Agent for treating neuronal diseases

• US 5,707,649 A
• Filed: 08/05/1995
• Issued: 01/13/1998
• Est. Priority Date: 08/13/1993
• Status: Expired due to Term

• Current Assignee: Seikagaku Corporation
• Original Assignee: Seikagaku Corporation
• Inventors: Inokuchi, Jinichi, Usuki, Seigou
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): Sikha, Murthy
• Application Number:
  US08/464,683
• Time in Patent Office: 892 Days
• Field of Search: 424/450, 544/106, 544/89
• US Class Current: 424/450
• CPC Class Codes: A61K 31/5375 1,4-Oxazines, e.g. morpholine
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: 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
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 295/125 with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
• CPC Class Codes: C07D 295/13 to an acyclic saturated chain

Abstract

Disclosed is an agent for curing neuronal diseases caused by disorders of peripheral nervous system or central nervous system, which comprises a 2-acylaminopropanol derivative represented by the formula (I): ##STR1## wherein R¹ represents a phenyl group or cyclohexyl group each of which may be substituted by 1 to 3 same or different substituents selected from the group consisting of alkyl, alkoxy, hydroxy and nitro, or represents an alkyl group, and n represents an integer of 0 to 16! or a pharmaceutically acceptable salt thereof as an effective ingredient. It accelerates neurite extension and synapse formation by elevating biosynthesis of endogenous sphingoglycolipid of neurocytes, particularly ganglioside, whereby it can be used for curing various diseases of central nervous system and peripheral nervous system.

Claims

1. A liposome preparation composition for treating neuronal diseases treatable by elevating biosynthesis of endogenous glycosphingolipids (GSLs) of neurocytes comprising at least one 2-acylaminopropanol derivative of the formula ##STR4## wherein R¹ is phenyl or cyclohexyl, each of which may be substituted by 1 to 3 members selected from the group consisting of alkyl, alkoxy, hydroxy and nitro, or R¹ is alkyl and n is an integer of 0 to 16 and said derivative has efficacy for accelerating biosynthesis of glycosphingolipids, accelerating neurite extension and/or accelerating synapse formation, or a pharmaceutically acceptable salt thereof and a phospholipid.

2. The liposome preparation composition according to claim 1, wherein n of the formula (I) is 6 to 16.

3. The liposome preparation composition according to claim 1, wherein R¹ of the formula (I) is phenyl.

4. The liposome preparation composition according to claim 1, wherein the 2-acylaminopropanol derivative represented by the formula (I) is a L-threo isomer.

5. The liposome preparation composition according to claim 4, wherein the 2-acylaminopropanol derivative is a L-threo isomer of 1-phenyl-2-decanoylamino-3-morpholino-1-propanol, or a salt thereof.

6. The liposome preparation composition according to claim 1 wherein the liposome is capable of maintaining an effective concentration for exhibiting a pharmaceutical effect in brain when intravenously administered.

7. The liposome preparation composition according to claim 1 wherein the liposome is a nanosphere liposome.

8. A method of treating neuronal diseases treatable by elevating biosynthesis of endogenous glycosphingolipids (GLSs) of neurocytes in warm-blooded animals comprising administering to warm-blooded animals an amount of a liposome composition comprising at least one 2-acylaminopropanol derivative of the formula ##STR5## wherein R¹ is phenyl or cyclohexyl, each of which may be substituted by 1 to 3 members selected from the group consisting of alkyl, alkoxy, hydroxy and nitro, or R¹ is alkyl and n is an integer of 0 to 16 and said derivative has efficacy for accelerating biosynthesis of glycospyhingolipids, accelerating neurite extension and/or accelerating synapse formation, or a pharmaceutically acceptable salt thereof and a phospholipid sufficient to treat said neuronal diseases.

9. The method of claim 8 wherein the compound of Formula I is a L-threo isomer.

10. The method of claim 8 wherein the compound of Formula I is the L-threo isomer of 1-phenyl-2-decanoylamino-3-morpholino-1-propanol or a non-toxic, pharmaceutical acceptable acid addition salt thereof.