Methods and compositions for the treatment of symptoms of Williams Syndrome

• US 10,588,948 B2
• Filed: 03/18/2016
• Issued: 03/17/2020
• Est. Priority Date: 06/26/2008
• Status: Active Grant

• Current Assignee: Curemark LLC
• Original Assignee: Curemark LLC
• Inventors: Fallon, Joan M.
• Primary Examiner(s): Yamasaki, Robert J
• Application Number:
  US15/074,115
• Publication Number:
  US 20160206708A1
• Time in Patent Office: 1,460 Days
• Field of Search: None
• 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 Williams Syndrome in a patient diagnosed with Williams Syndrome who has been determined to have a fecal chymotrypsin (FCT) level of 8.4 U/gram or less, comprising administering to the patient an effective amount of a pharmaceutical composition comprising digestive enzymes;

wherein said digestive enzymes comprise a protease, a lipase, and an amylase;

wherein the effective amount of the pharmaceutical composition comprises at least 5,000 U.S.P. Units of protease and no more than 10,000 U.S.P. Units of lipase per kilogram weight of the patient, per day; and

wherein Williams Syndrome is treated.

2. The method of claim 1, wherein the pharmaceutical composition further comprises one or more enzymes selected from the group consisting of a hydrolase, a cellulase, a sucrase, and a maltase.

3. The method of claim 1, wherein the digestive enzymes comprise pancreatic enzymes.

4. The method of claim 1, wherein the pharmaceutical composition comprises a mixture of proteases comprising chymotrypsin and trypsin.

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

6. The method of claim 5, wherein the digestive enzymes are derived from the animal source, and 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 1, wherein the pharmaceutical composition comprises the amylase in an amount of from about 10,000 to about 60,000 U.S.P. units/dose.

9. The method of claim 1, wherein the pharmaceutical composition comprises at least one protease and at least one lipase;

and wherein a ratio of total protease to total lipase in United States Pharmacopeia (U.S.P.) units ranges from about 1;

1 to about 20;

1.

10. The method of claim 9, wherein the ratio of total protease to total lipase ranges from about 4:

1 to about 10;

1.

11. The method of claim 1, wherein the one or more symptoms of Williams Syndrome are selected from the group consisting of abdominal pain, concentration, sensorineural hearing loss, severe weakness in visiospatial construction, a phobia, and a combination thereof.

12. The method of claim 1, wherein the pharmaceutical composition is a dosage formulation selected from the group consisting of a pill, a tablet, a capsule, a microcapsule, a mini-capsule, a time released capsule, a mini-tab, a sprinkle, and a combination thereof.

13. The method of claim 1, wherein the pharmaceutical composition comprises the protease in an amount of from about 10,000 to about 70,000 U.S.P. units/dose.

14. The method of claim 1, wherein the effective amount of the pharmaceutical composition comprises at least 5,000 U.S.P. Units of protease and no more than 7,500 U.S.P. Units of lipase per kilogram weight of the patient, per day.

15. The method of claim 14, wherein one or more symptoms of Williams Syndrome are selected from the group consisting of abdominal pain, concentration, sensorineural hearing loss, severe weakness in visiospatial construction, a phobia, and a combination thereof.