TR201612691A1 - ORAL PHARMACEUTICAL COMPOSITIONS - Google Patents

Abstract

The present invention includes; seasonal or perennial allergic rhinitis, asthma associated with allergic rhinitis (allergic asthma, chronic asthma, bronchial asthma), chronic and acute bronchitis, Chronic Obstructive Pulmonary Disease (COPD), emphysema, bronchospasm, lung diseases, sinusitis, lower and upper respiratory tract infections, influenza, colds, colds, cough, expectoration, community acquired pneumonia (bronchiectasis), chronic respiratory system diseases, such as prophylactic and / or symptomatic and / or therapeutic suitable for use in mucolytic properties of the active agent and / or pharmaceutical pharmaceutically acceptable derivatives and / or pharmaceutically acceptable derivatives of the group of H1 receptor antagonists which is a non-sedative antihistamine; and pharmaceutically acceptable derivatives of the leukotriene receptor antagonist group. b contact / s.

Description

DESCRIPTION ORAL PHARMACEUTICAL COMPOSITIONS FIELD OF THE INVENTION The present invention; seasonal or perennial allergic rhinitis, asthma with allergic rhinitis (allergic asthma, chronic asthma, bronchial asthma), chronic and acute bronchitis, Chronic Obstructive Lung diseases such as Lung Disease (COPD), emphysema, bronchospasm, sinusitis, lower and lower upper respiratory tract infections, flu, colds, colds, cough, sputum chronic respiratory system such as diuretic, community-acquired pneumonia, bronchiectasis To be used in the prophylactic and/or symptomatic and/or therapeutic treatment of Suitable active substance with mucolytic properties and/or pharmaceutically acceptable derivatives are in the group of H1 receptor antagonists, which is a non-sedative antihistamine. appropriate active ingredient and/or pharmaceutically acceptable derivatives and leukotriene Acceptable as a suitable active substance and/or pharmaceutical in the receptor antagonist group It relates to pharmaceutical composition(s) comprising the combination therapy with its derivatives.

The present invention shows that the suitable active substance with mucolytic properties is Ambroxol, trans-4-(2-Amino- 3,5-dibromobenzylamino)-cyclohexanol (Formula 1) and/or pharmaceutically acceptable possible derivatives; H1 receptor antagonist, a non-sedating antihistamine Levocetirizine, 2-[4-[(4-chlorophenyl)(phenyl)methyl]piperazin-1-yl]ethoxy]acetic acid (Formula II) and/or pharmaceutically acceptable derivatives thereof; Montelukast, 1-(((1(R)-(3-(2-(7-chloro-) 2-quinolinyl)-ethenyl)phenyl)-3-(2-(1-hydroxy-1-methyl-ethyl)phenyl)-propyl)thio)methyl)cyclopropane acetic acid (Formula III) and/or pharmaceutically acceptable derivatives, and used in combination as active ingredients in appropriate pharmaceutical forms relates to pharmaceutical composition/s.

Formula I: Formula ll: Formula [11: In addition, the invention includes Ambroxol and/or pharmaceutically acceptable derivatives, Levocetirizine and/or pharmaceutically acceptable derivatives and Montelukast and/or used in combination with pharmaceutically acceptable derivatives formulations of the compositions suitable for oral administration and prophylactic and/or It also includes their use in symptomatic and/or therapeutic treatment. PRIOR ART (KNOWN STATE OF THE ART) Chronic Obstructive Pulmonary Disease (COPD) consists of chronic bronchitis and emphysema. leading to progressive dyspnea characterized by obstruction of the incoming airways It is a chronic respiratory disease.

Obstructive lung diseases are common all over the world and are the most important cause of mortality. is one of the reasons. According to the statistics of the World Health Organization, 600 million He has COPD. It is estimated that there are about 3 million people with COPD in our country.

Regardless of the disease causing the obstruction, the obstruction can be seen in the following three It comes with one of the mechanisms: a) Due to pathological events in the lumen b) Due to pathological events occurring in the walls of the respiratory tract c) Due to pathological events around the bronchi Type A chronic obstructive pulmonary diseases (Emphysema type) and type B chronic obstructive pulmonary diseases There are two main types of COPD, lung diseases (Bronchitis) type.

