TR201606697A2 - Dabi̇gatranin yeni̇ oral farmasöti̇k formülasyonlari - Google Patents
Dabi̇gatranin yeni̇ oral farmasöti̇k formülasyonlari Download PDFInfo
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- TR201606697A2 TR201606697A2 TR2016/06697A TR201606697A TR201606697A2 TR 201606697 A2 TR201606697 A2 TR 201606697A2 TR 2016/06697 A TR2016/06697 A TR 2016/06697A TR 201606697 A TR201606697 A TR 201606697A TR 201606697 A2 TR201606697 A2 TR 201606697A2
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- A61K9/00—Medicinal preparations characterised by special physical form
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- 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
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
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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
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4866—Organic macromolecular compounds
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Preparation (AREA)
Abstract
Mevcut buluş dabigatran eteksilat serbest bazı ve siklodekstrinin en az bir farmasötük olarak uygun yardımcı madde içeren yeni oral farmasötik formülasyonları ile ilgilidir.
Description
Tarifname
DABIGATRANIN YENI ORAL FARMASOTIK FORMULASYONLARI
Bulus Alani
uygun yardimci maddesini içeren yeni oral farmasötik formülasyonlari ile ilgilidir.”
Teknigin bilinen durumu
WO 98/37075'ten zaten bilinen dabigatran eteksilat (Formül I), rekabetçi reversibl
(tersinebilir) non-peptid bir trombin antagonistidir. Bu vasküler olmayan atriyal fibrilasyonlu
hastalarda inme ve sistemik emboli riskini azaltmak için endike olan bir direkt trombin
inhibitörüdür. Trombin, faktör Xlll aktivasyonu ile fibrin monomerlerinin çapraz-baglanmasiyla
fibrin monomerlerini fibrine dönüstüren ve trombin üretimini faktör V ve VIII aktivasyonu
yoluyla daha da artiran çok fonksiyonlu bir enzimdir. Ayrica, trombositleri aktive eder, protein
C'nin aktivasyonu yoluyla pihtilasma önleyici aktivite olusturur ve çok sayida hücresel islemi
baslatir.
Formül I: Dabigatran eteksilat serbest bazi
Ayrica, PRADAXA® ticari ismi altinda (75, 110, 150 mg dozunda) piyasada mevcut olan
Dabigatran eteksilat'in, bir metan sülfonik asit ilave tuzu, dabigatran eteksilat mesilat (DEM)
pelet bilesimi EP1870100”da anlatilmistir. Bu bilesim, organik asitten ve çekirdegi kaplayan
bir aktif tabakadan olusan bir çekirdek malzeme ile formüle edilir.
Dabigatran eteksilatin metansülfonat tuzu haricindeki diger asit ilave tuzlari daha önceden
dabigatran eteksilatin okzalat tuzu hakkindadir ve dabigatran eteksilatin hidroklorür tuzu ise
EP1877395 nolu patent basvurusunda tanimlanmistir.
Onceki teknikte açiklanan bu dabigatran eteksilat tuzlari, farmasötik formülasyonlarin
gelistirilmesi için önemli olan suda çözünürlük ve stabilite gibi fiziko-kimyasal özellikleri ile
karsilastirilmistir. Ayrica, önceki teknikte, dabigatran eteksilatin zayif bir bazik bilesik olup, bu
nedenle, asidik ortamda yüksek çözünürlüge sahip oldugu bilinmektedir.
Aktif maddelerin emilmesi, genis bir yüzey alani ve bazik bir ortama sahip olan ince
bagirsagin yavas peristaltik hareketleri nedeniyle genellikle ince bagirsakta gerçeklesir.
