Artificial blood substitute

Plasma volume expanders and artificial blood substitutes... 

The Green Cross Corporation, who have also been very active in the field of artificial blood substitutes, have synthesised a wide range of potential materials stemming from their first practical product Fluosol-DA, a mixture of perfluo-rodecalin and perfluorotripropylamine. 

At the most fundamental level, monolayers of surfactants at an air-liquid interface serve as model systems to examine condensed matter phenomena. As we see briefly in Section 7.4, a rich variety of phases and structures occurs in such films, and phenomena such as nucleation, dendritic growth, and crystallization can be studied by a number of methods. Moreover, monolayers and bilayers of lipids can be used to model biological membranes and to produce vesicles and liposomes for potential applications in artificial blood substitutes and drug delivery systems (see, for example, Vignette 1.3 on liposomes in Chapter 1). 

Poloxamer 188 has also been used as an emulsifying agent for fluorocarbons used as artificial blood substitutes and in the preparation of solid-dispersion systems. 

The Simons ECF process was subsequently developed to an industrial production process by the 3M Company. It currently provides the precursors to the palette of more than 250 large-scale fluorine-containing compounds produced by this company [27]. These products include fluorotensides, fire-fighting chemicals, per-fluorinated solvents, and artificial blood substitutes. 

Their pronounced ability to dissolve molecular oxygen in combination with their non-toxicity and complete physiological inertness makes perfluorocarbon fluids attractive for applications as respiratory fluids and as components of artificial blood substitutes [102] (Scheme 4.44). Many perfluorocarbons and perfluorinated amines can dissolve up to 40-50% v/v oxygen at 1 atm and 37 °C. It has been speculated that this unusual oxygen-dissolving capacity is related to the molecular shape and the occurrence of "cavities in perfluorocarbon fluids [103]. 

Scheme4.44 Compounds used as respiratory fluids (e.g. perfluorodecalin) or as components of artificial blood substitute mixtures [102a].

Highly substituted alkyl fluorides, called perfluoroalkanes, are often used as artificial blood substitutes. These perfluoroalkanes have the ability to transport Oj through the bloodstream as blood does. Some even have twice the O2 transport capability and are used to treat gangrenous tissue. The structure of perfluorodecalin is shown below. How many moles of fluorine must be reacted with one mole of decalin to produce perfluorodecalin ... 

Li S, Nickels J, Palmer AF. Liposome-encapsulated actin-hemoglobin (LEAcHb) artificial blood substitutes. Biomaterials 2005 26 3759-3769. 

Buo.soI-DA Pcrfluorodecalin Perfluorotripro-pyl amine Green Cross and Alpha TliCTa-peutics (Japan) Artificial blood substitute... 

FIuosoI-DA (Green Cross and Alpha Therapeutics, Japan), which consists of perfluorodecalin and perfluorotripropylamine, has already been marketed as an artificial blood substitute worldwide. 

How many units of blood are required each year in the United States Why do cancer patients require transfusions To what extent can artificial blood substitutes be used ... 

Geyer, R. P., 1975, Potential uses of artificial blood substitutes, Fed. Proc. 34 1525-1528. 

Patients given an artificial blood substitute w hich contained 2.7% poloxamer 188 as an emulsifier show ed signs of complement activation (Vercellotti, 1982). That their reaction w as due to the poloxamer component was confirmed by infusing poloxamer 188 alone into rabbits and producing similar symptoms. Incubation of human plasma wdth poloxamer 188 caused C3 conversion and decreased CH50, indicators of complement activation. However, the significance of this observation is in some doubt. Complement activation as determined from CH50 was not detected in vivo in the rat (Williams, 1988). Furthermore, poloxamer 188 has since been... 

Lane, T.A. and Lamkin, G.E. (1984) Paralysis of phagocyte migiyition due to an artificial blood substitute. 

Lane, T.A, and Kmkonis, V. (1988) Reduction in the toxicity of a component of an artificial blood substitute by supercritical fluid fractionation. Transfusion, 28, S75-378. 

