Agent for severe infectious diseases and mixed infections

FIELD: medicine.

SUBSTANCE: medicinal agent contains alpha and/or beta and/or gamma human recombinant interferon, tocopherol acetate or other tocopherol derivatives, ascorbic acid and/or its salts, pantothenic acid or calcium pantothenate, or dexapanthenol, riboflavin or levocarnitine, and orotic acid and/or ornithine or its derivative - citrulline malate, or Glutoxim, antibacterial, antimycotic agents, additives: emulsifiers, stabilisers, preservatives, antioxidants and base. The formulation is suppositories in certain component ratio.

EFFECT: efficiency for severe infectious diseases and mixed infections.

9 cl, 18 ex

 

The invention relates to pharmacology and medicine and relates to designing new drugs, broad-spectrum based on interferon for the treatment of severe infectious diseases of various etiologies, including mixed infections, and complicated fungal flora, including postoperative infectious-inflammatory complications.

Infectious pathology has always occupied a leading place in popularity among people all over the world. In Russia, as elsewhere in the world, in recent decades, an increasing number of infectious diseases: a growing incidence of both viral and bacterial infections. Very relevant was the problem of treatment of bacterial infections because of their wide spread of antibiotic-resistant strains of pathogens: an extremely significant problem and primary infection with antibiotic-resistant variants of pathogens, and the formation of resistance and polyresistance pathogens during therapy of infectious diseases. Intractable at present, the treatment of tuberculosis due to these problems, which is one of the key reasons for the significant rise in the incidence of tuberculosis at the present time in many countries of the world.

Severe infectious diseases such as pneumonia, osteomyelitis, like the Gita, postoperative complications, including sepsis, extinctio, nosocomial diseases, etc. require primarily targeted etiotropic therapy effective antimicrobials. However, the formation of microbial resistance to antibiotics of all groups not only reduces the clinical effectiveness of treatment with these drugs, but often leads to deterioration of the patient due to the utter lack of effect and the occurrence of side reactions, including toxic. The most typical of these problems in the treatment of tuberculosis, because this disease is generally, multicomponent and very prolonged antibiotic therapy. The development of new drugs that can overcome the resistance of pathogens of infectious diseases, especially nosocomial infections, tuberculosis, mixed infections to medicines, to improve the tolerability of these drugs, to ensure higher effectiveness of treatment and to reduce the recovery time is relevant in the present.

In recent years there has been a significant increase in the incidence of urogenital infections: up to 80-90% of women of childbearing age have those or other urogenital diseases. Due to the nature of the clinics listed diseases not practically diagnostics is iroute in the early stages of the disease and, as a rule, turn into chronic, persistent form. They are also often complicated by the accession of other pathogens, including fungal infections. These diseases are difficult to cure, accompanied by a significant inhibition of nonspecific factors of protection and immune system, and disorders of the reproductive system and cause premature birth, intrauterine pathology of the fetus, miscarriage of the fetus, infertility in both men and women.

Severe infectious-inflammatory processes are always accompanied by complications, severe toxic manifestations, circulatory disorders, trophism of tissues and organs, their functional disorders, side effects of antibiotic therapy. Outlined leads to disorders of metabolism, dysbacteriosis, fatigue, weight reduction, severe General condition of the patient, slow down the process of repair, recovery.

Even acute infectious disease detected at an early stage of the disease, it is often difficult to treat with antibacterial drugs and pass in the chronic form. The reason for this is often the stability of the microflora to antibiotics: primary - due to the wrong choice of drug or acquired as a result of prolonged use of the drug, as well as features is Sudetes (Association of pathogens), activation of conditionally pathogenic flora, joining fungal flora. The lack of effectiveness of the drug leads to the need to either increase the dose or replacement of the antibiotic, which, in turn, leads to increased side effects, toxic effects on the liver and other organs, the formation of a dysbacteriosis, immunosuppression, poor condition of the patient. It is proved that the most important role in limiting the population growth of any pathogenic microorganisms is the bacteria of the intestinal symbionts. Normal microflora that inhabit the lumen of the gastrointestinal tract, produces substances with antibacterial activity, which prevent the introduction of pathogens, excessive growth and development of conditionally pathogenic flora. E. coli, enterococci, bifidobacteria and lactobacilli have strong antagonistic properties. However, dysbiotic processes typical for patients with severe inflammatory pathology, exclude this link from the system protect the body of the sick: the oppression of the natural defensive reactions is one of the most important mechanisms contributing to the ineffectiveness of the antibiotic therapy.

Today proved antibiotics inhibit the growth of microorganisms, but the ultimate elimination of their function IMM is nitya. This proves that the treatment of infectious diseases, impacting only the pathogen, is almost impossible. Therapy must be comprehensive and mandatory component in treatment regimens should be the impact on the body's defenses.

In practical health care is a wide range of drugs affecting the immune system, but the most studied and promising among them are interferon. In our country and abroad are different dosage form of interferon preparations for systemic and topical use. Long experience of their application evidence of the effectiveness of these drugs. Proven no side effects rectal use of many drugs, including interferon. It is shown that this method of interferon is not developing antiinterference antibodies, which significantly reduce the effectiveness of therapy.

Extensive clinical trials of interferon, in particular Viferon, for the study of clinical efficacy in the treatment of infectious diseases with enhanced immunological studies have shown that on the background of VETERINARII normalization of immune and cytokine status and clinical rehabilitation is value is positive faster than without the use of interferon. Have experience of joint use of the drug "Viferon, suppositories" (recombinant interferon Alfa-2) with antibiotics, indicating the high efficiency when treating a number of infections (urea and Mycoplasma, chlamydia, vaginosis, candidiasis and other) and other infectious and inflammatory diseases.

It is known that negative antibiotic is toxic to the liver and other organs, allergic reactions, side effects gastro-intestinal tract, however, many antibiotics are broken down by enzymes in the gastrointestinal tract, which reduces their effectiveness. Since many antibiotics are effective for rectal administration, in recent years, preferred this way of introduction, particularly in pediatric practice. The rectal route of administration is especially appropriate, since it is proved that the use of antibiotics in suppozitornyj form also leads to fewer side effects. It is shown that in the treatment of many infectious and inflammatory diseases with antibiotics in combination with veterinaria more effectively removed side effects of antibiotics, significantly improving their portability.

