Combined antituberculous pharmaceutical composition

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutical field, and concerns a combined antituberculous pharmaceutical composition in a solid dosage form including a therapeutically effective amount of an active principle which is represented by a combination of sodium para-aminosalicylate and isoniazid, and pharmaceutically acceptable auxiliary substances, in the following proportions, wt % of total composition: sodium para-aminosalicylate - 36.8-90.41; isoniazid-1.08-3.38; auxiliary substances - the rest.

EFFECT: invention provides longer high blood serum concentration of active preparations, as well as prevents development of mycobacterium drug resistance to isoniazid.

4 cl, 8 tbl, 3 ex

 

The invention relates to the field of medicine and relates to a pharmaceutical composition having anti-TB activity, executed in the form of a solid dosage form that contains as an active start to the combination of sodium aminosalitsilata parameters and isoniazid, and pharmaceutically acceptable excipients. The composition is characterized by a high therapeutic efficacy. Antituberculosis drug-based polymer and sodium para-aminosalitsilata meets all regulatory requirements Gosfarmakapei XI ed. (2), C) and has a shelf life of 2 years.

The invention relates to medicine, specifically to a combined anti-TB drugs, and can be used for treatment of tuberculosis.

Epidemiological indicators of TB in the world, despite significant progress achieved in recent decades, heterogeneous, in some countries, the morbidity and mortality of tuberculosis remain at a sufficiently high level. Along with this serious problem is drug resistance of Mycobacterium tuberculosis to anti-TB drugs.

The main chemotherapeutic remedies to treat various forms of tuberculosis is isonicotinic acid hydrazide, especially isoniazid, of which the first has a high bacterial activity against Mycobacterium tuberculosis. Featuring high therapeutic activity of isoniazid and has a strong toxic effect. The isonicotinic acid hydrazide are particularly active in the fresh, sharp processes. However, if it is applied relatively quickly develops resistance of Mycobacterium tuberculosis, which reduces its effectiveness.

Resistance develops much slower in case of simultaneous use of several drugs. Due to the difficulties of combination therapy, and the duration of the selection of effective drugs, TB patients exercise therapy irregularly, or discontinue it, which leads to the development of secondary drug resistance and relapse. As a consequence, the world Health Organization (who) recommends the rejection of mono - and combined therapy and necessitates the use of combined anti-TB drugs in a single dosage form.

In the patent of Russian Federation №2248797, 2005 proposed combined anti-tuberculosis drug, which contains sodium para-aminosalitsilata and targeted supplements. However, the presence of only one active component requires the use of additional anti-TB drugs (prototype).

In the patent of Russian Federation №2146130, 2000, the painted pharmaceutical composition, which consists of isoniazid or ftivazid, or pyrazinamide. Standard chemotherapy of tuberculosis consists of isoniazid and rifampicin, which usually add other anti-TB drugs, so the presence in the composition of only two effective components requires the use of additional drugs.

Known drug analogues has some weaknesses: during the course of use of the above drugs, there are marked toxic effect and the occurrence of side effects. In addition, in the known combined compositions of the mutual influence of ingredients leads to a significant reduction in the bioavailability of the active substance, and, as a consequence, the low efficiency of treatment of tuberculosis, and the development of resistance of Mycobacterium tuberculosis to drugs.

The objective of this invention is to provide pharmaceutical compositions with anti-TB activity in the form of solid dosage forms containing the active beginning of the combination of isoniazid and sodium aminosalitsilata parameters, which will provide more long-lasting high concentration of both drugs in serum; reduce therapeutic dose of sodium aminosalitsilata parameters with preserved bacteriostatic effect, the call is lit to prevent the development of drug resistance of mycobacteria to isoniazid, that will help to expand the Arsenal of anti-TB drugs for treatment of tuberculosis, including drug-resistant.

The problem is solved in that the proposed pharmaceutical composition with anti-TB activity includes a therapeutically effective amount of the current to the beginning, which contains a combination of isoniazid and sodium aminosalitsilata parameters, and pharmaceutically acceptable excipients, the following ratio of ingredients, wt.% from the total mass of the composition:

sodium para-aminosalitsilata - 36,8 - 90,41;

isoniazid - 1,08 - 3,38;

excipients - the rest.

