TR201603387A1 - PHARMACEUTICAL FORMULATIONS USED IN THE TREATMENT OF GASTROINTESTINAL DISEASES - Google Patents

Abstract

The present invention includes; pain associated with functional bowel disorders, transitional disorders, stomach pain, irregular bowel diseases (constipation, diarrhea ..), correcting the normal contraction of the intestine and the relaxation of the intestinal muscles, reducing spasm, bloating, irritable bowel syndrome, also (gallbladder and bile duct) suitable for use in the therapeutic and / or prophylactic and / or symptomatic treatment of symptoms related to other intestinal disorders (also in the preparation of barium enema), in the relief of stomach or intestinal complaints caused by medical conditions in the intestine or bile duct, and / or pharmaceutical The present invention relates to pharmaceutical compositions (s) wherein acceptable derivatives are used alone or as combination therapy as monotherapy.

Description

DESCRIPTION USED IN THE TREATMENT OF GASTROINTESTINAL DISEASES PHARMACEUTICAL FORMULATIONS FIELD OF THE INVENTION The present invention; pain due to functional bowel disorders, transition disorders, stomach pain, irregular bowel diseases (constipation, diarrhoea..), impaired normal contraction of the bowel It helps to relax the intestinal muscles by correcting the process, reducing spasm, bloating, irritable bowel syndrome, as well as other bowel (including gallbladder and bile duct) in symptoms associated with disorders of the intestine (also in preparation of a barium enema), intestinal or stomach or intestinal complaints caused by medical conditions in the bile duct therapeutic and/or prophylactic and/or symptomatic treatment as a suitable active substance and/or pharmaceutical with antispasmodic properties to be used acceptable derivatives as monotherapy alone or in combination therapy relates to the pharmaceutical composition(s) for which it is used.

The present invention; antispasmodic active ingredient Pinaverium, 4-(2-bromo0-4,5- (Formula 1) and/or pharmaceutically acceptable derivatives as monotherapy alone relates to the pharmaceutical composition(s) for which it is used alone or in combination.

Formula I: In addition, the invention includes the use of Pinaverium and/or its pharmaceutically acceptable derivatives. used alone as monotherapy or used as a combination therapy formulations of pharmaceutical compositions suitable for oral administration and prophylactic and/or symptomatic and/or therapeutic uses. PRIOR ART (KNOWN STATE OF THE ART) Irritable bowel syndrome (IBS) with no known organic cause, stress or emotional a bowel that occurs or increases during periods of high tension is the disease. irritable bowel syndrome (IBS); abdominal pain, changes in bowel function (bowel frequency and/or constipation), bloating, including feeling of incomplete evacuation functional bowel characterized by a diverse consortium of abdominal symptoms Irritable bowel syndrome is the most common, affecting approximately 12% of the world's population. It is a multifactorial disease in gastroenterology practices (Halvorson et al., 2006; Mertz, 2003). In the development of acute gastroenteritis and irritable bowel syndrome in recent years, has been accepted to play a critical role (Neal et al., 1997; Parry and Forgacs, 2005; Rodri'guez and Riigömez, 1999).

Studies have shown that approximately one-third of patients with irritable bowel syndrome symptoms of one started after acute enteric infection (Gwee et al., It has been accepted as a new subtype of irritable bowel syndrome (Gwee et al. IBS with persistent or recurrent abdominal pain or discomfort in the bowel The variability in the habit, the relief of the patient with defecation, and the complaints are organic It is characterized by the absence of physical or laboratory findings to explain

Strongly mild stimulation in patients with postinfectious irritable bowel syndrome Visceral hypersensitivity responding to abdominal pain is emphasized. Trimebutin and Some antispasmodics, such as pinaverium, are used to reduce muscle ion channels to relieve pain. inhibition of muscle mass contraction by modulation of irritable bowel seidrome is thought to be related.

Traditionally, therapies for abdominal pain; calcium channel blockers (eg. pinaverium), smooth muscle relaxants (eg mebeverine), and opioid receptor ligands (eg trimebutin), anticholinergic agents (eg Cimetropium bromide, dicyclomine) Pinaverium is a quaternary ammonium derivative with selective action in the gastrointestinal tract. It is an antispasmodic and musculotropic drug, for functional gastrointestinal disorders used. It also shows a small antimuscarinic effect. Like a calcium channel blocker acts and helps to restore the normal contraction process of the intestine, helps him relax.

