Patent GB-886553-A (GB)
Title: Substitutes for blood plasma and process for their manufacture
IPC: C07K14/78
Filed: 1959-01-22
Abstract: A substitute for blood plasma is produced by (i) subjecting a collagen degradation product to mild hydrolytic degradation to yield a hydrolysate of molecular weight of 2,000 to 20,000, e.g. 5,000 to 10,000, cross-linking the hydrolysate at pH about 7 by reaction with a proportion of a polyfunctional isocyanate smaller than that calculated for the total reaction of all the amino and guanidino groups present in the hydrolysate; (ii) cross-linking a collagen degradation product at pH about 7 by reaction with a proportion of a polyfunctional isocyanate smaller than that calculated for the total reaction of all the amino and guanidino groups present, subjecting the cross-linked product to mild hydrolytic degradation to yield a hydrolysate having a molecular weight of 10,000 to 100,000, e.g. 30,000 to 60,000; and the solution obtained from (i) or (ii) is adjusted to pH about 7, if it does not have that value, and is rendered isotonic.  The collagen degradation product may be gelatin. The proportion of the isocyanate may amount to 20% to 80% of that calculated for the total reaction of all the amino and guanidino groups present.  The isocyanate may be aromatic, hydroaromatic or aliphatic of formula OCN-(CH2)x-NCO where X is a whole number from 2 to 20, e.g. hexamethylene, diisocyanate, which may be used in solution or suspension in tetrahydrofurane, acetone or water.  The concentration of the cross-linked hydrolytic degradation product in solution may be 4% to 6% and the solution may be rendered isotonic by addition of sodium chloride or physiological salt mixture.  The hydrolysis may be acidic, alkaline, or fermentative, e.g. using trypsin, pepsin and tissue enzymes.  An aqueous gelatin solution of 5% strength may be (i) hydrolysed under pressure at 120 DEG C. to yield a hydrolysate having a molecular weight of 5,000 to 10,000 and the hydrolysate cross-linked with hexamethylene diisocyanate at 20 DEG C. to 30 DEG C., or (ii) may be cross-linked by reaction with hexamethylene diisocyanate at 20 DEG C. to 30 DEG C. and subsequently hydrolysed under pressure at 120 DEG C. to yield a hydrolysate having a molecular weight of 10,000 to 100,000.ALSO:A substitute for blood plasma is produced by (i) subjecting a collagen degradation product to mild hydrolytic degradation to yield a hydrolysate of molecular weight of 2000 to 20,000, e.g. 5000 to 10,000, cross-linking the hydrolysate at pH about 7 by reaction with a proportion of a polyfunctional isocyanate smaller than that calculated for the total reaction of all the amino and guanidino groups present in the hydrolysate; or (ii) cross-linking a collagen degradation product at pH about 7 by reaction with a proportion of a polyfunctional isocyanate smaller than that calculated for the total reaction of all the amino or guanidino groups present, subjecting the cross-linked product to mild hydrolytic degradation to yield a hydrolysate having a molecular weight of 10,000 to 100,000, e.g. 30,000 to 60,000; and the solution obtained from (i) or (ii) is adjusted to pH about 7, if it does not have that value, and is rendered isotonic.  The collagen degradation product may be gelatin.  The proportion of the isocyanate may amount to 20 to 80% of that calculated for the total reaction of all the amino and guanidino groups present.  The isocyanate may be aromatic, hydro-aromatic, or aliphatic of formula OCN-(CH2)x-NCO where x is a whole number from 2 to 20, e.g. hexamethylene diisocyanate, which may be used in solution or suspension in tetrahydrofurane, acetone or water. The concentration of the cross-linked hydrolytic degradation product in solution may be 4 to 6% and the solution may be rendered isotonic by addition of sodium chloride or physiological salt mixture.  The hydrolysis may be acidic, alkaline, or fermentative, e.g. using trypsin, pepsin and tissue enzymes.  An aqueous gelatine solution of 5% strength may be (i) hydrolysed under pressure at 120 DEG  C. to yield a hydrolysate having a molecular weight of 5000 to 10,000 and the hydrolysate cross-linked with hexamethylene diisocyanate at 20 DEG  to 30 DEG C., or (ii) may be cross-linked by reaction with hexamethylene diisocyanate at 20 DEG  to 30 DEG  C. and subsequently hydrolysed under pressure at 120 DEG  C. to yield a hydrolysate having a molecular weight of 10,000 to 100,000.