WO2010033045A1 - Compositions and methods for prevention or treatment of beta amyloid deposition - Google Patents
Compositions and methods for prevention or treatment of beta amyloid deposition Download PDFInfo
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- WO2010033045A1 WO2010033045A1 PCT/RU2008/000593 RU2008000593W WO2010033045A1 WO 2010033045 A1 WO2010033045 A1 WO 2010033045A1 RU 2008000593 W RU2008000593 W RU 2008000593W WO 2010033045 A1 WO2010033045 A1 WO 2010033045A1
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- pharmaceutically acceptable
- acceptable salt
- succinic acid
- mammal
- protein deposition
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/14—Quaternary ammonium compounds, e.g. edrophonium, choline
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/194—Carboxylic acids, e.g. valproic acid having two or more carboxyl groups, e.g. succinic, maleic or phthalic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/205—Amine addition salts of organic acids; Inner quaternary ammonium salts, e.g. betaine, carnitine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/06—Antiglaucoma agents or miotics
Definitions
- the present invention relates to pharmaceutical compositions and methods for the prevention or treatment of beta amyloid protein deposition in mammalian tissues. More specifically, the present invention relates to compositions and methods for the prevention or treatment of beta amyloid protein deposition associated with Alzheimer's disease.
- Beta amyloid is a group of proteins formed after sequential cleavage of the amyloid precursor protein (APP) by secretases. The most common isoforms of beta amyloid are 40 and 42 amino acids length proteins. Beta amyloid protein deposition are believed to be responsible for the pathology of a number of neurodegenerative diseases including, but not limited to, Alzheimer's disease. The production and accumulation of beta amyloid protein is central to the pathogenesis of Alzheimer's disease (AD). Cummings JL, Alzheimer's disease. N. Engl. J. Med., 2004, 351: 56-67. The pathological amyloid cascade progresses from the generation of the beta amyloid protein, from the amyloid precursor protein (APP), through multiple secondary steps, to cell death.
- AD Alzheimer's disease
- beta amyloid protein deposition is considered to be a promising approach for the prevention and treatment of AD.
- Beta amyloid protein deposition in retinal cells of the eyes has been linked to pathogenesis of glaucoma and age- related macular degeneration (AMD). McKinnon et al., IOVS, 2002, 43(4): 1077- 1087.
- AMD age-related macular degeneration
- succinic acid or salts thereof is useful for preventing or treating beta amyloid protein deposition in mammals in need thereof.
- the present invention provides a method of preventing or treating amyloid beta protein deposition in a mammal in need thereof comprising administering to said mammal an effective amount of succinic acid or a pharmaceutically acceptable salt thereof.
- uccinic acid which is also named butanedioic acid, refers to a compound of formula HOOCCH 2 CH 2 COOH, CAS RN 110-15-6.
- a pharmaceutically acceptable salt refers to nontoxic base addition salts.
- the pharmaceutically acceptable salts of the present invention are prepared by a reaction of succinic acid with a pharmaceutically acceptable organic or inorganic base by methods well-known from the art.
- bases include, but are not limited to, nontoxic alkali metal and akaline earth bases, for example, calcium, lithium, sodium, and potassium hydroxide; ammonium hydroxide and nontoxic organic bases, such as triethylamine, butylarnine, dimethylethanolamine, diethanolamine, triethanolamine, 2-ethyl-6-methyl-3- hydroxypyridine, and choline base.
- the pharmaceutically acceptable salt of the present invention is a monocholine salt of a formula (I) (CH 3 )SNCH 2 CH 2 OH " 0OCCH 2 CH 2 COOH (I)
- the pharmaceutically acceptable salt of the present invention is dicholine salt of a formula (II)
- an effective amount refers to the amount of the succinic acid or a pharmaceutically acceptable salt thereof that is required for preventing or treating amyloid beta protein deposition in the subject. Effective amounts may vary, as recognized by those skilled in the art, depending on route of administration, excipient usage, and the possibility of co-usage with other agents.
- the effective amount of succinic acid or a pharmaceutically acceptable salt thereof for the use in the method of the present invention is 0.1 to 100 mg/kg body weight per day. More preferably, the effective amount of succinic acid or a pharmaceutically acceptable salt thereof for use in the method of the present invention is 1 to 10 mg/kg body weight per day.
- the succinic acid or a pharmaceutically acceptable salt thereof may be administered to a mammal by a variety of routes.
