Amelioration of the development of cataracts and other ophthalmic diseases

• US 8,383,648 B2
• Filed: 06/18/2008
• Issued: 02/26/2013
• Est. Priority Date: 05/17/2002
• Status: Expired due to Fees

• Current Assignee: Colby Pharmaceutical Company
• Original Assignee: Colby Pharmaceutical Company
• Inventors: Matier, William L., Patil, Ghanshyam
• Primary Examiner(s): CHONG, YONG SOO
• Application Number:
  US12/141,166
• Publication Number:
  US 20080274983A1
• Time in Patent Office: 1,714 Days
• Field of Search: 514/18, 514/315, 514/317, 514/327
• US Class Current: 514/315
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/198 Alpha-amino acids, e.g. alanine or edetic acid [EDTA] betaine A61K31/205; proline A61K31/401; tryptophan A61K31/405; histidine A61K31/4172; peptides not degraded to individual amino acids A61K38/00
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: A61K 31/4525 containing a five-membered ring with oxygen as a ring hetero atom
• CPC Class Codes: A61K 31/454 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
• CPC Class Codes: A61K 31/4545 containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
• CPC Class Codes: A61K 31/496 Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• CPC Class Codes: A61K 31/5377 not condensed and containing further heterocyclic rings, e.g. timolol
• CPC Class Codes: A61K 31/541 Non-condensed thiazines containing further heterocyclic rings
• CPC Class Codes: A61K 38/063 Glutathione
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0048 Eye, e.g. artificial tears
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/12 for cataracts
• CPC Class Codes: A61P 39/06 Free radical scavengers or antioxidants
• CPC Class Codes: C07D 211/94 Oxygen atom, e.g. piperidine N-oxide
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 405/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 413/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 417/12 linked by a chain containing hetero atoms as chain links

Abstract

Ophthalmically acceptable compositions used in arresting the development of cataracts or macular degeneration comprising a pharmaceutically acceptable carrier or diluent and a compound having the formula:

• • where R₁ and R₂ are, independently, H or C₁ to C₃ alkyl;
  • R₃ and R₄ are, independently C₁ to C₃ alkyl; and
  • where R₁ and R₂, taken together, or R₃ and R₄, taken together, or both may be cycloalkyl;
  • R₅ is H, OH, or C₁ to C₆ alkyl;
  • R₆ is or C₁ to C₆ alkyl, alkenyl, alkynyl, or substituted alkyl or alkenyl;
  • R₇ is C₁ to C₆ alkyl, alkenyl, alkynyl, or substituted alkyl or alkenyl
  • or where R₆ and R₇, or R₅, R₆ and R₇, taken together, form a carbocycle or heterocycle having from 3 to 7 atoms in the ring.

Claims

1. A composition comprising a pharmaceutically acceptable carrier or diluent and a compound having the formula:

2. The composition of claim 1 wherein the substituted alkyl or alkenyl has at least one alkoxy, alkylthio, alkylamino, dialkylamino, aryloxy, arylamino, benzyloxy, benzylamino or heterocyclic or YCO—

Z where Y is O, N, or S and Z is alkyl, cycloalkyl or heterocyclic or aryl substituent.

3. The composition of claim 1 wherein the heterocycle is a 5, 6, or 7 membered ring with at least one oxygen, nitrogen, or sulfur atom in the ring.

4. The composition of claim 1 wherein R₆ and R₇, taken together, are furoyl or tetrahydrofuroyl.

5. The composition of claim 1 wherein each of R₁ through R₄ is C₁ to C₃ alkyl.

6. The composition of claim 1 wherein each of R₁ through R₄ is methyl.

7. The composition of claim 1 wherein R₆ is C₁ to C₆ alkyl substituted with at least one C₁ to C₆ alkoxy or benzyloxy group.

8. The composition of claim 1 wherein each of R₁ through R₄ is methyl, R₅ is H or methyl, R₆ is methyl substituted with benzyloxy or C₁ to C₆ alkoxy, and R₇ is methyl.

9. The composition of claim 1 wherein each of R₁ through R₄ is methyl, R₅ is methyl, R₆ is ethoxy methyl, and R₇ is methyl.

10. The composition of claim 1 wherein each of R₁ through R₄ is methyl, R₅ is methyl, R₆ is benzyloxy methyl, and R₇ is methyl.

11. The composition of claim 1 wherein each of R₁ through R₄ is methyl, R₅ is methyl, R₆ is hydroxymethyl, and R₇ is methyl.

12. The composition of claim 1 wherein each of R₁ through R₄ is methyl and R₅, R₆, and R₇ form a furanyl group.

13. The composition of claim 1 wherein each of R₁ through R₄ is methyl, R₅ is H and R₆, and R₇ form a tetrahydrofuranyl group.

14. The composition of claim 1 adapted for pharmaceutical use as an eye drop.

15. The composition of claim 1 further comprising a reducing agent.

16. The composition of claim 15 wherein the reducing agent is a sulfhydryl compound.

17. The composition of claim 1 further comprising mercaptopropionyl glycine, N-acetyl cysteine, β

-mercaptoethylamine, or glutathione.