WO2004054573A1

WO2004054573A1 - Method and composition for inhibiting carbohydrate digestion

Info

Publication number: WO2004054573A1
Application number: PCT/NL2003/000888
Authority: WO
Inventors: Katien Maria Jozefa VAN LAERE; Gerrit Jan Witte; Evan Abrahamse; Ingeborg Frances PALM
Original assignee: N.V. Nutricia
Priority date: 2002-12-13
Filing date: 2003-12-15
Publication date: 2004-07-01
Also published as: AU2003294185A1

Abstract

The present invention relates to a method for the treatment and prevention of a diet responsive condition through inhibition of carbohydrate digestion in the intestine, by a component obtainable from Epimedium.

Description

METHOD AND COMPOSITION FOR INHIBITING CARBOHYDRATE

DIGESTION

FIELD OF THE INVENTION

The present invention relates to a method for the treatment and prevention of a diet responsive condition, the method comprising the enteral administration of a Epimedium flavonoid type component obtainable from Epimedium plant material.

BACKGROUND OF THE INVENTION

Diabetes afflicts a significant number of people, approximately 5 % of the population, and yet the treatment of diabetes leaves a lot to be desired. For patients with Type I diabetes, insulin is an absolute necessity. It is typically administered by injection, needs to be co-ordinated with a balanced diet and exercise, and must be carefully monitored. For subjects with Type II diabetes (over 90% of all cases of diabetes), weight loss is advisable, but is frequently usually difficult to achieve. Tablets, such as oral hypoglycemic agents, or insulin may be required. Despite all this effort, diabetes complications such as blindness, kidney failure, nerve damage, and atherosclerosis, still are a major problem.

Also overweight and obesity are major problems within the Western community. Due to increased consumption, decreased exercise and changes in the nutritional value of foodstuffs, many humans and companion animals are suffering from overweight or have difficulty maintaining a desirable weight. Many methods have been proposed to solve this problem, for example, via the administration of functional ingredients (e.g. nutritional supplements) which facilitate the reduction of overweight.

In effect, overweight is caused by the ingestion of excess calories. Calories are for example ingested via high caloric meals. Within the art, several strategies are known for reducing caloric intake. These strategies include for example replacing the high caloric meals for low caloric meals (e.g. meal replacers); the ingestion of medicaments that reduce the absorption of high caloric components from the meal (e.g. carbohydrase inhibitors and lipase inhibitors); and the administration of appetite reducing agents.

Hence, there is a need for compositions that prevent, treat and/or ameliorate diabetes and overweight.

Presently, many herbal preparations are used while the active ingredient(s) responsible for the effects are unknown. Without the active ingredient(s) identified, the efficacy of the plant material cannot be predicted. The result is that people, who have the desire to treat or prevent obesity or diabetes, may ingest plant material that does not have an optimal effect, e.g. a plant extract that contains only an ineffective amount of the active ingredient(s).

Additionally, without the active ingredient having been identified, it is unclear which mechanism(s) is triggered following the ingestion of the plant material. This may result in an ineffective administration regimen. For instance, ingestion of a carbohydrase inhibitor about 4 hours before a carbohydrate containing meal generally provides a very limited weight reducing or blood sugar content decreasing effect.

Plant material from Epimedium species are known to have a variety of beneficial effects on health. Extracts of Epimedium species enriched in icariside I or anhydroicaritin have for example been described to treat sexual dysfunction in

US6399579. Furthermore, US6123944 describes the use of Epimedium extracts enriched in icariin for the treatment or prevention of osteoporosis. CN1211424 describes a Chinese medicine for reducing fat and loosing weight, that is prepared from 11 Chinese-medicinal materials such as lotus leaf, haw, tuckahoe, Epimedium and red sage root. CN1161851 describes a Chinese medicine for curing diabetes, which is prepared by using effective components of the Chinese medicinal herbs of anemarrhena root, adenophora root, dried rehmannia root, cornus fruit, alisma tuber, Epimedium and saliva root. JP 03068547 describes flavonoids contained in inter alia Epimedium grandiflorum for use as aldose reductase inhibiting agents.

The present inventors have identified an Epimedium flavonoid type component (EFT component) that is capable of reducing intestinal carbohydrase activity. The finding that the EFT component is capable of reducing intestinal carbohydrase activity enables the manufacture of compositions from the Epimedium flavonoid type component containing plants or plant parts, wherein the efficacy of the (herbal) composition can be predicted based on its the chemical composition.

