TR201511176A2 - ANTIULSERATIVE PHARMACEUTICAL COMPOSITIONS - Google Patents

Abstract

The present invention; Gastro-oesophageal reflux disease (GERD), erosive reflux esophagitis, relapses, healed reflux esophagitis, dyspepsia, nephropathic cystinosis, pyrosis, stomach ailments (heartburn, heartburn, bloating, indigestion) manifested by high acid secretion, with an appropriate antibiotic combination. Helicobacter pylori eradication, Helicobacter pylori associated duodenal ulcers, Helicobacter pylori associated peptic ulcers recurrence, continuous NSAID (non-steroidal anti-inflammatory drugs) treatment in patients requiring NSAID use associated gastric ulcers associated with NSAID use in patients at risk Duodenal ulcers, Zollinger-Ellison Syndrome, gastric or duodenal ulcers, gastric or duodenal ulcers for the short-term maintenance of hemostasis and proton pump inhibitors in the group of proton pump inhibitors for use in the prophylactic, symptomatic or therapeutic treatment of recurrent bleeding. relates to pharmaceutical composition (s) in which acceptable derivatives are used alone as monotherapy or in combination therapy with other suitable active agent (s).

Description

DESCRIPTION ANTIULCERATIVE PHARMACEUTICAL COMPOSITIONS FIELD OF THE INVENTION The present invention; Gastro-esophageal reflux disease (GERD), erosive relapse 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 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 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. active ingredient Dexrabeprazole, (RS)-2-[(4-(3-methoxypropoxy)-3-methyl-pyridin-2-yl) methylsulfinyl]-1H-benzoimidazole (Formula I) and/or pharmaceutically acceptable derivatives and used alone as monotherapy in appropriate pharmaceutical forms. or when this active substance is used as a combined treatment with other suitable active agent/s relates to pharmaceutical composition(s).

FormulaI: In addition, the invention does not use Dexrabeprazole and/or its pharmaceutically acceptable derivatives alone. or pharmaceutical containing this active ingredient in combination with other suitable active agent(s) formulations of the compounds 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.

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. can make it more prone. The main triggers of gastric refluxate are pepsin and hydrochloric acid.

Acid can be quickly neutralized with sodium bicarbonate, but pepsin up to 5" It can remain active at pH° and is only irreversibly inhibited at pH above 77. 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.

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.

In this case, gastroesophageal reflux disease is mentioned. Endoscopic and/or esophageal The presence of damage that can be detected by histopathological methods is called reflux esophagitis. is named.

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.

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.

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 closing the stomach and preventing the production of stomach acid.

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.

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 decomposes, 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 proximal part of the small intestine. The composition may be coated with an enteric coating to ensure retention. is talking about.

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.

Oral dosage forms for rabeprazole are mentioned.

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 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 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 the pharmaceutical composition(s) used as a combined treatment with the appropriate active agent/s.

Appropriate antiulcerative agent in the group of proton pump inhibitors in the invention substance, including, but not limited to, omeprazole, lansoprazole, pantoprazole, esomeprazole, timoprazole, leminoprazole, rabeprazole, dexrabeprazole and/or pharmaceutically acceptable preferably dexrabeprazole sodium is selected from among its derivatives.

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.

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.

The pharmaceutical formulation of the invention may contain one or more layers. Sufficient therapeutic control the release of the drug in order to ensure the effect and minimize the side effects. alternating, controlled, extended, continuous, immediate or delayed layers to provide A release pharmaceutical may be formulated with one or more of the dosage forms.

In delayed release systems, the release of the active substance from the system is in a certain region. is happening. It is generally used for enteric coated tablets.

To increase the stability of enteric coating formulation, to prevent acid-induced degradation It is expressed as the substance or substance mixture used for These enteric coatings before it starts to decompose, it resists stomach acid and at the same time, it It provides a slow drug release in the upper part of the small intestine or in the upper part of the small intestine.

