Composition based on probiotic bacteria and its application in prevention and /or treatment of respiratory pathologies and/or infections and in improvement of intestine function

FIELD: medicine.

SUBSTANCE: composition for preventive and/or therapeutic treatment of respiratory pathologies and/or infections, or influenza, or for simultaneous improvement and/or regulation of organism's intestine function, includes mixture of bacterial strains, selected from: Bifidobacterium lactis LMG P-21384, Lactobacillus casei subspecies rhamnosus DSM 16605, Lactobacillus plantarum LMG P-21021 or Lactobacillus plantarum, LMG P-21020 or Lactobacillus plantarum LMG P-21022 or5 Lactobacillus plantarum LMG P-21023. Composition is applied for manufacturing medication for preventive and/or therapeutic treatment of respiratory pathologies and/or infections or for simultaneous improvement and/or regulation of organism's intestine function. Set for peroral introduction includes, at least, one composition of probiotic strains, at least one, pharmacologically active substance packed separately for introduction of said components.

EFFECT: efficiency of increasing systemic immune protection and immunity of mucous respiratory system membranes, improves or regulates organism's intestine function.

15 cl

 

The present invention relates to compositions based on probiotic bacteria, optionally combined with prebiotic substances, and its application in the prevention and/or treatment of respiratory pathologies and/or infections and improving bowel function, which is exposed in therapeutic treatments taken to eliminate these pathological conditions.

In the last fifty years working in the food area of probiotic bacteria acquires ever-increasing importance.

It should be understood that "probiotic" means living species-specific microorganisms which absorb or apply in sufficient quantities can cause the consumer specific functional and healing effects on the health of the host organism.

When the effect of the probiotic microorganism plays a pharmacologically active role in pathological conditions of the host organism, this probiotic microorganism can be defined by the term "biotherapeutic agent, showing the potential ability to provide effective aid in drug therapy.

Thus, considering the fact that the healing properties of probiotics can be used for General system good condition is, and to be directed to address specific disorders and conditions, their application refers to a variety of applications, from food areas to pharmaceutical.

In the pharmaceutical field probiotic bacteria typically use in the prevention and treatment of pathologies of the intestine of different nature and origin.

Possible healing effects of probiotic bacteria is also the object of study, for example, in patients with diabetes mellitus type 2, chronic autoimmune and inflammatory diseases, neoplastic diseases, high serum cholesterol levels.

However, the use of probiotic bacteria in prevention and/or therapeutic treatment of respiratory pathologies is not known.

In particular, the use of probiotic bacteria, in Association or not, with suitable substances with prebiotic properties, for the prevention and/or treatment of respiratory pathologies and/or infections and at the same time to improve and/or regulation of bowel function, which is at risk (in fact, very often at risk) as a result of therapeutic treatments that are being taken to eliminate these pathological conditions is not known.

Usually respiratory pathology and/or infection treated with use is the use of antibiotics and/or anti-inflammatory drugs, sometimes steadily and for a long time.

Unfortunately, the side effects caused by use of these medicines, are often painful, dangerous and weakens the body.

The present invention is a prophylactic and/or therapeutic treatment of respiratory pathologies and/or infections of different nature and origin, without causing undesirable side effects, such as those that occur with traditional treatment with antibiotics and/or anti-inflammatory drugs.

Another objective of the present invention is a prophylactic and/or therapeutic treatment of respiratory pathologies and/or infections of different nature and origin, while improving and/or regulation of bowel function body, which is often exposed in the above mentioned pathological conditions.

These and other objectives, which will be more apparent from the following detailed description, have been supplied by the applicant, who unexpectedly found that a composition comprising a suitable mixture of probiotic bacteria that are able to give an adequate response to the challenges described above.

Thus, an object of the present invention is the use of a composition comprising a mixture of probiotic bacteria to manufacture the Oia drugs for prevention and/or therapeutic treatment of respiratory pathologies and/or infections as described in the attached independent claim.

Another object of the present invention is a composition for the above application, including a mixture of probiotic bacteria belonging to the genus Lactobacillus and/or the genus Bifidobacterium, the signs of which are described in the attached independent claim.

Set for the coordinated introduction of specified composition in combination with one or more than one pharmacologically active substance, as described in the attached independent claim of the invention, forms an additional object of the present invention.

The preferred embodiment of the present invention described in the accompanying dependent claims.

In the preferred embodiment of the composition according to the present invention is used for the manufacture of a medicine for the prevention and/or therapeutic treatment of respiratory pathologies and/or diseases.

In another preferred embodiment the composition according to the present invention is used for the manufacture of a medicine for the prevention and/or therapeutic treatment of respiratory pathologies and/or infections while improving and/or regulation of bowel function body.

In yet another preferably the eighth embodiment of the composition according to the present invention is used for the manufacture of influenza vaccine.

In an additional preferred embodiment of the composition according to the present invention includes a mixture of probiotic bacteria three species belonging to the genus Lactobacillus and the genus Bifidobacterium.

In an additional preferred embodiment of the composition according to the present invention further includes at least one substance having prebiotic properties.

The term "prebiotic" is usually understood as substances or dietary components (such as fiber), which are not digested and not absorbed in the body, which when reaching a safe colon selectively stimulate the growth and activity of groups of microorganisms that are beneficial to health of the individual.

Association of probiotic with prebiotic substances or food network composition, commonly referred to by the term "symbiotic".

In yet another preferred embodiment of the specified composition additionally includes at least one probiotic bacterium.

In an additional preferred embodiment of the specified composition additionally contains at least one pharmacologically active substance.

