TR201503136A2 - Dronedaron ve esansiyel yağ asitlerinin farmasötik kompozisyonları. - Google Patents
Dronedaron ve esansiyel yağ asitlerinin farmasötik kompozisyonları. Download PDFInfo
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- TR201503136A2 TR201503136A2 TR2015/03136A TR201503136A TR201503136A2 TR 201503136 A2 TR201503136 A2 TR 201503136A2 TR 2015/03136 A TR2015/03136 A TR 2015/03136A TR 201503136 A TR201503136 A TR 201503136A TR 201503136 A2 TR201503136 A2 TR 201503136A2
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- IZUPJOYPPLEPGM-UHFFFAOYSA-M sodium;hydron;phthalate Chemical compound [Na+].OC(=O)C1=CC=CC=C1C([O-])=O IZUPJOYPPLEPGM-UHFFFAOYSA-M 0.000 description 1
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- TUHBEKDERLKLEC-UHFFFAOYSA-N squalene Natural products CC(=CCCC(=CCCC(=CCCC=C(/C)CCC=C(/C)CC=C(C)C)C)C)C TUHBEKDERLKLEC-UHFFFAOYSA-N 0.000 description 1
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- BAQAVOSOZGMPRM-QBMZZYIRSA-N sucralose Chemical compound O[C@@H]1[C@@H](O)[C@@H](Cl)[C@@H](CO)O[C@@H]1O[C@@]1(CCl)[C@@H](O)[C@H](O)[C@@H](CCl)O1 BAQAVOSOZGMPRM-QBMZZYIRSA-N 0.000 description 1
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- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 1
- OENHQHLEOONYIE-JLTXGRSLSA-N β-Carotene Chemical compound CC=1CCCC(C)(C)C=1\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C OENHQHLEOONYIE-JLTXGRSLSA-N 0.000 description 1
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
- A61K31/202—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids having three or more double bonds, e.g. linolenic
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
- A61K31/343—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
Abstract
Mevcut buluş, dronedaron veya farmasotik olarak kabul edilebilir bir tuzu ile birlikte esansiyel yağ asitleri veya bunların esterleri veya karışımları ve en az bir farmasotik olarak kabul edilebilir bir ekspiyan içeren farmasotik bir kompozisyon ile ilgilidir.
Description
Tarifname
DRONEDARON VE ESANSIYEL YAG ASITLERININ FARMASÖTIK KOMPOZISYONLARI
Bulusun alani
Mevcut bulus, esansiyel yag asitleri veya esterleri veya bunlarin karisimlari ile birlikte
dronedaron veya onun farmasötik olarak kabul edilebilir bir tuzunu ve en az bir tane
farmasötik olarak kabul edilebilir yardimci madde içeren farmasötik bir kompozisyon ile
Bulusun geçmisi
Dronedaron, antiaritmik özelliklere sahip iyodinlenmemis (noniyodinize) bir benzofuran
türevidir. Dronedaron, amiodarondan bir iyot kisminin atilmasi ve bir metan sülfonil grubunun
eklenmesi bakimindan yapisal olarak farkli bir amiodaron analogudur. Bu modifikasyonlar,
tiroit üzerine olan etkileri ve diger advers etkileri azaltir ve dronedaronu daha kisa bir
yarilanma ömrü ile daha az lipofilik hale getirir. Dronedaronun kimyasal ismi N-[2-bütil-3-[4-
- formül l*de gösterilen yapiya sahiptir.
Formül l: Dronedaron Formül ll: Dronedaron hidroklorür
Dronedaron hidroklorür (formül ll ile gösterilen), paroksismal veya persistan atriyal fibrilasyon
(AF) öyküsü bulunan, sinüs ritminde seyreden hastalarda AF için hospitalize edilme riskini
azaltmak üzere endike gösterilen antiaritmik bir ilaçtir. FDA tarafindan 2009 yilinda
onaylanmistir ve halihazirda piyasada MULTAQT'V' ticari ismi altinda satilmaktadir. Tavsiye
edilen doz, sabah ve aksam ögünleri ile günde iki defa 400 mg'lik bir tabletin alinmasidir.
Yemekle verilmesini takiben, bagirsaklardan iyi derecede emilerek (en az %70 oraninda)
mutlak biyoyararlanimini düsük olup, yaklasik %4 civarindadir. Dronedaron, yüksek yagli bir
yiyecekle alindigi zaman bu mutlak biyoyararlanim yaklasik %15'e yükselmektedir.
basvurusu dronedaron HCl'nin tablet formülasyonlarini bildirmektedir. Ayrica dronedaron
kombinasyonýlaýrinar yönelik formülasyonlarini bildiren bir kaç patent basvurusu da
bulunmakta olup, bu basvurulardan hiç birisi esansiyel yag asitlerini içermemektedir.