The oral pharmaceutical dual-acting modified-release capsule and/or tablet of the present invention formulation; suitable pharmaceutically acceptable active ingredients as well as binder agent, dispersant, filler, buffering agent, surfactant, lubricant, glidant, diluent, preservative, flavoring agent, sweetening agent, viscosity enhancer agent, antifoaming agent, solubility enhancing agent, antistatic agent, wetting agent, pH setting agent, coloring agent, coating agent, solvent, softening agent, emulsifier, carrier, permeability agent, antioxidant, chelating agent, alkalizing agent, photoprotective agent, thickening agent, isotonia adjusting agent, gelling agent, microbial preservative, hardening agent, sivag, release controlling agent, plasticizer, antiadherent, film-forming agent, opacifying agent, wetting agent, granulation solvent and which may contain one or more excipients selected from the group consisting of a stabilizer. defines the composition.

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. expressed as substances or mixtures of substances used to give volume to units of is being done. As a binding agent; pregelatinized corn starch, pregelatinized starch, hydroxypropyl starch, gelatin, microcrystalline cellulose, cellulose, gums, polyvinyl pyrrolidone, polymethacrylates, sodium carboxymethyl cellulose, starch, paraffins, stearic acid, zainks, methyl cellulose, ethyl cellulose, polyethyleneglycol, magnesium aluminum silicate, carboxy methylcellulose, hydroxy propylcellulose, hydroxy ethylcellulose, propylene glycol, polyoxyethylene- polypropylene copolymer, polyethylene ester, polyethylene sorbitan ester, polyethylene oxide, polysaccharides, polaxamers, alginic acids, collagen, albumin, crospovidone, povidone, Copovidone, maltodextrin, hypromellose or mixtures of these can be used.

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, 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 silicon dioxide or mixtures thereof can be used.

The term "filler" in the invention; Practical for the production of tablets or capsules, for patient use expressed as substances or mixtures of substances used to be of appropriate size is being done. As a filler; talc, lactose, sucrose, dextrin, mannitol, lactilol, lactitol, xylitol, sorbitol, isomalt, microcrystalline cellulose, powdered cellulose, dextrose, dextrate, pregelatinized starch, modified 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 invention, the term "buffering agent" refers to substances that regulate the acidity and alkalinity of the composition. is expressed as. As a buffering agent; citric acid anhydrous, sodium citrate dihydrate, sodium phosphate, sodium dihydrogen phosphate, potassium citrate, phosphoric acid, ammonium hydroxide, citric acid, diisopropanolamine, sodium carbonate, sodium silicate, disodium orthophosphate, calcium carbonate, magnesium carbonate, magnesium hydroxide, magnesium aluminate, diethanol amine, sodium alginate, ethylenediamine, meglumine, hydrochloric acid, lactic acid, sodium citrate, sodium hydroxide, triethanolamine, trolamine, sodium benzoate, sodium hydrogen carbonate or mixtures thereof can be used.

In the invention, the term "surfactant" is applied when dissolved in water or an aqueous solution. It refers to the chemical compound that affects the voltage. As a surfactant polysorbates, sodiumlauryl sulfate, sodium stearyl fumarate, non-ionic polyoxyethylene polyoxypropylene co-polymer, hexadecyl trimethyl ammonium bromide, alkyl polyethylene oxide, poloxamers, octyl glucoside, sugar esters and glycerides of fatty acids, dodecyl betaine, dodecyl dimethylamine oxide, polyoxyl stearate, sodium stearate, polyethylene glycols, L-leucine, alkyl benzene sulfonate, fatty acids, quaternary ammonium compounds or mixtures thereof can be used.

In the invention, the "lubricant" reduces or inhibits the flow properties of a powder mixture. It is expressed as a healing agent or agent mixtures. 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 palinitostearate, sodium benzoate, sodium acetate, fumaric acid, zinc stearate, zinc oleate, zinc palmitate, paraffins, fatty alcohols or their mixtures can be used.

The term "glidant" in the invention; Tablet pressing immediately allows the flow of material into the matrix space. It is expressed as a substance with extra small particles and low density that facilitates it.

