Method and composition for treatment of inflammation and AIDS-associated neurological disorders

• US 20040039066A1
• Filed: 02/13/2003
• Published: 02/26/2004
• Est. Priority Date: 02/13/2002
• Status: Active Grant

• Current Assignee: Creagri Incorporated
• Original Assignee: Creagri Incorporated
• Inventors: Crea, Roberto
• Granted Patent: US 8,216,599 B2
• Time in Patent Office: Days
• US Class Current: 514/731
• 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 31/05 Phenols cannabinoids A61K31/658
• CPC Class Codes: A61K 31/7048 having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin , digitoxin or digoxin
• CPC Class Codes: A61P 1/02 Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 1/18 for pancreatic disorders, e.g. pancreatic enzymes
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 13/02 of urine or of the urinary tract, e.g. urine acidifiers
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• 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 27/02 Ophthalmic agents
• 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 31/04 Antibacterial agents
• CPC Class Codes: A61P 37/02 : Immunomodulators
• CPC Class Codes: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 37/08 : Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• 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: C07H 17/04 : Heterocyclic radicals containing only oxygen as ring hetero atoms

Abstract

A method of treating inflammation, an inflammatory condition, or AIDS-associated neurological disorder in a subject in need of such treatment is disclosed. The method includes administering to said subject a pharmaceutically effective amount of substantially purified hydroxytyrosol or a substantially purified mixture of hydroxytyrosol and oleuropein. Also disclosed are compositions for use in practicing the method.

Claims

1. A method of treating an AIDS-associated neurological disorder in a subject in need of such treatment, comprising administering to said subject a pharmaceutically effective amount of a treatment agent having a weight ratio of hydroxytyrosol to oleuropein of between about 1:

1 and about 200;

1.

2. The method of claim 1, wherein said weight ratio is between about 5:

1 and about 100;

1.

3. The method of claim 2, wherein said weight ratio is between about 10:

1 and about 50;

1.

4. The method of claim 2, wherein said agent is prepared by a process comprising the steps of:

(a) producing vegetation water from olives;

(b) adding acid to the vegetation water in an amount effective to produce a pH between about 1 and about 5;

(c) incubating the acidified vegetation water until at least 75% of oleuropein originally present in the vegetation water has been converted to hydroxytyrosol.

5. The method of claim 1, wherein said disorder is AIDS dementia.

6. The method of claim 1, wherein said administering comprises oral delivery.

7. The method of claim 1, wherein said administering further comprises administering a second disease treatment agent.

8. The method of claim 7, wherein said administering of the second treatment agent is before or after administration of the first treatment agent.

9. The method of claim 7, wherein said administering of a second treatment agent is coincident with administering the first treatment agent.

10. The method of claim 7, wherein said second agent is an antiretroviral agent.

11. The method of claim 1, wherein the agent is administered at a dosage of between about 0.1 mg/kg and 2000 mg/kg per day.

12. The method of claim 11, wherein the agent is administered at a dosage of between about 0.3 mg/kg and 1 mg/kg per day.

13. The method of claim 12, wherein the agent is administered at a dosage of about 0.6 mg/kg per day.

14. The method of claim 1, wherein said subject is a human.

15. The method of claim 1, wherein said agent is dried to provide a powder extract.

16. The method of claim 1, wherein said agent is in the form of a tablet, capsule, or pill.

17. The method of claim 1, wherein said agent is in the form of a liquid (drops).

18. A method of treating an AIDS-associated neurological disorder in a subject in need of such treatment, comprising administering to said subject a pharmaceutically effective amount of substantially purified hydroxytyrosol or a substantially purified mixture of hydroxytyrosol and oleuropein.

19. A method of treating a subject having an inflammatory condition characterized by a detectable clinical symptom or change in a level of a biochemical marker with respect to the normal range of the marker, the method comprising

administering to the subject a dose of an olive plant extract treatment agent having a weight ratio of hydroxytyrosol to oleuropein of between about 1:

1 and about 200;

1; and

continuing said administration until there is observed a return of the marker level to the normal range or a desired change in the clinical symptom,

where the marker or the clinical symptom is selected from the group consisting of

(i) the symptoms and markers in joint pain and swelling in the case of joint inflammation;

(ii) elevated levels of C-reactive protein in the case of coronary inflammation;

(iii) respiratory distress in the case of bronchial inflammation; and

(iv) elevated CSF levels of isoprostanes or functional or psychofunctional indicators in the case of neuro-inflammation.

