WO2012018284A1 - Лекарственное средство и способ профилактики инфицирования вич, профилактики и лечения заболеваний, вызываемых вич или ассоциированных с вич, в том числе спида - Google Patents
Лекарственное средство и способ профилактики инфицирования вич, профилактики и лечения заболеваний, вызываемых вич или ассоциированных с вич, в том числе спида Download PDFInfo
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- WO2012018284A1 WO2012018284A1 PCT/RU2011/000523 RU2011000523W WO2012018284A1 WO 2012018284 A1 WO2012018284 A1 WO 2012018284A1 RU 2011000523 W RU2011000523 W RU 2011000523W WO 2012018284 A1 WO2012018284 A1 WO 2012018284A1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/24—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
- C07K16/241—Tumor Necrosis Factors
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/39566—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against immunoglobulins, e.g. anti-idiotypic antibodies
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/0004—Homeopathy; Vitalisation; Resonance; Dynamisation, e.g. esoteric applications; Oxygenation of blood
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/24—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
- C07K16/249—Interferons
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
- C07K16/2815—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against CD8
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/545—Medicinal preparations containing antigens or antibodies characterised by the dose, timing or administration schedule
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
Definitions
- the invention relates to medicine and can be used both for effective prevention of HIV infection, prevention and treatment of diseases caused by HIV or associated with HIV, including AIDS.
- 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 CI, A61K39 / 395, 11.20.2002).
- this drug may not be effective for the prevention of HIV infection, as well as the prevention and treatment of a wide range of diseases caused by HIV or associated with HIV, including AIDS.
- the invention is directed to the creation of a comprehensive drug without pronounced side effects, which provides both effective prevention of HIV infection and the prevention and effective treatment of diseases caused by HIV or associated with HIV, including those manifested by infectious and / or parasitic diseases, malignant tumors and AIDS, in people infected with HIV.
- HIV or associated with HIV contains an activated - potentiated form of antibodies to an antigen - a protein or peptide of the immune system or, mainly, produced by the immune system that interacts with HIV or whose content and / or functional activity changes in connection with HIV infection.
- cytokines with the exception of gamma interferon, can be used as a dissolved antigen.
- receptors of immunocompetent cells are used as an antigen associated with the outer membrane of cells of the immune system.
- differentiation clusters with the exception of the CD4 molecule of T-lymphocytes, can be used as an antigen bound to the outer membrane of cells of the immune system.
- the activated - potentiated form of antibodies to dissolved antigens or the activated - potentiated form of antibodies to antigens associated with the outer membrane of cells of the immune system is used in the form of an activated - potentized aqueous or water - alcohol solution, the activity of which is due to the process of sequential multiple dilution of the matrix - initial - solution antibodies in an aqueous or aqueous - alcoholic solvent in combination with an external mechanical action - vertical shaking of each dilution.
- the claimed drug can be made in solid dosage form in the form of a pharmaceutical composition that contains a technologically necessary (effective) amount of a neutral carrier saturated with a mixture of aqueous or aqueous-alcoholic solutions of an activated - potentiated form of antibodies to dissolved antigens or an activated - potentiated form of antibodies to antigens associated with the outer membrane of the cells of the immune system, and pharmaceutically acceptable additives, which include, for example, lactose, microcrystalline cellulose and magnesium stearate.
- Aqueous or aqueous-alcoholic solutions of activated - potentiated forms of antibodies to dissolved antigens or to antigens associated with the outer membrane of the cells of the immune system can be obtained by repeatedly diluting the matrix - initial - antibody solution in combination with an external mechanical action - vertical shaking of each dilution, wherein the concentration of the matrix solution is 0.5 g to 5.0 mg / ml.
- the activated - potentiated form of antibodies can be used as a mixture of various, mainly hundred, dilutions according to homeopathic technology.
- an activated - potentiated form of antibodies to the antigen is used - a protein or a peptide the immune system, or mainly produced by the immune system, which interacts with HIV or whose content and / or functional activity changes due to HIV infection.
