Pharmaceutical preparation for local and external use, based on low-molecular interferon inducer

FIELD: medicine; pharmacology.

SUBSTANCE: invention represents pharmaceutical composition for treatment of purulo-destructive affections of skin and mucous membranes, applied for external and local use and characterised by that it contains Tilorone and base additives chosen from group: substance of antibacterial activity in respect to gram-positive and/or gram-negative bacteria, antimicotic, local anaesthetic, reparative process stimulator, hypooxidiser, biogenic elements and base, or their mixture in certain ratio.

EFFECT: extended application of Tilorone, restored local immunity and biocoenosis of skin and mucous membranes associated with treatment of purulo-destructive skin processes, provided anaesthetic effect; additional stimulation of reparative processes; improved microcirculation in lesion focus, reduced inflammatory reactions, ensured high therapeutic activity and useability, accelerated and improved healing.

10 cl, 19 ex

 

The invention relates to chemical-pharmaceutical industry, as well as to medicine and veterinary medicine, namely, pharmaceutical preparations for external and local application in the treatment of purulent-destructive processes of the skin and mucous membranes with clinical and laboratory signs of immune deficiency, such as chronic recurrent furunculus, herpetic lesions of the skin and mucous membranes, atopic dermatitis, bacterial pneumonia-fungal lesions, ulcers, postoperative suppuration of wounds and others, to accelerate and improve healing.

The intensity of infection depends on the number and virulence of the pathogen, the state of the natural barriers and the resistance of the microorganism. Susceptibility for most infections is an individual and is usually caused by a lack of immunity. Infectious factor occupies a leading position in the pathogenesis of these common inflammatory diseases of the skin and soft tissues, as acne, boils, carbuncle, impetigo, abscess, cellulitis and other

Infections caused by opportunistic microorganisms occur in people with defects in the immune system, on the one hand, and of the changed biological properties of conditionally pathogenic microorganisms and multiple the x antibiotic resistance, on the other hand. The balance between macro - and micro-organism may be affected by exogenous and endogenous factors (disturbance of activity of the neuroendocrine system, immune deficiency, depletion mechanisms of adaptation associated with chronic pathology and others). The failure of the immune response of the organism to infectious factor entails a chronic infectious process.

The degree of pathogenicity of microorganisms is individual and defines the different activity of the immune answer of an organism to them. It is associated with the ability to attach to sensitive cells (adhesion), to multiply on their surface, to penetrate into these cells or underlying tissues, to overcome nonspecific and specific immunity factors, to exert an immunosuppressive effect (kutasevich AF, her A.N. "The place of external preparations containing guideway acid in the treatment of infectious and inflammatory diseases of the skin and soft tissues", 2006, www.consilium.com.ua/stuff/doctor/dermato venerologiya/Infekcii-koji-i-podkojnoi-kietchatki/Mesto-narujnyh-preparatov/).

Inflammatory skin diseases are among the most frequent pathologies in dermatology. This is due to the edge location of the skin, which leads to the contact and interaction with a variety of exogenous factors. The impact of biological factors (m is croorganisms) on the skin is almost constant.

The microorganisms present on the skin surface, under appropriate conditions can penetrate into the dermis, deponeras in the structural units of the lymphatic system and taking an active part in the formation of toxic-allergic component in the complex system the development of various pathological conditions dermatological profile.

Activated saprofita the microflora of the skin during development dermatopathologist processes has a significant impact on the development and course of primary skin diseases. Many drugs local and systemic application used in the treatment of dermatoses, inhibit the reactivity and immune defense of the organism, increasing the virulence and activity of saprophytic microorganisms. Resident microflora begins to take an active part as a background or pathogenic factor that has a significant impact on the development and course of many diseases ("Evaluation of the effectiveness of drug Fusiderm with pustular skin infections and acne" www.consilium.com.ua/stuff/doctor/dermatovenerologiya/Infekcii-koji-i-podkojnoi-kletchatki/fuziderm-preparat/).

In the treatment of purulent-destructive processes in the skin are widely used for local application of antibiotics and their combinations with corticosteroids, for example, ointment or cream Triderm" - whom inromania steroid remedy, containing a glucocorticoid (betamethasone), antimycotics (clotrimazole) and an antibiotic (gentamicin). Contraindications for the purpose of topical corticosteroids are fungal, meningitis, viral diseases of the skin, perioral dermatitis. With long-term use of halogenated steroids observed skin atrophy, telangiectasia, steroid acne, hypertrichosis, secondary infection. When used on large areas of skin may develop systemic side effects typical of glucocorticosteroids (Aghasyan. "Preparations for the treatment of dermatitis", www.remedium,ru/drugs/drugs/detail.php&ID=10143 t).

Preparations containing corticosteroids (ointments, drops)should not be used in viral diseases of the eyes and skin (including drugs with the addition of antibacterial agents), as well as in connection with the suppression of regeneration processes, the formation of common salt (Handbook of drugs. Hormones of the adrenal cortex and their synthetic analogs", http//pharm.stirol.net/med_search.php?action=show&namenum=751).

Using steroids can disrupt T-cell immune system, which plays an important role in the development of pyoderma (Taaloole, Mpharane. Bacterial skin infection: the problem of choosing the optimal antibiotic", www.rmj,ru/articles_3825.htm).

Thus, the local treatment with corticosteroids in combination with antibacterial drugs do not always lead to the desired result, as it does not restore the immune function of the skin and even more disturbed by her microbiocenosis.

In the dermis of the skin and mucous membranes is a network of lymphatic and blood vessels, are cells of the immune system (T and b-limfocitica, Dandridge cells, natural killer cells and others)that ensures the participation of the skin and mucous membranes in the immune response. Inflammation, especially when purulent-destructive processes, develops a pronounced swelling, skin or mucous membrane infiltrate neutrophils, lymphocytes, eosinophils, they accumulate free radicals and other toxic products of metabolism, which enhance the degradation. In these conditions it is extremely difficult drug to inflammatory foci in their oral and injectable use.

Interferons (alpha, beta and gamma) protect the body from infection by viruses, bacteria and protozoa, inhibit the growth of malignant cells potentiate lymphotoxin. The action of interferon is carried out through a system of cellular synthesis of nucleic acids by a series of enzymes and inhibitors, leading to degradation of foreign genetic information. Interferons stimulate phagocytosis, the activity of natural killer cells, antigen expression. On the other hand, they can ENT is a thief in the formation of antibodies, the development of anaphylactic shock, inflammation, hypersensitivity of the delayed type, which makes interferons true immunomodulators, and interferon - important in the regulation of cellular homeostasis (//med.rehaexpo.ru/2005/participants/direct/production_4073.stm).

Exogenous interferons have drawbacks - allergenicity, toxicity, high price. An alternative way, devoid of the disadvantages of exogenous interferon, is a stimulation of the synthesis of the body's own (endogenous) interferons. It is with drugs-interferonogenous (www.provisor.com.ua/arhive/2000/N20/cyclopheron.htm).

Known drug tricresol, which is an adaptogen and an immunomodulator (interferon inducer), which when used in the form of tablets in complex therapy reduces the period of resuscitation in the treatment of patients with purulent-necrotic wounds, inhibits the growth of herpes, improving the immune status of the organism (Mgorshkov, You "Traceson - founder of a new class of immunomodulators and Immunostimulants (review)". Chemical and pharmaceutical journal. Volume 41, No. 1, 2007, p.3-7).

Traceson has interference activity. In the first hours after administration of trekrezan produced alpha-interferon, which later through the day is replaced by interferon-gamma (Pdelab and other "Immunomodulator Traceson: profile of General and immunotropic activity", http://www.nitek-group.ru/ru/innovations/trecrezane/profile.htm).

However, tricresol not modulate the production of beta-interferon, which reduces its immunomodulatory effects, in comparison with other immunomodulators, such as tilorone. The antioxidant properties of Tricreatine used in cosmetic compositions for topical use (lifting cream "Traceson", http://old.ros-expo.com/wares_full/7486.html).

Not currently known drugs for local application on the basis of trekrezan restoring the immune properties of the skin and mucous membranes in the treatment of purulent-destructive processes.

Known drug meglumine acridonacetate (trade name - cycloferon), which is a small molecule inducer of interferon, which has antiviral, immunomodulatory and anti-inflammatory effect. The main target cells of the drug is T - and b-lymphocytes. It stimulates the production of alpha-, beta - and gamma-interferon (up to 60-80 IU/ml and above) by leukocytes, macrophages, epithelial cells, and tissues of the spleen, liver, lungs, brain, enters the cytoplasm and nuclear structure, activates the synthesis of "early" interferons. Immunomodulatory effect is expressed in the correction of immune status in immunodeficiency States of various origins. The drug has low toxicity. It has no m is tahunnya, teratogenic, embryotoxic and carcinogenic effects.

In the form of tablets of 0.15 g (description of the drug, www.regmed.ru/InstrShow2.asp?InstrLinkNx=a83ba87ba88ba75b and in the form of 12.5% (0.125 g/ml) aqueous solution for intramuscular and intravenous cycloferon is used for the treatment of HIV infection, nairoviruses infection (serous meningitis tick-borne nature, multiple sclerosis, arachnoiditis), viral hepatitis (A, B, C, D), CMV and herpes infections, flu, cancer, immunodeficiency (postoperative period, burns, bronchitis, pneumonia and other), gastric ulcer and 12 duodenal ulcer, cancer, rheumatoid arthritis, deforming osteoarthrosis, spondylosis, skin diseases, atopic dermatitis, eczema, dermatitis, viral papillomas (description of the drug, www.biomedservis.ru/preparat/pr_ cycloferon_liniment.htm).

