DIETETIC OR PHARMACEUTICAL COMPOSITIONS FOR THE RESTORATION OF ADENINE NUCLEOTIDE CELL CONTENT IN SKELETAL AND CARDIAC MUSCLES

Abstract: Dietetic or pharmaceutical compositions containing a (D)-ribose and magnesium (L)-aspartate mixture for use as nutritional integrators are herein described.

Description: DIETETIC OR PHARMACEUTICAL COMPOSITIONS FOR THE RESTORATION OF ADENINE NϋCLEOTIDE CELL CONTENT IN SKELETAL AND CARDIAC MUSCLES The present invention relates to dietetic or pharmaceutical compositions containing a mixture of (D)-ribose and magnesium (L)-aspartate in various ratios . One of the most important problems in the skeletal and cardiac muscle physiopathology is to restore, or to maintain adenine nucleotide cell content within physiological limits during or after a prolonged and/or exhausting physical effort, by a necessary or advisable nutritional intervention. On the contrary, the balance between energy requirement and energy availability would be jeopardized. This unfavourable situation occurs when dephosphorylation of ATP into ADP, and subsequently into AMP, continues till adenosine, inosine and ipoxanthine production. These products are released by the cell (R.M. Berne; Am. J. Physiol. , 204,317,1963), and therefore are lost for the purpose of a possible restoration of adenine nucleotides. Theoretically, the problem of adenine nucleotide degradation could be solved by means of some biochemical-nutritional possibilities, for example, administration of adenosine (K. Reibel and M.J. Rovetto; Am. J. Physiol., 237,247,1979) or inosine (V.T. Wiedmeier, R. Rubio and R.M. Berne; J. Mol. Cell. Card.; 4,445,1972), which however proved to be rather uneffective. It has now been found that the administration of (D)-ribose surprisingly enhances adenine nucleotide synthesis, thus resulting in a higher availability of 5-phosphoribosyl-l-pyrophospate, which is the limiting factor of adenine nucleotide biosynthesis. Accordingly, administration of (D)-ribose prevents and reduces adenine nucleotide decrease in muscles during strong stress conditions. Therefore, dietetic or pharmaceutical compositions containing (D)-ribose, optionally combined with magnesium (L)-aspartate, are an object of the present invention. In fact, it is well known that about 55% magnesium ions in the human body are located in the bones, while the remaining are in the soft tissues. A decrease in muscle Mg + has particularly been observed during magnesium deficiency and during intense physical exercises. Magnesium ion mobilization, particularly the loss thereof from muscle cells during physical exercise, can be explained by the high activity of the Mg + dependent enzymes, which are involved in the energy metabolism (creatinine phosphokinase, glycogen phosphorylase and yosin ATPase). The correlation between Mg + loss and exercise intensity can depend on: i) a reduced kidney concentrating capacity which is induced directly by the physical exercise or indirectly by the increase of the hormones inducing Mg ion tubular reabsorption (aldosterone, antidiuretic hormone, thyroid hormones) whose hematic concentration can remain high up to 14 hours after the end of the physical exercise; ii) acidosis, due to lactate accumulation, which can induce magnesiuria through a decrease in magnesium tubular reabsorption. Accordingly, the (D)-ribose and magnesium (L)- aspartate combination assures a correct adenine nucleotide increase and, at the same time, allows to balance muscle Mg + concentration both in magnesium deficiencies and during physical exercises. Administration of the compositions of the present invention is also useful in pathologic conditions wherein a prompt restoration of weary muscles is necessary, for example in diabetes, alcoholism, cardiopathies, pregnancy. The dietetic compositions of the present invention can contain from 200 to 2000 mg of (D)-ribose. When present in the composition, the magnesium (L)-aspartate unitary dose can range from 100 to 1000 mg. Weight ratios of (D)-ribose to magnesium (L)-aspartate are not critical and will generally range from 1:1 to 5:1. The compositions of the present invention can further contain other active ingredients or integrators with adjuvant, complementary or useful activities. Examples of said elements which are profitably used are: - mineral salts and/or vitamins - potassium aspartate. The dietetic or pharmaceutical compositions of the invention can be prepared according to conventional techniques and excipients. Said compositions are prepared by admixing (D)-ribose and magnesium (L)- aspartate with physiologically acceptable excipients having pleasant appearance, smell and taste. Examples of excipients known in the food industry are diluents, sweeteners, binders, flavoring aids, lubricants and non-sticking agents, natural and artificial food dyes. Examples of diluents are: microcrystalline cellulose, glycine, lactose; maize, patatoes and rice starch; mannitol, sorbitol, sucrose, fructose; examples of sweeteners are: saccharin sodium, saccharin acid, aspartame, honey; examples of binders are: starch, polyvinylpyrrolidone, polyvinyl alcohol, hydroxyme- thylcellulose; examples of flavor aids are: citric acid and the salts thereof, tartaric acid and the salts thereof, sodium glutamate, sodium chloride, orthophosphoric acid and the salts thereof, menthol; examples of lubricants and non-sticking agents are: magnesium stearate, talc, 200 to 6000 PEGs (polyethylene glycols) , glyceryl behenate, glycerin, mineral oil, silicone oils, levynite; examples of food dyes are: chlorophyll, bilberry anthocyanins; E104, E110; titanium dioxide, iron oxides; examples of dietetic compositions are: chewable, effervescent or swallowable tablets, syrups, fruit beverages, soluble granulate sachets, fruit jellies, candies. The following examples further illustrate the invention. EXAMPLE 1 Chewable tablets 1 Tablet contains (D)-Ribose mg 200 Magnesium (L)-aspartate mg 200 Maize starch mg 50 Lactose mg 50 Magnesium stearate mg 5 EXAMPLE 2 Drinkable solution 250 ml of solution contain: 1 Tablet contains: (D)-Ribose mg 500 Magnesium (L)-aspartate mg 500 Mannitol q.s. to g 1,5 Polyvinylpyrrolidone mg 50 Chewable tablets 1 Tablet contains: (D)-Ribose Mannitol q.s. to Polyvinylpyrrolidone Citric acid Sodium chloride Orange flavor Magnesium stearate Talc Sugar pills 1 Sugar pill contains: (D)-Ribose Magnesium (L)-aspartate Maize starch Talc Levylite Magnesium stearate Sucrose E110 Carnauba wax

