Compositions and methods relating to reduction of symptoms of autism

• US 20030170226A1
• Filed: 12/06/2002
• Published: 09/11/2003
• Est. Priority Date: 10/01/1999
• Status: Active Grant

• Current Assignee: Prothera Incorporated (Soho Flordis International Pty., Ltd.)
• Original Assignee: Prothera Incorporated (Soho Flordis International Pty., Ltd.)
• Inventors: Houston, Devin B.
• Granted Patent: US 6,899,876 B2
• Time in Patent Office: Days
• US Class Current: 424/94.63
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 38/4813 Exopeptidases (3.4.11. to 3.4.19)
• CPC Class Codes: C12N 9/0059 Catechol oxidase (1.10.3.1), i.e. tyrosinase
• CPC Class Codes: C12N 9/48 acting on peptide bonds (3.4)
• CPC Class Codes: C12Y 110/03001 Catechol oxidase (1.10.3.1), i.e. tyrosinase
• CPC Class Codes: C12Y 304/14005 Dipeptidyl-peptidase IV (3.4.14.5)

Abstract

Methods and compositions that can reduce the symptoms of autism in a human patient comprising administering a physiologically effective amount of one or both of a purified casomorphin inhibitor selected from the group consisting of a casomorphinase and a casomorphin ligand, and a physiologically effective amount of a purified gluteomorphin inhibitor selected from the group consisting of a gluteomorphinase and a gluteomorphin ligand, to a human patient in sufficient quantities to reduce the effects of the autism. In some embodiments, the compositions and methods further comprise a physiologically effective amount of an enkephalin inhibitor, preferably an enkephalinase, and a physiologically effective amount of an endorphin inhibitor, preferably an endorphinase.

Claims

1. A composition able to reduce the symptoms of autism in a human patient, comprising a physiologically effective amount of a purified microbial casomorphin inhibitor selected from the group consisting of a casomorphinase and a casomorphin ligand, a physiologically effective amount of a purified microbial gluteomorphin inhibitor selected from the group consisting of a gluteomorphinase and a gluteomorphin ligand, and at least one of the group consisting of a physiologically acceptable carrier, adjuvant, excipient, buffer and diluent.

2. The composition of claim 1 wherein the composition comprises casomorphinase that is a proline protease.

3. The composition of claim 2 wherein the proline protease is a peptidase and comprises a dipeptidase activity of dipeptidyl peptidase IV.

4. The composition of claim 1 wherein the composition comprises the casomorphin ligand.

5. The composition of claim 1 wherein the composition comprises gluteomorphinase selected from the group consisting of a tyrosinase and a phenylalaninase.

6. The composition of claim 1 wherein the composition comprises the gluteomorphin ligand.

7. The composition of any one of claims 1 to 6 wherein the composition is suitable for oral administration and wherein the casomorphin inhibitor and the gluteomorphin inhibitor are not enterically coated.

8. The composition of claim 1 wherein the microbe is Aspergillus oryzae or Aspergillus niger.

9. The composition of any one of claims 1 to 6 wherein the casomorphin inhibitor and the gluteomorphin inhibitor are enterically coated.

10. The composition of claim 1 wherein the at least one of the group consisting of the physiologically acceptable carrier, adjuvant, excipient, buffer and diluent comprises maltodextrin L-lysine or lactase.

11. The composition of claim 1 wherein the composition further comprises a physiologically effective amount of an enkephalin inhibitor.

12. The composition of claim 11 wherein the enkephalin inhibitor comprises an enkephalinase.

13. The composition of claim 1 or 11 wherein the composition further comprises a physiologically effective amount of an endorphin inhibitor.

14. The composition of claim 13 wherein the endorphin inhibitor comprises an endorphinase.

35. A food comprising a composition according to any one of claims 1, 31 and 33.

36. A food supplement comprising a composition according to any one of claims 1, 31 and 33.

42. A kit comprising a vessel containing a composition according to any one of claims 1, 31, 33, 35 and 36 and instructions directing the use of the composition to reduce the symptoms of autism in a human patient.

44. A vessel containing a composition according to any one of claims 1, 31, 33, 35 and 36 and a label comprising instructions directing the use of the composition to reduce the symptoms of autism in a human patient.

15. A method of reducing the symptoms of autism in a human patient, comprising administering to the patient a composition comprising a physiologically effective amount of a purified microbial casomorphin inhibitor-selected from the group consisting of a casomorphinase and a casomorphin ligand, a physiologically effective amount of a purified microbial gluteomorphin inhibitor selected from the group consisting of a gluteomorphinase and a gluteomorphin ligand, and at least one of the group consisting of a physiologically acceptable carrier, adjuvant, excipient, buffer and diluent.

16. The method of claim 15 wherein the composition comprises casomorphinase that is a proline protease.

17. The method of claim 16 wherein the proline protease is a peptidase and comprises a dipeptidase activity of dipeptidyl peptidase IV.

