Cilostazol and Edaravone Combination for Ischemic Stroke Treatment
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Solution Overview
Problem
Current treatments for cerebrovascular diseases, particularly ischemic cerebrovascular diseases, lack effective solutions for reducing cerebral infarction and neurological deficits, as existing medications do not adequately address the underlying pathophysiological mechanisms of cerebral ischemia-reperfusion injury.
Innovation Solution
A pharmaceutical composition combining cilostazol and edaravone, administered in specific weight ratios, is used to treat cerebrovascular diseases, where cilostazol inhibits platelet aggregation and promotes vasodilation, while edaravone provides antioxidant activity, synergistically enhancing therapeutic efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If single medication is used for treating ischemic cerebrovascular diseases, then the treatment is simple, but the efficacy in reducing cerebral infarction and neurological deficits is insufficient
Solution Approach 1:
The patent combines two distinct medications (cilostazol and edaravone) into a single pharmaceutical composition. Cilostazol provides antiplatelet aggregation and vasodilation effects, while edaravone provides antioxidant activity. This merging of multiple therapeutic mechanisms into one composition resolves the contradiction by achieving synergistic efficacy without requiring multiple separate administrations.
Solution Approach 2:
The pharmaceutical composition uses a composite approach by formulating cilostazol and edaravone together in specific weight ratios (1:1, 1:2, 1:5, 2:1, 5:1, or 2:5). This composite medication leverages the complementary pharmacological properties of both substances to achieve enhanced therapeutic effects that neither drug could provide alone, directly addressing the insufficiency of single medication treatment.
2Reliability
If cilostazol is used alone, then platelet aggregation is inhibited and vasodilation is promoted, but antioxidant protection is insufficient
Solution Approach 1:
The patent merges cilostazol (which inhibits platelet aggregation and promotes vasodilation) with edaravone (which provides antioxidant activity) into a single composition. This combination allows the treatment to simultaneously address multiple pathophysiological mechanisms of cerebral ischemia-reperfusion injury without requiring separate therapeutic interventions.
Solution Approach 2:
The pharmaceutical composition achieves multi-functionality by incorporating two drugs with different mechanisms of action. The composition can simultaneously inhibit platelet aggregation, promote vasodilation, and provide antioxidant protection, making it a universal treatment for the complex pathophysiology of ischemic cerebrovascular diseases.
3Reliability
If edaravone is used alone, then antioxidant activity is provided, but antiplatelet and vasodilation effects are insufficient
Solution Approach 1:
The patent combines edaravone (antioxidant) with cilostazol (antiplatelet and vasodilator) into a single pharmaceutical composition. This merging allows the treatment to comprehensively address multiple aspects of cerebral ischemia-reperfusion injury including oxidative stress, platelet aggregation, and vascular tone regulation.
Solution Approach 2:
The pharmaceutical composition achieves universality by providing multiple therapeutic functions in one agent. It simultaneously delivers antioxidant protection from edaravone and antiplatelet aggregation plus vasodilation from cilostazol, making it suitable for the multifaceted pathophysiology of ischemic cerebrovascular diseases without requiring multiple separate mechanisms.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The combination of cilostazol and edaravone significantly reduces the area of cerebral infarction and ameliorates neurological deficits in animal models, demonstrating a synergistic effect in treating ischemic cerebrovascular diseases by reducing cerebral infarction and improving neurological outcomes.
Implementation Method 1
Cilostazol is a selective inhibitor of phosphodiesterase 3 (PDE3). The binding rate of cilostazol to plasma protein is about 95%, and most of cilostazol exist in a relatively stable prototype. Cilostazol has broad-spectrum pharmacological activity and has clinical value for many diseases, such as peripheral thrombotic disease and intermittent claudication.
Implementation Method 2
Studies have shown that edaravone has antioxidant activity, and can significantly ameliorate the neurological deficit symptoms in animals with cerebral ischemia-reperfusion, reduce the area of cerebral infarction, reduce the degree of brain injury, alleviate cerebral edema, and inhibit lipid peroxidation in damaged brain tissue.
Data Source
AI summary
Disclosed is the use of a composition containing cilostazol or a pharmaceutically acceptable salt thereof and edaravone in the preparation of a drug for treating cerebrovascular diseases, especially ischemic cerebrovascular diseases. The experiment result shows that the tail vein administration of 1-15 mg/kg of cilostazol or 1.67-8.33 mg/kg of edaravone on rats with a focal cerebral ischemia-reperfusion injury can significantly ameliorate neurological defects in rats with an MCAO and reduce a cerebral infarction area; and performing compound combination within the dosage range (the mass ratio of cilostazol:edaravone is 1:5 to 5:1) can be synergistic. The tail vein administration of 3.33-16.67 mg/kg of cilostazol or 3.33-16.67 mg/kg of edaravone on mice with a focal cerebral ischemia-reperfusion injury can significantly ameliorate neurological defects in mice with an MCAO and reduce a cerebral infarction area.