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Biotech / Medical : SANGUINE CORP. (SGNC) -- Ignore unavailable to you. Want to Upgrade?

To: Little Engine who wrote (1542)	6/21/1998 5:17:00 PM
From: chirodoc	Read Replies (1) \| Respond to of 5402

<<<<<)Meanwhile, the profit picture for the existing market looks bleak. .......incorrect, illogical and biased. ......regarding blood substitutes, medical authorities have expressed a DIRE need for a safe blood substitute. .......your statement is like saying the profit picture for viagra looks bleak. you obviously have not been reading the medical literature. curtis

To: Little Engine who wrote (1542)	6/21/1998 5:23:00 PM
From: chirodoc	Respond to of 5402

New perfluorochemicals Two new types of preparations have been developed (50-55). One type is based on perfluoroctyl bromide (C8F17Br) and perfluorodichoroctane (C8F16Cl2). Both types allows the use of higher concentrations of PFC. Oxygent™ (Alliance Pharmaceutical Corp., San Diego) is prepared from perfluoroctyl bromide (C8F17Br) with egg yolk lecithin as the surfactant. The use of egg yolk lecithin instead of Pluronic surfactant has solved the problem of complement activation( Reiss 1991). Another approach, Oxyfluor (HemoGen, St. Louis) is based on the use of perfluoro-dichoroctane (C8F16Cl2) with triglyceride and egg yolk lecithin (Goodin et al 1994). The observation of side effects when the dose is about 1.8 g PFC/ kg means that at least at present, the use of the new improved preparations of PFC-based blood substitutes is limited to a lower dosage. Oxygent are being used in Phase II clinical trials (Wahr et al 1994) in surgical patients breathing 100% oxygen. The use of 0.9g/kg of oxygent appears to be able to avoid need for the use of 1-2 units of blood. The present emphasis is therefore to study the use of PFC in surgery to offset the need for this amount of blood during surgery. This is to be combined with autologous blood predeposition and reinfusion after surgery. (3) Other Potential Areas of Applications. There are a number of other potential applications for perfluorochemicals (44, 46, 53, 54). At present, these will be limited to the lower dosage level as described above. Thus in thrombosis or embolism, the small PFC particles and the increased oxygen pressure may help the affected tissue. Use in patients who because of religious belief cannot use human blood cells is an important and obvious area. Other applications not related to its use as blood substitutes are not within the scope of the present discussion. (4) Present status & future perspectives of perfluorochemicals The biggest advantage of perfluorochemicals is that it they are synthetic material that can be chemically produced in large amounts without having to depend on donor blood or other biological sources. Much has been done in the last 10 years to improve this approach. The earlier problem of complement activation has been solved by changing the surfactant. Higher concentrations of the new perfluorochemicals can now be used to increase oxygen carrying capacity. At present this is limited by the rather low dosage of 0.9g/Kg for human use. This low dosage is partly because of side effects observed in humans at dosage of 1.8g/Kg. Here , the patients still have to breathe a 100% oxygen. With further research and development, the problem related to side effects at higher dosage is likely to be resolved. If this can be resolved then the highest dosage will only be limited by the dosage which would not cause significant suppression of the reticuloendothelial system. In this regard, ever improving perfluorochemicals with decreasing residual time in the reticuloendothelial system are being made available. It is likely that further improvements in perfluorochemicals may also lead to further improvements in oxygen carriage thus further reducing the level of oxygen required for breathing. ------------------------------------------------------------------------ III. FUTURE DEVELOPMENTS OF BLOOD SUBSITUTES - click to access article ------------------------------------------------------------------------ REFERENCES References cited in the above article Click References on Blood Substitutes by Chang et al (1957-1998) Click Selected recent publications on blood substitutes from Chang's Groupÿ Click References citedÿ in the above article 1.Chang TMS. Hemoglobin corpuscles. Report of a research project of B.Sc. Honours Physiology, McGill University, 1-25, 1957. Medical Library, McGill University (also reprinted in J. Biomaterials, Artificial Cells and Artificial Organs 16:1-9, 1988 ) 2 Chang TMS. Semipermeable microcapsules. Science. 