The way to suppress hiv infection

 

(57) Abstract:

The invention relates to medicine and can be used to suppress HIV, which causes AIDS in humans. The essence of the invention lies in the fact that to suppress HIV infection using the exogenous DNA complexes with polyvalent metals. The method has high antiviral activity and low toxicity. table 2.

The invention relates to medicine, namely to Virology, and can be used to suppress HIV, which causes AIDS in humans.

Increased morbidity and increased mortality from AIDS at the impossibility of effective treatment makes an urgent search for new drugs to combat HIV infection.

Known methods of suppressing HIV infection, including the introduction of nucleotide analogues, in particular 3-Azi-3-deoxythymidine-AZT. However, this drug is only effective in the early stages of the disease and even in therapeutic doses has a high toxicity, which in clinical practice complications (headache, anemia, disorders of gastro-intestinal tract), restricting its use. Known methods, including the introduction dittoe of the invention to develop the effectiveness of the method of inhibiting HIV infection, combining high efficiency with low toxicity.

The proposed method lies in the fact that the use of complex sodium salt of deoxyribonucleic acid (DNA) with polyvalent metals (zinc, Nickel, cobalt, iron) in the ratio of from 1:1 to 1:1000, and the introduction of the drug carried out subcutaneously, intraperitoneally, intranasally or in the spinal canal, depending on the form of the disease in therapeutically equivalent doses.

Essential features of the invention should be considered using the framework of the method of complex sodium salt of DNA with polyvalent metals, previously on these indications has not been used, their ratio, as well as the dosages and modes of administration. For the first time the possibility to obtain antiviral effect in various routes of administration of the drug, which is very important in different clinical forms of AIDS pulmonary, gastrointestinal, CNS damage.

Complex sodium salt of DNA metal consists of compounds of sodium salt of low molecular weight DNA, belongs to low-polymeric, contains not less than 80% of native sodium salt of DNA derived from the ROE of sturgeon, and has the following characteristics: Mol. m 270-500103Dalow adenine 29,0 thymine 27,0 guanine 22,0 cytosine 20,0 and polyvalent metal, namely, zinc (Zn), cobalt (Co), Nickel (Ni), iron (Fe).

To suppress HIV in vitro systems used complexes of DNA-PA with zinc, cobalt, Nickel and iron with varying concentrations of the components. Were used for comparison of AZT production company "Wellcome". Antiviral activity of the preparations was assessed using the methods recommended for this purpose by the who. Were used to culture human cell lines CEM-SS and MT-4. Cells were cultured at a concentration (0,03-0,05) x 105cells in 1 ml of medium RM 1640 with 10% fetal serum of calves, 300 mg/ml L-glutamine, 100 µg/ml gentamicin and were grown in the form of suspension. Cell viability was checked by staining them a 0.4% solution Trypanosoma blue. As sources of viruses used strains of HIV/IVS, and HIV-1 HTLV/IIIB.

Cell suspension was placed in a 24-hole panel, were treated with different doses of the drug and was infected with HIV. Multiplicity of infection was 0,01 TPA50on the cell. Then the culture was incubated at 37aboutC in an atmosphere containing 5% CO2when the humidity of 98% for 5-7 days before the determination of the cytopathic effect of the virus in cell culture.

To assess which is 1.

The table shows that the introduction into the culture medium of complex DNA-metal marked inhibition of HIV in vitro. Moreover, the optimal ratio of DNA-metal is in the range of 1:1-1:1000. This virusstatus effect combined with low cytotoxicity. When introduced into cultured environment of the drug AZT high cytotoxicity with moderate antiviral activity.

Further, the toxicity of the drugs using the proposed method was investigated in experimental animals in vivo.

The tests were conducted in parallel on all 4 coded drugs in comparison with azidothymidine in doses of 5, 10, 20, 35, and 50 mg/kg toxicity Studies of four drugs and azidothymidine was conducted on the nonlinear white mice weighing 6-7 g using different concentrations of drug per kilogram of animal weight in a volume of 0.2 ml in the form of subcutaneous, intranasal and intraperitoneal injection in a volume of 0.03 ml in the form intracerebrally injection. The animals were kept under observation for 2 weeks, then counted LD50method Curber. Per dose LD50took a lethal dose of the drug that caused the death of 50% of the animals.

The proposed complexes DNA-Na-metal have expressed antovic-activity; their antiviral activity combined with low toxicity in almost any way in a dose of 10-50 mg/kg, antiviral activity is manifested in almost any way of introduction.

P R I m e R 1. In the experiment used the culture transplantable cell line CEM-SS and MT-4. Cells were cultured at a concentration of 0.03 - 0,05106cells in 1 ml of medium RM 1640 with 10% fetal serum of calves, 300 μg/ml L-glutamine, 100 µg/ml gentamicin and were grown in the form of suspension. Cell viability was checked by staining with 0.4% solution tripanosoma the main panel, were treated with different doses of the complex DNA-Na-Zn at a ratio of DNA and metal (M/M) 1: 1; 4:9; 3:10; 0,5:350; 1:1000; 1:1100 and was infected with HIV. Multiplicity of infection was 0,01 D50on the cell. Then the culture was incubated at 37aboutC in an atmosphere containing 5% CO2when the humidity of 98% for 5-7 days before the determination of the cytopathic effect of the virus in cell culture. To assess the formation of the viral antigen used enzyme-linked immunosorbent assay.

In the experiment, it was shown that the number of entities as a percentage of control virus at a ratio of DNA-metal 3:10 was 25%, with 69% of viable cells; at a ratio of 0.5:350 35% at 81.2 per cent of viable cells; at a ratio of 1:1000 70% and 84.3 percent of viable cells, with a ratio of 1:1100 100% and 86.2% of viable cells.

