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, 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, 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 Bipolar Disorder in a subject diagnosed with Bipolar Disorder, wherein the subject to be treated does not have Autism, comprising administering to the subject a pharmaceutical composition that comprises digestive enzymes; wherein the digestive enzymes comprise a protease, an amylase, and a lipase, and wherein a total protease and a total lipase in the pharmaceutical composition in United Stages Pharmacopeia (U.S.P.) units are present in a ratio of protease to lipase of from about 1:1 to about 20:1, whereby Bipolar Disease is treated in the subject.

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

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

4. The method of claim 1, wherein the digestive enzymes comprise animal enzymes, microbial enzymes, plant enzymes, or are synthetic.

5. The method of claim 4, wherein the digestive enzymes comprise animal enzymes from a pig.

6. The method of claim 1, wherein the pharmaceutical composition comprises the amylase, a mixture of proteases, and the lipase, and wherein the mixture of proteases comprises chymotrypsin and trypsin.

7. The method of claim 6, wherein the mixture of proteases comprises the chymotrypsin, and wherein the chymotrypsin is present in the pharmaceutical composition in an amount of from about 2 to about 5 mg/dose.

8. The method of claim 6, wherein the mixture of proteases comprises the trypsin, and wherein the trypsin is present in the pharmaceutical composition in an amount of from about 60 to about 100 mg/dose.

9. The method of claim 1, wherein the digestive enzymes comprise the amylase, and wherein the amylase is present in the pharmaceutical composition in an amount of from about 10,000 to about 60,000 U.S.P. units/dose.

10. The method of claim 1, wherein the total protease and the total lipase in the pharmaceutical composition in U.S.P. units are present in a ratio of protease to lipase of from about 4:1 to about 10:1.

11. The method of claim 1, wherein the pharmaceutical composition comprises 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, and a combination thereof.

12. The method of claim 1, wherein the digestive enzymes comprise the protease, and wherein the protease is present in the pharmaceutical composition in an amount of from about 10,000 to about 70,000 U.S.P. units/dose.

13. The method of claim 1, wherein the digestive enzymes comprise the lipase, and wherein the lipase is present in the pharmaceutical composition in an amount of from about 4,000 to about 30,000 U.S.P. units/dose.

Description

DETAILED DESCRIPTION

(1) The present disclosure provides pharmaceutical compositions and methods for treating symptoms associated with certain neurological or mental health disorders, such as Alzheimer's, 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.

(2) 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 USP 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.

(3) 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.

(4) 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.

(5) One exemplary formulation for the treatment of the symptoms of neurological and mental health disorders, such as Alzheimer's, bipolar disorder, obsessive compulsive disorder, and oppositional defiant disorder is as follows: Amylase 10,000-60,000 U.S.P. units Protease 10,000-70,000 U.S.P. units Lipase 4,000-30,000 U.S.P. units Chymotrypsin 2-5 mg Trypsin 60-100 mg Papain 3,000-10,000 USP units/mg Papaya 30-60 mg

(6) Additional formulations comprising one or more digestive enzymes may be advantageous including formulations in which the ratio of total proteases to total lipases (in USP 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, 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.

(7) Patients below the age of 18 are typically given a dosage such that the formulation would deliver at least 5,000 USP units of protease and no more than 10,000 USP units of lipase per kilogram weight of patient, per day. Beneficially the formulation would deliver at least 5,000 USP units of protease and no more than 7,500 USP units of lipase per kilogram weight of patient per day. Patients above the age of 18 are typically given no less than 5,000 USP units of protease per kilogram weight of patient per day.

(8) 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.

(9) 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.

(10) For the fecal chymotrypsin test, a stool sample is collected from each of the subjects. Each stool sample can be analyzed using an enzymatic photo spectrometry 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, 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.

(11) 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.