USE OF DIPYRIDAMOLE OR MOPIDAMOL FOR TREATMENT AND PREVENTION OF FIBRIN-DEPENDENT MICROCIRCULATION DISORDERS

• US 20080113934A1
• Filed: 12/18/2007
• Published: 05/15/2008
• Est. Priority Date: 10/22/1999
• Status: Abandoned Application

• Current Assignee: Wolfgang Eisert
• Original Assignee: Wolfgang Eisert
• Inventors: Eisert, Wolfgang
• Application Number:
  US11/958,504
• Publication Number:
  US 20080113934A1
• Time in Patent Office: Days
• US Class Current: 514/56
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/366 having six-membered rings, e.g. delta-lactones
• CPC Class Codes: A61K 31/401 Proline; Derivatives thereof, e.g. captopril
• CPC Class Codes: A61K 31/4743 condensed with ring systems having sulfur as a ring hetero atom
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61K 31/60 Salicylic acid; Derivatives thereof
• CPC Class Codes: A61K 31/727 Heparin; Heparan
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 13/02 of urine or of the urinary tract, e.g. urine acidifiers
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/16 Otologicals
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/00 : Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/10 : for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 39/02 : Antidotes
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/00 : Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 7/02 : Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/12 : Antihypertensives
• CPC Class Codes: A61P 9/14 : Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers

Abstract

A method of treatment of the human or non-human animal body for treating fibrin-dependent microcirculation disorders is disclosed, for example, microcirculation disorders caused by metabolic diseases, inflammatory reactions or autoimmune diseases; peripheral microcirculation disorders or microcirculation disorders associated with increased cell fragmentation comprising administering to a human or non-human animal body in need of such treatment an effective amount of a pharmaceutical composition containing a pyrimido-pyrimidine selected from dipyridamole, mopidamol and the pharmaceutically acceptable salts thereof, and the use of said pyrimido-pyrimidine for the manufacture of a corresponding pharmaceutical composition.

Claims

1. A method for treating or preventing in a mammal fibrin-dependent microcirculation disorders or disease states where such microcirculation disorders are involved comprising administering to said mammal an effective amount of a pharmaceutical composition comprising a pyrimido-pyrimidine selected from dipyridamole, mopidamol, and the pharmaceutically acceptable salts thereof alone in a monopreparation.

6. The method of claim 1 or 2 wherein the pyrimido-pyrimidine is dipyridamole.

7. The method of claim 1 or 2 wherein the mammal is a human.

8. The method of claim 1 or 2 wherein the fibrin-dependent microcirculation disorder is selected from the group consisting of:

microcirculation disorders caused by metabolic diseases where vascular damages are involved, microcirculation disorders caused by inflammatory reactions, microcirculation disorders caused by autoimmune diseases, peripheral microcirculation disorders, and microcirculation disorders associated with increased cell fragmentation.

9. The method of claim 8 wherein the fibrin-dependent microcirculation disorder is selected from the group consisting of:

diabetic angiopathy, diabetic microangiopathy, diabetic gangrene, diabetic retinopathy, diabetic neuropathy, ulcus cruris, morbus crohn, autoimmune chronic-active hepatitis, idiopathic hepatitis, primary-biliary cirrhosis, multiple sclerosis, Raynaud'"'"'s disease, tinnitus, sudden loss of hearing, tumor diseases, thrombotic-thrombocytopenic purpura (TTP), nephrosclerosis, prerenal hypertension, haemolytic-uremic syndrome (HUS), arterial hypertension, vascular dementia, Alzheimer'"'"'s disease, Sudeck'"'"'s disease, central-veneous thrombosis of the eye, ischemic optic neuropathy, homocystine-induced vasculopathy, ischemic heart diseases, coronary heart diseases, myocardial infarction, myocardial reinfarction, and atherosclerosis.

10. The method of claim 1 or 2 wherein a plasma level of about 0.2 to 5 μ

mol/L of the pyrimido-pyrimidine is maintained.

11. The method of claim 1 or 2 wherein the pyrimido-pyrimidine is administered using an oral sustained release formulation, an immediate release formulation, or a parenteral formulation.

12. The method of claim 1 or 2 wherein the pyrimido-pyrimidine is administered orally in a daily dosage of 25 to 450 mg or parenterally in a dosage of 0.5 to 5 mg/kg body weight during 24 hours.

14. The method of claim 8 wherein a plasma level of dipyridamole or mopidamol of about 0.2 to 50 μ

mol/L is maintained when treating a microcirculation disorder associated with increased cell fragmentation.

15. The method of claim 14 further comprising administering an oral daily dosage of about 10 to 30 mg of acetylsalicylic acid (ASA).

2. A method for treating in a mammal fibrin-dependent microcirculation disorders or disease states where such microcirculation disorders are involved comprising administering to said mammal an effective amount of a pharmaceutical composition comprising a pyrimido-pyrimidine selected from dipyridamole, mopidamol, and the pharmaceutically acceptable salts thereof in combination with an agent selected from the group consisting of:

acetylsalicylic acid (ASA), clopidogrel, ticlopidine and the pharmaceutically acceptable salts thereof, fibrinogen receptor antagonists, heparin, heparinoids, antithrombins, ACE inhibitors, Angiotensin II antagonists, calcium-antagonists and lipid-lowering agents;

wherein ASA is administered orally in a daily dosage of 10 to 30 mg.

3. The method of claim 2 wherein the agent is acetylsalicylic acid (ASA), clopidogrel or ticlopidine or the pharmaceutically acceptable salts thereof.

4. The method of claim 2 wherein the agent is a lipid-lowering agent.

5. The method of claim 4 wherein the lipid-lowering agent is a statin.

13. The method of claim 2 wherein the pharmaceutical composition comprises the pyrimido-pyrimidine in combination with acetylsalicylic acid (ASA) as the other antithrombotic agent, administered orally in a daily dosage of 10 to 30 mg of ASA together with 50 to 300 mg of the pyrimido-pyrimidine.