ES2804649B2 - Hypoleptinémic composition and its use - Google Patents

Description

DESCRIPTION

Hypoleptinémic composition and its use

TECHNICAL SECTOR

The present invention is framed in the field of dietetics, food supplements, and the food industry (in particular the sector of functional foods), and in the field of medicine and the pharmaceutical industry. In particular it relates to a composition with a hypoleptinémic effect and its use.

BACKGROUND OF THE INVENTION

Western society continues malpractice consuming excess foods rich in fat and sugar and practice a sedentary lifestyle. In our country, 16% of adults suffer from obesity, 38% are overweight, and forecasts indicate that in 2050 60% of the European population will be obese ( WHO, Overweight and obesity, 2016).

Although current public policies try to change the dietary and physical activity practices of our society, and it is essential to do so, surely we must start from the premise that society will change little (or nothing) its customs. Therefore, it is socially essential and economically it is advisable to continue investigating new strategies that allow correcting, even partially, bad practices in relation to food and exercise.

In this sense, a good strategy could lie in the development of new nutritional supplements and / or new functional foods with the capacity to effectively treat obesity and the metabolic alterations associated with obesity, such as arterial hypertension, by means of control of blood levels of the hormone leptin.

Leptin is a hormone that regulates food intake and energy expenditure to keep body weight constant. At a physiological level, leptin is responsible for generating the satiety signal in the brain. To do this, this hormone (which is synthesized by adipose tissue in an amount proportional to the body's fat mass) stimulates certain areas of the hypothalamus by sending a signal that informs that there is sufficient adipose tissue. The consequence is that it causes a reduction in caloric intake and an increase in energy expenditure. Consequently, individuals who do not synthesize or produce this hormone they do not have this mechanism of satiety and intake brake with the consequent risk of developing obesity ( Flak et al. Molecular Endocrinology 2016; 30,3-12).

However, and contrary to expectations, leptin levels in obese subjects exceed normal levels, and furthermore, in this context of obesity, a resistance to the signal of this hormone has been described, that is, despite the fact that it is detect elevated levels of leptin in the blood, the body does not respond adequately ( Maffei et al. Nature Medicine 1995; 1: 1155-1161).

It has even been described that when leptin levels in the blood are very high, as in obese subjects, there is an increase in sympathetic activity at the central level which in turn causes an increase in blood pressure ( Simonds et al. Cell 2014; 159: 1404-1416).

With this, it is easy to understand that leptin is a key element in both the regulation of body weight and blood pressure through its action in the brain. Therefore, regulating the blood levels of this hormone could be a good therapeutic strategy to simultaneously combat both obesity and its most important metabolic disorders, such as high blood pressure.

There are different scientific studies that show how some bioactive components of the diet, administered individually, can have important benefits for the functionality of leptin at different levels ( Aragonés et al. Molecular Nutrition and Food Research 2016; 60: 1789-1803) . However, none of these components by themselves has been able to simultaneously reverse the various metabolic alterations that are generated in a situation of obesity. What's more, none of them have been able to have a global effect on body weight and high blood pressure.

Surprisingly, the authors of the present invention have developed a composition that comprises different bioactive components that is capable of acting simultaneously on the different metabolic alterations associated with obesity, and with special interest, on blood leptin levels and sensitivity to leptin. , thus providing a treatment for obesity and its most important metabolic disorders, such as high blood pressure.

OBJECT OF THE INVENTION

In a first aspect, the present invention refers to a composition characterized in that it comprises:

a) an extract of anthocyanins;

b) a proanthocyanidin extract;

c) conjugated linoleic acid; Y

d) a chicken leg hydrolyzate (HPP), comprising the peptides of sequence SEQ ID N ° 1 (QVGPLIGRYCG) and / or SEQ ID N ° 2 (AVFQHNCQE).

In a second aspect, the present invention relates to a medicine, a food supplement, a beverage or a food product comprising a composition according to the first aspect of the invention.

In a third aspect, the present invention relates to the composition according to the first aspect of the invention for use in medicine.

In a fourth aspect, the present invention relates to the composition according to the first aspect of the invention for use in the treatment of obesity, overweight and / or hypertension.

