CZ443399A3 - Therapeutically active composition - Google Patents

Abstract

Pharmaceutical composition for the treatment of irritant syndrome colon that contains vehicle and vanilloid compound. The carrier vehicle allows it to be vanilloid the compound released at the bottom of the GI tract. Listed the vaniloid compound desensitizes the nerves in the lower GI tract, resulting in an irritable bowel syndrome

Description

Therapeutically active compositions

Field of the invention

The invention relates to compositions for the treatment of irritable bowel syndrome (IBS), and more particularly to locally acting compositions which are active in the regions of the gastrointestinal (GI) tract lying behind the stomach.

BACKGROUND OF THE INVENTION

Irritable bowel syndrome (IBS) is one of the diseases commonly known as functional disorders of the gastrointestinal tract, including diseases such as non-cardiac chest pain, non-ulcer dyspepsia, and chronic constipation or diarrhea. These diseases are all characterized by chronic or recurrent gastrointestinal symptoms for which no organic or biochemical cause can be found.

In the UK alone, inflammatory bowel syndrome is the reason for 30-50% of all subsequent gastroenterological examinations in patients.

Multiple factors such as physiological, emotional, cognitive and behavioral factors are considered to be the cause of IBS and often occur during periods of stress. The diagnosis of IBS is based on the excretion method and the observed symptoms in each case. Generally accepted criteria for IBS, known as Rome criteria, include continuous or recurrent symptoms lasting at least three months which include:

1. abdominal pain or discomfort that is alleviated by defecation and / or is associated with a change in stool frequency and / or associated with a change in stool consistency; and • · · · · · · · · · · · · · · · · · · · · · · ·

2. two or more of the following symptoms, at least a quarter of the symptoms including: altered stool frequency, altered stool form, altered stool passage, mucus passage, and / or meteorism or abdominal tension.

Conventional methods of treating IBS are based on the severity of the condition and the nature of the symptoms of each patient, and whether psychological factors are involved. Treatment of IBS may include one or more of the following: lifestyle changes, pharmacological treatment, and psychological treatment. However, there is no general treatment method applicable to all types of IBS.

In certain cases it is recommended to exclude foods that worsen the symptoms of IBS. However, this type of treatment is effective only when the cause of IBS is diet-related.

Pharmacologically active agents are often used to treat IBS. Anti-diarrheal drugs (e.g., loperamide), smooth muscle relaxants (e.g., mebeverine hydrochloride or alverine citrate), or antidepressants may be effective in treating IBS. However, there is no single pharmacological agent fully effective for alleviating or treating IBS.

Psychotherapy can also be used to treat IBS. Again, however, this treatment also does not provide a universal approach to treating the symptoms of IBS, since not all cases of IBS are caused by psychological factors.

One method of treating pathological conditions of the small and large intestine is disclosed in U.S. Patent No. 5,443,114. This patent discloses that the external application of capsaicin to the skin in specific areas affects certain nerves in the skin leading to spinal segments. The method of said patent suggests the possibility of using topical application of a dose of 0.03 mg of capsaicin to the anterior and posterior regions of the spinal nerves T12 to S3 to treat IBS. However, the clear mechanism of the embodiment of the invention is not known.

It is unlikely that the regimen of administering the composition to the patient alone will be effective, since the composition needs to be applied to specific sites that the patient may not always easily recognize. In addition, it is probably difficult to control the dosage of the formulation of U.S. Pat. No. 5,431,914 as it is in the form of a topically administered cream.

Accordingly, there remains a need for a composition that alleviates symptoms of irritable bowel syndrome that is easy to handle, can be administered in a single dosage form, and can be administered by the patients themselves.

SUMMARY OF THE INVENTION

To alleviate the problems associated with IBS, the invention provides, in its first aspect, a pharmaceutical composition for use in treating irritable bowel syndrome, diarrhea, constipation, abdominal pain and / or meteorism or abdominal tension in a mammal, preferably a human, said composition comprising:

i) one or more vaniloid compounds, pharmaceutically acceptable salts, analogs and / or derivatives thereof (component a); and (ii) a pharmaceutically acceptable carrier (component b);

wherein said component b) is selected to allow the release of component a) in the region of the gastrointestinal tract lying between the stomach and the rectum of the mammal.

