij i kalijev jodid. Stoga u jednoj cjelini izum prikazuje kombinaciju SSRI (ili njegovog analoga ili njegovog metabolita) i bilo kojeg prethodno navedenog sredstva, te metoda tretmana astme s njima.
Davanje
U određenoj cjelini bilo koje metode iz izuma, NsIDI i NsIDE se daju u razmaku unutar 10 dana, u razmaku unutar pet dana, u razmaku unutar dvadeset četiri sata ili istovremeno. Spojevi mogu biti formulirani zajedno u jednom pripravku ili mogiu biti formulirani i dani odvojeno. Jedan ili oba spoja mogu biti dani pri niskoj dozi ili visokoj dozi, a svaka je ovdje definirana. Može biti poželjno dati pacijentu neke druge spojeve kao što je kortikosteroid, NASID (npr. naproksen natrij, diklofenak natrij, diklofenak kalij, aspirin, sulindak, diflunisal, piroksikam, imdometacin, ibuprofen, nabumeton, kolin magnezijev trisalicilat, natrijev salicilat, salicilnu kiselinu, fenoprofen, flurbiprofen, ketoprofen, meklofenamat natrij, meloksikam, oksaprozin, sulindak i tolmetin), inhibitore COX-2 (npr. rofekoksib, celekoksib, valdekoksib, te lumirakoksib), modulator glukokortikoidnog receptora ili DMARD. Kombinacijske terapije iz izuma su posebno korisne za tretman imunoinflamatornih poremećaja u kombinaciji s ostalim anti-citokisnkim sredstvima ili sredstvima koja moduliraju imuni odgovor na pozitivni učinak bolesti, kao što sui sredstva koja djeluju na staničnu adheziju ili biologici (npr. sredstva koja blokiraju djelovanje IL-6, IL-1, IL-2, IL-12, IL-15) ili TNF� (npr. etanercept, adelimumab ili CDP-870). U ovom primjeru (u kojem sredstvo blokira učinak TNF�), kombinacijska terapija smanjuje produkciju citokina, etanercept ili infliksimab djeluju na ostatak dijela upalnih citokina uvrzavajući tretman.
Terapija se prema izumu može izvesti sama ili skupa s drugom terapijom i može se izvoditi doma, u ambulanti liječnika, u klinici , u vanjskoj dijelu bolnice te u bolnici. Tretman može početi u bolnici tako da liječnik može iz blizine motriti terapijski učinak i po potrebi izvesti prilagodbe. Trajanje terapije ovisi o vrsti tretirane bolesti ili poremećaja, starosti i stanju pacijenta, stupnju i tipu bolesti pacijenta te o reakciji pacijenta na tretman. Uz to, osoba kod koje postoji veći rizik od razvitka upalne bolesti (npr. osoba koja prolazi kroz hormonsku promjenu povezanu s dobom) može primiti tretman za inhibiciju ili odgodu nastupa simptoma.
Načini davanja za raličite cjeline uključuju, ali nisu na njih ograničeni, topičko, transdernalno i sistemsko davanje (kao što je intravenozno, intramuskularno, subkutalno, inhalacijom, rektalno, bukalno, vaginalno, intraperitonealno, intraartikularno, ofatlmno ili oralno davanje). Kako se ovdje koristi, "sistemsko davanje" se odnosi na nedermalni način davanja, a posebno isključuje topički i transdermalni način davanja.
U kombinacijskoj terapiji se doziranje, učestalost i način davanja svake komponente kombinacije se može nevisno kontrolirati. Primjerice, jedan spoj može biti dan oralno tri puta dnevno, dok se drugi spoj može davati jedanput dnevno. Kombinacijska terapija se može davati u ciklusima davanja i nedavanja koji uključuju periode odmora tako da se pacijentovo tijelo može oporaviti od još nepredviđenih nuzpojava. Spojevi se također može formulairati zajedno tako da se spojevi isporuče jednim davanjem.
Formulacija farmacetuskih pripravaka
Davanje kombinacije iz izuma (npr. NsIDI/NsIDIE kombinacije) se može izvesti bilo kojim pogodnim načinom koji kao rezultat ima smanjivanja razina proinflamatornih citokina na ciljanom mjestu. Spoj može sadržavati bilo koju pogodnu količinu bilo kojeg pogodnog nosača koji je općenito je prisutan u količini od 1-95% po masi ukupne mase pripravka. Prirpavak može biti u obliku doze koja je pogodna za oralno, parenteralno (npr. intravenzono, intramuskuparno), rektalno, kutalno, nazalno, vaginalno, inghalacijsko, preko kože (flaster) ili okularno davanje. Stoga prirpavak može biti u obliku npr. tableta, kapsula, pilula, prašaka, granula, suspenzija, emulzija, otopina, gelova uključujući hidrogelove, pasta, masti, krema, flastera, obloga, pogodnom za naprave za isporuku osmozom, supozitorija, klistira, implanta koji se mogu injektirati, sprejeva ili aerosola. Farmacetuski pripravci se mogu formulirati prema uobičajenoj farmaceutskoj praksi (vidi npr. Remington: Scince and Practice in Pharmacy, 20. izdanje, 2000, izd. A. R. Gennaro, Lippnicott Williamis & Wlikins, Philadelphia, i Encyclopedia of Pharmaceutical Technology, izd. J. Swarbrick i J. C. Boylan, 1988-1999, Marcel Dekket, New York).
Svak spoj iz izuma može biti formuliran na razne načine poznate u struci. Primjerice, prvo i drugo sredstvo može biti formulirano zajedno ili odvojeno. Poželjno je da su prvo i drugo sredstvo formulirani zajedno za istovremeno ili skoro istovremeno davanje sredstava. Takav zajedno formulirani pripravk može sadržavati SSRI i steroid formuliran i istoj pilulu, kaspuli, tekućini itd. Također se podrazumijeva da se navođenjem formulacije "NsIDI/NsIDIE kombinacija" koristi tehnologija za formulacija koja je također korisna za formulaciju pojednih sredstava u kombinaciji, kao i druge kombinacije iz izuma. Upotrebom različith strategija za formulaciju za različita sredstva se pogoduje farmakokinteičkom profilu svakog sredstva.
Pojedinačno i odvojeno formulirana sredstva mogu biti pakirana u komplete. Neograničavajući primjeri uključuju komplete koji sadrže npr. dvije pilule, pilulu i prašak, supozitorij i tekućinu u bočici, dvije topičke kreme itd. Komplet može sadržavati komponente koje pomažu pri davanju jedinice doze pacijentu, kao što su bočice za pripravu praškastih oblika, injekcije za injektiranje, uobičajeni IV sustavi za isporuku, inhalatori itd. Uz to, komplet jedinice doze može sadržavati upute za pripravu i davanje pripravaka. Komplet može biti pripravljen kao jedinica doze za jednog pacijenta, za višestruku upotrebu za određenog pacijenta (pri konstantnoj dozi ili u kojem se količina pojedinog spoja mijenja kako napreduje terapija), ili komplet sadrži višestruke doze pogodne za davanje više pacijenata ("bulk pakiranje"). Komponente kompleta mogu biti smještene u kartone, blistere, bočice, epruvete i slično.
Formulacije s kontroliranim oslobađanjem
Davanje kombinacije NsIDI/NsIDIE iz izuma u kojima su jedno ili oba aktivna sredstva formulirana za kontrolirano oslobađanje je korisno kada NsIDI ili NsIDIE imaju (i) uski terapijski indeks (npr. razlika između koncetracije u plazmi koja vodi štetnim nuzefektima ili toksičnoj reakciji i koncetracija u plazmi koja ima terapijski učinak je mala; općenito je terapijski indeks, TI, definiran kao omjer medijalne letalne doze (LD50) i medijalne efektivne doze (ED50)); (ii) uski "prozor" apsorpcije u gastro-intestilnalnom traktu; (iii) kratko biološko poluvrijeme; ili (iv) farmakokinetički profil svake komponente mora biti modificiran da se dobije djelovanje svakog sredstva kad se koriste zajedno, a u kolčini koje je terapijski učinkovita za sprječavanje izlučivanja citokina. PRema toma formulacije s odgođenim djelovanjem se mogu koristiti da bi se izbjello učestalo doziranje koje nože biti potrebno da bi se održala terapijska razina u plazmi obaju sredstava. Primjerice, opaženo je da prefeirani farmaceutski prirpavci u izumi imaju poluvrijeme i srednje vrijeme zadržavanja od 10 do 20 sati jednog ili oba sredstva u kombinaciji iz izuma.
Mogu se koristiti mnoge strategije da se dobije kontrolirano oslobađanje u kojem brzina oslobađanja nadvlada brzinu metabolizma terapijskog spoja. Primjerice, kontrolirano oslobađanje se može dobiti odgovarajućim odabirom parametara formulacije i sastojaka, (npr. upotrebu odgovarajućih pripravaka s kontroliranim oslobađanjem i upotrebu presvlačenja). Primjeri uključuju jednostruke ili višestruke jedinične pripravke tableta ili kapsula, uljaste otopine, suspenzije, emulzije, mikrokapsule, mikrosfere, nanočestice, flastere i liposome. Mehanizam oslobađanja se može kontolirati tako da se NsIDI i/ili NsIDIE oslobađaju u intervalima vremena, a oslobađanje može biti istovremeno ili odgođeno oslobađanje jednog sredstva iz kombinacije, a kad je rano oslobađanje određenog sredstva preferirano u odnosu na drugo.
Formulacije s kontroliranim oslobađanjem mogu sadržavati polimere koji se degradiraju ili se ne degradiraju, hidrogel, organogel, ili drugi fizički konstrukt koji modificiraju bioapsorpciju, poluvrijeme života ili biodegradaciju sredstva. Formulacija s kontroliranim oslobađanjem može biti materijal koji se namaže ili na drugi način nanese na pogođeno mjesto iznutra ili izvana. U jednom primjeru, izum prikazuje biorazgradljivi veterinarski pripravak ili implant koji se operativno umeće na ili blizu mjesta od interesa (primjerice u susjedstvu artritičnog zgloba). U sljedećem primjeru, implanti s formulacijom s kontroliranim oslobađanjem mogu biti umetnuti u organ, kao što je niži probavni trakt, a za tretman upalne bolest crijeva.
Hidrogelovi se u ovom izumu mogu koristiti u kombinacijama NsIDI/NsIDIE s kontroliranim oslobađanjem. Takvi polimeri nastaju od makromera s regijom koja može polimerizirati a ne razgrađuje se, a rastavljeni su barem jednom regijom koja se može razgraditi. Primjerice, u vodi topljiva regija koja se ne razgrađuje može tvoriti jezgru makromera i imati najmanje dvije regije koje se razgrađuju, a koje su spojene na jezgru tako da nakon razgradnje regija koja se ne razgrađuje (koja je polimerizirani gel) su odijeljene kao što je opisano u U. S. Patentu br. 5,626,863. Hidrogeli mogu sadržavati akrilate koji lako polimeriziraju pomoću nekoliko sustava za inicijaciju kao što je eozinska boja, ultraljubičasto ili vidljivo svjetlo. Hidrogelovi mogu također sadržavati polietilenglikole (PEG) koji su vrlo hidrofilni i biokompatibilni. Hidrogelovi mogu također uključivati oligoglikolnu kiselinu koja je poli(�-hidroksi kiselina) koja se lako ragrađuje hidrolizom esterske veze u glikolnu kiselinu koja je netoksični metabolit. Ostale lančane ekstenzije mogu uključivati polmliječnu kiselinu, polikaprolakton, poliortoestere, polianhidride i polipeptide. Cijela mreža može gelirati u biorazgradljivu mrežu koja se može koristiti da potakne i homogeno dispergira kombincije SSTI/steroida iz izuma, a za isporuku kontroliranom brzinom.
Kitosan i smjese kitosana s natrijevom karboksimetil-celulozom (CMC-Na) su korišteni kao vezikuli za odgođeno oslobađanje lijekova, kao što je opisnao od Inouye et al., Drug Design and Delivery 1:297-305, 1987. Smjese tih spojeva i sredstva kombinacije SSRI/steroid, a kad su komprimirani pod 200 kg/cm2, tvore tablete iz kojih se aktvino sredstvo oslobađa polako nakon davanja subjektu. Profil oslobađanja se može mijenjati promjenom omjera kitosana. CMC-Na i aktivne(ih) tvari. Tablete mogu također sadržavati druge aditive uključujući laktozu, CaHPO4 dihidrat, saharozu, kristaliničnu celulozu ili natrijevu kroskaramelozu. Nakoliko primjera je dano u Tablici 5.
Tablica 5
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Baichwal u U. S. Patentu br. 6,245,356 oisuje oralni oblik doze s odgođenim oslobađanjem koji sadrži aglomerirane čestige terapijski učinkovitog aktivnog lijeka (primjerice kombinaiju NsIDI/NsIDIE ili njihove komponente u ovom izumu) u amorfnom obliku, sredstvo za tvorbu gela, sredstvo za povećavanje mogućnosti ionizacije gela i inertno otapalo. Sredstvo za geliranje može biti msjesa ksantan gume i gume sjemenke rogača koja može biti umrežena s ksantan gumom, a kada je guma izložena tekućini iz okoline. Prefeirano sredstvo za ubrzavanje geliranja djeluje tako da poveća jakost umrežavanja između ksantan gume i gume sjemenke rogača i time produljuje odlobađanje komponente lijeka iz formulacije. Uz ksantan gumu i gumu sjemenke rogača, prihvatljiva sredstva za geliranje koja se također mogu koristiti uključuju ona gelirajuća sredstva koja su dobro poznata u struci. Primjeri uključuju prirodne i modificirane prirodne gume kao što su alginati, karagenan, pektin, guma guas, modificirani škrob, hidoksipropil-metilceluloza. Metoceluloza i ostali celulozni materijali ili polimeri kao što su primjerice natrijeva karboksimetilceluloza i hidroksipropil-celuloza i smjese prethodno navedenih.
U sljedećoj formulaciji korisnoj za kombinaciju iz izuma, Baichwal i Stainfort su u U.S. Patentu br. 5,135,757 opisali granulaciju uz slobodni protok za polagano oslobađanje za upotrebu kao farmaceutski ekscipijens koji sadrži od oko 20 do oko 70 posto ili više po masi hidrofilnog materijala koji uključuje heteropolisaharide (kao što je primjerice ksantan guma ili njeni derivati) i polisaharidne mateirjal koji može umrežavati heteropolisaharide (kao što je primjerice galakromanas, a najpreferiranija je guma sjemenke rogača u prisutnosti vodenih otopina i tvore od oko 30 do oko 80 posto po masi inertnog farmaceutskog filtera (kao što je primjerice laktoza, dekstroza, saharoza, sorbitol, ksilitol, fruktoza ili njihove smjese). Nakon miješanja ekscipijensa s kombinacijom NsIDI/NsIDIE ili kombinacijskim sredstvom iz izuma, smjesa je izravno komprimirana u čvrsti oblik doze kao što su tablete. Tako nastale tablete polako oslobađaju lijek pri varenju kad su izložene želučanoj tekućini. Mijenjanjem količine ekcipijensa relativno prema lijeku može se postići profil polaganog oslobađanja.