The proposed combination of active ingredients in the specified relationship is new for combined anti-TB drugs, are chosen empirically and allows to obtain a technical result that is appropriate to the task.

The proposed combination of active ingredients in the specified ratio found experimentally and is optimal, ensuring that drug all the requirements of Gosfarmakapei XI editions and shelf life at least 2 years.

Conducted a number of clinical no comparative studies of the efficacy and safety of the proposed combined anti-TB drug.

In the first IP is ladouanie this drug was included in the regimen 23 first identified in patients with destructive pulmonary tuberculosis with drug-resistant M. tuberculosis. The drug used in the treatment of patients undergoing inpatient treatment.

The drug was administered 1 time per day orally. The dose was selected on the basis of sodium para-aminosalitsilata - 10 g/day (9 tablets). The drug was administered in combination with isoniazid 10 mg/kg of body weight (optional 1 tablet (300 mg), rifampicin 10 mg/kg of body weight of 1 times a day, pyrazinamide 30-35 mg/kg, 1 time per day, ethambutol 25-30 mg/kg 1 time per day (all drugs taken per os). The course of treatment is 6 months. All patients were smear-positive, which is confirmed by the results of microscopy and culture of sputum. Most patients (87%) were identified MBT strains resistant to anti-TB drugs. Monoresistance, mainly to aminoglycosides or isoniazid, was 13,0% of patients. The MDR, resistance to isoniazid and rifampin and other antituberculosis drugs, but not their combination, were observed in 65.2%. Multi-drug resistance to the combination of isoniazid and rifampicin installed in 8.7% of patients.

The analysis of the dynamics of intoxication syndrome, clinical manifestations and normalization of the clinical analysis of blood of patients showed high efficiency of chemotherapy using the proposed pharmaceutical composition. After 1 month of treatment in patients with intoxication syndrome was palestianian in 78,3±8,6% (18 out of 23 patients). On the third month of treatment intoxication syndrome was arrested in all patients.

Thus, the use of chemotherapy with the use of the proposed pharmaceutical composition in newly diagnosed patients with destructive pulmonary tuberculosis smear positive, allows the first month of treatment to arrest the syndrome of intoxication in 2/3 of patients. When this resistance clinical effect was maintained during the entire course of treatment.

In table 1 presents the frequency and timing of termination of allocation of the office of microscopy.

Table 1
Frequency and timing of bacteriological conversion in patients according to the method of microscopy (M±m)
The number of patientsSmear conversion (months)MBT(+) after 3 months.
123
23
100
14
60,9±10,2
7
30,4±9,6
2
8,7±5,9
0

As can be seen from table 1 patients after 3 months of treatment smear conversion Pro is made in all patients.

Frequency and timing of bacteriological conversion in patients (detection by culture) are presented in table 2.

Table 2
Frequency and timing of bacteriological conversion in patients according to the method of sputum (M±m)
The number of patientsSmear conversion (months)MBT(+) after 3 months.
123
2312821
10052,2±10,434,8±9,98,7±5,94,3±4,2

In newly diagnosed patients with destructive pulmonary tuberculosis cases in the use of chemotherapy, including the proposed pharmaceutical composition, as well as rifampicin, pyrazinamide and ethambutol allows to achieve sputum conversion during the intensive phase of treatment for 3 months in most patients. One patient with preserved BA is televidenie registered multi-drug resistant pathogen.

The frequency and timing of the closing of cavities in the lungs of patients in the observed groups are presented in table 3.

Table 3
The frequency and timing of the closing of cavities in the lungs of patients (m±M)
The number of patientsOf them with CV (+)Closing CV (months)CV (+) after 4 months.
to 2to 4
23235162
10010021,7±8,669,6±9,68,7±5,9

Two patients (multidrug-resistant MBT) after 4 months of treatment cavity saved. It should be noted that half of the patients as a result of chemotherapy was prepared for subsequent surgical treatment.

Thus, the application of the proposed pharmaceutical composition in combination with other anti-TB drugs in newly diagnosed patients on structurem pulmonary smear positive, provides high efficiency of treatment, not only in terms of bacteriological conversion, but also on the rate of closure of cavities in the lungs.

The safety of clinical use of the drug was provided with consideration of patient history and the results of laboratory blood tests and monitoring of the patient during the study.

