A detailed discussion of colloids is given by Mls.hleL(.19.8.4). and Baron...(1992).
Albumin is the fraction of plasma which provides the major part of the circulation's colloid osmotic pressure, and therefore it has been used as a plasma substitute. Although it is naturally occurring, there is a certain amount of heterogeneity in circulating albumin. Albumin for infusion is virtually free rom disease transmission since it is heated to 60 °C for approximately 10 h following fractionation. This fractionation process contributes further heterogeneity since the final product contains some dimers and longer-chain polymers. Storage of albumin solutions may produce further heterogeneity through the formation of unstable polymers which may affect in vivo characteristics.
Albumin is the main provider of colloid osmotic pressure in the plasma and has a number of other functions:
1. transport of various molecules;
2. free-radical scavenging;
3. binding of toxins;
Human albumin solutions have been used successfully as plasma substitutes, and in view of their natural occurrence are considered by many as the gold standard with which synthetic plasma substitutes are compared. The major limitations to the use of human albumin solutions are their high production costs and limited supplies.
Gelatin is a degradation product of animal collagen and therefore is inexpensive and readily available. Gelatin polypeptides are chemically modified to reduce the gel melting point while retaining sufficient molecular size for intravascular retention. In the manufacture of urea-bridged gelatin (polygeline) polypeptides of molecular weight 12 000 to 15 000 Da are formed by thermal degradation of cattle bone gelatin and subsequently cross-linked by hexamethyl di-isocyanate. In the manufacture of succinylated gelatin polypeptides of molecular weight approximately 23 000 Da are produced by thermal degradation of calf skin collagen. These polypeptides are reacted with succinic acid anhydride to replace amino groups with acid carboxyl groups. No cross-links are formed, but the increased net negative charge on the molecule produces a conformational change to open coils. Although little increase in molecular weight is produced by this reaction, molecular size is increased allowing better intravascular retention.
Dextrans are high-molecular-weight polysaccharides. They are natural substances produced by the action of the enzyme dextran sucrase during the growth of various strains of the bacteria Leuconostoc in media containing sucrose. After partial hydrolysis of raw dextran (molecular weight between 10 7 and 108 Da), the resulting hydrolysate is fractionated to produce dextran molecules of average molecular weight 75 000 Da. Since 1953, Leuconostoc mesenteroides B512 has been the strain used for the manufacture of clinical dextrans. Other strains had been shown to produce dextran molecules with greater degrees of branching, and these molecules were associated with more immunological reactions. Over 90 per cent of the branches in dextran molecules produced by L. mesenteroides B512 are a1-6 glucosidic bonds, giving relatively few side-chains. The original clinical dextran has undergone changes in the fractionation procedure such that the average molecular weight is now 70 000 Da (dextran 70).
Unmodified starch is unsuitable as a plasma substitute since it is broken down rapidly by amylase. The hydroxyethylation of starch protects the polymer against breakdown by amylase. Waxy starches consisting of 98 per cent amylopectin are used in the manufacture of hydroxyethyl starch. Amylopectin, which is a highly branched polysaccharide resembling natural glycogen, is suspended in water and dilute hydrochloric acid and hydrolysis is allowed to continue until the viscosity of the solution approximates that of dextran 75. The solution is neutralized and treated with ethylene oxide in the presence of sodium hydroxide as a catalyst. Thus glucose units are substituted with hydroxyethyl groups at positions C2, C3, and C6 ( Mishler l984). The characteristics of hydroxyethyl starch solutions are dependent on the range of molecular weights, the degree of substitution of glucose units by hydroxyethyl groups, and the ratio of C2 to C6 substitution. In general, higher molecular weights, higher degrees of substitution, and a high ratio of C2 to C6 substitution are associated with more prolonged effects.
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