Acarbose Chemische Eigenschaften,Einsatz,Produktion Methoden
Beschreibung
Acarbose, a complex oligosaccharide isolated from Actinoplanes, is reportedly
useful as an adjuvant therapy in diabetes. By inhibiting alpha-glucosidase,
acarbose delays carbohydrate metabolism in the gastrointestinal tract and modulates
changes in food induced blood sugar levels.
Chemische Eigenschaften
Off-White Solid
Verwenden
Acarbose is pseudo-oligosaccharide with a terminal C7-cyclitol patented in 1975 by Bayer. Acarbose is a component of the amylostatin complex produced by a species of Actinoplanes and Streptomyces. Acarbose acts as a potent inhibitor of alpha-glucosidases and saccharases. Since 1990, acarbose has been used therapeutically for the treatment of type 2 diabetes.
Definition
ChEBI: A tetrasaccharide derivative consisting of a dideoxy-4-{[4,5,6-trihydroxy-3-(hydroxymethyl)cyclohex-2-en-1-yl C7 cyclitol moiety [called valienol (or valienamine)] linked via nitrogen to isomaltotriose.
Weltgesundheitsorganisation (WHO)
Acarbose, ana-glucosidase inhibitor, is used as an adjunctive
therapy in the control of postprandial hyperglycaemia in non-insulin-dependent
diabetes mellitus. Use of two or more hypoglycaemic drugs is not recommended.
Allgemeine Beschreibung
Acarbose is a naturally occurring oligosaccharide,which is obtained from the microorganism Actinoplanes utahensis. It is a white to off-white powder that is soluble in water and has a pKa of 5.1. As one mightexpect, its affinity for α-glucosidase is based on it being apolysaccharide that the enzyme attempts to hydrolyze. Thisallows acarbose to act as a competitive inhibitor, which inturn reduces the intestinal absorption of starch, dextrin, anddissacharides.
It is sold as 25-, 50-, and 100-mg tablets (Precose,generics) dosed with the first bite of each meal, up to t.i.d. Acarbose potently inhibits the glucoamylase activity of MGAM α-glucosidases and the sucrase activity of α-glucosidases, where as isomaltase activity is at most moderately inhibited at concentrations in the range of those in theintestinal lumen upon oral dosing, and trehalase and lactaseare not significantly inhibited. Some inhibition of pancreaticα-amylases may also contribute to the clinical effects.
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Clinical Use
Based on the structure of acarbose, it should come as nosurprise that little intact acarbose reaches the systemic circulation;instead, acarbose is extensively biotransformed by the actionof microbes and digestive enzymes in the gut. Only about35% of the radioactivity in a dose of
14C-labeled acarbose administeredorally to men was excreted in the urine, appearingas several metabolites, some of which are phase II conversionproducts of 4-methylpyrogallol (O-methyl, O-sulfate, orO-glucuronide conjugates); the methylpyrogallol fragmentarises from the terminal valienamine pseudosugar. That thesebiotransformation products are mostly formed in the gut isshown by the fact that nearly 90% of an intravenously administereddose of acarbose is excreted intact in urine.
Sicherheitsprofil
Low toxicity by ingestion,subcutaneous, and intravenous routes. Human systemiceffects: liver function impaired. When heated todecomposition it emits toxic vapors of NOx.
Acarbose Upstream-Materialien And Downstream Produkte
Upstream-Materialien
Downstream Produkte