Adverse reactions to drugs are installed in 2 of 23 patients (8,7±5,9%). Adverse reactions were mild in severity, wore disposable in nature and were stopped by the application of pathogenetic treatment methods.

Adverse reactions manifested as disorders of the gastrointestinal tract (dyspepsia, toxic reactions). Application hepatoprotective, anti-acid and antispasmodic drugs, and vitamin complexes, helped to arrest adverse reactions without canceling the combination of anti-TB drugs.

Clinical study the effectiveness and acceptability of the proposed combined anti-TB drugs for the treatment of patients with newly diagnosed destructive pulmonary tuberculosis showed his rather high efficacy and acceptable safety of the drug to the body of the patient in the intensive phase of chemotherapy.

In addition, the combination of anti-TB drugs in one Lekarstvo the th form (isoniazid, sodium para-aminosalitsilata enables synergistic effect of drugs and nonspecific anti-inflammatory effect of sodium aminosalitsilata parameters and optimizes the organization of the treatment process.

In another clinical study involved 30 patients with newly diagnosed pulmonary tuberculosis. Clinical characteristics of studied patients are presented in table 4-7.

Table 4
Clinical characteristics of patients with tuberculosis
Just sickSex M/FAgeOffice+*The presence of cavities
3019/1119-543023

Moderate
Table 5
The frequency of tuberculosis intoxication
Just sickThe nature of tuberculosis intoxication
PronouncedNo
301911-

The study was dominated by patients with severe intoxication (63,3%).

A high degree of drug resistance to the drugs of the first line, the exception isoniazid - resistance - 1.0 microgram/ml, was observed in 17, reasonable - in 13 patients who participated in the research. Cavity decay was observed in 11 patients with infiltrative tuberculosis, 2 - disseminated, 4 - caseous pneumonia, and in 6 with fibrous-cavernous tuberculosis.

Table 7
The prevalence of tuberculosis in the lungs
The group of patientsThe prevalence of the process
2 lung1 light1 share2 segment
N=309 (30,0%)11 (36.7 per cent)8 (26,7%)2 (6,7%)

In 66.6% of patients who Yavlena greater prevalence of tuberculosis - from one to two lungs.

Drug resistance of MBT was detected in all 30 patients. A high degree of drug resistance was observed in 17, reasonable - in 13 patients. In 16 of the 30 patients had acute onset and progressive course, 14 - subacute expressed productive reaction. Two patients during 2 and 3 years suffered from diabetes.

In the study, it was noted that the main route of metabolism of the drug - acetylation in the liver and partially in the intestine under the influence of the enzyme N-acetyltransferase. When receiving the considered drug acetylation of isoniazid was significantly slowed down, and therefore its concentration in the blood was increased 2.4 times and remained longer time in comparison with isoniazid as monotherapy. This effect is particularly important when treating patients, which by reason of their metabolism will quickly acetimidoyl isoniazid, have low concentrations of isoniazid in the blood creates conditions for the formation of resistance of Mycobacterium tuberculosis to isoniazid.

In the third clinical study involved 30 patients with pulmonary tuberculosis, from which were selected Mycobacterium tuberculosis multidrug-resistant and which was shown by the treatment according to the following standard IV regime of chemotherapy using primary and backup PTP.

Analysis of portability regimes of TB treatment, including drug according to the invention, was carried out on 30 patients: 24 men (80,0%) and 6 women (20,0%) aged 20 to 60 years, mean age was 40,27 years (σ=12,54). Analysis of the effectiveness of modes of TB treatment, including drug according to the invention, was carried out on 28 patients who completed the full course of treatment (2 patients drug according to the invention was cancelled due to nekupiruemy reactions).

Research results the frequency of adverse reactions to TB treatment among patients taking the drug according to the invention, in a combination of anti-TB therapy are presented in table 8.