Chronic Bronchitis is caused by chronic inflammation and thickening of the bronchial walls, It is a disease that progresses with excessive mucus production in the bronchial tree. The weather in this disease The degree of narrowing of the passageways may be enough to impair breathing and coughing frequently. result in crises. The symptoms of patients with chronic bronchitis are cough and excessive expectoration of mucus from inflammation. excessive in practice most days for at least two years and at least three months of two years is an expectation. In chronic bronchitis pathology, the structural feature is the most important. hypertrophy of mucous glands in the bronchi and chronic inflammatory disease in the small airways the presence of changes. Chronic bronchitis is more serious and more frequent respiratory infections, narrowing and blockage of the bronchi, difficulty breathing or can cause weakness.

If emphysema; one of the most common chronic lung diseases leading to respiratory failure is one. A condition that occurs when the air sacs (alveoli) in the lungs are stretched and enlarged. is a disease. This expansion causes the air to rupture the thin walls that separate the vesicles from each other. and therefore causes loss of flexibility in the lungs. As a result, air entry into the lungs and The balance of blood gases (oxygen-carbon dioxide) in the air sacs is disturbed. Advanced In emphysema cases, the lungs are enlarged, withered, and dried. Their flexibility They are like a pillow because there is no left over. When the chest is opened, the lungs do not deflate, because air remains in them due to loss of elasticity. The predominant symptom in patients with emphysema Drugs that affect mucus are mucolytics, mucokinetics (expectors) and It can be grouped into 3 classes as inucoregulators.

- Mucolytics break down mucoproteins in mucus, thereby reducing the viscosity of sputum. are drugs that can make it liquified by reducing it. The main ones are; N-acetylcysteine (NAC) and S- is carboxyinethyl cysteine (carbocysteine). N-acetylcysteine is a glutathione precursor. It also benefits from the inhibitory effect of free radicals.

° Mucokinetics (expectors) increase mucus flow to expel sputum with coughing makes it easy to throw. The most known drugs of this group are; iodides, glyceryl guajacolate and is bromexin.

- Mucoregulators impair the synthesis of sialomucin, reducing viscosity and secretion. increases. Scarbocysteine is the most widely used in Europe. These drugs are oral or parenteral. given via.

Pharmacological and non-pharmacological treatment of moderate to severe COPD therapies are used. In the study by Cazzola et al. antibiotics, bronchodilators, corticosteroids and mucolytic agents.

Ambroxol is used for acute and chronic diseases associated with respiratory secretion disorders. diseases, especially acute and chronic bronchitis, bronchial asthma, bronchiectasis and surgery It is useful in the treatment and prophylaxis of post-interventional bronchopulmonary complications.

Ambroxol reduces the density and stickiness of the secretions collected in the respiratory tract. has features. Thus, the patient has less difficulty in expelling his secretions and his breathing it gets easier.

Asthma occurs in the bronchial airways, which are the tubes that carry air from the outside of the body to the lungs. It is a chronic inflammation.

Kaline et al. in patients with allergic rhinitis, with oral leukotriene receptor antagonist therapy It has been reported that clinical improvement occurs in 30% to 50% of the complaints (Kaliner M. et al., Moreover; Numerous studies have shown that appropriate treatment of allergic rhinitis in patients with asthma symptoms, decreased bronchial sensitivity, and protection against bronchospasm showed that it resulted in

Leukotriene receptor antagonists are among the drugs used in the treatment of asthma in our country. is located. These include the effects of leukotrienes, which have important roles in the pathogenesis of asthma, They show by blocking the receptor or at the synthesis stage.

Montelukast for the treatment and prevention of leukotriene-mediated diseases and disorders can be used. Leukotriene antagonists, among others, for asthma, allergic rhinitis (seasonal and continuous), atopic dermatitis, chronic urticaria, sinusitis, nasal polyps, chronic obstructive pulmonary disease, conjunctivitis, migraine, cystic fibrosis and viral It is useful in the treatment of wheezing secondary to bronchiolitis.

Levocetirizine, the (R) enantiomer of cetirizine, is a potent and selective piperazine derivative. It is a peripheral H 1 -receptor antagonist.

Use of levocetirizine in the treatment of seasonal or perennial allergic rhinitis WO 9406429 It is explained in document no. Formulations in the form of tablets, capsules for release are described.

In document WO 9949843 a novel and therapeutically advantageous hard, quick-release for cetirizine It is mentioned that the preparation of melting effervescent formulations is mentioned.