146(3643):524, 1964. 3 Chang TMS. Ph.D. thesis. McGill University, 1965. 4 Chang TMS. Artificial cells. Monograph. Charles C Thomas, Springfield, IL, 1972. 5 Klein HG. Oxygen Carriers and Transfusion Medicine. Artificial Cells, Blood Substitutes and Immobilization Biotechnology, An International Journal, 22:123-135,1994 6 Bowersox JC & Hess JR. Trauma and Military Applications of Blood Substitutes. Artificial Cells, Blood Substitutes and Immobilization Biotechnology, An International Journal, 22: 145- 159, 1994 7 Amberson WR. Blood substitute. Biol. Rev. 12:48, 1937. 8 Chang TMS (ed) Blood Substitutes and Oxygen Carriers. Marcel Dekker Publisher pp 784,1992 9 Chang TMS, Reiss JG & Winslow R (Guest editors). Symposium volume on "Blood Substitutes: General" Artificial Cells, Blood Substitutes and Immobilization Biotechnology, An International Journal, 22,: 123-360,1994. 10 Winslow R (Guest Editor). Symposium Volume on "Blood substitutes: Modified Hemoglobin" Artificial Cells, Blood Substitutes and Immobilization Biotechnology, An International Journal, 22: 360-944,1994. 11 Chang TMS, (editor-in-chief). Abstracts on Blood Substitutes from the XI Congress of the International Society for Artificial Cells, Blood Substitutes & Immobilization Biotechnology. Artificial Cells, Blood Substitutes and Immobilization Biotechnology, An International Journal, Volume 22(5): A75-A177, 1994. 12 Djordjevich L, Miller IF. Synthetic erythrocytes from lipid encapsulated hemoglobin. Exp. Hematol. 8:584, 1980. 13 Farmer MC, Rudolph AS, Vandegriff KD, Havre MD, Bayne SA, Johnson SA. Liposome-encapsulated hemoglobin: oxygen binding properties and respiratory function. J. Biomaterials, Artificial Cells and Artificial Organs. 16:289-299, 1988. 14 Rudolph AS. Encapsulated hemolgobin: Current Issues and Future Goals. Artificial Cells, Blood Substitutes and Immobilization Biotechnology, An International Journal, 22,: 347-360, 1994. 15 Tsuchida E. Stabilized Hemoglobin Vesicles. Artificial Cells, Blood Substitutes and Immobilization Biotechnology, An International Journal, 22: 467-479, 1994 16 Yu WP & Chang TMS Submicron Biodegradable Polymer Membrane Hemoglobin Nanocapsules as Potential Blood substitutes: A Preliminary Report. Artificial Cells, Blood Substitutes and Immobilization Biotechnology, An International Journal, 22: 889-894, 1994. 17 Bunn HF, Jandl JH. The renal handling of hemoglobin. Trans Assoc Am Physicians 81:147, 1968. 18 Benesch R, Benesch RE, Yung S, Edalji R. Hemoglobin covalently bridged across the polyphosphate binding site. Biochem Biophys Res Commun 63:1123, 1975. 19 DeVenuto F, Zegna AI. Blood exchange with pyridoxalated-polymerized hemoglobin. Surg Gynecol Obstet 155:342, 1982. 20 Moss GS, Gould SA, Sehgal LR, Sehgal HL, Rosen AL. Hemoglobin solution - from tetramer to polymer. J. Biomaterials, Artificial Cells and Artificial Organs. 16:57-69, 1988. 21 Dudziak R, Bonhard K. The development of hemoglobin preparations for various indications. Anesthesist 29:181, 1980. 22 Gould SA, Sehgal LR, Sehgal HL, Moss GS (Northfield Co). Clinical Experience with human polymerized hemoglobin #H13, Abstract, Vth International Symposium on Blood Substitutes, San Diego,March 17-20,1993 23 Pliura DH (Hemosol Co.). Human Hemoglobin-based Blood Substitutes. Artificial Cells, Blood Substitutes and Immobilization Biotechnology, An International Journal, 22,: A146, 1994. 24 Mok W, Chen DE, Mazur A. Covalent linkage of subunits of hemoglobin. Fed. Proc. 34:1458, 1975. 25 Walder JA, Zaugg RH, Walder RY, Steele JM & Klotz IM. Diaspirins that cross-link alpha chains of hemoglobin: Bis(3,5-dibromosalicyl) succinate and bis(3,5-dibormosalicyl) fumarate. Biochemistry 18: 4265-4270, 1979. 