Food composition containing immunoglobulins and oligosaccharides

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention presents the method and composition for treatment and-or prevention of infection, and said method includes oral introduction of the composition to a mammal, and said composition involves galactose-containing indigestible oligosaccharide and immunoglobulin of milk or colostrum of hyperimmunised cows.

EFFECT: development of the effective method for the compositions for treatment and-or prevention of infection.

15 cl, 1 tbl, 4 ex

 

The present invention provides a method of prevention and/or treatment of intestinal infections and/or infections of the respiratory tract, the method includes the introduction of food compositions, including antibodies and nevereverever oligosaccharides.

The level of technology

The respiratory tract and intestines are the traditional sites of infection by pathogenic microorganisms. Despite the fact that the body is the master often has an active immune system, frequent infections of the respiratory tract and intestines due to the fact that they are in direct contact with the environment and exposed to pathogenic microorganisms (such as viruses, bacteria, protozoa, fungi, etc)that can be transmitted, for example, through direct contact, through the air and through food. There are many microorganisms that cause disease in children and others. For subjects whose immune systems are weakened, the risk of infection and severe illness is even higher.

Respiratory syncytial virus (RSV) is a major cause of serious diseases of the lower respiratory tract in infants and older children. Primary RSV infection most often occurs in children aged from 6 weeks to 2 years. It is believed that RSV is the cause of 75% of the all children bronchiolitis and up to 40% of all childhood pneumonia. The group of children with an increased risk of RSV infection include premature infants and children with bronchopulmonary dysplasia, congenital heart disease, congenital or acquired immunodeficiency, and mucoviscidosis. The mortality rate in children under 2 years of age with heart disease or lung, who were hospitalized with RSV infection is 3% - 4%. The choice of treatment methods are diagnosed with RSV disease is very limited. Severe RSV disease of the lower respiratory tract often requires significant maintenance therapy, including the introduction of humidified oxygen and auxiliary breathing.

Epidemiological studies have also shown that the frequency of asthma and allergic diseases in children up to 12 years old is significantly higher in cases when they are at an early age were hospitalized with RSV infection.

Acute otitis media (AOM) is the most frequent diagnosis identified in outpatient examination by doctors of children aged from 1 year to 4 years. Is a clear correlation between the presence of virus in the nasopharynx and the occurrence of otitis media; using highly sensitive molecular methods (e.g., PCR) respiratory viruses detected in up to 90% of cases. RSV, adenoviruses and influenza viruses are the most common viruses and RSV composition is jet from 10 to 70% of viral isolates biological fluid, allocated from the middle ear. In the examination of children aged 2 to 24 months, suffering from bronchiolitis, found that 86% of them has a place AOM; RSV was isolated in 71% of patients. In most cases, a viral infection of the nasopharynx and distal tubes caused dysfunction Evstafieva pipe leading to the temporary negative pressure in the middle ear, which contributed, thus, the secondary viral or bacterial middle ear infection. The most common bacteria involved in mixed RSV-bacterial infection, areStreptococcus pneumoniaeandHaemophilus influenzae. In addition, we show that the increased synthesis of proinflammatory cytokines and cell adhesion molecules in the middle ear, RSV infected, can contribute to inflammation in otitis media.

RSV is also very common in older people and along with the flu is a major cause of death, but still there is no available vaccine to prevent death caused by RSV.

Rotavirus infection can cause gastroenteritis. Most often infected by the virus exposed infants and small children. Children aged from 3 months to 2 years rotavirus is the most common cause of diarrhea as a consequence of hospitalization. Rotavirus causes diarrhea in the winter months and is sobaypanhellenic centres child protection and children's hospitals. Almost all children 3 years have rotavirus infection. Symptoms of infection of young children can be very different from vomiting, diarrhea, fever, dehydration and pain to more serious long-term complications, such as lactose intolerance, intolerance to carbohydrates, early protein intolerance and increased susceptibility to other infections. Rotavirus is a major cause of child mortality in countries with less developed health care systems.

It is known that the prevention of respiratory and intestinal infections difficult to implement, there is a very small number of vaccines to prevent infections of the respiratory tract or gastrointestinal tract, particularly RSV and rotavirus. An attempt was made to prevent RSV infection in young children, which constitute the high risk of death from RSV, with regular intramuscular injections of monoclonal antibodies. This monoclonal antibody has the effect of reducing the number of serious episodes of RSV in children at risk. However, this method is very invasive, very expensive and available only for a small proportion of people at risk of RSV infection and subsequent disease to which it leads.

In newborn infants, breastfeeding mother is ill milk, respiratory and intestinal infections were less frequent and occur with less weight. In the art it is believed that fewer infections and lower severity of their course to some extent due to the fact that breast milk contains immunoglobulin(s), neutralise(s) the activity of the virus and/or other microorganism.

Treatment of intestinal infections and respiratory tract infections are often difficult. In most cases, treatment is aimed only at alleviating symptoms. Treatment of rotavirus infection is limited to oral and/or intravenous rehydration. For the treatment of respiratory infections there are only a few effective medicines, and often the treatment requires pulmonary injection of the drug. In young children this leads to serious stress. Thus, today there is a need for more effective means, which preferably can be entered without stress or, at least, reducing stress, which are newborn babies and children.

Some pathogens that enter the body through the intestinal tract or the respiratory tract and cause systemic disease. For example, the herpes virus may initially come through on the respiratory tract and then to penetrate into other parts of the body and stay there, to cause disease after some time.

In the publication WO9613271 describes the composition conducive to maintaining healthy gastrointestinal tract, which includes an effective amount useful for human intestinal microorganism and an effective amount of immunoglobulin composition comprising concentrated immunologically active immunoglobulins. Another composition for restoring and maintaining the health of the intestine consists of 40-60% (mass.) immunoglobulin composition comprising concentrated immunologically active immunoglobulins and 40-60% of the mass. soluble dietary fiber selected from inulin, fructo-oligosaccharides, pectin, guar gum and mixtures thereof.

The invention

In a multicenter clinical trial was unexpectedly found that oral administration of infant food composition containing galactooligosaccharide, can be used to reduce the frequency and/or severity of infections, especially infections of the respiratory tract. Anti-infective action galactosaemia soluble dietary fiber, such as galactooligosaccharide (GOS), has not previously been described.

In addition, the applicants of the present invention found that galactooligosaccharide stimulate the immune system. Those on whom lugenia led to the assumption, the ability galactosaemia prebiotic components (e.g., WTP) to reduce the infection is the result of a combination of increased immune response and positive stimulation of intestinal flora. Studies of the mechanism of action galactosaemia oligosaccharides at the present time has resulted in additional improvement of child nutrition and the development of compositions and methods for reducing infections according to the present invention.

The present invention provides a composition that includes galactosidase prebiotic components and one or more of the antibodies with activity against one or more pathogenic microorganisms, such as one or more species of pathogenic viruses, bacteria, fungi, etc. Preferably, the immunoglobulins obtained from colostrum or milk of mammals, processed antigens, for example, from colostrum or milk cows, hyperimmunizing against one or more pathogens of man.

In particular, the combination of the immunostimulating action of the STATE and action of antibodies, neutralizing respiratory virus, provides a useful combination of treatment and prevention of respiratory tract infections caused by viruses.

In another preferred embodiment, altoadige of the invention the combination of the stimulating action of bifidobacteria Bifidobacteria, immunostimulating action of the STATE and actions of an antibody that neutralizes viruses, especially effective in the treatment and/or prevention of intestinal infections such as rotavirus.

Oligosaccharides and one or more immunoglobulins act synergistically. Protivoradarnyh immunoglobulin binds rotavirus, which is subsequently neutralized by the immune system of the intestine.

Oligosaccharides stimulate the growth of Bifidobacterium Bifidobacterium, which leads to a decrease in rotavirus infection. Oligosaccharides also stimulate the restoration of normal bowel flora in rotavirus infection and after it. This leads to a reduction in the severity and duration of diarrhea, as well as to decrease the possibility of re-infection by pathogens. In addition, both ingredients can be combined in baby food, which makes additional intervention unnecessary.

In another preferred embodiment, the present invention relates to a combination of one or more immunoglobulins, galactosaemia oligosaccharides and acidic oligosaccharides. Acidic oligosaccharides prevent the adhesion of pathogens to the epithelial cells, which leads to an additional reduction of infections (frequency and/or severity of infections and/or risk re-infection.

