TR2022007368A2 - ANTIVIRAL COMPOSITIONS - Google Patents
ANTIVIRAL COMPOSITIONSInfo
- Publication number
- TR2022007368A2 TR2022007368A2 TR2022/007368 TR2022007368A2 TR 2022007368 A2 TR2022007368 A2 TR 2022007368A2 TR 2022/007368 TR2022/007368 TR 2022/007368 TR 2022007368 A2 TR2022007368 A2 TR 2022007368A2
- Authority
- TR
- Turkey
- Prior art keywords
- pharmaceutically acceptable
- acceptable salt
- tenofovir alafenamide
- composition according
- composition
- Prior art date
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 49
- 230000000840 anti-viral effect Effects 0.000 title claims abstract description 22
- 239000004480 active ingredient Substances 0.000 claims abstract description 23
- 150000003839 salts Chemical class 0.000 claims description 90
- 229960004946 tenofovir alafenamide Drugs 0.000 claims description 33
- LDEKQSIMHVQZJK-CAQYMETFSA-N tenofovir alafenamide Chemical compound O([P@@](=O)(CO[C@H](C)CN1C2=NC=NC(N)=C2N=C1)N[C@@H](C)C(=O)OC(C)C)C1=CC=CC=C1 LDEKQSIMHVQZJK-CAQYMETFSA-N 0.000 claims description 33
- 239000007941 film coated tablet Substances 0.000 claims description 15
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 14
- SVUJNSGGPUCLQZ-FQQAACOVSA-N tenofovir alafenamide fumarate Chemical group OC(=O)\C=C\C(O)=O.O([P@@](=O)(CO[C@H](C)CN1C2=NC=NC(N)=C2N=C1)N[C@@H](C)C(=O)OC(C)C)C1=CC=CC=C1.O([P@@](=O)(CO[C@H](C)CN1C2=NC=NC(N)=C2N=C1)N[C@@H](C)C(=O)OC(C)C)C1=CC=CC=C1 SVUJNSGGPUCLQZ-FQQAACOVSA-N 0.000 claims description 11
- 239000002775 capsule Substances 0.000 claims description 8
- MEJAFWXKUKMUIR-FHPNUNMMSA-N (e)-but-2-enedioic acid;propan-2-yl (2s)-2-[[[(2r)-1-(6-aminopurin-9-yl)propan-2-yl]oxymethyl-phenoxyphosphoryl]amino]propanoate Chemical group OC(=O)\C=C\C(O)=O.O([P@@](=O)(CO[C@H](C)CN1C2=NC=NC(N)=C2N=C1)N[C@@H](C)C(=O)OC(C)C)C1=CC=CC=C1 MEJAFWXKUKMUIR-FHPNUNMMSA-N 0.000 claims description 7
- 229960005107 darunavir Drugs 0.000 claims description 6
- CJBJHOAVZSMMDJ-HEXNFIEUSA-N darunavir Chemical compound C([C@@H]([C@H](O)CN(CC(C)C)S(=O)(=O)C=1C=CC(N)=CC=1)NC(=O)O[C@@H]1[C@@H]2CCO[C@@H]2OC1)C1=CC=CC=C1 CJBJHOAVZSMMDJ-HEXNFIEUSA-N 0.000 claims description 6
- NCDNCNXCDXHOMX-XGKFQTDJSA-N ritonavir Chemical compound N([C@@H](C(C)C)C(=O)N[C@H](C[C@H](O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1SC=NC=1)CC=1C=CC=CC=1)C(=O)N(C)CC1=CSC(C(C)C)=N1 NCDNCNXCDXHOMX-XGKFQTDJSA-N 0.000 claims description 6
- 229960003586 elvitegravir Drugs 0.000 claims description 5
- JUZYLCPPVHEVSV-LJQANCHMSA-N elvitegravir Chemical compound COC1=CC=2N([C@H](CO)C(C)C)C=C(C(O)=O)C(=O)C=2C=C1CC1=CC=CC(Cl)=C1F JUZYLCPPVHEVSV-LJQANCHMSA-N 0.000 claims description 5
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- NCDNCNXCDXHOMX-UHFFFAOYSA-N Ritonavir Natural products C=1C=CC=CC=1CC(NC(=O)OCC=1SC=NC=1)C(O)CC(CC=1C=CC=CC=1)NC(=O)C(C(C)C)NC(=O)N(C)CC1=CSC(C(C)C)=N1 NCDNCNXCDXHOMX-UHFFFAOYSA-N 0.000 claims description 3
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- MCGSCOLBFJQGHM-SCZZXKLOSA-N abacavir Chemical compound C=12N=CN([C@H]3C=C[C@@H](CO)C3)C2=NC(N)=NC=1NC1CC1 MCGSCOLBFJQGHM-SCZZXKLOSA-N 0.000 claims description 3
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- RWWYLEGWBNMMLJ-YSOARWBDSA-N remdesivir Chemical compound NC1=NC=NN2C1=CC=C2[C@]1([C@@H]([C@@H]([C@H](O1)CO[P@](=O)(OC1=CC=CC=C1)N[C@H](C(=O)OCC(CC)CC)C)O)O)C#N RWWYLEGWBNMMLJ-YSOARWBDSA-N 0.000 claims description 3
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- 239000000243 solution Substances 0.000 claims description 3
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- JFVZFKDSXNQEJW-CQSZACIVSA-N tenofovir disoproxil Chemical compound N1=CN=C2N(C[C@@H](C)OCP(=O)(OCOC(=O)OC(C)C)OCOC(=O)OC(C)C)C=NC2=C1N JFVZFKDSXNQEJW-CQSZACIVSA-N 0.000 claims description 3
- 229960004626 umifenovir Drugs 0.000 claims description 3
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- 238000011282 treatment Methods 0.000 abstract description 5
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- 229940079593 drug Drugs 0.000 description 10
- 238000009472 formulation Methods 0.000 description 9
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- VCMJCVGFSROFHV-WZGZYPNHSA-N tenofovir disoproxil fumarate Chemical compound OC(=O)\C=C\C(O)=O.N1=CN=C2N(C[C@@H](C)OCP(=O)(OCOC(=O)OC(C)C)OCOC(=O)OC(C)C)C=NC2=C1N VCMJCVGFSROFHV-WZGZYPNHSA-N 0.000 description 6
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Abstract
Mevcut buluş oral yolla kullanıma uygun etken madde olarak antiviral madde ihtiva eden kompozisyonlarla ilgilidir. Buluşa ait kompozisyonlar HIV, AIDS ve kronik Hepatit B tedavisinde kullanılabilmektedir.The present invention relates to compositions containing antiviral substances as active ingredients suitable for oral use. The compositions of the invention can be used in the treatment of HIV, AIDS and chronic Hepatitis B.