- An activated - potentiated form of antibodies to dissolved antigens or an activated - potentiated form of antibodies to antigens associated with the outer membrane of cells of the immune system is 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 repeated dilution of the matrix - initial - solution antibodies in an aqueous or aqueous - alcoholic solvent in combination with external mechanical action - vertical shaking each wow breeding.
- aqueous or aqueous-alcoholic solutions of activated - potentiated forms of antibodies to dissolved antigens or to antigens associated with the outer membrane of cells of the immune system are obtained by repeatedly diluting the matrix - initial - antibody solution in combination with an external mechanical action - vertical shaking of each dilution, this concentration of the matrix solution is 0.5 g to 5.0 mg / ml
- the activated-potentiated form is an antibody form prepared according to the homeopathic potentiation technology by repeatedly sequentially diluting the matrix - initial - antibody solution in combination with an external action - vertical shaking of each dilution, which is active in pharmacological models and / or clinical methods prevention of HIV infection; prevention and treatment of diseases caused by HIV or associated with HIV, including AIDS.
- the proposed use of the activated - potentiated form of antibodies to dissolved antigens e.g., tumor necrosis factor - human alpha or alpha - interferon
- antigens associated with the outer membrane of cells of the immune system e.g., CD8 receptor
- the claimed drug has a high prophylactic efficacy against HIV, preventing infection of cells with human immunodeficiency virus and its intracellular replication and, therefore, can be used both for effective treatment and for the prevention of viral diseases prone to chronic course, including including for secondary prevention of HIV infection.
- antiretroviral drugs including complex ones, including reverse transcriptase inhibitors (for example, based on zidovudine), which allows to reduce the dose of antiretroviral drugs while maintaining high therapy efficiency, increases the safety of therapy and reduces the number of adverse events.
- antiretroviral drugs including complex ones, including reverse transcriptase inhibitors (for example, based on zidovudine), which allows to reduce the dose of antiretroviral drugs while maintaining high therapy efficiency, increases the safety of therapy and reduces the number of adverse events.
- the drug is prepared mainly as follows.
- 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.
- 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.
- Polyclonal antibodies can be obtained by active immunization of animals.
- the animals are given a series of injections of the substance required in accordance with the invention - an antigen or conjugated antigen (a protein or peptide of the immune system or, mainly, produced by the immune system that interacts with HIV or whose content and / or functional activity changes due to with HIV infection).
- an antigen or conjugated antigen a protein or peptide of the immune system or, mainly, produced by the immune system that interacts with HIV or whose content and / or functional activity changes due to with HIV infection.
- an antigen or conjugated antigen a protein or peptide of the immune system or, mainly, produced by the immune system that interacts with HIV or whose content and / or functional activity changes due to with HIV infection.
- an antigen or conjugated antigen a protein or peptide of the immune system or, mainly, produced by the immune system that interacts with HIV or whose content and / or functional activity changes due to with HIV infection.
- polyclonal antibodies to the tumor necrosis factor alpha which are used as a matrix (primary) solution with a concentration of 0.5 - 5.0 mg / ml for the subsequent preparation of the activated - potentiated form.
- Preferred for the preparation of the claimed drug is the use of polyclonal antibodies, which can be obtained by immunization of rabbits as follows.
- polyclonal antibodies to tumor necrosis factor-alpha can be obtained using a whole tumor necrosis factor-alpha molecule of the following sequence:
- TNF-a tumor necrosis factor-alpha
- 1-3 intravenous injections are performed to increase the level of antibodies.
- 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.
- 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.
- 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;
- 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 tumor necrosis factor-alpha with antigen (tumor necrosis factor-alpha) attached to an insoluble column matrix, followed by elution of the antibodies with concentrated salt solutions.
- buffer solution of polyclonal antibodies to tumor necrosis factor-alpha with a concentration of 0.5 - 5.0 mg / ml, preferably 2.0 h - 3.0 mg / ml matrix (initial) solution for the subsequent preparation of the activated - potentiated form of antibodies.
