CN103550225B - The application of Phyllanthoid A in preparation treatment or preventing chronic heart failure medications - Google Patents

Abstract

The present invention provides Phyllanthoid? A application in the preparation of medicines for the treatment or prevention of chronic heart failure, specifically proposed Phyllanthoid? The therapeutic effect of A on acute and chronic heart failure is disclosed for the first time. Since the skeleton type belongs to a new skeleton type, and its activity in treating chronic heart failure is strong, it has outstanding substantive features. It is obviously useful for treating chronic heart failure. Significant progress.

Description

Application of Phyllanthoid A in preparation of medicine for treating or preventing chronic heart failure

technical field

The present invention relates to a new application of compound Phyllanthoid A, in particular to the application of Phyllanthoid A in the preparation of medicines for treating or preventing chronic heart failure.

Background technique

Heart failure (HF) refers to a pathophysiological state in which abnormal cardiac function causes the pumping volume of the heart to fail to meet the needs of tissue metabolism. The etiology and inducement are due to the overload of the heart, the myocardium itself, and the restriction of diastole, which causes the initial myocardial damage to cause structural dysfunction and progressive onset; while infection, anemia, pregnancy, childbirth, cardiac rhythm disorder, pulmonary embolism, hyperthyroidism, diabetes, and cardiac arrest Drug-induced exacerbation of HF. Pathogenesis In the past, it was believed that the mechanism of HF development was abnormal hemodynamics; in the late 1980s, it was recognized that the activation of neuroendocrine hormones played an important role (activation of sympathetic ↑ NE ↑ RAS ↑ etc.); after the 1990s, it gradually became clear that " Myocardial remodeling is the basic mechanism leading to the occurrence and development of heart failure.

The compound Phyllanthoid A involved in the present invention is a new compound published in 2013 (Jian-QiangZhao, et al., Two New Highly Oxygenated and Rearranged Limonoids from Phyllanthuscochinchinensis. Organic Letters, 2013, 15 (10) 2414-2417.), the compound has a new skeleton type, and the current use is only Inhibiting the proliferation of breast cancer cells (Jian-QiangZhao, et al., Two New Highly Oxygenated and Rearranged Limonoids from Phyllanthuscochinchinensis. Organic Letters, 2013, 15 (10) 2414-2417.), the use of Phyllanthoid A involved in the present invention in the preparation of drugs for the treatment or prevention of chronic heart failure is the first disclosure.

Contents of the invention

The purpose of the present invention is to provide the application of Phyllanthoid A in the preparation of medicines for treating or preventing chronic heart failure according to the current situation that no report on Phyllanthoid A has the activity of treating or preventing chronic heart failure has been found in the existing Phyllanthoid A research.

The structure of the compound PhyllanthoidA is shown in formula (I):

The use of Phyllanthoid A involved in the present invention in the preparation and treatment of chronic heart failure is disclosed for the first time. Since the skeleton type is a brand-new skeleton type, and its activity for treating chronic heart failure is strong, it has outstanding substantive features, and it is also used for the treatment of chronic heart failure. Decay is clearly a marked improvement.

detailed description

For the preparation method of the compound Phyllanthoid A involved in the present invention, please refer to the literature (Jian-QiangZhao, et al., Two New Highly Oxygenated and Rearranged Limonoids from Phyllanthus scchinchinensis. Organic Letters, 2013, 15 (10) 2414-2417.)

The present invention will be described in further detail below through examples, but the protection scope of the present invention is not limited by any specific examples, but is defined by the claims.

Embodiment 1: the preparation of the compound PhyllanthoidA tablet involved in the present invention:

Take 5 grams of compound Phyllanthoid A and add 195 grams of dextrin, mix well, and make 1000 tablets by conventional tableting.

Embodiment 2: the preparation of compound PhyllanthoidA capsules involved in the present invention:

Get 5 grams of compound Phyllanthoid A, add 195 grams of starch, mix well, and pack into capsules to make 1000 capsules.

The following pharmacodynamic experiments will further illustrate its drug activity.

Experimental example 1: Effect of Phyllanthoid A on rats with chronic heart failure

Test method and results: 100 rats, half male and half male, were injected intraperitoneally with doxorubicin hydrochloride 2 mg/kg, once a week, for 6 weeks in total. Randomly divided into 10 groups, namely NS group, captopril tablet 12.5mg/kg group, intragastric administration of PhyllanthoidA0.2mg/kg group, intragastric administration of PhyllanthoidA2.5mg/kg group, intragastric administration of PhyllanthoidA5.0mg /kg group. From the 5th week, each group was administered Phyllanthoid A by intragastric administration every day for 21 days. Anesthetized by intraperitoneal injection of 20% urethane 1.1g/kg, the trachea was surgically stripped and intubated, and the right common artery was freed at the same time, and a self-made ventricular cannula (diameter 1mm, filled with 1% heparin) was inserted through it, and the blood pressure curve was traced; Continue to insert, make it enter the left ventricle through the left arterial valve, trace the intraventricular pressure curve, automatically analyze and process the left ventricular systolic pressure (LVSP), the maximum increase rate of ventricular pressure (+dp/dtmax), the maximum decrease rate of ventricular pressure ( -dp/dtmax) and measured myocardial maximum contraction velocity (Vpm) and other data. Another 10 rats were taken as the normal control group, without administration of doxorubicin hydrochloride, and the rest of the operations were the same as above, and the T test between groups was used for statistical processing.

Table 1 Effect of Phyllanthoid A on cardiac function in rats with chronic heart failure (n=10)

Compared with NS group, △: p<0.05, △△: p<0.01

Table 1 test result shows that PhyllanthoidA oral administration 0.2mg/kg group can increase the LVSP of the heart failure rat caused by doxorubicin hydrochloride, +dp/dtmax, the reduction of -dp/dtmax and Vpm (compared with NS group , P<0.05); intragastric administration of PhyllanthoidA at 2.5mg/kg and 5.0mg/kg can significantly increase the LVSP, +dp/dtmax, -dp/dtmax and Vpm of heart failure rats induced by doxorubicin hydrochloride decreased (compared with NS group, P<0.01).

Conclusion: Phyllanthoid A has significant effect on treating or preventing chronic heart failure, and can be used to prepare medicines for treating or preventing chronic heart failure.

Claims (1)

1. The application of 1.PhyllanthoidA in preparation treatment or preventing chronic heart failure medications, described compound PhyllanthoidA structure is as shown in formula I:

   Formula I.