MXPA99011247A - Therapeutically active compositions - Google Patents

Abstract

A pharmaceutical composition for the treatment of irritable bowel syndrome which composition includes a carrier vehicle and a vanilloid compound is provided. The carrier vehicle enables the vanilloid compound to be released in the lower GI tract. The vanilloid compound has the effect of desensitising nerves in the lower GI tract leading to the relief of symptoms of irritable bowel syndrome.

Description

THERAPEUTICALLY ACTIVE COMPOSITIONS The present invention relates to compositions for the treatment of irritable bowel syndrome (IBS) and more especially to compositions locally active in the region posterior to the stomach of the gastrointestinal tract Gl. Irritable bowel syndrome (IBS) is part of a range of ailments that are generally known as Functional Gastrointestinal Disorders and include diseases such as chest pain of non-cardiac origin, non-ulcer dyspepsia, and chronic constipation or diarrhea. All these diseases are characterized by chronic or recurrent gastrointestinal symptoms for which it is not possible to find a structural or biochemical cause. In the United Kingdom alone, irritable bowel syndrome is the cause of 30-50% of referrals to gastroenterology. It is thought that irritable bowel syndrome (IBS) has its origin in various factors of a physiological, emotional, cognitive and behavioral nature and it is common to appear during periods of stress. The diagnosis of IBS is made by exclusion and is based on the symptoms observed in a specific case. The commonly accepted criteria for diagnosing IBS, known as "Rome" criteria, require at least three months of recurrent or continuous symptoms of the following type: 1. Abdominal pain or discomfort that is relieved by detection and / or is related to a change in the frequency of the depositions, and / or related to a change in the consistency of the depositions; and 2. Two or more of the following symptoms present at least a quarter of the time: altered frequency of bowel movements, altered bowel shape, altered passage of bowel movements, passage of mucus and / or swelling or sensation of abdominal distension. Conventional IBS treatments depend on the severity and nature of the symptoms in each patient and also on the fact that psychological factors are involved or not. The treatment of IBS may include one or more of the following recommendations: lifestyle change, pharmacological treatment or psychological treatment. However, there is no general treatment applicable to all cases. In some cases, it is advised to eliminate the diet of foods that aggravate the symptoms of IBS.

However, this type of treatment is only effective when the underlying cause of IBS is related to diet. Pharmacologically active agents are often used to treat IBS. Antidiarrheals (for example, loperamide), relaxants of the smooth muscular system (for example, mebeverine hydrochloride or alverine citrate) or antidepressants may be effective for the treatment of IBS. However, there is no single pharmacologically active agent that is totally effective in relieving IBS symptoms or curing it. It can be used to treat the IBS psychological elements. Again, however, these treatments do not provide a universal means of curing IBS symptoms because not all causes of IBS can be attributed to psychological factors. In the U.S. patent No. 5431914 is disclosed a method for the treatment of pathological conditions of the small intestine and large intestine. This patent reveals that the external application of capsaicin on the skin in certain regions affects certain cutaneous nerves that are inserted into segments of the spine. Thus, it is suggested that the topical application of a 0.03 mg dose of capsaicin on the anterior and posterior region of the spinal nerves T12 and S3 ^ can be used for the treatment of IBS. However, no clear explanation of the mechanism of action of this invention is known. This method of self-administration is not likely to be effective because the composition should be applied in a specific location whose location is not immediately apparent to the patient. On the other hand, it is likely that it will not be easy to control the doses of the composition described in U.S. Pat. No. 5431914, since the presentation is in the form of a topical cream. There is thus a need for a composition capable of relieving the symptoms of irritable bowel syndrome whose ideal presentation is easy to apply and which can be administered in unit dosage forms that the patient himself can handle. According to a first aspect of the present invention, and to alleviate the problems of irritable bowel syndrome IBS, a pharmaceutical composition is disclosed which will be used in the treatment of irritable bowel syndrome, diarrhea, constipation, pain and / or abdominal inflammation or abdominal distension in mammals, especially in human patients, composition whose composition comprises: i) one or more vanillin compounds, pharmaceutically acceptable salts, analogues and / or derivatives thereof (component (a)); and ii) an acceptable carrier for pharmaceutical use (compound (b)), wherein component b) is selected to allow component (a) to be released into the gastrointestinal tract between the stomach and rectum of the mammal. Preferably, the compound (a) is present in suitable amounts to alleviate the symptoms of irritable bowel syndrome. The composition according to the present invention preferably contains between 0.001 and 30% of component (a) more preferably between 0.01 and 20% of this compound and more preferably still between 0.1 and 10% by weight of the composition pharmaceutically acceptable. Preferably, the composition according to the present invention contains between 70 and 99.999% of component (b), more preferably contains between 80 and 99.999% and more preferably still contains between 90 and 99.9% by weight of said composition . According to a second aspect of the present invention, a pharmaceutically acceptable composition as described above with respect to the first aspect of the invention is presented, but also includes a cover or enteric coating (component (c)) that covers the components ( a) and (b). According to a third aspect of the present invention, there is presented a process for alleviating the symptoms related to irritable bowel syndrome (IBS) in mammals, preferably in human patients affected by said symptoms, a process comprising the following steps: preferably oral administration of a therapeutically effective amount gives the pharmaceutical composition according to the first or second aspect of the present invention described above, administration intended to alleviate the symptoms described related to irritable bowel syndrome (IBS). According to a fourth aspect of the present invention, a process according to the third aspect of this invention described above is presented, a process in which the pharmaceutical composition has the prolonged release form, form that allows the release of the active substance (i.e. , of at least 75% of component (a) of the pharmaceutical composition) in the gastrointestinal region posterior to the stomach and anterior to the rectum of the patient under treatment.