- Polyclonal antibodies to human alpha interferon are prepared according to the above method, using the adjuvant and the whole molecule of human alpha interferon as one of the immunogen (antigen) for immunizing rabbits:
- Polyclonal antibodies to the CD8 receptor are prepared according to the above method, using the adjuvant and the whole molecule of the CD8 receptor as follows for immunization of rabbits with the following amino acid sequence: 1 MALPVTALLL PLALLLHAAR PSQFRVSPLD RTWNLGETVE LKCQVLLSNP TSGCSWLFQP
- polyclonal antibodies to the CD8 receptor as an immunogen (antigen) for immunization of rabbits with an adjuvant and, for example, one polypeptide fragment of the CD8 receptor selected from the following sequences:
- PLALLLHAAR PSQFRVSPLD 81-100:
- VVKSGDKPSL SARYV Preferred for the preparation of the drug is the use of a mixture of three water - alcohol dilutions of the primary matrix solution of antibodies diluted, respectively, 100 12 , 100 30 , and 100 200 times, which corresponds to hundred dilutions of C 12, SZO and C 200 prepared according to homeopathic technology .
- a mixture of these components is applied to a neutral carrier.
- 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 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 separate 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, pp. 14-29).
- External processing in the process of reducing the concentration can also be performed by ultrasound, electromagnetic or other physical effects.
- one part of the matrix (initial) antibody solution for example, tumor necrosis factor-alpha with a concentration of 2.5 mg / ml
- the matrix (initial) antibody solution for example, tumor necrosis factor-alpha with a concentration of 2.5 mg / ml
- a neutral aqueous or alcohol-alcohol solvent for example, a neutral aqueous or alcohol-alcohol solvent
- 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 C 12.
- the 12th hundredth dilution of C12 is a solution obtained by diluting 12 times in succession in different containers of the first part of the initial matrix solution of antibodies to human gamma-interferon with at a concentration of 2.5 mg / ml in 99 parts of a neutral solvent, i.e. the solution obtained by diluting the matrix solution in 100 to 12 times. Similar operations with an appropriate dilution ratio are carried out to obtain dilutions of C 30 and C 50.
- each dilution for example, C 12, C 30, C 50
- each dilution is prepared separately according to the technology described above before dilution into 3 dilutions less than the final (respectively, to obtain C 9, 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 hundred p Institution).
- the resulting mixture was successively diluted twice in a ratio of 1 to 100, potentiating the resulting solution after each dilution.
- 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 C 12, SZO, C50. It is possible to use each component in the form of a mixture of other different dilutions, for example, decimal and or hundredths (D 20, C 30, C 100 or C12, SZO, C200, etc.) prepared according to homeopathic technology, the effectiveness of which is determined experimentally .
- 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 - boiling layer ⁇ m, 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 Coy stream fed under the grate heated air at a temperature not higher than 40 ° C.
- 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 - boiling layer ⁇ m, a pre-prepared aqueous or aqueous-alcoholic solution of an activated pot
- the calculated amount of lactose (10 h - 91% of the tablet mass), saturated with the activated - potentiated form of antibodies according to the above method, is loaded into the mixer and mixed with lactose, moistened with the activated - potentiated form of antibodies, in the amount of Hch - 10% of the 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 hours - 10% of the tablet mass and magnesium stearate in the 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).
- direct dry pressing for example, in a Korsch tablet press - XL 400.
- Tablets receive tablets weighing 300 mg, impregnated with an aqueous - alcoholic solution of an activated - potentiated form of antibodies to the tumor necrosis factor - alpha in an ultra-low dose of each component prepared from a matrix solution diluted in 100 12 , in 100 30 in 100 50 , which is equivalent to a mixture of hundred dilutions of C12, SZO and C50 prepared according to homeopathic technology.
- the claimed drug is recommended to take 1-2 tablets 2-4 times a day.
- the antiretroviral effect of the claimed drug was studied by inhibiting HIV replication in a culture of human peripheral blood mononuclear cells infected with an in vitro strain of HIV-1-LAI.
