Pharmaceutical Compositions Comprising Polymeric Binders with Non-Hydrolysable Covalent Bonds and Their Use in Treating Celiac Disease

• US 20080254099A1
• Filed: 10/27/2006
• Published: 10/16/2008
• Est. Priority Date: 11/14/2005
• Status: Active Grant

• Current Assignee: Valorisation-Recherche, Limited Partnership
• Original Assignee: Valorisation-Recherche, Limited Partnership
• Inventors: Leroux, Jean-Christophe, Eddine, Mohamad Nasser
• Granted Patent: US 8,883,133 B2
• Time in Patent Office: Days
• US Class Current: 424/439
• CPC Class Codes: A21D 2/28 Organic sulfur compounds
• CPC Class Codes: A23L 33/25 Synthetic polymers, e.g. vinylic or acrylic polymers
• CPC Class Codes: A61K 31/74 Synthetic polymeric materials
• CPC Class Codes: A61K 31/795 Polymers containing sulfur
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/02 Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
• CPC Class Codes: A61P 1/12 Antidiarrhoeals
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection

Abstract

A pharmaceutical composition comprising a polymeric binder including a high molecular weight synthetic polymer having a backbone constituted of non hydrolysable covalent bonds, said polymer being able to form electrostatic bonds at a pH lower than the isoelectric point of gluten and peptides derived from the degradation of gluten, and being able to bind to gluten or peptides derived from the degradation of gluten in the gastrointestinal tract, and a pharmaceutically acceptable carrier. Methods of using the polymeric binder for binding gluten or a peptide derived from the degradation of gluten, for decreasing the degradation of gluten into toxic peptides or for decreasing interaction of gluten or peptides derived from the degradation of gluten with the gastrointestinal mucosa.

Claims

1. A pharmaceutical composition comprising a polymeric binder including a high molecular weight synthetic polymer having a backbone constituted of non hydrolysable covalent bonds, said polymer being able to form electrostatic bonds at a pH lower than the isoelectric point of gluten and peptides derived from the degradation of gluten, and being able to bind to gluten or peptides derived from the degradation of gluten in the gastrointestinal tract, and a pharmaceutically acceptable carrier.

2. The pharmaceutical composition of claim 1, wherein said polymeric binder is able to form hydrophobic interactions with gluten or peptides derived from the degradation of gluten.

3. The pharmaceutical composition of claim 1, wherein said polymeric binder is able to form hydrogen bonds.

4. The pharmaceutical composition of claim 1, wherein said polymeric binder is able to specifically bind to gluten or peptides derived from the degradation of gluten in the gastrointestinal tract.

5. The pharmaceutical composition of claim 1, wherein said polymeric binder is able to bind to gluten or peptides derived from the degradation of gluten in the intestinal tract.

6. The pharmaceutical composition of claim 1, wherein said polymeric binder is a copolymer of hydroxyethyl methacrylate (HEMA) and 4-styrene sulfonic acid sodium salt hydrate (SStNa).

7. The pharmaceutical composition of claim 1, wherein said polymeric binder is a copolymer of hydroxyethyl methacrylate (HEMA) and sulfopropyl methacrylate potassium salt (SPMAK).

8. The pharmaceutical composition of claim 1, wherein said polymeric binder is a polymer of 4-styrene sulfonic acid sodium salt hydrate (SStNa).

9. The pharmaceutical composition of claim 1, wherein said polymeric binder is a polymer of sulfopropyl methacrylate potassium salt (SPMAK).

10. The pharmaceutical composition of claim 1, wherein said polymeric binder is linear.

11. The pharmaceutical composition of claim 1, wherein said polymeric binder is star-shaped.

12. The pharmaceutical composition of claims 11, wherein said polymeric binder is a 3 to 18-arm star-shaped copolymer.

13. The pharmaceutical composition of claims 11, wherein said polymeric binder is a 5 to 18-arm star-shaped copolymer.

14. The pharmaceutical composition of claims 11, wherein said polymeric binder is a 5-arm star-shaped copolymer.

15. The pharmaceutical composition of claims 11, wherein said polymeric binder is a 8-arm star-shaped copolymer.

16. The pharmaceutical composition of claims 11, wherein said polymeric binder is a 18-arm star-shaped copolymer.

17. The pharmaceutical composition of claim 6, wherein said copolymer of HEMA and SStNa has a HEMA/SStNa molar percentage ratio between about 93.5/6.5 and about 1/99.

18. The pharmaceutical composition of claim 6, wherein said copolymer of HEMA and SStNa is linear HEMA/SStNa (51.5/48.5 mol %).

19. The pharmaceutical composition of claim 6, wherein said copolymer of HEMA and SStNa is linear HEMA/SStNa (43/57 mol %)

20. The pharmaceutical composition of claim 7, wherein said copolymer of HEMA and SPMAK has a HEMA/SPMAK molar percentage ratio between about 93.5/6.5 and about 1/99.

21. The pharmaceutical composition of claim 7, wherein said copolymer of HEMA and SPMAK has a HEMA/SPMAK molar percentage ratio between about 86/14 and about 1/99.

22. The pharmaceutical composition of claims 7, wherein said copolymer of HEMA and SPMAK is linear HEMA/SPMAK (45/55 mol %).

23. The pharmaceutical composition of claim 1, further comprising a zonulin antagonist or an HLA DQ2 inhibitor.

24. A method of using the polymeric binder of claim 1, comprising administering to a patient suffering from celiac disease a pharmaceutically effective amount of said polymeric binder.

25. The method of claim 24, which is for binding gluten or a peptide derived from the degradation of gluten in the patient.

26. The method of claim 24, which is for decreasing the degradation of gluten into toxic peptides in the patient.

27. The method of claim 24, which is for decreasing interaction of gluten or peptides derived from the degradation of gluten with the gastrointestinal mucosa of the patient.

28. The method of claim 24, wherein said administration is performed before or during a gluten-containing meal of said patient.

29. The method of claim 24, wherein said administration is performed after a gluten-containing meal of said patient.

38. Food comprising the polymeric binder of claim 1.

39. The food of claim 38, wherein said food is a gluten-containing food.

40. The food of claim 39, wherein said food is bread.

41. A method of using the food of claim 38, comprising administering said food to a patient suffering from celiac disease during the patient'"'"'s meal.

42. The method of claim 41, which is for binding gluten or a peptide derived from the degradation of gluten contained in the meal of the patient.

43. The method of claim 41, which is for decreasing the degradation into toxic peptides of gluten contained in the meal of the patient.

44. The method of claim 41, which is for decreasing interaction of gluten or peptides derived from the degradation of gluten with the gastrointestinal mucosa of the patient.

45. A method of making food for a patient suffering from celiac disease, comprising incorporating into said food the polymeric binder of claim 1.

46. The method of claim 41, wherein said food is a gluten-containing food.

31-37. -37. (canceled)