# US 10,369,143 B2 · Methods and compositions for treatment of disorders ameliorated by muscarinic receptor activation

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- Number: US 10,369,143 B2
- Document ID: US10369143B2
- Status: Granted
- Kind: B2
- Application number: 16/270,206
- Filed: 2019-02-07
- Published: 2019-06-06
- Granted: 2019-08-06
- Earliest claimed: 2009-07-22
- Assignees: PureTech Health LLC
- Applicants: PureTech Health LLC
- Inventors: Eric Elenko; Philip E. Murray, III; Andrew C. Miller
- Web page: https://patentgrep.com/patent/US10369143B2

## CPC

- A61K 31/46: 8-Azabicyclo [3.2.1] octane; Derivatives thereof, e.g. atropine, cocaine
- A61K 9/20: Pills, tablets, {discs, rods (A61K9/0004, A61K9/0007, A61K9/0056, A61K9/0065 take precedence; for reconstitution of a drink A61K9/0095)}
- A61K 9/48: Preparations in capsules, e.g. of gelatin, of chocolate {(A61K9/0004 takes precedence; bite capsules A61K9/0056)}
- A61K 9/4825: {Proteins, e.g. gelatin (gelatin capsule shells with substantial amounts of other macromolecular substances A61K9/4816)}
- A61K 9/485: {Inorganic compounds}
- A61K 9/4858: {Organic compounds}
- A61K 9/4866: {Organic macromolecular compounds}
- A61K 9/4891: {Coated capsules; Multilayered drug free capsule shells (with drug coating for immediate release A61K9/4808; osmotic devices A61K9/0004)}
- A61K 31/138: Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine (atenolol A61K31/165; pindolol A61K31/404; timolol A61K31/5377)
- A61K 31/222: with compounds having aromatic groups, e.g. dipivefrine, ibopamine
- A61K 31/4025: not condensed and containing further heterocyclic rings, e.g. cromakalim
- A61K 31/4178: not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
- A61K 31/438: The ring being spiro-condensed with carbocyclic or heterocyclic ring systems
- A61K 31/44: Non condensed pyridines; Hydrogenated derivatives thereof
- A61K 31/4439: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465)
- A61K 31/4725: containing further heterocyclic rings
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61K 47/26: Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
- A61K 47/38: Cellulose; Derivatives thereof
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/14: for treating abnormal movements, e.g. chorea, dyskinesia
- A61P 25/18: Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
- A61P 25/24: Antidepressants
- A61P 25/26: Psychostimulants, e.g. nicotine, cocaine
- A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A61P 25/30: for treating abuse or dependence
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Provided herein is a method of treating a central nervous system disorder in a patient in need thereof, wherein the central nervous system disorder is selected from schizophrenia, Alzheimer's disease, Huntington's disease, Parkinson's disease, and Lewy Body dementia. The method comprises orally administering an initial dose of between 75 mg and 300 mg xanomeline and an initial dose of between 20 mg and 200 mg trospium chloride to the patient during a 24-hour period. Provided that the patient tolerates said administration, an increased dose of trospium chloride and an increased dose of xanomeline are orally administering to the patient, wherein the increased dose of trospium chloride is greater than the initial dose of the trospium chloride, and wherein the increased dose of xanomeline is greater than the initial dose of the xanomeline.

## Claims

### Claim 1

A method of treating a central nervous system disorder in a patient in need thereof, wherein the central nervous system disorder is selected from schizophrenia, Alzheimer's disease, Huntington's disease, Parkinson's disease, and Lewy Body dementia, the method comprising:
orally administering an initial dose of between 75 mg and 300 mg xanomeline and/or a salt thereof and an initial dose of between 20 mg and 200 mg trospium chloride to the patient during a 24-hour period, wherein the initial dose of trospium chloride is in an amount effective to reduce a side effect associated with the initial dose of xanomeline and/or the salt thereof; and
orally administering to the patient an increased dose of trospium chloride and an increased dose of xanomeline and/or the salt thereof,
wherein the increased dose of trospium chloride is greater than the initial dose of the trospium chloride, and
wherein the increased dose of xanomeline and/or the salt thereof is greater than the initial dose of the xanomeline and/or the salt thereof.