Esansiyel yag asitleri (EFAlar) insanlarda saglik için gerekli olan, ancak vücutlarinda
sentezlenemeyen karboksilik asitlerdir. "Esansiyel yag asidi" terimi, biyolojik prosesler için
gerekli olan yag asitlerine karsilik gelmektedir. Esansiyel yag asitleri vücutta
sentezlenemediklerinden dolayi, diyetle alinmalari gerekmektedir. Omega-3 (n-3) ve omega-
6 (n-6) yag asitleri olmak üzere iki çesit esansiyel yag asidi ailesi bulunmaktadir. Bu yag
asitleri, hidrojen (H) atomlari ile doyurulmamis olduklarindan dolayi (ve atomlar arasinda
birden fazla çift bag içerdiklerinden dolayi) 'poliansatüre (çoklu doymamis) yag asitleri '
(PUFAlar) olarak ta isimlendirilmektedirler.
Avrupa Gida Güvenligi Kurumu, Amerikan Kalp Birligi ve diger bilimsel ve düzenleyici
organlar, esansiyel yag asitlerinin, özellikle de omega 3 yag asitlerinin kardiyovasküler saglik
için önemli oldugunu dogrulamaktadir. Omega 3 yag asidi tüketimi, plazma trigliserit
fazla molekülün bir dozaj formu halinde kombine edilmesi hastalarin yasam kalitesini ve
hasta kompliyansini artirmaktadir. Bu sebeple, teknikte dronedaron ve esansiyel yag
asitlerini içeren uygun bir farmasötik dozaj formülasyonuna ihtiyaç vardir.
dissolusyon özelliklerine sahip tek bir dozaj formu içerisinde kombine edilmesi kolay degildir.
Kombine edilen ilaçlar ayrica birbiri ile veya kullanilan diger yardimci maddeler ile reaksiyona
girebilir ve istenmeyen stabilite problemlerine yol açabilir. Bunlar haricinde farkli çözünürlük
özelliklerinden dolayi üretim prosesi süresince beklenmeyen çok sayida sorunla
karsilasilabilir. Ayni terapötik alanda veya hatta ayni endikasyonu tedavi etmek için kullanilan
ilaçlarin, asgari eklemeli terapötik etkilerin meydana gelmesi umuduyla her zaman için ayni
ve etkili dozaj formlari içerisinde kombine edilemedigi iyi bilinmektedir.
Bir düzenlemeye göre bahsedilen esansiyel yag asidi, omega 3 yag asitleri, omega 6 yag
asitleri veya bunlarin karisimlarini içeren gruptan seçilmektedir.
Bu düzenlemeye göre bahsedilen omega 3 yag asidi, onlarin metil esterleri veya etil
esterleridir.
Bir düzenlemeye göre bahsedilen omega 3 yag asidi, toplam formülasyonun agirlikça %0.1
miktarda bulunmaktadir.
Bu düzenlemeye göre bahsedilen omega 3 yag asidi, 30 ila 2500 mg arasi, tercihen 30 ila
miktardadir.
Bir düzenlemeye göre, mevcut bulusta kullanilan dronedaron veya farmasötik olarak kabul
edilebilir bir tuzu, dronedaron hidroklorürdür (HCI).
Bu düzenlemeye göre, dronedaron hidroklorür, toplam formülasyonun agirlikça %30 ila
miktarda bulunmaktadir.
arasi ve daha tercihen de 200 ila 800 mg arasi bir miktardadir.
Mevcut bulusta dronedaron HCl, antiaritmik bir ajan olarak, hastalarda özellikle kardiyak
aritmi olmak üzere kardiyovasküler hastaliklarin tedavisinde ve ciddi ve yasami tehdit eden
yan etkilerin önlenmesi amaciyla omega 3 yag asitleri ile kombinasyon halinde
kullanilmaktadir.
Bir düzenlemede her bir ilaç molekülü için güvenilir ve etkili dissolusyon profillerine sahip
stabil bir farmasötik kompozisyon saglayan, omega 3 yag asidi ile kombinasyon halinde
dronedaron HCI içeren farmasötik bir dozaj gelistirilmistir.
Bu düzenlemede, dronedaron HCl'nin omega 3 yag asidine olan 0.010 - 35.0 (a/a), tercihen
formülasyonun hastalar tarafindan kolaylikla yutulabilecek arzu edilen agirlikta bir dozaj
formuna kolaylikla islenmesine yardimci oldugu bulunmustur.
Bu düzenlemede, mevcut bulustaki bir dozaj formunda formüle edilen farmasötik
kompozisyon, hem dronedaron HCl hem de omega 3 yag asidi için istenen dissolusyon
profilini saglamaktadir.
dozaj formundadir.