The compositions of the present invention are useful, preferably for prophylaxis and/or treatment of the following pathologies:

flu-like syndromes, often characterized by fever and lianyi in varying degrees of respiratory system (commonly referred to in the field abbreviated ILI, what does Influenza Like Illness, influenza-like condition);

- bronchiectasia pathology of different nature (including pathology of chronic type);

pathology related to the upper respiratory tract, such as, for example, laryngitis and tracheitis (commonly known in this field abbreviated URTI, which means Upper Respiratory Tract Infections, infections of the upper respiratory tract);

- the common cold;

- cough.

The compositions of the present invention include at least one species of probiotic bacteria.

Preferably, these compositions include a mixture of probiotic bacteria of several types.

More preferably these types of probiotic bacteria are appropriately selected from those which belong to the genus Lactobacillus and/or the genus Bifidobacterium.

In a particularly preferred embodiment these compositions consist of a mixture consisting of the following three bacterial species: Bifidobacterium lactis, Lactobacillus casei subspecies rhamnosus, Lactobacillus plantarum.

Mainly, particularly preferred bacterial strains belonging to the above-mentioned mixture of the three bacterial species, follow from those chosen from:

- Bifidobacterium lactis, identification number LMG P-21384 (deposited in the Belgian focal collections of microorganisms (Belgian Coordinated Collections of Microorganisms, BCCM LMG Collection) January 31, 2002);

the Lactobacillus casei ssp. rhamnosus, identification number DSM 16605 (deposited at German collection of microorganisms and cell cultures (Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH, DSMZ) July 20, 2004);

Lactobacillus plantarum, identification number LMG P-21021 (deposited in the Belgian focal collections of microorganisms (Belgian Coordinated Collections of Microorganisms, BCCM LMG Collection) October 16, 2002);

Lactobacillus plantarum, identification number LMG P-21020 (deposited in the Belgian focal collections of microorganisms (Belgian Coordinated Collections of Microorganisms, BCCM LMG Collection) October 16, 2002);

Lactobacillus plantarum, identification number LMG P-21022 (deposited in the Belgian focal collections of microorganisms (Belgian Coordinated Collections of Microorganisms, BCCM LMG Collection) October 16, 2002);

Lactobacillus plantarum, identification number LMG P-21023 (deposited in the Belgian focal collections of microorganisms (Belgian Coordinated Collections of Microorganisms, BCCM LMG Collection) 16 October 2002).

In another particularly preferred embodiment the compositions of the present invention optionally include at least one substance having prebiotic properties.

The specified prebiotic preferably includes carbohydrates that are not digested and not absorbed in the body.

These carbohydrates are preferably chosen from: fructo-oligosaccharides or FOS), short-chain fructo-about what hosharian, inulin, isomalt-oligosaccharides, pectins, galacto-oligosaccharides (or STATE), arabinogalactan, Xylo-oligosaccharides (or KOS), chitosan-oligosaccharides (or HOS), glucomannan, beta-glucans, konjaku (Konjac), the guar, Arabic, xanthan gums, modified and resistant starches, Polydextrose, D-tagatose.

Particularly preferred prebiotics are short-chain fructo-oligosaccharides (for simplicity referred to here below FOS-CC.); these FOS-CC. are nevereverever glucide, usually obtained by transformation of beet sugar, including sucrose molecule, which is bound to three molecules of glucose.

In another particularly preferred embodiment the compositions of the present invention further include, in addition to the described mixture consisting of videopreteen three bacterial species, at least one probiotic bacterium.

Preferably, this additional probiotic is selected from the following bacterial species:

Bifidobacterium adolescentis, Bifidobacterium angulatum, Bifidobacterium animalis, Bifidobacterium bifidum, Bifidobacterium breve, Bifidobacterium catenulatum, Bifidobacterium denticolens, Bifidobacterium dentium, Bifidobacterium gallicum, Bifidobacterium infantis, Bifidobacterium inopinatum, Bifidobacterium longum, Bifidobacterium pseudocatenulatum, Enterococcus faecium, Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus casei ssp. paracasei, Lactobacillus delbrueckii subspecies bulgarics, Lactobacillus fermentum, Lactobacillus GG, Lactobacillus pentosus, Lactobacillus salivarius, Saccharomyces boulardi, Streptococcus thermophilus, Lactococcus lactis ssp. lactis, Lactococcus lactis subspecies diacetylactis.

Additional particularly preferred bacterial strains belonging to these probiotic bacterial species are strains selected from:

- Lactobacillus acidophilus, identification number LMG P-21381 (deposited in the Belgian focal collections of microorganisms (Belgian Coordinated Collections of Microorganisms, BCCM LMG Collection) January 31, 2002);

The Lactobacillus casei ssp. paracasei, identification number LMG P-21380 (deposited in the Belgian focal collections of microorganisms (Belgian Coordinated Collections of Microorganisms, BCCM LMG Collection) January 31, 2002);

- Lactobacillus pentosus, identification number LMG P-21019 (deposited in the Belgian focal collections of microorganisms (Belgian Coordinated Collections of Microorganisms, BCCM LMG Collection) October 16, 2002);

- Lactobacillus delbrueckii subspecies bulgaricus, identification number DSM 16607 (deposited at German collection of microorganisms and cell cultures (Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH, DSMZ) July 20, 2004;

- Lactobacillus delbrueckii subspecies bulgaricus, identification number DSM 16606 (deposited at German collection of microorganisms and cell cultures (Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH, DSMZ) on 20 July 2004.

In another particularly preferred embodiment the compositions of N. the present invention further include at least one pharmacologically active substance, to have the ability to conduct combined action to ensure that these are of the active substance.

Mostly, these associations show synergism, respectively, giving the possibility to use relatively low doses of pharmaceutically active substances with a significant reduction of possible side effects caused by the introduction of this drug in particular.

Preferred pharmacologically active substances are, for example, a substance selected from:

antibiotics, anti-inflammatory drugs, immunomodulators, mucolytics are presented, antispasmodic agents, vitamins.