U sljedećoj formulacija korisnoj za kombinaciju iz izuma, Shell u U.S. Patentu br. 5,007,790 opisuje oblike doze lijeka u otopini s u kojem je oslobađanje lijeka kontrolirano s topljivosti lijeka. Oblik doze sadrži tabletu ili kapsulu koja sadrži više čestica u disperziji ograničene topljivosti (kao što je primjerice prednisolon, paroksetin ili bilo koje sredstvo uz kombinacije SSRI/sreroid iz ovog izuma) u hodrofilnom umreženom polimeru koji bubri u vodi kojim se održava u naraspadnutom obliku dulje od vremena života doze, ali se zatim brzo otapa. Pri varenju, čestice bubre i potiču ostajanje u želucu i dozvoljavaju želučanim tekućinama da prodru u čestice, otapaju lijek koji izlazi iz čestica, osiguravaju da lijek koji dolazi do želuca u obliku otopine koja je manje štetna u želucu od lijeka u čvrstom obliku. Programirano ubrzano otapanje polimera ovisi o prirodi polimera i stupnju umreženosti. Polimer je nefibrilne građe i uglavnom topljiv u vodi u neumreženom stanju, a stupanj umreženosti je dovoljan da omogući da polimer ostane netopljiv u želljenom periodu vremena, normalno najmanje od 4 sata do 8 sati do 12 sati, a izbor ovisi o ugrađenom lijeku i medicinskom tretmanu. Primjeri pogodnih umreženih polimera koji se mogu koristiti u izumu su želatina, albumin, natrijev alginat, karboksimetil-celuloza, polivinilni alkohol i hitin. Ovisno o polimeru, umrežavanje se može postiži termičkim ili radijacijskim tretmanom upotrebom sredstava za umrežavanje kao što su aldehidi, poliaminokiseline, metalni ioni i slično.
Silikonske mikrosfere za lijek za gastointestinalnu isporuku lijeka kontroliranu s pH koje su korisne u formulaciji kombinacije NsIDI/NsIDIE iz izuma su opisane u Carelli et al. Int. J. Pharmaceuutics 179: 73-83, 1999. Hidrogelini proteini osjetljivi na pH načinjeni od različitih proporcija poli(metakrilne kiseline-kometilmetakrilata) (Eudragit L1000 ili Euragit S100) i umreženog polietilenglikola 8000 su polupropusni za tak opisane mikrosfere, kapsulirani su u silikonske mikrosfere raspona veličine 500 do 1000 �m.
Formulacije s polaganim oslobađanjem sadrže presvučeni sloj koji nije lako topljiv u vodi ali kojeg voda sporo napada i uklanja ili preko kojeg voda može polako prodirati. Stoga, primjerice kombinacije NsIDI/NsIDIE iz izuma može biti presvučen sprejanjem otopinom veziva pod uvjetima kontinuiranog prevođenja u tekućinu, kao što je opisnao od Kitamori et al. U. S. Patent br. 4,036,948. Primjeri u vodi topljivih veziva uključuju preželatinizirani škrob (npr. preželatizirani kukuruzni škrob, preželatizirani škrob bijelog krumpira), preželatizirani modificirani škrob, u vodi topljivu celulozu, hidroksipropilmetil-celulozu, karboksimetil-celulozu), polivinil-pirolidon, polivinil-alkohol, dekstrin, gumu arabiku i želatinu, veziva topljiva u organskim otapalima kao što su derivati celuloze (npr. celuloza-acetat-ftalat, hidroksipropilmetil-celuloza, ftalat, etilceluloza).
Kombinacije iz izuma ili njihove komponente sa svojstvom odgođenog oslobađanja mogu također biti formulirane tehnikom sprej sušenja. Sljedeća kombinacija NsIDI/NsIDIE s odgođenim oslobađanjem se može pripraviti mikrokapsuliranjem kombinacije sredstava u membrane koje djeluju kao ćelije za mikrodijalizu. Takvom tvorbom želučana tekućina prodire u stjenke mikrokapsule i mikrokapsule bubre, ostavljajući aktivno sredstvo(a) da izlazi usljed dijalize (vidi primjerice Tsuei et al., U. S. Patent br. 5,589,194). Jedan komercijalno pristupačan sustav za odgođeno oslobađanje ove vrste sadrži mikrokapsule koje imaju membranu od gume akacije/etanola. Taj produkt se može nabaviti od Eurand Limited (Francuska) pod trgovačkim nazivom Diffucaps™. Tako formulirane mikrokapsule se mogu biti u običnoj želatinskoj kapsuli ili mogu biti tabletirane.
Formulacije s produljenim ili kontrolirano odgođenim oslobađanjem SSRI i kortikosteroida su dobro poznate. Primjerice Paxil CR® komercijalno pristupačan od GlaxoSmithKline je oblik produljenog oslobađanja paroksetin hidroklorida u polimernoj matrici koja se može razgraditi (GEOMATRIX™, vidi također U.S. Patente br. 4,839,177, 5,102,666 i 5,422,123) koje također imaju enteralnu presvlaku za odgodu početka oslobađanja lijeka dok tableta nije došla u želudac. Primjerice, U. S. Patent 5,102,666 opisuje polimerni pripravak s kontroliranim oslobađanjem koji sadrži reakcijski kompleks nastao interacijom (1) kalcijeve polikarbofilne komponente koja bubri u vodi, ali je u vodi netopljiva, vlaknasto umreženi polimer s karboksilnim funkcionlanim skupinama, a polimer sadrži (a) mnoštvo ponavljajućih jedinica od kojih barem 80% sadrži barem jednu karboksilnu funkcionlanu skupinu, te (b) oko 0.05 do oko 1.5% sredstva za umreženje koji ne sadrži polialkenilni polieter, a postotak je zasnovan na masama nepolimerizirane ponavljajuće jedinice i sredstva za umrežavanje s (2) vodom u prisutnosti aktivnog sredstva odabranog od SSRI kao što je paroksetin. Prisutna količina kalcijeva polikarbonila je od oko 0.1 do oko 99% po masi, primjerice oko 10%. Količina prisutnog aktivnog sredstva je od oko 0.0001 do oko 65% po masi, primjerice između oko 5 i 20%. Količina vode prisutnoa je od oko 5 do oko 200% po masi, primjerice između 5 i 10%. Interakcija je provedena na pH između oko 3 i oko 10, primjerice oko 6 do 7. Kalcijev polikarofil je originalno prisutan u obliku kalcijeve soli koja sadrži od oko 5 do oko 25% kalcija.
Primjeri ostalih formulacija s produljenim oslobađanjem su pisani u U. S. Patentu br. 5,422,123. Tako je sustav s kontoliranom oslobađanjem aktivne tvari u kojem je SSRI kao što je parokserin sadrži (a) jezgru koja sadrži učinkovitu količinu aktivne tvari u ima definirani geometrijski oblik te (b) nosač nanešen na jezgru pri čemu jezgra sadrži materijal koji bubri u kontaktu s vodom ili vodenom tekućinom i polimer koji tvori gel, pri čemu je omjer polimera koji bubri i polimera koji tvori gel u rasponu od 1:9 do 9:1, te (2) jedan polimerni materijl koji i bubri i tvori gel, pri emu je nosač elastični nosač nanešen na rečenu jezgru tako da djelomice pokriva površinu jezgre i mijenja se usljed hidratacije jezgre i polako se otapa ili polako tvori gel u vodenoj tekućini. Nosač može sadržavati polimer kao što je polihidroksimetil-celuloza, plastifikatore kao što je glicerid, veziva kao što je polivinilpirolidon, hidrofilna sredstva kao što je laktoza ili silikagel i/ili hidrofobna sredstva kao što je magnezijev stearat i gliceridi. Polimer(i) tipično čini 30 do 90% po masi nosača, primjerice od 35 do 40%. Plastifikator je načinjen od najmanje 2% po masi nosača, primjerice oko 15 do 20%. Vezivo(a), hidrofilno sredstvo(a) i hidrofibno sredstvo(a) su tipično do oko 50% po masi nosača, primjerice oko 40 do 50%.
U sljedećem primjeru, formulacija s produljenim oslobađanjem venlafaksina (Effexor XR®) je komercijalno prostupačna od Wyeth Pharmaceuticals. Ta formulacija sadrži venaflaksin hidroklorid, mikrokristalnu celulozu i hidroksipropilmetil-celulozu, prsvučene sa smjesom etil-celuloze i hidrosipropilmetil-celulize (vidi U. S. Patente br. 6,403,120 i 6,419,958).
Formulacije s kontroliraim oslobađanjem buidesonida (kpasule od 3 mg) za tretman upalne bolesti crijeva su na raspolaganju od AstraZeneca (prodavan kao "Entocort™"). Da se omoguće ove niske razine doze aktivne tvari moguće, aktivna tvar, t.j. glukokortikoid, kao što je prednisolon ili prednison je usitnjena, pogodno miješana s pozntim razrijeđivačima kao što je škrob i laktoza i granulirana s PVP (polivinilpirolidon). Nadalje, granule su presvučene vanjskim slojem za odgođeno oslobađanje koji je otporan na pH od 10. Unutarnji sloj je načinjen od Eudragir®RL (kopolimer akrilnog i metakrilnog estera s niskim sadržajem kvaternih amonijevih skupina) i vanjskog sloja načinjenog od Eudragir®L (anionski polimer sintetiziran iz metakrilne kiseline i metilnog estera metakrilne kiseline).
Dvoslojna tableta može biti formulirana za kombinaciju NsIDI/NsIDIE iz izuma u kojem je su različito granulirana pojedina sredstava u kombinaciji dvaju sredstava komprimirana na dvoslojnoj preši, čime nastaje jedna tableta. Primjerice, 2,5 mg, 25 mg, 37,5 mg ili 50 mg paroksetina je formulirano za kontrolirano oslobađanje što čemi se dobiva paroksetina t1/2 od 15 do 20 sati koji se može kombinirati u istu talbetu s 3 mg prednisolona, a koja je formulirana tako da je t1/2 približno isto kao od paroksetina. Primjeri formulacija paroksetina s produljenim oslobađanjem uključuju dvoslojne tablete koje se mogu naći u U.S Patentu br. 6,548,084. Uz kontroliranu brzinu oslobađanja prednisolona in vitro, enteralno ili presvlaka za odgođeno oslobađanje može biti ulljučena tako da odgodi početak oslobađanja lijeka tako da je Tmax prednisolona približno kao od paroksetina (t.j. 5 do 10 sati).
Ciklodekstrini su ciklički polisaharidi koji sadrže prirodne D-(+)-glukopiranozne jedinice s �-(1,4)-vezom. Obično se koriste allfa-, beta- i gama ciklodekstrini koji sadrže šest, sedam ili osam glukoripranoznih jedinica, a pogodni primjeri su navedeni u WO 91/11172, WO 94/02518 i WO 98/55148. Struktura cikličkog ciklodekstrina ima oblik krafne koja ima unutarnju nepolarnu ili hidrofobnu šupljinu, sekundarne hidroksilne skupine su smještena na jednom kraju ciklodesktrinske strukture, a primarne hidroksilne ksupnie smještene na drugoj strani. Strana na kojoj su smještene sekundarne hidorksilne skupine ima veći promjer nego strana na kojoj su smještene primarne hidroksilne skupine. Hidrofobnost unutarnje šupljine ciklodekstrina dozvoljav ugradnju različitih spojeva (Compreghensive Supramileculat Chemistry, vol. 3, J. Atwood et al. ed, Pergamon Press (1996), Cserhati, Analitical Biochemistry 225: 328-32, 1995, Husain et al., Applied Spectroscopy 46: 652-8, 1992. Ciklodekstini su korišteni kao vezikuli za isporuku različitih terapijskih spojeva, tvorbom inkluzijksih kompleksa s različitim lijekovima koji mogu stati u hidrofobnu šupljinu ciklodekstrina ili tvorbom nekovalentnih asocijacijskih kompleksa s drugim biološki aktivnim molekulama. U.S. Patent br. 4,727,064 opisuje farmaceutske pripravke koji sadrže lijek koji je vrlo slabo topljiv u vodi i amorfan je, u vodi topljivu na ciklodekstrinu zasnovanu smjesu u kojoj lijek tvori inkulzijski kompleks sa smjesom ciklodekstrina.
Tvorba kompeksa lijek-ciklodeksrin može modificirati topjlivost lijeka, brzinu razgradnje, bioraspoložljivost i/ili stablinost.
Sulfobutileter-�-ciklodekstrin (SBE-�-CD, komercijalno pristupačan od CyDex, Inc. Overland Park, Ka, USA i prodavan je kao CAPTISOL®) se također može koristiti kao pomoć u pripravi formulacija s odgođenim oslobađanjem sredstava iz kombinacije iz ovog izuma. Primjerice, tableta za odgođeno oslobađanje je prirpavljena tako da sadrži prednisolon i SBE-�-CD komprimiran u hodroksipropilmetil-celuloznu matricu (vidi Rao et al. J. Pharm. Sci, 90: 807-16, 2001). U sljedećem primjeru upotrebe različitih ciklodekstrina, EP 1109806 B1 opisuje komplekse ciklodekstrina i paroksetina, gdje �-, �- ili �-ciklodekstrini [uključujući eptakis(2,6-di-O-metil)-��-ciklodekstrin, (2,3,6-tri-O-metil)-��-ciklodekstrin, monosukcinil-eptakis(2,6-di-O-metil)-��-ciklodekstrin ili 2-hidroksipropil-�-ciklodetrin] u bezvodnom ili hidratiziranom obliku se može dobiti omjer sredstva i ciklodekstrina u kompleksu od 1:0.25 do 1:20.
Polimerni ciklodekstrini su također pripravljeni, kao što je opisnao u U.S. Patetnoj prijavi serijskog br. 10.21,294 i 10/021,312. Tako nastali polimerni ciklodekstrini mogu biti korisni za sredstvo za formulaciju kombinacije ovog izuma. Ti višefunkcionalni polimerni ciklodekstrini su komercijalno pristupačni od Inset Therapeutics, Inc., Pasadena, CA, USA.
Kao alternativa izravnom kompleksiranju sa sredstvima, cikodekstrini mogu biti korišteni kao dodatni aditiv npr. nosač, razrjeđivač ili solubilizator. Formulacije koje sadrže ciklodekstrin i druga sredstva kombinacije iz ovog izuma (t.j. NsIDI i/ili NsIDIE) se mogu prirpaviti prema metodama sličnim pripravi formulacija ciklodekstrina opisanih ovdje.
Liposomske formulacije
Jedna ili obje komponente kombinacije NsIDI/NsIDIE iz izuma ili smjese dviju komponenata se mogu ugraditi u liposomske nosače za davanje. Liposomski nosači su sastavljeni od tri opća tipa lipidnih komponenata koje tvore vezikule. Prvi tip sadrži lipide koji tvore vezikulle koji će tvoriti volumenoznu vezikulnu strukturu u liposomu. Općenito, lipidi koji koje tvore vezikule mogu sadržavati bilo koji od amfipatskih lipida koji imaju hidrofobnu polarnu glavu i koji (a) mogu sponatno tvoriti dvoslojne vezikule u vodi, kao što su primjerice fosfolipidi, ili (b) su stabilno ugrađeni u lipidni dvosloj s hidrofobnim dijelom u kontaktu s unutarnjom hidrofobnom regijom dvoslojne membrane, a njegova polarna glava je orijentirana prema vanjskoj polarnoj površini membrane.
Lipidi koji koje tvore vezikule ovog tipa prefrirano imaju dva ugljikovodična lanca, tipično acilne lance i polarnu glavu. U ovu klasu su uključeni fosfolipidi kao što je fosfoftalidilkolin (PC), PE, fosfatidna kiselina (PA), fosfatidil-inozitol (PI) isfingomielin (SM), dok je tipična duljina dvaju ugljikovodičnih lanaca između 14-22 atoma ugljika, te imaju različite stupnjeve nezasićenja. Gore opisani lipidi i fosfolipidi čiji acilni lanci imaju različit stupanj zasićenja se mogu dobiti komercijalno ili preparirati prema publiciranim metodama. Ostali lipidi koji su uključeni u izum su glikolipidi i steroli, kao što je kolesterol.
Druga opća komponenta uključuje lipid koji tvor vezikul koji je preveden u derivat s polimeronom lancem, koji će u pripravku tovriti polimerni sloj. Lipidi koji tvore vezikule koji se mogu koristiti kao druga opća komponenta lipida koji tvore vezikule su svi oni opisani za prvu opću komponentu lipida koji tvore vezikule. Lipidi koji tvore vezikule s diaclinim lancima, kao što su fosfolipidi su preferirani. Jedna primjer fosfolipida je fosfatidiletanolamin (PE) koji ima reaktivnu amino-skupinu koja je kovalentno vezana na aktivirani polimer. Primjeri PE je disteril PE (DSPE).