In the context of the present invention, it is understood that component (a) of the present invention is a compound or a mixture of compounds having a biologically active vanillin group. The component (a) therefore includes natural or synthetic vanillin substances, pharmaceutically acceptable salts thereof (natural or synthetic), as well as acceptable derivatives for pharmaceutical use and / or analogs thereof (natural or synthetic). Within the scope of natural vanillin substances are pure or purified extracts of active vanillin compounds. As examples of natural vanillin substances suitable for use in the present invention, we therefore cite the natural extracts and the purified extracts of vanillin substances such as: pepper (capsicum), cayenne pepper, black pepper, pepper, cinnamon, cloves, nutmeg, mustard, ginger, turmeric, papaya seed and a cactus-like plant called Euphorbia resinifera. The inclusion of synthetic vanillin compounds such as synthetic capsaicin as defined in WO 96/40079 includes or comprises component a) in the compositions of the present invention, the description of such compounds as exemplified in WO 96/40079 it is incorporated here as a reference. The composition of the present invention can, therefore, include both a natural extract containing a vanillin compound (obtained by extraction of the natural product) and / or a pure vanillin compound (obtained by synthesis or by refining the natural extract). Thus, in the case of capsaicin, for example, it can also be found in the natural dihydrocapsaicin extract. As far as the pharmaceutically acceptable salts of component (a) are concerned, the therapeutic activity resides in the derivative part of vanillin, the identity of any salt part being of minor importance even if present. From the viewpoint of therapeutic and prophylactic applications, examples of acceptable salts for pharmaceutical use include those derived from mineral acids, such as hydrochloric acid, hydrobromic acid, phosphoric acid, ethaphosphoric acid, nitric acid and sulfuric acid, and organic acids such as tartaric acid, acetic acid, trifluoroacetic acid, citric acid, malic acid, lactic acid, fumaric acid, benzoic acid, glycolic acid, gluconic acid, succinic acid and methanesulfonic and arylsulfonic acids, for example, p-toluenesulfonic acids. In a preferred embodiment of the present invention, the active vanillin compounds of component (a) are selected from capsaicin ((E) - (N) - [(4-hydroxy-3-methoxyphenyl) -methyl] -8-methyl- 6-nonen-amide); eugenol (2-methoxy-4- (2-propenyl) phenol); zingerone (4- (4-hydroxy-3-methoxyphenyl (-2-butanone); curcumin (1,7-bis (4-hydroxy-3-methoxyphenyl) -1,6-hepta-diene-3,5-dione ), piperine (1- [5- (1,3-benzodioxol-5-yl) -l-oxo-2,4-pentadienyl] piperine), resiniferous toxin (6,7-diepoxy-6,7-didehydro- 5-deoxy-21-diphenyl-21- (phenyl-methyl) -20- (4-hydroxy-3-methoxybenzeneacetate)) or pharmaceutically acceptable salts, analogs, derivatives or equivalents thereof, most preferred are capsaicin, eugenol and resiniferous toxin, with capsaicin still more preferred Component (b) of the present invention may comprise and / or include one or more acceptable excipients or diluents for pharmaceutical use, including, but not limited to, excipients or diluents. although the list is not limiting: mixtures of polyalcohols such as glycerol and fatty acid esters such as Gelucire (registered trademark of Gattefosse), a carbomer such as Carbopol 947P (trademark of Goodrich), the car calcium bonate, microcrystalline cellulose, bicarbonate of partner, lactose, croscarmellose sodium, magnesium stearate, talc, sodium dioctyl sulfosuccinate, hydroxypropylmethyl cellulose, methyl paraben, tris (hydroxymethyl) methylamine, acid monohydrate citrus, cocoa butter, gelatin, glycerin and / or hydrogenated vegetable oils. Preferably, the composition is in oral administration form. A composition according to one embodiment of the present invention, therefore, is preferably administered orally in a prolonged release form of component (a) in the lower part of the gastrointestinal tract to induce desensitization thereof, thus protecting the patient from pain or discomfort related to the inner part of the gastrointestinal tract. The composition can be administered in single doses in the form of tablets, capsules, gel, powder, spheroids or granules. In a particularly advantageous embodiment, the composition is administered in the form of a tablet, capsule, spheroid or granule coated with an enteric coating. li Preferably, the excipients and / or diluents are present in amounts comprised between 0.1 mg and 150 mg; more preferably they are present in amounts comprised between 10 mg and 100 mg per unit of the dose. Preferably, a unit dose of a tablet comprises: i) 0.01 to 300 mg of component (a); ii) one or more of the following elements: 0.1 to 500 mg of microcrystalline cellulose; 0.1 to 200 mg of lactose or some equivalent sugar; 0.1 to 90 mg of croscarmellose salt, preferably croscarmellose sodium; 0.1 to 20 mg of a stearate salt, preferably, magnesium stearate; and iii) an enteric coating of 1 to 500 μm in thickness. All the above weights are relative to 1000 mg of the composition. Preferably, a unit dose of a capsule comprises: i) 0.01 to 300 mg of component (a); ii) one or several members of a mixture of 0.1 to 250 mg of glycerol polyalcohol and fatty acid esters; 0.1 to 500 mg of microcrystalline cellulose; 0.1 to 200 mg of lactose or a sugar equivalent; 0.1 to 90 mg of croscarmellose salt, preferably croscarmellose sodium; 0.1 to 20 mg of talc; 0.1 to 20 mg of a stearate, preferably magnesium stearate; and iii) an enteric shell gives 1 to 500 μm in thickness. All the above weights are relative to 1000 mg of the composition. Preferably, a gel dose unit comprises: i) 0.01 to 300 mg of component (a); ii) at least 0.1 to 999.99 mg of a pharmaceutically acceptable polymer gel; and iii) water, preferably deionized water. All the above weights are relative to 1000 mg of the composition. Preferably, a powder dose unit comprises: i) 0.01 to 300 mg of component (a); and ii) one or more of the following components: 0.1 to 200 mg of a carbonate, preferably calcium carbonate; 0.1 to 500 mg of microcrystalline cellulose; and 0.1 to 50 mg of bicarbonate, preferably sodium bicarbonate. All the above weights are relative to 1000 mg of the composition. Preferably, a spheroidal unit dosage form comprises: i) 0.01 to 300 mg of component (a); and ii) one or more of the following components 0.1 to 500 mg of microcrystalline cellulose; 0.1 to 200 mg of lactose or equivalent sugar; 0.1 to 90 mg of croscarmellose salt, preferably croscarmellose sodium; and iii) an enteric coating of 1 to 500 μm in thickness. All the above weights are relative to 1000 mg of the composition. Preferably, the granular dosage unit comprises: i) 0.01 to 300 mg of component (a); and ii) one or more of the following components 0.1 to 200 mg of Carbopol; 0.1 to 200 mg of a carbonate, preferably calcium carbonate; 0.1 5500 mg of microcrystalline cellulose; 0. 1 to 50 mg of bicarbonate, preferably sodium bicarbonate. All the above weights are relative to 1000 mg of the composition. The capsules or spheroids can be filled with a liquid or solid element. The important thing is that the mode of presentation allows the release, preferably the prolonged release, of the component (a) in the inner part of the intestinal tract. Another suitable form of presentation is the tablets in dies or the wax dies whose formation will be evident to those skilled in the art. Preferably, each unit dose contains between 0.01 and 300 mg of component (a) per 1000 mg of the total composition; more preferably it contains between 0.1 and 25 mg of said component and more preferably still contains between 1 and 20 mg of said component.