The composition according to the invention preferably is produced in a mixture with suitable excipients, such as carriers, lubricants, dispersing agents, corrigentov, sweeteners, stabilizers, preservatives, antioxidants, additives such as amino acids, vitamins, enzymes commonly used in the manufacture of drugs in the pharmaceutical field.

Solely as a non-limiting example, among the particularly preferred excipients and additives may be mentioned starch, twin, aromatic additives, such as Mandarin, grapefruit, strawberries, blueberries, fruit, sucrose, glucose, Acesulfame, aspartame, ascorbic who I acid, parabens, glutamine, arginine, superoxide dismutase, glutathione.

Especially preferred compositions of the present invention is a composition for oral administration.

Typical preferred embodiments are, for example, capsules, granules, solutions or suspensions ready for drinking, powders or granules in sachet (for suspension or dissolution in water or non-carbonated and non-alcoholic beverages at the point of use or similar forms, tablets, effervescent preparations.

The compositions of the present invention can also be manufactured in the form of a coated form with glazed coated, encapsulated or microencapsulating form in order to be sustainable in the environment of the stomach.

These compositions can also be made in the form of controlled release, to selectively release the active substance in the intestinal tract, especially the colon.

Among the preferred embodiments of the present invention may be mentioned those preparations in which the preferred bacterial strains according to the invention is preferably used in dried form.

Freeze drying of these strains, alone or in a mixture with suitable excipients, is carried out by use of techno is ohii and equipment, usually used in the methods of freeze drying of pharmaceutical and/or food compositions.

The compositions of the present invention is made in a conventional manner, depending on the type of drug that wish to obtain using preparative technologies, well-known specialists in the field of pharmaceutics.

Solely as a non-limiting example, granular preparations for suspension or dissolution in water at the time the application is made by mixing to homogeneity of the components of the composition (active substances, coadjuvant, excipients), reducing them to the desired particle size distribution and degree of moisture before packaging them in a single dose zapaivanie Sasha.

In turn, the composition of the controlled release is made, for example, by microencapsulation or application microsporidia on microgranular mixture of substances that make up the drug, suitable mixtures of biocompatible polymers (such as, for example, Eudragit different types and patterns)that are resistant to gastric juice and is capable of releasing these components after sufficient residence time in the gastrointestinal tract or at pH values typical of the large intestine.

Microencapsulating the mixture, thus obtained, is, for example, is used to obtain tablets, capsules and granules, depending on the selected commercial product.

Regarding dose, bacterial species that make up a mixture of probiotic bacteria, which characterize the present invention are present in a total weight ratio of from 0.1:10 to 10:1, preferably in a total weight ratio of from 0.5:1 to 2:1, more preferably in a total weight ratio of approximately 1:1.

In a particularly preferred case, when the mixture of probiotic bacteria consists of three bacterial species Bifidobacterium lactis, Lactobacillus casei subspecies rhamnosus, Lactobacillus plantarum, these bacterial species preferably are present in a mass ratio of 1:1:1.

Additional probiotic, if any, present in a mass ratio of from 0:1 to 100:1, relative to the total quantity content of bacterial species of the above-mentioned mixture; preferably, the mass ratio of from 2:1 to 15:1; more preferably from 5:1 to 10:1.

Additional probiotic, if any, present in a mass ratio of from 0:1 to 10:1, relative to the total quantity content of bacterial species of the above-mentioned mixture; preferably, the mass ratio of from 0.5:1 to 3:1.

Each individual bacterial species indicated a mixture of probiotic bacteria of the present invention is present in a concentration of 1106coloniae the shedding units (CFU)/dose up to 110 12CFU/dose, preferably from 1109CFU/dose up to 11011CFU/dose.

In a particularly preferred embodiment of the present invention produce a granulate for oral administration Packed in single dose sachets to be dissolved in water before use.

Solely as a non-limiting example of some preferred compositions according to the invention are presented below.

Composition And

In single dose sachets 5 g of the granulate for oral administration containing:

a) 0.1 g Bifidobacterium lactis, identification number LMG P-21384, at a concentration of 11011CFU/g of bacterial strain, corresponding to 2109CFU/g of the composition;

b) 0.1 g Lactobacillus case/ subspecies rhamnosus, identification number DSM 16605, at a concentration of 11011CFU/g of bacterial strain, corresponding to 2109CFU/g of the composition;

in) - 0.1 g Lactobacillus plantarum, identification number LMG P-21020, at a concentration of 11011CFU/g of bacterial strain, corresponding to 2109CFU/g of the composition;

g) 3 g of FOS - CC.;

d) - 1.7 g of glucose.

Composition B

In single dose sachets 5 g of the granulate for oral administration containing:

a) 0.5 g Bifidobacterium lactis, identification number LMG P-21384, at a concentration of 11012CFU/g bacterial strain corresponding to 11011CFU/g of the composition;

b) - 0,2G Lactobacillus casei subspecies rhamnosus, identification number DSM 16605, at a concentration of 11011CFU/g bacterial strain corresponding to 4109CFU/g of the composition;

in) - 0.1 g Lactobacillus plantarum, identification number LMG P-21022, at a concentration of 11011CFU/g of bacterial strain, corresponding to 2109CFU/g of the composition;

g) - 4 g FOS-CC.;

d) - 0.2 g of Acesulfame.

Composition

In single dose sachets 5 g of the granulate for oral administration containing:

a) - 0.2 g Bifidobacterium lactis, identification number LMG P-21384, at a concentration of 11011CFU/g bacterial strain corresponding to 4109CFU/g of the composition;

b) - 0.2 g of Lactobacillus casei subspecies rhamnosus, identification number DSM 16605, at a concentration of 11011CFU/g bacterial strain corresponding to 4109CFU/g of the composition;

in) - 0.1 g Lactobacillus plantarum, identification number LMG P-21023, at a concentration of 11012CFU/g of bacterial strain, corresponding to 21010CFU/g of the composition;

g) - 3.5 g FOS-CC.;

d) - 0.5 g of Lactobacillus delbrueckii subspecies bulgaricus, identification number DSM 16607, at a concentration of 1107CFU/g bacterial strain corresponding to 1106CFU/g of the composition;

(e) - 0.2 g of Acesulfame;

W) - 0.3 g of vitamin C.

