TR201605487A1

TR201605487A1 - ANTIULSERATIVE PHARMACEUTICAL COMPOSITIONS

Info

Publication number: TR201605487A1
Application number: TR2016/05487A
Authority: TR
Inventors: Karaağaç Mi̇na
Original assignee: Mina Karaagac
Priority date: 2016-04-27
Filing date: 2016-04-27
Publication date: 2017-11-21

Abstract

Mevcut buluş; Gastro-özofajiyal reflü hastalığının (GÖRH), eroziv reflü özofajitin, nükslerin, iyileşmiş reflü özofajitin, dispepsinin, nefropatik sistinozisin, pirozisin, yüksek asit salgısı ile kendini gösteren mide rahatsızlıklarının (mide yanması, ekşime, şişkinlik, hazımsızlık), uygun bir antibiyotik kombinasyonu ile birlikte Helicobacter pylori eradikasyonunun, Helicobacter pylori ile ilişkili duodenum ülserlerinin, Helicobacter pylori ile ilişkili peptik ülserlerde nükslerin, sürekli NSAİİ (non-steroidal anti-inflamatuvar ilaçlar) tedavisi gereken hastalarda NSAİİ kullanımı ile ilişkili gastrik ülserlerinin, risk altındaki hastalarda NSAİİ kullanımı ile ilişkili gastrik ve duodenal ülserlerinin, Zollinger Ellison Sendromu?nun, gastrik veya duodenal ülserlerde hemostazın kısa süreli sürdürülmesi ve tekrar kanamanın profilaktik, semptomatik veya terapötik tedavisinde kullanılmak üzere proton pompa inhibitörleri grubunda yer alan antiülseratif özellikteki uygun etken maddenin ve/veya farmasötik olarak kabul edilebilir türevlerinin monoterapi olarak tek başına kullanıldığı veya bu etken maddenin diğer uygun aktif ajan/lar ile kombine tedavi olarak kullanıldığı farmasötik bileşim/ler ile ilgilidir.The present invention includes; Gastro-esophageal reflux disease (GERD), erosive reflux esophagitis, relapses, improved reflux esophagitis, dyspepsia, nephropathic cystinosis, pyrosis, gastric disorders manifested by high acid secretion (heartburn, souring, bloating, indigestion) together with Helicobacter pylori eradication, Helicobacter pylori-related duodenal ulcers, Helicobacter pylori-related peptic ulcers, recurrent NSAIDs (non-steroidal antidepressants of the proton pump inhibitors for use in the prophylactic, symptomatic or therapeutic treatment of duodenal ulcers, Zollinger Ellison Syndrome, short-term maintenance of hemostasis in gastric or duodenal ulcers, and re-bleeding The present invention relates to a pharmaceutical composition (s) wherein the active agent and / or pharmaceutically acceptable derivatives thereof having the ulcerative properties are used alone as monotherapy or in combination with other suitable active agents.

Description

TARIFNAME ANTIÜLSERATIF FARMASÖTIK TERKIPLER BULUSUN ILGILI OLDUGU ALAN Mevcut bulus; Gastro-özofajiyal reflü hastaliginin (GÖRH), eroziv reflü özofajitin, nükslerin, iyilesmis reflü özofajitin, dispepsinin, nefropatik sistinozisin, pirozisin, yüksek asit salgisi ile kendini gösteren mide rahatsizliklarinm (mide yanmasi, eksime, siskinlik, haziinsizlik), uygun bir antibiyotik kombinasyoiiu ile birlikte Helicobacter pylori eradikasyonunun, Helicobacter pylori ile iliskili duodenum ülserlerinin, Helicobacter pylori ile iliskili peptik ülserlerde nükslerin, sürekli NSAII (non-steroidal anti-intlamatuvar ilaçlar) tedavisi gereken hastalarda NSAII kullaniini ile iliskili gastrik ülserlerinin, risk altindaki hastalarda NSAII kullanimi ile iliskili gastrik ve duodenal ülserlerinin, Zollinger Ellison Sendromu°nun, gastrik veya duodenal ülserlerde hemostazin kisa süreli sürdürülmesi ve tekrar kanamanin profilaktik, semptomatik veya terapötik tedavisinde kullanilmak üzere proton pompa inhibitörleri grubunda yer alan antiülseratif özellikteki uygun etken maddenin ve/veya farmasötik olarak kabul edilebilir türevlerinin monoterapi olarak tek basina kullanildigi veya bu etken maddenin diger uygun aktif ajan/lar ile kombine tedavi olarak kullanildigi farrnasötik bilesim/ler ile Mevcut bulus; proton pompa inhibitörleri grubunda yer alan uygun antiülseratif özellikteki etkeii maddenin Rabeprazol, (RS)-2-[(4-(3-methoxypropoxy)- 3-methyl-pyridin-2-yl) methylsulfinyl]- lH-benzoimidazole (Formül 1) ve/veya farmasötik olarak kabul edilebilir türevleri oldugu ve uygun farmasötik formlarda monoterapi olarak tek basina kullanildigi veya bu etken maddenin diger uygun aktif ajan/lar ile kombine tedavi olarak kullanildigi farmasötik bilesimler ile ilgilidir. DESCRIPTION ANTIULCERATIVE PHARMACEUTICAL COMPOSITIONS FIELD OF THE INVENTION The present invention; Gastro-esophageal reflux disease (GERD), erosive reflux esophagitis, recurrences, with healed reflux esophagitis, dyspepsia, nephropathic cystinosis, pyrosis, high acid secretion manifested stomach ailments (heartburn, loss of appetite, bloating, unhappiness), Helicobacter pylori eradication with an appropriate antibiotic combination, Helicobacter pylori-associated duodenal ulcers, Helicobacter pylori-associated peptic relapses in ulcers that require continuous NSAID (non-steroidal anti-inflammatory drugs) therapy Gastric ulcers associated with NSAID use in patients, NSAID use in patients at risk of gastric and duodenal ulcers, Zollinger-Ellison Syndrome, gastric or duodenal ulcers, short-term maintenance of hemostasis and prophylactic re-bleeding, proton pump inhibitors for use in symptomatic or therapeutic treatment as the appropriate active substance and/or pharmaceutical with antiulcerative properties in the group acceptable derivatives of this active substance are used alone as monotherapy or with pharmaceutical composition(s) used in combination therapy with other suitable active agent(s) The present invention; Suitable antiulcerative properties in the group of proton pump inhibitors. Rabeprazole, (RS)-2-[(4-(3-methoxypropoxy)-3-methyl-pyridin-2-yl) methylsulfinyl]-1H-benzoimidazole (Formula 1) and/or pharmaceutically acceptable derivatives and used alone as monotherapy in appropriate pharmaceutical forms. or when this active ingredient is used as a combined treatment with other suitable active agent/s relates to pharmaceutical compositions.

Formül I: Ayrica bulus, Rabeprazol ve/veya farrnasötik olarak kabul edilebilir türevlerini tek basina veya bu etken maddeyi diger uygun aktif ajan/lar ile kombinasyon halinde içeren farrnasötik bilesimlerin oral veya parenteral uygulama için uygun olan fonnülasyonlarini ve profilaktik, semptomatik veya terapötik kullanimlarini da kapsamaktadir. ÖNCEKI TEKNIK (TEKNIGIN BILINEN DURUMU) Mide asitinin mideden özefagusa (yemek borusu) kaçmasina reflü denir. Hastaligin gerçek adi Gastro Özofageal Reflü (GÖR) 'dür. Genelde yemek borusundaki bir fitik veya kapakçigin zayifligi reflüye neden olur. Stres, gazli içecekler, çay ve kahve türü içecekler reflüyü arttirir. Formula I: In addition, the invention does not use Rabeprazole and/or its pharmaceutically acceptable derivatives alone. or pharmaceutical containing this active ingredient in combination with other suitable active agent(s) formulations of the compositions suitable for oral or parenteral administration and prophylactic, includes symptomatic or therapeutic uses. PRIOR ART (KNOWN STATE OF THE ART) Reflux is the escape of stomach acid from the stomach to the esophagus (esophagus). The real name of the disease Gastro Esophageal Reflux (GER). Usually a hernia or valve in the esophagus weakness causes reflux. Stress, carbonated drinks, tea and coffee-type drinks increase reflux.

Mide içeriklerinin yemek borusuna dogru geri akisi, yemek borusunun skuamöz epitelyumuna zarar verebilir ve yemek borusu mukozasini, Baret özofagusu ve yemek boiusu karsinomuna yatkin hale getirebilir. Gastrik refluksatin temel kiskirticilari, pepsin ve hidroklorik asittir.Backflow of stomach contents into the esophagus into the squamous epithelium of the esophagus may damage the esophageal mucosa, Baret's esophagus, and esophageal carcinoma of the esophagus. can make it more prone. The main triggers of gastric refluxate are pepsin and hydrochloric acid.