In the form of liquid ointment - liniment containing 5% N-metilglyukaminovoy salt greenexpo acid, 0.1% of an antiseptic katapola and 1,2-propylene glycol as the basis to 100% (the description of the drug www.znaharka.ru/index.php?productID=92430), cycloferon is used topically for the treatment of genital herpes, urethritis, balanoposthitis (nonspecific, Candida, gonorrhea, and Trichomonas etiology), vaginitis (bacterial and Candida), trichomonosis, skin diseases. The drug is compatible with all drugs (including antibiotics, vitamins, drugs, immunomodulators, interferons (description of the drug www.regmed.ru/InstrShow2.asp?InstrLinkNx=a72ba78ba75ba74b).

Set high antibacterial and antichlamydial effect of the drug due to the activation of the immune system, as well as anti-inflammatory and antiproliferative effect of the drug. Immunomodulatory effect of cycloferon in the form of liniment is expressed in the correction of local immunity in immunodeficient States of different origin and autoimmune diseases (drug description www.znaharka.ru/index.php?productID=92430).

The main cells producing interferon after administration of the drug in the form of liniment are lymphoid elements of the mucous membrane: the macrophages. T - and b-lymphocytes, and epithelial cells (http://www.biomedservice.ru/preparat/pr_cycloferon_liniment.htm). The main area of application of 5% of cycloferon liniment is the treatment of herpetic infections, and infections, sexually transmitted diseases.

It is known that the immune response to the action of cold is not more than 40% of patients (www.mtu-net.ru/doctor99/5nklassifik1polioxidoniy2905.htm).

The drug is available for local and external use in the form of liniment. This form is convenient for vnutribryushnogo introduction, but inconvenient for outdoor use, as it is not fixed on the surface of the lesion or wound and quickly settled on dries.

Known for one of the most powerful inducers of endogenous interferon - Celoron (www.amixin.ru). which is available as an oral drug (trade name "Amiksin", the statement on the drug http://www.resmed.ru/InstrShow2.asp?InstrLinkNx=41ba48ba44ba43b or "Lawmax", the statement on the drug, http://www.resmed.ru/InstrShow2.asp?InstrLinkNx=a41ba48ba44ba43b).

It is used in the treatment of viral hepatitis a, b, C; Kirpichenko and CMV infection, the treatment of infectious-allergic and viral encephalomyelitis (multiple sclerosis, leukoencephalitis, weanteefult), chlamydial infections of the urogenital and respiratory tract, prevention of influenza and other acute respiratory viral infections.

Tilaran is a low molecular weight synthetic inducer of interferon stimulated in the body of interferons alpha, beta and gamma. The main producers of interferon in response to oral administration of tilorone are cells of the intestinal epithelium, hepatocytes, T-lymphocytes, neutrophils and granulocytes. After oral ingestion, the maximum production of interferons is in the sequence of intestine - liver blood through 4-24 hours.

Tilaran in human leukocytes induces the synthesis of interferon stimulates the stem cells in the bone marrow, depending on the dose increases antibody production, reduces the degree of immunosuppression, restores sootnoshenie the T-suppressor and T-helper cells. The antiviral mechanism of action is associated with inhibition of translation virusspecific proteins in infected cells, resulting in suppression of reproduction of viruses. It is effective against pathogens of viral hepatitis, herpes viruses, including cytomegalovirus (instructions on the drug, http://www.resmed.ru/InstrShow2.asp?InstrLinkNx=a41ba48ba44ba43b).

After oral administration tilaran rapidly absorbed from the digestive tract. Its bioavailability is 60%. Tilaran quickly into the blood and distributed in organs, tissues and biological fluids. About 80% of tilorone associated with plasma proteins. Report the drug virtually unchanged in faeces (70%) and urine (9%) with a half - life is 48 hours. Tilaran in the body does not undergo metabolism and is not cumulated (information about the drug "Amiksin", http://www.vidal.ru/vidal_main/doc_5533.htm).

Tilaran as a modulator of cytokine reactions and antioxidant, oral is used in secondary prophylaxis of multiple sclerosis (Vigalance and other "Secondary prevention of multiple sclerosis using the domestic drug Amiksin modulator of cytokine reactions and antioxidant", //home.peterstar.ru/nwams/amixin2.html).

It is known that tilaran oral is used in complex therapy of tick-borne encephalitis (V. Tarasov. "Tick-borne encephalitis, Honey is health paper No. 34, 2003, www.neuronet.ru/bibliot/b001/mg34_03.html).

Tilaran is not only effective antiviral agent, but also increase the body's resistance to infections caused by bacteria, fungi and protozoa. He has an activating effect on macrophages. This increases not only the absorption capacity of phagocytes, but also development of these cells reactive oxygen species, providing a bactericidal effect. Tilaran has a stimulating effect on the phagocytic and bactericidal function of macrophages, while reducing the intensity of the reaction of lipid peroxidation. It activates natural killer cells, which play a leading role in antitumor defense of the organism.

Tilaran as immunomodulator has an antitumor effect against virusinduced tumors. In combination with anticancer drugs, it encourages a more significant inhibition of tumor growth, reduces the frequency and degree of metastasis, sometimes completely preventing it. In large doses tilaran directly suppresses tumor growth. Tilaran in combination with cytotoxic drugs can reduce their dosage in half without changing the quantitative characteristics of the antitumor effect. It also reduces the severity of side effects of radiation therapy, and the introduction of the sick in front of operation the m intervention provides a more rapid healing of wounds, prevents metastasis and the development of infection. Tilaran has anti-inflammatory activity, allowing you to use it effectively in the treatment of diseases such as multiple sclerosis, rheumatoid arthritis, silicosis. It inhibits platelet aggregation, while the magnitude of the effect is not inferior to aspirin, and the duration exceeds it. The local application on the damaged herpes skin and eyes it provides a direct inactivation of the virus of herpes (Toolipohja, Naholosko. "TILARAN: PROFILE of BIOLOGICAL ACTIVITY I. PHARMACOLOGICAL PROPERTIES http://magazine.odmu.od.ua/antropo/2006/1/18 .pdf).

Tilaran well compatible with antibiotics and traditional means of treatment of viral diseases (www.amixin.com.ua).

It is easily soluble in water (about 10% at 20° (C) in 95% ethanol (about 3.3% at 20° (C) (Pharmacopeia enterprise Fund 42-0416-4243-03). This makes it promising for use in preparations for local and external use.

However, currently no known pharmacological agents in the form of finished dosage forms for local and external use containing the active substance - tilaran.

Object of the present invention is to provide pharmaceutical preparations for local and external application based on the active substances of low molecular weight is of inductor interferon.

Technical results that may be obtained by using the present invention: expanding the field of application of the known active substances - tilaran, restoration of local immunity and biocenosis of the skin and mucous membranes in the treatment of purulent-destructive processes of the skin, getting the anaesthetic effect; stimulation of reparative processes; improvement of microcirculation in the lesion, inflammation reactions, ensuring a high therapeutic activity and convenience in use, acceleration and improvement of healing.

To solve the stated problem, the present invention features a pharmaceutical product for local and external use containing the active substance is a small molecule inducer of interferon, the target additive and the base, which as a low molecular weight interferon inducer contains Celoron, for example, in the following ratio of components (wt.%):

tilaranof 0.001-10,000
target additive0,000001-30,500000
basethe rest of it.

The target additive is a substance having antibacterial activity against gram-positive and/or gramatical the selected bacteria, or antimycotics, or local anesthetic substance, or a stimulator of reparative processes, or yooxygen, or biogenic elements in the form of physiologically acceptable compounds or their physiologically acceptable mixture, for example, the next number in the preparation composition (wt.%):

a substance having antibacterial activity
against gram-positive and/or
gram-negative bacteria0,01-13,00
antimycotics0,50-3,00
local anesthetic substance0,50-4,00
stimulator reparative processes0,50-4,00
yooxygen0,001-1,000
biogenic elements0,000001-5,50.

As compounds having antibacterial activity against gram-positive and/or gram-negative bacteria may be, for example, an antibiotic, or bacteriolytic complex and proteolytic enzymes, such as isoamylase, or Trilon B, or ethyldimethylamine acid, or their mixture, for example, the next number in the preparation composition (wt.%):

antibioticfrom 0.01 to 5.00
the bacteriolytic complex and
proteolytic enzymes0,1-5,0
Trilon B0,01-2,00
ethyldimethylamine acid0,01-1,00.

When this antibiotic is, for example, gentamicin sulfate, or sodium salt guideway acid, or their mixture.

As antimycotics may be, for example, clotrimazole or ciclopiroxolamine.

In the proposed local anesthetic drug substance can be, for example, cinoxacin, trimekain, piromekain, lidocaine, anastasin or their mixture.

In the proposed drug substance, which is a stimulator of reparative processes may be, for example, methyluracil, atsemin, etagen, calcium Pantothenate, solcoseryl, katapola or their mixture.

In the proposed drug antioxidant may be, for example, succinic acid.

Part of the preparation may include the following biogenic elements in the form of physiologically acceptable compounds, for example zinc, or manganese, or their physiologically acceptable mixture, the next time their content in the product (wt.%):

zinc0,000020-5,0
manganese0,000001-0,5.