Description
Tarifname ANTIVIRAL KOMPOZISYONLAR Bulusun Ilgili Oldugu Alan Mevcut bulus oral yolla kullanima uygun etken madde olarak antiviral madde ihtiva eden kompozisyonlarla ilgilidir. Daha da özel olarak tenofovir alafenamid veya farmasötik olarak kabul edilibilir tuzunu ihtiva eden hasta uyuncu ve stabilitesi yüksek kompozisyonlarla ilgilidir. Teknigin Bilinen Durumu Antiviral ilaçlar, viral enfeksiyonlari tedavi etmek için kullanilan bir ilaç sinifidir. Çogu antiviral, belirli virüsleri hedeflerken, genis spektrumlu bir antiviral, çok çesitli virüslere karsi etkilidir. Çogu antibiyotigin aksine, antiviral ilaçlar hedef patojenlerini yok etmez; bunun yerine gelisimini engellerler. Tenofovir alafenamid, tenofovirin bir ön ilacidir. Gilead Sciences tarafindan HIV/AIDS ve kronik hepatit B tedavisinde kullanilmak üzere gelistirilmistir ve tenofovir alafenamid fumarat (TAF) seklinde uygulanir. Yaygin olarak kullanilan ters transkriptaz inhibitörü tenofovir disoproksil fumarat (TDF) ile yakindan iliskili olan TAF, bu ajandan daha fazla antiviral aktiviteye ve lenfoid dokulara daha iyi dagilima sahiptir. Tenofovir Alafenamid istemlerde, fumarat tuzu ve HIV enfeksiyonlarini tedavi edici özelligi oldugu açiklanmistir. Tenofovir Alafenamid Monofumarat fazla kristalli formunun farmasötik bilesimlerin hazirlanmasini içeren farmasötik bilesimlerle ilgilidir. Farmasötik bilesimleri, özellikle HIV enfeksiyonlari gibi Viral enfeksiyonlarin tedavisi ve /Veya profilaksisi için ilaç olarak kullanilabilir. 05 HONOH Tenofovir Alafenamid Hemifumarat açiklamaktadir. Bagimli istemlerde tenofovir alafenamid hemifumarat üretim metodlari da açiklanmaktadir. Bulusun Kisa Açiklamasi Bulus, antiviral aktif madde ve en az bir farmasötik olarak kabul edilebilir eksipiyan ihtiva den bir kompozisyon ile ilgilidir. Bulusun tercih edilen yapilanmasinda, antiviral aktif madde, abakavir veya farmasötik olarak kabul edilebilir bir tuzu, asiklovir veya farmasötik olarak kabul edilebilir bir tuzu, adefovir veya farmasötik olarak kabul edilebilir bir tuzu, amantadin veya farmasötik olarak kabul edilebilir bir tuzu, ampligen veya farmasötik olarak kabul edilebilir bir tuzu, umifenovir veya farmasötik olarak kabul edilebilir bir tuzu, darunaVir veya farmasötik olarak kabul edilebilir bir tuzu, elvitegravir veya farmasötik olarak kabul edilebilir bir tuzu, famsiklovir veya farmasötik olarak kabul edilebilir bir tuzu, lopinaVir veya farmasötik olarak kabul edilebilir bir tuzu, norVir veya farmasötik olarak kabul edilebilir bir tuzu, oseltamiVir veya farmasötik olarak kabul edilebilir bir tuzu, peramiVir veya farmasötik olarak kabul edilebilir bir tuzu, remdesiVir veya farmasötik olarak kabul edilebilir bir tuzu, ritonaVir veya farmasötik olarak kabul edilebilir bir tuzu, sofosbuVir veya farmasötik olarak kabul edilebilir bir tuzu, tenofovir alafenamid veya farmasötik olarak kabul edilebilir bir tuzu, tenofovir disoproksil veya farmasötik olarak kabul edilebilir bir tuzu arasindan seçilebilir. Tercihen tenofovir alafenamid veya farmasötik olarak kabul edilebilir bir tuzu olabilir. Bulusta tercih edilen antiviral aktif madde, film kapli tablet, kapsül, süspansiyon, surup, solüsyon formunda olabilir. Bulusa uygun kompozisyon film kapli tablet formunda olabilir. Bulusa ait kompozisyon tenofovir alafenamid veya farmasötik olarak kabul edilebilir bir tuzu 5- 200 mg arasinda olabilir. Bulus tercih edilen yapilanmasi tenofovir alafenamid veya farmasötik olarak kabul edilebilir tuzu -100 mg arasinda olabilir. Bulusa ait kompozisyonda tercihen tenefovir alafenamid veya farmasötik olarak kabul edilebilir bir tuzu 10-50 mg arasinda olabilir. Bulusait kompozisyonda tercihen tenofovir alafenamid veya farmasötik olarak kabul edilebilir bir tuzu 25 mg olabilir. Bulusa ait antiviral aktif madde, amorf veya kristal yapida olabilir. Tercihen kristal yapida olabilir. Bulusta tercihen antiviral etken madde tenofovir alafenamid veya farmasötik olarak kabul edilebilir bir tuzu olabilir. Tercihen tenofovir alafenamid monofumarat veya tenofovir alafenamid hemifumarat olabilir Bulus tercih edilen yapilanmasinda antiviral etken madde tenofovir alafenamid monofumarat olabilir. Bulus tercih edilen yapilanmasinda antiviral etken madde tenofovir alafenamid hemifumarat olabilir. Bulus bir baska yönüyle, HIV, AIDS ve kronik hepatit B tedavisinde kullanilmak üzere bir kompozisyon saglamaktadir. Bulusun Amaci Bulusun amaci, antiviral etken madde olarak tenofovir alafenamid veya farmasötik olarak kabul edilebilir bir tuzu ve en az bir farmasötik olarak kabul edilebilir