METHODS AND COMPOSITIONS FOR THE TREATMENT OF SYMPTOMS OF NEUROLOGICAL AND MENTAL HEALTH DISORDERS

Abstract

A therapeutic composition for the treatment of the symptoms of neurological and mental health disorders, such as Alzheimer's disease, bipolar disorder, obsessive compulsive disorder, and oppositional defiant disorder, and the method for preparing the therapeutic agents is disclosed. The therapeutic agent is a stable pharmaceutical preparation containing, but not limited to, digestive/pancreatic enzymes. The therapeutic agent may be manufactured by a variety of encapsulation technologies. Delivery of the therapeutic agent may be made orally, through injection, by adherence of a medicated patch or other method. Further, a method of using fecal chymotrypsin level as an indicator of the presence of neurological and mental health disorders, such as Alzheimer's disease, bipolar disorder, obsessive compulsive disorder, and oppositional defiant disorder, or the likelihood of an individual to develop these disorders is disclosed.

Claims

1. A method for treating one or more symptoms associated with a neurological or mental health disorder in a patient diagnosed with the neurological or mental health disorder 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 neurological or mental health disorder is selected from the group consisting of: Alzheimer's disease, bipolar disorder, obsessive compulsive disorder, oppositional defiant disorder, and a combination thereof.

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

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

5. The method of claim 3, wherein the proteases comprise chymotrypsin and trypsin.

6. 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.

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

8. 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.

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

10. The method of claim 1, wherein the pharmaceutical composition comprises: 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 U.S.P. units, and papaya from about 30 to about 60 mg.

11. 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 U.S.P. units) ranges from about 1:1 to about 20:1.

12. The method of claim 11, wherein the ratio of proteases to lipases ranges from about 4:1 to about 10:1.

13. The method of claim 2, wherein the one or more symptoms of Alzheimer's disease is selected from the group consisting of: memory loss, language deterioration, impaired ability to mentally manipulate visual information, poor judgment, confusion, restlessness, mood swings, and a combination thereof.

14. The method of claim 2, wherein the one or more symptoms of the manic phase of bipolar disorder is selected from the group consisting of: euphoria, extreme optimism, inflated self-esteem, poor judgment, rapid speech, racing thoughts, aggressive behavior, agitation, increased physical activity, risky behavior, spending sprees, increased drive to perform or achieve goals, increased sexual drive, decreased need for sleep, tendency to be easily distracted, inability to concentrate, drug abuse, and a combination thereof.

15. The method of claim 2, wherein the one or more symptoms of the depressive phase of bipolar disorder is selected from the group consisting of: sadness, hopelessness, suicidal thoughts or behavior, anxiety, guilt, sleep problems, appetite problems, fatigue, loss of interest in daily activities, problems concentrating, irritability, chronic pain without a known cause, and a combination thereof.

16. The method of claim 2, wherein the one or more symptoms of OCD involving obsessions is selected from the group consisting of: fear of being contaminated by shaking hands or by touching objects others have touched, doubts that the individual has locked the door or turned off the stove, repeated thoughts that the individual has hurt someone in a traffic accident, intense distress when objects are not orderly, lined up properly or facing the right way, images of hurting the individual's child, impulses to shout obscenities in inappropriate situations, avoidance of situations that can trigger obsessions, such as shaking hands, replaying pornographic images in the individual's mind, dermatitis because of frequent hand washing, skin lesions because of picking at the skin, hair loss or bald spots because of hair pulling, and a combination thereof.

17. The method of claim 2, wherein the one or more symptoms of OCD involving compulsions is selected from the group consisting of: washing hands until the skin becomes raw, checking doors repeatedly to make sure they are locked, checking the stove repeatedly to make sure it is off, counting in certain patterns, and a combination thereof.

18. The method of claim 2, wherein the one or more symptoms included in the definition of ODD is selected from the group consisting of: losing one's temper; arguing with adults; actively defying requests; refusing to follow rules; deliberately annoying other people; blaming others for one's own mistakes or misbehavior; being touchy, easily annoyed or angered, resentful, spiteful, or vindictive, and a combination thereof.

19. 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.