In a fifth aspect, the present invention relates to the composition according to the first aspect of the invention for use as an adjuvant in the treatment of obesity, overweight and / or hypertension.

Other objects, features, advantages and aspects of the present application will be apparent to the person skilled in the art from the description and the appended claims.

BRIEF DESCRIPTION OF THE FIGURES

Figure 1 shows the ability of the composition of the invention (MIX) to activate hypothalamic neurons sensitive to leptin after its administration in Wistar rats fed a cafeteria diet. In Figure 1A the white arrows show anorectic cells, producing peptides that inhibit appetite, which present active leptin signaling pathway (ACTH (red) positive and pSTAT3 (green) positive). The micrograph shows ACTH in red, pSTAT3 in green, and DAPI in blue. Figure 1B shows the cell count of anorectic neurons activated by leptin of the animals that have taken MIX (white column) and of the animals that have not taken it (black column). The data represent the mean ± SEM for a minimum of 6 animals. * indicates a P <0.05 with respect to the control group.

Figure 2 shows the reduction in the increase in body weight of the animals with a cafeteria diet to which the composition of the present invention (MIX) has been administered for 3 weeks compared to the controls. Data represent the mean ± SEM for a minimum of 6 animals. * indicates a P <0.05 with respect to the control group.

Figure 3 shows the antihypertensive effect of the composition of the present invention (MIX) after its chronic administration for 3 weeks in animals with a cafeteria diet compared to control animals. * indicates a p <0.05 with respect to the control group.

DETAILED DESCRIPTION OF THE INVENTION

As used in the present application, the singular forms "a / an", "an" and "the" include their corresponding plurals, unless the context clearly indicates otherwise. Unless otherwise defined, all technical terms used herein have the meanings commonly understood by one of ordinary skill in the art to which this invention pertains.

The present invention relates in a first aspect to a composition (hereinafter referred to as the composition of the invention) comprising:

a) an extract of anthocyanins;

b) a proanthocyanidin extract;

c) conjugated linoleic acid; Y

d) a chicken leg hydrolyzate (HPP), comprising the peptides of sequence SEQ ID N ° 1 (QVGPLIGRYCG) and / or SEQ ID N ° 2 (AVFQHNCQE).

As shown in Example 1, the composition of the invention has a hypoleptinemic effect, that is, it is capable of reducing leptin levels in the blood. Thus, in a particular embodiment, the composition of the invention is a hypolepinemic composition.

Advantageously, in addition to reducing leptin levels in the blood, the composition of the invention is capable of increasing leptin sensitivity by increasing the number of anorectic neurons, which are responsible for regulating appetite and body weight. Thus, the body regains control of the energy balance. This results in a reduction statistically significant for body weight and adiposity index, in addition to inducing a clear antihypertensive effect (see Examples 2 and 3).

These data are of great social interest, since until now it has not been possible to develop any drug or functional food that corrects the increase in body weight so effectively and without side effects, and that, in addition, reduces systolic blood pressure from the first week of administration (see Figure 3).

In a particular embodiment, the extract comprising anthocyanins Anthocyanins blackcurrant (Ribes nigrum L.) and / or blueberry (Vaccinium myrtillus), preferably comprises anthocyanins blackcurrant (Ribes nigrum L.) and / or blueberry (Vaccinium myrtillus ). More particularly, the anthocyanin extract comprises at least 25% cyanidin 3-O-glucoside, preferably 30% -35% cyanidin 3-O-glucoside, and at least 50% cyanidin 3-O-glucoside. delphinidin, preferably 55% -60% delphinidin 3-O-glucoside. Anthocyanin extracts (ANT) that meet these characteristics are commercially available (eg MEDOX®). As shown in the examples, individual use of this ingredient does not have a statistically significant effect on reducing leptin levels. However, advantageously, in combination with the rest of the ingredients of the composition of the invention, it provides an unexpected and statistically significant reduction in blood levels of this hormone which, in turn, is associated with a reduction in body weight, of adiposity and blood pressure index (see Tables 1-4).