In a particularly effective embodiment, the present invention provides a composition including galactosidase oligosaccharides, immunoglobulin with neutralizing activity against respiratory virus and immunoglobulin with neutralizing activity against intestinal virus. The present composition can be easily made using cows, hyperimmunizing against both viruses, and the Association product of the secretion of the mammary glands such cows with galactosialidosis the oligosaccharides.

The presented composition especially effective in the prevention and reduction of infection in infants without the need to introduce them by injection or oral multiple antigens in the form of active vaccine or injection of monoclonal antibodies. In practice, preferably the present composition is administered orally and can be administered in the form of a food product or pharmaceutical preparation, preferably the present composition is included in the food composition.

Detailed description of preferred embodiments of the present invention

In accordance with one aspect, the present invention provides a method of treatment and/or prevention of infection, and this method includes the introduction of composition, including galactosidase nepera alively oligosaccharide, containing at least two end sharidny fragment, where at least one terminal saccharide is selected from the group comprising glucose and galactose; and at least one terminal saccharide is selected from the group comprising galactose and fucose; and immunoglobulin having activity against one or more pathogenic organisms.

In accordance with another aspect, the present invention provides a composition suitable for the treatment or prevention of infection or disease and includes galactosidase nevereverever oligosaccharide containing at least two end sharidny fragment, where at least one terminal saccharide is selected from the group comprising glucose and galactose; and at least one terminal saccharide is selected from the group comprising galactose and fucose; and immunoglobulin possessing activity against pathogenic microorganisms.

Oligosaccharides

The present invention includes an introduction galactosidase neperebrodivsego oligosaccharide (GAL-oligo)containing at least two end sharidny fragment, where at least one end charigny fragment selected from the group comprising glucose and galactose; and at least one terminal saccharide is selected from the group comprising galactose and fucose. Preferably the, sugars in GAL-oligo are β-related.

The term "terminal saccharide" refers to a saccharide, which is connected with a portion of another saccharide (e.g., galactose, glucose, fructose, or fucose). GAL-oligo in accordance with the present invention preferably contains not more than 4 terminal saccharides, preferably not more than 2.

The term "nevereverever oligosaccharides", when used in the present invention refers to saccharides which are not digested or partially digested by the action of acids or digestive enzymes present in the upper division of the human gastrointestinal tract (small intestine and stomach), but which are fermented by the flora of the human intestine. In a preferred embodiment of the invention GAL-oligo contains at least one terminal glucose and one end fucose. Even more preferably, presents galactosidase nevereverever oligosaccharide comprises at least one terminal galactose and at least one terminal glucose. Preferably, the oligosaccharide in General, includes 2 end sharidny fragment and from 2 to 60 sharidny fragments.

Preferably, GAL-oligo is selected from the group including transplantological, galactooligosaccharide, lacto-N-tetraaza (lacto-N-tetraose - LNT), lacto-N-neoteris (lacto-N-neotetraose - neo-LNT), fucosyl is the TOZ, fokusirovannyi LNT and fokusirovannyi neo-LNT. In a particularly preferred embodiment, the method according to the present invention includes the introduction of transplantationfollow ([galactose]n-glucose, where n is an integer in the interval from 1 to 60, for example 2, 3, 4, 5, 6, ..., 59, 60; preferably n is selected from 2, 3, 4, 5, 6, 7, 8, 9 or 10). Transplantological (CBT), for example, sold under the trade name VivinaTM(Borculo Domo Ingredients, Netherlands). Preferably sugars in transplantologer are β-related.

The composition according to the present invention can be provided in powder and liquid form. The composition according to the invention preferably comprises from 0.1 to 12 grams GAL-oligo per 100 grams of composition based on dry weight, preferably from 0.5 to 8 grams, more preferably from 1.0 to 7.5 grams. After reconstitution of the powder with the liquid and the introduction of liquid medication to the infant specified number of GAL-oligo provide the desired effect without causing intestinal discomfort.

Immunoglobulins

The composition according to the present invention contains at least one immunoglobulin having neutralizing activity against one or more pathogenic microorganisms. The specified immunoglobulin preferably possesses it is religouse activity against one or more types of viruses, bacteria, protozoan microorganisms, parasites, or prion. In a preferred embodiment, the immunoglobulin(s) has(have) activity, neutralizing the virus.

The terms "activity" or "neutralizing activity related to immunoglobulin or a mixture of immunoglobulin (such as IgG and IgA), means the ability of the immunoglobulin(s) to bind pathogenic(e) microorganism(s)against whom(s) effect(s) of the immunoglobulin(s) and the harmful effect of which(s) he(s) impact(s) under conditions in viv, in particular, the ability to bind antigens used for immunization of the animal. The activity can be examined using tests of binding in vivo or in vitro. The terms "specific immunoglobulin" or "specific immunoglobulins belong to the immunoglobulin(s), (e) will neutralize(comply) with one pathogenic microorganism (for example, one virus or viral strain, one kind or one strain of bacteria and so on), namely the one against which he/they is(are).

Preferably the composition comprising the antibody (or mixture of antibodies)with(th) neutralizing activity against one or more viruses that infect the respiratory tract (i.e. immunoglobulin having neutralizing activity against respiratory virus) and/or immunoglo the Ulin (or mixture of antibodies), with(th) neutralizing activity against one or more viruses that infect the intestines (i.e. immunoglobulin having neutralizing activity against intestinal virus). More preferably, the composition according to the present invention contains the immunoglobulins (or Ig-mixture)that can neutralize the virus is selected from the group comprising myxovirus (Myxovirus), orthomyxovirus (Orthomyxovirus), rhinovirus (Rhinovirus), Echovirus (Echoviruses),Coxsackie virus (Coxsackieviruses), adenoviruses (Adenovirus), respiratory syncytial virus (Respiratory Syncytial Virus (RSV)meta pneumovirus man (human)Meta pneumovirus - MPV), coronavirus (Coronavirus), herpes virus (Herpes virus), measles virus (Measles virus), rotavirus (Rotavirus), caliciviruses (Calicivirus),Astrovirusand cytomegalovirus (Cytomegalovirus). The most preferred composition comprising the immunoglobulin (or Ig-mix)with(th) neutralizing activity against respiratory syncytial virus, and/or immunoglobulin (or Ig-mix)with(th) neutralizing activity against rotavirus.

Preferably the immunoglobulin obtained or can be obtained from milk and/or colostrum, obtained from hyperimmunizing mammals, preferably hyperimmunizing farm animals,most preferably hyperimmunizing cows. Preferably the immunoglobulin obtained or can be obtained from milk hyperimmunizing cows. Methods of producing immunoglobulins from hyperimmunizing mammal known qualified and are described, for example, in GB1573995. The immunoglobulin used in accordance with the present invention, preferably is a mixture of immunoglobulins, which can be obtained from hyperimmunizing mammals. A mixture of immunoglobulins from hyperimmunizing animals may differ from mixtures of immunoglobulins from negabaritnyeperevozki mammals, these mixtures of immunoglobulins in contrast to mixtures of immunoglobulins from normal milk have a high content of immunoglobulin aimed at a specific microorganism such as a virus. Immunoglobulin preferably may be obtained or derived from farm animals, hyperimmunizing antigen respiratory virus and/or antigen intestinal virus, most preferably the antigen respiratory virus antigen intestinal virus. Colostrum and milk of these cows contain immunoglobulin with neutralizing activity against respiratory virus immunoglobulin with neutralizing activity against intestinal virus. Immunoglobulin preferably m is can be obtained or derived from farm animals, hyperimmunizing antigen respiratory syncytial virus and/or rotavirus antigen, most preferably from farm animals, hyperimmunizing antigen respiratory syncytial virus and rotavirus antigen. In an alternative embodiment of the present invention the composition comprises a mixture of milk and/or a mixture of colostrum, in which at least one milk one or colostrum contains immunoglobulin (or Ig-mix)with(s) neutralizing activity against one or more types of viruses that infect the respiratory tract, and at least one milk or colostrum, which contains immunoglobulin having neutralizing activity against one or more types of viruses that infect the intestinal tract. Therefore, the composition can be obtained from colostrum or milk of various animals, one group of animals produces immunoglobulin against one or more respiratory viruses, and another group of animals produces immunoglobulin against one or more gastrointestinal viruses.

