RU2579262C1 - Medicinal agent for treating infectious diseases - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: effective treatment and prevention of various infectious viral diseases are ensured by administering a medicinal agent containing an activated potentiated form of anti-human gamma-interferon antibodies in a combination with an activated potentiated form of anti-CD4 T-lymphocyte receptor antibodies.

EFFECT: effective treatment of infectious, including viral diseases ensured by synergetic action of the components of the medicinal agent.

14 cl, 7 tbl, 5 ex

Description

The invention relates to medicine and can be used for the effective treatment and prevention of various infectious viral diseases, including the prevention of HIV infection, the prevention and treatment of diseases caused by HIV or associated with HIV, including AIDS, the treatment of acute and chronic viral infectious diseases, such as acute viral hepatitis A, B, C and other viral hepatitis, herpes virus infection, various types of influenza and acute respiratory viral infections, as well as for effective treatment Ia and prevention of bacterial infections caused by various pathogens, e.g., pseudotuberculosis, pertussis, yersiniosis, pneumonia, etc. of various etiologies

The prior art knows a medicine for the treatment of infectious diseases, including viral etiology, based on the activated form of ultra-low doses of antibodies to interferon (RU 2192888 C1, A61K 39/395, 11/20/2002). However, this drug has limited therapeutic capabilities and is of little use for the treatment of diseases caused by HIV, acute and chronic viral infections, including various types of viral hepatitis and herpes virus infections, as well as for the treatment and prevention of bacterial infections caused by various pathogens, such as pseudotuberculosis, whooping cough, yersiniosis, pneumonia of various etiologies

The invention is directed to the creation of a medicinal product for the effective treatment and prevention of a wide range of various viral infectious diseases, including the prevention of HIV infection, the prevention and treatment of diseases caused by HIV or associated with HIV, the treatment of acute and chronic viral infections, including acute viral hepatitis A, B , C and other viral hepatitis, herpes virus infection, as well as for the effective treatment and prevention of bacterial infections caused by various pathogens, for example pre-tuberculosis, whooping cough, yersiniosis, pneumonia of various etiologies.

The solution of this problem is provided by the fact that the drug for the treatment of infectious diseases according to the invention contains an activated potentiated form of antibodies to human gamma interferon in combination with an activated potentiated form of antibodies to CD4 T-lymphocyte receptor.

In this case, the activated potentiated form of antibodies to human gamma-interferon and antibodies to the CD4 T-lymphocyte receptor is used in the form of a homeopathically activated potentiated aqueous or aqueous-alcoholic solution, the activity of which is due to the process of multiple dilution of the matrix solution of the corresponding antibodies in an aqueous or aqueous-alcoholic solvent in combined with the external mechanical effects of each dilution.

In addition, the drug may be in solid dosage form and contain an effective amount of a neutral carrier granule saturated with an activated potentiated form of antibodies to human gamma interferon and an activated potentiated form of antibodies to CD4 T-lymphocyte receptor, and pharmaceutically acceptable additives.

In this case, aqueous or aqueous-alcoholic solutions of homeopathically activated potentiated forms of antibodies to human gamma-interferon and antibodies to the CD4 receptor of T-lymphocytes were obtained by repeated serial dilution and intermediate external exposure from the corresponding matrix affinity purified antibodies with a concentration of 0.5 ÷ 5.0 mg / ml

Moreover, each of the components is used in the form of a mixture of various, mainly hundred, homeopathic dilutions.

When performing the solid dosage form, pharmaceutically acceptable additives include lactose, microcrystalline cellulose and magnesium stearate.

A drug containing an activated potentiated form of antibodies to human gamma-interferon and antibodies to the CD4 receptor T lymphocytes is used to treat viral infectious diseases, including the prevention of HIV infection, the prevention and treatment of diseases caused by HIV or associated with HIV, including the number of AIDS; for the treatment of various viral hepatitis; for the treatment of chronic viral hepatitis C; for the treatment of herpes virus infection; for the treatment of diseases caused by influenza virus; for the treatment of acute respiratory viral infections.

In addition, a drug containing an activated potentiated form of antibodies to human gamma interferon and antibodies to the CD4 receptor for T lymphocytes is used to treat bacterial infections caused by various pathogens, including the treatment of pseudotuberculosis, whooping cough, yersiniosis, and pneumonia of various etiologies.

The claimed drug is complex and may contain the active components in an equal volume ratio, each component can be prepared in the form of a mixture of three appropriate matrix solutions, diluted, respectively, in 100 ¹² , 100 ³⁰ , and 100 ⁵⁰ (or 100 ²⁰⁰ ) times, which is equivalent to hundreds of dilutions of C12, C30, C50 (or C200), prepared according to homeopathic technology.

The claimed drug is recommended to be taken, preferably 1-3 tablets 2-6 times a day (preferably 2-4 times a day).

The proposed combination of activated potentiated forms of antibodies to human gamma-interferon and antibodies to CD4 receptor T-lymphocytes provides an unexpected synergistic therapeutic effect, experimentally confirmed in adequate models, which consists in increasing the effectiveness of therapeutic effects and reducing viral load both in the prevention of HIV infection and and in the prevention and treatment of diseases caused by HIV or associated with HIV, including AIDS, as well as acute and chronic viral diseases, including herpes, acute viral hepatitis A, B, C and other viral hepatitis, various types of influenza and acute respiratory viral infections, as well as in the treatment and prevention of bacterial infections caused by various pathogens, for example, pseudotuberculosis, whooping cough , yersiniosis, pneumonia of various etiologies. Moreover, the claimed drug expands the arsenal of products intended for the effective treatment and prevention of a wide range of various viral infectious diseases, as well as for the effective treatment and prevention of bacterial infections caused by various pathogens,

It is possible to use the claimed drug in complex therapy in combination with other antiviral drugs, antibacterial drugs and symptomatic agents.

The claimed drug is prepared mainly as follows.

To prepare the activated potentiated form of the active components, monoclonal or, mainly, polyclonal antibodies are used, which can be obtained by known technologies - the techniques described, for example, in the book: Immunological methods, ed. G. Frimel, M., "Medicine", 1987, p. 9-33; or, for example, in an article by Laffly E., Sodoyer R. Hum. Antibodies. Monoclonal and recombinant antibodies, 30 years after. - 2005 - Vol. 14. - N 1-2. P. 33-55.

Polyclonal antibodies can be obtained by active immunization of animals. For this purpose, according to a specially developed scheme, the animals are given a series of injections with the substance required in accordance with the invention — an antigen or a conjugated antigen, for example, human gamma interferon, CD4 receptor. As a result of this procedure, a monospecific antiserum with a high antibody content is obtained, which is used to obtain the activated potentiated form. If necessary, the antibodies present in the antiserum are purified, for example, by affinity chromatography, using fractionation by salt precipitation or ion exchange chromatography.