Bu düzenlemede, bu farmasötik kompozisyonlar agizdan, parenteral, intranazal, dilalti,
transdermal, transmukozal, oftalmik, intravenöz, pulmoner, intramusküler veya rektal
uygulama yollari ile uygulanmaktadir ve tercihen de agizdan uygulanmaktadir.
tabletler, çok katmanli tabletler, agiz içi tabletler, dil alti tabletler, efervesan kompozisyonlar,
suppozituarlar, oküler sistemler, parenteral sistemler, kremler, jeller, merhemler, drajeler,
Dronedaron ve omega 3 yag asitleri farkli çözünürlük özelliklerine sahiptirler. Bu sebeple
formunun gelistirilmesi esnasinda çok sayida sorunla karsilasilabilecegi göz önünde
bulundurulmalidir.
Mevcut bulusta tum problemlerin ustesinden gelinmis ve dronedaron HCl ve omega 3 yag
asidini kombine eden farmasotik bir kompozisyon gelistirilmistir Bu duzenlemede bahsedilen
farmasotik kompozisyon tablet veya çift katmanli tablet veya kapsul veya yumusak jelatin
kapsul pellet veya in-lay tablet tablet içinde tablet formunda formule edilmektedir
madde surfaktanlar, tamponlayici ajanlar, stabilizörler, baglayicilar, seyrelticiler, disperze
edici ajanlar, kayganlastiricilar, glldanlar, dagiticilar, plastiklestiriciler, koruyucular,
tatlandiricilar, aroma katici ajanlar, renklendiricl ajanlar, yaglar veya bunlarin karisimlarini
içeren gruptan seçilmektedir.
Bir düzenlemede mevcut bulusta sürfaktan madde, dronedaron HCI ve omega 3 yag asidinin
çözünme farkinin üstesinden gelebilmek amaciyla kullanilmistir. Surfaktan madde
kullanildiginda dronedaron HCI ve omega 3 yag asidinin tablet veya çift katmanli tablet veya
kapsül veya yumusak jelatin kapsül pellet veya in-lay tablet veya tablet içinde tablet
formunda kombine edilebildigi görülmüstür.
Bu düzenlemeye göre surfaktan madde sodyum lauril sülfat, magnezyum laurii sülfat,
dioktilsülfosüksinat, polisorbatlar, setostearil alkol, poliokzietilen alkil esterleri,
gliserilmonolauratsaponinler, sorbitanlaurat ve bunlarin karisimlarini içeren gruptan
seçilmektedir, tercihen de sodyum lauril sülfattir.
Bu düzenlemede bahsedilen farmasötik kompozisyon, dronedaron HCI ve omega 3 yag
asitlerini içeren tablet veya çift katmanli veya kapsül veya yumusak jelatin kapsül veya pellet
veya in-lay tablet veya tablet formunda formüle edilmektedir.
Baska bir düzenlemede bahsedilen farmasötik kompozisyon omega 3 yag asidi ile
doldurulmus yumusak jelatin mikrokapsülleri içerebilir. Omega 3 yag asidi yumusak jelatin
mikrokapsüller, jelatin veya gliserol veya su veya bunlarin karisimlarini içerebilir.
Baska bir düzenlemede bahsedilen farmasötik kompozisyon, dronedaron HCl pelletleri
içerebilir.
Mevcut bulusun bu düzenlemesinde bahsedilen dronedaron HCl pelletler mannitol veya
prejelatinize nisasta veya karbomer veya kroskarmelloz sodyum veya polivinilpirolidon (PVP)
veya seker pellet veya polimetakrilatlar veya polivinil alkol veya seker pellet veya
mikrokristalin selüloz (MCC) pellet veya hidroksipropil selüloz veya silikon dioksit veya
magnezyum stearat renklendirici ajan veya bunlarin karisimlarini içermektedir.
Bu düzenlemeye göre mevcut bulusta kullanilan bahsedilen dronedaron HCl pelletler bir
kaplama içermektedir. Ayrica kaplama, dronedaron HCl'nin kimyasal ve fiziksel olarak
etkilesimini engelleyen inert bir kaplamadir. Kaplama, dronedaron HCI ve omega 3 yag
asidinin stabil kalmasini garanti eder. Baska bir Önemli gerekçe ise farkli salim özelliklerine
sahip ilaç moleküllerine ait formülasyonlarin, ayni dozaj formu içerisinde verilebilmesidir. Bu
sebeple kardiyovasküler hastaliklarin güvenilir ve etkili tedavisi için her bir ilaç molekülünün
arzu edilen salim profillerine ulasilmis olur.