Immunoglobulin preferably represents at least one or more (mix) immunoglobulin selected from the group including IgM, IgY, IgG and IgA, most preferably IgG and/is whether IgA. Preferably the composition according to the present invention contains IgG and IgA. Both classes are effective in preventing infection of epithelial cells by pathogenic microorganisms and both detected in colostrum and milk. It has also been shown that avian IgY effective in the prevention of infection of epithelial cells by pathogenic microorganisms. Preferably the composition according to the present invention contains the immunoglobulin(s), allocated(e) of milk, where the specified milk obtained from hyperimmunizing cows. Thus, preferably the mass ratio of IgG/IgA is in the range from 1 to 100.

The immunoglobulin is preferably received at least one dairy source selected from the group including colostrum or milk products, preferably fresh milk, fresh dairy products, micro-filtered milk with a long shelf life, whole colostrum powder, skim colostrum powder, milk powder, concentrate protein, colostrum, milk protein concentrate, milk protein isolate, isolate protein, colostrum protein concentrate of whey and isolate protein whey.

Baby receiving breast milk as a significant portion of the power supply, receives approximately from 0.2 g to 2 g of immunoglobulin in the day. The method according to the present izobreteny which preferably includes the introduction in the interval from 0.05 gram of immunoglobulin per kg of body weight up to 2 grams of immunoglobulin per kg of body weight per day, more preferably in the range from 0.1 grams/kg body weight to 1 gram/kg of body weight of immunoglobulin in the day.

The composition according to the present invention, in particular the composition of the product baby food, contains in the range of from 0.25% (wt.) up to 5% (mass.) immunoglobulin based on the dry weight of the composition according to the invention.

The present composition preferably contains at least 1% (mass.) immunoglobulin(s), with(their) neutralizing activity against respiratory syncytial virus based on the total weight of the immunoglobulin, preferably at least 2% (mass.), even more preferably, at least a 2.5% (mass.), preferably not more than 90% (mass.). The composition according to the present invention preferably contains at least 1% (mass.) immunoglobulin(new)with(their) neutralizing activity against rotavirus, based on the total weight of the immunoglobulin, preferably at least 2% (mass.), even more preferably, at least a 2.5% (mass.), preferably not more than 90% (mass.).

The mass ratio of GAL-oligo: immunoglobulin composition according to the present invention preferably ranges from 0.01 to 100, more preferably in the range from 0.1 to 10.

The present composition preferably provides from 01 to 30 g of immunoglobulin(new) per day. When the composition is administered to the infant, it preferably provides reception from 0.2 to 5 g immunoglobulin a day. When the composition is injected adults, it preferably provides reception from 0.5 to 15 g of immunoglobulin in the day.

In yet another preferred embodiment of the present invention, the composition according to the present invention includes an immunoglobulin having neutralizing activity against one or more pathogens selected from the group including Helicobacter pylori, Enterotoxigenic Escherichia coli (ETEC) and Shigella (shigella).

Digestible galactose saccharide

The composition according to the present invention preferably includes digestible carbohydrate containing digestible galactose saccharide. The composition contains at least 5% (mass.) digestible galactose of saccharide based on the total dry weight of the composition, and the specified saccharide selected from the group comprising galactose and digestible galactosidase saccharide that contains at least two end sharidny fragment; where at least one end charigny fragment selected from the group comprising glucose and galactose; and at least one terminal saccharide is selected from the group comprising galactose and fucose. The preferred composition used is used in the present method, contains at least 5% (mass.) digestible galactose of saccharide based on the total dry weight of the composition according to the invention, preferably at least 10% (mass.), even more preferably, at least 25% (mass.).

The term "digestible galactose saccharide", when used in the present invention, refers to mono-, di-, tri -, or polysaccharides, which are digested in the intestines of healthy humans by the action of acids or digestive enzymes present in the upper digestive tract of a (small intestine and stomach). In the present method preferably uses lactose.

Preferably digestible galactose saccharide is a lactose. Preferably, at least 50% (mass.) carbohydrate composition used in the present method, is lactose, preferably at least 75% (mass.), even more preferably, at least 90% (wt.). The term "carbohydrate", when used in the present invention, refers to an easily digestible to the carbohydrate, respectively well-known practice. The composition used in the present method, preferably contains at least 10% (mass.) lactose of saccharide based on the total dry weight of the present composition, preferably at least 25% (mass.), even more preferred the equipment, at least 40% (mass.), most preferably, at least 50% (mass.) To ensure optimal nutrition of the infant, i.e. composition, which is very similar in composition to breast milk, the method according to the present invention preferably includes the introduction of a composition comprising from 40 to 60% (mass.) lactose based on the total dry weight of the composition.

In yet another preferred embodiment of the present invention the current invention relates to the introduction of from about 2 to 50 grams of lactose per reception, preferably about 10 to 25 grams of lactose per dose. Reception (portion) is preferably from 5 to 500 ml, more preferably from 100 to 300 ml.

The mass ratio of digestible galactose saccharide: galactosialidosis nevereverever oligosaccharide is preferably more than 1, more preferably more than 5, even more preferably more than 10. The ratio is preferably less than 1000, more preferably less than 100.

The combination of oligosaccharides

In a particularly preferred embodiment, the present invention presents a method includes the introduction of this GAL-oligo and the second neperebrodivsego oligosaccharide selected from the group comprising nevereverever dextrins, xylooligosaccharide, Ara is unoriginality, glucooligosaccharide, mannooligosaccharide, frukooligosaharidov - fructans - Levanova type (β-D-(2→6)fructofuranosyl)n-α-D-glucopyranosid) and fructans hinolinovogo type (β-D-((2→1)fructofuranosyl)n-α-D-glucopyranosid). Preferably the second oligosaccharide selected from the group comprising inulin, hydrolyzed inulin and fructo-oligosaccharides.

The composition according to the present invention preferably includes from 0.5 to 12 grams of the second neperebrodivsego oligosaccharide, more preferably from 1 to 8 grams of the second neperebrodivsego of oligosaccharide per 100 grams dry weight of the present composition. DP of the second oligosaccharide preferably less than 40, more preferably in the range from 10 to 30.

Optimally, the present composition is in the range from 1 to 12 grams of water soluble not digested oligosaccharides (i.e. with or without the second second, third, etc. water-soluble neperebrodivsego oligosaccharide) per 100 grams dry weight of the present composition, more preferably only in the interval from 2 to 9 grams.

The preferred mass ratio:

A. (oligosaccharides with DP in the range from 2 to 5): (oligosaccharides with DP in the range from 6 to 9);

b. (oligosaccharides with DP in the range from 10 to 60): (oligosaccharides with DP in the range from 6 to 9),

in both cases, be content exceeding 1.

Preferably both mass ratios are more than 2, even more preferably more than 5.

The presented method preferably includes the introduction of from 0.5 to 10 grams of transplantationfollow with DP in the range from 1 to 10 per 100 grams dry weight of the composition, more preferably in the range from 2 to 5 grams. The present invention preferably comprises in the range of from 0.5 to 20 grams of fructooligosaccharide with DP in the range of from 15 to 40 per 100 grams dry weight of the composition, more preferably in the range from 1 to 5 grams. The term "fructooligosaccharide" refers to nevereverever the polysaccharide carbohydrate comprising a chain of at least 10 β-linked fructose fragments.

Acidic oligosaccharides

In an additional preferred embodiment of the invention the second nevereverever oligosaccharide is an acid oligosaccharide. The term acid oligosaccharide refers to an oligosaccharide comprising at least one acidic group selected from the group comprising N-acetylneuraminic acid (N-acetylneuraminic acid), N-glycolylneuraminic acid (N-glycoloylneuraminic acid), free or esterified carboxylic acid group, sulfuric acid group and phosphoric acid. Acid oligosaccharide is preferably polyhexes. Before occhialino, at least one of the above-mentioned acid groups located on the end hexose fragment acid oligosaccharide. Preferably the acid oligosaccharide contains a carboxylic acid at the end hexose fragment where the specified carboxylic acid group can be free or esterified. Methods of obtaining esterified pectinoid hydrolysates, which can suitably be used in the method and composition according to the present invention, is presented in WO 01/60378 and/or WO 02/42484, which are included in the description by reference.