Preferably, component a) is present in an amount to alleviate the symptom

IBS.

Preferably, the composition of the invention comprises from 0.001 to 30% of component a), more preferably comprises from 0.01 to 20% of this component and most preferably comprises from 0.1 to 10% by weight of this component in said pharmaceutical composition.

Preferably, the composition of the invention comprises from 70 to 99.999% of component b), more preferably it comprises from 80 to 99.99% of this component, and most preferably it comprises from 90 to 99.9% by weight of this component in said composition.

In a second aspect of the invention, the present invention provides a pharmaceutical composition as described above in the first aspect of the invention, but wherein the composition further comprises an enteric coating (component c) in which components a) and b) are encapsulated.

In a third aspect of the invention, the invention provides a method of alleviating irritable bowel syndrome (IBS) symptoms in affected mammals, preferably humans affected by said symptoms, said method comprising the following step:

administering, preferably orally, a therapeutically effective amount of a pharmaceutical composition according to either the first or second aspect of the invention as described above for the use of a pharmaceutical composition according to either the first or second aspect of the invention. • alleviating the symptoms associated with irritable bowel syndrome (IBS).

In a fourth aspect of the invention, the invention provides a method according to the third aspect of the invention as described above, wherein the pharmaceutical composition is in the form of a controlled release formulation wherein the use results in substantial release (ie, at least 75% of component a) in the pharmaceutical composition) in the gastrointestinal tract of the patient in treatment in the area behind the stomach and before the rectum.

In the context of the present invention, it should be clarified that component a) is a compound or a mixture of compounds having a biologically active vanilyl group. Thus, component (a) includes both naturally occurring and synthetic vaniloids, pharmaceutically acceptable salts of the vaniloid compounds (both naturally occurring and synthetic) as well as pharmaceutically acceptable derivatives and / or analogs (both naturally occurring and synthetic) thereof.

Naturally occurring vaniloid compounds also include crude and purified extracts of active vaniloid compounds.

Examples of natural vaniloid compounds suitable for use in the present invention therefore include both raw extracts and purified extracts of active vaniloid compounds from: paprika, red pepper, black pepper, annual pepper, cinnamon, clove, mace, mustard, ginger, turmeric, papaya and cactus fruits similar plants Buphorbia res ini fera.

Synthetic vanilloid is also believed to be w / w. Compounds such as those disclosed in WO 96/40079 may form component (a) in the compositions of the invention or may be included therein, and a description of such compounds as examples is given in WO 96 / 40079, which is incorporated herein by reference.

The compositions of the invention may therefore comprise both an extract comprising crude vaniloid compounds (obtained by extraction of the natural product) and / or pure vaniloid compound itself (obtained either synthetically or by purification of the crude extract). Thus, for example, in the case of, for example, capsaicin, the presence of dihydrocapsaicin in the crude extract is also acceptable.

When a pharmaceutically acceptable salt form is used as component (a), the therapeutic activity of the residues of the vanilloid moiety and the identity of each salt component, if present, is of minor importance.

For therapeutic and prophylactic purposes, examples of pharmaceutically acceptable salts include salts derived from mineral acids such as hydrochloric, hydrobromic, phosphoric, metaphosphoric, nitric and sulfuric, and from organic acids such as tartaric, acetic, trifluoroacetic, citric, malic. lactic, fumaric, benzoic, glycolic, gluconic, succinic and methanesulfonic and aryl sulfonic acids such as p-toluenesulfonic acid.

