TECHNICAL FIELD

The invention concerns a health food supplement or pharmaceutical composition for the improvement of speed and endurance capacity.

BACKGROUND OF THE INVENTION

Maintaining one's muscles in a healthy state is critical for physical performance, and overall wellbeing. Physical activity has been promoted as an important aspect of a healthy lifestyle. This situation leads to what is referred to as 'locomotive syndrome'. Prolonged muscle disuse can lead to loss of muscle tissue and reduced muscle strength. Muscle disuse can be due to immobilization, injury, disease, bed rest, hospitalization, weightlessness, and the like. The loss of muscle tissue and muscle strength is generally exacerbated by aging. This loss of muscle tissue and muscle strength may impair a subject's mobility, which discourages physical activity and leads to even further loss of muscle tissue. Exercise may not always be feasible, especially if the subject is elderly with significant degenerative conditions, recovering from serious illness, or has been immobilized for an extended period of time. Therefore, nutritional interventions that can prevent or slow the loss of muscle strength before, during and after the period of muscle disuse can be highly desirable.

There are a number of commercially available nutritional supplements advertised for promoting muscle growth or for increasing running speed. For example, administration of litchi fruit extracts and green tea extracts were studied for their effects during exercise and positive effects on exercise performance and recovery have been reported. Many products aim at restoring glycogen levels and improving muscle anabolism by developing product formulations containing carbohydrates and proteins. Thus, there remains a need for identifying novel compounds with ergogenic effects, preferably food grade and from natural origin, to improve exercise performance, locomotive syndrome and recovery.

SUMMARY OF THE INVENTION

The present invention provides a health food supplement and a pharmaceutical composition for the improvement of speed and/or for stimulating muscle strength and/or improving endurance capacity comprising as active ingredient an extract of Allium species, an extract of Citrus species and an extract of Paullinia species and an extract of Theobroma species.

The invention, in one aspect is a method for the improvement of speed and endurance capacity comprising the administration of a health food supplement comprising as active ingredient an extract of Allium species, an extract of Citrus species and an extract of Paullinia species and an extract of Theobroma species.

In another aspect, the invention consists in a health food supplement and/or a composition, in particular a pharmaceutical composition, comprising as active ingredient an extract of Allium species, an extract of Citrus species and an extract of Paullinia species and an extract of Theobroma species for use in the treatment and/or prevention of frailty conditions in sick or elderly patients.

BRIEF DESCRIPTION OF THE DRAWINGS

Fig. 1 shows the effects of the composition administration on speed.

DETAILED DESCRIPTION OF THE INVENTION The terms " administration", "administering" or "being administered" as used herein, unless otherwise specified, should be understood to comprise at least one of: a) providing the composition to a subject; and b) the act of consuming the pharmaceutical composition or the health food supplement. Unless otherwise indicated, the composition is administered to the subject orally or enterally.

The term "muscle disuse" as used herein, unless otherwise specified, refers to a substantial lack of activity of a particular muscle, muscle type, or muscle group due to partial or full immobilization, injury, illness, bed rest, ageing, hospitalization, weightlessness, and the like.

The term "muscle recovery" as used herein, unless otherwise specified, refers to use of a particular muscle, muscle type, or muscle group, after a period of muscle disuse. Muscle recovery may include gentle stretching, contraction, and movement of the muscles and structured rehabilitation after the muscles have been inactive. Muscle recovery may, but does not necessarily, include strenuous exercise, including weight- bearing, resistance, walking (gait speed) and cardiovascular exercise, to quickly rebuild and increase muscle mass and muscle strength.

The term "health food supplement" as used herein, unless otherwise specified, refers to products in various forms including, but not limited to, liquids, solids, powders, semi-solids, semi-liquids, nutritional supplements, and any other food product known in the art.

The term "period of muscle disuse" refers to the interval of time that the muscle or muscles are substantially inactive. For the purpose of this disclosure, a period of muscle disuse is at least 4 hours of substantially continuous muscle inactivity. However, it should be understood that occasional short intervals of mild muscle use, such as sitting up in bed or walking only a short distance (less than 100 meters), may be included within a period of muscle disuse. This period may be about 4 hours, about 8 hours, about 12 hours, about 24 hours, about 48 hours, about 72 hours, about one week, about two weeks, about one month, about two months, about three months, about six months, about nine months, about twelve months, or longer than twelve months in duration.

