Recombinant alkaline phosphatase for use in treating sepsis-associated acute kidney injury

A technology for sepsis and kidney injury, applied in the field of use of recombinant alkaline phosphatase for the treatment of sepsis-related acute kidney injury, and can solve the injury, loss of renal function, high cost, morbidity and mortality, etc. question

Pending Publication Date: 2021-01-22
AM PHARMA
View PDF7 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The development of AKI in sepsis patients is associated with increased mortality (Kellum et al. Critical Care Medicine 2016;193:281-7), while survivors are at risk of developing chronic kidney disease (Chawla et al. Kidney Int 2011;79:1361 -9; Oppert et al. Nephrol Dial Transplant 2008;23:904-9; Vaara et al. Crit Care 2012; 16:R197), resulting in a huge burden for patients and society
[0003] Prevention and / or adequate treatment of AKI is very important because, first, AKI is associated with high costs, morbidity and mortality, and second, prolonged AKI can lead to chronic kidney injury (CKI), which may lead to irreversible renal function lost

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
  • Recombinant alkaline phosphatase for use in treating sepsis-associated acute kidney injury
  • Recombinant alkaline phosphatase for use in treating sepsis-associated acute kidney injury
  • Recombinant alkaline phosphatase for use in treating sepsis-associated acute kidney injury

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0273] Human recombinant alkaline phosphatase for sepsis-associated acute kidney injury

[0274] Sepsis-associated acute kidney injury (AKI) adversely affects long-term renal outcome and survival. In preclinical studies, administration of the detoxifying enzyme alkaline phosphatase improved renal function and survival. We studied human recombinant alkaline phosphatase (RecAP) in patients with sepsis-associated AKI ( figure 2 ) efficacy and safety.

[0275] In part 1 of the adaptive phase 2a / 2b STOP-AKI trial, patients were randomly assigned to receive RecAP 0.4, 0.8, or 1.6 mg / kg or placebo once daily for 3 days to determine the optimal dose.

[0276] In part 2, this dose is compared to a placebo. The primary endpoint was the time-adjusted area under the endogenous creatinine clearance curve (AUC) from days 1 to 7. 1-7 ECC), with renal replacement therapy (RRT) as a key secondary endpoint. Long-term renal function, major adverse renal events (MAKE) at days 28, 60, and 9...

Embodiment 2

[0435] Determination of RecAP enzyme activity and protein concentration

[0436] Activity assay:

[0437] The determination of recAP enzyme activity is based on the conversion (hydrolysis) of 4-nitrophenol phosphate to yellow 4-nitrophenol. The change in optical density at 405 nm per unit time is a measure of alkaline phosphatase activity. The assay buffer consists of 0.25M glycine buffer (pH 9.6) and 2mM MgCl at 25°C 2 and 0.1mM ZnCl 2 and 8.5 mM 4-nitrophenol phosphate.

[0438] The unit (U) definition for recAP (expressed as U / mL) is the amount of enzyme that causes the hydrolysis of 1 μmol of 4-nitrophenol phosphate per minute at pH 9.6 and 25°C.

[0439] Protein concentration:

[0440] Determination of total protein concentration in RecAP drug substances and drug products is performed by UV / Vis analysis. RecAP solutions were analyzed at 280 nm and absorbance was a measure for protein content (mg / mL) using the following formula:

[0441] Concentration (mg / mL) = [A / (...

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

No PUM Login to view more

Abstract

The present disclosure relates to the use of alkaline phosphatases, and in particular improved alkaline phosphatases such as RecAP, for the prevention, treatment, cure, or amelioration of the symptomsof acute kidney injury caused, e.g., by sepsis. The application relates to methods of preserving renal function renal function, shortening the duration of renal replacement therapy, increasing the creatinine clearance, decreasing the risk of death in subjects with sepsis-associate acute kidney injury (SA-AKI) or at risk of SA-AKI.

Description

Background technique [0001] In animals, the kidneys perform several functions such as excretion of waste products, acid-base homeostasis, regulation of osmotic pressure, regulation of blood pressure and secretion of hormones. In order for the kidneys to perform these tasks, despite their relatively small size, the kidneys receive approximately 20% of the cardiac output. Thus, disruption of blood flow to the kidney (renal blood flow, RBF) has a direct impact on many functions of the kidney. For example, decreased excretion of nitrogenous wastes and disturbances in fluid and electrolyte balance may then occur. In the long term, RBF decreases, and other toxic events, such as ischemia (reperfusion injury), use of contrast media or (other) nephrotoxic drugs (such as antibiotics), can be so stressful on the kidney that it leads to Acute Kidney Injury (AKI). [0002] Acute kidney injury (AKI) is observed in up to 60% of patients in the intensive care unit (ICU), and its incidence ...

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(China)
IPC IPC(8): A61K38/43A61P29/00A61P13/12
CPCA61K38/43A61P13/12A61K9/0019A61K38/465C12Y301/03001
Inventor 鲁洛夫·彼得·皮克斯拉温德拉·拉尔·梅赫塔帕特里克·托马斯·默里迈克尔·约安尼迪斯埃瑞克·简·范·德·伯格雅克·萨洛蒙·罗伯特·阿伦特
Owner AM PHARMA
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap