Combination product comprising melagatran and factor VIIa inhibitor

• US 20030153506A1
• Filed: 12/06/2002
• Published: 08/14/2003
• Est. Priority Date: 06/10/2000
• Status: Abandoned Application

• Current Assignee: Astrazeneca AB (Astrazeneca PLC)
• Original Assignee: Astrazeneca AB (Astrazeneca PLC)
• Inventors: Bylund, Ruth, Mattsson, Christer
• Application Number:
  US10/297,727
• Publication Number:
  US 20030153506A1
• Time in Patent Office: Days
• US Class Current: 514/18
• 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 38/55 Protease inhibitors
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• 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 31/04 Antibacterial agents
• CPC Class Codes: A61P 39/00 General protective or antinoxious agents
• CPC Class Codes: A61P 41/00 Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 7/04 Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
• CPC Class Codes: A61P 7/08 Plasma substitutes; Perfusion solutions; Dialytics or haemodialytics; Drugs for electrolytic or acid-base disorders, e.g. hypovolemic shock artificial tears A61P27/04
• CPC Class Codes: A61P 7/10 Antioedematous agents; Diuretics
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/02 Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
• CPC Class Codes: A61P 9/04 Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
• 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 9/14 Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers

Abstract

There is provided a combination product comprising: (A) melagatran or a pharmaceutically-acceptable derivative thereof; and (B) a Factor VIIa inhibitor or a pharmaceutically-acceptable derivative thereof, wherein each of components (A) and (B) is formulated in admixture with a pharmaceutically-acceptable adjuvant, diluent or carrier, as well as the use of such a combination product in the treatment of a condition where anticoagulant therapy is indicated.

Claims

1. A combination product comprising:

(A) melagatran or a pharmaceutically-acceptable derivative thereof; and

(B) a Factor VIIa inhibitor or a pharmaceutically-acceptable derivative thereof,

wherein each of components (A) and (B) is formulated in admixture with a pharmaceutically-acceptable adjuvant, diluent or carrier.

2. A combination product as claimed in claim 1 which comprises a pharmaceutical formulation including melagatran or a pharmaceutically-acceptable derivative thereof, and a Factor VIIa inhibitor or a pharmaceutically-acceptable derivative thereof, in admixture with a pharmaceutically-acceptable adjuvant, diluent or carrier.

3. A combination product as claimed in claim 1 which comprises a kit of parts comprising components:

(a) a pharmaceutical formulation including melagatran or a pharmaceutically-acceptable derivative thereof, in admixture with a pharmaceutically-acceptable adjuvant, diluent or carrier; and

(b) a pharmaceutical formulation including a Factor VIIa inhibitor or a pharmaceutically-acceptable derivative thereof, in admixture with a pharmaceutically-acceptable adjuvant, diluent or carrier,

which components (a) and (b) are each provided in a form that is suitable for administration in conjunction with the other.

4. A kit of parts as claimed in claim 3, wherein components (a) and (b) are suitable for sequential, separate and/or simultaneous use in the treatment of a condition where anticoagulant therapy is indicated.

5. A combination product as claimed in any one of claims 1 to 3, wherein the derivative of melagatran is a prodrug of melagatran.

6. A combination product as claimed in claim 5, wherein the prodrug is of the formula

R¹O₂C—

CH₂—

(R)Cgl-Aze-Pab—

OH,

wherein R¹ represents linear or branched C_1-6 alkyl and the OH group replaces one of the amidino hydrogens in Pab.

7. A combination product as claimed in claim 5, wherein R¹ represents methyl, ethyl, n-propyl, i-propyl or t-butyl.

8. A combination product as claimed in claim 5, wherein R¹ represents ethyl.

9. A combination product as claimed in any one of claims 1 to 3, wherein the derivative of the Factor VIIa inhibitor is a prodrug of that inhibitor.

10. A method of making a kit of parts as defined in claim 3, which method comprises bringing a component (a), as defined in claim 3, into association with a component (b), as defined in claim 3, thus rendering the two components suitable for administration in conjunction with each other.

11. A kit of parts comprising:

(I) one of components (a) and (b) as defined in claim 3;

together with (II) instructions to use that component in conjunction with the other of the two components.

12. A method of treatment of a condition where anticoagulant therapy is indicated, which comprises administration of a combination product as defined in any one of claims 1 to 3 or a kit of parts as defined in claim 11 to a patient suffering from, or susceptible to, such a condition.