In accordance with the invention dosage forms for local and external use on the basis of tilorone are liquid dosage forms, such as solutions, suspensions and emulsions in the form of liniments, buttery soft medicinal forms, such as ointments, gels, creams, and also formed of soft medicinal forms suppositories and capsules for rectal or vaginal application.

As the basis in the preparation for topical application containing tilaran offers hyperosmolar substances or physiologically acceptable mixture of hyperosmolar substances in combination with the components that are specified, for example, rheological, Foundation requirements, depending on the dosage form of the drug.

It is known that in the intact Horny layer of the epidermis there are no channels through which could penetrate deep into the skin particles with sizes above 10 nm. Moreover, the larger the molecule, the lower its permeability through the TRANS-epidermal water barrier. It is established that substances with molecular weight of 100 kilodaltons not overcome TRANS-epidermal water barrier, i.e. this value is the limit of the permeability of the skin. Through the microchannels, which determine the permeability of the skin, characterized by the most probable intercellular path transport link is through the top of the flake keratin layer of the epidermis.

The most important role in the implementation of barrier-protective functions in the permeability of the skin plays state of water molecules present in the microcapillary holes Horny and shiny skin layers. Water inside the microchannels is substantially in the structured condition, which significantly slows down the process of Brownian motion, which is responsible for the alignment of the concentration gradient, i.e. permeability.

Ordered structural organization of water in the micro capillary holes of the stratum corneum prevents intensive water evaporation from the skin surface, creating an additional barrier to the dehydration process. Nevertheless, water, oxygen, nitrogen and other low-molecular substances sufficiently easily diffuse through the skin. When this substance is able to react (contact) with fragments of the epidermis, including cellular systems, initially reach saturation in the epidermis, and then begin to interact with the deeper layers of the skin.

The intercellular substance of the epidermis and dermis gel is formed, for example, hyaluronic acid or of substances similar to it. This kind of gel having a mesh structure is convenient to associate a variety of low - and high-molecular substances (salts, sugars, amino acids, vitamins, is aptidon, proteins, metabolic products of the cells of the epidermis and so on). The living cells of the epidermis with greater or lesser efficiency of the delayed portion of the substances that pass through the cornea and shiny layers.

With regular use the same type of drug and cosmetics for external use processed these funds fragments of skin are in a constant state of saturation at which the concentration in the skin remains virtually unchanged. However, many low molecular weight components of the applied drug may quite easily overcome TRANS-epidermal water barrier. 60% plasma and 45% of the plasma proteins penetrate daily from microcapillaries of the circulatory system tissues, including the epidermis. Returning to the circulatory and lymphatic system, they carry with them associated protein metabolites (products of cell activity - toxins) and catabolites (biologically active substances, peptides, proteins, etc. are synthesized inside the cell). Substances to break the TRANS-epidermal water barrier, also appear in the blood and in accordance with this affect all tissues of the body.

When the destruction of living cells of the skin (for example, when purulent-destructive processes) of the cells are substances that stimulate primarily the local immune system (T-lymphocytes), is activating the s near the damage of macrophages (Langerhans cells), which, in turn, synthesize and release into the environment a variety of stimulators of cell division, promoting the elimination of violations of the cellular system.

Langerhans cells reside in the basal layer of the epidermis. They have from 2 to 5 processes, penetrating to the granular layer and penetrating into the basement membrane. The role of these cells in the first place is reduced to the speed regulation of cell division in the basal layer, in a variety of types of violations of its structure (Angelina. "theory of soft cosmetic effects. Modern cosmetology", Novosibirsk, "Nauka", 2000. www.golkom.ru/book/48_1.htm).

Thus, a basic requirement for products for local and external use with tilorone is the efficient transport of active substances to the cells responsible for the stimulation of local immunity and restore the immune properties of the skin and mucous membranes.

When local treatment of purulent-destructive skin lesions is important to the transport of active agents to the lesion through the TRANS-epidermal water barrier in the case of subcutaneous location of the hearth or in the depth of the wound if its superficial location. In addition, an important factor in successful therapy of purulent-destructive skin lesions is effective transport of toxic products of metabolism from the chaga lesions to the skin surface. Most fully satisfy these requirements hydrophilic base with hyperosmolar properties.

Osmolar hydrophilic solvents, for example aqueous solutions of salts, alcohols and aqueous solutions (for example, ethyl or isopropyl), glycerine, low molecular weight polyethylene oxides (e.g. PEO-400), propylene glycols (for example, 1,2-propylene glycol), and others, can easily penetrate through the TRANS-epidermal water barrier or deep wounds, transporting dissolved active substance to the lesion and displacing toxic products of metabolism out of the affected area. Due to their Smolarek properties they bind water, in cellular systems, thorn and granular layers, which leads to decreasing of cellular systems, and consequently increase the intercellular space and the cross section of microchannels, i.e. to increase the permeability of the epidermis. In addition, they thin the hyaluronic acid gel that fills the intercellular space, which is an additional factor increasing the permeability of the epidermis.

If hyperosmotic conditions are created by adding salt systems, the permeability of the epidermis which will increase even further due to changes in the structure of the micro capillary channels Horny and shiny layers, since the saturation of the cavities channels positively anagennisi metal ions (like Na +structure of the channels are transformed into the structure (mechanism type "flip-flop") with the increased diameter of the channel due to the electrostatic repulsion of the positive charges localized on the metal atoms (monographs Angelina "Theory soft cosmetic effects. Modern cosmetology", Novosibirsk, "Nauka", 2000, www.golkom.ru/book/48_1.htm).

To restore the immune function of skin and mucous membrane in the present invention is used for local and external use of small molecule inducer of interferon - tilaran. In the form of drugs for local and external application it can be used for local therapy in dermatology in the treatment of purulent-destructive processes of the skin and soft tissues, such as recurrent furunculus, acne vulgaris, burns, nonhealing wounds of soft tissues, etc. in Addition, promising its use as drugs for local and external use in Allergology and immunology in complex treatment of allergic dermatoses, especially associated with fungal and herpes infection, and the treatment of urogenital infections, sexually transmitted diseases.

The local impact of tilaran increases expression on the cell membrane antigens major histocompatibility complex (HLA) class 1 and class 2 (HLA-DR), increasing the et number and increases the activity of NK-cells, causes targeted polarization Th0->Th1, modulates the inflammatory response depending on the phase of inflammation, has a positive influence on the state of local immunity, has direct and indirect effect on viruses, intracellular bacteria, fungi.

Celoron, being a low-molecular substance (molecular weight 483,5), dissolved in a hydrophilic liquid and hyperosmolar basis, with local and external use easily penetrates deep to the skin and mucous membranes, responsible for local immunity in the area of impact of the drug.

Tilaran having antioxidant properties, penetrates into the affected tissue of the hydrophilic base, reducing secondary tissue necrosis around the wound or lesion.

Using liquid low molecular weight hydrophilic and hyperosmolar basics and tilorone made solutions for local applications, lotions, liniments, emulsions and suspensions having a high penetrating power.

Add to hydrophilic solvents hydrophilic thickeners with sorption properties, such as high molecular weight polyethylene oxides (e.g., PEO-1500), proksanola (for example, procesadora-268), polyvinylpyrrolidone medical (for example, with molecular weight of 12600±2700 or 8000±2000) or other substances possess is their sorption properties (for example, alginate calcium or magnesium), enhances the transport of toxic products of metabolism from the hearth subcutaneous lesions or depth of the wound to the skin surface.

So, for example, molecules PEO-1500, due to relatively high molecular weight stably retain the primary localization: they remain in the microchannels of the stratum corneum of the epidermis or in the wound cavity and actively associated inflammatory exudate, transporting it to the surface of the skin, with which the liquid evaporates. The released molecules PEO-1500 newly added to the water itself, and the process is repeated ("Theory and practice of local treatment of purulent wounds". Edited by Prof. Bamzatenka. Kiev, Health, 1995, str-235). Soft hydrophilic and hyperosmolar basis consisting of low molecular weight hydrophilic solvent with hyperosmolar properties, hydrophilic thickener-sorbent and tilorone, are made of mild forms for local and external use: ointments, creams, gels, suppositories, with high penetration and absorption capacity.

Liquid and soft hydrophilic compositions on hyperosmolar basis also filled gelatin capsules for rectal and vaginal application.

For a comprehensive impact on the center of purulent-destructive lesions in the proposed drug entered a substance having antibacterial Inoi activity against gram-positive and/or gram-negative bacteria.

This substance is, for example, the antibiotic gentamicin sulfate, sodium salt guideway acid or their mixture.

Gentamicin sulfate is a porous powder, easily soluble in water, but practically insoluble in alcohol. He belongs to a group of antibiotics-aminoglycosides. Bacteriostatic action against many gram-positive and gram-negative microorganisms, including Proteus, E. coli, Salmonella, etc. there are strains of staphylococci resistant to penicillin. Gentamicin sulfate for local application is used as a 1% ointment on paravenously the basis for the treatment of pyoderma, paronychia, sycosis, infected seborrheic dermatitis, folliculitis, furunculosis, acne vulgaris, secondary bacterial infection, fungal and viral infections of the skin (www.nizhpharm.ru/user/products/p1127.htmt). Such basis as hydrophobic, does not provide the penetration of the antibiotic through the TRANS-epidermal water barrier to the lesion.