In a particular embodiment according to any one of the previous embodiments, the proanthocyanidin extract is an extract of proanthocyanidins from grape seeds. More particularly, the proanthocyanidin extract comprises 18% -25% monomeric procyanidins, 18% -25% dimeric procyanidins, 15% -20% trimeric procyanidins, 35% -45% oligomeric procyanidins, and 1% -2% of phenolic acids. Proanthocyanidin extracts that meet these characteristics are commercially available (eg Vitaflavan®). As shown in the examples, individual use of this ingredient does not have a statistically significant effect on reducing leptin levels. However, advantageously, in combination with the rest of the ingredients of the composition of the invention, it provides an unexpected and statistically significant reduction in blood levels of this hormone which, in turn, is associated with a reduction in body weight, of adiposity and blood pressure index (see Tables 1-4).

Conjugated linoleic acid (CLA) is widely known to those skilled in the art and is commercially available (e.g. Tonalin®). As shown in the examples, individual use of this ingredient does not have a statistically significant effect on reducing leptin levels. However, advantageously, in combination with the rest of the ingredients of the composition of the invention, it provides an unexpected and statistically significant reduction in blood levels of this hormone which, in turn, is associated with a reduction in body weight, of adiposity and blood pressure index (see Tables 1-4).

In a particular embodiment according to any one of the previous embodiments, e1HPP comprises the peptides of sequence SEQ ID N ° 1 (QVGPLIGRYCG) and SEQ ID N ° 2 (AVFQHNCQE). In a particular embodiment, the HPP is obtained from chicken foot powder solubilized in water and heated at 100 ° C for 1.5 h at pH 7.5 and subsequently hydrolyzed with Protamex® at 50 ° C for 2 h at pH 7. In A preferred embodiment, e1HPP is the chicken leg hydrolyzate 1 described in patent application ES 2606954 A1. As shown in the examples, individual use of this ingredient does not have a statistically significant effect on reducing blood leptin levels (see Table 1).

In a particular embodiment according to any one of the preceding embodiments, the composition comprises 25mg-500mg, preferably 25mg-150mg, of the anthocyanin extract; or 10mg-250mg, preferably 10mg-100mg, of the proanthocyanidin extract; or 50mg-500mg, preferably 50mg-200mg, of conjugated linoleic acid; or 10mg-500mg, preferably 30mg-100mg, of the HPP. Preferably, the composition comprises 25mg-500mg of the anthocyanin extract; 10mg-250mg of the proanthocyanidin extract; 50mg-500mg Conjugated Linoleic Acid; and 10mg-500mg of the HPP. More preferably, the composition comprises 25mg-150mg, more preferably still 100mg, of the anthocyanin extract; 10mg-100mg, more preferably still 55mg, of the proanthocyanidin extract; 50mg-200mg, more preferably still 100mg, of conjugated linoleic acid; and 30mg-100mg, more preferably still 25mg, of the HPP. Advantageously, compositions with these amounts of the different components have proven to be effective in reducing blood leptin levels, in reducing body weight and adiposity index, and in reducing blood pressure. In addition, they have been shown to be effective in improving sensitivity to leptin.

In a particular embodiment according to any one of the previous embodiments, the composition does not comprise licorice polyphenols and / or caffeine and / or phytoncide.

The composition of the present invention can be incorporated into food products, food supplements, beverages and can be used in the manufacture of pharmaceutical products. Thus, in a second aspect, the invention relates to a medicine, a food supplement or supplement, a drink or a food product, preferably a functional food product, comprising the composition according to any one of the embodiments of the first aspect of the invention .

Food supplement or supplement refers to any food component that provides specific nutritional or medicinal components and does not provide the full energy value required (i.e., generally less than 2,000 or 2,500 kcal / day) and includes food supplements in powder or tablet form , as well as diet products, such as diet drinks. Ingredients that can be added to food before consumption or a preparation that can be consumed as such are also included.

