Erythroprotective agent for phenylhydrazine poisoning

FIELD: medicine, pharmaceutics.

SUBSTANCE: what is presented is using water-soluble hybrid macromolecular compounds O-(3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionyl-(1→6)-α-D-glucan and polyethylene glycol bis-3-(3,5-di-tert-butyl-4-hydroxyphenyl)-propionate as erythroprotective agents for phenylhydrazine poisoning. It is shown that the course intravenous introduction of the compounds has manifested erythroprotective action.

EFFECT: invention extends the range of agents applicable in integrated therapy of phenylhydrazine poisoning.

1 tbl, 3 ex

 

The invention relates to medicine, specifically to pharmacology, and relates to tools used in therapy in the administration of phenylhydrazine.

It is known tool that has retroprojector the action of the extract of Rhaponticum carthamoides [1].

The objective of the invention is to expand the Arsenal of tools used in therapy in the administration of phenylhydrazine.

The problem is solved by the use of a hybrid macromolecular compounds (HMS).

HMS synthesized by the developed technique [2, 3] and are water-soluble products of chemical modification of 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionic acid (KF) of hydroxyl-containing polymers: dextran ((1→6)-α-D-glucan with a molecular mass of 40 kDa (D) and polyethylene glycol with molecular weight of 20 kDa (PEG).

D-CF - O-(3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionyl)-(1→6)-α-D-glucan content KF 10.8 wt.%.

PEG-KF - glycol bis-3-(3,5-di-tert-butyl-4-hydroxyphenyl)-propionate, the content of KF 2.7 wt.%.

It is known that D-KF and the PEG-SF exhibit the properties of antioxidants [2-7], increase the survival of animals in acute blood loss [5], improves blood rheology on the model of Hyper viscosity of blood [6, 7].

The application of D-KF and PEG-KF as a means possessing retroprojector action in the administration of phenylhydrazine, the letter is ur not described.

Brand new in the present invention is that the qualities of the tools used in therapy in the administration of phenylhydrazine, use E-KF, PEG-KF. This type of compounds are explicitly derived for the expert from the prior art. Dr. KF, PEG-KF can be used in therapy in the administration of phenylhydrazine.

Thus, this solution meets the criteria of the invention: "novelty", "inventive step", "industrial applicability".

New properties of D-KF, PEG-KF were found experimentally.

The experiments were carried out on 33 rats male Wistar rats weighing 350-430,

Animals were divided into 4 groups: 1 - intact (n=8), 2 - control (saline) (n=9), 3 - experienced 1 (L-KF) (n=8), 4 - experimental 2 (PEG-KF) (n=8).

Model phenylhydrazine intoxication reproduced by a single injection to rats of phenylhydrazine in a dose of 50 mg/kg intraperitoneally. Blood for the study were taken from the common carotid artery under ether anesthesia on day 4 of the experiment. As the stabilizer used a 3.8% solution of sodium citrate in the ratio of blood 1:9. We measured the following parameters characterizing the rheological properties of blood: hematocrit, spontaneous erythrocyte aggregation, deformability of erythrocytes.

The compounds were injected daily (those who tell 4 days first time - 1 hour after poisoning phenyl) into the tail vein of the rats at a dose of 10 mg/kg in a volume of 0.2 ml saline solution was injected in equiano number.

Erythrocyte aggregation was investigated electrometrically method [8]. To characterize the aggregation ability of erythrocytes (AE) used the index of the bottom half of the curve aggregation T1/2. Study the deformability of erythrocytes was performed by laser diffraction [9]. For a quantitative estimation of erythrocyte deformability was calculated index of erythrocyte deformability (IDE).

Statistical processing was performed using the SRP "Statistica for Windows 6.0". Expected average value, the standard error of the mean; to identify the differences between groups used the nonparametric test Mann-Whitney U-test.

The results are shown in the examples.

Example 1. In the control group of animals to 4 days after a single injection of phenylhydrazine Wistar rats was observed the increase in T1/295% reduction in IDA 37% (table. control).

Thus, a single intraperitoneal injection of phenylhydrazine to rats resulted in severe intoxication, characterized by a violation of AE and lower TE.

