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A method for the treatment of generalized forms of anthrax infection

A method for the treatment of generalized forms of anthrax infection
IPC classes for russian patent A method for the treatment of generalized forms of anthrax infection (RU 2214834):
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The invention relates to medicine, infectious diseases and can be used for the treatment of generalized forms of anthrax infection. Enter daily antibacterial agent in combination with serum drug for antibacterial drug used broad-spectrum antibiotics, as serum drug is used F (AB)2-fragment antibodies protivovirusnogo immunoglobulin and impose additional immunomodulator, and an antibiotic administered daily at a daily dose equivalent to celovekoboga, drug - F (AB)2-fragment antibodies protivovirusnogo immunoglobulin administered daily intravenously in a daily dose equivalent to celovekoboga, as immunomodulator polyoxidonium use daily in a daily dose equivalent to celovekoboga, intramuscularly or intravenously, all medications given to the disappearance of clinical signs of disease. This invention improves the effectiveness and safety of treatment of anthrax infection. 3 table.

The invention relates to medicine, namely to methods for treating infectious diseases, and magazine-toxic shock.

Well-known classical method etiopathogenetic therapy of severe forms of anthrax infection, involving injection of antibiotic, (especially doxycycline), and symptomatic means (Guide to the clinic, diagnosis and treatment of infectious diseases. Under the editorship of academician RDMN C. I. Pokrovsky, Professor K. S. Ivanova, M. , 1994, instructions and guidelines for laboratory diagnosis, prevention and treatment of anthrax in humans, M., 1982) and / or intramuscular, but not intravenous protivovirusnogo horse globulin (instructions for use HP protivovirusnogo globulin. M., 1997, the developer scientifically defense Ministry, approved by the RF Ministry of health, 1998).

The shortcomings of the existing method for the treatment of generalized forms of anthrax infection, accompanied by severe bacteremia and toxemia with dissemination of capsule cells of the pathogen in organs of the reticuloendothelial system, the ineffectiveness of antibiotics against toxin suppression antibiotic and toxin protective reactions of an organism and the occurrence of anaphylactic shock after administration of large doses of alien high molecular weight protein, is anct Petersburg, 1998).

Object of the invention is the finding of new etiopathogenetic funds and schemes of their combined use for effective and safe treatment of experimental anthrax infection that occurs with the picture of infectious-toxic shock.

The problem is solved due to the fact that the antibiotics injectable form is complemented by injection and primarily intravenous low molecular weight toxin-neutralizing and decapsulates immunologically active F (AB)2fragments of antibodies protivovirusnogo immunoglobulin injection (intramuscular or intravenous) administration of the immunomodulator - polyoxidonium, stimulate immunocompetent cells of the reticuloendothelial system-potentiating effect of the antibiotic and has detoxifying properties.

A method for the treatment of anthrax infection that occurs with the picture of infectious-toxic shock in experimental animals, as follows.

When infection that occurs with the picture of infectious-toxic shock with bacteremia and toxemia, simultaneously with symptomatic and broad-spectrum antibiotics (ub>2slice in one human-dose and immunomodulator in one human-dose daily until the disappearance of clinical signs of disease.

Enablement of the claimed invention is shown in the following examples.

Example 1. Getting preparation of F (AB)2fragment (scientifically MO of the Russian Federation, registration No. 12, 2000, the regulation of production, 6152).

Therapeutic immunoglobulin prepared in a scientifically MO of the Russian Federation on regulation of the R.-739 h 1 and R-740 2 hours and meets the requirements of FS 42-37-70-99 mixed with ammonium sulfate. From the resulting solution of the immunoglobulin (Ig G), concentrated by dialysis and subjected to digestion by pepsin. Digested protein separated by gel-filtration on Sephadex. Eluate gather and unite, concentrated using ammonium sulfate and after dialysis sterilized and dispensed in compliance with the rules of asepsis 5 ml in vials with a capacity of 10.0 ml.