20. 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 a neurological or mental health disorder if the determined fecal chymotrypsin level is 8.4 U/gram or less and the patient exhibits at least one symptom associated with the neurological or mental health disorder, wherein the neurological or mental health disorder is selected from the group consisting of: Alzheimer's disease, bipolar disorder, obsessive compulsive disorder, oppositional defiant disorder, and a combination thereof.

21. The method of claim 20, wherein the fecal chymotrypsin level is between about 8.4 and about 4.2 U/gram.

22. The method of claim 20, wherein the fecal chymotrypsin level is less than 4.2 U/gram.

23. The method of claim 20, wherein the level of chymotrypsin present in the fecal sample is determined using an enzymatic photo spectrometry method.

24. The method of claim 20, 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 the neurological or mental health disorder.

25. The method of claim 24, further comprising determining if the administration of the pharmaceutical composition reduces or ameliorates one or more symptoms associated with the neurological or mental health disorder.

26. The method of claim 25, further comprising comparing the post-administration measurement of one or more symptoms of the neurological or mental health disorder to a pre-administration measurement of the one or more symptoms of the neurological or mental health disorder.

27. 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 a neurological or mental health disorder, wherein the neurological or mental health disorder is selected from the group consisting of: Alzheimer's disease, bipolar disorder, obsessive compulsive disorder, oppositional defiant disorder, and a combination thereof.

28. The method of claim 27, further comprising determining if the patient exhibits one or more symptoms of the neurological or mental health disorder.

29. The method of claim 27, wherein the benefit comprises a reduction or amelioration of one or more symptoms associated with the neurological or mental health disorder.

30. The method of claim 27, wherein the level of chymotrypsin present in the fecal sample is determined using an enzymatic photo spectrometry method.

31. The method of claim 27, further comprising administering to the patient an effective amount of a pharmaceutical composition comprising one or more digestive enzymes.

32. 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 U.S.P. units) ranges from about 1:1 to about 20:1.

33. The pharmaceutical composition of claim 32, wherein the ratio of total proteases to total lipases ranges from about 4:1 to about 10:1.

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

35. The pharmaceutical composition of claim 34, wherein the pharmaceutical composition further comprises papaya.

36. The pharmaceutical composition of claim 34, wherein the ratio of total proteases to total lipases ranges from about 1:1 to about 20:1.

37. A pharmaceutical preparation for treating an individual exhibiting one or more symptoms of a neurological or mental health disorder comprising a therapeutically effective amount of a digestive enzyme, wherein the neurological or mental health disorder is selected from the group consisting of: Alzheimer's disease, bipolar disorder, obsessive compulsive disorder, oppositional defiant disorder, and a combination thereof.

38. The pharmaceutical preparation of claim 37, wherein the digestive enzyme is selected from the group consisting of: amylase, lipase, protease, and a combination thereof.

39. The pharmaceutical preparation of claim 37, wherein the digestive enzyme is further selected from the group consisting of: chymotrypsin, trypsin, pancreatin, papaya, papain, and a combination thereof.

40. The pharmaceutical preparation of claim 37, wherein the enzyme is derived from a source selected from the group consisting of animal enzymes, plant enzymes, synthetic enzymes, and a combination thereof.

41. The pharmaceutical preparation of claim 37, 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.

42. The pharmaceutical preparation of claim 37, 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.

43. The pharmaceutical preparation of claim 38, wherein the amount of amylase ranges from about 10,000 to about 60,000 U.S.P. units/mg.

44. The pharmaceutical preparation of claim 38, wherein the amount of protease ranges from about 10,000 to about 70,000 U.S.P. units/mg.

45. The pharmaceutical preparation of claim 38, wherein the amount of lipase ranges from about 4,000 to about 30,000 U.S.P. units/mg.

46. The pharmaceutical preparation of claim 39, wherein the amount of pancreatin ranges from about 2,000 to about 6,000 U.S.P. units/mg.

47. The pharmaceutical preparation of claim 39, wherein the amount of chymotrypsin ranges from 2 to 5 mg.

48. The pharmaceutical preparation of claim 39, wherein the amount of papain ranges from about 3,000 to about 10,000 U.S.P. units/mg.