Bununla birlikte, asidik bir ortami olan mideden emilim, hizli peristaltik hareketler ve midenin
yüksek yüzey alani nedeniyle, yok denecek kadar azdir. Bu nedenle aktif maddelerin bazik
bir ortam olan ince bagirsakta çözünmesi önemlidir. Dabigatran, zayif bir bazik bilesik olup,
bazik ortamlarda çözündürülmeli ve dabigatranin çözünümü pH'dan bagimsiz olmalidir
Bu durumda, teknikte hala, kolay bir islem ile, pH'dan bagimsiz salinan dabigatran eteksilat
serbest bazini içeren stabil ve biyoyararlanimi uygun olan farmasötik formülasyonlar
gelistirilmesine ihtiyaç vardir. Bu ihtiyaç ile, formülasyon, yukarida açiklanann dabigatran
eteksilat serbest bazinin çözünürlük ve stabilite sorunlarini güvenli bir sekilde asmak için
siklodekstrin kullanimi ile birlestirilmektedir.
Bulusun detayli tanimlamasi
Mevcut bulusta amaç, güvenli ve etkili çözünüm profiline sahip ve kolay bir islem ile
dabigatran eteksilat serbest bazi ve siklodekstrin içeren yeni stabil formülasyonlar
saglamaktir.
Bu amaca göre, mevcut bulus, dabigatran eteksilat serbest bazi ve siklodekstrin içeren
farmasötik formülasyonlar ile ilgili olup, burada dabigatran eteksilat serbest bazinin miktari
toplam formülasyonun agirliga göre % 5.0 ila 85.0 ve siklodekstrin miktari ise toplam
formülasyonun agirliga göre %10 ila 50.0 arasidir.
Bir örnege göre, mevcut bulusta kullanilan oranlar, tedavi için gereken etkin dozu saglamakta
ve dabigatran eteksilat serbest bazinin stabil olmasini saglamaktadir.
Mevcut bulusta, siklodekstrin kullanilmasi dabigatran eteksilat serbest bazi için güvenli ve
etkin çözünme profilli ile uygun stabilite elde edilmesi açisindan çok önemlidir. Bu durumda,
siklodekstrin dabigatran eteksilat serbest bazinin çözünürlügünü güvenli bir sekilde artirir.
Farmasötik olarak aktif maddelerin çogunun yeterli çözünürlügü olmamasi ve çözünürlügü
olmayan geleneksel ilaç formülasyonlarinin (yani dabigatran eteksilat serbest bazinin)
nedeniyle, çözünürlüge yardimci olacak, organik çözücülerin, yüzey aktif maddelerin ve asiri
pH sartlarinin bir kombinasyonunu içermesi, genellikle tahris veya diger yan etkilere neden
olurlar. Siklodekstrin tahrislere sebep olmaz ve aktif bilesimlerin stabilizasyonu, ilaç
moleküllerinin volatilitesinde azalma ve kötü kokularin ya da aci tadin maskelenmesi gibi
farkli avantajlar sunar. Dahasi, dabigatran eteksilat serbest bazinin aci veya kötü tadini
maskelemek için bir tadlandirici ya da lezzet verici madde kullanimini gerektirmez.
Sonuç olarak, mevcut bulusta uygun miktarlarda siklodekstrin kullanilmasi, gelistirilmis bir
biyoyararlanima ve artirilmis bir farmakolojik etkiye yol açarak dabigatran eteksilat serbest
Baska bir örnege göre, mevcut bulusta siklodekstrin kullanilmasi dabigatran eteksilat serbest
bazinin hidrolize, oksidasyona, isiya, isiga ve metal tuzlarina karsi direncini artirmak
suretiyle, stabilitesini gelistirir.
Baska bir örnege göre, mevcut bulusta dabigatran eteksilat serbest bazi, kardiyak aritmi ve
kan pihtilasma tedavisinde ve hastalarda ciddi veya hayati tehdit edici yan etkileri önlemek
için bir antikoagülan, yani pihtilasma önleyici olarak kullanilir.
Bir diger örnege göre, mevcut bulustun farmasötik formülasyonlari ayrica en az bir dagitici
Uygun dagiticilar, sodyum nisasta glikolat, çapraz bagli polivinil pirolidon (krospovidon),
prejelatinize nisasta, düsük ikameli hidroksipropil selüloz, sodyum karboksimetil selüloz,
kalsiyum karboksimetil selüloz, karboksimetil selüloz, dokusat sodyum, guar zamki,
poliakrilin potasyum, sodyum alginat, misir nisastasi, alginik asit, alginatlar, iyon degistirme
reçineleri, magnezyum alüminyum silika, sodyum dodesil sülfat, poloksamer, sodyum glisin
karbonat veya bunlarin karisimlari olup bunlarla da sinirli degillerdir. Tercih edilen
ayristiricilar, sodyum nisasta glikolat ve çapraz bagli polivinil pirolidondur (krospovidon).
