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Methods for administration and methods for treating cardiovascular diseases with resiniferatoxin

A resin toxin and cardiovascular technology, applied in cardiovascular system diseases, pharmaceutical formulas, medical preparations containing active ingredients, etc., can solve problems affecting nerves, etc., and achieve the effect of easy application

Pending Publication Date: 2019-04-02
BOARD OF RGT UNIV OF NEBRASKA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This migration of RTX may lead to unwanted denervation elsewhere in the spine, potentially affecting nerves unrelated to CSAR

Method used

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  • Methods for administration and methods for treating cardiovascular diseases with resiniferatoxin
  • Methods for administration and methods for treating cardiovascular diseases with resiniferatoxin
  • Methods for administration and methods for treating cardiovascular diseases with resiniferatoxin

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0070] Figures 3A to 4 B shows the experimental results of a rat study according to one embodiment of the present application. Figure 3A Shown are experimental data from a rat model showing isolectin B4 (IB4) and TRPV1 responses in rat populations that did not receive epidural RTX injections and that received epidural RTX injections. Figure 3B Experimental data from a rat model showing mean arterial pressure (MAP) and renal sympathetic nerve activity measured over a 26-week period in the RTX-naïve (vehicle) and epidural RTX-treated groups (RSNA). Figure 3C Experimental data from a rat model are shown showing MAP and RSNA measured over a 26 week period for the RTX-naïve (vehicle) and epicardial RTX-treated populations.

[0071] Figure 3A It was shown that isolectin B4 (IB4) and TRPV1 expression was reduced in DRG neurons of various sizes after RTX treatment compared to vehicle-only treatment which showed visually significantly increased expression. Figure 3B Responses...

Embodiment 2

[0074] Figure 4 Experimental results of a rat study according to one embodiment of the present application are shown. Figure 4Images showing the dorsal horn of the T2 spinal cord stained for TRPV1 and substance P (SP), comparing subjects receiving RTX injections to control subjects. Epidural application of RTX ablated nearly all SP-containing C-fiber afferents (peptidergic) and most isolectin B4 (IB4)-positive C-fiber afferents projecting to the dorsal horn of the thoracic spinal cord at the T1 to T4 DRG level ( non-peptidergic). Figure 4 showed decreased expression of TRPV1 protein and disruption of IB4-containing cell bodies, indicating ablation of small-diameter neurons. Ablation of neurons in the dorsal horn of the spinal cord expressing SP by RTX. IB4 is an indicator of small diameter afferent nerves and SP is an indicator of neuroinflammation. In each case, the reduced expression was evident from the reduced signal in the images of RTX-treated subjects compared to...

Embodiment 3

[0076] Figure 5 Experimental results of a rat study according to one embodiment of the present application are shown. Figure 5 Experimental data showing cardiac function in each of four Sprague-Dawley rat populations: sham-operated rats administered vehicle only (column A), sham-operated rats administered RTX epidurally (column B), induced chronic Rats with heart failure (CHF) administered vehicle only (column C) and rats with induced chronic heart failure (CHF) and epidurally administered RTX (column D), (n=9-16 per group). Experimental data include: body weight, heart weight, ratio of heart weight to body weight (HW / BW), ratio of wet lung weight to body weight (WLW / BW), left ventricular end systolic pressure (LVESP), left ventricular end diastolic pressure (LVEDP ), the maximum value of the first derivative of left ventricular pressure (dp / dt max ), the minimum value of the first derivative of left ventricular pressure (dp / dt min ) and infarct size. Statistically signi...

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Abstract

The present application provides methods for treating cardiovascular conditions. The methods can include administering a Transient Receptor Potential Vanilloid 1 (TRPV1) receptor agonist to an epidural space. The methods can be used to treat a variety of conditions such as hypertension, prehypertension, mild hypertension, severe hypertension, refractory hypertension, congestive heart failure and myocardial scarring.

Description

[0001] related application [0002] This application claims the serial number of U.S. Provisional Patent Application entitled "Methods for Administration and Methods for Treating Cardiovascular Diseases with Resiniferatoxin" filed April 13, 2016 62 / 322,079, the disclosure of which is incorporated by reference in its entirety. [0003] governmental support [0004] This invention was made with government support under Grant 1R01HL126796-01A1 (Zucker / Wang) from the National Institutes of Health. The government may have certain rights in this invention. field of invention [0005] The present disclosure relates to the ameliorating or preventive treatment of cardiovascular disease and provides methods of epidurally administering a transient receptor potential vanilloid subtype 1 (TRPV1) agent, such as resintoxin (RTX), to provide cardiosympathetic afferents Ablation or denervation to treat or preventively treat patients with one or more cardiovascular diseases. The present dis...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/357A61K9/08A61K31/165
CPCA61K9/0019A61K31/357A61K9/0085A61K45/06A61K31/4468A61P9/00A61P9/04A61P9/12A61K2300/00
Inventor 欧文·H·朱克王汉军
Owner BOARD OF RGT UNIV OF NEBRASKA
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