MXPA01011235A - Compositions for treatment of disorders of the oesophagus - Google Patents

Abstract

Pharmaceutical compositions having improved bioadhesive properties are produced by combining an alginate, xanthan gum and/or a carageenan gum and a glucomannan and/or a galactomannan. The composition can provide both a protecting and a healing effect on mucosal surface.

Description

COMPOSITIONS FOR THE TREATMENT OF ESOPHAGUS DISORDERS FIELD OF THE INVENTION The present invention relates to compositions capable of releasably adhering to a surface. More particularly, the present invention relates to such compositions for use in coating a biological surface, for example, a mucosal surface and / or releasing an active ingredient to the biological surface.

BACKGROUND OF THE INVENTION It is known that many compositions are bioadhesive (ie capable of adhering to biological surfaces, for example mucous membranes, skin, mucosal surfaces, epithelium, etc.) and the value of this property is well recognized. For example, bioadhesives can be used to attach active agents to specific sites in the body for local administration of drugs, or to cover particular parts of the body. However, when the bioadhesives are applied to such surfaces in aqueous solution they can be easily washed off or mechanically removed, because the adhesion strength of each individual bioadhesive molecule to the surface is not very high. This can lead to additional problems if the bioadhesive materials contain active agents that are intended to be used at a particular site, but are washed away to other sites. This is especially true where bioadhesives are applied to the upper gastrointestinal (Gl) tract where flushing through the outlet and / or swallowed mucosa is a particular problem. The prior art does not provide a composition that is capable of adhering to biological surfaces and that can provide physical protection, for example, against episodes of gastric reflux as well as exerting a healing effect on the surface, for example, by releasing a pharmaceutically active ingredient to the surface. There is therefore a need for a bioadhesive pharmaceutical composition which is capable of coating a biological surface to protect and heal the surface and / or to release an active ingredient to the surface through the Gl tract. The need extends to a pharmaceutical composition which is capable of releasably adhering to desired regions of the esophagus immediately after ingestion and before the composition reaches the stomach, the composition being capable of exhibiting a protective and direct healing effect, whether this arises as a result of the barrier properties alone or as a consequence of incorporation of additional active ingredients in the formulation which can have a beneficial effect on the healing process, immediately after ingestion and before contact with the stomach. It is still desirable that the compositions are capable of resisting washout by biological fluids such as saliva or fluids that are subsequently ingested by the user and / or refluxed from the stomach. In addition to the foregoing, it is important that when in liquid form, the compositions are of such viscosity that they are capable of being provided in and reproducibly distributed from a single container in a form that is immediately ready for use by the consumer.

BRIEF DESCRIPTION OF THE INVENTION We have now found a novel composition for detachable adhesion on biological surfaces of mammals that satisfy some or all of the above needs. The viscosity and adhesion of the resulting formulations are such that these compositions show good adhesion, stability and washout resistance. According to a first aspect of the present invention, there is provided a pharmaceutical composition for the treatment of disorders of the esophagus, the composition comprising: a) 0.1 to 11.0 parts by weight, preferably 2.5 to 8 parts by weight of alginate ( the component a) hereinafter; b) 0.01 to 3.1 parts by weight, preferably 0.1 to 1.5 parts by weight of a gum selected from xanthan gum, carrageenan and mixture thereof (hereinafter component b); and c) 0.01 to - 3.0 parts by weight, preferably 0.1 to 1.5 parts by weight of a gum selected from a galactomannan, a glucomannan and mixtures thereof (hereinafter component c). The term "alginate" is intended to encompass alginic acids, salts of alginic acids (alginate salts), alginic acid derivatives, for example esters such as propylene glycol and mixtures thereof. The alginate is preferably a monovalent salt of alginic acid, for example the sodium, potassium or ammonium salt, more preferably the sodium salt. Such alginates can be supplied by FMC Biopolymer AS, for example the Protonal LFR5 / 60 and the Protonal LF10L. Preferably, the composition includes 1 to 10 parts by weight of alginate, more preferably between 2 and 9 parts by weight and more preferably between 3 and 8 parts by weight. Preferably component b) includes a larger amount of xanthan gum. More preferably, a component b) consists essentially of xanthan gum. In the context of this specification, a larger amount means that more than 50% by weight, preferably more than 70% by weight, even more preferably 90% by weight, especially more than 95% by weight, is present. reference component. Component c) can be any pharmaceutically acceptable glucomannan or galactomannan, including enzymatically altered derivatives thereof. Preferably, however, component c) includes a larger amount of a galactomannan. Preferably, component c) consists essentially of a galactomannan, especially locust bean gum.

Preferably components b) and c) are present in a total amount of 0.2 to 2.5 parts by weight, more preferably 0.7 to 2 parts by weight, more preferably 1 to 1.6 parts by weight. Preferably, components b) and c) are present in amounts in ratios from 1:10 to 10: 1, more preferably from 2: 8 to 8: 2.

