Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K38/00—Medicinal preparations containing peptides
  • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
  • A61K38/43—Enzymes; Proenzymes; Derivatives thereof
  • A61K38/45—Transferases (2)
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
  • A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors

Definitions

• the subject of this invention is the application of adenylate kinase to disaggregation of already formed blood platelets (thrombocytes) aggregates and to the inhibition of platelets aggregation.
• Clopidogrel is an antithrombotic agent that lowers the blood platelets ability to create thrombus. Clopidogrel blocks the ADP-dependent mechanism of aggregation through modifying the structure of the purine receptor present on the blood platelets surface. After the first week of Clopidogrel treatment, the blood platelets activity decreases to 40-60%.
• Clopidogrel is applied to prevent from thrombus formation in patients after myocardial infarction or ischemic stroke and in generalized atherosclerosis. It is often used together with acetylsalicylic acid. Both of them have a similar therapeutic effect, however, they differ in mechanism of action. Their simultaneous applying is essential in some cases. Clopidogrel is a quite well tolerated medicine. The most dangerous of the eventual side effects is bleeding or haemorrhage. The medicine can also induce diarrhoea, stomach ache and indigestion. Before intended surgical intervention, the medication discontinuation should be taken into consideration, if the permanent dosage is not absolutely necessary.
• ADP adenine diphosphonucleotide
• Adenylate kinase from Bacilus stearothermophilus has the similar Km values for both ATP and ADP as substrates.
• the enzyme catalyzes the reaction according to the following scheme: adenylate kinase
• ATP is the competitive inhibitor of P2Y 12 receptor. It means that the increase of ATP concentration in blood inhibits the activity of the P2Y 12 receptor and as a result - thrombocytes aggregation.
• AMP the second product of the reaction above, is degradated by 5 '-nucleotidase present on the thrombocytes surface to adenosine (Ado), according to the following reaction:
• adenosine activates adenosine receptors A2a and triggers the increase in adenylate cyclase activity and cAMP concentration. It results in decreasing the calcium ions concentration within thrombocytes. These changes lead to inhibition of blood platelets aggregation.
• AKBs The catalytic activity of AKBs causes the inhibition of platelets aggregation in result of three factors: eliminating of ADP present in blood, increase in ATP and Ado concentration. Therefore activity of adenylate kinase from Bacilus stearothermophilus decreases the blood platelets ability to aggregation and inhibits thrombus formation.
• the experimental results show that in the presence of AKBs the aggregation of blood platelets activated by collagen is not only stopped but also the already formed aggregates are dissolved (Tabela 1, 2).
• AKBs The action of AKBs is highly beneficial.
• our enzyme In opposite to other enzymatic preparations that hydrolyse the thrombus that is already formed, our enzyme not only prevents from blood coagulation by inhibiting the platelets aggregation but also dissolves the aggregates. As a result of its action, no thrombus is formed.
• Adenylate kinase from Bacilus stearothermophilus can be used to the inhibition of blood coagulation in blood banks, to inhibition of uncontrolled blood coagulation in blood vessels and to reduce the disadvantageous effects of myocardial and cerebral infarction.
• the analyses of deaggregative properties of adenylate kinase from Bacilus stearothermophilus will be described in following examples.
• the platelet-rich plasma obtained from pig blood was used to experiments concerning the deaggregative function of AKBs.
• the platelets aggregation was initiated by 7.5 ⁇ g/ml collagen.
• Succesive samples were analysed with different amounts of adenylate kinase addded before collagen or 1 and 5 minutes after initiation of the platelets aggregation with collagen.

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• Pharmacology & Pharmacy (AREA)
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• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• Diabetes (AREA)
• General Chemical & Material Sciences (AREA)
• Chemical Kinetics & Catalysis (AREA)
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• Proteomics, Peptides & Aminoacids (AREA)
• Epidemiology (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

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• 2009
  • 2009-06-08 PL PL388214A patent/PL388214A1/pl not_active Application Discontinuation
• 2010
  • 2010-06-07 WO PCT/PL2010/000043 patent/WO2010143985A1/en not_active Ceased

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