Monoclonal antibodies are obtained, for example, using hybridoma technology. Moreover, the initial stage of the process includes immunization, based on the principles already developed in the preparation of polyclonal antisera. Further stages of the work include obtaining hybridoma cells producing clones of antibodies of the same specificity. Their isolation is carried out by the same methods as in the case of polyclonal antisera.

Preferred for the preparation of the claimed drug is the use of polyclonal antibodies, which are used as a matrix (initial) solution with a concentration of preferably 0.5–5.0 mg / ml for the subsequent preparation of the activated potentiated form.

It is preferable for the preparation of each component to use a mixture of three aqueous or water-alcohol dilutions of the initial matrix solution of antibodies diluted, respectively, at 100 ¹² , 100 ³⁰ and 100 ⁵⁰ (or 100 ²⁰⁰ ) times, which is equivalent to hundreds of dilutions of C12, C30 and C50 ( or C200) prepared according to homeopathic technology.

When preparing the claimed drug in solid dosage form, a mixture of these components is applied to a neutral carrier.

To obtain polyclonal antibodies to human gamma-interferon, an adjuvant and, for example, a whole human gamma-interferon molecule of the following sequence are used as immunogen (antigen) for immunization of rabbits:

1 MKYTSYILAF QLCIVLGSLG CYCQDPYVKE AENLKKYFNA GHSDVADNGT LFLGILKNWK

61 EESDRKIMQS QIVSFYFKLF KNF KDDQSIQ KS VETIKEDM NVKFFNSNKK KRDDFEKLTN

121 YSVTDLNVQR KAIHELIQVM AELSPAAKTG KRKRSQMLFR GRRASQ.

It is possible to obtain a polyclonal antibody to human gamma interferon as an immunogen (antigen) for immunization of rabbits using an adjuvant and, for example, one polypeptide fragment of human gamma interferon selected from the following sequences:

7-55:

ILAF QLCIVLGSLG CYCQDPYVKE AENLKKYFNA GHSDV;

24-166:

QDPYVKEAE NLKKYFNAGH SDVADNGTLF LGILKNWKEE SDRKIMQSQIVSFYFKLFKN FKDDQSIQKS VETIKEDMNV KFFNSNKKKR DDFEKLTNYS VTDLNVQRKAIHELIQVMAGRSPA;

24-166:

QDPYVKEAE NLKKYFNAGH SDVADNGTLF LGILKNWKEE SDRKIMQSQI VSFYFKLFKN FKDDQSIQKS VETIKEDMNV KFFNSNKKKR DDFEKLTNYS VTDLNVQRKAIHELIQVMAGRSPA;

69-123:

QS QIVSFYFKLF KNFKDDQSIQ KSVETIKEDM NVKFFNSNKK KRDDFEKLTN YSV;

100-145:

M NVKFFNSNKK KRDDFEKLTN YSVTDLNVQR KAIHELIQVM AELSP;

92-130:

SVETIKEDM NVKFFNSNKK KRDDFEKLTN YSVTDLNVQR;

123-147:

VTDLNVQR KAIHELIQVM AELSPAA;

24-166:

MQDPYVKEAE NLKKYFNAGH SDVADNGTLF LGILKNWKEE SDRKIMQSQI VSFYFKLFKN FKDDQSIQKS VETIKEDMNV KFFNSNKKKR DDFEKLTNYS VTDLNVQRKA IHELIQQMLFR;

5-45:

SYILAF QLCIVLGSLG CYCQDPYVKE AENLK;

94-114:

ETIKEDM NVKFFNSNKK KRDD;

24-166:

MQDPYVKEAE NLKKYFNAGH SDVADNGTLF LGILKNWKEE SDRKIMQSQI VSFYFKLFKN FKDDQSIQKS VETIKEDMNV KFFNSNKKKR DDFEKLTNYS VTDLNVQRKAIHELIQQMRSRL.

Before blood sampling for 1-3 days, 1-3 intravenous injections are performed to increase the level of antibodies. During immunization, small blood samples are taken from rabbits to evaluate the amount of antibody. The maximum level of the immune response to the administration of most antigens is achieved 40-60 days after the first injection. After the end of the first cycle of immunization of rabbits for 30 days, they restore health and re-immunization, including 1-3 intravenous injections. To obtain antisera from immunized rabbits, blood is collected in a 50 ml centrifuge tube. Using a wooden spatula, the formed clots are removed from the walls of the tube and the wand is placed in the clot formed in the center of the tube. Blood is placed in a refrigerator (temperature 4 ° C) at night. The next day, the clot attached to the spatula is removed and the remaining liquid is centrifuged at 13000 g for 10 minutes. The supernatant (supernatant) is an antiserum. The resulting antiserum should be yellow. You can add 20% NaN ₃ to the antiserum to a final concentration of 0.02% and store until use in a frozen state at a temperature of -20 ° C (or without adding NaN ₃ at a temperature of -70 °).

Isolation of anti-gamma interferon antibodies from antiserum is possible as follows:

1) 10 ml of rabbit antiserum is diluted in 2 times 0.15 M NaCl add 6.26 g of Na ₂ SO ₄ , mix and incubate for 12-16 hours at 4 ° C;

2) the precipitate formed is removed by centrifugation, dissolved in 10 ml of phosphate buffer and then dialyzed against the same buffer overnight at room temperature;

3) after removing the precipitate by centrifugation, the solution is applied to a column with DEAE-cellulose, balanced with phosphate buffer;

4) the antibody fraction is determined by measuring the optical density of the eluate at 280 nm.

Antibodies are purified by affinity chromatography on a column with antigen by binding of antibodies to gamma interferon with an antigen (gamma interferon) attached to an insoluble matrix of the column, followed by elution of the antibodies with concentrated salt solutions.

Thus obtained buffer solution of polyclonal rabbit antibodies to human gamma-interferon purified on an antigen with a concentration of 0.5 ÷ 5.0 mg / ml, preferably 2.0 ÷ 3.0 mg / ml, is used as a matrix ( initial) solution for the subsequent preparation of the activated potentiated form.

Polyclonal antibodies to the CD4 receptor are prepared according to the above method, using the adjuvant and the CD4 receptor molecule of the following amino acid sequence as immunogen (antigen) for immunizing rabbits:

26-458:

MNRGVPFRHL LLVLQLALLP AATQGKKVVL GKKGDTVELT CTASQKKSIQ FHWKNSNQIK ILGNQGSFLT KGPSKLNDRA DSRRSLWDQG NFPLIIKNLK IEDSDTYICE VEDQKEEVQL LVFGLTANSD THLLQGQSLT LTLESPPGSS PSVQCRSPRG KNIQGGKTLS VSQLELQDSG TWTCTVLQNQ KKVEFKIDIV VLAFQKASSI VYKKEGEQVE FSFPLAFTVE KLTGSGELWW QAERASSSKS WITFDLKNKE VSVKRVTQDP KLQMGKKLPL HLTLPQALPQ YAGSGNLTLA LEAKTGKLHQ EVNLWMRAT QLQKNLTCEV WGPTSPKLML SLKLENKEAK VSKREKAVWV LNPEAGMWQC LLSDSGQVLL ESNIKVLPTW STPVQPMALI VLGGVAGLLL FIGLGIFFCV RCRHRRRQAE RMSQIKRLLS EKKTCQCPHR FQKTCSPI.