For use in a medicine or food supplement, the composition of the invention, according to any one of the embodiments of the first aspect of the invention, can be combined with any carrier, diluent, adjuvant, excipient, etc. suitable, to obtain the drug or supplement in the desired administration form. That is, the medicament or food supplement comprises the composition according to any one of the embodiments of the first aspect of the invention and a pharmaceutically or physiologically acceptable carrier, diluent, adjuvant, excipient. Thus, they can be presented in any form of administration, solid or liquid, and administered by any appropriate route, oral, respiratory, rectal or topical. Advantageously, said composition, medicine or food supplement is administered orally. Examples of such formulations, which can be prepared using well known methods and excipients, such as those described in, "Remington's Pharmaceutical Sciences Handbook" Mack Pub. Co., NYUSA, are tablets, capsules, syrups and the like for oral administration, whereas suitable forms for parental administration are sterile solutions or suspensions in acceptable liquids, implants, etc. Preferred examples of excipients are microcrystalline cellulose, xanthan gum, magnesium stearate, silicon dioxide, and combinations thereof.

For use in a beverage or food product, the composition of the invention, or its components, according to the first aspect of the invention can be combined with any common food ingredient. The term "beverage" is intended to include liquids and syrups, as well as powdered formulations to be dissolved in water or another liquid component for the preparation of instant beverages.

The composition of the invention, or the medicines, food supplements, beverages or food products that comprise it, serve to, among others, reduce body weight and blood pressure, thus treating obesity, overweight and hypertension. Thus, in a third aspect, the present invention relates to a composition according to any one of the embodiments of the first aspect of the invention, for use in medicine or therapy. Likewise, it refers to the use of a composition according to any one of the embodiments of the first aspect of the invention, for the preparation of a medicament.

Likewise, in a fourth aspect, the present invention relates to the use of a composition according to any one of the embodiments of the first aspect of the invention, for the preparation of a medicine, a food supplement, a beverage or a food product for the treatment obesity, overweight and / or hypertension.

The fourth aspect of the invention also relates to a composition according to any one of the embodiments of the first aspect of the invention, for use in the treatment of obesity, overweight and / or hypertension.

The definition given by the World Health Organization (WHO) for obesity, overweight and hypertension is applicable in the present invention. Currently, the WHO defines overweight as a body mass index (BMI) equal to or greater than 25, while it defines obesity as a BMI equal to or greater than 30. Similarly, it defines hypertension as values equal to or greater than 130 mmHg of systolic and / or equal to or greater than 80 mmHg diastolic.

Furthermore, the fourth aspect of the invention relates to a method of treating obesity, overweight and / or hypertension in a subject (mammal, preferably human), comprising the administration, preferably of a therapeutically effective amount, to said subject of a composition according to any one of the embodiments of the first aspect of the invention or of a medicine, food supplement, beverage or food product according to the second aspect of the invention. In a preferred embodiment, the administration is carried out orally.

In a particular embodiment according to any one of the three preceding paragraphs of the fourth aspect of the present invention, the treatment is the treatment of obesity or overweight. In another particular embodiment according to any one of the three preceding paragraphs of the fourth aspect of the present invention, the treatment is the treatment of hypertension.

The composition of the present invention can be combined with other treatments for these pathologies. Thus, in a fifth aspect, the invention relates to a composition according to any one of the embodiments of the first aspect of the invention, for use as an adjuvant in the treatment of obesity, overweight and / or hypertension.

Similarly, the fifth aspect refers to a method of treating obesity, overweight and / or hypertension in which the composition of the invention is administered as an adjuvant to a subject. It also relates to the use of the composition of the invention to prepare an adjunct for the treatment of obesity, overweight and / or hypertension.

Regarding any of the embodiments of the fourth and fifth aspects of the invention, the dosage will depend on various factors such as weight of the subject, sex, type and severity of the conditions to be treated, etc. Preferably, the composition of the invention is administered at a dose such that the dose of each of its components is 25 mg per day and per kg of the subject to which they are administered (mg / kg / day) to 500 mg. / kg / day of anthocyanin extract; 10 mg / kg / day to 250 mg / kg / day of the proanthocyanidin extract; from 50 mg / kg / day to 500 mg / kg / day of conjugated linoleic acid; and from 10 mg / kg / day to 500 mg / kg / day of the HPP. More preferably, the composition is administered such that the dose is from 25 mg / kg / day to 150 mg / kg / day, more preferably still 100 mg / kg / day, of the anthocyanin extract; from 10 mg / kg / day to 100 mg / kg / day, more preferably still 55 mg / kg / day, of the proanthocyanidin extract; from 50 mg / kg / day to 200 mg / kg / day, more preferably still 100 mg / kg / day, of conjugated linoleic acid; and from 30 mg / kg / day to 100 mg / kg / day, more preferably still 25 mg / kg / day, of the HPP.

