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Use of derivatives with C-O-P bonds in patients with renal failure

A technology of renal function and application, applied in the directions of medical preparations, drug combinations, drug delivery, etc. containing active ingredients

Inactive Publication Date: 2016-05-25
SANIFIT THERAPEUTICS SA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Within this large family comprising C-O-P bonds, some compounds have been found to inhibit various types of calcification, but these treatments have not been proven useful in the presence of kidney damage, as known studies are either related to normal kidney function, or In the case of uremia, the compound was not found to be effective

Method used

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  • Use of derivatives with C-O-P bonds in patients with renal failure
  • Use of derivatives with C-O-P bonds in patients with renal failure
  • Use of derivatives with C-O-P bonds in patients with renal failure

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 2

[0133] Example 2. In vitro determination of the affinity of IP6 for hydroxyapatite (HAP).

[0134] Purpose: The purpose of this study is to analyze the affinity of IP6 to its target, and thus obtain the affinity curve of IP6 to HAP.

[0135] Test: 4 different amounts of HAP were incubated with increasing concentrations of IP6 at 37°C, pH 7.4, for 4 hours with constant agitation. The total amount of IP6 bound to the surface of the target (HAP) was quantified.

[0136] Results: A dose-dependent adsorption curve was obtained and saturated at a concentration of 7.6 μM or higher. The maximum adsorption of IP6 on the HAP surface ranged from 4.8 mg when 300 mg of target was used to 6.42 mg when 25 mg HAP was used, and was achieved in the presence of 7.6 μΜ IP6 over 8 hours. To characterize the binding behavior of IP6, the EC of its adsorption on HAP was calculated 50 and E max . Calculations were performed using a nonlinear regression model (Log[agonist] vs. response-slope varia...

Embodiment 3

[0138] Example 3. In vitro determination of the binding kinetics of IP6 to HAP.

[0139] Objective: To analyze the binding rate of IP6 and HAP.

[0140] Test: 130 mg HAP was incubated with 7.6 μM IP6 (3 replicates) for different time intervals at 37° C., pH 7.4, with constant agitation.

[0141] Results and Discussion: Rapid binding of IP6 to HAP was observed ( figure 2 ), and reached the adsorption maximum at 60 min. Approximately 80% of maximum binding was achieved after 5 minutes.

Embodiment 4

[0142] Example 4. In vitro affinity of IP6 for HAP. Release research.

[0143] Objective: To analyze the release rate of IP6 from HAP.

[0144] Test: 130 mg HAP was incubated with 7.6 μM IP6 for different time intervals at 37° C., pH 7.4, while stirring continuously. Subsequently, HAP with adsorbed IP6 was placed in IP6-free solution, and the amount of IP6 released from the HAP surface was evaluated at different time points.

[0145] Results and Discussion: A relatively slow release of IP6 from the surface of HAP was observed ( image 3 ). After 2 days of incubation, 80% of IP6 remained bound to the surface of HAP.

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PUM

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Abstract

The invention relates to the use of a derivative with C-O-P bonds in the form of controlled release for the treatment of patients with renal failure. The invention also relates to the use of said derived compounds together with other active substances, that can particularly be selected from the list comprising a calcimimetic, a vitamin, a phosphorus chelator, thiosulfate, biphosphonate, pyrophosphate, citrate, a diuretic, an antihypertensive and an anticholesterolemic agent.

Description

technical field [0001] The present invention relates to the use of a long-acting form of a compound comprising a C-O-P bond for the treatment of a disease in a patient suffering from renal failure, irrespective of whether the compound is being treated otherwise. Background technique [0002] Renal failure (also known as renal impairment or kidney disease) is a condition that results in a progressive loss of kidney function with a reduction in the glomerular filtration rate (GFR) or index. Although the initial stages of renal injury can be asymptomatic, as the disease progresses, uremia presents. Uremia is a concept that describes the contamination of the blood caused by the kidneys not properly filtering and eliminating toxins. [0003] Kidney disease can be classified as: [0004] - Acute Kidney Injury: Progressive loss of kidney function, usually resulting in oliguria and fluid and electrolyte imbalances. Treatment must be with dialysis until the cause can be identified...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/00A61K31/6615A61P3/14
CPCA61K45/06A61K31/6615A61P13/12A61P17/00A61P19/02A61P19/06A61P19/08A61P19/10A61P21/00A61P29/00A61P3/14A61P9/00A61K2300/00A61K9/00A61K9/20A61K45/00
Inventor J·皮瑞罗佰斯塔德C·萨尔塞多罗卡M·D·费勒瑞尼斯B·艾森阿门瓜尔P·H·朱伯特
Owner SANIFIT THERAPEUTICS SA
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