RU2500422C2 - Combined drug for treating viral infections and method of treating viral infections - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: present group of inventions refers to medicine, namely therapy, and concerns treating viral infections. That is ensured by administering a combined drug containing human activated potentiated gamma-interferon, CD4 receptor and histamine antibodies.

EFFECT: administering the same combined drug provides treating various viral diseases, such as acute respiratory viral infections, herpes viral infections, acute intestinal viral infections, etc, by action on the various components of the immune system.

10 cl, 5 ex, 2 dwg, 8 tbl

Description

The invention relates to medicine and can be used to treat viral infections, including acute respiratory viral infections, herpes virus infections, acute intestinal infections of viral etiology, enteroviral meningitis, hemorrhagic fever with renal syndrome, tick-borne encephalitis.

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 in some cases may not provide sufficient therapeutic efficacy.

The invention is aimed at increasing the effectiveness of the treatment of various viral infections, including acute respiratory viral infections, herpes virus infections, acute intestinal infections of viral etiology, enterovirus meningitis, hemorrhagic fever with renal syndrome, tick-borne encephalitis.

The solution to this problem is ensured by the fact that a comprehensive drug for the treatment of viral infections, containing an activated - potentiated form of antibodies to human gamma-interferon, according to the invention, contains, as additional active components, an activated-potentiated form of antibodies to the CD4 receptor (to the antigen - CD4) and an activated-potentiated form of anti-histamine antibodies.

In this case, the activated - potentiated form of antibodies to human gamma-interferon (IFN-γ), the activated-potentiated form of antibodies to the CD4 receptor and the activated-potentiated form of antibodies to histamine are used in the form of an activated-potentiated aqueous or aqueous-alcoholic solution, the activity of which is due to the process of sequential multiple dilution of the matrix - initial - solution of antibodies in an aqueous or aqueous-alcohol solvent in combination with an external mechanical action - vertical tryahivaniem each dilution, with final dilutions contain ultralow doses (SMD) antibodies.

In this case, the complex drug can be made in solid dosage form in the form of a pharmaceutical composition and contain the technologically necessary (effective) amount of a neutral carrier saturated with a mixture of the activated-potentiated form of antibodies to human gamma-interferon, the activated-potentiated form of antibodies to the CD4 receptor and activated -potentiated forms of antibodies to histamine, and pharmaceutically acceptable additives, which include, for example, lactose, microcrystalline cellulose th and magnesium stearate.

In this case, aqueous or aqueous-alcoholic solutions of activated-potentiated forms of antibodies to human gamma interferon, to the CD4 receptor and to histamine are obtained by repeated serial dilution of the matrix - initial - solution of antibodies to human gamma interferon, to the CD4 receptor and to histamine in combination with external influence - vertical shaking of each dilution, while the concentration of matrix solutions is 0.5-5.0 mg / ml.

Preferably, each of the components of the claimed medicinal product is used in the form of a mixture of various, mainly hundred, dilutions prepared according to homeopathic technology.

The solution of this problem is also provided by the fact that in the method of treating viral infections by introducing into the body an activated - potentiated form of antibodies to human gamma interferon, according to the invention, an activated (potentiated form of antibodies to the CD4 receptor and activated - potentiated are additionally (simultaneously combined) introduced form of antibodies to histamine.

Preferably, the activated - potentiated form of antibodies to human gamma-interferon, the activated potentiated form of antibodies to CD4 receptor and the activated - potentiated form of antibodies to histamine are used in the form of an activated - potentiated aqueous or aqueous-alcoholic solution of each component, the activity of which is due to the process of sequential multiple dilution of the matrix - initial - a solution of antibodies in an aqueous or aqueous-alcoholic solvent in combination with an external mechanical effect by shaking - vertical shaking of each dilution.

Moreover, the indicated viral infection is, for example:

- acute respiratory viral infection caused by parainfluenza virus, adenovirus, respiratory syncytial viruses, coronaviruses;

- herpes virus infection (labile herpes, ophthalmic herpes, genital herpes, herpes zoster, chickenpox, infectious mononucleosis;

- acute intestinal infection of viral etiology caused by calicivirus, coronavirus, rotavirus, enterovirus;

- enteroviral meningitis;

- hemorrhagic fever with renal syndrome;

- tick-borne encephalitis.

