RU2291690C2 - Pharmaceutical anti-herpetic composition - Google Patents

Abstract

FIELD: medicine, biomolecular pharmacology, pharmacy.

SUBSTANCE: invention proposes a pharmaceutical composition that comprises virion vaccine anti-herpetic preparation containing simple herpes viruses of serotype 1 and 2 inactivated with formalin or γ-radiation, an immunocompetent substance and a pharmaceutically acceptable carrier. The composition comprises polyoxydonium, valine, lysine and isoleucine and also a combination consisting of at least two amino acids, not less, chosen from the following group: phenylalanine, leucine, alanine, threonine, histidine, arginine and methionine. The composition is made as a formulation on a solid carrier as tablet, lozenge, granules, sachet or powder placed into capsule, or on a liquid carrier as solution, gel, emulsion, syrup or liniment, or on a soft carrier as ointment, cream, paste, suppository, implant, chew or pastille. The composition can comprise zinc, chrome, selenium and nickel. The composition can be administrated in body by different ways: topical, oral, sublingual, intranasal, rectal, vaginal, parenteral or subconjunctival route. The composition provides the intense immunomodulating on body as a whole.

EFFECT: valuable medicinal and pharmaceutical properties of composition.

8 cl, 1 tbl, 13 ex

Description

The invention relates to the field of biomolecular pharmacology, in particular to the creation of a new pharmaceutical antiherpetic composition.

Currently, the following anti-herpes virus drugs are known: acyclovir, virazole, foscarnet, vidarabine, etc. [1]. However, chemotherapeutic agents are not always effective enough, because they do not have a specific effect on only the herpes virus, in principle, are polyactive and can be used for other viral diseases.

The corresponding vaccines have specific activity against the herpes virus. A number of antiherpetic vaccines, including those based on inactivated virions, have been developed both in Russia and abroad, for example, they are described in RF patents No. 2014084, 1994, No. 2085582, 1997, No. 2085583, 1997, U.S. Patent Nos. 4,816,250, 1989, No. 5,215,745.1993, No. 5602023, 1997.

Although the vaccines listed in these works are specific and are based on inactivated and attenuated herpes virus strains, not all of them are suitable for treating humans. To successfully fight the virus in a highly organized organism, it is necessary to take into account humoral and cellular factors, the state of the immune system, the degree of virus damage, the stage of the disease (latent infection, exacerbation), and the psychophysiological state of a person.

Known mechanisms of the action of the herpetic virus on immunocompetent cells and immune status in general suggest the need for inclusion in antiviral preparations of compounds that specifically affect the immune system, as well as substances that normalize cellular metabolism when the body is affected by the herpes simplex virus, especially with sluggish, recurring and poorly amenable to therapy, with a tendency to chronic diseases. It is advisable to include immunocompetent substances, such as interferons and antioxidants, in the complex therapy, as recommended in our previous developments (see, for example, RF patent 2142816, 1999), which also shows one of the patient-friendly dosage forms (in the form of a suppository ) This development is considered the closest analogue of the present invention. Despite the significant advantages of the aforementioned vaccine preparation, it does not take into account some important aspects of the patient's condition affected by the herpes virus. In patients with chronic forms, there is a violation of cellular and humoral immunity, there is an increased secretion of glucocorticoid hormones, a sharp violation of the exchange of cells and tissues affected by the virus.

It is known that the higher living beings need the immune system in order to fight against infectious diseases, that is, with the simplest living pathogen organisms: bacteria, microbes, fungi, viruses, etc. Does invertebrate animals, such as insects, have immunity? The search for an answer to this question led to the discovery of a new class of unique substances. In 1980, a team of researchers led by Hans Boman from Stockholm University (Sweden) was able to establish the following: the silkworm caterpillar Hyalphora cecropia was injected with a solution infected with bacteria, and then the substances that the infected caterpillar secreted were collected and analyzed. As a result, two new chemical compounds were obtained - peptide molecules consisting of 35-39 amino acids with antimicrobial activity. They were called cecropins [2].