Preferirano polimer u derivatiziranom lipidu je polietilanglkol (PEG), preferirano PEG lanac koji ima molekulsku masu između 1000-15000 Daltona, preferiranije između 2000 i 10000 daltona, najpreferiranije između 2000 i 5000 Daltona. Drugi hidrofilni polimeri koji mogu sadržavati sljedeće: polivinilpirolidon, polimetiloksazolin, polietiloksazolin, polihidroksipropil-metakrilamid, polimetakril-amid i polimetilakrilamid, polimliječna kiselina, poliglikolna kiselina i derivatizirana celuloza kao što je hidroksimetilceluloza ili hidroksietilceluloza.
Uz to, mogu biti pogodni blok kopolimeri ili slučajni kopolimeri ovih polimera, posebno oni koji sadrže segmente PEG. Metode prirpave derivatiziranih lipida s hidrofilnim polimerima, kao što je PEG su dobro ponati, kao što je npr. opisano u U.S. Patentu br. 5,013,556.
Treća opća komponente lipida koji tvori vezikul može biti lipidno sidro kojim se ciljani dio vezuje na liposom preko polimernog lanca sidra. Uz to, ciljana skupina je smještena na distalnom kraju polimernog lanca tako da biološka aktivnost ciljanog dijela nije izgubljena. Lipidno sidro sadrži hidrofobni dio koji služi da vezuje lipid u vanjskom sloju liposoma dvoslojne površine, polarnu glavu na koju se unutarnji kraj polimer kovalentno vezan, te slobodni (vanjski) polimerni kraj koji može biti aktiviran za kovalentno vezivanje na ciljani dio. Metode priprave lipidnih molekula koji su sidro ovog tipa su opisane niže.
Lipidne komponente koje se koriste pri tvorbi liposoma su preferirano prisutne u sljedećim morlanim omjerima: od oko 70-90 posto lipida koji tvore veziluke, 1-25 posto polimerom derivatiziranih lipida i 0.1-5 posto lipidnog sidra. Jedan primjer formulacije sadrži 50-70 molarnih postotaka nederivatiziranog PE, 20-40 molarnih postotaka kolesterola, 0.1-1 molarnog postotka PE-PEG (3500) polimera s kemijski reaktivnom skupinom na slobodnom kraju za vezivanje na ciljani dio, 5-10 morlanih postotaka derivatiziranog PE s PEG 3500 polimerom i 1 molarni postotak alfa-tokoferola.
Liposomi su preferirano pripravljeni tako da su homogene veličine odabrane u rasponu između 0.03 i 0.5 mikrona. Jedna učinkovita metoda ujednačavanja čestica za REV i MVL obuhvaća protiskivanje vodene suspenzije liposoma preko serije polikarbonatnih membrana koji imaju odabranu veličinu pora u raspomu od 0.03 i 0.2 mikrona, tipično 0.05, 0.08, 0.1 ili 0.2 mirona. Veličina pora membrane odgovara grubo najvećoj veličini liposoma dobivenih protiskivanjem dva ili više puta preko iste membrane. Metode homogencijacije su također korisne za smanjivanje veličine liposoma od 100 nm ili manje.
Liposomske formulacije iz ovog izuma sadrže najmanje jednu površinski aktivnu tvar. Pogodne površinski aktivne tvari korisne za ovdje opisane forimulacije kombinacija SSRI/steroida sadrže spojeve koje pripradaju sljedeim klasama: polietoksilirane masne kiseline, diesteri polietoksiliranih PEG-masnih kiselina, smjese mono-estera i di-estera, esteri polietilenglikol-glicerol masne kiseline, produkti transesterifikacije alcohola i ulja, poliglicerizirane masne kiseline, esteri propilenglikol masne kiselina, smjese estera propilenglikola i estera glicerola, mono- i digliceridi, sterol i derivati sterola, esteri polietilenglikol-sorbitana i masne kiseline, polietilenglikol-alkil-eteri, esteri šećera, polietilenglikol-alkilfenoli, blok kopolimeri polioksietilen-polioksipropilena, esteri sorbitana i masnih kiselina, esteri nižih alkohola i masnih kiselina, i ionske površinski aktivne tvari. Komercijalno pristupačni primjeri svake klase ekscipijeana su prikazani niže.
Poliethoksilated masne kiseline se mogu koristiti kao ekscipijsi za ovdje opisanu formulaciju kombinacije SSRI/steroida. Primjeri komercijalno pristupačnih površinski aktivnih tvari koje su polietoksilirani monoesteri masnih uključuju: PEG 4400-monolaurat (Crodet L series, Croda), PEG 4-100 monooleat (Crodet O series, Croda), PEG 4-100 monostearat (Crodet S serije, Croda, i Myrj Series, Atlas/ICI), PEG 400 distearat (Cithrol 4DS series, Croda), PEG 100, 200, ili 300 monolaurat (Cithrol ML series, Croda), PEG 100, 200, ili 300 monooleat (Cithrol MO series, Croda), PEG 400 dioleat (Cithrol 4DO series, Croda), PEG 400-1000 monostearat (Cithrol MS series, Croda), PEG-1 stearat (Nikkol MYS1lEX, Nikko, i Coster KI, Condea), PEG-2 stearat (Nikkol MYS-2, Nikko), PEG-2 oleat (Nikkol MYO-2, Nikko), PEG-4 laurat (Mapeg® 200 ML, PPG), PEG-4 oleat (Mapeg® 200 MO, PPG), PEG-4 stearat (Kessco® PEG 200 MS, Stepan), PEG-5 stearat (Nikkol TMGS-5, Nikko), PEG-5 oleat (Nikko] TMGO-5, Nikko), PEG-6 oleat (Algon OL 60, Auschem SpA), PEG-7 oleat (Algon OL 70, Auschem SpA), PEG-6 laurat (Kessco® PEG300 ML, Stepan), PEG-7 laurat (Lauridac 7, Condea), PEG-6 stearat (Kessco(O PEG300 MS, Stepan), PEG-8 laurat (Mapeg® 400 ML, PPG), PEG-8 oleat (Mapeg® 400 MO, PPG), PEG-8 stearat (Mapeg® 400 MS, PPG), PEG-9 oleat (Emulgante A9, Condea), PEG-9 stearat (Cremophor S9, BASF), PEG-10 laurat (Nikkol MYL- 10, Nikko), PEG-10 oleat (Nikkol MYO-10, Nikko), PEG-12 stearat (Nikkol MYS-10, Nikko), PEG-12 laurat (Kessco® PEG 600 ML, Stepan), PEG- 2 oleat (Kessco® PEG 600 MO, Stepan), PEG-12 ricinoleat (CAS # 9004-97-1), PEG-12 stearat (Mapeg® 600 MS, PPG), PEG-15 stearat (Nikkol TMGS-15, Nikko), PEG-15 oleat (Nikkol TMGO-15, Nikko), PEG-20 laurat (Kessco® PEG 1000 ML, Stepan), PEG-20 oleat (Kessco® PEG 1000 MO, Stepan), PEG-20 stearat (Mapeg® 1000 MS, PPG), PEG-25 stearat (Nikkol MYS-25, Nikko), PEG-32 laurat (Kessco® PEG 1540 ML, Stepan), PEG-32 oleat (Kessco® PEG 1540 MO, Stepan), PEG-32 stearat (Kesseo® PEG 1540 MS, Stepan), PEG-30 stearat (Myrj 51), PEG-40 laurat (Crodet L40, Croda), PEG-40 oleat (Crodet O40, Croda), PEG-40 stearat (Emerest® 2715, Henkel), PEG-45 stearat (Nikkol MYS-45, Nikko), PEG-50 stearat (Myrj 53), PEG-55 stearat (Nikkol MYS-55, Nikko), PEG-100 oleat (Crodet O-100, Croda), PEG-100 stearat (Ariacel 165, ICI), PEG-200 oleat (Albunol 200 MO, Taiwan Surf.), PEG-400 oleat (LACTOMUL, Henkel), i PEG-600 oleat (Albunol 600 MO, Taiwan Surf.). Formulacije jedne ili obaju komponenata kombinacije SSRI/steroid prema izumu mogu sadržavati jednu ili više od gornjih polietoksiliranih masnih kiselina.
Diesteri polietilenglikola i masne kiseline se također mogu koristiti kao ekscipijensi za ovdje opisane kombinacije SSRI/steroid. Primjeri komercijalno pristupačnih diestera polietilenglikola i masne kiseline su sljedeći: PEG-4 dilaurat (Mapeg® 200 DL, PPG), PEG-4 dioleat (Mapeg® 200 DO, PPG), PEG-4 distearat (Kessco® 200 DS, Stepan), PEG-6 dilaurat (Kessco® PEG 300 DL, Stepan), PEG-6 dioleat (Kessco® PEG 300 DO, Stepan), PEG-6 distearat (Kessco® PEG 300 DS, Stepan), PEG-8 dilaurat (Mapeg® 400 DL, PPG), PEG-8 dioleat (Mapeg® 400 DO, PPG), PEG-8 distearat (Mapeg® 400 DS, PPG), PEG-10 dipalmitat (Polyaldo 2PKFG), PEG- 12 dilaurat (Kessco® PEG 600 DL, Stepan), PEG-12 distearat (Kessco® PEG 600 DS, Stepan), PEG-12 dioleat (Mapeg® 600 DO, PPG), PEG-20 dilaurat (Kessco® PEG 1000 DL, Stepan), PEG-20 dioleat (Kessco® PEG 1000 DO, Stepan), PEG-20 distearat (Kessco® PEG 1000 DS, Stepan), PEG-32 dilaurat (Kessco® PEG 1540 DL, Stepan), PEG-32 dioleat (Kessco® PEG 1540 DO, Stepan), PEG-32 distearat (Kessco® PEG 1540 DS, Stepan), PEG-400 dioleat (Cithrol 4DO series, Croda), i PEG-400 distearat (Cithrol 4DS series, Croda). Formulacije kombinacija SSRI/steroid prema izumu mogu sadržavati jedan ili više od gornjih estera polietilenglikola i masne kiseline.
Smjese mono- i diestera PEG-masna kiselina se mogu koristiti kao ekscipijnesi za ovdje opisane formulacije kombinacije SSRI/steroida. Primjeri komercijalno pristupačnih smjesa mono - i diestera jesu: PEG 4-150 mono, dilaurat (Kessco® PEG 200-6000 mono, Dilaurate, Stepan), PEG 4-150 mono, dioleat (Kessco® PEG 200-6000 mono, Dioleate, Stepan), i PEG 4-150 mono, distearat (Kessco® 200-6000 mono, Diostearate, Stepan). Formulacije kombinacije SSRI/steroida prema izumu mogu sadržavati jednu ili više od gornjih smjesa mono- i diestera PEG-masna kiselina.
Uz ovo, esteri polietilenglikol-glicerola i masne kiseline mogu biti ekscipijensi za ovdje opisane formulacije kombinacije SSRI/steroida. Primjeri komercijalno pristupačnih esteri polietilenglikol-glicerola i masne kiseline su sljedeći: PEG-20 gliceril-laurat (Tagatl® L, Goldschmidt), PEG-30 gliceril-laurat (Tagat® L2, Goldschmidt), PEG-15 gliceril-laurat (Glicerox L series, Croda), PEG- 40 gliceril-laurat (Glicerox L series, Croda), PEG-20 gliceril-stearat (Capmul® EMG, ABITEC) i Aldo® MS-20 KFG, Lonza), PEG-20 gliceril-oleat (Tagatg® O, Goldschmidt) i PEG-30 gliceril-oleat (Tagat® O2, Goldschmidt). Formulacije kombinacije SSRI/steroida prema izumu mogu sadržavati jednu ili više od gornjih estera polietilenglikola i masne kiseline.
Transesterifikacijski produkti alkohola i ulja se također mogu koristiti kao ekscipijensi za ovdje opisane formulacije kombinacija SSRI/steroida. Primjeri komercijalno pristupačnih transesterifikacijskih produkata alkohola i ulja su sljedeći: PEG-3 ricinusovo ulje (Nikkol CO-3, Nikko), PEG-5, 9, i 16 ricinusovo ulje (ACCONON CA series, ABITEC), PEG-20 ricinusovo ulje, (Emalex C-20, Nihon Emulsion), PEG-23 ricinusovo ulje (Emulgante EL23), PEG-30 ricinusovo ulje (Incrocas-30, Croda), PEG-35 ricinusovo ulje (Incrocas-35, Croda), PEG-38 ricinusovo ulje (Emulgante EL 65, Condea), PEG-40 ricinusovo ulje (Emalex C-40, Nihon Emulsion), PEG-50 ricinusovo ulje (Emalex C-50, Nihon Emulsion), PEG-56 ricinusovo ulje (Eumulgin® PRT 56, Pulera SA), PEG-60 ricinusovo ulje (Nikkol CO-60TX, Nikko), PEG-100 ricinusovo ulje, PEG-200 ricinusovo ulje (Eumulgin® PRT 200, PuIcra SA), PEG-5 hidrirano ricinusovo ulje (Nikkol HCO-5, Nikko), PEG-7 hidrirano ricinusovo ulje (Cremophor WO7, BASF), PEG-10 hidrirano ricinusovo ulje (Nikkol HCO-10, Nikko), PEG-20 hidrirano ricinusovo ulje (Nikkol HCO-20, Nikko), PEG-25 hidrirano ricinusovo ulje (Simulsol® 1292, Seppic), PEG-30 hidrogenirano ricinusovo ulje (Nikkol HCO-30, Nikko), PEG-40 hidrirano ricinusovo-ulje (Cremophor RH 40, BASF), PEG-45 hidrirano ricinusovo ulje (Gerex ELS 450, Auschem Spa), PEG-50 hidrirano ricinusovo ulje (Emalex HC-50, Nihon Emulsion), PEG-60 hidrirano ricinusovo ulje (Nikkol HCO-60, Nikko), PEG-80 hidrirano ricinusovo ulje (Nikkol HCO-80, Nikko), PEG-100 hidrirano ricinusovo ulje (Nikkol HCO-100, Nikko), PEG-6 kukuruzno ulje (Labrafil® M 2125 CS, Gattefosse), PEG-6 bademovo ulje (Labrafil® M 1966 CS, Gattefosse), PEG-6 ulje koštice marelice (Labrafil® M 1944 CS, Gaftefosse), PEG-6 malinovo ulje (Lpalminih koštica (Labrafil® M 2130 BS, Gattefosse), PEG-6 uljepalminih koštica (Labrafil® M 2130 CS, Gattefosse), PEG-6 triolein (Labrafil® M 2735 CS, Gattefosse), PEG-8 kukuruzno ulje (Labrafil® WL 2609 BS, Gattefosse), PEG-20 gliceridi kukuruza (Crovol M40, Croda), PEG-20 gliceridi badema (Crovol A40, Croda), PEG-25 trioleat (TAGAT® TO, Goldschmidt), PEG-40 ulje palminih koštica (Crovol PK 70), PEG-60 gliceridi kukuruza (Crovol M70, Croda), PEG-60 gliceridi badema (Crovol A70, Croda), PEG-4 kaprilni/kapratni trigliceridi (Labrafac® Hydro, Gattefosse), PEG-8 kaprilni/kapratni gliceridi (Labrasol, Gattefosse), PEG-6 kaprilni/kapratni gliceridi (SOFTIGEN®767, Huls), lauroil-makrogol-32 glicerid (GELUCIRE 44/14, Gattefosse), glicerid steraoil-makrogola (GELUCIRE 50/13, Gattefosse), mono, di, tri, tetra esteri biljnih ulja i sorbitola (SorbitoGliceride, Gattefosse), pentaeritritil-tetraizostearat (Crodamol PTIS, Croda), pentaeritritil-distearat (Albunol DS, Taiwan Surf), pentaeritritil-tetraoleat (Liponate PO-4, Lipo Chem.), pentaeritritil-tetrastearat (Liponate-PS4, Lipo-Chem pentaeritritil-tetrakaprilat tetrakaprat (Liponate PE-8 10, Lipo Chem.) i pentaeritritil-tetraoktanoat (Nikkol Pentarate 408, Nikko). Također su kao ulje u ovu kategoriju površinski aktivnih tvari uključeni u ulju topljivi vitamini kao što su vitamini A, D, E, K itd. Stoga su derivati tih vitamina, kao što je je tokoferil PEG-1000 sukcinat (TPGS, od Eastman) također pogodna površinski ativna sredstva. Formulacije kombinacije SSRI/steroida prema izumu mogu sadržavati jednu ili više od gornjih transesterifikacijskih produkata alkohola i ulja.
