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Claims for Patent: 5,196,444

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Claims for Patent: 5,196,444

Title: 1-(cyclohexyloxycarbonyloxy)ethyl 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]benzimidazole-7-c arboxylate and compositions and methods of pharmaceutical use thereof
Abstract:1-(Cyclohexyloxycarbonyloxy)ethyl 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]benzimidazole-7-car boxylate or a pharmaceutically acceptable salt thereof has potent angiotensin II antihypertensive activity, thus being useful as therapeutic agents for treating circulatory system diseases such as hypertensive diseases, heart diseases (e.g. hypercardia, heart failure, cardiac infarction, etc.), strokes, cerebral apoplexy, nephritis, etc.
Inventor(s): Naka; Takehiko (Kobe, JP), Nishikawa; Kohei (Kyoto, JP), Kato; Takeshi (Higashiosaka, JP)
Assignee: Takeda Chemical Industries, Ltd. (Osaka, JP)
Application Number:07/687,238
Patent Claims: 1. A stable crystal of 1-(cyclohexyloxycarbonyloxy)ethyl 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl)-biphenyl-4-yl]methyl]benzimidazole-7-ca rboxylate.

2. A stable crystal according to claim 1, which has approximately the following lattice spacings:

3.5 angstrom; middle

3.7 angstrom; weak

3.8 angstrom; middle

4.0 angstrom; middle

4.1 angstrom; weak

4.3 angstrom; weak

4.4 angstrom; middle

4.6 angstrom; middle

4.8 angstrom; middle

5.1 angstrom; middle

5.2 angstrom; weak

6.9 angstrom; weak

7.6 angstrom; weak

8.8 angstrom; middle

9.0 angstrom; strong

15.9 angstrom; weak.

3. A pharmaceutical composition for antagonizing angiotensin II which comprises a therapeutically effective amount of 1-(cyclohexyloxycarbonyloxy)ethyl 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]benzimidazole-7-car boxylate or a pharmaceutically acceptable salt thereof in admixture with a pharmaceutically acceptable carrier, excipient or diluent therefor.

4. A pharmaceutical composition for antagonizing angiotensin II which comprises a therapeutically effective amount of a crystal according to claim 1 in admixture with a pharmaceutically acceptable carrier, excipient or diluent therefor.

5. A pharmaceutical composition for antagonizing angiotensin II which comprises a therapeutically effective amount of a crystal according to claim 2 in admixture with a pharmaceutically acceptable carrier, excipient or diluent therefor.

6. A method for antagonizing angiotensin II in a mammal which comprises administering to said mammal a therapeutically effective amount of 1-(cyclohexyloxycarbonyloxy)ethyl 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]benzimidazole-7-car boxylate or a pharmaceutically acceptable salt thereof.

7. A method for antagonizing angiotensin II in a mammal which comprises administering to said mammal a therapeutically effective amount of a crystal according to claim 1.

8. A method for antagonizing angiotensin II in a mammal which comprises administering to said mammal a therapeutically effective amount of a crystal according to claim 2.

9. 1-(Cyclohexyloxycarbonyloxy)ethyl 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]benzimidazole-7-car boxylate or a pharmaceutically acceptable salt thereof.
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