P R I m m e R 2. The experiment as in example 1.

Suspension cells were treated with different doses of the complex DNA-Na-Nickel under the same ratios as in example 1. The experiment shows that the number of entities as a percentage of control virus at a ratio of DNA:Nickel 3:10 to 0.5:350 zero when the viability of the cells 71 and 79% at a ratio of 1:1000 68% at 84.3 percent viable is riment, as in example 1.

Suspension cells were treated with different doses of the complex DNA-Na-cobalt with the same proportions of components as in example 1. The experiment shows that the number of entities as a percentage of control virus at a ratio of DNA-Na-cobalt 3:10 corresponds to 10% when cell viability is 78.4% at a ratio of 0.5:350 15% cell viability 87,1, with a ratio of 1:1000 66% at the viability of 76.3% and at a ratio of 1:1100 viability respectively amounted to 82.1%

P R I m e R 4. The experiment as in example 1.

Suspension cells were treated with different doses of the complex DNA-Na-iron, with the same proportions of components as in example 1. The experiment shows that the number of entities as a percentage of control virus at a ratio of DNA-Fe 3:10, 0,5:350 corresponds to 0 when the viability of the cells, respectively 79,3 and 82.1% At a ratio of DNA-Fe 1:1000 number of entities 61% in cell viability 81,7, with a ratio of 1:1100 100% when the viability of 84.5%

Thus, the presented examples illustrate high anti-HIV activity of the proposed method with low toxicity.

This method is compared with the known has sledujusij at any way of introduction, that allows you to choose an adequate way of introducing the product in the various clinical forms of AIDS. The method can be recommended for clinical studies.

The WAY to SUPPRESS HIV INFECTION, including the introduction of a preparation of nucleic acids, characterized in that use of the drug derived from the ROE of sturgeon, containing not less than 80% of native sodium salt of DNA mol.m. 270 500 103D. when the molar ratios of adenine nucleotides 29,0, thymine 27,0, guanine 22,0, cytosine, 20,0, in combination with non-toxic polyvalent metal in a molar ratio of 1 to 1 1 to 1000, which is injected subcutaneously, intraperitoneally or into the spinal canal, depending on the clinical form of the disease, selecting adequate therapeutic dose.

 

Same patents:
The invention relates to pharmaceutical industry and relates to a method of production of a medicinal product antiarthrosis action of chitin obtained from secondary raw materials from the processing of shrimp, krill and other crustaceans harvested fish industry
The invention relates to the creation of biologically active food additives
The invention relates to medicine and can be used for industrial preparation of sodium salt of DNA for pharmacology
The invention relates to medicine, specifically to Oncology, and can be used in the treatment of subcutaneous fibrosarcoma

The invention relates to the production of biologically active substances, and in particular to a method for producing sodium salts of native DNA, which can find application in pharmaceutical industry

The invention relates to medicine, namely to Oncology

The invention relates to medicine, in particular to the treatment of viral infections, and is intended for the treatment of viral hepatitis B

Antivirus tool // 2035180
The invention relates to the field of medicine and relates to topically applied, accumulation in the skin-activated tools

The invention relates to the field of application of the carbohydrates glucose molasses

-glycyrrhizic acid with debutalbum ester of l-glutamic acid, exhibiting anti-inflammatory and antiulcer activity" target="_blank">

The invention relates to new chemical compound, specifically to glycopeptide-glycyrrhizic acid with debutalbum ester of L-glutamic acid: 3-0-[2-0[(N--D-glucopyranosyloxy-L-glutamic acid disutility ether)-N-D-glucopyranosyloxy-L-glutamic acid BEUtility ether-(3, 20)-11,30-dioxo-30-(N-D-glutamic acid disutility ether)-30-norolean-12-EN General formula I,

< / BR>
where R L-Glu(OBu)2exhibiting anti-inflammatory and antiulcer activity

-glycyrrhizic acid with 6-amino-2-thio-uracil, exhibiting anti-aids activity" target="_blank">

The invention relates to new biologically active compound, particularly to Amida-glycyrrhizic acid with 6-amino-2-thio-uracil: 3-0-[2-0-(-D-glucopyranosyloxy)--D-glucopyranosyloxy] -(3, 20)-11,30-dioxo-30-(N-6-amino-2-thio-uracil)-30-norolean-12-EN Fort - mules I

exhibiting anti-AIDS activity

-glycyrrhizic acid with 6-aminouracil exhibiting anti-aids activity" target="_blank">

The invention relates to new biologically active compound, particularly, to Amida-glycyrrhizic acid with 6-aminouracil: 3-0-[2-0-(-D-glucopyranosyloxy)--D-glucopyranosyloxy] -(3, 20)-11,30-dioxo-30-(11-6-aminouracil)-30-norolean-12-ene of the formula (I)

exhibiting anti-AIDS activity

-glycyrrhizic acid dimethyl ester, l-aspartic acid, exhibiting anti-aids activity" target="_blank">

The invention relates to new chemical compound, specifically to glycopeptide-glycyrrhizic acid dimethyl ester, L-aspartic acid: 3,0-[2-0-(N--Dr. glyukopiranozil - uranyl-L-aspartic acid dimethyl ester)-N--Dr. glyukopiranozil uranyl-L-aspartic acid dimethyl ester] - (3, 20)-11,30-dioxo-30-(N-L-aspartic acid dimethyl ester)-30-norolean-12-ene of the formula I

where I R - L - Asp (OMe)2;

II R - OH manifesting anti-AIDS activity

The invention relates to new biologically active chemical compounds, as well as the coordination compound CIS-chloro-N1 (21-tetrahydrofuryl)-5-floralarrangements (II) exhibiting antitumor activity
Up!