As a glidant; talc, magnesium stearate, hydrogenated vegetable oil, calcium stearate, stearic acid, colloidal silicon dioxide, sodium stearylfumate, polyoxyethyleneglycol, leucine, sodium benzoate, sodium chloride, sodium acetate, sodium fumarate, silica, colloidal anhydrous silica, polyethyleneglycol, cellulose derivatives, starch or their mixtures can be used.

The term "diluent" 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; lactose, maltose, sucrose, dextrin, mannitol, lactylol, xylitol, sorbitol, isomalt, microcrystalline cellulose, dextrose, dextrate, pregelatinized starch, modified starch, corn starch, lactose anhydrous, lactose monohydrate, dibasic calcium phosphate, hydroxy propyl methylcellulose, tribasic calcium phosphate, polyhydric alcohols or cellulose ethers, calcium hydrogen phosphate dihydrate, calcium sulfate trihydrate, calcium sulfate dihydrate, maltodextrin, calcium carbonate, kaolin, sodium hydroxide or their mixes can be used.

The term "preservative" in the invention; water and water-soluble, oil and fat-soluble substances It is expressed as substances that provide protection against microorganisms.

2-phenoxyethanol, sodium benzoate, benzoic acid, benzyl alcohol as preservatives, ethylenediaminetetraacetic acid, sodium methyl parahydroxy benzoate, sodium propyl parahydroxy benzoate, sorbic acid, potassium sorbate, benzetonium chloride, chlorocresol, benzalkonium chloride, butyl paraben, methyl paraben, propyl paraben, ethyl paraben, butyl hydroxy anisole (BHA), butyl hydroxy toluene (BHT), calcium acetate, citric acid, disodium edetate, glycerine, propyl gallate, sodium bisulfite, sodium citrate, sodium metabisulfite, boric acid, sorbic acid, sodium propionate, propylene glycol or mixtures thereof can be used.

In the invention, the term "flavoring agent" is defined as substances used to add flavoring to the mixture. is being done. As a flavoring agent; natural aroma oils (peppermint oil, wintergreen oil, parsley oil, orange oil, grape, citrus, grapefruit, lemon oil, etc.), orange flavor, banana flavor, peach flavor, grapefruit flavor, lemon flavor, apple flavor, strawberry flavor, vanilla flavor, mint flavor, tutti-fiiritti flavor, raspberry flavor, menthol, mentane, anethole, cinnamon, methyl salicylate, eucalyptal, sage, blackberry, citrus fruits or their mixes can be used.

As a "flavoring agent" in the invention; sodium saccharin, sucrose, D-glucose, galactose, xylose, maltose, maltodextrin, maltol, erythritol, lactitol, isomalt, isomaltol, corn syrup, D-tryptophan, glycyrrhizic acid, monoammonium glycyrrhizinate, fructose, maltitol, dextrose, sucrose, xylitol, sorbitol, mannitol, lactose, aspartame, acesulfame potassium, neohesperidin dihydrochalcone, sucralose, sodium cyclamate or their mixtures can be used.

In the invention, the term "viscosity increasing agent" means that it increases the thickness of the liquid and causes it to flow slowly. It is expressed as an agent or agent mixtures that provide Viscosity increasing agent aspect; xanthan gum, guar gum, acacia, povidone, alginic acid, ethylcellulose, gelatin, hydroxyethyl cellulose, hydroxypropyl cellulose, cetyl alcohol, polyvinyl pyrrolidone, hydroxy propyl methyl cellulose, polydextrose, carrageenan, methyl cellulose, sucrose, sorbitol, xylitol, hydroxypropyl methylcellulose, polyvinyl alcohol, ketaryl alcohol, colloidal silicon dioxide or mixtures thereof can be used.

In the invention, the term "antifoaming agent" refers to the initiation of the foaming reaction while the product is stored. It is expressed as substances that stabilize the product against the water in the existing system by preventing is being done. As antifoaming agent; simethicone emulsion, dimethylsiloxane, silicone oil, monosodium carbonate, anhydrous trimagnesium dicitrate or their mixtures can be used.