Preferably, the acid oligosaccharide comprises one, preferably two terminal fragment of uronic acid, which can be free or esterified. Preferably, the end fragment of a uronic acid selected from the group comprising galacturonic acid, glucuronic acid, Euronaval acid, mannurone acid, Rybarikova acid and alternova acid. These fragments can be free or esterified. In an even more preferred embodiment of the invention, the end exony fragment contains a double bond, which is located between C4and C5the provisions limit hexoses fragment. Preferably, one end exonic fragments includes a double bond. To Nava hexose (for example, uronic acid) preferably has the structure represented in figure 1.

Figure 1: Preferred end hexana acid group

where R is preferably selected from the group comprising hydrogen, hydroxyl or acid group, preferably a hydroxyl group (see above); and at least one Deputy, selected from the group comprising R2, R3, R4and R5represents the group N-acetylneuraminic acid, N-glycolylneuraminic acid, free or esterified group, carboxylic acid group, sulfuric acid group and phosphoric acid, and the remainder of R2R3, R4and R5represent a hydroxyl group and/or hydrogen. Preferably one Deputy from the group comprising R2, R3, R4and R5represents the group N-acetylneuraminic acid, N-glycolylneuraminic acid, free or esterified group, carboxylic acid group, sulfuric acid group and phosphoric acid, and the remaining R2, R3, R4and R5represent a hydroxyl group and/or hydrogen. Even more preferably, one Deputy from the group comprising R2, R3, R4and R5represents a free or esterified carboxylic group to the slots, and the remaining R2, R3, R4and R5represent a hydroxyl group and/or hydrogen; and n is an integer and represents the number exonic fragments (see also degree of polymerization (Degree of Polymerisation DP) below), which can be any exony fragment. Accordingly, n is an integer in the range from 1 to 5000, which means the number exonic fragments, and these hexose fragments preferably represent groups of uronic acids, even more preferably, the fragments of the galacturonic acid. The group of carboxylic acids on these fragments can be free or partially esterified and, preferably, are at least partially methylated. Most preferably, R2and R3represent a hydroxyl group, R4represents hydrogen and R5represents a free or esterified carboxylic group of the acid.

Acid oligosaccharide, which is used in the method according to the invention has a degree of polymerization (DP) in the range from 1 to 5000, preferably in the range from 1 to 1000, more preferably in the range from 2 to 250, more preferably in the range from 2 to 50, most preferably in the range from 2 to 10. If you are using a mixture of sour is the shaft oligosaccharides with different degrees of polymerization, the average value of DP mixture of acid oligosaccharide is preferably in the range from 2 to 1000, more preferably in the range from 3 to 250, even more preferably in the range from 3 to 50.

Acid oligosaccharide is preferably characterized by a degree of methoxylation of more than 20%, preferably more than 50%, even more preferably more than 70. Preferably the degree of methylation of acidic oligosaccharides is more than 20%, preferably more than 50%, even more preferably more than 70%.

Acid oligosaccharide is preferably introduced in a quantity in the range from 10 mg to 100 g per day, preferably in the range from 100 milligrams to 50 grams per day, more preferably in the range from 0.5 to 20 grams per day.

Respiratory tract infections and bowel

The present invention provides a method of treatment and/or prevention of respiratory tract infections and/or infections of the intestine. The most frequent and severe infections of the respiratory tract and intestines in infants and young children are typically caused by a viral infection, however, the invention is also suitable for the treatment and/or prevention of infections caused by other pathogens, such as, but without limitation, pathogenic bacteria, protozoan bacteria, parasites, prio is s, mushrooms, etc. the Term "pathogens" in this description refers to Microsporum or podtropolis organisms or tools, including viruses and prions, which can cause disease in humans. In a preferred embodiment, the present invention provides a method of treatment and/or prevention of respiratory tract infections caused by myxoviruses (Myxovirus), orthomyxoviruses (Orthomyxovirus), rhinoviruses (Rhinovirus), echoviruses (Echoviruses),the Coxsackie virus (Coxsackieviruses), adenovirus (Adenovirus),Parainfluenzavirus, respiratory syncytial virus (Respiratory Syncytial Virus (RSV), meta-pneumovirus man (human)Meta pneumovirus - MPV), cov (Coronavirus), herpes virus (Herpes virus), measles virus (Measles virus), cytomegalovirus (Cytomegalovirus),Histoplasma capsulatum, Coccidioides immitis, Blastomyces dermatitidis, Cryptococcus Aspergillus, Mucorales.The method according to the present invention is particularly suitable for the treatment and/or prevention of infection with respiratory syncytial virus and/or rotavirus.

In a preferred embodiment, the present method relates to the treatment and/or prevention of infectious respiratory diseases, preferably selected from the group including tuberculosis, bronchitis, bronchiolitis, tracheitis, pneumonia, sissit, rhinitis, severe acute respiratory syndrome (severe acute respirtory syndrome - SABS), croup, epiglottitis, histoplasmosis, coccidioidomycosis, blastomycosis, cryptococcosis, aspergillosis, monorails, pneumonia and otitis media. In a particularly preferred embodiment, the invention provides a method of treating and/or preventing viral pneumonia and/or bronchitis. The method according to the present invention is also suitable for the treatment and/or prevention of symptoms of respiratory tract infections selected from the group that includes the inflammation of the lungs, congestion of the lungs, excessive production of mucus, respiratory disorders (i.e. difficulty breathing, especially breathing. The presented method is also suitable for the treatment and/or prevention of asthma.

In an additional preferred embodiment, the present invention provides a method of treatment and/or prevention of intestinal infections, including gastroenteritis, more preferably viral gastroenteritis. The method according to the present invention is also suitable for the treatment and/or prevention of the symptoms and consequences of viral gastroenteritis is selected from the group including watery diarrhea, vomiting, fever, chills and abdominal pain. The presented method is suitable for the treatment and/or prevention of more serious long-term complications, such as impaired absorption of lactose, not perenosimost lactose, the early appearance of intolerance to the protein and increased susceptibility to other infections.

Providing a way to prevent primary infection of the gut and respiratory tract pathogens that cause systemic disease, the present invention can also contribute to the prevention of systemic diseases, including herpes simplex I and II types.

The treatment group

The method according to the present invention is particularly suitable for the treatment and/or prevention of respiratory and intestinal infections in humans, preferably (healthy) children aged 0 to 10 years, preferably children aged between 0 and 4 years, more preferably, infants up to 1 year. This method can also be used to treat and/or prevent the above diseases, infections and symptoms in premature infants (infants born before the expiration of 37 weeks of pregnancy). The method is applicable for the treatment of infants and young children at high risk due to other complications of health or other complications or disorders of the environment.

This method is especially suitable for the treatment and/or prevention of respiratory and/or intestinal infections in mammals with reduced immunity, preferably in the elderly (people over the example is about 60 years), subjects infected with human immunodeficiency virus (HIV), subjects suffering from one or more of the following diseases: nephrotic syndrome, multiple myeloma, lymphoma, disease Hodgson, subjects undergoing surgery organ transplantation and for the treatment of subjects with chronic diseases of the heart, kidneys and lungs (in particular, chronic obstructive pulmonary disease (chronic obstructive pulmonary disease - COPD), emphysema lung, sarcoidosis, cystic fibrosis, bronchiectasis, cancer of the lung, atelectasis, respiratory failure, industrial lung disease, asthma), diabetes mellitus, and alcoholism. This method is mainly used for the treatment or prevention of COPD patients, HIV infection and/or diabetes, and patients whose health is weakened by another disease.

In an additional preferred embodiment of the present invention the method includes the introduction of this song people, mainly hospitalized patients who are on auxiliary breathing or ventilator in the intensive care unit and patients are particularly vulnerable to viral infections.

Thus, in accordance with another aspect, the present invention relates to method significant others and/or reduce the duration of the course and the severity of the disease, which, as expected, is the result of intestinal infection. This invention, in accordance with another aspect, provides a grouping of immunostimulatory effects not digested oligosaccharides with immunoglobulin, which may contribute to the prevention of penetration into the body of pathogens and infection of the body specified by microorganisms, leading to systemic disease other than respiratory or intestinal diseases.

