Use of beta-lactamase inhibitors as neuroprotectants

• US 20020002159A1
• Filed: 02/13/2001
• Published: 01/03/2002
• Est. Priority Date: 08/16/1999
• Status: Active Grant

• Current Assignee: Revaax Pharmaceuticals, LLC
• Original Assignee: Revaax Pharmaceuticals, LLC
• Inventors: Koppel, Gary A.
• Granted Patent: US 6,426,342 B2
• Time in Patent Office: Days
• US Class Current: 514/210.09
• CPC Class Codes: A61K 31/424 condensed with heterocyclic ring systems, e.g. clavulanic acid
• CPC Class Codes: A61K 31/43 Compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula , e.g. penicillins, penems
• CPC Class Codes: A61K 31/431 containing further heterocyclic rings, e.g. ticarcillin, azlocillin, oxacillin
• CPC Class Codes: A61K 9/0056 Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system

Abstract

Novel neuroprotectant compositions and methods are described. β-Lactamase inhibitors are used to prevent or reduce loss of neuronal cells and neuronal cell function in patients afflicted with or susceptible to disease states or conditions known to result in or cause neuronal tissue insult.

Claims

1. A method of treatment of a patient suffering from or susceptible to a condition known to result in loss of neuronal cells or loss of neuronal cell function, to reduce neuronal cell loss or function resulting from such condition, said method comprising the step of administering to said patient a neuroprotective amount of a bacterial β

-lactamase inhibitor.

2. A method for preventing neuronal damage or the progression of neuronal damage in a patient suffering from or susceptible to disease states causing such neuronal damage, said method comprising the step of administering to the patient a neuroprotective amount of a bacterial β

-lactamase inhibitor.

3. A method of treatment of a patient suffering from or susceptible to a condition known to result in or from loss of neuronal cells or loss of neuronal cell function to reduce loss of neuronal cells or neuronal cell function resulting from such condition, said method comprising the step of administering to said patient a neuroprotective amount of clavulanic acid, a pharmaceutically acceptable salt thereof, or an active ester thereof.

4. A method for preventing neuronal damage or the progression of neuronal damage in a patient suffering from or susceptible to such neuronal damage, said method comprising the step of administering to said patient a neuroprotective amount of clavulanic acid, a pharmaceutically acceptable salt thereof, or an active ester thereof.

5. A method of manufacturing a pharmaceutical composition useful for preventing neuronal damage or the progression of neuronal damage in a patient suffering from or susceptible to such damage, said method comprising the steps of preparing a pharmaceutical mixture consisting essentially of a bacterial β

-lactamase inhibitors and a pharmaceutically acceptable carrier, and using portions of said mixture to prepare dosage forms containing a neuroprotective amount of said β

-lactamase inhibitor.

6. The method of claim 5 wherein the β

-lactamase inhibitor is a compound comprising a β

-lactam ring structure.

7. The method of claim 5 wherein the unit dosage form is an oral dosage form.

8. The method of claim 5 wherein the unit dosage form is a parenteral dosage form.

9. The method of claim 5 wherein the unit dosage form is a suppository.

10. The method of claim 5 wherein the unit dosage form comprises a patch for transdermal delivery of the β

-lactamase inhibitor.

11. The method of claim 5 wherein the unit dosage form is a lozenge for buccal or sublingual administration of the β

-lactamase inhibitor.

18. The method of claim 5 wherein the pharmaceutically acceptable carrier is selected to provide controlled release of the β

-lactamase inhibitor after administration of the dosage form.

19. The method of claim 5 wherein the pharmaceutically acceptable carrier is selected to provide controlled release of the clavulanic acid, salt or ester after administration of the dosage form.

12. A method of manufacturing a pharmaceutical composition useful for preventing neuronal damage or the progression of neuronal damage in a patient suffering from or susceptible to such damage, said method comprising the steps of preparing a pharmaceutical mixture consisting essentially of clavulanic acid, or a pharmaceutically acceptable salt or ester form thereof.

13. The method of claim 12 wherein the unit dosage form is an oral dosage form.

14. The method of claim 12 wherein the unit dosage form is a parenteral dosage form.

15. The method of claim 12 wherein the unit dosage form is a suppository.

16. The method of claim 12 wherein the unit dosage form comprises a patch for transdermal delivery of the clavulanic acid or pharmaceutically acceptable salt or ester thereof.

17. The method of claim 12 wherein the unit dosage form is a lozenge for buccal or sublingual administration of the clavulanic acid or pharmaceutically acceptable salt or ester thereof.

20. A neuroprotective pharmaceutical composition consisting essentially of a neuroprotective amount of a β

-lactamase inhibitor and a pharmaceutically acceptable carrier therefor.