Asit, sodyum bikarbonat ile hizli bir sekilde nötralize olabilir, ancak pepsin, 5“e kadar olan pH°larda aktif kalabilir ve sadece 7”nin üzerindeki pH“larda geri çevrilemez sekilde inhibe olur. Pepsin, peptid baglarinin belirli aminoasitler arasinda bölünmesini katalize eden proteolitik bir enzimdir. Sonuç olarak pepsin, yemek borusu üzerinde sürekli zarar verici bir etkiye sahip olabilir. Acid can be quickly neutralized with sodium bicarbonate, but pepsin is It can remain active at pH° and is only irreversibly inhibited at pH above 7 It is possible. Pepsin catalyzes the cleavage of peptide bonds between certain amino acids. It is a proteolytic enzyme. As a result, pepsin has a persistent damaging effect on the esophagus. may have an effect.

Aslinda gastroözofagial reflü özellikle yemek sonrasindaki dönemlerde ve uykunun REM fazinda (rapid eye movement) olmak üzere gün içinde 10-50 kez kadar olabilen fizyolojik bir olaydir. Fizyolojik gastroözofagial reflü kisa sürdügünden farkina varilmaz veya çok hafif semptomlar olusturabilir. Ancak gastroözofagial reflü gün içinde sik araliklarla tekrarladiginda, uzun sürdügünde ve özellikle uyku sirasinda olustugunda artik patolojik gastroözofagial reflü söz konusudur ki bu tablo genellikle özefagus mukozasinda degisik derecelerde olabilen hasarlanma ve çesitli semptomlarla birliktedir. In fact, gastroesophageal reflux, especially in the postprandial periods and REM sleep It is a physiological condition that can occur up to 10-50 times a day, especially in the phase (rapid eye movement). is an event. Physiological gastroesophageal reflux may not be noticed or very mild because it lasts for a short time. may cause symptoms. However, gastroesophageal reflux occurs frequently during the day. When it recurs, lasts for a long time and especially occurs during sleep, it is no longer pathological. there is gastroesophageal reflux, which is usually different in the esophageal mucosa. It is associated with various degrees of damage and symptoms.

Bu durumda gastroözofagial reflü hastaligindan bahsedilir, Özefagusda endoskopik ve/veya histopatolojik yöntemlerle saptanabilen bir hasarlanmanin varligi ise reflü özofajiti olarak adlandirilir. In this case, gastroesophageal reflux disease is mentioned. Endoscopic and/or The presence of damage that can be detected by histopathological methods is called reflux esophagitis. is named.

Yemek borusundaki geri akis az miktarda mide suyunun, yiyecek ve/veya safra asidinin yemek borusunun alçak bölüinlerine girmesi ile ortaya çikmakta ve kendisini mide eksimesi seklinde gösterebilen agri ile birlikte olusan yemek borusu iltihabina neden olmaktadir. The reflux in the esophagus results in a small amount of gastric juice, food, and/or bile acid. It occurs when it enters the lower parts of the esophagus and causes stomach upset. It causes inflammation of the esophagus, which occurs together with pain, which can show in the form of pain.

Tedavide en çok tercih edilen ilaçlar antiasitler, aljinik asit içeren ilaçlar, H2 Reseptörleri ve proton pompasi inhibitörleridir. Ileri durumlarda cerrahi tedavi tercih edilebilir. The most preferred drugs in treatment are antacids, drugs containing alginic acid, H2 Receptors and are proton pump inhibitors. In advanced cases, surgical treatment may be preferred.

Rabeprazol sodyum, diger anti-sekretuar ilaçlarla kiyaslandiginda proton pompasi inhibitörlerinin daha hizli cevap verdigi, gastrik asit salgilamasini etkili ve sürekli biçimde inhibe edebilen bir proton pompasi inhibitörüdür. Proton pompasi inhibitörleri, midede proton pompasi olarak bilinen bir sistemi (Hidrojen-Potasyum adenozin trifosfat enzim sistemi) kapatarak ve mide asidi üretimini engelleyerek is görürler. Rabeprazole sodium has a proton pump boost compared to other anti-secretory drugs. It effectively and continuously stimulates gastric acid secretion, to which inhibitors respond more rapidly. It is a proton pump inhibitor. Proton pump inhibitors, proton in the stomach a system known as a pump (Hydrogen-Potassium adenosine triphosphate enzyme system) They work by shutting down and inhibiting the production of stomach acid.

Proton pompa inhibitörlerinin klinik deneylerde mide ülseri, onikiparmak bagirsagi ülseri, yemek borusu geri akisi ve yemek borusu olmadan gastro yemek borusu geri akisi ile ilgili hazimsizlik rahatsizligi olan hastalarda semptomlarin giderilmesinde etkili oldugu kanitlanmistir. In clinical trials of proton pump inhibitors, gastric ulcer, duodenal ulcer, pertaining to gastro-esophageal reflux with and without esophageal reflux It is effective in relieving symptoms in patients with indigestion. has been proven.

Mide asidi bastirici özellikteki proton pompa inhibitörlerinin asit ortaminda kararsiz bir yapiya sahip olmasi büyük ölçüde asidik bir ortam olan mide içerigine temas ederek parçalanmasina neden olur, bu yüzden oral yoldan uygulamaya yönelik farmasötik bilesimlerin gelistirilmesi gerekmektedir. Bundan yola çikarak; etken maddenin midedeki gastrik asitten dolayi bozulmasini önlemek ve ince bagirsagm yakin bölümünde serbest kalmasini saglamak için bilesim bir enterik kaplama ile kaplanabilir. bahsetmektedir. Proton pump inhibitors with gastric acid suppressing properties are unstable in the acid environment. having a structure by contacting the stomach contents, which is a highly acidic environment causes degradation, therefore pharmaceuticals for oral administration compositions need to be developed. Based on this; active ingredient in stomach to prevent deterioration due to gastric acid and free in the near part of the small intestine. The composition may be coated with an enteric coating to ensure retention. is talking about.

WO9601624 numarali patent basvurusunda, Rabeprazol gibi asitte bozulan H+K+ATPase inhibitörü veya bunlarin alkalin tuzlarini içeren çoklu ünite tablet dozajlarinin tarif edildigi farmasötik forrnülasyonlardan bahsetmektedir. In the patent application number WO9601624, acid degraded H+K+ATPase like Rabeprazole where dosages of multiple unit tablets containing the inhibitor or alkaline salts thereof are described. refers to pharmaceutical formulations.

Rabeprazol için oral dozaj biçimlerinden bahsedilmektedir.Oral dosage forms for rabeprazole are mentioned.

BULUSUN AÇIKLAMASI Mevcut bulus; Gastro-özofajiyal reflü hastaliginin (GÖRH), eroziv reflü özofajitin, nükslerin, iyilesmis reflü özofajitin, dispepsinin, nefropatik sistinozisin, pirozisin, yüksek asit salgisi ile kendini gösteren mide rahatsizliklarinin (mide yanmasi, eksime, siskinlik, hazimsizlik), uygun bir aiitibiyotik kombinasyonu ile birlikte Helicobacter pylori eradikasyonunun, Helicobacter pylori ile iliskili duodenum ülserlerinin, Helicobacter pylori ile iliskili peptik ülserlerde nükslerin, sürekli NSAII (non-steroidal anti-inflamatuvar ilaçlar) tedavisi gereken hastalarda NSAII kullanimi ile iliskili gastrik ülserlerinin, risk altindaki hastalarda NSAII kullanimi ile iliskili gastrik ve duodenal ülserlerinin, Zollinger Ellison Sendromu'nun, gastrik veya duodenal ülserlerde hemostazin kisa süreli sürdürülmesi ve tekrar kanamanin profilaktik, semptomatik veya terapötik tedavisinde kullanilmak üzere proton pompa inhibitörleri grubunda yer alan antiülseratif özellikteki uygun etken maddenin ve/veya farmasötik olarak kabul edilebilir türevlerinin monoterapi olarak tek basina kullanildigi veya bu etken maddenin diger uygun aktif ajan/lar ile kombine tedavi olarak kullanildigi farmasötik bilesim/ler ile Mevcut bulusun bir diger yönü oral kullanilmak üzere proton pompa inhibitörleri grubunda yer alan antiülseratif özellikteki uygun etken maddenin ve/veya farmasötik olarak kabul edilebilir türevlerinin monoterapi olarak tek basina kullanildigi veya bu etken maddenin diger uygun aktif ajan/lar ile kombine tedavi olarak kullanildigi farmasötik bilesimler ile ilgilidir. DESCRIPTION OF THE INVENTION The present invention; Gastro-esophageal reflux disease (GERD), erosive reflux esophagitis, recurrences, with healed reflux esophagitis, dyspepsia, nephropathic cystinosis, pyrosis, high acid secretion manifested stomach disorders (heartburn, loss of appetite, bloating, indigestion), Helicobacter pylori eradication with an appropriate combination of antibiotics, Helicobacter pylori-associated duodenal ulcers, Helicobacter pylori-associated peptic relapses in ulcers that require continuous NSAID (non-steroidal anti-inflammatory drugs) therapy gastric ulcers associated with NSAID use in patients gastric and duodenal ulcers, Zollinger Ellison Syndrome, gastric or duodenal ulcers, short-term maintenance of hemostasis and prophylactic re-bleeding, proton pump inhibitors for use in symptomatic or therapeutic treatment as the appropriate active substance and/or pharmaceutical with antiulcerative properties in the group acceptable derivatives of this active substance are used alone as monotherapy or with pharmaceutical composition(s) used in combination therapy with other suitable active agent(s) Another aspect of the present invention is in the group of proton pump inhibitors for oral use. of the appropriate active substance with antiulcerative properties and/or pharmaceutical acceptance. that its derivatives are used alone as monotherapy or that this active substance is used in other It relates to pharmaceutical compositions where it is used as a combined treatment with appropriate active agent/s.