eksipiyan ihtiva eden kompozisyonlarda süper dagitici ve daha iyi yaglayici ajanlar kullanilmasiyla teknikte bilinen formülasyonlara kiyasla daha stabil, hastaya yararli ve hasta uyuncunun yüksek oldugu formülasyonlarin hazirlanmasi amaçlanmistir. Bulusun Ayrintili Açiklamasi Bulusa ait kompozisyon etken madde olarak en az bir antiviral etken madde ve en az bir farmasötik olarak kabul edilebilir eksipiyan ihtiva eder. Mevcut bulusa ait ilaç kompozisyonu, tablet, katmanli tablet, film kapli tablet, enterik kapli, modifiye salimli tablet, kontrollü salimli tablet, uzatilmis salimli tablet, agizda dagilan tablet, efervesan tablet, geciktirilmis salimli tablet, yavas veya hizli salimli tablet, pellet, mini tablet, mikro tablet, kapsül içinde pellet, kapsül içinde granül, kapsül içinde mini tablet, kapsül içinde mikro tablet, kapsül, sase, solüsyon ve süspansiyon seklinde olabilir. Tercihen söz konusu ilaç kompozisyonu film kapli tablet, kapsül veya uzatilmis salimli tablet formundadir. Daha da özel olarak film kapli tablet veya uzatilmis salimli tablet formlari tercih edilmektedir. Mevcut bulus tercih edilen yapilanmasinda film kapli tablet formunda olabilir. Bulus tercih edilen yapilanmasinda uzatilmis salimli tablet formuda olabilir. Bulusun tercih edilen yapilanmasinda, antiviral etken madde, abakavir veya farmasötik olarak kabul edilebilir bir tuzu, asiklovir veya farmasötik olarak kabul edilebilir bir tuzu, adefovir veya farmasötik olarak kabul edilebilir bir tuzu, amantadin veya farmasötik olarak kabul edilebilir bir tuzu, ampligen veya farmasötik olarak kabul edilebilir bir tuzu, umifenovir veya farmasötik olarak kabul edilebilir bir tuzu, darunavir veya farmasötik olarak kabul edilebilir bir tuzu, elvitegravir veya farmasötik olarak kabul edilebilir bir tuzu, famsiklovir veya farmasötik olarak kabul edilebilir bir tuzu, lopinavir veya farmasötik olarak kabul edilebilir bir tuzu, norvir veya farmasötik olarak kabul edilebilir bir tuzu, oseltamivir veya farmasötik olarak kabul edilebilir bir tuzu, peramivir veya farmasötik olarak kabul edilebilir bir tuzu, remdesivir veya farmasötik olarak kabul edilebilir bir tuzu, ritonavir veya farmasötik olarak kabul edilebilir bir tuzu, sofosbuvir veya farmasötik olarak kabul edilebilir bir tuzu, tenofovir alafenamid veya farmasötik olarak kabul edilebilir bir tuzu, tenofovir disoproksil veya farmasötik olarak kabul edilebilir bir tuzu arasindan seçilebilir. Bulus tercih edilen yapilanmasinda antiviral etken madde, tenofovir alafenamid veya farmasötik olarak kabul edilebilir bir tuzu olabilir. Daha özel olarak tenofovir alafenamidin fumarik asit tuzu olabilir. Bulusa ait kompozisyon tenofovir alafenamid veya farmasötik olarak kabul edilebilir bir tuzu 5- 200 mg arasinda, tercihen 10-100 mg arasinda ihtiva edebilir. Daha özel olarak tenofovir alafenamid veya farmasötik olarak kabul edilebilir bir tuzu 10-50 mg arasinda ihtiva edebilir. Bulusun tercih edilen yapilanmasinda tenofovir alafenamid veya farmasötik olarak kabul edilebilir bir tuzunun miktari 25 mg olabilir. Mevcut bulusun tercih edilen yapilanmasinda tenofovir alafenamidin fumarik asite orani 1:0.1 ila arasinda olabilir. Bulusta bahsedilen tenofovir alafenamid monofumarat ilaç yapisinda, tenofovir alafenamidin fumarik asite orani 1:1'dir. Bulusta bahsedilen tenofovir alafenamid hemifumarat ilaç yapisinda, tenofovir alafenamidin Bulusun tercih edilen yapilanmasinda film kapli tablet kompozisyonlari ile daha stabil, hasta uyuncu ve biyoyararlanimi yüksek kompozisyonlar elde edilmistir. Bulustaki uzatilmis salimli tablet kompozisyonlari ile daha stabil, hasta uyuncu ve biyoyararlanimi yüksek kompozisyonlar elde edilmistir. Bulusa uygun kompozisyonlar eksipiyan olarak dolgu maddeleri, baglayici maddeler, dagitici maddeler ve süper dagitici maddeler, koruyucu maddeler, aroma ajanlari, kaplama ajanlari, seyreltici ajanlar tamponlayci ajanlari, jellestirici ajanlari, yaglayici ajanlar ve bunlar gibi yaygin olarak mevcut baska eksipiyanlar da bulunabilir. Dolgu maddeleri, tableti belli bir agirliga getirmek için kullanilirlar. Dolgu maddesi olarak nisasta, mikrokristal selüloz, laktoz, monobazik ve dibazik kalsiyum fosfat, kalsiyum sülfat, mannitol, sorbitol, ksilitol, sodyum klorür, dekstrin ve kaolin ile sinirli kalmamak sartiyla diger dolgu maddeler kullanilmaktadir. Dagitici maddeler, tablet içeriginin mide ortaminda hizla parçalanmasini saglamak ve böylece ilacin kana karismak veya lokal etki göstermek üzere salimini saglayan eksipiyanlardir. Tablet dagiticilari ile ilaç salimi ve biyoyararlanimi