(57) Abstract:The invention relates to medicine. The proposed use of aradena as antiherpetic funds. The drug exhibits antiviral activity. table 2. The invention relates to the field of medicine and, in particular, ophthalmology.Currently in ophthalmic practice as antiviral agents for the treatment of eye diseases, caused by herpes simplex virus, found the use of the following medications: 0.1% of R-R GO 3% ointment Vicurban, Halpin, Bonafton, Interferon, Zovirax [Y. F., Michuk Viral diseases of the eye" - M "Medicine" 1981, 272 S.].However, the use of the above drugs are not always effective. This is due to many reasons - low-solubility drugs, inability to provide therapeutic concentrations at the site of reproduction of the virus, toxic effect of chemotherapeutic agents on membranes of the eyes, as well as the development of resistance to all the prescribed drugs. Therefore, for the successful therapy of diseases of the eye caused by the herpes simplex virus, need for new antiviral drugs and medications that improve trophism and regeneration by the VA is a 5-iodine-2 deoxyuridine (IMU), of 0.1% eye drops ARE widely used in ophthalmic practice for the treatment of eye diseases, caused by herpes simplex virus, and in addition, ARE still the main drug - a "marker" in the experimental evaluation of new anti-herpes funds (Y. F., Michuk "Eye infections" - Russian Honey. J., 1999, T. 7, N 1, 16-19].Known drug atadan belonging to the group of stimulants regenerative processes in tissues, which are based on the activation processes of biosynthesis of nucleic acids. Atadan in medical practice for the treatment of thermal and radiation injuries of the skin, with long-term non-healing wounds in the form of a powder and 1% injection solution [Etagen: Avenue M, cbti Honey. prom., 1985 - 18 C.].We have previously shown that the drug atadan in the form of a 0.5% aqueous solution as a reparative drug is effective in the treatment of ocular viral diseases involving destruction (ulcerative lesions) and trophic disorders of the cornea.It is established that the combination as a specific anti-herpes drug instillation antiviral drug GO and as reparative means a 0.5% aqueous solution of aradena, to the cure [Patent N 2122844 from 17.06.96 "a Method for the treatment of herpetic keratitis with ulceration" Y. F. Michuk and others].However, further experimental studies showed that the drug atadan independently exhibits antiviral activity against herpes simplex virus.Antiherpetic activity of this drug in the existing literature is not described.The essence of the invention lies in the fact that the drug reparative actions atadan exhibits antiviral activity against herpes simplex virus in the in vitro system to model cell culture and in vivo in experimental herpetic keratitis rabbits ' eyes.Example 1. Antiherpetic activity of aradena in vitro.The test was performed on the tissue culture of fibroblasts of chicken embryo, which was prepared by the standard technique.Cell suspension at a concentration of 1 million/CL in ml contributed to 0.2 ml in each well of 96-aceing culture plates. Cells were incubated 48 hours in an incubator at 37oC (85% medium 199+15% bovine serum, without preservative). Then the monolayers were washed once with Hanks solution and infected with herpes simplex virus strain "1-C" type 1 consecutive 10-multiple dilutions. The virus and made the test drug in the following concentrations: 1000; 100; 10; 1,0; 0,10; 0,01 µg/ml of cell Culture was placed in a thermostat at 37oC. the Results were considered by the cytopathic effect after 48 and 72 hServed as control monolayers of cells treated only with the virus without drug (control virus), and monolayers of cells treated with the tested concentrations of the drug without virus (control toxicity).The results are given in table 1.Thus, it was established that atadan has antiviral activity in vitro against herpes simplex virus by inhibiting viral replication at concentrations 100,0-0.1 ág/ml And it is shown that at a concentration of 100 µg/ml atadan reduces the infectious titer of 3 lg 48 h after infection and 2.5 lg 72 hours of the Toxic effect of the drug on the cells at these concentrations is not marked.Example 2. Antiherpetic activity of aradena in vivo. Study of antiviral activity in vivo has been studied in experimental models of ophthalmic herpes rabbits. In the experience took 10 rabbits (20 eyes). Reproduction of experimental models of ophthalmic herpes was carried out according to the usual method, by scarification of the cornea and subsequent rubbing virusanderica when due according to the clinical criteria of the group. Experimental group received instillation of 0.5% solution of aradena 3-4 times a day; the control group of animals received placebo. Treatment was continued until complete healing of the rabbits in the experimental group. About the effectiveness of the drug was assessed in terms of epithelialization of the cornea, as well as in terms of cure.The research results are summarized in table 2.As can be seen from the presented results, the instillation of 0.5% aqueous solution of aradena provides a pronounced therapeutic effect, accelerate the process of epitomization of the cornea, to accelerate the recovery of animals in a significantly short period of time (p<0.05), and also noted a higher percentage of recovered animals in the experimental group compared with the control (p<0,05) due to its anti-herpes activity. The use of aradena as antiherpetic funds.