In another preferred embodiment the pharmaceutical composition of the present invention may also contain one or more than one headlamp is Ekologicheskie active substance.

These pharmacologically active substances can appropriately be made in the form of the drug in a mixture with other components of the composition, so that they can take one introduction.

These pharmacologically active substances can also be made in the form of discrete packages, so to be able to independent the introduction (if necessary, also at different times) components, however, so that a synergistic effect can be seen, depending on the needs of the patient.

In this case, make independent packages containing composition of the present invention and pharmacologically active(s) substance(s), respectively.

The above discrete packaging then include suitable set to provide the patient the opportunity to take them sequentially or separately, to ensure the use of appropriate coordinated therapy depending on its own needs.

Just as an example, a set, such as mentioned above may contain several sachets or capsules for oral administration of the compositions of the present invention in combination with a suitable number of doses of antibiotic and/or multivitamin complex and/or mucolytics sufficient for weekly therapy.

Solely as a non-limiting example, in a confirmation shall eridania wide potential applicability of the present invention, below are the results of clinical trials carried out using one of the preferred compositions according to the invention.

In a prospective study, double-blind, randomized against placebo, evaluated the ability of the composition And of the present invention to improve the protection of the body and return to a normal state of health in relation to respiratory infections.

The motivation underlying the clinical study, is that the data of the medical literature shows a link between susceptibility to seasonal influenza-like infections involving the respiratory system (ILI and ARI) and the lack of immunity of the mucous membranes.

In particular, what has been observed over the years is the increase of the above-mentioned pathologies of those subjects, who for various reasons (such as, for example, physical stress, chronic diseases, aging) had low protection due to low immunity of the mucous membranes.

The study included 237 registered entities, of which 122 were treated with drug a And 115 took a placebo.

The average age of these two different groups amounted to 35.8 years (with a standard deviation of 15.3 years) and 34.1 years (with a standard deviation of 16.3 years).

Each patient first group was assigned when the m per os granulate the drug And, contained in the sachet (by pre-dissolving in water or another non-alcoholic beverage)every morning for 30 days in a row.

For the placebo group was assigned to receive the sachet containing 5 g of glucose (with the same forms of administration and dosages).

For health reasons during the course of treatment registered subjects kept daily records, in which the doctors of this study (or paramedical personnel responsible for monitoring daily reported the presence of pathologies involving the respiratory system (within one month or two months).

To determine the number of cases of disease, duration and subjective severity of acute respiratory infections, as well as the condition of bowel function.

To compare the incidence between the two groups used the Chi-squared adjusted Iatse (Yates), while for comparison the duration and severity of cases between groups used ANOVA (ANalysis Of VAriance, analysis of variants), except in the case of heterogeneity options (defined by criteria Bartlett), where it was replaced by the criterion of Kruskall Wallace. For statistical analysis used the program Epi Info, version 6.04d.

At the same time, as we were in the main part of the clinical IP is to study, assessed the reliability of the protection provided by the body when using symbiotic composition And, in another group of subjects with good health and without any pathology involving the respiratory system.

On these subjects have been doing research on quantitative and qualitative dosage secretion at the level of secretory immunoglobulin IgA mucosal before, during and within 30 days after the administration of the composition A.

These experiments showed a statistically significant decrease in the duration of States, considered as a whole (-1,32 days; p=0,016) and, in particular, conditions caused by infections of the upper respiratory tract (URTI; -2,83 days; p=0,034).

In addition, there was a trend towards reduction of other categories considered pathologies, such as bronchitis, flu, colds, coughs.

Analytical determination of secretory IgA in saliva samples of subjects who were treated with composition A, showed increased production of IgA, starting with 5-6-x days from the start of treatment, and this increase continued until about 4-14 days after discontinuation of treatment.

These data confirm the efficiency of symbiotic composition And to improve the immune system of protection and immunity of the mucous membranes of the respiratory system, the condition that, among other things, the AET ability to prevent and fight infections, caused by the influenza virus, and parainfluenza.

Also check related to bowel function (compromised when the above-mentioned pathologies), which, after receiving a symbiotic composition showed improvement, showed statistical significance in reducing swelling, and regular bowel function.

These tests indicate that regular prolonged use of symbiotic pharmaceutical compositions of the present invention is able to influence positively on the health of the organism as a preventive action, and as a therapeutic action on respiratory disease and/or infection.

In particular, in relation to the preventive aspect, it can be noted that regular intake of symbiotic pharmaceutical compositions of the present invention can effectively protect the body from the occurrence of the above-mentioned pathologies, competing with the traditional flu vaccine, but without causing negative symptoms (e.g., generalized discomfort, rare, transient fever, pain in bones and joints and allergic reactions).

Accordingly, the symbiotic composition of the present invention can also be used for the manufacture of drugs acting is th as influenza vaccine.

In addition, it was also shown that taking pharmaceutical compositions of the present invention simultaneously able to improve and/or to regularize bowel function of the body frequently exposed to the risk in the above mentioned pathologies.