In principle, antimicrobial substances, which are short molecules of 24-40 amino acids, have been known for a long time. More than half a century ago, the antimicrobial peptides gramicidin and nisin were isolated, which are widely used in the pharmaceutical and food industries. Plant antibacterial peptides and bee venom peptides have long been described. Nevertheless, Beaumann's discovery aroused interest. Firstly, the selected peptides at first glance very much resembled the long-known substance melittin contained in bee venom, but with one slight difference - unlike melittin, cecropins killed bacteria cells of only Escherichia coli type (the so-called gram-negative bacteria) and did not work at all neither to other microorganisms, nor to cells of higher organisms. Among researchers, the prevailing opinion was that antimicrobial peptides are produced by the secretory organs of only lower animals that do not have a developed immune system. It has been shown that mammals - rabbits, cows and even humans - can secrete similar substances. Moreover, this occurs mainly in the intestine, respiratory tract and ureters. Peptides are constantly produced even in a calm state of the body, and upon infection or damage to organs there is a surge in their synthesis.

Antimicrobial peptides, although somewhat inferior to antibiotics in effectiveness, act much faster and, most importantly, destroy bacteria that are resistant to known antibiotics. However, peptides that do not hemolize mammalian cells can be used in the clinic as antibiotics and antifungal agents. The named peptides can "crack down" with viruses in various ways. Firstly, some of them simply interact with the virus directly, blocking its activity. In this way, they inactivate viruses, such as stomatitis and even HIV. Secondly, peptides can block the multiplication of HIV virions in an infected body. This is how cecropins and melittin act [3].

The technical task of the present invention is the creation of a new, more effective and progressive complex preparation, which would not only selectively and strongly affect the herpes simplex virus, but would also provide an intensive immunomodulating effect on the body as a whole, as well as normalize metabolism in cells infected with the virus and tissues.

The problem is solved in that the virion vaccine antiherpetic drug, which contains herpes simplex viruses of serotypes 1 or 2, inactivated by formalin or γ-radiation, and an acceptable saline solution, additionally contains polyoxidonium, as well as valine, lysine, isoleucine, in addition, a combination consisting of at least 2 amino acids selected from the group: phenylalanine, leucine, alanine, threonine, histidine, arginine, methionine. The pharmaceutical composition has the following ratio of components:

antiherpetic drug - 10 ⁶ -10 ⁷ plaque forming units / ml

polyoxidonium 0.03-0.06 g valine 0.18-0.25 g lysine 0.15-0.30 g isoleucine 0.11-0.22 g combination of 2 metabolic amino acids 0.12-0.27 g physiologically acceptable solution up to 100 ml

Additionally, the composition may contain a number of auxiliary substances: solid, soft and liquid, as well as their mixture.

The composition may additionally contain a combination of 2-3 water- and fat-soluble vitamins selected from the group: thiamine, riboflavin, nicotinamide, pyridoxine, ascorbic acid retinol, tocopherol, or a mixture thereof in a total amount of from 0.05 to 3, 5%.

Such a preparation is suitable in the treatment of herpes simplex types 1 and 2, for this, a combination of amino acids and vitamins corresponding to each type of herpes is selected, and the dose and frequency of use, depending on the patient's condition.

Our studies have shown that the best effect for subjects with various forms of herpes is a high-tech synthetic drug polyoxidonium (PO) [4].

In vivo, software has a more complex and multifaceted effect on the immune system. Since the development of any immune response begins with cells of the monocyte-macrophage system and since the cytokines produced by monocytes / macrophages have a pleiotropic effect, the increase of their functional activity under the influence of PO leads to the activation of both cellular and humoral immunity. So, in particular, with the introduction of PO together with low doses of antigen, the synthesis of antibodies to this antigen is increased by 5-10 times compared to the control. It is important to note that such an increase can be observed in animals with a genetically determined weak reaction to this antigen. Thus, the software has the ability to set in motion all the factors protecting the body from foreign antigenic agents and this movement spreads naturally, as it does with the development of the immune response in the body. These observations have allowed us to choose among the many modern immunomodulators specifically on polyoxidonium for its successful use as part of a complex pharmaceutical antiherpetic composition. Empirically, we were able to establish that the very effective components in the composition of the composition are the essential amino acids valine and lysine, as well as some other amino acids that lead to accelerated epithelization of the skin tissue affected by the virus, such a composition, especially with the addition of trace elements, which enhances the immune response to the introduction of the drug allows it to be used for a more effective fight against herpes simplex virus infections of serotypes 1 and 2. A detailed description of the influence of trace elements in the immune system This is given in the application filed earlier (see above).

