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US 5,976,569 AGranted
Diketopiperazine-based delivery systems
AssigneeEmisphere Technologies, Inc.
InventorSam J. Milstein
Life of this patent
Estimating the term…
Abstract
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.
Claims38
A delivery composition comprising:
- (a) an active agent;
- and
- (b) a diketopiperazine having the formula:
- ##STR5## wherein R.sup.1, R.sup.2, or R.sup.1 and R.sup.2 independently are hydrogen, C.sub.1 -C.sub.24 alkyl, C.sub.1 -C.sub.24 alkenyl, phenyl, naphtyl, (C.sub.1 -C.sub.10 alkyl)phenyl, (C.sub.1 -C.sub.10 alkenyl)phenyl, (C.sub.1 -.sub.10 alkyl)naphthyl, (C.sub.1 -C.sub.10 alkenyl)naphthyl, phenyl (C.sub.1 -C.sub.10 alkyl), phenyl (C.sub.1 -C.sub.10 alkenyl), naphthyl (C.sub.1 -C.sub.10 alkyl), and naphthyl (C.sub.1 -C.sub.10 alkenyl);
- R.sup.1 or R.sup.2, or both R.sup.1 and R.sup.2, optionally, are independently substituted with C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkenyl, C.sub.1 -C.sub.4 alkoxy, --OH, --SH, and --CO.sub.2 R.sup.3 or any combination thereof;
- wherein R.sup.3 is hydrogen, C.sub.1 -C.sub.4 alkyl, or C.sub.1 -C.sub.4 alkenyl;
- R.sup.1, R.sup.2, or R.sup.1 and R.sup.2, 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 C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkenyl, C.sub.1 -C.sub.6 alkoxy, --OH, --SH, or CO.sub.2 R.sup.4 wherein R.sup.4 is hydrogen, C.sub.1 -C.sub.6 alkyl;
- or C.sub.1 -C.sub.6 alkenyl;
- and
- R.sup.1 and R.sup.2 are not both hydrogen.
8 more elements
A pharmacological composition comprising:
- (a) at least one pharmacologically active agent;
- and
- (b) a diketopiperazine having the formula:
- ##STR6## wherein R.sup.1, R.sup.2, or R.sup.1 and R.sup.2 independently are hydrogen, C.sub.1 -C.sub.24 alkyl, C.sub.1 -C.sub.24 alkenyl, phenyl, naphthyl, (C.sub.1 -C.sub.10 alkyl)phenyl, (C.sub.1 -C.sub.10 alkenyl)phenyl, (C.sub.1 -C.sub.10 alkyl)naphthyl, (C.sub.1 -C.sub.10 alkenyl)naphthyl, phenyl (C.sub.1 -C.sub.10 alkyl), phenyl (C.sub.1 -C.sub.10 alkenyl), naphthyl (C.sub.1 -C.sub.10 alkyl), and naphthyl (C.sub.1 -C.sub.10 alkenyl);
- R.sup.1 or R.sup.2, or both R.sup.1 and R.sup.2, optionally, are independently substituted with C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkenyl, C.sub.1 -C.sub.4 alkoxy, --OH, --SH, and --CO.sub.2 R.sup.3 or any combination thereof;
- wherein R.sup.3 is hydrogen, C.sub.1 -C.sub.4 alkyl, or C.sub.1 -C.sub.4 alkeny;
- R.sup.1, R.sup.2, or R.sup.1 and R.sup.2, optionally, are independently interrupted by oxygen, nitrogen, sulfur, or any combination thereof;
- said phenyl, naphthyl, or phenyl and naghthyl groups, optionally, are independently substituted by C.sub.1 -C.sub.6 alkyl, C.sub.1 C.sub.6 alkenyl, C.sub.1 -C.sub.6 alkoxy, --OH, --SH, or CO.sub.2 R.sup.4 wherein R.sup.4 is hydrogen, C.sub.1 -C.sub.6 alkyl, or C.sub.1 -C.sub.6 alkenyl;
- and
- R.sup.1 and R.sup.2 are not both hydrogen.