Bu örnege göre, istenen toplam dagitici miktari toplam formülasyonun agirliga göre %05 -
,u arasidir. Bu miktar ayrica dabigatran eteksilat serbest bazinin gerektigi gibi çözünmesini
de saglar.
Mevcut bulusun bir örnegine göre, farmasötik formülasyonlar, agizdan verilen kati dozaj
seklindedir.
Ornege göre farmasötik formülasyonlar, tabletler, kaplanmis ya da kaplanmamis tabletler,
kapsüller, çok katmanli tabletler, bukkal tabletler, dil alti tabletleri, tablet içinde tabletler,
dolgu tabletler, efervesan tabletler, hemen salims aglayan tabletler, modifiye salimli tabletler,
agizda dagilan tabletler, film kapli tabletler, enterik kapli tabletler, haplar, sert veya yumusak
jelatin kapsüller, tozlar, mini tabletler, pelletler, kaplanmis boncuk sistemleri, gran'uller,
drajeler, posetler, filmler, oral yol ile uygulanabilir filmler seklindedir.
Yukarida belirtilen zorluklar açisindan yardimci maddelerinin seçimi önemlidir. Bu örnege
göre dagitici disinda en az bir farmasötik olarak kabul edilebilir yardimci maddesi, dolgu
maddeleri, baglayicilar, yaglayicilar, glidantlar, asitler, erime bilesenleri, plastiklestiriciler ve
bunlarin karisimlarindan olusan gruptan seçilir.
Uygun dolgu maddeleri, mannitol, mikrokristalin selüloz, Iaktoz, dibazik kalsiyum fosfat,
püskürt'ulerek kurutulmus mannitol, dekstroz, sukroz, dikalsiyum fosfat, sorbitol, ksilitol,
inositol, kaolin, inorganik tuzlar, kalsiyum tuzlari, polisakaritler, sodyum klor'ür, dekstratlar,
bikarbonat, kalsiyum karbonat ya da bunlarin karisimlarini içerebilir, ancak bunlarla da sinirli
degildir.
Uygun baglayicilar arasinda, ksantan zamki, polivinilpirolidon, polietilen glikol, polivinil alkol,
nisasta, glukoz, glukoz surubu, dogal zamklar, sukroz, sodyum alginat, hidroksipropil metil
selüloz, hidroksipropil selüloz, karboksi metil selüloz, metil selüloz, jelatin, karagenan, guar
zamki, karbomer, polimetakrilatlar, metakrilat polimerleri, kollajen, agar, alginat, alginik asit,
hiyalüronik asit, pektin, polisakaritler, karbomer, poloksamer, poliakrilamid, alüminyum
hidroksit, Iaponit, bentonit, polioksietilen alkil eter, polidekstroz, polietilen oksit ya da bunlarin
karisimlari olabilir, ancak bunlarla sinirli degildir.
Uygun Iubrikanlar arasinda, magnezyum stearat, kalsiyum stearat, çinko stearat, balmumu,
borik asit, hidrojene bitkisel yag, sodyum klorat, magnezyum lauril sülfat, sodyum oleat,
sodyum asetat, sodyum benzoat, polietilen glikol, stearik asit, yag asidi, fumarik asit, gliseril
palmito sülfat, sodyum stearil fumarat, sodyum lauril sülfat ya da bunlarin karisimlari olabilir,
ancak bunlarla sinirli degildir.
Uygun glidanlar arasinda, talk, alüminyum silikat, silikon dioksit, nisasta ya da bunlarin
karisimlari olabilir, ancak bunlarla sinirli degildir.
Uygun asitler, tartarik asit, sitrik asit, askorbik asit, fumarik asit, malik asit, nikotinik asit,
adipik asit, asetilsalisilik asit ya da bunlarin karisimlarindan olusan gruptan seçilir.