Prevention or treatment of intestinal disorders in patent document EP2641598 pharmaceutical in the form of coated tablets or capsules for oral administration used the composition and the auxiliary substances used are mentioned.

In the patent document numbered EP2020234, pinaverium broinure is derived from diinethicone or Synergistic combinations of simethicone are mentioned.

DESCRIPTION OF THE INVENTION The present invention; pain due to functional bowel disorders, transition disorders, stomach pain, irregular bowel diseases (constipation, diarrhoea..), impaired normal contraction of the bowel It helps to relax the intestinal muscles by correcting the process, reducing spasm, bloating, irritable bowel syndrome, as well as other bowel (including gallbladder and bile duct) in symptoms associated with disorders of the intestine (also in preparation of a barium enema), intestinal or stomach or intestinal complaints caused by medical conditions in the bile duct therapeutic and/or prophylactic and/or symptomatic treatment Appropriate active substance and/or pharmaceutical with antispasmodic properties to be used acceptable derivatives as monotherapy alone or in combination therapy relates to the pharmaceutical composition(s) for which it is used.

Another aspect of the present invention is; Appropriate active ingredient with antispasinodic properties and/or pharmaceutically acceptable derivatives alone or as monotherapy relates to the preparation of pharmaceutical composition(s) in which it is used in combination.

The active substance used in the invention with antispasmodic properties, including but not limited to together, oxyphencycline, kamilofin, inebeverine, trimebutin, rosiverine, dicycloverine, dihexiverine, diphemerine, piperidolate, benzylone, glycopyrronium, oxyphenonium, penthienate, propantheline, otilonium, inetanthelin, tridihexethyl, isopropamide, hexocyclium, poldin, mepenzolate, bevonium, pipenzolate, diphemanil, thiemonium, pyrifinium, timepidium, fenpiverinium, dimethylaminopropionylphenothiazine, nicofetamide, thyropramide, papaverine, drotaverine, moxaverine, alosetron, tegaserod, silansetron, prucalopride, fenpiprane, diisopromine, chlorbenzoxamine, pinaverium, fenoverin, idanpramine, proxazole, alverin, trepibuton, isoinethepten, caroverin, Iloroglucinol, triinethyldiphenylpropylamine, silicones and/or pharmaceutically acceptable derivatives, preferably pinaverium bromide is selected as.

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, one or more of acids, ethers, crystalline and amorphous forms or free forms is expressed.

The pharmaceutical composition for oral administration may be in solid or liquid dosage forms.

These dosage forms are; tablet (uncoated, chewable, mouth soluble, dispersible, water dispersible, film coated, single layer, double layer, intestinal release coated, mini tablet, controlled release, sustained release, immediate release, extended release, delayed release release, modified release, buccal), capsule (hard, soft, enteric-coated, film-coated, controlled release, sustained release, immediate release, extended release, delayed release, modified release), powder, granule, caplet, disc, oral film, bulk powder (multidose), pellet, sachet, water-dispersible powder, water-dispersible granule, effervescent tablet, effervescent granule, effervescent powder, microcapsule, dental tablets, pilula, syrup, solution, suspension, The elixir may be formulated in a dosage form such as drops, positions, emulsions or sprays.

In the present invention, tablet(s) prepared for oral use have one or more coatings. may contain.

coated tablets; The active ingredient is usually in the core, partially in the core and It is prepared in the form of formulas containing partially coating or only coating.

Coating materials must be physiologically harmless and incompatible with the active substance. should not be.

Coating types ; sugar coating, film coating and intestinal soluble (enteric) coating can be counted as

Sugar-coated tablets are compressed tablets having a coating consisting of sugar. are tablets. The coating may be colored and may have an offensive taste or coating of active substances with odor and sensitive to oxidation It is extremely useful in terms of protecting materials.

Film-coated tablets are a thin film applied using a water-soluble material. Compressed tablets coated with a layer or film. In line with this, the movie Maker A range of polymeric materials can be used with properties Film coatings, sugar Although it has the same general properties as the coatings, it is necessary for the coating process. It brings with it the important additional advantage of significantly reducing the time.

Purposes of Coating; o Protection of the active substance against light, oxygen and moisture - Masking off the offending odor and taste of the active ingredient o Correction of the aesthetic appearance of the tablet 0 Obtaining colored tablets with very little dyestuff o Increasing the easy swallowing of the tablet by the patient o Proof of mechanical strength during production, packaging and transportation o Protection of the active substance against digestive secretions 0 Avoidance of side effects, eg stomach irritation o Facilitating the identification of the drug, thus ensuring safety in drug use. increase o Increasing the stability of the active ingredient o Editing of controlled release characteristics can be counted as

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 a delayed-release pharmaceutical formulated with one or more of the dosage forms can be done.