The above pathogenetic features infe the conservation and inflammatory diseases and the absence in the Arsenal of practical health services registered a complex immunomodulatory drugs with the necessary range of actions cause the feasibility of developing new drugs with a broader mechanism of action for the treatment of severe infections and mixed infections with consideration of the peculiarities of pathogenesis and severity of these infections caused by the human metabolism with severe toxic manifestations, asthenia, weight loss, imbalance of the immune and cytokine systems.

Proceeding from the above, the obvious desirability of developing suppozitornyj forms of immunomodulators in conjunction with antibiotics and other antibacterial drugs and components that contribute to a more rapid rehabilitation of patients, anabolic, antiasteniceski, antitoxic, antihypoxant effects for the treatment of severe infections and mixed infections.

It is now known drug with antiviral and immunomodulatory activity, Kipferon (patent RU №2073522, class AC 38/21, 39/395, 1997) based on recombinant human interferon alpha type with complex immunoglobulin preparation containing immunoglobulins of classes a, M, G, and has antiviral and immunomodulatory activity. However, in this preparation contains antibodies derived from human blood, and as all the blood, this drug is potentially dangerous since t is his vision of his human contamination by viruses or other agents, that significantly limits the scope of its application. The composition of this drug does not provide additional effects peculiar to develop the drug.

Known medicinal product Generon (patent RU №2201212, class AC 9/00, 2003), which has an immunomodulatory, antiviral, antibacterial, regenerative, reparative, membrane - and hepatoprotective action. Lack of Gepirone is the lack of the antimicrobial composition, metabolic, anabolic, antiasteniceski, antihypoxant, anti-inflammatory, anti-toxic components, which significantly reduces the range of its validity.

Known drug Viferon (patent RU №2024253, class AC 9/02, 1994)containing genetically engineered interferon Alfa-2, the antioxidants ascorbic acid and alpha-tocopherol. It is shown that the specific activity of the interferon increases significantly in the presence of antioxidants. This drug is taken as the nearest equivalent. However, this tool does not have the latitude range of the developed product.

The present invention is the creation of integrated tools based on interferon for the treatment of severe forms of infectious diseases and mixed infections, including complicated by fungal infections.

Technical rez is litecom is to increase the efficiency and spectrum of action of new drugs for the treatment of severe forms of infectious diseases and mixed infections to facilitate a more complete and rapid rehabilitation of the patient: antiasteniceski, anabolic (non-hormonal), antitoxic, antihypoxant, antioxidant effects that reduce the risk and the degree of complications of diseases, which has an immunomodulatory and a wide spectrum of antibacterial and antimycotic action.

The technical result is ensured by the introduction of the drug active components of broad-spectrum. The drug interferon-based with a vitamin complex (tocopherol acetate or other derivatives of tocopherol, ascorbic acid and/or a salt thereof, Pantothenic acid or calcium pantothenat, or dexpanthenol, Riboflavin or carnitine) also contains Orotava acid and/or ornithine (or its derivative of citrulline malate), Glutoxim, antibacterial, antimycotic, excipients: emulsifiers, stabilizers, preservatives, antioxidants, based on the following ratios of components per 1 g of the drug in suppozitornyj the form:

Human recombinant interferon alpha and/or beta and/or gamma type100 thousand - 25 million IU
Tocopherol acetate or other derivatives of tocopherol 0,001-to 0.055 g
Ascorbic acid and/or its salts0,01-0,05 g
Pantothenic acid or calcium pantothenat, or
dexpanthenol0.03 to 0.3 g
Riboflavin or0,002-0,004 g
Levocarnitine0.05 to 0.15 g
Orotic acid and/or0.05-0.2 g
Ornithine or citrulline malate0.01 to 0.2 g
Glutoxim0,0015-0.005 g
Antibacterial substances0.005 to 0.3 g
Antimycotic substances0.005 to 0.2 g
Excipients and basethe rest of it.

Interferon is a polyfunctional low molecular weight protein, possesses immunomodulatory properties, antiviral and antibacterial activity. It is known that the nature of the action depends on the dose: when using small and medium doses more pronounced immunomodulatory, genereruemee, antibacterial action. These doses used in the treatment of disease of mild to moderate severity, and chronic forms of diseases, disorders of the immune system. High-dose interferon determine antiproliferative, antiviral effects. Their use is justified in Oncology, severe viral infections (with lesions of the Central nervous system, internal organs, severe viral hepatitis and others).

Tocopherol acetate or other derivatives of tocopherol in combination with ascorbic acid and its salts belong to the group of funds that regulate metabolic processes. They have antioxidant properties, limit the damaging effects of lipid peroxidation, stabilize cell membranes. Proven synergene these components when combined with interferon enhancing the antiviral activity of interferon.

Pantothenic acid, calcium Pantothenate, dexpanthenol have a metabolic effect, have antitoxic property, used in the treatment of toxicosis of pregnancy, liver disease, reduces the toxic effect of drugs, including antibiotics, accelerate the regeneration, have anti-allergic effect, compensate for the deficiency of Pantothenic acid supports armalloy secretory and kinetic bowel function, stimulate the reproduction of the normal flora of the intestines, help to restore the ecological community. The inclusion of these components in the integrated product extends the range of action of the drug, reduces the risk of side effects and toxic effects of infection and antibiotic therapy.

Severe infectious-inflammatory diseases are accompanied by disturbances of metabolic processes, severe anaemia, asthenia, disturbance processes regeneneration, repair, disorders of the major systems and organs, depending on the etiology and pathogenesis of the disease. In this regard, in addition to causal antibacterial drugs drugs tonic, antiasteniceski, symptomatic drugs, contributing to more rapid rehabilitation of patients. These drugs include anabolic (non-steroidal), antiasteniceski, antitoxic, anti-oxidant, antihypoxant, regenerating, reparatie, immunomodulating drugs.