- the effectiveness of inhibiting HIV replication was evaluated by the content of the main nucleocapid protein p24 of HIV in supernatants.
- affinity purified rabbit polyclonal antibodies to tumor necrosis factor alpha were used, prepared by order of a specialized biotechnological company, on the basis of which an activated, potentiated form of water dilutions of ultra low dose antibodies to tumor necrosis factor alpha was prepared, obtained using homeopathic technology super-dilution of the initial matrix solution (concentration of 2.5 mg / ml) in 100 12 , 100 30 , 100 50 times, equivalent to a mixture of hundred g homeopathic dilutions C 12, SZO, C50 (hereinafter - SMD AT to the full name alpha). Evaluation of the antiviral activity of the complex drug was carried out with using mononuclear cells of human peripheral blood infected with an in vitro strain of HIV-1-LAI.
- Human peripheral blood mononuclear cells were isolated from the blood of healthy seronegative donors by centrifugation in a density gradient of ficoll-hypak. Cells were activated for 3 days using 1 ⁇ g / ml phytohemmagglutin R and 5 IU / ml recombinant human interleukin-2.
- the preparations were added to a well containing 100 ⁇ l of activated human peripheral blood mononuclear cells 24 hours or 15 minutes after the cells were infected with HIV-1-LAI strain at a dose of 100 TCID50 (50 ⁇ l of the HIV-1-LAI strain inoculum).
- SMD AT for TNF alpha (12.5 ⁇ l) or azidothymidine (active ingredient zidovudine) at a dose of 1000 nM (reference drug) was mixed with RPMI1640 medium (DIFCO) until a final volume of 50 ⁇ l was reached.
- the antiretroviral effect of the claimed drug was studied by inhibiting HIV replication in a culture of human peripheral blood mononuclear cells infected with an in vitro strain of HIV-1-LAI.
- the effectiveness of inhibiting HIV replication was evaluated by the content of the main nucleocapid protein p24 of HIV in supernatants.
- affinity purified rabbit polyclonal antibodies to CD8 were used, prepared by order of a specialized biotechnological company, on the basis of which an activated - potentized form of water dilutions of antibodies to CD8 in an ultra-low dose was obtained, obtained by homeopathic technology 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 hundred homeopathic dilutions C 12, SZO, C50 (hereinafter - SMD AT to C08) .
- the antiviral activity of the complex preparation was evaluated using mononuclear cells of human peripheral blood infected with an in vitro strain of HIV-1-LAI.
- Human peripheral blood mononuclear cells were isolated from the blood of healthy seronegative donors by centrifugation in a density gradient of ficoll-hypak. Cells were activated for 3 days using 1 ⁇ g / ml phytohemmagglutin R and 5 IU / ml recombinant human interleukin-2.
- the preparations were added to a well containing 100 ⁇ l of activated human peripheral blood mononuclear cells 24 hours or 15 minutes after the cells were infected with HIV-1-LAI strain at a dose of 100 TCID50 (50 ⁇ l of the HIV-1-LAI strain inoculum).
- DMD AT to CD8 (12.5 ⁇ l) or azidothymidine (active ingredient - zidovudine) at a dose of 1000 nM (reference drug) was mixed with RPMI1640 medium (DIFCO) until a final volume of 50 ⁇ l was reached.
- SMD AT to CD8 inhibit HIV replication by 87 ⁇ 11% when added to the well 24 hours before, and by 40 ⁇ 4% when added to the well 15 minutes after infection of cells with HIV-1-LAI strain, respectively.
- Azidothymidine at a dose of 1000 nM inhibited HIV replication by 99 ⁇ 0 and 99 ⁇ 1% when added to the well 24 hours before and 15 minutes after infection of cells with the HIV-1-LAI strain, respectively.
- TCID50 is the dose that infects 50% of tissue culture cells.
- Human peripheral blood mononuclear cells were isolated from the blood of healthy seronegative donors by centrifugation in a density gradient of ficoll-hypak. Cells were activated for 3 days using 1 ⁇ g / ml phytohemmagglutin R and 5 IU / ml recombinant human interleukin-2.