In a preferred embodiment of the invention, the active vaniloid compounds of the invention included in component a) are selected from the group consisting of capsaicin ((E) - (N) - [(4-hydroxy-3-methoxyphenyl) -methyl] -8-methyl-6 -nonenamide); eugenol (2-methoxy-4- (2-propenyl) phenol); zingeron

9 9 9 9 99 99

(4- (4-hydroxy-3-methoxyphenyl) -2-butanone); kurkutnin (1,7-bis (4-hydroxy-3-methoxyphenyl) -1,6-heptadiene-3,5-dione); piperidine (1- [5- (1,3-benzodioxol-5-yl) -1-oxo-2,4-pentadienyl] piperidine; resinephatoxin (6,7-deepoxy-6,7-didehydro- 5-deoxy-21-defenyl-21- (phenylmethyl) -20- (4-hydroxy-3-methoxybenzeneacetate)) or pharmaceutically active salts, analogs, derivatives or equivalents thereof. More preferred compounds include capsaicin, eugenol and resiniferatoxin, wherein capsaicin is most preferably.

Component (h) of the invention may form and / or comprise one or more pharmaceutically acceptable excipients or diluents. Such additives or diluents include, but are not limited to, mixtures of glycerol polyalcohol and fatty acid esters such as Gelucire (TM from Gattefosse), carbomer such as Carbopol 947P (TM from Goodrich), calcium carbonate, microcrystalline cellulose, sodium bicarbonate, sodium croscarmellose salt, magnesium stearate, talc, sodium dioctylsulfosuccinate, hydroxypropyl methylcellulose, methylparaben, tris (hydroxymethyl) methylamine, citric acid monohydrate, cocoa butter, gelatin, glycerol, and / or hydrogenated vegetable oils.

A preferred dosage form of the composition of the invention is oral. The composition according to one embodiment of the invention is therefore preferably administered orally as a controlled release formulation, which releases component a) in the lower GI tract to induce desensitization, thereby preventing the patient from experiencing pain or discomfort associated with lower trouble. parts of the GI tract.

Said composition may be in unit dosage form such as a tablet, capsule, gel, powder, spheroid / or granule.

· · · * * * * * * * *

Particularly preferred embodiments of said composition include embodiments in the form of a tablet, capsule, spheroid or granule that is provided with an enteric coating.

Preferably, the additives and / or diluents are present in an amount of from 0.1 mg to 1500 mg, most preferably in an amount of from 10 mg to 100 mg per dosage unit.

Preferably, the dosage unit in the form of a tablet comprises:

i) 0.01 to 300 mg of component a);

(ii) any one or more of the group consisting of:

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 in the form of a salt, preferably croscarmellose sodium;

0.1 to 20 mg of the stearate salt, preferably in the form of magnesium stearate; and iii) an enteric coating having a thickness of 1 to 500 µm, wherein all said weights are based on 1000 mg of the composition.

Preferably, the dosage unit in capsule form comprises:

i) 0.01 to 300 mg of component a);

··· · * · · ·

9 • 9 9 9 9 ·

9 9 9 9 9 • 9 9 9 9 9

9 9 9 9 9 9

9 9 9 9 9 Η (ii) any or more of the group consisting of:

0.1 to 250 mg of a mixture of polyalcohol-glycerol and fatty acid esters;

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 in the form of a salt, preferably croscarmellose sodium;

0.1 to 20 mg of talc;

0.1 to 20 mg of the stearate salt, preferably in the form of magnesium stearate; and iii) an enteric coating having a thickness of 1 to 500 µm, wherein all said weights are based on 1000 mg of the composition.

The dosage unit in the form of a gel preferably 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, wherein all said weights are based on 1000 mg of the composition.

00 • * 0 ·

9 0 ·

0 9 0 ·

0 0 »

0 · 0 · 00 0 • 0 0 0 0

0 0

0 0 0 0 0 0

0 0 0 0 0 0 0

The powder dosage unit preferably comprises:

i) 0.01 to 300 mg of component a); and (ii) any or more of the components comprising:

0.1 to 200 mg of carbonate, preferably calcium carbonate;

0.1 to 500 mg of microcrystalline cellulose; and

0.1 to 50 mg of bicarbonate, preferably sodium bicarbonate, wherein all the weights are based on 1000 mg of the composition.

