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Method for increasing bactericidal activity and providing virusocidal and fungicidal action on antibiotics

IPC classes for russian patent Method for increasing bactericidal activity and providing virusocidal and fungicidal action on antibiotics (RU 2477124):
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FIELD: medicine, pharmaceutics.

SUBSTANCE: method under the invention provides detoxification and polymerisation of antibiotics in 0.15±0.05% glutaric aldehyde at 38-40°C for 3-5 days, and then in 0.1% alkyl dimethyl benzyl ammonium chloride at 38-40°C for 3-5 days.

EFFECT: method provides effective bactericidal, virusocidal and fungicidal action of antibiotics and enables extending their therapeutic spectrum of application.

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The invention relates to Microbiology and biotechnology.

It is known that polymerization and detoxification of bacterial toxins and inactivation of viruses, bacteria are mainly formaldehyde, which is used from 1923 to obtain formulatin and anatoxins.

At the same time, detoxification and polymerization of antibiotics on the principle of making anatoxins are not conducted.

To increase the effectiveness of antibiotics injected into their structure pieperazinove radical, fluorine, clavulanic acid, creating a new generation of so-called "strong" antibiotics or combine with others. Combined use of some antibiotics with other leads to the emergence of drug-resistant microorganisms, while increasing nephro-, OTO-, neurotoxicity, etc.

The creation of new dosage forms and combinations of antibiotics does not provide a significant breakthrough and reduce toxicity in pharmakinetic antimicrobial drugs. We first increased the bactericidal activity of antibiotics using 0,15±0,05% solution of formaldehyde on the principle of making anatoxina (iglewski A.A., Kolomiets V.M. way of increasing the effectiveness of antibiotics. Patent No. 2400218 priority from 06 April 2009).

At the same time, the use of formaldehyde because of the carcinogenic properties, education in processorname highly toxic substances, precipitation at +9°C and below, contraindications for oral administration in many countries it is forbidden (Madunice NV Expert Committee on biological standardization who. Biologics, No. 1, 2001. - P.21-22).

Currently studied that the glutaric aldehyde amino acids has greater antibacterial, antiviral and fungicidal action than the aldehyde and formic acid - formaldehyde.

The prototype was taken way to increase the effectiveness of antibiotics by detoxification and polymerization 0,15±0,05% solution of formaldehyde (iglewski A.A., iglewski D.A. Modern aspects of increasing the effectiveness of antibiotics. Journal of the Kursk state agricultural Academy, No. 6. 2010 - P.64-65).

The above-mentioned disadvantages of the use of formaldehyde and relatively inadequate bactericidal efficiency compared with glutaraldehyde and especially in combination with Quaternary ammonium compounds, including alkyldimethylbenzylammonium, identified the need for detoxification and polymerization of antibiotics for resistance to bacterial enzymes, but also provide increased antibacterial antiviral and antifungal actions.

An object of the invention is to increase the effectiveness of antibiotics.

The technical result is achieved by polymerization and detoxification of antibi the ticks first 0,15±0,05% solution of glutaraldehyde at 38-40°C for 3-5 days, and then 0.1% of alkyldimethylbenzylammonium in the same mode.

The studies have used lincospectin, enrofloxacin, baytril, erythromycin, Amoksiklav, tetracycline, gentamicin, streptomycin, kanamycin, amoxicillin and Cefazolin, nystatin.

Modified antibiotics detoxification and polymerization were studied for effectiveness against bacteria, fungi, and viruses.

Application 0,15±0,05% solution of glutaraldehyde with 0.1% solution of alkyldimethylbenzylammonium (Quaternary ammonium compound) in the proposed method allows to check detoxification and polymerization of antibiotics on the principle of obtaining anatoxins and inactivated vaccines to increase their bactericidal activity and to provide antiviral and fungicidal action.

In the patent and scientific and technical literature technical solutions are not found, similarly stated, using glutaraldehyde with alkyldimethylbenzylammonium that allows to make a conclusion about the compliance of the offer with the condition of patentability "novelty".

The use of glutaraldehyde, alkyldimethylbenzylammonium and mode of detoxification and polymerization can achieve the effect specified in the invention, i.e. the claimed method meets the condition of patentability "inventive step".

Proposed is the range of the method according to the principle of anatoxina creates the basis and the prospect of making new antibiotics, able to overcome the well-known defense mechanisms of microorganisms to expand therapeutic range of their application, therefore, declared the proposal meets the conditions of patentability "industrial applicability".

The results obtained are illustrated by the following examples.