It should be noted that the introduction of amino acids into the composition (valine and lysine, in addition, a combination consisting of at least 2 amino acids selected from the group: phenylalanine, leucine, alanine, threonine, histidine, arginine, methionine) combinations accelerated re-epithelization of the affected tissue (from 15 to 30% compared with the prototype) depending on the type of virus.

Of particular importance for the present invention is the introduction to the composition of the composition of the essential amino acid isoleucine.

Isoleucine has a unique property, which was used for the first time in the anti-herpes vaccine composition - this amino acid, obtained only from the outside (for example, with food), stimulates the production in the human body (mainly in the intestine) of antimicrobial peptides like cecropins, which can destroy herpes viruses.

The invention is illustrated by the following:

Our numerous experiments on animals: rabbits and guinea pigs showed that the addition of isoleucine to the composition significantly increases the healing effect of herpetic lesions compared to using the composition without adding this particular amino acid. In rabbits, 10-12% earlier in time, healing begins with experimental herpes keratitis, and in guinea pigs with experimental genital herpes - 9-15% (compared with our previously stated work).

Other amino acids used by us have the following properties, in addition to the well-known ones, which were taken into account by us when choosing amino acids for our purposes.

Histidine - is part of carnosine and anserine, plays an important role in the formation of hemoglobin, is necessary for the production of red blood cells. Helps regulate blood sugar and energy production.

Leucine - is necessary for the growth and healing of bones, muscles. With its metabolism, energy is released, helps stabilize blood sugar levels. It was found that its deficiency can provoke in some cases hypoglycemia, growth retardation, weight loss, changes in the kidneys and thyroid gland.

Lysine - strengthens the immune system, promotes bone growth and collagen formation, improves concentration, has direct antiherpetic activity. Lack of lysine in food leads to impaired blood formation (the number of red blood cells decreases, their hemoglobin content decreases). Deficiency can lead to muscle depletion, impaired bone calcification, changes in the liver and lungs, especially in elderly patients.

Methionine - used for the synthesis of choline, it is known as a “lipotropic” agent, as it reduces the supply of fat in the liver and the body as a whole and lowers cholesterol. Creates new bone tissue, prevents nail diseases, protects the kidneys and is a natural chelating agent for heavy metals. It is of great importance for the functions of the adrenal glands and the synthesis of adrenaline, which is very important for the regulation of metabolism in virus-infected cells.

Phenylalanine - associated with the function of the thyroid gland and adrenal glands, is involved in the formation of the nucleus for the synthesis of thyroxine - the main hormone of the thyroid gland, is involved in the formation of adrenaline. In the body, it can be converted to tyrosine, which is used to synthesize the two main neurotransmitters, dopamine and epinephrine, which regulate cell metabolism at the neurohumoral level. Effective in controlling pain and itching. In addition, due to the selection of cholecystokinin, phenylalanine has an appetite suppressing effect.

Valine - with a deficiency of valine, the myelin coating of nerve fibers can be damaged and a negative hydrogen balance of the body can occur, which is extremely dangerous for patients affected by a viral infection.

Alanine - strengthens the immune system, is involved in glucose metabolism.

Arginine - a deficiency can cause hair loss, constipation, liver disease and slow healing of wounds, including those caused by damage to viral toxins.

Important additions to the present invention are various dosage forms in the form of which our composition can be practically used.

The composition is prepared by standard methods using the following techniques:

A composition formulated primarily using solid carriers in its final form is a tablet, dragee, granule, sachet or powder placed in a capsule. A composition formulated primarily using liquid carriers in the final product is a solution, gel, emulsion, suspension, mixture, syrup or liniment. A composition formulated primarily using soft carriers is an ointment, cream, paste, suppository, implant or chewable tablet or lozenge.