At the same time, they can use a mixture of different dilutions of antibodies to human gamma-interferon prepared in the form of a single drug - a single dosage form in combination (in combination) with a mixture of different dilutions of antibodies to the CD4 receptor and to histamine prepared using homeopathic technology.

In addition, each of the active ingredients is a mixture of various hundred-percent dilutions prepared according to homeopathic technology.

In addition, the claimed drug, as complex, contains active ingredients in a volume ratio of 1: 1: 1, with each component being used as a mixture of three appropriate matrix solutions diluted 100 ¹² , 100 ³⁰ , and 100 ⁵⁰ times, which is equivalent hundred dilutions of C12, C30, C50, prepared according to homeopathic technology.

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

In the treatment of viral infections, separate use is possible in the form of three separately prepared preparations both in the form of solutions and in solid dosage forms (tablets), each of which contains an activated - potentiated form of antibodies to human gamma-interferon, and an activated - potentiated form of antibodies to CD4 receptor and, accordingly, activated - potentiated form of antibodies to histamine.

According to the invention, the activated - potentiated form of antibodies is the form of antibodies, for example, to human gamma-interferon, to CD4 receptor or to histamine, prepared by homeopathic potentiation technology by repeatedly serial dilution of the matrix - initial - antibody solution in combination with an external effect - vertical shaking each dilution that is active in pharmacological models and / or clinical methods of treating viral infections.

The proposed combination of activated-potentiated forms of antibodies to human gamma-interferon, to the CD4 receptor and to histamine provides an unexpected synergistic therapeutic effect, experimentally confirmed in an adequate model, which consists in increasing the effectiveness of the treatment of viral infections, including acute respiratory viral infections, herpes virus infections, acute intestinal infections of viral etiology, enteroviral meningitis, hemorrhagic fever with renal syndrome, tick-borne encephalitis. This technical effect is due to the enhanced immunotropic effect of the combined activated - potentiated forms of antibodies to human gamma interferon, to the CD4 receptor and to histamine, causing an increase in the functional activity of the CD4 receptor, gamma interferon receptors and histamine.

Moreover, it is possible to use the claimed complex drug for the prevention of bacterial complications of viral infections, to prevent the development of superinfection, and it is also possible to use it in combination with other antiviral drugs and symptomatic agents.

A drug is prepared mainly as follows.

For the preparation of the activated - potentiated form of the active components, monoclonal or, mainly, polyclonal antibodies are used, which can be obtained by known technologies - methods described, for example, in the book: Immunological methods, ed. G. Fremel, M., "Medicine", 1987, S. 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.

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

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 in an individual form is carried out by the same methods as in the case of polyclonal antisera.

Polyclonal antibodies can be obtained by active immunization of animals. To do this, according to a specially developed scheme, the animals are given a series of injections of the substance required in accordance with the invention — an antigen or conjugated antigen: human gamma-interferon, CD4 receptor and histamine. 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.

Example 1

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 KNFKDDQSIQ KSVETIKEDM

NVKFFNSNKK KRDDFEKLTN

121 YSVTDLNVQR KAIHELIQVM AELSPAAKTG KRKRSQMLFR

GRRASQ

It is possible to use polyclonal antibodies to human gamma-interferon as an immunogen (antigen) for immunization of rabbits with 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 SDRKIMQSQI VSFYFKLFKN FKDDQSIQKS VETIKEDMNV KFFNSNKKKR DDFEKLTNYS VTDLNVQRKA IHELIQVMAGRSRA

24-166:

QDPYVKEAE NLKKYFNAGH SDVADNGTLF LGILKNWKEE SDRKIMQSQI VSFYFKLFKN FKDDQSIQKS VETIKEDMNV KFFNSNKKKR DDFEKLTNYS VTDLNVQRKA IHELIQVMAGRSPA

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 IHELIQQMGRR RAS

5-45:

SYILAF QLCIVLGSLG CYCQDPYVKE AENLK

94-114:

ETIKEDM NVKFFNSNKK KRDD,

24-166:

MQDPYVKEAE NLKKYFNAGH SDVADNGTLF LGILKNWKEE SDRKIMQSQI VSFYFKLFKN FKDDQSIQKS VETIKEDMNV KFFNSNKKK DDFEKLTNYS VTDLNVQRKA IHELIQQMRRSR