Riboflavin and carnitine belong to the group of b vitamins are metabolically have anabolic, antiasteniceski properties, increase efficiency, resistance to physical stress. These properties are very important in the treatment of severe infectious diseases using multi-component circuits antibiotico is rapee, since it helps to improve the tolerance to antibiotic therapy, to alleviate the condition of patients.

Orotic acid is a non-steroidal anabolic agent, activates the regeneration and reparation of tissues, increases the appetite, has a General stimulating effect on metabolism, normalizes liver function, promotes regeneration of hepatocytes, but also improves the portability of antibiotics has antioxidant properties. Ornithine and citrulline malate (a derivative of ornithine) have also antiasteniceski action, normalizes metabolic processes. These components improve the portability of antibacterial drugs, contribute to the normalization of metabolic processes, improve appetite, speed up the recovery process. Glutoxim stimulates hematopoiesis, increases the body's resistance to external influences, is also an antioxidant, hepatoprotective and immunomodulatory agent.

Severe infectious-inflammatory diseases caused by tuberculosis, extincta, antibiotic-resistant infection, complicated by fungal infections and anaerobic flora, require a reasonable choice of drugs for the treatment taking into account the General condition of the patient. Only a comprehensive causal, pathogenetic, symptomatical treatment can lead to recovery of the patient.

the Drugs of choice in these cases are antibiotics last generations: first of all cephalosporins, broad-spectrum III and IV generations, resistant to beta-lactamase chromosomal and plasmid types, Ceftriaxone, ceftazidime, Cefotaxime, cefepime, cefpirome, aplidin, cefozopran, rethinam, celapram and other Use of these drugs is accompanied by relatively pronounced side effects. In addition, it is known that many drugs in this group cause painful reactions at the injection requires the use of anesthetic drugs that are contraindicated in patients with allergic diseases. Development of drugs in suppository will avoid the mentioned disadvantages of parenteral introduction of this group.

Cephalosporins as antibiotics and other groups, are not always sufficiently effective when mixed bacterial infections involving anaerobic flora, which necessitates the use of drugs such as metronidazole, tinidazole, Ornidazole. This medication broad-spectrum, active primarily against anaerobic flora, simple, widely used in the practice of the treatment of infectious-inflammatory diseases due to the nature of the microbial landscape of this pathology, highly effective in the treatment of many bacterial infections, including chlamydia, Mycoplasma, including urogenital used in preparation for surgery is so

Difficult to cure and mixed infections, complicated by fungal infections. Spectrum of antimycotic drugs recent years has greatly expanded. In the treatment of infections, complicated by fungal infections, uses a whole Arsenal of drugs of different classes, such as flucytosine, fluconazole, miconazole, ketoconazole, Itraconazole, natamycin, amphotericin, termination, pimafucin and Most other new and promising due to a broader mechanism of action are sertaconazole, butoconazole, fenticonazole nitrate and other

Simultaneous reception of antibacterial and antimycotic drugs provides a higher treatment efficiency, but also increases the likelihood of side effects, primarily from the gastrointestinal tract, affecting the heavy patient.

The antituberculous substances specific drugs are used in the form of plain products, but often in the form of two, three, four, pathcomponent schemes, which leads to severe allergic reactions, poisoning, severe toxic hepatitis with the necessity of the abolition of specific drugs. Most often used to treat tuberculosis isoniazid, rifampicin, pyrazinamide and streptomycin, ethambutol, protionamide, ethionamide kanamycin, florimitsin, cyclometer, PAS, tibon and others, as well as various mnogokomponentnye the scheme of treatment of tuberculosis. Violation of dosages, courses, use of antituberculous substances of drugs leads to reduced efficiency and contribute to the emergence of antibiotic-resistant strains of tuberculosis. The effectiveness of Mycobacterium tuberculosis can be enhanced by combining the use of a fluoroquinolone (ofloxacin, ciprofloxacin, lomefloxacin and others).

Presented demonstrates the feasibility of integrated development of drugs for the treatment of severe infections with all the features of the pathogenesis of infectious and inflammatory diseases and immune system together with immunomodulatory, non-steroidal anabolic, antiasteniceski, antihypoxant, antioxidant, antitoxic components of appropriate anti-TB therapy.

Suppozitornyj form of the drug can be entered into the integrated product a number of components that provide listed a range of beneficial effects and to reduce or completely remove the side effects of heavy antibiotic therapy, including toxic, allergic reactions.

The following examples show the possibility of using the specified components in suppozitornyj form of the drug per 1 g suppozitornoj mass.

Example 1

Human recombinant interferon
alpha or beta500 time
Tocopherol acetate0.04 g
Ascorbic acid0.02 g
Calcium Pantothenate or Pantothenic acid0.05 g
Riboflavin or0.002 g
Levocarnitine0.05 g
Orotic acid or0.05 g
Ornithine0.02 g
Glutoxim0.0015 g
Ceftriaxone or Cefotaxime0.15 g
Itraconazole or fluconazole0.15 g
Excipients and baserest

Example 2

Human recombinant interferon alpha1 million ME
Tocopherol hydrosylate0.05 g
Sodium ascorbate0.025 g
Calcium Pantothenate0.15 g
Levocarnitine0.1 g
Orotic acid0.15 g
Glutoxim0.005 g
Ceftazidim0.015 g
Flucytosine0.15 g
Excipients and baserest

Example 3

Human recombinant interferon alpha3 million ME
Tocopherol polietilenglikolsuktsinata0,045 g
Ascorbic acid and0.005 g
Ascorbyl palmitate0.02 g
Dexpanthenol0.075 g
Riboflavin0.003 g
0.015 g
Glutoxim0.002 g
Cefepime or aplidin0.25 g
Terbinafine or amphotericin0.02 g
Excipients and baserest