Positieve acid, for example, in the form of sodium salt is a crystalline powder, soluble in water and alcohol. Effect on staphylococci, meningococci, gonococci. Against pneumococci and streptococci much less active. Staphylococci resistant to penicillins, streptomycin is, to chloramphenicol, erythromycin and other antibiotics, sensitive to guideway acid. The drug is not active against Escherichia coli, Salmonella, Proteus and other gram-negative bacteria, and fungi, and protozoa. When combined guideway acid with other antibiotics there has been a considerable strengthening of its action on sensitive microorganisms her. It affects germ cell bakteriostaticheski.

The mechanism of action is associated with a rapid inhibition of protein synthesis. Advantage guideway acid in the treatment of chronic torpid forms of infections of skin and soft tissues, as well as secondarily infected dermatoses is its wide pharmaceutical profile, low resistance and lack of cross-resistance with other antibiotics, as well as high interroga ability. Positieve acid is able to influence the local immune response of the skin, inhibiting the secretion of interleukins, tumor necrosis factor. It is also known that positieve acid at clinical concentrations of an inhibitor of chemotaxis of neutrophils and inhibits the function of T-lymphocytes. Sodium salt guideway acid has a high permeability through the intact skin (kutasevich AF, her A.N. "The place of external preparations containing guideway acid in the treatment of infectious especiallyh diseases of the skin and soft tissues", www.consilium.com.ua/stuff/doctor/dermatovenerologiya/Infekcii-koji-i-podkojnoi-kletchatki/Mesto-narujnyh-preparatov/).

For local and external use positieve acid is used in the form of gels. For example, in the form of a 2% gel Fuzidinu containing acid guideway 2 g of zinc oxide 3 g glycerol 20 g of sodium carboxymethyl cellulose 3.5 g, nipagina 0.08 g, distilled water to 100 g Prescribed this gel with purulent-inflammatory diseases caused by sensitive to guideway acid by microorganisms (superficial folliculitis, furunculosis, pyoderma, impetigo, hydradenitis, superficial and limited burns, deep wounds, abrasions and other), or 2% gel Prishtina containing acid guideway 2 g, prednisolone 0.5 g, zinc oxide 3 g and other substances distilled water to 100 g of This gel is used externally for inflammatory skin diseases and in treatment of dermatoses (eczema, neurodermatitis and other) (www.prodenas.ru/go.php?name=bme&mtype=b&type=DRUG&sid=1366&file=pv).

Positieve acid as sodium salt is also used in ointments, for example in the ointment Fucked containing 2% sodium salt guideway acid, 1% methyluracil, and auxiliary substances: polyvinylpyrrolidone (PVP) low-molecular medical 12600±2700, anhydrous lanolin, vaseline medical, distilled water (www.biosintez.com/preparat.asp?id=183).

Another substance, work is their home purulent-destructive lesion with antibacterial activity against gram-positive bacteria, is the complex of bacterial plankton and proteolytic enzymes.

Known complexes bacteriolytic enzymes that lyse gram-positive microorganisms resistant to antibiotics (patent RU 1549227, C12N 9/00, 1995.12.20; EN 2193063, C12N 9/00, 2002.11.20).

Complex bacteriolytic enzymes (patent RU 1549227), used in medicine under the name isoamylase, and in veterinary medicine - Litmash, consists of three bacteriolytic enzymes immobilized on the polysaccharide, which increases their stability. The polysaccharide provides long-term (over several years) high activity of its constituent enzymes, and immune-stimulating properties of the drug isoamylase.

Bacteriolytic enzymes included in the active complex of the drug destroys the cells of a wide range of gram-positive pathogens such as staphylococci and streptococci, including those with multiple resistance to antibiotics, the radio micrococci, meningococci, gonococci, gram-positive bacilli. Due to the presence in the complex of proteases and enzymes, possessing at the same time and proteolytic activity, the product cleans the wounds of necrotic masses. Fragments of the destroyed cells possess immune stimulating effects.

Clinical trials of the drug showed that Litani the Aza in the treatment of purulent wounds of soft tissues accelerates compared with other traditional and non-traditional means in the course of the wound process. Faster decrease the microflora content, faster than normal they, faster rejection of necrotic masses, faster granulation and even the epithelial tissues. The duration of treatment of patients with purulent wounds of soft tissues were reduced in many cases in 2 times.

Isoamylase stimulates reparative processes, providing, in addition to necroticism and bacteriolytic action, influence on the course of the 2nd phase of inflammation, not only by reducing the 1st phase, which is typical for all enzyme preparations used to treat in such cases, but also by directly stimulating effect on the cells of granulation tissue, acting directly on the cells of proliferate. Clinical studies have also shown that the topical treatment of deep burns 1% solution lizoamidazy it helps cleanse the wounds of necrotic tissue and purulent discharge, in addition, it is effective in the treatment of oily seborrhea and mild acne.

On the basis of this complex developed pharmaceutical product manufactured in the form of dried powder, Packed in 10 ml vials of 50 PE 100 PE with hermetically sealed with rubber stoppers. The package includes a base - solvent in ampoules of 5 ml at a rate of 1 vial of 50 PE (monograph FS-3329-96 and FS 42-3332-96). The preparation is applied as a liquid in phosphate buffer solution with a concentration of 5 PE (LE 50) in 1 ml; 10 PE (LE 100) in 1 ml; 25 PE (LE 250) in 1 ml Therapeutic range of concentrations lizoamidazy in the solution is from 0.5 to 5%.

As substances that violate the structure of the membranes of gram-negative microorganisms, in the proposed solution used as ethylenediaminetetraacetic acid (EDTA), its disodium salt (Trilon B), or their mixture.

EDTA reduces the resistance of bacteria to antibiotics and other antimicrobial substances, especially those which ions of calcium and magnesium are antagonists manifestations of their antimicrobial action, for example, polymyxins and aminoglycosides. Therefore, EDTA can be used in conjunction with aminoglycosides in the proposed drug, such as gentamicin sulfate, to reduce the resistance of microorganisms to them. Continuous exposure to EDTA with various kinds of microorganisms in the cells of the latter is the nucleic acid, leading to their lysis. In addition to effects on cell membrane and metabolism of bacteria EDTA induces loss of plasmids in strains of transductant Staphylococcus, and prevents genetic transfer of R-plasmids in staphylococci that inhibits the transduction of sustainability, for example, to erythromycin 200 times.

Trilon B has the expressed damaging effect on the microbial cell, as is chelat forming substance, binding ions of bivalent metals, which leads to loss of membrane lipopolysaccharide complex. In the result, the cell wall becomes fragile, increases its permeability to various substances, including antimicrobial action.

Trilon B exerts a bacteriostatic effect against strains of gram-negative and gram-positive pyogenic bacteria: Staphylococcus and Bacillus blue-green pus in a concentration of 0.075%, Proteus and Escherichia coli - 0,15%.

For the treatment of purulent-destructive skin lesions with polyvalent microflora Trilon B must be used with antimicrobial means of directed action. In these cases, Trilon B, increasing the permeability of the walls of microbial cells, enhances the sensitivity of microorganisms to antimicrobial agents such as antibiotics. Trilon B has a conservation action for drugs ("Theory and practice of local treatment of purulent wounds". Edited by Prof. Bamzatenka. Kiev, Health, 1995, str-144).

Because the mechanisms of action of antibiotics, EDTA and trylon B on gram-negative and gram-positive microorganisms are different, to enhance the lysis of gram-negative and gram-positive microorganisms suitable joint application which of these substances in one medicinal product, for example, in the form of complexes: gentamicin sulfate (0,5-1,00%) and EDTA (0.01%of -0,20%); EDTA (0,01-0,20%) and Trilon B (0,05-2,0%), gentamicin sulfate (0.5 to 1.0%), EDTA (0.01 to 0.20 per cent) and Trilon B (0,05-2,0%).

For complex effects for fungal infections of the skin in the proposed drug is introduced antimycotics, such as clotrimazole or ciclopiroxolamine.

Clotrimazole is an antifungal drug for topical and local use, a derivative of imidazole. Its mechanism of action consists in inhibition of the synthesis of ergosterol, an essential for building cell membranes of fungi, which leads to violation of its permeability and the subsequent lysis of the cells. The drug also causes increased permeability of phospholipid membranes of liposomes, vacuolization of the cytoplasm, reducing the number of ribosomes. In addition, clotrimazole inhibits peroxidase activity, which facilitates the accumulation of fungal cell hydrogen peroxide, which takes part in its destruction. He has a broad spectrum of action: effective against dermatophytes, yeast fungi, antibacterial effect on Staphylococcus and Streptococcus spp. When applied externally, the concentration of the drug in the epidermis than in the dermis and subcutaneous tissue.

Clotrimazole after application on the skin is absorbed in the quantity not exceeding 1%but penetrates into the stratum corneum of the epidermis it accumulates. To a small extent absorbed from mucous membranes (3%). The absorbed drug is metabolized in liver and excreted by the kidneys; the half-life is 3-5 hours (//medi.ru/doc/g2713.htm). The preparation is applied as a 1% ointment, 1% cream, 2% gel and 1% solution for topical use.

Ciclopiroxolamine - antimycotics broad-spectrum, highly active against dermatomitsetov and yeast fungi, gram-positive and gram-negative bacteria, mycoplasmas and Trichomonas. The fungicidal action of the drug is associated with inhibition of transmembrane transport of amino acids, K+ and phosphate in growing cells of fungi. This drug almost no toxic effect on the body, well released from the base, selectively accumulate in the epidermis and its derivatives (www.medicreferat.com.ru/pageid-1053-4 .html). The medication comes in the form of a 1% solution for topical use, 1% cream (www.yarapteka.ru/modules.php?name=spr&inf=283).