DESCRIPTION OF THE INVENTION The present invention; seasonal or perennial allergic rhinitis, asthma with allergic rhinitis (allergic asthma, chronic asthma, bronchial asthma), chronic and acute bronchitis, Chronic Obstructive Lung diseases such as Lung Disease (COPD), emphysema, bronchospasm, sinusitis, lower and lower upper respiratory tract infections, flu, colds, colds, cough, sputum chronic respiratory system such as diuretic, community-acquired pneumonia, bronchiectasis To be used in the prophylactic and/or symptomatic and/or therapeutic treatment of Suitable active substance with mucolytic properties and/or pharmaceutically acceptable derivatives are in the group of H1 receptor antagonists, which is a non-sedative antihistamine. appropriate active ingredient and/or pharmaceutically acceptable derivatives and leukotriene Acceptable as a suitable active substance and/or pharmaceutical in the receptor antagonist group It relates to pharmaceutical composition(s) comprising the combination therapy with its derivatives.

Another aspect of the present invention is; suitable agent with mucolytic properties for oral use substance and/or pharmaceutically acceptable derivatives, a non-sedative Appropriate active ingredient in the group of H1 receptor antagonists, which are antihistamines and/or pharmaceutically acceptable derivatives and leukotriene receptor antagonist Suitable active ingredient and/or pharmaceutically acceptable derivatives of combination therapy with and suitable pharmaceutically acceptable excipients relates to the preparation of pharmaceutical composition(s) containing The appropriate active substance with mucolytic properties used in the invention is not limited to these. together; erdosteine, acetylcysteine, ambroxol, broinhexine, carbocysteine, domiodol, as eprazinone, letostein, neltenexin, sobrerol, stepronin, thiopronin and/or pharmaceutical it is preferably selected as ambroxol hydrochloride from among its acceptable derivatives.

Appropriate active ingredient in the group of H1 receptor antagonists used in the invention though not frustrated with them; diphenhydramine, dimenhydrinate, doxylamine, antazoline, mepyramine, chlorpheiiiramine, fexofenadine, loratadiii, azelastine, cetiriziii, cyclizine, clemastine, desloratadine, dexchloropheniramine, dimetinden, ebastine, levocetirizine, emedastine, meclozine, olopatadine, pheniramine, promethazine, quetiapine, rupatadine and/or pharmaceutically acceptable It is preferably selected as levocetirizine among its derivatives.

The appropriate active ingredient in the leukotriene receptor antagonist group used in the invention though not frustrated with them; zafirlukast, montelukast, pobilukast, tomelukast, preferably among verlukast, pranlukast and/or pharmaceutically acceptable derivatives Montelukast is chosen as sodium.

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, ainides, 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, dry powder, granule, caplet, disc, mouth soluble film, bulk powder (multi-dose), pellet, sachet, water-dispersible powder, water-dispersible granule, effervescent tablet, effervescent granule, effervescent powder, microcapsule, dental tablets, pilula, syrup, solution, as a dosage form such as suspension, elixir, drops, position, emulsion, or spray. can be formulated.

The finished product is obtained by mixing the active substance and auxiliary substances in powder form. chassis can be formulated.

Some of the granules prepared for oral administration are swallowed, some are chewed, some are used by dissolving or dispersing in water or other suitable liquid.

Granules contain one or more active ingredients, excipients, color and fragrance if necessary. They also contain donor substances. They can also be prepared without auxiliary substances. Granules single They can be packaged in dose or multidose form. Multi-dose preparations, at the desired dose They are packaged with a suitable scale so that they can be taken. Single dose granules bag, paper supplied in single-unit containers such as packs or vials. production, packaging, storage and their distribution should be carried out away from microbial contamination. volatile or Granules containing substances to be protected should be stored in tightly closed containers.

Effervescent granules: They are uncoated granules. Usually acid substances, carbonates or containing bicarbonates and reacting rapidly with water to release carbon dioxide are granules. It is dissolved or dispersed in water before application. As an active substance carrier they are used. It contains acidic substances such as citric acid, tartaric acid, fuinaric acid in its formulations. they contain alkaline substances such as sodium carbonate, sodium bicarbonate and sodium biphosphate.

Coated granules: They are mostly multi-dose preparations and contain various excipients. It consists of granules coated in one or more layers with their mixture. Coater Substances used as solvents are often in the form of solutions or suspensions and It is applied in conditions where it is evaporated. Appropriate release of the active substance to the coated granules. A suitable dissolution test, for example, for solid dosage forms one of the tests described can be applied.

Modified release granules: The release rate, location or location of the active substance or substances. designed to modify the timing, containing special excipients, or They are coated or uncoated granules, individually or together, prepared by processes.

A suitable dissolution on these granules to show the mode of release of the active substance. test is applied.