SUBSTANCE: invention provides topical blood circulation improving remedy containing simultaneously nitroglycerine and aminophylline. Remedy can be provided in the form of emulsion, gel, or ointment, which are administered 1-2 times a day.
EFFECT: strengthened blood circulation activation effect, which is prolonged to 24 hours.
5 cl, 9 ex
FIELD: organic chemistry, heterocyclic compounds, biochemistry.
SUBSTANCE: invention relates to new compounds - purine derivatives of the general formula (I): in free form or salt wherein X means oxygen or sulfur atom or group NR5; R1 means alkyl, alkenyl, cycloalkyl, benzocycloalkyl, cycloalkylalkyl or aralkyl group that can be substituted optionally with hydroxy-, carboxy-group or alkoxycarbonyl; or if X means NR5 then R1 can mean alternatively heterocyclic group taken among benzylpiperidyl or the formula: ; or group of the formula (II): ; R2 means hydrogen atom, alkyl or alkoxy-group; R3 means hydrogen atom, alkoxy-, carboxy-group, carboxyalkyl, alkoxycarbonyl, -N(R9)R10, (C1-C4)-alkylene-SO2N(R11)R12 or -CON(R13)R14; or if two substitutes R2 and R3 are joined to adjacent carbon atoms in indicated benzene ring then in common with carbon atoms to which they are joined they mean heterocyclic group comprising 5-10 ring atoms among them one or two atoms mean heteroatoms taken among nitrogen, oxygen and sulfur atom; R4 means hydrogen atom, alkoxy-, carboxy-group, carboxyalkyl, -SO2N(R11)R12, -N(R9)R10 or -CON(R13)R14; or if two substitutes R3 and R4 are joined to adjacent carbon atoms in indicated benzene ring then in common with carbon atoms to which they are joined they mean heterocyclic group comprising 5-6 ring atoms among them one or two atoms mean heteroatoms taken among nitrogen, oxygen or sulfur atom; R5 means hydrogen atom or alkyl; R6, R7 and R8 mean hydrogen atom, or one of these radicals means -SO2NH2, -N(CH3)COCH3, -CONH2 and two others mean hydrogen atom; R9 means hydrogen atom or alkyl; R10 means hydrogen atom, -COR15 wherein R15 means alkyl, alkoxy-group; or R9 and R10 in common with nitrogen atom to which they are joined mean heterocyclic group comprising 5 or 6 ring atoms among them one or two atoms mean heteroatoms taken among nitrogen and oxygen atom; R11 means hydrogen atom or alkyl; R12 means hydrogen atom, alkyl, hydroxyalkyl, carboxyalkyl or alkoxycarbonylalkyl; or R11 and R12 in common with nitrogen atom to which they are joined mean heterocyclic group comprising 5 or 6 ring atoms among them one or two atoms mean heteroatoms taken among nitrogen and oxygen atom; R13 and R14 each and independently of one another means hydrogen atom or alkyl with exception of 2-(para-n-butylanilino)-6-methoxypurine, 2-(para-n-butylanilino)-6-(methylthio)purine, 2,6-di-(phenylamino)-purine, 2,6-di-(para-tolylamino)-purine and 2-(para-tolylamino)-6-(phenylamino)-purine.