Furthermore, the inventors have surprisingly found that oral administration of an effective amount of the flavonoid type component reduces blood glucose levels in rats. The blood glucose-lowering properties are indicative for the suitability to use the present flavonoid type component or extracts enriched therein in the treatment or prevention of diabetes.

Additionally, weight gain or loss for an individual is essentially the difference between the amount of calories absorbed and the amount of calories burned. Enteral ingestion of the carbohydrase inhibitor will reduce the uptake of carbohydrates present in a meal or snack. The reduced absorption of carbohydrates results in weight loss or less weight gain due to the lower consumption of calories. Hence the EFT component or extract enriched therein can be advantageously used in a method for the treatment or prevention of obesity.

SUMMARY OF THE INVENTION

One aspect of the present invention relates to a method for the prevention or treatment of a diet responsive condition, said method comprising enterally administering to the mammal an effective amount of the Epimedium flavonoid type component of formula (I) hereinafter defined, obtainable from Epimedium plant material.

In a further aspect the present invention provides a method for the reduction of intestinal carbohydrate absorption and/or delaying intestinal carbohydrate absorption in mammals, said method comprising the administration of a carbohydrate absorption reducing amount of the Epimedium flavonoid type component of formula (I) hereinafter defined. In yet a further particular aspect, the present invention provides a method for the treatment or prevention of overweight in a mammal, said method comprising administering to the mammal an effective amount of the Epimedium flavonoid type component of formula (I) hereinafter defined.

In yet a further aspect, the present invention relates to a composition enriched in the present EFT component, particularly a composition comprising at least 0.5 wt.% of the Epimedium flavonoid type component of formula (I) hereinafter defined.

DETAILED DESCRIPTION OF PREFERED EMBODIMENTS

Description of the figures:

Figure 1 represents the results of the experiments performed in Example 2 and illustrates the in vivo effects of EFT component on postprandial glucose response. 1 = control; 2 = Epimedium P.E. and 3 = P7

Figure 2 represents the results of the experiments performed in Example 2 and illustrates the in vivo effects of EFT component on postprandial insulin response. 1 = control; 2 = Epimedium P.E. and 3 = P7

Figure 3 represents the chromatogram of the experiments performed in example 1. The arrow indicates the peak of the EFT component according to the present invention.

Chemical structure

The present invention relates to a method for the treatment and/or prevention of a diet responsive condition, comprising administering to a mammal an effective amount of Epimedium flavonoid type component (EFT component) or a pharmaceutically acceptable salt thereof, wherein the EFT component has the formula (I)

in which:

Ri is hydrogen or carbohydrate;

R₂ is hydrogen or carbohydrate;

R₃ is a (C₂-C₁₂) alkyl, (C₂-Cι₂) alkoxy, (C₂-Cι₂) alkenyl, (C2-C12) alkynyl, cycloalkyl, aryl or heteroaryl.

R-_t, R₅, R₆, R , R₈, R and Rio independently represent hydrogen, hydroxy or amme;

Preferably Ri represents a carbohydrate, more preferably a carbohydrate comprising one or more hexose units, even more preferably a monosaccharide residue or oligosaccharide residue, most preferably a di- or trisaccharide, particularly a disaccharide. Preferably the disaccharide has the structure: rhamnose-X or glucose-X, in which X represents a saccharide selected from the group consisting of rhamnose and xylose and wherein preferably the rhamnose or xylose, more preferably the rhamnose, is covalently attached to the basic flavonoid structure. Preferably R₂ represents a carbohydrate, more preferably carbohydrate comprising one or more hexose units, even more preferably a monosaccharide residue or oligosaccharide residue, most preferably a monosaccharide. In the event R₂ represents a monosaccharide, the monosaccharide is preferably selected from the group consisting of fructose, galactose, rhamnose, glucose and xylose. Preferably R₂ represent glucose. Preferably R₃ is a (Cι-Cι₂) alkyl, (C₂-Cι₂) alkenyl, (C -Cι₂) alkoxy or (C₂-C₁₂) alkynyl, more preferably a (C -Cι₂) alkenyl. Most preferably R₃ represents

CH₂- CH =C— (CH₃)₂ Preferably j, R₅, R₇, R₈ and R₉ are hydrogen.

Preferably R₆ and R₉ are hydroxy or amine, more preferably hydroxy.