Example 4

Human recombinant interferon alpha5 million ME
Tocopherol acetateto 0.055 g
Calcium ascorbate0.025 g
Calcium Pantothenate0.1 g
Levocarnitine0.05 g
Orotic acid0.15 g
Citrulline malate0.02 g
Cefpirome0.2 g
Natamycin0.15 g
Excipients and baserest

PR is measures 5

Human recombinant interferon
alpha or beta,3 million ME
Tocopherol Dimineata0.04 g
Ascorbic acid and0.015 g
Calcium ascorbate0.015 g
Pantothenic acid0.05 g
Riboflavin0.003 g
Citrulline malate0.02 g
Cefoperazon0.25 g
Sertaconazole0.15 g
Excipients and baserest

Example 6

Human recombinant interferon
alpha10 million ME
Tocopherol acetate0.04 g
Ascorbyl palmit the t 0.02 g
Pantothenic acid0.1 g
Levocarnitine0.075 g
Orotic acid0.1 g
Cefozopran0.15 g
Fenticonazole nitrate0.1 g
Excipients and baserest

Example 7

Human recombinant interferon alpha15 million IU
Tocopherol acetate0.05 g
Sodium ascorbate or calcium0,022 g
Calcium Pantothenate0.1 g
Riboflavin0.004 g
Citrulline malate or0.05 g
Glutoximto 0.055 g
Celepram or cefetamet0.2 g
Budokon is angry 0.15 g
Excipients and baserest

Example 8

Human recombinant interferon
beta and/or gamma type500 thousand IU
Tocopherol hydrosocialto 0.055 g
Calcium ascorbate0.025 g
Calcium Pantothenate0.15 g
Levocarnitine0.1 g
Orotic acid0.015 g
Glutoxim0.002 g
Rifampicin and ciprofloxacin0.25 g
Levorin or ivoryton0.02 g
Excipients and baserest

Example 9

Human recombinant interferon
alpha type150 thousand IU
Tocopherol acetate0.04 g
Ascorbic acid0.015 g
Pantothenic acid0.05 g
Riboflavin0.001 g
Orotic acid0.075 g
Ceftriaxone or cefetamet0.1 g
Ornidazole0.05 g
Sertaconazole0.1 g
Excipients and baserest

Example 10

Human recombinant interferon alpha25 million IU
Tocopherol acetate0,045 g
Sodium ascorbate0.025 g
Dexpanthenol0.05 g
Riboflavin0.003 g
Citral is on malate 0.05 g
Ethambutol and kanamycin (1:1)0.25 g
Omoconazole or econazole0.1 g
Excipients and baserest

Example 11

Human recombinant interferon beta500 thousand IU
Tocopherol polyethylene glycol0.04 g
Ascorbic acid0.01 g
Sodium ascorbate0.015 g
Pantothenic acid0.1 g
Orotic acid0.1 g
Pyrazinamide or isoniazid0.15 g
Tinidazole0.1 g
Excipients and baserest

Example 12

15 million IU
Human recombinant interferon alpha
Tocopherol hydrosylate0.05 g
Ascorbic acid0.01 g
Ascorbyl palmitate0.015 g
Calcium Pantothenate0.15 g
Levocarnitine0.01 g
Glutoxim0.002 g
Ethionamide or protionamide0.2 g
Terbinafine or amphotericin0.02 g
Excipients and baserest

For the solution of technological tasks - create suppozitornyj dosage forms are used excipients - emulsifiers, stabilizers, antioxidants, preservatives and the basics.

Widely in medical preparations as the emulsifier is tween-80, tween-60, span-80, span-60, phospholipids - phosphatidylserin, fastidioso, phosphatidyletanol, phosphatidylethanolamine, emulsifiers T-1, T-2, lanolin, derivatives of lauric alcohol, in particular sodium lauryl sulphate and other Use of these substances allows AEC to ensure a more even distribution of medicinal substances in finished form, a more complete release of the active ingredient from the dosage form, better penetration of active ingredients through the mucous membranes of the skin, increase the absorption of active substances.

Stabilization of the physical, chemical, biological properties are provided comprehensively: use of macromolecular compounds, amino acids, surfactants, preservatives, antioxidants.

It is known that the use of high-molecular substances (WWII) increases chemical, biological stability of medicines, provides the necessary structural and mechanical properties. Stabilizing action by micelle formation and binding of molecules of medicinal substances with micelles, followed by a slower release of drug substances, i.e. achieved additionally, the effect of sustained release of active components. As WWII can be used dextrans with different molecular weights, gidroksietilirovanny starch (HES), polyvinylpyrrolidone, polyvinyl alcohol, silicon dioxide, amorphous, inert, cellulose and its derivatives.

Ethylenediaminetetraacetic acid (EDTA) or the disodium salt of her (ADETEF sodium) are antioxidants, kompleksoobrazuyushchie that contributes to the stabilization of medicinal drugs the the ATA.

Amino acids and antioxidants also contribute to the stabilization of the activity of polypeptides and proteins. The use of these amino acids leads to an increased number of biological properties: antioxidant, antihypoxant, detoxifying, due to the properties of these amino acids.

As preservatives for protection of the drug from the bacterial contamination use of substances from a number of: benzyl alcohol, benzakonia chloride, benzoic acid, sorbic acid or potassium salt of sorbic acid, parabens.

The following examples show the use of auxiliary substances per 1 g suppozitornoj mass.

