阅读说明：本技术 一种防治心肌缺血的药物组合物及其制备方法和用途 (Pharmaceutical composition for preventing and treating myocardial ischemia and preparation method and application thereof ) 是由 姜文兵 于 2020-07-20 设计创作，主要内容包括：本发明公开了塞克硝唑在制备治疗和/或预防心肌缺血的药物中的应用。本发明还公开了一种用于治疗和/或预防心肌缺血的药物组合物,所述药物组合物包含塞克硝唑和药学上可接受的赋形剂。药效学实验结果显示塞克硝唑对实验性心肌缺血性损伤具有保护作用,能够明显缩小心肌梗死面积,减轻心肌受损程度,降低血清MDA含量,增加SOD活性酶含量,能够有效的抗急性心肌缺血,保护心肌,从而改善心肌缺血的症状。(The invention discloses an application of secnidazole in preparing a medicament for treating and/or preventing myocardial ischemia. The invention also discloses a pharmaceutical composition for treating and/or preventing myocardial ischemia, which comprises secnidazole and pharmaceutically acceptable excipient. Pharmacodynamic experiment results show that secnidazole has a protective effect on experimental myocardial ischemic injury, can obviously reduce myocardial infarction area, relieve myocardial damage degree, reduce serum MDA content, increase SOD active enzyme content, can effectively resist acute myocardial ischemia, protects myocardium, and thus improves symptoms of myocardial ischemia.)

1. The secnidazole is used in preparing medicine for preventing and/or treating myocardial ischemia.

2. Use according to claim 1, characterized in that: the myocardial ischemia is acute myocardial ischemia.

3. A pharmaceutical composition for the treatment and/or prevention of myocardial ischemia, characterized in that: the pharmaceutical composition comprises secnidazole and pharmaceutically acceptable excipient.

4. The pharmaceutical composition of claim 3, wherein: the pharmaceutically acceptable excipient comprises a solid lipid material.

5. The pharmaceutical composition of claim 4, wherein: the solid lipid material is selected from one or more of glyceryl palmitate, glyceryl behenate and glyceryl caprylate.

6. The pharmaceutical composition according to claim 4 or 5, characterized in that: the pharmaceutical composition is prepared in the form of solid lipid particles.

7. The pharmaceutical composition of claim 6, wherein: the solid lipid particles are prepared by an anti-solvent precipitation method.

8. The pharmaceutical composition according to any one of claims 3 to 7, wherein: the pharmaceutical composition also comprises other effective components, wherein the other effective components comprise nifedipine, verapamil, aspirin, clopidogrel, metoprolol and atorvastatin, and preferably, the other effective components are nifedipine.

9. Use of a pharmaceutical composition according to any one of claims 3 to 8 for the preparation of a medicament for the treatment and/or prevention of myocardial ischemia.

10. Use according to claim 9, characterized in that: the myocardial ischemia is acute myocardial ischemia.

Technical Field

The invention relates to the technical field of medicines, in particular to a pharmaceutical composition for preventing and treating myocardial ischemia and a preparation method and application thereof.

Background

Myocardial ischemia (myocardial ischemia) refers to a pathological condition in which the blood perfusion of the heart is reduced, the oxygen supply of the heart is reduced, the energy metabolism of the heart muscle is abnormal, and the heart cannot work normally. According to the nomenclature of "ischemic heart disease" and the diagnostic criteria published by the world health organization, myocardial ischemia is classified into the following four categories: angina pectoris, myocardial infarction, ischemic cardiomyopathy and sudden death. Acute myocardial ischemia is clinically manifested by symptoms such as acute angina, acute myocardial infarction and the like, and serious patients can endanger the life of patients. The acute myocardial infarction is usually caused by secondary thrombosis on the basis of coronary atherosclerotic lesions, is a clinically serious fatal disease, and has a total mortality rate of 30 percent. With the improvement of living standard of people, the prevalence rate of myocardial ischemia in China is on the trend of rising year by year at present, the myocardial ischemia becomes a common disease and a frequently encountered disease of middle-aged and elderly people, and the myocardial ischemia is also shown in some young people of 20-30 years old.

In recent years, with the intensive research on the mechanism of myocardial ischemia injury, experimental research shows that oxygen radicals are generated during myocardial ischemia, the oxygen radicals can be converted into hydroxyl radicals, and meanwhile, during myocardial ischemia, indexes related to the radicals in the myocardium are remarkably changed, the content of Malondialdehyde (MDA) is remarkably increased, and the activity of SOD is remarkably reduced. SOD is superoxide dismutase which can eliminate oxygen free radical, and the activity reduction of SOD indicates that a large amount of free radicals are generated in myocardium, thereby causing oxidative stress injury to myocardial tissues, causing myocardial cell membrane lipid peroxidation, damaging membrane function and exacerbating myocardial ischemia.