Violation of microcirculatory is one of the main factors in the pathogenesis of the inflammatory process. It includes not only the blood flow through the arterioles, capillaries and venules, but also the transcapillary exchange, providing the necessary for living tissue homeostasis. Disorders microcirculation divided into intravascular changes, disorders of the vascular and extravascular changes. Shortly after the initial range of products, used to improve the processes of microcirculation in the tissues of the wound, to a considerable extent can be implemented at the expense of their antihistamine, anti-inflammatory and dehydrating steps.

The use of trylon B in the proposed product provides an improvement of microcirculation in the tissues of the wound, as Trilon B reduces the activity of histamine. Being a water-soluble antioxidant, Trilon B also reduces secondary tissue necrosis around the wound or lesion when it is used in the proposed drug ("Theory and practice of local treatment of purulent wounds". Edited by Prof. Bamzatenka. Kiev, Health, 1995, str-185).

Succinic acid (or a salt thereof, e.g. the succinate) is geboortedatum, normalizes the content of histamine and serotonin in the body, improves microcirculation in organs and tissues (Aigain "Oxidative stress and the use of antioxidants in neurology, www.medmoskva.ru/news/Out.aspx?Item=19107). As the load increases on any of the systems of the body maintain its operation is ensured mainly by the oxidation of succinic acid.

Power system products using succinic acid, hundreds of times superior to all other systems of energy production in the body. It provides a broad range of nonspecific therapeutic action of succinic acid and its salts. To the ome, succinic acid has effects such as act-protective and anti-viral (Savalanche "Reamberin - a new tool for infusion therapy in the practice of medicine critical conditions", www.critical.ru/consult/pages/reamberin.htm).

One of the main goals of treatment of purulent-destructive lesions of skin and mucosa is the problem of suppression of pain.

To solve this problem in the proposed drug as the target additives applied local anesthetic substance, which can be used cinoxacin (a derivative of quinoline), with bacterial and antioxidant activity, lidocaine, trimekain, keeping the activity in an acidic environment, which is characterized by a purulent wound, piromekain, benzocaine, dibucaine.

Lidocaine, trimekain and piromekain the most promising part of the proposed drug in a hydrophilic base.

For the proposed drug on the basis of fats should be used, for example, benzocaine (benzocaine) and dibucaine.

The proposed remedy based tilorone contains material wound healing actions (methyluracil, atsemin, etagen, calcium Pantothenate, solcoseryl, katapola or their mixture) to provide additional stimulation of repair processes in the wound.

Methyluracil, being a derivative of pyrimidine, the region is AET anabolic and anti-catabolic activity. The substance does not have a local irritant, accelerates cell regeneration processes, reducing the healing time of wounds, stimulates cellular and humoral defense factors, anti-inflammatory, stimulates Erythro - and leucopoiesis.

The atsemin accelerates tissue regeneration and epithelization processes. It is used for the treatment of nonhealing wounds and burns.

Atadan stimulates reparative processes in epithelial and hematopoietic tissues, activating the metabolism of nucleic acids, indicated for the treatment of thermal and radiation injuries of the skin, the mucous membrane of the rectum, nonhealing granulating wounds, etc.

Solcoseryl - extract blood of cattle, released from proteins and non-antigenic activity. Substance accelerates the growth of granulation and epithelization of wounds, improves metabolic processes in the tissues ("Theory and practice of local treatment of purulent wounds". Edited by Prof. Bamzatenka. Kiev, Health, 1995, str-187, 191-196).

The katapola stimulates tissue regeneration. In addition, it has anti-inflammatory, burn and antispycheck action (http://www.recipe.ru/docs/ls/index.php?filter=bysearch&filter_param=Katapol&action=descr-drug-table&drugid=5777).

Pantothenic acid as calcium Pantothenate (vitamin b5) is a promising ranozazhivlyayuschim the tool. Is used to treat burns and slowly healing wounds. Pantothenic acid, as a component of coenzyme A, plays a key role in the metabolism of carbohydrates, proteins and fats, so it is important for the maintenance and repair of all tissues. She is involved in reactions that provide energy to the cells and takes part in the synthesis of essential compounds, such as sterols (e.g. cholesterol), hormones (such as growth hormones, stress and sex hormones), neurotransmitters (e.g. acetylcholine), phospholipids (components of cell membranes), porphyrin (a component of hemoglobin, antibodies, and is also involved in drug metabolism (Basic vitamins", the DSV Nutritional Products, www.dsm.com/ru_RU/html/dnpru/hnh_maininfovit_index_basics_panto.htm).

Zinc is a component of over 200 enzymes (www.osteoform.ru/products/calc.htm). It provides the transfer of carbon dioxide, the stability of biological membranes, promotes the healing of wounds (http://vitamini.solvay-pharma.ru/elements/article.aspx?id=1816). Zinc participates in the processes of division and differentiation of cells, formation of T-cell immunity, the functioning of many enzymes, insulin, pancreas, antioxidant enzyme superoxide dismutase, sex hormone dehydrocorticosterone, plays an important role in the regeneration processes of the skin, hair, nails, secretion of the sebaceous glands. the n promotes absorption of vitamin E and maintenance of the normal concentration of this vitamin in the blood.

Zinc strengthens the immune system, promotes healing, because it plays an important role in protein synthesis (www.microelements.ru/Zn). Insufficient concentration of zinc in the body leads to dysfunction of the immune system. When zinc deficiency is the accumulation of toxic metals, poorly healing wounds, develop skin diseases. Zinc supplements stimulate the production of white blood cells - one of the antitumoral immune system components, and support the overall activity of T-lymphocytes and natural antitumor cells (natural killer cells) (//mirzdorovia.com.ua/spravka2.php).

Manganese is an essential element for the protection of body cells. It is needed for wound healing. The absorption of manganese contribute to zinc and vitamin C (//mirzdorovia.com.ua/spravka2.php). Manganese inhibits free radical oxidation, ensures the stability of the structure of cell membranes; provides for the development of connective tissue; involved in regulation of the metabolism of vitamins C, E, C. Cutaneous manifestations of manganese deficiency are disorders of pigmentation of the skin, the appearance of fine scaly rash, vitiligo, stunting hair and nails. Its deficiency also leads to disorder of the immune system, allergic reactions, (www.microelements.ru/Mn).

As the preservative in the proposed pharmaceutical product is used, for example, imagin, possessing antimicrobial activity. In addition, Trilon B and hyperosmolar basis also have a preservative effect.

From a microbiological point of view due to the presence of an external polysaccharide membranes and hydrophilic capsules in gram-negative and gram-positive bacteria, which prevent the penetration of microbial cells hydrophobic antibacterial substances, hydrophilic base is preferable, as are the conductors of medicines in the microbial cell ("Theory and practice of local treatment of purulent wounds". Edited by Prof. Bamzatenka. Kiev, Health, 1995, str).

The hydrophilic base, which can be applied with Trilon in the proposed drug, divided into two groups:

water - soluble bases which, as a rule, contain purified water, hydrophilic non-aqueous solvents include polyethylene oxide, for example PEO-400, 1,2-propylene glycol, glycerin, ethyl cellosolve, dimexide, and water-soluble polymers include polyethylene oxide, for example PEO-1500, proxanol is chosen, for example proxanol is chosen-268, polyvinylpyrrolidone, for example 8000±200 or 12600±2700;

- vodosnabzhenie basis, which in addition to water-soluble polymers and hydrophilic non-aqueous solvents contain lipophilic substances: higher fatty alcohols, vaseline, vaseline oil, lanolin, waxes (these are the basics, as a rule, pre the tute emulsion type oil/water and require the presence of emulsifier type oil/water).

Basics with hyperosmolar properties play an important role in the local treatment of purulent-destructive lesions. They provide an outflow of purulent exudate from a wound or lesion, have anti-inflammatory effect due to absorption of fluid and reduce swelling, and also protect tissues from overhydration. Often they contribute to the strengthening of action of antibacterial agents.

In addition, the use of hyperosmolar basis also improves microcirculation in the tissues of the wound due to its dehydrating action. When applied the basis consisting of hyperosmolar substances, has an indirect anti-inflammatory effect due to the absorption of fluid and reduce swelling of the wound or skin lesion.

For substances with high hyperosmolar properties include oxides - water-soluble polymerization products of ethylene oxide, which are physiologically indifferent compounds. In this class of substances are hydrophilic nonaqueous solvents - PEO-400, 1,2-propylene glycol, glycerin, ethyl cellosolve, Dimexidum and polymers (polyethylene oxide, for example PEO-1500, proxanol is chosen-268, polyvinylpyrrolidone). They are easy to apply on the wound surface and evenly it is distributed, improving the contact with the juvenile tissues and content wounds, well mesivta with wound exudate and retain their homogeneity, low toxicity and have no irritant action on the tissues, do not violate their physiological functions.

The ability of polyethylene oxides (PEO) to provide antimicrobial drug interstitial action fundamentally distinguishes this ointment base from fat frameworks or solutions of antibiotics (antiseptics), antimicrobial action of which is limited only by the surface of the wound, although it was deep microflora determines the intensity and direction of flow of a purulent process.

The main property of PEO is that they have a strong dehydrating (water-absorbing) action on the fabric. Due to its high ability to hydrogenate itself, these polymers actively absorb wound exudate, and with it, and microbial toxins, Pro-inflammatory cytokines - products of tissue destruction, as well as various biologically active substances of lysosomal enzymes and other mediators of the inflammatory process, thereby interrupting its progressive course. Of fundamental importance is the fact that in the festering wound or skin lesion dehydrating effect PEO covers not only fabrics, but also contained in the wound or lesion microbial cells.