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 13000g 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 °). The selection of anti-gamma interferon antibodies from the antiserum is possible as follows:

1. 10 ml of rabbit antiserum is diluted 2 times with 0.15 M Nad, 6.26 g of Na ₂ SO ₄ are added, stirred and incubated 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 removal of 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 anti-gamma interferon antibodies 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 obtained according to the above method, using an immunogen (antigen) for immunization of rabbits with an adjuvant and a whole molecule or one polypeptide fragment of the CD4 receptor, selected, for example, from the following amino acid sequences:

412-458:

IGLGIFFCV RCRHRRRQAE RMSQIKRLLS EKKTCQCPHR FQKTCSPI

26-60:

MNRGVPFRHL LLVLQLALLP AATQGKKVVL GKKGD

105-119:

A DSRRSLWDQG NFPL

115-139:

G NFPLIIKNLK IEDSDTYICE VEDQ

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

The preparation of polyclonal antibodies to histamine can be carried out according to the above method for the preparation of polyclonal antibodies to human gamma interferon using immunogen (antigen) for immunization of rabbits with adjuvant and histamine (4- (2-aminoethyl) -imidazole, or beta - imidazolyl-ethylamine with the chemical formula C ₅ H ₉ N ₃ .

Preferred for the preparation of the claimed drug is the use of polyclonal antibodies to human gamma-interferon, to CD4 (for example, to CD4 receptor of T-lymphocytes) and to histamine, which as a matrix (initial) solution with a concentration of 0.5 ÷ 5.0 mg / ml 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 above matrix solution, in 9 parts (for decimal dilution D) or in 99 parts (for hundredth dilution C) or in 999 parts (for a thousandth dilution M) of a neutral solvent in combination with multiple vertical shaking (potentiation, or "dynamization") of each dilution obtained and using individual containers for each subsequent dilution to obtain the desired potency - the dilution ratio according to the homeopathic method (see, for example, V. Schwabe "Homeopathic medicines", M., 1967, p. 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 C12 dilution, one part of a matrix (initial) antibody solution, 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 or more times) vertically shake - potentiate, getting the 1st hundredth C1 dilution. From the 1st hundredth C1 dilution prepare the 2nd hundredth dilution C2. 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 first 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 ¹² times. Similar operations with the appropriate dilution ratio are carried out to obtain a dilution of C30 and C50.

When using, for example, the activated - potentiated form of antibodies to human gamma - interferon in the form of a mixture of different, 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 make, in accordance with the composition of the mixture, one part of each component in one container and mixed with the required amount of solvent (respectively, with 97 parts for a hundred denia). 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-percent dilutions of 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 the claimed medicinal product, aqueous or aqueous-alcoholic solutions of the active ingredients are mixed, mainly in a volume ratio of 1: 1: 1 and used in liquid dosage form.

The claimed drug can also be made in solid dosage form in the form of a pharmaceutical composition that contains a technologically necessary (effective) amount of a neutral carrier - for example, lactose - saturated by soaking in a mixture of aqueous or aqueous-alcoholic solutions of an activated - potentiated form of anti-gamma antibodies to human interferon, an activated — potentiated form of antibodies to the CD4 receptor and an activated — potentiated form of antibodies to histamine, and a pharmaceutical Eski acceptable additives, including mainly lactose, microcrystalline cellulose and magnesium stearate.