Uygun erime bilesenleri jelusir (stearil makrogol gliserid - stearoil polioksilgliseridler),
poloksamer 188 (polioksietilen - polioksipropilen blok kopolimeri), polietilen glikol, soluplus,
katyonik metakrilat içeren gruptan seçilir.
Uygun plastiklestiriciler, dietil ftalat, farkli molekül agirliklarinda polietilen glikoller, propilen
glikol, gliserin, trietil sitrat, triasetin, dibütil ftalat, tributil sitrat, hint yagi, dibütil sebakat,
diasetile monogliseridler ya da bunlarin karisimlarini içerebilir ancak bunlarla sinirli
degillerdir.
Bu bulus, ayrica asagidaki örnekler referans alinarak tanimlanir. Ornekler bu bulusun
kapsamini sinirlamak amaciyla verilmemistir, ancak yukaridaki ayrintili tanimlama isiginda
göz Önüne alinmalidir.
Örnek 1: Direk Baski
Agirliga göre toplam formülasyonda:
Üretim prosesi: Dabigatran eteksilat serbest bazi ile siklodekstrin geometrik seyreltme
yöntemi ile karistirilir ve sürekli olarak diger yardimci maddeler ilave edilir. En son magnezyum
stearat katilip kisa bir süre karistirilir. Sonunda, karisim tabletler halinde sikistirilir ya da
kapsüllere doldurulur. Istege bagli olarak tabletler Opadry ABM (Polivinil alkol) ya da Kollicoat
Ornek 2: Kuru Gran'ülasyon
Agirliga göre toplam formülasyonda:
°/o 0,1 - 2,0 silikon dioksit
Uretim prosesi: Dabigatran eteksilat serbest bazi, siklodekstrin, dibazik kalsiyum fosfat,
krospovidon, ksantan zamki ve silikon dioksit karistirilir. Bu karisim, magnezyum stearatin yari
miktari ile karistirilir ve daha sonra silindir sikistirioi ile granüle edilir. Magnezyum stearatin geri
kalani, bu granülllere eklenir ve karistirilir. Son olarak, kansim tabletler halinde sikistirilir ya da
kapsüllere doldurulur. Istege bagli olarak tabletler Opadry ABM (Polivinil alkol) ya da Kollicoat
Ornek 3: Sicak-eriyik ekstr'Lizyonu
Agirliga göre toplam formülasyonda:
°/o 5.0 - 85.0 dabigatran eteksilat serbest baz
Uretim prosesi: Dabigatran eteksilat serbest bazi, jelusir ile karistirilir ve birlikte eritilip
ekstruderden geçirildikten sonra sogutulup elekten geçirilir. Elde edilen grani'illere, siklodekstrin,
mannitol, krospovidone, silikon dioksid ve magnezyum stearat eklenerek bir süre karistirilir.
Son olarak, karisim, tabletler halinde sikistirilir ya da kapsüllere doldurulur. Istege bagli olarak,
tabletler opadry ABM (Polivinil alkol) ya da Kollicoat IR (polivinil alkol / polietilen glikol graft
kopolimeri) ile kaplanabilir.
Ornek 4: Yas Granülasyon
Agirliga göre toplam formülasyonda:
°/o 0.1 - 2.0 silikon dioksit
Uretim prosesi: Siklodekstrin solüsyonu, uygun bir çözücü ya da çözücü karisimiyla hazirlanir.
Dabigatran eteksilat serbest bazi, dibazik kalsiyum fosfat ve krospovidon'un yarisi siklodekstrin
solüsyonu ile karistirilip granule edilir. Bu granüller elekten geçirilip kurutulur. Kuru granüller
tekrar elekten geçirilip kalan yardimci maddeler ile karistirilir. Sonra bu karisima magnezyum
stearat eklenip kisa bir süre daha karistirilir.
Son olarak karisim, tabletler halinde sikistirilir ya da kapsüllere doldurulur. lstege bagli olarak
tabletler opadry ABM (Polivinil alkol) ya da Kollicoat IR (polivinil alkol / polietilen glikol graft
kopolimeri) ile kaplanabilir.