Poliglicerilizirane masne kiseline se također mogu koristiti kao ekscipijensi za ovdje opisane formulacije kombinacija SSRI/steroida. Primjeri komercijalno pristupačnih poligliceriliziranih masnih kiselina su sljedeći: poligliceril-2 stearat (Nikkol DGMS, Nikko), poligliceril-2 oleat (Nikkol DGMO, Nikko), poligliceril-2 izostearat (Nikkol DGMIS, Nikko), poligliceril-3 oleat (Caprol® 3GO, ABITEC), poligliceril-4 oleat (Nikkol Tetraglyn 1-O, Nikko), poligliceril-4 stearat (Nikkol Tetraglyn 1-S, Nikko), poligliceril-6 oleat (Drewpol 6-1-O, Stepan), poligliceril-10 laurat (Nikkol Decaglyn 1-L, Nikko), poligliceril-10 oleat (Nikkol Decaglyn 1-O, Nikko), poligliceril-10 stearat (Nikkol Decaglyn 1-S, Nikko), poligliceril-6 ricinoleat (Nikkol Hexaglyn PR-15, Nikko), poligliceril-10 linoleat (Nikkol Decaglyn 1-LN, Nikko), poligliceril-6 pentaoleat (Nikkol Hexaglyn 5-O, Nikko), poligliceril-3 dioleat (Cremopbor GO32, BASF), poligliceril-3 distearat (Cremophor GS32, BASF), poligliceril-4 pentaoleat (Nikkol Tetraglyn 5-O, Nikko), poligliceril-6 dioleat (Caprol® 6G20, ABITEC), poligliceril-2 dioleat (Nikkol DGDO, Nikko), poligliceril-10 trioleat (Nikkol Decaglyn 3-O, Nikko), poligliceril-10 pentaoleat (Nikkol Decaglyn 5-O, Nikko), poligliceril-10 septaoleat (Nikkol Decaglyn 7-O, Nikko), poligliceril-10 tetraolcate (CaproI® i OG4O, ABITEC), poligliceril-10 dekaizostearat (Nikkol Decaglyn 10-IS, Nikko), poligliceril-101 decaoleat (Drewpol 10-10-O, Stepan), poligliceril-10 mono, dioleat (Caprol® PGE 860, ABITEC) i poligliceril poliricinoleat (Polimuls, Henkel). Formulacije kombinacije SSRI/steroida prema izumu mogu sadržavati jednu ili više od gornjih poligliceriliziranih masnih kiselina.
Uz ovo, esteri propilenglikola i masne kiseline se mogu koristiti kao ekscipijensi za ovdje opisane formulacije kombinacija SSRI/steroida. Primjeri komercijalno pristupačnih estera propilenglikola i masne kiseline su sljedeći: propilenglikol-monokaprilat (Capryol 90, Gattefosse), propilenglikol-monolaurat (Lauroglikol 90, Gattefosse), propilenglikol-oleat (Lutrol OP2000, BASF), propilenglikol-miristat (Mirpyl), propilenglikol-monostearat (LIPO PGMS, Lipo Chem.), propilenglikol-hidroksistearat, propilenglikol-ricinoleat (PROPYMULS, Henkel), propilenglikol-izostearat, propilenglikol-monooleat (Myverol P-O6, Eastman), propilenglikol-dikaprilat-dikaprate (Captex® 200, ABITEC), propilenglikol-dioktanoat (Captex® 800, ABITEC), propilenglikol-kaprilat-kaprat (LABRAFAC PG, Gattefosse), propilenglikol-dilaurat, propilenglikol-distearat (Kessco® PGDS, Stepan), propilenglikol-dikaprilat (Nikkol Sefsol 228, Nikko) i propilenglikol-dikaprate (Nikkol PDD, Nikko). Formulacije kombinacije SSRI/steroida prema izumu mogu sadržavati jednu ili više od gornjih estera propilenglikola i masne kiseline.
Smjese estera propilenglikola i estera glicerola se također mogu koristiti kao ekscipijensi za ovdje opisane formulacije kombinacija NsIDI/NsIDIE. JEdna preferirana msjesa je sastavljena od estera oleinske kiseline propilenglikola i glicerola (Aralcel 186). Primjeri tih površinski aktivnih tvari jesu: oleinski (ATMOS 300, ARLACEL 186, ICI) i sterarinski (ATMOS 150). Formulacije kombinacije SSRI/steroida prema izumu mogu sadržavati jednu ili više od gornjih smjesa estera propilenglikola i estera glicerola.
Nadalje, mono- i digliceridi se mogu koristiti kao ekscipijnesi za ovdje opisane formulacije kombinacije NsIDI/NsIDIE. Primjeri komercijalno pristupačnih smjesa mono- i diglicerida jesu: monopalmitolein (C16:1) (Larodan), monoelaidin (C18:1) (Larodan), monokaproin (C6) (Larodan), monokaprilin (Larodan), monokaprin (Larodan), monolaurin (Larodan), gliceril-monomiristat (C14) (Nikkol MGM, Nikko), gliceril-monooleat (C18:1) (PECEOL, Gattefosse), gliceril-monooleat (Myverol, Eastman), glicerol-monooleat/linoleat (OLICINE, Gattefosse), glicerol-monolinoleat (Maisine, Gattefosse), gliceril-ricinoleat (Soffigen® 701, Huls), gliceri-monolaurat (ALDO® MLD, Lonza), glicerol-monopalmitat (Emalex GMS-P, Nihon), glicerol-monostearat (Capmul® GMS, ABITEC), gliceril mono- i di oleat (Capmul® GMO-K, ABITEC), gliceril-palmitil/stearil (CUTINA MD-A, ESTAGEL-G18), gliceril-acetat (Lamegin® EE, Grunau-GmbH) gliceril-laurat (Imwitor® 312, Huls), gliceril-citrat/laktat/oleat/linoleat (Imwitor® 375, Huls), gliceril-kaprilat (Imwitor® 308, Huls), gliceril-kaprilat/kaprat (Capmul® MCM, ABITEC), kaprilna kiselina te mono- i digliceridi (Imwitor® 988, Huls), kaprilini/caprični gliceridi (Imwitor® 742, Huls), Mono-i diacetilirani monogliceridi (Myvacet® 9-45, Eastman), gliceril-monostearat (Aldo® MS, Arlacel 129, ICI), mono i digliceridi liječne kiseline (LAMEGIN GLP, Henkel), dikaproin (C6) (Larodan), dikaprin (C10) (Larodan), dioktanoin (C8) (Larodan), dimiristin (C14) (Larodan), dipalmitin (C16) (Larodan), distearin (Larodan), gliceril-dilaurat (C12) (Capmul® GDL, ABITEC), gliceril-dioleat (CapmuI® GDO, ABITEC), glicerolni esteri masne kiseline (GELUCIRE 39/01, Gattefosse), dipalmitolein (C16:1) (Larodan), 1,2 i 1,3-diolein (C18:1) (Larodan), dielaidin (C18:1) (Larodan) i dilinolein (C 18:2) (Larodan). Formulacije kombinacije SSRI/steroida prema izumu mogu sadržavati jednu ili više od gornjih smjesa mono- i diglicerida.
Sterol i derivati sterola se također mogu koristiti kao ekscipijensi za ovdje opisane formulacije kombinacija SSRI/steroida. Primjeri komercijalno pristupačnih sterola i derivata sterola su sljedeći: kolesterol, sitosterol, lanosterol, PEG-24-kolesterol-ether (Solulan C-24, Amerchol), PEG-30 kolestanol (Phytosterol GENEROL series, Henkel), PEG-25 fitosterol (Nikkol BPSH-25, Nikko), PEG-5 sojasterol (Nikkol BPS-5, Nikko), PEG-10 sojasterol (Nikkol BPS-10, Nikko), PEG-20 sojasterol (Nikkol BPS-5, Nikko), PEG-10 sojasterol (Nikkol BPS-20, Nikko) te PEG-30 sojasterol (Nikkol BPS-30, Nikko). Formulacije kombinacije SSRI/steroida prema izumu mogu sadržavati jednu ili više od gornjih sterola i derivata sterola.
Esteri polietilenglikol-sorbitana i masne kiseline se također mogu koristiti kao ekscipijensi za ovdje opisane formulacije kombinacija NsIDI/NsIDIE. Primjeri komercijalno pristupačnih estera polietilenglikol-sorbitana i masne kiseline su sljedeći: PEG- 10 sorbitan-laurat (Liposorb L-10, Lipo Chem.), PEG-20 sorbitan-monolaurat (Tween® 20, Atlas/ICI), PEG-4 sorbitan-monolaurat (Tween®-21, AtIas/lCl), PEG-80 sorbitan-menolaurat (Hodag PSML-80, Calgene), PEG-6 sorbitan-monolaurat (Nikkol GL-1, Nikko), PEG-20 sorbitan-monopalmitat (Tween® 40, Atlas/ICI), PEG-20 sorbitan-monostearat (Tween® 60, Atlas/ICI), PEG-4 sorbitan-monostearat (Tween® 61, Atlas/ICI), PEG-8 sorbitan-monostearat (DACOL MSS, Condea), PEG-6 sorbitan-monostearat (Nikkol TS106, Nikko), PEG-20 sorbitan-tristearat (Tween® 65, Atlas/ICI), PEG-6 sorbitan tetrastearat (Nikkol GS-6, Nikko), PEG-60 sorbitan-tetrastearat (Nikkol GS-460, Nikko), PEG-5 sorbitan-monooleat (Tween® 81, Atlas/ICI), PEG-6 sorbitan-monooleat (Nikkol TO-106, Nikko), PEG-20 sorbitan monooleat (Tween® 80, Atlas/ICI), PEG-40 sorbitan oleat (Emalex ET 8040, Nihon Emulsion), PEG-20 sorbitan trioleat (Tweeng 85, Atlas/ICI), PEG-6 sorbitan-tetraoleat (Nikkol GO-4, Nikko), PEG-30 sorbitan-tetraoleat (Nikkol GO-430, Nikko), PEG- 40 sorbitan-tetraoleat (Nikkol GO-440, Nikko), PEG-20 sorbitan-monoisostearat (Tween® 120, Atlas/ICI), PEG sorbitol-heksaoleat (Atlas G-1086, ICI), polisorbat 80 (Tween® 80, Pharma), polisorbat 85 (Tween® 85, Pharma), polisorbate 20 (Tween® 20, Pharma), polisorbate 40 (Tween® 40, Pharma), polisorbat 60 (Tween® 60, Pharma), i PEG-6 sorbitol-heksastearat (Nikkol GS-6, Nikko). Formulacije kombinacije SSRI/steroida prema izumu mogu sadržavati jednu ili više od gornjih estera polietilenglikol-sorbitana i masne kiseline.
Uz ovo, alkilni esteri propilenglikola se mogu koristiti kao ekscipijensi za ovdje opisane formulacije kombinacija NsIDI/NsIDIE. Primjeri komercijalno pristupačnih alkilnih estera propilenglikola su sljedeći: PEG-2 oleil-eter, olet-2 (Brij 92/93, Atlas/ICI), PEG-3 oleil-eter, olet-3 (Volpo 3, Croda), PEG-5 oleil-eter, olet-5 (Volpo 5, Croda), PEG-10 oleil-etber, olet-10 (Volpo 10, Croda), PEG-20 oleil-eter, olet-20 (Volpo 20, Croda), PEG-4 lauril-eter, lauret-4 (Brij 30, Atlas/ICI), PEG-9 lauryl eter, PEG-23-lauril-eter, lauret-23 (Brij 35, Atlas/ICI), PEG-2 cetil-eter (Brij 52, ICI), PEG-10 cetil-eter (Brij 56, ICI), PEG-20 cetil-eter (Brij 58, ICI), PEG-2 stearil-eter (Brij 72, ICI), PEG-10 stearil-eter (Brij 76, ICI), PEG-20 stearil-eter (Brij 78, ICI) i PEG-100 stearil-eter (Brij 700, ICI). Formulacije kombinacije SSRI/steroida prema izumu mogu sadržavati jednu ili više od gornjih alkilnih estera propilenglikola.
Esteri šećera se također mogu koristiti kao ekscipijensi za ovdje opisane formulacije kombinacija NsIDI/NsIDIE. Primjeri komercijalno pristupačnih estera šećera su sljedeći: saharoza-distearat (SUCRO ESTER 7, Gattefosse), saharoza-distearat/monostearat (SUCRO ESTER 11, Gattefosse), saharoza-dipalmitat, saharoza-monostearat (Crodesta F-160, Croda), saharoza-monopalmitat (SUCRO ESTER 15, Gattefosse) i saharoza-monolaurat (Saccharose monolaurat 1695, Mitsubishi-Kasei). Formulacije kombinacije SSRI/steroida prema izumu mogu sadržavati jednu ili više od gornjih estera šećera.
Politilenglikolni alkil-fenoli su također korisni ekscipijensi za formulaciju ovdje opisane kombinacije NsIDI/NsIDIE. Primjeri komercijalno pristupačnih polietilenglikol alkil-fenola su sljedeći: PEG-15-100 serija nonilfenola (Triton X series, Rohm & Haas). Formulacije kombinacije SSRI/steroida prema izumu mogu sadržavati jednu ili više od gornjih polietilenglikol alkil-fenola.
Polioksietilen-polioksipropilenski blok polimeri su također korisni ekscipijensi za formulaciju ovdje opisane kombinacije NsIDI/NsIDIE. Ove površinski aktivne tvari su na raspolaganu pod raznim trgovačkim nazivima uključujući jednu ili više Synperonic PE serije (ICI), Pluornic® serije (BASF), Lutrol (BASF), Supronic, Monolan, Pluracare i Pludorac. Generilčki termin za kopolimere je "poloksamer" (CAS 9003-11-6). Ti polimeri imaju formulu (X):
HO(C2H4O)a(C3H6O)b(C2H4O)aH
(X)
gdje "a" i "b" označuju broj polioksietilenskih i polioksipropilenskih jedinica. Ti kopolimeri imaju molekulsku masu u raspomu od 1000 do 15000 dlatona, a omjer etilen-oksida/propilen/oksida je između 0.1 i 0.8 po masi. Formulacije kombinacije SSRI/steroida prema ovom izumu mogu sadržavati jednu ili više od gornjih polioksietilen-polioksipropilenskih blok polimera.
Polioksietileni kao što je PEG 300, PEG 400 i PEG 600 mogu se koristiti kao ekscipijensi za formulaciju ovdje opisanih kombinacija SSRI/steroida.
Esteri sorbitana i masnih kiselina se također mogu koristiti kao ekscipijensi za formulaciju ovdje opisane kombinacije NsIDI/NsIDIE. Primjeri komercijalno pristupačnih estera sorbitana i masnih kiselina su sljedeći: sorbitan-monolaurat (Span-20, Atlas/ICI), sorbitan-monopalmitat (Span-40, Atlas/ICI), sorbitan-monooleat (Span-80, Atlas/ICI), sorbitan-monostearat (Span-60, Atlas/ICI), sorbitan-trioleat (Span-85, Atlas/ICI), sorbitan-seskvioleat (Arlacel-C, ICI), sorbitan-tristearat (Span-65, Atlas/ICI), sorbitan-monoizostearat (Crill 6, Croda) i sorbitan-seskvistearat (Nikkol SS-15, Nikko). Formulacije kombinacije SSRI/steroida prema izumu mogu sadržavati jednu ili više od gornjih estera sorbitana i masnih kiselina.