Mevcut bulusun bu düzenlemesinde, dronedaron HCl pelletler nisasta, laktoz, seker alkol (D-
mannitol, eritritol, vb), düsük substitüe hidroksipropil selüloz, hidroksipropil selüloz,
hidroksipropil metilselüloz, polivinilpirolidon, polivinil alkol, metilselüloz, hidroksietil
metilselüloz, selüloz asetat fitalat, metakrilik asit kopolimerleri (Eudragit L tipleri (metakrilik
asit, etil akrilat kopolimerleri), Eudragit RL ve RS tipleri (etil akrilat, metil metakrilat ve
amonyum metakrilat kopolimeri), Eudragit-S tipleri (Metakrilik asit, metil metakrilat
kopolimeri)), hidroksipropil metilselüloz fitalat (HPMCP), hidroksipropil metilselüloz asetat
süksinat, polivinil asetat fitalat ve metakrilik asit ko-polimeri tip C'yi içeren gruptan seçilen bir
kaplama bulundurmaktadir.
Uygun tamponlayici ajanlar alkali metal sitrat, sitrik asit/sodyum sitrat, tartarik asit, fumarik
asit, sorbik asit, sitrik asit, süksinikasit, adipik asit, askorbik asit, sorbik asit, glutarik asit,
potasyum hidrojen tartarat, sodyum hidrojen tartarat, potasyum hidrojen fitalat, sodyum
hidrojen fitalat, potasyum dihidrojen fosfat, sodyum dihidrojen fosfat, disodyum hidrojen
fosfat, hidroklorik asit/sodyum hidroksit veya bunlarin karisimlarini içerebilir, ancak bunlarla
sinirli degildir ve tercihen sitrik asit, fumarik asit, askorbik asit, sodyum dihidrojen fosfat veya
Uygun stabilizörler sitrik asit, fumarik asit, tartarik asit, sodyum sitrat, sodyum benzoat,
sodyum dihidrojen fosfat, kalsiyum karbonat, magnezyum karbonat, arjinin, lizin, meglamin,
tokoferol, bütilhidroksianizol (BHA), bütilhidroksianitoluen (BHT), askorbik asit, gallik asit
esterleri veya bunlarin karisimlarini içerebilir, ancak bunlarla sinirli degildir ve tercihen de
sitrik asit, fumarik asit, arjinin veya bunlarin karisimlarini içerir.
Uygun baglayicilar ksantan zamki, prejelatinize nisasta, polivinilpirolidon, polimetakrilatlar ve
türevleri, polietilen glikol, polivinil alkol, nisasta, glikoz, glikoz surubu, dogal zamklar, sükroz,
sodyum aljinat, hidroksipropil metil selüloz, hidroksipropil selülozi karboksi metil selüloz, metil
selüloz gibi selüloz türevleri, jelatin, karragenan, guar zamki, karbomer, metakrilat
polimerlari, kollajenler, jelatin gibi proteinler, agar, aljinat, alginik asit, hiyaluronik asit, pektin,
polisakkaritler, karbomer, polokzamer, poliakrilamid, alüminyum hidroksit, Iaponit, bentonit,
polioksietilen-alkil eter, polidekstroz, polietilen oksit veya bunlarin karisimlarini içerebilir,
ancak bunlarla sinirli degildir.
Uygun seyrelticiler mannitol, laktoz, mikrokristalin selüloz, spreyle kurutulmus mannitol,
nisasta, dekstroz, sükroz, fruktoz, maltoz, sorbitol, ksilitol, inozitol, kaolin, inorganik tuzlar,
kalsiyum tuzlari, polisakkaritler, dikalsiyum fosfat, sodyum klorür, dekstratlar, laktilol,
Uygun disperze edici ajanlar kalsiyum silikat, magnezyum alüminyum silikat veya bunlarin
karisimlarini içerebilir, ancak bunlarla sinirli degildir.
Uygun glidanlar silikon dioksit, talk, alüminyum silikat, kolloidal silikon dioksit, nisasta veya
bunlarin karisimlarini içerebilir, ancak bunlarla sinirli degildir.
sodyum benzoat, sitrik asit, benzoik asit, bütillenmis hidroksitoluen, borik asit, sorbik asit,
benzil alkol, benzalkonyum klorür, parahidroksibenzoik asitler veya bütillenmis hidroksianizol
veya bunlarin karisimlarini içerebilir, ancak bunlarla sinirli degildir.
Uygun antioksidanlar bütil hidroksianizol, bütil hidroksitoluen, askorbik asit, beta-karoten,
alfa-tokoferol, propil gallat, gentisik asit, sodyum askorbat, sodyum bisülfat, sodyum
metabisülfat, monotiyogliserol, sistein, sodyum tiyoglikollat, aseton sodyum bisülfit, sodyum
bisülfat, sodyum ditiyonit, gentisik asit etanolamin, monosodyum glutamat, sodyum
formaldehid sülfoksilat, alfa tokoferol, veya bunlarin karisimlarini içerebilir, ancak bunlarla
sinirli degildir.