The amount of component (a) required depends on the vanillin compound used, in particular, the intensity of the symptoms of the patient treated, the nature of the oral composition and the age, weight and general condition of the patient. The dose administered will depend, ultimately, on the opinion of the doctor who is treating the patient, or it may be chosen within a predetermined interval for the patient to administer it himself. In any case, an effective amount of component (a) for the treatment of irritable bowel syndrome (IBS) will generally be between 0.01 mg and 40 mg daily and more frequently between 0.1 mg and 10 mg daily. This amount can be administered in a single daily dose or, as usually happens, in several sub-doses (two, three, four, five or six) whose total sum reaches the dose specified above. The amount of component (a) contained in the composition will, of course, depend on the amount of component (b), salt as the particular vanillin compound (s) included in the component (to) . For example, capsaicin is much more effective than eugenol and, therefore, the dose of capsaicin needed to achieve the same effect as that of another vanillin compound such as eugenol, may be 10 or 100 times lower. An effective amount of component (a) can be determined when the vanillin compound is present in salt form by establishing a proportion with the effective amount of the free active vanillin compound per se. As stated above, the composition can be fully coated so that the release of component (a) is carried out in the area of the gastrointestinal tract between the stomach and the rectum. The enteric coating applied to the unit dose can have a thickness range between 1 and 500 μm, preferably between 5 and 100 μm and more preferably between 20 and 50 μm. A suitable enteric coating comprises pH-sensitive biodegradable polymers, as, for example, those included in the Opadry Aqueous Enteric manufactured by Colorcon. It is convenient, however, the inclusion of other post-stomach (enteric) release mechanisms of the compound (a), for example, the use of biodegradable polymers not sensitive to pH and other materials useful for the enteric release known in the art.