Advantageously, as has been demonstrated in the examples, the administration of these doses has proven to be effective in reducing leptin levels in the blood and in improving leptin sensitivity, resulting in a reduction in body weight and blood pressure index. adiposity, and a reduction in blood pressure.

EXAMPLES

With the intention of illustrating the present invention, although in no way limiting, the following examples are provided:

EXAMPLE 1

Effect of the composition of the present invention (MIX) on blood leptin levels and leptin sensitivity.

1.1.- Leptin levels

To evaluate the effect of the composition of the invention and of each of its ingredients separately on leptin levels, male Wistar rats were fed for 12 weeks with a cafeteria diet (CAF) composed of 35% fat and 51% carbohydrates. From the ninth week of the cafeteria diet, the animals were distributed into different groups, with a minimum of 6 animals in each group, specifically administered a daily oral dose of MIX, or of each of its ingredients. separately. Specifically, proanthocyanidin extract (PRO, commercial product Vitaflavan®) was administered at a dose of 25 mg / kg / day, chicken leg hydrolyzate (HPP, chicken leg hydrolyzate 1 described in Spanish patent application ES 2606954 A1) at a dose of 55 mg / kg / day, conjugated linoleic acid (CLA, commercial product Tonalin®) at a dose of 100 mg / kg / day, or anthocyanin extract (ANT, commercial product MEDOX®) at a dose 100 mg / kg / day along with the cafeteria diet for 3 weeks. The MIX comprises PRO, HPP, CLA and ANT and a daily oral dose was administered providing 25 mg / kg / day of PRO, 55 mg / kg / day of HPP, 100 mg / kg / day of CLA and 100 mg / kg / day of ANT. Unless otherwise indicated, all the doses indicated in these examples are given in relation to the body weight of the animal.

Leptin blood concentrations were measured in triplicate in animal plasma samples using ELISA kits from Millipore (Madrid, Spain). Plasma was obtained by centrifugation (1,500 x g for 15 min at 4 ° C) of peripheral blood at the end of the experimental period (week 12) and was stored at -80 ° C until the moment of use. In addition, to evaluate the activation of anorectic neurons, producing appetite-inhibiting peptides, the hypothalamus of the animals was excised and immediately stored in liquid nitrogen until evaluation (see below).

The composition of the present invention (MIX) showed a statistically significant reduction in plasma leptin levels after daily administration for 3 weeks ( Table 1 ). Specifically, the composition of the present invention reduced more than 32% the level of leptin in the blood. Likewise, the plasma concentrations of leptin after the administration of the components of the composition separately at the same concentrations in which they are found in the MIX, were only timidly reduced in a statistically non-significant way in the animals that took PRO, ALC or ANT, being in the three cases, a much lower percentage than that observed with the MIX. Furthermore, the administration of HPP produced an increase in leptin levels.

In Table 1 the data represent the mean ± SEM of the percentage reduction with respect to the control of leptin levels in blood of the animals treated for 3 weeks with the MIX or with each of its ingredients separately.

Table 1 .- Percentage reduction in blood leptin levels.

* indicates p <0.05

Surprisingly, the composition has a synergistic effect in lowering leptin levels in the blood. The results in Table 1 show that the ingredients are only capable of reducing leptin levels in the blood in a statistically significant way when they are combined in a single mixture (composition of the invention), and not when they are administered individually. Therefore, these results indicate that the composition of the invention may have a key role in the regulation of leptin signaling, and consequently, it may have a very beneficial effect in the control of body weight and / or in the regulation of other pathologies related to obesity and leptin levels such as high blood pressure.

1.2.- Sensitivity to leptin

In the control animals and in those animals to which the MIX had been administered during the 3 weeks, the sensitivity to leptin at the hypothalamic level was also determined. To do this, an immunofluorescence analysis was performed in the hypothalamus with a monoclonal antibody specific for anorectic neurons, producing appetite-inhibiting peptides (ACTH neurons, in red in Figure 1), and with a second specific monoclonal antibody to assess whether the Leptin signaling pathway is activated in ACTH neurons (phosphorylated anti-STAT3 antibody, or pSTAT3, in green in Figure 1).