The composition contains active components, auxiliary substances necessary for the preparation of a particular pharmaceutical form, mixed according to standard technology, and additionally contains 2-3 microelements selected from the group: zinc, chromium, selenium and nickel. A set of trace elements in the form of soluble chelate forms is introduced into the composition of the dosage form in an amount of 0.01-0.08% by its total weight.

A pharmaceutical antiherpetic composition can be used by administering it to an organism affected by the herpes virus in an effective dose in the form of a suitable dosage form in a suitable way selected from the group: oral, sublingual, intranasal, rectal, vaginal, parenteral, subconjunctival.

The following explains how various pharmaceutical forms suitable for use can be prepared on the basis of our composition.

EXAMPLE 1

Tablets - dosage form obtained by pressing active and auxiliary substances, intended for internal, external, sublingual, implantation or parenteral use. Granules can also be attributed to the same group of solid dosage forms. Granules - a dosage form for internal use in the form of grains of round, cylindrical or irregular shape, containing a mixture of active components and excipients. The granules may be coated.

As auxiliary substances, alginic acid and its sodium salt, acetyl cellulose, acetylphthalyl cellulose and its sodium salt, aerosil, water, wax, glycol, glucose, dextrin, gelatin, kaolin, carboxymethyl cellulose (CMC) and its sodium salt, tartaric acid can be used citric acid, stearic acid and its calcium and magnesium salts, starch, magnesium carbonate, magnesium oxide, mannitol, liquid paraffin, vegetable oil, methyl cellulose, microcrystalline cellulose (MCC), wheat flour, sodium bicarbonate, sodium chloride horide, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, polyvinylpyrrolidone (PVP), polyethylene glycol (PEG), natural gums, ruberozum, sugar, milk sugar, sorbitol, tween-80, titanium dioxide, tropeolin 0, flavorozum, cerulezum, ethylcellulose.

You can make tablets for a different method of their use:

1. Oral tablets, where the active substances are released in the gastrointestinal tract (GIT): gastro-soluble (soluble in the stomach), enteric-soluble (soluble in the intestine), dulciblette - chewable tablets (assimilated starting from the oral cavity), seuliblette- (cheek) , sublingual (sublingual), irgiblette - tablets - samples.

2. Injectable - these are aseptically prepared tablets that are dissolved in an aseptically prepared solution. The tablets are individually packaged in vials. Apply ampoules with a solvent.

3. Implantablette - tablets for implantation (p / skin, in / muscle). Absorb within 6-12 months. The tablets must be sterile, individually wrapped. Obtaining tablets is a compaction of bulk material (they take a sample of dry ingredients of our composition), add the necessary auxiliary substances and press to form the final product - tablets, which have strength, porosity, density, moisture permeability. Tablets and granules may contain additional excipients.

ADHESIVE SUBSTANCES

- starch paste 3-15%, sugar syrup - up to 64%, gum solutions, gelatin 5-10%, Na CMC - 1% solution.

- ethyl cellulose 4-8% solution, hydroxyethyl cellulose, zein 5% solution, PVP solution - up to 10%, polyethylene glycol (M.M. 4000, 6000) 1-3, 5% solutions.

For tablets and granules, the following coloring materials are used:

Indigo, Red 2C, tropeolin 00, eosin, ruberozum, carotene, chlorophyll, erythrosine, amyrint.

The composition of tablets and granules can be prolongers that provide the action of the active composition up to 24 hours:

- monodistearin, monodiglycerides, white wax, palm oil, cellulose phthalate, paraffin, 3-laurin, sunflower oil.

In addition, solid dosage forms may contain THINNERS - glucose, sucrose, lactose, starch, dextrin, glycine, basic magnesium carbonate, calcium sulfate, phosphate, urea, as well as polyhydric alcohols: mannitol, xylitol, MCC.

Tablets and granules may contain RIPPERS that:

- provide rapid mechanical destruction of the tablets in contact with liquids, because increase the total contact surface of the liquid phase and the solid. Increase the absorption of active ingredients. By mechanical action they are divided into: gas-forming, swellable, improving the wettability and permeability of tablets.