DETAILED DESCRIPTION OF THE PREFERRED MODALITIES OF THE INVENTION In a preferred embodiment of the present invention, b) is present in an amount greater than c) so that the ratio of b): c) is in the range of 1.5: 1 to 3.5 : 1, more preferably in the range of 2: 1 to 3: 1, especially of approximately 2.3: 1. It will be appreciated that the compositions according to the present invention can be presented in solid form, for example as a chewable tablet, in granular or powder form, as a gel or as a liquid. It is preferred, however, that the composition be in the form of a liquid, more preferably a pourable liquid. The pourable media flows at room temperature (e.g., 20-24 ° C) (possibly flowing with vigorously reasonable stirring) so that doses of, for example, 5 ml can be measured with reasonable accuracy. For example, reproducible doses as low as 5 ml can be dispensed from bottles having neck diameters of 1.5 cm or more. Preferably the composition has a viscosity of between 500 and 10,000 mPa.s, more preferably between 1000 and 8,000 mPa.s measured in a Brookfield viscometer at 20 ° C and using a No. 3 spindle or needle. When in liquid form, it is preferred that the compositions be aqueous liquids. In a more preferred embodiment there is thus provided an aqueous bioadhesive pourable liquid composition for coating a biological surface for the treatment and / or prevention of esophagitis with reflux, gastritis, dyspepsia and esophageal disorders associated with reflux, the composition comprising: a) from 0.1 to 11% by weight, preferably from 2.5 to 8% by weight of alginate salt (hereinafter component a); b) from 0.01 to 3.1% by weight, preferably from 0.1 to 1.5% by weight of xanthan gum, (hereinafter component b); and c) from 0.01 to 3.0% by weight, preferably from 0.1 to 1.5% by weight of galactomannan or glucomannan (hereinafter component c).

Any component described herein as included in a composition according to the invention can be included in the aqueous composition of the most preferred embodiment. When a quantity is established in parts by weight in relation to a modality, the same value or numerical values expressed as "% by weight" can be applied to the most preferred modality. Thus, by way of example, it was previously described that a composition may include from 1 to 10 parts by weight of alginate. This can be expressed as 1 to 10% by weight when applied to the most preferred formulation and so on. The mixtures of xanthan gum and a glucomannan, or galactomannan, for example locust bean gum, have been widely used as thickening and gelling agents in food industries. However, an aqueous mixture of 1.0% by weight xanthan gum and black bean gum or 0.4% by weight black acacia has a viscosity of about 35,000 mPa.s at 20 ° measured on a Brookfield Viscometer using the spindle or needle No. 3. Indeed, it has a consistency similar to that of jelly which is disadvantageous when in principle it is difficult to pour in a reproducible manner doses, for example 5 ml from a bottle and secondly, such a thick product It does not enjoy wide acceptance by the consumer due to the sensation it gives in the mouth, appearance and the like. The inventors have surprisingly found that the addition of certain alginate components to the mixture actually reduces the viscosity of the blend to levels within consumer acceptance. The composition has been found to exhibit superior bioadhesive properties, particularly on mucosal tissues, such as the esophagus. In a preferred embodiment of the present invention, the composition is also useful for treating and / or relieving the effects of gastric reflux by forming a floating mass which floats on the stomach contents of a consumer of the product., Floating mass which prevents the reflux of the gastric content into the esophagus or proceed the gastric contents towards the esophagus. It will be appreciated that the composition preceding the gastric contents into the esophagus during a reflux episode may be beneficial since the physical barrier of the composition that adheres or covers the esophagus due to its superior bioadhesive properties will be recharged during such an episode. According to this preferred embodiment of the present invention, the composition further includes any one or more of the additional ingredients selected from the group consisting of agents that form a pharmaceutically acceptable gas, a source of di or trivalent metal ions, buffering agents, preservatives, sweeteners and flavorings. Preferably, the pharmaceutically acceptable gas forming agents are the carbon dioxide forming agents (C02), and preferably alkali metal bicarbonates, for example, sodium bicarbonate, potassium bicarbonate and / or mixtures thereof. . The concentration of alkali metal bicarbonate in the compositions of the invention is preferably from 0.1 to 8% by weight, more preferably from 0.5 to 5% by weight, still more preferably from 1 to 3 parts by weight and more preferably from 1.5 to 3 parts by weight. Preferably, the source of di or trivalent metal ions is suitable for crosslinking the alginate molecules in the composition to form an effective floating mass in the stomach. Those metal ions preferably become available when the compositions reach the stomach, but are not available before this (since the compositions will gel very early). Suitable metal ions are aluminum, and preferably, calcium ions. More preferably, the compositions comprise calcium carbonate. The compositions of the present invention therefore preferably further comprise from 0.1 to 5 parts by weight of calcium carbonate, more preferably from 0.5 to 3.5 parts by weight of calcium carbonate, more preferably from 0.75 to 3 parts by weight. weight. The agents for adjusting the pH, ie the buffering agents, for example, monopotassium phosphate and / or dipotassium phosphate, can be included in the composition in an amount of 0.01 to 1 part by weight. The compositions of the present invention may further comprise preservatives to prevent contamination and. Subsequent deterioration by microorganisms. Examples of suitable preservatives are para-hydroxybenzoic acid esters and their salts, which are preferably used in combination. Examples of such esters include methyl, ethyl, propyl and butyl para-hydrobenzoate.