Even more preferably the EFT component has one of the following structures (formula II or formula III):

Formula II

C H3 C H3

Formula III

The present invention also provides the composition according to formula III. The EFT component as described in formula III, or a phannaceutically acceptable salt thereof is particularly suitable for use as a medicament. Hence the present invention also provides the EFT component as described in formula I, or a pharmaceutically acceptable salt thereof, wherein Ri is disaccharide rhamnose-xylose; and R₆ is hydrogen, for use as a medicament.

Compositions enriched in the EFT component

In a particular aspect, the present invention relates to a composition comprising: at least 0.5 wt.%, preferably at least 1 wt.% more preferably at least 2.5 wt.%, more preferably at least 5 wt.%, even more preferably at least 10 wt.%, most preferably at least 50 wt.% of the EFT component based on dry weight of the composition; and a pharmaceutical acceptable carrier. These compositions can be advantageously used in a method for the treatment or prevention of diet responsive conditions.

Sources of the EFT component

The EFT component may be chemically manufactured, biochemically produced (e.g. in a fermentation process) or be obtained from vegetable material, optionally followed by subsequent chemical modification. Preferably, the EFT component is provided by and/or obtained from Epimedium plant material. The term Epimedium plant material refers to any plant material obtained from one or more plants belonging to the genus Epimedium, including material obtained by extracting, commuting, drying or other chemical or physical treatment of Epimedium plants or parts thereof. Preferred plant sources of the EFT component are E. acuminatum, E. baicaliquizhounense, E. baojingenensis, E. brevicornum, E. clongatum, E. caotum, E. davidii, E. ecalcaratum, E. fargesii, E. glandolospilosum, E. haiyangense, E. hunanense, E. leptorrhizum, E. koreanum, E. platypetalum, E. pubesens, E. reticulatum, E. sagittatum, E. simplicifolium, E. sutchuenense, E. truncatum, E. wushanense and/or E. zushanense.

The Epimedium plant material used in accordance with the present invention may be obtained from whole plants or from one or more parts thereof, for example stems, stalks, roots, shoots, rhizomes, tubers, fruits (including seeds), foliage, kernels, husks, hulls or mixtures thereof. According to a preferred embodiment the Epimedium plant material is administered in the form of a plant isolate, more preferably in the form of an Epimedium plant extract. The tenn "isolate" as referred to herein, encompasses any fraction that can be obtained from a plant material by means of isolation techniques known in the art, particularly one selected from extraction, distillation or squeezing, and that displays the desired functional properties described herein before. The term "extract" as used in the present invention refers to an isolate that has been obtained by means of solvent extraction.

hi the preparation of the isolate, the whole plant or a part thereof is preferably first subjected to physical processes prior to the preparation of the isolate. The plants or plant parts are typically subjected to one or more of the following processes prior to the isolation step: grinding, flaking, freezing, drying, commuting and the like. The Epimedium plant or plant parts are thereafter preferably subjected to one or more isolation processes selected from the group consisting of solvent extraction, cold pressing, hot pressing, distillation, chromatography and filtering, more preferably the Epimedium plant material is subjected to solvent extraction (including supercritical extraction and percolation).

Preferably the solvents used to prepare the Epimedium extract are polar solvents, more preferably a solvent selected from the group consisting of alcohols, water and mixtures thereof, most preferably selected from the group consisting of water, ethanol and mixtures thereof. In a preferred embodiment, the present invention relates to an Epimedium extract containing at least 0.5 wt.%, preferably at least 1 wt.% more preferably at least 2.5 wt.%, more preferably at least 5 wt.%, even more preferably at least 10 wt.%, most preferably at least 50 wt.% of the EFT component based on dry weight of the Epimedium plant extract. Preferably, the extract enriched in the EFT component is combined with a pharmaceutical acceptable carrier. These compositions can be advantageously used in a method for the treatment or prevention of diet responsive conditions. Treatment

The present invention provides a method for the treatment or prevention of a diet responsive condition in a mammal. The term "diet responsive condition" as used herein refers to any disease or physical state that can be caused or grow worse by the ingestion of proteins, carbohydrates or fats. The present method particularly aims to inhibit intestinal carbohydrate absorption and hence is particularly suitable for a suppressing fluctuations in blood glucose levels, prevention of diabetes, inhibition of insulin level increase and/or obesity, as these conditions all benefit from the inhibited intestinal absorption of carbohydrates. The present invention preferably does not relate to the treatment of complications of diabetes and/or complications accompanied by diabetes, such as cataract, retinopathy or nephropathy

Inhibition of intestinal carbohydrate absorption within the context of this invention refers specifically to a decrease of the intestinal enzyme activity that is associated with the hydrolysis of di-, tri-, oligo- and polysaccharides. Thus the present method leads to a decreased net absorption of monosaccharides from dietary digestible carbohydrates or to an absorption of monosaccharides over an increased surface area of the small intestine (i.e. absorption spread out over a longer period of time).