Bulusta proton pompa inhibitörleri grubunda yer alan antiülseratif özellikteki uygun etkeii madde, bunlarla sinirli olmamakla birlikte, omeprazol, lansoprazol, pantoprazol, esomeprazol, timoprazol, lemiiioprazol, rabeprazol ve/veya farmasötik olarak kabul edilebilir türevlerinin arasindan tercihen Rabeprazol sodyum olarak seçilir. Appropriate antiulcerative effect in the group of proton pump inhibitors in the invention substance, including, but not limited to, omeprazole, lansoprazole, pantoprazole, esomeprazole, timoprazole, lemiiioprazole, rabeprazole and/or pharmaceutically acceptable derivatives Among them, preferably Rabeprazole is selected as sodium.

Bulusta “farmasötik olarak kabul edilebilir türevleri” terimi ile farmasötik olarak kabul edilebilir uygun tuzlar, esterler, solvatlar, hidratlar, kompleksler, polimorflar, enantiyomerler, önilaçlar, asit adisyon tuzlari, analoglar, izomerler, rasematlar, amidler, enantiyomer tuzlari, bazik tuzlar, konjugeler, tautomerler, anhidratlar, anhidritler, bazlar, asitler, eterler, kristal ve amorf formlar veya serbest formlarindan bir veya daha fazlasi ifade edilmektedir. In the invention, the term "pharmaceutically acceptable derivatives" is defined as pharmaceutically acceptable. Suitable salts, esters, solvates, hydrates, complexes, polymorphs, enantiomers, prodrugs, acid addition salts, analogs, isomers, racemates, amides, enantiomer salts, basic salts, conjugates, tautomers, anhydrates, anhydrides, bases, acids, ethers, crystal and amorphous forms or one or more of their free forms are meant.

Oral uygulama için hazirlanan farmasötik bilesim/ler kati ya da sivi dozaj formlarinda olabilir. Bu dozaj formlari; tablet (çignenebilir tablet, agizda çözünen tablet, dagilabilen tablet, suda dagilabilen tablet, film kapli tablet, barsakta açilan kaplamali (enterik) tablet, mini tablet, kontrollü salimli tablet (Sürekli salimli tablet, hemen salimli tablet, uzatilmis salimli tablet, geciktirilmis salimli tablet vb.), kapsül (sert, yumusak, enterik kapli, film kapli), kontrollü salimli kapsül (sürekli salimli kapsül, hemen salimli kapsül, uzatilmis salimli kapsül, geciktirilmis salimli kapsül), toz, granül, kaplet, disk, agizda çözünen film, yigin toz (çok dozlu), pellet, sase, suda dagilabilen toz, suda dagilabilen granül, efervesan tablet, efervesan granül, efervesan toz, jelül, pilül, surup, solüsyon, süspansiyon, eliksir, damla, posyon, emülsiyon veya sprey gibi bir dozaj sekli halinde formüle edilebilir.Pharmaceutical composition/s prepared for oral administration in solid or liquid dosage forms it could be. These dosage forms are; tablet (chewable tablet, mouth soluble tablet, dispersible tablet, dispersible tablet, film-coated tablet, coated (enteric) tablet that opens in the intestine, mini tablet, controlled-release tablet (sustained-release tablet, immediate-release tablet, extended-release tablet tablet, delayed-release tablet, etc.), capsule (hard, soft, enteric-coated, film-coated), controlled-release capsule (sustained-release capsule, immediate-release capsule, extended-release capsule capsule, delayed-release capsule), powder, granule, caplet, disc, oral film, bulk powder (multi-dose), pellet, sachet, water-dispersible powder, water-dispersible granule, effervescent tablet, effervescent granule, effervescent powder, gel, pill, syrup, solution, suspension, elixir, drops, may be formulated in a dosage form, such as a post, emulsion, or spray.

Bulusta kulla006Eilan oral farrnasötik enterik kapli tablet forrnülasyonu, uygun etken madde/ler yaninda en az bir dagitici madde, en az bir seyreltici/dolgu maddesi, en az bir alkalilestirici ajaii, en az bir baglayici madde, en az bir, en az bir lubrikant, en az bir seal/ara kaplama ajani, en az bir enterik kaplama ajani ve granülasyon sivisinin da dahil oldugu gruptan seçilen bir veya daha fazla yardimci madde içerebilen bir bilesimi tanimlar. Oral pharmaceutical enteric-coated tablet formulation used in the invention, suitable agent substance(s) as well as at least one dispersant, at least one diluent/filler, at least one alkalizing ajaii, at least one binder, at least one, at least one lubricant, at least one seal/intermediate coating agent, including at least one enteric coating agent and granulation fluid. defines a composition that may contain one or more excipients selected from the group.

Bulusta “dagitici madde” terimi, dozaj formunun su içinde kolay ve hizli bir sekilde dagilmasini saglayan maddeler olarak ifade edilmektedir. Dagitici madde olarak; agar agar, kalsiyum karbonat, sodyum karbonat, aljinik asit, patates nisastasi, misir nisastasi, bugday nisastasi, prejelatinize nisasta, sodyum nisasta glikolat gibi nisastalar, mikrokristalin selüloz, çapraz-bagli polivinil pirolidon, sodyum aljinat, hidroksipropil selüloz, düsük sübstitue hidroksipropil selüloz, çapraz bagli hidroksipropil selüloz, kroskarmelloz sodyum, kil, iyon degistirici reçine, krospovidon, ksilitol, D-sorbitol, D-mannitol, laktoz, sükroz, üre, yüksek molekül agirlikli polimerler, povidon, aljinik asit, ksantan zamki, kolloidal silikon dioksit veya bunlarin karisimlari kullanilabilir. Bulusta tercihen sodyum nisasta glikolat ve/veya düsük sübstitue hidroksipropil selüloz kullanilmaktadir. Bulusta kullanilan dagitici madde miktari %0.1-40 agirlik oranindadir. In the invention, the term "dispersant" means that the dosage form can be easily and quickly dissolved in water. It is expressed as substances that allow it to disperse. As a dispersant; agar agar, calcium carbonate, sodium carbonate, alginic acid, potato starch, corn starch, wheat starch, pregelatinized starch, starches such as sodium starch glycolate, microcrystalline cellulose, cross-linked polyvinyl pyrrolidone, sodium alginate, hydroxypropyl cellulose, low substitute hydroxypropyl cellulose, cross-linked hydroxypropyl cellulose, croscarmellose sodium, clay, ion modifier resin, crospovidone, xylitol, D-sorbitol, D-mannitol, lactose, sucrose, urea, high molecular weight polymers, povidone, alginic acid, xanthan gum, colloidal silicon dioxide or mixtures of these can be used. In the invention preferably sodium starch glycolate and/or low substituted hydroxypropyl cellulose is used. The dispersant used in the invention the amount is 0.1-40% by weight.