Esteri nižih alkohola (C2 do C4) i masnih kiselina (C8 do C18) su pogodni za upotrebu u izumu kao površinski aktivne tvari. Primjeri takvih površinski aktivnih tvari su: etil-oleat (Crodamol EO, Croda), izopropil-miristat (Crodamol IPM, Croda), izopropil palmitat (Crodamol IPP, Croda), etil-linoleat (Nikkol VF-E, Nikko) i izopropil-linoleat (Nikkol VF-IP, Nikko). Formulacije kombinacije SSRI/steroida prema izumu mogu sadržavati jednu ili više od gornjih estera nižeg alkohola i masnih kiselina.
Pored toga, ionske površinski aktivne tvar se mogu koristiti kao ekscipijensi za ovdje opisanu formulaciju kombinacija NsIDI/NsIDIE. Primjeri korisnih ionskih površinski aktivnih tvari jesu: natrijev kaproat, natrijev kaprilat, natrijev kaprat, natrijev laurat, natrijev miristat, natrijev miristolat, natrijev palmitat, natrijev palmitoleat, natrijev oleat, natrijev ricinoleat, natrijev linoleat, natrijev linolenate, natrijev stearat, natrijev lauril-sulfate (dodecil), natrijev tetradecil-sulfate, natrijev lauril-sarkozinat, natrijev dioktil-sulfosukcinat, natrijev kolat, natrijev taurokolat, natrijev glikokolat, natrijev deoksikolat, natrijev taurodeoksikolat, natrijev glikodeoksikolat, natrijev ursodeoksikolat, natrijev kenodeoksikolat, natrijev taurokenodeoksikolat, natrijev glico-keno-deoksikolat, natrijev kolilsarkonizat, natrijev N-metiltaurokolat, fosfatidi žumanjka, hidrirani lecitin soje, dimiristoil-lecitin, lecitin, hidroksilirani lecitin, lizofosfatidilkolin, kardiolipin, sfingomielin, fosfatidilkolin, fosfatidil-ethanolamin, fosfatidna kiselina, fosfatidil-glicerol, fosfatidil-serin, dietanolamin, fosfolipidi, polioksietilen-10 oleil-eter-fosfat, produkti esterifikacije mastnih alkohola ili etoksilati masnih alkohola s fosfornom kiselinom ili anhidridom, eter-karboksilati (oksidacijom terminalne OH skupine etoksilata masnih alkohola), sukcinilirani monogliceridi, natrijev stearil-fumarat, stearoil-propilenglikol hidrogensukcinat, mono/diacetilirani esteri vinske kiseline mono- i diglicerida, esteri limunkse kiseline mono- i diglicerida, gliceril-lakto esteri masne kiseline, acil-laktilates, laktilni esteri masne kiseline, natrijev stearoil-2-laktilat, natrijev stearoil- laktilat, alginatne soli, propilenglikol-alginat, toksilirani alkil-sulfati, alkilbenzene-sulfoni, �-olefin-sulfonati, acil-izetionati, acil-taurati, alkil-gliceril-eter sulfonates, natrijev oktil-sulfosukcinat, natrijev undecilenamideo-MEA-sulfosukcinat, heksadecil-triamonijev bromid, decil-trimetil amonijev bromid, cetil-trimetil amonijev bromide, dodecil-amonijev klorid, alkil-benzildimetilamonijeve soli, diizobutil-fenoksietoksidimetilbenzil-amonijeve soli, alkilpiridinijeve soli, betaini (trialkilgllcin), lauril-betain (N-lauryl-N,N-dimetilglicin) i etoksilirani amini (polioksietilen-15 amin kokosa). Zbog jednostavnosti, tipični protuionu su prikazani gore. Bit će jasno stručnjaku da, međutim, da se može koristiti bilo koji bioprihvatljivi protuion. Primjerice, mada su masne kiseline prikazane kao natrijeve soli, ostali kationi kao protuioni se također mogu koristiti, kao što su primjerice kationi alkalijskim metala ili amonijev ion. Formulacije kombinacije NsIDI/NsIDIE prema izumu mogu sadržavati jednu ili više od gornjih ionskih površinski aktivnih tvari.
Ekscipijsni prisutni u formulacijama iz izuma su prisutni u takvim količinama da nosač tvori bistru ili mutnu vodenu disperziju NsIDI, NsIDIE ili kombinacije NsIDI/NsIDIE smještene unutar liposoma. Relativna količina površinski aktivnog ekscipijensa potrebnog za liposomski pripravak ili za čvrstu lipidnu nanočestičnu formulaciju se određuje uoptrebom poznate metodologije. Primjerice, liosomi mogu biti prirpavljeni različitim tehnikama kao što su oni opisani u Szoka et al, 1980. Multilamelarni vezikuli (MLV), a mogu se pripraviti jednostavnim tehnikama hidratacije lipidnog filma. U tom posutpku smjesa lipida koji tvore liposom tipa koji je detaljno priazan gore je otopljen u pogodnom orgnaskom otapalu i uparen je u posudi tako da nastane tanki film koji je zatim prekriven vodenim medijem. Lipidni film hidratizira i tvori MLV čija je tipična veličina oko 0.1 do 10 mikrona.
Ostale poznate tehnike tvorbe liposomskih formulacija se po potrebi nogu koristiti. Primjerice upotreba liposoma za olakšavanje prihvata u stanicu je opisana u U.S. Patentima br. 4,897,355 i 4,394,448.
Dodatna primjena
Spojevi iz izuma se mogu koristiti u imunomodulatorskom ili mehanističkom testu da se odredi da li je druga kombinacija ili jedno sredstvo učinkovito kao kombinacija za inhibiciju izlučivanja ili produkcije proinflamatornih citokina ili za moduliranje imunog odgovora upotrebom opće poznatih testova, primjerice koji su ovdje opisani. Primjerice, spoj kandidat se može kombinirati sa NsIDIE (ili njegovim metabolitom ili njegovim analogom) ili NsIDI i primijeniti na stimulirani PBMC. Nakon pogodnog vremena u stanicama se ispituje se izlučivanje citokina ili produkcija drugog pogodnog imunog odgovora. Relativni učinci jedne kombinacije prema drugoj i prema jednom sredstvu se uspoređuju i učinovit spoj ili kombinacija se identificiraju.
Kombinacije iz izuma su također korisni alati za rasvjetljavanje mehanističkih informacija. Takva ingformacija može voditi razvitku novih kombinacija ili jednog sredstva za inhibiciju upala uzrokovanih proinflamatornim citokinima. Mogu se koristiti poznate metode u struci za određivanje bioloških puteva ili mreže puteva na koje je djelovano dovođenjem u kontakt stanica stimuliranih da proizvode proinflamatorne citokine sa spojevima iz izuma. Takve metode mogu uključivati analizu staničnih sastojke koji su eksprimirani ili su manji nakon kontakta sa spojevima iz izuma u uspredbi s netretiranim spojevima koji su pozitivne i negativne kontrole i/ili novih jednostrukih sredstava i kombinacije ili analiziranje neke druge metaboličke aktivnosti u stanici kao što je enzimska aktivnost, prihvat hrane i proliferacija. Analizirane stanične komponente mogu uključivati transkripte gena i ekspresiju proteina. Pogodne metode mogu obuhvaćati standardne biokemijske tehnike, radioobilježavanje spojeva iz izuma (npr. 14C ili 3H obilježavanje) i opažanje vezivanja spojeva na proteine, npr. upotrebom 2d gelova, profiliranje ekspresije gena. Kad je takav spoj identificiran on se može koristiti u in vivo modelu da se dalje procijeni alat ili razviju nova protuupalna sredstva.
Sljedeći primjeri su prikazani da ilustriraju izum. Njihovo značenje nije da ograniče izum na bilo koji način.
Primjer 1: Test za smanjivanje aktivnost proinflamatornih citokina
Razrijeđenim matricama spojeva je testirano smanjivanju IFN�, IL-1�, IL-2, IL-4, IL-5 i TNF�, kao što je niže opisano.
INF�
100 �L suspenzije razrijeđenih humanih bijelih krvnih stanica koje su se nalazile u svakoj jažici polistirenske ploče s 384 jažica (NalgeNunc) je stimulirano da izlučuju IFN� djelovanjem s konačnom koncetracijom od 10 ng/mL forbol-12-miristat-13-acetata (Sigma, P-1585) i 750 ng/mL ionomicina (Sigma, I-0634). Različite koncentracije testiranog spoja su dodane u vrijeme stimulacije. Nakon 16-18 sati inkubacije pri 37°C u humidiziranom inkubatoru, ploče su centrifugirane i supernatant je prenešen na ploču mutnog polistirena s 384 jažica (NalgeNunc, Maxisorb) presvučene anti-IFN� antitijelom (Endogen, #M-700A-E). Nakon dva sata inkubacije, ploča je prana (Tecan Power Washer 384) s fiziološkom otopinom s fosofnatnim puferom (PBS) koja sadrži 0.1% Tween 20 (polietilensorbitan-monolaureat) i inkubirano je još jedan sat s drugim anti-IFN� antitijelom koji je obilježen biotinom (Endogen, M701B) i peroksidazom iz hrena (HRP) vezanom na steptavidin (PharMingen, #13047E). Nakon pranja ploće s 0.1% Tween20/PBS, HRP-luminescentni supstrat je dodan u svaku jažicu i mjeren je intenzitet svjetla upotrebom LJL Analyst luminometra za ploču.
IL-2
100 �L suspenzije razrijeđenih humanih bijelih krvnih stanica koje su se nalazile u svakoj jažici polistirenske ploče s 384 jažica (NalgeNunc) je stimulirano da izlučuju IL-2 djelovanjem s konačnom koncetracijom od 10 ng/mL forbol-12-miristat-13-acetata (Sigma, P-1585) i 750 ng/mL ionomicina (Sigma, I-0634). Različite koncentracije testiranog spoja su dodane u vrijeme stimulacije. Nakon 16-18 sati inkubacije pri 37°C u humidiziranom inkubatoru, ploče su centrifugirane i supernatant je prenešen na ploču mutnog polistirena s 384 jažica (NalgeNunc, Maxisorb) presvučene anti-IL-2 antitijelom (PharMingen #555051). Nakon dva sata inkubacije, ploča je prana (Tecan Power Washer 384) s PBS koji sadrži 0.1% Tween 20 i inkubirano je još jedan sat s drugim anti-IFN� antitijelom koji je obilježen biotinom (Endogen, M701B) i peroksidazom iz hrena (HRP) vezanom na steptavidin (PharMingen, #13047E). Nakon pranja ploće s 0.1% Tween20/PBS, HRP-luminescentni supstrat je dodan u svaku jažicu i mjeren je intenzitet svjetla upotrebom LJL Analyst luminometra za ploču.
TNF��stimulirano forbol 12-miristat-13 acetatom
Učinci testoranog spoja u kombinaciji na izlučivanje TNF� su testirani u humanim bijelim puferiranim krvnih stanica iz koje su stimulirane forbol-12-miristat-13-acetatom na sljedeći načni. Humane bijele puferirane stanice su razrijeđene u mediju 1:50 (RPMI; Gibco BRL, #11875-085), 10% seruma goveđeg fetusa (Gibco BRL; #25140-097), 2% penicilin/steptomicin (Gibco BRL; #15140-122) i 50 �L razrijeđenih bijelih stanica je smješteno u svaku jažicu polistirenske ploče za testiranje. Lijek je dodan u naznačenoj koncentraciji. Nakon inkubacije od 16-18 sati pri 37 °C sa 5% CO2 u vlažnom inkubatoru je ploča centrifugirana i supernatant je prenešen na bijelu neprozirnu polistirensku ploču s 384 jažica (NalgeNunc, Microsorb) presvučene anti-TNF� antitijelom (PharMingen #551220). Nakon dva sata inkubacije, ploča je prana (Tecan Power Washer 384) s PBS koja sadrži 0.1% Tween 20 i inkubirano je još jedan sat s drugim anti-TNF� antitijelom koji je obilježen biotinom (PharMingen #554511) i HRP vezan na steptavidin (PharMingen, #13047E). Ploča je ponovo prana sa 0.1% Tween 20/PBS. HRP-luminescentni supstrat je dodan u svaku jažicu i mjeren je intenzitet svjetla upotrebom LJL Analyst luminometra za ploču.
TNF��stimuirano lipopolisaharidom
100 �L suspenzije razrijeđenih humanih bijelih krvnih stanica koje su se nalazile u svakoj jažici polistirenske ploče s 384 jažica (NalgeNunc) je stimulirano da izlučuju TNF� djelovanjem s konačnom koncetracijom od 2 �g/mL lipopolisaharida (Sigma, L-4130). Različite koncentracije testiranog spoja su dodane u vrijeme stimulacije. Nakon 16-18 sati inkubacije pri 37°C u humidiziranom inkubatoru, ploče su centrifugirane i supernatant je prenešen na ploču mutnog polistirena s 384 jažica (NalgeNunc, Maxisorb) presvučene anti-TNF� antitijelom (PharMingen #551220). Nakon dva sata inkubacije, ploča je prana (Tecan Power Washer 384) s PBS koja sadrži 0.1% Tween 20 i inkubirano je još jedan sat s drugim anti-TNF� antitijelom koji je obilježen biotinom (PharMingen #554511) i HRP vezan na steptavidin (PharMingen, #13047E). Nakon pranja ploće s 0.1% Tween 20/PBS, HRP-luminescentni supstrat je dodan u svaku jažicu i mjeren je intenzitet svjetla upotrebom LJL Analyst luminometra za ploču.
Postotak inhibicije
Postotak inhibicije (%I) je za svaku jažicu izračunat upotrebom sljedeće formule:
%I=[(pros. netretiranih jažica - tretirane jažice)/( prosj. netretiranih jažica)] x 100
Prosječna vrijednost netratiranih jažica (pros. netretiranih jažica) je aritmetrička sredina od 40 jažica s iste ploče koje su tretirane samo vezikulom. Negativna vrijednost inhibicije potječe od lokalnih varijacija u tretiranim jažicama u usporedbi s netretiranim jažicama.
Primjer 2: Priprava spojeva
Početne otopine koje sadrže NsIDI i NsIDIE su načinjene u dimetilsulfoksidu (DMSO) konačne koncentracije između 0 i 40 �M. Ploče su pripravljene tako da sadrže razrijeđenje početne otopine gore opisanog spoja. Ploče su čuvane na -20 °C do upotrebe spoja.
Otopina NsIDI
Početna otopina koja sadrži ciklosporin A je načinjena pri koncentraciji od 1.2 mg/mL u DMSO. Početna otopina takrolimusa je načinjena pri koncentraciji od 0.04 mg/mL u DMSO.
Otopina NsIDIE
Početne otopine sertralina, fluoksetina ili fluvovaksima su načinjene pri koncentraciji od 10 mg/mL u DMSO. Početna otopina triklosana je načinjena pri koncentraciji od 10 mg/mL u DMSO. Početna otopina loratadina je načinjena pri koncentraciji od 10 mg/mL u DMSO. Početna otopina klorpromazina ili etopropazina je načinjena pri koncentraciji od 10 mg/mL u DMSO.
Ploče su pripravljene tako da sadrže razrijeđene početne otopine gore opisanih spojeva. Ploče su čuvane na -20°C do upotrebe spoja.