Claims: CLAIMS 1. Dietetic or pharmaceutical compositions containing (D)-ribose as active ingredient. 2. Dietetic or pharmaceutical compositions according to claim 1 further containing magnesium (L)-aspartate. 3. Dietetic or pharmaceutical compositions according to claim 1 or 2 containing from 200 to 2000 mg of (D)- ribose and from 100 to 1000 mg of magnesium (L)- aspartate. 4. Dietetic or pharmaceutical compositions according to anyone of the preceding claims, containing other active ingredients or integrators with adjuvant, complementary or anyway useful activities. 5. Dietetic or pharmaceutical compositions according to claim 4, further containing at least another active ingredient or integrator selected from the group consisting of mineral salts, vitamins and potassium aspartate. 6. Dietetic or pharmaceutical compositions according to anyone of the preceding claims, in the form of effervescent, chewable and swallowable tablets, syrups, fruit drinks, soluble granulate sachets, fruit jellies, candies.

Inventors: CESCHEL GIANCARLO, PALAZZI CAMILLO MARIA FRANCESC, PROCIDA CARLA, RONCHI CELESTINO, CESCHEL, GIANCARLO, PALAZZI, CAMILLO, MARIA, FRANCESCO, GIULIO, PROCIDA, CARLA, RONCHI, CELESTINO
Applicants: DEPHA TEAM SRL, DEPHA TEAM S.R.L.
Application year: 1992
Main classification: A23L2
IPC codes: A23L1