Gas-forming - act upon contact with water, a tablet reacts with water and gases are released that break the solid dosage form (for example, a filler is a mixture of tartaric acid and sodium carbonate or calcium carbonate).

Swelling - swelling on contact with water. Amylopectin, agar-agar, alginic acid, gelatin, cellulose derivatives (MCC, Na MCC aerosil). Substances that improve wettability and water permeability: Non-inogenic surfactants are adsorbed on particles, Tween-80 (not more than 1%), starch, and also mixtures: starch (sucks in water) + NaMCC (swells).

Tablets may contain SLIDING SUBSTANCES

- talc, finely divided dried starch, skim milk powder, PEG (M.M. 400-600), aerosil (particle diameter 4-40 nm), talcumin. Anti-sticking (lubricating) substances are hydrophobic substances that reduce friction on the surface of particles. They increase the disintegration time of the tablets, as with increasing pressure, they melt and form films. These include: stearic acid and its salts, paraffins, fats, petroleum jelly, ceresin, silicones (not more than 1%). Combined action: (talc + calcium stearate).

EXAMPLE 2

Capsules - a dosage form consisting of a drug enclosed in a shell. Capsules are intended for oral administration, as well as for rectal and vaginal routes of administration. There are two types of capsules: hard caps with caps (Capsulae durae operculatae) and soft capsules with a whole shell (Capsulae molles). To obtain the capsule shell, gelatin, water, as well as various excipients (glycerin, sorbitol, sugar, titanium dioxide, acid red 2C, tropeolin 0, sodium or potassium metabisulfite, nipagin and others) are used, approved for medical use. The contents of the capsules consists of the active components of the composition with the possible introduction of various auxiliary substances that are approved for medical use. The contents of the capsule may be solid, liquid or pasty. Capsules must have a smooth surface without damage and visible air and mechanical inclusions.

Hard capsules, depending on capacity, make eight numbers - from 000 (the largest size) to 5 (the smallest size), see table.

Table room 000 00 0 one 2 3 four 5 Average capsule capacity, ml 1.37 0.95 0.68 0.5 0.37 0.3 0.21 0.13

Soft capsules can have a spherical, ovoid, oblong or cylindrical shape with hemispherical ends, with a seam and without a seam. Capsules can be of various sizes, with a capacity of up to 1.5 ml. For our composition, optimal 0.5-1.2 ml. The capsule shell may be rigid or flexible depending on the purpose of the capsule.

EXAMPLE 3

Eye drops - a dosage form intended for installation in the eye. Eye drops should be isotonic with tear fluid. As stabilizers, preservatives, prolongators and other auxiliary substances, sodium chloride, sodium sulfate, sodium nitrate, sodium metabisulfite, sodium thiosulfate, sodium phosphate salts of monosubstituted and disubstituted, boric acid, sorbic acid, nipagin, cellulose derivatives and others are used. Eye drops should be prepared under aseptic conditions and be sterile.

EXAMPLE 4

MEDICINES FOR Parenteral Administration

Medicines for parenteral use include sterile aqueous and non-aqueous solutions, suspensions, emulsions and dry solids (powders, porous masses, tablets), which are dissolved in a sterile solvent immediately before administration. As solvents, water for injection, fatty oils, ethyl oleate are used. Ethyl alcohol, glycerin, propylene glycol, polyethylene oxide 400, benzyl benzoate, benzyl alcohol and other solvents can be used as part of a complex solvent.