18. The method of claim 15 wherein the casomorphin inhibitor comprises the casomorphin ligand.

19. The method of claim 15 wherein the composition comprises gluteomorphinase selected from the group consisting of a tyrosinase and a phenylalaninase.

20. The method of claim 15 wherein the gluteomorphin inhibitor comprises the gluteomorphin ligand.

21. The method of any one of claims 15 to 20 wherein the composition is suitable for oral administration and wherein the casomorphin inhibitor and the gluteomorphin inhibitor are not enterically coated.

22. The method of claim 15 wherein the microbe is Aspergillus oryzae or Aspergillus niger.

23. The method of any one of claims 15 to 20 wherein the casomorphin inhibitor and the gluteomorphin inhibitor are enterically coated.

24. The method of claim 15 wherein the at least one of the group consisting of the physiologically acceptable carrier, adjuvant, excipient, buffer and diluent enhances the oral administration of the composition to a human patient.

25. The method of claim 15 wherein at least one of the group consisting of the physiologically acceptable carrier, adjuvant, excipient, buffer and diluent comprises a maltodextrin, L-lysine or lactose.

26. The method of claim 15 wherein the composition further comprises a physiologically effective amount of an enkephalin inhibitor.

27. The method of claim 26 wherein the enkephalin inhibitor comprises an enkephalinase.

28. The method of claim 15 or 26 wherein the composition further comprises a physiologically effective amount of an endorphin inhibitor.

29. The method of claim 28 wherein the endorphin inhibitor comprises an endorphinase.

30. A method of manufacturing a medicament able to reduce the symptoms of autism in a human patient, comprising combining a physiologically effective amount of a purified microbial casomorphin inhibitor selected from the group consisting of a casomorphinase and a casomorphin ligand, a physiologically effective amount of a purified microbial gluteomorphin inhibitor selected from the group consisting of a gluteomorphinase and a gluteomorphin ligand, and at least one of the group consisting of a physiologically acceptable carrier, adjuvant, excipient, buffer and diluent

31. A composition able to reduce the symptoms of autism in a human patient, comprising a physiologically effective amount of a purified microbial casomorphin inhibitor, a physiologically effective amount of a purified microbial gluteomorphin inhibitor, and at least one of the group consisting of a physiologically acceptable carrier, adjuvant, excipient, buffer and diluent, wherein the casomorphin inhibitor comprises a proline protease grown by a process selected from the group consisting of tray fermentation and deep-tank fermentation and purified by a process comprising alcohol precipitation and filtration, and wherein the gluteomorphin inhibitor comprises a tyrosinase grown by a process selected from the group consisting of tray fermentation and deep-tank fermentation and purified by a process comprising alcohol precipitation and filtration.

32. A method of reducing the symptoms of autism in a human patient, comprising administering to the patient a composition comprising a physiologically effective amount of a purified microbial casomorphin inhibitor, a physiologically effective amount of a purified microbial gluteomorphin inhibitor, and at least one of the group consisting of a physiologically acceptable carrier, adjuvant, excipient, buffer and diluent, wherein the casomorphin inhibitor comprises a proline protease grown by a process selected from the group consisting of tray fermentation and deep-tank fermentation and purified by a process comprising alcohol precipitation and filtration, and wherein the gluteomorphin inhibitor comprises a tyrosinase or a phenylalaninase grown by a process selected from the group consisting of tray fermentation and deep-tank fermentation and purified by a process comprising alcohol precipitation and filtration.

33. A composition able to reduce the symptoms of autism in a human patient, comprising a microbial means to inhibit casomorphin, a microbial means to inhibit gluteomorphin, and at least one of the group consisting of a physiologically acceptable carrier, adjuvant, excipient, buffer and diluent.

34. A method of reducing the symptoms of autism in a human patient, comprising a step of administering to the patient a composition comprising a microbial means to inhibit casomorphin, a microbial means to inhibit gluteomorphin, and at least one of the group consisting of a physiologically acceptable carrier, adjuvant, excipient, buffer and diluent.

37. A method of reducing the symptoms of autism in a human patient, comprising administering to the patient a composition comprising a physiologically effective amount of a purified microbial casomorphinase, and at least one of the group consisting of a physiologically acceptable carrier, adjuvant, excipient, buffer and diluent.

38. The method of claim 37 wherein the casomorphinase comprises a proline protease.

39. The method of claim 38 wherein the proline protease is a peptidase and comprises a dipeptidase activity of dipeptidyl peptidase IV.

40. The method of claim 38 wherein the composition is suitable for oral administration and wherein the casomorphinase is not enterically coated.

41. The method of claim 40 wherein the casomorphinase is derived from a fungus selected from the group consisting of Aspergillus oryzae or Aspergillus niger.