Uygun tatlandiricilar aspartam, potasyum asesülfam, sodyum sakkarinat, neohesperidin
dihidrokalkon, sükraloz, sakkarin, sükroz, glikoz, laktoz, früktoz gibi sekerler veya mannitol,
sorbitol, ksilitol, eritritol gibi seker alkollerini veya bunlarin karisimlarini içerebilir, ancak
bunlarla sinirlidegildir.
Uygun opaklastiricilar titanyum dioksit, silikon dioksit, talk, kalsiyum karbonat, behenik, setil
alkol veya bunlarin karisimlarini içerebilir, ancak bunlarla sinirli degildir.
Uygun aroma katici ajanlar mentol, nane, tarçin, çikolata, vanilya veya visne, portakal, çilek,
üzüm, siyah frenküzümü, ahududu, muz, kirmizi meyveler, yabani meyveler gibi meyve
esanslari veya bunlarin karisimlarini içerebilir, ancak bunlarla sinirli degildir.
Uygun renklendirici ajanlar ferrik oksit, titanyum dioksit, Food, Drug & Cosmetic (FD&C)
boyalari (FD&C mavisi, FD&C yesili, FD&C kirmizisi, FD&C sarisi, FD&C koyu kirmizisi
gibi), poncau, indigo Drug & Cosmetic (D&C) mavisi, indigotin FD&C mavisi, karmoizin
indigotin (indigo Karmin); demir oksitler (kirmizi, sari, siyah demir oksit gibi), kinolin sarisi,
ates kirmizisi, karmin, karmoizin, gün batimi sarisi boyalarini veya bunlarin karisimlarini
içerebilir, ancak bunlarla sinirli degildir.
Uygun yaglar soya fasülyesi yagi, balik yagi, kril yagi, fok yagi, hodan yagi, keten tohumu
yagi, aksam sefasi yagi, kenevir tohumu yagi, kabak çekirdegi tohumu yagi, üzüm çekirdegi
yagi, rüseym (çim) yagi, yalanci safran yagi, skualen yagi, skualen, susam tohumu yagi,
arasidonik asit, konjuge linoleik asit, biberiye yagi, limon yagi, nane yagi, su kaplumbagasi
yagi, nar çekirdegi yagi, yalanci igde meyvesinin yagi, ayçiçegi yagi, sia yagi, kurt üzümü
yagi, yer igdesi yagi, yasemin yagi, tatli badem yagi, zencefil yagi, maydonoz tohumu yagi,
portakal yagi, pisi baligi karacigeri yagi, bugday embriyosu yagi, aloe vera yagi, sarimsak
yagi, avokado yagi, hintotu yagi, cüce palmiye ekstrakti yagi, zeytinyagi, mineral yag, orta
Zincirli trigliserin, lavanta yagi, fosfolipidler, pirinç kepegi yagi, makademia cevizi yagi,
yerfistigi yagi, fitosterol, fitotanol, hint fasulyesi tohumu yagi, hindistan cevizi yagi, yer fistigi
yagi, hurma çekirdegi yagi, kanola yagi, avokado yagi, aksam sefasi yagi, pirinç kepegi yagi,
hodan yagi, ayçiçegi yagi, soya fasülyesi yagi, palmiye yagi, misir yagi ve yalanci safran
yagi veya bunlarin karisimlarini içerebilir, ancak bunlarla sinirli degildir.
Örnek 1: Tablet
bunlarin ester
karisimlari.
Kopovidon
(polivinilpirolid
kopolimerl)
Üretim prosesi: Dronedaron HCl,
kopovidon elekten geçirilir ve karistir
Tablet basimi islemi gerçeklestirilir.
Örnek 2: çift katmanli tablet
Bilesenler
karisimlari
Mikrokristalin sel
Dronedaron HCl 3.00- 95.00
Omega 3 yag asidi veya
Mikrokristalin selüloz (MCC) 5.00 - 90.00
Sodyum lauril sülfat 0.10 - 15.00
Magnezyum stearat
Dronedaron HCl katmani _
Omega 3 yag asidi veya
bunlarin esterleri veya
Sodyum lauril sülfat
O. 10 - 95.00
leri veya
on-vlnil asetat 0.10 - 25.00
0.10-3.00
omega 3 yag asidi, MCC, sodyum lauril sülfat ve
ilir. Daha sonra magnezyum ilave edilir ve karistirilir.
