GB2235860A

GB2235860A - Antioxidant containing blood substitutes

Info

Publication number: GB2235860A
Application number: GB8914589A
Authority: GB
Inventors: Barry A Scherr
Original assignee: Individual
Current assignee: Individual
Priority date: 1989-06-26
Filing date: 1989-06-26
Publication date: 1991-03-20
Also published as: GB8914589D0

Abstract

Blood substitutes containing iron e.g. hemoglobin are formulated so that they are less toxic by the addition of the antioxidant, (+)-Cyanidanol-3, or a strong antioxidant such as Butylated hydroxytoluene or Butylated hydroxyanisole.

Description

Blood Substitutes-Antioxidant Formulas In the use of blood substitutes which are derived from hemoglobin or other iron-containing substances, it has been found that many of the tissues of the body are adversely affected. This effect is found in total or partial transfusions or in the use of blood substitutes during angioplasty or perfusion of transplant tissue.

The addition of a strong antiotidant can prevent this problem.

One novelty, therefore, of this invention is the use of the antioxidant (+)-cyanidanol-3 in the preparation or administration of blood substitutes which pre derived from hemoglobin or other iron containing molecules.

Other strong antioxidants which may be utilized include butylated hydroxytoluene, and butylated hydroxyanisole.

Other similar strong antioxidants may be suitable.

Example 1 The hemoglobin solution is prepared from outdated erythrocyte concentrates by a method of several steps as described by Bonhard K. and Kothe N. The erythrocyte concentrates are pooled, repeatedly washed with 10 percent glucose solution, chemically sterilized with B-propiolacta , hemolyzed by the addition of distilled water; stroma removal by precipitation, centrifugation, and filtration, concentration of the hemoglobin to 22 percent weight by volume; its conversion to desoxyhemoglobin; reaction with pridoxal-- phosphate; cross-linking with glutardialdellyde and reduction with sodium borohydridc.

Each unit is then reconstituted with 500 ml. of phosphate buffer solution of pH 7.3 containing 100 mg. of (+)-Cyanidanol 3.

Although the example here given utilizes adult human hemoglobin which is then destromatized, cross-linked and mo91fied with a 2,3 diphosphoglycerate substitute, it is ciear that any iron containing blood substitute may be utilized without deviating from the novelty of the principle described herein.

Although the example here given utilizes (+)-Cyanidanol-3 as the strong antioxidant, it is clear that butylated hydroxytoluene, butylated hydroxyanisole, or any other suitably strong and relatively nontoxic antioxidant may be utilized without deviating from the novelty of the principle described herein.

Example 2 The hemoglobin solution is prepared from outdated erythrocyte concentrates by a method of several steps as described by Bonhard K. and Kothe N. The erythrocyte concentrates are pooled, repeatedly washed with 10 percent glucose solution, chemically sterilized with B-propiolactone, hemolyzed by the addition of distilled watery stroma removal by precipitation, centrifugation, and filtration, concentration of the hemoglobin to 22 percent weight by volume; its conversion to desoxyhemoglobin; reaction with bis 3,5 dibromosalicylfumarate; not crosslinked and reduced with sodium borohydride.

Each unit is then reconstituted with 500 ml of phosphate buffer solution of pH 7.3 containing 10 mg of Butylated Hydroxyanisole and/or 10 mg of Butylated hydroxytoluene dispersed with 1 mg of Tween 80.

Claims

The invention is not limited to the precise construction herein disclosed but, rather, includes all modification and improvements, encompassed within the scope of the following claims.

I claim: 1. The use of the antioxidant (+)-Cyanidanol-3 in the formulation of blood substitutes which contain iron or are derived from iron-containing substances, such as, but not limited to hemoglobin.
2. The use of other strong antioxidants, including but not limited to butylated hydroxytoluene and/or butylated hydroxyanisole, in formulating blood substitutes which contain iron, including, but not limited to those derived from hemoglobin.
3. The concomitant administration of antioxidants, includ ng, but not limited to (+)-Cyanidanol-3, butylated hydroxytoluene, and/or butylated hydroxyanisole during the use or administration of blood substitutes containing iron, such as those derived from hemoglobin.