The present method is particularly suitable for (prophylactically) treating obesity as the reduction in carbohydrate absorption will usually also lead to a reduction of body weight, a reduction of body weight increase or a reduction in production of body fat. Another advantageous application of the method is its use for suppressing fluctuations in blood glucose levels, preferably inhibition of postprandial blood glucose level increase, which is particularly beneficial for diabetics. Hence the present invention is particularly suitable for the dietary management of diabetes.

In a particularly prefered embodiment the present invention provides a method for the treatment of diabetes, said method comprising enterally administering to the mammal an effective amount of EFT component or a pharmaceutically acceptable salt thereof, wherein the EFT component has the structure of formula I and wherein R₂ represents a carbohydrate.

Suppression of blood glucose fluctuations, and particularly the blood glucose 'peaks', is also of benefit for obese people as the resulting gradual absorption of carbohydrates usually leads to less body fat formation than is observed for rapid absorption of the same amount of carbohydrates. Furthermore, the present inhibition of absorption of carbohydrates is also suitable for use in a method for achieving sustained energy release.

Hence, the present invention can be advantageously used in a method for the treatment or prevention of diabetes and overweight.

Administration regimen Best results are obtained with the present method if the preparation is administered no more than 60, preferably no more than 30 minutes before or after consumption of a foodstuff containing a significant amount, e.g. at least 20 g, of digestible carbohydrates. The term "digestible carbohydrates" as used herein includes carbohydrates which are readily degraded within the intestine to directly absorbable carbohydrates. Carbohydrates that are readily degraded within the intestine are those carbohydrates that can be digested by one or more of the salivatory, pancreatic or brush border enzymes of a given mammal, hi case of humans these enzymes include glucoamylase (glucosidase), isomaltase, α-limit dextrinase, sucrase, lactase, pancreatic amylase and/or salivatory amylase. Examples of digestible carbohydrates are sucrose and digestible starches.

Dosages of EFT component

The present method preferably comprises the administration of an effective amount of the EFT component. Preferably, a daily amount of between 0.1 and 250 mg EFT component per kg of body weight is administered to a mammal, more preferably between 0.5 and 100 mg/kg body weight, even more preferably between 1 and 50 mg/kg body weight, most preferably between 2.5 and 20 mg/kg body weight.

Administration According to a prefened embodiment the present method comprises the oral administration of the EFT component. Preferably the EFT component is swallowed after application to the oral cavity. Preferably the EFT component is provided in a dosage. The dosage used in the present method can be applied in any suitable form, such as bars, pills, capsules, gels, liquid etc, however is preferably provided in the form of a pill, tablet or capsule. Preferably a dosage does not consist of more than 3 tablets, capsules or pills, even more preferably consists of a single pill, capsule or tablet. Advantageously, at least two dosages, more preferably at least three dosages, are administered in one day. In the present method a daily dosage of the preparation as used in the present invention can include one or more pills, tablets or capsules. Preferably a daily dosage consists of 1 to 6 pills, tablets or capsules.

A dosage is preferably in a solid or semisolid form, more preferably in a form selected from the group consisting of pills, capsules, tablets, caplet, microparticles and microspheres. The solid or semisolid dosage form preferably has a weight between 0.1 and 30 grams, more preferably between 0.2 and 10 grams.

According to a further preferred embodiment the EFT component is provided in a unit dosage form. The term "unit dosage form" refers to a physically discrete unit suitable for unitary administration to human subjects and other mammals, wherein each unit contains a predetermined quantity of Epimedium plant material and a pharmaceutically acceptable carrier. These carriers may be selected from sugars, starches, cellulose and its derivatives, malt, gelatine, talc, calcium sulphate, vegetable oils, synthetic oils, polyols, alginic acid, phosphate buffered solutions, emulsifiers, isotonic saline, and pyrogen-free water.

Preferably the unit dosage form has a caloric value below 100 kcal, more preferably below 50 kcal even more preferably below 10 kcal. A dosage preferably has a weight between 0.2 and 4 grams, even more preferably between 0.5 and 3 grams.