arasinda dorudan iliski vardir. Süper dagiticilar daha düsük miktarlarda benzer etkiyi gösteren eksipiyanlardir. Dagitici madde olarak, krospovidon, kroskarmelloz sodyum, hidroksipropilmetil selüloz, PVP, poliplasdon XL, poliplasdon XL 10, kollidon CL ve sodyum nisasta glikolat ile sinirli kalmamak sartiyla diger dagitici maddeler de kullanilmaktadir. Baglayici maddeler, tablette mekanik ve fiziksel stabilite saglamak için kullanilmaktadir. Baglayici madde olarak PVP, HPMC, glukoz, sukroz, sorbitol, jelatin, sodyum aljinat ile sinirli kalmamak sartiyla diger baglayici maddeler de kullanilmaktadir. Koruyucu maddeler ilaçlarin kullanimi ömrünü uzatmak için kullanilirlar. Koruyucu madde olarak paraben ve tuzlari, sodyum benzoat ve potasyum benzoat ile sinirli kalmamak sartiyla diger koruyucu maddeler kullanilmaktadir. Aroma ajanlari, ilacin tadini maskelemek ve hasta tarafindan daha kolay kullanimi saglamak için kullanilmaktadir. Aroma ajanlari olarak da mentol gliserin ve portakal aromasi ile sinirli kalmamak sartiyla diger aroma ajanlari da kullanilmaktadir. Kaplama ajanlari, tabletleri dis etkenlere karsi korumak, tat ve kokulari maskelemek ve ilacin hedef organda emilimini saglamak. Kaplama ajanlari olarak da Karnauba Mumu (Carnauba waX], HPMC, HPC, MC ve poliVinil asetat OPADRY® gibi kullanima hazir kaplama ajanlari ile de sinirli kalmamak sartiyla diger kaplama ajanlari da kullanilmaktadir. Film kaplama, salim hizina etki ettigi gibi ayni zamanda bilesimin dis ortam kosullarina karsi korunmasini da saglar. Tamponlayici ajanlar, bu maddeler asit, baz, tamponlama ajani, pH düzenleyici olarak da bilinirler. Tamponlayici ajanlar olarak da asetik asit, potasyum hidroksit, fumarik asit, monosodyum sitrat, sodyum klorür ve sitrik asit monohidrat ile sinirli kalmamak sartiyla tamponlayici ajanlar da kullanilmaktadir. guar gum, arap zamki, ksantan gum, sodyum karboksimetil selüloz ve karragenan ile sinirli kalmamak sartiyla jellestirici ajanlar da kullanilmaktadir. Yaglayici ajanlar, sürtünmeyi azaltmak, farmasötik üretiminin basarisini saglamak için genellikle formülasyonlarda kullanilan bilesenlerdir. Yaglayici ajanlar olarak da, magnezyum stearat, kalsiyum stearat, sodyum stearil fumarat, sodyum lauril sülfat, talk ve kolloidal silikon dioksit ile sinirli kalmamak sartiyla yaglayici ajanlar kullanilmaktadir. Seyreltici ajanlar tercihen, mikrokristalin selüloz, prejelatinize nisasta, nisasta, karboksimetilselüloz kalsiyum, magnezyum alüminyum silikat, metilselüloz, laktoz monohidrat, dibazik kalsiyum fosfat, mikrokristalin selüloz fosfat, hidroksipropil selüloz, karboksimetilselüloz sodyum, krospovidon, düsük sübstitüe edilmis hidroksipropil selüloz, sodyum aljinat ve silisifiye mikrokristalin selüloz içeren bir grupla sinirli kalmamak sartiyla aralarindan seçilmektedir Bulusa ait kompozisyonda tenofovir alafenamid veya farmasötik olarak kabul edilebilir bir tuzu, farmasötik olarak kabul edilebilir en bir eksipyan sodyum laruil sülfat olabilir. Sodyum lauril sülfat yaglayici ajan olarak kullanildiginda sinifindaki yaglayicilara göre daha iyi yaglayici verimliligi ile beraber tablet çözünmesinde bozulmaya yol açmaz ve stabiliteyi artirir. Film kapli tablet formülasyonlarinda sodyum lauril sülfat kullanilmasiyla hasta yararlanimi daha yüksek formülasyonlar elde edilmistir. Bulusa ait film kapli tablet kompozisyonu tercih edilen yapilanmasinda tenofovir alafenamid veya farmasötik olarak kabul edilebilir bir tuzu ve farmasötik olarak kabul edilebilir eksipiyan olarak bir süper dagitici olan poliplasdon XL 10 ve film kapli tablette yaglama ajani olarak sodyum lauril sülfat kullanilmasyila tablette stabiliteyi ve hasta yararlanimini artirmistir. Bulusa ait kompozisyon ilaveten bir veya birden fazla etken madde ihtiva edebilir. Bulusa ait kompozisyona ilave etken madde, kobisistat, biktegravir veya farmasötik olarak kabul edilebilir tuzu, darunavir veya farmasötik olarak kabul edilebilir bir tuzu, emtrisitabin, rilpivirin veya farmasötik olarak kabul edilebilir bir tuzu veya elvitegravir arasindan seçilebilir. Bulusun tercih edilen yapilanmasinda tenofovir alafenamid veya farmasötik olarak kabul edilebilir bir tuzuna ilaveten emtrisitabin ihtiva edebilir. Bulus bir diger yapilanmasinda tenofovir alafenamid veya farmasötik olarak kabul edilebilir bir tuzuna ilaveten biktegravir sodyum ve emtrisitabin ihtiva edebilir. Bulus bir diger yapilanmasinda tenofovir alafenamid veya farmasötik olarak kabul edilebilir tuzuna ilaveten kobisistat, darunavir veya farmasötik olarak kabul edilebilir bir tuzu ve