Combinations for the treatment of inflammatory disorders

• US 6,897,206 B2
• Filed: 07/09/2002
• Issued: 05/24/2005
• Est. Priority Date: 07/09/2001
• Status: Expired due to Fees

• Current Assignee: Zalicus Inc. (EPIRUS Biopharmaceuticals, Inc.)
• Original Assignee: CombinatoRx, Inc. (EPIRUS Biopharmaceuticals, Inc.)
• Inventors: Manivasakam, Palaniyandi, Keith, Curtis, Zimmermann, Grant, Borisy, Alexis, Jost-Price, Edward Roydon, Sackeyfio, Robyn, Hurst, Nicole, Fong, Jason
• Primary Examiner(s): Dodson, Shelley A.
• Assistant Examiner(s): George, Konata M.
• Application Number:
  US10/191,149
• Publication Number:
  US 20030078246A1
• Time in Patent Office: 1,050 Days
• Field of Search: 514169-171, 514/825, 514/826, 514/863, 514/866
• US Class Current: 514/171
• 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 31/55 having seven-membered rings, e.g. azelastine, pentylenetetrazole
• CPC Class Codes: A61K 31/551 having two nitrogen atoms, e.g. dilazep
• CPC Class Codes: A61K 31/553 having at least one nitrogen and one oxygen as ring hetero atoms, e.g. loxapine, staurosporine
• CPC Class Codes: A61K 31/56 Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/10 Laxatives
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• 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 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 Immunomodulators
• 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: G01N 2500/10 : involving cells
• CPC Class Codes: G01N 33/6863 : Cytokines, i.e. immune system proteins modifying a biological response such as cell growth proliferation or differentiation, e.g. TNF, CNF, GM-CSF, lymphotoxin, MIF or their receptors

Abstract

The invention features a method for treating a patient having an inflammatory disorder, by administering to the patient (i) a tricyclic antidepressant (e.g., amoxapine); and (ii) a corticosteroid (e.g., prednisolone) simultaneously or within 14 days of each other in amounts sufficient to reduce or inhibit inflammation.

Claims

1. A method for treating a patient having an inflammatory disorder, said method comprising administering to said patient (i) a tricyclic antidepressant;

and (ii) a corticosteroid, wherein the drugs (i) and (ii) are administered simultaneously or within 14 days of each other, in amounts sufficient to reduce or inhibit inflammation in said patient, wherein said tricyclic antidepressant and/or said corticosteroid is administered orally, intravenously, ocularly, or by inhalation.

2. The method of claim 1, wherein said tricyclic antidepressant is amoxapine, 8-hydroxyamoxapine, 7-hydroxyamoxapine, loxapine, loxapine succinate, loxapine hydrochloride, 8-hydroxyloxapine, amitriptyline, clomipramine, doxepin, imipramine, trimipramine, desipramine, nortriptyline, clothispine, perlapine, fluperlapine, or protriptyline.

3. The method of claim 2, wherein said tricyclic antidepressant is amoxapine.

4. The method of claim 1, wherein said corticosteroid is dexamethasone, betamethasone, triamcinolone, triamcinolone acetonide, triamcinolone diacetate, triamcinolone hexacetonide, beclomethasone, dipropionate, beclomethasone dipropionate monohydrate, flumethasone pivalate, diflorasone diacetate, fluocinolone acetonide, fluorometholone, fluorometholone acetate, clobetasol propionate, desoximethasone, fluoxymesterone, fluprednisolone, hydrocortisone, hydrocortisone acetate, hydrocortisone butyrate, hydrocortisone sodium phosphate, hydrocortisone sodium succinate, hydrocortisone cypionate, hydrocortisone probutate, hydrocortisone valerate, cortisone acetate, paramethasone acetate, methylprednisolone, methylprednisolone acetate, methylprednisolone sodium succinate, prednisolone, prednisolone acetate, prednisolone sodium phosphate, prednisolone tebutate, clocortolone pivalate, flucinolone, dexamethasone 21-acetate, betamethasone 17-valerate, isoflupredone, 9-fluorocortisone, 6-hydroxydexamethasone, dichlorisone, meclorisone, flupredidene, doxibetasol, halopredone, halometasone, clobetasone, diflucortolone, isoflupredone acetate, fluorohydroxyandrostenedione, beclomethasone, flumethasone, diflorasone, fluocinolone, clobetasol, cortisone, paramethasone, clocortolone, prednisolone 21-hemisuccinate free acid, prednisolone metasulphobenzoate, prednisolone terbutate, or triamcinolone acetonide 21-palmitate.

