Neurotherapeutic clavulanate composition and method

• US 6,610,681 B1
• Filed: 08/16/2000
• Issued: 08/26/2003
• Est. Priority Date: 08/16/1999
• Status: Expired due to Term

• Current Assignee: Revaax Pharmaceuticals, LLC
• Original Assignee: Revaax Pharmaceuticals, LLC
• Inventors: Koppel, Gary A.
• Primary Examiner(s): Russel, Jeffrey E.
• Application Number:
  US09/640,362
• Time in Patent Office: 1,105 Days
• Field of Search: 519/210.06
• US Class Current: 514/210.06
• 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 31/5365 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 13/08 of the prostate
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 15/10 for impotence
• CPC Class Codes: A61P 21/02 Muscle relaxants, e.g. for tetanus or cramps
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/08 : Antiepileptics; Anticonvulsants
• CPC Class Codes: A61P 25/14 : for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/16 : Anti-Parkinson drugs
• CPC Class Codes: A61P 25/18 : Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/20 : Hypnotics; Sedatives
• CPC Class Codes: A61P 25/22 : Anxiolytics
• CPC Class Codes: A61P 25/24 : Antidepressants
• 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 25/32 : Alcohol-abuse
• CPC Class Codes: A61P 25/34 : Tobacco-abuse
• CPC Class Codes: A61P 29/00 : Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/00 : Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/06 : Antihyperlipidemics
• CPC Class Codes: A61P 3/10 : for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/12 : Antihypertensives
• CPC Class Codes: Y02A 90/10 : Information and communication technologies [ICT] supporting adaptation to climate change, e.g. for weather forecasting or climate simulation

Abstract

Administration of clavulanic acid and related compounds at low dosages provides significant neurotropic effects in warm-blooded vertebrates evidenced inter alia by anxiolytic and anti-aggressive behavior and enhanced cognition believed to be mediated by inhibition of neurogenic enzyme activity. Therapeutic methods for using such compounds and their pharmaceutical formulations are described.

Claims

1. A method of treatment of behavioral disorders in a patient in need of such treatment wherein the behavioral disorder is selected from aggressive disorder, obsessive-compulsive disorder, anxiety, depression or ADHD, said method comprising the step of administering a compound selected from the group consisting of clavulanic acid, pharmaceutically acceptable salts thereof, and active ester forms thereof hydrolyzable in vivo to clavulanic acid to said patient in an amount effective to modify patient behavior.

2. The method of claim 1 wherein the compound is administered as an antiaggressive agent to control impulsivity and violence in said patient, wherein said patient is afflicted with autism, Tourette'"'"'s syndrome, mental retardation, psychosis, mania, or senile dementia or wherein said patient has a personality disorder and history of inappropriate aggression.

3. The method of claim 1 wherein the compound is administered to a human patient suffering a behavioral disorder comprising anxiety.

4. The method of claim 1 wherein the compound is administered to a human patient suffering a behavioral disorder comprising ADHD.

5. The method of claim 1 further comprising the step of administering an effective amount of a P-glycoprotein efflux pump inhibitor.

6. The method of claim 1 wherein the neurologically active compound is administered in combination with an effective amount of a P-glycoprotein efflux pump inhibitor.

7. A method of treating prostate disease selected from prostate cancer or benign prostatic hyperplasia in a human patient, said method comprising the step of administering to said patient a composition comprising a compound selected from the group consisting of clavulanic acid, pharmaceutically acceptable salts, and ester forms thereof, wherein said compound is administered in an amount effective to retard the progress of the disease or to reduce the symptoms of the disease.

8. A pharmaceutical formulation in unit dosage form for neurotherapeutic use comprising about 0.1 to about 10 mg of clavulanic acid or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier, said formulation being free of clinically effective amounts of another β

-lactam antibiotic.

9. The formulation of claim 8 in an oral dosage form.

10. The formulation of claim 8 in a parental dosage form.

11. The formulation of claim 8 in a prolonged release dosage form.

12. The formulation of claim 8 in a lozenge dosage form.