The preferred concentrations for the preservatives are 0.01 to 0.5 parts by weight. The compositions of the present invention may also include colorants, sweeteners (for example sodium saccharin) and / or flavorings. Preferably, the ingredients are present in an amount of 0.01 to 1 part by weight. In the composition according to this embodiment of the present invention, the gums, for example, the xanthan gum and the locust bean gum act as bioadhesive agents, as well as (very valuable) the suspending agent, thereby enjoying a dual function and avoiding the need for a separate suspending agent, for example, carbomer. Preferably, therefore, the compositions according to the present invention do not contain suspending agents other than gums, for example xanthan gum and locust bean gum. The carbomer has traditionally been used as a suspending agent in compositions that include an alginate for the formation of a floating mass in the stomach to prevent gastric reflux, the carbomer, in the absence of alginate, is a known bioadhesive but loses this property in the presence of of alginate. Xanthan gum and locust bean gum, in contrast to carbomer, are suitable suspending agents while present in an improved bioadhesive composition. Xanthan gum and locust bean gum are thus suitable for replacing carbomer as a suspending agent in compositions of this type.

The compositions of the present invention may also include additional ingredients to improve the desired properties of the composition. For example, additives such as simethicone may be added to increase the hydrophobicity of the formulation to improve its resistance to washout. Xanthan gum is commercially available from Kelco and Rhone Poulenc. The locust bean gum is commercially available from Carob S.A. and Rhone Poulenc. The composition according to the invention may further include an active ingredient selected from the group consisting of acetaminophen, ibuprofen, naproxen, diclofenac, ketoprofen, choline salicylate, benzamine ,. bupronorphine, hydrocortisone, betamethasone; decongestants (for example pseudoephedrine, phenylephrine, oxymetazoline, xylometazoline); cough suppressants (e.g. dextromethorphan, codeine, folocodine); expectorants (e.g., guaifenesin, n-acetylcysteine, bromhexine); antiseptics (for example triclosan, chloroxylenol, amylmetacresol, hexylresorcinol, dichlorobenzyl alcohol, benzyl alcohol); cardiovascular agents (for example glycerin trinitrate); local anesthetics (for example benzocaine, lignocaine); antacid agents (for example, calcium carbonate, sodium bicarbonate, magnesium trisilicate, aluminum hydroxide, magaldrate); antiulcer agents (for example, carbenoxolone, sucralfate, cimetidine, ranitidine, nizatidine, famotidine, omeprazole, pantoprazole); antihistamines (for example loratidine, terfenadine, diphenhydramine, chlorphenhydramine, triprolidine, acrivastine); antinauseous agents (for example prochlorperazine, sriptan); gut regulating agents (for example diphenoxylate, loperamide, sennosides); antifungal agents (for example clotrimazole) and antibiotics (for example fusafungin, thyrothricin). Although the compositions according to the present invention are endowed per se for the targeted release or sustained release of such an active ingredient, it will be appreciated that such an ingredient is preferably not contained in the composition. However, where an active ingredient is included, the composition may include less than 3% by weight, more preferably less than 2% by weight, more preferably less than 1 part by weight of the active ingredient. The present invention represents a completely novel method to the problem of gastric reflux since the esophagus can be coated in a protective manner with the composition immediately after ingestion of the composition to provide a physical barrier against the acid of gastric reflux. further, the coating may include ingredients which make the barrier, in effect, act as a chemical barrier (considering the inclusion of the ingredients that are capable of neutralizing or deactivating the acid or pepsin that are responsible for the irritation in the esophagus) , as well as a physical barrier. It will be appreciated that the compositions according to the invention may adhere to other biological surfaces of the body of a mammal, for example, the oral cavity, the back of the throat and the underside of the tongue or stomach. In a preferred embodiment of the present invention there is provided a pourable, bioadhesive, aqueous liquid composition, comprising: Monopotassium phosphate l. OOg dipotassium phosphate 4. 00g Baking soda 16. 8g Methyl paraben 4. 00g Propyl paraben 0. 60g Sodium saccharin l. OOg xanthan gum 9. 80g Calcium carbonate 8.00g Locust bean gum 4.20g Sodium alginate LFR5 / 60 50.00g Flavor 0.70g Deionized water up to lOOOml The compositions according to the present invention can be presented in containers containing multiple doses, for example, bottles containing from 50 to 1000 ml of a liquid product. The consumer can then distribute the correct dose from the container for consumption. The composition of the present invention can be provided in unit dosage form. Thus, for example, the composition can be presented in solid form as discrete tablets or capsules. Alternatively, the composition may be presented in liquid form as a chewable capsule, optionally including a plurality of compartments, each containing a full volume, which together total the desired dose. Preferably, however, the composition is presented in liquid or gel form in sachets. The sachets may vary in volume from 1 to 25 ml, preferably from 5 to 20 ml.