1. Composition for prophylactic and/or therapeutic treatment of respiratory pathologies and/or infections or flu and simultaneous improvements and/or regularization of bowel function body, comprising a mixture of bacterial strains, consisting of strains selected from the species Bifidobacterium lactis, species of Lactobacillus casei subspecies rhamnosus and species Lactobacillus plantarum, where bacterial strains belonging to these bacterial species selected from:
Bifidobacterium lactis, identification number LMG P-21384;
Lactobacillus casei subspecies rhamnosus, identification number DSM 16605;
Lactobacillus plantarum, identification number LMG P-21021;
Lactobacillus plantarum, identification number LMG P-21020;
Lactobacillus plantarum, identification number LMG P-21022;
Lactobacillus plantarum, identification number LMG P-21023.

2. The composition according to claim 1, where the specified composition additionally includes at least one prebiotic selected from: fructo-oligosaccharides, of short-chain fructo-oligosaccharides, inulin, isomalto-oligosaccharides, pectins, galactooligosaccharides, arabinogalactan, xylooligosaccharides, chitosan-oligosaccharides, glucomannan, beta-glucan is, konjaku (Konjac), the guar, Arabic, xanthan gums, modified and resistant starches, Polydextrose, D-tagatose; preferably of short-chain fructo-oligosaccharides.

3. The composition according to claim 1, where the specified composition additionally includes at least one probiotic selected from the bacterial species: Bifidobacterium adolescentis, Bifidobacterium angulatum, Bifidobacterium animalis, Bifidobacterium bifidum, Bifidobacterium breve, Bifidobacterium catenulatum, Bifidobacterium denticolens, Bifidobacterium dentium, Bifidobacterium gallicum, Bifidobacterium infantis, Bifidobacterium inopinatum, Bifidobacterium longum, Bifidobacterium pseudocatenulatum, Enterococcus faecium, Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus casei ssp. paracasei, Lactobacillus delbrueckii subspecies bulgaricus, Lactobacillus fermentum, Lactobacillus GG, Lactobacillus pentosus, Lactobacillus salivarius, Saccharomyces boulardi. Streptococcus thermophilus, Lactococcus lactis ssp. lactis, Lactococcus lactis subspecies diacetylactis.

4. The composition according to claim 3, where the specified probiotic selected from bacterial strains:
Lactobacillus acidophilus, identification number LMG P-21381;
Lactobacillus casei ssp. paracasei, identification number LMG P-21380;
Lactobacillus pentosus, identification number LMG P-21019;
Lactobacillus delbrueckii subspecies bulgaricus, identification number DSM 16607;
Lactobacillus delbrueckii subspecies bulgaricus, identification number DSM 16606.

5. The composition according to claim 1, where the specified composition additionally contains at least one pharmacologically active substance, and the specified pharmacologically active substance directly prisutstvie the em in a mixture with other components of the specified composition or manufactured in the form of the drug and Packed separately from the specified composition.

6. The composition according to claim 1, where the three bacterial species of this mixture are present in a total weight ratio of from 0.1:1 to 10:1, preferably in a total weight ratio of from 0.5:1 to 2:1, more preferably in a ratio of about 1:1.

7. The composition according to claim 1, where each individual bacterial species in a dose amount of 1106colony forming units (CFU)/dose up to 11012CFU/dose, preferably from 1109CFU/dose up to 11011CFU/dose.

8. The composition according to claim 2, where the specified prebiotic is present in a mass ratio of from 0:1 to 100:1, relative to the total amount of these three bacterial species, preferably in a mass ratio of from 2:1 to 15:1; more preferably from 5:1 to 10:1.

9. The composition according to claim 1, used in the form of a granulate for oral administration, contains:
a) 0.1 g Bifidobacterium lactis, identification number LMG P-21384, at a concentration of 11011CFU/g of bacterial strain, corresponding to 2109CFU/g of the composition;
b) 0.1 g Lactobacillus casei, subspecies rhamnosus, identification number DSM 16605, at a concentration of 11011CFU/g of bacterial strain, corresponding to 2109CFU/g of the composition;
C) 0.1 g Lactobacillus plantarum, identification number LMG P-21020, at a concentration of 11011CFU/g of bacterial strain, corresponding to 2109CFU/g of the composition;
g) 3 g FOS - CC.;
the) 1.7 g of glucose.

10. The use of a composition according to claim 1 for the manufacture of medicinal products for preventive and/or therapeutic treatment of respiratory pathologies and/or infections or flu and simultaneous improvements and/or regularization of bowel function body.

11. The use of claim 10, where the specified composition additionally includes at least one prebiotic selected from: fructo-oligosaccharides, of short-chain fructo-oligosaccharides, inulin, isomalto-oligosaccharides, pectins, galactooligosaccharides, arabinogalactan, xylooligosaccharides, chitosan-oligosaccharides, glucomannan, beta-glucans, konjaku (Konjac), the guar, Arabic, xanthan gums, modified and resistant starches, Polydextrose, D-tagatose; preferably short-chain fructo-oligosaccharides.

12. The use of claim 10, where the specified composition additionally includes at least one probiotic selected from the bacterial species:
Bifidobacterium adolescentis, Bifidobacterium angulatum, Bifidobacterium animalis, Bifidobacterium bifidum, Bifidobacterium breve, Bifidobacterium catenulatum, Bifidobacterium denticolens, Bifidobacterium dentium, Bifidobacterium gallicum, Bifidobacterium infantis, Bifidobacterium inopinatum, Bifidobacterium longum, Bifidobacterium pseudocatenulatum, Enterococcus faecium, Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus casei ssp. paracasei, Lactobacillus delbrueckii subspecies bulgaricus, Lactobacillus fermentum, Lactobacillus GG, Lactobacillus pentosus, Lactobacillus salivarius, Saccharomyces boulardi, Streptococcus thermophilus, Lactococcus lactis is advid lactis, Lactococcus lactis subspecies diacetylactis.

