RU2478233C2 - Method for endothelial dysfunction correction by solution of homoeopathic dilutions of tumour necrosis factor alpha antibodies - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: endothelial dysfunction is induced in experimental Wistar male rats for 28 days by daily intraperitoneal introduction of N-nitro-L-arginine methyl ester (L-NAME) 12.5 mg/kg a day. An agent for dysfunction correction is a mixture of solutions of homoeopathic dilutions of tumour necrosis factor-alpha (TNF-α) antibodies - C12, C30, C200. This mixture is introduced at the same time for 28 day intragastrically 2 times a day in a dose of 4.5 ml/kg.

EFFECT: effective endothelial dysfunction correction.

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Description

The invention relates to medicine, in particular to experimental cardiopharmacology, and can be used to correct endothelial dysfunction.

The prior art method for the correction of endothelial dysfunction with a mixture of solutions of homeopathic dilutions of polyclonal rabbit antibodies to endothelial synthase of human nitric oxide - C12, C30, C200, described in RF patent No. 2306953 C1 (A61K 39/395, 09/27/2007). However, from the known method does not follow the possibility of correction of endothelial dysfunction by introducing a mixture of solutions of homeopathic dilutions of polyclonal rabbit antibodies to tumor necrosis factor-alpha (TNF-α).

The invention is aimed at correcting endothelial dysfunction by introducing a mixture of solutions of homeopathic dilutions of polyclonal antibodies to TNF-alpha.

The solution to this problem is ensured by the fact that against the background of modeling L-NAME-induced endothelial dysfunction in the experiment by intraperitoneal administration to the laboratory animal for 28 days, the NO synthesis blocker N-nitro-L-arginine methyl ester (L-NAME) at a dose of 12.5 mg / kg / day, it is corrected by introducing a mixture of solutions of homeopathic dilutions of antibodies to tumor necrosis factor-alpha (TNF-α) - C12, C30, C200, intragastrically, 2 times a day, 4.5 ml / kg (9 ml / kg / day).

The claimed method, which introduces a mixture of solutions of homeopathic dilutions of antibodies to TNF-α - C12, C30, C200, leads to a decrease in the adhesion of endothelium, resulting in reduced binding of inflammatory cells to its surface, which prevents the occurrence of inflammation of the vessel wall, thrombosis and the occurrence of endothelial dysfunctions. The claimed solution expands the arsenal of tools designed to correct endothelial dysfunction.

The claimed method can be carried out as follows.

The experiments were performed on white Wistar male rats weighing 250-300 g. N-nitro-L-arginine methyl ether (L-NAME) was administered intraperitoneally at a dose of 12.5 mg / kg / day. On the 29th day from the start of the experiment, under anesthesia (sodium thiopental 50 mg / kg), a catheter is inserted into the left carotid artery to record blood pressure (BP), bolus administration of pharmacological agents is carried out in the right femoral vein. Hemodynamic parameters: systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) are measured continuously using the TSD104A sensor and the MP100 hardware and software complex manufactured by Biopac System, Inc., USA. Functional tests: endothelium-dependent vasodilation (ESV) - intravenous administration of acetylcholine (AH) at a dose of 40 μg / kg, endothelium-independent vasodilation (ENZV) - intravenous administration of sodium nitropruside (NP) at a dose of 30 μg / kg.

The degree of development of endothelial dysfunction is estimated using the coefficient of endothelial dysfunction (QED), which is the ratio of the area of the triangle above the trend of the reaction of blood pressure recovery in response to the introduction of NP to the area of the triangle above the trend of the reaction of blood pressure recovery in response to the introduction of AH.

When statistical data processing was calculated, the average value, the standard deviation. Differences were considered significant at p <0.05.

Processing of the obtained experimental data during functional tests for endothelium-dependent (acetylcholine 40 μg / kg iv) and endothelium-independent (nitropruside 30 mg / kg iv) vascular relaxation in experimental animals revealed that intraperitoneal administration of N-nitro-L-arginine methyl ester (L-NAME) at a dose of 12.5 mg / kg for 28 days causes an increase in the coefficient of endothelial dysfunction to 3.5 ± 0.5 srvc. units (see table), whereas in the control group (intragastric administration of distilled water, at a dose of 9 ml / kg / day), it amounted to 1.2 ± 0.1 srvc. units

In the group of animals, where against the background of the introduction of N-nitro-L-arginine methyl ester (L-NAME) at a dose of 12.5 mg / kg for 28 days, a mixture of solutions of homeopathic dilutions of polyclonal antibodies to TNF-α - C12, C30 was intragastrically administered , C200, QED amounted to 1.8 ± 0.2 srvc. units, which is significantly lower than in the group with modeling of pathology.

Thus, the obtained results allow us to state the correction of L-NAME-induced endothelial dysfunction with the introduction of N-nitro-L-arginine methyl ester (L-NAME) at a dose of 12.5 mg / kg for 28 days with a mixture of solutions of homeopathic dilutions of polyclonal antibodies to TNF-α - C12, C30, C200, with intragastric administration at a dose of 9 ml / kg, reducing QED to the level of that in the control group of animals - 1.2 ± 0.1 srvc. units

Claims (1)

A method for correcting endothelial dysfunction with a solution of homeopathic dilutions of antibodies to tumor necrosis factor-alpha, characterized in that in the experiment, Wistar male rats are induced to induce endothelial dysfunction by daily intraperitoneal administration of N-nitro-L-arginine methyl ester (L-NAME) into the rats for 28 days a dose of 12.5 mg / kg per day, while a mixture of solutions of homeopathic dilution of antibodies to tumor necrosis factor-alpha (TNF-α) - C12, C30, C200, which is administered at the same time, is used as a means for correcting dysfunction intragastrically for 28 days, 2 times a day with 4.5 ml / kg.