EXAMPLE 5

Ointments are a mild dosage form intended for application to the skin, wounds or mucous membranes. The ointment consists of a base and a pharmaceutical composition, evenly distributed in the base. For the preparation of ointments with our composition, the bases approved for medical use are used: lipophilic - hydrocarbon (petroleum jelly, hydrocarbon alloys), fat (natural, hydrogenated fats and their alloy with vegetable oils and fat-like substances), silicone and others; hydrophilic - gels of high molecular weight carbohydrates and proteins (cellulose, starch, gelatin, agar esters), gels of inorganic substances (bentonite), gels of synthetic high molecular weight compounds (polyethylene oxide, polyvinylpyrrolidone, polyacrylamide) and others; hydrophilic-lipophilic - anhydrous alloys of lipophilic bases with emulsifiers (an alloy of vaseline with lanolin or other emulsifiers), emulsion bases of the water / oil type (an alloy of vaseline with water lanolin, a water / vaseline and others emulsion) and oil / water (used as emulsifiers sodium, potassium, triethanolamine salts of fatty acids, tween-80) and others. Preservatives may be added to the ointment. Surfactants and other excipients approved for medical use.

EXAMPLE 6

Patches - a dosage form for external use, with the ability to adhere to the skin. The patch has an effect on the skin, subcutaneous tissue, and in our case the general effect on the body. The patch can be in the form of a plastic mass on the substrate and without it, or in the form of a gasket fixed to the adhesive tape with the composition of our composition. The composition of the plaster mass as excipients may include natural or synthetic rubbers permitted for medical use, their mixtures, as well as other polymers, fat-like substances, natural oils, fillers and antioxidants. In appearance, the plaster mass is a homogeneous mixture that is dense at room temperature and softens at body temperature.

EXAMPLE 7

Powders - a solid dosage form for internal and external use, consisting of the crushed substances of our composition and having the property of flowability. There are powders divided into separate doses and undivided.

The powder from our composition is complex, it is prepared taking into account the properties of the ingredients and their quantities. If there are ingredients in different amounts in a complex powder, the mixing begins with substances included in smaller quantities, gradually adding the remaining ingredients.

EXAMPLE 8

Syrups are concentrated aqueous solutions of sucrose, which may contain medicinal substances, fruit food extracts. Syrups are thick, clear liquids with a characteristic taste and smell depending on the composition. Syrups are prepared by dissolving sugar when heated in water or in extracts from plant materials. Medicinal syrups are also obtained by adding medicinal components to sugar syrup. The resulting syrups are filtered and poured into dry sterile vessels. If necessary, preservatives (alcohol, nipagin, sorbic acid, nipazole) or other preservatives approved for medical use are added to syrups.

EXAMPLE 9

Suppositories are solid dosage forms that melt at room temperature and melt at body temperature. Suppositories are used for introduction into the body cavity. Distinguish rectal suppositories (suppositories) - Suppositoria rectalia; vaginal - Suppositoria vaginalia and sticks - bacilli. Rectal suppositories may take the form of a cone, a cylinder with a pointed end, or some other shape. Vaginal suppositories can be spherical (balls) - globyli; ovoid - ovula or in the form of a flat body with a rounded end (pessary) - pessaria. As lipophilic bases for the manufacture of suppositories, cocoa butter, cocoa butter alloys with paraffin and hydrogenated fats, vegetable and animal hydrogenated fats, solid fat, lanol, alloys of hydrogenated fats with wax, hard paraffin and other bases approved for medical use are used. As hydrophilic bases, gelatin-glycerin gels, alloys of polyethylene oxides with various molecular weights and other substances approved for medical use are used. The gelatin-glycerin base is made from medical gelatin, glycerin and water. In the manufacture of suppositories can be used butyloxytulol, butyloxyanisole, citric acid, emulsifier No. 1; emulsifier T-1, emulsifier T-2, tween-80, wool wax alcohols, aerosil and other auxiliary substances approved for medical use. The active components, if necessary, are crushed, sieved, mixed with the base directly or after dissolving or grinding with a small amount of water, glycerin, paraffin oil or other suitable solvent. The method of obtaining one of the possible types of suppositories using our composition is described in detail in the previously filed application No. 2003131814.

EXAMPLE 10

Suspensions - a liquid dosage form containing, as a dispersed phase, one or more powdered powdered medicinal substances distributed in a liquid dispersion medium. Suspensions are distinguished for internal, external and parenteral use. Suspensions for parenteral administration are administered only intramuscularly.

