IP Library Granted Patent US 7,060,733
Granted Patent B2
US 7,060,733 · App. 10/218,518 · Granted Jun 13, 2006

Methods for treating pancreatitis with curcumin compounds and inhibitors of reactive oxygen species

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Quick Facts
Patent No.
US 7,060,733
App. No.
10/218,518
Granted
Jun 13, 2006
Kind
B2
Abstract

Disclosed are methods of treating, preventing, modulating, attenuating, or inhibiting a disease or a disorder associated with inflammation related to NF-κB activation in a subject which comprises administering to the subject at least one curcumin compound. Also disclosed are combination therapies comprising the administration of at least one curcumin compound and at least one ROS inhibitor. Pharmaceutical compositions and kits are also disclosed.

Claims (26)

1. A method of treating, modulating, attenuating, or inhibiting pancreatitis which comprises administering to a subject diagnosed with pancreatitis a curcumin compound having the following structural formula

wherein R 1 to R 6 are each independently hydrogen, NO 2 , alkyl, alkoxyl, acyl, hydroxyl, amino, alkylamino, dialkylamino, alkoxyl, carboxyl, or carbamoyl.

2. The method of claim 1 , which further comprises administering to the subject at least one reactive oxygen species (ROS) inhibitor selected from the group consisting of N-acetylcysteine, vitamins C, A and E, beta-carotene, allopurinol, carvediol, and coenzyme Q.

3. The method of claim 1 , which further comprising administering to the subject at least one supplementary active compound selected from the group consisting of corticosteroids, glucocorticoids, cyclooxygenase (COX) inhibitors, analgesics, substance P inhibitors, vanilloid receptor inhibitors, and other non-steroidal anti-inflammatory agents.

4. A method of modulating or attenuating the expression of IL-6, TNFα, KC, IL-8, or iNOS in pancreatic tissue in a subject diagnosed with pancreatitis comprising administering to said subject a curcumin compound having the following structural formula

wherein R 1 to R 6 are each independently hydrogen, NO 2 , alkyl, alkoxyl, acyl, hydroxyl, amino, alkylamino, dialkylamino, alkoxyl, carboxyl, or carbamoyl.

5. The method of claim 4 , which further comprises administering to the tissue at least one reactive oxygen species (ROS) inhibitor selected from the group consisting of N-acetylcysteine, vitamins C, A and E, beta-carotene, allopurinol, carvediol, and coenzyme Q.

6. The method of claim 4 , which further comprises administering to the tissue at least one supplementary compound selected from the group consisting of corticosteroids, glucocorticoids, cyclooxygenase (COX) inhibitors, analgesics, substance P inhibitors, vanilloid receptor inhibitors, and other non-steroidal anti-inflammatory agents.

7. A method of preventing or inhibiting the amount of IκBα and IκBβ from decreasing in pancreatic tissue in a subject diagnosed with pancreatitis comprising administering to said subject a curcumin compound having the following structural formula

wherein R 1 to R 6 are each independently hydrogen, NO 2 , alkyl, alkoxyl, acyl, hydroxyl, amino, alkylamino, dialkylamino, alkoxyl, carboxyl, or carbamoyl.

8. The method of claim 7 , which further comprises administering to the tissue at least one reactive oxygen species (ROS) inhibitor selected from the group consisting of N-acetylcysteine, vitamins C, A and E, beta-carotene, allopurinol, carvediol, and coenzyme Q.

9. The method of claim 7 , which further comprises administering to the tissue at least one supplementary compound selected from the group consisting of corticosteroids, glucocorticoids, cyclooxygenase (COX) inhibitors, analgesics, substance P inhibitors, vanilloid receptor inhibitors, and other non-steroidal anti-inflammatory agents.

10. A method of preventing or inhibiting the degradation of IκBα and IκBβ in pancreatic tissue in a subject diagnosed with pancreatitis comprising administering to said subject a curcumin compound having the following structural formula

wherein R 1 to R 6 are each independently hydrogen, NO 2 , alkyl, alkoxyl, acyl, hydroxyl, amino, alkylamino, dialkylamino, alkoxyl, carboxyl, or carbamoyl.

11. The method of claim 10 , which further comprises administering to the subject at least one reactive oxygen species (ROS) inhibitor selected from the group consisting of N-acetylcysteine, vitamins C, A and E, beta-carotene, allopurinol, carvediol, and coenzyme Q.

12. The method of claim 10 , which further comprises administering to the tissue at least one supplementary compound selected from the group consisting of corticosteroids, glucocorticoids, cyclooxygenase (COX) inhibitors, analgesics, substance P inhibitors, vanilloid receptor inhibitors, and other non-steroidal anti-inflammatory agents.

13. A method of inducing apoptosis and decreasing necrosis of pancreatic tissue in a subject diagnosed with pancreatitis comprising administering to said subject a curcumin compound having the following structural formula

wherein R 1 to R 6 are each independently hydrogen, NO 2 , alkyl, alkoxyl, acyl, hydroxyl, amino, alkylamino, dialkylamino, alkoxyl, carboxyl, or carbamoyl.

14. The method of claim 13 , which further comprises administering to the subject at least one reactive oxygen species (ROS) inhibitor selected from the group consisting of N-acetylcysteine, vitamins C, A and E, beta-carotene, allopurinol, carvediol, and coenzyme Q.

15. The method of claim 13 , which further comprises administering to the subject at least one supplementary compound selected from the group consisting of corticosteroids, glucocorticoids, cyclooxygenase (COX) inhibitors, analgesics, substance P inhibitors, vanilloid receptor inhibitors, and other non-steroidal anti-inflammatory agents.

16. A method of inhibiting AP-1 activation, NF-κB activation, trypsin activation, or neutrophil infiltration, in pancreatic tissue in a subject diagnosed with pancreatitis comprising administering to said subject a curcumin compound having the following structural formula

wherein R 1 to R 6 are each independently hydrogen, NO 2 , alkyl, alkoxyl, acyl, hydroxyl, amino, alkylamino, dialkylamino, alkoxyl, carboxyl, or carbamoyl.

17. The method of claim 16 , which further comprises administering to the tissue at least one reactive oxygen species (ROS) inhibitor selected from the group consisting of N-acetylcysteine, vitamins C, A and E, beta-carotene, allopurinol, carvediol, and coenzyme Q.

18. A method of activating or increasing caspase activity in pancreatic tissue in a subject diagnosed with pancreatitis comprising administering to said subject a curcumin compound having the following structural formula

wherein R 1 to R 6 are each independently hydrogen, NO 2 , alkyl, alkoxyl, acyl, hydroxyl, amino, alkylamino, dialkylamino, alkoxyl, carboxyl, or carbamoyl.

19. The method of claim 18 , which further comprises administering to the tissue at least one reactive oxygen species (ROS) inhibitor selected from the group consisting of N-acetylcysteine, vitamins C, A and E, beta-carotene, allopurinol, carvediol, and coenzyme Q.

Assignments (4)
CONFIRMATORY LICENSE Recorded Jul 16, 2010
From: UNIVERSITY OF CALIFORNIA
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 024701/0097 →
EXECUTIVE ORDER 9424, CONFIRMATORY LICENSE Recorded Oct 27, 2008
From: UNIVERSITY OF CALIFORNIA
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 021743/0910 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 6, 2004
From: REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE
To: VETERANS' AFFAIRS, THE UNITED STATES OF AMERICA AS REPRESENTED BY THE DEPARTMENT OF
Reel/Frame 015304/0809 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 15, 2002
From: PANDOL, STEPHEN J; GUKOVSKY, ILYA Y.
To: REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE
Reel/Frame 013194/0276 →