Alternatively, or in conjunction with the mode of administration already described, the composition may be administered rectally in mammals, for example by means of enemas or suppositories. t The formulation for the enema preferably comprises; i) 0.01 to 300 weight percent by volume (% w / v) of component (a); and ii) one or more of the following 0.01 to 10% w / v elements of a dioctyl sulfosuccinate salt, preferably dioctyl sodium sulfosuccinate; 0.01 to 10% w / v hydroxypropylmethyl cellulose (HPMC); 0.001 to 10% w / v methyl paraben 0.001 to 10% w / v tris (hydroxymethyl) methylamine; 0.001 to 10% weight / volume of acetic acid monohydrate; and iii) to complete, water, preferably deionized water. Preferably, a suppository contains: i) 0.01 to 300 mg of component (a); and ii) one or more of the following elements 0.1 to 999.99 mg of cocoa butter, gelatin, glycerin and / or hydrogenated vegetable oils; and iii) to complete, water, preferably deionized water. All the above weights are relative to 1000 mg of the composition. According to another additional aspect of the present invention, the use of one or more vanillin compounds, pharmaceutically acceptable salts, analogues and / or derivatives thereof for the treatment of irritable bowel syndrome, diarrhea, constipation is presented. , abdominal pain and / or inflammation or abdominal distension in a mammal, said use comprising the release of a therapeutically effective amount of the described vanillinic compound (s) of salts acceptable for pharmaceutical use of the same, of their analogues and / or derivatives, in an area of the gastrointestinal tract comprised between the stomach and the rectum of the mammal. According to another additional aspect of the present invention, the use of one or more vanillin compounds, pharmaceutically acceptable salts, analogues and / or derivatives thereof for the manufacture of a medicament for the treatment of irritable bowel syndrome is disclosed. , diarrhea, constipation, pain and / or abdominal swelling or abdominal distension in a mammal, in which one or more of said compounds, pharmaceutically acceptable salts, analogs and / or derivatives thereof are released in an area of the gastrointestinal tract between the stomach and the rectum of the mammal. According to another aspect of the present invention, a method for treating irritable bowel syndrome, diarrhea, constipation, pain and / or abdominal swelling or abdominal distention in a mammal is disclosed, which method comprises administering to a mammal which requires a therapeutically effective amount of a pharmaceutical composition comprising i) one or more vanillin compounds, pharmaceutically acceptable salts, analogues and / or derivatives thereof (component (a)); and ii) an acceptable carrier for pharmaceutical use (component (b)) which is chosen so that component (a) is released in an area of the gastrointestinal tract between the stomach and the rectum of the mammal. According to another additional aspect of the present invention, a process for the manufacture of a composition according to the present invention is disclosed, with said process including the mixing steps of the component (a) with the component (b). It will be convenient if the compositions are prepared according to any method known in the pharmacy art, for example by associating the component (a) with the component (b) and the addition of one or more excipients and / or diluents. All the materials described in this specification are available in the commercial circuit, coming from various sources. The following examples illustrate the different forms of the compositions according to the present invention.