Example 13

Human recombinant interferon alpha20 million IU
Tocopherol Dimineata0,045 g
Ascorbic acid0.01 g
Sodium ascorbate0.01 g
Dexpanthenol0.1 g
Levocarnitine0.075 g
Citrulline malate0.01 g
Florimitsin or strap is amicin 0.15 g
Natamycin or pimafucin0.15 g
Phosphatidylserin or phosphatidyletanol0.005 g
Emulsifier T-1 or T-20.01 g
Glutamic acid0.015 g
Polyvinylpyrrolidone or polyvinylalcohol0.02 g
Benzyl alcohol : 0,009 g
Baserest

Example 14

Human recombinant interferon alpha500 thousand IU
Tocopherol acetate0,045 g
Calcium ascorbate0.015 g
Calcium Pantothenate0.1 g
Riboflavin0.003 g
Citrulline malate0.01 g
Lomefloxacin or ofloxacin0.2 g
Metronidazole0.1 g
Sertaconazole0.15 g
Tween-80 or0.005 g
Spen-800.005 g
Sodium lauryl or0.002 g
Phosphatidylcholine0.005 g
Dextran-600.04 g
ADETEF sodium0.001 g
Sorbic acid or potassium salt of her0.002 g
Baserest

Bases can be selected from the range: hydrophobic base for suppositories - cocoa butter, hard fat or other hydrogenated vegetable fats or ready suppozitornoj bases type Witepsol, or Maspol, or Labopol, or similar cocoa butter - Kuva-900, couva-500, or Packer-21, or Hisomel 100, 500, or other similar fats, silicones. Hydrophilic base - derivatives of cellulose, polyethylene oxides, polyvinylpyrrolidone, polymers and copolymers of acrylic and methacrylic acids, alginates derived collagen, gelatin, di is xidi silicon.

As difiles basics - oxides with solid fats or other fats.

Example 15

Human recombinant interferon alpha3 million ME
Tocopherol acetate0.035 g
Ascorbic acid0.015 g
Calcium ascorbate0.01 g
Dexpanthenol0.15 g
Riboflavin0.004 g
Orotic acid0.05 g
Citrulline malate0.015 g
Butoconazole0.15 g
Phosphatidylcholine or phosphatidylethanolamine0.004 g
Tween-800.01 g
Silicon dioxide0.05 g
Glycine0.01 g
EDTA0.01 g
Bansal one chloride 0.0001 g
Cocoa butter and hydrogenated oil (1:3)rest

Example 16

Human recombinant interferon-gamma100 thousand ME
Tocopherol hydrosylate0.05 g
Calcium ascorbate0.02 g
Calcium Pantothenate0.1 g
Levocarnitine0.075 g
Orotic acid0.05 g
Glutoxim0.0025 g
Cefepime and/or Ornidazole0.25 g
Phosphatidylcholine0.005 g
Emulsifier T-1 or T-2 or lanolin0.01 g
Dextran 400.03 g
Glycine0.01 g
Benzoic acid or its sodium salt0.01 g
Cocoa butter and/or Parker - 21, or Maspol (1:3)rest

Example 17

Human recombinant interferon alpha1 million IU
Tocopherol Dimineata0.05 g
Ascorbyl palmitate0.02 g
Calcium Pantothenate0.1 g
Riboflavin0.0025 g
Glutoxim0.0015 g
Ceftriaxone0.25 g
Flucytosine0,1
Tween-800.015 g
Sodium lauryl0.02 g
Polyvinylpyrrolidone0.025 g
Glutamic acid0.02 g
Trilon B0.001 g
Nipagin and nipazol (1:3)0.002 g
Pole jingleball 400 and polyethylene glycol 1400
in the ratio of 1:3rest

Example 18

Human recombinant interferon alpha25 million ME
Tocopherol acetate0.02 g
Ascorbic acid0.01 g
Sodium ascorbate0.015 g
Pantothenic acid0.1 g
Levocarnitine0.05 g
Riboflavin0.0025 g
Orotic acid0.0025 g
Pyrazinamide and/or ethambutol and kanamycin0.25 g
Butoconazole0.2 g
Tween-800.005 g
Sodium lauryl0.0005 g
Benzalkonium chloride0,00001 g
Polyvinylpyrrolidone and the and polyvinyl alcohol 0.025 g
The polyethylene oxide 1500 with confectionery fat (3:1)rest

Made suppositories traditional methods. Preparation of bases for suppositories is in pre-sterilized vessels (reactors) with rotating blades and controllable heating. Main components in powdered form are introduced into the vessel, the mixture is homogenized, sterilized. Separately preparing active ingredients are crushed, are prepared in the basis, then we make the liquid substance in the last queue is interferon. After stirring the mixture under pressure enters the metering device for filling in the relevant forms ("Technology of soft medicinal forms", St. Petersburg, spec lit, 2004).

We studied the safety of funds in suppozitornyj form (recipe No. 16) on Guinea pigs weighing 250-300, the Drug was administered daily for one candle for 5 days 10 animals, observing animals continued throughout the period of drug administration and during the week after the injection. For a specified period, all animals were alive, has not lost in body weight, were outwardly healthy and normal behavior. Thus, studies suggest besur is gnosti drug.

Rabbits in the laboratory model of sepsis compared the effectiveness of funds by recipe No. 16) and the comparison drug (Viferon in suppozitornyj form). Twenty rabbits intraperitoneally introduced infecting dose of Staphylococcus aureus, causing 90-100% mortality. Immediately after the introduction of 10 animals started to get the claimed means in 1 suppository 2 times a day, and the other 10 received Viferon. The group funds remained alive all animals, while ill, but survived 4 rabbit. In the group treated Viferon, killed all the animals.

In rabbits infected with cutaneous Staphylococcus aureus was also shown higher efficiency funds by recipe No. 17) in comparison with drug Viferon in suppozitornyj form. Bacteria were creeping into scarification skin of 10 rabbits. Immediately after the introduction of the infecting dose of the pathogen has begun to carry out the treatment with the above drugs. The introduction of the drug was performed according to the same schemes: one candle twice a day. Was shown higher efficiency funds in example No. 17 in comparison with the drug Viferon: clinical signs of local infection in the group with the stated means appeared in 2 animals (5) and the disappearance of symptoms of inflammatory process, maceration of the skin, abscesses about the state on average for three days earlier in a group with the stated means, than in the comparison group, where sick all 5 animals with clinical manifestations ranging from 7 to 10 days.

Presented indicates a higher efficiency funds and opportunities for its use in the treatment of infectious-inflammatory diseases.