Ornek 5: Pelet kaplama
Agirliga göre toplam formülasyonda:
°/o 0.1 - 2.0 silikon dioksit
Uretim prosesi: Dabigatran eteksilat serbest bazi ve siklodekstrinin bir hidoralkolik/alkolik
solüsyonu pullulan eklenerek hazirlanir. Seker pelletleri bu solüsyon ile kaplanir. Aktif madde ile
kaplanan seker pelletleri, polimetil metakrilat türevleri ile kaplanir. Bu topaklar ilk olarak silikon
dioksit ile daha sonra magnezyum stearat ile karistirilir.
Son olarak, Bu topak karisimi, tabletler halinde sikistirilir ya da kapsüllere doldurulur. istege
bagli olarak tabletler opadry ABM (Polivinil alkol) ya da Kollicoat IR (polivinil alkol / polietilen
glikol graft kopolimeri) ile kaplanabilir.
Claims (1)
- ISTEM LER Dabigatran eteksilat serbest bazi ve siklodekstrin içeren farmasötik formülasyonlar. lstem 1'e göre farmasötik formülasyonlar olup, özelligi dabigatran eteksilat serbest bazi miktarinin, toplam formülasyonun agirliga göre % 5.0 ile 85.0'i arasinda olmasidir. toplam formülasyonun agirliga göre %10 ila 50.0'si arasinda olmasidir. istem 1'e göre farmasötik formülasyonlar olup, ayrica en az bir dagitici içerir. istem 4,e göre farmasötik formülasyonlar olup, özelligi dagiticilarin sodyum nisasta glikolat, çapraz-bagli polivinil pirolidon, magnezyum alüminyum silika, sodyum dodesil sülfat, sodyum karboksimetil selüloz, karboksimetil kalsiyum, düsük ikameli hidroksipropil metil selüloz, poloksamer veya bunlarin karisimlarini içeren gruptan seçildigi . istem 5'e göre farmasötik formülasyonlar olup, özelligi dagiticilarin tercihen sodyum nisasta glikolat ve çapraz bagli polivinil pirolidon veya bunlarin karisimlari olmasidir. istem 6'ya göre farmasötik formülasyonlar olup, özelligi dagiticilarin toplam miktarinin, toplam formülasyonun agirliga göre % 0.5 - 30'u arasinda olmasidir. istem 1 veya 4'e göre farmasötik formülasyonlar olup, ayrica dagitici disinda dolgu maddeleri, baglayicilar, Iubrikanlar, glidanlar, asitler, erime bilesenleri, plastiklestiriciler veya bunlarin karisimlarindan olusan gruptan seçilmis en az bir farmasötik olarak kabul edilebilir yardimci maddesi içerir. Onceki istemlerden herhangi birine göre farmasötik formülasyonlar olup, toplam formülasyonda agirlikça asagidakileri içerir °/o 5.0 - 85.0 dabigatran eteksilat serbest bazi 10.0nceki istemlerden herhangi birine göre farmasbtik formülasyonlar olup, toplam form'L'iIasyonda agirlikça asagidakileri içerir , Onceki istemlerden herhangi birine göre farmasötik formülasyonlar olup, toplam form'L'iIasyonda agirlikça asagidakileri içerir , °/o 0.1 - 2.0 silikon dioksit 12.0nceki istemlerden herhangi birine göre farmas'otik formülasyonlar olupi toplam T“FDP-.OP'PJ formülasyonda agirlikça asagidakileri içerir , 13.0nceki istemlerden herhangi birine göre farmasötik formülasyonlar olup, toplam 99.69› formülasyonda agirlikça asagidakileri içerir, istem 9 ila 13'e göre farmasötik formülasyonlar olup. özelligi bahsi geçen farmasötik form'ülasyonlarini tabletler, kaplanmis ya da kaplanmamis tabletler, kapsüller, çok katmanli tabletler, bukkal tabletler, dil alti tabletleri, tablet içinde tabletler, dolgu tabletler, efervesan tabletler, hizli salim saglayan tabletler, modifiye salimli tabletler, agizda dagilan tabletler, film kapli tabletler, enterik kapli tabletler, haplar, sert veya yumusak jelatin kapsüller, tozlar, mini tabletler, pelletler, kaplanmis boncuk sistemleri, gran'üller, drajeler, posetler, filmler, oral yoldan uygulanabilir filmler seklinde olmalaridir., istem 14'e göre farmasötik form'ülasyonlar olup, özelligi söz konusu farmasötik formülasyonlarin tablet veya kapsül seklinde olmasidir.