Fatal 23,3
Table 8
The number of patients with adverse reactions to TB treatment among 30 patients who took the drug according to the invention, in combination antituberculosis therapy
Characteristic adverse reactionsDisposableOnly
n%n%n%
Caused by the medicinal product according to the invention
gastrointestinal disorders310,026,7516,7
allergic26,726,7
Not caused by the medicinal product according to the invention, but occurred in patients receiving this drug
gastrointestinal disorders713,3826,7
from the side of the musculoskeletal system26,726,7
on kidneys13,313,3
CNS13,313,3
All adverse reactions1240,0723,31963,3
No adverse reactions1136,7
Total 30100,0

As can be seen from the table. 8, the incidence of adverse reactions caused by the medicinal product according to the invention was 23,3%, while the elimination of the drug was required in only 2 of 6.7%. Most adverse reactions observed gastro-intestinal tract, only 2 patients reported itching and urticaria. These symptoms decreased or held for symptomatic therapy or upon discontinuation of the drug.

According to the literature, severe adverse reactions observed in approximately 10% of patients (Shmelev N.A., Stepanyan AS Side effects of anti-TB drugs. M - 1977. - 280 S.; Astakhov, V., Lepakhin VK Drugs. Adverse effects and safety control. M.: Eksmo, 2008. - 256 S.)receiving sodium para-aminosalitsilata (these include liver, kidney, and hematological changes hemolytic anemia, leukopenia, agranulocytosis). These data refer to 60-80 years of the past century, when the PAS was used very widely, but the regimen was limited to 3 drugs. In the conducted study such phenomena are not observed.

In modern literature also presents the data on a very high level of Megilat is selected reactions of sodium para-aminosalitsilata in combination therapy - 78,1%, and it is believed that this drug is one of the worst in this sense [Mishin V.Y., Chukanov, V., Grigoriev YG Side effects of anti-TB drugs in the standard and individualized chemotherapy regimens. M., 2004, 206 S.]. As was established based on the research results, the relatively low level of adverse reactions in this case due to the peculiarities of the combined drug, which due to pharmacokinetic interactions of components allows you to assign sodium para-aminosalitsilata in smaller doses than when administered as a single drug in the treatment of tuberculosis.

The proposed remedy is carried out in a variety of solid dosage forms - tablets, capsules, granules, powders. As auxiliary substances may be used substances commonly used in the pharmaceutical industry for the production of solid dosage forms, such as ethylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, carboximetilkrahmal sodium, silicon dioxin colloid, talc, magnesium stearate, hypromellose, diethylphthalate, polyethylene glycol, triethylcitrate, titanium dioxide, metacrilato acid copolymer, various colors, flavors and/or flavoring. predpochtitelno, a new pharmaceutical composition is performed in the form of pills, which can be coated with a film cover. The presence of the latter improves the appearance and organoleptic properties of the dosage form, protects it from mechanical damage.

The most common ways of obtaining tablets are three technological scheme: wet granulation, dry granulation and direct pressing (Technology of medicinal forms. / Edited by Ivanova L.A. - M.: Medicine, 1991, Vol.2, 142).

The closest technical specificity to the proposed drug is a method of wet granulation, comprising the following steps: mixing ingredients, moisturizing, granulation, drying, dusting, tableting.

Way to get a new TB composition involves several steps.

Mixing, hydration, granulation and drying of isoniazid and sodium aminosalitsilata parameters are organized separately, in order to avoid chemical interaction between the two components.

The invention is illustrated by the following examples which are only illustrative but not restrictive.

Example 1.

(Trust supplements: Isoniazid - 2,23%, Sodium para-aminosalitsilata - 76,84%)

Mixing, hydration, granulation and drying of isoniazid and sodium para-aminosalitsilata PR the lead separately, in order to avoid chemical interaction between the two components.

The sifted powder isoniazid in number 33,30 g is loaded into the mixer and moisturize 7,5-8,5% solution kollidon from 10.0 to 12.0% ethyl cellulose solution in ethanol, obtained from 1.3 g of kollidon, 1.7 g of ethyl cellulose, 12.3 g of ethyl or isopropyl alcohol. Pass the wet mass through a granulator, wet granules are dried at 35-45°C. to a residual moisture content of 0.5-1.5%.

The sifted powders of sodium aminosalitsilata parameters in the number 1145,0 g of microcrystalline cellulose in the amount of 47.0 g is loaded into the mixer, stirred for 10-15 min at a speed of 52 rpm Then the resulting mixture is moistened 10,5-11,5% solution kollidon in ethanol, obtained from 33,7 g kollidon and 266,0 g of ethyl or isopropyl alcohol. Pass the wet mass through a granulator, wet granules are dried at 35-45°C. to a residual moisture content of 10.0 to 14.0 percent.