1. Drug for the treatment of severe forms of infectious diseases and mixed infections, characterized in that it contains human recombinant interferon alpha and/or beta and/or gamma-tocopherol acetate or other derivatives of tocopherol, ascorbic acid and/or a salt thereof, Pantothenic acid or calcium Pantothenate, or dexpanthenol, Riboflavin or carnitine, and Orotava acid and/or ornithine or its derivative citruline malate, or Glutoxim, antibacterial, antimycotic substances, auxiliary substances: emulsifiers, stabilizers, preservatives, antioxidants and the substrate in the form of suppositories, with the following ratio of components 1 g suppozitornoj mass of the drug:

Human recombinant interferon alpha
and/or beta and/or gamma type100 thousand ME - 25 million ME
Tocover the La acetate or other derivatives
tocopherol0,001-to 0.055 g
Ascorbic acid and/or its salts0,01-0,05 g
Pantothenic acid or calcium Pantothenate,
or dexpanthenol0.03 to 0.3 g
Riboflavin or0,002-0,004 g
Levocarnitine0.05 to 0.15 g
Orotic acid and/or0.05-0.2 g
Ornithine or citrulline malate or0.01 to 0.2 g
Glutoxim0,0015-0.005 g
Antibacterial substances0.005 to 0.3 g
Antimycotic substances0.005 to 0.2 g
Excipients and baserest

2. The drug according to claim 1, characterized in that as a derivative of tocopherol, it contains tocopherol Dimineata, tocopherol hydrosylate, tocopherol, polyethyleneglycols ccinet.

3. The drug according to claim 1, characterized in that salts of ascorbic acid contains sodium ascorbate, calcium ascorbate, ascorbyl palmitate.

4. The drug according to claim 1, characterized in that as an antibacterial substances it contains substances selected from the group of cephalosporins of III-IV generations: Ceftriaxone, Cefotaxime, ceftazidime, cefoperazone, cefepime, cefpirome, aplidin, cefozopran, celepram, and drugs of various classes of anti-TB spectrum: isoniazid, rifampicin, pyrazinamide, protionamide, ethambutol, kanamycin, fluoroquinolone.

5. The drug according to claim 1, characterized in that as an antimycotic substance containing drugs, selected from the range: Itraconazole, flucytosine, sertaconazole, butoconazole, omoconazole, econazole, natamycin, levorin, ivoryton, miconazole, amphotericin b, termination, pimafucin.

6. The drug according to claim 1, characterized in that as stabilizers contains substances selected from a number of: dextran 40, dextran 60, polyvinylpyrrolidone, polyvinyl alcohol, gidroksietilirovanny starch, glycine, glutamic acid, glycine, silica, EDTA, ADETEF sodium, polyethylene glycol, alginates.

7. The drug according to claim 1, characterized in that as the emulsifiers contains twins, spiny, phospholipids, lanolin, derivatives of lauric alcohol (valium and others)

8. The drug according to claim 1, characterized in that as preservatives contains substances selected from the group, benzalkonium chloride, benzyl alcohol, sorbic acid, benzoic acid, parabens.

9. The drug according to claim 1, characterized in that as the basis contains substances selected from the group of hydrophobic base for suppositories - cocoa butter, hard fat, confectionery fat, or other hydrogenated vegetable fats or ready suppozitornoj bases type Witepsol, Maspol, Labopol, couva-900, 500, 300, Packer 21, Hisomel 100, 50 or other similar fats, as hydrophilic bases - derived cellulose, polyethylene oxides, polyvinylpyrrolidone, reconstitue polymers, copolymers of acrylic and methacrylic acids (Aresol, carbopol, carbomer, ZACAPA, Eudragit), silicones derived collagen, gelatin, derivatives of alginic acid, as defiling basics - oxides with solid fats.



 

Same patents:

FIELD: medicine.

SUBSTANCE: invention concerns medicine, be more specific to oncology, and concerns the substances stimulating maturing of dendritic cells (DC). Application of fucoidan from Fucus evanescens or polysaccharide composition from Fucus evanescens consisting of fucoidan in amount of 60-80% and poly-mannuronic acid in amount of 20-40%, as an agent possessing ability to induce maturing of dendritic cells is offered. The declared fucoidan preparations have a standardised composition and, hence, possess direct biological effect. They keep the properties for long time (3 years).

EFFECT: increase of DC functional activity under the influence of the declared substances.

8 dwg

FIELD: medicine, veterinary science.

SUBSTANCE: invention concerns veterinary science, in particular, to ways of reception of immunomodulatory and antiseptic compounds for prevention and treatment of infectious diseases of animals. The way of reception of a complex immunotropic antiseptic preparation for prevention and treatment of infectious diseases of animals includes mixing of an amber acid, novocaine, Dorogov's antiseptic-stimulator of the second fraction and formalin in water at a following parity of components, wt %: amber acid 1; DAS №2 4; novocaine 0.25; formalin 0.4; the distilled water - the rest, and sterilisation using autoclave treatment which is performed in a 1 atm regimen. Within 20 minutes. The received compound possesses antiseptic, immunomodulatory and trophicostimulating activity at a parenteral way of introduction.

EFFECT: rising of efficiency of the received preparation at treatment and prevention of infectious diseases of animals.

2 tbl

FIELD: medicine.

SUBSTANCE: invention concerns medicine, namely to creation of immunogene compositions and vaccines for prevention or treatment of the infections caused by Gram-negative bacteria. The immunogene compositions containing a transferrin-binding fiber and Hsf, and a way of their reception are offered. It is shown, that the combination of these two antigens synergically influences on production of antibodies with high activity in the analysis of bactericidal Serum. The composition can be used in vaccines against Gram-negative bacteria, including Neisseria meningitides, Neisseria gonorrhoeae.

EFFECT: creation of immunogene compositions and vaccines for prevention or treatment of the infections caused by Gram-negative bacteria.

56 cl, 10 ex, 1 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention concerns area of medical products, in particular to application of complex bonds of iron (III) with carbohydrates or their derivatives for reception of a medical product for improvement of immune protection and-or activity of a brain at patients without an anaemia caused by deficiency of iron or deficiency of iron in which complex bond of iron (III) is iron (III)-polymaltose complex bond or complex bond of iron (III) with a product of oxidation one or several maltodextrins.

