FR2687291A1 - Food for athletes and method for preparing it - Google Patents

Abstract

When muscles are worked, stocks of alkaline substances (essentially sodium bicarbonate) naturally contained in the blood make it possible, up to a certain limit, to maintain the acid/base equilibrium. In order to increase these stocks and thus limit their reduction in competitive sport as well as to promote their subsequent reconstitution, the teaching of the present invention relates to a food for an athlete containing an alkaline substance, essentially sodium bicarbonate, in a form adapted to a delayed and prolonged release of the alkaline substance into the blood of the athlete. Typically, this form includes: - a grain (pellet) manufactured from a powder of the alkaline substance, on which the precoating is applied, - a precoating of the alkaline substance with an insulating product such as Pharmacoat 606, - and a coating of the alkaline substance with a gastroresistant product such as Eudragit L100. The invention also relates to a method for manufacturing such a food.

Description

 The present invention relates to a sports food and its manufacturing process.

 The human organism naturally contains so-called buffer stocks, made up of alkaline substances which have the role of ensuring the acid-base balance of the blood. These substances are mainly sodium bicarbonate. They are present in the blood and are used to neutralize the lactic acidosis which appears during muscular effort.

 In the case of the sportsman, the test can lead the organism to a degree of acidosis inducing the almost total exhaustion of the stocks of buffer. This acidosis occurs in fact in any continuous or discontinuous exercise, comprising phases whose intensity exceeds 60% of the subject's maximum aerobic power. It therefore seems interesting to provide the sportsman's body with sodium bicarbonate to increase his buffer stocks, but also to limit the decrease and encourage their reconstitution after the event.

 A problem is therefore to find a way to administer an alkaline substance and more specifically sodium bicarbonate to an athlete so that the substance in question is released at the appropriate time in the blood of the athlete.

 A solution according to the invention consists of a sports food containing an alkaline substance, essentially sodium bicarbonate, in a form suitable for a delayed and prolonged release of the active substance in question in the blood of the sportsman. In fact, the law authorizes the addition of sodium bicarbonate to food intended for a particular destination, without specifying the maximum authorized concentration.

 However, an athlete usually eats about two to three hours before the event so as to have completed the gastric phase of digestion when providing effort.

The absorption of the food according to the invention allows it to benefit at the same time from the additional supply of sodium bicarbonate but also from slow carbohydrates which intervene in the support of blood sugar during exercise. Another problem is then to find the form suitable for a delayed and prolonged release of the active substance.

 One solution according to the invention consists in using preparations of drugs with a delayed effect. Among these, there is preferably a coating of the active substance with a gastro-resistant product. This type of product is insoluble in acids or in water. Thus it can protect the active substance against the attack of acidic gastric juices. On the contrary, it is soluble in alkalis, which authorizes a release of the active substance in the intestines, and from there its passage into the blood.

The Eudragit L 100 (marketing name) is suitable from this point of view.

 This particular form of the food according to the invention also has another advantage.

It prevents a neutralization of bicarbonate by gastric juice as well as its direct contact with the stomach mucosa, which is known to be the cause of chronic gastritis in case of repeated intakes.

 However, the properties required for an enteric product make it impossible for it to come into direct contact with the envisaged alkaline substance. The alkalinity of the latter would in fact soon dissolve the gastro-resistant product. Another problem is therefore to be able to coat the sodium bicarbonate with Eudragit L 100 in particular.

 One solution according to the invention consists in providing a pre-coating of the alkaline substance suitable for isolating the latter from the enteric coating. This pre-coating is advantageously carried out using a film-forming alcoholic solution based on hydroxypropyl methyl cellulose such as Pharmacoat 606 (marketing name). One can also think of a pyrrolidone-based solution such as Sepifilm SN (ND) (market name). It is especially applied to grains containing sodium bicarbonate in powder form.

 In many sports such as cycling, running, cross-country skiing, the sum of the duration of the tests and the normal duration of recovery, in particular acid-base, necessary for total compensation and a return to The initial physiological state is 4 to 8 hours. Another problem, finally, is to adapt the quantities of alkaline substance, of pre-coating product and of gastro-resistant product in order to achieve an alkalinization duration of this order of magnitude.

 A solution according to the invention consists in providing for 1 kg of grains based on sodium bicarbonate, 750 ml of Pharmacoat 606 and from 1350 to 1500 ml of Eudragit L 100.

 A process for obtaining such a preparation is also part of the present invention. As shown in its description below, however, it confines itself to using conventional methods in the preparation of delayed medicaments.