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 the 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.

Direct compression, wet or dry granulation in the preparation of tablet(s) of the invention applicable.

Direct compression of the powdered material without disturbing the physical structure of the material. It is obtained by compression. Widely used as a direct compaction tool The excipient studied in this way is microcrystalline cellulose (Avicel, FMC).

Many techniques are used in the preparation of dosage forms. one of them granulation method. Granulation; as the growth of fine dust particles is defined. Granulation for pharmaceutical purposes; a preparation for tableting This is the stage of filling hard gelatin capsules or granules as a final product. It is also applied for the purpose of being placed in a package.

The purpose of the granulation is to give the unit drug % of the particles of the powder substance participating in the mixture. is to create a unit of weight that will be equivalent to the quantities. Pharmaceutical powder mixes (active substance or auxiliary substances) in a unit by preventing their separation. It is necessary to ensure that they remain in a homogeneous form, this is achieved by granulation. possible.

The methods to be chosen in granulation can be classified in 3 main categories: wet granulation, dry granulation and other granulation methods.

Age Granulation: In the wet granulation method, high speed fluidized bed granulation, spray drying and extrusion pelleting methods are used. Mourning In granulation, the active ingredient and the binder (solution) are mixed for a certain period of time. sieved and dried in a fluidized bed dryer. This dried mixture is the other filling. It is mixed with the ingredients until it reaches a certain homogeneity. My wife's last 3-5 slider is added in minutes. Samples are taken from the final mixture obtained and sent to the laboratory. sent. According to the results of the laboratory, for the tablet press or for the desired pharmaceutical form. stages can be passed.

Age granulation methods: 1. Age granulation method (Classical method) 2. Granulation by fluidized bed method 3. Granulation by Spray-Drying method 4. Microgranulation method . Extrusion-Spheronization method 6. Method of preparing granules with high-level mixers The wet granulation process is as follows: The process is called granulation.) - Screening of agglomerated particles as wet, ° Drying of the sifted powder mixture is widely used in the drying process. using bed dryers, ° Homogenizing in double-conical or V-type mixers - Adding lubricant to this resulting mixture and mixing for another 5 minutes, (This the mixture is called the final product.) Dry Granulation: In the dry granulation method, pre-compression and inter-roll compression methods are used. In dry granulation, it is usually 1/3 of the lubricant is mixed with other powder mixtures. This is because dust gets into the cylinders. prevents it from sticking. The remainder of the lubricant is added to the mix after dry granulation. and stirred for 3-5 minutes. Samples are taken from the final mixture formed after the mixture and It is sent to the laboratory for various tests. According to the laboratory results, tablet compression or The steps can be passed for the desired pharmaceutical form.

The pharmaceutical formulation prepared for oral use in the present invention; pharmaceutically Acceptable suitable active ingredients as well as binder, dispersant, filler agent, buffering agent, surfactant, lubricant, glidant, diluent, preservative, flavoring agent, sweetening agent, viscosity increasing agent, antifoam agent, solubilizing agent, antistatic agent, wetting agent, pH adjusting agent, coloring agent, coating agent, solvent, softening agent, emulsifier, carrier, permeabilizing agent, antioxidant, chelating agent, alkalizing agent, photoprotective agent, kivain enhancing agent, isotonia adjusting agent, gelling agent, microbial preservative substance, curing agent, sivag, release controlling agent, plasticizer, antiadherent, film builder agent, opacifying agent, wetting agent, granulation solvent and may contain one or more excipients selected from the group consisting of a stabilizer. defines a compound.

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, gums, 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 Starches such as starch, pregelatinized starch, sodium starch glycolate, microcrystalline cellulose, cross-linked polyvinyl pyrrolidone, sodium alginate, hydroxypropyl cellulose, cross bound 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 their mixes can be used.

The term "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 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" is used to regulate the acidity and basicity of the composition. referred to as items. 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 oitophosphate, 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 their mixtures 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.

"Lubricant" in the invention is the flow of a powder mixture that reduces or inhibits friction. It is expressed as agent or agent mixtures that improve its properties. lubricant aspect; 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.