- Cells were infected with the HIV-1-LAI strain, delivering 50 ⁇ l of the inoculum of the HIV-1-LAI strain, corresponding to a dose of 100 TCID50 (dose infecting 50% of tissue culture cells).
- the preparation of SMD AT for IFN-a and the comparison preparation azidothymidine were added to wells containing 100 ⁇ l of activated human peripheral blood mononuclear cells, 24 hours or 15 minutes after infection of the cells with HIV-1-LAI strain.
- the preparation of SMD AT to IFN-a (12.5 ⁇ l) and the drug azidothymidine in a dose of 1000 nM was mixed with RPMI1640 medium (DIFCO) until a final volume of 50 ⁇ l was reached.
- DIFCO RPMI1640 medium
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Priority Applications (11)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US13/814,659 US20130224219A1 (en) | 2010-08-06 | 2011-07-15 | Drug and method for the prophylaxis of hiv infection and for the prophylaxis and treatment of diseases caused by or associated with hiv, including aids |
| UAA201300101A UA112747C2 (uk) | 2010-08-06 | 2011-07-15 | Лікарський засіб і спосіб профілактики інфікування віл, профілактики і лікування захворювань, що викликаються віл або асоційовані з віл, у тому числі сніду |
| GB1303983.9A GB2498276B (en) | 2010-08-06 | 2011-07-15 | Medicinal agent and mode of prevention of HIV contamination, prevention and treatment of diseases caused by HIV and HIV-associated diseases including AIDS. |
| CN2011800403882A CN103209705A (zh) | 2010-08-06 | 2011-07-15 | 预防hiv感染以及对由hiv引起的疾病和hiv相关疾病、包括aids进行预防和治疗的药剂和方法 |
| EA201300136A EA030411B1 (ru) | 2010-08-06 | 2011-07-15 | Лекарственное средство и способ профилактики инфицирования вич, профилактики и лечения заболеваний, вызываемых вич или ассоциированных с вич, в том числе спида |
| DE112011102649T DE112011102649T5 (de) | 2010-08-06 | 2011-07-15 | Medikament und Verfahren zur Prävention einer HIV-Kontamination, Prävention und Behandlung von Krankheiten, die durch HIV verursacht werden, und von mit HIV zusammenhängen-den Krankheiten, einschließlich AIDS |
| CA2807540A CA2807540A1 (en) | 2010-08-06 | 2011-07-15 | Medicinal agent and mode of prevention of hiv contamination, prevention and treatment of diseases caused by hiv and hiv-associated diseases including aids |
| JP2013523123A JP2013538195A (ja) | 2010-08-06 | 2011-07-15 | Hiv汚染の予防、aidsを含むhivによって引き起こされる疾患及びhivに関連する疾患の予防及び治療のための医薬及び方法 |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014116789A1 (en) * | 2013-01-25 | 2014-07-31 | Thymon, Llc | Immunogenic and prophylactic compositions, methods of making same, and method for treating and preventing tnf-mediated disease and hiv-1 infection |
| JP2016516205A (ja) * | 2013-03-18 | 2016-06-02 | イリイチ・エプシテイン オレグ | バイパシー医薬の調節効力の程度を測定する方法 |
| US9388240B2 (en) | 2013-01-25 | 2016-07-12 | Thymon, Llc | Compositions for selective reduction of circulating bioactive soluble TNF and methods for treating TNF-mediated disease |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2181297C2 (ru) | 2000-06-20 | 2002-04-20 | Эпштейн Олег Ильич | Способ лечения патологического синдрома и лекарственное средство |
| RU2309732C1 (ru) * | 2006-03-13 | 2007-11-10 | Олег Ильич Эпштейн | Спрессованная твердая оральная форма лекарственного препарата и способ получения твердой оральной формы лекарственного препарата |
