IT201600075072A1 - Pharmaceutical or dietary supplement composition for the treatment of intestinal constipation - Google Patents

Description

DESCRIPTION

Field of application

The present invention relates to the pharmaceutical industry and to food supplements and functional foods.

In particular, the invention refers to a tamarind-based composition for the regulation of gastrointestinal motility and the prevention and / or treatment of intestinal constipation.

Known art

Constipation or constipation is a disorder of intestinal motor activity, very common, particularly in industrialized countries. This is one of the most frequent gastrointestinal disorders and on average about 13 million Italians suffer from it, of which about 9 million are women.

Constipation is basically a disorder related to defecation and consists in the difficulty of clearing the intestine. Constipation manifests itself with a significant reduction in the frequency of bowel movements and in the volume of stools, abdominal pain and swelling, bloating and difficulty in evacuating. Constipation is a symptom rather than a disease and in most cases it is temporary and not serious.

Among the most frequent causes of constipation are a lack of fiber in the diet, poor physical activity, irritable bowel syndrome, pregnancy, travel, dehydration and problems with bowel function.

The most frequent cause of constipation is due to a diet low in fiber or excessively high in fat. Proper nutrition, high in vegetables, fresh fruit, wholemeal bread and cereals, is essential for the prevention of constipation. An abundant intake of liquids allows you to keep the stool soft, facilitating its expulsion and constant physical activity is equally important for maintaining an adequate tone of the intestinal muscles.

If dietary and behavioral measures are not sufficient to prevent constipation, the use of laxatives is generally used.

Laxatives are generally classified into four categories:

bulk laxatives, or laxatives that increase the volume of stool, thus favoring intestinal transit; among these we can mention psyllium seeds, agar-agar, bran, fucus and guar gum;

- contact laxatives, which act by increasing contractions of the intestinal walls, activating peristalsis: among these we can mention cascara, Senna, frangula, rhubarb, castor oil, phenolphthalein, bisacodyl and sodium picosulfate;

emollient laxatives, which work by mixing with, softening and lubricating stools; among these we mention glycerin and vaseline oil;

osmotic laxatives, which act by retaining and recalling liquids from the intestine, so as to form voluminous and soft stools and to accelerate their transit in the large intestine; these include lactulose, mannitol, magnesium salts, sorbitol and tamarind.

Each of the categories of laxatives listed above has drawbacks. In particular, contact laxatives can cause diarrhea and abdominal cramps and their prolonged use can deteriorate the functionality of the intestinal muscles with worsening of constipation. Emollient laxatives can interfere with resorption of fat-soluble vitamins and calcium. Osmotic laxatives, especially in high doses, can cause abdominal cramps, nausea and vomiting, as well as dehydration and kidney problems. Bulk laxatives are the relatively safer ones but are not always sufficient to resolve constipation and also, if taken in excessive doses, can cause bloating and intestinal obstructions.

The Applicant has carried out research aimed at developing a food supplement composition for the regulation of gastrointestinal motility, suitable for preventing and / or treating constipation, without causing unwanted side effects.

The research activity was inspired by what is known in the scientific literature about the effects of tamarind (Tamarindus indica). Tamarind is mentioned as a mild laxative in several pharmacopoeias and is used in various traditional medicines, particularly in Africa. The pulp of the fruit is used from the tamarind, which contains high concentrations of malic acid and tartaric acid, as well as potassium acid tartrate, reducing sugars, vitamin B and minerals (Havinga et al., 2010). Organic acids, in particular, have a laxative effect by osmotic action. Tartaric acid has both a direct and indirect osmotic effect: as a result of its fermentation by the microflora of the colon, in fact, short chain fatty acids (SCFA = short chain fatty acids) are produced, which in turn attract water and increase stool re-hydration (Spiller et al., 2003).

Tamarind is considered safe and no noteworthy side effects are reported in the literature except for the possibility of causing abdominal discomfort, like other osmotic laxatives.

Patent application IN 2209 / CHE / 20 11 describes a laxative comprising various plant ingredients, including senna, hartiki and bahera as active ingredients with laxative action, tamarind as an enhancer of aroma and palatability and ginger to aid digestion.