- the succinic acid or a pharmaceutically acceptable salt thereof is administered by a route selected from the group consisting of oral, oromucosal, sublingual, buccal, intranasal, topical, parenteral, intraocular, intramuscular, subcutaneous, intravenous, and intraperitoneal administration.
- the succinic acid or a pharmaceutically acceptable salt thereof is administered for a period of one day or longer. More preferably, the succinic acid or a pharmaceutically acceptable salt thereof is administered by courses for a period of 5 to 7 days, singly-a-day, with break between courses of two to four weeks. [0015] Preferably, the mammal is a human.
- amyloid beta protein deposition refers to a process of increase and deposition of amyloid beta protein in a mammalian body. Such amyloid beta protein deposition induces or is associated with a variety of disease states, including Alzheimer's disease, Down's syndrome, glaucoma, and age-related macular degeneration (AMD). Preferably, such deposition is associated with Alzheimer's disease.
- beta amyloid protein refers to a protein formed by sequential cleavage of the amyloid precursor protein (APP), and dimers and oligomers thereof, and aggregates thereof including protein constituents of fibril deposits and amyloid plaques.
- APP amyloid precursor protein
- Nonexclusive examples of such proteins include beta amyloid peptides of 39 to 43 amino acid residues in length.
- the term "preventing or treating” refers to the management and care of a mammal for the purpose of (a) preventing the amyloid beta protein deposition from occurring in a subject which may be predisposed to such deposition but has not yet been diagnosed as having it; (b) inhibiting the amyloid beta protein deposition, i.e., arresting its development; or (c) relieving the amyloid beta protein deposition, i.e., causing regression of the amyloid beta protein deposition.
- a beta amyloid protein-induced disease is treated or prevented in a subject, such as a human or another mammal, by administering to the subject an effective amount of succinic acid or a pharmaceutically acceptable salt thereof.
- a subject such as a human or another mammal
- succinic acid or a pharmaceutically acceptable salt thereof is administered to the subject an effective amount of succinic acid or a pharmaceutically acceptable salt thereof.
- succinic acid or a pharmaceutically acceptable salt thereof refers to a disease state that is characterized by beta amyloid deposition and the formation and aggregation of beta amyloid protein fibril deposits or plaques, such as, for example, Alzheimer's disease, Down's syndrome, glaucoma, and age-related macular degeneration (AMD).
- AMD age-related macular degeneration
- Alzheimer's disease refers to a condition associated with formation of neuritic plaques comprised primarily of beta amyloid protein primarily in the hippocampus and cerebral cortex, as well as neurofibrillary tangles and impairment in both learning and memory.
- the present invention provides the use of succinic acid or a pharmaceutically acceptable salt thereof for manufacturing a pharmaceutical composition for preventing or treating amyloid beta protein deposition in a mammal in need thereof.
- the present invention provides a pharmaceutical composition for preventing or treating amyloid beta protein deposition in a mammal in need thereof comprising (a) succinic acid or a pharmaceutically acceptable salt thereof and (b) a pharmaceutically acceptable carrier.
- the term « pharmaceutically acceptable carrier” refers to a pharmaceutically-acceptable material, composition or vehicle, such as a liquid or solid filler, diluent, excipient, solvent, or encapsulating material, involved in carrying or transporting a chemical agent from one organ or portion of the body to another organ, or portion of the body.
- Some examples which can serve as pharmaceutically acceptable carriers include: sugars, such as lactose, glucose and sucrose; starches, such as corn starch and potato starch; cellulose and its derivatives, such as sodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate; powdered tragacanth; malt; gelatin; talc; excipients , such as cocoa butter and suppository waxes; oils, such as sesame oil, olive oil, corn oil and soybean oil; glycols, such as propylene glycol; polyols, such as glycerin, sorbitol, mannitol and polyethylene glycol; esters, such as ethyl oleate and ethyl laurate; agar; buffering agents, such as magnesium hydroxide and aluminum hydroxide; alginic acid; pyrogen-free water; isotonic saline; Ringer's solution; ethyl alcohol; phosphate buffer solutions;
- compositions of the invention are prepared by known procedures using well-known ingredients.
- the composition of the invention can comprise optional ingredients.
- Such optional ingredients generally are used individually at levels from about 0.0005% to about 10.0%, preferably from about 0.005% to about 1.0% by weight of the composition.