Dehydration of microbial cells leads to a significant reduction of their biological activity, and including, the mouth is echeveste to the action of certain medicines. Therefore, in the presence of PEO tenfold increases antimicrobial activity of antibiotics. Is also important that the dissolution of antibiotics, sulfonamides and other substances in PEO increases their dispersion with increasing therapeutic activity, which also contributes to a more rapid release of the fundamentals of antimicrobial substances.

PEO is an active conductor of drugs through the skin barrier. Importantly, this penetrating without damage to the cells the ability of PEO increases in conditions of inflammation.

The hydrophilic base on the oxides can dissolve in the secrets of the mucous membranes, to fully release the medicinal substance, not to irritate, have a long shelf-life, high physiological indifference, which facilitates their use in liquid, buttery and formed of soft medicinal forms.

Important biomedical requirement ointment soft medicinal forms, is the ability to moisten the wound surface and to spread it, due to the surfactant properties of solvents, polymers, surfactants and bases in General. The most pronounced surface activity are alcohols and ethyl cellosolve, which is unsuitable for inclusion in the composition of the new in high concentrations.

From glycols preferably the use of 1,2-propylene glycol and PEO-400, compared with glycerol, with a weak surface-active properties.

When mixed solvent PEO-400 polymer PEO-1500 latter acts as a thickener, which, depending on the number in the total mass of the drug provides the desired texture created the dosage form. In addition, PEO-1500 is an osmotically active substance, absorbing purulent exudate due to the binding of water molecules with hydroxyl and ether groups.

Proxanol is chosen-268 - block copolymer of propylene oxide and ethylene as osmotically active substance provides a more uniform nature of the absorption and has a longer period of osmotic action. The total mass of absorbed water solutions proxanol is chosen-268 24 hours significantly exceeds that in the case of the use of PEO-1500. This is due to the higher mass of proxanol is chosen-268 (8.7 times greater than that of PEO-1500).

The kinetics of water absorption solvents and polymers depends on their molecular weight, concentration, and molecular structure. For example, PEO-400 absorbs more water than the 1,2-glycol, and has a longer period of osmotic action. Sorption activity of 1,2-propylene glycol is maintained for 4-6 hours. This dependence is beleno as more low molecular weight compared to the PEO-400, and a lower hydrophilic-lipophilic balance (products HLB), which for propylene glycol is 9,38. The products HLB value is greater, the greater the hydrophilicity has substance. Therefore, the higher products HLB and molecular weight, the stronger and longer to manifest the osmotic action of a substance at a given concentration. 1,2-propylene glycol, PEO-400, PEO-1500, proxanol is chosen-268 can be preservatives in developing dosage forms ("Theory and practice of local treatment of purulent wounds". Edited by Prof. Bamzatenka. Kiev, Health, 1995, str; 227-235).

On the basis of polyethylene oxide PEO-1500 industrial produced hydrogel "Geco", which is a colorless gel-like mass formed by ionizing radiation to a solution of polyethylene oxide in water. The gel is biologically inert, non-toxic. It is variable in a wide range of structural viscosity, diluted by adding alcohol, glycerin, with vigorous stirring, the pH of a 20% aqueous suspension of 4.0 to 8.0. Chemical composition: PEO-1500 - 3,5%; distilled water - 96%; preservative (sodium benzoate) is 0.5%. Used as the basis for the production of ointments, creams, gels, liniments in the pharmaceutical and cosmetic industry www.medpeterburg.ru/news/Out.aspx?tem=21284). The gel has on the enzyme stabilizing effect (patent RU №2089177, AK 7/48, 1997.09.10).

imaxe - 30% solution of dimethyl sulfoxide (DMSO) is used as an anti-inflammatory drug for external use, inactivating hydroxyl radicals and improves the course of metabolic processes in inflammation. He also has a local anesthetic, analgesic and antimicrobial effects, has a moderate fibrinolytic activity. Penetrates the skin, mucous membranes, membrane microbial cells increases their sensitivity to antibiotics) and other biological membranes without damaging them and can hold a variety of medicines in the depth of the wound ("Theory and practice of local treatment of purulent wounds". Edited by Prof. Bamzatenka. Kiev, Health, 1995, page 172-174).

Polyvinylpyrrolidone is a synthetic polymer that is inert to the body and not splitting enzyme systems, is the basis of detoxification blood fluid connecting toxic substances of different patterns and prints them out of the body (Crosslease fluid, www.nedug.ru/libraru/doc.aspx?item=38053).

Hyaluronic acid is a polysaccharide from the family of glucosaminoglycans, has the ability to bind to 1000 times more water than it weighs itself. Hyaluronic acid has the highest water absorption compared to other moisturizing agents such as glycerin and sorbitol. While my absorption is Naya water held within the gel and does not evaporate even at lower relative humidity of the surrounding air. Due to its high hydrophilicity, hyaluronic acid forms with water a high-viscosity gel that moisturizes the skin and mucous membranes. Hyaluronic acid is non-toxic. In the composition of the gels of hyaluronic acid has antimicrobial, wound healing and anti-inflammatory, promotes regeneration of the epithelium, prevents the formation of granulation tissue, adhesions, scarring, normalize circulation, does not cause clinical complications.

Hyaluronic acid has a positive effect on the course of local inflammatory processes, binds microflora, as well as the products of its decay and life, has a pronounced anti-inflammatory action and local anesthetic effect. At the same time, hyaluronic acid performs and mechanical protection of the Russian Academy of Sciences, as it forms thin film that prevents the penetration into the wound environmental factors - disease-causing agents. Gels based on hyaluronic acid used for the treatment of local and systemic inflammatory processes, thermal and chemical burns, trophic ulcers, chronic venous insufficiency, radiation skin lesions, cracks, abrasions, and also for the treatment of nonhealing wounds of different etiology (patent RU №2195262, AK 9/06, 2002.12.27).

Sodium hyaluronate is the sodium salt of hyaluronic acid soluble in water to form a viscous colorless gel with a pH of 6.0 and 7.5 (0.1% solution). In its activity of sodium hyaluronate is a complete analogue of hyaluronic acid, promotes tissue regeneration without the formation of scars, has the ability to stimulate cell migration and proliferation. Used in concentrations ranging from 0.01 to 0.5%.

Crasneanscki glycerokinase - new ointment base for cosmetic and medicinal preparations outdoor applications, as it combines the beneficial properties inherent in many other ointment bases. This gel is a good conductor of various drugs, anti-inflammatory, antitumor and antioxidant activity, capable to protect the tissue from drying out, fill them with oxygen, it is non-toxic, economical, stable during storage. The presence of silicon is beneficial for all types of tissues: epithelial, connective, skin, bone, contributes to reduction processes, increases blood flow. Due to the fact that glycerate silicon and glycerokinase based on them easily penetrate through the skin and conduct the medicinal substance, the dose of these substances in the pharmaceutical compositions can be lowered (www.uran.ru/gazetanu/2007/04/nu11/wvmnu_p3_11_042007.htm). Given the high transcutaneous activity kremniiorganicheskie of glycomolecules it can be used to create drugs local and external use, transdermally therapeutic systems. This gel can be used as a source of essential trace elements - silicon regulation silicon metabolism in the body (Bojakowska YEAR "Development crasneanscki of glycerokinase and comparative evaluation of their transcutaneous activity, dissertation, www.vita.chel.su/files/docs/diss/bojakovskii.doc).

View of the dosage form of the proposed pharmaceutical product depends on the molecular weight used hyperosmolar substances, their ratio in the mixture, the rheological properties of the mixture, and the quantitative ratio of hyperosmolar basis with other components of a pharmaceutical product. Based on these quantitative ratios and rheological properties of the mixture, dosage form of the proposed pharmaceutical product for local and external use can be a liquid, gel, cream, ointment or suppository.

Most preferred for external use is an ointment form, as it is well recorded and retained on the wound surface, longer has therapeutic activity, cheaper to manufacture, convenient in use, which increases the motivation of the patient to treatment.

Using tilorone, compounds having antibacterial activity against gram-positive and/or gram-negative MIC the organisms, or antimycotics, or mestnoanesteziruyuschee substances, or stimulator of reparative processes, or hypoacidity, or biogenic elements in the form of physiologically acceptable compounds or their physiologically acceptable compounds and hydrophilic bases with hyperosmolar properties of the proposed composition of hydrophilic liquids for external and local use, hydrophilic ointments, hydrophilic creams, hydrophilic gels, which can also be used for the manufacture of suppositories and gelatin or other capsules for rectal and vaginal application.

Hydrophilic liquid, as hyperosmolar (solutions, emulsions, suspensions in the form of liniments), increase the permeability of the skin, effectively conveying the active substance - tilaran, and targeted supplements in the area of purulent-destructive lesions.

Hydrophilic ointments are hyperosmolar, resulting in the application, in addition to efficient transport of active substances and specific additives in the area of purulent-destructive lesions may absorb a significant amount of exudate and bring it to the surface of the skin or mucous membrane.

Hydrophilic creams prepared on the basis of emulsions of the water/oil or water/oil/water, stabilized with suitable emulsifiers. It also applies to lainnya dispersed system, consisting of dispersed in water or mixed water-glycol solvents, higher fatty alcohols or acids, stable hydrophilic surface-active substances. Creams are a two - or multiphase dispersed system, a dispersive medium which when installed the storage temperature, as a rule, has a Newtonian type currents and low values of rheological parameters. The effect of hydrophilic creams on the basis of similar effect ointments, hydrophilic on the basis of, but they have a lower viscosity than ointments, therefore, more easily penetrate through the TRANS-epidermal water barrier and the depth of the wound. On rheological properties they occupy an intermediate position between the liquid and ointment.

