Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Microporous zirconium silicate and diuretics for the reduction of potassium and treatment of chronic kidney and/or chronic heart disease

a technology of microporous zirconium silicate and diuretic, which is applied in the direction of drug composition, extracellular fluid disorder, metabolic disorder, etc., can solve the problems of voltage-gated sodium channels, depolarization of cell membrane potential, and acute hyperkalemia, so as to reduce the risk of hyperkalemia

Inactive Publication Date: 2014-10-09
ZS PHARMA
View PDF4 Cites 10 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

This patent text describes the use of preferred forms of microporous zirconium silicate to treat kidneys and cardiovascular disease. When used with diuretics, the microporous zirconium silicate improved kidneys' ability to filter and reduced the risk of developing high potassium levels. This means that using this treatment can help treat kidneys and cardiovascular disease by reducing the risk of complications.

Problems solved by technology

Acute hyperkalemia is a serious life threatening condition resulting from elevated serum potassium levels.
Increased extracellular potassium levels result in depolarization of the membrane potential of cells.
This depolarization opens some voltage-gated sodium channels, but not enough to generate an action potential.
This leads to impairment of the neuromuscular-, cardiac- and gastrointestinal organ systems, and this impairment is responsible for the symptoms seen with hyperkalemia.
However, as Kayexalate® has been shown to cause intestinal obstruction and potential rupture.
Further, diarrhea needs to be simultaneously induced with treatment.
The only commercial pharmacologic modality that actually increases elimination of potassium from the body is Kayexalate®; however, due to the need to induce diarrhea, Kayexalate® cannot be administered on a chronic basis, and even in the acute setting, with the accompanying need to induce diarrhea, combined with only marginal efficacy and a foul smell and taste, reduces its usefulness.
The inventors have found that known ZS compositions may exhibit undesirable effects when utilized in vivo for the removal of potassium in the treatment of hyperkalemia.
Further, known ZS compositions have had issues with crystalline impurities and undesirably low cation exchange capacity.
However, this approach has frequently led to hyperkalemia.
Notably, CVD is well known to be common and often fatal in people with CKD.
The administration of this combination has been shown to increase the risk of developing hyperkalemia, especially in patients with diabetes mellitus and renal impairment.

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Microporous zirconium silicate and diuretics for the reduction of potassium and treatment of chronic kidney and/or chronic heart disease
  • Microporous zirconium silicate and diuretics for the reduction of potassium and treatment of chronic kidney and/or chronic heart disease
  • Microporous zirconium silicate and diuretics for the reduction of potassium and treatment of chronic kidney and/or chronic heart disease

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0114]A solution was prepared by mixing 2058 g of colloidal silica (DuPont Corp. identified as Ludox™ AS-40), 2210 g of KOH in 7655 g H2O. After several minutes of vigorous stirring 1471 g of a zirconium acetate solution (22.1 wt. % ZrO2) were added. This mixture was stirred for an additional 3 minutes and the resulting gel was transferred to a stainless steel reactor and hydrothermally reacted for 36 hours at 200° C. The reactor was cooled to room temperature and the mixture was vacuum filtered to isolate solids which were washed with deionized water and dried in air.

[0115]The solid reaction product was analyzed and found to contain 21.2 wt. % Si, 21.5 wt. % Zr, K 20.9 wt. % K, loss on ignition (LOI) 12.8 wt. %, which gave a formula of K2.3ZrSi3.2O9.5*3.7H2O. This product was identified as sample A.

example 2

[0116]A solution was prepared by mixing 121.5 g of colloidal silica (DuPont Corp. identified as Ludox® AS-40), 83.7 g of NaOH in 1051 g H2O. After several minutes of vigorous stirring 66.9 g zirconium acetate solution (22.1 wt. % ZrO2) was added. This was stirred for an additional 3 minutes and the resulting gel was transferred to a stainless steel reactor and hydrothermally reacted with stirring for 72 hours at 200° C. The reactor was cooled to room temperature and the mixture was vacuum filtered to isolate solids which were washed with deionized water and dried in air.

[0117]The solid reaction product was analyzed and found to contain 22.7 wt. % Si, 24.8 wt. % Zr, 12.8 wt. % Na, LOI 13.7 wt. %, which gives a formula Na2.0ZrSi3.0O9.0*3.5H2O. This product was identified as sample B.

example 3

[0118]A solution (60.08 g) of colloidal silica (DuPont Corp. identified as Ludox® AS-40) was slowly added over a period of 15 minutes to a stirring solution of 64.52 g of KOH dissolved in 224 g deionized H2O. This was followed by the addition of 45.61 g zirconium acetate (Aldrich 15-16 wt. % Zr, in dilute acetic acid). When this addition was complete, 4.75 g hydrous Nb2O5 (30 wt. % LOI) was added and stirred for an additional 5 minutes. The resulting gel was transferred to a stirred autoclave reactor and hydrothermally treated for 1 day at 200° C. After this time, the reactor was cooled to room temperature, the mixture was vacuum filtered, the solid washed with deionized water and dried in air.

[0119]The solid reaction product was analyzed and found to contain 20.3 wt. % Si, 15.6 wt. % Zr, 20.2 wt. % K, 6.60 wt. % Nb, LOI 9.32 wt. %, which give a formula of K2.14Zr0.71Nb0.29 Si3O9.2*2.32H2O. Scanning Electron (SEM) of a portion of the sample, including EDAX of a crystal, indicated th...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

PropertyMeasurementUnit
diameteraaaaaaaaaa
particle sizeaaaaaaaaaa
particle sizeaaaaaaaaaa
Login to View More

Abstract

The present invention relates to novel methods of using microporous zirconium silicate to reduce the risk of hyperkalemia and to lower aldosterone levels in the treatment of chronic kidney disease and / or chronic heart disease with therapies comprising diuretics. The invention provides a safe way to reduce the risk of hyperkalemia and to lower aldosterone. The invention also relates to treatment of other conditions that can occur either alone or in connection with hyperkalemia, chronic kidney disease, and / or chronic heart disease.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application claims priority to U.S. Provisional Application No. 61 / 808,897, filed Apr. 5, 2013, U.S. Provisional Application No. 61 / 914,362, filed Dec. 10, 2013, and U.S. Provisional Application No. 61 / 930,331, filed Jan. 22, 2014, the disclosures of which are hereby incorporated by reference in their entireties.BACKGROUND OF THE INVENTION[0002]1. Field of the Invention[0003]The present invention relates to combination therapy and co-therapy methods for the treatment of diseases and / or disorders associated with excess cation levels using microporous zirconium silicate and diuretic compounds. The present invention can be used in the treatment of various disorders associated with excess potassium, including but not limited to hyperkalemia. The present invention can also be used in the treatment of chronic kidney and chronic heart disease. The invention provides a safe way to lower potassium levels in patients prone to or at risk to dev...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(United States)
IPC IPC(8): A61K33/24C01B39/00A61K45/06
CPCA61K33/24C01B39/00A61K45/06A61K31/4184A61K38/06A61P13/12A61P3/12A61P43/00A61P5/40A61P7/12A61P9/00A61P9/04Y02A50/30A61K2300/00A61K9/16
Inventor KEYSER, DONALD JEFFREYGUILLEM, ALVARO F.
Owner ZS PHARMA
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com