Delivery agents for enhancing mucosal absorption of therapeutic agents
Inventors
Byun, Youngro • Lee, Seulki • Moon, Hyuntae
Assignees
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Publication Number
US-7906137-B2
Publication Date
2011-03-15
Expiration Date
Abstract
A delivery agent for delivering a biologically active agent to a warm-blooded animal includes a hydrophobic moiety covalently bonded to a hydrophilic moiety. The hydrophobic moiety can include bile acids, sterols, or hydrophobic small molecules. The hydrophilic moiety can include α-amino acids, dipeptides or tripeptides, or hydrophilic small molecules. An illustrative delivery agent is Nα-deoxycholyl-L-lysine-methylester. The delivery agent and the biologically active agent are mixed together to form a complex, which is then administered to the animal. These complexes are particularly useful for oral administration of biologically active agents, but other routes of administration may be used.
Core Innovation
The invention describes delivery agents for delivery of a biologically active agent by forming a mixture in which the delivery agent comprises a hydrophobic moiety covalently bonded to N-L-lysine-methylester. The hydrophobic moiety is selected from bile acids, sterols, and hydrophobic small molecules, and includes named examples such as cholic acid, deoxycholic acid, and deoxycholyl-L-lysine-methylester (DCK).
The delivery agents are formed by covalently linking a hydrophobic moiety to a positively or negatively charged hydrophilic moiety, including -amino acids, dipeptides, tripeptides, and hydrophilic small molecules. The mixtures of the delivery agent with therapeutics form complexes associated with electrostatic charge, lipophilicity, solubility, and oral delivery behavior, and are described as improving oral absorption.
The document states that DCK improves stability and affects molecular interactions of biologically active agents. It is described that DCK stabilizes insulin against proteolysis and reduces insulin aggregation state, and that oral delivery of insulin with DCK increases plasma insulin and lowers blood glucose in diabetic rats. It is also described that oral LMWH combined with DCK increases plasma antiFXa activity.
Claims Coverage
The independent claims define 2 inventive features: a composition mixture and a dosage form for delivering a biologically active agent to a warm-blooded animal. Both center on a delivery agent comprising a hydrophobic moiety covalently bonded to N-L-lysine-methylester, with broad biologically active agent coverage and hydrophobic-moiety options.
Covalent hydrophobic moiety to N-L-lysine-methylester delivery agent in a composition mixture
A composition comprising a mixture of a biologically active agent and a delivery agent, wherein the delivery agent comprises a hydrophobic moiety selected from bile acids and N-L-lysine-methylester covalently bonded to the hydrophobic moiety.
Dosage form using a hydrophobic moiety covalently bonded to N-L-lysine-methylester for delivery to a warm-blooded animal
A dosage form for delivery of a biologically active agent to a warm-blooded animal, the dosage form comprising a mixture of the biologically active agent and a delivery agent, wherein the delivery agent comprises a hydrophobic moiety selected from bile acids, sterols, and small hydrophobic molecules having a molecular weight of less than about 500 daltons and N-L-lysine-methylester covalently bonded to the hydrophobic moiety.
The claim coverage centers on mixtures and dosage forms in which a delivery agent is constructed by covalently bonding a hydrophobic moiety to N-L-lysine-methylester, with broad inclusion of biologically active agents and hydrophobic-moiety options.
Stated Advantages
Improves oral absorption.
Stabilizes insulin against proteolysis.
Reduces insulin aggregation.
Increases plasma insulin and lowers blood glucose when insulin is orally administered with DCK in diabetic rats.
Increases plasma antiFXa activity for oral LMWH combined with DCK.
Documented Applications
Oral administration of insulin with DCK to diabetic rats, resulting in increased plasma insulin and lowered blood glucose.
Oral delivery of insulin with DCK where DCK stabilizes insulin against proteolysis and reduces insulin aggregation.
Oral administration of low molecular weight heparin (LMWH) with DCK, resulting in increased plasma antiFXa activity.
Delivery of a biologically active agent to a warm-blooded animal via a dosage form selected from tablet, capsule, powder, liquid, or emulsion.
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