49. The pharmaceutical preparation of claim 39, wherein the amount of papaya ranges from about 30 to about 60 mg.

50. The pharmaceutical preparation of claim 39, wherein the amount of trypsin ranges from about 60 to about 100 mg.

51. The pharmaceutical preparation of claim 37, wherein a symptom of the neurological or mental health disorder is ameliorated.

52. The method of claim 51, wherein the symptom of Alzheimer's disease is selected from the group consisting of: memory loss, language deterioration, impaired ability to mentally manipulate visual information, poor judgment, confusion, restlessness, mood swings, and a combination thereof.

53. The method of claim 51, wherein the symptom of the manic phase of bipolar disorder is selected from the group consisting of: euphoria, extreme optimism, inflated self-esteem, poor judgment, rapid speech, racing thoughts, aggressive behavior, agitation, increased physical activity, risky behavior, spending sprees, increased drive to perform or achieve goals, increased sexual drive, decreased need for sleep, tendency to be easily distracted, inability to concentrate, drug abuse, and a combination thereof.

54. The method of claim 51, wherein the symptom of the depressive phase of bipolar disorder is selected from the group consisting of: sadness, hopelessness, suicidal thoughts or behavior, anxiety, guilt, sleep problems, appetite problems, fatigue, loss of interest in daily activities, problems concentrating, irritability, chronic pain without a known cause, and a combination thereof.

55. The method of claim 51, wherein the symptom of OCD involving obsessions is selected from the group consisting of: fear of being contaminated by shaking hands or by touching objects others have touched, doubts that the individual has locked the door or turned off the stove, repeated thoughts that the individual has hurt someone in a traffic accident, intense distress when objects are not orderly, lined up properly or facing the right way, images of hurting the individual's child, impulses to shout obscenities in inappropriate situations, avoidance of situations that can trigger obsessions, such as shaking hands, replaying pornographic images in the individual's mind, dermatitis because of frequent hand washing, skin lesions because of picking at the skin, hair loss or bald spots because of hair pulling, and a combination thereof.

56. The method of claim 51, wherein the symptom of OCD involving compulsions is selected from the group consisting of: washing hands until the skin becomes raw, checking doors repeatedly to make sure they are locked, checking the stove repeatedly to make sure it is off, counting in certain patterns, and a combination thereof.

57. The method of claim 51, wherein the symptom included in the definition of ODD is selected from the group consisting of: losing one's temper; arguing with adults; actively defying requests; refusing to follow rules; deliberately annoying other people; blaming others for one's own mistakes or misbehavior; being touchy, easily annoyed or angered, resentful, spiteful, or vindictive, and a combination thereof.

58. A method of treating an individual having a neurological or mental health disorder 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 wherein the neurological or mental health disorder is selected from the group consisting of: Alzheimer's disease, bipolar disorder, obsessive compulsive disorder, oppositional defiant disorder, and a combination thereof.

59. The method of claim 58, 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 neurological or mental health disorder.

60. The method of claim 58, 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.

Description

DETAILED DESCRIPTION

[0078] The present disclosure provides pharmaceutical compositions and methods for treating symptoms associated with certain neurological or mental health disorders, such as Alzheimer's disease, Bipolar disorder, OCD, or ODD, Pervasive Development Disorders, and Dysautonomias. The pharmaceutical compositions described herein include one or more digestive enzymes, which are postulated by the present inventor to assist in proper digest protein and thus to ameliorate the gastrointestinal dysfunction that is associated with the described disorders.

[0079] In certain embodiments, the pharmaceutical compositions can include 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 U.S.P. units) ranges from about 1:1 to about 20:1. In some cases, the ratio of total proteases to total lipases ranges from about 4:1 to about 10:1. In some embodiments, the pharmaceutical composition is lipid encapsulated.

[0080] In some cases, a pharmaceutical composition for use herein comprises at least one amylase, at least one protease, and at least one lipase. In certain embodiments, the composition can comprise at least one amylase, at least two proteases, and at least one lipase. In certain embodiments the pharmaceutical composition includes multiple proteases, including, without limitation, chymotrypsin and trypsin. In certain embodiments, the composition can further include one or more hydrolases, papain, bromelain, papaya, celluloses, pancreatin, sucrases, and maltases.

