METHODS AND COMPOSITIONS FOR THE TREATMENT OF SYMPTOMS OF WILLIAMS SYNDROME

• US 20090324572A1
• Filed: 06/26/2009
• Published: 12/31/2009
• Est. Priority Date: 06/26/2008
• Status: Active Grant

• Current Assignee: Curemark LLC
• Original Assignee: Curemark LLC
• Inventors: Fallon, Joan M.
• Granted Patent: US 9,320,780 B2
• Time in Patent Office: Days
• US Class Current: 424/94.2
• 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 36/185 Magnoliopsida (dicotyledons)
• CPC Class Codes: A61K 38/465 acting on ester bonds (3.1), e.g. lipases, ribonucleases
• CPC Class Codes: A61K 38/47 acting on glycosyl compounds (3.2), e.g. cellulases, lactases
• CPC Class Codes: A61K 38/48 acting on peptide bonds (3.4)
• CPC Class Codes: A61K 38/4826 Trypsin (3.4.21.4) Chymotrypsin (3.4.21.1)
• CPC Class Codes: A61K 38/4873 Cysteine endopeptidases (3.4.22), e.g. stem bromelain, papain, ficin, cathepsin H
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C12Y 302/01001 Alpha-amylase (3.2.1.1)
• CPC Class Codes: C12Y 302/01002 Beta-amylase (3.2.1.2)
• CPC Class Codes: C12Y 302/01003 Glucan 1,4-alpha-glucosidase (3.2.1.3), i.e. glucoamylase
• CPC Class Codes: C12Y 304/21001 Chymotrypsin (3.4.21.1)
• CPC Class Codes: C12Y 304/21004 Trypsin (3.4.21.4)
• CPC Class Codes: C12Y 304/22002 Papain (3.4.22.2)
• CPC Class Codes: G01N 2333/976 Trypsin; Chymotrypsin
• CPC Class Codes: G01N 2800/2814 Dementia; Cognitive disorders
• CPC Class Codes: G01N 33/6893 related to diseases not provided for elsewhere
• CPC Class Codes: G01N 33/6896 Neurological disorders, e.g. Alzheimer's disease

Abstract

A therapeutic composition for the treatment of the symptoms of Williams Syndrome and the method for preparing the therapeutic agents is disclosed. The therapeutic composition is a stable pharmaceutical composition comprising one or more digestive and/or pancreatic enzymes. The therapeutic composition may be manufactured by a variety of encapsulation technologies. Delivery of the therapeutic composition may be made orally, through injection, by adherence of a medicated patch or other method. Further, a method of using fecal chymotrypsin level as a biomarker for the presence of Williams Syndrome, or the likelihood of an individual to develop Williams Syndrome is disclosed.

Claims

1. A method for treating one or more symptoms associated with Williams Syndrome in a patient diagnosed with Williams Syndrome comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition comprising one or more digestive enzymes.

2. The method of claim 1 wherein the one or more digestive enzymes comprise one or more enzymes selected from the group consisting of proteases, hydrolases, amylases, celluloses, sucrases, maltases, papaya, papain, bromelain, and lipases.

3. The method of claim 1 wherein the one or more digestive enzymes comprise one or more pancreatic enzymes.

4. The method of claim 2 wherein the proteases comprise chymotrypin and trypsin.

5. The method of claim 1 wherein the one or more digestive enzymes are independently derived from an animal source, a microbial source, or a plant source, or are synthetically prepared.

6. The method of claim 5 wherein the animal source is a pig.

7. The method of claim 1 wherein the pharmaceutical composition comprises at least one amylase, a mixture of proteases comprising chymotrypsin and trypsin, at least one lipase, and papain.

8. The method of claim 7 wherein the pharmaceutical composition further comprises papaya.

9. The method of claim 1 wherein the pharmaceutical composition comprises per dose:

amylases from about 10,000 to about 60,000 U.S.P, proteases from about 10,000 to about 70,000 U.S.P, lipases from about 4,000 to about 30,000 U.S.P, chymotrypsin from about 2 to about 5 mg, trypsin from about 60 to about 100 mg, papain from about 3,000 to about 10,000 USP units, and papaya from about 30 to about 60 mg.

10. The method of claim 1 wherein the pharmaceutical composition comprises at least one protease and at least one lipase and wherein the ratio of total proteases to total lipases (in USP units) ranges from about 1:

1 to about 20;

1.

11. The method of claim 10 wherein the ratio of proteases to lipases ranges from about 4:

1 to about 10;

1.

12. The method of claim 1 wherein the one or more symptoms of Williams Syndrome are selected from chronic abdominal pain, sensorineural hearing loss, severe weakness in visiospatial construction, attention deficit disorders, phobias, and a combination thereof.

13. The method of claim 1 wherein the pharmaceutical composition is a dosage formulation selected from the group consisting of:

pills, tablets, capsules, microcapsules, mini-capsules, time released capsules, mini-tabs, sprinkles, and a combination thereof.

14. A method of diagnosing a patient comprising:

obtaining a fecal sample from the patient;

determining a level of chymotrypsin present in the fecal sample; and

diagnosing the patient as having Williams Syndrome if the determined fecal chymotrypsin level is 8.4 U/gram or less and the patient exhibits at least one symptom associated with Williams Syndrome.

15. The method of claim 14 wherein the fecal chymotrypsin level is between 8.4 and 4.2 U/gram.

16. The method of claim 14 wherein the fecal chymotrypsin level is less than 4.2 U/gram.

17. The method of claim 14 wherein the level of chymotrypsin present in the fecal sample is determined using an enzymatic photospectrometry method.

