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(12) Patent Application Publication (10) Pub. No.: US 2006/0018839 A1 Leni Et Al US 20060018839A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2006/0018839 A1 leni et al. (43) Pub. Date: Jan. 26, 2006 (54) METHODS AND COMPOSITIONS USING Publication Classification CHOLINESTERASE INHIBITORS (51) Int. Cl. A6IL 9/04 (2006.01) (75) Inventors: John Ieni, Bloomfield, NJ (US); A6IK 9/70 (2006.01) Raymond Pratt, Baltimore, MD (US) A6IK 3III.3 (2006.01) (52) U.S. Cl. ............................. 424/45; 424/449; 514/662 Correspondence Address: (57) ABSTRACT VENABLE LLP The invention provides methods for treating and/or prevent P.O. BOX 34385 ing Alzheimer's disease, psychiatric illnesses, encephalitis, WASHINGTON, DC 20045-9998 (US) meningitis, fetal alcohol Syndrome, Karsakoff's Syndrome, anoxic brain injury, cardiopulmonary resuscitation injuries, diabetes, Sjogren's Syndrome, mental retardation, develop (73) Assignee: Eisai Co., Ltd., Tokyo (JP) mental delay, menopause, Strokes, macular degeneration, neuronal loSS associated with macular degeneration, Sleep disorders, Severe Alzheimer's disease, jet lag, post-traumatic (21) Appl. No.: 10/988,600 StreSS disorder, anxiety disorders, panic attacks, obsessive compulsive disorder, amnesia, and other disorders by administering to a patient in need thereof at least one (22) Filed: Nov. 16, 2004 cholinesterase inhibitor. The invention also provides novel pharmaceutical compositions that can be administered to the Related U.S. Application Data eyes or to the nose of patients. In one embodiment, the cholinesterase inhibitor is donepezil, a Stereoisomer thereof and/or a pharmaceutically acceptable Salt thereof. In other (63) Continuation of application No. PCT/US03/15279, embodiments, the cholinesterase inhibitor can be one or filed on May 16, 2003. more of phenserine, tolserine, phenethylnorcymSerine, gan Stigmine, epastigmine, tacrine, phySOstigmine, pyridoStig (60) Provisional application No. 60/447,724, filed on Feb. mine, neoStigmine, rivastigmine, galantamine, citicoline, 19, 2003. Provisional application No. 60/380,852, Velnacrine, huperzine, metrifonate, heptastigmine, edropho filed on May 17, 2002. nium, TAK-147, T-82, and upreazine. US 2006/0018839 A1 Jan. 26, 2006 METHODS AND COMPOSITIONS USING 0008. The invention is described in more detail below. CHOLINESTERASE INHIBITORS DETAILED DESCRIPTION OF THE RELATED APPLICATIONS INVENTION 0001. This application is a continuation of PCT Applica 0009. “Patient” refers to animals, preferably mammals, tion No. PCT/US03/15279 filed May 16, 2003, which claims more preferably humans. The term “patient” includes adults priority to U.S. Application No. 60/447,724 filed Feb. 19, and children, and men and women. Children includes neo 2003, and U.S. Application No. 60/380,852 filed May 17, nates, infants, and adolescents. 2002. 0010) “Cognitive impairment” refers to an acquired defi cit in one or more of memory function, problem Solving, FIELD OF THE INVENTION orientation and/or abstraction that impinges on a patient's ability to function independently. 0002 The invention provides methods for treating and/or preventing cognitive impairments, dementia, and other dis 0011 “Dementia” refers to a global deterioration of intel orders by administering a therapeutically effective amount lectual functioning in clear consciousness, and is character ized by one or more Symptoms of disorientation, impaired of at least one cholinesterase inhibitor. A preferred cholinest memory, impaired judgment, and/or impaired intellect. The erase inhibitor is donepezil, a Stereoisomer thereof, and/or a Symptoms of “dementia” are generally worse than, and can pharmaceutically acceptable Salt thereof. encompass, the Symptoms of “cognitive impairment.” BACKGROUND OF THE INVENTION 0012. The invention provides methods for treating and preventing cognitive impairments and/or dementia caused 0003) Cholinesterase inhibitors are described in U.S. Pat. by radiation in a patient in need thereof by administering a No. 4,895,841 and WO 98/39000, the disclosures of which therapeutically effective amount of at least one cholinest are incorporated by reference herein in their entirety. The erase inhibitor. The radiation may be, for example, a radia cholinesterase inhibitors described in U.S. Pat. No. 4,895, tion treatment used for cancer or an accidental exposure to 841 include donepezil hydrochloride or ARICEPT(F), which radioactive materials. has proven to be a highly Successful drug for the treatment 0013 The invention provides methods for treating and of Alzheimer's disease. There is a need in the art for new and preventing visuospatial deficits in a patient in need thereof improved treatments for other diseases, disorders, and Syn by administering a therapeutically effective amount of at dromes that may be characterized by Symptoms of cognitive least one cholinesterase inhibitor. Visuospatial deficits refer impairments. The invention is directed to these, as well as to problems with perceiving, processing and/or interpreting other, important ends. information through the Visual System. Visuospatial deficits can include impairments in Visuoperceptual abilities and SUMMARY OF THE INVENTION Visuoconstructive abilities. 