Specialty: harmless, sterile, apyrogenic, the titer of antibody in the reaction diffusion precipitation of the 1:8...1:16; index immunity to white mice not less than 4.0 srvc. unit

Example 2. Therapeutic and prophylactic efficacy of F (AB)2slice and globulin in experimental anthrax.

Efficacy F (AB)50. Analysis of the data in table 1 shows that at the different ways of introducing therapeutic effectiveness of the drug containing F (AB)2slice in two and more times higher than that of globulin. It should be noted that this effect of the drug containing F (AB)2the fragment was provided at a dose by more than an order of magnitude lower than that of globulin. Most effective drug F (AB)2fragment is administered intravenously, while regulations on globulin does not provide for this method of administration due to the danger of severe complications.

Example 3. Therapeutic efficacy of the drug F (AB)2portion and an antibiotic with the delayed date of introduction of the antibiotic.

Experiments evaluating the efficacy of drug F (AB)2slice his own use in terms of early detection of the pathogen by polymerase chain reaction (up to 6 hours) and performance assessment scheme (up to 6 hours) and evaluation of the effectiveness of the scheme for its application when delayed for 48 hours (the time that an antibiogram) the period of treatment with doxycycline or pefloxacin were performed on kalaimamani drugs are presented in table 2. As follows from the data in table 2, subcutaneous administration of the drug, F (AB)2slice through 6 hours after infection (at the time of diagnosis of infection by polymerase chain reaction) in next 5 days ensures the survival of animals up to 40... 50% (the first option). In the absence of treatment in the first 2 days to obtain data on antibiotic-sensitivity and the beginning of treatment only after 48 hours of antibiotics survives 0...20% of the animals (the second option). Combined application of the first and second options, including the start of drug treatment, F (AB)2-slice and the subsequent delayed (after 48 hours) application of antibiotic susceptible to this pathogen increases survival of animals up to 80...100%. Thus, to obtain data on the antibiotic susceptibility of the microbe early drug use F (AB)2fragment suppresses the infection to the beginning of the course of antibiotic therapy.

Example 4. Assessment of the effectiveness of the combined use of the drug, F (AB)2slice with antibiotic and polyoxidonium in the treatment of generalized forms of experimental anthrax infection.

The effectiveness of the combined use of the preparation of F (AB)2-FR is the third drug), studied at later stages of development anthrax toxic shock in experiments on rabbits and baboons Hamadryad. The results are shown in table 3. Analysis of the data presented in table 3 shows that in generalized form of anthrax infection, accompanied by bacteremia and toxemia, intravenous doxycycline for a few hours before the death of the control (untreated) animals survive only 20...30% of the animals (scheme 1). The combination of antibiotics with polyoxidonium increases the effectiveness of antibiotic to 40...60% (scheme 2), but not fully cured animals. The best in these conditions was the scheme intravenous drug F (AB)2fragment (survived 80. . .90% of the animals), and particularly the scheme of its combination with intravenous injection of antibiotic - survived up to 90% of the sick animals (schemes 3 and 4).

As can be seen from table 3, the most effective was the circuit 5, which in injectable form was applied to the entire complex of therapeutic drugs, including Coccinellidae and decapsulate serum drug F (AB)2slice antibiotic - doxycycline and immunomodulatory component of the complex - polyoxidonium, which I generalized forms of anthrax infection, includes daily introduction of antibacterial agents in combination with serum preparation, characterized in that as an antibacterial drug used broad-spectrum antibiotics, as serum drug is used F (AB)2-fragment antibodies protivovirusnogo immunoglobulin and additionally immunomodulator, and an antibiotic administered daily at a daily dose equivalent to celovekoboga, to the disappearance of clinical signs of disease, drug - F (AB)2- fragment antibodies protivovirusnogo immunoglobulin administered daily intravenously in a daily dose equivalent to celovekoboga, to the disappearance of clinical signs, and as an immunomodulator polyoxidonium use daily in a daily dose equivalent to celovekoboga, intramuscularly or intravenously to the disappearance of clinical signs of disease.

 

 

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