Hemospan: design principles for a new class of oxygen therapeutic

Artif Organs. 2009 Feb;33(2):133-8. doi: 10.1111/j.1525-1594.2008.00697.x.


Hemoglobin-based oxygen carriers have been under development for decades, but safety concerns have prevented commercial approval. Early designs for modified hemoglobins by polymerization or intramolecular cross-linking reactions increased molecular size and decreased oxygen affinity, but all exhibited side effects of vasoconstriction and reduced blood flow. A new strategy has been established by applying principles of oxygen transport to cell-free hemoglobin. Sangart has developed a new oxygen therapeutic, Hemospan, using site-specific, poly(ethylene) glycol conjugation chemistry designed on two principles: (i) increased macromolecular size to prolong intravascular retention time, and (ii) increased oxygen affinity to prevent premature oxygen offloading in arterioles. In contrast to early-generation products, Hemospan infusion maintains normal arteriolar vascular tone and capillary flow. Phase I and Phase II clinical trials have been completed, showing that Hemospan is well-tolerated in humans, with evidence of efficacy to impart hemodynamic stability in surgical patients under anesthesia. Phase III trials in orthopedic surgery have recently completed enrollment in Europe.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Substitutes / chemistry*
  • Blood Substitutes / metabolism
  • Blood Substitutes / pharmacology
  • Blood Substitutes / therapeutic use*
  • Clinical Trials as Topic
  • Drug Design
  • Hemoglobins / chemistry*
  • Hemoglobins / metabolism
  • Hemoglobins / pharmacology
  • Hemoglobins / therapeutic use*
  • Humans
  • Maleimides / chemistry*
  • Maleimides / metabolism
  • Maleimides / pharmacology
  • Maleimides / therapeutic use*
  • Oxygen / metabolism
  • Oxygen / therapeutic use
  • Polyethylene Glycols / chemistry*
  • Polyethylene Glycols / metabolism
  • Polyethylene Glycols / pharmacology
  • Polyethylene Glycols / therapeutic use*


  • Blood Substitutes
  • Hemoglobins
  • Maleimides
  • maleimide-polyethylene glycol-modified hemoglobin, MP4
  • Polyethylene Glycols
  • Oxygen