26 Przybelski R, Kisicki J, Daily E, Bounds M and Mattia-Goldberg C.(Baxter Healthcare Co.) Diaspirin Cross-linked hemoglobin (DCLHb) phase I clinical safety assessment in normal healthy volunteers. #H16 Abstract, Vth International Symposium on Blood Substitutes, San Diego,March 17-20,1993 27 Bucci E, Fronticelli C, Razynska A, Militello V, Koehler R & Urbaitis. Hemoglobin Tetramers Stabilized with Polyaspirins. in "Blood Substitutes & Oxygen Carrier" Chang TMS (ed), Marcel Dekker Publisher, New York 76-85, 1992. 28 Wong JT. Rightshifted dextran-hemoglobin as blood substitute. Biomaterials, Artificial Cells and Artificial Organs. 16:237-245, 1988. 29 Nho, K, Glower D, Bredehoeft S, Shankar H, Shorr R, Abuchowski A. PEG-bovine hemoglobin: Safety in a canine dehydrated hypovolemic-hemorrhagic shock model. J. Biomaterials, Artificial Cells and Immobilization Biotechnology 20:511-524 1992. 30 Iwashita Y. Relationship between chemical properties and biological properties of pyridoxalated hemoglobin-polyoxyethylene. J. Biomaterials, Artificial Cells and Immobilization Biotechnology 20:299-308 1992. 31 Frantantoni, JC, Points to consider in the safety evaluation of hemoglobin based oxygen carriers. Transfusion. 31:(4)369-371, 1991. 32 Chang TMS, Lister C, Nishiya T, Varma R. Effects of different methods of administration and effects of modifications by microencapsulation, cross-linkage or PEG conjugation on the immunological effects of homologous and heterologous hemoglobin. J. Biomaterials, Artificial Cells and Immobilization Biotechnology 20:611-618 1992. 33 Estep TN, Gonder J, Bornstein I, Young S, Johnson RC. Immunogenicity of diaspirin crosslinked hemoglobin solutions. J. Biomaterials, Artificial Cells and Immobilization Biotechnology 20:603-610 1992. 34 Chang TMS, Lister C. An in vitro screening test for modified hemoglobin to bridge the gap between animal safety studies and clinical use in patients. J. Biomaterials, Artificial Cells and Immobilization Biotechnology 20: 519-526, 1992. 35 Hughes GS & Jacobs E (Upjohn USA) The hemodynamic response to hemopure, a polymerized bovine hemoglobin solution, in normal subjects #H15 Abstract, Vth International Symposium on Blood Substitutes, San Diego,March 17-20,1993 134. 36 Shoemaker S, Gerber M, Evans G, Paik L, Scoggin C.(Somatogen Co.USA) Initial Clinical Experience with a Rationally designed Genetically Engineered Recombinant Human Hemoglobin. Artificial Cells, Blood Substitutes and Immobilization Biotechnology, An International Journal, 22,: 457-465,1994. 37 Fratantoni, JC. Points to consider on efficacy evaluation of hemoglobin and perfluorocarbon based oxygen carriers. Transfusion 34:712-713, 1994 38 O'Donnell JK, Swanson M, Pilder S, Martin M, Hoover K, Huntress V, Karet C, Pinkert C, Lago W, Logan J. Production of human hemoglobin in transgenic swine. J. Biomaterials, Artificial Cells and Immobilization Biotechnology 20(1):149, 1992. 39 D'Agnillo F & TMS Chang. Cross-linked hemoglobin-superoxide dismutase-catalase scavenges oxygen-derived free radicals and prevents methemoglobin formation and iron release. J. Biomaterials, Artificial Cells and Immobilization Biotechnology 21:609-622, 1993 40 Chang, TMS Artificial cells with cofactor regenerating multienzyme systems. Methods in Enzymology 112:195-203,1985. 41 Clark LC, Jr, Gollan F. Survival of mammals breathing organic liquids equilibrated with oxygen at atmospheric pressure. Science 152:1755, 1966. 42 Chang, TMS Semipermeable aqueous microcapsules ("artificial cells"): with emphasis on experiments in an extracorporeal shunt system. Trans Am Soc Artif Intern Organs 12:13-19. 1966 43 Sloviter H, Kamimoto T. Erythrocyte substitute for perfusion of brain. Nature 216:458, 1967. 44 Geyer RP, Monroe RG, Taylor K. Survival of rats totally perfused with a fluorocarbon- detergent preparation. In Organ Perfusion and Preservation (eds. JC Norman, J Folkman, WG Hardison, LE Rudolf, FJ Veith), Appleton Century Crofts, New York, 1968, pp 85-96. 45 Naito R, Yokoyama K. 1978. An improved perfluorodecalin emulsion. In Blood Substitutes and Plasma Expanders (eds. GA Jamieson, TJ Greenwalt), Alan R Liss Inc, New York, 1978, p 81. 