According to a further aspect of the present invention, there is provided a method for treating and / or preventing esophagitis due to reflux, gastritis, dyspepsia and / or disorders of the esophagus associated with reflux, which method comprises administering a quantity pharmaceutically. effective and pharmaceutical composition comprising: a) from 0.1 to 11% by weight, preferably from 2.5 to 8 parts by weight of alginate, (hereinafter component a); b) from 0.01 to 3.3% by weight, preferably from 0.1 to 1.5 parts by weight of a gum selected from xanthan gum, carrageenan gum and mixtures thereof (hereinafter component b); and c) from 0.01 to 3.0% by weight, preferably from 0.1 to 1.5 parts by weight of a gum selected from a galactomannan, d-glucomannan, and mixtures thereof (hereinafter component c) to a patient who need the same. In a preferred embodiment of this aspect of the present invention there is provided a method for treating and / or preventing reflux esophagitis, gastritis, dyspepsia and / or esophageal disorders associated with reflux, which method comprises administering a quantity pharmaceutically effective of an aqueous bioadhesive pourable liquid composition comprising: a) from 0.1 to 11% by weight, preferably from 2.5 to 8% by weight of alginate salt, (hereinafter component a); b) from 0.01 to 3.0% by weight, preferably from 0.1 to 1.5% by weight of xanthan gum (hereinafter component b); and c) from 0.01 to 3.0% by weight, preferably from 0.1 to 1.5% by weight of galactomannan or glucomannan (hereinafter component c) to a patient in need of it. According to a further aspect of the present invention there is provided the use of a composition according to the invention for the preparation of a medicament for the treatment of irritation and / or lesions in the esophagus, diseases and irritations of the mouth, throat, pharynx and / or stomach and / or other diseases caused by or associated with reflux, treatment which comprises administering a pharmaceutically effective amount of the medication to a patient in need thereof.

According to a further aspect of the present invention there is provided the use of a composition comprising; a) from 0.1 to 11% by weight, preferably from 2.5 to 8 parts by weight of alginate, (hereinafter component a); b) from 0.01 to 3.0% by weight, preferably from 0.1 to 1.5 parts by weight of a gum selected from xanthan gum, carrageenan gum and mixtures thereof (hereinafter component b); and c) from 0.01 to 3.0% by weight, preferably from 0.1 to 1.5 parts by weight of a gum selected from a galactomannan, a glucomannan, and mixtures thereof - (hereinafter the component for coating a biological surface in the treatment and / or prevention of reflux esophagitis, gastritis, dyspepsia and / or esophageal disorders associated with reflux. In a preferred embodiment of this aspect of the present invention is provides the use of an aqueous bioadhesive pourable liquid composition comprising: a) from 0.1 to 11% by weight, preferably from 2.5 to 8% by weight of alginate salt, ( the component a) hereinafter; b) from 0.01 to 3.0% by weight, preferably from 0.1 to 1.5% by weight of xanthan gum (hereinafter component b); and c) from 0.01 to 3.0% by weight, preferably from 0.1 to 1.5% by weight of galactomannan or glucomannan (hereinafter component c) to cover a biological surface in the treatment and / or prevention of reflux esophagitis, gastritis, dyspepsia and / or esophageal disorders associated with reflux. According to a further aspect of the present invention there is provided a composition comprising; a) from 0.1 to 11 parts by weight, preferably from 2.5 to 8 parts by weight of alginate (hereinafter component a); b) from 0.01 to 3.0 parts by weight, preferably from 0.1 to 1.5 parts by weight of a gum selected from xanthan gum, carrageenan gum and mixtures thereof (hereinafter component b); and c) from 0.01 to 3.0 parts by weight, preferably from 0.1 to 1.5 parts by weight of a gum selected from a galactomannan, a glucomannan, and mixtures thereof (hereinafter component c) for use in a method of treatment and / or prevention of reflux esophagitis, gastritis, dyspepsia and disorders of the esophagus associated with reflux, which method comprises administering a pharmaceutically effective amount of the composition to a patient in need thereof. In the preferred embodiment of the invention as described, all references in% by weight are% by weight per volume. Any feature in any aspect of any invention or embodiment described herein may be combined with any feature of any aspect of any other invention or embodiment described herein. The invention will now be illustrated by means of the following examples.