Gastro-resistant granules: resistant to gastric fluid and Delayed, designed for the release of the active substance(s) in an intestinal fluid releasing granules. These properties are due to the fact that the granules are combined with a gastric fluid-resistant material. It is provided by coating (enteric coated granules) or by other suitable means. This an appropriate test on the granules to determine the appropriate release of the active substance. For example, one of the tests described for solid dosage forms can be applied.

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 pelletizing 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 tablet compression 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: - Grinding the active ingredient (if necessary), - Mixing with powder substances, - Ensuring the aggregation of the particles of the powder mixture with the addition of binder, The process is called granulation.) - Screening of quinineated particles as wet, o Drying of the sifted powder mixture is widely used in the drying process. using bed dryers, - Dry grinding after drying, - 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.) - It is the transition to tablet pressing or the stages for the desired pharmaceutical form.

Dry Granulation: In the dry granulation method, 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 It can be passed to the appropriate stages for the desired pharmaceutical form.

Tablet(s) for oral use may contain one or more coatings.

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 time.

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

The pharmaceutical formulation(s) of the invention may contain one or more layers. Sufficient To ensure the therapeutic effect and to minimize the side effects, the release of the drug should be reduced. layer/s are changed, modified, controlled, extended, continuous, with one or more of the immediate or delayed release pharmaceutical dosage forms can be formulated.

Its pharmacokinetic properties are not in accordance with the user's expectations, for example half-life. short-lived, rapid/high peak with undesirable effects concentration, which has not good bioavailability due to various reasons, etc. for drugs By changing the pharmaceutical forms, the release patterns in the gastrointestinal tract are aimed More optimized preparations are being developed. These have been changed many times, They are referred to as controlled, slowed and extended release formulations.

The compositions of modified oscillating formulations are important for their function.

Modified-release drug formulations, although they may be more expensive, short half-life, peak, in which adherence to treatment is important for treatment success For drugs that reach concentration rapidly, with varying phaimacokinetics, it is more They are useful and ultimately reduce the cost of treatment. Modified release systems They are classified as transdermal systems and oral systems. delayed release In systems, the release of the active substance from the system occurs in a certain region. Generally It is 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.

capsules; gelatin, cellulose esters, polyvinyl alcohol, etc. for single-dose drug administration. They are containers made of one of the materials. Doses, solid and partial substances into capsules, Liquid drugs that do not dissolve the capsule can be placed. Capsules are generally divided into two; rigid/two-piece capsules and soft capsules.

Hard capsules consist of two parts: the container and the lid part. Bitter taste, swallowed capsules of difficult, air-perishable powders and drugs that are required to be rapidly absorbed. is anticipated to be given. The main ingredient of hard gelatin capsules is a macromolecular It consists of high-value gelatin, which is a protein. Hard gelatin capsules gelatin, gum arabic, It is prepared from a mixture of paint and water with special techniques and special machines. hard capsules It is prepared by dipping method. The principle of this method is made of stainless steel on the surface of these rods by immersing them in the melted capsule wall solution. is the formation of the capsule wall film. Gelatin, dyes, preservatives and water, hard They are the substances that make up the gelatin capsule wall.

Hard capsules can be filled in powder, granule, pellet, tablet, liquid, and semi-solid forms.

There are two basic requirements for any formulation filled into capsules. The formulation must be filled in the correct dose and the active substance must be extracted from the capsule for the treatment of the patient. should be released in sufficient quantity. For the preparation of hard gelatin capsule formulations active ingredient, fillers, flow-improving agents, glidants, anti-friction inhibitors, lubricants, dispersants, surfactants are used.

Soft capsules: single gelatin prepared with mixtures of glycerin, sorbitol, gum arabic and water. They are round, elliptical and tube-shaped capsules consisting of pieces. Required items After being placed, they are closed to not open. Soft capsules, gelatin of a liquid content It is prepared by enclosing it with the capsule wall. They are more flexible than hard capsules.

Soft capsules are round, oval, oblong (oblong stick) or tubular they may be. They consist of one piece. Soft gelatin capsules are usually included in solution or Liquid drug forms in suspension form are filled. However, semi-solids and powders are also can be filled. Production of soft capsules, insoluble substances, low-dose active substances, highly active compounds, oxygen sensitive substances, bad taste suitable for materials. In the production of soft gelatin capsules, the capsule wall a successive sequence of preparation, filling of the material and closure of the capsule. consists of the name.