13. The application indicated in paragraph 12, where the specified probiotic is selected from the following bacterial strains:
Lactobacillus acidophilus, identification number LMG P-21381;
Lactobacillus casei ssp. paracasei, identification number LMG P-21380;
Lactobacillus pentosus, identification number LMG P-21019;
Lactobacillus delbrueckii subspecies bulgaricus, identification number DSM 16607;
Lactobacillus delbrueckii subspecies bulgaricus, identification number DSM 16606.

14. The use of claim 10, where the specified composition additionally contains at least one pharmacologically active substance, and the specified pharmacologically active substance directly present in a mixture with other components of the specified composition or manufactured in the form of the drug and Packed separately from the specified composition.

15. Set for prophylactic and/or therapeutic treatment of respiratory pathologies and/or infections or flu and simultaneous improvements and/or regularization of bowel function body, intended for oral administration comprising as components:
the composition according to claim 1 and at least one pharmacologically active substance, separately Packed for independent or sequential introduction of these components.



 

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2 ex, 2 tbl

FIELD: medicine.

SUBSTANCE: basic, mass and standard procedure for bovine tuberculosis diagnosing is a mammal tuberculin protein purified derivate skin test. A method for producing a mycobacterial antigen involves removing free lipids of mycobacterial cells with acetone; destructing mycobacterial cell walls by dimethyl sulfoxide (DMSO) incubation in a sixfold volume at 37C. The prepared supernatant is dialysed for 3 days against distilled water After the dialysis, a supernatant is kept at plus 4C for 3 months and separated from the precipitation.

EFFECT: tests have shown high specificity of the prepared (DMSO-m) antigens and usability in lifetime differential diagnostics of bovine tuberculosis by immune-enzyme assay of blood serums.

1 dwg, 1 tbl, 3 ex

FIELD: medicine.

SUBSTANCE: method provides collection of an investigated material from a surface with a tampon made of an elastic finely porous material wetted in a solution inhibiting the development of other microorganisms. The collected investigated material with tampons is kept in the same solution for 18-24 hours. The investigated material is separated from a tampon and centrifuged. The precipitation is neutralised with 1% citric acid (in the ratio 1:1). No more than one-third of the investigated material is separate from the precipitation. The separated precipitation portion is placed on a phase-contrast slide to conduct phase-contrast microscopy. The residual precipitation is placed on a nutrient medium to be cultivated thereon if more exact quantitative assessment of mycobacterial pollution of the investigated surface is required.

EFFECT: invention allows reducing mycobacteria detection time.

2 tbl, 1 ex

FIELD: medicine.

SUBSTANCE: method provides recovery of a diagnostic anthrax allergen directly from a concentrated suspension of vegetative cells of a vaccine strain Bac. anthracis STI-1. The strain is grown on a nutrient medium based on a muriatic hydrolyzate of a fish flour by deep cultivation. The produced bacterial mass is washed in a separator to produce the concentrated suspension of vegetative cells. An allergenic protein fraction is recovered by alkaline hydrolysis, and the prepared hydrolyzate is fractioned. A protein allergen fraction is recovered from a supernatant of the recovered fraction by fractioning with an acetic acid solution; further the precipitation containing an end product is dissolved, dialyzed to produce a purified anthrax protein allergen. The preparation is presented in liquid and lyophilised forms.

EFFECT: method allows higher safety of producing the preparation and reduced length of a technological process, with preserving long-storage activity, effectiveness both in evaluating the anti-anthrax immunity stress, and diagnosing the infection.

4 cl, 4 tbl

FIELD: medicine.

SUBSTANCE: Bradyrhizobium japonicum BKM B-245 5D nodule bacterial strain used for manufacturing of a bacterial fertiliser stably improving soya seed crop by 3.0 centner/ha on the average. The strain is recovered from soya nodules of the mid-ripening variety October 70, grown up on brown forest soil of Svobodnensky District of the Amur Region. The seed grain is cultivated with using an agarised nutrient medium containing mannitol. Then it is placed in thermostats at temperature 27-28C for 7 days. The seeds are inoculated on the soya seeding day with using a bacteria-molybdenum compound. The prepared 1.25 % molybdenum solution (ammonium molybdate 25 g/l) 2.5 ml is introduced in test tubes with streaks of the nodule bacterial strain being tested. A streak from a nutrient medium swarm is washed off with the molybdenum solution. By shaking a test tube, a homogeneous bakteria-molybdenum compound (2.5 ml) used for immediate processing of the soya seeds (250 g) is produced. Then, the soya seeds are intimated, dried in the shade and sowed in the prepared soil.

EFFECT: higher crop capacity and quality of the soya seeds, high adaptive capability.

1 tbl, 1 ex

FIELD: medicine.

SUBSTANCE: Sinorhizobium fredii nodule bacterial strain is recovered from a natural population of nodule bacteria common in soils of a southern zone of the Amur Region and deposited in the Russian National Collection of Microorganisms, No. B-2458D, and also stored in the collection of the State Scientific Institution Russian Soya Research Institution, No. BB-49k.

EFFECT: stable improvement of soya seed crop.

1 ex, 1 tbl

FIELD: food industry.

SUBSTANCE: fresh white cabbage in an amount of 1.00 kg is milled and filled with tap water (1:3). One boils it for 9-11 minutes and cools to 48-50C, adds milled cattle pancreas. One adjusts pH to be 8.2-8.3 with 20% of solution of sodium hydrate (8 ml). One adds 1% of chloroform. Hydrolysis is performed in a heat-chamber at a temperature of 38-42C during 4-5 days. In the first 1.5-2 hours one stirs the mixture every 10-15 minutes, then one stirs it every 5.5-6.0 hours. Daily one measures amine nitrogen level which comes to be 0.20.05% on the 3d day. The heat-chamber is switched off. The produced hydrolysate is left to condition for 24 hours and filtered. One prepares a nutritive medium by way of adding the following components to the cabbage hydrolysate (650.0-700.0 ml) diluted with distilled water until amine nitrogen content is 0.12% (g/l): yeast extract - 15.0-20.0, sulfurous magnesium - 0.1-0.2, lipoic acid - 0.04-0.05, sodium citrate - 1.5-2.0, sodium acetate - 4.0-5.0, hepatic water - 0.05-0.1, fermentative peptone - 9.0-10.0, growth stimulant (fermentative hydrolysate of Tibetan milk mushroom) - 0.5-1.0, glucose - 18.0-20.0, microbiological agar - 8.0-8.5 and distilled water to 1 l.