Konačni signal sredstva na ploči je generiran prenošenjem 1 �L početne otopine sa specifične ploče na ploču za razrjeđivanje koja sarži 100 �L medija (RPMI, Gibco BRL, #11875-085), 10% seruma goveđeg fetusa (Gibco BRL, #25140-097), 2% peniciln/streptomicin (Gibco BRL, #15140-122)) upotrebom Packard Mini-Trak za rukovanje tekućinom. Razrijeđene ploče su zatim miješane i alikvot od 5 �L je prenešen na ploču za testiranje kojoj je prethodno dodano 50��L/jažici RPMI medija koji sadrži odgovarajući stimulant da se aktiviran IFN�, IL-1�, IL-2 ili TNF� (vidi Primjer 1, supra).
Primjer 3: Kombinacija ciklosporina A i sertralina smanjuje izlučivanja IL-2 in vitro
Izlučivanje IL-2 je mjereno s ELISA kao što je opisno gore nakon stimulacije s forbol-12-miristat-13-acetatom i ionomicinom. Učinci različitih koncentracija ciklosporina A, sertralina i kombinacije sretralina i ciklosporina A su uspoređene s kontrolnim jažicama. Te jažice su stimulirane forbol-12-miristat-13-acetatom i ionomicinom, ali nisu primile ciklosorin A ili sertralin.
Rezultati ovog eksperimenta su prikazani u Tablici 6. Učinci samih sredstava i kombinacije su prikazani kao postotak inhibicije izlučivanja IL-2.
Podaci pokazuju da u ovom testu ciklosporin A maksimalno inhibira produkciju IL-2 za 83.5% pri koncentraciji od 1 �M. Dodatak 8 �M sertralina smanjuje koncentraciju ciklosporina A potrebnu za istu ihibiciju na 0.031 �M, što je smanjivanje koncentracije ciklosporina A 32 puta.
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Primjer 4: Kombinacija ciklosporina A i sertralina smanjuje izlučivanja IFN� in vitro
Izlučivanje IFN� je mjereno s ELISA kao što je opisno gore nakon stimulacije s forbol-12-miristat-13-acetatom i ionomicinom. Učinci različitih koncentracija ciklosporina A, sertralina i kombinacije sretralina i ciklosporina A su uspoređene s kontrolnim jažicama. Te jažice su stimulirane forbol-12-miristat-13-acetatom i ionomicinom, ali nisu primile ciklosorin A ili sertralin. Rezultati ovih istraživanja su prikazani niže u Tablici 7. Učinci samih sredstava i kombinacije su prikazani kao postotak inhibicije izlučivanja IFN�.
Podaci pokazuju da u ovom testu ciklosporin A maksimalno inhibira produkciju IFN� za 95.5% pri koncentraciji od 1 �M. Dodatak 8 �M sertralina pokazuje učinak smanjivanja s ciklosporinom A i skoro udvostručavanje inhibicije IFN� od 0.062 �M ciklosporina A, dostižući 83.4% inhibicije
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Primjer 5: Kombinacija ciklosporina A i sertralina smanjuje izlučivanja TNF� in vitro
Izlučivanje TNF� je mjereno s ELISA kao što je opisno gore nakon stimulacije s forbol-12-miristat-13-acetatom i ionomicinom. Učinci različitih koncentracija ciklosporina A, sertralina i kombinacije sretralina i ciklosporina A su uspoređene s kontrolnim jažicama. Te jažice su stimulirane forbol-12-miristat-13-acetatom i ionomicinom, ali nisu primile ciklosorin A ili sertralin. Rezultati ovih istraživanja su prikazani niže u Tablici 8. Učinci samih sredstava i kombinacije su prikazani kao postotak inhibicije izlučivanja TNF�.
Podaci pokazuju da u ovom testu ciklosporin A maksimalno inhibira produkciju TNF�� za 94.2% pri koncentraciji od 1 �M. Dodatak 8 �M sertralina pokazuje učinak smanjivanja s ciklosporinom A i udvostručavanje inhibicije TNF�.od 0.062 �M ciklosporina A, dostižući 85.4% inhibicije
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Primjer 6: Kombinacija ciklosporina A i fkuoksetina smanjuje izlučivanja IL-2 in vitro
Izlučivanje IL-2 je mjereno s ELISA kao što je opisno gore nakon stimulacije s forbol-12-miristat-13-acetatom i ionomicinom. Učinci različitih koncentracija ciklosporina A, fluoksetina i kombinacije ciklosporina A i fluoksetina su uspoređene s kontrolnim jažicama. Te jažice su stimulirane forbol-12-miristat-13-acetatom i ionomicinom, ali nisu primile ciklosorin A ili fluoksetin. Rezultati ovih istraživanja su prikazani niže u Tablici 28. Učinci samih sredstava i kombinacije su prikazani kao postotak inhibicije izlučivanja IL-2.
Podaci pokazuju da u ovom testu dodatak 21 �M fluoksetina u kombinaciji s 0.062 �M ciklosporina A inhibira islučivanje IL-2 za 98.8%, a povećanje inhibivije s 0.062��M ciklosporina je pokazano samo.
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Primjer 7: Kombinacija takrolimusa i fkuoksetina smanjuje izlučivanja IL-2 in vitro
Izlučivanje IL-2 je mjereno s ELISA kao što je opisno gore nakon stimulacije s forbol-12-miristat-13-acetatom i ionomicinom. Učinci različitih koncentracija takrolimusa, fluoksetina i kombinacije takrolimusa i fluoksetina su uspoređene s kontrolnim jažicama. Te jažice su stimulirane forbol-12-miristat-13-acetatom i ionomicinom, ali nisu primile takrolimus ili fluoksetin. Rezultati ovih istraživanja su prikazani niže u Tablici 10. Učinci samih sredstava i kombinacije su prikazani kao postotak inhibicije izlučivanja IL-2.
Podaci pokazuju da u ovom testu takrolimus maksimalno inhibira produkciju IL-2 za 87% pri koncentraciji od 0.05 �M. Dodatak 10 �M fluoksamina pokazuje učinak smanjivanja s ciklosporinom, dostižući inhibiciju od 85% IL-2 s takrolimusom.
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Primjer 8: Kombinacija ciklosporina A i paroksetina smanjuje izlučivanja IL-2 in vitro
Izlučivanje IL-2 je mjereno s ELISA kao što je opisno gore nakon stimulacije s forbol-12-miristat-13-acetatom i ionomicinom. Učinci različitih koncentracija ciklosporina A, paroksetina i kombinacije ciklosporina A i paroksetina su uspoređene s kontrolnim jažicama. Te jažice su stimulirane forbol-12-miristat-13-acetatom i ionomicinom, ali nisu primile ciklosorin A ili paroksetin. Rezultati ovih istraživanja su prikazani niže u Tablici 11. Učinci samih sredstava i kombinacije su prikazani kao postotak inhibicije izlučivanja IL-2.
Podaci pokazuju da u ovom testu ciklosporin A inhibira produkciju IL-2 za 97.7% pri koncentraciji od 1 �M. Dodatak 8.9 �M paroksetina pokazuje učinak smanjivanja s ciklosporinom A, dostižući inhibiciju od 90.7% IL-2 s s 0.062 �M ciklosporinom A.
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Primjer 9: Kombinacija ciklosporina A i paroksetina smanjuje izlučivanja IL-2 in vitro
Izlučivanje IL-2 je mjereno s ELISA kao što je opisno gore nakon stimulacije s forbol-12-miristat-13-acetatom i ionomicinom. Učinci različitih koncentracija ciklosporina A, paroksetina i kombinacije sretralina i paroksetina su uspoređene s kontrolnim jažicama. Te jažice su stimulirane forbol-12-miristat-13-acetatom i ionomicinom, ali nisu primile ciklosorin A ili paroksetin. Rezultati ovih istraživanja su prikazani niže u Tablici 12. Učinci samih sredstava i kombinacije su prikazani kao postotak inhibicije izlučivanja IL-2.
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Primjer 10: Kombinacija ciklosporina A i maprotilina smanjuje izlučivanja IL-2 in vitro
Izlučivanje IL-2 je mjereno s ELISA kao što je opisno gore nakon stimulacije s forbol-12-miristat-13-acetatom i ionomicinom. Učinci različitih koncentracija ciklosporina A i maprotilina te kombinacije maprotilina i ciklosporina A su uspoređene s kontrolnim jažicama. Te jažice su stimulirane forbol-12-miristat-13-acetatom i ionomicinom, ali nisu primile ciklosorin A ili maprolitin.
Rezultati ovih istraživanja su prikazani niže u Tablici 13. Učinci samih sredstava i kombinacije su pokazani kao postotak inhibicije izlučivanja IL-2. Ti rezultati su uprosječeni od eksperimenata izvedenih s bijelim krvnim stanicama uzetih od dvaju različitih davatelja.
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Primjer 11: Kombinacija ciklosporina A i maprotilina smanjuje izlučivanja TNF� in vitro
Izlučivanje TNF� je mjereno s ELISA kao što je opisno gore nakon stimulacije s lipopolisaharidom. Učinci različitih koncentracija ciklosporina A i maprotilina te kombinacije maprotilina i ciklosporina A su uspoređene s kontrolnim jažicama. Te jažice su stimulirane forbol-12-miristat-13-acetatom i ionomicinom, ali nisu primile ciklosorin A ili paroksetin. Rezultati ovih istraživanja su prikazani niže u Tablici 14. Učinci samih sredstava i kombinacije su pokazani kao postotak inhibicije izlučivanja TNF�. Ti rezultati su uprosječeni od eksperimenata izvedenih s bijelim krvnim stanicama uzetih od dvaju različitih davatelja.
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Primjer 12: Kombinacija ciklosporina A i triklosana smanjuje izlučivanja IL-2 in vitro
Izlučivanje IL-2 je mjereno s ELISA kao što je opisno gore nakon stimulacije s forbol-12-miristat-13-acetatom i ionomicinom. Učinci različitih koncentracija ciklosporina A i triklosana te kombinacije triklosana i ciklosporina A su uspoređene s kontrolnim jažicama. Te jažice su stimulirane forbol-12-miristat-13-acetatom i ionomicinom, ali nisu primile ciklosorin A ili triklosan.
Rezultati ovih istraživanja su prikazani niže u Tablici 15. Učinci samih sredstava i kombinacije su pokazani kao postotak inhibicije izlučivanja IL-2. Ti rezultati su uprosječeni od eksperimenata izvedenih s bijelim krvnim stanicama uzetih od dvaju različitih davatelja.
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Primjer 13: Kombinacija ciklosporina A i triklosana smanjuje izlučivanja TNF� in vitro
Izlučivanje TNF� je mjereno s ELISA kao što je opisno gore nakon stimulacije s lipopolisaharidom. Učinci različitih koncentracija ciklosporina A i triklosana te kombinacije triklosana i ciklosporina A su uspoređene s kontrolnim jažicama. Te jažice su stimulirane forbol-12-miristat-13-acetatom i ionomicinom, ali nisu primile ciklosorin A ili paroksetin. Rezultati ovih istraživanja su prikazani niže u Tablici 16. Učinci samih sredstava i kombinacije su pokazani kao postotak inhibicije izlučivanja TNF�. Ti rezultati su uprosječeni od eksperimenata izvedenih s bijelim krvnim stanicama uzetih od dvaju različitih davatelja.
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Primjer 14: Kombinacija ciklosporina A i loratadina smanjuje izlučivanja IL-2 in vitro
Izlučivanje IL-2 je mjereno s ELISA kao što je opisno gore nakon stimulacije s forbol-12-miristat-13-acetatom i ionomicinom. Učinci različitih koncentracija ciklosporina A i lorataidna te kombinacije loratadina i ciklosporina A su uspoređene s kontrolnim jažicama. Te jažice su stimulirane forbol-12-miristat-13-acetatom i ionomicinom, ali nisu primile ciklosorin A ili loratadin.
Rezultati ovih istraživanja su prikazani niže u Tablici 15. Učinci samih sredstava i kombinacije su pokazani kao postotak inhibicije izlučivanja IL-2. Ti rezultati su uprosječeni od eksperimenata izvedenih s bijelim krvnim stanicama uzetih od dvaju različitih davatelja.
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Primjer 15: Kombinacija ciklosporina A i loratadina smanjuje izlučivanja TNF� in vitro
Izlučivanje TNF� je mjereno s ELISA kao što je opisno gore nakon stimulacije s lipopolisaharidom. Učinci različitih koncentracija ciklosporina A i loratadina te kombinacije loratadina i ciklosporina A su uspoređene s kontrolnim jažicama. Te jažice su stimulirane forbol-12-miristat-13-acetatom i ionomicinom, ali nisu primile ciklosorin A ili loratadin. Rezultati ovih istraživanja su prikazani niže u Tablici 18. Učinci samih sredstava i kombinacije su pokazani kao postotak inhibicije izlučivanja TNF�. Ti rezultati su uprosječeni od eksperimenata izvedenih s bijelim krvnim stanicama uzetih od dvaju različitih davatelja. Niže prikazani rezultati su od jednog eksperiemnta.
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Primjer 16: Kombinacija ciklosporina A i desloratidina smanjuje izlučivanja TNF� in vitro
Izlučivanje TNF� je mjereno s ELISA kao što je opisno gore nakon stimulacije s lipopolisaharidom. Učinci različitih koncentracija ciklosporina i desloratidina su uspoređeni s kontronim jažicama stimuliranim ciklosporinom A ili loratidinom. Rezultati ovih istraživanja su prikazani niže u Tablici 19.
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Primjer 17: Kombinacija ciklosporina A i loratidina smanjuje izlučivanja TNF� in vitro
Izlučivanje TNF� je mjereno s ELISA kao što je opisno gore nakon stimulacije s lipopolisaharidom. Učinci različitih koncentracija ciklosporina i loratidina su uspoređeni s kontronim jažicama stimuliranim ciklosporinom A ili loratidinom. Rezultati ovih istraživanja su prikazani niže u Tablici 20.
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Primjer 18: Kombinacija ciklosporina A i klorpromazina smanjuje izlučivanja IL-2 in vitro
Izlučivanje IL-2 je mjereno s ELISA kao što je opisno gore nakon stimulacije s forbol-12-miristat-13-acetatom i ionomicinom. Učinci različitih koncentracija ciklosporina A i klorpromazina te kombinacije klorpromazina i ciklosporina A su uspoređene s kontrolnim jažicama. Te jažice su stimulirane forbol-12-miristat-13-acetatom i ionomicinom, ali nisu primile ciklosorin A ili klorpromazin.
Rezultati ovih istraživanja su prikazani niže u Tablici 21. Učinci samih sredstava i kombinacije su pokazani kao postotak inhibicije izlučivanja IL-2. Ti rezultati su uprosječeni od eksperimenata izvedenih s bijelim krvnim stanicama uzetih od dvaju različitih davatelja. Niže prikazani rezultati su od jednog eksperimenta.
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Primjer 19: Kombinacija ciklosporina A i klorpromazina smanjuje izlučivanja TNF� in vitro
Izlučivanje TNF� je mjereno s ELISA kao što je opisno gore nakon stimulacije s lipopolisaharidom. Učinci različitih koncentracija ciklosporina A i klorpromazina te kombinacije klorpromazina i ciklosporina A su uspoređene s kontrolnim jažicama. Te jažice su stimulirane forbol-12-miristat-13-acetatom i ionomicinom, ali nisu primile ciklosorin A ili klorpromazin. Rezultati ovih istraživanja su prikazani niže u Tablici 22. Učinci samih sredstava i kombinacije su pokazani kao postotak inhibicije izlučivanja TNF�. Ti rezultati su uprosječeni od eksperimenata izvedenih s bijelim krvnim stanicama uzetih od dvaju različitih davatelja.
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Primjer 20: Kombinacija ciklosporina A i etopropazina smanjuje izlučivanja IL-2 in vitro
Izlučivanje IL-2 je mjereno s ELISA kao što je opisno gore nakon stimulacije s forbol-12-miristat-13-acetatom i etopropazinom. Učinci različitih koncentracija ciklosporina A i etopropazina te kombinacije etopropazia i ciklosporina A su uspoređene s kontrolnim jažicama. Te jažice su stimulirane forbol-12-miristat-13-acetatom i ionomicinom, ali nisu primile ciklosorin A ili etopropazin.