18. The method of claim 14 further comprising administering to the patient an effective amount of a pharmaceutical composition comprising one or more digestive enzymes if the patient is diagnosed as having Williams Syndrome.

19. The method of claim 18 further comprising determining if the administration of the pharmaceutical composition reduces or ameliorates one or more symptoms associated with Williams Syndrome.

20. The method of claim 19 further comprising comparing the post-administration measurement of one or more Williams Syndrome symptoms to a pre-administration measurement of the one or more Williams Syndrome symptoms.

21. A method of identifying a patient likely to benefit from administration of a pharmaceutical composition comprising one or more digestive enzymes comprising:

obtaining a fecal sample from the patient;

determining a level of chymotrypsin present in the fecal sample; and

identifying the patient as likely to benefit from administration of the pharmaceutical composition if the determined fecal chymotrypsin level is 8.4 U/gram or less and the patient is diagnosed with Williams Syndrome.

22. The method of claim 21 further comprising determining if the patient exhibits one or more symptoms of Williams Syndrome.

23. The method of claim 21 wherein the benefit comprises a reduction or amelioration of one or more symptoms associated with Williams Syndrome.

24. The method of claim 21 wherein the level of chymotrypsin present in the fecal sample is determined using an enzymatic photospectrometry method.

25. The method of claim 21 further comprising administering to the patient an effective amount of a pharmaceutical composition comprising one or more digestive enzymes.

26. A pharmaceutical composition comprising one or more digestive enzymes, wherein the one or more digestive enzymes comprise at least one lipase and at least one protease, and wherein the ratio of total proteases to total lipases (in USP units) ranges from about 1:

1 to about 20;

1.

27. The pharmaceutical composition of claim 26 wherein the ratio of total proteases to total lipases ranges from about 4:

1 to about 10;

1.

28. A pharmaceutical composition comprising at least one amylase, a mixture of proteases comprising chymotrypsin and trypsin, at least one lipase, and papain.

29. The pharmaceutical composition of claim 28 wherein the pharmaceutical composition further comprises papaya.

30. The pharmaceutical composition of claim 28 wherein the ratio of total proteases to total lipases ranges from about 1:

1 to about 20;

1.

31. A pharmaceutical preparation for treating an individual exhibiting one or more symptoms of Williams Syndrome comprising a therapeutically effective amount of a digestive enzyme.

32. The pharmaceutical preparation of claim 31 wherein the digestive enzyme is selected from the group consisting of:

amylase, lipase, protease, and a combination thereof.

33. The pharmaceutical preparation of claim 31 wherein the digestive enzyme is further selected from the group consisting of:

chymotrypsin, trypsin, papaya, papain, and a combination thereof.

34. The pharmaceutical preparation of claim 31 wherein the enzyme is derived from a source selected from the group consisting of animal enzymes, plant enzymes, synthetic enzymes, and a combination thereof.

35. The pharmaceutical preparation of claim 31 wherein the preparation is manufactured using a technology selected from the group consisting of Prosolv®

technology, enteric coating, lipid encapsulation, direct compression, dry granulation, wet granulation, and a combination thereof.

36. The pharmaceutical preparation of claim 31 wherein the preparation is administered orally via a dosage formulation selected from the group consisting of:

pills, tablets, capsules, microcapsules, mini-capsules, time released capsules, mini-tabs, sprinkles, and a combination thereof.

37. The pharmaceutical preparation of claim 32 wherein the amount of amylase ranges from 10,000 to 60,000 USP units/mg.

38. The pharmaceutical preparation of claim 32 wherein the amount of protease ranges from 10,000 to 70,000 USP units/mg.

39. The pharmaceutical preparation of claim 32 wherein the amount of lipase ranges from 4,000 to 30,000 USP units/mg.

40. The pharmaceutical preparation of claim 33, wherein the amount of pancreatin ranges from 2,000 to 6,000 USP units/mg.

41. The pharmaceutical preparation of claim 33, wherein the amount of chymotrypsin ranges from 2 to 5 mg.

42. The pharmaceutical preparation of claim 33, wherein the amount of papain ranges from 3,000 to 10,000 USP units/mg.

43. The pharmaceutical preparation of claim 33, wherein the amount of papaya ranges from 30 to 60 mg.

44. The pharmaceutical preparation of claim 33 wherein the amount of trypsin ranges from 60 to 100 mg.

45. The pharmaceutical preparation of claim 31 wherein a symptom of the Williams Syndrome is ameliorated.

46. The pharmaceutical preparation of claim 31 wherein the symptom of the Williams Syndrome is selected from the group consisting of:

chronic abdominal pain, sensorineural hearing loss, severe weakness in visiospatial construction, attention deficit disorders, phobias, and a combination thereof.

47. A method of treating an individual having WS with a therapeutically effective amount of digestive enzymes comprising the steps of:

measuring a level of fecal chymotrypsin in a stool sample of the individual;

comparing the level of fecal chymotrypsin with a normal fecal chymotrypsin level; and

administering the digestive enzymes to the individual if the level of fecal chymotrypsin in the individual is less than the normal fecal chymotrypsin level.

48. The method of claim 47 further comprising the steps of:

administering the digestive enzymes to the individual in order to promote protein digestion; and

administering the digestive enzymes to the individual in order to ameliorate a symptom of the Williams Syndrome.

49. The method of claim 47 wherein the stool sample is measured using a technique selected from the group consisting of:

enzymatic photospectrometry, colorimetry, treatment with substrates, assays, and a combination thereof.