EFFECT: process simplification and a high-quality product production.

2 cl, 9 ex

FIELD: medicine.

SUBSTANCE: nutrient medium contains an enzymatic hydrolyzate of beef containing 0.7-0.9 % of amine nitrogen, an enzymatic hydrolyzate of Basketplant, glucose, microbiological agar and distilled water in the preset amounts.

EFFECT: higher lactic acid bacilli yield.

6 ex

FIELD: medicine.

SUBSTANCE: application of ambroxol or its pharmaceutically acceptable salts is proposed to produce medical composition intended for treatment or prophylactics of infections caused by human rhinovirus. It is proven that ambroxol suppresses replication of human rhinovirus in vitro.

EFFECT: ambroxol in medical composition is suitable for treatment or prophylactics of all symptoms of rhinovirus infection and has direct antivirus effect.

9 cl, 6 tbl, 6 ex

FIELD: chemistry.

SUBSTANCE: invention describes a novel compound - a sodium salt of 2-ethylthio-6-nitro-1,2,4-triazole[5,1-c]-1,2,4-triazin-7-one dihydrate of formula (1)

.

EFFECT: higher antiviral activity which can be used in medicine, stockbreeding and poultry farming.

2 tbl

FIELD: chemistry.

SUBSTANCE: in adamantane amino-derivatives of general formula (1), R=OH, R1=R2=R3=H, R4=C2H5, X=Cl, n=1 (I); R=Br, R1=R2=R3=H, R4=C2H5, X=Br, n=1 (II); R=OH, R1=R2=H, R3+R4=-CH2CH2CH2CH2-, X=Cl, n=1 (III); R=Br, R1=R2=H, R3+R4=-CH2CH2CH2CH2-, X=Br, n=1 (IV); R=OH, R1=R2=CH3, R3=R4=H, X=CI, n=1 (V); R=CH3, R1=-CH2OH, R2=R3=R4=H, X=Cl, n=1 (VI).

EFFECT: higher antiviral activity of derivatives towards influenza virus.

1 cl, 1 tbl, 9 ex

FIELD: medicine.

SUBSTANCE: drug contains mixed dihydroquercetin, arabinogalactan and ascorbic acid taken in mass ratio 1: (16-18):1 respectively. The drug can be tabletted.

EFFECT: drug exhibits good tolerance with no adverse and allergic reactions.

5 tbl, 2 cl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to biotechnology, virology and medicine. The invention concerns methods of prevention and treatment of virus diseases, particularly caused by the strains subtype H5N1 bird influenza virus, a preparation of interferon inducer exhibiting antiviral action, or preparations of interferon inducer and neuraminidase inhibitor. The method involves introduction of said preparation of interferon inducer or interferon inducer and neuraminidase inhibitor Ozeltamivir. Ridostine is used as a preparation of interferon inducer. The invention can be used in medicine.

EFFECT: ensured higher efficacy, lowered toxicity and good tolerance by using a preparation of interferon inducer based on duplex and single RNA recovered from received from Saccharomyces cerevisiae killer yeast together with neuraminidase inhibitor and development of more optimum regimen.

2 cl, 4 tbl, 4 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to novel substituted 2-(5-hydroxy-2-methyl-1H-indol-3-yl)acetic acids. The substituted 2-(5-hydroxy-2-methyl-1H-indol-3-yl)acetic acids of general formula 1 and their pharmaceutically acceptable salts and/or hydrates , where: R1 is an amino group substitute selected from hydrogen; optionally substituted C1-C5 alkyl; optionally substituted C1-C5 alkylsulphonyl, optionally substituted arylsulphonyl or optionally substituted heterocyclylsulphonyl; acyl; R2 is an alkyl substitute selected from hydrogen, substituted amino group, optionally substituted hydroxy group, substituted mercapto group, substituted alkylamino group; R3 is hydrogen, C1-C3 alkyl; R4 is a substitute selected from hydrogen, C1-C3 alkyl substituted with an amino group, optionally substituted with phenyl or heterocyclyl; R5 is one or more substitutes of the cyclic system selected from trifluoromethyl, carboxyl, alkyloxycarbonyl, possibly substituted aryl, heterocyclyl, substituted aminomethyl, cyano group, or R5 is hydrogen provided that when R1 is a substitute selected from hydroxy-substituted C1-C3 alkyl, amino-substituted C1-C3 alkyl, and R2, R3, R4 and R6 are as described above, or R2 is an alkyl substitute selected from substituted amino group, optionally substituted hydroxy group, substituted mercapto group, substituted alkylamino group, and R1, R3, R4 and R6 are as described above; or R5 is fluorine.

EFFECT: obtaining novel substituted 2-(5-hydroxy-2-methyl-1H-indol-3-yl)acetic acids which have antiviral activity, especially against the influenza virus and hepatitis C virus (HCV).

19 cl, 3 tbl, 20 ex

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to virology, and can be applied for prevention of disease, caused by virus of avian flu of A subtype H5N1. For this purpose sublingually introduced is preparation of human alpha-2 interferon "Reaferon EC - Lipint" in doze not less than 5000-10000 MU/kg of weight. Introduction in realised once per day after 2 days during 6 days, and then in the same simple dose one time per day every 3-4 days for not longer than 3 weeks.

EFFECT: invention describes novel effective method of said disease prevention.

