CN102861008A - Application of Aphanamixoid A in medicine for treating acute renal failure - Google Patents

Abstract

The invention relates to a new medical application of Aphanamixoid A, that is, the application of Aphanamixoid A in the preparation of medicines for treating acute renal failure. The use of AphanamixoidA involved in the present invention in the preparation of anti-acute renal failure drugs is disclosed for the first time. Since the skeleton type is a brand-new skeleton type, and its inhibitory activity on acute renal failure is unexpectedly strong, there is no inspiration from other compounds It has the possibility of having outstanding substantive features, and at the same time, it is obviously a significant progress in the treatment of acute renal failure.

Description

Application of Aphanamixoid A in the Treatment of Acute Renal Failure

technical field

The present invention relates to the field of medicinal chemistry. Specifically, the present invention relates to a new medical application of Aphanamixoid A, that is, the application of Aphanamixoid A in the preparation of medicines for treating acute renal failure. the

Background technique

Acute renal failure (Acute Renal Failure, ARF) is a clinical syndrome caused by a variety of reasons, which can be seen in patients from various clinical departments. It has a high incidence and often brings serious consequences. ) sharp decline in mental function, clinical manifestations of acute oliguria (urine output <400mLPd) or anuria (urine output <100mLPd), obstacles in the excretion of nitrogen metabolites in the body, rapid azotemia, water and electrolytes, acid-base Balance disorder, and cause the corresponding dysfunction of the system of the whole body. The main factors causing acute renal failure are the sharp reduction of renal blood flow, as well as the oxidative stress and cell damage caused by renal tissue ischemia, which eventually lead to the destruction of renal tissue structure and the deterioration of its function. At present, there is no clinically recognized effective drug for the treatment of acute renal failure. Symptoms can only be improved by correcting water and electrolyte balance, correcting acidosis and other symptomatic treatment measures. In the later stage, hemodialysis is required to maintain body functions. There are few clinical drugs that have obvious effects on improving renal blood perfusion disorder and reducing renal tissue damage. the

The compound Aphanamixoid A involved in the present invention is a published in 2012 (Cai, J. Y. et al., 2012. Aphanamixoid A, a Potent Defensive Limonoid, with a New Carbon Skeleton from Aphanamixis polystachya. Organic Letters 14 (10), 252 –2527.), a new skeleton compound, which has a new skeleton type, and its current use only involves 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.), the use of Aphanamixoid A in the preparation of anti-acute renal failure drugs involved in the present invention is the first disclosure, because the skeleton type belongs to a new skeleton type, and its The anti-acute renal failure inhibitory activity is unexpectedly strong, there is no possibility of giving any inspiration from other compounds, it has outstanding substantive features, and it is obviously a significant progress for anti-acute renal failure. the

Contents of the invention

The object of the present invention is to provide the purposes of Aphanamixoid A for the treatment of acute renal failure, that is, the purposes of preparing medicine for the treatment of acute renal failure. the

The Aphanamixoid A of the present invention has obvious therapeutic effect on acute renal failure. the

Through our research, we found that Aphanamixoid A can improve the symptoms of anuria or oliguria in acute renal failure and protect the function of the kidneys. the

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

the

The use of Aphanamixoid A involved in the present invention in the preparation of anti-acute renal failure drugs is disclosed for the first time. Since the skeleton type is a brand-new skeleton type, and its inhibitory activity on acute renal failure is unexpectedly strong, there is no inspiration from other compounds It has the possibility of having outstanding substantive features, and at the same time, it is obviously a significant progress in the treatment of acute renal failure. the

Detailed ways

The preparation method of the compound Aphanamixoid A involved in the present invention can be found in literature (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

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. the

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

Get 20 grams of compound Aphanamixoid A, add 180 grams of conventional excipients for tablet preparation, mix well, and make 1000 tablets with a conventional tablet press. the

Embodiment 2: the preparation of compound Aphanamixoid A capsule involved in the present invention:

Get 20 grams of compound Aphanamixoid A, add conventional adjuvants such as starch 180 grams for the preparation of capsules, mix well, and pack into capsules to make 1000 tablets. the

The following pharmacodynamic experiments will further illustrate its drug activity. the

Experimental example 1 Therapeutic effect of Aphanamixoid A on rats with acute renal failure

(1) Experimental method

Rat animal model of acute renal failure induced by intramuscular injection of glycerol. 60 healthy male SD rats of 180~220g were selected and randomly divided into 5 groups: sham operation group (intramuscular injection of saline); model group (intramuscular injection of glycerol); Aphanamixoid A Ⅰ group (0.3 mg/Kg); Aphanamixoid A Ⅱ group (0.6 mg/Kg); Aphanamixoid A group III (1.2 mg/Kg), the rats in each group were injected with normal saline or Aphanamixoid A into the tail vein immediately after glycerol modeling, and administered again after 12 and 24 hours. the

(2) Observation indicators

After the last administration of Aphanamixoid A or normal saline, 60 rats were put into metabolic cages to collect urine for 24 hours. Six hours after the urine retention, they were anesthetized by intraperitoneal injection of 4% chloral hydrate. The blood flow of the posterior bilateral kidneys was taken as the average value as the renal blood flow of a single animal; blood was taken to prepare serum, and blood BUN and Cre were measured; kidneys were taken to prepare 10% renal cortex homogenate, and the renal cortex homogenate MDA, GSH, and NO were measured (All were operated according to the instructions of the kit). the

(3) Experimental results

1. Aphanamixoid A can increase renal blood flow in mice with acute renal failure

Table 1 Effect of Aphanamixoid A on renal blood flow in mice with acute renal failure

*P<0.05vs acute renal failure model group

2. Aphanamixoid A has a protective effect on renal function in mice with acute renal failure

The 24-hour urine output of the rats in the model group was significantly lower than that of the sham operation group, which were 4.57±0.74ml and 11.82±2.36ml respectively; the 24-hour urine output of the middle and high doses of Aphanamixoid A group was significantly higher than that of the model group (P<0.05) , the urine output of the three drug treatment groups was dose-dependent, which were 5.48±0.87ml in group Ⅰ, 7.82±1.32ml in group Ⅱ, and 9.68±1.50ml in group Ⅲ. It shows that Aphanamixoid A can improve the symptoms of oliguria in rats with acute renal failure. the

After 24 hours of intravenous injection of normal saline in rats with acute renal failure, the serum BUN was 25.53±1.62mmol/L, and the Cre was 168.56±13.01umol/L, which were significantly higher than those in the sham operation group, indicating that the animals in the model group had serious renal damage. Medium and high doses of Aphanamixoid A can dose-dependently improve the renal function of rats with acute renal failure (P<0.05). See Table 2. the

Table 2 Comparison of renal function indexes of rats in each test group

*P<0.05vs acute renal failure model group

Conclusion: Aphanamixoid A can improve the symptoms of anuria or oliguria in acute renal failure, protect the function of the kidney, and can be used to prepare anti-acute renal failure drugs. the

Claims (1)

1. The application of Aphanamixoid A in the treatment of acute renal failure drugs, the structure of the compound Aphanamixoid A is shown in formula (I): Formula (Ⅰ).