The antifoaming agent can be added directly to other excipients of the effervescent granule or external phase tablet. by mixing in powder form or into an excipient mixture of both effervescent granules and tablets. can be shared and added.

As a solubilizing agent in the invention; sodium caseinate, polysorbate, methacrylic acid copolymer or mixtures thereof can be used.

The term "antistatic agent" in the invention; to reduce or eliminate static electricity in the content It is expressed as the substance or substance mixture used. The aforementioned antistatic as an agent; long Chain aliphatic amines and amides, quaternary ammonium salts, phosphoric acid esters, polyethylene glycol esters, polyols, mono and diglyceride, fatty acid esters or mixtures of these can be used.

In the invention, the term "wetting agent" is readily available in the dispersion medium of hydrophobic drugs. It is expressed as substances used to help dispersal. wetting agent as substance; sodium lauryl sulfate, sodium docusate, polysorbates, sorbitan monolaurate, 0kt0xinol-9, nonoxynol-10, poloxamers, sodium carboxymethyl cellulose, bentonite, benzalkonium chloride, tetradecyltrimethyl ammonium bromide, cetylpyridinium chloride, glyceryl monostearate, macrogol cetostearyl ether, sorbitan tristearate, aluminum magnesium silicate or mixtures of these can be used.

In the invention, the term "pH adjusting agent" is used to regulate the acidity and basicity of the composition. referred to as items. As a pH adjusting agent; citric acid anhydrous, sodium citrate dihydrate, sodium phosphate, sodium dihydrogen phosphate, potassium citrate, phosphoric acid, ammonium hydroxide, citric acid, diisopropanolamine, sodium carbonate, sodium silicate, disodium orthophosphate, calcium carbonate, magnesium carbonate, magnesium hydroxide, magnesium aluminate, diethanol amine, sodium alginate, ethylenediamine, meglumine, hydrochloric acid, lactic acid, sodium citrate, sodium hydroxide, sodium chloride, triethanolamine, trolamine, sodium benzoate, sodium hydrogen carbonate or their mixtures can be used.

In the invention, the term "coloring agent" is a pleasant-looking and optically intermediate between the two formulations. are expressed as substances that provide discrimination. As a coloring agent, iron oxide such as, but not limited to, yellow iron oxide, red iron oxide pigments, ß-carotene, red beet powder, chlorophyll, tartrazine, yellow orange, quinoline yellow, erythrosine, titanium dioxide pigments, caramel, sunset blond or mixtures thereof can be used.

In the invention, the term "coating agent" refers to the formulation content to degrade by moisture in the air. Substance used to protect against odor and to facilitate swallowing of unpleasant-tasting forms. or as substance mixtures. As a coating material; methyl cellulose, hydroxyethylcellulose, hydroxybutylcellulose, hydroxypropylmethylcellulose, ethylcellulose, hydroxymethyl cellulose, hydroxypropylcellulose, carboxymethylethylcellulose, sodium carboxymethyl amylopectin, polyVinyl acetate phthalate, polyoxyethylene glycol, polyVinyl alcohol, polyVinyl acetal diethyl aminoacetate, aminoalkyl methacrylate copolymer, methacrylic acid copolymer, hydroxypropyl methyl cellulose acetate, dioxy methyl cellulose succinate, carboxy methyl ethyl cellulose, polyacrylic acids, methacrylic acid copolyiners, methyl acrylate, ethylacrylate, methylmethacrylate, ethylmethacrylate, acrylic and methacrylic acid esters, hypromellose acetate succinate, hydroxymethyl cellulose succinate acetate, cellulose butyrate phthalate, cellulose hydrogen phthalate, cellulose propyanate phthalate, cellulose acetate phthalate, hydroxypropylmethylcellulose phthalate, cellulose acetate trimellitate, triethyl citrate, gelatin, selak, castor oil, chitosan, alginic acid, Irish moss, galactomanones, tragacanth, Indian glue, gum arabic, guar gum, xanthan gum or mixtures of these can be used. Alcohols such as purified water, ethyl alcohol, methyl alcohol, isopropyl alcohol, butyl alcohol as solvents, acetone, diacetone, polyols, polyethers, esters, alkyl ketones, methylene chloride, methyl acetate, ethyl acetate, isopropyl acetate, castor oil, ethylene glycol monoethyl ether, diethylene glycol monobutyl ether, diethylene glycol monoethyl ether, dimethyl sulfoxide, dimethyl formamide, tetrahydrofuran or mixtures of these can be used.