Example 1: rigid gelatin capsule Each capsule contains; Capsaicin 10 mg Gelucire (registered trademark of 90 mg Gattefosse) 53/10 The ingredients are melted with heat until reaching 65-75 ° C and the capsule is filled with 100 mg of the molten component which is then allowed to solidify. The capsules are then coated with an enteric coating that ensures intestinal release. The Gelucire (registered trademark of Gattefosse) is composed of mixtures of glycerol polyalcohol and fatty acid esters and capsaicin that allow the dispersion of this lipophilic material.

Example 2: Bioadhesive granules Each capsule contains 10 mg of capsaicin in granulated form. The granules are formed by the following ingredients (the given weight of each ingredient is that necessary to provide enough granules to achieve the desired dose per capsule): Capsaicin 10 mg Carbopol 947P (registered trademark 80 mg of Goodrich) Calcium carbonate 80 mg Cellulose microcrystalline 200 mg Sodium bicarbonate 15 mg Carbopol, calcium carbonate and microcrystalline cellulose in the form of dry powder are mixed in a high-speed food processor. The capsaicin is dissolved in isopropanol and mixed with the resulting powder mixture. The solvent is then dried at 20 ° C, powdered sodium bicarbonate is added and mixed with the dry mass. The resulting mixture is granulated with water and then dried at 40 ° C in a fluid bed dryer until the moisture content is less than 5% w / w. The granules are placed in rigid gelatin capsules of size one, which are then coated with an enteric coating polymer.

Example 3: enteric coated tablet Capsaicin 10 mg Microcrystalline cellulose 172 mg Lactose 85 mg Croscarmellose sodium 30 mg Magnesium stearate 3 mg The ingredients are mixed and compressed directly to form tablets. Then the tablets are covered with a cover or enteric coating that ensures the release of capsaicin after passing through the stomach. As an example of such enteric cover, we can mention Opadry Aqueous Enteric (manufactured by Colorcon).

Example 4: Rigid gelatin capsule Capsaicin 10 mg Microcrystalline cellulose 170 mg Lactose 85.5 mg Croscarmellose sodium 30 mg Talc 3 mg Magnesium stearate 1.5 mg The ingredients are mixed and then filled with solid gelatin capsules (eg, size 2). The capsules are then coated with an enteric coating, for example, Opadry Aquedus Enteric (manufactured by Colorcon).