It is possible to obtain a polyclonal antibody to the CD4 receptor as an immunogen (antigen) for immunization of rabbits using an adjuvant and, for example, one polypeptide fragment of the CD4 receptor selected from the following sequences:

412-458:

IGLGIFFCV RCRHRRRQAE RMSQIKRLLS EKKTCQCPHR FQKTCSPI;

26-60:

MNRGVPFRHL LLVLQLALLP AATQGKKVVL GKKGD;

105-119:

A DSRRSLWDQG NFPL;

115-139:

G NFPLIIKNLKIEDSDTYICE VEDQ.

Preferred for the preparation of the claimed drug is the use of buffer solutions of polyclonal antibodies to human gamma interferon and to the CD4 T-lymphocyte receptor with a concentration of 0.5 ÷ 5.0 mg / ml, preferably 2.0 ÷ 3.0 mg / ml, which as a matrix (primary) solution is used for subsequent preparation of the activated potentiated form.

The activated potentiated form of each component is prepared by uniformly decreasing the concentration as a result of successive dilution of 1 part of each solution to be diluted, starting from the aforementioned matrix solution, in 9 parts (for decimal dilution D) or in 99 parts (for hundred parts C) or in 999 parts (for a thousandth dilution of M) of a neutral solvent in combination with repeated vertical shaking (potentiation, or "dynamization") of each dilution obtained and using separate containers for each subsequent dilution to obtain the desired potency-fold dilution according to the homeopathic method (see, for example, V. Schwabe "Homeopathic medicines", M., 1967, S. 14-29).

External processing in the process of reducing the concentration can also be performed by ultrasound, electromagnetic or other physical effects.

For example, to prepare the 12th hundredth dilution of C12, one part of a matrix (initial) solution of antibodies, for example, to human gamma interferon, with a concentration of 2.5 mg / ml, is diluted in 99 parts of a neutral aqueous or aqueous-alcoholic solvent and repeatedly (10 and more times) vertically shake potentiate, getting the 1st hundredth C1 dilution. From the 1st hundredth dilution C1, the second hundredth dilution C2 is prepared. This operation is repeated 11 times, obtaining the 12th hundredth dilution of C12. Thus, the 12th hundredth dilution of C12 is a solution obtained by diluting successively 12 times in different containers of the 1st part of the initial matrix solution of antibodies to human gamma-interferon with a concentration of 2.5 mg / ml in 99 parts of a neutral solvent, those. the solution obtained by diluting the matrix solution in 100 to ¹² times. Similar operations with the appropriate dilution ratio are carried out to obtain dilutions of C30 and C50 or C200.

When using, for example, the activated potentiated form of antibodies to human gamma-interferon in the form of a mixture of various, mainly hundred, dilutions, each dilution (for example, C12, C30, C50) is prepared separately according to the technology described above, until the dilution is 3 dilutions less than the final ( respectively, to obtain C9, C27, C47), and then, in accordance with the composition of the mixture, one part of each component is added to one container and mixed with the required amount of solvent (respectively, with 97 parts for hundredth dilution ) Next, the resulting mixture was successively diluted twice in a ratio of 1 to 100, potentiating the resulting solution after each dilution. In this case, an activated potentiated form of antibodies is obtained, for example, against human gamma-interferon in an ultra-low dose obtained by diluting the matrix solution 100 ¹² , 100 ³⁰ , 100 ⁵⁰ times, equivalent to a mixture of hundred-fold dilutions C12, C30, C50.

It is possible to use each component in the form of a mixture of other different dilutions, for example, decimal and or hundredths (D20, C30, C100 or C12, C30, C200, etc.) prepared according to homeopathic technology, the effectiveness of which is determined experimentally.

To obtain a medicinal product, aqueous or aqueous-alcoholic solutions are mixed, mainly in an equal volume ratio and used in liquid dosage form.

The claimed drug can also be used in solid dosage form in the form of a pharmaceutical composition, which contains the technologically necessary (effective) amount of a neutral carrier - for example, lactose - saturated, by impregnation to saturation with a mixture prepared by the above technology, of aqueous or aqueous-alcoholic solutions activated potentiated forms of antibodies, and pharmaceutically acceptable additives, including mainly lactose, microcrystalline cellulose and magnesium st earat.

Obtaining a solid oral form of the claimed drug is carried out in a fluidized bed installation (for example, of the Hüttlin Pilotlab type manufactured by Hüttlin GmbH) by irrigation until saturation of the granules of a neutral substance - lactose (milk sugar) with a particle size of 50 ÷ 500 microns, pre-prepared aqueous or aqueous-alcoholic solution of the activated potentiated form of the antibody components, mainly in the ratio of 1 kg of antibody solution to 5 or 10 kg of lactose (1: 5-1: 10) with simultaneous Coy in a heated air stream supplied under the grate at a temperature of not higher than 40 ° C. The estimated amount of 10 ÷ 34 mass parts of the dried granules saturated with the activated potentiated form of antibodies is loaded into the mixer and mixed with 25 ÷ 85 mass. parts of the total load mass of “unsaturated” pure lactose (to reduce the cost and some simplification and acceleration of the process without reducing the effectiveness of the therapeutic effect). Then, magnesium stearate is added to this mixture in an amount of 0.1 ÷ 1 mass. parts of the total mass of the load and microcrystalline cellulose in an amount of 3 ÷ 10 mass. parts of the total mass of the load, with the formation of round tablets weighing 150 ÷ 500 mg, mainly weighing 300 mg, impregnated with a water-alcohol solution (3.0-6.0 mg / table.) of the activated potentiated form in an ultra-low dose of each component prepared from matrix solution, diluted in 100 ¹² 100 ³⁰ 100 ⁵⁰ (100 or ²⁰⁰⁾ times, the equivalent of a mixture of centesimal dilutions C12, C30 and C50 (or C200), prepared according to homeopathic technology.

For experimental studies, antibodies were used, prepared by order of a specialized biotechnological company.

