The method of obtaining antiviral agents

 

(57) Abstract:

The invention relates to medicine. Spend processing of platonida potassium under the action of ultrasound in advanced mode acoustic cavitation ammonium salt of carboxylic acid. As this salt is used humic substances isolated from oxidized medical lignin oxygen in aqueous alkaline medium at a temperature of 150-170C and a pressure of 2.0-2.5 MPa for 0.5 to 1.5 hours the Invention improves the stability of the product. table 2.

The invention relates to biotechnology and can be used in technologies for antiviral agents of broad-spectrum.

A method of obtaining antiviral agents capable of handling platonida potassium Ethylenediamine (Synthesis of complex compounds of platinum group metals. - M.: Nauka, 1964, page 44).

Also known is a method of obtaining antiviral agents, providing a synthesis of CIS-dichlorodiammineplatinum (II) - MDC - processing platonida potassium ammonium salt of carboxylic acid, which use ammonium acetate, followed by filtration and crystallization of the desired product upon cooling. Synthesis vecsey source of ammonium scarce, this synthesized product is toxic (Biological aspects of coordination chemistry, edited Yatsymirsky K. B., Kiev: Naukova Dumka, 1978, page 152).

Closest to the claimed method is a method of obtaining antiviral agents on request N 93037252/14, MKI A 61 L 31/28, 33/24, which provides processing of platonida potassium ammonium salt of carboxylic acid, the ammonium salt use ligno-humic salts of carboxylic acids, which are pre-synthesized by the oxidation of lignin in alkaline medium, followed by separation of ligno-humic acids and their neutralization by ammonia. Processing platonida potassium ammonium salts of carboxylic acids are produced in the advanced mode of acoustic cavitation.

Oxidation of lignin in alkaline medium leads to an increase in the molecular weight of the product - "LinoColor" or "humic substances", which leads to an increase in turbidity and aggregate instability of the solution "humic substances". Therefore, this method does not provide a quality and stable medicinal drugs with a broad spectrum of antiviral activity.

The problem is solved in that a method for obtaining protivovirusnye mode advanced acoustic cavitation, when this oxidation is subjected to medical lignin in an alkaline medium at a temperature of 150-170oC for 0.5-1.5 hours at 2.0-2.5 MPa.

As you know, under the influence of ultrasound in the process platonida potassium ammonium salts of ligno-humic acid is the aggregation of substances in solution. Simultaneously there is an increase in the number of reactive centers.

By increasing the number of active centers are formed complex macromolecular aggregate structure.

Modes of oxidation was determined experimentally and was chosen for reasons of optimum sizes of molecules of high molecular compounds.

Oxidation of medical lignin in an alkaline environment, it is advisable to carry out at a temperature of 150-170oC.

When the temperature drops below for complete oxidation is necessary to increase the processing time, and when the temperature rises above decomposition of high-molecular compounds to low molecular weight, leading to increased turbidity and reduced stability of the solution.

The pressure in the reactor determines the partial pressure of oxygen in the processed product that entry to the need to increase the temperature or time of processing.

At a pressure of 2.5 MPa, the intensity of the process is increased, what, how, and when excessive temperature increase leads to the destruction of high-molecular compounds and reduce the stability of the final product.

Thus, only when the selected modes oxidation produces molecules of the optimal size, which ensures the production of high-quality and stable products.

To confirm the antiviral activity resulting from the use of the claimed method of preparation, the applicant proposes to amend the description of examples of the use of this drug for the suppression of influenza virus and rous sarcoma.

Thus, the inventive method differs from the prototype in that as ligno-humic acids, products of alkaline hydrolysis of lignin, can be used oxidized chelators on the basis of lignin, such as "Polifan", "Lignosol" etc.

Oxidation of medical lignin in the specified process conditions provided quality and stable medicinal drugs with a broad spectrum antiviral action, which distinguishes it from the products for RF application N 93037252.

"Lignosol" (paste Politeama) VFS 42-2203-93.

All used as starting materials are permitted to be inside the body.

Special studies have shown that the oxidation of medical lignin in terms of the proposed method does not generate harmful substances such as polycyclic aromatic hydrocarbons, nitrosamines and polychlorinated dicyclo-p-dioxins.

Study of antiviral activity obtained according to the proposed method means against herpes simplex viruses was performed using a transplantable culture of kidney cells of the embryo monkeys (MA-104) and primary cell culture of chicken fibroblast.

Used herpes simplex viruses 1 and 2 serotypes (strains "CONDITION" N 571 and "NR" N 572).

The tests were carried out after the preliminary assessment of toxicity in these cell cultures. In the examples used for dilution that make up 1/2 the minimum toxic dose, and took them for a working dose of the drug.

Digislide the Yu medical lignin (mark "Polifan", reg. N 80/1211/3) - non-specific enteral sorbent was oxidized by oxygen in the air.