To obtain a solid oral form of the claimed drug, a fluidized bed is installed (for example, Huttlin Pilotlab type manufactured by Huttlin GmbH) irrigation until saturation of granules of a neutral substance - lactose (milk sugar) with a particle size of 50 ÷ 500 is introduced into the fluidized bed - boiling layer microns, a pre-prepared aqueous or aqueous-alcoholic solution of an activated - potentiated form of antibodies to the CD4 receptor, mainly in the ratio of 1 kg of antibody solution to 5 or 10 kg of lactose (1: 5-1: 10) with simultaneous drying a second feed stream under heated air grille at a temperature not higher than 40 ° C. The estimated amount of lactose (10 ÷ 91% of the tablet mass), saturated activated - potentiated form of antibodies according to the above method, is loaded into the mixer and mixed with lactose, moistened activated - potentiated form of antibodies, in an amount of 3 ÷ 10% of tablet mass and with pure lactose in an amount of not more than 84% of the tablet mass (to reduce the cost and some simplification and acceleration of the process without reducing the effectiveness of the therapeutic effect). Then, microcrystalline cellulose is added to this mixture in an amount of 5-10% of the tablet mass and magnesium stearate in an amount of 1% of the tablet mass. The resulting tablet mass is uniformly mixed and tabletted by direct dry pressing (for example, in a Korsch tablet press - XL 400) with the formation of round tablets weighing 150 ÷ 500 mg. After tabletting, 300 mg tablets are obtained, impregnated with an aqueous-alcoholic solution of an activated, potentiated form of antibodies to human gamma interferon, to the CD4 T-lymphocyte receptor and to histamine in an ultra-low dose of each component prepared from a matrix solution diluted in 100 ¹² , in 100 ³⁰ to 100 ⁵⁰ , which is equivalent to a mixture of hundreds of dilutions of C12, C30 and C50, prepared according to homeopathic technology. Preferably, the claimed pharmaceutical composition is recommended to take 1-2 tablets 2-4 times a day.

Example 1

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 water-alcohol solutions (b mg / tablet) 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 ultralow 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 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 aqueous-alcoholic solutions (b mg / tablet) 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 a mixture of hundred-percent homeopathic dilutions C12, C30, C200 ( SMD AT to IFN-γ + AT to CD4 + AT to 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 rabbit anti-human gamma interferon polyclonal antibodies purified on antigen, in an ultra-low dose obtained by super-dilution of the matrix solution in 100 ¹² , 100 ³⁰ , 100 ⁵⁰ times, equivalent to a mixture of hundreds of homeopathic dilutions of 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-HCA, 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 1 as the median (Me), first and third quartiles (Q1, Q3) indicate its positive dynamics obtained in patients of groups 1-3 by the end of the 24-week 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.

Table 1 Dynamics of viral load in the studied groups HCV RNA, copy / ml The average decrease in viral load,% SMD AT to IFN-γ + AT to CD4 (Me [Q1-Q3]) Originally 66200 [450-81400] 75 After 24 weeks of treatment 12500 [50-30560] SMD AT to IFN-γ + AT to CD4 + AT to H (Me [Q1-Q3]) Originally 58900 [600-24500] 70 After 24 weeks of treatment 15600 [50-45700] SMD AT to IFN-γ (Me [Q1-Q3]) Originally 84700 [350-72800] 55 After 24 weeks of treatment 22400 [150-58500] The control group (Me [Q1-Q3]) Originally 79500 [300-55600] - After 24 weeks of treatment 87900 [450-64300]

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 observed 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 N, 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 2

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 / tablet) 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 gomeopatiche FIR 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 aqueous-alcoholic 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 in 100 ¹² , 100 ³⁰ , 100 ²⁰⁰ times, equivalent to a mixture of hundred-percent homeopathic dilutions of C12, C30, C200 (SMD anti-IFN-γ + a nti-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-dilution of the initial matrix solution in 100 ¹² , 100 ³⁰ , 100 ⁵⁰ times, the equivalent mixture of hundreds of homeopathic dilutions of 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 COBAS AMPLICOR automatic PCR analyzer (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 2 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 SMD anti-IFN-γ + anti-CD4 composition reduced the number of copies of HIV-1 RNA in 58% of naive patients (in 7 of 12 people of subgroup 1A), while the 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 3) showed a more pronounced than in the control group increase in the number of CD4 lymphocytes after 6 weeks of therapy 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).

table 2 Dynamics of viral load depending on the treatment regimen Viral load, copies / ml The average decrease in viral load,% SMD anti-IFN-γ + anti-CD4 (Me [Q1-Q3]) Originally 5769 [368-62584] 16.9 After 6 weeks of treatment 4575 [337-58526] APT and SMD aHTH-IFN-γ + aHTH-CD4 (Me [Q1-Q3]) Originally 5238 [385-59695] 18.2 After 6 weeks of treatment 4408 [320-50197] SMD anti-IFN-γ + anti-CD4 + anti-H (Me [Q1-Q3]) Originally 5638 [385-61742] 17.3 After 6 weeks of treatment 4754 [278-57426] APT and SMD anti-IFN-γ + anti-CD4 + anti-H (Me [Q1-Q3]) Originally 5189 [350-59798] 18.9 After 6 weeks of treatment 46108 [269-47987] SMD anti-IFN-γ (Me [Q1-Q3]) Originally 5813 [150-33356] 9.5 After 6 weeks of treatment 5786 [150-38359] APT and SMD anti-IFN-γ (Me [Q1-Q3]) Originally 4680 [274-9838] 14.2 After 6 weeks of treatment 4652 [272-8874] APT (Me [Q1-Q3]) Originally 5547 [385-58996] 13.3 After 6 weeks of treatment 5308 [338-57709]