5. The method of claim 4, wherein said corticosteroid is prednisolone.

6. The method of claim 1, wherein said tricyclic antidepressant is administered in a dosage amount equivalent to 1-600 milligrams of amoxapine.

7. The method of claim 6, wherein said tricyclic antidepressant is administered in a dosage amount equivalent to 100-300 milligrams of amoxapine.

8. The method of claim 1, wherein said corticosteroid is administered in a dosage amount equivalent to 0.05-200 milligrams of prednisolone.

9. The method of claim 8, wherein said corticosteroid is administered in a dosage amount equivalent to 0.05-5 milligrams of prednisolone.

10. The method of claim 9, wherein said corticosteroid is administered in a dosage amount equivalent to 0.1-3 milligrams of prednisolone.

11. The method of claim 1, wherein said tricyclic antidepressant and said corticosteroid are administered within ten days of each other.

12. The method of claim 11, wherein tricyclic antidepressant and said corticosteroid are administered within five days of each other.

13. The method of claim 12, wherein tricyclic antidepressant and said corticosteroid are administered within twenty-four hours of each other.

14. The method of claim 13, wherein tricyclic antidepressant and said corticosteroid are administered simultaneously.

15. The method of claim 1, wherein said inflammatory disorder is an immunoinflammatory disorder.

16. The method of claim 15, wherein said immunoinflammatory disorder is rheumatoid arthritis, psoriasis, ulcerative colitis, Crohn'"'"'s disease, or stroke induced brain cell death.

17. The method of claim 16, wherein said immunoinflammatory disorder is rheumatoid arthritis.

18. The method of claim 1, wherein said inflammatory disorder is an autoimmune disease.

19. The method of claim 18, wherein said autoimmune disease is asthma, multiple sclerosis, type I diabetes, systemic lupus erythematosus, scleroderma, systemic sclerosis, or Sjö

gren'"'"'s syndrome.

30. The method of claim 1, wherein said tricyclic antidepressant is amoxapine and said corticosteriod is prednisolone.

31. The method of claim 30, wherein said immunoinflammatory disorder is rheumatoid arthritis.

32. The method of claim 30, wherein said immunoinflammatory disorder is psoriasis.

33. The method of claim 30, wherein said immunoinflammatory disorder is ulcerative colitis.

34. The method of claim 30, wherein said immunoinflammatory disorder is Crohn'"'"'s disease.

20. A method for treating a patient having an inflammatory disorder, said method comprising administering to said patient a pharmaceutical composition comprising a pharmaceutically acceptable carrier and the drugs (i) amoxapine and (ii) prednisolone, at dosages that together reduce or inhibit inflammation in said person wherein said composition is administered orally, intravenously, ocularly, or by inhalation.

21. The method of claim 20, wherein drug (i) is present in said composition in an amount of 1-600 milligrams.

22. The method of claim 21, wherein drug (i) is present in said composition in an amount of 100-300 milligrams.

23. The method of claim 20, wherein drug (ii) is present in said composition in an amount of 0.05-200 milligrams.

24. The method of claim 23, wherein drug (ii) is present in said composition in an amount of 0.05-5 milligrams.

25. The method of claim 24, wherein drug (ii) is present in said composition in an amount of 0.1-3 milligrams.

26. The method of claim 20, wherein said inflammatory disorder is rheumatoid arthritis.

27. The method of claim 20, wherein said inflammatory disorder is psoriasis.

28. The method of claim 20, wherein said inflammatory disorder is ulcerative colitis.

29. The method of claim 20, wherein said inflammatory disorder is Crohn'"'"'s disease.