Example 1 mg / lOml Monopotassium phosphate 20.00 Dipotassium phosphate 40.00 Sodium bicarbonate 168.00 Ethyl paraben 20.00 Butyl sodium paraben 2.22 Saccharin sodium 10.00 Xanthan gum 49.00 Calcium carbonate 80.00 Robinia bean gum 21.00 Sodium alginate LFR5 / 60 300.00 Flavor 7.00 Water Deionized up to 10 ml Method of manufacture 1. Add the gum bean gum to the water, heat to 40 ° C and mix. 2. Add the sodium alginate and mix. 3. Add - sodium bicarbonate, phosphates, ethyl paraben, sodium butyl paraben and sodium saccharin and mix. 3. Add the xanthan gum and mix. 4. Add the calcium carbonate and mix. 5. Add the flavor and gauge to the desired volume and mix.

Example 2 Monopotassium phosphate 0.2% Dipotassium phosphate 0.4% Sodium bicarbonate 2.67% Ethyl paraben 0.2% Butyl sodium paraben 0.022% Sodium saccharine 0.1% Xanthan gum 0.49% Calcium carbonate 1.60% Locust bean gum 0.21% Sodium alginate LFR5 / 60 5.00% Taste 0.07% Deionized water for 100% of the volume (All percentages are by weight by volume of the composition). The method of manufacturing is the same as that of Example 1.

Example 3 mg / lOOOml Monopotassium phosphate 2.00 Dipotassium phosphate 4.00 Sodium bicarbonate 16.8 Ethyl paraben 2.00 Butyl sodium paraben 0.22 Sodium saccharine 1.00 Xanthan gum 9.80 Calcium carbonate 8.00 Locust bean gum 4.20 Sodium alginate LFR5 / 60 50.00 Flavor 0.70 Deionized water lOOOml Manufacturing method 1. Add phosphates, parabens, saccharins and sodium bicarbonate to a portion of the water and mix. 2. Add the xanthan gum and mix. 3. Add the calcium carbonate and mix. 4. Add the locust bean gum and mix. 5. Add the sodium alginate and mix. 6. Add the flavor, measure to the desired volume and mix.

Example 4 mg / lOml Monopotassium phosphate 20.00 Dipotassium phosphate 40.00 Sodium bicarbonate 168.00 Ethyl paraben 20.00 Butyl sodium paraben 2.20 Saccharin sodium 10.00 Xanthan gum 49.00 Calcium carbonate 80.00 Locust bean 21.00 Simethicone 100.00 Sodium alginate LFR5 / 60 100.00 Sodium alginate LF10L 100.00 Flavor 0.70 Deionized water up to lOml Manufacturing method 1. Add phosphates to the water and mix. 2. Add the sodium bicarbonate, ethyl paraben, sodium butylparaben and sodium saccharin to (1) and mix. 3. Add the xanthan gum to (2) and mix. 4. Add the calcium carbonate to (3) and mix. 5. Add the locust bean gum to (4) and mix. 6. Add the simethicone to (5) and mix. 7. Dry combine the two sodium alginates and add to (6) and mix. 8. Add the flavor and gauge to the desired volume with water and mix.

Example 5 mg / lOml Monopotassium phosphate 20.00 Dipotassium phosphate 40.00 Sodium bicarbonate 168.00 Ethyl paraben 20.00 Butyl sodium paraben 2.22 Sodium saccharin 10.00 Xanthan gum 49.00 Calcium carbonate 80.00 Locust bean gum 21.00 Sodium alginate LF10L 250.00 Flavor 7.00 Deionized water up to 10 ml method is the same as that of Example 3, Example 6 Monopotassium phosphate l.OOg Dipotassium phosphate 4.00g Sodium bicarbonate 16.8g Methyl paraben 4.00g Propyl paraben 0.60g Sodium saccharine l.OOg Xanthan gum 9.80g Calcium carbonate 8.00g Locust bean gum 4.20g Sodium alginate LFR5 / 60 50.00 g Flavor 0.70g Deionized water to lOOOml Method of handling 1. Add the locust bean gum to a portion of the water and heat to 40 ° C. 2. To a separate portion of the water add sodium alginate, phosphates, sodium bicarbonate, parabens and saccharin and mix. 3. To a third portion of the water add xanthan gum and mix. 4. Add (2) to (1) and mix. 5. Add - (3) to (4) and mix. 6. Add calcium carbonate, flavor, gauge to the desired volume and mix.

