Crystalline salts of a plasma kallikrein inhibitor

Patent metadata

Field	Value
Publication number	US-11117867-B2
Application number	US-202016784016-A
Country	US
Kind code	B2
Filing date	Feb 6, 2020
Priority date	Nov 2, 2018
Publication date	Sep 14, 2021
Grant date	Sep 14, 2021

Abstract

Disclosed are crystalline salts of Compound I, methods of preparing them, and related pharmaceutical preparations thereof. Also disclosed are methods of treatment using the crystalline salts of the invention.

First claim

We claim:

1. A pharmaceutical composition, comprising a crystalline salt of Compound I,

and a pharmaceutically acceptable carrier;
wherein the pharmaceutical composition is an oral dosage form; and the oral dosage form contains about 75 mg to about 250 mg of the crystalline salt of Compound I.

2. The pharmaceutical composition of claim 1 , wherein the crystalline salt of Compound I is a hydrochloride salt.

3. The pharmaceutical composition of claim 1 , wherein the crystalline salt of Compound I is a bis(hydrochloride) salt.

4. The pharmaceutical composition of claim 3 , wherein the oral dosage form contains about 75 mg to about 175 mg of the crystalline salt of Compound I.

5. The pharmaceutical composition of claim 3 , wherein the oral dosage form contains about 100 mg to about 250 mg of the crystalline salt of Compound I.

6. The pharmaceutical composition of claim 3 , wherein the oral dosage form contains about 100 mg to about 200 mg of the crystalline salt of Compound I.

7. The pharmaceutical composition of claim 3 , wherein the oral dosage form contains about 100 mg to about 175 mg of the crystalline salt of Compound I.

8. The pharmaceutical composition of claim 3 , wherein the oral dosage form contains about 125 mg to about 250 mg of the crystalline salt of Compound I.

9. The pharmaceutical composition of claim 3 , wherein the oral dosage form contains about 125 mg to about 200 mg of the crystalline salt of Compound I.

10. The pharmaceutical composition of claim 3 , wherein the oral dosage form contains about 125 mg to about 175 mg of the crystalline salt of Compound I.

11. The pharmaceutical composition of claim 3 , wherein the oral dosage form contains about 150 mg of the crystalline salt of Compound I.

12. The pharmaceutical composition of claim 3 , wherein the oral dosage form is a capsule, an ingestible tablet, a buccal tablet, a troche, an elixir, a suspension, a syrup, a powder, or a wafer.

13. The pharmaceutical composition of claim 3 , wherein the oral dosage form is a capsule.

14. A method of treating a disease or condition characterized by aberrant plasma kallikrein activity, comprising administering to a subject in need thereof the pharmaceutical composition of claim 1 .

15. The method of claim 14 , wherein the disease or condition characterized by aberrant plasma kallikrein activity is selected from the group consisting of stroke, inflammation, reperfusion injury, acute myocardial infarction, deep vein thrombosis, post fibrinolytic treatment condition, angina, edema, angioedema, hereditary angioedema, sepsis, arthritis, hemorrhage, blood loss during cardiopulmonary bypass, inflammatory bowel disease, diabetes mellitus, retinopathy, diabetic retinopathy, diabetic macular edema, diabetic macular degeneration, age-related macular edema, age-related macular degeneration, proliferative retinopathy, neuropathy, hypertension, brain edema, increased albumin excretion, macroalbuminuria, and nephropathy.

16. The method of claim 15 , wherein the disease or condition characterized by aberrant plasma kallikrein activity is angioedema.

17. The method of claim 15 , wherein the disease or condition characterized by aberrant plasma kallikrein activity is hereditary angioedema.

18. A method of preventing or treating angioedema attacks in a subject with hereditary angioedema, comprising administering to a subject in need thereof the pharmaceutical composition of claim 1 .

19. A method of reducing the frequency of angioedema attacks in a subject with hereditary angioedema, comprising administering to a subject in need thereof the pharmaceutical composition of claim 1 .

20. A method of treating an acute angioedema attack in a subject with hereditary angioedema, comprising administering to a subject in need thereof the pharmaceutical composition of claim 1 .

Assignees

• Biocryst Pharm Inc

Inventors

• El-Kattan Yahya
• Babu Yarlagadda S

Classifications

• A61P7/00

  Drugs for disorders of the blood or the extracellular fluid · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P27/02

  Ophthalmic agents · CPC title

• A61P7/04

  Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents · CPC title

• A61P19/02

  for joint disorders, e.g. arthritis, arthrosis · CPC title