emtrisitabin ihtiva edebilir. Bulus bir diger yapilanmasinda tenofovir alafenamid veya farmasötik olarak kabul edilebilir tuzuna ilaveten kobisistat, elvitegravir ve emtrisitabin ihtiva edebilir. Bulus bir diger yapilanmasinda tenofovir alafenamid veya farmasötik olarak kabul edilebilir tuzuna ilaveten emtrisitabin ve rilpivirin veya farmasötik olarak kabul edilebilir bir tuzunu ihtiva edebilir. Bulusta bahsedilen biktegravir veya farmasötik olarak kabul edilebilir tuzu biktegravir sodyum olabilir. Bulusta bahsedilen darunavir veya farmasötik olarak kabul edilebilir tuzu darunavir etanolat olabilir. Bulusta bahsedilen rilpivirin veya farmasötik olarak kabul edilebilir bir tuzu rilpivirin hidroklorür olabilir. Bulus bir baska yönüyle, HIV, AIDS ve kronik hepatit B tedavisinde kullanilmak üzere bir kompozisyon saglamaktadir. ÖRNEKLER Örnek 1: Tenofovir Alafenamid Monofumarat Film Kapli Tablet Formülasyonlari Bilesen Agirlik (mg) Aktif Maddeler Tenofovir Alafenamid 25.00 Monofumarat Yardimci Maddeler Sodyum Lauril Sülfat 22.5 Poliplasdon XL 10 47.50 Dibazik Sodyum Fosfat 345.00 Film Kaplama OPADRY 10.00 Toplam 450.00 Örnek 2: Tenofovir Alafenamid Monofumarat Film Kapli Tablet Formülasyonlari Bilesen Agirlik (mg) Aktif Maddeler Tenofovir Alafenamid 25.00 Monofumarat Yardimci Maddeler Magnezyum Stearat 22.75 Kroskarmelloz Sodyum 35.00 Laktoz monohidrat 22.25 Mikrokristalin Selüloz 235.00 Film Kaplama OPADRY® 10.00 Toplam 350.00 Örnek 3: Tenofovir Alafenamid Hemifumarat Film Kapli Tablet Formülasyonlari Bilesen Agirlik (mg) Aktif Maddeler Tenofovir Alafenamid 25.00 Hemifumarat Yardimci Maddeler Magnezyum Stearat 22.75 Kroskarmelloz Sodyum 35.00 Laktoz monohidrat 22.25 Mikrokristalin Selüloz 235.00 Film Kaplama OPADRY® 10.00 Toplam 350.00 Örnek 4: Tenofovir Alafenamid Hemifumarat Film Kapli Tablet Formülasyonlari Bilesen Agirlik (mg) Aktif Maddeler Tenofovir Alafenamid 25.00 Hemifumarat Yardimci Maddeler Sodyum Lauril Sülfat 22.5 Poliplasdon XL 10 47.50 Dibazik Sodyum Fosfat 345.00 Film Kaplama OPAD RY® 10.00 Toplam 450.00 Yukaridaki örneklerden herhangi birine göre formülasyonun hazirlanmasi için öncelikle aktif madde karisimi hazirlanir. Daha sonra ayri bir ortamda yardimci maddeler bir araya getirilir. Son olarak, aktif madde karisimi ile yardimci madde karisimi homojen sekilde bir araya getirilir. Son adim olarak OPADRY® ile kaplanarak nihai formülasyon elde edilir. TR TR Description ANTIVIRAL COMPOSITIONS Field of Invention The present invention relates to compositions containing antiviral substances as active ingredients suitable for oral use. More particularly, it relates to compositions containing tenofovir alafenamide or its pharmaceutically acceptable salt with high patient compliance and stability. State of the Art Antiviral drugs are a class of drugs used to treat viral infections. While most antivirals target specific viruses, a broad-spectrum antiviral is effective against a wide variety of viruses. Unlike most antibiotics, antiviral drugs do not destroy their target pathogens; instead, they inhibit its development. Tenofovir alafenamide is a prodrug of tenofovir. It was developed by Gilead Sciences for use in the treatment of HIV/AIDS and chronic hepatitis B and is administered as tenofovir alafenamide fumarate (TAF). Closely related to the widely used reverse transcriptase inhibitor tenofovir disoproxil fumarate (TDF), TAF has greater antiviral activity and better distribution into lymphoid tissues than this agent. Tenofovir Alafenamide is described in the claims as a fumarate salt and has therapeutic properties against HIV infections. It relates to pharmaceutical compositions comprising the preparation of the highly crystalline form of Tenofovir Alafenamide Monofumarate into pharmaceutical compositions. The pharmaceutical compositions can be used as drugs for the treatment and/or prophylaxis of Viral infections, especially HIV infections. 