United States Patent:   5,976,569

Assignee:  Emisphere Technologies, Inc. (Tarrytown, NY)

Filed:  April 29, 1997

Compositions useful in the delivery of active agents are provided. These delivery compositions include (a) an active agent; and either (b)(1) a carrier of (i) at least one amino acid and (ii) at least one diketopiperazine or (b)(2) at least one mono-N-substituted, di-N-substituted, or unsubstituted diketopiperazine. Methods for preparing these compositions and administering these compositions are also provided.

SUMMARY OF THE INVENTION

Compositions useful in the delivery of active agents are provided. These delivery compositions comprise (a) an active agent; and (b) a carrier comprising (i) at least one amino acid or an ester or an amide thereof and (ii) at least one diketopiperazine. Preferably, the carrier comprises (i) at least two amino acids which are the same or different and (ii) at least one diketopiperazine. In an alternate embodiment, the delivery compositions comprise (a) an active agent, and (b) at least one mono-N-substituted, di-N-substituted, or unsubstituted diketopiperazine.

Biologically active agents and pharmacologically active agents may be incorporated as the active agent, and these compositions may be in the form of microspheres.

Also contemplated is a method for preparing these compositions wherein at least one active agent is mixed with a carrier as described above or wherein the carrier is solubilized in a solvent, and the carrier solution is contacted with the active agent and a precipitator solution in which the carrier is insoluble.

In a further embodiment, the compositions are administered, preferably orally, to animals.

Claim 1 of 38 Claims

1. A delivery composition comprising:

(a) an active agent; and

(b) a diketopiperazine having the formula:

wherein R¹, R², or R¹ and R² independently are hydrogen, C₁ -C₂₄ alkyl, C₁ -C₂₄ alkenyl, phenyl, naphtyl, (C₁ -C₁₀ alkyl)phenyl, (C₁ -C₁₀ alkenyl)phenyl, (C₁ -₁₀ alkyl)naphthyl, (C₁ -C₁₀ alkenyl)naphthyl, phenyl (C₁ -C₁₀ alkyl), phenyl (C₁ -C₁₀ alkenyl), naphthyl (C₁ -C₁₀ alkyl), and naphthyl (C₁ -C₁₀ alkenyl);

R¹ or R², or both R¹ and R², optionally, are independently substituted with C₁ -C₄ alkyl, C₁ -C₄ alkenyl, C₁ -C₄ alkoxy, --OH, --SH, and --CO₂ R³ or any combination thereof; wherein R³ is hydrogen, C₁ -C₄ alkyl, or C₁ -C₄ alkenyl;

R¹, R², or R¹ and R², optionally, are independently interrupted by oxygen, nitrogen, sulfur, or any combination thereof;

said phenyl, naphthyl, or phenyl and naphthyl groups, optionally, are independently substituted by C₁ -C₆ alkyl, C₁ -C₆ alkenyl, C₁ -C₆ alkoxy, --OH, --SH, or CO₂ R⁴ wherein R⁴ is hydrogen, C₁ -C₆ alkyl; or C₁ -C₆  alkenyl; and

R¹ and R² are not both hydrogen.

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