| MX2013000543A (es) | 2010-07-15 | 2013-10-28 | Oleg Iliich Epshtein | Un metodo para aumentar el efecto de una forma activa potenciada de un anticuerpo. |
| FR2962652A1 (fr) | 2010-07-15 | 2012-01-20 | Oleg Iliich Epshtein | Composition pharmaceutique d'association et son utilisation dans des procedes pour traiter les maladies ou affections associees a des maladies neurodegeneratives |
| PH12013500144A1 (en) | 2010-07-21 | 2018-03-21 | Oleg Iliich Epshtein | A method of treating attention deficit hyperactivity disorder |
| RU2013111962A (ru) | 2013-03-18 | 2014-09-27 | Олег Ильич Эпштейн | Способ определения выраженности модифицирующей активности, ассоциированной с носителем |
Citations (3)
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| RU2192888C1 (ru) | 2001-02-15 | 2002-11-20 | Эпштейн Олег Ильич | Лекарственное средство и способ лечения патологического синдрома |
| RU2195317C1 (ru) * | 2001-04-18 | 2002-12-27 | Эпштейн Олег Ильич | Способ коррекции патологических иммунных реакций и лекарственное средство |
| RU2205025C1 (ru) * | 2001-12-26 | 2003-05-27 | Гольдберг Евгений Данилович | Способ коррекции иммунного ответа и лекарственное средство |
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| DE4236069A1 (de) * | 1992-10-26 | 1994-04-28 | Werner Dr Bergmann | Arzneimittel, insbesondere für orale Einnahme |
| AU2275395A (en) * | 1994-03-31 | 1995-10-23 | Biomedical Explorations, Llc | Therapeutic homeopathic dilutions of growth factors and methods of their use |
| US20030228310A1 (en) * | 1996-12-23 | 2003-12-11 | Advanced Biotherapy, Inc. | Treatment of skin diseases |
| US6090388A (en) * | 1998-06-20 | 2000-07-18 | United Biomedical Inc. | Peptide composition for prevention and treatment of HIV infection and immune disorders |
| JP2000143537A (ja) * | 1998-11-13 | 2000-05-23 | Nippon Zoki Pharmaceut Co Ltd | 細胞接着分子発現抑制剤 |
| RU2181297C2 (ru) * | 2000-06-20 | 2002-04-20 | Эпштейн Олег Ильич | Способ лечения патологического синдрома и лекарственное средство |
| RU2001134982A (ru) * | 2001-12-26 | 2004-02-20 | Олег Ильич Эпштейн | Способ коррекции иммунного ответа и лекарственное средство |
| RU2201255C1 (ru) * | 2001-12-26 | 2003-03-27 | Эпштейн Олег Ильич | Лекарственное средство и способ регуляции сосудистого тонуса |
| UA76640C2 (uk) * | 2002-08-02 | 2006-08-15 | Олєг Ільіч Епштєйн | Спосіб корекції патологічних імунних реакцій та гомеопатичний лікарський засіб |
| AU2006281981A1 (en) * | 2005-08-15 | 2007-02-22 | Cephalon Australia Pty Ltd | Chimeric antibodies with new world primate regions |
| DE602007006429D1 (de) * | 2006-02-10 | 2010-06-24 | Zymogenetics Inc | Lösliches il-17rcx4 und verfahren zu dessen anwendung bei entzündungen |
| RU2309732C1 (ru) * | 2006-03-13 | 2007-11-10 | Олег Ильич Эпштейн | Спрессованная твердая оральная форма лекарственного препарата и способ получения твердой оральной формы лекарственного препарата |
| MX345039B (es) * | 2008-06-25 | 2017-01-16 | Esbatech Alcon Biomed Res Unit | Anticuerpos estables y solubles que inhiben el tnfa. |
| CZ2013159A3 (cs) * | 2010-08-06 | 2013-06-12 | Iliich Epshtein@Oleg | Kombinovaná farmaceutická kompozice a zpusoby lécby a prevence infekcních chorob |
