Compounds

Abstract

The present invention relates to compounds which are capable of exerting an inhibitory effect on the Na+ glucose cotransporter SGLT in order to hinder glucose and galactose absorption, as well as on lipase thus reducing dietary triglyceride metabolism, for use in the treatment of conditions which benefit therefrom (diabetes. Metabolic Syndrome, obesity, prevention of weight gain or aiding weight loss). These compounds comprise a non-absorbable, non-digestible polymer having a glucopyranosyl or galactopyranosyl or equivalent moiety stably and covalently linked thereto, said glucopyranosyl or galactopyranosyl moiety being able to occupy the glucose-binding pocket of a SGLT transporter.

1 . A compound comprising a non-absorbable non-digestible polymer having a glucopyranosyl or galactopyranosyl or equivalent moiety stably and covalently linked thereto, wherein said glucopyranosyl or galactopyranosyl or equivalent moiety can occupy the glucose-binding pocket of sodium-dependent glucose transporter (SGLT). 
     
     
         2 . A compound according to  claim 1 , wherein the moiety is glucopyranose or galactopyranose. 
     
     
         3 . A compound according to  claim 1 , wherein said compound is capable of inhibiting the SGLT. 
     
     
         4 . A compound according to  claim 1 , wherein said compound is capable of inhibiting lipase activity. 
     
     
         5 . A compound according to  claim 1 , wherein said compound has an overall positive charge at physiological pH. 
     
     
         6 . A compound according to  claim 1 , wherein said polymer is a synthetic polymer. 
     
     
         7 . A compound according to  claim 1 , wherein said polymer is selected from alginate, β-glucan, microcrystalline cellulose, Chitosan, cyclodextrins, dextran, gellan gum, xanthan gum, acacia gum, carrageenan, agar, pectin, fructans, galactomannan, guar gum, locust bean gum, gum karaya, gum tragacanth, resistant starch, Konjac mannan, pullulan, sucrose polymers, alkyl cellulose, cellulose esters, cellulose ethers, hydroxyalkyl celluloses, nitrocelluloses, poly[lactide-co-glycolide], polyalkylene glycols, polyalkylene oxides, polyalkylene terephthalates, polyalkylenes polyamides, polyanhydrides, polycarbonates, polyglycolides, polymers of acrylic and methacrylic esters, polysiloxanes, polyurethanes, polyvinyl alcohols, polyvinyl esters, polyvinyl ethers, polyvinyl halides, polyvinylpyrrolidone, polyorthoester blends and copolymers thereof. 
     
     
         8 . A compound according to  claim 1 , wherein said polymer is selected from polyallylamine, polylysine, polyethyleneimine, polyvinylamine, methyl hydroxypropyl cellulose, cellulose acetate, cellulose propionate, cellulose acetate butyrate, cellulose acetate phthalate, carboxymethyl cellulose, cellulose triacetate, cellulose sulphate, poly(methyl methacrylate), poly(ethyl methacylate), poly (butyl methacrylate), poly (isobutyl methacrylate) poly(hexyl methacrylate), poly (isodecyl methacrylate), poly(lauryl methacrylate), poly (phenyl methacrylate), poly (methyl acrylate) poly (isopropyl acrylate), poly (isobutyl acrylate), poly (octadecyl acrylate), polyethylene, polypropylene, poly (ethylene glycol), poly (ethylene oxide), poly (ethylene terephthalate), polyvinyl alcohols), poly(vinyl acetate), poly (vinyl chloride), polystyrene, polyvinylpyrrolidone, polyurethane, polylactides, poly (butyric acid), poly (valeric acid), poly[lactide-co-glycolide], polyanhydrides, polyorthoesters, poly(fumaric acid), and poly(maleic acid). 
     
     
         9 . A compound according to  claim 1 , wherein glucopyranosyl galactopyranosyl or equivalent moieties are conjugated to 10-80% of the units composing the polymer backbone. 
     
     
         10 . A compound according to  claim 1 , wherein the compound comprises a hydrophobic alkyl moiety which allows it to hind to chylomicron micelles. 
     
     
         11 . A pharmaceutical composition comprising a compound according to  claim 1 , together with a pharmaceutically acceptable carrier, diluent or excipient. 
     
     
         12 . A non-pharmaceutical composition comprising a compound according to  claim 1 , together with a physiologically acceptable carrier, diluent or excipient. 
     
     
         13 . A non-pharmaceutical composition according to  claim 12 , wherein the compositions is in the form of a drink or a solid foodstuff. 
     
     
         14 . A pharmaceutical or non-pharmaceutical composition comprising a mixture of different compounds according to  claim 1 , together with a physiologically acceptable carrier diluent or excipient. 
     
     
         15 . A pharmaceutical or non-pharmaceutical composition comprising compound according to  claim 1 , wherein said composition is in enteric-coated form. 
     
     
         16 . (canceled) 
     
     
         17 . A method of treating a condition which benefits from reduced glucose absorption in the intestine or reduced dietary triglyceride metabolism, comprising administering to a subject with the condition an effective amount of the compound according to  claim 1 . 
     
     
         18 . The method according to  claim 17 , wherein said condition is selected from the group consisting of obesity, hyperlipaemia, type II diabetes, type I diabetes, hyperglycemia, hyperinsulinemia, hypertriglyceridemia, Metabolic Syndrome, dumping syndrome and atherosclerosis 
     
     
         19 . A kit comprising
 (a) one or more compounds according to  claim 1  and; (h) one or more compounds which are known in the art to inhibit lipase, to bind fat and/or to inhibit SGLT, as a combined preparation for separate, simultaneous or sequential administration to a patient.   
     
     
         20 . A method of preventing weight gain or aiding weight loss in a subject which comprises administration to said subject of a compound according to  claim 1 .