The results showed a very significant increase in the number of anorectic neurons (positive for the anti-ACTH antibody) that showed the active leptin signaling pathway (neurons positive for the anti-STAT3p antibody) in the animals treated with the composition of the present invention (MIX) with respect to control animals ( Figure 1 ). Thus, the ability of the composition of the present invention to regain sensitivity to leptin at the hypothalamic level, and consequently, to activate the neuronal cells responsible for regulating body weight is demonstrated. This is a great advantage of the composition of the present invention since by influencing anorectic neurons it can regulate weight gain / loss, thus providing an effective body weight control system, which translates into a useful composition for the patient. Treatment of obesity and overweight.

EXAMPLE 2

Effect of the composition of the present invention (MIX) on body weight and adiposity

2.1.- Body weight

To evaluate the effect of MIX on the weight gain of the animals, the same test as in Example 1 was carried out and the weight was monitored weekly until the end of the experimental period (ie until the end of the 3 weeks of treatment). As can be seen in Figure 2 , the results show how the animals treated with the composition of the invention (MIX) present a statistically significant reduction (greater than 7%) in the body weight gain induced by the cafeteria diet. Interestingly, this reduction is observed from the second week of treatment (week 11 and 12 of the experiment) despite the fact that the animals continue to consume the cafeteria diet, which is obesogenic, on a daily basis. These results perfectly correlate both with the increased sensitivity to leptin in hypothalamic cells and with the reduction in blood leptin levels shown in Example 1.

Likewise, when the body weight of the animals was evaluated at week 12 of the experiment, none of the components of the composition of the invention separately presented a significant reduction in body weight as observed in the animals that took the MIX ( Table 2 ).

In Table 2 the data represent the mean ± SEM of the percentage reduction with respect to the body weight control in week 12 of the animal experiment to the control of leptin levels in blood of the animals treated for 3 weeks with the MIX or with each of its ingredients separately.

Table 2 .- Percentage of body weight reduction at the end of the experiment (12 weeks).

* indicates p <0.05

As can be seen from Table 2, there is a synergy in the composition of the present invention in reducing body weight. In fact, three of the four ingredients of the composition cause an increase in body weight, and despite this, the composition of the invention achieves a significant reduction in body weight of more than 7%. Again, it is again shown that the ingredients of the composition have solely and exclusively an effect in reducing body weight when they are administered simultaneously in combination in a single composition, and not when they are administered individually. a

2.1.- Adiposity index

In these same animals, the effect of MIX and its ingredients separately on the adiposity index, that is, the percentage of total body mass that is composed of fat, was also evaluated. This index is an indicator of obesity widely used in animal studies and is calculated as the total sum of the weights of the different adipose tissues of each animal expressed as a percentage with respect to the total body weight of the animal.

The results are shown in Table 3, in which the mean ± SEM of the percentage of reduction with respect to their control of the adiposity index is represented in week 12 of the experiment of animals treated with the MIX or with each of its ingredients by separated.

Table 3.- Percentage of reduction of the adiposity index.

* indicates p <0.05

As seen in Table 3, the results clearly show how the administration of MIX for 3 weeks produces a very evident reduction in the adiposity index (greater than 13%) in the animals that took the MIX. Likewise, this beneficial effect was not observed in any of the ingredients administered individually, again indicating the ability of the ingredients of MIX to reduce the weight and body fat of animals found in an obesogenic environment, solely and exclusively when they are administered in a single mixture and dose, and not when administered individually.

Example 3: Effect of the composition of the present invention (MIX) on blood pressure.

3.1. - Blood pressure with obesity

To evaluate the antihypertensive effect of MIX, blood pressure (systolic and diastolic) was manually monitored once a week until the end of the experimental period. The experimental design was the same as in Example 1.

Figure 3 shows the antihypertensive effect of MIX after its chronic administration for 3 weeks. As can be seen, MIX reduces the systolic blood pressure of the animals from the first week of administration, and tends to continue to lower it even more as the weeks of treatment pass, despite the fact that the animals continue to consume the cafeteria diet daily. , which in control animals continues to raise blood pressure.