46 eyer RP, Bolin, Nemo GJ (eds.), "Advances in Blood Substitute Research", Publisher Alan R. Liss Inc., New York 1-468 pages. Mitsuno T, Naito R, eds. Perfluorochemical Blood Substitutes. Excerpta Medica, Amsterdam, 1979. 47ÿ Mitsuno T, Ohyanagi . Present status of clinical studies of fluosol-DA (20%) in Japan. In Perfluorochemical Oxygen Transport (ed. KK Tremper), Little Brown & Co, Boston, 1985, pp 169-184. Blood substitute 48 Ohyanagi H, Toshima K, Sekita M, Okamoto M, Itoh T, Mitsuno T, Naito R, Suyama T, Yokoyama K. Clinical study of perfluorochemical whole blood substitute. Clinical Therapeutics 2:306, 1979. 49 Faithfull, NS Oxtgen delivery from fluorocarbon emulsions - aspects of convective and diffusive transport.J. Biomaterials, Artificial Cells and Artificial Organs. 20:797-804, 1992 50 Goodin T. Results of a Phase I clinical trial of a 40 v/v% emulsion of HM351 (OxyfluorTM) in healthy volunteers. 2nd Annual IBC conference on Blood substitutes & Related Products. Whasington DC (1994) 51ÿ Goodin TH, Grossbard EB, Kaufman RJ, Richard TJ, Kolata RJ, Allen JS, Layton TE. A Perfluorochemical emulsion for prehospital resuscitation of experimental hemorrhagic shock: a prospective, randomized controlled study. Crit Care Med 22:680-689(1994) 52 Reiss, J (guest editor) Blood Substitutes and Related Products: The Fluorocabon Approach,Artificial Cells, Blood substitutes & Immobilization Biotechnology, An International Journal 22:945-1511,1994. 53 Riess JG Fluorocabron-based in vivo oxygen transport and delivery systems. Vox Sang 61:225-239, 1991. 54 Wahr JA, Trouwborst, Spence RK et al. A pilot study of the efficay of an oxtgen carrying emulsion OxtgentTM, in patients undergoing surgical blood loss. Anesthesiology 80:A397, 1994. 56 Chang TMS Monograph Blood substitutes: principales, methods,products and clinical trials. Vol I (monograph) Vol II (editor), Karger-Landes System, Basel & Austin. Some recent publications on blood substitutes from Chang's group 1. T.M.S. CHANG (monograph) (1997) Blood Substitutes: Principles, Methods, Products and Clinical Trials. Volume I . Karger-Landes click here. 2. T.M.S. CHANG (editor) (1998) Blood Substitutes: Principles, Methods, Products and Clinical Trials. Volume II. Karger-Landes click here 3. F. D'AGNILLO & TMS CHANG (1997) Production of hydroxyl radical generation in a rat hindlimb model of ischemia-reperfusion injury using crosslinked hemoglobin-superoxide dismutase-catalase. Artificial Cells, Blood Substitutes & Immobilization Biotechnology, an internationaljournal 25:163-180 4. S. RAZACK, F. D'AGNILLO & TMS CHANG (1997 )Crosslinked hemoglobin-superoxide dismutase-catalase scavenges free radicals in a rat model of intestinal ischemia-reperfusion injury. Artificial Cells, Blood Substitutes & Immobilization Biotechnology, an international journal 25: 181-1924. 5. T.M.S. CHANG(1997) Recent And Future Developments in Modified Hemoglobin and Microencapsulated Hemoglobin as Red Blood Cell Substitutes. Artificial Cells, Blood Substitutes & Immobilization Biotechnology, an international journal 25: 1-24 6. Yu WP & TMS CHANG (1996):Submicron polymer membrane hemoglobin nanocapsules as potential blood substitutes: preparation and characterization. Artificial Cells, Blood Substitutes & Immobilization Biotechnology,an international journal 24:169-184 7. D'Agnillo, F & TMS Chang (1998) Absence of hemoprotein-associated free radical events following oxidant challenge of crosslinked hemoglobin-superoxide dismutase-catalase. Free radical Biology and medicine. 24(6):906-912 8. D'AGNILLO,F & TMS CHANG (1998). Crosslinked Hemoglobin-Superoxide Dismuatase-Catalase as a blood substitute with antixoidant properties. NATURE BIOTECHNOLOGY (in press)

To: Little Engine who wrote (1542)	6/21/1998 5:30:00 PM
From: chirodoc	Respond to of 5402