Food recipe

Drug therapy of respiratory tract infections in infants ages 0 to 4 years is often very difficult, because you must enter a large number of medicines pulmonary way. Effective vaccines to prevent respiratory disease for this age group of patients no. Prevention by means of monoclonal antibodies for injection is invasive, costly and only partially effective. The present invention provides a method of treatment and/or prevention of respiratory infections, including oral administration of the nutritional composition. Therefore, the presented method allows to solve the problem of pulmonary or intramuscular injection.

Food composition suitable for use according to the presented method, predpochtitelno contains from 10 to 60% (EN.) lipid, from 5 to 50% (EN.) protein, 15 to 90% (EN.) carbohydrate. More preferably, the food composition comprises from 7.5 to 12.4% (EN.) protein, 40 to 55% (EN.) carbohydrates, and 35 to 50% (EN.) fat % (EN.) ("n." is an abbreviation for energy percentage and indicates the contribution of each component as a percentage in the total caloric content of the product).

The food composition preferably also contains at least one polyunsaturated fatty acid with long chain long chain polyunsaturated fatty acid LC-PUFA), preferably selected from the group comprising eicosapentaenoic acid (EPA, n-3), docosahexaenoyl acid (DHA, n-3) and arachidonic acid (AA, n-6), because they further reduce respiratory tract infections and/or their symptoms. Preferably, the composition according to the present invention contains AA and DHA, more preferably AA, DHA and EPA. This combination neperebrodivsego(s) of the oligosaccharide(s) and LC-PUFA effect of synergy.

Preferably the composition according to the present invention includes at least 0,1% (mass.), preferably, at least 0.25 per cent (mass.), more preferably, at least 0.5 percent (mass.), even more preferably, at least about 0.75% (mass.) LC-PUFA with 20 and 22 carbon atoms based on the total fat content. The content of LD-c PUFA 20 and 22 carbon atoms in the composition according to present the invention preferably does not exceed 15% (mass.) total fat content, preferably not more than 10% (mass.), even more preferably does not exceed 5% (mass.) total fat content.

The EPA content preferably does not exceed 15% (mass.) total fat content, more preferably does not exceed 5% (mass.), most preferably does not exceed 1% (mass.), and preferably, is at least 0.05 per cent (mass.), more preferably, at least 0,1% (mass.) total fat content. The DHA content preferably does not exceed 10% (mass.), more preferably does not exceed 5% (mass.), most preferably does not exceed 1% (mass.), but is at least 0,1% (mass.) total fat content. The composition according to the present invention preferably includes at least 0,1% (mass.) AA, even more preferably at least 0.25 per cent (mass.) AA, most preferably at least 0.5 percent (wt.) AA is based on the total fat content. The AA content preferably does not exceed 5% (mass.), more preferably does not exceed 1% (mass.) total fat content.

The composition is suitable for administration to adults, can include increased amounts LC-PUFS. The content of EPA in this case preferably does not exceed 15% (mass.) total fat content, more preferably less than 10% (mass.), but is preferably at least 0.05% of (mass.), more preferably,at least 0,1% (mass.) total fat content. The DHA content preferably does not exceed 15% (mass.), more preferably does not exceed 10% (mass.) and is at least 0,1% (mass.) total fat content. The composition according to the present invention preferably includes at least 0,1% (mass.) AA, even more preferably at least 0.25 per cent (mass.) AA, most preferably at least 0.5 percent (wt.) AA is based on the total fat content. The AA content preferably does not exceed 15% (mass.), more preferably does not exceed 10% (mass.) total fat content.

The method according to the present invention does not include a method involving the introduction of a composition containing a female human milk. Therefore, preferably the method according to the present invention includes the introduction of a composition comprising a substance nonhuman origin, which preferably is a food product suitable for oral administration to a human, more preferably a fibrous carbohydrate, fat and/or protein of human origin, preferably of plant, animal, microbial or synthetic origin.

Pharmaceutical formulation

The present invention provides a method of treatment and/or prevention of respiratory and/or intestinal infections including oral administration of the pharmaceutical composition, containing nevereverever oligosaccharides and immunoglobulin. Preferred pharmaceutical preparations can be presented in liquid or solid form. Drugs in liquid form may include an immunoglobulin obtained from colostrum, milk or egg yolk in a variety of ways to remove contaminating bacteria and increase shelf life. The preferred method for removal of bacteria is microfiltration. Pharmaceutical compositions in solid form include powders for reconstitution, tablets, chewable tablets and capsules. A qualified expert in the art can prepare medications, including composition according to the invention for delivery of active ingredients in the greatest quantity in certain sections of the intestine.

Probiotics

In an additional embodiment, the method according to the present invention includes the introduction describes the(s) above neperebrodivsego(s) of the oligosaccharide(s) and/or immunoglobulin and probiotic. Preferably, the probiotic is selected from the group includingLactobacillus, Lactococcus, Bifidobacterium, Enterococcus, Propionibacterium, Pediococcus, BacillusandStreptococcusmore preferably from the group includingLactobacillusandBifidobacterium. Probiotic preferably is a non-pathogenic bacteria that produce lactic acid. Op the food neperebrodivsego(s) saccharide(s) and probiotic bacteria exhibits a synergistic action.

EXAMPLES

EXAMPLE 1

The effectiveness of transplantationfollow in the standard formulation of baby food for infants for the prevention of respiratory tract infections in infants under one year

Method: a multidisciplinary clinical trial carried out in Italy in 7 centers with the participation of 56 pediatricians. At the time of termination of breastfeeding children are divided into two groups. Children group (n=69) enter Nutrilon™ 1 or 2, provided the oligosaccharides at a final concentration of 0.36 g of transalaShare/100 ml (Vivinal-GOS™; Borculo Domo Ingredients, Netherlands) and 0.04 g of fructooligosaccharide/100 ml (Raftiline HP™, Orafti, Tienen, Belgium). Infants in the control group (n=82) give Nutrilon standard™ 1 or 2. Nutrilon™ 1 includes 45% (EN.) carbohydrates; 8% (EN.) protein and 47% (EN.) fat; approximately 97% (mass.) lactose based on the total carbohydrate content; and 7.3 grams of lactose per 100 ml; about 54 grams of lactose per 100 g based on the dry weight of the entire composition.

Nutrilon™ 2 includes 47% (EN.) carbohydrates; 10% (EN.) protein and 43% (EN.) fat; approximately 96% (mass.) lactose based on the total carbohydrate content; and 7.9 grams of lactose per 100 ml; about 54 grams of lactose per 100 g based on the dry weight of the entire composition.

Results: the age of the children varies from 2 to 9 months and children see in the next 6 months. Both groups did not show the any differences in dietary intake. In group a there are 32 episodes of upper respiratory tract infection. In the control group In the total number of episodes of infections of the upper respiratory tract is 60. Thus, the number of cases of upper respiratory infections was significantly lower (p<0.01) in group a than in group C.

EXAMPLE 2

Immunostimulatory effect of a composition containing nevereverever galactosidase oligosaccharides

The experimental set-up: child nutrition, including nevereverever galactosidase oligosaccharides test the reaction of the delayed-type hypersensitivity (delayed-type hypersensitivity - DTH) by oral ingestion of a food, including nevereverever galactosidase oligosaccharides mouse. DTH is an option for Th1 immune response and is determined by the variation of magnification sizes of ear swelling after local stimulation by antigen. To obtain DTH responses in mice as stimulation DTH in both ears injected intradermal injection of 25 µl of detalizirovano Influvac.

Neutral oligosaccharide mix (GF)containing galactooligosaccharide (GOS) (Vivinal-GOS™ (Borculo Domo Ingredients, Netherlands)and fructo-oligosaccharides (FOS) (Raftiline HP™, Orafti, Tienen, Belgium) use a mass ratio of GOS:FOS equal to 9:1. Experiencing a diet containing 1; 2.5 and 5% (mass.) GF from the calculation of the total mass of power.

Results: the Introduction of a nutrition content of GF 1 or 2.5% (mass.) statistically significant increases DHT response (see table 1). The results obtained are indicative of immunostimulating actions not digested galactosaemia oligosaccharides, which may increase switching in the power fructooligosacharides.