Table 3 Indicators of subpopulations of circulating lymphocytes in patients of the studied groups in the dynamics of observation Observation period CD4, cells / μl (M ± SE) CD4 / CD8 (M ± SE) SMD anti-IFN-γ + anti-CD4 (n = 12) Originally 516 ± 33 0.46 ± 0.09 After 6 weeks of treatment 712 ± 24 0.58 ± 0.07 * APT and SMD anti-IFN-γ + anti-CD4 (n = 13) Originally 499 ± 41 0.50 ± 0.08 After 6 weeks of treatment 728 ± 29 0.60 ± 0.06 * SMD anti-IFN-γ + anti-CD4 + anti-H (n = 11) Originally 509 ± 45 0.49 ± 0.06 After 6 weeks of treatment 706 ± 27 0.58 ± 0.08 * APT and SMD anti-IFN-γ + anti-CD4 + anti-H (n = 12) Originally 521 ± 37 0.48 ± 0.09 After 6 weeks of treatment 734 ± 22 0.62 ± 0.10 * SMD anti-IFN-γ (n = 11) Originally 513 ± 98 0.38 ± 0.19 After 6 weeks of treatment 563 ± 26 0.44 ± 0.12 APT and SMD anti-IFN-γ (n = 16) Originally 491 ± 49 0.55 ± 0.06 After 6 weeks of treatment 623 ± 45 0.67 ± 0.05 * APT (n = 22) Originally 510 ± 29 0.44 ± 0.06 After 6 weeks of treatment 595 ± 35 0.50 ± 0.12 * significant differences compared to baseline, p <0.05

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-IFN-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-IFN-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 drugs, we can assume 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 over the previous 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 both in naive HIV-infected patients and in patients receiving Apt.

Example 3

For experimental study of the claimed technical solution, 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 (AT GI), to the CD4 receptor (AT CD4), to histamine (AT G), in ultra-low doses (SMD), obtained by super-dilution of the initial matrix solution in 100 ¹² , 100 ³⁰ , 100 ²⁰⁰ times each component, equivalent to a mixture of hundreds of homeopathic dilutions C12, C30, C200, applied to lactose in the form of an aqueous-alcoholic mixture of homeopathic dilutions of C12, C30, C200 each (AT GI + AT CD4 + AT G). The placebo group received 300 mg tablets containing lactose monohydrate, microcrystalline cellulose, magnesium stearate.

The ongoing double-blind, placebo-controlled study included patients aged 18-60 years of both sexes, with acute respiratory viral infection with signs of intoxication and catarrhal syndrome. The study included patients with a body temperature of 37.8 ° C or more (provided that such temperature was recorded from the moment the disease started), the duration of the disease was not more than 48 hours before treatment, without serious concomitant diseases. Patients undergo a rapid test for the presence of influenza antigens. Patients with positive test results are not included in the study. All patients give written voluntary consent to participate in the study before starting all study procedures. Patients fill out diaries in which they record body temperature twice a day, concomitant therapy, etc. Patients receive AT GI + AT CD4 + AT G or placebo, depending on the treatment group, 8 tablets on the first day and three tablets per day from the second to fifth days. Patients can take antipyretic drugs if necessary. The use of antiviral, immunomodulatory, antihistamines and antibiotics is not allowed. Before the first dose and at the last visit, patients give blood and urine samples for laboratory tests in order to monitor the safety of the therapy. Treatment lasts 5 days, follow-up - 2 days. Thus, on average, each patient takes part in the study within 7 days.

The effectiveness of therapy was evaluated by the timing of reaching body temperature of 37.0 ° C or less, the number of antipyretic doses was also compared.