EFFECT: development of preparations for improvement of immune protection and-or activity of a brain at patients without an anaemia caused by deficiency of iron or deficiency of iron.

7 cl, 1 tbl, 1 ex

FIELD: medicine; pharmacology.

SUBSTANCE: substance of technical decision seeks to produce immunopotentiating composition based on nanotechnology products, specifically fullerenes and superdispersed diamond powders (nanodiamonds) produced by detonation synthesis. Composition contains modified fullerene of general formula C60-X, where C60 is fullerene nucleus, X is formylporphyrin, as well as superdispersed diamond powder in ratio as follows, wt %: porphyrin modified fullerene C60 - 50; superdispersed diamond powder - 50.

EFFECT: synergetic effect of immunopotentiating components activity with simultaneous considerable reduction in price concerning prototype composition.

2 tbl, 1 dwg

FIELD: medicine.

SUBSTANCE: autoblood is daily sampled in patient as 2 ml/kg of weight. Sampled blood is mixed with 20 ml of 0.06% sodium hypochlorite with further ultraviolet radiation with the help of "Isolda" device for 20 minutes. Then blood is intravenously injected to by drop infusion. Treatment is carried out daily for 5 days.

EFFECT: enhanced efficiency of treatment of patients with chronic obstructive bronchitis.

2 ex, 2 tbl

FIELD: medicine; immunology.

SUBSTANCE: human immune system is stimulated with using osmium iridium mineral dispersed to 0.1 mcm. Then dispersed osmium iridium is separately mixed with medicinal bitumen in ratio 1:1000. Produced composition is processed in vacuum chamber at pressure 0.01-0.001 atm and temperature 20-30°C within 2-4 hours and in autoclave at pressure 5-10 atm and temperature 60-80°C within 5-10 hours. Produced composition is injected to human body.

EFFECT: method allows for immune system stimulation, improved organism protected from adverse factors affecting self-regulation and self-regeneration processes.

2 tbl

FIELD: chemistry, immunology.

SUBSTANCE: extraction of dried cook water of sea cucumber Cucumaria frondosa or dried powder tissues of Cucumaria frondosa by chloroform and methanol mix is performed during boiling with reflux condenser to obtain organic extract; extract is evaporated, evaporated extract is re-dissolved in water, obtained colloid solution is decanted, ethylacetate is added to solution, water phase is decanted and undergoes chromatography in teflon or silica gel columns. Immune system activity of mammals, including lizosomic activity, phagocitosis and active oxygen form generation in macrophags of mammals, infected with bacterial cells, viruses and protozoa, is stimulated by oral, intraperitoneal or intramuscular or combined introduction of frondosite A dosage of 1 to 15 mcg/kg, preferably 10 mcg/kg.

EFFECT: implementation of claimed objective.

11 cl, 18 ex

FIELD: medicine.

SUBSTANCE: composition includes a deoxyribonucleic acid, vitamins B1, B6, acidum ascorbinicum, L-arginin, vitamins B12, PP, acidum folicum and vitamin P, in any biologically comprehensible form in the following quantities. The invention provides expansion of assortment of the preventive preparations possessing as invigorating, immunomodulating, antistress, and angioprotecting actions, besides, at influence on an organism of all substances listed in a composition gives a synergistic effect, besides application of components of a composition in the declared doses, allows to level those by-effects inherent to components of a preparation, applied separately.

EFFECT: increased preventive; invigorating; immunostimulating and angioprotecting actions.

3 cl, 5 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention concerns medicine. A soft drink on the basis of herbs consists of the concentrated vegetative extract obtained from an admixture of herbs, chosen of Sida sps., Boerhaavia diffusa, Vitis vinifera, Tinospora cordifolia and Withania somnifera, along with green palm sugar, the agent causing a fermentation, and carbonised water, in which proportion Sida sps.: Boerhaavia diffusa: Vitis vinifera: Tinospora cordifolia: Withania somnifera in a powdery admixture makes (15-20 : (5-10 : (15-20 : (5-10 : (5-10); Proportion of wt/wt: green palm sugar: the concentrated vegetative extract makes from 1 : 3 to 1 : 4; wt/wt, a proportion of carbonised water: the admixture of the concentrated vegetative extract, green palm sugar and the agent causing a fermentation, makes from 1 : 3 to 1 : 5. Perform: (a) obtaining of parts of Sida sps., Boerhaavia diffusa, Vitis vinifera, Tinospora cordifolia and Withania somnifera; (b) crushing of parts of plants and their mixing with obtaining of a powdery admixture; (c) water addition to a powdery admixture from a stage (b) for obtaining of a water extract; (d) concentration of a water extract from the stage (c); (e) filtration of the concentrated extract from the stage (d); (f) admixture of green palm sugar to the filtered extract from the stage (e); (g) addition of Sacromyces strain and the agent causing fermentation, to the admixture from the stage (f); (h) fermentation of the admixture from the stage (g) during the period of time from 3 till 6 days; (i) filtration of the fermented admixture from the stage (h); (j) concentration of the fermented filtrate from the stage (i) with obtaining of the basic solution and (k) mixing of the basic solution (j) with the carbonised water in wt/wt proportion from 1 : 3 to 1 : 5 with obtaining of a soft drink on the basis of herbs.

EFFECT: creation of a soft drink on the basis of herbs.

11 cl, 5 tbl, 8 ex

FIELD: medicine.

SUBSTANCE: invention concerns pharmaceutical industry, food industry, bioengineering and can be used in manufacturing of medical immunobiological preparations, biologically active additives and food additives. The invention represents versions of the bacteriophage composition which contain species-specific virulent bacteriophages and induced-virulence bacteriophages of Appelman's lytic activity 10-4 with respect to test strains and bacteria isolates recovered from a human body in phage lysate filtrate of nonlysogenic bacteria or phage lysate concentrate filtrate of nonlysogenic bacteria, and desired additives.

EFFECT: invention provides stable virulence of bacteriophages, adaptation thereof to circular agents of bacterial infections.

