Aprotinin

CAS No. 9087-70-1

Source of the Raw Material

Bovine Lung from BSE-free countries

Dosage Form

Injection Vials and Bulk
Liquid for IV use

Strengths

• 100,000 K.I.U./vial
• 500,000 K.I.U./vial
• 1,000.000 K.I.U./vial

Introduction

The presence of proteinase inhibitors represents an important factor in the biological regulation of enzymes and enzyme systems. Their role is of particular importance in proteinase systems that are regulated or limited by their interference.
Proteinase inhibitors are found in great distribution in vertebrates and invertebrates as well as plants. Many inhibitors show similar properties and features and have been the subjects of biochemical research for a long time.
The polyvalent proteinase inhibitor Aprotinin was discovered in the bovine pancreas by Kunitz and Northrop in 1936. It has also been found in other bovine organs, particularly the lungs. After its subsequent isolation, its peptide character, its molecular weight (MW), and its effect on the enzymes trypsin and chymotrypsin were determined and fully described. Subsequent investigations over the ensuing decades described its effects as an inhibitor of the coagulation and fibrinolytic systems. Its amino acid sequence and the tertiary structure have also been elucidated.
Today, modern methods of separation through protein chemistry allow for extremely high purification and large scale production of Aprotinin.

Biochemistry

The polyvalent proteinase inhibitor Aprotinin is represented by a polypeptide structure of 58 amino acids that have a molecular weight of 6512 daltons.
The presence of 3 pairs of side-by-side situated cystein groups interconnected by disulfide bridges is of special significance. These pairs are responsible for the high inner stability of the molecule.
Four lysine groups form the active molecule centers; the tertiary structure shows a pear-shaped unit that fits exactly into the 'binding cavity' of the serine proteinase. Due to its inner stability, the inhibitor molecule is not altered by complex formation with the enzyme. This way, the enzyme is only blocked, not destroyed.
Following the law of mass action, the formation of the enzyme-inhibitor complex is reversible. As soon as the concentration of the free inhibitor drops below a certain level, the active enzyme is again regenerated as shown in the following diagram:

Since the half-life of Aprotinin is only about 60 minutes, a dosage scheme must be established that will avoid too strong a drop in the free inhibitor concentration.
The activity of our own Aprotinin, which is produced with our own technology, is determined according to the European Pharmacopoeia and is expressed in European Pharmacopoeia Units. 1 Ph Eur Unit corresponds to 1800 Kallikrein Inhibiting Units (KIU)