OXYGENATED BLOOD SUBSTITUTES, PLASMA EXPANDERS, ERYTHROPOIETIN AND OTHER GROWTH FACTORS H. Franklin Bunn, M.D. From: 1995 Bloodless Medicine and Surgery National Conference Abstracts Conventional treatment of patients who have a clinically significant decrement in red cell mass is transfusion with stored compatible human red cells. Current anxieties notwithstanding, red cell transfusions have reached a remarkably high level of safety and efficacy. Nevertheless, there is growing interest in the development of alternate strategies, owing to both limitations in our voluntary blood donation programs and an increase in complex surgical procedures that require extensive blood replacement. This shortfall coupled with widespread concerns about transmission of HIV and other blood borne infections has spurred the development of autologous and directed donations, with augmentation of the patient's endogenous red cell production by administration of cytokines. An alternative approach is the use of a blood substitute capable of transporting oxygen to tissues. Erythropoietin and other hematopoietic growth factors Erythropoietin (Epo) is a glycoprotein hormone that regulates the production of red blood cells. The cloning of the Epo gene has permitted large-scale production of recombinant human Epo (rhepo) that is nearly identical to the endogenous hormone. Extensive clinical experience clearly documents the efficacy and safety of rhepo in the treatment of the anemia of renal failure. Patients with chronic inflammatory disorders such as cancer and rheumatoid arthritis may also derive benefit from therapy and in some cases, the need for transfusions is obviated. Anemias associated with primary bone marrow disorders are generally not responsive to rhepo but a substantial minority of patients with myelodysplasia have a significant increment in red cell mass, especially if rhepo is combined with granulocyte colony stimulating factor. There is considerable interest in the use of rhepo in preoperative and postoperative settings to stimulate the patient's red blood cell production. In certain settings, this may permit a greater volume of autologous blood to be collected in anticipation of elective surgery. Even in the absence of preoperative phlebotomy, rhepo appears to be of value. A large randomized placebo-controlled study from Canada demonstrated the efficacy of pre- and postoperative administration of rhepo (days -10 to +3) in decreasing transfusion requirements of patients undergoing elective hip replacement. In addition, administration of rhepo may be of benefit in more acute surgical settings. rhepo may permit more rapid recovery in the post-operative period. In particular, it may be a useful adjunct following perioperative hemodilution. In these different applications, patients serve as their own blood banks. Oxygen carrying blood substitutes A cell-free oxygen transporting blood substitute would obviate many of the current concerns about conventional red cell transfusion therapy. Moreover, a stable oxygen-carrying solution could have benefits and applications not possible with red cell transfusions. Such a solution would be ideal for the treatment of acute hypovolemic shock both in domestic emergency rooms as well as in the battlefield. A colloid that delivers oxygen would also be invaluable in third world countries where the cost and logistics of blood donations and banking are formidable. More restricted applications include the treatment of patients such as Jehovah's Witnesses who refuse blood transfusions, the priming of blood oxygenation pumps, ex vivo organ perfusion prior to transplantation, and in vivo perfusion in order to enhance sensitivity to radiation therapy. Among potential blood substitutes that transport oxygen, attention has focused on perfluorocarbons and a variety of hemoglobin preparations, either in free solution or encapsulated into lipid vesicles. Perfluorocarbons are synthetic compounds that reversibly bind oxygen, but non-cooperatively and at high O2 tension. As such, they depart substantially from the physiological role of red cells. In contrast, hemoglobin sealed into membranes comes closest to mother nature, but the obstacles in the development of such artificial red cells are formidable. An alternative approach which has attracted considerable attention is the preparation of hemoglobin solutions designed to meet the following criteria: low toxicity and antigenicity; efficacy as a plasma expander; prolonged survival in the