0.10 - 95.00
üloz (MCC)
Silikon dioksit 0.10 - 2.00
Magnezyum stearat 0.10 - 3.00
Üretim prosesi: Dronedaron HCl, mannitol ve krospovidon karistirilir. Omega 3 yag asidi,
MCC, sodyum lauril sülfat ve krospovidon ayri ayri karistirilir. Her bir karisim, önce silikon
dioksit ile sonrasinda ise magnezyum stearat ile karistirilir. Daha sonra çift katmanli tablet
Örnek 3: Pellet (kaglamal
Dronedaron HCl 3.00 - 95.00
0.10 - 95.00
Omega 3 yag asidi veya
bunlarin esterleri veya
karisimlari
Sodyum laurii sülfat
içerisine doldurulur.
Örnek 4: Yumusak ielatin kapsül
3.00 - 95.00
0. 10 - 95.00
bunlarin esterleri veya
karisimlari -
Antioksidanlar
Yumusak jelatin kapsül _
Opaklastirici
Aroma katici ajan
Üretim prosesi: Dronedaron HCl, sodyum laurii sülfat ve antioksidanlar homojen bir karisim
elde edinceye kadar karistirilir. Bu kati toz karisim, kapsülün iç fazi için omega 3 yag asidi ve
soya yagi ile karistirilir.
Gliserol, jelatin ve su homojen bir karisim elde edinceye kadar karistirilir. Bu karisima aljinat,
renklestirici ajan, opaklastirici ve aroma katici ajan eklenir.
Son karisim, vakumla bosluklara yapistirilir, silindirlerin bosluklarina jelatin astar alinir.
Doldurma, biçim verme ve kapaklama prosesleri gerçeklestirilir. Ve sonrasinda kapsüller
kesilir ve kurutulur.
Dronedaron HCI pelletler _
Dronedaron HCI 3.00 - 95.00
Omega-3 yag asidi
yumusak jelatin kapsül
Omega 3 yag asidi veya 0.10-9500
bunlarin esterleri veya î
karisimlari
Sodyum laurii sülfat 0.1 0 - 10.00
Antioksidanlar 0.10 - 10.00
Jelatin 30.00 - 90.00
Gliserol 5.00 - 50.00
Renklestirici ajan 0.10 - 10.99 .
Opaklastirici 0.10 - 10.00
Aroma katici ajan 0.10 -10.00
Üretim prosesi:
Gliserol, jelatin v
Örnek 6: Dronedaron HCI ka süli erisin
Dronedaron HCl ve mannitol karistirilir, karbomer solüsyonu püsk
edilir. Bu islak kütleden ekstrüzyon/sferonizasyon pe
Pelletler kapsülün iç fazi için omega 3 yag asidi,
kapaklama prosesleri gerçeklestirilir. Ve sonrasinda kapsüller kesil
Dronedaron HCI ve karbomer karistirilir ve eritme islemi süre
ekstrüderden (sikma aracindan) geçirilir. Karisim daha sonra sogutulur ve el
antioksidan ve sodyum laurii sülfat ile
e su homojen bir karisim elde edinceye kadar karistirilir. Bu karisima
stirici ajan, opaklastirici ve aroma katici ajan ilave edilir. Son karisim, vak
bosluklara yapistirilir, silindirlerin bosluklarina jelatin astar alinir. Doldurma,
Bilesenler
Miktar (%)
Yumusak jelatin
mikrokapsüller
Omega 3 yag asidi veya 0.10 - 95.00
bunlarin esterleri veya
karisimlari
Jelatin 30.00 - 90.00
Gliserol 5.00 - 50.00
Dronedaron HCI
3.00 - 95.00
ekten geçirilir.
lletleme teknigi ile pelletler üretilir.
biçim verme ve
ir ve kurutulur.
-3 umu ak 'elatin mikroka süller
TMannitoi 5.00 - 90.00
Krospovidon 5.00 - 40.00
Prejelatinize nisasta 0.10 - 30.00
Üretim prosesi: Gliserol, jelatin ve su homojen bir karisim elde edinceye kadar karistirilir.
Son karisim, vakumla bosluklara yapistirilir, silindirlerin bosluklarina jelatin astar alinir.
Mikrokapsülleri'n..-içerisinde omega 3 yag asidi doldurulur ve doldurma, biçim verme ve
kapaklama prosesleri gerçeklestirilir. Ve sonrasinda mikrokapsüller kesilir ve kurutulur.
Dronedaron HCI, mannitol, krospovidon ve prejelatinize nisasta homojen bir karisim elde
edinceye kadar karistirilir. Kapsüllerin içerisine toplam karisim ve yumusak jelatin
mikrokapsüller doldurulur.