Table 1
The content of oligosaccharides in the diet (% wt.)DHT response
0 (control)100
1% (mass.) GF132∗
a 2.5% (wt.) GF129∗
∗ indicates significant difference from control (P<0,05)

EXAMPLE 3

Anti-infective composition

Baby food with 40% (EN.) lipids, 11% (EN.) proteins and 49% (n) carbohydrates, including:

a) milk obtained from cows, hyperimmunizing the rotavirus antigen and the antigen of E. coli and, therefore, containing the immunoglobulin (IgG), which has a neutralizing activity against rotavirus and activity against E. coli;

b) transplantological (Vivinal-GOS™ (Borculo Domo Ingrdients, Netherlands));

(C) lactose.

EXAMPLE 4

Anti-infective composition

Baby food with 40% (EN.) lipids, 11% (EN.) proteins and 49% (EN.) carbohydrates, including:

a) milk obtained from cows, hyperimmunizing the rotavirus antigen and antigen syncytial virus and, therefore, containing the immunoglobulin (IgG), which has a neutralizing activity against respiratory syncytial virus;

b) transplantological (Vivinal™ (Borculo Domo Ingredients, Netherlands));

(C) lactose.

1. Use
A. galactosidase neperebrodivsego oligosaccharide containing at least two end sharidny fragment, where at least one end charigny fragment selected from the group comprising glucose and galactose; and at least one terminal saccharide is selected from the group comprising galactose and fucose; and
b. immunoglobulin possessing activity against pathogenic microorganisms,
for the manufacture of a composition for treatment and/or prevention of respiratory tract infections and/or intestinal infections, and this composition does not contain breast milk.

2. The use according to claim 1, where the composition is administered to the infant.

3. The use according to any one of claims 1 or 2, where the composition is administered orally.

4. The use according to any one of claims 1 or 2, where the immunoglobulin is administered in amounts which TBE 0.05 g per kg of body weight up to 2 g per kg of body weight per day.

5. The use according to any one of claims 1 or 2, where the composition used in the method of treatment and/or prevention of gastroenteritis.

6. The composition is suitable for treatment and/or prevention of respiratory tract infections and/or intestinal infections, including:
A. galactosidase nevereverever oligosaccharide containing at least two end sharidny fragment, where at least one end charigny fragment selected from the group consisting of glucose and galactose; and at least one terminal saccharide is selected from the group consisting of galactose and fucose; and
b. immunoglobulin possessing activity against pathogenic microorganisms,
moreover, the composition does not contain breast milk.

7. The composition according to claim 6, additionally comprising a fibrous carbohydrate, fat and/or vegetable protein, animal (not human), microbial or synthetic origin.

8. The composition according to claim 6 or 7, where the immunoglobulin obtained or can be obtained from milk or colostrum hyperimmunizing mammals.

9. Composition according to any one of p or 7, comprising an immunoglobulin having neutralizing activity against respiratory syncytial virus.

10. Composition according to any one of p or 7, comprising an immunoglobulin having neutralizing activity against rotavirus is.

11. Composition according to any one of p or 7, where the composition includes from 0.25 to 5 wt.% immunoglobulin based on the dry weight of the composition.

12. Composition according to any one of p or 7, comprising from 10 to 60 EN.% lipid, between 5 and 50 EN.% protein and 15 to 90 EN.% carbohydrate, where the CN.% represents the relative amount that each component contributes to the total value of the composition.

13. Composition according to any one of p or 7, further comprising nevereverever oligosaccharide selected from the group consisting of fructo-oligosaccharides, hydrolyzed inulin and inulin.

14. The composition according to item 12, where immunoglobulins includes immunoglobulins having a neutralizing activity against rotavirus.

15. The use of a composition according to any one of p-14 for the manufacture of a composition for treatment and/or prevention of infection.



 

Same patents:

FIELD: medicine.

SUBSTANCE: medicinal agent with activity of alpha interferon represents a conjugate with a molecule of branched polyethylene glycol of general formula: , where: INF - polypeptide of alpha interferon; R - radicals of 2-aminoethanol -HN-CH2-CH2-O-, 3-aminopropanol -HN-CH2-CH2-CH2-O-, homoserine -HN-CH(COOH)-CH2-CH2-O-; n and n1 - identical or different =50-170, wherein residual branched polyethylene glycol molecular weight 5000-15000 Da are covalently bound with amino groups of polypeptide of alpha interferon.

EFFECT: said agent is an effective antiviral and antiproliferative preparation.

2 cl, 3 tbl, 9 ex

Antiviral agent // 2381807

FIELD: medicine.

SUBSTANCE: invention refers to chemical-pharmaceutical industry, namely to preparation of an antiviral agent of brown algae. The antiviral agent contains fucoidane made of brown aglae fucus or laminaria and representind a salt solution to 30 kDa of vegetative polysaccharide complex concentrated 0.01-15% containing fucoidane, laminarane and alginate made of brown aglae fucus or laminaria, with the salt solution containing a preserving agent from the group: sodium benzoate concentrated 0.01-0.3%, or potassium sorbate concentrated 0.02-0.3% or formaldehyde concentrated 0.01-0.3%, and as a salt solution, it contains an aqueous solution of sodium chloride concentrated 0.85-0.95% - the rest. The vegetative polysaccharide complex contains fucoidane, laminarane and alginate in any ratio, preferentially the vegetative polysaccharide complex contains fucoidane concentrated 10-99.9%.

EFFECT: extended range of antiviral activity with respect to: herpes virus types 1 and 2, cytomegalovirus, adenovirus, hepatitis C virus without expressed by-effects.

3 cl

FIELD: chemistry.

SUBSTANCE: present invention relates to piperidine-amino-benzidazoles having formula (I) and to addition salts or stereochemically isomeric forms, where Q is C1-6alkyl optionally substituted with one or two substitutes, each independently selected from a group consisting of trifluoromethyl, C3-7cycloalkyl, Ar2, hydroxyl, Ar2 - oxy-, hydroxycarbonyl, aminocarbonyl, C1-4alkylcarbonyl, aminocarbonyloxy, C1-4alkoxycarbonyl, Ar2(CH2)ncarbonyloxy, C1-4alkoxycarbonyl-(CH2)noxy, mono- or di(C1-4alkyl)aminocarbonyl, aminosulfonyl, mono(C1-4alkyl)aminosulfonyl, or heterocycle selected from a group consisting of pyrrolidinyl, dihydropyrrolyl, imidazolyl, triazolyl, homopiperidinyl, pyridyl and tetrahydropyridyl; or where Q is C1-6alkyl substituted with two substitutes, where substitute is an amino group and the other is C1-6alkyloxycarbonyl; G is -CH2-; R1 is pyridyl optionally substituted with two substitutes selected from a group consisting of hydroxyl, C1-6alkyl; each n equals 1; one of R2a and R3a is C1-6alkyl and the other is hydrogen; when R2a is not hydrogen, R2b is C1-6alkyl and R3b is alkyl; and R3a, R2a, R2b all represent hydrogen; or R5 is hydrogen; t equals 2; Ar2 is phenyl or phenyl substituted with one or more, for example 2 substitutes selected from halogen, C1-6alkyloxy, aminosulfonyl and C1-4alkoxycarbonyl. The invention also relates to a pharmaceutical composition based on compound of formula I and use of the said compounds in making medicinal agents.

EFFECT: novel piperadine-amino-benzimidazoles are obtained, having inhibitory effect on respiratory syncytial virus replication.