05 HONOH Tenofovir Alafenamide Hemifumarate explains. Tenofovir alafenamide hemifumarate production methods are also disclosed in the dependent claims. Brief Description of the Invention The invention relates to a composition comprising an antiviral active ingredient and at least one pharmaceutically acceptable excipient. In the preferred embodiment of the invention, the antiviral active ingredient is abacavir or a pharmaceutically acceptable salt thereof, acyclovir or a pharmaceutically acceptable salt thereof, adefovir or a pharmaceutically acceptable salt thereof, amantadine or a pharmaceutically acceptable salt thereof, ampligen or a pharmaceutically acceptable salt thereof. umifenovir or a pharmaceutically acceptable salt thereof, darunaVir or a pharmaceutically acceptable salt thereof, elvitegravir or a pharmaceutically acceptable salt thereof, famciclovir or a pharmaceutically acceptable salt thereof, lopinaVir or a pharmaceutically acceptable salt thereof, norVir or a pharmaceutically acceptable salt thereof, oseltamiVir or a pharmaceutically acceptable salt thereof, peramiVir or a pharmaceutically acceptable salt thereof, remdesiVir or a pharmaceutically acceptable salt thereof, ritonaVir or a pharmaceutically acceptable salt thereof, sofosbuVir or a pharmaceutically acceptable salt thereof a salt thereof, tenofovir alafenamide or a pharmaceutically acceptable salt thereof, tenofovir disoproxil or a pharmaceutically acceptable salt thereof. Preferably it is tenofovir alafenamide or a pharmaceutically acceptable salt thereof. The antiviral active substance preferred in the invention may be in the form of film-coated tablets, capsules, suspensions, syrups or solutions. The composition according to the invention may be in the form of a film-coated tablet. The composition of the invention may contain between 5 and 200 mg of tenofovir alafenamide or a pharmaceutically acceptable salt thereof. The preferred embodiment of the invention may be between -100 mg of tenofovir alafenamide or its pharmaceutically acceptable salt. The composition of the invention may preferably contain between 10 and 50 mg of tenefovir alafenamide or a pharmaceutically acceptable salt thereof. The invention composition may preferably contain 25 mg of tenofovir alafenamide or a pharmaceutically acceptable salt thereof. The antiviral active substance of the invention may be amorphous or crystalline. Preferably, it may have a crystal structure. Preferably, the antiviral active ingredient in the invention may be tenofovir alafenamide or a pharmaceutically acceptable salt thereof. Preferably, it can be tenofovir alafenamide monofumarate or tenofovir alafenamide hemifumarate. In the preferred embodiment of the invention, the antiviral active ingredient can be tenofovir alafenamide monofumarate. In the preferred embodiment of the invention, the antiviral active ingredient may be tenofovir alafenamide hemifumarate. In another aspect, the invention provides a composition for use in the treatment of HIV, AIDS and chronic hepatitis B. Purpose of the Invention The object of the invention is to use super-dispersant and better lubricating agents in compositions containing tenofovir alafenamide or a pharmaceutically acceptable salt as the antiviral active ingredient and at least one pharmaceutically acceptable excipient, which is more stable, beneficial to the patient and has patient compliance compared to the formulations known in the art. It is aimed to prepare formulations with high Detailed Description of the Invention The composition of the invention contains at least one antiviral active ingredient as active ingredient and at least one pharmaceutically acceptable excipient. The drug composition of the present invention may be used as a tablet, layered tablet, film-coated tablet, enteric coated, modified release tablet, controlled release tablet, extended release tablet, orodispersible tablet, effervescent tablet, delayed release tablet, slow or rapid release tablet, pellet, mini It can be in the form of tablets, micro tablets, pellets in capsules, granules in capsules, mini tablets in capsules, micro tablets in capsules, capsules, sachets, solutions and suspensions. Preferably, the drug composition is in the form of a film-coated tablet, capsule or extended-release tablet. More specifically, film-coated tablet or extended-release tablet forms are preferred. In its preferred embodiment, the present invention may be in film-coated tablet form. In its preferred embodiment, the invention may be in extended-release tablet form. In the preferred embodiment of the invention, the antiviral active ingredient is abacavir or a pharmaceutically acceptable salt thereof, acyclovir or a pharmaceutically acceptable salt thereof, adefovir or a pharmaceutically acceptable salt thereof, amantadine or a pharmaceutically acceptable salt thereof, ampligen or a pharmaceutically acceptable salt thereof. umifenovir or a pharmaceutically acceptable salt thereof, darunavir or a pharmaceutically acceptable salt thereof, elvitegravir or a pharmaceutically acceptable salt thereof, famciclovir or a pharmaceutically acceptable salt thereof, lopinavir or a pharmaceutically acceptable salt thereof, norvir