Example 7 A comparative study of the composition according to a preferred embodiment of the invention was carried out with a known liquid gastrointestinal product (Gaviscon Liquid (Registered Trade Mark)). The adhesion of the compositions to an artificial surface was determined as an indicator of the esophageal bioadhesion. The products were applied to a Visking pipe length placed at an angle to the horizontal in a humid environment. The products were eluted from the pipe with a constant flow of water and the amount of product remaining on the pipe was verified by weight. At least three experiments were carried out in duplicate with each product and the recorded times were averaged. The results of the comparative study are shown below.

Table 3: Comparative Study of Esophageal Bioadhesion by Example 3, Example 5 and Gaviscon Liquid (RTM) Example 8 per tablet 1. Alginate H120L 250mg 2. Xanthan gum 35mg 3. Lozenge gum 15mg 4. Xylitol 300mg 5. Mannitol 1225mg 6. Povidone K30 lOOmg 7. Taste 25mg 8. Magnesium stearate 50mg Manufacturing method 1. Combine dry 1, 2, 3, 4, and 5. 2. Granulate using a solution of 6 in isopropanol, dry at 50 ° C. 3. Pass the dry granules through a 1000 micron mesh. 4. Add 7 and 8 to the granules, mix for 3 minutes and press into tablets.

EXAMPLE 9 The formulation of Example 3 is packaged in pouches coated with a thin sheet of metal, each maintaining 10 ml of the composition. The contents of the pouches can be distributed by tearing a portion of the pouch and extruding the contents of the pouch in the mouth.

Example 10 Different aqueous mixtures of 1.0% w / v of xanthan gum and 0.4% w / locust bean gum were produced, including different contents of sodium alginate and their viscosities were measured. The results are shown below. Table 1: Viscosity v of Sodium alginate of% by weight for 1.0% by weight of Xanthan gum and 0.4% of locust bean gum. As can be seen from Table 1 above, sodium alginate concentrations between 2.5% by weight and 10% by weight reduce the viscosity of a mixture of 1.0% by weight of xanthan gum and 0.4% of locust bean gum up to below 7000 mPa.s. Such a product is then pourable and enjoys consumer acceptance.

Example 11 Using a constant concentration of sodium alginate of 5% by weight / volume and varying the concentration of xanthan gum and total locust bean gum, the following table was obtained.

Table 2: Viscosity v Total% by weight of Xanthan Gum and Locust Gum Table 2 clearly illustrates that particularly acceptable viscosities are achieved with a total gum content of less than 2% by weight. It is noted that in relation to this date, the best method known to the applicant to carry out the aforementioned invention, is that which is clear from the present description of the invention.

Claims (30)

