Water-soluble compositions of bioactive lipophilic compounds

Abstract

Water-soluble compositions comprising a lipophilic compound and a solubilizing agent of the general formula: {X—OOC—[(CH2)n—COO]m}p—Y  (I) wherein: X is a residue of a hydrophobic moiety, Y is a residue of a hydrophilic moiety, p is 1 or 2, m is 0 or 1, and n is an integer greater than or equal to 0 are disclosed. The lipophilic compound is preferably selected from the group consisting of water-insoluble ubiquinones, ubiquinols, vitamins, provitamins, polyene macrolide antibiotics, and mixtures thereof. The hydrophobic moiety is preferably a sterol or a tocopherol and the hydrophilic moiety is preferably a polyalkylene glycol. In some embodiments, the sterol is cholesterol or sitosterol, the tocopherol is α-(+)-tocopherol, the polyalkylene glycol is a polyethylene glycol or its methyl monoether having an average molecular weight between 400 and 1000, p is equal to 1 or 2, m is equal to 0 or 1 and n is an integer between 2 and 18.

Description

[0001] Cross-reference to related applications: This application is a continuation-in-part of our co-pending U.S. application Ser. No. 09 / 511,239, filed 23 Feb. 2000.FIELD OF THE INVENTION [0002] The present invention relates to water-soluble compositions of bioactive lipophilic compounds, to compounds useful for the preparation of such compositions, to methods of preparing such compounds and compositions, and to the use of such compositions as therapeutics and cosmetics. BACKGROUND OF THE INVENTION [0003] Many bioactive compounds are highly lipophilic (hydrophobic), meaning that they are soluble in lipids (oils) and some organic solvents, while being substantially insoluble or only sparsely soluble in water. The lack of solubility of a bioactive compound in aqueous media is an important factor limiting its therapeutic applications, making difficult an efficient administration of the compound to a patient. When administered in the form of an oil solution or some kind of water and / or...

AI Technical Summary

Problems solved by technology

The lack of solubility of a bioactive compound in aqueous media is an important factor limiting its therapeutic applications, making difficult an efficient administration of the compound to a patient.

When administered in the form of an oil solution or some kind of water and / or oil suspension or emulsion, lipophilic compounds usually show a poor bioavailability, meaning a low concentration and a long build-up time of the compound in the systemic circulation.

When such a solution is admixed with blood or gastrointestinal fluids, however, the lipophilic compound usually precipitates as a solid or liquid emulsion, with a resulting low bioavailability.

Furthermore, for many lipophilic compounds no organic, water-miscible solvents exist.

However, this approach usually relies on the presence of certain functional groups in the original compound, so it is not universally applicable.

In addition, synthetic methods of improving solubility of a compound by chemical modifications are relatively complicated and expensive.

When the auxiliary organic solvent cannot be completely removed from the composition, this solvent must be pharmaceutically acceptable, which limits the choice of applicable solvents.

The reconstituted aqueous solutions show only a limited stability, depending mostly on the pH of the solution.

Solvent-free compositions are not disclosed, as they would likely be unstable or inhomogeneous.

Even though various methods of improving solubility of lipophilic compounds, such as Coenzyme Q10, in aqueous media are known in the prior art, they are not equal in terms of simplicity, scope of applicability, stability of the prepared formulations, etc.

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