CN103462996A - Application of Neonectrolide A in preparing medicament for treating acute renal failure - Google Patents

Abstract

The invention relates to novel medicine application of Neonectrolide A, namely application of Neonectrolide A in preparing a medicament for treating acute renal failure, which is disclosed for the first time. The frame model belongs to a brand-new frame model, and Neonectrolide A has a strong activity in inhibiting acute renal failure, has a highlighted substantial characteristic, and is remarkably progressed in resisting acute renal failure.

Description

The application of Neonectrolide A in preparation treatment acute renal failure medicine

Technical field

The present invention relates to the new purposes of compound N eonectrolide A, relate in particular to the application of Neonectrolide A in preparation treatment acute renal failure medicine.

Background technology

Acute renal failure (Acute Renal Failure, ARF) be the clinical syndrome caused by many reasons, be found in the clinical departments patient, sickness rate is high and often have serious consequences, for in a short time, (a few hours are to a couple of days) siddhi can sharply descend its characteristics, clinical manifestation is acute oliguria (urine amount<400mLPd) or anuria (urine amount<100mLPd), in body, nitrogen matter metabolite is discharged and is produced obstacle, azotemia appears rapidly, water and electrolyte, acid base imbalance, and cause each system corresponding function imbalance of whole body.The principal element that causes acute renal failure is the sharply minimizing of renal blood flow, and the oxidative stress and the cell injury that cause due to the nephridial tissue ischemia, finally causes the deterioration of renal tissue structural damage and function.There is no clinically at present the generally acknowledged effective medicine for the treatment of acute renal failure, only can be by correcting water-electrolyte balance, the symptomatic treatment measures such as correction acidosis improve symptom, and the later stage also needs to maintain the body function by hemodialysis.There is the clinical medicine of obvious curative effects rare improving the kidney perfusion obstacle and alleviate aspect Renal tissues damage.

The compound N eonectrolide A the present invention relates to is one and within 2012, delivers (Jinwei Ren, et al., Neonectrolide A, a New Oxaphenalenone Spiroketal from the Fungus Neonectria sp.Organic Letters, 2012, 14(24) 6226 – 6229.) noval chemical compound, this compound has brand-new framework types, the Partial tumors cell is had to inhibition proliferation function (Jinwei Ren, et al., Neonectrolide A, a New Oxaphenalenone Spiroketal from the Fungus Neonectria sp.Organic Letters, 2012, 14(24) 6226 – 6229.), the purposes of the Neonectrolide A the present invention relates in preparation treatment acute renal failure medicine belongs to open first.

Summary of the invention

The object of the invention is to, according in existing Neonectrolide A research, not finding that it has the present situation of the report of anti-acute renal failure activity, provides the application of Neonectrolide A in the anti-acute renal failure medicine of preparation.

Research by us is found, anuria when Neonectrolide A can improve acute renal failure or oliguria symptom, the function of protection kidney.

Described compound N eonectrolide A, structure is as shown in formula I:

Formula I

The purposes of the Neonectrolide A the present invention relates in the anti-acute renal failure medicine of preparation belongs to open first, because framework types belongs to brand-new framework types, and it suppresses active strong for acute renal failure, possess outstanding substantive distinguishing features, obviously there is significant progress for anti-acute renal failure simultaneously.

The specific embodiment

The preparation method of compound N eonectrolide A involved in the present invention is referring to document (Jinwei Ren, et al., Neonectrolide A, a New Oxaphenalenone Spiroketal from the Fungus Neonectria sp.Organic Letters, 2012,14(24) 6226 – 6229.)

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

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

Get 5 and digest compound Neonectrolide A, add dextrin 195 grams, mix, conventional tabletting is made 1000.

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

Get 5 and digest compound Neonectrolide A, add starch 195 grams, mix, encapsulatedly make 1000.

Further illustrate its pharmaceutically active below by pharmacodynamic experiment.

The therapeutical effect of experimental example 1:Neonectrolide A to the acute renal failure rat

(1) experimental technique

Adopt intramuscular injection glycerol to cause the Acute Renal Failure Rats animal model.Select 60 of the healthy male SD rats of 180～220g, Nanjing Medical University's Experimental Animal Center is divided into 5 groups at random: sham operated rats (intramuscular injection normal saline); Model group (intramuscular injection glycerol); Neonectrolide A I group (0.3mg/Kg)); Neonectrolide A II group (0.6mg/Kg)); Neonectrolide A III group (1.2mg/Kg)), each organizes rat tail vein injection saline or Neonectrolide A immediately after the glycerol modeling, after 12 and 24 hours, is administered once again.

(2) observation index

60 rat lasts give to put into metabolic cage collection twenty-four-hour urine after Neonectrolide A or normal saline, stay latter 6 hours of urine with 4% chloral hydrate intraperitoneal injection of anesthesia, reach the rear bilateral renal blood flow for the treatment of after adopting laser Doppler flowmetry to measure modeling, average as single animal renal blood flow; Get blood and prepare serum, measure blood BUN and Cre; Get kidney, prepare 10% renal cortex homogenate, measure renal cortex homogenate MDA, GSH, NO(all by the operation of test kit description).

(3) experimental result

1.Neonectrolide A can increase acute renal failure Mouse Kidney blood flow

The impact of table 1Neonectrolide A on acute renal failure Mouse Kidney blood flow

* P<0.05 contrasts with the acute renal failure model group

2.Neonectrolide A is to the protective effect of acute renal failure Mouse Kidney function tool

The model group rat significantly reduces than rats in sham-operated group twenty-four-hour urine amount, is respectively 4.57 ± 0.74ml and 11.82 ± 2.36ml; Middle and high dosage Neonectrolide A group twenty-four-hour urine amount is significantly higher than model group (P<0.05), and the urine measurer of three medication therapy groups has dose dependent, is respectively I group 5.48 ± 0.87ml, II group 7.82 ± 1.32ml, III group 9.68 ± 1.50ml.Illustrate that Neonectrolide A can improve the oliguria symptom of acute renal failure rat.

Acute renal failure rat intravenous injection normal saline is after 24 hours, and serum BUN is 25.53 ± 1.62mmol/L, and Cre is 168.56 ± 13.01umol/L, apparently higher than sham operated rats, illustrates that model group animal renal function injury is serious.Middle and high dosage Neonectrolide A can improve the renal function (P<0.05) of acute renal failure rat in dose dependent ground.In Table 2.

Each rats in test groups renal function index of table 2 relatively

* P<0.05 contrasts with the acute renal failure model group

Conclusion: anuria when Neonectrolide A can improve acute renal failure or oliguria symptom, the function of protection kidney, can be used for preparing anti-acute renal failure medicine.

Claims (1)

1.Neonectrolide the application of A in preparation treatment acute renal failure medicine, described compound N eonectrolide A structure is as shown in formula I:

Formula I.