0004. The invention provides methods for treating and/or 0014. The invention provides methods for treating and preventing Alzheimer's disease, vascular dementia, demen preventing Williams Syndrome in a patient in need thereof tia associated with Parkinson's disease, visuospatial deficits, by administering a therapeutically effective amount of at Williams Syndrome, encephalitis, meningitis, fetal alcohol least one cholinesterase inhibitor. Williams syndrome is a Syndrome, Korsakoff's Syndrome, anoxic brain injury, car developmental disorder that is characterized by Visuospatial diopulmonary resuscitation injuries, diabetes, Sjogren's Syn deficits. Most patients with Williams syndrome have mild or drome, mental retardation, developmental delay, meno moderate mental retardation (mean IQ ranging from 55-60), pause, pre-menstrual Syndrome, Strokes, macular but Some have borderline normal intelligence or Severe degeneration, Sleep disorders, cognitive impairments caused mental retardation. by high cholesterol levels, jet lag, post-traumatic StreSS 0015 The invention provides methods for treating and disorder, anxiety disorders, panic attacks, obsessive-com preventing cognitive impairments and/or dementia associ pulsive disorder, amnesia and other disorders by adminis ated with or caused by encephalitis by administering to a tering to a patient at least one cholinesterase inhibitor. patient in need thereof at least one cholinesterase inhibitor. 0005 The invention provide novel nasally administrable “Encephalitis” refers to an inflammation of the brain. Symp pharmaceutical compositions comprising at least one cho toms can include a Sudden fever, headache, vomiting, pho linesterase inhibitor and a nasal delivery System. tophobia, Stiff neck and back, confusion, drowsiness, clum SineSS, unsteady gait, and irritability. Other Symptoms 0006 The invention provides methods of treating include loSS of consciousness, poor responsiveness, Seizures, migraines in a patient in need thereof by the nasal admin muscle weakness, Sudden Severe dementia, memory loSS, istration of a pharmaceutical composition comprising at withdrawal from Social interaction, and impaired judgment. least one cholinesterase inhibitor and a nasal delivery Sys tem. 0016. The invention provides methods for treating and preventing cognitive impairments and/or dementia associ 0007. The invention provides ophthalmic compositions ated with or caused by meningitis by administering to a comprising at least one cholinesterase inhibitor. The oph patient in need thereof a therapeutically effective amount of thalmic compositions of the invention can be used, for at least one cholinesterase inhibitor. “Meningitis” refers to example, to treat macular degeneration, Sjogren's Syn an infection of the membranes that Surround the brain and drome, and glaucoma. Spinal cord. Symptoms can appear Suddenly and can include US 2006/0018839 A1 Jan. 26, 2006 a high fever, Severe and persistent headache, Stiff neck, 0021. The invention provides methods for treating and nausea, and vomiting. Other Symptoms can include confu preventing cognitive impairments and/or dementia caused Sion, Sleepiness, and difficulty waking up. Symptoms of by cardiopulmonary resuscitation by administering to a meningitis in infants can include irritability or tiredness, patient in need thereof a therapeutically effective amount of poor feeding and fever. at least one cholinesterase inhibitor. “Cardiopulmonary resuscitation” refers to the administration of heart compres 0.017. The invention provides methods for treating and Sion and artificial respiration to restore circulation and preventing Sjogren's Syndrome by administering to a patient breathing. PoSSible post-resuscitation complications can in need thereof a therapeutically effective amount of at least include cognitive impairments, cardiovascular dysfunction, one cholinesterase inhibitor. “Sjogren's syndrome' refers to microcirculatory dysfunction, hypoxia and the release of a chronic autoimmune disorder in which immune cells toxic enzymes and free radicals, multiple organ dysfunction attack and destroy the glands that produce tears and Saliva. Syndrome, Seizures, Systemic inflammatory response Syn The Symptoms of Sjogren's Syndrome can include dry eyes drome, Septic shock, and Sepsis Syndrome. and a dry mouth. Additional Symptoms can include skin, nose, and/or
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