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Medicament, containing effector of glutathione metabolism together with alpha-lipoic acid for use in kidney replacement therapy

A glutathione and effector technology, applied in medical preparations containing active ingredients, metabolic diseases, drug combinations, etc.

Inactive Publication Date: 2008-11-26
SERUMWERK BERNBURG AG
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, there is only limited transferability of these laboratory experiments to clinical research (FEBS-Lett 1996;394:9-13)

Method used

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  • Medicament, containing effector of glutathione metabolism together with alpha-lipoic acid for use in kidney replacement therapy
  • Medicament, containing effector of glutathione metabolism together with alpha-lipoic acid for use in kidney replacement therapy
  • Medicament, containing effector of glutathione metabolism together with alpha-lipoic acid for use in kidney replacement therapy

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0054] Effects on cellular thiol status in human peripheral immune cells

[0055] Peripheral immune cells of healthy donors (n=9) were isolated from peripheral blood by density gradient centrifugation. In this case, a donor-dependent relative proportion of about 90% lymphocytes usually represents the major part of the total monocyte number obtained. 10% of monocytes are monocytes.

[0056] The resulting monocytes were placed in a specific cell culture medium and incubated at 37°C, 98% relative humidity and 5% relative air-CO 2 Under the condition of content, culture in gas incubator. The metabolism of the initially resting immune cells was activated by mitogenic stimulation (0.5 μg / ml of lectin). To test the effect of the combinations used according to the invention on the thiol status in thiol-deficient immune cells, these cells were artificially reduced in thiols. This can be done by culturing in thiol-deficient medium (RPMI 1603) according to the test procedure. A cont...

Embodiment 2

[0067] Effects on Cell Activation State in Peripheral Human T Lymphocytes

[0068] Under the culture conditions described in Example 1, human T lymphocytes were stimulated with 1.0 μg / ml of lectin. Specific markers of cell activation were quantified by detection of monoclonal antibodies using a cytofluorometer during the 72 hour incubation period. The effect of the combinations used according to the invention on the activation markers CD69 (early activation antigen), CD25 (intermediate activation antigen) and CD71 (late activation antigen) of T lymphocytes was investigated. exist image 3 The combination of α-lipoic acid and ambroxol is shown in ( image 3 a), and the combination of alpha-lipoic acid and enalapril ( image 3b) Effect on the activation index of T lymphocytes. Compared with normal T lymphocytes (activation index = 1.0), a marked decrease in activation capacity was noted in thiol-deficient cells, confirming a disturbance in cell function. The known effect of...

Embodiment 3

[0070] Effects on the cellular thiol status of peritoneal macrophages during renal replacement therapy

[0071] Peritoneal macrophages were isolated from the peritoneal dialysate of patients with high renal impairment, placed in cell culture medium, and incubated in a gas incubator at 37°C, 98% relative humidity, and 7.5% relative air-CO 2 Cultivated under conditions of content. To test the effect of the combinations used according to the invention on the thiol status of peritoneal macrophages, the fractions were treated with alpha-lipoic acid, the effector of glutathione metabolism ambroxol or the ACE inhibitor enalapril or with The combinations alpha-lipoic acid / ambroxol or alpha-lipoic acid / enalapril were treated, while in each case one fraction was used as untreated control.

[0072] Determination of cellular thiol status was carried out using the measurement method described in Example 1. Membrane expression of thiols was determined by mean fluorescence intensity (mfi) ...

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Abstract

The invention relates to a medicament containing an effector of the glutathione metabolism together with alpha -lipoic acid, its salts and / or prodrugs as a combined preparation for the simultaneous, separate or time-controlled treatment of a defective thiol-disulfide status in kidney replacement therapy and of clinical characteristics, which indicate a disorder of the thiol-disulfide status of immunocytes. The correction of a defective thiol metabolism is of fundamental importance as a basic therapy for treating a large number of diseases of different origin, in particular however in circumstances requiring an essential kidney replacement therapy.

Description

technical field [0001] The present invention relates to the application of the combination of α-lipoic acid and effectors of glutathione metabolism in the treatment of cell thiol state disorder and accompanying diseases in renal replacement therapy. Background technique [0002] Fine tuning of the thiol-disulfide state is one of the most important fundamental requirements for biological metabolic capabilities. The central regulator in this system is the tripeptide glutathione, which reaches high concentrations (up to 10 mM) in the reduced form inside the cell. In addition to glutathione, proteins bearing thiol groups are also important units of the thiol-disulfide state of each cell in the molecule, especially in the form bound to the cell membrane. [0003] The metabolism of disulfide bond breaking and thiol group formation regulated by various enzymes is, as a whole, essential for every normal cell function due to the diversity of its biological functions, especially in c...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/385A61K31/401A61K31/403A61K31/137A61P13/12A61K45/00A61K31/381A61P3/00A61P39/06A61P43/00
CPCA61K31/137A61K31/385A61K31/401A61K31/403A61P13/12A61P3/00A61P37/00A61P39/06A61P43/00A61K2300/00
Inventor 迈克尔·特格尔齐格弗里德·安佐格格哈德·弗里斯迪特尔·克格斯特
Owner SERUMWERK BERNBURG AG
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