Example 1

Evaluation of the antiretroviral activity of the claimed complex drug containing activated potentiated forms of aqueous dilutions of polyclonal affinity purified rabbit antibodies to the CD4 receptor in ultra-low doses (SMD) obtained by super-dilution of the initial matrix solution (concentration 2.5 mg / ml) in 100 ¹⁰ , 100 ³⁰ , 100 ⁵⁰ times equivalent mixture of centesimal homeopathic dilutions C12, C30, C50 and activated potentiated form aqueous dilutions of affinity-purified rabbit polyclonal antibodies to interferon -gamma in ultralow doses (RMA) obtained sverhrazvedeniem initial matrix solution (2.5 mg / ml) 100 ^12, 100 ^30, 100 ⁵⁰ times equivalent mixture of centesimal homeopathic dilutions C12, C30, C50 in the ratio of 1: 1 ( SMD AT to CD4 + IFN-γ), as well as a drug containing activated potentiated forms of aqueous dilutions of polyclonal affinity purified rabbit antibodies to CD4 receptor in ultra-low doses (SMD) obtained by super-dilution of the initial matrix solution (concentration 2.5 mg / ml) 100, 100 ³⁰ , 100 ⁵⁰ times equivalent a mixture of hundreds of homeopathic dilutions C12, C30, C50 (SMD AT to CD4) and a drug containing activated potentiated forms of aqueous dilutions of polyclonal affinity purified rabbit antibodies to interferon gamma in ultra-low doses (SMD) obtained by super-dilution of the initial matrix solution (concentration 2.5 , mg / ml) in 100 ¹² , 100 ³⁰ , 100 ⁵⁰ times, equivalent to a mixture of hundredths of homeopathic dilutions C12, C30, C50 (SMD AT to IFN-γ), was carried out using mononuclear cells of human peripheral blood infected in vitro mm HIV-1-LAI. Azidothymidine (Sigma - AZ169-100 mg, lot 107K1578) was used as a comparison drug.

Human peripheral blood mononuclear cells were isolated from the blood of a healthy seronegative donor by centrifugation in a density gradient of ficoll-hypak. Cells were activated for 3 days using 1 μg / ml phytohemagglutin P and 5 IU / ml recombinant human interdeukin-2 in RPMI1640 medium (DIFCO) with 10% fetal calf serum (complement was removed by heating for 45 minutes at 56 ° C), 1% antibiotic solution (PSN Gibco containing 50 μg / ml penicillin, 50 μg / ml streptomycin and 100 μg / ml neomycin).

Cells were infected with the HIV-1-LAI strain, delivering 50 μl of the inoculum of the HIV-1-LAI strain, corresponding to a dose of 100 TCID50 (dose infecting 50% of tissue culture cells).

To evaluate antiretroviral activity, the preparations were added to the wells 15-30 minutes after infection of the cells with the HIV-1-LAI strain. On the 7th day after infection of the cells, the supernatant was collected, used to evaluate the effect of the drugs on inhibition of HIV replication.

Before entering into wells containing 150 μl of cell culture, the preparations were diluted with RPMI1640 medium (DIFCO) until a final volume of 50 μl was reached. The preparation of SMD AT to CD4 and the preparation of SMD AT to IFN-γ were diluted 8 times in RPMI1640 medium (DIFCO) (1/8 dilution), and the preparation of SMD AT to CD4 + IFN-γ was diluted in RPMI1640 (DIFCO) medium in 4 times (dilution 1/4). Thus, the number of components of the preparation of SMD AT to CD4 + IFN-γ introduced into the experimental well during testing is identical to the number of components of the preparation of SMD AT to CD4 and components of the preparation SMD AT to IFN-γ as tested as single drugs, which allows a comparison of the effectiveness the preparation of SMD AT to CD4 + IFN-γ with its individual components that make up its composition. The reference drug azidothymidine was diluted with RPMI1640 medium (DIFCO) until a concentration of 8 nM was reached.

Drug efficacy was determined by inhibition of HIV replication, which was assessed by the enzymatic activity of HIV reverse transcriptase in supernatants of human peripheral blood mononuclear cells using the FIV RT RetroSys kit manufactured by INNOVAGEN (lot 10-059C). To calculate% inhibition of HIV replication, the supernatant of cells to which the test drugs or azidothymidine were not added was used as control (Table 1).

Thus, under the conditions of this experimental model, it was shown that the antiretroviral activity of the drug DMD AT to CD4 + IFN-γ is superior to the antiretroviral activity of the drug DMD AT to CD4 and IFN-γ.

Example 2

Evaluation of the antiretroviral activity of the claimed complex drug containing activated potentiated forms of aqueous dilutions of polyclonal affinity purified rabbit antibodies to the CD4 receptor in ultra-low doses (DMD) obtained by super-dilution of the initial matrix solution (concentration 2.5 mg / ml) in 100 ¹² , 100 ³⁰ , 100 ⁵⁰ times equivalent mixture of centesimal homeopathic dilutions C12, C30, C50 and activated potentiated form aqueous dilutions of affinity-purified rabbit polyclonal antibodies to interferon -gamma in ultralow doses (RMA) obtained sverhrazvedeniem initial matrix solution (2.5 mg / ml) 100 ^12, 100 ^30, 100 ⁵⁰ times equivalent mixture of centesimal homeopathic dilutions C12, C30, C50 in the ratio of 1: 1 ( SMD AT to CD4 + IFN-γ), as well as a drug containing activated potentiated forms of aqueous dilutions of polyclonal affinity purified rabbit antibodies to CD4 receptor in ultra-low doses (SMD) obtained by super-dilution of the initial matrix solution (concentration 2.5 mg / ml) 100 ¹² , 100 ³⁰ , 100 ⁵⁰ times, equivalent a mixture of hundreds of homeopathic dilutions C12, C30, C50 (SMD AT to CD4) and a drug containing activated potentiated forms of aqueous dilutions of polyclonal affinity purified rabbit antibodies to interferon gamma in ultra-low doses (SMD) obtained by super-dilution of the initial matrix solution (concentration 2, 5 mg / ml) in 100 ¹² , 100 ³⁰ , 100 ⁵⁰ times, equivalent to a mixture of hundreds of homeopathic dilutions C12, C30, C50 (SMD AT to IFN-γ), was carried out using macrophages obtained from mononuclear cells of human peripheral blood, and infected with an in vitro strain of HIV-1-Ba-L. Azidothymidine (Sigma - AZ169-100 mg, lot 107K1578) was used as a comparison drug.

Human peripheral blood macrophages were obtained from mononuclear cells of human peripheral blood, which were isolated from the blood of two healthy seronegative donors by centrifugation in a density gradient of ficoll-hypak. Human peripheral blood mononuclear cells were grown for 3 days in RPMI1640 medium (DIFCO) supplemented with 10% fetal calf serum (complement was removed by heating for 45 minutes at 56 ° C), 1% antibiotic solution (Gibco PSN containing 50 μg / ml penicillin, 50 μg / ml streptomycin and 100 μg / ml neomycin), 15 ng / ml GM-CSF (granulocyte-macrophage colony stimulating factor). The cells were then placed on culture plates (150,000 cells / well in a 48-well plate), grown for 7 days together with 1 ng / ml GM-CSF and 10 ng / ml M-CSF (macrophage colony stimulating factor) so that the cells could differentiate completely into macrophages.

