Efforts have focused on molecules that can carry
oxygen, and most work has focused on recombinant
hemoglobin, which normally carries oxygen, and
perfluorocarbons (PFC), chemical compounds which can carry and release oxygen. The first approved oxygen-carrying blood substitute was a
perfluorocarbon-based product called
Fluosol-DA-20, manufactured by
Green Cross of Japan. It was approved by the
Food and Drug Administration (FDA) in 1989. Because of limited success, complexity of use and side effects, it was withdrawn in 1994. However, Fluosol-DA remains the only oxygen therapeutic ever fully approved by the FDA. As of 2017, no hemoglobin-based product had been approved. In order to "load" sufficient amounts of oxygen into it, people who had been given it had to breathe pure oxygen by mask or in a
hyperbaric chamber. It was approved by the FDA in 1989, and was approved in eight other countries. Its use was associated with a reduction in ischemic complications and with an increase in pulmonary edema and congestive heart failure. Due to difficulty with the emulsion storage of Fluosol use (frozen storage and rewarming), its popularity declined and its production ended in 1994. In 2002 a Phase III study was halted early due an increase in incidences of strokes in the study arm.
Haemoglobin based Haemoglobin is the main component of red blood cells, comprising about 33% of the cell mass. Haemoglobin-based products are called haemoglobin-based oxygen carriers (HBOCs). Efforts to overcome this toxicity have included making
genetically engineered versions,
cross-linking,
polymerization, and encapsulation. It reached Phase III clinical trials, in which it failed due to increased mortality in the trial arm, mostly due to severe vasoconstriction complications. Hemolink (Hemosol Inc., Mississauga, Canada) was a haemoglobin solution that contained cross-linked an o-rafinose polymerised human haemoglobin. and declared bankruptcy in 2005. Hemopure was developed by Biopure Corp and was a chemically stabilized, cross-linked bovine (cow) haemoglobin in a salt solution intended for human use; the company developed the same product under the trade name Oxyglobin for veterinary use in dogs. Oxyglobin was approved in the US and Europe and was introduced to veterinary clinics and hospitals in March 1998. Hemopure was approved in South Africa and Russia. Biopure filed for bankruptcy protection in 2009. Its assets were subsequently purchased by HbO2 Therapeutics in 2014. PolyHeme was developed over 20 years by
Northfield Laboratories and began as a military project following the Vietnam War. It is human haemoglobin, extracted from red blood cells, then polymerized, then incorporated into an electrolyte solution. In April 2009, the FDA rejected Northfield's
Biologic License Application and in June 2009, Northfield filed for bankruptcy. Dextran-Haemoglobin was developed by Dextro-Sang Corp as a veterinary product, and was a conjugate of the polymer dextran with human haemoglobin. Hemotech was developed by HemoBiotech and was a chemically modified haemoglobin. Somatogen developed a genetically engineered and crosslinked tetramer it called Optro. It failed in a phase II trial and development was halted. which led to Curacyte shutting down. Similarly, Hemospan was developed by Sangart, and was a
pegylated haemoglobin provided in a powdered form. While early trials were promising Sangart ran out of funding and closed down. describes a large-scale ex-vivo production of mature human blood cells using
hematopoietic stem cells. The cultured cells possessed the same haemoglobin content and morphology as native red blood cells. The authors contend that the cells had a near-normal lifespan, when compared to natural red blood cells. Scientists from the experimental arm of the
United States Department of Defense began creating artificial blood for use in remote areas and transfuse blood to wounded soldiers more quickly in 2010. The blood is made from the
hematopoietic stem cells removed from the
umbilical cord between human mother and newborn using a method called blood
pharming. Pharming has been used in the past on animals and plants to create medical substances in large quantities. Each cord can produce approximately 20 units of blood. The blood is being produced for the
Defense Advanced Research Projects Agency by Arteriocyte. The
Food and Drug Administration has examined and approved the safety of this blood from previously submitted O-negative blood. Using this particular artificial blood will reduce the costs per unit of blood from $5,000 to equal or less than $1,000.
Synthetic O2 carriers Unlike biologically based and perfluorinated solvent systems described above, a number of synthetic compounds have been evaluated for their ability to reversibly bind O2. Beyond the medical applications, such O2 binding agents could be supply oxygen for welding and other uses. Cobalt analogues of myoglobin received particular attention; no practical results were found. ==See also==