Rezultati ovih istraživanja su prikazani niže u Tablici 23. Učinci samih sredstava i kombinacije su pokazani kao postotak inhibicije izlučivanja IL-2. Ti rezultati su uprosječeni od eksperimenata izvedenih s bijelim krvnim stanicama uzetih od dvaju različitih davatelja.
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Primjer 21: Kombinacija ciklosporina A i etopropazina smanjuje izlučivanja TNF� in vitro
Izlučivanje TNF� je mjereno s ELISA kao što je opisno gore nakon stimulacije s lipopolisaharidom. Učinci različitih koncentracija ciklosporina A i etopropazina te kombinacije etopropazina i ciklosporina A su uspoređene s kontrolnim jažicama. Te jažice su stimulirane forbol-12-miristat-13-acetatom i ionomicinom, ali nisu primile ciklosorin A ili etopropazin. Rezultati ovih istraživanja su prikazani niže u Tablici 24. Učinci samih sredstava i kombinacije su pokazani kao postotak inhibicije izlučivanja TNF�. Ti rezultati su uprosječeni od eksperimenata izvedenih s bijelim krvnim stanicama uzetih od dvaju različitih davatelja.
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Primjer 22: Kombinacija ciklosporina A i loperamida smanjuje izlučivanja IL-2 in vitro
Izlučivanje IL-2 je mjereno s ELISA kao što je opisno gore nakon stimulacije s forbol-12-miristat-13-acetatom i loperamidom. Učinci različitih koncentracija ciklosporina A i loperamida te kombinacije loperamida i ciklosporina A su uspoređene s kontrolnim jažicama. Te jažice su stimulirane forbol-12-miristat-13-acetatom i ionomicinom, ali nisu primile ciklosorin A ili loperamid.
Rezultati ovih istraživanja su prikazani niže u Tablici 25. Učinci samih sredstava i kombinacije su pokazani kao postotak inhibicije izlučivanja IL-2. Ti rezultati su uprosječeni od eksperimenata izvedenih s bijelim krvnim stanicama uzetih od dvaju različitih davatelja.
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Primjer 23: Kombinacija ciklosporina A i loperamida smanjuje izlučivanja TNF� in vitro
Izlučivanje TNF� je mjereno s ELISA kao što je opisno gore nakon stimulacije s lipopolisaharidom. Učinci različitih koncentracija ciklosporina A i loperamida te kombinacije loperamida i ciklosporina A su uspoređene s kontrolnim jažicama. Te jažice su stimulirane forbol-12-miristat-13-acetatom i ionomicinom, ali nisu primile ciklosorin A ili loperamid. Rezultati ovih istraživanja su prikazani niže u Tablici 26. Učinci samih sredstava i kombinacije su pokazani kao postotak inhibicije izlučivanja TNF�. Ti rezultati su uprosječeni od eksperimenata izvedenih s bijelim krvnim stanicama uzetih od dvaju različitih davatelja.
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Ostale cjeline
Različite modifikacije i varijacije opisane metode i sustava iz izuma će biti očite stručnjacima, a bez da skrenu s obujma izuma. Mada je izum opisan u vezi sa specifičnim željenim cjelinama, valja razumjeti da izum kako je prijavljen u zahtjevima ne treba nepotrebno biti ograničen na specifične cijeline. Doista, namjera je da različite modifikacije opisanih načina za izvođenje izuma, koje su očite stručnjacima u polju medicine, imunologije, farmakologije, endokrinologije ili srodnih polja, budu unutar obujma izuma.
Claims (75)
1. Pripravak, naznačeno time da sadrži nesteroidni o imunofilinu ovisan imunodepresiv (NsIDI) i pojačivač NsIDI (NsIDIE), a u količinama koje su zajedno dovoljne za in vivo smanjivanje izlučivanja ili produkcije proinflamatornog citokina ili za tretman imunoupalnog poremećaja.
2. Pripravak iz patetnog zahtjeva 1, naznačeno time da rečeni NsIDI jeste inhibitor kalcineurina.
3. Pripravak iz patetnog zahtjeva 2, naznačeno time da rečeni inhibitor kalcineurina jeste ciklosporin, takrolimus, askomicin, pimekrolimus ili ISAtx247.
4. Pripravak iz patetnog zahtjeva 1, naznačeno time da rečeni NsIDI jeste FK506-vezujući protein.
5. Pripravak iz patetnog zahtjeva 4, naznačeno time da rečeni FK506-vezujući protein jeste rapamicin ili everolimus.
6. Pripravak iz bilo kojeg od prethodnih patetnih zahtjeva, naznačeno time da rečeni NsIDIE jeste selektivni inhibitor prihvata serotonina (SSRI), triciklički antidepresiv (TCA), fenoksifenol, antihistamin, fenotiazin ili agonist �-opioidnog receptora.
7. Pripravak iz patetnog zahtjeva 6, naznačeno time da je rečeni SSRI odabran iz sljedeće skupine: fluoksetin, sertralin, paroksetin, fluvoksamin, citalopram i escitalopram.
8. Pripravak iz patetnog zahtjeva 6, naznačeno time da je rečeni TCA odabran iz sljedeće skupine: maprotilin, protriptilin, desipramin, amitriptilin, amoksapin, klomipramin, dotiepin, doksepin, desipramin, imipramin, lofepramin, mainserin, oksaprotilin, oktriptilin i trimipramin.
9. Pripravak iz patetnog zahtjeva 6, naznačeno time da rečeni fenoksifenol jeste triklosan.
10. Pripravak iz patetnog zahtjeva 6, naznačeno time da je rečeni antihistaminik odabran iz sljedeće skupine: etanolamini, etilendiamini, fenotiazini, alkilamini, piperazini, piperidini i atipični antihistamini.
11. Pripravak iz patetnog zahtjeva 6, naznačeno time da je rečeni antihistamin odabran iz sljedeće skupine: desloratidin, trietilperazin, bromdifenilhidramin, prometazin, ciproheptadin, loratadin, klemizol, azatadin, cetirizin, klorfeniramin, dimenhidramin, doksilamin, feksofenadin, meklizin, pirilamin, tripelenamin.
12. Pripravak iz patetnog zahtjeva 6, naznačeno time da rečeni fenotiazin jeste klorpromazin ili etopropazin.
13. Pripravak iz patetnog zahtjeva 6, naznačeno time da rečeni agonist �-opioidnog receptora jeste derivat piperidin-butiramida.
14. Pripravak iz patetnog zahtjeva 6, naznačeno time da rečeni agonist �-opioidnog receptora jeste loperamid, meperidin ili difenoksilat.
15. Pripravak bilo kojeg od prethodnih patentnih zahtjeva, naznačeno time da rečeni pripravak dalje sadrži nesteroidni protuuplani lijek (NSAID), inhibitor COX-2, biologik, imunomodulator koji ima malu molekule, antireumatski lijek koji modificira bolest (DMARD), ksantin, antikolinergični spoj, agonist beta-receptora, bronhodilatator, nesteroidni inhibitor klacineurina, analog vitamina D, psoralen, retinoid i 5-aminosalicilnu kiselinu.
16. Pripravak iz patetnog zahtjeva 15, naznačeno time da rečeni NSAID jeste ibuprofen, diklofenak ili naproksen.
17. Pripravak iz patetnog zahtjeva 15, naznačeno time da rečeni inhibitor COX-2 jeste rofekoksib, celekoksib, valdekoksib ili lumirakoksib.
18. Pripravak iz patetnog zahtjeva 15, naznačeno time da rečeni biologik jeste adellimumab, etanercept ili infliksimab.
19. Pripravak iz patetnog zahtjeva 15, naznačeno time da rečeni DMARD jeste metotreksat ili leflunomid.
20. Pripravak iz patetnog zahtjeva 15, naznačeno time da rečeni ksantin jeste teofilin.
21. Pripravak iz patetnog zahtjeva 15, naznačeno time da rečeni agonist beta-receptora jeste ibuterol-sulfat, bitolterol-mezilat, epinefedrin, formoterol-fumarat, izoproteronol, levalbuterol hidroklorid, metaproterenol-sulfat, pirbuterol-acetat, salmaterol ksinafoat ili terbutalin.
22. Pripravak iz patetnog zahtjeva 15, naznačeno time da rečeni analog vitamina D jeste kalcipotrien ili kalcipotriol.
23. Pripravak iz patetnog zahtjeva 15, naznačeno time da rečeni psoralen jeste metoksalen.
24. Pripravak iz patetnog zahtjeva 15, naznačeno time da rečeni retinoid jeste acitretin ili tazoreten.
25. Pripravak iz patetnog zahtjeva 15, naznačeno time da rečena 3-aminosalicilna kiselina jeste mezalamin, sulfasalazin, dinatrijev balsalazid ili natrijev oksalazin.
26. Pripravak iz patetnog zahtjeva 15, naznačeno time da rečeni imunomodulator koji ima malu molekulu jeste VX 702, SCIO 469, doramapimod, RO 30201195, SCIO 323, DPC 333, pranalaksan, mikofenolat ili merimepodib.
27. Pripravak iz patetnih zahtjeva 1-27, naznačeno time da rečeni pripravak formuliran za topičko davanje.
28. Pripravak iz patetnih zahtjeva 1-27, naznačeno time da rečeni pripravak formuliran za sistemsko davanje
29. Upotreba pripravka naznačeno time da sadrži NsIDI i NsIDIE, u količinama koje su zajedno dovoljne za in vivo smanjivanje izlučivanja ili produkcije proinflamatornog citokina ili za tretman imunoupalnog poremećaja.
30. Upotreba pripravka, naznačeno time da sadrži NsIDI i NsIDIE u količinama koje su zajedno dovoljne za in vivo smanjivanje izlučivanja ili produkcije proinflamatornog citokina ili za tretman imunoupalnog poremećaja.
31. Upotreba iz patetnog zahtjeva 30 ili 31, naznačeno time da rečeni autoimuni poremećaj jeste reumatoidni artritis, Crohnova bolest, ulcerativni kolitis, astma, kronična opstruktivna bolest pluća, reumatična polimialgija, arteritis velikih stanica, sistemski eritematozni lupus, atopični sermatitis, multipla skleroza, miastemia gravis, psorijaza, ankilozni spondijalitis ili artritis uzrokovan psorijazom.
32. Upotreba iz bilo kojeg od patentnih zahtjeva 30-32, naznačeno time da rečeni NsIDI jeste ciklosporin, takrolimus, ISAtx247, askomicin, pimekrolimus, rapamicin ili everolimus.
33. Upotreba iz bilo kojeg od patentnih zahtjeva 30-33, naznačeno time da rečeni NsIDIE naznačeno time da rečeni NsIDIE jeste SSRI, TCA, fenoksifenol, antihistamin, fenotiazin ili agonist �-opioidnog receptora.
34. Upotreba iz patetnog zahtjeva 34, naznačeno time da je rečeni SSRI odabran iz sljedeće skupine: fluoksetin, sertralin, paroksetin, fluvoksamin, citalopram i escitalopram.
35. Upotreba iz patetnog zahtjeva 34, naznačeno time da je rečeni TCA odabran iz sljedeće skupine: maprotilin, protriptilin, desipramin, amitriptilin, amoksapin, klomipramin, dotiepin, doksepin, desipramin, imipramin, lofepramin, mainserin, oksaprotilin, oktriptilin i trimipramin.
36. Upotreba iz patetnog zahtjeva 34, naznačeno time da rečeni fenoksifenol jeste triklosan.
37. Upotreba iz patetnog zahtjeva 34, naznačeno time da je rečeni antihistamin odabran iz sljedeće skupine: desloratidin, trietilperazin, bromdifenilhidramin, prometazin, ciproheptadin, loratadin, klemizol, azatadin, cetirizin, klorfeniramin, dimenhidramin, doksilamin, feksofenadin, meklizin, pirilamin, tripelenamin.
38. Upotreba iz patetnog zahtjeva 34, naznačeno time da rečeni fenotiazin jeste klorpromazin ili etopropazin.
39. Upotreba iz patetnog zahtjeva 34, naznačeno time da rečeni agonist �-opioidnog receptora jeste loperamid, meperidin ili difenoksilat.
40. Upotreba iz bilo kojeg od patentnih zahtjeva 30-40, naznačeno time da rečeni pripravak dalje sadrži davanje NSAID, inhibitor COX-2, biologik, DMARD , imunomodulator male molekule, ksantin, antikolinergični spoj, agonist beta-receptora, bronhodilatator, nesteroidni inhibitor klacineurina, analog vitamina D, psoralen, retinoid i 5-aminosalicilnu kiselinu.
41. Upotreba iz patetnog zahtjeva 41, naznačeno time da rečeni NSAID jeste ibuprofen, diklofenak ili naproksen.
42. Upotreba iz patetnog zahtjeva 41, naznačeno time da rečeni inhibitor COX-2 jeste rofekoksib, celekoksib, valdekoksib ili lumirakoksib.
43. Upotreba iz patetnog zahtjeva 41, naznačeno time da rečeni biologik jeste adellimumab, etanercept ili infliksimab.
44. Upotreba iz patetnog zahtjeva 41, naznačeno time da rečeni DMARD jeste metotreksat ili leflunomid.
45. Upotreba iz patetnog zahtjeva 41, naznačeno time da rečeni ksantin jeste teofilin.
46. Upotreba iz patetnog zahtjeva 41, naznačeno time da rečeni antikolinergični spoj jeste ipratropij ili tiotropij.
47. Upotreba iz patetnog zahtjeva 41, naznačeno time da rečeni agonist beta-receptora jeste ibuterol-sulfat, bitolterol-mezilat, epinefedrin, formoterol-fumarat, izoproteronol, levalbuterol hidroklorid, metaproterenol-sulfat, pirbuterol-acetat, salmaterol ksinafoat ili terbutalin.
48. Upotreba iz patetnog zahtjeva 41, naznačeno time da rečeni analog vitamina D jeste kalcipotrien ili kalcipotriol.
49. Upotreba iz patetnog zahtjeva 41, naznačeno time da rečeni psoralen jeste metoksalen.
50. Upotreba iz patetnog zahtjeva 41, naznačeno time da rečeni retinoid jeste acitretin ili tazoreten.
51. Upotreba iz patetnog zahtjeva 41, naznačeno time da rečena 3-aminosalicilna kiselina jeste mezalamin, sulfasalazin, dinatrijev balsalazid ili natrijev oksalazin.
52. Upotreba iz patetnog zahtjeva 41, naznačeno time da rečeni imunomodulator male molekule jeste VX 702, SCIO 469, doramapimod, RO 30201195, SCIO 323, DPC 333, pranalaksan, mikofenolat ili merimepodib.
53. Upotreba iz bilo kojeg od patetnih zahtjeva 30-53, naznačeno time da rečeni pripravak formuliran za topičko davanje.
54. Upotreba iz bilo kojeg od patetnih zahtjeva 30-53, naznačeno time da rečeni pripravak formuliran za sistemsko davanje.
55. Paket, naznačeno time da sadrži:
(i) pripravak koji sadrži NsIDI i NsIDIE, te
(ii) upute za davanje rečenog NsIDI i rečenog NsIDIE pacijentu kojem je dijagnosticiran razvitak imunoupalnog poremećaja ili je riizičan na njegov razvitak.
56. Paket, naznačeno time da sadrži:
(i) NsIDI,
(ii) NsIDIE, te
(iii) upute za davanje rečenog NsIDI i rečenog NsIDIE pacijentu kojem je dijagnosticiran razvitak imunoupalnog poremećaja ili je rizičan na njegov razvitak.
57. Paket, naznačeno time da sadrži:
(i) NsIDI, te
(ii) upute za davanje rečenog NsIDI i rečenog NsIDIE pacijentu kojem je dijagnosticiran razvitak imunoupalnog poremećaja ili je rizičan na njegov razvitak.
