Protection and enhancement of erythropoietin-responsive cells, tissues and organs

An erythropoietin, cell technology, applied in the directions of erythropoietin, cytokines/lymphokines/interferons, extracellular fluid diseases, etc. And other issues

Inactive Publication Date: 2004-06-16
THE KENNETH S WARREN INST
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although studies have established that intracranial injection of erythropoietin protects nerve cells from hypoxic nerve injury, intracranial administration is an impractical and unacceptable route of administration for therapeutic use, especially for For normal individuals
In addition, previous studies of erythropoietin administered to anemic patients had concluded that peripherally administered erythropoietin was not transported into the brain (Marti et al., 1997, Kidney Int. 51:416-8; Juul et al. , 1999, Pediatr.Res.46:543-547; Buemi et al., 2000, Nephrol.Dial.Transplant.15:422-433.)

Method used

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  • Protection and enhancement of erythropoietin-responsive cells, tissues and organs
  • Protection and enhancement of erythropoietin-responsive cells, tissues and organs
  • Protection and enhancement of erythropoietin-responsive cells, tissues and organs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0175] Erythropoietin crosses the tight blood-cerebrospinal fluid barrier

[0176] Mature male Sprague-Dawley rats were anesthetized and administered recombinant human erythropoietin by intraperitoneal injection. Cerebrospinal fluid (CSF) was sampled every 30 minutes from the cisterna magna until 4 hours, and erythropoietin concentrations were determined using a sensitive specific enzyme-linked immunoassay. like figure 1As shown, the initial erythropoietin concentration in CSF was 8 mU / ml. After a delay of several hours, the measured erythropoietin concentration in CSF started to increase and was significantly different from the initial concentration at a level of p<0.01 at 2.5 hours and later. Peak concentrations of about 100 mU / ml are within the range (0.1-100 mU / ml) known to exert protective effects in in vitro assays. The time to peak occurred at about 3.5 hours, which was significantly delayed from the time to peak serum concentrations (less than 1 hour). The results ...

Embodiment 2

[0178] Maintenance of function in hearts prepared for transplantation

[0179] Wistar male rats weighing 300 to 330 g were given erythropoietin (5000 U / kg body weight) or vehicle 24 h prior to heart removal for ex vivo studies, then followed by Delcayre et al., 1992, Amer. J. Physiol .263: The protocol for H1537-45 was performed. Animals were sacrificed under pentobarbital anesthesia (0.3 mL) and heparinized (0.2 mL) by intravenous injection. The heart was allowed to initially equilibrate for 15 minutes. The left ventricular balloon was then inflated to a volume with an end-diastolic pressure of 8 mmHg. Left ventricular pressure-volume curves can be constructed by inflating the balloon volume in 0.02 ml aliquots. Zero volume is defined as the point at which the left ventricular end-diastolic pressure is zero. When the pressure-volume curve was complete, the left ventricular balloon was deflated to bring the end-diastolic pressure back to 8 mmHg and this control period was ...

Embodiment 3

[0182] Erythropoietin protects myocardium from ischemic injury

[0183] Mature male rats administered recombinant human erythropoietin (5000 U / kg body weight) 24 hours earlier were anesthetized and coronary occlusions were prepared. At the beginning of the experiment, erythropoietin was supplemented once, and the left main coronary artery was occluded for 30 minutes and then released. The same dose of erythropoietin was administered daily for one week after treatment. The animals' heart function was then studied. like image 3 As shown, animals that received sham injections (saline) exhibited a large increase in left-sided end-diastolic pressure, showing an enlarged, stiff heart secondary to myocardial infarction. In marked contrast to sham-treated controls, animals receiving erythropoietin did not suffer a decline in cardiac function (significance level of difference at p<0.01).

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Abstract

Several methods and compositions are provided for the protection or promotion of mammals, including humans, by systemic or local administration of modulators of erythropoietin receptor activity, such as erythropoietin or modified erythropoietin The function or viability of an erythropoietin-responsive cell, tissue, organ or body part in vivo, in situ or ex vivo.

Description

[0001] Priority is claimed under 35 U.S.C. § 119(e)(1) to provisional application no. 60 / 259,245, filed December 29, 2000, which is hereby incorporated by reference in its entirety. Background of the Invention [0002] For many years, the only clear physiological role of erythropoietin was to control the production of red blood cells. Recently, several lines of evidence suggest that, as a member of the cytokine superfamily, erythropoietin exerts other important physiological functions mediated by its interaction with the erythropoietin receptor (erythropoietin-R). These roles include mitosis, regulation of calcium flux into smooth muscle cells and nerve cells, and effects on intermediary metabolism. It is believed that erythropoietin provides a compensatory response to improve the microenvironment of hypoxic cells and regulates programmed cell death caused by metabolic stress responses. Although studies have established that intracranial injection of erythropoietin protects n...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/00A61K38/16A61K45/00A61K38/18A61K38/19A61K38/24A61K38/27A61K45/06A61P3/10A61P7/00A61P9/00A61P9/04A61P9/10A61P21/04A61P25/00A61P25/02A61P25/08A61P25/14A61P25/16A61P25/18A61P25/22A61P25/28A61P25/32A61P27/02A61P27/06A61P29/00A61P43/00C07K14/52C07K14/575
CPCA61K45/06A61K38/1816A61P1/04A61P1/16A61P11/00A61P13/12A61P15/00A61P21/00A61P21/02A61P21/04A61P25/00A61P25/02A61P25/08A61P25/14A61P25/16A61P25/18A61P25/20A61P25/22A61P25/24A61P25/28A61P25/32A61P27/02A61P27/06A61P29/00A61P3/00A61P35/00A61P3/08A61P43/00A61P5/38A61P7/00A61P7/04A61P9/00A61P9/02A61P9/04A61P9/10A61P9/12A61P3/10A61K2300/00A61K38/22
Inventor M·布赖恩斯A·切拉米C·切拉米
Owner THE KENNETH S WARREN INST
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