At the time of the analysis, 78 patients completed the therapy (40 patients received AT GI + AT CD4 + AT G, 38 received a placebo). The proportion of patients with a body temperature of 37.0 ° C or less is presented in Figure 1. As can be seen from Figure 1, therapy AT GI + AT CD4 + AT G by the end of the second day from the start of therapy allowed to achieve a decrease in body in patients in 17.4% of cases more often than in the placebo group (p <0.05). At the same time, the number of antipyretic drugs in the groups was statistically significantly lower at the same time in the AT GI + AT CD4 + AT G group (3.5 ± 0.25 antipyretic drugs since the start of AT GI + AT CD4 + AT therapy G by the end of the second day of treatment, versus 3.9 ± 0.32 in the placebo group, p <0.005). The superiority of AT GI + AT CD4 + AT G over placebo, which began already on the morning of the second day of treatment, continued throughout the entire treatment period.

The safety analysis included data from all 78 patients who participated in the study and completed treatment within the protocol established deadlines, there were no early drop-out patients. During the entire observation period, AT GI + AT CD4 4 + AT G was well tolerated. Adverse events associated with taking AT GI + AT CD4 + AT G were not observed. A blood test at the beginning and end of the treatment period did not reveal pathological abnormalities. A general urinalysis on the first and final day of the study also did not reveal any pathology in any patient.

When comparing the data with the results of a 2005 double-blind, placebo-controlled, randomized study of the clinical efficacy and safety of therapeutic use of a drug containing activated - potentiated forms of polyclonal affinity purified rabbit antibodies to human gamma interferon (AT GI) in ultra-low doses (SMD) obtained by ultra-dilution the initial matrix solution is 100 ¹² , 100 ³⁰ , 100 ²⁰⁰ times equivalent to a mixture of hundred-percent homeopathic dilutions C12, C30, C200 (SMD AT to GI) with influenza and other acute respiratory viral infections (State Research Institute of Influenza RAMS, St. Petersburg, 2005), it was found that the drug AT GI + AT CD4 + AT G is more effective in comparison with SMD AT and GI reduces the temperature (Figure 1, Table 4 and Table 5).

Example 4

For experimental study of the claimed technical solution, 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 (AT GI), to the CD4 receptor molecule of T-lymphocytes (AT CD4), to histamine (AT G), in ultra-low doses (SMD) obtained by super-dilution of the initial matrix solution in 100 ¹² , 100 ³⁰ , 100 ²⁰⁰ times of each component, equivalent to a mixture of hundred homeo pathological dilutions of C12, C30, C200 (AT GI + AT CD4 + AT G). As a comparison drug used the drug Tamiflu® (active ingredient - oseltamivir, F. Hoffmann-La Roche Ltd. - Switzerland) (Oseltamivir).

The ongoing open comparative controlled clinical trial of AT GI + AT CD4 + AT G and Tamiflu® includes patients aged 18-60 years of both sexes, with influenza A or B with signs of intoxication and catarrhal syndrome. The study included patients with a body temperature of 37.8 ° C or more (provided that such temperature was recorded from the moment the disease started), the duration of the disease was not more than 48 hours before treatment, without serious concomitant diseases. Patients undergo a rapid test for the presence of influenza antigens. Patients with negative test results are not included in the study. All patients give written voluntary consent to participate in the study before starting all study procedures. Patients fill out diaries in which they record body temperature twice a day, concomitant therapy, etc. Patients receive AT GI + AT CD4 + AT G, 8 tablets on the first day and three tablets a day from the second to the fifth days, or Tamiflu® 75 mg twice daily, according to manufacturer's instructions. Patients can take antipyretic drugs if necessary. The use of antiviral, immunomodulatory, antihistamines and antibiotics is not allowed. Before the first dose and at the last visit, patients give blood and urine samples for laboratory tests in order to monitor the safety of the therapy. Treatment lasts 5 days, follow-up - 2 days. Thus, on average, each patient takes part in the study within 7 days.

The effectiveness of therapy was evaluated by the timing of reaching body temperature of 37.0 ° C or less, the number of antipyretic doses was also compared.

At the time of the analysis, the study completed 17 patients (6 patients of the AT TI + AT CD4 + AT G group and 11 patients of the Tamiflu® administration group).