Bulusta “seyreltici/dolgu maddesi” terimi; tablet ya da kapsüllerin üretim için pratik, hasta kullaniinina uygun büyüklükte olmasi için kullanilan madde veya madde karisimlari olarak ifade edilmektedir. Seyreltici/dolgu maddesi olarak; talk, laktoz, sukroz, dekstrin, mannitol, laktilol, laktitol, ksilitol, sorbitol, izomalt, mikrokristalin selüloz, toz selüloz, dekstroz, dekstrat, prejelatinize nisasta, modifiye nisasta, nisasta, misir nisastasi, laktoz anhidröz, laktoz monohidrat, dibazik kalsiyum fosfat, silisik asit, kaolin, hidroksi propil metilselüloz, tribazik kalsiyum fosfat, polihidrik alkoller veya selüloz eterleri, kalsiyum hidrojen fosfat dihidrat, kalsiyum sülfat trihidrat, selüloz kalsiyum sülfat, kalsiyum sülfat dihidrat, maltodekstrin, kalsiyum karbonat, kaolin, sodyum hidroksit veya bunlarin karisimlari kullanilabilir. Bulusta tercihen mannitol kullanilmaktadir. Bulusta kullanilan seyreltici/dolgu maddesi miktari %0.]- 90 tercihen %5-60 agirlik oranindadir. The term "diluent/filler" in the invention; practical, patient for the production of tablets or capsules as a substance or a mixture of substances used to be in a suitable size for its use is expressed. As a diluent/filler; talc, lactose, sucrose, dextrin, mannitol, lactilol, lactitol, xylitol, sorbitol, isomalt, microcrystalline cellulose, powdered cellulose, dextrose, dextrate, pregelatinized starch, modified starch, starch, corn starch, lactose anhydrous, lactose monohydrate, dibasic calcium phosphate, silicic acid, kaolin, hydroxy propyl methylcellulose, tribasic calcium phosphate, polyhydric alcohols or cellulose ethers, calcium hydrogen phosphate dihydrate, calcium sulfate trihydrate, cellulose calcium sulfate, calcium sulfate dihydrate, maltodextrin, calcium carbonate, kaolin, sodium hydroxide or their mixtures can be used. in the find preferably mannitol is used. The amount of diluent/filler used in the invention is 0%.]- 90% is preferably 5-60% by weight.

Bulusta alkalilestirici ajan olarak; sodyum karbonat, sodyum bikarbonat, sodyum hidroksit, sodyum silikat, primer aminler, sekonder aminler, tersiyer aminler, siklik aminler, kalsiyum gliserofosfat, kalsiyum glukonat, kalsiyum asetat, N,N” dibenziletilendiamin, dietanolamin, etilendiamin, meglümin, disodyum hidrojen ortofosfat, sodyum alüminat, kalsiyum karbonat, kalsiyum hidroksit, magnezyum karbonat, magnezyum hidroksit, magnezyum sülfat, moiiosodyum glutamat, polakrillin sodyum, sodyum al jinat, dibazik kalsiyum fosfat, tribazik kalsiyum fosfat, kalsiyum sülfat, magnezyum asetat, magnezyum silikat, magnezyum alüminat, hafif magnezyum oksit veya bunlarin karisimlari kullanilabilir. Bulusta tercihen hafif magnezyum oksit kullanilmaktadir Bulusta kullanilan alkalilestirici ajan miktari %5-60 tercihen %10-40 agirlik oranindadir. As an alkalizing agent in the invention; sodium carbonate, sodium bicarbonate, sodium hydroxide, sodium silicate, primary amines, secondary amines, tertiary amines, cyclic amines, calcium glycerophosphate, calcium gluconate, calcium acetate, N,N” dibenzylethylenediamine, diethanolamine, ethylenediamine, meglumine, disodium hydrogen orthophosphate, sodium aluminate, calcium carbonate, calcium hydroxide, magnesium carbonate, magnesium hydroxide, magnesium sulfate, moiiosodium glutamate, polakrillin sodium, sodium alginate, dibasic calcium phosphate, tribasic calcium phosphate, calcium sulfate, magnesium acetate, magnesium silicate, magnesium aluminate, light magnesium oxide or mixtures of these can be used. preferably in the invention light magnesium oxide is used. The amount of alkalizing agent used in the invention is 5-60% preferably 10-40% by weight.

Bulusta “baglayici madde” terimi; içerikteki maddeleri bir arada tutmak, tablet, pellet veya granüllerin gerekli olan mekanik güçte formüle edilmesini saglamak ve düsük aktif dozaj birimlerine hacim vermek için kullanilan madde veya madde karisimlari olarak ifade edilir.The term "binding agent" in the invention; keeping the ingredients together, tablets, pellets or ensuring that the granules are formulated with the required mechanical strength and low active dosage. It is expressed as the substance or mixture of substances used to give volume to the units.

Bahsi geçen baglayici madde olarak; prejelatinize misir nisastasi, prejelatinize nisasta, jelatin, niikrokristalin selüloz, selüloz, zamklar, polivinil pirolidon, polimetakrilatlar, sodyuni karboksi metil selüloz, nisasta, parafinler, stearik asit, metil selüloz, etil selüloz, polietilenglikol, karboksi metilselüloz, hidroksi propilselüloz, hidroksi etilselüloz, krospovidon, povidon, kopovidon, hipromelloz veya bunlarin karisimlari kullanilabilir.As the aforementioned binding substance; pregelatinized corn starch, pregelatinized starch, gelatin, nitrocrystalline cellulose, cellulose, gums, polyvinyl pyrrolidone, polymethacrylates, sodium carboxy methyl cellulose, starch, paraffins, stearic acid, methyl cellulose, ethyl cellulose, polyethyleneglycol, carboxy methylcellulose, hydroxy propylcellulose, hydroxy ethylcellulose, crospovidone, povidone, copovidone, hypromellose or their mixtures can be used.

Bulusta tercihen hidroksi propilselüloz kullanilmaktadir. Bulusta kullanilan baglayici madde miktari %0.l-10 tercihen %0.5-5 agirlik oranindadir. Hydroxypropylcellulose is preferably used in the invention. The binder used in the invention the amount is 0.1-10%, preferably 0.5-5% by weight.

Bulusta “lubrikant” terimi, sürtünmeyi azaltan veya engelleyen bir toz karisiminin akis Özelliklerini iyilestiren ajan veya ajan karisimlari olarak ifade edilmektedir. Lubrikant olarak; talk, kalsiyum stearat, magnezyum stearat, alüminyum stearat, polietilen glikol, tristearin, stearik asit, sodyum lauril sülfat, magnezyum lauril sülfat, kolloidal silikon dioksit, stearik asit, sodyum stearil fumarat, polioksietilen glikol, oleik asit, tripalmitil, potasyum oleat, hidrojene bitkisel yaglar, lösin, alanin, glisin, kaprilik asit, gliseril behenat, gliseril palmitostearat, sodyum benzoat, sodyum asetat, fumarik asit, çinko stearat, çinko oleat, çinko palmitat, parafinler, yag alkolleri veya bunlarin karisimlari kullanilabilir. Bulusta tercihen magnezyum stearat kullanilmaktadir. Bulusta kullanilan lubrikant miktari %0.0l-10 agirlik oranindadir. In the invention, the term "lubricant" refers to the flow of a powder mixture that reduces or inhibits friction. It is expressed as agent or agent mixtures that improve its properties. As a lubricant; talc, calcium stearate, magnesium stearate, aluminum stearate, polyethylene glycol, tristearin, stearic acid, sodium lauryl sulfate, magnesium lauryl sulfate, colloidal silicon dioxide, stearic acid, sodium stearyl fumarate, polyoxyethylene glycol, oleic acid, tripalmityl, potassium oleate, hydrogenated vegetable oils, leucine, alanine, glycine, caprylic acid, glyceryl behenate, glyceryl palmitostearate, sodium benzoate, sodium acetate, fumaric acid, zinc stearate, zinc oleate, zinc palmitate, paraffins, fatty alcohols or their mixtures can be used. preferably in the invention magnesium stearate is used. The amount of lubricant used in the invention is 0.0l-10% by weight. is in the ratio.

Bulusta granülasyon sivisi; etanol, gliserin, aseton, propilen glikol, izopropil alkol, saf su, metilen klorür veya bunlarin karisimlari arasindan seçilir. Bulusta tercihen granülasyon sivisi olarak etanol kullanilmaktadir. Granulation fluid in the invention; ethanol, glycerin, acetone, propylene glycol, isopropyl alcohol, purified water, methylene chloride or mixtures thereof. In the invention preferably granulation liquid ethanol is used.

Bulusta kullanilan seal/ara kaplama ajani agirligi 0.01-15 mg olup toplam tablet agirliginin bir plastifiyan, en az bir yapisma Önleyici ajan ve en az bir kaplama sivisinin dahil oldugu gruptan seçilen bir veya daha fazla yardimci madde içerebilen bir bilesimi tanimlar. The weight of the seal/intercoat agent used in the invention is 0.01-15 mg, which is equal to the total tablet weight. a plasticizer, at least one Anti-adhesive agent, and at least one coating liquid. defines a composition that may contain one or more excipients selected from the group.

