Product and method for increasing uridine concentration in blood plasma

Abstract

The invention pertains to the use of soluble sodium in the manufacture of a composition or kit of parts for (therapeutically) improving and prolonging blood plasma uridine levels and tissue availability of uridine, and/or for treating or preventing impaired blood plasma uridine levels and tissue availability of uridine, and/or for preventing/treating disorders associated with impaired blood plasma and tissue availability of uridine, in a mammal, preferably a human being, by orally co-administering soluble sodium and uridine in a molar ratio of soluble sodium to uridine of more than 1:1, preferably more than 1.5:1, more preferably more than 2:1, even more preferably at least 2.5:1, even more preferably at least 2.8:1, more preferably 3:1-15:1, most preferably 3:1-10:1, particularly 3:1-5:1.

We claim: 
     
         1 . A method for:
 (i) therapeutically improving and prolonging blood plasma uridine levels and tissue availability of uridine; and/or   (ii) treating disorders associated with impaired blood plasma and tissue availability of uridine,   in a human being in need thereof, wherein the method comprises orally administering to the human being a composition comprising:
 a) sodium in a form soluble in water; and 
 b1) 1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidine-2,4-dione (uridine), or 
 b2) uridine and/or one or more sodium-free uridine derivatives selected from the group consisting of deoxyuridine, uridine nucleotide, and RNA, 
   in a molar ratio of sodium in a form soluble in water:(sum of uridine and sodium-free uridine derivatives) of more than 1:1.   
     
     
         2 . The method according to  claim 1 , wherein the molar ratio of sodium in a form soluble in water:(uridine and sodium-free uridine derivatives) is more than 1.5:1. 
     
     
         3 . The method according to  claim 2 , wherein the molar ratio of sodium in a form soluble in water:(uridine and sodium-free uridine derivatives) is more than 2:1. 
     
     
         4 . The method according to  claim 1 , wherein the human being is at increased risk of or suffering from neurological disorders including neurodegenerative disorders or brain trauma; diabetes; insulin resistance; stroke; endothelial damage; or fatty liver. 
     
     
         5 . The method according to  claim 4 , wherein the human being suffers from or is at risk of a memory and/or cognitive disorder, memory decline and/or cognitive dysfunction, such as Age Associated Memory Impairment (AAMI); Alzheimer's Disease; Parkinson's disease; Pick's disease; and/or dementia, including vascular dementia, frontotemporal dementia, semantic dementia or dementia with Lewy bodies, and/or Mild Cognitive Impairment (MCI). 
     
     
         6 . The method according to  claim 5 , wherein the human being suffers from or is at risk of Alzheimer's Disease or dementia. 
     
     
         7 . The method according to  claim 1 , wherein the uridine is provided in an amount of about 30-1000 mg per day. 
     
     
         8 . The method according to  claim 7 , wherein the uridine is provided in an amount of 200-800 mg per day. 
     
     
         9 . The method according to  claim 1 , comprising further administering at least one of docosahexaenoic acid (22:6; DHA), eicosapentaenoic acid (20:5; EPA) and docosapentaenoic acid (22:5; DPA), or esters thereof. 
     
     
         10 . The method according to  claim 1 , wherein the composition further comprises:
 choline, or salts or esters thereof; and   at least one vitamin B selected from the group of vitamin B6, vitamin B12 and vitamin B9.   
     
     
         11 . The method according to  claim 1 , wherein the uridine nucleotide is uridine monophosphate (UMP). 
     
     
         12 . A method for:
 (i) therapeutically improving and prolonging blood plasma uridine levels and tissue availability of uridine; and/or   (ii) treating disorders associated with impaired blood plasma and tissue availability of uridine,   in a human being in need thereof, wherein the method comprises orally administering to the human being a composition comprising:
 a) sodium in a form soluble in water; and 
 b) disodium uridine monophosphate (Na 2 UMP) and/or sodium uridine diphosphate (NaUDP), optionally in combination with uridine and/or one or more sodium-free uridine derivatives,
 (i) in a molar ratio of added sodium in a form soluble in water (i.e. other than sodium in a form soluble in water provided in the form of Na 2 UMP and NaUDP) to uridine (as the sum of uridine (i.e. the ribosyl uracil) calculated from Na 2 UMP, NaUDP, and the optional uridine and sodium-free uridine derivatives) of more than 1:1; and/or 
 (ii) in a molar ratio of total sodium in a form soluble in water (as the sum of sodium provided in the form of Na 2 UMP and NaUDP, and added sodium in a form soluble in water) to uridine (as the sum of uridine (i.e. the ribosyl uracil) calculated from Na 2 UMP, NaUDP, and the optional uridine and sodium-free uridine derivatives) of at least 2.5:1, 
 
   and wherein the composition comprises a total amount of uridine of about 30-1000 mg uridine per ml.   
     
     
         13 . The method according to  claim 12 , wherein the molar ratio (i) is more than 2:1. 
     
     
         14 . The method according to  claim 12 , wherein the molar ratio (ii) is at least 2.8:1. 
     
     
         15 . The method according to  claim 12 , comprising 200-800 mg uridine per 100 ml. 
     
     
         16 . A nutritional composition comprising uridine and sodium in a form soluble in water in a molar ratio of sodium in a form soluble in water to uridine of more than 1:1, wherein the composition comprises a total amount of uridine of about 30-1000 mg uridine per ml, further comprising:
 at least one of docosahexaenoic acid (22:6; DHA), eicosapentaenoic acid (20:5; EPA) and docosapentaenoic acid (22:5; DPA), or esters thereof; and/or   at least one, of:
 choline, or salts or esters thereof; and 
 at least one vitamin B selected from the group of vitamin B6, vitamin B12 and vitamin B9. 
   
     
     
         17 . The nutritional composition according to  claim 16 , comprising 200-800 mg uridine per 100 ml. 
     
     
         18 . The nutritional composition according to  claim 16 , wherein the molar ratio is more than 1.5:1. 
     
     
         19 . The nutritional composition according to  claim 16 , comprising 500-5000 mg DHA per 100 ml. 
     
     
         20 . The nutritional composition according to  claim 16 , comprising 80 mg to 3000 mg choline per 100 ml of the composition.