The proportion of patients with a body temperature of 37.0 ° C or less in the groups did not statistically differ between themselves throughout the treatment period. By the beginning of 4 days of treatment in both groups was achieved almost complete recovery of patients (Figure 2). By the beginning of the second day of treatment in both groups, a third of patients had normalized body temperature. The average number of antipyretic doses in the groups also did not have statistically significant differences and at the beginning of the 4th day of treatment was 7.6 ± 0.84 in the AT GI + AT CD4 + AT G group and 7.4 ± 0.90 in the group taking Tamiflu®, respectively.

The safety analysis included data from all 17 patients participating in the study and completing treatment within the protocol established terms; there were no early drop-out patients. During the entire observation period, the drug was well tolerated, adverse events were not observed. A blood test at the beginning and end of the treatment period did not reveal pathological abnormalities. A general urinalysis on the first and final day of the study also did not reveal any pathology in any patient.

When comparing the data with the results of a 2005 double-blind, placebo-controlled, randomized study of the clinical efficacy and safety of therapeutic use of a drug containing activated - potentiated forms of polyclonal affinity purified rabbit antibodies to human gamma interferon (AT GI) in ultra-low doses (SMD) obtained by ultra-dilution initial matrix solution 100 ^12, 100 ^30, 100 ^{to 200} times equivalent mixture of centesimal homeopathic dilutions C12, C30, C200 (SMD aT HY) In case of influenza and other acute respiratory viral infections (State Research Institute of Influenza, Russian Academy of Medical Sciences, St. Petersburg, 2005), it was found that AT GI + AT CD4 + AT G is more effective than AT GI in reducing the temperature (see Figure 2, Table 6 and Table 7).

Example 5

For experimental study of the claimed technical solution, 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 (AT GI), to the CD4 receptor molecule of T-lymphocytes (AT CD4), to histamine (AT G), in ultra-low doses (SMD) obtained by super-dilution of the initial matrix solution in 100 ¹² , 100 ³⁰ , 100 ²⁰⁰ times of each component, equivalent to a mixture of hundred homeo pathological dilutions of C12, C30, C200 (AT GI + AT CD4 + AT G). As the reference drug using the drug containing activated - potentiated form of polyclonal affinity-purified rabbit antibody to gamma interferon, human (AT GOP) in ultralow doses (RMA) obtained sverhrazvedeniem initial matrix solution 100 ^12, 100 ^30, 100 ^{to 200} times equivalent mixture hundredths of homeopathic dilutions of C12, C30, C200 (SMD AT GI). The placebo group received 300 mg tablets containing lactose monohydrate, microcrystalline cellulose, magnesium stearate.

In the ongoing double-blind, placebo-controlled study of the efficacy and safety of the drug AT GI + AT CD4 + AT G in acute respiratory viral infections and in the ongoing open comparative controlled study of the efficacy and safety of the drug AT GI + AT CD4 + AT G in influenza, the number of people developing against the background of an acute infectious process was additionally evaluated complications, including bacterial (bacterial pneumonia, tracheitis, otitis media, glomerulonephritis, etc.).

In those cases when the defense system is perfect, the infectious process may be interrupted or, remaining localized, not accompanied by the development of severe clinical symptoms, i.e. the adequacy of protective reactions leads to rapid inactivation of the pathogen, the restoration of impaired body functions and recovery. A different picture arises in an organism highly susceptible to an infectious agent and lacking the perfect mechanism of specific and nonspecific protection (immune compromised patients). In such cases, pathogens reproduced in an increasing number and the products of their interaction with epithelial and immune cells, as well as the destroyed cells themselves enter the blood, causing the development of severe forms of the course of the disease, the formation of complications and a possible adverse outcome.

The use of the drug AT GI + AT CD4 + AT G both in case of influenza and ARVI significantly reduces the frequency of bacterial complications compared with placebo (Table 8), and, as a result, reduces the need for antibiotic therapy. The drug AT GI + AT CD4 + AT G prevents the development of secondary immunodeficiency at the stage of convalescence, providing an immunomodulating effect and increasing the body's natural defenses. The ability of AT GI + AT CD4 + AT G to reduce the incidence of bacterial complications was greater than that of SMI AT GI.