1. CLAIMS Having described the invention as above, the content of the following claims is claimed as property. The use of a composition, comprising: a) from 0.1 to 11.0 parts by weight, preferably from 2.5 to 8 parts by weight of alginate (hereinafter component a); b) from 0.01 to 3.0 parts by weight, preferably from 0.1 to 1.5 parts by weight of a gum selected from xanthan gum, carrageenan and mixtures thereof (hereinafter component b); and c) from 0.01 to 3.0 parts by weight, preferably from 0.1 to 1.5 parts by weight of a gum selected from a -galactomannan, a glucomannan and mixtures thereof (hereinafter component c), in the preparation of a medicament for the treatment and / or prevention of irritation and / or lesions in the esophagus, diseases and / or irritations of the mouth, throat, pharynx and / or stomach and / or other diseases caused or associated with reflux.
2. 2. The use according to claim 1, wherein the alginate is a monovalent salt, preferably a sodium, potassium or ammonium salt, more preferably a sodium salt of alginic acid.
3. 3. The use according to claim 1 or 2, characterized in that the composition has a viscosity between 500 and 10000 mPa.s measured in a Brookfield viscometer at 20 ° C using a spindle or needle of number 3.
4. 4. The use of conformity with any of claims 1 to 3, wherein components b) and c) are present in the composition in a total amount of 0.2 to 2.5 parts by weight, preferably 0.7 to 2 parts by weight, more preferably from 1 to 1.6 parts by weight.
5. 5. The use according to any of claims 1 to 4, wherein components b) and e) are present in the composition in amounts of 1:10 to 10: 1, preferably 2: 8 to 8: 2.
6. 6. The use according to any of claims 1 to 5, wherein component c) consists essentially of a galactomannan, preferably locust bean gum.
7. The use according to any of the preceding claims, wherein the composition contains a source of carbon dioxide, preferably an alkali metal bicarbonate, more preferably sodium bicarbonate and / or potassium bicarbonate.
8. 8. The use according to claim 7, wherein the composition contains a source of di or trivalent cations, preferably calcium ions.
9. The use according to any of the preceding claims, wherein the composition further includes an active ingredient selected from the group consisting of acetaminophen, ibuprofen, naproxen, diclofenac, ketoprofen, choline salicylate, benzydamine, buprenorphine, hydrocortisone, betamethasone; decongestants (e.g., pseudoephedrine, phenylephrine, oxymetazoline, xylometazoline); cough suppressants (eg, dextromethorphan, codeine, folocodine); expectorants (e.g., guaifenesin, n-acetylcysteine, bromhexine); antiseptics (for example triclosan, chloroxylenol, amyl methacresol, hexylresorcinol, dichlorobenzyl alcohol, benzyl alcohol); cardiovascular agents (for example glyceryl trinitrate); local anesthetics (for example benzocaine, lignocaine); antacid agents (for example calcium carbonate, sodium bicarbonate, magnesium trisilicate, aluminum hydroxide, magaldrate); anti-ulcer agents (for example, carbenoxolone, sucralfate, cimetidine, ranitidine, nizatidine, famotidine, omeprazole, pantoprazole); antihistamines (for example loratidine, terfenadine, diphenhydramine, chlorphenhydramine, triprolidine, acrivastine); antinausea agents (for example prochlorperazine, sumatriptan); gut regulating agents (diphenoxylated, loperamide, sennosides); antifungal agents (for example clotrimazole) and antibiotics (for example fusafungin, thyrothricin).
10. The use according to any of the preceding claims, wherein the composition comprises: Monopotassium phosphate 1.00 g Dipotassium phosphate 4.00 g Sodium bicarbonate 16.8 g Methyl paraben 4.00 g Propyl paraben - - 0.60 g Sodium saccharin 1.00 g Xanthan gum 9.80 g Calcium carbonate 8.00 g Locust bean gum 4.20 g Sodium alginate LFR5 / 60 50.00 g Flavor 0.70 g Deionized water up to 1000 ml
11. 11. The use according to any of the preceding claims, wherein the composition is presented in unit dosage form, preferably in a pouch.
12. The use according to any of the preceding claims, wherein the medicament is for coating a biological surface in the treatment and / or prevention of reflux esophagitis, gastritis, dyspepsia and esophageal disorders associated with reflux.
13. 13. A pharmaceutical composition for the treatment of disorders of the esophagus, characterized in that the composition comprises: a) from 0.1 to 11.0 parts by weight, preferably from 2.5 to 8 parts by weight of alginate in the form of a monovalent salt (hereinafter hereinafter component a); b) from 0.01 to 3.0 parts by weight, preferably from 0.1 to 1.5 parts by weight of a gum selected from xanthan gum, carrageenan and mixtures thereof (hereinafter component b); and c) from 0.01 to 3.0 parts by weight, preferably from 0.1 to 1.5 parts by weight of a gum selected from a galactomannan, a glucomannan and mixtures thereof (hereinafter component c).
14. 14. A composition according to claim 13, characterized in that the alginate is a sodium, potassium or ammonium salt, more preferably a sodium salt of alginic acid.
15. 15. A composition according to claim 13 or 14, characterized in that it has a viscosity of between 500 and 10000 mPa.s measured in a Brookfield viscometer at 20 ° C using a spindle or no. 3.
16. A composition according to any of claims 13 to 15, characterized in that components b) and c) are present in the composition in a total amount of 0.2 to 2.5 parts by weight, preferably 0.7 to 2 parts. by weight, more preferably, 1 to 1.6 parts by weight.
17. 17. A composition according to any of claims 13 to 16, characterized in that components b) and c) are present in the composition in amounts in amounts of 1:10 to 10: 1, preferably 2: 8 to 8. :2.
18. 18. A composition according to any of claims 13 to 17, characterized in that component c) consists essentially of a galactomannan, preferably locust bean gum.
