Alterations in endothelin receptors following hemorrhage and resuscitation by centhaquin

A technology of endothelin and receptor agonist, which is applied in cardiovascular system diseases, vector-borne diseases, and medical preparations containing active ingredients, etc. It can solve the problem of blood perfusion loss, hypothermia, immunosuppression, multiple organ failure and death in patients And other issues

Pending Publication Date: 2021-03-09
MID WESTERN UNIVERSITY BIRENDRANAGAR +1
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Despite resuscitation with intravenous fluids to restore circulation and oxygen delivery, patients may still suffer from irreversible loss of blood perfusion, coagul

Method used

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  • Alterations in endothelin receptors following hemorrhage and resuscitation by centhaquin
  • Alterations in endothelin receptors following hemorrhage and resuscitation by centhaquin
  • Alterations in endothelin receptors following hemorrhage and resuscitation by centhaquin

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0078] method

[0079] Animals Prior to use, Sprague-Dawley male rats (340 to 380 g) (Envigo, Indianapolis, IN) were incubated at controlled temperature (23±1° C.), humidity (50±10%) and light (6:00 AM to 6 :00PM) feeding. Food and water are provided continuously. Animal care and use for experimental procedures were approved by the Midwestern University Institutional Animal Care and Use Committee. All anesthesia and surgical procedures were in accordance with guidelines established by the Animal Care Committee.

[0080] Pharmaceuticals and Chemicals Centhaquin citrate (PMZ-2010) was synthesized at Pharmazz India Private Limited, Greater Noida, India. Using urethane (urethane) (Sigma-Aldrich StLouis, MO, USA), hypertonic saline injection USP (Hospira, Inc, Lake forest IL, USA), and heparin sodium injection (APP Pharmaceuticals, LLC, Schaumburg , IL, USA). Endothelin-1 enzyme immunoassay kit (catalog number 900-020A, Assay Designs, Inc., Ann Arbor, MI, USA), IL-6 ELISA kit ...

Embodiment 2

[0115] The following example identifies low doses of centhaquin citrate (2-[2-(4-(3-methylphenyl)-1-piperazinyl)]ethyl-quinoline) citrate in hemorrhagic shock Salt significantly lowers blood lactate and increases mean arterial pressure (MAP), pulse blood pressure (PP), and cardiac output (CO) (Gulati et al., 2012; Gulati et al., 2013; Lavhale et al., 2013; Papapanagiotou et al., 2016). A comparative study between centhaquin and existing resuscitation agents, which fall into 3 different classes: (a) fluids, such as lactated Ringer's, hypertonic saline; (b) adrenergic agents, such as norepinephrine prime, and (c) fresh blood. Our results using (i) a rat model of constant pressure hemorrhage, (ii) a rabbit model of uncontrolled traumatic hemorrhage and (iii) a pig model of massive hemorrhage showed that centhaquin was very effective in reducing mortality after hypovolemic shock Effective (Gulati et al., 2012; Gulati et al., 2013; Lavhale et al., 2013; Papapanagiotou et al., 2016...

Embodiment 3

[0134]Conducting a prospective multicenter randomized double-blind parallel phase II study (CTRI / 2017 / 03 / 008184) of PMZ-2010 (centhaquin) as a resuscitative agent in hypovolemic shock due to excessive bleeding compared with saline . All subjects will receive standard shock treatment (the type of treatment and care that will be provided by the registry). Patients were randomly assigned to the control group (N=7) who received standard care and saline, or the PMZ-2010 group (N=12) who received standard care and PMZ-2010. The interim analysis revealed comparable demographics of patients in the two groups (Table 2).

[0135] Table 2. An interim analysis showing comparable demographics of patients in the two arms of the phase II study.

[0136]

[0137] The study drug, PMZ-2010, met its primary endpoint for safety and no adverse events were reported. Treatment required fewer doses in PMZ-2010 than in controls (Table 3). Of the total hospital stay, patients treated with PMZ-20...

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Abstract

The present disclosure is related to methods and compositions for treating or preventing kidney injury or failure, comprising administering an endothelin B (ETB) receptor agonist and/or an alpha 2 adrenergic agent.

Description

[0001] Cross References to Related Applications [0002] This application claims priority under 35USC §119(e) to U.S. Provisional Patent Application No. 62 / 666,675, filed May 3, 2018, and Indian Application No. 201841019588, filed May 25, 2018, the disclosures of which are incorporated by reference in their entirety Incorporated into this article. technical field [0003] The present disclosure relates to methods and compositions for treating or preventing renal injury or failure comprising administration of endothelin B (ET B ) receptor agonists and / or alpha 2 Adrenergic agent. [0004] Incorporation by reference of electronically submitted materials [0005] As a separate part of this disclosure, this application contains a Sequence Listing in computer readable form (Filename: 50000A_Seqlisting.txt; Size: 673 bytes; Created: May 2, 2019), which is hereby incorporated by reference in its entirety. Background technique [0006] Hemorrhagic shock often results in inadequa...

Claims

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Application Information

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IPC IPC(8): A61P9/00A61P35/00A61P43/00A61P13/12A61P25/00
CPCA61P13/12Y02A50/30A61K31/496A61K38/2285A61K2300/00A61K38/1709
Inventor A·古拉提M·拉夫哈尔B·卡蒂娅A·K·辛格
Owner MID WESTERN UNIVERSITY BIRENDRANAGAR
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