Table 8 The incidence of bacterial complications A drug Patient count Bacterial complications Otitis count /% Tracheitis number /% Pneumonia qty /% Total Qty /% AT GI + AT CD4 + AT G (ARVI) 40 0/0 1 / 2.5 0/0 1 / 2.5 Placebo (ARVI) 38 3 / 7.9 7 / 18.4 0/0 10 / 26.3 AT GI + AT CD4 + AT G (Flu) 6 0 / 0/0 0/0 0/0 Tamiflu® (Flu) eleven 0/0 2 / 18.2 1/9.1 3 / 27.2 SMD AT GI (Influenza and SARS) * thirty 1 / 3.3 2 / 6.7 0/0 3/10.0 Placebo (Flu & ARVI) * thirty 4 / 13.3 5 / 16.7 0/0 9/30 * - According to a double-blind, placebo-controlled randomized study of the clinical efficacy and safety of the therapeutic use of the drug SMD AT GI for influenza and other acute respiratory viral infections (GU Research Institute of Influenza RAMS, St. Petersburg, 2005).

Claims (10)

1. A pharmaceutical composition for treating viral infections, containing an activated - potentiated form of antibodies to human gamma interferon, characterized in that it contains additional components in the form of an activated - potentiated form of antibodies to the CD4 T-lymphocyte receptor and an activated - potentiated form of antibodies to histamine. 2. The pharmaceutical composition according to claim 1, characterized in that the activated — potentiated form of antibodies to human gamma-interferon, the activated — potentiated form of antibodies to the CD4 T-lymphocyte receptor, and the activated — potentiated form of antibodies to histamine are used in the form of an activated — potentiated aqueous or an aqueous-alcoholic solution, the activity of which is due to the process of successive multiple dilutions in an aqueous or aqueous-alcoholic solvent in combination with external mechanical stress m - shaking each dilution. 3. The pharmaceutical composition according to claim 1, characterized in that the pharmaceutical composition is made in solid dosage form and contains an effective amount of an activated — potentiated form of antibody to human gamma-interferon saturated with an aqueous or aqueous-alcoholic solution, an activated — potentiated form of antibody to the CD4 receptor T-lymphocytes and activated - potentiated forms of antibodies to histamine granules of a neutral carrier and pharmaceutically acceptable additives. 4. The pharmaceutical composition according to claim 1, characterized in that the aqueous or aqueous-alcoholic solutions of activated - potentiated forms of antibodies to human gamma interferon, to CD4 receptor T-lymphocytes and to histamine are obtained by repeated serial dilution in combination with external exposure shaking each dilution from matrix solutions of affinity purified antibodies to human gamma interferon, to the CD4 T-lymphocyte receptor and to histamine with a concentration of 0.5-5.0 mg / ml. 5. The pharmaceutical composition according to claim 1, characterized in that each of the components in the form of activated - potentiated forms of antibodies to human gamma interferon, to the CD4 receptor of T-lymphocytes and to histamine is used as a mixture of various, mainly hundred, dilutions prepared by homeopathic technology. 6. The pharmaceutical composition according to claim 3, characterized in that the pharmaceutically acceptable additives include lactose, microcrystalline cellulose and magnesium stearate. 7. A method of treating viral infections by introducing into the body an activated - potentiated form of antibodies to human gamma-interferon, characterized in that it additionally simultaneously and simultaneously combines the activated - potentiated form of antibodies to the CD4 T-lymphocyte receptor and the activated - potentiated form of antibodies to histamine. 8. The method according to claim 7, characterized in that the activated - potentiated form of antibodies to human gamma-interferon, the activated - potentiated form of antibodies to the CD4 T-lymphocyte receptor and the activated - potentiated form of antibodies to histamine are used in the form of activated - potentiated water or an aqueous-alcoholic solution of each component, the activity of which is due to the process of successive multiple dilutions in an aqueous or aqueous-alcoholic solvent in combination with an external mechanical effect - shaking each dilution. 9. The method according to claim 7, characterized in that said viral infection is an acute respiratory viral infection, herpes virus infection, acute intestinal infection of viral etiology, enteroviral meningitis, hemorrhagic fever with renal syndrome, tick-borne encephalitis. 10. The treatment method according to claim 7, characterized in that a mixture of different dilutions of antibodies to human gamma-interferon in combination with a mixture of different dilutions of antibodies to CD4 T-lymphocyte receptor and histamine is used, prepared as a single drug - a single dosage form, cooked by homeopathic technology.

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