circulation; adequate oxygen carrying capability and efficient oxygen unloading to tissues; long shelf life. Extensive preclinical testing and recent clinical trials have been performed on human hemoglobin through the kidneys. Bovine hemoglobin has intrinsically low oxygen affinity simulating that of human hemoglobin in red cells. An alternative and attractive strategy is the production of human hemoglobin in E. Coli, thus enabling appropriate genetic mutations to optimize function. These include creation of peptide linkers to enhance plasma survival and amino acid replacements that permit a finely regulated lowering of oxygen affinity. References 1.Surgeoner DM, Wallace EL, Hao SHS, Chapman RH: Collection and transfusion of blood in the United States, 1982-1988. New Eng J Med 322:1646, 1990. 2.Toy PTCY, Strauss RG, Stehling LC, et al: Predeposited autologous blood for elective surgery. A national multicenter study. New Eng J Med: 316:517, 1987. 3.Goodnough LT, Rudnick S, Price TH, et al: Increased preoperative collection of autologous blood with recombinant human erythropoietin therapy. New Eng J Med 321:1163, 1989. 4.Canadian Orthopedic Preoperative Erythropoietin Study Group. Effectiveness of perioperative recombinant human erythropoietin in elective hip replacement. Lancet 341:1227, 1993. 5.Bunn HF, Esham WT. Bull RW: The renal handling of hemoglobin I glomerular filtration. J Exp Med 129:909-924, 1969. 6.Rabiner SF, Helbert JR, Lopas H, Friedman LH: Evaluation of a stroma-free hemoglobin solution for use as a plasma expander. J Exp Med 126:1127, 1967. 7.Gould SA, Sehgal LR, Rosen AL, Sehgal HL, Moss, GS: The efficacy of polymerized pyridoxylated hemoglobin solution as an O2 carrier. Ann Surg 211:394, 1990. 8.Vlahakes GJ, Lee R, Jacobs EE, LaRaia PJ, Austen, WG: Hemodynamic effects of oxygen transport properties of a new blood substitute in a model of massive blood replacement. J Thorac Cardiovasc Surg 100:379, 1990. 9.Hoffman SJ, Looker DL, Roehrich JM, Cozart PE, Durfee SL, Tedesco JL, Stetler GL: Expression of fully functional tetrameric human hemoglobin in Escherichia coli. Proc Natl Acad Sci 87:8521, 1990. 10.Looker D, Abbott-Brown D, Cozart P, Durfee S, Hoffman S, Mathews A, Miller-Roehrich J, Shoemaker S, Trimble S, Fermi G, Komiyama N, Nagai K, Stetler G. A human recombinant haemoglobin designed for use as a blood substitute. Nature 356:258, 1992. 11.Otto BR, Verweij-van Vught AMJJ, MacLaren DM: Blood substitutes and infection. Nature 358:23, 1992.

To: Little Engine who wrote (1542)	6/21/1998 5:57:00 PM
From: Prospector	Respond to of 5402

Great Job Little Engine We need to build on your research... Prospector ( good Job Engine!!!!! )

To: Little Engine who wrote (1542)	6/21/1998 9:29:00 PM
From: drdan	Read Replies (1) \| Respond to of 5402

Some answers to your questions.... 1) Sanguine has done transfusion work in the Japanese,Canadian, British, German populatons and with the Jehovah's Witnesses, totalling thousands of patients. You can find the specifics onthe info thread. 2) The side effects attributed to Fluosol was due to the emulsion used to keep the Fluosol molecules from clumping....that problem has been worked out since subsequent data showed no incidence of embolism, allergic reactions, etc.Again, this info is all on the info thread. Regardless of how long it took to approve Fluosol for angioplasties, pher02 should not take as long to be approved for trauma, surgical and chronic transfusion indications. My best GUESS would be three years. 3)I am not sure what you mean by "the existing market." If you mean angioplasty, you may be right.However, the main use will be in transfusion situations and for heart-bypass machines .When you consider that the transfusion market is tens of billions of dollars a year , and pher02 will cost about 10% of a pint of blood($30vs. $300 for a pint of blood), I would say that the profit margin will be quite fine for Sanguine once Pher02 hits the market for transfusion use. Don't forget that the other uses would generate additional revenue.BTW, the first approval is to be for heart-bypass machines, a market in which about 300,000 procedures are done in the US yearly.