Solid oral compositions based on s-adenosyl methionine and/or nadh and process for obtaining them

Abstract

This invention relates to solid oral compositions based on SAMe and/or NADH or their salts in association with calcium oxide and/or calcium hydroxide and a process for obtaining them. This invention also relates to a method for stabilising a solid oral composition based on SAMe and/or NADH or their salts, making use of calcium oxide, calcium hydroxide optionally in association with malic acid, glutamic acid, xylitol, calcium sulphate hemihydrate, magnesium oxide and/or mixtures thereof. This invention also relates to the use of SAMe or its salts in association with calcium oxide and/or calcium hydroxide with the possible further addition of melatonin and/or 1-theanine and/or 1-tryptophan and/or 5-hydroxytryptophan for the treatment of depressive states.

1 . A composition comprising SAMe and/or NADH or its salts in association with calcium oxide and optionally pharmaceutically acceptable excipients. 
   
   
       2 . A composition according to  claim 1 , in which the said SAMe is S-adenosyl methionine paratoluene sulphonate, S-adenosyl methionine-1,4-butene disulphonate, S-adenosyl methionine sulphate, S-adenosyl methionine tosylate. 
   
   
       3 . A composition according to  claim 1 , in which the SAMe is present in a quantity varying from approximately 30 to approximately 90% by weight with respect to the weight of the composition. 
   
   
       4 . A composition according to  claim 3 , in which the SAMe is present in a quantity varying from approximately 50 to 85% by weight with respect to the weight of the composition. 
   
   
       5 . A composition according to  claim 1 , in which the NADH is present in a quantity varying from approximately 1 to approximately 90% by weight with respect to the weight of the composition. 
   
   
       6 . A composition according to  claim 5 , in which the NADH is present in a quantity varying from approximately 5 to 50% by weight with respect to the weight of the composition. 
   
   
       7 . A composition according to  claim 1 , in which the calcium oxide is present in a quantity varying from approximately 1 to approximately 40% by weight with respect to the weight of the composition. 
   
   
       8 . A composition according to  claim 1 , in which the calcium oxide is present in a quantity varying from approximately 2 to approximately 20% by weight with respect to the weight of the composition. 
   
   
       9 . A composition according to  claim 1 , comprising at least one further active ingredient preferably selected from 1-melatonin, 1-theanine and/or 1-tryptophan and/or 5-hydroxytryptophan or mixtures thereof. 
   
   
       10 . A composition according to  claim 1 , in which at least one of the pharmaceutically acceptable excipients is calcium sulphate hemihydrate and/or glucono-delta-lactone. 
   
   
       11 . A composition according to  claim 1 , in the form of a direct mixture, tablet, capsule, granulate or powder. 
   
   
       12 . A composition according to  claim 1 , in the form of a tablet, preferably an ordinary, coated, film-coated and/or gastroresistant tablet. 
   
   
       13 . A composition according to  claim 1 , characterised in that it is in the form of a gastroresistant tablet. 
   
   
       14 . A process for the preparation of a tablet according to  claim 1 , comprising the following stages:
 a) mixing of the SAMe and/or NADH and/or their salts with calcium oxide and pharmaceutically acceptable excipients,   b) precompression and subsequent granulation of the mixture obtained in stage a),   c) mixing of the granulate obtained in stage b) with pharmaceutically acceptable excipients such as calcium sulphate hemihydrate, xylitol, malic acid, glutamic acid, glucono-delta-lactone, magnesium oxide, hydrogenated fatty acids, precipitated silica, magnesium stearate, saccharose, glycerol behenate,   d) compression of the mixture obtained in stage c), with the optional addition of sweeteners and/or flavourings,   e) optional coating of the tablet obtained in stage d) with hydrogenated fatty acids,   f) optional aqueous phase film-coating of the tablet obtained in stage e).   
   
   
       15 . A process according to  claim 14  in which the SAMe is S-adenosyl methionine paratoluene sulphonate, S-adenosyl methionine-1,4-butene disulphonate, S-adenosyl methionine sulphate, S-adenosyl methionine tosylate. 
   
   
       16 . A process according to  claim 14 , in which the said calcium oxide is calcium oxide alone. 
   
   
       17 . A process according to  claim 14 , in which the absolute moisture content is less than approximately 50%-60% and the temperature is maintained around 20° C. and 25° C., in particular around 20° C. 
   
   
       18 . A process according to  claim 14 , in which in stage c) at least one further active ingredient preferably selected from 1-melatonin, 1-theanine and/or 1-tryptophan and/or 5-hydroxytryptophan and/or mixtures thereof may be added to the mixture. 
   
   
       19 . A process according to  claim 14 , in which the coating mentioned in stage e) is applied using hydrogenated fatty acids in a quantity of between 0.4 and 1.5% by weight with respect to the weight of the tablet. 
   
   
       20 . A process according to  claim 14 , in which the aqueous phase film-forming mentioned in stage f) is performed using a varnish preferably selected from gum Lac and/or its salts (Shellac™), methacrylic acid, cellulose acetophthalates, titanium dioxide, talc, triethyl citrate, PVP K30, curcumin, lutein, hydroxypropylcellulose, hydroxypropylmethylcellulose and/or mixtures thereof. 
   
   
       21 . A process according to  claim 20 , in which the varnish lies within a range between approximately 1.0 and approximately 5.0% by weight with respect to the composition. 
   
   
       22 . Compositions which can be obtained through the process in  claims 14 . 
   
   
       23 . A method for the treatment of depressive states which comprises the administration of SAMe or its salts in association with calcium oxide to a patient in such a need. 
   
   
       24 . A method according to  claim 23  in which magnesium oxide is further added to the said calcium oxide. 
   
   
       25 . A method according to  claim 23 , in which the said SAMe is S-adenosyl methionine paratoluene sulphonate, S-adenosyl methionine-1,4-butene disulphonate, S-adenosyl methionine sulphate, S-adenosyl methionine tosylate. 
   
   
       26 . A method according to  claim 23 , in which the said calcium oxide is calcium oxide alone. 
   
   
       27 . A method for stabilising a composition based on SAMe or its salts comprising use of the mixture of SAMe and its salts with calcium oxide. 
   
   
       28 . A method for stabilising a composition based on NADH or its salts comprising use of the mixture of NADH and its salts with calcium oxide. 
   
   
       29 . A method according to  claim 27 , in which SAMe or its salts is present in a quantity of between approximately 30 and approximately 90% by weight calculated in relation to the weight of the composition. 
   
   
       30 . A method according to  claim 27 , in which SAMe or its salts is present in a quantity of between approximately 50 and approximately 85% by weight calculated in relation to the weight of the composition. 
   
   
       31 . A method according to  claim 28 , in which NADH or its salts is present in a quantity of between approximately 1 and approximately 90% by weight calculated in relation to the weight of the composition. 
   
   
       32 . A method according to  claim 28 , in which NADH or its salts is present in a quantity of between approximately 5 and approximately 50% by weight calculated in relation to the weight of the composition. 
   
   
       33 . A method according to  claim 27  in which the calcium oxide is present in a quantity which varies from approximately 1 to approximately 40% by weight with respect to the weight of the composition. 
   
   
       34 . A method according to  claim 33 , in which the calcium oxide is present in a quantity which varies from approximately 2 to approximately 20% by weight with respect to the weight of the composition. 
   
   
       35 . A method according to  claim 33 , comprising the addition of pharmaceutically acceptable excipients.