or a pharmaceutically acceptable salt thereof, oseltamivir or a pharmaceutically acceptable salt thereof, peramivir or a pharmaceutically acceptable salt thereof, remdesivir or a pharmaceutically acceptable salt thereof, ritonavir or a pharmaceutically acceptable salt thereof, sofosbuvir or a pharmaceutically acceptable salt thereof. a salt thereof, tenofovir alafenamide or a pharmaceutically acceptable salt thereof, tenofovir disoproxil or a pharmaceutically acceptable salt thereof. In its preferred embodiment, the antiviral active ingredient may be tenofovir alafenamide or a pharmaceutically acceptable salt thereof. More specifically, tenofovir may be the fumaric acid salt of alafenamide. The composition of the invention may contain between 5 and 200 mg of tenofovir alafenamide or a pharmaceutically acceptable salt thereof, preferably between 10 and 100 mg. More specifically, it may contain between 10-50 mg of tenofovir alafenamide or a pharmaceutically acceptable salt thereof. In the preferred embodiment of the invention, the amount of tenofovir alafenamide or a pharmaceutically acceptable salt thereof may be 25 mg. In the preferred embodiment of the present invention, the ratio of tenofovir alafenamide to fumaric acid may be between 1:0.1 and 1:0.1. In the tenofovir alafenamide monofumarate drug structure mentioned in the invention, the ratio of tenofovir alafenamide to fumaric acid is 1:1. In the tenofovir alafenamide hemifumarate drug structure mentioned in the invention, compositions with more stability, patient compliance and high bioavailability have been obtained with film-coated tablet compositions of tenofovir alafenamide in the preferred embodiment of the invention. With the extended-release tablet compositions of the invention, compositions that are more stable, have higher patient compliance and bioavailability have been obtained. The compositions according to the invention may also contain as excipients such as fillers, binding agents, dispersing agents and superdispersants, preservatives, flavoring agents, coating agents, diluting agents, buffering agents, gelling agents, lubricating agents and other commonly available excipients. Fillers are used to bring the tablet to a certain weight. Starch, microcrystalline cellulose, lactose, monobasic and dibasic calcium phosphate, calcium sulfate, mannitol, sorbitol, xylitol, sodium chloride, dextrin and kaolin, and other fillers, but not limited to them, are used as fillers. Disintegrants are excipients that ensure rapid disintegration of the tablet content in the stomach environment and thus release the drug to enter the blood or have a local effect. There is a direct relationship between tablet disintegrants and drug release and bioavailability. Superdisintegrants are excipients that show similar effects in lower amounts. Other disintegrants, including but not limited to crospovidone, croscarmellose sodium, hydroxypropylmethyl cellulose, PVP, polyplasdone XL, polyplasdone Binding agents are used to provide mechanical and physical stability in the tablet. Other binding agents, including but not limited to PVP, HPMC, glucose, sucrose, sorbitol, gelatin and sodium alginate, are also used as binding agents. Preservatives are used to extend the life of drugs. Other preservatives, including but not limited to paraben and its salts, sodium benzoate and potassium benzoate, are used as preservatives. Flavoring agents are used to mask the taste of the medicine and make it easier for the patient to use. Other flavoring agents, including but not limited to menthol glycerin and orange flavor, are also used. Coating agents protect the tablets against external factors, mask tastes and odors, and ensure the absorption of the drug in the target organ. Other coating agents, including but not limited to ready-to-use coating agents such as Carnauba WaX (Carnauba waX), HPMC, HPC, MC and polyvinyl acetate OPADRY®, are also used. Film coating not only affects the release rate but also the effect of the composition on the external environment. These substances are also known as acid, base, buffering agent, pH regulator, but are not limited to acetic acid, potassium hydroxide, fumaric acid, monosodium citrate, sodium chloride and citric acid monohydrate. Buffering agents are also used, including but not limited to guar gum, gum arabic, sodium carboxymethyl cellulose and carrageenan. Lubricating agents are generally used in formulations to reduce friction and ensure the success of pharmaceutical production. Lubricating agents are used, including but not