Neurotherapeutic composition and method therefor

• US 20030158172A1
• Filed: 08/20/2002
• Published: 08/21/2003
• Est. Priority Date: 02/14/2001
• Status: Abandoned Application

• Current Assignee: Gary A. Koppel, Michael O. Chaney
• Original Assignee: Gary A. Koppel, Michael O. Chaney
• Inventors: Koppel, Gary A., Chaney, Michael O.
• Application Number:
  US10/224,124
• Publication Number:
  US 20030158172A1
• Time in Patent Office: Days
• US Class Current: 514/192
• 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 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/197 the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid carnitine A61K31/205
• 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 31/395 having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
• 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 31/4353 ortho- or peri-condensed with heterocyclic ring systems
• CPC Class Codes: A61K 31/536 ortho- or peri-condensed with carbocyclic ring systems
• CPC Class Codes: A61K 31/5365 ortho- or peri-condensed with heterocyclic ring systems
• CPC Class Codes: A61K 31/5383 ortho- or peri-condensed with heterocyclic ring systems
• CPC Class Codes: A61K 31/545 Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula: , e.g. cephalosporins, cefaclor, or cephalexine
• CPC Class Codes: A61K 31/546 containing further heterocyclic rings, e.g. cephalothin
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/22 Anxiolytics

Abstract

Neurotherapeutically pharmaceutical effective compositions are prepared using carboxypeptidase E inhibitors. One class of carboxypeptidase E inhibitors found to exhibit significant neurotropic activity are β-lactam compounds, particularly penam and cephem β-lactam antibiotics and non-antibiotic derivatives thereof.

Claims

1. A method of manufacturing a pharmaceutical composition useful for treatment of behavioral disorders and enhancing cognitive function in patients in need of such therapy, said method comprising the steps of combining an inhibitor of carboxypeptidase E with a pharmaceutically acceptable carrier and forming a unit dosage form comprising a neurotherapeutically effective amount of the carboxypeptidase E inhibitor.

2. The method of claim 1 wherein the carboxypeptidase E inhibitor is a compound comprising a β

-lactam ring structure.

3. The method of claim 2 wherein the carboxypeptidase E inhibitor is selected from the group consisting of penams, cephems, 1-oxa-1-dethia cephems, clavams, clavems, azetidinones, carbapenams, carbapenems and carbacephems.

4. The method of claim 2 wherein the carboxypeptidase E inhibitor is a penam or cephem compound.

5. The method of claim 2 wherein the carboxypeptidase E inhibitor is a penicillin or cephalosporin.

6. The method of claim 2 wherein the carboxypeptidase E inhibitor is a penam sulfoxide or sulfone.

7. The method of claim 2 wherein the carboxypeptidase E inhibitor is a cephem sulfoxide.

8. The method of claim 2 wherein the carboxypeptidase E inhibitor is a cephem sulfone.

9. The method of claim 2 wherein the carboxypeptidase E inhibitor is a sulfoxide or sulfone derivative of a penicillin or a cephalosporin.

10. The method of claim 2 wherein the carboxypeptidase E inhibitor is a 1-dethia-1-oxa-cephem.

11. The method of claim 2 wherein the carboxypeptidase E inhibitor is moxalactam or a pharmaceutically acceptable salt or ester thereof.

12. The method of claim 1 wherein the carboxypeptidase E inhibitor is a compound of the formula

13. A neurotherapeutic pharmaceutical composition in unit dosage form comprising a neurotherapeutically effective amount of a carboxypeptidase E inhibitor with the proviso that when the carboxypeptidase E inhibitor is a β

-lactam antibiotic, the neurotherapeutically effective amount of the carboxypeptidase E inhibitor in the unit dosage form is less than an antibiotically effective amount of the carboxypeptidase E inhibitor if such β

- lactam antibiotic were to be administered in a unit dosage form designed for the same route of administration.

14. The neurotherapeutic composition of claim 13 wherein the carboxypeptidase E inhibitor is a compound comprising a β

- lactam ring structure.

15. The neurotherapeutic composition of claim 13 wherein the carboxypeptidase E inhibitor is a penicillin or cephalosporin.

16. The neurotherapeutic composition of claim 13 wherein the carboxypeptidase E inhibitor is a cephem sulfoxide or sulfone.

17. The neurotherapeutic composition of claim 13 wherein the carboxypeptidase E inhibitor is a penam sulfoxide or sulfone.

18. The neurotherapeutic composition of claim 13 wherein the carboxypeptidase E inhibitor is a 1-dethia-1-oxa-cephem compound.

19. The neurotherapeutic composition of claim 13 wherein the carboxypeptidase E inhibitor is moxalactam or a pharmaceutically acceptable salt or ester thereof.

20. A neurotherapeutic pharmaceutical composition comprising a neurotherapeutically effective amount of a cephem sulfoxide and a pharmaceutically acceptable carrier thereof.

21. A neurotherapeutic pharmaceutical composition comprising a neurotherapeutically effective amount of a cephem sulfone and a pharmaceutically acceptable carrier thereof.

22. A neurotherapeutic pharmaceutical composition comprising a neurotherapeutically effective amount of a penam sulfoxide and a pharmaceutically acceptable carrier thereof.

23. A neurotherapeutic pharmaceutical composition comprising a neurotherapeutically effective amount of a penam sulfone and a pharmaceutically acceptable carrier thereof.