Ceredase Online, Description, Chemistry, Ingredients - Alglucerase

Ceredase Online, Description, Chemistry, Ingredients - Alglucerase

Ceredase
(alglucerase injection)

DESCRIPTION

Ceredase (alglucerase injection) is a modified form of the enzyme, Beta- glucocerebrosidase (Beta-D-glucosyl-N- acylsphingosine glucohydrolase, EC 3.2.1.45). Alglucerase is a monomeric glycoprotein of 497 amino acids with carbohydrates making up approximately 6% of the molecule (M = 59,300 as determined by SDS-PAGE). The unmodified enzyme (b-glucocerebrosidase) also contains 497 amino acids and contains approximately 12% carbohydrate (M(r) = 67,600). The carbohydrates on the unmodified enzyme consist of N-linked carbohydrate chains of the complex and high mannose type. Glucocerebrosidase and alglucerase catalyze the hydrolysis of the glycolipid, glucocerebroside, within the lysosomes of the reticuloeridotlielial system.

Alglucerase is prepared by modification of the oligosaccharide chains of human Beta-glucocerebrosidase. The modification alters the sugar residues at the non-reducing ends of the oligosaccharide chains of the glycoprotein so that they are predominantly terminated with mannose residues which are specifically recognized by carbohydrate receptors on macrophage cells. Ceredase is supplied as a clear sterile non-pyrogenic solution of alglucerase in a citrate buffered solution (53 mM citrate, 143 mM sodium) containing I% albumin human USP. The enzyme is supplied in two concentrations, 400 units per bottle (80 units/mL) and 50 units per bottle (10 units/mL) with a fill volume of 5 mL per bottle. An enzyme unit (U) is defined as the amount of enzyme required to hydrolyze in one minute one micromole of the synthetic substrate, 4 methylumbelliferyl-Beta-glucoside.

Ceredase is purified from a large pool of human placental tissue collected from selected donors. Steps have been introduced into the manufacturing process to reduce further the risk of viral contamination. However, no procedure has been shown to be totally effective in removing viral infectivity. (See PRECAUTIONS). Each lot of product has been tested and found negative for hepatitis B surface antigen (HBsAg) and for human immunodeficiency virus antigen (HIV-1) and antibody (HIV-1/2).

Human chorionic gonadotropin (hCG), a naturally occurring hormone in human placenta, has been detected in Ceredase. Although it is likely the hCG is partially deglycosylated, in vitro studies demonstrate biological activity of approximately 3 units of hCG activity per unit of Ceredase. Preliminary studies suggest that the deglycosylated hCG in Ceredase is rapidly cleared at a rate which is approximately forty times greater than that of native hCG. Therefore, in vivo biological activity and clearance of the material may be different to the naturally occurring hormone and is currently under investigation.