The spheroid dosage unit preferably comprises:

i) 0.01 to 300 mg of component a);

ii) any one or more of the group consisting of

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 in the form of a salt, preferably croscarmellose sodium; and (iii) an enteric coating having a thickness of 1 to 500 µm

9 9 9 4 5

4 9 9 4 5

. 9 4 4 4 4 9

9 9 4 · 4 9 9 · ♦ ··

4 »

4 4 * • · 4 <

• * »·

4 4 9

Wherein all the weights are based on 1000 mg of the composition.

The granular dosage unit preferably comprises:

i) 0.01 to 300 mg of component a); and (ii) any or more of the components comprising:

0.1 to 200 mg of carbopol;

0.1 to 200 mg of carbonate, preferably calcium carbonate;

0.1 to 500 mg of microcrystalline cellulose; and

0.1 to 50 mg of bicarbonate, preferably sodium bicarbonate, wherein all the weights are based on 1000 mg of the composition.

The capsules or spheroids may be liquid or solid. An important feature is that the transport method allows release, preferably controlled release of component a) in the lower part of the GI tract. Other suitable delivery systems, such as tablets containing matrix or wax matrices, are known to those skilled in the art.

Preferably, each dosage unit contains from 0.01 to 300 mg, preferably 0.1 to 25 mg, and most preferably 1 to 20 mg of component a) per 1000 mg of the composition.

4; 3 i

4

4 44 4 4

4 4 4 4 4

4 4 4 4 4

4 4 4

44 44 4 ·

The amount of component (a) required will depend upon the vaniloid compound employed, the severity of the condition being treated, the type of oral composition used, and the age, weight and condition of the patient.

The dose administered may be determined by the attending physician, or may be within a predetermined range for self-administration by the patient. However, an effective amount of component (a) for treating IBS is generally in the range of 0.01 mg to 40 mg per day and more usually in the range of 0.1 to 10 mg per day. This amount may be administered in a single daily dose or in multiple daily subdoses (such as two, three, four, five, or six) as mentioned above.

However, the amount of component (a) contained in the composition is, of course, dependent on component (b) as well as the particular vaniloid compound (s) contained in component (a). For example, capsaicin is more potent than eugenol, and therefore the dose of capsaicin required to achieve the same effect compared to that of another vaniloid compound such as eugenol may be 10 or 100 times lower.

The effective amount of component a) in the case where the vaniloid compound is in the form of a salt can be expressed as an effective amount of the free active vaniloid compound as such.

As mentioned above, said composition may be provided with an enteric coating to provide release of component a) in the gastrointestinal tract between the stomach and rectum. The enteric coating may be used for a single dose form with a layer thickness range of between 1 and 500 µm.

Preferably between 5 and 100 µm, and most preferably between 20 and 50 µm.

A suitable enteric coating comprises, for example, pH-sensitive biodegradable polymers, such as those included in Opadry Agueous Enteric, manufactured by Coorcon.

It will be appreciated, however, that other methods of releasing component a) in the area behind the stomach may be used, for example β-non-sensitive biogradable polymers, or other means suitable for delivery to the intestine known in the art.

Alternatively, or in conjunction with the above description, rectal administration to a mammal is also possible, for example in the form of an enema or suppository.

The enteric preparation preferably comprises:

i) 0.01 to 300% w / v (% w / v) of component a); and ii) any one or more of the group consisting of

0.01 to 10% w / v dioctyl sulfosuccinate salts, preferably sodium dioctyl sulfosuccinate;

0.01 to 10% hydroxypropyl methylcellulose (HPMC);

0.001 to 10% w / v methylparaben;

0.001 to 10% w / v tris (hydroxymethyl) methylamine;

♦ 4 44 ♦ 4 • 4 4 · 4 · 44 ♦ 44 • 4 11

4 4 ♦ «4 t 1 · *» 4 ♦ • 4 · 4 4 4 4 4 4 • 4 4 9 1 11 ·.

