# US 8,772,263 B2 · Methods and compositions for protecting or treating muscarinic receptors through administration of pyrophosphate analog in subjects exposed to toxic or carcinogenic metals or metal ions

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- Number: US 8,772,263 B2
- Document ID: US8772263B2
- Status: Granted
- Kind: B2
- Application number: 11/220,115
- Filed: 2005-09-06
- Published: 2006-01-12
- Granted: 2014-07-08
- Earliest claimed: 2000-05-01
- Assignees: HealthPartners Research Foundation
- Applicants: William H. Frey, II; John Randall Fawcett
- Inventors: William H. Frey, II; John Randall Fawcett
- Web page: https://patentgrep.com/patent/US8772263B2

## CPC

- A61K 31/6615: Compounds having two or more esterified phosphorus acid groups, e.g. inositol triphosphate, phytic acid
- A61K 31/352: condensed with carbocyclic rings, e.g. methantheline {(cannabinoids A61K31/658)}
- A61K 31/409: having four such rings, e.g. porphine derivatives, bilirubin, biliverdine (hemin, hematin A61K31/555)
- A61K 31/66: Phosphorus compounds
- A61K 31/661: Phosphorus acids or esters thereof not having P—C bonds, e.g. fosfosal, dichlorvos, malathion {or mevinphos}
- A61K 31/662: Phosphorus acids or esters thereof having P—C bonds, e.g. foscarnet, trichlorfon
- A61K 31/663: Compounds having two or more phosphorus acid groups or esters thereof, e.g. clodronic acid, pamidronic acid
- A61K 31/7072: having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
- A61K 31/7076: containing purines, e.g. adenosine, adenylic acid
- A61K 31/708: having oxo groups directly attached to the purine ring system, e.g. guanosine, guanylic acid
- A61K 31/7084: Compounds having two nucleosides or nucleotides, e.g. nicotinamide-adenine dinucleotide, flavine-adenine dinucleotide
- A61K 31/7105: Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 25/00: Drugs for disorders of the nervous system
- 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 33/00: Antiparasitic agents
- A61P 35/00: Antineoplastic agents
- A61P 39/00: General protective or antinoxious agents
- A61P 39/06: Free radical scavengers or antioxidants
- 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

Methods and compositions for protecting muscarinic receptor(s) in a subject from at least one carcinogenic or toxic metal by administration of a pyrophosphate analog. Methods and compositions for preventing at least one disease induced or caused by metals compromising the function of muscarinic receptors in a subject by administration of a pyrophosphate analog. Methods and compositions for reducing toxic action of metal ions and for reducing poisoning by metals by administering a pyrophosphate analog.

## Claims

### Claim 1

A method for treating at least one muscarinic receptor from dysfunction resulting from exposure to at least one toxic metal or metal ion in a subject in need thereof, comprising:
delivering an effective amount of pamidronate directly to the CNS of the subject and bypassing the blood-brain barrier by intranasally administering to the upper one-third of the subject's nasal cavity the effective amount of pamidronate; and
treating the at least one muscarinic receptor in the subject in need thereof.

### Claim 2 (depends on 1)

The method of claim 1, wherein the metal is selected from the group consisting of Arsenic, Cobalt, Chromium, Nickel, Mercury, Lead, Iron, Copper, Vanadium, and Cadmium, and their alloys.

### Claim 3 (depends on 1)

The method of claim 1, wherein the metal ion is selected from the group consisting of Fe++, Hg++, Cd++, Cu++, As++, and Pb++.

### Claim 4 (depends on 1)

The method of claim 1, wherein the dose of pamidronate administered to the subject is within the range of about 0.001 mg/kg to about 100 mg/kg.

### Claim 5 (depends on 1)

The method of claim 1, wherein the dose of pamidronate administered to the subject is within the range of about 0.01 mg/kg to about 10 mg/kg.

### Claim 6 (depends on 1)

The method of claim 1, wherein the dose of pamidronate administered to the subject is within the range of about 0.1 mg/kg to about 1 mg/kg.

### Claim 7 (depends on 1)

The method of claim 1, wherein the subject suffers from Alzheimer's disease.

### Claim 8

A method for treating at least one muscarinic receptor from dysfunction resulting from exposure to at least one of the toxic metals Arsenic, Cobalt, Chromium, Nickel, Mercury, Lead, Iron, Copper, Vanadium, and Cadmium in a subject in need thereof, comprising:
delivering an effective amount of pamidronate directly to the CNS of the subject and bypassing the blood-brain barrier by intranasally administering to the upper one-third of the subject's nasal cavity the effective amount of pamidronate, wherein the dose of pamidronate administered to the subject is within the range of about 0.1 mg/kg to about 1 mg/kg; and
treating the at least one muscarinic receptor in the subject in need thereof.

### Claim 9

A method for treating at least one muscarinic receptor from dysfunction resulting from exposure to at least one of the carcinogenic metals Arsenic, Cobalt, Chromium, Nickel, Lead, and Cadmium in a subject in need thereof, comprising:
delivering an effective amount of pamidronate directly to the CNS of the subject and bypassing the blood-brain barrier by intranasally administering to the upper one-third of the subject's nasal cavity the effective amount of pamidronate, wherein the dose of pamidronate administered to the subject is within the range of about 0.1 mg/kg to about 1 mg/kg; and
treating the at least one muscarinic receptor in the subject in need thereof.