- suitable optional ingredients include, but are not limited to, buffers, lubricants, colorants, carriers, and etc.
- Example 1 This example demonstrates the method of the present invention.
- Rats in treatment groups received two courses of i.p. injections of disodium succinate or dicholine succinate in dose of 25 mg/kg once-a-day for seven days with break of three weeks.
- Data are presented as beta amyloid accumulation mean ⁇ SEM in brain quantified by ELISA in brain diethylamine extracts.
- the ophthalmic gel preparation Compound of formula (II) is mixed with above-mentioned ingredients in the conventional manner to prepare the gel.
Abstract
The present invention relates to methods of preventing or treating amyloid beta protein deposition in a mammal in need thereof comprising administering to said mammal an effective amount of succinic acid or a pharmaceutically acceptable salt thereof. Further, invention relates to the use of succinic acid or a pharmaceutically acceptable salt thereof for manufacturing a pharmaceutical composition for preventing or treating amyloid beta protein deposition in a mammal in need thereof. Further, pharmaceutical composition for preventing or treating amyloid beta protein deposition in a mammal in need thereof comprising (a) succinic acid or a pharmaceutically acceptable salt thereof and (b) a pharmaceutically acceptable carrier. Preferably, the mammal is a human. Preferably, the amyloid beta protein deposition is associated with Alzheimer's disease, Down's syndrome, glaucoma, and age-related macular degeneration (AMD).
Description
COMPOSITIONS AND METHODS FOR PREVENTION OR TREATMENT OF
BETA AMYLOID DEPOSITION
Field of the Invention [0001] The present invention relates to pharmaceutical compositions and methods for the prevention or treatment of beta amyloid protein deposition in mammalian tissues. More specifically, the present invention relates to compositions and methods for the prevention or treatment of beta amyloid protein deposition associated with Alzheimer's disease.
Background of the invention
[0002] Beta amyloid is a group of proteins formed after sequential cleavage of the amyloid precursor protein (APP) by secretases. The most common isoforms of beta amyloid are 40 and 42 amino acids length proteins. Beta amyloid protein deposition are believed to be responsible for the pathology of a number of neurodegenerative diseases including, but not limited to, Alzheimer's disease. The production and accumulation of beta amyloid protein is central to the pathogenesis of Alzheimer's disease (AD). Cummings JL, Alzheimer's disease. N. Engl. J. Med., 2004, 351: 56-67. The pathological amyloid cascade progresses from the generation of the beta amyloid protein, from the amyloid precursor protein (APP), through multiple secondary steps, to cell death. Accordingly, prevention or treatment of beta amyloid protein deposition is considered to be a promising approach for the prevention and treatment of AD. Beta amyloid protein deposition in retinal cells of the eyes has been linked to pathogenesis of glaucoma and age- related macular degeneration (AMD). McKinnon et al., IOVS, 2002, 43(4): 1077- 1087. Thus, there is a great need in safe and effective agents for preventing or treating beta amyloid protein deposition to prevent or treat beta amyloid-induced diseases, e.g. Alzheimer's disease, glaucoma, and AMD.
[0003] Current approaches to the treatment of beta amyloid protein deposition include development of gamma-secretase inhibitors to modulate processing APP and low beta amyloid levels in tissues and development of vaccines against beta amyloid and plaques thereof. However, nothing is published or disclosed in the art
related to the use of succinic acid or salts thereof for preventing or treating beta amyloid protein deposition in subjects in need thereof.
[0004] Surprisingly, it has been found that succinic acid or salts thereof is useful for preventing or treating beta amyloid protein deposition in mammals in need thereof.
[0005] It is an object of the present invention to provide the use of succinic acid or a pharmaceutically acceptable salt thereof in methods and compositions useful for preventing or treating amyloid beta protein deposition in a mammal in need thereof.
Detailed Description of the Invention
[0006] The present invention provides a method of preventing or treating amyloid beta protein deposition in a mammal in need thereof comprising administering to said mammal an effective amount of succinic acid or a pharmaceutically acceptable salt thereof.
[0007] As used herein, the term "succinic acid", which is also named butanedioic acid, refers to a compound of formula HOOCCH2CH2COOH, CAS RN 110-15-6.