The term "subject" as used herein, unless otherwise specified, refers to a mamal, including but not limited to, a human, a domesticated farm animal (e.g., cow, horse, pig, or chicken), or a pet (e.g., dog or cat). In certain preferred embodiments, the subject is a human.

The terms 'performance' and 'exercise performance' refers to movements of a subjects that can be maintained for the duration of an exercise to achieve a desired result of strength, speed and endurance.

In particular, the present invention provides a health food supplement or a pharmaceutical composition for improvement of speed and/or for stimulating muscle strength and/or improving endurance capacity comprising as active ingredient an extract of Allium species, an extract of Citrus species and an extract of Paullinia species and an extract of Theobroma species. The active ingredients are administered in effective doses. The term "effective dose" is well understood in the art. In pharmacology, effective dose is the median dose that produces the desired effect of a drug. The effective dose is often determined based on analyzing the dose-response relationship specific to the drug.

According to the invention the health food supplement or pharmaceutical composition comprises from 30% to 80% by weight of an extract of Allium species, from 1 .5% to 25% by weight of an extract of Citrus species, from 0.05% to 5.0% by weight of an extract (atomized or not) of Paullinia species and from 0.05% to 5.0% by weight of an extract (atomized or not) of Theobroma species, based on the total weight of the four active ingredients.

According to a specific embodiment, the health food supplement or pharmaceutical composition comprises from 30% to 80% by weight of an extract of Allium species, from 1 .5% to 25% by weight of an extract of Citrus species, from 0.05% to 5.0% by weight of an extract (atomized or not) of Paullinia species, from 0.05% to 5.0% by weight of an extract (atomized or not) of Theobroma species, from 1 .0% to 8.0% by weight of sodium chloride and from 15% to 50% by weight of an excipient, additive, adjuvant and the like based on the total weight of the composition. Excipient, additives, adjuvants and the like for use in such compositions are known to the skilled person and do not require elucidation here.

The invention, in one aspect consists of a method for stimulating the muscle strength and/or for improving the speed comprising the administration of a pharmaceutical composition or a health food supplement comprising as active ingredient an extract of Allium species, an extract of Citrus species and an extract of Paullinia species and an extract of Theobroma species.

In some embodiments, the supplement or composition is orally administered to the subject in a liquid solid or liquid carrier.

In certain embodiments, the administrated composition or supplement contains from 30% to 80% by weight of an extract of Allium species, from 1 .5% to 25% by weight of an extract of Citrus species, from 0.05% to 5.0% by weight of an extract (atomized or not) of Paullinia species and from 0.05% to 5.0% by weight of an extract (atomized or not) of Theobroma species, based on the total weight of the four active ingredients. The composition or the supplement is administered daily or weekly for a period of at least one month, preferably several months or beyond (long-term use). The composition or the supplement is used after a period of muscle disuse or in a situation that requires a booster treatment to increase muscle strength and tone.

In another aspect, the invention consists in a composition comprising as active ingredient an extract of Allium species, an extract of Citrus species and an extract of Paullinia species and an extract of Theobroma species for use in the treatment and/or the prevention of frailty conditions in a sick or an elderly patient.

In yet another aspect, the present invention consists in a method of treating and/or preventing frailty conditions comprising administering to the subject an effective amount of a composition comprising from 30% to 80% by weight of an extract of Allium species, from 1 .5% to 25% by weight of an extract of Citrus species, from 0.05% to 5.0% by weight of an extract (atomized or not) of Paullinia species and from 0.05% to 5.0% by weight of an extract (atomized or not) of Theobroma species, based on the total weight of the four active ingredients.

Frailty is a clinical syndrome with symptoms as low body weight due to unintentional weight loss, exhaustion, weakness, slow walking and low physical activity. Frailty is characterized by a decreased reserve and resistance to stressors, in turn resulting from cumulative decline across multiple physiologic systems, and causing a vulnerability to adverse outcomes. A major aspect of frailty is that it affects muscle mass and strength. Some clinical investigation has been done on the effect of various treatments on individual frailty symptoms. This includes, e.g., the effect of anabolic steroids on muscle mass, which is well known to the skilled person.

In the treatment of frailty, the supplement or composition according to the present invention will generally be administered daily or weekly for a period of at least one month, preferably for several months, generally at least 3 months to 12 months, preferably for 4 to 8 months, and most preferably for 6 months, or for long-term use.

According to another embodiment the supplement or composition according to the invention can also be used for the prevention of frailty in patients that are prone to become frail, in particular after an hospitalization.