Hydrophilic gels (hydrogels) prepared on bases consisting of water, hydrophilic or mixed non-aqueous solvent (glycerol, 1,2-propylene glycol, polyethylene oxide PEO-400) and the hydrophilic gelling (carbomer, derivatives of cellulose, tragakant, sodium hyaluronate, hyaluronic acid and others). In addition, the currently developed new hydrophilic gels mentioned above. Gels are one-, two - or multiphase dispersed liquid dispersive medium, the rheological properties due to the presence of geleobrazovanie in sravnitel is but small concentrations.

In this dosage form, geleobrazovanie additionally can act as stabilizers of disperse systems: suspensions or emulsions.

Hydrophilic gels, containing bound water, do not have such a dehydrating effect, as liquids, creams or ointments, hydrophilic on the basis hyperosmolar properties. They moisturize the inflammation, protecting the wound from drying out. This reduces heat dissipation gel-coated part of the surface, causing it to warm. Under a layer of gel, the moisture does not evaporate, the top layers of skin or mucous membrane marirosa (razmokajut), which promotes absorption through the thickness of the skin of various medicinal substances contained in the composition of the gel. When this active substance and the target of the additive contained in the hydrophilic layer of gel on the skin surface or mucous membrane, diffuse through the TRANS-epidermal water barrier to the lesion. Gels are appropriate to apply in the process of healing, when there is no need for drainage of lesion of toxic products purulent-destructive lesions.

Hydrophilic suppositories prepared on hydrophilic hyperosmolar the basics, easy to dissolve in the rectal or vaginal application, homogeneously distributed mucous medicinal substances have on the body CA is local, and resorptive action.

Gelatin capsules for rectal and vaginal application of more promising compared to suppositories with technology, biopharmaceutical and economic point of view. Gelatinous sheath protects the medicinal substance from the effects of environmental factors and has advantages over the suppositories, as it can capsulitis substances in the form of ointment, liniment, cream, gel, emulsion, suspension, etc.

Drug release is faster and easier than suppositories, as under the influence of the slightly alkaline environment of the mucous membranes (pH of 7.3 and 7.6) gelatin membranes swell, and in this state, even a weak effect on them enough to rupture and release the contents. The amount of medicinal substance in the capsule, providing the desired therapeutic effect, is a double dose suppositories.

Thus, the production of rectal and vaginal funds in the gelatin shell saves costly biologically active ingredients and to reduce the cost of drugs. Rectal gelatin capsules with the proposed pharmaceutical product meet all the requirements of an ideal suppositories and can be used in medicine for the treatment of proctologic diseases, and VA is analnye capsules - for the treatment of diseases of the genitourinary system in women.

Synthetic immunomodulator - small molecule inducer of interferon - Celoron - in offer pharmaceutical drug restores the local immunity of the skin and mucous membranes, which promotes more rapid healing of purulent-destructive lesions, increases the body's resistance to skin diseases and diseases of the mucous membrane due to the suppression of viral, bacterial and fungal infections. Antioxidant properties of tilorone also promote more rapid healing by reducing tissue necrosis.

Substances with antibacterial activity against gram-positive and/or gram-negative bacteria, strengthen the impact of tilorone on the healing of purulent-destructive lesions of skin and mucosa. So, antibiotics have a bacteriostatic action against many gram-positive and gram-negative microorganisms.

The bacteriolytic complex and proteolytic enzymes of the type isoamylase in the proposed pharmaceutical drug analyzes gram-positive microorganisms, including antibiotic-resistant, and due to its proteolytic activity clears the lesions of necrotic masses, providing the immunostimulatory de is due. In addition, isoamylase stimulates reparative processes due to the stimulating effect on the cells of granulation tissue.

The use of the proposed drug substances broad range of trylon-B, violate the structure of the membranes of gram-negative microorganisms, provides the lysis of gram-negative microorganisms. However, alternatively, the proposed substance, in the form of monocomponent, and in the form of a mixture of components, each of which has its own mechanism of lysis of gram-negative microorganisms, which greatly enhances the destruction of their cells.

The combined use of antibiotics, bacteriolytic complex and proteolytic enzymes with Trilon B or EDTA, or their mixture significantly enhances the antibacterial effect of the proposed drug. In addition, the substance of broad-spectrum - Trilon B provides improved microcirculation in the tissues of the lesion by reducing the activity of histamine, as well as being water-soluble antioxidant, reduces secondary tissue necrosis around the wound.

The use of antimycotics in the proposed drug together with tilorone provides a comprehensive exposure to the drug for fungal infections of the skin.

The application of the proposed local anesthetic drug substances, as monocomponent, and MESI components, significantly suppresses pain syndrome in the treatment of purulent-destructive lesions of skin and mucosa. In this application of local anesthetic substances with antibacterial and antioxidant activity, such as cinoxacin, enhances therapeutic effect of the proposed pharmaceutical agents.

To provide additional stimulation of repair processes in the home purulent-destructive lesions in the proposed pharmaceutical agent applied in the form of monocomponent, and a mixture of components with different mechanism and spectrum of activity, a substance that stimulates reparative processes in the lesion.

The use of the proposed drug hypoacidity, for example succinic acid, or its salts, improves microcirculation in the lesion and relieves inflammation.

The use of hydrophilic and hyperosmolar basis in the proposed pharmaceutical product ensures fast delivery of active substances and specific additives, how to microbial cells and the cells of the tissue that enhances therapeutic activity of the proposed drug. In addition, the dehydration of the hydrophilic base cells of gram-positive and gram-negative microorganisms reduces their resistance to the damaging effects of substances with Antibac realnoe activity against gram-positive and/or gram-negative bacteria. It also enhances therapeutic activity of the preparations.

The use of hyperosmolar basics additionally improves microcirculation in the lesion due to its dehydrating action, and also provides additional anti-inflammatory effect due to absorption of fluid and reduce swelling of the lesion. Hyperosmolar Foundation provides outflow of purulent exudate from the lesion and prevents tissue from overhydration. It is easily applied to the surface of the lesion, well it is charged evenly it is distributed, improving the contact with the juvenile tissues and contents of the lesion, it penetrates beneath the scab, mixes well with wound exudate, while maintaining its homogeneity, low-toxic and does not intrude on the fabric, does not violate their physiological functions.

The dissolution of the active substance and the target additives in polietilenoksidnoy basis improves their dispersibility and the ability to more rapid release of the framework, thereby increasing therapeutic activity of the proposed drug. This basis is the conductor of the active substances through the skin barrier, with such penetrating without cell damage ability is enhanced in conditions of inflammation. Hydrophilic based on polyethyleneoxide the x is able to dissolve in the secrets of the mucous membranes, fully releasing the drug substance is not irritating when this mucous has a long shelf-life and high physiological indifference.

The use of biogenic elements in the proposed drug together with tilorone enhances immunity, promotes more rapid healing of purulent-destructive lesions.

The drug is produced by mixing the components with known methods.

The implementation of the present invention is illustrated by the following examples, but is not limited to them.

Example 1. Solution for external and local application No. 1.

100 g of 5% solution contains:

tilaran5,00
gentamicin sulfate0,10
Trilon B0,50
clotrimazole1,00
trimekain2,00
sodium chloride0,60
calcium chloride0,01
magnesium chloride0,0005
zinc chloride0,0052
manganese acetate0,0017
polyvinylpyrrolidone 8000±20006,00
purified waterto 100 g

Example 2. Solution for external and local p is imeneniya No. 2.

100 g of 3% solution contains:

tilaran3,00
sodium salt guideway acid2,00
EDTA0,20
methyluracil1,00
lidocaine1,00
succinic acid0,50
zinc chloride0,0052
manganese acetate0,0017
the polyethylene oxide - 40010,00
purified waterto 100 g

Example 3. Solution for external and local application No. 3.

In 100 g of 2% solution contains:

tilaran2,0
isoamylase2,0
Trilon B0,1
trimekain2,0
succinic acid0,5
the polyethylene oxide-40020,0
purified waterto 100 g

Example 4. Liniment No. 1.

100 g of 5% liniment contains:

tilaran5,0
sodium salt guideway acid2,0
ciclopiroxolamine 1,0
the katapola0,1
cinoxacin1,0
1,2-propylene glycol60,0
purified waterto 100 g

Example No. 5. Liniment No. 2.

100 g of 3% liniment contains:

tilaran3,0
gentamicin sulfate0,5
clotrimazole1,0
Trilon B0,1
trimekain3,0
1,2-propylene glycol50,0
proxanol is chosen-2685,0
purified waterto 100 g

Example 6. Liniment No. 3 (emulsion).

In 100 g of 2% emulsion contains, g:

tilaran2,0
calcium Pantothenate5,0
piromekain1,0
zinc chloride0,0052
manganese acetate0,0017
succinic acid0,5
1,2-propylene glycol20,0
purified waterto 100 g

Example 7. Cream No. 1.

100 g of 3% cream contains:

tilaran3,00
isoamylase2,00
Trilon B0,05
vaseline22,00
glycerin17,00
1,2-propylene glycol12,00
emulsifier No. 110,00
phosphate buffer solution14,00
purified waterto 100 g

Example 8. Cream No. 2.