Priority Applications (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| TR2016/06697A TR201606697A2 (tr) | 2016-05-20 | 2016-05-20 | Dabi̇gatranin yeni̇ oral farmasöti̇k formülasyonlari |
| PCT/EP2017/062021 WO2017198783A1 (en) | 2016-05-20 | 2017-05-18 | New oral pharmaceutical formulations of dabigatran |
| EP17171787.9A EP3246020A1 (en) | 2016-05-20 | 2017-05-18 | New oral pharmaceutical formulations of dabigatran |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| TR2016/06697A TR201606697A2 (tr) | 2016-05-20 | 2016-05-20 | Dabi̇gatranin yeni̇ oral farmasöti̇k formülasyonlari |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| TR201606697A2 true TR201606697A2 (tr) | 2017-12-21 |
Family
ID=58715132
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TR2016/06697A TR201606697A2 (tr) | 2016-05-20 | 2016-05-20 | Dabi̇gatranin yeni̇ oral farmasöti̇k formülasyonlari |
Country Status (3)
| Country | Link |
|---|---|
| EP (1) | EP3246020A1 (tr) |
| TR (1) | TR201606697A2 (tr) |
| WO (1) | WO2017198783A1 (tr) |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PE121699A1 (es) | 1997-02-18 | 1999-12-08 | Boehringer Ingelheim Pharma | Heterociclos biciclicos disustituidos como inhibidores de la trombina |
| PT1485094E (pt) | 2002-03-07 | 2012-10-09 | Boehringer Ingelheim Int | Forma de administração por via oral para 3-[(2-{[4- (hexiloxicarbonilamino-imino-metil)-fenilamino]-metil}-1-metil- 1h-benzimidazole-5-carbonil)-piridin-2-il-amino]-propionato de etilo ou os seus sais |
| DE102005020002A1 (de) | 2005-04-27 | 2006-11-02 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Physiologisch verträgliche Salze von 3-[(2-{[4-(Hexyloxycarbonylamino-imino-methyl)-phenylamino]-methyl}-1-methyl-1H-benzimidazol-5-carbonyl)-pyridin-2-yl-amino]-propionsäure-ethylester |
| WO2012077136A2 (en) | 2010-12-06 | 2012-06-14 | Msn Laboratories Limited | Process for the preparation of benzimidazole derivatives and its salts |
| JP2015504903A (ja) * | 2012-01-24 | 2015-02-16 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 新規の経口投与用ダビガトラン製剤 |
| WO2014060561A1 (en) * | 2012-10-19 | 2014-04-24 | Sanovel Ilac Sanayi Ve Ticaret A.S. | Oral pharmaceutical formulations comprising dabigatran |
| WO2014060545A1 (en) * | 2012-10-19 | 2014-04-24 | Sanovel Ilac Sanayi Ve Ticaret A.S. | Pharmaceutical compositions of dabigatran free base |
| EP3324946A1 (en) * | 2015-07-20 | 2018-05-30 | Sanovel Ilac Sanayi ve Ticaret A.S. | Pharmaceutical formulations of dabigatran free base |
-
2016
- 2016-05-20 TR TR2016/06697A patent/TR201606697A2/tr unknown
-
2017
- 2017-05-18 WO PCT/EP2017/062021 patent/WO2017198783A1/en active Application Filing
- 2017-05-18 EP EP17171787.9A patent/EP3246020A1/en not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| EP3246020A1 (en) | 2017-11-22 |
| WO2017198783A1 (en) | 2017-11-23 |
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