Cells were infected with HIV-1-Ba-L strain, delivering 100 μl of the inoculum of HIV-1-Ba-L strain, which corresponds to a dose of 1000 TCID50 (dose infecting 50% of tissue culture cells).

To assess antiretroviral activity, the preparations were added to the wells 24 hours before the cells were infected with the HIV-1-Ba-L strain, as well as on days 3, 7, 10, 14, 17 after the infection. On the 3rd, 7th, 10th, 14th, 17th day after infection of the cells, the supernatant was collected, which was used to assess the effect of drugs on inhibition of HIV replication.

Before entering into wells containing 750 μl of cell culture, the preparations were diluted with RPMI1640 medium (DIFCO) until a final volume of 250 μl was reached. The preparation of SMD AT to CD4 and the preparation of SMD AT to IFN-γ were diluted in RPMI1640 medium (DIFCO) 8 times (1/8 dilution), and the preparation of SMD AT to CD4 + SMD AT to IFN-γ was diluted in RPMI1640 medium (DIFCO ) 4 times (1/4 dilution rate). Thus, the number of components of each component in the composition of SMD AT to CD4 + SMD AT to IFN-γ, introduced into the experimental well during testing, is identical to the number of components in the composition of SMD AT to CD4 and the components in the composition of SMD AT to IFN-γ tested as monopreparations, which allows a comparison of the effectiveness of the drug SMD AT to CD4 + SMD AT to IFN-γ with its individual components that make up its composition. The reference preparation azidothymidine was diluted with RPMI1640 medium (DIFCO) to a concentration of 8 nM.

Drug efficacy was determined by inhibition of HIV replication, which was assessed by the enzymatic activity of HIV reverse transcriptase in supernatants of human peripheral blood macrophages using the FNV RT RetroSys kit manufactured by INNOVAGEN (lot 10-059C). To calculate% inhibition of HIV replication, a cell supernatant was used as a control for which the test preparation SMD AT to CD4 + SMD AT to IFN-γ, the preparation SMD AT to CD4, the preparation SMD AT to IFN-γ and the azidothymidine comparison drug were used (Tables 2 and 3).

Thus, under the conditions of this experimental model, it was shown that the antiretroviral activity of the drug SMD AT to CD4 + SMD AT to IFN-γ is superior to the antiretroviral activity of the drug SMD AT to IFN-γ and the drug SMD AT to CD4; the antiretroviral activity of the drug SMD AT to CD4 + SMD AT to IFN-γ is maintained throughout the experiment, in contrast to the antiretroviral activity of the drug SMD AT to IFN-γ and the drug SMD AT to CD4; the preparation of SMD AT to CD4 + SMD AT to IFN-γ exerts antiretroviral activity in an in vitro model of infected macrophages of human peripheral blood obtained from different seronegative donors, which indicates a more pronounced antiretroviral effect of the preparation SMD AT to CD4 + SMD AT to IFN-γ , in contrast to the preparation of SMD AT for IFN-γ and the preparation of SMD AT for CD4, the antiretroviral activity of which was detected in an in vitro model of infected macrophages of human peripheral blood obtained from only one seronegative donor.

Example 3

To study the properties of the claimed drugs for the treatment of patients of the active drug group No. 1, 300 mg tablets were used, impregnated with a pharmaceutical composition containing aqueous-alcoholic solutions (6 mg / table.) Of activated potentiated forms of polyclonal affinity-purified rabbit antibodies to human gamma interferon ( AT to IFN-γ) and CD4 receptor (AT to CD4) in ultra-low doses (SMD) obtained by super-dilution of the initial matrix solution in 100 ¹² , 100 ³⁰ , 100 ²⁰⁰ times, equivalent to a mixture of hundred homeopathically x dilutions C12, C30, C200 (SMD AT to IFN-γ + AT to CD4); for the treatment of patients of the active drug group No. 2, 300 mg tablets were used, impregnated with a pharmaceutical composition containing water-alcohol solutions (6 mg / table.) of activated potentiated forms of polyclonal affinity purified rabbit antibodies to human gamma interferon (AT to IFN-γ) , CD4 receptor (AT to CD4) and histamine (AT to H) in ultra-low doses (SMD) obtained by super-dilution of the initial matrix solution 100 ¹² , 100 ³⁰ , 100 ²⁰⁰ times equivalent to the mixture of hundred-percent homeopathic dilutions C12, C30, C200 (SMD AT to IFN-γ + AT to CD4 + AT H); for the treatment of patients of the active drug group No. 3, 300 mg tablets were used, impregnated with an aqueous-alcoholic solution (3 mg / tablet) of an activated potentiated form of polyclonal rabbit antibodies to human gamma interferon purified on antigen in an ultra-low dose obtained by super-dilution of the original matrix solution in 100 ¹² , 100 ³⁰ , 100 ⁵⁰ times, equivalent to a mixture of hundreds of homeopathic dilutions C12, C30, C50 (SMD AT to IFN-γ).

Evaluation of the effectiveness of three drugs containing SMD AT to IFN-γ + AT to CD4, SMD AT to IFN-γ + AT to CD4 + AT to H and SMD AT to IFN-γ in the treatment of chronic viral hepatitis C (CHC) was carried out in a comparative study in parallel groups involving 18 patients (14 men and 4 women) aged 27 to 52 years. The diagnosis of HCV was confirmed based on the profile of serum markers - AT to HCV and HCV RNA. All patients included in the study had 2 or 3 HCV genotypes, a low-symptom slowly progressive chronic hepatitis C course with low activity (less than a 3-fold increase in serum aminotransferase levels, or <100 U / L), none of the patients had previously received antiviral therapy. The study did not include patients with a positive serological test for HIV, RW, anti-NSA, HBsAg or HBcor Ab, with cirrhosis of the liver, severe concomitant diseases in the acute stage, thalassemia or other hemoglobinopathy, alcohol and / or drug / drug dependence, after organ transplants, constantly taking immunosuppressive drugs, pregnant and lactating women. Patients of the first three groups were prescribed therapy with any studied drug at a dose of 1 tablet 3 times a day for 24 weeks: for patients of group 1 (n = 5) - composition of SMD AT to IFN-γ + AT to CD4; 2 groups (n = 4) - composition of SMD AT to IFN-γ + AT to CD4 + AT to H; 3 groups (n = 4) - SMD AT to IFN-γ The control group (No. 4) consisted of 5 patients with persistent viremia and persistently normal levels of aminotransferases (<20 IU / L) who were not prescribed any therapy. During the study, medical examinations, monitoring of viral load and laboratory parameters were carried out, concomitant therapy was recorded, possible undesirable effects. At the 24th week, the HCV RNA viral load and the activity of alanine aminotransferase (ALT) were evaluated as criteria for the effectiveness of treatment.

