HMGB1 antagonist treatment of diabetic peripheral neuropathy
The present invention is related to the use of HMGB1 antagonists, specifically derivatives of K883 in the treatment and/or prevention and/or inhibition of neuropathy pain, and in particular diabetic neuropathy 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 and/or inhibiting neuropathic pain 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.
2. The method of claim 1 , wherein R 1 is CH and R 2 is N.
3. The method of claim 1 , wherein R 1 is N and R 2 is CH.
4. The method of claim 1 , wherein the peptidomimetic molecule is of the formula:
5. A method of treating neuropathic pain in a mammal exhibiting symptoms of diabetic peripheral neuropathy which comprises 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.
6. The method of claim 5 , wherein the peptidomimetic molecule is of the formula:
7. The method of claim 1 , wherein the mammal is a human.
8. The method of claim 1 , 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.
9. The method of claim 4 , wherein the peptidomimetic molecule is combined with an excipient comprising PBS:PEG 300:propylene glycol:polysorbate 80 at 50:40:5:5.
10. The method of claim 1 , wherein the therapeutically effective amount is orally administered to the mammal.
11. The method of claim 1 , wherein the therapeutically effective amount is intravenously administered to the mammal.
12. The method of claim 1 , wherein the neuropathic pain is diabetic neuropathic pain.
13. The method of claim 4 , wherein the mammal is human.
14. The method of claim 4 , 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 4 , wherein the therapeutically effective amount is orally administered to the mammal.
16. The method of claim 4 , wherein the therapeutically effective amount is intravenously administered to the mammal.
17. The method of claim 4 , wherein the neuropathic pain is diabetic neuropathic pain.
18. The method of claim 1 , wherein the peptidomimetic molecule has an aqueous solubility of greater than about 1 mg/ml.
19. The method of claim 1 , wherein the peptidomimetic molecule is stable for greater than 60 minutes in plasma or simulated stomach acid.
20. The method of claim 4 , wherein the peptidomimetic molecule is stable for greater than 60 minutes in plasma or simulated stomach acid.