Bulusta kullanilan enterik kaplama ajani agirligi 0.01-30 mg olup toplam tablet agirliginin plastifiyan, en az bir yapisma önleyici ajan, en az bir opaklastirici/boyar madde ve en az bir kaplama sivisinin da dahil oldugu gruptan seçilen bir veya daha fazla yardimci madde içerebilen bir bilesimi tanimlar. The weight of the enteric coating agent used in the invention is 0.01-30 mg, which is equal to the total tablet weight. plasticizer, at least one anti-adhesive agent, at least one opacifier/colourant and at least one one or more excipients selected from the group that includes the coating liquid Defines a composition that can contain

Filin kaplama polimeri olarak poliVinil alkol-kismen hidrolize, metil selüloz, etil selüloz, hidroksipropil selüloz, hidroksietil selüloz, hidroksipropil metil selüloz, metakrilik asit kopolimeri, polietilen glikol, polietilen oksit, hipromelloz, jelatin veya bunlarin karisimlari arasindan seçilir. Bulusta tercihen film kaplama poliineri olarak hidroksipropil metil selüloz kullanilmaktadir. Bulusta kullanilan film kaplama polimeri miktari %0.0l-lO agirlik oranindadir. PolyVinyl alcohol-partially hydrolyzed, methyl cellulose, ethyl cellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, methacrylic acid copolymer, polyethylene glycol, polyethylene oxide, hypromellose, gelatin or mixtures thereof is chosen among Hydroxypropyl methyl cellulose is preferably used as the film coating polyinner in the invention. is used. The amount of film coating polymer used in the invention is 0.01-10% by weight. is in the ratio.

Enterik kaplama polimeri olarak; etil akrilat ve metakrilik asit kopolimeri, polivinil asetat ftalat, inetakrilik asit kopolimeri, hidroksipropil metil selüloz asetat, dioksi metil selüloz süksinat, karboksi metil etil selüloz, metil akrilat, etilakrilat, metilmetakrilatv etilmetakrilat, akrilik ve metakrilik asit kopolimerleri, hipromelloz ftalat, hipromelloz asetat süksinat, selüloz butirat ftalat, selüloz hidrojen ftalat, selüloz propiyanat ftalat, selüloz asetat ftalatj selüloz asetat trimelitat, jelatin, selak veya bunlarin karisimlari kullanilmaktadir. Bulusta tercihen enterik kaplama poliineri olarak etil akrilat ve metakrilik asit kopolimeri kullanilmaktadir. Bulusta kullanilan enterik kaplama polimeri miktari %0.1-10 agirlik oranindadir. As enteric coating polymer; copolymer of ethyl acrylate and methacrylic acid, polyvinyl acetate phthalate, inethacrylic acid copolymer, hydroxypropyl methyl cellulose acetate, dioxy methyl cellulose succinate, carboxy methyl ethyl cellulose, methyl acrylate, ethylacrylate, methylmethacrylate and ethylmethacrylate, acrylic and methacrylic acid copolymers, hypromellose phthalate, hypromellose acetate succinate, cellulose butyrate phthalate, cellulose hydrogen phthalate, cellulose propyanate phthalate, cellulose acetate phthalate cellulose acetate trimellitate, gelatin, celak or their mixtures are used. in the find copolymer of ethyl acrylate and methacrylic acid, preferably as enteric coating polyinner is used. The amount of enteric coating polymer used in the invention is 0.1-10% by weight. is in the ratio.

Bulusta “plastifiyan” terimi, kompozisyonun esnekligini arttirmak, kirilma riskini azaltmak ve çekirdege adhezyonunu arttirmak için kullanilan madde veya madde karisimlari olarak ifade edilir. Kaplama tabakalarinin esnekligi ve sertligi gibi istenilen mekanik özelliklerin saglanmasi için plastifiyanlar kullanilmaktadir. Böylece kaplanmis farmasötik bilesigin asit direncinin düsmemesi saglanmis olur. Bahsi geçen plastifiyan olarak; polietilen glikol, gliserin, propilen glikol, setil alkol, polisorbat, asetil sitrat, trietilsitrat, asetil trietil sitrat, dibutil sebekat, dibutil tartarat, dibutil maleat, dibutil süksinat, dietil süksinat, arnil oleat, miristil asetat, butil oleat, butil stearat, triasetin, dietilftalat, dibutilftalat, asetillenmis monogliseridler veya bunlarin karisimlari kullanilabilir. Bulusta tercihen propilen glikol (seal/ara kaplamada), trietilsitrat ve/veya polietilen glikol (enterik kaplamada) kullanilmaktadir. Bulusta kullanilan plastifiyan miktari %0.01-5 agirlik oranindadir.In the invention, the term "plasticizer" is used to increase the flexibility of the composition, reduce the risk of breakage and Expressed as a substance or substance mixture used to increase adhesion to the nucleus is done. Desired mechanical properties such as flexibility and hardness of the coating layers Plasticizers are used to provide Thus, the coated pharmaceutical compound acid It is ensured that the resistance does not drop. As the aforementioned plasticizer; polyethylene glycol, glycerin, propylene glycol, cetyl alcohol, polysorbate, acetyl citrate, triethylcitrate, acetyl triethyl citrate, dibutyl sebecate, dibutyl tartrate, dibutyl maleate, dibutyl succinate, diethyl succinate, arnyl oleate, myristyl acetate, butyl oleate, butyl stearate, triacetin, diethylphthalate, dibutylphthalate, acetylated monoglycerides or mixtures thereof may be used. In the invention preferably propylene glycol (in seal/intercoat), triethylcitrate and/or polyethylene glycol (in enteric coating) is used. The amount of plasticizer used in the invention is 0.01-5% by weight.

Bulusta “yapisma önleyici ajan” terimi; kaplama sirasinda pelletlerin birbirine yapismasini, topaklanmasini ya da proses ekipmanlarina tutunmasini önlemek için kullanilan madde veya madde karisimlari olarak ifade edilir. Yapisma önleyici ajan olarak; talk, kolloidal silikon dioksit, magnezyum silikat veya bunlarin karisimlari kullanilabilir. Bulusta tercihen yapisma önleyici ajan olarak talk kullanilmaktadir. Bulusta kullanilan yapisma önleyici ajan miktari Bulusta opaklastirici/boyar madde olarak; bunlarla sinirli kalmamakla birlikte, sari demir oksit, kirmizi demir oksit gibi demir oksit pigmentleri, B-karoten, kirmizi pancar tozu, klorofil, tartrazin, sari portakal, kinolin sarisi, eritrosin, titanyum dioksit pigmentleri, karainel, titanyum dioksit, kalsiyum karbonat, çinko asetat, alüminyum stearat, çinko stearat veya bunlarin karisimlari kullanilabilirBulusta tercihen titanyum dioksit ve/veya sari demir oksit kullanilmaktadir. Bulusta kullanilan opaklastirici/boyar madde miktari %0001-10 agirlik oranindadir. The term "anti-adhesive agent" in the invention; sticking of pellets to each other during coating, substance used to prevent it from clumping or clinging to process equipment, or expressed as substance mixtures. As an anti-adhesive agent; talc, colloidal silicon dioxide, magnesium silicate or mixtures thereof can be used. Preferably adhesion in the invention Talc is used as a preventative agent. The amount of anti-adhesive agent used in the invention As an opacifier/dyer in the invention; while not getting frustrated with these, sari iron oxide, iron oxide pigments such as red iron oxide, B-carotene, red beet powder, chlorophyll, tartrazine, yellow orange, quinoline yellow, erythrosine, titanium dioxide pigments, caramel, titanium dioxide, calcium carbonate, zinc acetate, aluminum stearate, zinc stearate or Mixtures of these can be used in the invention, preferably titanium dioxide and/or yellow iron oxide is used. The amount of opacifier/dyer used in the invention is 0001-10% by weight. is in the ratio.

Bulusta kaplama sivisi; etanol, gliserin, asetoii, propilen glikol, izopropil alkol, saf su, metilen klorür veya bunlarin karisimlari arasindan seçilir. Bulusta tercihen kaplama sivisi olarak etanol ve/veya metilen klorür ve/veya saf su kullanilmaktadir. Coating liquid of the invention; ethanol, glycerin, acetoi, propylene glycol, isopropyl alcohol, purified water, methylene chloride or mixtures thereof. Preferably as a coating liquid in the invention ethanol and/or methylene chloride and/or purified water are used.

Mevcut bulustaki Rabeprazol ve/veya farmasötik olarak kabul edilebilir türevlerinin tek basina veya bu etken maddenin diger uygun aktif ajan/lar kombinasyon halinde kullanildigi farmasötik bilesimleri için uygun olan formülasyonlarina ait günlük doz araligi; 1-120 mg tercihen 10 mg, 20 mg olup hastanin bireysel ihtiyaçlarina ve uzmanin degerlendirrnesine göre ayarlanmaktadir. Rabeprazole and/or pharmaceutically acceptable derivatives of the present invention are the only when this active ingredient is used alone or in combination with other suitable active agent(s) the daily dose range of formulations suitable for pharmaceutical compositions; 1-120mg preferably 10 mg, 20 mg depending on the individual needs of the patient and the judgment of the specialist. is adjusted accordingly.