11 11 11 4 * 445

0.001 to 10% citric acid monohydrate; and iii) water make-up, preferably deionized water.

The suppository composition preferably comprises:

i) 0.01 to 300 mg of component a); and ii) any one or more of 0.1 to 999.99 mg of cocoa butter, gelatin, glycerin, and / or hydrogenated vegetable oils; and iii) water make-up, preferably deionized water, all of said weights being given per 1000 mg of co-injection.

It is a further aspect of the present invention to provide the use of one or more vaniloid compounds, pharmaceutically acceptable salts, analogs and / or derivatives thereof in the treatment of irritable bowel syndrome, diarrhea, constipation, abdominal pain and / or meteorism or abdominal tension in mammals. the release of a therapeutically effective amount of the vaniloid compound (s), pharmaceutically acceptable salts, analogs and / or derivatives thereof occurs in the gastrointestinal tract in the region between the stomach and rectum of the mammal.

Another aspect of the invention is that it provides the use of one or more vaniloid compounds, pharmaceutically acceptable salts thereof

ΒΒ ΒΒ

Β · Β · ♦ · Β

Β Β Β Β Β

Β · Β Β

· Β ΒΒ * Β ♦ • · Β

Β · Β ♦ · Β Β • Β ΒΒ

BB ΒΒΒΒ • Β ·

ΒΒΒ

Acceptable salts, analogs and / or derivatives in the manufacture of a medicament for the treatment of irritable bowel syndrome, diarrhea, constipation, abdominal pain and / or meteorism, or abdominal tension in a mammal, wherein to release one or more more vaniloid compounds, their pharmaceutically acceptable salts, analogs and / or derivatives occur in the gastrointestinal tract in the region between the stomach and rectum of the mammal.

In another aspect, the invention provides a method of treating irritable bowel syndrome, diarrhea, constipation, abdominal pain and / or meteorism or abdominal tension in a mammal, the method comprising administering to the mammal in need of treatment a therapeutically effective amount of a pharmaceutical composition comprising:

i) one or more vaniloid compounds, pharmaceutically acceptable salts, analogs and / or derivatives thereof (see component a); and ii) a pharmaceutically acceptable carrier (component b), wherein said component b) is selected to allow the release of component a) in the region of the gastrointestinal tract lying between the stomach and the rectal of the mammal.

Another aspect of the invention provides a method of making a composition of the invention, said method comprising the steps of mixing component a) with component b).

It will be appreciated that the compositions of the invention may be prepared by any method known in the pharmaceutical art, for example by combining component a) with component b) and with the additive (s) and / or diluents when used.

• 0 • 0 · * 0

0 0 0 0 0

0 0 0

0 0 0

Each of the components described in this specification is a material commercially available from various sources.

The compositions of the invention are further illustrated by the following examples.

DETAILED DESCRIPTION OF THE INVENTION

Example 1

Hard latin capsule

Each capsule contains:

capsaicin 10 mg

Gelucire (TM Gattefosse) 53/10 mg

The ingredients are melted by heating to about 65-75 ° C and the capsule is filled with 100 mg of melt, which is then. let it solidify. The capsules are then coated with an enteric coating allowing release in the intestine. Gelucire (TM from Gattefosse) consists of a mixture of polyalcohols of glycerol and fatty acid esters and capsaicin is dispersed in this lipophilic material.

Example 2

Bioadhesive granules

Each capsule contains 10 mg of capasicin in granular form. Said granulate is prepared from the following ingredients (the weight given for each ingredient is a weight sufficient to form the number of granules required for the contents of one capsule):

ΦΦ φ φ * · φ φ φ φ φ φ φ φ φ φ * * * * * * * * * * * * * *

-Φ 9 9

9 9 Φ

Φ Φ Φ Φ

Φ Φ Φ Φ

ΦΦ ΦΦ

capsaicin 45 mg Carbopol 947 P (Goodrich TM) 80 mg calcium carbonate 80 mg microcrystalline cellulose 200 mg sodium bicarbonate 15 Dec mg