The dry granules of isoniazid and sodium aminosalitsilata parameters passed through the granulator and optivault his 13.5 g of Aerosil, to 32.9 g of sodium carboxymethyl amylum, 20,0 g of microcrystalline cellulose, 8,1 g of magnesium stearate, 13.5 g of talc powder, mix to a uniform distribution apadravya substances in bulk. Ready tabletow mixture tabletirujut on the tablet press.

Get 998 tablets with a total weight of 1348,0 g 1.35 g ± 5% of each tab is etka containing isoniazid 0.0333 g ± 10% and sodium para-aminosalitsilata 1,145 g ± 5%.

Prepare a suspension of the primary shell, which 13,0 g hypromellose and of 1.62 g of ethyl cellulose dissolved in a mixture 142,40 g methylene chloride and 213,20 g of isopropyl alcohol, leave for an hour for the swelling. Then add to 7.95 g of talc, of 2.23 g of diethylphthalate and dispersed in a colloid mill for 15 minutes

Prepare a suspension of the final cover, which 3.0 g of macrogol 6000 and 5.0 g of dye "sunset" yellow dissolved in 10.0 g of water. To the resulting solution was added 228,0 g of isopropyl alcohol, 16,50 g of talc, 5.7 g of titanium dioxide and is dispersed in a colloidal mill for 15 minutes

The resulting suspension is added to a solution consisting of 75,0 g of a copolymer of methacrylic acid, 10.0 g of triethylcitrate dissolved in a mixture 376,0 g of isopropyl alcohol and 410,0 g of acetone.

Get two film-forming suspension total weight 1519,6 g, which in turn known method is applied on the obtained above 998 tablets containing isoniazid 0.0333 g ± 10% and sodium para-aminosalitsilata 1,145 g ± 5%. Weight gain pills is 9,40%. The appearance of the coated tablets - oval, orange. The cross section tablet white or white with a yellowish tint. The obtained tablets satisfy all the requirements of the pharmaceutical agent.

Example 2. (EXT target the Cai: Isoniazid - 1,08%, Sodium para-aminosalitsilata - and 36.80%)

Mixing, hydration, granulation and drying of isoniazid and sodium aminosalitsilata parameters are organized separately, in order to avoid chemical interaction between the two components.

The sifted powder isoniazid in number 16,09 g is loaded into the mixer and moisturize 7,5-8,5% solution kollidon from 10.0 to 12.0% ethyl cellulose solution in ethanol, obtained from 12.1 g kollidon, 8,11 g of ethyl cellulose, 150,0 g of ethyl or isopropyl alcohol. Pass the wet mass through a granulator, wet granules are dried at 35-45°C. to a residual moisture content of 0.5-1.5%.

The sifted powders of sodium aminosalitsilata parameters in the number 548,32 g of microcrystalline cellulose in the amount of 643,68 g is loaded into the mixer, stirred for 10-15 min at a speed of 52 rpm Then the resulting mixture is moistened 10,5-11,5% solution kollidon in ethanol, obtained from 33,7 g kollidon and 266,0 g of ethyl or isopropyl alcohol. Pass the wet mass through a granulator, wet granules are dried at 35-45°C. to a residual moisture content of 10.0 to 14.0 percent.

The dry granules of isoniazid and sodium aminosalitsilata parameters passed through the granulator and optivault his 13.5 g of Aerosil, to 32.9 g of sodium carboxymethyl amylum, 20,0 g of microcrystalline cellulose, 8,1 g of magnesium stearate, 13.5 g of talc powder, mix until uniform distribution is apadravya substances in bulk. Ready tabletow mixture tabletirujut on the tablet press.

Get 999 tablets with a total weight of 1348,6 g 1.35 g ± 5% each tablet containing isoniazid 0,01609 g ± 10% and sodium para-aminosalitsilata 0,54832 g ± 5%.

The coatings of example 1.

Example 3. (Trust supplements: Isoniazid - 3,38%, Sodium para-aminosalitsilata - 85,23%)

Mixing, hydration, granulation and drying of isoniazid and sodium aminosalitsilata parameters are organized separately, in order to avoid chemical interaction between the two components.