6 cl, 2 tbl

FIELD: medicine.

SUBSTANCE: antibacterial agent selective effect contains action a bacteriophage concentrate, a herbal extract, a stabilising additive, an essence, an antioxidant, a preservative agent and prebiotics required for normal flora development - amino acid and sugar, as well as a sorbent and a protein-degrading enzyme in desired component ratio.

EFFECT: extended range of ecologically safe high-effective antibacterial agents.

5 cl, 2 tbl, 4 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, particularly to operative obstetrics, and concerns integrated prevention of purulent-septic caesarean section complications that is ensured by intraoperative regional introduction of an antibiotic. Uterine cavity and abdominal cavity are irrigated with ozonised 0.9% normal saline of ozone concentration to 4 mg/l. During two postoperative days, ozonised 0.9% normal saline of ozone concentration 1-2 mg/l is introduced intravenously drop-by-drop in amount 400 ml. Starting from the end of the postoperative day, anterior vaginal fornix is exposed to low frequency pulse magnetic field generated by a vaginal inductor introduced therein for 15 minutes daily during 5-7 days.

EFFECT: method provides accelerated regress of pain syndrome, and involution of uterus, allows reducing introduction of antibiotics.

1 dwg, 2 tbl, 1 ex

FIELD: medicine.

SUBSTANCE: invention concerns medicine, infectious diseases and can be used for plague treatment in experiment. Method involves introduction to white mice of Streptomycin 2-2.5 mg as an antibiotic and Immunofan 0.2-0.3 mkg as an immunomodulator combined in the same syringe, in 72-76 hours after contamination with high-virulent strain Y.pestis 461 in a dose 1000000-200000 "м.к." in amount 0.1-0.3 ml of dissolver.

EFFECT: application of the invention allows improving clinical effectiveness of late-staged plague, providing eradication of the agent ensured by combined introduction of Streptomycin and Immunofan.

1 tbl, 3 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine and pharmaceutics and concerns an inhibitor of propagation of the human immunodeficiency virus that is 4-nitro-6-trifluoromethyl-1,2,3-benzotritiol-1-oxide of formula .

EFFECT: inhibitor is characterised with high biological activity.

5 ex

FIELD: medicine.

SUBSTANCE: invention refers to medical products and concerns a pharmaceutical composition containing 2,4-dichlorbenzyl alcohol combined with amylmethacresol and used for treatment or prevention of viral infections caused by SARS coronaviruses. The pharmaceutical composition is presented in the liquid acidulous oral form, or acidified sucking or chewing solid dosage form. There is also disclosed application of 2,4-dihclorbenzyl alcohol and amylmethacresol for making a medicinal agent for treatment or prevention of viral infections caused by SARS coronaviruses.

EFFECT: invention aims at development of the agent for treatment of viral infections caused by SARS coronaviruses with Urbani phenotype.

9 cl, 9 tbl, 27 ex

FIELD: chemistry.

SUBSTANCE: claimed invention relates to copolymers of diallylaminophosphonium salts with sulphur dioxide demonstrating antimicrobial activity with respect to a number of bacteria, as well as to yeast-like fungi and spores, and can be applied as antiseptic and disinfecting means. Claimed copolymers of diallylaminophosphonium salts with sulphur dioxide aree characterised by general formula where A=Cl- or BF4-. They are soluble in methanol, DMSO, DMFA or if A=Cl- are soluble in water. They are obtained by copolymerisation of equimolar amounts of sulphur dioxide and diallylaminophosphonium salt, selected from tris(diethylamino)diallylaminophosphonium chloride or tris(diethylamino)diallylaminophosphonium tetrafluoroborate.

EFFECT: obtaining novel efficient and low-toxic compounds which do not cause corrosion of processed metals.

2 cl, 3 tbl, 4 ex

FIELD: chemistry.

SUBSTANCE: invention relates to derivatives of 2,3-dihydro-6-nitroimidazo[2,1-b]oxazol of general formula (1), as well as to their optically active forms and pharmacologically acceptable salts: where values of R1, R2 and n are given in i.1 of invention formula.

EFFECT: development of compounds, which have bactericidal action against Mycobacterium tuberculosis, polyresistant Mycobacterium tuberculosis and can be applied as antituberculosis medication.

3 cl, 16 ex, 183 tbl, 1515 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention concerns the technology of biologically active additives. Hydrolytic decomposition and extraction of the lignin-containing raw materials at bubbling through a reactionary admixture of an oxygen-containing gas, separation of a liquid phase, its acidification and separation of the precipitated residue as a target product is carried out.

EFFECT: reduction of a working cycle duration and increase of target product output possessing a wide spectrum of biological activity.

4 cl, 2 ex, 2 tbl

FIELD: medicine.

SUBSTANCE: invention concerns chemical-pharmaceutical industry, and concerns medicinal compound on the basis of glycyrrhizic acid derivatives, allowing to increase bioavailability of the bonds considerably and can be used in medicine, virology, pharmacology, for example as an inhibitor of human immunodeficiency virus reproduction. The medicinal compound for inhibition of human immunodeficiency virus reproduction includes sodium carbonate and glycyrrhizic acid derivatives, the mass parity as part of di - and tri glycyrrhizic acid nicotinates and sodium carbonate lies in the range from 1:1 to 1:3.

EFFECT: increase of biologically active component - admixtures of di - and tri glycyrrhizic acid nicotinates bioavailability.

3 ex, 3 tbl

FIELD: medicine.

SUBSTANCE: invention concerns medicine, in particular, to gastroenterology, and concerns treatment of chronic virus hepatitis B. For this purpose Roncoleukin is intravenously driply administered in a dose of 500 mg, with rate of 1-2 ml/min, during 4-6 h 2 times a week - 1 month. Then the specified preparation is administered subcutaneously, 1 ml 2 times a week within 2 months.

EFFECT: elimination of a cellular link of immunity imbalance, rapid normalisation of clinico-laboratory indicators without by-effects presentation.

2 ex

Up!