-
2010
- 2010-08-06 RU RU2010133045/15A patent/RU2535033C2/ru not_active IP Right Cessation
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2011
- 2011-07-15 US US13/814,659 patent/US20130224219A1/en not_active Abandoned
- 2011-07-15 ES ES201390021A patent/ES2555557R1/es active Pending
- 2011-07-15 EP EP11814861.8A patent/EP2601967A4/en not_active Ceased
- 2011-07-15 UA UAA201300101A patent/UA112747C2/uk unknown
- 2011-07-15 WO PCT/RU2011/000523 patent/WO2012018284A1/ru not_active Ceased
- 2011-07-15 GB GB1303983.9A patent/GB2498276B/en not_active Expired - Fee Related
- 2011-07-15 CA CA2807540A patent/CA2807540A1/en not_active Abandoned
- 2011-07-15 JP JP2013523123A patent/JP2013538195A/ja active Pending
- 2011-07-15 EA EA201300136A patent/EA030411B1/ru not_active IP Right Cessation
- 2011-07-15 DE DE112011102649T patent/DE112011102649T5/de not_active Withdrawn
- 2011-07-15 NZ NZ606992A patent/NZ606992A/en not_active IP Right Cessation
- 2011-07-15 CN CN2011800403882A patent/CN103209705A/zh active Pending
- 2011-07-15 AU AU2011286486A patent/AU2011286486B9/en not_active Ceased
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| RU2192888C1 (ru) | 2001-02-15 | 2002-11-20 | Эпштейн Олег Ильич | Лекарственное средство и способ лечения патологического синдрома |
| RU2195317C1 (ru) * | 2001-04-18 | 2002-12-27 | Эпштейн Олег Ильич | Способ коррекции патологических иммунных реакций и лекарственное средство |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014116789A1 (en) * | 2013-01-25 | 2014-07-31 | Thymon, Llc | Immunogenic and prophylactic compositions, methods of making same, and method for treating and preventing tnf-mediated disease and hiv-1 infection |
| US9388240B2 (en) | 2013-01-25 | 2016-07-12 | Thymon, Llc | Compositions for selective reduction of circulating bioactive soluble TNF and methods for treating TNF-mediated disease |
| US9580502B2 (en) | 2013-01-25 | 2017-02-28 | Thymon, Llc | Compositions for selective reduction of circulating bioactive soluble TNF and methods for treating TNF-mediated disease |
| AU2014215639B2 (en) * | 2013-01-25 | 2017-03-23 | Thymon, Llc | Compositions for selective reduction of circulating bioactive soluble TNF and methods for treating TNF-mediated disease |
| JP2016516205A (ja) * | 2013-03-18 | 2016-06-02 | イリイチ・エプシテイン オレグ | バイパシー医薬の調節効力の程度を測定する方法 |
Also Published As
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| ES2555557A2 (es) | 2016-01-04 |
| AU2011286486A2 (en) | 2013-05-02 |
| DE112011102649T5 (de) | 2013-06-20 |
| EA030411B1 (ru) | 2018-08-31 |
| EP2601967A4 (en) | 2014-05-07 |
| CN103209705A (zh) | 2013-07-17 |
| JP2013538195A (ja) | 2013-10-10 |
| GB2498276A (en) | 2013-07-10 |
| NZ606992A (en) | 2016-03-31 |
| CA2807540A1 (en) | 2012-02-09 |
| RU2535033C2 (ru) | 2014-12-10 |
| US20130224219A1 (en) | 2013-08-29 |
| EA201300136A1 (ru) | 2013-09-30 |
| GB201303983D0 (en) | 2013-04-17 |
| AU2011286486B2 (en) | 2017-02-02 |
| EP2601967A1 (en) | 2013-06-12 |
| GB2498276B (en) | 2018-05-23 |
| AU2011286486B9 (en) | 2017-02-23 |
| RU2010133045A (ru) | 2012-02-20 |
| AU2011286486A1 (en) | 2013-03-28 |
| UA112747C2 (uk) | 2016-10-25 |
| ES2555557R1 (es) | 2016-02-05 |
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