20. The method of claim 19, wherein the marker is a cytokine selected from the group consisting of tumor necrosis factor-α

, interleukin-1, interleukin-6, and interleukin-8.

21. The method of claim 19, wherein the marker is selected from the group consisting of corticotrophin, cortisol and prolactin.

22. The method of claim 19, wherein said weight ratio is between about 5:

1 and about 100;

1.

23. The method of claim 22, wherein said weight ratio is between about 10:

1 and about 50;

1.

24. The method, according to claim 19, wherein said inflammatory condition is selected from the group consisting of rheumatoid arthritis, osteoarthritis, and other inflammatory conditions involving acute joint inflammation, chronic joint inflammation, or both.

25. The method of claim 19, wherein said extract is prepared by a process comprising the steps of:

(a) producing vegetation water from olives;

(b) adding acid to the vegetation water in an amount effective to produce a pH between about 1 and about 5;

(c) incubating the acidified vegetation water until at least 75% of oleuropein originally present in the vegetation water has been converted to hydroxytyrosol.

26. The method of claim 19, wherein said administering comprises a method selected from the group consisting of oral delivery, intramuscular injection, intravenous injection, transdermal delivery, and transmucosal delivery.

27. The method of claim 26, wherein said administering comprises oral delivery.

28. The method of claim 19, wherein said administering further comprises administering a second disease treatment agent.

29. The method of claim 28, wherein said administering of the second treatment agent is before or after administration of the first treatment agent.

30. The method of claim 28, wherein said administering of a second treatment agent is coincident with administering the first treatment agent.

31. The method of claim 28, wherein the second treatment agent comprises one or more of the components selected from the group consisting of glucosamine sulfate, chondroitin sulfate, sea cucumber extract, hydrolyzed shark cartilage, collagen II, and methylsulfonylmethane.

32. The method of claim 19, wherein the agent is administered at a dosage of between about 0.1 mg/kg and 2000 mg/kg per day.

33. The method of claim 32, wherein the agent is administered at a dosage of between about 0.3 mg/kg and 1 mg/kg per day.

34. The method of claim 33, wherein the agent is administered at a dosage of about 0.6 mg/kg per day.

35. The method of claim 19, wherein said subject is a human.

36. The method of claim 19, wherein said agent is dried to provide a powder extract.

37. The method of claim 19, wherein said agent is in the form of a tablet, capsule, or pill.

38. The method of claim 19, wherein said agent is in the form of a liquid or liquid drops.

39. A method of treating an inflammatory condition in a subject in need of such treatment, comprising administering to said subject a pharmaceutically effective amount of substantially purified hydroxytyrosol or a substantially purified mixture of hydroxytyrosol and oleuropein.

40. The method of claim 39, wherein said inflammatory condition is in response to a condition selected from the group consisting of:

delayed type hypersensitivity reaction, a symptom of psoriasis, an autoimmune disease, organ transplant, pain, fever, and tissue graft rejection.

41. The method of claim 40, wherein the autoimmune disease is selected from the group consisting of:

Reynaud'"'"'s syndrome, autoimmune thyroiditis, EAE, multiple sclerosis and lupus erythematosus.

42. The method of claim 39, wherein the inflammatory condition is in response to a condition selected from the group consisting of:

adult respiratory distress syndrome (ARDS), multiple organ injury syndromes secondary to septicemia or trauma, reperfusion injury of myocardial or other tissues, acute glomerulonephritis, reactive arthritis, dermatoses with acute inflammatory components, acute purulent meningitis or other central nervous system inflammatory disorders, thermal injury, hemodialysis, leukapheresis, ulcerative colitis, Crohn'"'"'s disease, necrotizing enterocolitis, granulocyte transfusion associated syndromes, and cytokine-induced toxicity.

43. The method of claim 39, wherein said inflammatory condition results from a condition selected from the group consisting of asthma, psoriasis, skin sunburn, inflammatory pelvic disease, inflammatory bowel disease, urethritis, uvitis, senusitis, pneumonitis, encephalitis, meningitis, myocarditis, nephritis, osteomyelitis, myositis, hepatitis, gastritis, enteritis, dermatitis, gingivitis, appendicitis, pancreatitis, cholocystitis and cholangititis.

44. The method of claim 39, wherein the inflammatory condition is an acute inflammatory reaction.

45. The method of claim 39, wherein the inflammatory condition is an allergic inflammatory reaction.