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, inagnesium 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, ethylenediaminetetraacetic acid, sodium inethyl parahydroxy benzoate, sodium propyl para hydroxy 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), calciyuin acetate, citric acid, disodium edetate, glycerin, propyl gallate, sodium bisulfite, sodium citrate, sodium metabisulfite, boric acid, sorbic acid, sodium propionate, propylene glycol or their mixtures 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-ûiritti flavor, raspberry flavor, menthol, menthane, anethole, cinnamon, methyl salicylate, eucalyptal, sage, blackberry, citrus fruits or mixtures of these can be used.

As a "flavoring agent" in the invention; sodium saccharin, sucrose, D-glucose, galactose, xylose, inaltose, inaltodextrin, maltol, erythritol, lactitol, isomalt, isomaltol, corn syrup, D- tryptophan, glycyrrhizic acid, monoammonium glycyrrhizinate, fructose, maltitol, dextrose, sucrose, xylitol, sorbitol, mannitol, lactose, aspartame, acesulfain 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 ingredient 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 of these can be used.

In the invention, the term "antifoaming agent" refers to the initiation of the foaming reaction while the product is stored. as substances that stabilize the product against the water in the existing system by preventing is expressed. As antifoaming agent; simethicone einulsion, dimethylsiloxane, silicone oil, monosodium carbonate, anhydrous trimagnesium dicitrate or mixtures thereof can be used. Antifoaming agent directly into effervescent granulated or external phase tablet It can be mixed with other excipients in powder form or made into both effervescent granules and tablets. It can be added to the excipient mixture by portioning.

As a solubilizing agent in the invention; sodyuiii 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, octoxynol-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, ainonian hydroxide, citric acid, diisopropanolamine, sodium carbonate, sodium silicate, disodium orthophosphate, calcium carbonate, magnesium carbonate, magiezium 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 intermediate between the two formulations. They are expressed as substances that provide optical discrimination. Colorant as substances, but not limited to, yellow iron oxide, red iron oxide such as iron oxide pigments, ß-carotene, red beet powder, chlorophyll, tartrazine, yellow orange, quinoline yellow, erythrosine, titanium dioxide pigments, caramel, sunset yellow or mixtures of these can be used.

In the invention, the term "coating agent" describes the formulation content by moisture in the air. to protect against degradation and to facilitate swallowing unpleasant-tasting forms. It is expressed as the substance or substance mixture used. Coating agent aspect; methyl cellulose, hydroxyethylcellulose, hydroxybutylcellulose, hydroxypropylmethylcellulose, ethyl cellulose, hydroxymethyl cellulose, hydroxypropylcellulose, carboxymethylethylcellulose, sodium carboxymethyl amylopectin, polyvinyl acetate phthalate, polyoxyethylene glycol, polyvinyl alcohol(Opadry varieties), 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 copolymers, methyl acrylate, ethylacrylate, methylmethacrylate, ethylmethacrylate, acrylic and methacrylic acid esters, hypromellose, hypromellose phthalate, hypromellose acetate succinate, hydroxymethyl cellulose succinate acetate, cellulose butyrate phthalate, cellulose hydrogen phthalate, cellulose propyanate phthalate, cellulose acetate phthalate, hydroxypropylmethylcellulose phthalate, cellulose acetate trimellitate, gelatin, celak, castor oil, chitosan, alginic acid, carrageenan, galactomanones, tragacanth, castor oil, gum arabic, guar gum, xanthan gum or their mixtures can be used. Solvents such as water, ethyl alcohol, methyl alcohol, isopropyl alcohol, butyl alcohol. alcohols, 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 thereof may 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, solid petrolatum, 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-1S 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 inonostearate, isopropyl myristate, isopropyl palinitate, ketostearyl alcohol, dimethicone, mineral oils, white solid paraffin, cetearyl alcohol or their mixtures can be used. Moreover herbal emollient such as castor oil, coconut oil, olive oil and herbal inuins agents can also be used.

In the invention, the term "emulsifier" means homogeneous between two immiscible liquid 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, a white wax, a synthetic wax, carbomer, cetearyl alcohol, cyclomethicone, diglycerides, dimethicone, disodium monooleamido sulfosuccinate, pentaerythritol, glycerides, glyceryl moiooleate, glyceryl stearate, lanolin, hydrogenated magnesium 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 inonopalinitate, sorbitan palmitate, stearic acid, triethanolamine or sodium lauryl sulfates or their mixtures can be used.

Propylene glycol, purified water, castor oil, diisopropyl adipate, ethoxylated alcohol, fatty alcohol citrate, glycerine, 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 "permeabilizing agent" refers to a substance that facilitates the penetration of saliva and thus creating a hydrophilic network that contributes to better dispersion of the tablet. referred to as items. Precipitated silicas as permeation agent, maltodextrins, ß-cyclodextrins or mixtures thereof may be used.