[0008] As used herein, the term "a pharmaceutically acceptable salt" refers to nontoxic base addition salts. The pharmaceutically acceptable salts of the present invention are prepared by a reaction of succinic acid with a pharmaceutically acceptable organic or inorganic base by methods well-known from the art. Such bases include, but are not limited to, nontoxic alkali metal and akaline earth bases, for example, calcium, lithium, sodium, and potassium hydroxide; ammonium hydroxide and nontoxic organic bases, such as triethylamine, butylarnine, dimethylethanolamine, diethanolamine, triethanolamine, 2-ethyl-6-methyl-3- hydroxypyridine, and choline base.
[0009] Preferably, the pharmaceutically acceptable salt of the present invention is a monocholine salt of a formula (I)
(CH3)SNCH2CH2OH "0OCCH2CH2COOH (I)
or a pharmaceutically acceptable salt thereof.
[0010] More preferably, the pharmaceutically acceptable salt of the present invention is dicholine salt of a formula (II)
[(CHg)3NCH2CH2OH]2 "θOCCH2CH2GOθ" (H)
[0011] As used herein, the term "an effective amount" refers to the amount of the succinic acid or a pharmaceutically acceptable salt thereof that is required for preventing or treating amyloid beta protein deposition in the subject. Effective amounts may vary, as recognized by those skilled in the art, depending on route of administration, excipient usage, and the possibility of co-usage with other agents.
[0012] Preferably, the effective amount of succinic acid or a pharmaceutically acceptable salt thereof for the use in the method of the present invention is 0.1 to 100 mg/kg body weight per day. More preferably, the effective amount of succinic acid or a pharmaceutically acceptable salt thereof for use in the method of the present invention is 1 to 10 mg/kg body weight per day.
[0013] The succinic acid or a pharmaceutically acceptable salt thereof may be administered to a mammal by a variety of routes. Preferably, the succinic acid or a pharmaceutically acceptable salt thereof is administered by a route selected from the group consisting of oral, oromucosal, sublingual, buccal, intranasal, topical, parenteral, intraocular, intramuscular, subcutaneous, intravenous, and intraperitoneal administration.
[0014] Preferably, the succinic acid or a pharmaceutically acceptable salt thereof is administered for a period of one day or longer. More preferably, the succinic acid or a pharmaceutically acceptable salt thereof is administered by courses for a period of 5 to 7 days, singly-a-day, with break between courses of two to four weeks.
[0015] Preferably, the mammal is a human.
[0016] As used herein, the term "amyloid beta protein deposition" refers to a process of increase and deposition of amyloid beta protein in a mammalian body. Such amyloid beta protein deposition induces or is associated with a variety of disease states, including Alzheimer's disease, Down's syndrome, glaucoma, and age-related macular degeneration (AMD). Preferably, such deposition is associated with Alzheimer's disease.
[0017] As used herein, the term "beta amyloid protein" refers to a protein formed by sequential cleavage of the amyloid precursor protein (APP), and dimers and oligomers thereof, and aggregates thereof including protein constituents of fibril deposits and amyloid plaques. Nonexclusive examples of such proteins include beta amyloid peptides of 39 to 43 amino acid residues in length.
[0018] As used herein, the term "preventing or treating" refers to the management and care of a mammal for the purpose of (a) preventing the amyloid beta protein deposition from occurring in a subject which may be predisposed to such deposition but has not yet been diagnosed as having it; (b) inhibiting the amyloid beta protein deposition, i.e., arresting its development; or (c) relieving the amyloid beta protein deposition, i.e., causing regression of the amyloid beta protein deposition.
[0019] According to the methods of the present invention, a beta amyloid protein- induced disease is treated or prevented in a subject, such as a human or another mammal, by administering to the subject an effective amount of succinic acid or a pharmaceutically acceptable salt thereof. The term "beta amyloid-induced disease", as used herein, refers to a disease state that is characterized by beta amyloid deposition and the formation and aggregation of beta amyloid protein fibril deposits or plaques, such as, for example, Alzheimer's disease, Down's syndrome, glaucoma, and age-related macular degeneration (AMD).
[0020] As used herein, the term "Alzheimer's disease" refers to a condition associated with formation of neuritic plaques comprised primarily of beta amyloid protein primarily in the hippocampus and cerebral cortex, as well as neurofibrillary tangles and impairment in both learning and memory.
[0021] Further, the present invention provides the use of succinic acid or a pharmaceutically acceptable salt thereof for manufacturing a pharmaceutical composition for preventing or treating amyloid beta protein deposition in a mammal in need thereof.