An object of the present invention has been to provide a composition for the treatment of constipation, particularly suitable for the treatment of chronic and occasional constipation for which the use of mass laxatives does not provide benefits, based on active ingredients of origin natural and with an action that is as delicate as possible and free of side effects.

Summary of the invention

This purpose was achieved by making available a composition that includes an active ingredient with an osmotic laxative effect, consisting of tamarind extract, and a ginger extract (Zingiber officinale Rose.).

The ginger extract contained in the composition according to the invention prevents any, albeit limited, side effects of the tamarind extract mentioned above, thanks to its antiemetic, prokinetic and antispasmodic effects, which prevent abdominal discomfort that could be caused by tamarind. , consisting essentially of abdominal bloating and flatulence.

In a particular embodiment thereof, intended for the treatment of more difficult forms of constipation, the composition according to the invention also comprises a frangula extract (Frangula dodonei), in a weight ratio with respect to the tamarind extract lower or equal to 0.03.

Frangula extract is a contact laxative, the effect of which is due to the active anthraquinone ingredient glucofr anguiin A, and is considered the mildest of the anthraquinone laxatives. In clinical practice, standardized frangula preparations are generally used so as to contain 20-30 mg of glucofrangulin A.

A further optional component of the composition according to the present invention is the caraway extract (Carum carvi), which, in addition to having antispasmodic effects similar to those of the ginger extract, useful for preventing any abdominal discomfort caused by the extract of tamarind, also has a marked carminative effect and a choleretic and anti-fermentative action, selectively inhibiting intestinal pathogenic bacteria and helping to rebalance the bacterial flora,

The present invention also relates to a pharmaceutical or food supplement formulation suitable for oral administration, for the treatment of constipation, which comprises the composition described above and excipients acceptable from the pharmaceutical or food point of view.

This formulation comprises one or more dosage units, each of which includes from 4.0 to 6.0 g of dry extract of the fruit of Tamarindus indica L. 1: 4 and from 0.10 to 0.30 g of dry extract of rhizome of Zingiber officinale Roscoe and pharmaceutically or nutritionally acceptable excipients.

The aforesaid dosage unit can also comprise from 0.10 to 0.15 g of dry extract of Frangula dodonei bark and possibly also from 0.10 to 0.20 g of dry extract of Carum carvi fruit.

A dry extract of Zingiber officinale Roscoe rhizome titrated at 1% of total gingerols, a dry extract of Frangula dodonei Ard bark are preferably used. Titrated with 7.7% -9.0% glucofrangulin A and a dry extract of Carum carvi L. fruit titrated with 2.5% polyphenols and 0.8% essential oil.

Using the dry extract of Frangula dodonei bark mentioned above, the formulation according to the invention is such that each dosage unit comprises from 7.7 mg to 13.5 mg of glucofrangulin A,

Solid dosage forms for oral administration include, for example, capsules, tablets, powders, granules and gels. In such solid dosage forms the active compound can be mixed with at least one inert diluent such as for example sucrose, lactose, starch or maltodextrin. Normally these dosage forms also include additional substances other than inert diluents, such as sweetening agents, such as sorbitol, sucralose, steviol glycosides, flavorings and anti-caking agents, such as silicon dioxide.

The pharmaceutical preparations according to the present invention can be produced by using conventional pharmaceutical techniques, as described in the various pharmacopoeias or in manuals of the sector such as, for example, "Remington's Pharmaceutical Sciences Handbook", Mack Publishing, New York, 18th Ed., 1990 .

The average daily dosage of the compounds according to the present invention depends on many factors, such as for example the severity of constipation and the condition of the patient (age, weight, sex): The dose can generally vary from 2.0 g to 15.0 g, preferably from 2.7 to 11.0 g of composition according to the invention per day, possibly divided into several administrations.

In a further aspect, the present invention relates to a functional food containing the composition described above. Preferably, this functional food is such that a predetermined portion thereof contains from 4.0 to 6.0 g of dry extract of the fruit of Tamarindus indica L. 1: 4 and from 0.10 to 0.30 g of dry extract of rhizome of Zingiber officinale Roseo e.

Conveniently, this portion also contains from 0.10 to 0.15 g of dry extract of Frangula dodonei bark and possibly also from 0.10 to 0.20 g of dry extract of Carum carvi fruit.

