Lipophilic drug compositions - Patents

Lipophilic drug compositions

Agent: Alston & Bird LLP - Charlotte, NC, US
Inventor: Michael T. Sung
Class: 424464000 (USPTO), (Intl Class)
#20060147525
07/06/06

The invention is directed to biologically active lipophilic compositions comprising a biologically active covalently attached to, or encapsulated within, a lipid. Preferably, a biologically active agent is both covalently attached to a lipid and encapsulated within a lipid composition. Preferred lipid components include triglycerides and fatty acids. The resulting composition is preferably adapted for oral administration.
FIELD OF THE INVENTION
[0002] The invention relates to lipophilic drug compositions comprising biologically active agents in association with lipid components, methods of making such compositions, and methods of using such compositions in drug delivery.
SUMMARY OF THE INVENTION
[0007] The present invention provides biologically active lipophilic compositions, particularly solid compositions adapted for oral administration. The lipophilic compositions of the invention exhibit improved bioavailability and reduced toxicity as compared to non-lipophilic parent drug compounds. The invention involves covalently attaching a lipid molecule to a biologically active agent and/or encapsulating a biological active agent within a lipid composition. Preferably, the lipid molecule covalently attached to the biologically active agent is a non-amphipathic lipid, such as a triglyceride or a fatty acid. Similarly, the encapsulating lipid composition is preferably non-amphipathic. In a preferred embodiment, a biologically active agent is covalently attached to a C4-C30 fatty acid and then encapsulated within a mixture of at least one triglyceride and at least one fatty acid. The linkage between the biologically active agent and the lipid is preferably hydrolytically stable and enzymatically cleavable. Examples of suitable linkages include ethers, thioethers, imides, amides, sulfonamides, phosphonamides, disulfides, and carbamides.
[0008] The biologically active agent can be, for example, peptide, protein, enzyme, small molecule drug, dye, nucleoside, oligonucleotide, oligosaccharide, polysaccharide, vaccine, cell, or a virus. In one embodiment, the biologically active agent is the biologically active core structure of a known group of structurally similar compounds having a common biological activity, such as penicillins, floxins, ACE inhibitors, and the like. The biologically active core structure can be determined by analyzing the structurally similar compounds and selecting the structural components shared by the structurally similar compounds, the shared structural components forming the biologically active core structure.
[0009] The encapsulation of the biologically active agent can be readily accomplished by dissolving a first lipid composition (e.g., C4-C30 fatty acid) in a solvent, mixing the dissolved lipid with the biologically active agent with sufficient mixing intensity to form an emulsified mixture, adding a second lipid composition (e.g., one or more triglycerides) to the emulsified mixture while continuing to mix the emulsified mixture, solidifying the mixture, and drying the mixture to form a dry solid composition.
[0010] In another aspect, the present invention provides a biologically active lipophilic compound comprising a substituted or unsubstituted 5-nitrothiazole covalently attached to a lipid molecule, for example, having the structure:
[0011] wherein L is a linkage, such as an amide linkage, R is hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclic, or substituted heterocyclic, and LIPID is a residue of a C4-C30 fatty acid. The above-described 5-nitrothiazole derivative is useful for treating an infection in a mammal, such as a parasitic, bacterial, viral, or fungal infection.
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