[0022] Further, the present invention provides a pharmaceutical composition for preventing or treating amyloid beta protein deposition in a mammal in need thereof comprising (a) succinic acid or a pharmaceutically acceptable salt thereof and (b) a pharmaceutically acceptable carrier.
[0023] As used herein, the term « pharmaceutically acceptable carrier" refers to a pharmaceutically-acceptable material, composition or vehicle, such as a liquid or solid filler, diluent, excipient, solvent, or encapsulating material, involved in carrying or transporting a chemical agent from one organ or portion of the body to another organ, or portion of the body. Some examples which can serve as pharmaceutically acceptable carriers include: sugars, such as lactose, glucose and sucrose; starches, such as corn starch and potato starch; cellulose and its derivatives, such as sodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate; powdered tragacanth; malt; gelatin; talc; excipients , such as cocoa butter and suppository waxes; oils, such as sesame oil, olive oil, corn oil and soybean oil; glycols, such as propylene glycol; polyols, such as glycerin, sorbitol, mannitol and polyethylene glycol; esters, such as ethyl oleate and ethyl laurate; agar; buffering agents, such as magnesium hydroxide and aluminum hydroxide; alginic acid; pyrogen-free water; isotonic saline; Ringer's solution; ethyl alcohol; phosphate buffer solutions; and other non-toxic compatible substances employed in pharmaceutical formulations.
[0024] The compositions of the invention are prepared by known procedures using well-known ingredients. The composition of the invention can comprise optional ingredients. Such optional ingredients generally are used individually at levels from about 0.0005% to about 10.0%, preferably from about 0.005% to about 1.0% by weight of the composition. Examples of suitable optional ingredients include, but are not limited to, buffers, lubricants, colorants, carriers, and etc.
[0025] The following examples are presented to demonstrate the invention. The examples are illustrative only and are not intended to limit the scope of the invention in any way.
Example 1. [0026] This example demonstrates the method of the present invention.
Effect of succinic acid or salts thereof on the beta amyloid deposition was assessed in a rodent model of permanent bilateral carotid artery occlusion (2VO). 2VO animal model mimics morphological and behavioral pathology of Alzheimer's disease. Weinstock et a!.. J. Neural. Transm. 2004. I l l: 347-366. 2VO occlusion in rats aged ten months induces abnormal cleavage of APP resulting in the accumulation of extracellular deposits of beta amyloid in the brain cortex ten weeks later. Bennett SA, et al. Neurobiol Aging. 2000. 21(2):207-14. Rats were randomly assigned into groups by five rats per a group. Control sham- operated rats received two courses of i.p. injections of saline once-a-day for seven days with break of three weeks. Rats in treatment groups received two courses of i.p. injections of disodium succinate or dicholine succinate in dose of 25 mg/kg once-a-day for seven days with break of three weeks. Data are presented as beta amyloid accumulation mean ± SEM in brain quantified by ELISA in brain diethylamine extracts.
*Differs significantly of Control (P < 0.05).
Thus, treatment with succinic acid salts is useful for lowering beta amyloid deposition.
Example 2
[0027] This example demonstrates injection formulation comprising compound of formula (II).
Ingredient Content
Compound of formula (II) 200 mg Disodium phosphate USP/Ph Eur qs to pH 5.5 Water for injections USP/Ph Eur to 5.0 ml
Compound of formula (II) is dissolved in water for injection to the desired volume, 0.4M disodium phosphate is added to pH 5.0. In this manner, solution with concentration of compound of formula (I) of 5% is prepared. The solution is filtered through a sterilizing grade filter (0.2 μm), and filled into ampoules.
Example 3
[0028] This example demonstrates ocular formulation comprising compound of formula (II)
Ingredient Content
Compound of formula (II) 100 mg
Disodium phosphate USP/Ph Eur qs to pH 5.5
Ethylcellulose 60 mg
Water for injections USP/Ph Eur to 10.0 ml
The ophthalmic gel preparation: Compound of formula (II) is mixed with above-mentioned ingredients in the conventional manner to prepare the gel.
Claims
1. A method of preventing or treating amyloid beta protein deposition in a mammal in need thereof comprising administering to said mammal an effective amount of succinic acid or a pharmaceutically acceptable salt thereof.