limited to stearate, calcium stearate, sodium stearyl fumarate, sodium lauryl sulfate, talc and colloidal silicon dioxide. Diluting agents are preferably microcrystalline cellulose, pregelatinized starch, starch, carboxymethylcellulose calcium, magnesium aluminum silicate, methylcellulose, lactose monohydrate, dibasic calcium phosphate, microcrystalline cellulose phosphate, hydroxypropyl cellulose, carboxymethylcellulose sodium, crospovidone, low substituted hydroxypropyl cellulose, sodium alginate and silicified In the composition of the invention, tenofovir may be alafenamide or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient may be sodium laruyl sulfate. When sodium lauryl sulfate is used as a lubricating agent, it has better lubricating efficiency than other lubricants in its class, does not cause any deterioration in tablet dissolution and increases stability. By using sodium lauryl sulfate in film-coated tablet formulations, formulations with higher patient benefit have been obtained. The film-coated tablet composition of the invention, in its preferred embodiment, uses tenofovir alafenamide or a pharmaceutically acceptable salt thereof and polyplasdon The composition of the invention may additionally contain one or more active ingredients. The active ingredient added to the composition of the invention may be selected from cobicistat, bictegravir or a pharmaceutically acceptable salt thereof, darunavir or a pharmaceutically acceptable salt thereof, emtricitabine, rilpivirine or a pharmaceutically acceptable salt thereof, or elvitegravir. In a preferred embodiment of the invention, tenofovir may contain emtricitabine in addition to alafenamide or a pharmaceutically acceptable salt thereof. In another embodiment, the invention may include bictegravir sodium and emtricitabine in addition to tenofovir alafenamide or a pharmaceutically acceptable salt thereof. In another embodiment, the invention may include cobicistat, darunavir or a pharmaceutically acceptable salt thereof, and emtricitabine, in addition to tenofovir alafenamide or a pharmaceutically acceptable salt thereof. In another embodiment, the invention may include cobicistat, elvitegravir and emtricitabine in addition to tenofovir alafenamide or its pharmaceutically acceptable salt. In another embodiment, the invention may include emtricitabine and rilpivirine or a pharmaceutically acceptable salt thereof, in addition to tenofovir alafenamide or a pharmaceutically acceptable salt thereof. Bictegravir or its pharmaceutically acceptable salt may be bictegravir sodium as mentioned in the invention. Darunavir or its pharmaceutically acceptable salt as mentioned in the invention may be darunavir ethanolate. Rilpivirine or a pharmaceutically acceptable salt thereof as mentioned in the invention may be rilpivirine hydrochloride. In another aspect, the invention provides a composition for use in the treatment of HIV, AIDS and chronic hepatitis B. EXAMPLES Example 1: Tenofovir Alafenamide Monofumarate Film-Coated Tablet Formulations Component Weight (mg) Active Ingredients Tenofovir Alafenamide 25.00 Monofumarate Excipients Sodium Lauryl Sulfate 22.5 Polyplasdon XL 10 47.50 Dibasic Sodium Phosphate 345.00 Film Coating OPADRY 10.00 Total 45 0.00 Example 2: Tenofovir Alafenamide Monofumarate Film Coated Tablet Formulations Component Weight (mg) Active Ingredients Tenofovir Alafenamide 25.00 Monofumarate Excipients Magnesium Stearate 22.75 Croscarmellose Sodium 35.00 Lactose monohydrate 22.25 Microcrystalline Cellulose 235.00 Film Coating OPADRY® 10.00 Total 350.00 Example 3: Tenof ovir Alafenamide Hemifumarate Film-Coated Tablet Formulations Component Weight (mg) Active Ingredients Tenofovir Alafenamide 25.00 Hemifumarate Excipients Magnesium Stearate 22.75 Croscarmellose Sodium 35.00 Lactose monohydrate 22.25 Microcrystalline Cellulose 235.00 Film Coating OPADRY® 10.00 Total 350.00 Example 4: Tenofovir Alafenamide Hemifumarate Film-Coated Tablet Formulation General Component Weight (mg) Active Ingredients Tenofovir Alafenamide 25.00 Hemifumarate Excipients Sodium Lauryl Sulfate 22.5 Polyplasdon Then, the auxiliary substances are brought together in a separate environment. Finally, the active ingredient mixture and the excipient mixture are homogeneously combined. In the last step, the final formulation is obtained by coating with OPADRY®.TR TR
Claims (1)
Publications (1)
| Publication Number | Publication Date |
|---|---|
| TR2022007368A2 true TR2022007368A2 (en) | 2023-11-21 |
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