Michigan Molecular Institute (Midland, MI) earned U.S. Patent 7,794,699 for nano-structured blood substitutes.
According to inventors Steven N. Kaganove, Paul Satoh, Petar R. Dvornic, the nano-structured blood substitute represents an improved synthetic blood substitute which exhibits excellent long-term storage stability at both high and low temperatures is suitable for use in various biomedical and biotechnical applications, including resuscitation of trauma victims that have suffered massive hemorrhaging, and transfusions for human and veterinary surgical procedures. The artificial blood solution comprises an aqueous carrier, and a dendritic polymer that is capable of carrying oxygen dissolved in the aqueous carrier. The dendritic polymer comprises fluorocarbon moieties and hydrophilic moieties.
Over the past forty years the development of synthetic blood substitutes has attracted increasingly serious interest from the medical community. This once fanciful idea received increasing credence in the early 1980s as the dangers of HIV transmission by blood transfusions become apparent. As a consequence, blood screening technology has become increasingly sophisticated and the chances of exposure to HIV from a blood transfusion dropped from 1 in 5,000 in the early 1980s to about 1 in 600,000 today. Nonetheless, there are still a variety of problems and risks with banked blood that are expected to persist in the foreseeable future.
Development of a successful blood substitute would eliminate the need to match blood types when transfusing trauma victims, as well as the risk that HIV, hepatitis or other pathogens could be transmitted by transfusion. The emergence of new viral threats such as SARS and "bird flu" illustrate the ongoing vulnerability of the world-wide blood supply to new and/or under-appreciated diseases for which reliable screening technology may not yet exist. In addition, a ready supply of synthetic blood substitute would also stretch natural blood supplies, which often run short around the holidays. For example, as recently as 2000 almost 10 percent of U.S. hospitals reported that they had to postpone surgeries because of unanticipated blood shortages. Finally, even when safe from contamination, blood transfusions can have negative effects on the immune system of the recipient.
Although blood is responsible for a multitude of functions in the body, a synthetic blood substitute would serve only to replicate its gas transporting function in which fresh oxygen is carried to cells and organs, exchanged there for carbon dioxide, and carbon dioxide is then removed. These are the most immediate and critical functions of blood, particularly in cases where blood is lost through massive trauma.
Development of a successful blood substitute would eliminate the need to match blood types when transfusing trauma victims, as well as the risk that HIV, hepatitis or other pathogens could be transmitted by transfusion. The emergence of new viral threats such as SARS and "bird flu" illustrate the ongoing vulnerability of the world-wide blood supply to new and/or under-appreciated diseases for which reliable screening technology may not yet exist. In addition, a ready supply of synthetic blood substitute would also stretch natural blood supplies, which often run short around the holidays. For example, as recently as 2000 almost 10 percent of U.S. hospitals reported that they had to postpone surgeries because of unanticipated blood shortages. Finally, even when safe from contamination, blood transfusions can have negative effects on the immune system of the recipient.
Although blood is responsible for a multitude of functions in the body, a synthetic blood substitute would serve only to replicate its gas transporting function in which fresh oxygen is carried to cells and organs, exchanged there for carbon dioxide, and carbon dioxide is then removed. These are the most immediate and critical functions of blood, particularly in cases where blood is lost through massive trauma.
The improved artificial blood offers desirable combinations of properties for oxygen carriers capable of functioning as synthetic blood substitutes for various biomedical and biotechnical applications, including resuscitation of trauma victims that have suffered massive hemorrhaging, and transfusions for human and veterinary surgical procedures. Other applications for the oxygen carrier compounds of the invention include incorporation of the compounds in solutions containing contrast agents used in ultrasonic in vivo imaging, and as bioreactor additives for use in commercial cell culture applications.
FIG. 1 is a schematic representation of the dense-shell molecular architecture of a dendrimer.
The compounds of this invention have advantages over whole blood and blood derivatives, fluorocarbon blood substitutes, and modified hemoglobin blood substitutes. These advantages include improved long-term storage stability, and temperature stability. A further advantage with respect to whole blood and blood derivatives is that the oxygen carrying compounds of the invention may be used for cardiopulmonary resuscitation and transfusion without regard to the blood type of the patient. An expected further advantage of the oxygen carrying compounds of the invention with respect to conventional synthetically modified hemoglobin blood substitutes is reduced physiological side effects.
Specifically, the compounds of the invention are not expected to scavenge nitric oxide, and are not expected to cause undesirable vasoconstriction, and increased systemic and pulmonary artery pressure. A further advantage of the oxygen carrying compounds of the invention with respect to conventional fluorocarbon synthetic blood substitutes is that the synthetic oxygen carrying compounds of the invention can be synthesized to present exterior functional groups that are highly soluble in aqueous blood plasma, thereby eliminating the need for overcoming problems associated with development of stable fluorocarbon emulsion formulations.
The various advantages of the invention are achieved by providing a nano-structured blood substitute that comprises a fluorocarbon-containing dendritic polymer or a fluorocarbon-modified dendritic polymer compound having a dendritic polymer core and fluorocarbon spacers covalently bonded to the dendritic polymer core, and hydrophilic moieties covalently bonded to terminal groups of the fluorocarbon-containing dendritic polymer or to the fluorocarbon spacers of the fluorocarbon-modified dendritic polymer
The various advantages of the invention are achieved by providing a nano-structured blood substitute that comprises a fluorocarbon-containing dendritic polymer or a fluorocarbon-modified dendritic polymer compound having a dendritic polymer core and fluorocarbon spacers covalently bonded to the dendritic polymer core, and hydrophilic moieties covalently bonded to terminal groups of the fluorocarbon-containing dendritic polymer or to the fluorocarbon spacers of the fluorocarbon-modified dendritic polymer
For more information see U.S. Patent 7,794,699 Nano-structured blood substitutes
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