2. The method of claim 1, wherein the pharmaceutically acceptable salt of succinic acid is a monocholine salt of a formula (I)
{CH3)3NCH2CH2θH "0OCCH2CH2COOH (1)
or a pharmaceutically acceptable salt thereof.
3. The method of claim 1, wherein the pharmaceutically acceptable salt of succinic acid is dicholine salt of a formula (II)
[(CH3J3NCH2CH2OH]2 0OCCH2CH2COO (M)
4. The method of claim 1, wherein the effective amount of succinic acid or a pharmaceutically acceptable salt thereof is 0.1 to 100 mg/kg body weight per day.
5. The method of claim 1, wherein the succinic acid or a pharmaceutically acceptable salt thereof is administered by a route selected from the group consisting of oral, oromucosal, sublingual, buccal, intranasal, topical, parenteral, intraocular, intramuscular, subcutaneous, intravenous, and intraperitoneal administration.
6. The method of claim 1, wherein the succinic acid or a pharmaceutically acceptable salt thereof is administered for a period of one day or longer.
7. The method of claim 1 , wherein the mammal is a human.
8. The method of claim 1, wherein the amyloid beta protein deposition is associated with Alzheimer's disease, Down's syndrome, glaucoma, and age-related macular degeneration (AMD).
9. The method of claim 8, wherein the amyloid beta protein deposition is associated with Alzheimer's disease.
10. The use of succinic acid or a pharmaceutically acceptable salt thereof for manufacturing a pharmaceutical composition for preventing or treating amyloid beta protein deposition in a mammal in need thereof.
11. The use of claim 10, wherein the pharmaceutically acceptable salt of succinic acid is a monocholine salt of a formula (I)
(CH3)3NCH2CH2OH "0OCCH2CH2COOH (I)
or a pharmaceutically acceptable salt thereof.
12. The use of claim 10, wherein the pharmaceutically acceptable salt of succinic acid is dicholine salt of a formula (II)
[(CH3)3NCH2CH2θH]2 "θOCCH2CH2COθ" 00
13. The use of claim 10, wherein the pharmaceutical composition is administered by a route selected from the group consisting of oral, oromucosal, sublingual, buccal, intranasal, topical, parenteral, intraocular, intramuscular, subcutaneous, intravenous, and intraperitoneal administration.
14. The use of claim 10, wherein the mammal is a human.
15. The use of claim 10, wherein the amyloid beta protein deposition is associated with Alzheimer's disease, Down's syndrome, glaucoma, and age-related macular degeneration (AMD).
16. The use of claim 15, wherein the amyloid beta protein deposition is associated with Alzheimer's disease.
17. A pharmaceutical composition for preventing or treating amyloid beta protein deposition in a mammal in need thereof comprising (a) succinic acid or a pharmaceutically acceptable salt thereof and (b) a pharmaceutically acceptable carrier.
18. The pharmaceutical composition of claim 17, wherein the pharmaceutically acceptable salt of succinic acid is a monocholine salt of a formula (I)
(CH3)3NCH2CH2θH "0OCCH2CH2COOH (I)
or a pharmaceutically acceptable salt thereof.
19. The pharmaceutical composition of claim 17, wherein the pharmaceutically acceptable salt of succinic acid is dicholine salt of a formula (II)
[(CH3)3NCH2CH2θH]2 "θOCCH2CH2COθ" (H)
20. The pharmaceutical composition of claim 17, wherein said composition is administered by a route selected from the group consisting of oral, oromucosal, sublingual, buccal, intranasal, topical, parenteral, intraocular, intramuscular, subcutaneous, intravenous, and intraperitoneal administration.
21. The pharmaceutical composition of claim 17, wherein the amyloid beta protein deposition is associated with Alzheimer's disease, Down's syndrome, glaucoma, and age-related macular degeneration (AMD).
22. The pharmaceutical composition of claim 21, wherein the amyloid beta protein deposition is associated with Alzheimer's disease.
23. The pharmaceutical composition of claim 17, wherein the mammal is a human.
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| PCT/RU2008/000593 WO2010033045A1 (en) | 2008-09-16 | 2008-09-16 | Compositions and methods for prevention or treatment of beta amyloid deposition |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20110237668A1 (en) * | 2008-11-26 | 2011-09-29 | Igor Anatolievich Pomytkin | Choline salts of succinic acid for the treatment of depression, anxiety, schizophrenia, sleep disorder, and epilepsy |
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