EXAMPLE 11

Emulsions are a dosage form that is uniform in appearance, consisting of mutually insoluble finely dispersed liquids, intended for internal, external or parenteral use. Emulsions are generally stabilized by emulsifiers. The emulsion uses peach, olive or sunflower oil.

The invention is confirmed by the following results.

EXAMPLE 12 The results of testing various forms on a group of 152 experimental animals (herpes conjunctivitis of rabbits, genital herpes in guinea pigs) showed that the use of the new drug not only enhanced immunity, but also significantly prolonged the period of remission, accelerated the process of re-epithelization and healing of skin and mucous tissues , and in some cases, practically cure the disease in individual individuals (15% of all subjects with a chronic form of the disease). In our opinion, the inclusion of vital ingredients that regulate metabolic processes at all levels, namely: polyoxidonium, valine, lysine, isoleucine, vitamins of all groups, as well as a set of trace elements from the group: zinc, chromium, played an important role in this result , selenium and nickel.

EXAMPLE 13 Key performance indicators. The time to local recovery (complete re-epithelization) was reduced by 20-35%, the duration of remission increased on average to 7.5 months, the absence of the virus in the smear (PCR diagnosis) in 99.7% of cases, the activation of antiviral immunity, almost complete cure in 15% of observations of animals (in animals with chronic forms).

Due to the creation of a new highly immunogenic composition that affects the metabolism of the affected cell and the production of anti-herpes toxins by healthy cells, the antigenicity and stability of the specific activity of the drug are preserved, not only the antiviral properties are strengthened, but the body's resistance is increased and prolonged in acute and even chronic infections.

Literature

1. D.A. Kharkevich "Pharmacology", GEOTAR-MED, 2002, pp. 549-550.

2. Horwitz A.H., Williams R.E., Liu P.-S, Nadell R. “Antimicrob. Agents Chemother. ", 1999, 43, 2314-2316.

3. Khaitov P.M. "Immunogenetics and immunology: resistance to infection", Tashkent, 1991.

4. Petrov R.V., Khaitov P.M. New generation vaccines based on synthetic polions: creation history, phenomenology and mechanisms of action, implementation. International journal on immunorehabilitation. - 1999, N11, p. 13-36.

Claims (8)

1. A pharmaceutical antiherpetic composition comprising a virion vaccine antiherpetic drug that contains herpes simplex viruses of serotypes 1 or 2, inactivated by formalin or γ-radiation, an immunocompetent substance and a physiologically acceptable solution, characterized in that it contains polyoxidonium, valine, lysine and isoleucine, as well as a combination of at least 2 amino acids selected from the group phenylalanine, leucine, alanine, threonine, histidine, arginine, methionine in the following ratio of components in, g: Antiherpetic drug 10 ⁶ -10 ⁷ plaque forming units / ml Polyoxidonium 0.03-0.06 Valine 0.18-0.25 Lysine 0.15-0.30 Isoleucine 0.11-0.22 Combination of metabolic amino acids 0.12-0.27 Physiologically acceptable solution Up to 100 ml 2. The composition according to claim 1, characterized in that it can be made in the form of a dosage form, which additionally contains auxiliary substances, solid, soft, liquid, or mixtures thereof. 3. The composition according to claim 2, characterized in that when using mainly solid excipients, the dosage form is a tablet, dragee, granule, sachet or powder placed in a capsule. 4. The composition according to claim 2, characterized in that when using mainly liquid excipients, the dosage form is a solution, gel, emulsion, suspension, syrup or liniment. 5. The composition according to claim 2, characterized in that when using mainly mild excipients or a mixture of excipients, the final product is an ointment, cream, paste, suppository, lozenge, patch, implantable or chewable tablet. 6. The composition according to claim 1 or 2, characterized in that it may additionally contain one or more trace elements (ME) selected from the group of zinc, chromium, selenium and nickel. 7. The composition according to claim 6, characterized in that it further comprises ME in the form of soluble chelate forms in an amount of 0.01-0.08% per total weight of the composition. 8. The composition according to claim 1 or 2, characterized in that it can be introduced into the body in an effective dose by a route selected from the group: externally, internally, parenterally, sublingually, intranasally, rectally, vaginally, subconjunctively.