The functional food in question can be, for example, a cereal-based bar, a yogurt or similar dairy product, a baked product or a fruit juice.

Detailed description

The characteristics and advantages of the present invention will become clearer from the description of some embodiments reported hereinafter by way of illustration and not of limitation.

Example 1

Dosage unit of a formulation according to the invention: Dry extract of the fruit of Tamarindus indica L. 1: 4 5.5 g Dry extract of the rhizome of Zingiber officinale Roscoe 0.3 g Maltodextrin 1.5 g Stevia (powder extract) 0, 07 g Sorbitol 0.7 g Flavors 0.2 g Silicon dioxide 0.1 g Example 2

Dosing unit of a formulation according to the invention: Dry extract of the fruit of Tamarindus indica L. 1: 4 5.2 g Dry extract of the rhizome of Zingiber officinale Roscoe 0.25 g Dry extract of the bark of Frangiala dodonei 0.15 g Maltodextrin 1.0 g Sorbitol 0.6 g Sucralose 0.7 g Flavors 0.2 g Silicon dioxide 0.1 g Example 3

Dosing unit of a formulation according to the invention: Dry extract of the fruit of Tamarindus indica L. 1: 4 5.0 g Dry extract of the rhizome of Zingiber officinale Roscoe 0.20 g Dry extract of the bark of Frangula dodonei 0, 13 g Dry extract of Carum carvi fruits 0.15 g Maltodextrin 0.5 g Sorbitol 0.7 g Stevia {powder extract) 0.05 g Flavors 0.3 g Dye 0.3 g Silicon dioxide 0.1 g

The dry extracts mentioned in the examples above are more precisely the following: dry extract of Zingiber officinale Roscoe rhizome titrated at 1% of total gingerols, dry extract of Frangula dodonei Ard bark. titrated at 7.7-9.0% glucofrangulin A and dry extract of the fruit of Carum carvi L. titrated at 2.5% polyphenols and 0.8% essential oil.

The dosage units of Examples 1-3 were made in the form of sachet-type powder sachets, possibly divided into two parts, intended to be dispersed in water for oral administration.

Example 4

The composition according to example 3 was tested in patients suffering from chronic constipation, enrolled on the basis of the diagnostic criteria established in the Consensus Conference on the Diagnostic Criteria of Functional Bowel Disorders (called Rome III), or on the basis of the presence of at least two of the following characteristics: effort in defecation, presence of hard stools or fecalomas, sensation of incomplete evacuation, sensation of obstruction or anorectal blockage, need to resort to manual evacuation maneuvers, less than three discharges per week. This is in the absence of a diagnosis of irritable bowel syndrome.

1 1 patients were selected on the basis of the aforementioned criteria and these patients were divided into two groups A and B, composed respectively of 8 and 3 patients, based on the degree of constipation encountered, greater in group A.

Patients in group A were required to take a dosage unit according to Example 3 twice a day, in the form of a sachet of "sachet" type powder, diluted in 200 ml of water and mixed to obtain a clear and lump-free solution, until the first evacuation is obtained. Thereafter, the patient took only one dose unit per day for a total period (starting with the first dose unit taken) of two weeks.

Patients in group B were required to take half a dosage unit twice a day according to example 3, in the form of half a sachet of "sachet" type powder, diluted in 200 ml of water and mixed to obtain a clear and lump-free solution, until the first evacuation is obtained. Thereafter, the patient took only half a dose unit per day for a total period (starting with the first dose unit taken) of two weeks.

The clinical trial results are summarized in Table 1 below

Table 1

Group A Group A Group B Group B First Second First Second week week week week (average (average (average (arithmetic mean) arithmetic) arithmetic) arithmetic) No. of spontaneous bowel movements 3.6 4.1 2.0 3.6

No spontaneous evacuations not 3.5 3.5 2.0 3.6

induced by other laxatives

n. evacuations that have 0 0 0 0

manual maneuvers required

n. evacuations with consistency U 2.6 2.3 1.3

optimal

Days of diarrhea 0 0 0 0

Mean pain score 0.2 0 0 0

abdominal

n. of patients with more than 3 4 5 2 2

spontaneous evacuations

n. of patients who required 1 3 0 0

of another laxative

The abdominal pain score was assessed by asking patients to draw a score on a scale from 0 to 4, in which 0 indicates the absence of abdominal pain and 4 the maximum abdominal pain.