10 cl, 3 tbl, 5 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to novel derivatives of aminobenzimidazole and benzimidazole of general formula (I-b-1), additive salt or stereochemically isomeric form thereof, where G is a single bond or C1-10alkanediyl; R1 is halogenphenyl, pyridyl, pyrazinyl, quinolinyl, benzimidazoly or a radical of formula (c-4), where each of the said monocyclic or bicyclic heterorings can be optionally substituted with 1, 2 or 3 substitutes, independently selected from a group consisting of halogen, hydroxy, C1-6alkyl, C1-6alkyloxy, Ar1C1-6alkyloxy, C1-6alkyloxy-CH2-CH2-O-; m equals 2; Q is hydrogen, amino or mono(C1-4alkyl)amino; R3b is hydrogen or C1-6alkyl; R4a is selected from a group of substitutes consisting of hydrogen, Ar2C1-6alkyl, Het- C1-6alkyl, hydroxy C1-6alkyl, (hydroxyC1-6alkyl)oxy C1-6alkyl, C1-6alkyl, (Ar1C1-6alkyloxy)(hydroxy)C1-6alkyl, aminoC1-6alkyl, mono- and di(C1-6alkyl)amino-C1-6alkyl, carboxyl-C1-6alkyl, C1-6alkyloxycarbonyl C1-6alkyl, aminocarbonylC1-6alkyl, (C1-4alkyloxy)2-P(=O)-C1-6alkyl, aminosulphonylC1-6alkyl; R6a is hydrogen or C1-6alkyl; R6b is hydrogen, C1-6alkyl, Ar1 or Ar1C1-6alkyl; R6c is C1-6alkyl; Alk is C1-6alkanediyl; R9, R10, R11 are each independently selected from halogen, cyano, C1-6alkyl, Het-C1-6alkyl, Ar1C1-6alkyl, cyano C1-6alkyl, C2-6alkenyl, R6b-O-C3-6alkenyl, C2-6alkynyl, Ar1, R6b-O-, R6b-S-, R6b-O- C1-6alkyl-SO2-, polyhalo-C1-6alkyl, polyhaloC1-6alkyloxy, polyhaloC1-6alkylthio, R6c-C(=O)-, R6b-O-C(=O)-, N(R6aR6b)-C(=O)-, R6b-O-C1-6alkyl, R6b-O-C(=O)-C1-6alkyl, N(R6aR6b)-C(=O)-C1-6alkyl, R6c-C(=O)-NR6b-, N(R6aR6b)-S(=O)2-, H2N-C(=NH)-, and R10 and/or R11 can also be hydrogen; Ar1 is phenyl; Ar2 is phenyl; Het is a heteroring selected from imidazolyl or morpholinyl. The invention also relates to a pharmaceutical composition based on formula (I-b-1) compound, use of formula (I-b-1) compound to prepare a medicinal agent and a method of producing formula (I-b-1) compound.

EFFECT: novel aminobenzimidazole and benzimidazole derivatives with antiviral activity are obtained.

15 cl, 8 tbl, 31 ex

FIELD: medicine.

SUBSTANCE: invention concerns medicine, namely to vaccinal prevention, and can be used for specific prevention of hepatitis B in children with oncologic diseases in past history. That is ensured by revaccination in the children underwent the primary vaccination, 3-6 months after consolidating chemo- or radiation therapy. Herewith, at first hepatitis B antibody titres are determined. The titre 10 mMe/ml and less enables to administer the vaccine in a dose 0.5 ml. The titres are determined again 30 days later. The titre exceeding 10 mMe/ml, the vaccination is not applied, while the titre 10 mMe/ml ensures to introduce the second additional dose - 0.5 ml of the vaccine. Then 5 months later the titre more than 10 mMe/ml enables to consider the vaccination finished, and the third additional dose 0.5 ml of the vaccine is required with the titre less than 10 mMe/ml.

EFFECT: invention provides formation of steady protective hepatitis B antibody titres that allows to preventing viral infection in given category of patients.

5 ex, 1 tbl

FIELD: veterinary science.

SUBSTANCE: invention relates to veterinary virology and biotechnology. The vaccine contains an active substance and a target additive. The vaccine active substance is represented by a mixture of avirulent refined antigen material from the VNIIZZh strain of cattle rednose virus, Herpesviridae family, Varicellavirus genus, collection of Federal State Institution "Russian National Research Institute for Control, Standardisation and Certification of Veterinary Preparations", "VNIIZZh-DEP", and of avirulent refined antigen material from the VNIIZZh strain of cattle coronavirus, Coronaviridae family, Coronavirus genus, collection of Federal State Institution "Russian National Research Institute for Control, Standardisation and Certification of Veterinary Preparations", "VNIIZZh-DEP", taken at a ratio of 1:1 and in quantities ensuring protective immune activity of each antigen in the animal organism after receipt of the target product injection. With the animals having been immunised the vaccine induces a high level of antigens against the pathogens of cattle rednose and coronoviral infection and is capable to protect varied age and sex group cattle livestock against the above diseases.

EFFECT: with the animals having been vaccinated immunity is generated within 10-15 days after the vaccine re-injection and sustains for at least 6 months.

12 cl, 6 tbl, 3 ex

FIELD: veterinary science.

SUBSTANCE: invention relates to veterinary virology and biotechnology. The vaccine contains an active substance and a target additive. The vaccine active substance is represented by a mixture of avirulent refined antigen material from the VGNKI-4 strain of cattle paragrippe-3 virus, Paramyxoviridae family, Parainfluenza genus, Parainfluenza virus 3 subtype, collection of Federal State Institution "Russian National Research Institute for Control, Standardisation and Certification of Veterinary Preparations", "VGNI-4 DEP", avirulent refined antigen material from the VNIIZZh strain of cattle rednose virus, Herpesviridae family, Varicellavirus genus, collection of Federal State Institution "Russian National Research Institute for Control, Standardisation and Certification of Veterinary Preparations", "VNIIZZh-DEP", and of avirulent refined antigen material from the VNIIZZh strain of cattle coronavirus, Coronaviridae family, Coronavirus genus, collection of Federal State Institution "Russian National Research Institute for Control, Standardisation and Certification of Veterinary Preparations", "VNIIZZh-DEP". The strains are taken at a ratio of 1: 1: 1 and in quantities ensuring protective immune activity of each antigen in the animal organism after receipt of the target preparation injection.

EFFECT: with the animals having been immunised the vaccine induces a high level of antigens; immunity with them is generated within 10-15 days after the vaccine re-injection and sustains for at least 6 months.

15 cl, 7 tbl, 4 ex

FIELD: biotechnologies.

SUBSTANCE: vaccine contains cultural virus raw material, inactivant and oil adjuvant. As virus raw material, vaccine contains mono- or polyversions of blue tongue virus serotypes, which caused epizooty, and multiplied in elective cultures of cells with biological activity of 5.5-8.0 lg TCD (tissue cytopathic dose)50/cm3, at the following ratio of components in vaccine, wt %; cultural raw material of blue tongue virus - 40-60, inactivant-theotropine - 0.02-0.05, oil adjuvant - the rest.

EFFECT: vaccine is harmless, has high immunogenicity.

3 ex

FIELD: medicine.

SUBSTANCE: invention is related to 4-((2)-4'-hydroxybutene-2'-yl)-2-R-6-phenyl-1,2,4-triazolo[5,1-c][1,2,4]triazine-7-ons of common formula (1) ,

where R=H, CH3,SCH3 have antiviral action against herpesvirus of simple type 1 (HSV-1).

EFFECT: new derivatives have useful biological properties.

1 tbl

FIELD: medicine.

SUBSTANCE: in new compounds of formula (I): R1 is specified from the group including -OR7 and -NR8R9; where R7 means hydrogen; R8 and R9 are independently chosen from the group including hydrogen, aryl, substituted aryl containing one to three substitutes, preferentially one to two substitutes independently chosen from the group including alkenyl, substituted alkenyl containing one to three, preferentially one to two substitutes independently chosen from the group including carboxyl and carboxyl esters; R2 and R12 are independently chosen from the group including hydrogen, alkyl and alkyl substituted with 5-hydroxy-indolyl group; or R2 and R12 together with carbon atom whereto attached, form cycloalkyl group; R3 means hydrogen; each R4 independently means halogen; Q means oxygen; X means oxygen; R5 means alkylene; R6 is specified from the group consisting of substituted aryl containing one to three, preferentially one to two substitutes independently chosen from group consisting of acylamino, aryl, substituted aryl, containing one to three, preferentially from one to two substitutes chosen from halogen; and n is equal 0 to 3; or to its pharmaceutically acceptable salts. Besides the invention concerns a pharmaceutical composition, to the method of treatment or prevention of virus infections in mammals.

EFFECT: production of the new biologically active compound active with respect to treatment of virus infections in mammals, partially mediated with a member of flaviviridae virus family.

12 cl, 5 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing HIV protease inhibitor atazanavir sulphate in form of Form A crystals, which involves reacting a solution of a free base of atazanavir in an organic solvent in which atazanavir sulphate is virtually insoluble, at temperature ranging from 35°C to 55°C with a first portion of concentrated sulphuric acid in an amount sufficient for reaction with less than approximately 15 wt % free base of atazanavir, addition of nucleating centres of Form A atazanavir sulphate crystals, addition of an additional amount of concentrated sulphuric acid in several steps, where the acid is added at increasing rate to form atazanavir sulphate crystals and drying the atazanavir sulphate to form Form A crystals. A method of producing atazanavir sulphate in form of Form C crystals is also proposed.