The data on the viral load (the number of copies of HCV RNA) presented in Table 4 in the form of the values of the median (Me), the first and third quartiles (Q1, Q3) indicate its positive dynamics obtained in patients of groups 1-3 by the end of 24- weekly therapy. Admission of the drug SMD AT to IFN-γ + AT to CD4 led to a decrease in the number of copies of HCV RNA in 4 out of 5 people of the 1st group, while the average decrease in viral load was 75%. Similar indicators were obtained in patients who took the drug SMD AT to IFN-γ + AT to CD4 + AT to H for 24 weeks: antiviral activity was recorded in all patients (4 out of 4 people in group 2), the average decrease in viral load was 70% Moreover, in 2 patients (one from group 1 and group 2), a complete virological response was obtained at the end of therapy. The antiviral activity of the monocomponent drug SMD AT to IFN-γ was slightly lower, since a decrease in the number of copies of HCV RNA was noted in 3 of 4 patients of group 3, the average decrease in viral load was 55%. Among the participants in the study of the control group, no positive dynamics of the viral load was detected.

The antiviral activity of the studied drugs was combined with the positive dynamics of ALT level, which was registered in patients of groups 1-3 by the end of 24 weeks of treatment. Normalization of ALT level was noted in 2 patients of the SMD AT group to IFN-γ + AT to CD4, in 1 patient of the SMD AT group to IFN-γ + AT to CD4 + AT to H, and also in 1 patient of the SMD AT group to IFN-γ . In 1 patient of the control group, against the background of an increase in viral load, after 24 weeks of observation, the ALT indicator exceeded the upper limit of the norm (> 20 U / L).

During the observation, no adverse events associated with the administration of the studied drugs were detected, which indicated their good tolerability. The absence of pathological abnormalities from blood and urine tests, as well as biochemical parameters, including renal and hepatic markers, confirmed the safety of treatment.

Thus, as a result of the study, data were obtained on the efficacy and safety of drugs SMD AT to IFN-γ + AT to CD4, SMD AT to IFN-γ + AT to CD4 + AT to H and SMD AT to IFN-γ, in the treatment of patients with CHC. The most distinct antiviral effect was observed in the preparation of SMD AT to IFN-γ + AT to CD4 and SMD AT to IFN-γ + AT to CD4 + AT to H, which was confirmed by the positive dynamics of the viral load, as well as the complete virological response recorded in 2 patients to end of 24 weeks of therapy. The antiviral efficacy of drugs containing SMD AT to IFN-γ + AT to CD4, SMD AT to IFN-γ + AT to CD4 + AT to H and SMD AT to IFN-γ was combined with a decrease in chronic hepatitis C activity, which manifested itself in a decrease and even normalization of ALT level in some patients by the end of a 24-week course of therapy.

Example 4

To study the properties of the claimed drugs for the treatment of patients of the active drug group No. 1, 300 mg tablets were used, impregnated with a pharmaceutical composition containing aqueous-alcoholic solutions (6 mg / table.) Of activated potentiated forms of polyclonal affinity-purified rabbit antibodies to human gamma interferon ( anti-IFN-γ) and CD4 receptor (anti-CD4) at ultra low doses (RMA) obtained sverhrazvedeniem initial matrix solution 100 ^12, 100 ^30, 100 ^{to 200} times equivalent mixture of centesimal gomeopatiches their dilutions C12, C30, C200 (SMD anti-IFN-γ + anti-CD4); for the treatment of patients of the active drug group No. 2, 300 mg tablets were used, impregnated with a pharmaceutical composition containing water-alcohol solutions (6 mg / tablet) of activated potentiated forms of polyclonal affinity purified rabbit antibodies to human gamma interferon (anti-IFN-γ) , to the CD4 receptor (anti-CD4) and histamine (anti-H) in ultra-low doses (SMD) obtained by super-dilution of the initial matrix solution 100 ¹² , 100 ³⁰ , 100 ²⁰⁰ times, equivalent to a mixture of hundred-percent homeopathic dilutions C12, C30, C200 ( SMD anti-IFN-γ + ant i-CD4 + anti-H). To treat patients of the comparison group, 300 mg tablets were used, impregnated with an aqueous-alcoholic solution (3 mg / tablet) of an activated potentiated form of polyclonal rabbit antibodies to human gamma interferon purified on antigen in an ultra-low dose obtained by super-diluting the initial matrix solution in 100 ¹² , 100, ³⁰ , 100, ⁵⁰ times, the equivalent mixture of hundreds of homeopathic dilutions C12, C30, C50 (SMD anti-IFN-γ).

The antiretroviral activity of the SMD compositions anti-IFN-γ + anti-CD4 and SMD anti-IFN-γ + anti-CD4 + anti-H was evaluated in an open comparative clinical trial in patients infected with human immunodeficiency virus (HIV), which were observed in Territorial Center for the Prevention and Control of AIDS and Infectious Diseases. The study included 65 men and 32 women (a total of 97 patients) aged 18 to 48 years with a viral load of ≥150 copies of HIV-1 RNA in 1 ml of plasma and a CD4-lymphocyte level of at least 250 cells / μl (or ≥0 , 25 × 10 ⁹ / L). 34 of the 97 study participants were observed for asymptomatic infectious status and had not previously received treatment for HIV infection (naive patients). 63 of 97 patients were on antiretroviral therapy (APT) for 1-2 years. The study did not include patients with cirrhosis, viral hepatitis C, severe concomitant diseases in the acute stage, pregnant women, as well as people taking intravenous drugs. The study was conducted in the autumn-winter period, when there was a seasonal increase in the incidence of influenza and acute respiratory infections (ARVI).

75 patients were randomized into three groups, they were prescribed therapy with group 1 and 2 drugs or group 3 comparison drug in a prophylactic (against influenza / SARS) dosage - 1 tablet 1 time per day for 6 weeks, including: patients group 1 (n = 25) was assigned the composition of SMD anti-IFN-γ + anti-CD4 in the form of monotherapy (subgroup 1A: naive patients, n = 12) or in combination with APT (subgroup 1B, n = 13); group 2 patients (n = 23) were prescribed SMD anti-IFN-γ + anti-CD4 + anti-H compositions, including monotherapy (subgroup 2A: naive patients, n = 11) or in combination with APT ( subgroup 2B, n = 12); group 3 patients (n = 27) were prescribed SMD anti-IFN-γ, including monotherapy (subgroup 3A: naive patients, n = 11) or in combination with APT (subgroup 3B, n = 16). The control (fourth) group (n = 22) consisted of patients who continued to receive APT according to the previous scheme without adding any study drug (APT group).