The invention will be better understood on reading the detailed description which follows and on examining the appended drawings which represent, by way of nonlimiting examples, experimental kinetic curves. In the drawings:
- Figures 1 and 2 show the evolution of the pH of whole venous blood obtained
in two different subjects following the intake of a food according to the invention at a
first date,
- Figures 3 and 4 show the same evolution as the previous figures, but
following the intake of the food according to the invention on a second date,
- Figures 5 and 6 show the evolution of the partial pressure of carbon dioxide
in the blood of two subjects following the intake of the food according to the invention at the
first date,
- Figures 7 and 8 show the same evolution as the previous figures, but
following the intake of the food according to the invention on the second date,
- Figures 9 and 10 show the evolution of the excess excess in the blood obtained
in two different subjects after taking the food according to the invention at the
first date,
- Figures 11 and 12 show the same evolution as the previous figures,
but after taking the food according to the invention on the second date,
- Figures 13 and 14 as well as Figures 15 and 16 show the evolution of the
total amount of carbon dioxide that can be obtained from
bicarbonates, carbonates and carbon dioxide dissolved in the blood of
two different subjects following the intake of the food according to the invention at the first
date, however this quantity is calculated using Henderson's equation
Hasselbalch in Figures 9 and 10 while measured in Figures 13
and 14,
- Figures 17 and 18 as well as Figures 19 and 20 show the same
changes than the previous figures, but following the intake of the food according to
the invention on the second date.

 Rather than describing the structure of an example food according to the present invention, the following paragraphs give an advantageous manufacturing process. It is indeed more convenient to thus define this structure which, although remaining the essential object of the invention, is in truth relatively unknown in its detail due in particular to the interactions between the different substances when they are brought into contact .

This is how we start by making grains from sodium bicarbonate powder. For this, a conventional galenic granulation process is perfectly suitable. For example, in order to obtain 1 kg of grains, the following form can be used:
Sodium bicarbonate .............................. 500 g
Potato starch ............................ 250 g
Lactose ............................................ 250 g
Potato starch paste at 5% ..... 200 ml approximately and carry out the operations below:
1) Mixture
After weighing each component separately, they are placed in the
stainless steel tank of an Erweka planetary mixer. The mixing is done
for 2 minutes at speed 1.

2) Anchoring
Starch paste is prepared by dissolving the starch in cold water
potato which is then heated until boiling, which gives the
desired consistency (first broths). Anchoring is then carried out
into the Erweka mixer tank, gradually pouring in the quantity
desired amount of poison (200 ml for a 1 kg of powder). Duration of anchorage
is about 2 minutes with a mixer speed of I
then 2.

3) Granulation
It is carried out with the Erweka rotary granulator (rotation speed 2 for
a grid N022) by pressing lightly to obtain a short grain.

4) Drying
In the oven at 30 - 35 for a residual humidity of 5%.

5) Screening
On sieves with a mesh opening of 2 mm, fines smaller than 0.8 mm
being rejected.

 Then we proceed to the pre-coating of the grains. Good isolation of the latter is obtained in particular through the application of 750 ml of Pharmacoat 606 always for 1 kg of grains. Pharmacoat 606 is the name under which hydroxypropylmethyl cellulose is marketed for use in film-forming alcoholic solution. It is preferably applied in three layers.

 The first layer is obtained by "ladle" deposition in a turbine (rotational speed 1 turn / second) of the minimum quantity necessary to completely cover each grain, ie approximately 450 ml, variable volume depending on the state of surface and size of the grains from granulation. After drying in forced air for 30 minutes in the turbine, two other layers are added in the same way. Drying with warm air for at least 15 minutes takes place between their deposition. At the end of the deposition of the third layer of Pharmacoat, the drying of the sub-layer is ensured by spreading the grains on trays in a ventilated oven, thermostatically controlled at 40 "C for a minimum of 4 hours. The pre-coated grains are then sieved on a 3, 15 mm grid to remove any agglomerates.

 The thickness of the film obtained was not measured but could be calculated from the volumes of film former used and the average surface of the grains. This pre-coating process corresponds to the methods conventionally used to obtain the isolation of grains with this type of film former. It was checked with a binocular magnifier that the quantities given above make it possible to obtain a uniform layer.

Finally we proceed with the gastroresistant coating. Eudragit L, which is then preferably used, is an anionic copolymer based on methacrylic acid and methyl methacrylate. It is applied conventionally in successive layers according to the following cycle:
- "ladle" deposit of the minimum quantity necessary for full coverage
of each grain at the limit of grain aggregation between them, i.e. 180 to
200 ml of solution,
- immediate drying first in the turbine to avoid the formation of
agglomerates then in an oven (4 to 6 hours minimum at 40 - 420C) to obtain a
sufficient hardening of the layer, with simultaneous gentle mechanical mixing
to avoid or separate aggregates (duration 30 minutes),
- then deposit of successive layers. Increasing the number of layers
makes the grains more and more likely to constitute agglomerates.
requires depositing an increasingly reduced amount of film and lengthening the
drying time. Towards the fifth layer, it is about 150 ml. AT
from the third layer, significantly longer drying in the oven is
necessary before making the next layer.