Example 2. In the group of animals treated with D-KF, increased T1/2at 69%, while the giving of IDA by 19% as compared with intact performance. Compared with the control values, the introduction of D-KF reduced T1/2by 14% and increased IGE 28% (table. D-KF).

Thus, on the model of phenylhydrazine intoxication exchange rate intravenous KF-D at a dose of 10 mg/kg had expressed retroprojector action, manifested in enhancement of AE, IDA compared to control.

Example 3. In the group of animals treated with PEG-KF, increased T1/280% and reduce IDE 20% as compared with intact performance. Compared with the control values, the introduction of PEG-KF increased IDA 28% (table. PEG-KF).

Thus, on the model of phenylhydrazine intoxication exchange rate intravenous PEG-KF in the dose of 10 mg/kg had expressed retroprojector action, manifested in enhancement of IGE compared to control.

Table
The effect of intravenous L-KF and PEG-KF (10 mg/kg, 4 days) at T1/2and hide when phenylhydrazine intoxication
GroupT1/2cIDE, oted
The intact group (n=8)21,1±2,10,396±0,013
Control (n=9)41,2±3,8#0,250±0,012#
E-KF (n=8)35,6±2,2#*0,320±0,025#*
PEG-KF (n=8)38,0±1,1#MX 0.317±0,023#*
Note:#- the difference is significant with the intact group (p<0,05);
* - the difference is significant in comparison with control (p<0,05).

Sources of information

1. Carpenter MB, Aliyev I., Vasiliev, A.S., Plotnikova A.M., Karpova G.V., Abramova E.V. Retroprojector action of extract of Rhaponticum carthamoides intoxicated with phenylhydrazine in rats. // Bul. the experimental. Biol. and the honey. - 2005, Annex 1. - S-75.

2. Aref'ev A.I., an I.S., Voleva V.B. have been and other Hybrid macromolecular antioxidants based on hydrophilic polymers and spatial-obstructed phenols. "Izv. Russian Academy of Sciences. Ser. chem. - 2007. - V.4. - S.

3. Aref'ev D., Domnina N., E. Komarova, A. Bilibin Sterically hindered phenol-dextran conjugates: synthesis and radical scavenging activity. // Eur. Polym. J. - 1999. - Vol.35. - P.279.

4. Sergeeva O.Y, Domnina NS, Khrustaleva R.S. and other Hybrid macromolecular phenolic antioxidants. Properties and application in medicine. // VII international. proc. p the phenolic compounds: fundamental and applied aspects. - M., 2009. - S-246.

5. RF patent №2273483. Domnina NS, Khrustaleva R.S., Sergeeva O.Y and other water-Soluble polymeric antioxidant, a plasma substitute with antioxidant and antiradical activity (options) and the way to maintain blood pressure levels and processes of antioxidant protection in the body during acute blood loss. - Bull. No. 10, 2006.

6. RF patent №2425683. Carpenter MB, Aliyev I., Popova E.V., Domnina NS Means having a hemorheological activity. - Bull. No. 22, 2011.

7. Effects of Hybrid Macromolecular Phenolic Antioxidants on Rheological Characteristics of Blood in Rats. / Popova E.V., Plotnikov M.B., Aliev O.I. and all. // 2ndAnnual Russian-Korean Conference "Current issues of natural products chemistry and biotechnology", Novosibirsk, 2010. - P.115.

8. Carpenter MB, I. Aliyev, F. W. Popiel Modification microcalorimetry MKMF-1 for registration of aggregation of erythrocytes. // The wedge. lab. diagnosis. 1995. No. 3. - S-458.

9. Evans E., Mohandas N. Developments in red cell rheology at the institut de pathologie cellulaire. // Blood Cells. - 1986. - Vol.12. - P.43-45.

The use of hybrid macromolecular compounds O-(3-(3,5-di - tert-butyl-4-hydroxyphenyl)propionyl)-(1→6)-α-D-glucan, poly (ethylene glycol bis-3-(3,5-di-tert-butyl-4-hydroxyphenyl)-propionate as a means possessing retroprojector action in the administration of phenylhydrazine.



 

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