2 cl, 2 tbl, 3 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to novel substituted 4(6)-bromine-5-hydroxy-1H-indol-3-yl acetic acids and their esters, their pharmaceutically acceptable salts and/or hydrates which have antiviral activity, particularly against influenza virus having general formula or : where: R1 is an amino group substitute selected from a hydrogen atom, C1-C5alkyl optionally substituted with a hydroxy group, mono- or di(C1-C5 alkyl)amino group; acyl which is benzoyl optionally substituted with a halogen; or sulphonyl which is (C1-C5alkyl)sulphonyl, phenylsulphonyl optionally substituted with a C1-C5alkyl group, phenyl-C1-C3 alkylsulphonyl, 6-member nitrogen-containing heteroarylsulphonyl; R2 is an alkyl substitute selected from a hydrogen atom, a halogen atom, hydroxyl, amino, mono-(C1-C5 alkyl)- or di(C1-C5 alkyl)amino group; R3 is hydrogen optionally substituted with C1-C5alkyl; R4 is a hydroxyl group substitute selected from a hydrogen atom, C1-C5alkyl, C1-C5acyl; R5 is cyclic system substitute selected from hydrogen or mono(C1-C5 alkyl)- or di(C1-C5 alkyl)aminomethylene group. The invention also relates to a focused library, a medicinal agent and a pharmaceutical composition.

EFFECT: obtaining of compounds with antiviral activity.

26 cl, 1 tbl, 18 ex

FIELD: medicine.

SUBSTANCE: invention relates to pharmaceutical industry, in particular to medication for prevention and/or treatment of flu. Application of extract from air parts of Cistus genus plants for obtaining medication for prevention and/or treatment of flu.

EFFECT: described above medication base on extract from air parts of Cistus genus plants is efficient for prevention and treatment of flu.

7 cl, 10 dwg, 1 ex

FIELD: medicine.

SUBSTANCE: invention refers to pharmaceutical industry, particularly to a drug with antiviral activity with respect to viruses of influenza types A and B. Application of dihydroquercetin and/or its calcium salts as a drug with antiviral activity with respect to viruses of influenza types A and B.

EFFECT: drug shows improves antiviral activity with respect to viruses of influenza types A and B.

4 cl, 6 dwg, 3 tbl, 5 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (I): where: A is a monocyclic or polycyclic aryl or heteroaryl group, where the heteroaryl radical denotes a 5-10-member cyclic system containing at least one heteroaromatic ring and containing at least one heteroatom selected from O, S and N; optionally substituted with one or more substitutes independently selected from a group comprising halogen atoms, C1-4alkyl, C3-8cycloalkyl, C3-8cycloalkyl-C1-4alkyl, C1-4alkoxy and a hydroxyl group; B is a monocyclic nitrogen-containing heteroaryl group, where the heteroaryl radical denotes a 5-6-member heteroaromatic ring containing at least one heteroatom selected from S and N; optionally substituted with one or more substitutes selected from a group consisting of halogen atoms, C1-4alkyl, C3-8cycloalkyl, C3-8cycloalkyl-C1-4alkyl, aryl and C1-8alkylthio; either a) R1 is a group of formula: -L-(CR'R")n-G, where L is a binding group selected from a group consisting of a direct bond, -(CO)-, -(CO)NR'- and -SO2-; R' and R" is independently selected from hydrogen atoms; n assumes values from 0 to 1; and G is selected from a group consisting of a hydrogen atom and C1-4alkyl, aryl, heteroaryl, where the heteroaryl radical denotes a 5-6-member heteroaromatic ring containing at least one heteroatom selected from O, S and N; C3-8cycloalkyl and saturated heterocyclic groups, where heterocyclic group denotes a non-aromatic saturated 6-member carbocyclic ring in which one or two carbon atoms are substituted with a N heteroatom; where alkyl, C3-8cycloalkyl, aryl or heteroaryl groups are unsubstituted or substituted with one or more substitutes selected from halogen atoms; and R2 is a group selected from hydrogen atoms, halogen atoms and C1-4alkyl, C2-5alkynyl, C1-4alkoxy, -NH2 and cyano groups, where alkyl and alkynyl groups may be unsubstituted or substituted with one aryl group; or b) R2, R1 and -NH- group to which R1 is bonded form a group selected from groups of formulae and , where: Ra is selected from a hydrogen atom or groups selected from C1-4alkyl, C3-8cycloalkyl, aryl, aryl-C1-4alkyl, heteroaryl, where the heteroaryl radical denotes a 5-6-member heteroaromatic ring containing at least one heteroatom selected from O and N; saturated heterocyclic rings, where the heterocyclic group denotes a non-aromatic saturated 6-member carbocyclic ring in which one carbon atom is substituted with a heteroatom selected from O and N; and C1-4alkylthio; where the aryl or heteroaryl groups are unsubstituted or substituted with one or more groups selected from halogen atoms, cyano group, trifluoromethoxy and carbamoyl; Rb denotes hydrogen; and pharmaceutically acceptable salts thereof and N-oxides; provided that the compound is not selected from N-[6-(1-methyl-1H-indol-3-yl)-5-pyridin-2-ylpyrazin-2-yl]benzamide, N-[3-ethoxycarbonyl-6-(1-methyl-1H-indol-3-yl)-5-pyridin-2-ylpyrazin-2-yl]benzamide, and N-[3-ethoxycarbonyl-6-(1-methyl-1H-indol-3-yl)-5-pyridin-2-ylpyrazin-2-yl]formamide. The invention also relates to a pharmaceutical composition, use of compounds in any of claims 1-20, a method of treating a subject, as well as a composite product.

EFFECT: obtaining novel biologically active compounds having adenosine A2B receptor antagonist activity.

27 cl, 160 ex, 2 tbl

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