Örnek 7: Kapsül içerisinde omega-3 yumusak ielatin mikrokapsül ve dronedaron HCI
Bilesenler Miktar (%)
Yumusak jelatin
mikrokapsüller
Omega 3 yag asidi veya 0.10-95.00
bunlarin esterler'i veya
karisimlari
Jelatin 30.00 - 90.00
Gliserol 5.00 - 50.00
Dronedaron HCI pelletler
Dronedaron HCl 3.00 - 95.00
Mannitol 5.00 - 90.00
Prejelatinize nisasta 5.00 - 90.00
Polokzamer 0.10 - 30.00
Üretim prosesi: Gliserol, jelatin ve su homojen bir karisim elde edinceye kadar karistirilir.
Son karisim, vakumla bosluklara yapistirilir, silindirlerin bosluklarina jelatin astar alinir.
Mikrokapsüllerin içerisinde omega 3 yag asidi doldurulur ve doldurma, biçim verme ve
kapaklama prosesleri gerçeklestirilir. Ve sonrasinda mikrokapsüller kesilir ve kurutulur.
Dronedaron HCl, polokzamer, prejelatinize nisasta ve mannitol karistirilir ve sonrasinda
kaplama solüsyonu ile islak bir kütle elde edilir. Bu islak kütleden ekstrüzyon/sferonizasyon
pelletleme teknigi ile pelletler olusturulur.
Dronedaron HCI pelletler, yumusakjelatin mikrokapsüller ile kapsüllerin içerisine doldurulur.
Claims (1)
- ISTEMLER Esansiyel yag asitleri veya onlarin esterleri veya bunlarin karisimlari ile birlikte dronedaron veya onun farmasötik olarak kabul edilebilir bir tuzunu içeren farmasötik bir kompozisyon olup, en az bir tane farmasötik olarak kabul edilebilir yardimci madde içermesidir. Istemwri'e göre farmasötik bir kompozisyon olup özelligi, esansiyel yag asidinin omega 3 yag asitleri, omega 6 yag asitleri veya bunlarin karisimlarini içeren gruptan seçilmesidir. istem 2'ye göre farmasötik bir kompozisyon olup özelligi, esansiyel yag asidinin omega 3 yag asidi olmasidir. Istem 2 veya 3'e göre farmasötik bir kompozisyon olup özelligi, omega 3 yag asitlerinin hekzadekatrienoik asit, alfa Iinolenik asit, gamma Iinolenik asit, dihomo gamma Iinolenik asit, stearidonik asit, eikosatrienoik asit, eikosapentaenoik asit, dokozahekzaenoik asit, heneikosapentaenoik asit, dokozapentenoik asit, dokosahekzaenoik asit, tetrakozapentenoik asit, tetrakozahekzaenoik asit, arasidonik asit, nervonik asit veya bunlarin karisimlarini içeren gruptan seçilmesidir. istem 1'e göre farmasötik bir kompozisyon olup özelligi, omega 3 yag asidinin arasi ve daha tercihen %0.1 ila %70.0'i arasi bir miktarda bulunmasidir. Istem 1'e göre farmasötik bir kompozisyon olup özelligi, omega 3 yag asidinin 30 ila daha tercihen de 30 ila 250 mg arasi bir miktarda bulunmasidir. Istem 1'e göre farmasötik bir kompozisyon olup özelligi, dronedaron veya farmasötik olarak kabul edilebilir bir tuzunun dronedaron hidroklorür olmasidir. istem 1 veya 7'ye göre farmasötik bir kompozisyon olup özelligi, dronedaron hidroklorürün toplam formülasyonun agirlikça %30 ila %95.0'i arasi, tercihen %100 ila %90.0'i arasi ve daha tercihen %150 ila %70.0'i arasi bir miktarda bulunmasidir. Istem 8'e göre farmasötik bir kompozisyon olup özelligi, dronedaron hidroklorürün mg arasi bir miktarda buiunmasidir. Istem 1'e göre farmasötik bir kompozisyon olup özelligi, bahsedilen farmasötik kompozisyonun kati, sivi veya yari kati dozaj formunda olmasidir. istem 10'a göre farmasötik bir kompozisyon olup özelligi, bahsedilen farmasötik kompozisyonun tabletler, çift katmanli tabletler, kapsüller, yumusak jelatin kapsüller, pelletler, mikrokapsüller, tablet içinde tabletler, in-Iay tabletler, mini tabletler, çok katmanli tabletler, agiz içi tabletler, dil alti tabletler, efervesan kompozisyonlar, efervesan tabletler, hemen salimli tabletler, modifiye salimli tabletler, agizda dagilan tablet, film-kapli tabletler, agizda dagilan tabletler, midede dagilan tabletler, haplar, tozlar, kapli boncuk sistemleri, granüller, mikrosferler, iyon degistirici reçine sistemleri, steril solüsyonlar veya süspansiyonlar, steril oküler solüsyonlar, aerosoller, spreyler, damlalar, ampuller, suppozituarlar, oküler sistemler, parenteral sistemler, kremler, jeller, merhemler, drajeler, kaseler; filmler, agizdan