EFFECT: valuable biochemical properties of compounds.
11 cl, 4 tbl, 221 ex
FIELD: organic chemistry, biochemistry, biology.
SUBSTANCE: invention relates to a pharmaceutical composition eliciting the inhibitory effect on activity of serine protease (caspase-3) in the form of tablet, capsule or injections placed into acceptable package, to a method for its preparing and a method for treatment of diseases associated with enhanced activation of apoptosis. The composition comprises compound 2,3-dihydro-1H-benzo[g]pteridine-4-one of the general formula (1) (1)
or its salt with pharmacologically acceptable acid as an active component taken in pharmaceutically effective amount wherein X means oxygen (O) or sulfur (S) atom; R1 and R2 represent independently of one another hydrogen atom, inert substitute taken among the group including low- or non-reactive and optionally substituted radical, such as (C1-C7)-alkyl, (C2-C7)-alkenyl, (C2-C7)-alkynyl, (C1-C7)-alkoxy-group, (C7-C12)-aralkyl, (C7-C12)-heterocyclylalkyl, (C7-C12)-alkaryl, (C3-C10)-cycloalkyl, (C3-C10)-cycloalkenyl, phenyl, aryl, heterocyclyl; optionally substituted hydroxy-(C1-C5)-alkyl group; R3, R4, R5 and R6 represent independently of one another hydrogen, halogen atom, -CF3, -CN, inert substitute taking among the group including low- or non-reactive and optionally substituted radical, optionally substituted hydroxyl group, optionally substituted hydroxy-(C1-C5)-alkyl group, optionally substituted amino-group, optionally substituted amino-(C1-C7)-alkyl group, optionally substituted carboxy-(C1-C7)-alkyl group, optionally substituted (C1-C6)-alkylcarboxy-(C1-C6)-alkyl group, optionally substituted carbamoyl group, optionally substituted (C1-C6)-alkylcarbamoyl group, optionally substituted sulfamoyl group. Also, invention relates to applying compounds of the formula (1) for preparing pharmaceutical composition and experimental study (in vitro and in vivo) processes associated with apoptosis.
EFFECT: improved preparing method, valuable medicinal and biochemical properties of composition.
7 cl, 1 dwg, 2 tbl, 5 ex
SUBSTANCE: the present innovation deals with antiviral preparations that contain aliphatic alcohol C21-C28 in combination with either nucleoside or nucleotide analog or phosphoformic acid in pharmaceutically acceptable carrier. It is necessary to mention that n-docosanol is considered to be a preferable aliphatic alcohol. Concentration of aliphatic alcohol C21-C28 corresponds to 0.05% to 40% by weight. Concentration of either nucleoside or nucleotide analog or phosphoformic acid corresponds to 0.1% to 10% by weight. The innovation, also, deals with the ways to treat viral infections due to applying such compositions. Aliphatic alcohols C21-C28 synergistically intensify antiviral activity of nucleoside analogs directed against replication of several herpetic viruses and that of cow's pox.
EFFECT: higher efficiency of inhibition.
28 cl, 13 dwg, 21 ex, 6 tbl
FIELD: veterinary science.
SUBSTANCE: about 20-25 d before calving one should introduce intramuscularly 0.5%-sodium selenite solution for cows at the dosage of 10 ml. Twice before and twice after calving at 10-d-long interval - tetravit at the dosage of 10 ml at the content of 50000 IU vitamin A, 25000 IU vitamin D, 20 mg vitamin E and 5 mg vitamin F per 1 ml. Succinic acid should be introduced 20-25 d both before and after calving at the dosage of 1.0 g. The method provides efficient correction of the main values of homeostasis in cows after calving.
EFFECT: higher efficiency of normalization.
2 ex, 4 tbl