Example 5: Extrusion of spheroidal granules in a rigid gelatin capsule Capsaicin 10 mg Microcrystalline cellulose 130 mg Lactose 130 mg Croscarmellose sodium 15 mg The resulting powders are mixed and then a wet mass is prepared with them in a high-shear mixer / granulator. The mass is extruded through a screen (for example, 1 mm) and then given the spheroidal shape. The spheroids are dried in a fluid bed dryer and then coated with an enteric coating, for example, Opadry Aqueous Enteric. The rigid gelatin capsules (eg, size 2) are then filled with the coated spheroids.

Example 6: rigid gelatin capsule Each capsule contains: Resin-forming toxin 10 mg Gelucire (registered trademark of 90 mg Gattefosse) 53/10 The ingredients melt raising the temperature to 55-75 ° C and the capsules are filled with 100 mg of the melt, which is allowed to solidify. The capsules are then coated with an enteric coating that guarantees release in the intestine. Gelucire (registered trademark of Gattefosse) is composed of mixtures of glycerol polyalcohol and fatty acid esters that allow the dispersion of capsaicin in this lipophilic material. Example 7: Foaming enema The enema formulation contains: Ingredient% w / v Eugenol 0.15 Sodium dioctyl sulfosuccinate 1.0 Hydroxypropylmethylcellulose 1.3 (HPCM) Methyl paraben 0.15 Tri (hydroxymethyl) methylamine 0.15 Citric acid monohydrate 0.08 Deionized water up to 100 ml Citric acid , the tris and the methyl paraben are dissolved in 50 ml of deionized water and stirred. The HPMC is added to this first solution to obtain the solution A. The dioctyl sodium sulfosuccinate is dissolved separately in 25 ml of deionized water and the eugenol is added to obtain solution B. Solutions A and B are carefully mixed to avoid the formation of foam and complete 100 ml with deionized water.

Example 8: suppository Each suppository contains: Capsaicin 10 mg Gelatin 200 mg Glycerin 700 mg Deionized water 90 mg It is understood that the amounts specified in the table immediately above are for each suppository and therefore, must be multiplied by the amount of suppositories per batch expected to be produced. The ingredients are mixed and melted at 60-70 ° C. The melt is poured into disposable plastic molds in which the suppositories are formed and in which they remain until the patient withdraws them for application.

Example 9: treatment of irritable bowel syndrome (IBS) in a human patient Given a human patient suffering from one or more of the following symptoms: diarrhea, constipation, abdominal pain, abdominal inflammation, abdominal distension, altered frequency of bowel movements, altered form of the stools, altered passage of the stools or presence of mucus in the stools (symptoms all relationships with irritable bowel syndrome (IBS)), is administered a therapeutically effective amount of the composition of the present invention according to the Examples 1 to 8 either orally or rectally, with sufficient frequency (a single administration of the pharmaceutical composition or several administrations of the pharmaceutical composition) to alleviate one or more of the symptoms presented by the patient. 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 (14)

CLAIMS Having described the invention as above, the content of the following claims is claimed as property:

1. An oral-release pharmaceutical composition for use in the treatment of irritable bowel syndrome, diarrhea, constipation, abdominal pain and / or inflammation or abdominal distension in a mammal, characterized in that: i) capsaicin or resiniferatoxin, salts acceptable for pharmaceutical use, analogues and / or derivatives thereof (component a); and ii) an acceptable carrier for pharmaceutical use (compound b) wherein the composition is a unit dosage form with an osmotic delivery device or is enterically coated to provide release of component a) in the gastrointestinal tract between the stomach and the rectum of a mammal and component b) is selected to allow component a) to be released into the gastrointestinal tract between the stomach and the rectum of the mammal. 2d