One of the most significant contributions of bioengineering to the military is in the development of treatments for severe traumas sustained during warfare. For example, stem cell research may one day enable military physicians to regenerate functional tissues such as nerves, bone, cartilage, skin, and muscle—an invaluable tool for helping those who have lost limbs or other body parts as a result of explosives. The United States military was responsible for much of the early research done in creating safe, effective artificial blood substitutes that could be easily stored and relied on to be free of contamination on the batdefield. 

F.Hahn, A.Lange and H.Giertz, Anaphylactoid Reactions by Artificial Blood Substitutes, Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. 222, 603-614 (1954). 

Fluosol-DA Perfluoredecalin Perfluorotripropy- lamine Artificial blood substitutes Egg yolk lecithin, Pluronic F-68, Potassium oleate. Glycerol IV Alpha Therapeutics... 

Work concerning the artificial blood substitute studies was supported by a grant from the John A. Hartford Foundation, New York. Intralipid was generously furnished by Dr, Hakansson of Vitrum, Stockholm, Sweden and Aminofusin was generously supplied by Dr. Fekl, Pfrimmer and Co., Erlangen, West Germany. 

Human serum albumin (HSA) (Figure 5.10, for an exemplary structure) is the most abundant protein in plasma, constituting 55-60% of total serum protein content with a molecular weight of 66500 Da [425]. Like most human proteins, albumin is synthesized in the liver and has a half-life of 19 days in the body. Albumin is one of the most important proteins in the transportation of therapeutic drugs, as well as metabolic substrates [426]. Albumin as such can be used in the treatment of shock, burns, traumas, hypoalbuminemia and haemodialysis as an artificial blood substitute. An alternative to HSA has been engineered, which is a recombinant albumin and presents all the special features of the blood-derived one, together with good tolerability [427]. 

Several pharmaceutical products are formulated as emulsions (1) Parenteral emulsion systems, e.g. parenteral nutritional emulsions, lipid emulsions as drug carriers (2) Perfluorochemical emulsions as artificial blood substitute (3) Emulsions as vehicles for vaccines (4) topical formulations, e.g. for treatment of some skin diseases (dermatitis). 

The study of droplet rupture and coalescence by direct visual observation has been utilized in numerous essential studies [39-43]. Of principal importance are the experimental studies by Amelina et al. on the analysis of colloid stability in artificial blood substitutes [40-43]. These studies involved the use of various nonpolar phases, including perfluo-rinated systems, such as perfluorodecalin (PFD), perfluorotributylamine (PFTBA), per-fluoromethylcyclohexylpiperidine (PFMCHP), and conventional hydrocarbons, such as heptane. Stabilizing agents included Pluronic surfactants (ethylene oxide (EO)/propylene oxide (PO) block copolymers), as well-fluorinated surfactants, such as perfluorodiisononyl-ene with 20 mol of EO (( )-PEG). Tables 4.1 and 4.2 show some very characteristic results. 

The most effective emulsion and foam stabilizers are aerosol systems containing fluorocarbon propellants as surfactants. These are believed to form an oriented polymolecular structure at the propellant-water interface for optimum stability Sanders has found [90] that the surfactants must have a low solubility in both phases and have the ability to remain in the interfacial region. Hydrocarbon and fluorocarbon chains are not freely miscible and this perhaps explains the unusual behaviour of the surfactants in these systems. Addition of long-chain alcohols or acids enhance stability of the fluorocarbon emulsions and a hypothetical structure of the interfacial region has been proposed (Fig. 8.16). Davis et al. [91] have investigated the stability of fluorocarbon emulsions intended as artificial blood substitutes. Perfluorocarbon oils tended to produce unstable emulsions while oil phases such as perfluorotributylamine or per-fluorotetrahydrofuran formed more stable systems. These authors also refer to the possibility that as fluorocarbon-hydrocarbon mixtures have positive excess free energies, cohesive and adhesive forces between surfactant and oil phase will result. 

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