According to the present invention, the supplement or composition comprising an extract of Allium species, an extract of Citrus species, an extract of Paullinia species and an extract of Theobroma species is prepared as indicated in patent application WO2008/1 13912. It involves the preparation of a master solution containing the extracts of Allium species and Citrus species and then mixing this solution either with an extract of Paullinia species and an extract of Theobroma species.

According to the preferred conditions for carrying out this process, the method is characterized in that the master solution is prepared by picking, cleaning and milling the Allium and the Citrus, macerating for several hours in alcohol and filtering, then adjusting the alcoholic extract and mixing with the other ingredients. In using this method of preparation for the compositions according to this application, a recommended procedure is to prepare the master solution from the constituents, by picking, cleaning and milling the Allium and the Citrus, mixing with 96° alcohol, macerating in the cold for 60 hours, filtering the master solution through 0.22-micron filters to give a water-alcohol extract with a low content of particles. The ethanol is then evaporated, glycerin and preservatives are added. This master solution is then treated, by simple mixing, either with the extracts (atomised or not) of Paullinia species and Theobroma species.

The health food supplement or pharmaceutical composition of the present invention is formulated into a suitable composition and then, in accordance with the methods disclosed herein, administered to a subject in a form adapted to the chosen route of administration. In certain embodiments, the compositions disclosed herein include, but are not limited to, those suitable for oral administration. For example, oral administration typically refers to oral consumption, but may also include other forms of enteral administration (i.e., administration through the digestive track). Other forms of enteral administration suitable for use with the methods disclosed herein include nasogastric, gastric, or jejunal intubation.

In certain embodiments, the health food supplement or composition disclosed herein are formulated as medicaments. In certain embodiments, suitable forms of the composition as a medicament include caplets, tablets, pills, capsules, chewable tablets, quick dissolve tablets, effervescent tablets, solutions, suspensions, emulsions, multi-layer tablets, bi- layer tablets, soft gelatin capsules, hard gelatin capsules, lozenges, chewable lozenges, beads, granules, particles (including particles enabling sustained release), microparticles, sachets, and combinations thereof. In one exemplary embodiment, the composition may be in the form of a powder or liquid concentrate packaged in a sachet, the contents of which may be added to water or other potable liquid to form a beverage.

In certain embodiments, the health food supplement or composition according to the invention is formulated as a nutritional composition.

In certain embodiments, the compositions disclosed herein may comprise one or more compounds selected from human milk, prebiotics, probiotics and combinations thereof.

The most preferred compositions used according to the invention are those containing approximately 66% by weight of an extract of Allium cepa, approximately 9% by weight of an extract of Citrus lemon, approximately 0.1 1 % by weight of an extract (atomized or not) of Paullinia cupana and approximately 0.1 1 % by weight of an extract (atomized or not) of Theobroma cacao, based on the total weight of the four active ingredients.

The health food supplement or composition is administered in particular orally in accordance with the present disclosure to a subject as needed to preserve muscle strength during a period of muscle disuse or muscle recovery. The compositions may be administered to a subject solely during the period of muscle disuse or solely during the period of muscle recovery. However, to preserve muscle strength more fully, it is generally desirable to administer the present supplement or composition to the subject before, during the period of muscle disuse and the period of muscle recovery.