 At the seventh layer and after complete drying (overnight in an oven), a disintegration test in an acidic aqueous medium at pH 1.4 according to a known procedure for in vitro gastroresistance test (cf. for example the French Pharmacopoeia xe edition) is done. According to the result, the number of layers is increased so as to obtain a duration of gastroresistance at pH 1.4 and with mechanical stirring of 50 minutes for the most fragile grains and of one hour in general. Eight to ten coats are usually required. This corresponds to approximately 1350 to 1500 ml of Eudragit L 100 which is slightly more than the usual recommendations of 1 liter of 10% solution for 1 kg of grains. The use of a fluidized air bed device would significantly reduce the number of layers required and, therefore, the total volume of Eudragit. It would be indicated in the context of industrial manufacturing.

 However, these are grains coated and coated according to the method described in detail above which were administered to subjects to give the experimental results illustrated in the figures in the appendix. These correspond to measurements carried out on the blood drawn from these subjects from a microcatheter placed in an antebrachial vein (basilic or cephalic vein). There were a total of three subjects (indicated on the drawings by the initials of their names). The subjects AG and JDR had absorbed in June 1989 a food according to the method described above. The subjects JC and JDR had absorbed in October 1990 a food manufactured in the same way. Each time their blood was taken at regular intervals after the ingestion of food in order to draw up kinetic curves. They were collated below by type of measurement in order to facilitate comparison between subjects and between foods.

The measurements carried out are:
- for FIGS. 1 to 4, the pH of whole venous blood,
- for Figures 5 to 8, the partial pressure of carbon dioxide. Like pH,
it is directly measured, in this case by a blood gas analyzer.

- for figures 9 to 12, the BE, abbreviation of "Base Excess" or "Excès de
base "in French. This parameter is commonly used in clinical biology
to quantify the metabolic component of an acid-base disorder. A
normal blood has a BE equal to zero, i.e. it has neither
excess or defect in its buffer stock, including physiological concentration
is 25 to 27 mmol / l. In case of acidosis (end of exhausting effort for example) the
BE is around 10 mmol / l. Physiologically, it cannot
exist positive BE greater than 2 or 3mmoles / I.

Administration of sodium bicarbonate, as proposed herein
invention, leads to a rise in BE in parallel with the increase in
blood pH. The toxicity of bicarbonate is low, but it would eventually
harmful to exceed a blood pH of 7.50.

- for Figures 13 to 20, the total amount of carbon dioxide that is possible
to obtain from bicarbonates, carbonates and dissolved carbon dioxide
in the blood.

 This parameter is, with regard to FIGS. 13 to 16, calculated using a known physiological equation, that of Henderson-Hasselbalch. This is achieved, for example, through a computer program working from the measurements of the gas analyzers previously used.

These calculations admitting, however, basic physiological conditions which are not necessarily carried out, FIGS. 17 to 18 show the results of an actual assay using a specific device known under the trade name of Corning Carbon Dioxid
Analyze 965. As the differences between the calculated values and the measured values are small and reproducible, those deduced from the calculation can therefore be used.

 Thus, after a peak in alkalinity about an hour after the ingestion of a food according to the invention, there is a good subsequent maintenance of this alkalinity for at least 7 hours. This corresponds to what is generally sought, the duration of sporting events in particular in cycling, running and cross-country skiing added to that necessary for recovery being of this order of magnitude.

 In other sports, shorter or longer periods may be desirable. They could be obtained by adapting the dosage and / or by modifying the manufacture of the granules, either by modifying the composition of the starting grain, either by varying the number of layers or by mixing batches of different kinetic characteristics. It may also be necessary to reduce the risk of possible signs of digestive intolerance in people more sensitive to this function.

Claims (10)

Claims  1.- Sports food containing an alkaline substance, mainly sodium bicarbonate, in a form suitable for a delayed and prolonged release of the alkaline substance in the blood of the sportsman.  2. Food according to claim 1, characterized in that the form suitable for a delayed and prolonged release comprises a coating of the alkaline substance with an enteric product.  3. Food according to claim 2, characterized in that the gastro-resistant product is Eudragit L 100 (marketing name).  4. Food according to claim 2 or claim 3, characterized in that the form adapted to a release, delayed also comprises a pre-coating of the alkaline substance with an insulating product.  5. Food according to claim 4, characterized in that the insulating product is a film-forming alcoholic solution based on hydroxypropylmethyl cellulose.  6. Food according to claim 1, characterized in that the insulating product is Pharmacoat 606 (marketing name).  7. Food according to any one of claims 4 to 6, characterized in that the form adapted to a delayed release comprises a grain made from a powder of the alkaline substance on which the pre-coating is applied.  8. Food according to claim 7, characterized in that, for 1 kg of grains, the pre-coating is carried out with 750 ml of Pharmacoat 606 and the coating with from 1350 to 1500 ml of Eudragit L 100.  9.- Method for manufacturing a food according to any one of the preceding claims, characterized in that it comprises the steps of:  a) granulation giving grains based on the alkaline substance,  b) pre-coating of the grains with an insulating product,  c) coating the grains with an enteric product.  10.- Method according to claim 9, characterized in that the coating step is carried out by successive deposits of layers of gastro-resistant product, a disintegration test in acid medium being carried out from the seventh layer in order to determine, d 'after the duration of gastroresistance of the grains, if the deposition of an additional layer is necessary.