Example 1. Synthesis of modified antibiotics was performed by dissolving 1.0 g of the drug in 8.0 ml of distilled water with the addition of 1.0 ml of 1% solution of glutaraldehyde for detoxification and curing at 38-40°C for 3-5 days, and then brought to 1.0 ml of 1% solution of alkyldimethylbenzylammonium for the second stage in the same mode. Modified detoxification and polymerization of lincospectin, enrofloxacin, baytril, erythromycin, Amoksiklav, tetracycline, gentamicin, streptomycin, kanamycin, amoxicillin, Cefazolin and nystatin retained transparency, did not change its color and properties within 2 years of storage at +5°C to 25°C.

Example 2. Study of modified antibiotics toxicity

Daily subcutaneous and intramuscular injection of modified antibiotics for 5-7 days white mice in 0.1 ml (10 mg), cavies 2.0 ml (200 mg), piglets weighing 3-4 kg 10 ml (1 g) and calves weighing 40-50 kg 15-20 ml (1.5-2.0 g) did not cause necrotic changes in the injection of drugs and clincheck is marked toxic symptoms in the absence of death.

Example 3. Study of toxicity of modified antibiotics for oral use with water and food by watering and feeding within 7-10 days 1-2 ml (100-200 mg) chickens-broilers (50 goals), 27 calves 30-50 ml (3,0-5,0 g) and 35 pigs 10-20 ml (1-2 g) did not cause toxic signs and death.

Example 4. The study of the spectrum of the modified polymerization and detoxification of antibiotics using glutaraldehyde with alkyldimethylbenzylammonium held against staphylococci, E.coli, Salmonella, Pseudomonas aeruginosa, poxviruses of fibromatosis and myxomatosis virus canine distemper, parvovirus dogs, polykemi cats and mushrooms - Asp. niger Candida albicanis and Asp. flavus.

The results are presented in table 1.

Spectrum bactericidal and fungicidal action of modified antibiotics for 100 thousand of microorganisms in 1 ml 1 ág/ml, where To control, commercial antibiotic, and M is modified. From the data presented in table 1, it follows that the bactericidal effectiveness of antibiotics, modified detoxification and polymerization 0,15±0,05% solution of alkyldimethylbenzylammonium, virtually increased more than twice compared to commercial preparations against staphylococci, Escherichia, and Pseudomonas aeruginosa and Salmonella, which provided antifungal dei is a journey for Aspergillus niger, flavus and albikans with average minimum overwhelming concentration of 40-90 mg/ml, which correlate with therapeutic doses.

Subsequently it was established antiviral effect of modified antibiotics in concentrations of 10-20 µg/ml against poxviruses of fibromatosis and myxomatosis virus, plague and enteritis in dogs and polykemi cats with 103-105infectious doses in 1 ml.

Table 1
№ p/p Name antibiotic Types of test microorganisms
S.aureus E.coli Salm dublin Pseudomonas aeruginosa Asp. niger Asp. flavus Asp albicas
1. To-amoxicillin 17-19 15-16 15-17 21-25 - - -
M-amoxicillin 5-6 4-5 4-5 9-10 50-70 60-70 60-80
2. K-Amoxiclav 15-16 13-15 13-15 19-21 - - -
M-Amoxiclav 4-5 3-4 3-4 8-9 50-60 40-60 40-80
3. To erythromycin 15-17 13-15 15-16 21-23 - - -
M-erythromycin 4-5 3-4 3-4 9-10 70-90 70-90 90-100
4. K-gentamicin 1516 13-15 13-15 19-21 - - -
M-gentamicin 4-5 3-4 4-5 8-9 70-90 90-120 100-120
5. K-methicillin 12-13 11-12 11-13 18-19 - - -
M-methicillin 4-5 3-4 4-5 7-9 40-60 60-80 60-90
6. K-tetracycline 25-27 22-25 22-23 20-21
M-tetracycline 9-10 7-8 8-9 8-9 60-80 70-90 70-100
7. K-nystatin - - - - 100-120 110-130 110-130
M-nystatin - - - - 40-50 40-50 40-60
8. K-Cefazolin 13-15 9-11 9-11 18-19 - - -
M-Cefazolin 5-6 4-5 4-5 7-9 120-150 100-120 150-200
9. K-enrofloxacin 15-16 12-13 15-17 18-20 - - -
M-enrofloxacin 4-5 3-4 3-4 7-9 90-100 120-130 100-130
10. Lincospectin 12-13 9-11 12-13 19-21 - - -
M-lincospectin 5-6 4-5 4-5 7-9 100-120 110-130 110-130

The way to increase bactericidal activity and provide antiviral and antifungal effect of antibiotics, namely, that carry out detoxification and polymerization of antibiotics first 0,15±0,05%solution of glutaraldehyde at 38-40°C for 3-5 days, and the ATEM 0,1%solution alkyldimethyl ammonium at 38-40°C for 3-5 days.

 

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