EXAMPLES

Example 1: Preparation of composition enriched in EFT component

Sample solution was prepared by dissolving Epimedium extract (Epimedium P.E; Kingherb International, Changchun, China) in demineralised water at a concentration of 50 mg per ml and subsequently centrifuged (10 min, 10.000 g) and filtered using a 0.2 μ filter.

Fractionation

4 ml sample solution was fractionated using high performance liquid chromatography with Econosil C18, lOμ, 250x22 mm. The sample solution was loaded on the column and after 50 ml washing with eluent A (0.01 % trifluoro acetic acid in demiwater), fractions were eluted with a linear gradient from 0% eluent B(0.01 % trifluoro acetic acid in acetonitril) to 50% eluent B and 50% eluent A in 400 ml, at a flow rate of 7.5 ml/min. Components were detected by UN at λ = 220 nm and λ = 254 nm. Chromatogram 1 (Fig. 3) gives the elution profile of components.

The obtained fractions were analyzed for the α-amylase inhibition (see below). It was surprisingly found that the fraction 355-365 ml showed a very high capability of inhibiting α-amylase activity, using the following carbohydrase assay (see indicated peak in Chromatogram 1).

The EFT component was collected and analyzed using mass spectrometry to determine the structure of the EFT component.

a-Amylase inhibition assay

10 U/ml α-amylase (Porcine Pancreas, Sigma A-3176) in 0,1 M Phosphate buffer was incubated with 3.75 % potato starch solution (sigma S-2630) in 0,1 M Phosphate buffer, with or without fractions for 60 min at pH 6.5 and 37 °C. The reaction was terminated by addition of 1 M HC1 to obtain an end concentration of 0.1 M HC1. Reaction products; glucose and glucose oligomers dp 2- dp 7, were quantified by means of high performance anion exchange chromatography (HPAE-PAD), with pulsed amperomatic detection, using a dionex carbopac PA1 column with a linear Νa- acetate gradient (0-0.5 M in 40 min.) in 100 mM ΝaOH at a flow of 1 ml/min. The total amount of products of the incubation without fraction was expressed as 100 % α- amylase activity. Example 2: Effect of EFT component on postprandial blood glucose and blood insulin levels

Preparation of EFT component

To obtain sufficient EFT component (i.e. Epimedium composition enriched in EFT component) for administration to rats, the method as described in Example 1 was repeated 50 times and the pooled samples were freeze dried. The resulting powder (hereinafter refened to as P7) is about 44 times more potent in inhibiting carbohydrase activity on weight basis (see Table 1).

The degree of activity increase was determined by comparing the slope of linear regression (percentage inhibition of 10 mU amylase activity per μg dry matter) of different concentrations of Epimedium P.E. and P7 dilutions against α-amylase inhibitory activity.

TABLE 1

Animal treatment

Male Wistar rats (± 320 g, n=18) were kept in a temperature controlled room, and were given food and water ad libitum, except on experimental days (see below). After arrival animals were left three weeks to adjust to a new light-dark schedule (lights on 02.00h, lights off 14.00h). They were then equipped with a permanent blood sampling canula in the right jugular vein, after which at least 7 days of recovery was allowed.

The effects of administration of control, Epimedium P.E. or P7 on postprandial glucose levels were determined with a meal tolerance test, i.e. after a 1 hour fast, animals received the carbohydrate test meal (1.75 g cornstarch + 0.5 g sucrose with or without test component) via oral gavage. Just prior to administration of the carbohydrate test meal and at 5, 10, 15, 30, 60, and 120 minutes after administration of the test meal, blood samples (0.2 ml) were taken via the permanent canula and collected in ice- chilled, heparinized tubes for determination of plasma glucose (glucose oxidase- peroxidase method) and insulin (radioimmunoassay) concentrations. The treatment groups received either test meal (control), test meal with Epimedium P.E. (166 mg) or test meal with P7 (4 mg). The glucose response after the test meal was calculated by the area under the curve (AUC), relative to the basal levels.

Figure 1 shows the average difference in glucose response of rats that received either test meal (control), test meal with Epimedium P.E. or test meal with P7 (1 = control; 2 = Epimedium P.E. and 3 = P7). Figure 1 shows a reduced area AUC for both test groups receiving Epimedium P.E.. The results are indicative for the suitability of the present EFT component for use in a method for suppressing fluctuations in blood glucose levels, prevention of diabetes and/or treatment or prevention of obesity.