3.2. - Blood pressure without obesity

Additionally, to corroborate these antihypertensive effects, another study was carried out in spontaneously hypertensive rats (SHR) in which the different ingredients of MIX were tested separately and MIX in acute administration (a single dose) and the antihypertensive effect was evaluated at different hours post-administration ( Table 4 ). MIX was the only treatment that produced a significant reduction in systolic blood pressure at 2 h after its administration and it maintained this reduction until 8 h after its administration. None of the MIX ingredients separately showed this antihypertensive effect at 2h post-administration.

The results are shown in Table 4, in which the mean ± SEM of the percentage of reduction with respect to its control of the systolic blood pressure determined in SHR rats is represented after the acute administration of MIX or of each of its ingredients by separated.

Table 4.- Percentage reduction in systolic blood pressure 2h after treatment.

* indicates p <0.05

Thus, in this test it is seen that the composition of the present invention reduces blood pressure both in obese animals (Figure 3) and in non-obese animals (Table 4, hypertensive rats). This is a great advantage since thus, the composition of the present invention serves both for the treatment of hypertension associated with obesity and hypertension not associated with obesity. Furthermore, another advantage of the composition of the present invention is that it does not reduce blood pressure in normotensive animals (data not shown).

Claims (17)

1. - Composition characterized in that it comprises: a) an extract of anthocyanins; b) a proanthocyanidin extract; c) conjugated linoleic acid; Y d) a chicken leg hydrolyzate (HPP), comprising the peptides of sequence SEQ ID N ° 1 (QVGPLIGRYCG) and / or SEQ ID N ° 2 (AVFQHNCQE). 2. - Composition according to claim 1, wherein the anthocyanin extract comprises anthocyanins from black currants ( Ribes nigrum L.) and / or blueberries ( Vaccinium myrtillus). 3. - Composition according to claim 1 or 2, wherein the anthocyanin extract comprises at least 25% of cyanidin 3-O-glucoside and at least 50% of delphinidin 3-O-glucoside. 4. - Composition according to any one of claims 1 to 3, wherein the proanthocyanidin extract is a proanthocyanidin extract from grape seeds. 5. - Composition according to any one of claims 1 to 4, wherein the proanthocyanidin extract comprises 18% -25% of monomeric procyanidins, 18% -25% of dimeric procyanidins, 15% -20% of trimeric procyanidins, 35% - 45% oligomeric procyanidins, and 1% -2% phenolic acids. 6. - Composition according to any one of claims 1-5, wherein the composition comprises 25 mg-500 mg of anthocyanin extract. 7. - Composition according to any one of claims 1-6, wherein the composition comprises 10 mg-250 mg of the proanthocyanidin extract. 8. - Composition according to any one of claims 1-7, wherein the composition comprises 50 mg-500 mg of conjugated linoleic acid. 9. - Composition according to any one of claims 1-8, wherein the composition comprises 10 mg-500 mg of HPP. 10. - Composition according to any one of claims 1-9, wherein the composition comprises 25 mg-500 mg of anthocyanin extract; 10mg-250mg of the proanthocyanidin extract; 50mg-500mg Conjugated Linoleic Acid; and 10mg-500mg of 1HPP. 11. - Composition according to the preceding claim, wherein the composition comprises 25 mg-150 mg of anthocyanin extract; 10mg-100mg of the proanthocyanidin extract; 50mg-200mg Conjugated Linoleic Acid; and 30mg-100mg of the HPP. 12. - Medicine, food supplement, drink or food product characterized in that it comprises a composition according to any one of claims 1-11. 13. - Composition according to any one of claims 1-11 for use in medicine. 14. - Composition according to any one of claims 1-11, for use in the treatment of obesity, overweight and / or hypertension. 15. - Composition according to any one of claims 1-11, for use as an adjunct in the treatment of obesity, overweight and / or hypertension. 16. Composition for use according to claim 14 or 15, where the use is in the treatment of obesity or overweight. 17. - Composition for use according to claim 14 or 15, where the use is in the treatment of hypertension.