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Therapeutic agent for vasospasm accompanying bypass operation

A technique of vasospasm and bypass surgery, which is applied to cardiovascular system diseases, surgical drugs, medical preparations containing active ingredients, etc., and can solve difficult-to-treat problems

Active Publication Date: 2007-02-14
ASAHI KASEI PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] However, arterial spasm during bypass surgery is difficult to treat with general vasodilators nitro compounds and calcium antagonists, so vasodilators may not necessarily be used for the prevention or treatment of vasospasm associated with bypass surgery

Method used

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  • Therapeutic agent for vasospasm accompanying bypass operation
  • Therapeutic agent for vasospasm accompanying bypass operation
  • Therapeutic agent for vasospasm accompanying bypass operation

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0047] In patients who have undergone beating heart coronary artery bypass surgery (the left internal thoracic artery is anastomosed with the left anterior descending coronary artery in the diagonal branch), during and after surgery, isosorbide dinitrate (2 ~ 5mg / hr ), diltiazem (1-2 mg / hr), nicorandil (4-6 mg / hr), and catecholamines (dopamine 1-2 μg / kg min, dobutamine 1-2 μg / kg min) continuous intravenous administration. However, 3 hours after the operation, severe coronary artery spasm occurred. Coronary spasm was present in the right coronary artery not related to bypass surgery. Since intracoronary administration of isosorbide dinitrate (10 mg in total) was ineffective, fasudil hydrochloride was dissolved in physiological saline and administered into the right coronary artery at a rate of 1.5 mg / min for 15 minutes. As a result, coronary artery spasm was relieved (see FIG. 1 ). When spasm occurred and after administration of isosorbide dinitrate, the right coronary arter...

Embodiment 2

[0049] Isosorbide dinitrate (1-5 mg / hr), diltiazem (1-2 mg / hr), and catecholamines (dopamine, dobutamine, and norepinephrine each 1-2 μg / kg·min) were continuously administered intravenously. However, 5 hours after the operation, severe coronary artery spasm occurred. Coronary spasm was present in the right and left circumflex coronary arteries not related to bypass surgery. Since administration of isosorbide dinitrate (10 mg in total) into the right coronary artery was ineffective, fasudil hydrochloride was dissolved in physiological saline and administered into the right coronary artery at a rate of 1.5 mg / min for 15 minutes. As a result, coronary artery spasm was relieved (see FIG. 1 ). When spasm occurs and after administration of isosorbide dinitrate, the site far from the spasm site is a state that cannot be visualized. However, according to the administration of fasudil hydrochloride, the extremities can be visualized, which indicates that the spasm is relieved. The...

Embodiment 3

[0051] In patients who had undergone beating heart coronary artery bypass surgery (anastomosis of the right internal thoracic artery to the left anterior descending coronary artery and the left internal thoracic artery to the posterior collateral of the left circumflex coronary artery), intraoperative nitric acid Isosorbide (1-3 mg / hr), diltiazem (0.5-1 mg / hr), and catecholamines (dopamine 1-5 μg / kg min, dobutamine 1-2 μg / kg min, norepinephrine Sustained intravenous administration of 1-2 μg / kg·min of each element. However, severe coronary spasm developed immediately after the anastomosis. Spasticity occurred in the right coronary artery not related to the bypass and in the anastomotic site open shunt artery grafts (right internal thoracic artery and left internal thoracic artery). Since intracoronary and intragraft administration of isosorbide dinitrate (total 20 mg) was ineffective for these spasms, fasudil hydrochloride was dissolved in normal saline and administered to eac...

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Abstract

The present invention provides a preventive treatment agent and a preventive treatment composition for vasospasm associated with bypass surgery, which is a compound represented by general formula (I) (wherein, R1 represents hydrogen or hydroxyl) or an acid addition salt thereof or hydrate as an active ingredient, the prophylactic and therapeutic agent and composition for the prevention and treatment of vasospasm accompanied by bypass surgery are effective for the prevention or treatment of vasospasm accompanied by bypass surgery.

Description

technical field [0001] The present invention relates to a prophylactic and therapeutic agent and a prophylactic and therapeutic composition for vasospasm associated with bypass surgery. Background technique [0002] Arterial bypass surgery is performed when an artery is blocked or narrowed. Arterial spasm sometimes occurs during arterial bypass surgery, during or after coronary artery bypass surgery, etc. This arterial spasm has more intense and long-lasting characteristics than the arterial spasm that occurs during non-operation, and it is not easy to respond to nitro compounds and calcium antagonists even after the spasm occurs, so this arterial spasm is normal It becomes a big clinical problem at the time of bypass surgery (Non-Patent Document 1). [0003] On the one hand, the compound represented by the general formula (I) has inhibitory activity on kinases such as Rho kinase, myosin light chain phosphorylase, and protein kinase C, and exhibits vascular smooth muscle r...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D401/12A61K31/4375A61P9/00A61P43/00
CPCC07D401/12A61K31/4375A61P41/00A61P43/00A61P9/00
Inventor 下川宏明
Owner ASAHI KASEI PHARMA