2. The composition according to claim 1, characterized in that component b) releases component a) only after the composition has passed through the stomach. The composition according to claim 1 or claim 2, characterized by the unit dosage form formed as a tablet, a capsule, a gel, a powder, spheroids or granules. 4. The composition according to claim 3, characterized in that the unit dosage form contains 0.01 to 300 mg, preferably 0.1 to 20 mg of component a). The composition according to claim 1, characterized in that the dosage form in tablet form comprises: i) 0.01 to 300 mg of component a); ii) one or more of the following components 0.1 to 500mg of microcrystalline cellulose; 0.1 to 200mg of lactose, or equivalent sugar; 0.1 to 90 mg of croscarmellose salt, preferably croscarmellose sodium; 0.1 to 20 mg of stearate salt, preferably magnesium stearate; and 2 > iii) an enteric coating of 1 to 500 μm in thickness, all the weights are relative to lOOOmg of the composition. 6. The composition according to claim 1, characterized in that the dosage form in capsule form comprises: i) 0.01 to 300 mg of component a); ii) one or more of the following components 0.1 to 250 mg of polyol glycerol mixture and fatty acid esters; 0.1 to 500mg of microcrystalline cellulose; . 0.1 to 200mg of lactose or equivalent sugar; 0.1 to 90 mg of croscarmellose salt, preferably croscarmellose sodium; 0.1 to 20mg talcum; 0.1 to 20 mg of stearate salt, preferably magnesium stearate; and iii) an enteric coating of 1 to 500 μm in thickness, all weights are relative to lOOOmg of the composition. The composition according to claim 1, characterized in that the unit dosage form of gel comprises: i) 0.01 to 300 mg of component a); ii) at least 0.1 to 999.99 mg of a pharmaceutically acceptable polymer gel; and iii) water, preferably deionized water; all weights are relative to lOOmg of the composition. The composition according to claim 1, characterized in that the powder unit dosage form comprises: i) 0.01 to 300 mg of component a); and ii) one or more of the following components 0.1 to 200 mg of a carbonate, preferably calcium carbonate; 0.1 to 500mg of microcrystalline cellulose; and 0.1 to 50mg of bicarbonate, preferably sodium bicarbonate, all the weights are relative to lOOOmg of the composition. The composition according to claim 1, characterized in that the unit dosage form of spheroids comprises: i) 0.01 to 300 mg of component a); and ii) one or more of the following components 0.1 to 500 mg microcrystalline cellulose; 0.1 to 200mg of lactose or equivalent sugar;

0. 1 to 90 mg of croscarmellose salt, preferably croscarmellose sodium, and iii) an enteric coating of 1 to 500 μm in thickness, all weights are relative to lOOOmg of the composition. The composition according to claim 1, characterized in that the unit dosage form of granules comprises: i) 0.01 to 300 mg of component a); and ii) one or more of the following components 0.1 to 20 mg carbopol; 0.1 to 200 mg of a carbonate, preferably calcium carbonate; 0.1 to 500mg of microcrystalline cellulose; and 0.1 to 50mg of bicarbonate, preferably sodium bicarbonate, all the weights are relative to lOOOmg of the composition. 11. A composition characterized in that it contains capsaicin, substantially as described herein with reference to any of the Examples. 12. The use of capsaicin or resinoferatoxin, pharmaceutically acceptable salts, analogs and derivatives thereof in the treatment of irritable bowel syndrome, diarrhea, constipation, pain and / or abdominal swelling or abdominal distension in a mammal, such use comprises releasing a therapeutically effective amount of a vanillin compound in the gastrointestinal tract between the stomach and rectum of the mammal. 13. The use of capsaicin or resinoferatoxin, pharmaceutically acceptable salts, analogs and derivatives thereof for the manufacture of a medicament for the treatment of irritable bowel syndrome, diarrhea, constipation, and / or abdominal swelling or abdominal distention in a mammal, where the vanillin compounds are released into the gastrointestinal tract between the stomach and the rectum of the mammal. A process for the manufacture of a composition according to claim 1 in any of claims 1 to 12, characterized in that the process includes the steps of mixing capsaicin or resinoferatoxin, salts, analogs and pharmaceutically acceptable derivatives thereof with a vehicle pharmaceutically acceptable.