The term "softening agent" in the invention; water by forming a thin film on the skin It is expressed as substances that prevent it from flying. Vaseline as an emollient, petroleum jelly, liquid paraffin, sorbitol, glycerin, hydrocarbons, lanolin, waxes, fatty acids, cetyl alcohol, octyldodecanol, caprylic/capric triglyceride, cetyl stearyl alcohol, cocoa butter, diisopropyl adipate, glycerine, polyhydric alcohols and polyether derivatives, polyhydric alcohol esters, glyceryl monooleate, glyceryl stearate, linoleic acid, oleic acid, polypropylene glycol-15 stearyl ether (PPG-15 stearyl ether), polyethylene glycol, polyoxyethylene glycol fatty alcohol ethers, polyoxypropylene stearyl ether, propylene glycol stearate, stearic acid, stearyl alcohol, phospholipids, lecithin, steorols, cholesterol, cholesterol fatty acid esters and amides, urea, glyceryl monostearate, isopropyl myristate, isopropyl palmitate, ketostearyl alcohol, dimethicone, mineral oils, white solid paraffin, cetearyl alcohol or mixtures thereof can be used. Also, castor oil, coconut oil, Vegetable softening agents such as olive oil and vegetable waxes can also be used.

In the invention, the term "emulsifier" means a homogeneous liquid between two immiscible phases. are expressed as substances that provide dispersion. Polyethylene glycol as emulsifier stearate, polysorbate, polyglyceryl oleate, polyoxyethylene lauryl ether, ethoxylated lanolin, stearyl alcohol, cetostearyl alcohol, macrogol cetostearyl, glyceryl monostearate, cetyl alcohol, polyoxyethylene lauryl alcohol, polyoxy ethylene sorbitan monostearate, polyoxyethylene stearate, sorbitan monostearate, propylene glycol stearate, aluminum starch octenylsuccinate, ammonium hydroxide, white a beeswax, a synthetic wax, carbomer, cetearyl alcohol, cyclomethicone, diglycerides, dimethicone, disodium monooleamido sulfosuccinate, pentaerythritol, glycerides, glyceryl monooleate, glyceryl stearate, lanolin, magnesium hydrogenated stearate, mineral oil, monoglycerides, polyethylene glycol, polyethylene glycol distearate, polyethylene glycol monocetyl ether, polyethylene glycol monostearate, polyoxyethylene glycol, polyoxyl cetostearyl ether, polyoxyl stearate, simethicone, sorbitan monolaurate, sorbitan monooleate, sorbitan monopalmitate, sorbitan palmitate, stearic acid, triethanolamine or sodium lauryl sulfate or mixtures thereof may be used.

Propylene glycol, purified water, castor oil, diisopropyl adipate, ethoxylated alcohol, fatty alcohol citrate, glycerin, hexylene glycol, isopropyl alcohol, isopropyl myristate, isopropyl palmitate, mineral oil, phosphoric acid, polyethylene terephthalate glycol, polyethylene glycol, polyethylene glycol monostearate, polyoxyl ketostearyl ether, polyoxypropylene stearyl ether, polysorbate, octyldodecanol, propylene carbonate, saturated fatty acid triglycerides, benzoic acid, ethanol or mixtures thereof may be used.

In the invention, the term "permeable agent" refers to a product that facilitates the penetration of saliva and thus substances that create a hydrophilic network that contributes to better dispersion of the tablet is expressed as. Precipitated silicas as permeation agent, maltodextrins, ß-cyclodextrins or mixtures thereof may be used.

In the invention, the term “antioxidant” is a free radical that prevents oxidation caused by free radicals. It is expressed as substances that have the ability to capture and stabilize radicals.