In the invention, the term “antioxidant” prevents oxidation caused by free radicals, are substances that have the ability to capture and stabilize free radicals. is being done. As an antioxidant; tocopherol (Vitamin E), ascorbic acid (Vitamin C), A vitamin, vitamins such as vitamin K, carotenoids, carotenes (eg oi-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 mixtures of these 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 amino acids, 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 of these 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, gum tragacanth, alginate, carrageenan, xanthan gum, guar gum, cetostearyl alcohol, cetyl esters wax, 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, white soft paraffin, solid Vaseline, pectin, carbomer, polyvinylpyrrolidone or their mixtures 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 their mixes can be used.

In the invention, carbopol, carbomer, hydroxy propylmethylcellulose, methylcellulose, sodium carboxymethylcellulose, polyacrylate polymers or their mixes can be used.

In the invention, the term "microbial preservative" protects against microbial activity. referred to as items. 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, tragacanth gum, alginate, carrageenan, xanthan gum, guar gum, cetostearyl alcohol, cetyl esters wax, 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, solid petrolatum, pectin, carbomer, polyvinylpyrrolidone or mixtures thereof 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, vegetable oils such as cottonseed oil, polyethylene glycol, paraffin, anhydrous, white soft paraffin or their mixtures 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-methylinethacrylate 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, inethyl acrylate, ethylacrylate, methylmethacrylate, ethylmethacrylate, acrylic and inethacrylic acid esters, sodium alginate, hypromellose phthalate, hypromellose acetate succinate, cellulose butyrate phthalate, cellulose hydrogen phthalate, cellulose propyanate phthalate, cellulose acetate phthalate, cellulose acetate Trimelitate, gelatin, celak, xanthan gum or mixtures of these can be used.

In the invention, the term "plasticizer" is used to increase the flexibility of the coating, reduce the risk of film breakage. It is expressed as substances used to reduce the film and increase the adhesion of the film to the core. is being done. They must be compatible with the polymer and not be volatile.

As a plasticizer; polyethylene glycols (Macrogol), glycerin, propylene glycol, acetyl citrate, amyl oleate, myristyl acetate, butyl oleate, butyl stearate, triacetin, diethylphthalate, acetylated monoglycerides or mixtures thereof may be used.

In the invention, the term "antiadherent" refers to substances that prevent the formation of a rough tablet surface. is expressed. As an Aitiadherent; talc, colloidal silicoii dioxide (Aerosil, Syloid, Cab-O-Sil), magnesium stearate, corn starch, magnesium trisilicate or their mixes 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. They are expressed as the necessary components to create 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 their mixtures can be used.

In the invention, the term "opacifying agent" refers to the addition of the desired system to make it 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; the amount of moisture between the preparation and the air. are referred to as regulating and controlling substances. moisturizing agent aspect; glycerin, sorbitol, propylene glycol, urea, colloidal substances, liquid paraffin, petrolatum (petrolatum), liquid petrolatum, cellulose and cellulose-containing substances, gums (tragacanth), some electrolytes (Al salts, mercury salts borax) or their mixtures can be used.

Purified water, ethyl alcohol, methyl alcohol, isopropyl as granulation solvent in the invention Alcohols such as alcohol, butyl alcohol, methylene chloride or their mixtures can be used.

The term "stabilizer" in the invention; prevents crystallization or phase separation when added referred to as items. Benzoic acid, edetic acid, salicylic acid as stabilizer, sorbic acid, sodium dehydroacetate, tocopherol, butylated hydroxyanisole, butylated hydroxytoluene, propylgallate, castor oil, oleyl alcohol, poloxamer and poloxamines (polyoxyethylene and polyoxypropylene block copolymer), xanthan gum, sorbitan oil ethoxylleninis esters of acids, 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, tetraacetic ethylene diain acid (EDTA), diethylene triamine penta acetic acid or mixtures thereof can be used.

Appropriate active substance(s) and/or pharmaceutically acceptable in the present invention dosage range of formulations suitable for derivatives; Pinaverium and/or pharmaceutical 10-1200mg for acceptable derivatives; preferably 50mg and 100mg. adjusted to individual needs and expert judgment.

