Crystalline modifications of N-(4,5-bismethanesulfonyl-2-methylbenzoyl)guanidine hydrochloride and N-(4,5-bismethanesulfonyl-2-methylbenzoyl)guanidine salts

Patent metadata

Field	Value
Publication number	US-10981864-B2
Application number	US-201716076017-A
Country	US
Kind code	B2
Filing date	Jan 27, 2017
Priority date	Feb 8, 2016
Publication date	Apr 20, 2021
Grant date	Apr 20, 2021

Abstract

The present invention relates to novel crystalline modifications of N-(4,5-bismethanesulfonyl-2-methylbenzoyl)guanidine hydrochloride, novel N-(4,5-bismethanesulfonyl-2-methylbenzoyl)guanidine salts and their crystalline modifications and processes of manufacturing and pharmaceutical formulations thereof.

First claim

The invention claimed is:

1. A crystalline hydrochloride salt of Rimeporide, excluding crystalline modification HCl-H1.

2. The crystalline hydrochloride salt according to claim 1 , wherein the crystalline hydrochloride salt is an anhydrate form.

3. The crystalline hydrochloride salt according to claim 1 , said crystalline hydrochloride salt being designated as form HCl-A1, characterized by a powder X-ray diffraction pattern having one, two, three, four or five peaks at a diffraction angle (2 theta) of 14.0°±0.2°, 18.5°±0.2°, 19.6°±0.2°, 20.4°±0.2° and/or 22.1°±0.2°.

4. The crystalline hydrochloride salt according to claim 1 , said crystalline hydrochloride salt being designated as form HCl-A2, characterized by powder X-ray diffraction pattern having one, two, three, four or five peaks at a diffraction angle (2 theta) of 11.9±0.2°, 14.9°±0.2°, 17.7°±0.2°, 21.8°±0.2° and/or 22.5°±0.2°.

5. The crystalline hydrochloride salt according to claim 1 , said crystalline hydrochloride salt being designated as form HCl-A3, characterized by powder X-ray diffraction pattern having one, two, three, four or five peaks at a diffraction angle (2 theta) of 14.2°±0.2°, 17.1°±0.2°, 17.4°±0.2°, 18.5°±0.2° and/or 24.1°±0.2°.

6. An anhydrous crystalline salt of Rimeporide selected from phosphate salts, citrate salts, oxalate salts, maleate salts, sulfate salts, besylate salts, p-tosylate salts, malonate salts and succinate salts of Rimeporide.

7. The anhydrous crystalline salt according to claim 6 , said anhydrous crystalline salt being:
a) an anhydrous crystalline phosphate salt of Rimeporide designated as form Phosphate-NF1, characterized by a powder X-ray diffraction pattern having one, two, three, four or five peaks at a diffraction angle 2 theta of 13.9°±0.2°, 16.9°±0.2°, 17.3°±0.2°, 21.8°±0.2° and/or 22.1°±0.2°;
b) an anhydrous crystalline maleate salt of Rimeporide designated as form Maleate-NF1, characterized by a powder X-ray diffraction pattern having one, two, three, four or five peaks at a diffraction angle 2 theta of 7.6±0.2°, 11.1°±0.2°, 19.5°±0.2°, 20.3°±0.2° and/or 20.7°±0.2°;
c) an anhydrous crystalline maleate salt of Rimeporide designated as form Maleate-NF2, characterized by a powder X-ray diffraction pattern having one, two, three, four or five peaks at a diffraction angle 2 theta of 16.3±0.2°, 18.7°±0.2°, 20.4°±0.2°, 20.7°±0.2° and/or 25.3°±0.2°;
d) an anhydrous crystalline oxalate salt of Rimeporide, designated as form Oxalate-NF1, characterized by a powder X-ray diffraction pattern having one, two, three, four or five peaks at a diffraction angle 2 theta of 13.2°±0.2°, 16.4°±0.2°, 17.1°±0.2°, 21.3°±0.2° and/or 23.3°±0.2°;
e) an anhydrous crystalline citrate salt of Rimeporide, designated as form Citrate-NF1, characterized by a powder X-ray diffraction pattern having one, two, three, four or five peaks at a diffraction angle 2 theta of 11.9°±0.2, 15.0°±0.2, 18.1°±0.2, 19.5°+0.2 and/or 20.3°±0.2°;
f) an anhydrous crystalline sulfate salt of Rimeporide, designated as form Sulfate-NF3, characterized by a powder X-ray diffraction pattern having one, two, three, four or five peaks at a diffraction angle 2 theta of 12.9°±0.2°, 15.3°±0.2°, 21.2°±0.2°, 21.5°±0.2° and/or 22.8°±0.2°;
g) an anhydrous crystalline besylate salt of Rimeporide, designated as form Besylate-NF1, characterized by a powder X-ray diffraction pattern having one, two, three, four or five peaks at a diffraction angle 2 theta of 5.5°±0.2°, 11.5°±0.2°, 12.1°±0.2°, 19.0°±0.2° and/or 20.3°±0.2°;
h) an anhydrous crystalline p-tosylate salt of Rimeporide, designated as form Tosylate-NF1, characterized by a powder X-ray diffraction pattern having one, two, three, four or five peaks at a diffraction angle 2 theta of 5.3°±0.2°, 5.7°±0.2°, 11.1°±0.2°, 18.9°±0.2° and/or 20.6°±0.2°;
i) an anhydrous crystalline malonate salt of Rimeporide, designated as form Malonate-NF1, characterized by a powder X-ray diffraction pattern having one, two, three, four or five peaks at a diffraction angle 2 theta of 17.3°±0.2°, 18.2°±0.2°, 19.4°±0.2°, 20.1°±0.2° and/or 23.2°±0.2°; or
j) an anhydrous crystalline succinate salt of Rimeporide, designated as form Succinate-NF1, characterized by a powder X-ray diffraction pattern having one, two, three, four or five peaks at a diffraction angle 2 theta of 12.8°±0.2°, 13.9°±0.2°, 18.1°±0.2°, 18.4°±0.2° and/or 23.6°±0.2°.