As an antioxidant; tocopherol (Vitamin E), ascorbic acid (Vitamin C), Vitamin A, Vitamin K Vitamins such as carotenoids, carotenes (eg; α-carotene, ß-carotene, lycopene, lutein, zeaxanthin), minerals (Se, Zn), butyl hydroxy anisole (BHA), butyl hydroxy toluene (BHT), ethylgalate, propylgalate, dodecylgalate, taurine, organosulfur compounds (allium, allyl sulfide, indoles), low molecular weight antioxidants (GSH-Px, uric acid) or their mixtures can be used.

EDTA (ethylene diamine tetraacetic acid), disodium EDTA as chelating agent in the invention (disodium ethylene diamine tetraacetic acid) or calcium EDTA (calcium ethylene diamine) tetraacetic acid) or mixtures thereof can be used.

As an alkalizing agent in the invention; sodium carbonate, sodium hydrogen carbonate, 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, monosodium glutamate, polakrillin sodium, sodium alginate, dibasic calcium phosphate, tribasic calcium phosphate, calcium sulfate, magnesium acetate, magnesium silicate, magnesium aluminate, magnesium oxide or mixtures thereof can be used.

As a photoprotective agent in the invention; iron oxide derivatives, metal oxides, titanium oxide or mixtures of these can be used.

In the invention, the term "thickening agent" refers to the resistance of formulations to various pressures and forces. are expressed as substances used for strengthening. thickening agent aspect; cetyl alcohol, aluminum stearate, dimethicone, cetearyl alcohol, stearyl alcohol, gum arabic, tragacanth gum, alginate, carrageenan, xanthan gum, guar gum, cetostearyl alcohol, wax of cetyl esters, dextrin, glyceryl monostearate, hydroxypropyl cellulose, kaolin, polyethylene white petrolatum, propylene glycol stearate, starch, wax, white wax, bentonite, beeswax, white beeswax, synthetic beeswax, paraffin, white hard paraffin, white soft paraffin, petroleum jelly, pectin, carbomer, polyvinylpyrrolidone or mixtures thereof can be used.

In the invention, the term "isotonia adjusting agent" means the same osmotic pressure as the standard reference substance. referred to as substances. As the aforementioned isotonia adjusting agent; sodium chloride, mannitol, sorbitol, boric acid, potassium nitrate, glucose or mixtures thereof can be used.

In the invention, carbopol, carbomer, hydroxy propylmethylcellulose, methylcellulose, sodium carboxy methylcellulose, polyacrylate polymers or mixtures thereof can be used.

In the invention, the term "microbial preservative" is used as substances that protect against microbial activity. is expressed as. As the aforementioned microbial preservative; sodium benzoate, sodium methyl para hydroxybenzoate, sodium propyl para hydroxybenzoate, benzalkonium chloride, boric acid, sorbic acid, ethanol or their mixtures can be used.

In the invention, “hardening agent; The term means formulations against various pressures and forces. are expressed as substances used for strengthening. As a hardening agent; cetyl alcohol, aluminum stearate, dimethicone, cetearyl alcohol, stearyl alcohol, gum arabic, gum tragacanth, alginate, carrageenan, xanthan gum, guar gum, cetostearyl alcohol, wax of cetyl esters, dextrin, glyceryl monostearate, hydroxypropyl cellulose, kaolin, polyethylene white petrolatum, propylene glycol stearate, starch, wax, white wax, bentonite, beeswax, white beeswax, synthetic wax, paraffin, white solid paraffin, petroleum jelly, pectin, carbomer, polyvinylpyrrolidone or their mixes can be used.

As sivag in the invention; macrogol derivatives, petrolatum, wax modified vaseline, liquid petrolatum, white petrolatum, lanolin or lanolin derivatives, castor oil, coconut oil, olive oil, cotton vegetable oils such as seed oil, polyethylene glycol, paraffin, anhydrous, white soft paraffin or mixtures of these can be used.