uygulanabilen filmler, agizdan uygulanabilen filmler, solüsyonlar, solidler; eliksirler, tentürler, süspansiyonlar, suruplar, kolloidal dispersiyonlar, dispersiyonlar ve emülsiyonlar formunda olmasidir. istem 10'a göre farmasötik bir kompozisyon olup özelligi, bahsedilen farmasötik kompozisyonun tablet veya çift katmanli tablet veya kapsül veya yumusak jelatin kapsül veya pellet veya in-lay tablet veya tablet formunda formüle edilmesidir. istem 1'e göre farmasötik bir kompozisyon olup özelligi, asgari bir tane farmasötik olarak kabul edilebilir yardimci maddenin surfaktanlar, tamponlayici ajanlar, stabilizörler, baglayicilar, seyrelticiler, disperze edici ajanlar, kayganlastiricilar, glidanlar, dagiticilar, plastiklestiriciler, koruyucular, tatlandiricilar, aroma katici ajanlar, renklendirici ajanlar veya bunlarin karisimlarini içeren gruptan seçilmektedir. Istem 13'e göre farmasötik bir kompozisyon olup özelligi, surfaktan maddenin sodyum lauril sülfat, magnezyum lauril sülfat, dioktilsülfosüksinat, polisorbatlar, setostearil alkol, poliokzietilen alkil esterleri, gliserilmonolauratsaponinler, sorbitanlaurat ve bunlarin karisimlarini içeren gruptan seçilmesidir, tercihen de sodyum lauril sülfattir. istem 12'ye göre farmasötik bir kompozisyon olup özelligi, bahsedilen farmasötik kompozisyonun omega 3 yag asidi ile doldurulmus yumusak jelatin mikrokapsülleri içermesidir. Istem 15'e göre farmasötik bir kompozisyon olup özelligi, omega 3 yag asidi yumusak jelatin mikrokapsüllerin jelatin veya gliserol veya su veya bunlarin karisimlarini içermesidir. Istem 12'ye göre farmasötik bir kompozisyon olup özelligi, bahsedilen farmasötik kompozisyonun dronedaron HCI pelletler içermesidir. Istem 17'ye göre farmasötik bir kompozisyon olup özelligi, dronedaron HCI pelletlerin mannitol veya prejelatinize nisasta veya karbomer veya kroskarmelloz sodyum veya polivinilpirolidon (PVP) veya polimetakrilatlar veya polivinil alkol veya seker pellet veya mikrokristalin selüloz (MCC) pellet veya hidroksipropil selüloz veya silikon dioksit veya magnezyum stearat renklendirici ajan veya bunlarin karisimlarini içermesidir. Önceki istemlerden herhangi birine göre farmasötik bir kompozisyon olup özelligii özellikle kardiyak aritmi olmak üzere kardiyak hastaliklarin tedavisinde kullanima yönelik olmasidir.
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
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TR2015/03136A TR201503136A2 (tr) | 2015-03-16 | 2015-03-16 | Dronedaron ve esansiyel yağ asitlerinin farmasötik kompozisyonları. |
PCT/EP2016/055501 WO2016146608A1 (en) | 2015-03-16 | 2016-03-15 | Pharmaceutical compositions of dronedarone and essential fatty acids |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
TR2015/03136A TR201503136A2 (tr) | 2015-03-16 | 2015-03-16 | Dronedaron ve esansiyel yağ asitlerinin farmasötik kompozisyonları. |
Publications (1)
Publication Number | Publication Date |
---|---|
TR201503136A2 true TR201503136A2 (tr) | 2016-09-21 |
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FR2665444B1 (fr) | 1990-08-06 | 1992-11-27 | Sanofi Sa | Derives d'amino-benzofuranne, benzothiophene ou indole, leur procede de preparation ainsi que les compositions les contenant. |
FR2764800B1 (fr) | 1997-06-23 | 1999-09-10 | Sanofi Sa | Composition pharmaceutique solide contenant des derives de benzofuranne |
US20070254897A1 (en) * | 2006-04-28 | 2007-11-01 | Resolvyx Pharmaceuticals, Inc. | Compositions and methods for the treatment of cardiovascular disease |
BRPI0719183A2 (pt) * | 2006-10-13 | 2014-06-03 | Reliant Pharmaceuticals Inc | Tratamento com antiarrítmicos e ácidos graxos de ômega-3 e um produto de combinação destes |
CN102365087A (zh) * | 2009-02-02 | 2012-02-29 | 马太克生物科学公司 | 改善认知功能和降低心率的方法 |
-
2015
- 2015-03-16 TR TR2015/03136A patent/TR201503136A2/tr unknown
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