The results are indicative for the suitability of use of a composition enriched in the present EFT component for use in a method for suppressing fluctuations in blood glucose levels, prevention of diabetes and/or treatment or prevention of obesity, as for P7 only 4 mg had to be administered to the rats in order to achieve an effect similar to the administration of 166 mg Epimedium P.E.

Figure 2 shows the average difference in insulin response of rats that received either test meal (control), test meal with Epimedium P.E. or test meal with P7 ((1 = control; 2 = Epimedium P.E. and 3 = P7). Figure 2 shows a reduced area AUC for both test groups receiving Epimedium extract. The results are indicative for the suitability of the present EFT component for use in a method for reduction of insulin level increase, prevention of diabetes and/or treatment or prevention of obesity. The results are indicative for the suitability of use of a composition enriched in the present EFT component for use in a method for reduction of insulin level increase, prevention of diabetes and/or treatment or prevention of obesity, as for P7 only 4 mg had to be administered to the rats in order to achieve an effect similar to the administration of 166 mg Epimedium P.E. Example 3: Composition for prevention of diabetes

Composition comprising 5 mg P7 and a pharmaceutically acceptable carrier for use in a method for the prevention of diabetes, particularly diabetes type II, said method comprising orally administering said composition to a human.

Example 4: Composition for treatment and/or prevention of overweight Composition comprising 2 mg EFT component of Formula III and a pharmaceutically acceptable carrier for use in a method for the treatment and/or prevention of overweight, said method comprising orally administering said composition to a human.

Claims

CLAIMS:

1. Use of a therapeutically effective amount of Epimedium flavonoid type component (EFT component) for the manufacture of a composition for use in a method for the treatment or prevention of a diet responsive condition in a mammal, said method comprising enterally administering to the mammal an effective amount of EFT component or a pharmaceutically acceptable salt thereof; wherein the EFT component has the formula (I)

in which:

Ri is hydrogen or carbohydrate.

R₂ is hydrogen or carbohydrate.

R₃ is a (C2-C12) alkyl, (C2-C12) alkoxy, (C2-C12) alkenyl, (C₂-C_!2) alkynyl, cycloalkyl, aryl or heteroaryl.

R₄, R₅, R₆, R₇, R₈, R₉ and Rio independently represent hydrogen, hydroxy or amine.

2. Use according to claim 1 wherein said method comprises suppressing fluctuations in blood glucose levels, prevention of diabetes, reduction of insulin level increase and/or treatment or prevention of obesity.

3. Use according to claim 1 or 2, wherein Ri represents a carbohydrate, preferably a disaccharide.

4. Use according to any one of the preceding claims, wherein R₂ represents a carbohydrate, preferably a monosaccharide.

5. Use according to any one of the preceding claims, wherein R₃ is a (Cι-Cι₂) alkyl, (C₂-Cι₂), alkenyl (C₂-Cι₂) alkoxy or (C₂-Cι₂) alkynyl, preferably a (C₂-Cι ) alkenyl.

6. Use according to any one of the preceding claims, wherein R₃ represents: CH₂- CH =C— (CH₃)₂

7. The EFT component as described in claim 1, or a pharmaceutically acceptable salt thereof, wherein Ri is disaccharide rhamnose-xylose; and R₆ is hydrogen, for use as a medicament.

8. Use of a therapeutically effective amount of Epimedium flavonoid type component (EFT component) as described in claim 4 for the manufacture of a composition for use in a method for the treatment of diabetes, said method comprising enterally administering to the mammal an effective amount of EFT component or a pharmaceutically acceptable salt thereof.

9. Composition comprising at least 0.5 wt.% based on dry weight of the composition of a EFT component as defined in claim 1, wherein ₂ represents a carbohydrate, preferably a monosaccharide; and a phannaceutically acceptable carrier.

10. Composition according to claim 9, wherein Ri represents a carbohydrate, preferably a disaccharide.

11. Composition according to any one of the claims 9 or 10, wherein R₃ represents: CH₂- CH =C— (CH₃)₂.

12. Composition according to any one of the claims 9-11, comprising at least 1 wt.% of the EFT component based on the dry weight of the composition.

13. Oral unit dosage form comprising a composition as defined in any one the claims 9- 12.

14. Composition according to any one of claims 9-13 for use as a medicament.

15. Use of a composition as defined in any one of the claims 9-14 for the manufacture of a preparation for treating or preventing of a diet responsive condition in a mammal