As "release controlling agent" in the invention; polyvinyl acetate phthalate, polyethylene glycol-polyvinyl alcohol copolymer, polyacrylic acid derivatives, polysaccharide derivatives, methacrylate polymer, polymethacrylate, ethyl methacrylate copolymer, methacrylic acid-methylmethacrylate copolymer, methacrylic acid-ethyl acrylate copolymer, polylactic acid, polylactic acid copolymer, polyvinylpyrrolidone, polyvinylalcohol, glyceride, polyethylene oxide, glyceryl behenate, methacrylic acid copolymer, hydroxypropyl methyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose acetate, carboxy methyl ethyl cellulose, sodium carboxy methyl cellulose, ethyl cellulose, methyl acrylate, ethylacrylate, methylmethacrylate, ethylmethacrylate, acrylic and methacrylic acid esters, sodium alginate, hypromellose phthalate, hypromellose acetate succinate, cellulose butyrate phthalate, cellulose hydrogen phthalate, cellulose propyanate phthalate, cellulose acetate phthalate, cellulose acetate trimellitate, gelatin, selak, xanthan gum or their mixtures can be used.

In the invention, the term "plasticizer" is used to increase the flexibility of the coating, reduce the risk of film breakage. and substances used to increase the adhesion of the film to the core.

They must be compatible with the polymer and not be volatile. As a plasticizer; polyethylene glycols (Macrogol), glycerin, propylene glycol, acetyl citrate, arnyl oleate, myristyl acetate, butyl oleate, butyl stearate, triacetin, diethylphthalate, acetylated monoglycerides or their mixes can be used.

In the invention, the term "antiadherent" is expressed as substances that prevent the formation of rough tablet surface. is being done. As an antiadherent; talc, colloidal silicon dioxide (Aerosil, Syloid, Cab-O-Sil), magnesium stearate, corn starch, magnesium trisilicate or mixtures thereof can be used.

In the invention, the term "film-forming agent" refers to the use of a binder as a film, eg film or film. It is expressed as the necessary components to create it. As a film making agent; polyvinyl alcohol-partially hydrolyzed, methyl cellulose, ethyl cellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, polyethylene glycol, polyethylene oxide, Macrogol, gelatin or mixtures of these can be used.

In the invention, the term "Opacifying agent" refers to the additives added to make the desired system opaque. referred to as items. As an opacifying agent; titanium dioxide, calcium carbonate, zinc acetate, aluminum stearate, zinc stearate or mixtures thereof can be used.

The term "moisturizing agent" in the invention; regulating the amount of moisture between the preparation and the air and control substances. As a moisturizing agent; glycerine, sorbitol, propylene glycol, urea, colloidal substances, liquid paraffin, petrolatum (petrolatum), liquid petrolatum, cellulose and cellulose-based substances, gums (tragacanth), some electrolytes (Al salts, mercury salts (borax) or their mixtures can be used.

Purified water, ethyl alcohol, methyl alcohol, isopropyl alcohol, Alcohols such as butyl alcohol, methylene chloride or mixtures thereof may be used.

The term "stabilizer" in the invention; Substances that, when added, prevent crystallization or phase separation is expressed as. Benzoic acid, edetic acid, salicylic acid, sorbic acid as stabilizer, sodium dehydroacetate, tocopherol, butylated hydroxyanisole, butylated hydroxytoluene, propylgallate, castor oil, oleyl alcohol, poloxamer and poloxamines (polyoxyethylene and polyoxypropylene block copolymer), xanthan gum, ethoxylated of sorbitan fatty acids esters, polysorbates such as polysorbate 80 or Tween 80, ethoxylated mono- and diglycerides, ethoxylated lipids, ethoxylated fatty alcohols or fatty acids, diacetyl phosphate, phosphatidyl glycerol, saturated or unsaturated fatty acids, sodium cholate, sodium glycolate, sodium taurocholate, paraoxybenzoic acid, ethylene diamine tetraacetic acid (EDTA), diethylene triamine penta acetic acid or mixtures thereof can be used.

