CN102988347A

CN102988347A - Application of Aphanamixoid A for preparing medicine for treating or preventing chronic heart failure

Info

Publication number: CN102988347A
Application number: CN201210468788XA
Authority: CN
Inventors: 何晓涛
Original assignee: Individual
Current assignee: Individual
Priority date: 2012-11-19
Filing date: 2012-11-19
Publication date: 2013-03-27

Abstract

The invention provides application of Aphanamixoid A for preparing a medicine for treating or preventing chronic heart failure and particularly provides the therapeutic effect of Aphanamixoid A on acute and chronic heart failure. The application of Aphanamixoid A for preparing the medicine for treating or preventing chronic heart failure is disclosed for the first time; because the skeleton type belongs to a brand new skeleton type and the chronic heart failure curative activity of Aphanamixoid A is strong unexpectedly, the possibility that other compounds give any inspiration does not exist; Aphanamixoid A has outstanding substantive characteristics; and simultaneously, Aphanamixoid A has obvious progress for treating chronic heart failure.

Description

The application of Aphanamixoid A in the medicine of preparation treatment or preventing chronic heart failure

Invention field

The present invention relates to the application of Aphanamixoid A in the medicine of preparation treatment or preventing chronic heart failure.

Background technology

Heart failure (hear failure, HF) refers to that cardiac function causes the heart pump blood volume can not satisfy a kind of pathological and physiological condition of tissue metabolism's needs unusually.Cause of disease inducement causes initial myocardial damage because of cardiac overload, cardiac muscle itself, the limited any reason of diastole and causes structure function lowly and the morbidity of carrying out property; And infect, anemia, gestation, childbirth, cardiac arrhythmia, pulmonary infarction, hyperthyroidism, diabetes, inhibition heart medicine bring out and increase the weight of HF.Pathogeny thinks that in the past the mechanism of HF genesis is abnormal hemodynamics; The later stage eighties 20th century is recognized the activation of nerve-endocrine hormone play an important role (sympathetic ↑ NE ↑ RAS ↑ wait activation); Clear and definite gradually " Myocardial Remodeling " is the fundamental mechanism that causes the genesis of heart failure (remodelling) after the nineties.

The compd A phanamixoid A that the present invention relates to is one and delivered (Cai in 2012, J. Y. et al., 2012. Aphanamixoid A, a Potent Defensive Limonoid, with a New Carbon Skeleton from Aphanamixis polystachya. Organic Letters 14 (10), 2524 – 2527.) New skeleton compound, this chemical compound has brand-new framework types, present purposes only relates to insect antifeedant activity (Cai, J. Y. et al., 2012. Aphanamixoid A, a Potent Defensive Limonoid, with a New Carbon Skeleton from Aphanamixis polystachya. Organic Letters 14 (10), 2524 – 2527.), belong to open first for the purposes of the Aphanamixoid A that the present invention relates in preparation treatment chronic heart failure, because framework types belongs to brand-new framework types, and its treatment chronic heart failure is unexpectedly active strong, there is not the possibility that is provided any enlightenment by other chemical compounds, possess outstanding substantive distinguishing features, be used for the treatment of simultaneously chronic heart failure and obviously have significant progress.

Summary of the invention

The invention provides the application of Aphanamixoid A in the medicine of preparation treatment or preventing chronic heart failure.

Described compd A phanamixoid A structure is shown in formula I:

The purposes of the Aphanamixoid A that the present invention relates in preparation treatment chronic heart failure belongs to open first, because framework types belongs to brand-new framework types, and its treatment chronic heart failure is unexpectedly active strong, there is not the possibility that is provided any enlightenment by other chemical compounds, possess outstanding substantive distinguishing features, be used for the treatment of simultaneously chronic heart failure and obviously have significant progress.

The specific embodiment

The preparation method of compd A phanamixoid A involved in the present invention is referring to document (Cai, J. Y. et al., 2012. Aphanamixoid A, a Potent Defensive Limonoid, with a New Carbon Skeleton from Aphanamixis polystachya. Organic Letters 14 (10), 2524 – 2527.).

The present invention is further detailed explanation by the following examples, but protection scope of the present invention is not subjected to any restriction of specific embodiment, but limited by claim.

Embodiment 1: the preparation of compd A phanamixoid A tablet involved in the present invention:

Get 20 and digest compound Aphanamixoid A, add conventional adjuvant 180 grams of preparation tablet, mixing, conventional tablet machine are made 1000.

Embodiment 2: the preparation of compd A phanamixoid A capsule involved in the present invention:

Get 20 and digest compound Aphanamixoid A, add conventional adjuvant such as starch 180 grams of preparation capsule, mixing is encapsulatedly made 1000.

Further specify its pharmaceutically active below by pharmacodynamic experiment.

Experimental example Aphanamixoid A is on the impact of chronic heart failure rat

Test method and result

100 of rats, male and female half and half are got 100 lumbar injection doxorubicin hydrochloride 2mg/kg, and 1 time weekly, totally 6 weeks.Be divided at random 10 groups, namely NS organizes, Captopril tablets 12.5mg/kg group, gastric infusion Aphanamixoid A 0.2mg/kg group, gastric infusion Aphanamixoid A 2.5mg/kg group, gastric infusion Aphanamixoid A 5.0mg/kg group.Play giving every day Aphanamixoid A gavage each group the 5th week, administration 21 days.20% urethane 1.1g/kg intraperitoneal injection of anesthesia, peeling operation trachea and intubate, the total tremulous pulse in right side that dissociates simultaneously inserts homemade ventricle intubate (diameter 1mm is full of 1% heparin) through it, traces blood pressure curve; Continue again to insert, make it enter left ventricle by the left side arterial valve, trace the intraventricular pressure curve, Automatic analysis left ventricular systolic pressure (LVSP), maximum the climbing speed (+dp/dt of intraventricular pressure _Max), intraventricular pressure maximum falling speed (dp/dt _Max) and data such as the myocardium maximal velocity of contraction of actual measurement (Vpm) etc.Other gets 10 rats as Normal group, does not give doxorubicin hydrochloride, and all the other operate with above-mentioned, and statistical procedures is carried out in the T check between group.

Table 1 Aphanamixoid A is on the impact (n=10) of chronic heart failure Cardiac Function in Rat

Compare with the NS group, ^△: p＜0.05, ^{△ △}: p＜0.01

Table 1 result of the test shows can the raise LVSP of the Heart Failure Wistar Rats that caused by doxorubicin hydrochloride of Aphanamixoid A gastric infusion 0.2mg/kg group ,+dp/dt _Max,-dp/dt _MaxReduction (comparing P＜0.05 with the NS group) with Vpm; Can significantly the raise LVSP of the Heart Failure Wistar Rats that caused by doxorubicin hydrochloride of Aphanamixoid A gastric infusion 2.5mg/kg, 5.0mg/kg ,+dp/dt _Max,-dp/dt _MaxReduction (comparing P＜0.01 with the NS group) with Vpm.

Conclusion: Aphanamixoid A has the effect of significant treatment or preventing chronic heart failure, can be used for preparing the medicine for the treatment of or preventing chronic heart failure.

Claims

1.Aphanamixoid the application of A in the medicine of preparation treatment or preventing chronic heart failure, described compd A phanamixoid A structure is shown in formula I:

Formula I.