100 g of 5% cream contains:

tilaran3,00
gentamicin sulfate0,10
clotrimazole1,00
Trilon B0,05
dimexide2,00
vaseline22,00
glycerin17,00
1,2-propylene glycol12,00
emulsifier No. 110,00
phosphate buffer solution14,00
purified waterto 100 g

Example 9. Cream No. 3.

In 100 g of 2% cream contains:

tilaran2,00
methyluracil1,00
lidocaine1,00
zinc chloride0,0052
manganese acetate0,0017
succinic acid0,50
1,2-propylene glycol35,00
PEO-40025,00
proxanol is chosen-26818,00
purified waterto 100 g

Example 10. Ointment No. 1.

100 g of 3% ointment contains:

tilaran3,00
isoamylase2,00
Trilon B0,02
proxanol is chosen-26818,00
1,2-propylene glycol42,00
the polyethylene oxide PEO-40028,00
purified waterto 100 g

Example 11. Ointment No. 2.

100 g of 5% ointment contains:

tilaran5,00
gentamicin sulfate1,00
clotrimazole1,00
Trilon B0,10
EDTA0,10
trimekain2,00
proxanol is chosen-26824,00
1,2-propylene glycol24,00
purified waterto 100 g

Example 12. Ointment No. 3.

In 100 g of 2% ointment contains:

tilaran2,00
cinoxacin1,00
methyluracil3,00
the atsemin1,00
nipagin0,08
glycerin20,00
zinc chloride0,0052
manganese acetate0,0017
succinic acid0,50
the sodium carboxymethyl cellulose3,50
zinc oxide3,00
purified waterto 100 g

Example 13. Gel No. 1.

In 100 g of 2% gel contains:

tilaran2,00
isoamylase2,00
piromekain1,00
the gel of polyethylene oxide 1500to 100 g

Example 14. Gel No. 2.

100 g 3% gel contains:

tilaran3,00
Trilon B0,04
gentamicin sulfate0,10
clotrimazole1,00
piromekain 1,00
nipagin0,10
the polyethylene oxide PEO-40030,00
hyaluronic acid0,50
purified waterto 100 g

Example 15. Gel No. 3.

100 g 3% gel contains:

tilaran3,00
trimekain4,00
methyluracil2,00
nipagin0,10
zinc chloride0,0052
manganese acetate0,0017
succinic acid0,50
glycerokinase based
glycerate silicon50,0
purified waterto 100 g

Example 16. The mixture for the preparation of suppositories No. 1.

100 g of a 5% mixture for the preparation of suppositories contain g:

/tr>
tilaran5,0
Trilon B1,0
gentamicin sulfate0,1
trimekain4,0
atadan4,0
proxanol is chosen-26860,0
the polyethylene oxide-40015,0
purified waterto 100 g

From this mixture made 300 pieces rectal suppositories in the form of "cigars" with a diameter of 10 mm, weight 2.5 g, containing tilorone 0.125 g in one suppositories. The solubility of the hydrophilic suppositories basis is no more than 1 hour at a temperature of (37±1)°that meets the requirements of the global Fund XI (Art. Suppositories, p.151-153).

Example No. 17. The mixture for the preparation of suppositories No. 2.

100 g of a 5% mixture for the preparation of suppositories contain g:

tilaran5,00
isoamylase2,00
anastasin4,00
atadan4,00
zinc chloride0,0052
manganese acetate0,0017
proxanol is chosen-268PHP 64.00
the polyethylene oxide-40016,00
purified waterto 100 g

From this mixture made 300 pieces rectal suppositories in the form of "cigars" with a diameter of 10 mm, a weight of 2.0 g, containing tilorone 0.1 g in one suppositories. The solubility of the hydrophilic suppositories basis is no more than 1 hour at a temperature of (37±1)°that meets the requirements of the global Fund XI (Art. Suppositories,p.151-153).

Example 18. The mixture for the preparation of suppositories No. 3.

100 g of a 5% mixture for the preparation of suppositories contain g:

tilaran5,0
trimekain4,0
atadan4,0
dimexide3,0
succinic acid0,5
proxanol is chosen-26866,0
the polyethylene oxide-4008,0
purified waterto 100 g

From this mixture made 300 pieces rectal suppositories in the form of "cigars" with a diameter of 10 mm, weight 2.5 g, containing tilorone 0.125 g in one suppositories. The solubility of the hydrophilic suppositories basis is no more than 1 hour at a temperature of (37±1)°that meets the requirements of the global Fund XI (Art. Suppositories, p.151-153).

Example 19. Gelatin capsules.

Ointment of Example 10 is filled 500 piece gelatin capsules No. 00, the volume of 0.95 ml Raspadaemost received capsules less than 20 min, which meets the requirements of the global Fund XI (Art. Capsules, str).

Based on the proposed solutions created a number of new drugs in the form of liquid and soft dosage forms containing the active substance tilaran and targeted supplements.

The proposed remedies on the basis of tilorone, enter the specified target and hydrophilic additives hyperosmolar basis significantly expand the scope of application of the known active substances - tilorone, ensure restoration of local immunity and biocenosis of the skin and mucous membranes in the treatment of purulent-destructive processes of the skin and mucous membranes have a high therapeutic activity, give anaesthetic effect, stimulate reparative processes, improves microcirculation in the lesion, cropped inflammatory reaction in the skin, reduce secondary tissue necrosis in the affected areas associated with excessive free radical oxidation, easy to use.

Conducted an information search did not reveal identical and similar technical solutions.

The above set of features of the proposed pharmaceutical product (composition of the drug, the quantitative ratio of the components and dosage form) was not previously known, which indicates the novelty of the proposed solution. The set of essential features of the claimed pharmaceutical preparation for external use on the basis of tilorone should not be explicitly studied the prior art, has significant differences from the one considered analogues. Still similar decisions have been proposed, although the drug tilaran known since 1970 (I.E. Filippova, NA Golovenko "TILARAN: PROFILE of BIOLOGICAL ACTIVITY I. PHARMACOLOGICAL PROPERTIES", http://magazine.odmu.od.ua/antropo/2006/1/18 .pdf). Therefore, the applicant considered one of th the em that the claimed pharmaceutical product for local and external application on the basis of tilorone involves an inventive step.

The inventive pharmaceutical preparation may be recommended in the treatment of purulent-destructive lesions of skin and mucous membranes.

We offer pharmaceutical preparation for topical application on the basis of tilorone can be used for industrial mass production of liquid and soft medicinal forms, such as solutions, emulsions, suspensions, liniments, ointments, creams, gels, as well as for industrial production generated soft medicinal forms: suppositories and gelatin capsules for rectal and vaginal application.

1. Pharmaceutical composition for treatment of purulent-destructive lesions of skin and mucous membranes when external and local application, characterized in that it contains tilaran and special additive selected from the group: a substance having antibacterial activity against gram-positive and/or gram-negative bacteria, antimycotics, local anesthetic substance, a stimulator of reparative processes, yooxygen, biogenic elements and the base, or their mixture in the following ratio, wt.%:

tilaran0,005-10,00
a substance having
antibacterial activity
against gram
and/or gram-negative bacteria0,01-13,00
antimycotics0,50-3,00
local anesthetic substance0,50-4,00
stimulator reparative processes0,50-4,00
yooxygen0,001-1,00
biogenic elements0,000001-5,5
baserest

2. The pharmaceutical composition according to claim 1, characterized in that compounds having antibacterial activity against gram-positive and/or gram-negative bacteria, it contains a substance selected from the group of: an antibiotic, isoamylase, Trilon B, ethyldimethylamine acid.

3. The pharmaceutical composition according to claim 2, characterized in that it contains antibiotic gentamicin sulfate or sodium salt guideway acid or their mixture

4. The pharmaceutical composition according to claim 1, characterized in that as antimycotics it contains clotrimazole or ciclopiroxolamine.

5. The pharmaceutical composition according to claim 1, characterized by the fact that as a local anesthetic substances it contains substances that selected from the group cinoxacin, trimekain, piromekain, lidocaine, benzocaine, or their mixture.

6. The pharmaceutical composition according to claim 1, characterized in that as a stimulator of reparative processes it contains a substance selected from the group: methyluracil, atsemin, etagen, calcium Pantothenate, solcoseryl, katapola or their mixture.

7. The pharmaceutical composition according to claim 1, characterized in that as hypoacidity it contains succinic acid or its salts.

8. The pharmaceutical composition according to claim 1, characterized in that as the nutrients it contains zinc or manganese in the form of physiologically acceptable compounds or their physiologically acceptable mixture.

9. The pharmaceutical composition according to claim 1, characterized in that as the Foundation it contains hyperosmolar substances or physiologically acceptable mixture of hyperosmolar substances selected from the group: Dimexidum, glycerin, 1,2 propylene glycol, or their physiologically acceptable mixture with components that provide rheological requirements basis depending on the dosage form of the pharmaceutical composition selected from the group: proxanol is chosen-268, polyethyleneoxide-1500, polyvinylpyrrolidone, polyethylene oxide gel 1500, glycerokinase based glycerate silicon, calcium alginate or magnesium, natrocarbonatite cellulose, hyaluronic acid, petrolatum, emulsifying agent No. 1, zinc oxide.

10. The pharmaceutical composition according to claim 1, characterized in that it is made in the form of a liquid pharmaceutical form solution for external and local use, suspension or emulsion in the form of liniment or soft dosage forms (ointments or cream or gel or formed of soft medicinal forms of suppositories or capsules for rectal or vaginal application.



 

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