At baseline and after 6 weeks, all patients were assessed for viral load, CD4 and CD8 lymphocyte counts, and CD4 / CD8 immunoregulatory index. To determine the copies of HIV-1 RNA in blood plasma, we used the COBAS AMPLICOR HIV-1 MONITOR Kit, version 1.5 for the automatic PCR analyzer COBAS AMPLICOR (Roche, Switzerland). Phenotyping of circulating peripheral blood lymphocytes was performed on a FACSCount flow cytometer (Becton Dickinson, USA) using standard FACSCount Reagent Kit test systems containing antibodies to CD3, CD4, CD8 labeled with FITC, PE fluorochromes.

Table 5 presents the data on the viral load (the number of copies of HIV RNA) in the form of the median (Me), first and third quartiles (Q1, Q3) in patients of the studied groups in the dynamics of observation. As a result of the study, it was found that a 6-week intake of the anti-IFN-γ + anti-CD4 SMD composition led to a decrease in the number of copies of HIV-1 RNA in 58% of naive patients (in 7 out of 12 people of subgroup 1A), with an average decrease in viral the load was 16.9%. The combined use of the composition of SMD anti-IFN-γ + anti-CD4 and APT was no less effective, since a decrease in the number of copies of HIV-1 RNA was observed in 62% of the study participants (in 8 out of 13 people of subgroup 1B), and the average viral load reduction was 18.2% of the baseline. Approximately similar indicators were obtained using the SMD composition anti-IFN-γ + anti-CD4 + anti-H: antiviral activity was recorded in 55% of HIV-infected naive patients (in 6 out of 11 people of subgroup 2A) and in 67% of people who received the combination SMD anti-IFN-γ + anti-CD4 + anti-H and APT (in 8 of 12 people of subgroup 2B); the average decrease in viral load was 17.3% and 18.9%, respectively. The antiretroviral activity observed in the first two groups was slightly higher than the treatment results obtained in patients of the comparison group. After 6 weeks, monotherapy with SMD anti-IFN-γ reduced the number of copies of HIV-1 RNA in 36% of naive patients (in 4 of 11 people of subgroup 3A), while the decrease in viral load averaged 9.5%. The combined use of the monocomponent drug SMD anti-IFN-γ and APT increased the effectiveness of therapy, helping to reduce the viral load in 50% of the study participants (in 8 of 16 people of subgroup 3B) by an average of 14.2%. Similar treatment indices in individuals receiving only APT (control group 4) were 32% (in 7 of 22 people in group 4) and 13.3%, respectively.

Analysis of the indicators of the subpopulations of circulating lymphocytes in the dynamics of observation (Table 6) showed a more pronounced than in the control group increase in the number of CD4 lymphocytes after 6 weeks of therapy when using SMD anti-IFN-γ + anti-CD4, SMD anti-IFN-γ + anti -CD4 + anti-H and SMD anti-IFN-γ as monotherapy in naive patients (subgroups 1A, 2A and 3A) or in combination with APT (subgroups 1B, 2B and 3B). Moreover, the number of CD8 after 6 weeks of drug administration (mono-or combination therapy) did not change in any of the studied groups. The positive dynamics of CD4 lymphocytes during treatment led to an increase in the immunoregulatory index of CD4 / CD8, the most significant in the subgroups of patients taking SMD compositions anti-IFN-γ + anti-CD4 and anti-IFN-γ + anti-CD4 + anti H (mono - or combination therapy - groups 1 and 2) and SMD anti-IFN-γ in combination with APT (subgroup 3B).

The absence in patients during treatment of adverse events associated with the administration of the studied drugs indicated a good tolerance to the drugs. Repeated monitoring of laboratory parameters, including blood and urine tests, biochemical markers, confirmed the safety of treatment.

Thus, the study demonstrated the antiretroviral efficacy of the drug SMD anti-INF-γ + anti-CD4 and the drug SMD anti-IFN-γ + anti-CD4 + anti-H, apparently due to a change in the functional activity of CD4 receptors, which prevents the penetration of HIV into cells, as well as suppression of HIV replication inside the cell due to activation of transcription processes of antiviral protein mRNA. It was found that the decrease in viral load observed as a result of a 6-week intake of the drug SMD anti-IFN-γ + anti-CD4 and the drug SMD anti-IFN-γ + anti-CD4 + anti-H at a dose of 1 tablet per day exceeds the antiviral the effect that is recorded after 6 weeks of taking the monocomponent drug SMD anti-IFN-γ in the same dose or continuing according to the previous APT regimen. The combination of any drug SMD anti-IFN-γ + anti-CD4, SMD anti-INF-γ + anti-CD4 + anti-H or SMD anti-IFN with APT slightly enhances the antiviral activity of the latter, which is manifested in a decrease in the average value of the viral load after 6 weeks in a larger percentage of study participants.

The effect of SMD preparations anti-IFN-γ + anti-CD4 and anti-IFN-γ + anti-CD4 + anti-H on the ratio of CD4 / CD8 lymphocytes in HIV-infected patients (due to a slight increase in the absolute number of CD4 cells) was shown. most pronounced when used with APT. Given the simultaneous decrease in viral load in patients taking SMD anti-IFN-γ + anti-CD4 and SMD anti-IFN-γ + anti-CD4 + anti-H, it can be assumed that the increase in the number of CD4 cells is associated with an increase in the population of these cells due to healthy (uninfected) cells. The combination of APT with SMD anti-IFN-γ + anti-CD4, SMD anti-IFN-γ + anti-CD4 + anti-H or SMD anti-IFN is more effective in restoring the immunoregulatory index of CD4 / CD8 than the ongoing APT as before scheme.

The antiretroviral activity of SMD anti-IFN-γ + anti-CD4 and SMD anti-IFN-γ + anti-CD4 + anti-H drugs allows them to be used for prophylactic and therapeutic purposes in both naive HIV-infected patients and those receiving Apt.

Example 5

Investigation of the effect of a complex drug containing activated potentiated forms of polyclonal affinity-purified rabbit antibodies to CD4 (a mixture of ultra-low doses of aqueous homeopathic dilutions C12 + C30 + C50) and activated potentiated forms of polyclonal affinity-purified rabbit antibodies to interferon gamma (a mixture of ultra-low doses of aqueous homeopathic dilutions C12 + C30 + C50) in a 1: 1 ratio (hereinafter referred to as a complex preparation), as well as its constituent components (activated potentiated forms of polyclonal affinity purified rabbit antibodies to CD4 (a mixture of ultra-low doses of aqueous homeopathic dilutions C12 + C30 + C50) (hereinafter referred to as SMD AT to CD4) and activated potentiated forms of polyclonal affinity purified rabbit antibodies to interferon gamma (a mixture of ultra-low dose homeopathic dilutions C30 + C12 + C50) (hereinafter, SMD AT to IFN gamma)) in vitro for binding of the standard [ ³ H] pentazocine ligand to the recombinant human sigma 1 receptor was evaluated by the radioligand method. As a control of the tested drugs, a potentiated activated form of distilled water (a mixture of homeopathic dilutions C12 + C30 + C50) was tested (hereinafter potentiated water).