[0081] The one or more enzymes can be independently derived from animal, plant, microbial, or synthetic sources. In some embodiments, the one or more enzymes are derived from pig, e.g.: pig pancreas.

[0082] One exemplary formulation for the treatment of the symptoms of neurological and mental health disorders, such as Alzheimer's disease, bipolar disorder, obsessive compulsive disorder, and oppositional defiant disorder is as follows: amylase 10,000-60,000 U.S.P., protease 10,000-70,000 U.S.P., lipase 4,000-30,000 U.S.P., chymotrypsin 2-5 mg, Trypsin 60-100 mg, papain 3,000-10,000 U.S.P. units/mg, and papaya 30-60 mg.

[0083] Additional formulations comprising one or more digestive enzymes may be advantageous including formulations in which the ratio of total proteases to total lipases (in U.S.P. units) is from about 1:1 to about 20:1. In some embodiments, the ratio of total proteases to total lipases is from about 4:1 to about 10:1. Such formulations are useful for treating symptoms of neurological and mental health disorders, such as Alzheimer's disease, bipolar disorder, OCD, and ODD, as well as dysautonomias (e.g., familial dysautonomia, Parkinson's, Guillaine-Barre Syndrome, Aromatic-L-amino acid decarboxylase deficiency, tetrahydrobiopterin deficiency, familial paranganglioma syndrome; multiple system atrophy, dysautonomic symptoms associated with tumors such as pheochromocytoma, chemodectoma, and neuroblastoma; neurally mediated syncope, and SIDS) and pervasive development disorders such as autism, ADHD, ADD, and Asperger's.

[0084] Patients below the age of 18 are typically given a dosage such that the formulation would deliver 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 patient, per day. Beneficially the formulation would deliver 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 patient per day. Patients above the age of 18 are typically given no less than 5,000 U.S.P. units of protease per kilogram weight of patient per day.

[0085] The pharmaceutical compositions can be formulated in dosage forms for any route of administration, including oral, parenteral, IV, inhalation, and buccal dosage formulations. In certain embodiments, a dosage formulation may be administered by an oral preparation including, but not limited to, an encapsulated tablet, mini-tabs, microcapsule, mini-capsule, time released capsule, sprinkle or other methodology. In one embodiment, the oral preparation is encapsulated using one or more lipids. Alternatively, the oral preparation may be encapsulated using enteric coating or organic polymers. A formulation may also be prepared using PROSOLV® technology, direct compression, dry granulation, wet granulation, and/or a combination of these methods.

[0086] Fecal chymotrypsin level is a sensitive, specific measure of proteolytic activity, see e.g.: U.S. Pat. No. 6,660,831, incorporated by reference herein. Normal levels of chymotrypsin are considered to be greater than 8.4 U/gram. Decreased values (less than 4.2 U/gram) suggest diminished pancreatic output (pancreatic insufficiency), hypoacidity of the stomach or cystic fibrosis. Elevated chymotrypsin values suggest rapid transit time, or less likely, a large output of chymotrypsin from the pancreas.

[0087] For the fecal chymotrypsin test, a stool sample is collected from each of the subjects. Each stool sample can be analyzed using an enzymatic photospectrometry analysis to determine the level of fecal chymotrypsin in the stool; in some cases, the assay is performed at 30° C., see, e.g.: U.S. Pat. No. 6,660,831, incorporated by reference herein. Alternatively, other methods, such as the colorimetric method, use of substrates, use of assays, and/or any other suitable method may be used to measure the fecal chymotrypsin levels. The levels of fecal chymotrypsin in the samples of the individuals suspected of or diagnosed as having neurological and mental health disorders, such as Alzheimer's disease, Bipolar disorder, OCD, and ODD, are compared to the levels of fecal chymotrypsin in individuals not suspected or diagnosed with these neurological and mental health disorders to determine if the tested individuals exhibit lower fecal chymotrypsin values and to determine if the individuals would benefit from the administration of a composition as described herein.

[0088] The foregoing description of the embodiments of the invention has been presented for the purposes of illustration and description. It is not intended to be exhaustive or to limit the invention to the precise form disclosed. Many modifications and variations are possible in light of this disclosure. It is intended that the scope of the invention be limited not by this detailed description, but rather by the claims appended hereto.