As can be seen from the data of Table 1, the composition according to the present invention is effective in counteracting constipation already at a dose equal to half the dosage unit referred to in Example 3. Furthermore, the composition is very well tolerated, because it is not it caused abdominal pain if not very mild in only two patients of group A and did not cause episodes of diarrhea. There was also no abdominal swelling. Finally, the patients judged the taste of the composition according to the present invention pleasant.

It is significant to note that the frangula extract contained in the tested composition is present in such quantities as to provide approximately 10-12 mg of glucofrangulin A for each dosage unit, a dose that corresponds to approximately half of the minimum dose of glucofrangulin A used to obtain a laxative effect (monographs relating to frangula recommend typical doses of glucofrangulin A equal to 20 mg or 30 mg). This presupposes a synergistic effect of the frangula extract with the tamarind extract in determining a significant laxative effect of this composition even in the presence of quantities of frangula extract which in themselves would not have a therapeutically useful activity.

Some preliminary clinical tests carried out with the composition according to example 1, which does not contain frangula extract, have however shown good efficacy in patients suffering from mild constipation and excellent tolerability, evidenced by the absence of episodes of diarrhea and by the total absence of abdominal pain and abdominal swelling.

Claims (14)

CLAIMS 1. Composition with laxative effect which includes a tamarind extract (Tamarindus indica L.), and a ginger extract (Zingiber officinale Rose.). 2. Composition according to claim 1, further comprising a frangula extract (Frangula dodonei), in a weight ratio with respect to the tamarind extract lower than or equal to 0.03. 3. Composition according to claim 2, further comprising a caraway extract (Carum carvi), having a carminative effect. 4. Pharmaceutical or food supplement formulation suitable for oral administration, for the treatment of constipation, comprising the composition according to claim 1 and at least one excipient acceptable from the pharmaceutical or food point of view. 5. Formulation according to claim 4, comprising one or more dosage units, each of which comprises from 4.0 to 6.0 g of dry extract of the fruit of Tamarindus indica L. 1: 4 and from 0.10 to 0, 30 g of dry extract of Zingiber officinale Roscoe rhizome. 6. Pharmaceutical or food supplement formulation suitable for oral administration, for the treatment of constipation, comprising the composition according to claim 2 or 3 and at least one excipient acceptable from the pharmaceutical or food point of view. 7. Formulation according to claim 6, wherein each dosage unit comprises from 4.0 to 6.0 g of dry extract of the fruit of Tamarindus indica L. 1: 4, from 0.10 to 0.30 g of dry extract of rhizome of Zingiber officinale Roscoe and from 0.10 to 0.15 g of dry extract of Frangula dodonei bark and possibly also from 0.10 to 0.20 g of dry extract of Carum carvi fruit. 8. Formulation according to claim 7, wherein each dosage unit comprises from 7.7 mg to 13.5 mg of glucofrangulin A. 9. Formulation according to any one of claims 4 to 8, wherein said at least one excipient acceptable from the pharmaceutical or food point of view is selected from the group comprising diluents, such as sucrose, lactose, starch and maltodextrin, sweeteners, such as sorbitol, sucralose and steviol glycosides, anti-caking agents, such as silicon dioxide, and flavorings. 10. Formulation according to claim 9, characterized in that it is in the form of a water-soluble powder, packaged in sachets. 11. Functional food containing the composition according to claim 1. 12. Functional food according to claim 11, containing in each portion from 4.0 to 6.0 g of dry extract of the fruit of Tamarindus indica L. 1: 4 and from 0, 10 to 0.30 g of dry extract of rhizome of Zingiber officinale Roscoe. 13. Functional food according to claim 12, containing in each portion from 0.10 to 0.15 g of dry extract of Frangula dodonei bark and possibly also from 0.10 to 0.20 g of dry extract of Carum fruit caraway. Functional food according to any one of claims 11 to 13, selected from the group consisting of bars based on cereals, yoghurt and similar dairy products, baked goods and fruit juices.