The composition suspension

The content of Politeama - 1 kg

The content of alkali (sodium hydroxide) - 100 g

The density of the suspension is 1:9

The oxidation was performed in a reactor with mechanical stirring at a temperature of 160 5oC at a pressure of 2.5 MPa for 1 hour. The air flow rate was 5 l/min

The reaction mass is then cooled to room temperature and the solution filtered to separate the precipitate. The filtrate is acidified with sulfuric acid to pH 2-3. Dropped the precipitate was separated by filtration, washed with distilled water, and then water-alcohol mixture to establish a pH of 6.0-6.5 and dried at 105oC to constant weight. The obtained humic acid is neutralized with 5% aqueous solution of ammonia at the rate of 1 g of humic acid in 80 ml of the indicated solution, thermostatic in a boiling water bath to remove excess ammonia, filtered through filter paper and add 30% vol. of distilled water. In the resulting solution make 0.17-0.27 wt.% platonida potassium per 1 g of humic acids and create a process developed acoustic cavitation under the action of ultrasound with radiated power of 40 W/cm and a frequency of 22 kHz in ulturally fluid. To assess the antiviral activity used the drug solution with the working dose 0,03125 mg/ml to 0.8 ml of the prepared solution was made in a test tube with monocline cell cultures, and after contact for 1 hour but added 0.2 ml of herpes simplex viruses in decimal dilutions. The resulting system is incubated in a thermostat at 37oC with a daily visual inspection. Registration was carried out on 5-6 day when the cytopathic effect of the virus on the cells (JRC) has reached its maximum. Contagious virus was estimated by the method of reed and turns into a hissing drone. Antiviral activity of the preparations was assessed by the difference between the titres expressed in lg TCD 50/ml in the control and experimental tubes.

The proposed drug is taken, as described above at a concentration of 0,03125 mg/ml (working dose) inhibited infectious activity of herpes simplex virus 2 serotype ("EXT") in the experiment, 2.5 lg TCD

Antiviral activity of the proposed remedies in respect of herpes simplex virus 1 serotype ("CONDITION") is set to 10 times lower than in the same conditions compared to virus 2nd serotype ("NR") and was 100 TCD 50 ml.

Antiviral activity of rimantadine in equal equal to 0.125 mg/ml (working dose).

Thus, the antiviral activity of the proposed tools with a concentration in the working dose equal 0,03125 mg/ml, 500 TCD 50/ml in relation to herpes simplex virus 2 nd serotype (strain "NR") and 100 TCD 50/ml in relation to herpes simplex virus 1 serotype (strain "CONDITION"). Antiviral activity the proposed means 10-100 times higher compared to the activity of rimantadine containing working in a dose of 0.125 mg/ml of the drug.

EXAMPLE 3

To test the resulting use of the claimed method of the drug in the last volume of 0.2 ml was injected intramuscularly white mice for 1-3 days prior to their infection with influenza virus type A (PR-8). The control group of the drug is not received. The results are shown in table. 1

EXAMPLE 4

14-day chickens breed "White Livorno" oviparous line "Hisens", are highly sensitive to the rous sarcoma virus BH-RSV(RAV-1) serological subgroups A, has introduced a suspension of the virus in the flight membrane in doses of 100 ML-50 (left wing) and 100 ML-50 (right wing). For 4-6 days in chickens come necrosis.

To test the resulting use of the claimed method of the drug in the last volume of 0.2 ml was injected 24 and C is in table. 2

As the table shows, the use of the drug provides protection from virus, on average, 76%.

The way to obtain antivirals processing platonida potassium under the action of ultrasound in advanced mode acoustic cavitation ammonium salt lignohumic carboxylic acids obtained by the oxidation of lignin in alkaline medium, characterized in that the oxidation is subjected to medical lignin at 150-170C for 0.5-1.5 h at a pressure of 2.0-2.5 MPa.

 

Same patents:

The invention relates to medicine and can be used for the treatment of acute viral respiratory infections (ARI) in children

The invention relates to medicine and relates to a method of treatment of viral hepatitis In

The invention relates to new phosphonolipids carboxylic acids of formula I and their salts, where R1denotes a linear alkyl WITH9-C13, R2denotes a linear alkyl WITH8-C12, R3denotes hydrogen, a linear alkyl WITH1-C6or benzyl, n = 0-2, 0-3 m, which have antiviral activity and can find application in medicine

The invention relates to biochemistry, namely to obtain biologically active substances with antiviral activity

The invention relates to medicine, in particular to pharmacology relates to antiviral agents in the form of solid dosage forms containing acyclovir, microcrystalline cellulose, salt of stearic acid, low molecular weight polyvinylpyrrolidone, and, optionally, a dye in a certain ratio, and method of its production

The invention relates to medicine, namely dentistry

The invention relates to medicine, namely dentistry
The invention relates to the field of medicine and relates to means for the treatment of inflammatory diseases

The invention relates to biochemistry, in particular chemically modified oligonucleotide conjugatum that contain a complexing agent or complex, which is connected by the connecting component with oligonucleotides
The invention relates to medicine, namely dentistry
The invention relates to medicine, namely to dentistry

The invention relates to medicine, namely to dentistry
The invention relates to medicine, namely to dentistry
Up!