At present, the clinical treatment means aiming at myocardial ischemia mainly comprises surgical treatment and drug treatment, wherein the key point of the drug treatment of myocardial ischemia is to balance the supply and consumption of oxygen again, and the treatment mechanisms of the drug treatment of myocardial ischemia can be mainly divided into two types. One is to reduce myocardial oxygen consumption; another is to improve coronary blood flow. The medicines commonly used at present mainly comprise: an antiplatelet agent: common medicines comprise aspirin, clopidogrel and the like, and the medicines generally need to be taken for a long time; ② beta receptor blocker: the compound is the first choice for stable angina pectoris, can mutually make up for weakness when being used with nitrate, generally starts from small dose, and adjusts the dose according to treatment response and heart rate change; ③ calcium ion antagonists: common medicines include verapamil, nifedipine, etc. However, in clinical practice, the above drugs have various limitations for different populations or specific indications due to their own reasons. Therefore, at present, a new prevention and treatment means for myocardial ischemia still needs to be found clinically, and a new action target point is developed for the drug treatment of myocardial ischemia.

Disclosure of Invention

The invention aims to solve the technical problem of enriching clinical medication choices for treating and/or preventing myocardial ischemia, and provides a pharmaceutical composition for preventing and treating myocardial ischemia and a preparation method and application thereof.

The inventor finds that secnidazole has a protective effect on experimental myocardial ischemic injury through experiments, can obviously reduce myocardial infarction area, relieve myocardial damage degree, reduce serum MDA content, increase SOD active enzyme content, and can effectively resist acute myocardial ischemia, so that secnidazole can be expected to be useful in the aspect of treating myocardial ischemia.

Secnidazole (Secnidazole) as active component is one kind of nitroimidazole as antiprotozoal and anaerobe medicine, and has the chemical name of 1- (hydroxy-2-propyl) -2-methyl-5-nitroimidazole, structure and pharmacological action similar to that of metronidazole, white to similar-white or yellowish crystalline powder at normal temperature, no smell, bitter taste, and functions of resisting trichomonas and amebiasis. Originally developed successfully by Rhone-PoulencRorer pharmaceutical company, Rhone-Poulenc, France, by acting on the growth phase of protozoa or anaerobes, either to break DNA strands or to inhibit DNA synthesis, resulting in the death of protozoa and anaerobes. Clinically, the traditional Chinese medicine is usually used for treating urethritis and vaginitis caused by trichomonas vaginalis, acute amebiasis or giardiasis and the like. At present, no report is found clinically on the pharmacological activity or treatment effect of secnidazole in the aspect of treating myocardial ischemia.

The first aspect of the invention is the use of secnidazole in the manufacture of a medicament for the treatment and/or prevention of myocardial ischemia.

Further, the myocardial ischemia is acute myocardial ischemia.

In a second aspect of the present invention, there is provided a pharmaceutical composition for the treatment and/or prevention of myocardial ischemia, comprising secnidazole and a pharmaceutically acceptable excipient.

Further, the pharmaceutically acceptable excipient comprises a solid lipid material.

Still further, the solid lipid material is selected from one or more of glyceryl palmitate, glyceryl behenate or glyceryl caprylate.

In the process of research on secnidazole, the inventor finds that the secnidazole generates a metal peculiar smell when being orally taken, thereby generating gastrointestinal tract disorder, nausea, vomiting and other adverse reactions, and in addition, the secnidazole has poor water solubility (slightly soluble in water, about 34mg/mL under neutral conditions), so that the research and development of clinical dosage forms are also limited. Based on the problems, the inventor prepares the secnidazole-loaded solid lipid particles by an anti-solvent precipitation method, thereby improving the solubility of secnidazole, reducing gastrointestinal tract reaction of oral administration of secnidazole, improving metal peculiar smell of secnidazole and improving the compliance of patients in taking medicine.

Therefore, the present invention preferably prepares the pharmaceutical composition in the form of solid lipid particles.

More preferably, the solid lipid particles are prepared by an anti-solvent precipitation method.

Further, the pharmaceutical composition also comprises other effective components.

Further, the other effective components include nifedipine, verapamil, aspirin, clopidogrel, metoprolol, and atorvastatin. The other effective component is preferably nifedipine.

The third aspect of the invention provides the use of the pharmaceutical composition in the preparation of a medicament for the treatment and/or prevention of myocardial ischemia.

Further, the myocardial ischemia is acute myocardial ischemia.

Preferred embodiments of the present invention and effects thereof will be described below with reference to specific examples. It should be understood, however, that the description is for illustrative purposes only and is not intended to limit the claims of the present invention in any way.

Detailed Description