Substituted diketopiperazine analogs for use as drug delivery agents
View Patent ↗Disclosed are drug delivery systems for the delivery of small molecule and macromolecular drugs. More particularly, disclosed are substituted analogs of 3,6-di(alkyl-4 aminobutyl)-2,5-diketopiperazine (which may also be referred to DKP), their use in the formulation of both small molecule and macromolecular drugs including therapeutic, prophylactic and diagnostic agents, stabilizing agents and systems for their delivery.
1. A method of treating hyperglycemia in a patient in need thereof, comprising administering to the patient a composition comprising insulin and a substituted diketopiperazine having the general structure of:
wherein R is H or an alkyl group of 1-10 carbons; n or m=0-20; X is an amide, ester, sulfone, sulfoxide, amine, or ketone; and Y is an amide, acid, hydroxyl, phenol, phosphonic acid, or thiol.
2. The method of claim 1 wherein the hyperglycemia comprises diabetes.
3. The method of claim 2 wherein the diabetes is type 1 diabetes.
4. The method of claim 2 wherein the diabetes is type 2 diabetes.
5. The method of claim 1 wherein the administering comprises pulmonary delivery.
6. The method of claim 1 wherein R is hydrogen, n=2, m is C═C, X is —NHC(O)—, and Y is COOH.
7. The method of claim 1 wherein R is isopropyl, n=3, m is C═C, X is —NHC(O)—, and Y is COOH.
8. The method of claim 1 wherein the substituted diketopiperazine is (E)-3-(3-(3,6-dioxopiperazin-2-yl)propyl-carbamoyl)acrylic acid.
9. The method of claim 1 wherein the substituted diketopiperazine is (E)-3-(4-(5-isopropyl-3,6-dioxopiperazin-2-yl)-butylcarbamoyl)acrylic acid.
10. The method of claim 1 wherein the substituted diketopiperazine is (E)-3-(4-(3,6-dioxopiperazin-2-yl)butylcarbamoyl)-acrylic acid.
11. A method of treating hyperglycemia in a patient in need thereof, comprising administering to the patient a composition comprising insulin and a pharmaceutically-acceptable salt of a substituted diketopiperazine having the general structure of:
wherein R is H or an alkyl group of 1-10 carbons; n or m=0-20; X is an amide, ester, sulfone, sulfoxide, amine, or ketone; and Y is an amide, acid, hydroxyl, phenol, phosphonic acid, or thiol.
12. The method of claim 11 wherein the hyperglycemia comprises diabetes.
13. The method of claim 12 wherein the diabetes is type 1 diabetes.
14. The method of claim 12 wherein the diabetes is type 2 diabetes.
15. The method of claim 11 wherein the administering comprises pulmonary delivery.
16. The method of claim 11 wherein R is hydrogen, n=3, m is C═C, X is —NHC(O)—, and Y is COOH.
17. The method of claim 11 wherein R is hydrogen, n=2, m is C═C, X is —NHC(O)—, and Y is COOH.
18. The method of claim 11 wherein R is an isopropyl, n=3, m is C═C, X is —NHC(O)—, and Y is COOH.
19. The method of claim 11 wherein the cation is sodium.