The invention is mainly considered as an antispasmodic Pinaverium and/or pharmaceutical. derivatives are used alone as monotherapy or as combination therapy. relates to the pharmaceutical composition(s) for which it is used. Tablets of the pharmaceutical composition(s) of the invention and/or in capsule form. Another feature of the invention is the tablet dosage form. includes one or more coatings when deemed necessary. These tablet/s are required sugar coating, film coating and intestinal soluble (enteric) coating when seen includes one or more coatings selected from among Thus obtained pharmaceutical The formulation/s are surprisingly quite stable in terms of physical and chemical stability. exhibited a behavior. In addition, to ensure adequate therapeutic effect and side effects They have been found to be surprisingly effective for minimizing

Claims (10)

REQUESTS . Preparation of pharmaceutical composition(s) in which the appropriate active ingredient and/or pharmaceutically acceptable derivatives with antispasmodic properties are used alone or in combination as inonotherapy for oral use. . It is a pharmaceutical composition/s as in Claim V. Its feature is; suitable active ingredient with antispasmodic properties, oxyphencycline, kamilofin, mebeverine, trimebutin, rosiverine, dicycloloverine, dihexiverine, diphemerin, piperidolate, benzylone, glycopyrronium, oxyphenonium, pentienate, propantheline, otimebutin, rosiverin, methantheline, dihexiverine, diphemerin, piperidolate, pentionate, propantheline, otimebutinium, cyclopyridine, cyclopyridine, pentylene, cyclopyrronium, oxyfenonium, pentionate, propantheline, otimebutinium, ethylenzolatine, cyclopentyl, methantheline, cyclopyridine, cyclopentyl, , dipheinanil, thiemonium, pyrifinium, timipidyuin, fenpiverinyuin, dimethylaminopropionylphenothiazine, nicofetamide, thyroprainide, papaverine, drotaverine, moxaverine, alosetron, tegaserod, silansetron, prucalopride, phenpioverin, pyrucalopramine, phenpioverine, pyrucalonium, benzopyrazine, pyroxeronin, is selected from among caroverin, phloroglucinol, triinethyldiphenylpropylamine, silicones and/or pharmaceutically acceptable derivatives. . It is a pharmaceutical composition/s as in Claim V and its feature is; Suitable active ingredient with antispasinodic properties is preferably pinaverium broinure. . It is a pharmaceutical composition/s as in lstein 1 and its feature is; tablet (chewable tablet, orally soluble tablet, dispersible tablet, water-dispersible tablet, film-coated tablet, enteric tablet, mini-tablet, controlled-release tablet (sustained-release tablet, immediate-release tablet, extended-release tablet, delayed-release tablet) etc.), capsule (hard, soft, enteric-coated, film-coated), controlled-release capsule (sustained-release capsule, immediate-release capsule, extended-release capsule, delayed-release capsule), powder, granule, caplet, disc, oral soluble film, One or more pharmaceuticals selected from bulk powder (multidose), pellet, sachet, water-dispersible powder, water-dispersible granule, effervescent tablet, effervescent granule, effervescent powder, gel, pilula, liquid solution, ampoule, vial, infusion, or lyophilized powder contains the dosage form. . It is a pharmaceutical composition/s as in Claim 49 and its feature is; preferably the pharmaceutical dosage form is a tablet and/or capsule. . It is a pharmaceutical composition/s as in Claim 4 and its feature is; the tablet dosage form includes one or more coatings where deemed necessary. 7. It is a pharmaceutical composition/s as in Claim 4 and its feature is; It is a tablet/s containing one or more coatings selected from sugar coating, film coating and intestinal soluble (enteric) coating when deemed necessary. 8. It is a pharmaceutical composition/s as in Claim 4 and its feature is; It is the use of direct compression and/or wet and/or dry granulation methods/s in the preparation of tablet/s. 9. It is a pharmaceutical composition/s according to any of the above claims and its feature is; Dose range of formulations suitable for Pinaverium and/or its pharmaceutically acceptable derivatives; 10-1 is 200mg. 10. It is a pharmaceutical composition/s according to any of the above claims and its feature is; Pain due to functional intestinal disorders, transition disorders, stomach ache, irregular bowel diseases (constipation, diarrhea..), restoring the normal contraction of the intestine, relaxation of the intestinal muscles, reducing spasm, bloating, irritable bowel syndrome, bile duct and bile duct It is indicated for the therapeutic and/or prophylactic and/or symptomatic treatment of symptoms associated with other intestinal disorders (including in the preparation of barium enemas), the relief of stomach or intestinal complaints caused by medical conditions in the intestine or bile duct.