The need for synthetic blood is well known. Blood is becoming increasingly expensive, it is perishable, it must be matched to the blood type of the recipient and the transfusion itself can cause hepatitis if rigid procedures are not followed. In addition, blood donations tend to be somewhat seasonal and they often do not coincide with the generally random demands therefor.
A synthetic blood must have several characteristics. Initially, and quite obviously, it must have high oxygen and carbon dioxide solubility since its principal function is to transport oxygen and carbon dioxide. A synthetic blood also must be non-toxic and in this respect it is desirable that when the synthetic blood is replaced by natural blood there is no residue of the former left in vital body organs.
Another characteristic of blood substitutes is that they must have certain vapor pressure requirements. The blood substitutes leave the body by being exhaled and by vaporization through the skin. Preferably the substitute leaves the body at about the same rate that new natural blood is being generated by the body. If the vapor pressure of the substitute is too low it stays in the body too long, wheres if it is too high it evaporates throughout the body's surface and may create problems akin to the "bends".
Blood substitutes must also be capable of forming very stable emulsions with this capability being even more important with perfusion materials. Fluorocarbons are usually immiscible with blood and if used alone could cause embolisms. This problem is overcome by using it in an aqueous emulsion and obviously the emulsion should not separate in use or storage. In connection with perfusion materials this stability is even more strict because the oxygenators used to add oxygen to the perfusion material may catalyze emulsion breakdown. Another reason aqueous emulsions are employed is that salts are added to the water in order to maintain the body salt balance.
The Green Cross Corporation, Osaka, Japan, has published a pamphlet dated Sept. 11, 1974 on perfluoro emulsions as oxygen and carbon dioxide carriers Also Clark et al. report on some of the compounds described in the present invention in Microvascular Research, Volume 8/3, 1974, also presented at the Oxygen Transport to Tissue Symposium, Atlantic City, N.J., Apr. 11, 1974. Certain of the subject matter of this latter article is also taught in U.S. Pat. No. 3,911,138 issued Oct. 7, 1975 to Clark which broadly describes cyclic perfluorohydrocarbons useful as blood substitutes and the like.
The blood substitute and perfusion material of choice as described by these articles is perfluorodecalin. It has a number of desirable properties, but the compounds of the present invention are unexpectedly superior to perfluorodecalin in several respects, in particular emulsion stability, reduced liver retention time, and low toxicity, as described in detail below.
USPTO Backgrounds
USPTO Backgrounds