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Use of a dpp-4 inhibitor in podocytes related disorders and/or nephrotic syndrome

a podocyte related disorder and inhibitor technology, applied in the field of dpp4, can solve the problems of ineffective treatment, undesirable systemic adverse effects, and progressive kidney disease, and achieve the effects of reducing or delaying the onset or reducing the risk of or delaying the onset or slowing the progression of renal morbidity and/or mortality, and reducing or delaying the onset or progression

Inactive Publication Date: 2013-11-14
BOEHRINGER INGELHEIM INT GMBH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention is about a certain dipeptidyl peptidase-4 (DPP-4) inhibitor called linagliptin, which can be used to treat, prevent, and reduce the risk of disorders related to the kidneys. These disorders include disturbances in the function and loss of kidneys cells, as well as protect, repair, and regenerate them. The invention also involves the use of linagliptin in combination with other drugs like antidiabetics, antiplatelet agents, antihypertensives, and lipid lowering agents. The invention covers the prevention, delay, or reduction of the onset of kidney disease and death in patients with diabetes. The technical effects of the invention may be beneficial for patients with diabetic nephropathy, who are at higher risk of kidney disease and related complications.

Problems solved by technology

Injury to the podocyte results in proteinuria and often leads to progressive kidney disease.
Further, the nonspecific natures of these conventional agents can lead to undesirable systemic adverse effects.
If protein excretion can not be controlled by adequate therapy, these diseases often progress to end-stage renal disease.
With steroid hormone refractory minimal change nephropathy and focal segmental glomerulosclerosis (FSGS), however, there remain clinical circumstances where no effective treatment is available today.

Method used

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  • Use of a dpp-4 inhibitor in podocytes related disorders and/or nephrotic syndrome
  • Use of a dpp-4 inhibitor in podocytes related disorders and/or nephrotic syndrome
  • Use of a dpp-4 inhibitor in podocytes related disorders and/or nephrotic syndrome

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examples

Reduction in Loss of Podocytes; Expression of Podocalyxin as a Marker of Podocyte Integrity

[0316]The expression of podocalyxin is analyzed by immunohistochemistry using a podocalyxin specific antibody. Kidney sections from male diabetic db / db mice (10 weeks old at start and treated for 3 months) in the following groups are analyzed:

Diabetic control (n=10), linagliptin 3 mg / kg (n=8), enalapril 20 mg / kg (n=10) and heterozygous control mice (n=8).

[0317]All of the evaluations of the glomerular staining intensities are done semiquantitatively by two different experts of kidney pathology blinded for the slides.

[0318]The predefined scoring gradient is 0, 1, 2, and 3. 0 means no expression, whearas 3 is given when expression is highest. Group means are compared with a non-parametric test. P values less than 0.05 are considered significant.

[0319]FIG. 1 shows the expression of podocalyxin as a marker for podocyte integrity in linagliptin-, enalapril- or vehicle-treated diabetic db / db mice and...

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Abstract

The present invention relates to methods for treating and / or preventing podocytes related disorders and / or nephrotic syndrome comprising the administration of an effective amount of a certain DPP-4 inhibitor, as well as to the use of a certain DPP-4 inhibitor for treating and / or preventing a metabolic disease in a patient with or at risk of podocytes related disorders and / or nephrotic syndrome.

Description

FIELD OF THE INVENTION[0001]The present invention relates to a certain DPP-4 inhibitor (preferably linagliptin, optionally in combination with one or more other active agents) for use in treating, preventing and / or reducing the risk or likelihood of podocyte related disorders, disturbance of podocyte function, podocyte loss or injury, podocytopathy, glomerulopathy, nephrotic syndrome, minimal change disease (MCD, e.g. minimal change nephropathy), membranous nephropathy (MN, e.g. membranous glomerulonephritis) and / or focal segmental glomerulosclerosis (FSGS), and / or diseases related or associated therewith, to pharmaceutical compositions and combinations comprising such active components, and to certain therapeutic uses thereof.BACKGROUND OF THE INVENTION[0002]Disturbance of podocyte function as well as podocyte loss or injury are a hallmark of a variety of primary or secondary proteinuric glomerular diseases such as minimal change disease (such as e.g. minimal change nephropathy, or...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): C07D473/06A61K45/06A61K31/522
CPCC07D473/06A61K31/522A61K45/06A61K31/155A61K31/18A61K38/28A61P1/16A61P1/18A61P13/00A61P13/02A61P13/12A61P15/00A61P19/08A61P25/28A61P27/12A61P29/00A61P3/00A61P3/04A61P3/06A61P3/08A61P43/00A61P7/10A61P9/00A61P9/04A61P9/10A61P9/12A61P3/10A61K31/401A61K31/4184A61K2300/00
Inventor KLEIN, THOMASVON EYNATTEN, MAXIMILIANHOCHER, BERTHOLDMARK, MICHAELSHARKOVSKA, YULIYA
Owner BOEHRINGER INGELHEIM INT GMBH
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