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THE USE OF METHENAMINEHYDRORHODANIDE FOR PRODUCTION OF DRUGS AGAINST RNA VIRUSES
(The description from the patent application)

The invention is in the field of:

Section A   HUMAN NECESSITIES
A 61   THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS [7}
A 61 P   HUMAN NECESSITIES
31/12   . Antivirals
31/14   . . for RNA viruses
31/16   . . . for influenza or rhynoviruses
31/18   . . . for HIV
(A 61 P 31/12; A 61 P 31/14; A 61 P 31/16; A 61 P 31/18)

Severe human and animal`s viral infections caused specially by RNA viruses are a big medical and social problem of mankind in general. Follow this problem through the evolution as well as through the history, these infections were begining and surviving in the endemic focuses of infections, with the occasional epidemics of larger or smaller dimensions, rarely exceeded in pandemics. The need for increased economy cooperation between states and nations and technology development which enabled a wide migrations increased the possibility of spreading these deseases more offen from their endemic focusses of infections to the distant areas, with the possibility to outgrow into the pandemics. Such a global chalenges are one of the reasons for a global scientists` response worldwide organized on national or international level under the auspices of the World Health Organisation and financed from the public sources as well as of the private investors, all in the aim of finding the efficiant prevention methods and, when this is not possible, of finding the efficiant therapy.

Unfortunately, for the known antiviral drugs the accepted evaluation of experts is that they have a limitted and not-enough-efficiant effects. In general opinion, the ideal anti-viral remedy should interrupt a viral growth without the more significant damages of the cells` metabolism at the same time. Accordingly, it`s been searched for the substances with the selective effects on the viral enzymes in lower concentrations than those which damage the cells` enzymes. The big difficulty in this process makes the situation that the effects acheaved in vitro conditions offen don`t coincide with the effects in vivo conditions. Regardless all the difficulties, such an aproach to discover the antiviral drugs which would directly affect the viral enzymes due to reduce their replication for 50% at least, at the same time not to show a toxic effects on cells, resulted by several anti-viral drugs and a large number of a simmilar substances are in researching process specially for treating the viral hepatitis and acquired immuno-deficiency syndrome. On the other side, the question of a possibility to make the efficiant vaccines is very much interfere with intense changability of the viruses mentioned and modern technology – regardless the impressive development and results - still does not give the results correlate to dimension of a problem. 

This invention makes a quite new approach to fighting against the severe viral infections. Instead to insist on a direct extermination of viruses by a different ways of blocking the enzymes which are responsible for viral growth, it insists on a partial damaging the viruses and induce of the immuno-responce. This way the viruses would become more recognisable for a different ways of already induced immuno-responce and more susceptible to immunity system. In that sence, the methenaminehydrorhodanide was identified as the substance which was able to give desirable effects by a sinergy of formaldehyde as a degradation product of methenamine and rhodanide ion.

Methenaminehydrorhodanide is the salt of methenamine and hydrogen rhodanide (thyocyanate). In the first half of 20th century it`s been used in veterinary for healing the bacterial infections. Discoveries of sulphonamides, later and antibiotics, practicly, pushed it off the market and it`s therapeutical potentials wasn`t completely perceived. In acid environment methenamine decomposes to formaldehyde which is one of the most known and the strongest among non-specyfic antimicrobe substances (in conditions in vitro it affects all kind of micro-organisms including viruses). No wonder the formaldehyde has been offen used in vitro conditions to inactivate RNA-viruses so they could be used for immunization (Pasteur, Salk). Rhodanide ion also has non-specific anti-microbe effect. Thanks` to it`s chemistry it is capable to change the coloide organic sollutions from gel to sol, which is of great importance for disordering the integrity of RNA viruses` cover. Also, it`s presence in the organism corelates with different kinds of immuno-responce. Working in sinergy both compounds of methenaminehydrorhodanide in organism lead to the condition we called “immunity thunderstorm”. As non-specific antimicrobe compounds they damage the present microorganisms which, damaged this way, successfully induce the immuno-system in different kinds of responces. In such an immunity storm RNA viral particles are exposed to “thunder strokes” – their integrity partialy gets disturbed by formaldehyde and rhodanide ion make them more susceptible to different ways of immuno-responce. That is why the effects of methenaminehydrorhodanide could be considered as illusory non-specific. Basicly, conditions in vivo create the environment for inactivation of the viruses, simmilar to the inactivation in vitro conditions in vaccines` production.

Selectivity of the Methenaminehydrorhodanide`s effects it gets by the circumstance that the formaldehyde separates from methenamine where the inflammatory process is the most in progress (the presence of the highest number of viral particles), and that means that the environment is the most acidified. Selectivity is also acheaved by the fact that viral particles are smaller and more simple and sensitive apart of the cells which still have a certain damages` reparation mechanisms. This selectivity in effects is still limitted so as the indication were selected only severe RNA-viral infections of humans and animals, caused by:

  1. Coronavirus (severe acute respiratory syndrome - SARS); 
  2. Ebola and Marburg viruses; 
  3. Influenza A virus (Avian influenza – bird flu); 
  4. HIV (acquired immuno-deficiency syndrome - AIDS); 
  5. HTLV (non-Hogkin lymphome, T-cells` leucosis of humans, T-cells` leucosis of monkeys, cattle`s leucoses); 
  6. Prions (Kreutzfeld-Jakob`s desease, the scrapie of shipp and goats, spongeform encephalopaty of cattle - BSE); 
  7. Hepatitis C virus; 
  8. Hepatitis E virus; 
  9. Viruses from Arenaviridae family (LCM, Lasa, Junin, Machupo); 
  10. Mixed viruses and other microbes which cause the chronical infections (chronical sinusitis, pharyngitis, otitis etc.) of the body cavities (oral and nasal cavity, sinuses, pharynx, middle ear etc.);

Methenaminehydrorhodanide is the substance well soluble in water so it`s convenient for producing of all the pharmaceutical types of drugs for systems` use (all kinds of injections` sollutions, including those with long lasting effects), all kinds of solid shapes – powder, tablets, capsules, including those with long lasting effects), as well as for local treatments (creams, pastes, gels, solutions, aerosoles etc.) in veterinary and medicine as well.

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