EFFECT: improved method.

20 cl, 11 dwg, 6 tbl, 5 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutical industry, namely to a preparation with antituberculous action. The method for making the preparation with antituberculous action, characterised by that a dried blastema of sort Cladonia is mechanically treated with solid sodium alkali added. The prepared dry mixture is drawn in an aqueous-alcoholic mixture under certain conditions. The solution is separated from sediment by centrifugation and neutralised with citric acid.

EFFECT: produced preparation shows improved antituberculous action.

1 dwg

FIELD: medicine.

SUBSTANCE: invention is related to composition with high tuberculostatic activity.

EFFECT: reduced toxicity and by-effects of its components.

1 cl, 1 ex, 4 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to novel intermediate compounds - methyl 7-aryl-4,9-diaroyl-3-hydroxy-1-(2-hydroxyphenyl)-2,6-dioxo-1,7-diazaspiro[4.4]none-3,8-diene-8-carboxylates of formula III Ar1=Ar2=Ph, Ar3=C6H4Me-n (IIIa); and Ar1=C6H4Br-n, Ar2=C6H4OEt-n, Ar3=C6H4Me-n (IIIb), for synthesis of methyl 6,9-diaryl-11-aroyl-2-(o-hydroxyphenyl)-3,4,10-trioxo-7-oxa-2,9-diazatricyclo[6.2.1.01,5]undec-6-ene-8-carboxylates of formula IV where Ar1=Ar2=Ph, Ar3=C6H4Me-n (IVa); Ar1=C6H4Br-n Ar2=C6H4OEt-n, Ar3=C6H4Me-n (IVb), which exhibit antimicrobial activity and are used as precursors for synthesis of novel heterocyclic systems, and a method for synthesis of said compounds.

EFFECT: compounds have high effectiveness.

5 cl, 1 tbl, 5 ex

FIELD: chemistry.

SUBSTANCE: invention relates to the trihydrate of 8-cyano-1-cyclopropyl-7-(1S,6S-2,8-diazabicyclo-[4.3.0]nonan-8-yl)-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid of formula (I) .

EFFECT: novel compound is obtained, which is thermodynamically stable and has antibacterial activity.

1 cl, 3 tbl, 2 dwg, 3 ex

FIELD: medicine.

SUBSTANCE: for treatment of pulmonary tuberculosis in HIV-infected patients carried out is anti-tuberculosis therapy according to standard schedules. Additionally since first day of treatment galavit is administered intramuscularly in dose 100 mg one time per 3 days. On the whole 15 injections are made. Addition of galavit to treatment, with given schedule and duration of introduction, produces normalising effect on imbalance of cellular and humoral immune response in patients with HIV-associated tuberculosis.

EFFECT: increase of treatment efficiency due to reduction of abacillation terms and closing of disintegration cavities, resolution of infiltrative changes in lungs.

2 tbl, 2 ex

FIELD: medicine.

SUBSTANCE: invention relates to application of compound of formula I or II given below in preparation of medication for elimination or attenuation of microorganisms' growth in the way which includes subjection of said compound to exposure to source of light of photodynamic therapy or source of ultrasound of ultrasonic (sonodynamic) therapy, where X1, X2, X3 and X4 independently represent hydrogen atom, lipophylic part of molecule, phenyl group, lower alkyl, alkaryl or aralkyl group or cationic group of the following formula: -L-R1-N+(R2)(R3)R4 where: L represents binding (linking) part of molecule or is absent; R1 represents lower alkylene, lower alkenylene or lower alkinylene, which is optionally substituted with one or several substituents selected from lower alkyl, lower alkylene (optionally interrupted with oxygen), fluorine, OR5, C(O)R6, C(O)OR7, C(O)NR8R9, NR10R11 and N+R12R13R14; and R2, R3 and R4 independently represent H, aryl, lower alkyl, lower alkenyl or lower alkinyl, three latter of which are optionally substituted with one or several substituents selected from lower alkyl, lower alkylene (optionally interrupted with oxygen), aryl, OR5, C(O)R6, C(O)OR7, C(O)NR8R9, NR10R11 and N+R12R13R14; Z represents -CH or N; Y1, Y2, Y3 and Y4 are absent or independently represent aryl, lower alkyl, lower alkenyl or lower alkinyl, three latter of which are optionally substituted with one or several substituents selected from lower alkyl, lower alkylene (optionally interrupted with oxygen), aryl, OR5, C(O)R6, C(O)OR7, C(O)NR8R9, NR10R11 and N+R12R13R14, or, taken together with pyrrolic ring, to which they are bound, can form cyclic group; and R5, R6, R7, R8, R9, R10, R11, R12, R13 and R14 independently represent H or lower alkyl; M represents element of metal or metalloid; on condition that at least one of X1, X2, X3 and X4 is cationic group, defined above, and at least one of X1, X2, X3 and X4 represents hydrogen atom, phenyl group, lipophylic part of molecule or lower alkyl, alkaryl or aralkyl group, said microorganisms being selected from bacteria, mycoplasms, yeasts and/or fungi. Invention also relates to method of treating patient who needs treatment with antimicrobial agent and method of eliminating microorganisms in vitro, including contact of said microorganisms with compound of formula

and

EFFECT: novel application of porphyrin compounds as antimicrobial agent, said microorganisms being selected from bacteria, mycoplasms, yeasts or fungi.

67 cl, 13 dwg, 4 tbl, 7 ex

FIELD: chemistry.

SUBSTANCE: novel compound is N-(5-hydroxy-2,4-di-tert-butylphenyl)-4-oxo-1H-quinoline-3-carboxamide or its pharmaceutically acceptable salts. The invention also relates to a pharmaceutical composition.

EFFECT: obtaining a novel biologically active compound with CFTR activity modulation properties.

2 cl, 485 ex, 3 tbl

FIELD: medicine.

SUBSTANCE: invention relates to pharmaceutical composition, suitable for peroral introduction in form of solid medicinal form, which contains efficient amount of main salt of formula compound and composition with controlled rate of release, which contains solubilising agent, gel-forming agent and eater-soluble filler.

EFFECT: compositions are suitable for application in inhibiting of HIV integrase, treatment and prevention of HIV infection, and in treatment, prevention and retardation of AIDS development.

15 cl, 4 dwg, 8 ex

FIELD: medicine.

SUBSTANCE: for treatment of patients with pyoinflammatory diseases of lower extremities at the background of diabetes complex treatment is realised, which includes introduction of insulin, antiaggregants and antibacterial therapy. As antibacterial therapy, cell-associated introduction of preparations is realised. For this purpose isolated autoblood formed elements in amount 1-1.45 ml per 1 kg of patient's weight are mixed with 5 ml of 20% ceftriaxone solution and 0.3 ml of dymethylsulfoxide, incubated during 30 minutes, 1 ml of distilled water is added per 5 ml of isolated autoblood formed elements, and stood during 10-15 minutes. Obtained solution is introduced into artery, feeding affected region, 1 time a day during 7-10 days.

EFFECT: increase of concentration of antibacterial preparations in affected tissues due to reversible depositing of erythrocytes in microcirculatory channel of lower extremities.

2 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general formula (II) and their pharmaceutically acceptable salts and stereoisomers as β2-adrenergic receptor agonists, to a pharmaceutical composition based on the said compounds, a treatment method, to a method of producing said compounds, their use, as well as to crystalline hydrochloride of N-[5-((R)-2-{2-[4-((R)-2-amino-2-phenylethylamino)phenyl]ethylamino}-1-hydroxyethyl)-2-hydroxyphenyl]formamide. The compounds can be used for treating and preventing β2-adrenergic receptor mediated diseases such as asthma and chronic obstructive pulmonary disease. In general formula (II) , R1 is NHCHO, and R2 is hydrogen; or R1 and R2, taken together, represent -NHC(=O)CH=CH- or -CH=CHC(=O)NH-; each of R5 and R6 is independently selected from hydrogen or C1-6-alkyl.

EFFECT: improved method.

14 cl, 3 dwg, 12 ex

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