Patient oxygenation using stabilized fluorocarbon emulsions

Abstract

Storage stable fluorocarbon emulsions having a continuous aqueous phase and a discontinuous fluorocarbon phase, in which the fluorocarbon phase comprises a major amount of a first fluorocarbon or fluorocarbon mixture, and a minor amount of a second fluorocarbon or fluorocarbon mixture, in which the second fluorocarbon has a molecular weight greater than that of the first fluorocarbon and the second fluorocarbon includes a lipophilic moiety in its structure, whereby the second fluorocarbon serves to promote particle size stability in the emulsion while simultaneously providing favorably short organ retention times when administered to animals in vivo.

Description

RELATED APPLICATIONS [0001] This application is a continuation of prior U.S. patent application Ser. No. 10 / 007,053, filed Dec. 3, 2001, which is a continuation of prior U.S. patent application Ser. No. 09 / 263,924, filed Mar. 5, 1999, which is a continuation of U.S. patent application Ser. No. 08 / 854,547, filed May 12, 1997, which is a continuation of U.S. patent application Ser. No. 07 / 967,700, filed Oct. 27, 1992, now U.S. Pat. No. 5,628,930.BACKGROUND OF THE INVENTION [0002] The present invention relates to emulsions comprising highly fluorinated or perfluorinated compounds. More particularly, it relates to fluorocarbon emulsions having superior particle size stability during storage. [0003] Fluorocarbon emulsions find uses as therapeutic and diagnostic agents. Most therapeutic uses of fluorocarbons are related to the remarkable oxygen-carrying capacity of these compounds. One commercial biomedical fluorocarbon emulsion, Fluosol (Green Cross Corp., Osaka, Japan), is presently use...

AI Technical Summary

Benefits of technology

[0011] A major advantage of the present invention is the surprisingly short organ retention times of the stabilized emulsion. Perfluorodecyl bromide, for example, has a calculated half life in vivo in organs of the reticuloendothelial system (RES) of approximately 18 days, while those of nonlipophilic perfluorocarbons having about the same molecular weight vary from about 50 to 300 days. (See Table IV.) This distinction is critical; it spells the difference between formulations which are physiologically acceptable and those which are not. Note that none of the prior art stabilizers are lipophilic; thus, none share the advantageous properties of the present invention. For example, with reference to Table [V and FIG. 5, the stabilizers of the present invention all have critical solution temperatures (CSTs) and projected organ retention times much lower than those of the prior art stabilizers of Davis, et al., Kabalnov, and Meinert. Aside from the stabilizers of the present invention, conventional fluorocarbons exhibit a direct correlation between retention time in RES organs and molecular weight. Also, aside from the lipophilic fluorocarbons used in the present invention, the perfluorochemical structure has little effect on the strong retention time / molecular weight relationship. Thus, the presence of heteroatoms or cyclic structure has little effect on organ retention time.

Problems solved by technology

Emulsions lacking substantial particle size stability are not suitable for long term storage, or they require storage in the frozen state.

Emulsions with a short shelf life are undesirable.

Storage of frozen emulsions is inconvenient.

Further, frozen emulsions must be carefully thawed, reconstituted by admixing several preparations, then warmed prior to use, which is also inconvenient.

However, Ostwald ripening may only proceed where the perfluorocarbon molecules are capable of migrating through the continuous phase between droplets of the discontinuous phase.

Unfortunately, when the prior art included higher molecular weight fluorocarbons in fluorocarbon emulsions, organ retention times were also increased considerably.

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