Bulusta, Rabeprazol ve/veya farmasötik olarak kabul edilebilir türevlerinin kullanildigi farmasötik bilesimlerin oral uygulamasina yönelik bir veya daha fazla kaplama içeren enterik kapli tablet forrnülasyonu asagidakileri içerrnektedir; - yaklasik %1-40 agirlik oraninda Rabeprazol sodyum - yaklasik %0.1-90 agirlik oraninda bir veya daha fazla seyreltici/dolgu maddesi - yaklasik %5-60 agirlik oraninda bir veya daha fazla alkalilestirici ajan - yaklasik %0.l-40 agirlik oraninda bir veya daha fazla dagitici madde - yaklasik %0.l-10 agirlik oraninda bir veya daha fazla baglayici madde - yaklasik %0.01-10 agirlik oraninda bir veya daha fazla lubrikant - yaklasik %0.l-10 agirlik oraninda bir veya daha fazla seal/ara kaplama ajani (bu kaplama, yaklasik %0.01-10 agirlik oraninda bir veya daha fazla film kaplama polimeri, yaklasik bir veya daha fazla yapisma önleyici madde ve kafi miktarlarda bir veya daha fazla kaplama sivisi içermektedir.) - yaklasik %0.l-20 agirlik oraninda bir veya daha fazla enterik kaplama ajani (bu kaplama, yaklasik %0.l-10 agirlik oraninda bir veya daha fazla enterik kaplama polimeri, yaklasik bir veya daha fazla yapisma önleyici madde, yaklasik %0.001-10 agirlik oraninda opaklastirici/boyar madde ve kafi miktarlarda bir veya daha fazla kaplama sivisi içermektedir.) - ve kafi miktarda granülasyon sivisi Bulus esas olarak oral kullanilmak üzere proton pompa inhibitörleri grubunda yer alan antiülseratif özellikteki uygun etken maddeyi ve/veya farmasötik olarak kabul edilebilir türevlerinin monoterapisini veya bu etken maddenin diger uygun aktif ajan/lar ile kombinasyonunu ve farmasötik olarak kabul edilebilir uygun yardimci maddeleri içeren farmasötik bilesim/lerin hazirlanmasi ile ilgilidir. Bulusun farmasötik bilesimlerinin enterik kapli tablet formunda olmasi temeldir. Bu dogrultuda, bir çekirdege yüklenen asit ortami içinde kararsiz olan etken maddeyi içeren, mideye dirençli kaplamayi saglayan bir enterik kaplamaya yer veren, etken maddenin bozunmasini önlemek amaciyla etken maddeyi içeren kisim ile enterik kaplamanin bir veya daha fazla seal/ara tabakayla birbirinden ayrildigi kati farmasötik bilesimlerin hazirlanmasi söz konusudur. Böylece etken maddenin midedeki gastrik asitten dolayi bozunmasinin önlenmesi ve ince bagirsagin yakin bölümünde serbest kalmasi saglanir. Yukarida belirtildigi gibi hazirlanan farmasötik formlar fiziksel ve kimyasal kararlilik açisindan sasirtici sekilde stabil bir davranis sergilemistir.Rabeprazole and/or pharmaceutically acceptable derivatives are used in the invention. enteric containing one or more coatings for oral administration of pharmaceutical compositions The coated tablet formulation includes the following; - approximately 1-40% by weight Rabeprazole sodium - about 0.1-90% by weight of one or more diluents/fillers - about 5-60% by weight of one or more alkalizing agents - one or more dispersants in an approximate 0.1-40% weight ratio - about 0.1-10% by weight of one or more binders - about 0.01-10% by weight of one or more lubricants - about 0.1-10% by weight of one or more seal/intercoat agents (this coating, about 0.01-10% by weight of one or more film coating polymers, approx. one or more anti-adhesive agents and sufficient amounts of one or more coatings includes liquid.) - about 0.1-20% by weight of one or more enteric coating agents (this coating, about 0.1-10% by weight of one or more enteric coating polymers, approx. one or more anti-adhesive agents, approximately 0.001-10% by weight opacifier/dye and one or more coating liquids in sufficient quantities includes.) - and a sufficient amount of granulation fluid The invention mainly belongs to the group of proton pump inhibitors for oral use. appropriate active substance with antiulcerative properties and/or pharmaceutically acceptable monotherapy of its derivatives or with other suitable active agent/s of this active ingredient. combination and suitable pharmaceutically acceptable excipients. relates to the preparation of pharmaceutical composition(s). Enteric pharmaceutical compositions of the invention It is essential that it is in the form of coated tablets. In this direction, the acid medium loaded on a nucleus an enteric substance containing the unstable active ingredient, providing a stomach-resistant coating. containing the active substance in order to prevent the decomposition of the active substance, which includes the coating solid partition where the enteric coating is separated by one or more seals/interlayers preparation of pharmaceutical compositions. Thus, the active substance in the stomach prevention of degradation by gastric acid and free in the proximal part of the small intestine is ensured to remain. Pharmaceutical forms prepared as mentioned above can be physical and chemical In terms of stability, it has surprisingly exhibited a stable behavior.

Bulusun özellikleri asagidakilerle sinirli kalmamak üzere örnekler asagida verilmistir: Rabeprazol ve/veya farmasötik olarak kabul edilebilir türevlerinin kullanildigi farmasötik bilesimlerin oral uygulamasina yönelik bir veya daha fazla kaplama içeren enterik kapli tablet forrnülasyonu asagidakileri içermektedir; - yaklasik %1-40 agirlik oraninda Rabeprazol sodyum - yaklasik %0.1-90 agirlik oraninda mannitol - yaklasik %5-60 agirlik oraninda hafif magnezyum oksit - yaklasik %0.1-40 agirlik oraninda sodyum nisasta glikolat ve/veya düsük sübstitue hidroksipropil - yaklasik %O.l-10 agirlik oraninda hidroksipropil selüloz - yaklasik %0.01-10 agirlik oraninda magnezyum stearat - yaklasik %0.I-10 agirlik oraninda bir veya daha fazla seal/ara kaplama ajani (bu kaplama, yaklasik %0.01-10 agirlik oraninda hidroksipropil metil selüloz, yaklasik %0.0l-5 agirlik oraninda propilen glikol, yaklasik %0.01-8 agirlik oraninda talk ve kafi miktarlarda etanol ve/veya metilen klorür içermektedir.) - yaklasik %0.l-20 agirlik oraninda bir veya daha fazla enterik kaplama ajani (bu kaplama, yaklasik %0.1-10 agirlik oraninda etil akrilat ve metakrilik asit kopolimeri, yaklasik %0.01-5 agirlik oraninda trietilsitrat ve/Veya polietilen glikol, yaklasik %0.01-8 agirlik oraninda talk, yaklasik %0.001-10 agirlik oraninda titanyum dioksit ve/veya sari demir oksit ve kafi miktarlarda etanol ve/Veya saf su içermektedir.) - ve kafi miktarda etanol.Examples of the features of the invention are given below, but not limited to the following: Pharmaceutical use of rabeprazole and/or pharmaceutically acceptable derivatives Enteric-coated tablet containing one or more coatings for oral administration of the compositions Its formulation includes the following; - approximately 1-40% by weight Rabeprazole sodium - approx. 0.1-90% by weight of mannitol - approximately 5-60% by weight of light magnesium oxide - approximately 0.1-40% by weight sodium starch glycolate and/or low substituted hydroxypropyl - approx. 0.1-10% by weight of hydroxypropyl cellulose - approx. 0.01-10% by weight magnesium stearate - one or more seal/intercoat agents in a ratio of about 0.I-10% by weight (this coating approx. 0.01-10 wt% hydroxypropyl methyl cellulose, approx. 0.01-5% wt. propylene glycol, approximately 0.01-8% by weight talc, and sufficient amounts of ethanol and/or methylene chloride.) - about 0.1-20% by weight of one or more enteric coating agents (this coating, ethyl acrylate and methacrylic acid copolymer at a weight ratio of about 0.1-10%, about 0.01-5% by weight by weight triethylcitrate and/or polyethylene glycol, approximately 0.01-8% by weight talc, approximately 0.001-10% by weight of titanium dioxide and/or yellow iron oxide and sufficient amounts of ethanol and/or pure water.) - and a sufficient amount of ethanol.