Carbopol, calcium carbonate and microcrystalline cellulose in the form of dry powders are mixed in a high-speed food processing machine. Capsaicin is dissolved in isopropanol and mixed with the remaining powder mixture. Then, the solvent is removed by drying at 20 ° C, sodium bicarbonate in powder form is added and mixed with the dry mixture. The resulting mixture is granulated with water and dried at 40 ° C in a fluid bed dryer up to a moisture content of less than 5% w / w. These granules are then filled into size 1 hard gelatin capsules, which are then coated with an enteric 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 directly mixed press into form

tablet. The tablets are then coated with an enteric coating ensuring that capsaicin is not dissolved until it has passed through the stomach. An example of such an enteric coating is Opadry Aqueous Enteric (manufactured by Colorcon).

• 0 ··· · 00 ···· · 0 00 • 0 · 0 0 0 0-000

0 0 00 0 0000 • 000 000 000 000 ♦

00 0 0 00 0 0 00 «

0 00 00 09 00 00

Example 4

Hard gelatine 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 filled into hard gelatin capsules (e.g. size 2). The capsules are then coated with an enteric coating, for example with Opadry Aqueous Enteric.

Example 5

Extruded spheronized pellets in hard gelatin capsule

capsaicin 10 mg microcrystalline cellulose 130 mg lactose 130 mg croscarmellose sodium 15 mg

The powder components are mixed together and the resulting mixture is moistened in a high shear mixer / granulator. This mixture is then extruded through a sieve (e.g. 1 mm) and then spheronized. The spheroids are dried in a fluid bed dryer and then coated with an enteric coating, for example with Opadry Aqueous Enteric. The coated spheroids are filled into hard gelatin capsules (e.g., size 2).

Example 6

Hard gelatin capsule

ftft ftft ft ftft · - * · · · ftft · ftp · ftft · ftft ftft ftft ftftft ·

Each capsule contains:

Resiniferatoxin 10 mg

Gelucire (TM Gattefosse) 53/10 90 mg

The ingredients are melted by heating to about 65-75 ° C and the capsule is filled with 100 mg of melt, which is then allowed to solidify. The capsules are then coated with an enteric coating allowing release in the intestine. Gelucire (TM from Gattefosse) consists of a mixture of polyalcohols of glycerol and fatty acid esters, and capsaicin is dispersed in this lipophilic material.

Example 7 Foam enema component% w / v.

eugenol 0.15 sodium dioctylsulfosuccinate 1.0 hydroxypropylmethylcellulose (HPMC) 1.3 methylparaben 0.15 tris (hydroxymethyl) methylamine 0.18 citric acid monohydrate 0.08 deionized water to 100 ml

Dissolve citric acid, tris and methylparaben in 50 ml deionized water and mix. HPMC was then added to this solution to give solution A. Separately, sodium dioctyl sulfosulcinate was dissolved in 25 ml of deionized water, then eugenol was added to this solution to give solution B. Mix solutions A and B carefully to avoid foam formation and ► 4 4 4 4 4 4 4 4 4 4 4 «4 4 4 4 4 4 4 4 4 4 4 4 4 Make up to 100 ml with deionized water. Mix the solution to 100 ml with deionized water.

Example 8

Cípky

One cone contains:

capsaicin 10 mg gelatine 200 mg glycerine 700 mg deionized water 90 mg

The amounts indicated are amounts per suppository and must therefore be multiplied by the number of suppositories expected to be prepared in a given lot.

The components are mixed together and melted at a temperature between 60 ⁰ and 70 ° C. The molten mixture is poured into disposable plastic molds in which the suppositories are shaped and remain enclosed until removed by the patient.