8. A crystalline salt of Rimeporide selected from:
a) a crystalline fumarate salt of Rimeporide, designated as form Fumarate-NF1, characterized by a powder X-ray diffraction pattern having one, two, three, four or five peaks at a diffraction angle 2 theta of 4.9°±0.2°, 9.9°±0.2°, 17.1°±0.2°, 21.9°±0.2° and/or 25.3°±0.2°;
b) a crystalline tartrate salt of Rimeporide, designated as form Tartrate-NF1, characterized by a powder X-ray diffraction pattern having one, two, three, four or five peaks at a diffraction angle 2 theta of 15.1°±0.2°, 18.7°±0.2°, 19.9°±0.2°, 20.8°±0.2° and/or 22.8°±0.2°;
c) a crystalline malate salt of Rimeporide, designated as form Malate-NF1, characterized by, a powder X-ray diffraction pattern having one, two, three, four or five peaks at a diffraction angle 2 theta of 5.3±0.2°, 12.6°±0.2°, 17.2°±0.2°, 18.0°±0.2° and/or 18.4°±0.2°; or
d) a crystalline HBr salt of Rimeporide, designated as form HBr-NF1, characterized by a powder X-ray diffraction pattern having one, two, three, four or five peaks at a diffraction angle 2 theta of 10.7°±0.2°, 11.1°±0.2°, 20.6°±0.2°, 22.2°±0.2° and/or 23.7°±0.2°.

9. A pharmaceutical composition comprising a therapeutically effective amount of at least one crystalline compound according to claim 1 .

10. A pharmaceutical composition comprising a therapeutically effective amount of at least one crystalline compound according to claim 7 .

11. A pharmaceutical composition comprising a therapeutically effective amount of at least one crystalline compound according to claim 8 .

12. A method for treating muscular dystrophy, comprising administering to a human in need of such a treatment a therapeutically effective amount of crystalline compound according to claim 1 .

13. A method for treating muscular dystrophy, comprising administering to a human in need of such a treatment a therapeutically effective amount of crystalline compound according to claim 7 .

14. A method for treating muscular dystrophy, comprising administering to a human in need of such a treatment a therapeutically effective amount of crystalline compound according to claim 8 .

Assignees

• Merck Patent Gmbh

Inventors

• Becker Axel
• Gallon Gilmary
• Saal Christoph
• Kuehn Clemens

Classifications

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P9/12

  Antihypertensives · CPC title

• A61P11/00

  Drugs for disorders of the respiratory system · CPC title

• A61P25/00

  Drugs for disorders of the nervous system · CPC title