7 more elements
A method for preparing a delivery composition, said method comprising:
- (A) mixing
- (a) an active agent;
- and
- (b) a diketopiperazine having the formula:
- ##STR7## wherein R.sup.1, R.sup.2, or R.sup.1 and R.sup.2 independently are hydrogen, C.sub.1 -C.sub.24 alkyl, C.sub.1 -C.sub.24 alkenyl, phenyl, naphthyl, (C.sub.1 -C.sub.10 alkyl)phenyl, (C.sub.1 -C.sub.10 alkenyl)phenyl, (C.sub.1 -C.sub.10 alkyl)naphthyl, (C.sub.1 -C.sub.10 alkenyl)naphthyl, phenyl (C.sub.1 -C.sub.10 alkyl), phenyl (C.sub.1 -C.sub.10 alkeny), naphthyl (C.sub.1 -C.sub.10 alkyl), and naphthyl (C.sub.1 -C.sub.10 alkenyl);
- R.sup.1 or R.sup.2, or both R.sup.1 and R.sup.2, optionally, are independently substituted with C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkenyl, C.sub.1 -C.sub.4 alkoxy, --OH, --SH, and --CO.sub.2 R.sup.3 or any combination thereof;
- wherein R.sup.3 is hydrogen, C.sub.1-C.sub.4 alkyl, or C.sub.1 -C.sub.4 alkenyl;
- R.sup.1, R.sup.2, or R.sup.1 and R.sup.2, 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 C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkenyl, C.sub.1 -C.sub.6 alkoxy, --OH, --SH, or CO.sub.2 R.sup.4 wherein R.sup.4 is hydrogen, C.sub.1 -C.sub.6 alkyl, or C.sub.1 -C.sub.6 alkenyl;
- and
- R.sup.1 and R.sup.2 are not both hydrogen.
8 more elements
A method for preparing microspheres containing an active agent, said method comprising:
- (A) solubilizing, in a solvent, a diketopiperazine having the formula:
- ##STR8## wherein R.sup.1, R.sup.2, or R.sup.1 and R.sup.2 independently are hydrogen, C.sub.1 -C.sub.24 alkyl, C.sub.1 -C.sub.24 alkenyl, phenyl, naphthyl, (C.sub.1 -C.sub.10 alkyl)phenyl, (C.sub.1 -C.sub.10 alkenyl)phenyl, (C.sub.1 -C.sub.10 alkyl)naphthyl, (C.sub.1 -C.sub.10 alkenyl)naphthyl, phenyl (C.sub.1 -C.sub.10 alkyl), phenyl (C.sub.1 -C.sub.10 alkeny), naphthyl (C.sub.1 -C.sub.10 alkyl), and naphthyl (C.sub.1 -C.sub.10 alkenyl);
- R.sup.1 or R.sup.2, or both R.sup.1 and R.sup.2, optionally, are independently substituted with C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkenyl, C.sub.1 -C.sub.4 alkoxy, --OH, --SH, and --CO.sub.2 R.sup.3 or any combination thereof;
- R.sup.3 is hydrogen, C.sub.1 -C.sub.4 alkyl or C.sub.1 -C.sub.4 alkenyl;
- R.sup.1, R.sup.2, or R.sup.1 and R.sup.2, optionally, are independently interrupted by oxygen, nitrogen, sulfur, or any combination thereof;
- said phenyl, naphthyl, or phenyl and naphthyl grougs, optionally, are independently substituted by C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkenyl, C.sub.1 -C.sub.6 alkoxy, --OH, --SH, or CO.sub.2 R.sup.4 wherein R.sup.4 is hydrogen, C.sub.1 -C.sub.6 alkyl, or C.sub.1 -C.sub.6 alkenyl;
- and
- R.sup.1 and R.sup.2 are not both hydrogen, to yield a diketopiperazine solution;
- and
- (B) contacting said diketopiperazine solution with said active agent and a precipitator solution in which said diketopiperazine is insoluble.
7 more elements
A delivery composition comprising:
- (a) an active agent;
- and
- (b) a diketopiperazine having the formula ##STR9##
A pharmacological composition comprising:
- (A) at least one pharmacologically active agent;
- and
- (B) a carrier comprising a diketopiperazine having the formula:
- ##STR10##
1 more element
A method for preparing a delivery composition, said method comprising:
- (A) mixing
- (a) an active agent;
- and
- (b) a carrier comprising a diketopiperazine having the formula ##STR11##
1 more element
A method for preparing microspheres containing an active agent, said method comprising (A) solubilizing, in solvent, a carrier comprising a diketopiperazine having the formula ##STR12## and;
- (B) contacting said carrier solution with said active agent and a precipitator solution in which said carrier is insoluble.
Dependencies are inferred from the claim text.