Unit aerosol doses for anticoagulation

Patent metadata

Field	Value
Publication number	US-11547663-B2
Application number	US-202016890264-A
Country	US
Kind code	B2
Filing date	Jun 2, 2020
Priority date	Jan 20, 2015
Publication date	Jan 10, 2023
Grant date	Jan 10, 2023

Abstract

Disclosed herein are methods for prophylactic treatment of acute coronary syndrome (ACS) comprising administering, by inhalation, an effective amount of a pharmaceutical composition comprising at least one anticoagulant or antiplatelet agent to a subject in need thereof, wherein the anticoagulant or antiplatelet agent first enters the heart via the left atrium.

First claim

What is claimed is:

1. A method for treatment of acute coronary syndrome and/or thrombosis comprising:
administering, by inhalation, an effective amount of a pharmaceutical composition to a subject in need thereof, wherein the pharmaceutical composition comprises (a) a univalent direct thrombin inhibitor selected from the group consisting of argatroban, melagatran, ximelagatran, and dabigatran,
wherein at least about 5% of the univalent direct thrombin inhibitor is delivered to the coronary arteries.

2. The method of claim 1 , wherein the pharmaceutical composition further comprises a direct factor Xa inhibitor.

3. The method of claim 1 , wherein the pharmaceutical composition is administered by a condensation aerosol, a liquid nebulizer, a nebulizer, an active dry powder inhaler, a passive dry powder inhaler, or a metered dose inhaler.

4. The method of claim 1 , wherein the pharmaceutical composition is in the form of an aerosol, a dry powder, or nebulized droplets.

5. The method of claim 1 , wherein the pharmaceutical composition has a mass median aerodynamic diameter of less than about 10 μm.

6. The method of claim 1 , wherein the pharmaceutical composition is self-administered by the patient.

7. The method of claim 1 , wherein the effective amount is administered in between about 1 and about 10 inhalations.

8. The method of claim 1 wherein the acute coronary syndrome comprises ischemic events, clotting, angina, myocardial infarction, or any combination thereof.

9. The method of claim 1 , wherein the effective amount is between about 0.1 and 150 mg/kg.

10. The method of claim 2 , wherein the direct factor Xa inhibitor is at least one of rivaroxaban, apixaban, edoxaban, betrixaban, darexaban, TAK-442 (letaxaban), eribaxaban, or otamixaban.

11. A method for prevention of acute coronary syndrome and/or thrombosis in a patient comprising:
inhaling an effective amount of a pharmaceutical composition, the pharmaceutical composition comprising an antithrombotic compound,
wherein the antithrombotic compound comprises (a) a univalent direct thrombin inhibitor selected from the group consisting of argatroban, melagatran, ximelagatran, and dabigatran,
wherein at least about 5% of the univalent direct thrombin inhibitor is delivered to the coronary arteries and/or wherein about 10% to about 80% of the antithrombotic compound is delivered to the left atrium.

12. The method of claim 11 , wherein the administration prevents platelet aggregation.

13. The method of claim 11 , wherein the patient is suffering from at least one of stable angina, unstable angina, myocardial infarction, valvular heart disease, stroke, and atrial fibrillation.

14. The method of claim 11 , wherein the patient is a heart transplant or heart valve replacement patient.

15. The method of claim 11 , wherein the pharmaceutical composition further comprises a pharmaceutically acceptable excipient.

16. The method of claim 11 , wherein the pharmaceutical composition is delivered at a therapeutic level to the heart and coronary arteries and at a sub-therapeutic level to rest of the body other than the heart and coronary arteries.

17. The method of claim 11 , wherein the pharmaceutical composition further comprises a direct factor Xa inhibitor.

18. The method of claim 17 , wherein the direct factor Xa inhibitor is at least one of rivaroxaban, apixaban, edoxaban, betrixaban, darexaban, TAK-442 (letaxaban), eribaxaban, or otamixaban.

Assignees

• Incarda Therapeutics Inc
• Univ California

Inventors

• Narasimhan Rangachari
• Marcus Gregory

Classifications

• A61K31/37

  Coumarins, e.g. psoralen · CPC title

• A61K9/0078 Primary

  for inhalation via a nebulizer such as a jet nebulizer, ultrasonic nebulizer, e.g. in the form of aqueous drug solutions or dispersions · CPC title

• A61K9/0075

  for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles · CPC title

• A61K9/0073 Primary

  Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy; (nasal sprays A61K9/0043; inhalation of vapours of volatile or heated drugs, e.g. essential oils or nicotine, A61K9/007; devices A61M) · CPC title

• A61K31/4365

  the heterocyclic ring system having sulfur as a ring hetero atom, e.g. ticlopidine · CPC title