Nicotinamide compositions and the therapeutic use thereof

Abstract

The present invention relates to compositions and methods for the prophylaxis or treatment of deficiencies in essential amino acid absorption and metabolism and/or of a pathology or symptom associated there with. In particular the invention concerns the treatment and/or prevention of ADHD, ADD and autism spectrum disorders. The present inventors have developed a method for prophylaxis or treatment of such symptoms and/or pathologies associated with a deficiency in essential amino acid absorption and/or metabolism, which method, stated generally, relies on the administration of nicotinamide, typically in a long-acting formulation so as to overcome the deficiencies of existing formulations, which have proven unsuitable for effective treatment.

1 - 17 . (canceled) 
     
     
         18 . A floating drug delivery system (FDDS), comprising a particle having a hollow, gas-filled core bordered by a wall of at least one polymer selected from the group of aqueous soluble, erodible, disintegrating and biodegradable polymers, the wall being surrounded by a coating comprising an active ingredient. 
     
     
         19 . The floating drug delivery system according to  claim 18 , wherein the particle is a capsule. 
     
     
         20 . The floating drug delivery system according to  claim 18 , wherein the coating comprises a polymer that swells upon contact with water. 
     
     
         21 . The floating drug delivery system according to  claim 18 , wherein the coating comprises a combination of HPMC and starch. 
     
     
         22 . The floating drug delivery system according to  claim 18 , wherein the coating is selected from the group consisting of coatings resistant to gastric juice, release-controlling coatings, and mixtures thereof. 
     
     
         23 . The floating drug delivery system according to  claim 22 , wherein the release-controlling coating, comprises:
 (a) a swellable, poorly water-soluble or water-insoluble polymer;   (b) one or more enteric polymeric material(s);   (c) a mixture of at least two release controlling polymers; and/or   (d) a mixture of an enteric polymer and a release controlling polymer.   
     
     
         24 . The floating drug delivery system according to  claim 18 , having a density less than 0.95 g/cm 3 . 
     
     
         25 . The floating drug delivery system according to  claim 24 , having a density less than 0.9 g/cm 3 . 
     
     
         26 . The floating drug delivery system according to  claim 25 , having a density less than 0.8 g/cm 3 . 
     
     
         27 . The floating drug delivery system according to  claim 26 , having a density less than 0.7 g/cm 3 . 
     
     
         28 . The floating drug delivery system according to  claim 18 , which is capable of remaining in the stomach for at least 6 hours and/or of releasing active ingredient to the stomach and proximal small intestine for at least 6 hours. 
     
     
         29 . The floating drug delivery system according to  claim 18 , wherein the active ingredient is nicotinamide. 
     
     
         30 . A floating drug delivery device comprising a capsule having a hollow, gas-filled core, bordered by a wall of at least one aqueous soluble, erodible, disintegrating or degradable polymer, the wall being surrounded by a coating comprising at least one active ingredient. 
     
     
         31 . A method of treatment or prevention of a symptom or pathology associated with a deficiency in essential amino acid absorption and/or metabolism, the method comprising administering daily to a subject in need thereof ≦5 separate oral dosage units comprising nicotinamide in a total daily dosage of 10-500 mg/kg bodyweight of the subject. 
     
     
         32 . The method according to  claim 31 , wherein the symptom or pathology is selected from behavioral and/or psychiatric abnormalities, neurological disorders and/or symptomatic disorders. 
     
     
         33 . The method according to  claim 31 , wherein the symptom or pathology is selected from the group consisting of attention deficit hyperactivity disorder (ADHD); attention deficit disorder (ADD); autism spectrum disorders; apathy; anxiety; panic attacks; depression; obsessive-compulsive behaviour; hostility; hyperirritability; mania; memory loss; delirium; organic dementia; emotional liability; death wish; unmanageable behaviour; contact and play disability; restlessness; chaotic behaviour; stress-sensitive fits of crying and temper tantrums; extreme sleeping difficulties; epilepsy; psychomotor retardation; dizziness; bulbary paralysis; tremor; spasm; paresthesia; hyperesthesia; increased tendon reflexes; disorientation; anorexia; glossitis; defecation problems; constipation; dermatitis; atopic eczema; pellagra-like skin disorders; chronic kidney disease and nephrotoxicity. 
     
     
         34 . The method according to  claim 31 , wherein the dosage unit comprises a floating drug delivery system including a particle having a hollow, gas-filled core bordered by a wall of at least one polymer selected from the group of aqueous soluble, erodible, disintegrating and biodegradable polymers, the wall being surrounded by a coating comprising an active ingredient. 
     
     
         35 . A method for providing a floating drug delivery system (FDDS) according to  claim 18 , comprising the steps of:
 (a) providing a gas-filled particle, preferably a capsule, made of at least one aqueous soluble, erodible, disintegrating or degradable polymer;   (b) providing a coating dispersion comprising active ingredient, a polymer, optionally additive(s), in a volatile solvent;   (c) applying at least one layer of dispersion on the surface of particle; and   (d) allowing the evaporation of the volatile solvent such that a layer comprising active ingredient is formed at the surface of the particle.   
     
     
         36 . A method of diagnosing a deficiency in essential amino acid absorption and/or metabolism in a subject, the method comprising determining the urinary excretion of one or more indoles from the subject. 
     
     
         37 . The method according to  claim 26 , wherein the indole is an indican.