Only one of the dexrabeprazole and/or pharmaceutically acceptable derivatives of the present invention when this active ingredient is used alone or in combination with other suitable active agent(s) dosage range of formulations suitable for pharmaceutical compositions; l-120 mg preferably 10 mg, 20 mg, 25 mg, depending on the individual needs of the patient and the judgment of the specialist. is being set.

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). Dual-acting pharmaceutical compositions of the invention It is essential that it be in modified-release capsule and/or tablet form. The capsule in question A feature of the form of the capsule is one or more modified-release tablets and a capsule. or more enteric-coated tablets. Acid in the aforementioned formulations A product that provides a stomach-resistant coating containing the active ingredient that is unstable in its environment. containing the active ingredient in an enteric coating to prevent degradation of the active ingredient. solid, in which the portion containing the enteric coating is separated by one or more substrates The preparation of pharmaceutical compositions is also involved. 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. The capsule/s and/or tablet/s thus obtained are surprisingly physical. and exhibited a very stable behavior in terms of chemical stability. Also enough surprisingly effective to ensure therapeutic effect and minimize side effects they are not determined.

Claims (1)

REQUESTS . It is a pharmaceutical composition/s for oral use and its feature is; Including and preparing the use of antiulcerative dexrabeprazole and/or its pharmaceutically acceptable derivatives in the group of proton pump inhibitors alone as monotherapy or the use of this active substance in combination with other appropriate active agent/s. . It is a pharmaceutical composition/s as in Claim 1 and its feature is; tablet, multilayer tablet, bilayer tablet, enteric coated tablet, mini tablet, capsule, enteric coated capsule, powder, granule, spheroid, bead, pellet, water-dispersible powder, water-dispersible granule, effervescent tablet, effervescent granule, effervescent powder, It contains one or more pharmaceutical dosage forms selected from suspension, liposome, cream, gel, ointment, lotion, emulsion, liquid solution, ampoule, vial, infusion, or lyophilized powder. . It is a pharmaceutical composition/s as in Claim 2 and its feature is; The pharmaceutical dosage form is preferably capsule and/or tablet. . It is a pharmaceutical composition/s as in Claim 2 and its feature is; is to choose the same or different dosage forms in the capsule from the group that includes tablets, mini tablets, powders, granules, pellets, sphreoids. . It is a pharmaceutical composition/s as in Claim 4 and its feature is; It is the presence of antiulcerative dexrabeprazole and/or pharmaceutically acceptable derivatives in the group of proton pump inhibitors in the same or two different dosage forms in the capsule. . It is a pharmaceutical composition/s as in Claim Si and its feature is; dexrabeprazole and/or its pharmaceutically acceptable derivatives having one or more release profiles selected from modified, extended, sustained, immediate, delayed, modified release. . It is a pharmaceutical composition/s as in Claim 6 and its feature is; dexrabeprazole and/or its pharmaceutically acceptable derivatives preferably have a modified release profile. . It is a pharmaceutical composition/s as in Claim 5 and its feature is; It is the presence of dexrabeprazole and/or its pharmaceutically acceptable derivatives in capsule form as one or more modified-release tablets and one or more enteric-coated tablets. It is a pharmaceutical composition/s as in Claim 83 and its feature is; dexrabeprazole and/or pharmaceutically acceptable derivatives in the form of double-acting modified-release capsules and/or tablets. It is a pharmaceutical composition/s according to any of the above claims and its feature is; The dose range of dexrabeprazole and/or pharmaceutically acceptable derivatives is 1-120 mg, which is suitable for pharmaceutical compositions where this active ingredient is used alone or in combination with other suitable active agent/s. It is a pharmaceutical composition/s according to any of the above claims and its feature is; A combination of gastroesophageal reflux disease (GERD), erosive reflux esophagitis, relapses, healed reflux esophagitis, dyspepsia, nephropathic cystinosis, pyrosis, gastric disorders manifested by high acid secretion (heartburn, nausea, bloating), with 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 and/or symptomatic and/or therapeutic treatment of duodenal ulcers, Zollinger-Ellison Syndrome, short-term maintenance of hemostasis in gastric or duodenal ulcers and rebleeding.