Example 9

Treatment of IBS in humans

A patient suffering from one or more of the following symptoms: diarrhea, constipation, abdominal pain, meteorism, abdominal tension, alternating stool frequency or mucus passage (symptoms associated with irritable bowel syndrome) is administered a therapeutically effective amount of a pharmaceutical composition according to any one of Examples 1 to 8 either by oral or rectal administration, said pharmaceutical composition being administered frequently enough (one or more administrations of the pharmaceutical composition) to effect the administration of the pharmaceutical composition. 9 9 9 9 9 9 9 9 9 99 99 alleviating one or the symptoms of said patient.

Claims (10)

A pharmaceutical composition for use in the treatment of irritable bowel syndrome, diarrhea, constipation, abdominal pain and / or meteorism or abdominal tension in a mammal, said composition comprising: i) one or more vaniloid compounds, pharmaceutically acceptable salts, analogs and / or derivatives thereof (component a); and ii) a pharmaceutically acceptable carrier (component b), wherein said component b) is selected to allow the release of component a) in the region of the gastrointestinal tract lying between the stomach and the rectal of the mammal. 2. The composition of claim 1 wherein said composition is a composition administered orally and component (b) releases component (a) only after passage of the composition through the stomach. Composition according to either of Claims 1 and 2, characterized in that component a) is selected from the group consisting of capsaicin ((E) - (N) - [(4-hydroxy-3-methoxyphenyl) -methyl] -8-methyl -6-nonenamide); 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-heptadiene-3,5-dione); piperidine (1- [5- (1,3-benzodioxol-5-yl) -1-oxo-2,4-pentadienyl] piperidine; resiniferatoxin (6,7-deepoxy-6,7-didehydro-5-deoxy-21-defenyl-21- (phenylmethyl) -20- (4-hydroxy-3-methoxybenzeneacetate)), or a pharmaceutically acceptable salt, analog, or 9 9 9 9 9 9 9 9 99 99 99 99 99 9 9 9 9 9 9 9 9 9 9 9 9 9 • 9 99 99 derivatives or extracts or synthetic equivalents thereof. Composition according to any one of the preceding claims, characterized in that it is in unit dosage form such as a tablet, capsule, gel, powder, spheroids, granules or is administered by means of an osmotic delivery device. Composition according to claim 4, characterized in that the unit dose contains from 0.01 to 300 mg, preferably 0.1 to 20 mg of component a). The composition of any one of claims 2 to 5, wherein the composition comprises an enteric coating to provide release of component a) in the gastrointestinal tract between the stomach and rectum of the mammal. Use of one or more vaniloid compounds, pharmaceutically acceptable salts, analogs and derivatives thereof in the treatment of irritable bowel syndrome, diarrhea, constipation, abdominal pain and / or meteorism or abdominal tension in a mammal, said use comprising releasing a therapeutically effective amount of a vaniloid compound (compounds) in the gastrointestinal tract between the stomach and the rectum of the mammal. Use of one or more vaniloid compounds, pharmaceutically acceptable salts, analogs and derivatives thereof for the preparation of a medicament for the treatment of irritable bowel syndrome, diarrhea, constipation, abdominal pain and / or meteorism or abdominal tension in a mammal, said vaniloid compound ( of the compound) is released in the gastrointestinal tract between the stomach and the rectum of the mammal. 9. A method of treatment in the treatment of irritable bowel syndrome, ΦΦ φ φ · · · · φ φ φ φ · · · φ φ φ φ φ φ φ φ φ · · · · · · · · napětí napětí napětí napětí napětí napětí sav py characterized in that the method comprises administering a pharmaceutically effective amount to a mammal in need of treatment of a pharmaceutical composition, said composition comprising: i) one or more vaniloid compounds, pharmaceutically acceptable salts, analogs and / or derivatives thereof; and ii) a pharmaceutically acceptable carrier, wherein said carrier is selected to allow release of the vanilloid compound (s) in the region of the gastrointestinal tract lying between the stomach and the rectal of the mammal. A process for preparing a composition according to any one of claims 1 to 5, wherein said process comprises the steps of admixing one or more vaniloid compounds, pharmaceutically acceptable salts, analgesics or derivatives thereof with a pharmaceutically acceptable carrier.