Carbon-substituted diketopiperazine delivery systems
View Patent ↗Compositions useful in the delivery of active agents are provided. These delivery compositions include (a) an active agent; and (b) a carrier of at least one mono-C-substituted or di-C-substituted diketopiperazine. Methods for preparing these compositions and administering these compositions are also provided.
1. A delivery composition comprising:
(a) an active agent; and
(b) at least one di-C-substituted diketopiperazine of formula I:
wherein R and R 1 are each C 2 -C 24 alkenyl and have at least one functional group selected from the group consisting of O and carboxyl group, and at least one of R and R 1 contain a carboxyl group; and wherein R and R 1 are optionally interrupted by O or N, or a combination thereof.
2. A delivery composition as defined in claim 1 , comprising a microsphere.
3. A delivery composition as defined in claim 2 , wherein said microsphere comprises a microcapsule.
4. A delivery composition as defined in claim 2 , wherein said microsphere has a diameter of less than about 10 μm.
5. A delivery composition as defined in claim 1 , wherein said active agent comprises a fragrance.
6. A delivery composition as defined in claim 1 , wherein said active agent comprises a biologically active agent.
7. A delivery composition as defined in claim 6 , wherein said biologically active agent is selected from the group consisting of a peptide, a mucopolysaccharide, a carbohydrate, a lipid, a pesticide, or any combination thereof.
8. The delivery composition as defined in claim 7 , wherein said biologically-active agent is selected from the group consisting of human growth hormone, bovine growth hormone, growth hormone-releasing hormone, an interferon, interleukin-II, insulin, heparin, calcitonin, erythropoietin, atrial naturetic factor, an antigen, a monoclonal antibody, somatostatin, adrenocorticotropin, gonadotropin releasing hormone, oxytocin, vasopressin, vancomycin, desferrioxamine (DFO), or any combination of any of the foregoing.
9. A delivery composition as defined in claim 6 , wherein said biologically-active agent is selected from the group consisting of an interferon, interleukin-II, insulin, heparin, calcitonin, oxytocin, vasopressin, cromolyn sodium, vancomycin, DFO, or any combination of any of the foregoing.
10. A delivery composition as defined in claim 1 , wherein said diketopiperazine is derived from two α-amino acids.
11. A delivery composition as defined in claim 10 , wherein said two α-amino acids from which said diketopiperazine is derived are independently selected from the group consisting of glutamic acid, aspartic acid, tyrosine, phenylalanine, and optical isomers thereof.
12. A delivery composition as defined in claim 10 , wherein said two α-amino acids from which said diketopiperazine is derived are the same.
13. A delivery composition as defined in claim 10 , wherein said diketopiperazine is prepared by the thermal condensation of said two α-amino acids from which said diketopiperazine is derived.
14. A delivery composition as defined in claim 1 , further comprising (c) at least one enzyme inhibitor.
15. A dosage unit form comprising:
(A) a delivery composition as defined in claim 1 ; and
(B) (a) an excipient,
(b) a diluent,
(c) a disintegrant,
(d) a lubricant,
(e) a plasticizer,
(f) a colorant,
(g) a dosing vehicle, or
(h) any combination thereof.
16. A dosage unit form as defined in claim 15 , comprising an oral dosage unit form.
17. A method for preparing microspheres containing an active agent, said method comprising:
(A) solubilizing, in a solvent, at least one di-C-substituted diketopiperazine according to claim 1 ; and
(B) contacting said diketopiperazine solution with said active agent and a precipitator solution in which said diketopiperazine is insoluble.
18. A method as defined in claim 17 , wherein said diketopiperazine solution has a pH within a first range and said precipitator solution has a pH within a second range, said first range being different than said second range.