### Claim 2 (depends on 1)

The method of claim 1, wherein the central nervous system disorder is schizophrenia.

### Claim 3 (depends on 1)

The method of claim 1, wherein the central nervous system disorder is Alzheimer's disease.

### Claim 4 (depends on 1)

The method of claim 1, wherein the central nervous system disorder is Huntington's disease.

### Claim 5 (depends on 1)

The method of claim 1, wherein the central nervous system disorder is Parkinson's disease.

### Claim 6 (depends on 1)

The method of claim 1, wherein the central nervous system disorder is Lewy Body dementia.

### Claim 7 (depends on 1)

The method of claim 1, wherein the initial dose of xanomeline and/or the salt thereof and the initial dose of trospium chloride are in the same dosage vehicle.

### Claim 8 (depends on 1)

The method of claim 1, wherein the initial dose of xanomeline and/or the salt thereof and the initial dose of trospium chloride are in different dosage vehicles.

### Claim 9 (depends on 1)

The method of claim 1, wherein the increased dose of xanomeline and/or the salt thereof and the increased dose of trospium chloride are in the same dosage vehicle.

### Claim 10 (depends on 1)

The method of claim 1, wherein the increased dose of xanomeline and/or the salt thereof and the increased dose of trospium chloride are in different dosage vehicles.

### Claim 11 (depends on 1)

The method of claim 1, wherein the initial dose of trospium chloride is administered to the patient two times during the 24-hour period.

### Claim 12 (depends on 1)

The method of claim 1, wherein the increased dose of trospium chloride is administered to the patient two times during the 24-hour period.

### Claim 13 (depends on 1)

The method of claim 1, wherein the initial dose of trospium chloride is between 20 mg and 60 mg administered to the patient during the 24-hour period.

### Claim 14 (depends on 1)

The method of claim 1, wherein the initial dose of trospium chloride is between 60 mg and 200 mg administered to the patient during the 24-hour period.

### Claim 15 (depends on 1)

The method of claim 1, wherein the increased dose of trospium chloride is between 20 mg and 200 mg administered to the patient during the 24-hour period.

### Claim 16 (depends on 1)

The method of claim 1, wherein the increased dose of trospium chloride is between 20 mg and 60 mg administered to the patient during the 24-hour period.

### Claim 17 (depends on 1)

The method of claim 1, wherein the increased dose of trospium chloride is between 60 mg and 200 mg administered to the patient during the 24-hour period.

### Claim 18 (depends on 1)

The method of claim 1, wherein the initial dose of xanomeline and/or the salt thereof is between 75 mg and 225 mg administered to the patient during the 24-hour period and the initial dose of trospium chloride is between 20 mg and 60 mg administered to the patient during the 24-hour period.

### Claim 19 (depends on 1)

The method of claim 1, wherein the increased dose of xanomeline and/or the salt thereof is between 75 mg and 225 mg administered to the patient during the 24-hour period and the increased dose of trospium chloride is between 20 mg and 60 mg administered to the patient during the 24-hour period.

### Claim 20 (depends on 1)

The method of claim 1, wherein the initial dose of xanomeline and/or the salt thereof is 300 mg administered to the patient during a 24-hour period and the initial dose of trospium chloride is between 60 mg and 200 mg administered to the patient during a 24-hour period.

### Claim 21 (depends on 1)

The method of claim 1, wherein the increased dose of xanomeline and/or the salt thereof is 300 mg administered to the patient during a 24-hour period and the increased dose of trospium chloride is between 60 mg and 200 mg administered to the patient during a 24-hour period.

### Claim 22 (depends on 1)

The method of claim 1, wherein after the initial dose of xanomeline and the initial dose of trospium chloride are administered, the method further comprises orally administering an intermediate dose of between 75 mg and 300 mg xanomeline and/or the salt thereof and the initial dose of between 20 mg and 200 mg trospium chloride to the patient during a 24-hour period, wherein the intermediate dose of xanomeline is greater than the initial dose of the xanomeline and less than the increased dose of xanomeline and/or the salt thereof.

### Claim 23 (depends on 1)

The method of claim 1, wherein the salt of xanomeline is the salt of tartaric acid.