Rabeprazol ve/Veya farmasötik olarak kabul edilebilir türevlerinin kullanildigi farmasötik bilesimlerin oral uygulamasina yönelik bir veya daha fazla kaplama içeren enterik kapli tablet formülasyonu asagidakileri içermektedir; - yaklasik 1-120 mg Rabeprazol sodyum - yaklasik l-95mg mannitol - yaklasik 0.1-40mg hafif magnezyum oksit - yaklasik 0.1-35mg sodyum nisasta glikolat ve/veya düsük sübstitue hidroksipropil - yaklasik 0.1-15mg hidroksipropil selüloz - yaklasik 0.1-20mg magnezyum stearat - yaklasik 0.01-15mg seal/ara kaplama ajani (bu kaplama, yaklasik 0.1-10mg hidroksipropil metil selüloz, yaklasik 0.01-6mg propilen glikol, yaklasik 0.01-8mg talk ve kafi miktarlarda etanol ve/veya metilen klorür içermektedir.) - yaklasik 0.01-30mg enterik kaplama ajani (bu kaplama, yaklasik 0.1-20mg etil akrilat ve metakrilik asit kopolimeri, yaklasik 0.01-6mg trietilsitrat ve/veya polietilen glikol, yaklasik 0.1-8mg talk, yaklasik 0.01-5mg titanyum dioksit ve/veya sari demir oksit ve kati miktarlarda etanol ve/veya saf su içermektedir.) - ve kafi miktarda etanol. Üretim prosesi: Rabeprazol sodyum, mannitol, hafif magnezyum oksit, hidroksi propil selüloz ve sodyum nisasta glikolat granülatöre yüklenir ve belirli bir süre karistirilir. Hidroksi propil selüloz etanol içinde çözülür, karistirilir, granülasyon çözeltisi elde edilir. Basta hazirlanan karisima eklenir ve yas granülasyon yapilir. Elde edilen bu nemli karisim uygun bir kurutucu içinde, belirli bir kurutma kaybi degerine ulasana kadar kurtulur. Elde edilen granüller ögütülür.Pharmaceutical use of rabeprazole and/or pharmaceutically acceptable derivatives Enteric-coated tablet containing one or more coatings for oral administration of the compositions Its formulation includes the following; - approx. 1-120 mg Rabeprazole sodium - about l-95mg of mannitol - about 0.1-40mg light magnesium oxide - about 0.1-35mg sodium starch glycolate and/or low substituted hydroxypropyl - approx. 0.1-15mg hydroxypropyl cellulose - about 0.1-20mg magnesium stearate - approx. 0.01-15mg seal/intermediate coating agent (this coating is approx. 0.1-10mg hydroxypropyl methyl cellulose, approx. 0.01-6mg propylene glycol, approx. 0.01-8mg talc and in sufficient quantities Contains ethanol and/or methylene chloride.) - about 0.01-30mg of enteric coating agent (this coating contains about 0.1-20mg of ethyl acrylate and methacrylic acid copolymer, ca. 0.01-6mg triethylcitrate and/or polyethylene glycol, approx. 0.1-8mg of talc, approximately 0.01-5mg of titanium dioxide and/or yellow iron oxide and in solid quantities contains ethanol and/or purified water.) - and a sufficient amount of ethanol. Production process: Rabeprazole sodium, mannitol, light magnesium oxide, hydroxypropyl cellulose and sodium The starch glycolate is loaded into the granulator and mixed for a certain time. Hydroxypropyl cellulose Dissolved in ethanol, stirred, granulation solution is obtained. Pre-prepared mix is added and wet granulation is done. This moist mixture obtained is in a suitable dryer, is saved until it reaches a certain drying loss value. The granules obtained are ground.

Hidroksipropil selüloz ve sodyum nisasta glikolat uygun elekten geçirilir ve elde edilen kuru granüllerle uygun karistiriciya yüklenip belirli hizda ve belirli bir süre karistirilir. Daha önceden elenmis magnezyum stearat ekleiiir ve belirli bir süre karistirilir. Elde edilen granüller uygun tablet baski zimbasi ile sikistirilir. Elde edilen çekirdek tabletler uygun seal/ara kaplama ajani ile kaplanir. Daha sonra Seal/ara kaplanmis tabletler enterik kaplama ajani ile kaplanir. Hydroxypropyl cellulose and sodium starch glycolate are sieved through a suitable sieve and the resulting dry granules are loaded into the appropriate mixer and mixed at a certain speed and for a certain time. More pre-sieved magnesium stearate is added and mixed for a certain time. Obtained The granules are compressed with a suitable tablet press. The resulting core tablets are suitable coated with a seal/intercoat agent. Seal/intercoated tablets then enteric coated coated with the agent.

Seal/ara Kaplama Etanol”ün belirli bir kisminin üzerine hidroksipropilmetil selüloz ilave edilir ve çözülür. Etanol”ün kalan kismi üzerine metilen klorür, propilen glikol ve talk ilave edilir ve yüksek hizda karistirilir, Elde edilen iki karisim birlestirilir ve karistirilir. Hazirlanan Seal/ara kaplama çözeltisi ile uygun agirlikta kaplama yapilir. Seal/intermediate Coating Hydroxypropylmethyl cellulose is added to a certain part of the ethanol and is resolved. Methylene chloride, propylene glycol and talc are added to the remaining part of the ethanol and It is mixed at high speed, The two mixtures obtained are combined and mixed. Prepared Seal Coating with appropriate weight is done with the coating solution.

Enterik Kaplama Etanolî'in belirli bir kisminin üzerine etil akrilat ve inetakrilik asit kopolimeri ilave edilir ve yüksek hizda karistirilir. Saf su üzerine polietilen glikol, titanyum dioksit, sari demir oksit ve talkin bir kismi ilave edilir ve yüksek hizda karistirilir. Elde edilen iki karisim birlestirilir ve yüksek hizda karistirilir. Elde edilen karisima talkin bir kismi, trietil sitrat ve etanolün bir kismi ilave edilir ve yüksek hizda karistirilir. Hazirlanan enterik kaplama çözeltisi ile uygun agirlikta kaplama yapilir.Enteric Coating A copolymer of ethyl acrylate and inethacrylic acid is added to a certain portion of the ethanol and mixed at high speed. Polyethylene glycol, titanium dioxide, yellow iron oxide and Some of the talc is added and mixed at high speed. The two mixtures obtained are combined and mixed at high speed. The resulting mixture consists of part of talc, part of triethyl citrate and part of ethanol. part is added and mixed at high speed. Compatible with the prepared enteric coating solution heavy coating is done.

Claims

REQUESTS

. Preparation of pharmaceutical composition/s in which the appropriate active substance with antiulcerative properties and/or its pharmaceutically acceptable derivatives in the group of proton pump inhibitors for oral use are used alone as monotherapy or in which this active substance is used as a combined treatment with other suitable active agent/s.

. It is the pharmaceutical composition/s specified in Claim 1 and its feature is; is to select the appropriate antiulcerative active ingredient in the pump inhibitors group among omeprazole, lansoprazole, pantoprazole, esomeprazole, timoprazole, leminoprazole, rabeprazole and/or pharmaceutically acceptable derivatives.

. It is the pharmaceutical composition/s specified in claim 1 and its feature is; The appropriate antiulcerative active ingredient in the pump inhibitors group is preferably rabeprazole sodium.

. The enteric-coated tablet formulation containing one or more coatings for oral administration of pharmaceutical compositions using rabeprazole and/or pharmaceutically acceptable derivatives comprising: - about 1-40% by weight Rabeprazole sodium - about 0.1-90% by weight of one or more diluents/fillers - about 5-60% by weight of one or more alkalizing agents - about 0%. 1-40 weight percent one or more dispersants - about 0.1-10 weight percent one or more binders - about 0.01-10 weight percent one or more lubricants - about 0.1-10 weight percent one or more seal/intercoat agent (approximately 0.01-10% by weight one or more film coating polymers, approximately 0.01-5% by weight one or more plasticizers, approximately 0.01-8% by weight one or more adhesions) inhibitor and sufficient amounts of one or more coating fluids.) - about 0.1-20% by weight of one or more enteric coating agents (this coating is approximately 0.1-10% by weight of one or more enteric coating polymers, about 0.01-5% by weight of one or more plasticizers, about 0.01-8% by weight of one or more anti-adhesive agents, about 0.001% to 10% by weight of opaclasts/dyes and in sufficient quantities one or more powders contains plasma fluid.) - and sufficient amount of granulation fluid

. The enteric-coated tablet formulation containing one or more coatings for oral administration of pharmaceutical compositions using rabeprazole and/or pharmaceutically acceptable derivatives comprising: - ca. 1% -40 wt% Rabeprazole sodium - approx. 0%.] -90 wt.% mannitol - ca. 5-60 wt.% light magnesium oxide - approx. 0.1-4% by weight sodium starch glycolate and/or low substituted hydroxypropyl - approximately 0.1-10% by weight hydroxypropyl cellulose - approximately 0.01-10% by weight magnesium stearate - approximately 0.1-10% by weight one or more seal/intercoat agents (this coating is approximately 0.01-10% by weight hydroxypropyl Contains methyl cellulose, approx. amounts of ethanol and/or methylene chloride.) - one or more enteric coating agents in approx. 0.1-20 wt% (this coating is a copolymer of ethyl acrylate and methacrylic acid in approx. 0.1-10 wt.%) , contains approximately 0.01-5% by weight of triethylcitrate and/or polyethylene glycol, approximately 0.01-8% by weight of talc, approximately 0.001-10% by weight of titanium dioxide and/or yellow iron oxide and sufficient amounts of ethanol and/or purified water. attached.) - and a sufficient amount of ethanol.