58. Paket, naznačeno time da sadrži:
(i) NsIDIE, te
(ii) upute za davanje rečenog NsIDI i rečenog NsIDIE pacijentu kojem je dijagnosticiran razvitak imunoupalnog poremećaja ili je rizičan na njegov razvitak.
59. Paket iz bilo kojeg od patentnih zahtjeva 56-59, naznačeno time da rečeni NsIDI jeste ciklosporin, takrolimus, ISAtx247, askomicin, pimekrolimus, rapamicin ili everolimus.
60. Paket iz bilo kojeg od patentnih zahtjeva 56-59, naznačeno time da rečeni NsIDIE jeste SSRI, TCA, fenoksifenol, antihistamin, fenotiazin ili agonist �-opioidnog receptora.
61. Paket iz bilo kojeg od patentnih zahtjeva 56-59, naznačeno time da je rečeni SSRI odabran iz sljedeće skupine: fluoksetin, sertralin, paroksetin, fluvoksamin, citalopram i escitalopram.
62. Paket iz bilo kojeg od patentnih zahtjeva 56-59, naznačeno time da je rečeni TCA odabran iz sljedeće skupine: maprotilin, protriptilin, desipramin, amitriptilin, amoksapin, klomipramin, dotiepin, doksepin, desipramin, imipramin, lofepramin, mainserin, oksaprotilin, oktriptilin i trimipramin.
63. Paket iz bilo kojeg od patentnih zahtjeva 56-59, naznačeno time da rečeni fenoksifenol jeste triklosan.
64. Paket iz bilo kojeg od patentnih zahtjeva 56-59, naznačeno time da je rečeni antihistamin odabran iz sljedeće skupine: desloratidin, trietilperazin, bromdifenilhidramin, prometazin, ciproheptadin, loratadin, klemizol, azatadin, cetirizin, klorfeniramin, dimenhidramin, doksilamin, feksofenadin, meklizin, pirilamin, tripelenamin.
65. Paket iz bilo kojeg od patentnih zahtjeva 56-59, naznačeno time da rečeni fenotiazin jeste klorpromazin ili etopropazin.
66. Paket iz bilo kojeg od patentnih zahtjeva 56-59, naznačeno time da rečeni agonist �-opioidnog receptora jeste loperamid, meperidin ili difenoksilat.
67. Metoda identifikacije kombinacija spojeva korisnih za srječavanje izlučivanja proinflamatornih citokina kod pacijenta koji ima potrebu za takvim tretmanom, naznačeno time da rečena metoda obuhvaća sljedeće korake:
(a) dovođenje u kontakt stanica in vitro s NaIDI i spojem kandidatom, te
(b) određivanje je li kombinacija rečenog NsIDI i rečenog spoja kadnidata smanjuje razinu citokina u krvnim stanicama koje su stimulirane da izlučuju citokine, a prema stanicama koje su došle u kontakt s rečenim NsIDI ali nisu došle u kontakt s rečenim spojem kandidatom ili su došle u kontakt s rečenim spojem kadidatom ali nisu došle u kontakt s rečenim NsIDI, pri čemu smanjivanje razina rečenog citokina pokazuje da je rečena kombinacija korisna za tretman pacijenta koji ima potrebu za takvim tretmanom.
68. Metoda iz patentnog zahtjeva 68, naznačeno time da rečeni NsIDIE jeste SSRI, TCA, fenoksifenol, antihistamin, fenotiazin ili agonist �-opioidnog receptora.
69. Metoda iz patentnog zahtjeva 68, naznačeno time da je rečeni SSRI odabran iz sljedeće skupine: fluoksetin, sertralin, paroksetin, fluvoksamin, citalopram i escitalopram.
70. Metoda iz patentnog zahtjeva 68, naznačeno time da je rečeni TCA odabran iz sljedeće skupine: maprotilin, protriptilin, desipramin, amitriptilin, amoksapin, klomipramin, dotiepin, doksepin, desipramin, imipramin, lofepramin, mainserin, oksaprotilin, oktriptilin i trimipramin.
71. Metoda iz patentnog zahtjeva 68, naznačeno time da rečeni fenoksifenol jeste triklosan.
72. Metoda iz patentnog zahtjeva 68, naznačeno time da je rečeni antihistamin odabran iz sljedeće skupine: desloratidin, trietilperazin, bromdifenilhidramin, prometazin, ciproheptadin, loratadin, klemizol, azatadin, cetirizin, klorfeniramin, dimenhidramin, doksilamin, feksofenadin, meklizin, pirilamin, tripelenamin.
73. Metoda iz patentnog zahtjeva 68, naznačeno time da rečeni fenotiazin jeste klorpromazin ili etopropazin.
74. Metoda iz patentnog zahtjeva 68, naznačeno time da rečeni agonist �-opioidnog receptora jeste loperamid, meperidin ili difenoksilat.
75. Metoda iz patentnog zahtjeva 68, naznačeno time da rečeni NsIDI jeste ciklosporin, takrolimus, pimekrolimus, askomicin, rapamicin, everolimus ili ISAtx247.
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Families Citing this family (36)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB9812110D0 (en) | 1998-06-06 | 1998-08-05 | Levelrecall Limited | Yttrium oxide based gas mantle |
US6861056B2 (en) * | 2001-06-05 | 2005-03-01 | Advanced Biotherapy, Inc. | Compositions and methods for treating hyperimmune response in the eye |
GB0307864D0 (en) * | 2003-04-04 | 2003-05-14 | Novartis Ag | Pharmaceutical composition |
US20050192261A1 (en) * | 2003-09-15 | 2005-09-01 | Jost-Price Edward R. | Methods and reagents for the treatment of immunoinflammatory disorders |
AU2004294343A1 (en) * | 2003-12-01 | 2005-06-16 | Vertex Pharmaceuticals Incorporated | Treating infectious diseases using ICE inhibitors |
GB0327840D0 (en) * | 2003-12-01 | 2003-12-31 | Novartis Ag | Organic compounds |
US20070020299A1 (en) | 2003-12-31 | 2007-01-25 | Pipkin James D | Inhalant formulation containing sulfoalkyl ether cyclodextrin and corticosteroid |
AR054249A1 (es) * | 2005-04-13 | 2007-06-13 | Astion Dev As | Tratamiento de enfermedades del tejido conectivo de la piel |
TW200711649A (en) * | 2005-06-17 | 2007-04-01 | Combinatorx Inc | Combination therapy for the treatment of immunoinflammatory disorders |
US20060293381A1 (en) * | 2005-06-23 | 2006-12-28 | Kaihei Kojima | Fungicidal effect by regulating signal transduction pathways |
ITMI20051826A1 (it) * | 2005-09-29 | 2007-03-30 | Novachem S A | Kit per la somministrazione parenterale di medicamenti |
WO2007041677A2 (en) * | 2005-10-03 | 2007-04-12 | Combinatorx, Incorporated | Soft tissue implants and drug combination compositions, and use thereof |
US20070128289A1 (en) * | 2005-12-07 | 2007-06-07 | Zhao Jonathon Z | Nano-and/or micro-particulate formulations for local injection-based treatment of vascular diseases |
ES2431291T3 (es) * | 2006-01-10 | 2013-11-25 | Colgate-Palmolive Company | Métodos para modular receptores de superficie celular para prevenir o reducir la inflamación |
AU2011205053B2 (en) * | 2006-02-02 | 2013-02-07 | Novartis Ag | Tuberous Sclerosis treatment |
HUE037890T2 (hu) | 2006-02-02 | 2018-09-28 | Novartis Ag | Sclerosis tuberosa kezelése |
US8207188B2 (en) * | 2006-04-07 | 2012-06-26 | Michalis Nicolaou | Treatment of diseases modulated by a H4 receptor agonist |
US20080234345A1 (en) * | 2006-09-08 | 2008-09-25 | Gene Logic Inc. | Method for reducing or alleviating inflammation in the digestive tract |
EP2559434A3 (en) * | 2007-02-12 | 2013-05-29 | Mike Nicolaou | Treatment of COPD using a histidine decarboxylase inhibitor sole or combined with an anti-H1 drug or with a leucotriene receptor antagonist |
CN101940571A (zh) * | 2007-04-13 | 2011-01-12 | 南方研究所 | 抗血管生成剂和使用方法 |
ES2493641T3 (es) * | 2007-06-28 | 2014-09-12 | Cydex Pharmaceuticals, Inc. | Administración nasal de soluciones acuosas de corticosteroides |
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 |
US9061010B2 (en) * | 2007-09-18 | 2015-06-23 | The Board Of Trustees Of The Leland Stanford Junior University | Methods of treating a Flaviviridae family viral infection and compositions for 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 |
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 |
EP2309858A4 (en) | 2008-07-31 | 2011-09-14 | Dekel Pharmaceuticals Ltd | COMPOSITIONS AND METHOD FOR THE TREATMENT OF INFLAMMATORY DISEASES |
JP2012520884A (ja) * | 2009-03-18 | 2012-09-10 | ザ ボード オブ トラスティーズ オブ ザ リランド スタンフォード ジュニア ユニバーシティー | フラビウイルス科ウイルス感染症を治療する方法および組成物 |
AR076177A1 (es) | 2009-04-01 | 2011-05-26 | Colgate Palmolive Co | MÉTODO PARA IDENTIFICAR UN COMPUESTO uTIL PARA TRATAR UNA ENFERMEDAD O CONDICIoN DE LA CAVIDAD ORAL |
RU2526912C2 (ru) | 2009-04-01 | 2014-08-27 | Колгейт-Палмолив Компани | Композиции карбонатных соединений, препятствующих образованию биопленки, для использования при уходе за полостью рта |
TWI481870B (zh) | 2009-04-01 | 2015-04-21 | Colgate Palmolive Co | 用於軟組織疾病診斷及作為用於口腔保健干預的標靶之蛋白質生物標記 |
MY170956A (en) | 2009-04-01 | 2019-09-20 | Colgate Palmolive Co | Menthol-derivative compounds and use thereof as oral and systemic active agents |
KR101388235B1 (ko) * | 2011-09-20 | 2014-04-24 | 가톨릭대학교 산학협력단 | 메클리진을 포함하는 관절염 예방 및 치료용 조성물 |
TWI830262B (zh) | 2015-06-30 | 2024-01-21 | 美商伊格集團國際股份有限公司 | 克立咪唑(clemizole)化合物於預防及治療肝癌之用途 |
US10765630B2 (en) | 2018-03-16 | 2020-09-08 | SEN-JAM Pharmaceutical LLC | Methods and compositions to treat enteropathic arthritis |
KR102422449B1 (ko) * | 2019-10-18 | 2022-07-20 | 연세대학교 산학협력단 | 결핵 및 비결핵항산균 감염 질환의 예방, 개선 또는 치료용 조성물 |
KR20230039979A (ko) * | 2021-09-15 | 2023-03-22 | 서울대학교산학협력단 | 아토피 피부염 예방 또는 치료용 겔 조성물 |
Family Cites Families (21)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB1101104A (en) * | 1965-06-02 | 1968-01-31 | Joseph Glasser | Compositions for the treatment of psoriasis |
US4444780A (en) * | 1982-08-30 | 1984-04-24 | Ortho Pharmaceutical Corporation | Method for treating atopic dermatitis |
WO1992008474A2 (en) * | 1990-11-20 | 1992-05-29 | The National Heart & Lung Institute | Treatment of lung diseases |
WO1996011009A1 (en) * | 1994-10-05 | 1996-04-18 | Cari Loder | Treatment of multiple sclerosis (ms) and other demyelinating conditions using lofepramine in combination with l-phenylalanine, tyrosine or tryptophan and possibly a vitamin b12 compound |
GB9619631D0 (en) * | 1996-09-20 | 1996-11-06 | British Biotech Pharm | Combination therapy |
FI104363B (fi) * | 1997-05-19 | 2000-01-14 | Timo Kalevi Korpela | Immunosuppressanttien ja interferonien farmakologisten keskinäisten vaikutusten parantaminen lisäaineilla |
US6372234B1 (en) * | 1997-05-27 | 2002-04-16 | Sembiosys Genetics Inc. | Products for topical applications comprising oil bodies |
BR9810403A (pt) * | 1997-07-01 | 2000-08-29 | Pfizer | Sais da sertralina e formas de dosagem de liberação sustentada da sertralina |
IN188720B (hr) * | 1997-11-06 | 2002-11-02 | Panacea Biotec Ltd | |
US6140337A (en) * | 1997-12-23 | 2000-10-31 | Schering Corporation | Methods for the treatment of mental disorders |
US6423721B1 (en) * | 1998-09-10 | 2002-07-23 | Schering Corporation | Methods and compositions for treating sinusitis, otitis media and other related disorders using antihistamines |
US6492400B1 (en) * | 1998-12-18 | 2002-12-10 | Bristol-Myers Squibb Pharma Company | N-ureidoalkyl-piperidines as modulators of chemokine receptor activity |
US20020006961A1 (en) * | 1999-05-14 | 2002-01-17 | Katz Stanley E. | Method and composition for treating mammalian nasal and sinus diseases caused by inflammatory response |
US20020061281A1 (en) * | 1999-07-06 | 2002-05-23 | Osbakken Robert S. | Aerosolized anti-infectives, anti-inflammatories, and decongestants for the treatment of sinusitis |
CA2408889A1 (en) * | 2000-05-08 | 2001-11-15 | David Haines | Immunosuppressive compositions |
ATE469907T1 (de) * | 2000-10-02 | 2010-06-15 | Univ Emory | Triptolid-analoga zur behandlung von autoimmunkranheiten und entzündungen |
US6599914B2 (en) * | 2001-04-24 | 2003-07-29 | Schering Corporation | Inhibition of cytokine generation |
US7034059B2 (en) * | 2001-07-02 | 2006-04-25 | Sepracor Inc. | Methods of using norfluoxetine |
BR0314713A (pt) * | 2002-09-24 | 2005-07-26 | Combinatorx Inc | Processos e reagentes para o tratamento de doenças e distúrbios associados com nìveis aumentados de citocinas pró-inflamatórias |
US20050192261A1 (en) * | 2003-09-15 | 2005-09-01 | Jost-Price Edward R. | Methods and reagents for the treatment of immunoinflammatory disorders |
AU2004275777A1 (en) * | 2003-09-24 | 2005-04-07 | Combinatorx, Incorporated | Therapeutic regimens for administering drug combinations |
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- 2004-02-12 MX MXPA05008649A patent/MXPA05008649A/es unknown
- 2004-02-12 US US10/777,518 patent/US20040224876A1/en not_active Abandoned
- 2004-02-12 AU AU2004212919A patent/AU2004212919A1/en not_active Abandoned
- 2004-02-12 WO PCT/US2004/004077 patent/WO2004073614A2/en active Application Filing
- 2004-02-12 PL PL378108A patent/PL378108A1/pl not_active Application Discontinuation
- 2004-02-12 CA CA002514061A patent/CA2514061A1/en not_active Abandoned
- 2004-02-12 KR KR1020057015072A patent/KR20050110634A/ko not_active Application Discontinuation
- 2004-02-12 JP JP2006503514A patent/JP2006517969A/ja not_active Withdrawn
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NO20053678L (no) | 2005-09-12 |
MXPA05008649A (es) | 2005-11-23 |
IS8023A (is) | 2005-09-13 |
EP1599212A2 (en) | 2005-11-30 |
AR043188A1 (es) | 2005-07-20 |
CA2514061A1 (en) | 2004-09-02 |
AU2004212919A1 (en) | 2004-09-02 |
WO2004073614A2 (en) | 2004-09-02 |
PL378108A1 (pl) | 2006-03-06 |
US20040224876A1 (en) | 2004-11-11 |
TW200902047A (en) | 2009-01-16 |
JP2006517969A (ja) | 2006-08-03 |
KR20050110634A (ko) | 2005-11-23 |
TW200509958A (en) | 2005-03-16 |
WO2004073614A3 (en) | 2004-11-11 |
EP1599212A4 (en) | 2006-02-08 |
NO20053678D0 (no) | 2005-07-29 |
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