Syrups are active in high skin solutions of sucrose or other sugars. liquid medicine formed by the dissolution of substances and auxiliary substances by various methods are shapes. Syrups prepared by dissolving only 64% sucrose in water It is called Simple Surup (Sirupus Simplex). Syrups contain 85% w/v sugar according to USP 24.

In addition to sugar and other sweeteners, it is added to syrups to prevent crystallization, increase solubility. and adding sorbitol or glycerin to alter the taste and aromatic substances to impart flavor Preparation methods of syrups: Prepared by simple thawing, either hot or cold - Syrups prepared with extracts and tinctures - Prepared by maceration and digestion method - Syrups prepared with fruit juices - Prepared by percolation - Resolution method can be listed as those prepared with.

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, thickening 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, suspension one or more excipients selected from the group including the agent and stabilizer Defines a composition that can contain

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 polyiners, 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 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 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 dimethylainin 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, tripalniityl, 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, 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.

As preservatives, 2-phenoxyethanol, sodium beiizoate, benzoic acid, benzyl alcohol, ethylenediaminetetraacetic acid, sodium methyl 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 aiiisol (BHA), butyl hydroxy toluene (BHT), calcium 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 expressed 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-furitti aroma, 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, 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 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 emulsion, dimethylsiloxang 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; 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. slacker as substance; sodium lauryl sulfate, sodium docusate, polysorbates, sorbitan monolaurate, 0kt0xinol-9, nonoxynol-IO, 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, iodine 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 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. Purified water as solvent, ethyl alcohol, niethyl 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.

In the invention, the term "soft material"; 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, glycerine, hydrocarbons, lanolin, waxes, fatty acids, cet] 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-1S stearyl ether (PPC-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 their mixtures can be used. Moreover herbal softeners such as castor oil, coconut oil, olive oil and vegetable waxes 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, cetostearyl 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 monooleate, 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 monopalmitate, 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 can be used.

In the invention, the term "permeabilizing agent" refers to a substance that facilitates saliva penetration and thus creating a hydrothermal 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. are being acquired. As an antioxidant; tocopherol (vitamin E), ascorbic acid (vitamin C), A Vitamins such as vitamin K, carotenoids, carotenes (eg, d-carotene, ß- carotene, lycopene, l'utein, zeaxanthin), minerals (Se, Zn), butyl hydroxy anisole (BHA), butyl hydroxy toluene (BHT), ethylgalate, pr0pilgalate, 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 amines, secondary amines, tertiary amines, cyclic amines, calcium glycerophosphate, calcium gluconate, calcium acetate, N,N” dibenzylethylenediamine, diethanolamine, ethylenediamine, meglumine, disodyuin hydrogen orthophosphate, sodium aluminum, 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 inethyl 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 formulations against various pressures and forces. are expressed as substances used for strengthening. As a hardening agent; set] 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 balmuinu, 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 polyiner, polyinethacrylate, ethyl inethacrylate copolyiner, methacrylic acid-methylmethacrylate copolyiner, 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, ethylinethacrylate, 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 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, arnyl 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 antiadherent; talc, colloidal silicon 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. 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 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 paratin, petrolatum (petrolatum), liquid petrolatum, cellulose and cellulose-containing substances, gums (tragacanth), some electrolytes (A1 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.

In the invention, the term "suspension agent" is used to increase viscosity and slow settling. used for the purpose. In the invention, xanthan gum, guar gum, carrageenan, ethylcellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, polyvinylpyrrolidone, hydroxypropyl methylcellulose (HPMC), methyl cellulose or mixtures thereof 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 ethoxylated 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, ethylene diamine tetraacetic acid (EDTA), diethylene triamine penta acetic acid or mixtures thereof can be used.

Appropriate active ingredient(s) and/or pharmaceutically acceptable in the present invention Ainbroxol in the pharmaceutical composition containing derivatives and/or pharmaceutically acceptable the amount of available derivatives is 5-750mg, preferably 15mg and 30mg; Levocetirizine and/or the amount of pharmaceutically acceptable derivatives; 0.1-70mg preferably 1mg, 2.5mg and 5mg; Quantity of Montelukast and/or pharmaceutically acceptable derivatives; 0.1-80mg preferably ng, 4mg, Smg and lOing are based on the individual needs of the patient and the specialist. adjusted according to its assessment.

