Extended release of neuregulin for improved cardiac function

A heart cell, heart hypertrophy technology, applied in the treatment or delay of various heart diseases or disorders, the field of prevention, can solve invasive, expensive, restrictive and other problems

Inactive Publication Date: 2009-03-25
ZENSUN (SHANGHAI) SCI & TECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

For example, heart transplantation is obviously more expensive and invasive than medical treatment, and is further limited by th

Method used

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  • Extended release of neuregulin for improved cardiac function
  • Extended release of neuregulin for improved cardiac function
  • Extended release of neuregulin for improved cardiac function

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0177] Phosphorylation of AKT and ERK in the left ventricle of normal rats after infusion of NRG by different methods Situation

[0178] In order to compare the effect of NRG on left ventricular cardiomyocyte signaling with different administration methods, we used intravenous injection (hereinafter referred to as "IV"), intramuscular injection (hereinafter referred to as "IM") and intravenous infusion (hereinafter referred to as "IM"). IVGTT") to infuse NRG.

[0179] Wistar male rats (Shanghai Experimental Animal Center, Chinese Academy of Sciences), weighing 180±20 g, were numbered and weighed and grouped. Each group contained three rats. A group of rats received an IV injection of 4ml / kg (volume / body weight) vehicle (10mM Na 2 HPO 4 -NaH 2 PO 4 , 150 mM NaCl, 0.2% human serum albumin (HSA), 5% mannitol, pH 6.0) as a control group. The other four groups of rats received IM injection of 4ml / kg (volume / body weight) of NRG (37.3U / ml recombinant human NRG fragment (177...

Embodiment 2

[0183] The function of the heart in rats with left ventricular coronary artery ligation after NRG treatment by different methods

[0184] Because osmotic pumps are a method of sustained release of NRG (like IVGTT), we examined whether perfusing NRG with osmotic pumps is as effective as conventional IV injection in restoring function in myocardial infarction (MI) hearts.

[0185] A. Coronary artery ligation and ultrasound in rat left ventricle

[0186] Wistar male rats (Shanghai Experimental Animal Center, Chinese Academy of Sciences), weighing 200±20 g, were anesthetized by intraperitoneal injection of ketamine 100 mg / kg (drug / body weight). The neck and chest are shaved and disinfected. An incision is made in the anterior mid-position of the neck to expose the trachea. An 18G catheter overneedle was inserted into the trachea between the 3rd and 5th cartilages. When the needle is withdrawn, a plastic catheter is pushed into the trachea 1-2 cm and fixed to connect to a rodent...

Embodiment 3

[0206] Cardiac function of rats with myocardial infarction after continuous intravenous infusion of neuregulin with a syringe pump (Zhejiang University Medical Instrument Co., Ltd., WZS50-F2)

[0207] In this example, a syringe pump was used to continuously administer neuregulin to the patient. The syringe pump can continuously pump the solution into the blood stream at a certain speed through a needle inserted into the tail vein of the rat. With syringe pumps, it is easy to control the time and rate of infusion. Intravenous infusion of neuregulin into MI rats by syringe pump was performed daily at different rates and at different times to optimize the time period and infusion rate of the treatment.

[0208] Grouped rats were intravenously injected with 4ml / kg (volume / body weight) vehicle, injected daily, for 10 days (group A), or intravenously injected with 10 μg / kg neuregulin (2.5 μg / ml), injected daily, for a total of 10 days. 10 days (group B), or intravenous infusion of...

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Abstract

The present invention provides extended release compositions comprising neuregulin for preventing, treating or delaying various diseases or disorders. The present invention also provides methods for preventing, treating or delaying various diseases or disorders by extended release of neuregulin.

Description

[0001] Cross References to Related Applications [0002] This application claims priority to US Provisional Application Serial No. 11 / 755,124, filed December 30, 2005, and US Provisional Application Serial No. 60 / 758,626, filed January 13, 2006. field of invention [0003] The present invention relates to compositions and methods for the sustained administration of neuregulin to mammals for the prevention, treatment or delay of various cardiac diseases or disorders. Background of the invention [0004] Cardiac (ventricular) hypertrophy is an important adaptive physiological response to increased cardiac operating stress or demands. One of the early cellular changes that occurs after hypertrophic stimuli is mitochondrial synthesis and myofibril expansion (wall thickening) with a proportional increase in individual cell size, but no (or minimal) increase in cell number. [0005] When the ventricles are stressed, the initial response is an increase in sarcomere length. This i...

Claims

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Application Information

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IPC IPC(8): A61K38/17A61P9/00C07K14/475
Inventor 周明东
Owner ZENSUN (SHANGHAI) SCI & TECH CO LTD
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