19. 19. A composition according to any of claims 13 to 18, characterized in that it contains a source of carbon dioxide, preferably an alkali metal bicarbonate, more preferably sodium bicarbonate and / or potassium bicarbonate.
20. 20. A composition according to claim 19, characterized in that it contains a source of di or trivalent cations, preferably calcium ions.
21. 21. A composition according to any of claims 13 to 20, characterized in that it further includes an active ingredient selected from the group consisting of acetaminophen, ibuprofen, naproxen, diclofenac, - - ketoprofen, choline salicylate, benzamine, buprenorphine, hydrocortisone, betamethasone; decongestants (e.g., pseudoephedrine, phenylephrine, oxymetazoline, xylometazoline); cough suppressants (eg, dextromethorphan, codeine, folocodine); expectorants (e.g., guaifenesin, n-acetylcysteine, bromhexine); antiseptics (for example triclosan, chloroxylenol, amyl methacresol, hexylresorcinol, dichlorobenzyl alcohol, benzyl alcohol); cardiovascular agents (for example glyceryl trinitrate); local anesthetics (for example benzocaine, lignocaine); antacid agents (for example calcium carbonate, sodium bicarbonate, magnesium trisilicate, aluminum hydroxide, magaldrate); anti-ulcer agents (for example, carbenoxolone, sucralfate, cimetidine, ranitidine, nizatidine, famotidine, omeprazole, pantoprazole); antihistamines (for example loratidine, terfenadine, diphenhydramine, chlorphenhydramine, triprolidine, acrivastine); antinausea agents (for example prochlorperazine, sumatriptan); gut regulating agents (diphenoxylated, loperamide, sennosides); antifungal agents (for example clotrimazole) and antibiotics (for example fusafungin, thyrothricin).
22. 22. A composition for the treatment of reflux esophagitis, gastritis, dyspepsia and / or disorders of the esophagus associated with reflux, the composition is characterized because it comprises: Monopotassium phosphate 1.00 g Dipotassium phosphate 4.00 g Sodium bicarbonate 16.8 g Methyl paraben 4.00 g Propyl paraben 0.60 g Sodium saccharin 1.00 g Xanthan gum 9.80 g Calcium carbonate 8.00 g Locust bean gum 4.20 g Sodium alginate LFR5 / 60 50.00 g Flavor 0.70 g Deionized water up to 1000 ml
23. 23. The composition according to any of claims 13 to 22, characterized in that it is presented in a unit dose form, preferably in a pouch.
24. 24. A method of treatment and / or prevention of reflux esophagitis, gastritis, dyspepsia and / or esophageal disorders associated with reflux, which method is characterized by the administration of a pharmaceutically effective amount of a composition comprising: a ) from 0.1 to 11.0 parts by weight, preferably from 2.5 to 8 parts by weight of alginate (hereinafter component a); b) from 0.01 to 3.0 parts by weight, preferably from 0.1 to 1.5 parts by weight of a gum selected from xanthan gum, carrageenan and mixtures thereof (hereinafter component b); and c) from 0.01 to 3.0 parts by weight, preferably from 0.1 to 1.5 parts by weight of a gum selected from a galactomannan, a glucomannan and mixtures thereof (hereinafter component c) to a patient in need of the same.
25. 25. The use of a composition comprising: a) from 0.1 to 11.0 parts by weight, preferably from 2.5 to 8 parts by weight of alginate (hereinafter component a); b) from 0.01 to 3.0 parts by weight, preferably from 0.1 to 1.5 parts by weight of a gum selected from xanthan gum, carrageenan and mixtures thereof (hereinafter component b); and c) from 0.01 to 3.0 parts by weight, preferably from 0.1 to 1.5 parts by weight of a gum selected from a galactomannan, a glucomannan and mixtures thereof (hereinafter component c), to cover-- biological surface in the treatment and / or prevention of reflux esophagitis, gastritis, dyspepsia and disorders of the esophagus associated with reflux.
26. 26. A composition, characterized in that it comprises: a) from 0.1 to 11.0 parts by weight, preferably from 2.5 to 8 parts by weight of alginate (hereinafter component a); b) from 0.01 to 3.0 parts by weight, preferably from 0.1 to 1.5 parts by weight of a gum selected from xanthan gum, carrageenan and mixtures thereof (hereinafter component b); and c) from 0.01 to 3.0 parts by weight, preferably from 0.1 to 1.5 parts by weight of a gum selected from a galactomannan, a glucomannan and mixtures thereof (hereinafter component c), for use in a method of treatment and / or prevention of reflux esophagitis, gastritis, dyspepsia and / or disorders of the esophagus associated with reflux, which method comprises administering a pharmaceutically effective amount of the composition to a patient in need of it.
27. 27. An aqueous bioadhesive pourable liquid composition for covering a biological surface in the treatment and / or prevention of reflux esophagitis, gastritis, dyspepsia and esophageal disorders associated with reflux, the composition is characterized in that it comprises: a) from 0.1 to 11.0 parts by weight, preferably 2.5 to 8% by weight of alginate salt (hereinafter component a); b) from 0.01 to 3.0% by weight, preferably from 0.1 to 1.5% by weight of a xanthan gum (hereinafter component b); and c) from 0.01 to 3.0% by weight, preferably from 0.1 to 1.5% by weight of galactomannan or glucomannan (hereinafter component c).
28. 28. The pharmaceutical composition according to the invention characterized in that it is substantially as described or exemplified herein above.
29. 29. A method of treatment and / or prevention of reflux esophagitis, gastritis, dyspepsia and esophageal disorders associated with reflux, according to the invention, characterized in that it is substantially as described or exemplified herein above.
30. 30. The use of a composition according to the invention, substantially as described or exemplified herein above.