HMGB1 antagonist treatment of severe sepsis
The present invention is related to the use of HMGB1 antagonists such as K883 in the treatment and/or prevention and/or inhibition of severe sepsis in mammals, e.g., humans, and pharmaceutical compositions for the same comprising HMGB1 antagonists in an effective amount to treat and/or prevent and/or inhibit this condition.
1. A method of treating or inhibiting sepsis in a mammal that is undergoing surgery or is being administered anticoagulants, which comprises administering to the mammal a therapeutically effective amount of a peptidomimetic small molecule of the formula:
wherein:
R 1 is CH or N; and
R 2 is CH or N,
provided that at least one of R 1 or R 2 is N,
prior to the surgery or the administration of the anticoagulants.
2. The method of claim 1 , wherein the therapeutically effective amount is orally administered to the mammal.
3. The method of claim 1 , wherein the therapeutically effective amount is intravenously administered to the mammal.
4. The method of claim 1 , wherein the mammal is human.
5. The method of claim 1 , wherein R 1 is CH and R 2 is N.
6. The method according to claim 1 , wherein R 1 is N and R 2 is CH.
7. The method of claim 1 , wherein the peptidomimetic molecule is of the formula:
8. A method of treating and/or inhibiting sepsis in a mammal in need thereof comprising administering to the mammal a therapeutically effective amount of a peptidomimetic molecule of the formula
wherein:
R 1 is CH or N; and
R 2 is CH or N,
provided that at least one of R 1 or R 2 is N.
9. The method of claim 8 , wherein R 1 is CH and R 2 is N.
10. The method according to claim 8 , wherein R 1 is N and R 2 is CH.
11. The method of claim 8 , wherein the peptidomimetic molecule is of the formula:
12. The method of claim 11 , wherein the sepsis is severe sepsis.
13. The method of claim 11 , wherein the peptidomimetic molecule is combined with an excipient comprising PBS:PEG 300:propylene glycol:polysorbate 80 at 50:40:5:5.
14. The method of claim 11 , wherein the method of administration is selected from the group consisting of oral delivery, parenteral delivery, buccal delivery, sublingual delivery, nasal delivery, inhalation delivery, nebulization delivery, topical delivery, transdermal delivery and suppository delivery.
15. The method of claim 11 , wherein the therapeutically effective amount is orally administered to the mammal.
16. The method of claim 11 , wherein the therapeutically effective amount is intravenously administered to the mammal.
17. The method of claim 11 , wherein the mammal is human.
18. The method of claim 8 , wherein the sepsis is severe sepsis.
19. The method of claim 8 , wherein the mammal is a human.
20. The method of claim 8 , wherein the method of administration is selected from the group consisting of oral delivery, parenteral delivery, buccal delivery, sublingual delivery, nasal delivery, inhalation delivery, nebulization delivery, topical delivery, transdermal delivery and suppository delivery.