. It is the pharmaceutical composition/s specified in claim 4 and its feature is; dispersant material: starches such as agar agar, calcium carbonate, sodium carbonate, alginic acid, potato starch, corn starch, wheat starch, pregelatinized starch, sodium starch glycolate, microcrystalline cellulose, cross-linked polyvinyl pyrrolidone, sodium alginyl pyrrolidone, hydroxypropyl hydroxypropyl cellulose, sodium alginate, hydroxypropylene cellulose, cross-linked hydroxypropyl cellulose, croscarmellose sodium, clay, ion exchange resin, crospovidone, xylitol, D-sorbitol, D-mannitol, lactose, sucrose, urea, high molecular weight polymers, povidone, alginic acid, xanthan gum, colloidal silicone gum or their selection from among their mixtures.

It is the pharmaceutical composition/s specified in claim 6 and its feature is; the dispersant is preferably sodium starch glycolate and/or low substituted hydroxypropyl cellulose.

It is the pharmaceutical composition/s specified in Claim 4 and its feature is; talc, lactose, sucrose, dextrin, mannitol, lactilol, lactitol, xylitol, sorbitol, isomalt, nicrocrystalline cellulose, powdered cellulose, dextrose, dextrate, pregelatinized starch, modified starch, monohydrate starch, corn starch, corn starch , dibasic calcium phosphate, silicic acid, kaolin, hydroxy propyl methylcellulose, tribasic calcium phosphate, polyhydric alcohols or cellulose ethers, calcium hydrogen phosphate dihydrate, calcium sulfate trihydrate, cellulose calcium sulfate, calcium sulfate dihydrate, maltodextrin, calcium carbonate, kaolin, sodium hydroxide or their selection from among their mixtures.

It is the pharmaceutical composition/s specified in Claim 8 and its feature is; the diluent/filler is preferably mannitol.

It is the pharmaceutical composition/s specified in Claim 47 and its feature is; Sodium carbonate, sodium bicarbonate, sodium hydroxide, sodium silicate, primary amines, secondary amines, tertiary amines, cyclic amines, calcium glycerophosphate, calcium gluconate, calcium acetate, N,N` dibenzylethylenediamine, diethanolamine, ethylenediaine, meglutinine, disodium disodium of the alkalizing agent , sodium aluminate, calcium carbonate, calcium hydroxide, magnesium carbonate, magnesium hydroxide, magnesium sulfate, monosodium glutamate, polakrillin sodium, sodium alginate, dibasic calcium phosphate, tribasic calcium phosphate, calcium sulfate, magnesium acetate, magnesium silicate, magnesium aluminate, light magnesium oxide or their mixtures.

It is the pharmaceutical composition/s specified in Claim 10 and its feature is; preferably the alkalizing agent is light magnesium oxide.

. It is the pharmaceutical composition/s specified in Claim 49 and its feature is; binder pregelatinized corn starch, pregelatinized starch, gelatin, microcrystalline cellulose, cellulose, gums, polyvinyl pyrrolidone, polymethacrylates, sodium carboxy methyl cellulose, starch, paraffins, stearic acid, methyl cellulose, methyl cellulose, ethyl cellulose, polyethyleneglycol, carboxylic ethylcellulose, ethylcellulose, crospovidone, povidone, copovidone, hypromellose or mixtures thereof.

13. It is the pharmaceutical composition/s specified in claim 12 and its feature is; preferably the binder is hydroxypropylcellulose.

14. It is the pharmaceutical composition/s specified in claim 4 and its feature is; lubricant talc, calcium stearate; magnesium stearate, aluminum stearate, polyethylene glycol, tristearin, stearic acid, sodium lauryl sulfate; magnesium lauryl sulfate, colloidal silicon dioxide, stearic acid; sodium stearyl fumarate; polyoxyethylene glycol, oleic acid, tripalmityl, potassium oleate, hydrogenated vegetable oils, leucine, alanine, glycine, caprylic acid, glyceryl behenate, glyceryl palmitostearate, sodium benzoate; sodium acetate, fumaric acid, zinc stearate, zinc oleate, zinc palinitate, paraffins, fatty alcohols or mixtures thereof.

It is the pharmaceutical composition/s specified in Claim 14 and its feature is; the lubricant is preferably magnesium stearate.

It is the pharmaceutical composition/s specified in Claim 4 and its feature is; granulation fluid is selected from ethanol, glycerine, acetone, propylene glycol, isopropyl alcohol, purified water, methylene chloride or mixtures thereof.

It is the pharmaceutical composition/s specified in Claim 167 and its feature is; the granulation liquid is preferably ethanol.

It is the pharmaceutical composition/s specified in Claim 4 and its feature is; The film coating polymer is selected from polyvinyl alcohol-partially hydrolyzed, inethyl cellulose, ethyl cellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, methacrylic acid copolymer, polyethylene glycol, polyethylene oxide, hypromellose, gelatin or mixtures thereof.

It is the pharmaceutical composition/s specified in Claim 18 and its feature is; preferably the film coating polymer is hydroxypropyl methyl cellulose.

It is the pharmaceutical composition/s specified in Claim 4 and its feature is; ethyl acrylate and methacrylic acid copolymer of enteric coating polymer, polyvinyl acetate phthalate; methacrylic acid copolymer, hydroxypropyl methyl cellulose acetate, dioxy methyl cellulose succinate; carboxy methyl ethyl cellulose, methyl acrylate, ethylacrylate, methylmethacrylate, ethylmethacrylate; acrylic and methacrylic acid copolymers, hypromellose phthalate, hypromellose acetate succinate, cellulose butyrate phthalate, cellulose hydrogen phthalate; cellulose propyanate phthalate, cellulose acetate phthalate, cellulose acetate trimellitate, gelatin; It is to choose from among selak or their mixtures.

21. It is the pharmaceutical composition/s specified in claim 20 and its feature is; preferably the enteric coating polymer is a copolyiner of ethyl acrylate and inethacrylic acid.

22. It is the pharmaceutical composition/s specified in Claim 47 and its feature is; plastifiyanin polyethylene glycol, glycerine, propylene glycol, cetyl alcohol, polysorbate, acetyl citrate, triethylcitrate, acetyl triethyl citrate, dibutyl sebecate, dibutyl tartrate, dibutyl maleate, dibutyl succinate, diethyl succinate, amyl oleate, myristylate, butyl acetate, butyl oleate triacetin is selected from diethylphthalate, dibutylphthalate, acetylated monoglycerides or mixtures thereof.

23. It is the pharmaceutical composition/s specified in Claim 22 and its feature is; preferably propylene glycol (in seal/intercoat), triethylcitrate and/or polyethylene glycol (in enteric coating).

24. It is the pharmaceutical composition/s as specified in claim 4, and its feature is that the anti-adhesive agent is selected from among talc, colloidal silicon dioxide, magnesium silicate or mixtures thereof.

25. It is the pharmaceutical composition/s specified in claim 24 and its feature is; preferably the anti-adhesive agent is talc.

26. It is the pharmaceutical composition/s specified in claim 4 and its feature is; opacifying/dyestuffs, including but not limited to, iron oxide pigments such as yellow iron oxide, red iron oxide, ß-carotene, red beet powder, chlorophyll, tartrazine, yellow orange, quinoline yellow, erythrosine, titanium dioxide pigments, caramel, titanium dioxide, Calcium carbonate, zinc acetate, aluminum stearate, zinc stearate or mixtures thereof.

27. It is the pharmaceutical composition/s specified in the request 26° and its feature is; preferably titanium dioxide and/or yellow iron oxide.

28. It is the pharmaceutical composition/s specified in claim 4 and its feature is; coating liquid is selected from ethanol, glycerin, acetone, propylene glycol, isopropyl alcohol, purified water, methylene chloride or mixtures thereof.

29. It is the pharmaceutical composition/s specified in claim 28 and its feature is; the coating liquid is preferably ethanol and/or methylene chloride and/or purified water.

30. It is a pharmaceutical composition/s according to any one of the above-mentioned claims and its feature is; The dose range of formulations suitable for pharmaceutical compositions where rabeprazole and/or pharmaceutically acceptable derivatives are used alone or in combination with other suitable active agent/s is 1-120 mg. It is a pharmaceutical composition/s according to any of the above-mentioned claims and its feature is; Gastro-oesophageal reflux disease (GERD), erosive-refluxed esophagitis, relapses, improved reflux Esophagitis, dyspepsia, nephropathic cystinosis, pyrosis, stomach ailments manifested by high acid secretion (heartburn, vomiting, bloating), a combination of antibiotics, indigestion Concomitant use of Helicobacter pylori eradication, Helicobacter pylori-associated duodenal ulcers, relapses in Helicobacter pylori-associated peptic ulcers, gastric ulcers associated with NSAID use in patients requiring continuous NSAID (non-steroidal anti-inflammatory drugs) therapy, and gastric ulcers associated with NSAID use in patients at risk It is indicated for the prophylactic, symptomatic or therapeutic treatment of duodenal ulcers, Zollinger Ellison Syndrome, short-term maintenance of hemostasis in gastric or duodenal ulcers and rebleeding.