The invention mainly consists of Ambroxol and/or Mucolytic Ambroxol for oral use. pharmaceutically acceptable derivatives of Hl, a non-sedative antihistaminic Levocetirizine in the group of receptor antagonists and/or pharmaceutically acceptable Montelukast, which is in the group of leukotriene receptor antagonists and/or combination therapy with pharmaceutically acceptable derivatives and pharmaceutically by the preparation of pharmaceutical composition(s) containing suitable acceptable excipients. is relevant. Thus, the prepared Ainbroxol and/or pharmaceutically acceptable derivatives, Levocetirizine and/or pharmaceutically acceptable derivatives and Combination with Montelukast and/or pharmaceutically acceptable derivatives Containing formulation/s synergistically combined, breaking bacterial resistance together with the antibacterial activity of pharmaceutical formulations and thus the therapeutic increased effectiveness and surprisingly in terms of physical and chemical stability It was observed that they exhibited a very stable behavior.

Claims (1)

REQUESTS 1. Appropriate active substance and/or pharmaceutically acceptable derivatives with mucolytic properties for oral use, suitable active substance and/or pharmaceutically acceptable derivatives in the group of H1 receptor antagonists, which is a non-sedative antihistamine, and appropriate derivatives in the group of leukotriene receptor antagonists. Preparation of pharmaceutical composition(s) containing the active substance and/or its combination therapy with pharmaceutically acceptable derivatives and suitable pharmaceutically acceptable excipients. . It is a pharmaceutical composition/s as in the request, and its feature is; is to select the appropriate active ingredient with mucolytic properties among erdosteine, acetylcysteine, ambroxol, bromhexine, carbocysteine, domiodol, eprazinone, letostein, neltenexin, sobrerol, stepronin, thiopronin and/or pharmaceutically acceptable derivatives. . It is a pharmaceutical composition/s as in Claim 1 and its feature is; A suitable active ingredient with mucolytic properties is preferably ambroxol hydrochloride. . It is a pharmaceutical composition/s as in claim 1 and its feature is; Suitable active agents in the group of H1 receptor antagonists are inaddenine diphenhydramine; dimenhydrinate, doxylamine, antazoline, mepyramine; Selection of acceptable intermediates from chlorpheniramine, fexofenadine, loratadine, azelastine, cetirizine, cyclizine, clemastine, desloratadine, dexchloropheniramine, dimetinden, ebastine, levocetirizine, emedastine, meclozine, olopatadine, pheniramine, proinetadine, quetiapine, or rupatadin as acceptable derivatives, and rupatadine. . It is a pharmaceutical composition/s as in Claim 1 and its feature is; The appropriate active ingredient in the group of H1 receptor antagonists is preferably levocetirizine. . It is a pharmaceutical composition/s as in the request, and its feature is; The appropriate active ingredient in the leukotriene receptor antagonist group is selected among zafirlukast, montelukast, pobilukast, tomelukast, verlukast, pranlukast and/or pharmaceutically acceptable derivatives. . It is a pharmaceutical composition/s as in claim 1 and its feature is; The appropriate active ingredient in the leukotriene receptor antagonist group is preferably montelukast sodium. . It is a pharmaceutical composition/s as in request 1 and its feature is; tablet of pharmaceutical dosage form (uncoated, chewable, orally soluble, dispersible; water-dispersible, film-coated; mono-layer, double-layer, intestinal release coated, mini-tablet, controlled-release, sustained-release, immediate-release, extended-release, delayed-release, modified release, buccal), capsule (hard, soft, enteric coated, film coated, controlled release, sustained release, immediate release, extended release, delayed release, modified release), powder, dry powder, granule, caplet, disc, oral soluble 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, elixir, drops, position, emulsion or comprising one or more pharmaceutical dosage forms selected from sprays. It is a pharmaceutical composition/s according to any of the above claims and its feature is; 5-750mg of the amount of Ambroxol and/or pharmaceutically acceptable derivatives in the pharmaceutical composition containing the appropriate active ingredient/s and/or its pharmaceutically acceptable derivatives; 0.1-70mg of the amount of levocetirizine and/or its pharmaceutically acceptable derivatives; Montelukast and/or its pharmaceutically acceptable derivatives are pharmaceutical composition/s according to any one of the above claims and its feature is; seasonal or perennial allergic rhinitis, asthma with allergic rhinitis (allergic asthma, chronic asthma, bronchial asthma), chronic and acute bronchitis, chronic obstructive pulmonary disease (COPD), emphysema, lung diseases such as bronchospasm, sinusitis, lower and upper respiratory tract It is indicated for the prophylactic and/or symptomatic and/or therapeutic treatment of chronic respiratory system diseases such as infections, influenza, colds, cough, expectoration, community-acquired pneumonia, bronchiectasis.