Sigma-1 receptor is an intracellular receptor localized in the cells of the central nervous system, the cells of most peripheral tissues and immunocompetent cells. This receptor, by controlling intracellular calcium homeostasis, regulates intracellular signaling cascades leading to activation of the corresponding transcription factors and transcription of a whole family of genes encoding, in particular, resistance factors to infectious agents and cytokines. In this regard, the ability of drugs to influence the effectiveness of the interaction of ligands with the sigma-1 receptor indicates the presence of antiviral and immunomodulating components in the spectrum of their pharmacological activity, which allows us to consider these drugs as effective drugs for the treatment and prevention of various infectious diseases.

In the experiment (for measuring total binding), 20 μl of the complex preparation or 10 μl of SMD AT to CD4 or SMD AT to IFN gamma were added to the incubation medium. Thus, the number of SMD AT to CD4 and SMD AT to IFN gamma introduced into the experimental well when testing the complex preparation was identical to the number of SMD AT to CD4 and SMD AT to IFN gamma tested as single drugs, which allows a comparison of the effectiveness of the complex preparation with its individual components that make up its composition. Potentiated water was introduced into the incubation medium in a volume of 20 μl and 10 μl. Then 160 μl (~ 200 μg protein) of the homogenate of the cell membranes of the Jurkat line (human leukemic T-lymphocyte line), and lastly 20 μl of the tritium-labeled [ ³ H] pentazocine radioligand (15 nM), were added. To measure nonspecific binding, instead of preparations or potentized water, 20 μl of unlabeled ligand, haloperidol (10 μM), was added to the incubation medium.

Radioactivity was measured on a scintillation counter (Topcount, Packard) using a scintillation mixture (Microscint 0, Packard) after incubation for 120 minutes at 22 ° C in 50 mM Tris-HCl buffer (pH = 7.4) and filtering on glass fiber filters (GF / B, Packard). Specific binding (in experiment or control) was calculated as the difference between total (in experiment or control) and non-specific binding.

The results are presented as percent inhibition of specific binding in the control (distilled water was used as a control) (see Table 7).

Note

% specific binding in the control = (specific binding in the experiment / specific binding in the control) * 100%;

% inhibition of specific binding in the control = 100% - (specific binding in the experiment / specific binding in the control) * 100%).

- Results reflecting inhibitions above 50% represent significant effects of the test compounds.

- Results reflecting inhibitions of 25% to 50% indicate mild to moderate effects.

- Results reflecting an inhibition of less than 25% are considered minor effects of the test compound and are within the background level.

Thus, in the conditions of this experimental model it is shown that:

1. The complex preparation is more effective than its individual components (SMD AT to CD4 and SMD AT to IFN gamma) inhibits the binding of the standard radioligand [ ³ H] pentazocine to the recombinant human sigma 1 receptor.

2. SMD AT to CD4, introduced into the experimental well in a volume of 10 μl, inhibits the binding of the standard radioligand [ ³ H] pentazocine to the recombinant human sigma 1 receptor, but the severity of the effect is less than the severity of the effect of the complex drug.

3. SMD AT for IFN gamma, introduced into the experimental well in a volume of 10 μl, did not affect the binding of the standard radioligand [ ³ H] pentazocine to the recombinant human sigma 1 receptor.

4. Potentiated water introduced into the experimental well in a volume of 10 μl or 20 μl did not affect the binding of the standard radioligand [ ³ H] pentazocine to the recombinant human sigma 1 receptor.

Claims (14)

1. A drug for the treatment of infectious diseases, characterized in that it contains an activated potentiated form of antibodies to human gamma interferon in combination with an activated potentiated form of antibodies to CD4 T-lymphocyte receptor. 2. The drug according to claim 1, characterized in that the activated potentiated form of antibodies to human gamma interferon and antibodies to the CD4 T-lymphocyte receptor is used in the form of a homeopathically activated potentiated aqueous or aqueous-alcoholic solution, the activity of which is due to the process of repeated dilution of the matrix a solution of the corresponding antibodies in an aqueous or aqueous-alcoholic solvent in combination with the external mechanical effect of each dilution. 3. The drug according to claim 1 or 2, characterized in that it is made in solid dosage form and contains an effective amount of granules of a neutral carrier saturated with an activated potentiated form of antibodies to human gamma-interferon and an activated potentiated form of antibodies to CD4 T-lymphocyte receptor, and pharmaceutically acceptable additives. 4. The drug according to claim 1 or 2, characterized in that the aqueous or aqueous-alcoholic solutions of homeopathically activated potentiated forms of antibodies to human gamma interferon and antibodies to the CD4 T-lymphocyte receptor are obtained by repeated serial dilution and intermediate external exposure from the corresponding matrix affinity purified antibodies with a concentration of 0.5 ÷ 5.0 mg / ml 5. The drug according to claim 4, characterized in that each of the components is used in the form of a mixture of various, mainly hundred, homeopathic dilutions. 6. The drug according to claim 3, characterized in that the pharmaceutically acceptable additives include lactose, microcrystalline cellulose and magnesium stearate. 7. The drug according to claim 1, characterized in that the activated potentiated form of antibodies to human gamma interferon and antibodies to the CD4 T-lymphocyte receptor is used to treat viral infectious diseases. 8. The drug according to claim 7, characterized in that the activated potentiated form of antibodies to human gamma interferon and antibodies to the CD4 receptor of T lymphocytes is used to prevent HIV infection, prevent and treat diseases caused by HIV or associated with HIV, including including AIDS. 9. The drug according to claim 7, characterized in that the activated potentiated form of antibodies to human gamma interferon and antibodies to the CD4 T-lymphocyte receptor is used to treat various viral hepatitis. 10. The drug according to claim 8, characterized in that the activated potentiated form of antibodies to human gamma interferon and antibodies to the CD4 T-lymphocyte receptor is used to treat chronic viral hepatitis C. 11. The drug according to claim 7, characterized in that the activated potentiated form of antibodies to human gamma interferon and antibodies to the CD4 receptor of T lymphocytes is used to treat herpes virus infection. 12. The drug according to claim 7, characterized in that the activated potentiated form of antibodies to human gamma interferon and antibodies to the CD4 receptor T lymphocytes are used to treat diseases caused by influenza virus. 13. The drug according to claim 7, characterized in that the activated potentiated form of antibodies to human gamma interferon and antibodies to the CD4 T-lymphocyte receptor is used to treat acute respiratory viral infections. 14. The drug according to claim 1, characterized in that the activated potentiated form of antibodies to human gamma interferon and antibodies to the CD4 T-lymphocyte receptor is used to treat bacterial infections caused by various pathogens, including for the treatment of pseudotuberculosis, pertussis, yersiniosis, pneumonia of various etiologies.