The subject may also be a child or an adult who is susceptible to loss of muscle strength due to muscle disuse resulting from a portion of the subject's body being immobilized. The subject may be a child or an adult who is susceptible to loss of muscle strength due to muscle disuse as a result of a severe illness. The subject may be a child or an adult who is susceptible to loss of muscle strength due to muscle disuse that occurs while recovering from surgery. The subject may be a child or an adult who is susceptible to loss of muscle strength due to muscle disuse that occurs during hospitalization. The subject may be a child, a pregnant woman, or an adult who is susceptible to loss of muscle strength due to muscle disuse that occurs during prolonged bed rest. The subject may be an adult or older adult who is susceptible loss of muscle strength due to muscle disuse resulting from prolonged inactivity. The subject may be an elderly, having an age of 60 or older. The subject may be a child or an adult who is interested in preventing loss of muscle strength. The subject may also be interested to stimulate its muscle strength or to increase its running speed. In certain embodiments, the compositions can be administered to subjects during periods of muscle disuse. In certain embodiments, the compositions disclosed herein are administered to the subject when the period of muscle disuse lasts at least 4 hours. In certain embodiments, the compositions are administered to the subject when the period of muscle disuse lasts from about 4 hours to about 72 hours, including from about 4 hours to about 48 hours, including from about 4 hours to about 24 hours, including from about 4 hours to about 12 hours, including from about 8 hours to about 72 hours, including from about 8 hours to about 48 hours, including from about 8 hours to about 24 hours, including from about 12 hours to about 72 hours, including from about 12 hours to 48 hours, and including from about 12 hours to about 24 hours. In other embodiments, the compositions are administered to the subject when the period of muscle disuse lasts from about 24 hours to about 36 months, including from about 24 hours to about 24 months, including from about 24 hours to about 12 months, including from about 24 hours to about 6 months, including from about 24 hours to about 3 months, including from about 24 hours to about 2 months, including from about 24 hours to about 1 month, including from about 24 hours to about 2 weeks, including from about 24 hours to about 1 week, including from about 48 hours to about 36 months, including from about 48 hours to about 24 months, including from about 48 hours to about 12 months, including from about 48 hours to about 6 months, including from about 48 hours to about 3 months, including from about 48 hours to about 2 months, including from about 48 hours to about 1 month, including from about 48 hours to about 2 weeks, including from about 48 hours to about 1 week, including from about 72 hours to about 12 months, including from about 72 hours to about 6 months, including about 72 hours to about 3 months, including from about 72 hours to about 1 month, including from about 72 hours to 2 weeks, including from about 72 hours to about 1 week, including from about 1 week to about 12 months, including about 1 week to about 6 months, including from about 1 week to about 3 months, including from about 1 week to about 1 month, including from about 2 weeks to about 12 months, including from about 3 weeks to about 12 months, including from about 4 weeks to about 12 months, including about 6 weeks to 12 months, including from about 2 months to about 12 months, including from about 3 months to about 36 months, including from about 3 months to about 24 months, and including from about 3 months to about 12 months. In accordance with the preceding and other embodiments, the compositions disclosed herein can be administered to a subject for a period of muscle disuse lasting at least 4 hours, at least 8 hours, at least 12 hours, at least 24 hours, at least 48 hours, at least 72 hours, at least 1 week, at least 10 days, at least 2 weeks, at least 1 month, at least 3 months, at least 6 months, at least 12 months, at least 24 months, at least 36 months, or for more than 36 months.

In certain embodiments, the compositions can be administered to subjects during periods of muscle disuse. Alternatively the compositions can be administered to subjects to improve their muscle strength.

In order to obtain a significant measurable effect on the improvement of speed or endurance and on the stimulation of muscle strength, it is necessary to perform the administration of the supplement or composition chronically. When using the supplement or composition according to the invention, doses may vary within relatively wide limits and must be set according to the subject being treated (for a treatment or for a prevention) and the condition concerned. The supplement or composition according to the invention may normally contain from 0.4 to 1000 mg, preferably from 2 to 400 mg, of active ingredients as defined above. In terms of daily dosage for each of the four active ingredient contained in the supplement or composition according to the invention, especially when the administration is made in liquid form, the respective amounts are preferably:

from 1 mg to 40 g of an extract of Allium species,

from 0.075 mg to 12.5 g of an extract of Citrus species,

from 0.0025 mg to 2.5 g of an extract (atomized or not) of Paullinia species from 0.0025 mg to 2.5 g of an extract (atomized or not) of Theobroma species.

The following example illustrates specific embodiments and/or features disclosed herein. The example is provided solely for the purposes of illustration and should not be construed as limitations of the present disclosure. Numerous variations over this specific example are possible without departing from the spirit and scope of the general inventive concept.

EXAMPLE OF TREATMENT

Mice have received, by oral route, a treatment containing:

- an extract of Allium cepa (containing querceting): 65.84 % (by weight)

- an extract of Citrus lemon: 9.06 %

- an atomised extract of Paullinia cupana: 0.1 1 %

- an atomised extract of Theobroma cacao: 0.13 %

(hereafter composition A).

This solution has been prepared as indicated in example 1 of patent application WO 2008/1 13912.

Protocol schedule

10 mice, split in 2 groups: 5 taking the composition A and 5 taking the placebo Day 0-7: acclimatization

Day 7-13: running measurement

Mice received ad libitum access to water and chow.

Mice drunk 1 ml/day of either composition A or Placebo.

Figure 1 represents the Mean Dark Cycle Activity (evaluation of speed).

Mean running speeds (meters/minute, n=10) were lower for the placebo group mice compared with the composition group mice (higher speed) during each 4 hour-increments of the dark (active) cycle. This is demonstrative of the improvement provided by the administration of the composition.