The sifted powder isoniazid in number 50,36 g is loaded into the mixer and moisturize 7,5-8,5% solution kollidon from 10.0 to 12.0% ethyl cellulose solution in ethanol, obtained from 1.3 g of kollidon, 1.7 g of ethyl cellulose, 12,30 g of ethyl or isopropyl alcohol. Pass the wet mass through a granulator, wet granules are dried at 35-45°C. to a residual moisture content of 0.5-1.5%.

The sifted powders of sodium aminosalitsilata parameters in the number 1269,92 g of microcrystalline cellulose in the amount of 15,12 g is loaded into the mixer, stirred for 10-15 min at a speed of 52 rpm Then the resulting mixture is moistened 10,5-11,5% solution kollidon in ethanol, obtained from 8.69 g of kollidon and 70,31 g of ethyl or isopropyl alcohol. Pass the wet mass through a granulator, wet granules are dried at 35-45°C. to a residual wet the t 10,0-14,0%.

The dry granules of isoniazid and sodium aminosalitsilata parameters passed through the granulator and optivault its 0.5 g of Aerosil, 0.6 g of sodium carboxymethyl amylum, 1.0 g of microcrystalline cellulose, 0,63 g of magnesium stearate, 0.18 g of talc powder, mix to a uniform distribution apadravya substances in bulk. Ready tabletow mixture tabletirujut on the tablet press.

Receive 997 tablets with a total weight of 1346,0 g 1.35 g ± 5% each tablet containing isoniazid 0,0536 g ± 5% and sodium para-aminosalitsilata 1,26992 g ± 5%.

The coatings of example 1.

1. Combined TB pharmaceutical composition in the form of a solid dosage form comprising a therapeutically effective amount of the current to the beginning, which contains a combination of sodium aminosalitsilata parameters and isoniazid, and pharmaceutically acceptable excipients, the following ratio of ingredients, wt.% from the total mass of the composition:

sodium paraaminosalicylic36,8-90,41
isoniazid1,08-3,38
excipientsrest

2. The pharmaceutical composition according to claim 1, characterized in, is that it is made in tablet form.

3. The pharmaceutical composition according to claim 2, characterized in that it contains as excipients ethylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, carboximetilkrahmal sodium, silicon dioxin colloid, talc, magnesium stearate, hypromellose, diethylphthalate, polyethylene glycol, triethylcitrate, titanium dioxide, metacrilato acid copolymer, various colors, flavors and/or flavoring.

4. The pharmaceutical composition according to claim 2 or 3, characterized in that it has a shell.



 

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Marking articles // 2413962

FIELD: physics.

SUBSTANCE: article in form of a solid pharmaceutical product which is not in powdered form has a diffraction microstructure formed on its surface which enables its identification and authentication. The solid pharmaceutical product is prepared by pressing powdered or granular material. The pharmaceutical product or its surface is not completely transparent but absorbs and scatters. The method of making the said article involves formation of a diffraction microstructure on the surface of the pharmaceutical product during the pressing step by placing the original negative onto a die mould.

EFFECT: possibility of identifying and authenticating a solid pharmaceutical product.

13 cl, 6 dwg

FIELD: medicine.

SUBSTANCE: invention represents a pharmaceutical composition containing bacteriophage (Sextaphage® (Pyobacteriophage Polyvalent)) or Bacteriophage Salmonellous groups A, B, C, D, E) dried up with excipients (methyl cellulose, lactose, calcium carbonate, calcium or magnesium stearate) in the form of gastric-resistant uncoated tablets, differing by the fact that the relation of parity bacteriophage to excipients makes 1:1 to 1.25:1, and the composition contains in addition - sorbite and sodium alginate. One tablet of weight 0.16-0.2 g contains bacteriophages with Appelman titre not less than 10-3, and the ingredients of the components are in a certain ratio, wt %.

EFFECT: higher gastric resistance of tablets and stabilisation of bacteriophages.

2 cl, 3 ex

FIELD: food industry.

SUBSTANCE: food additive characterised by the minerals it contains being a component of a salt hydrate melt in the form of ions, the said nutrient substances represented by at least calcium; the salt hydrates melt is amorphously hardening and is represented by a salt-water system with water content in the food additive corresponding to the most hydrated ion coordination number. The food additive is used as admixture during production of food products, chewing gum, beverages, toothpaste, mouth wash liquids and oral cavity hygiene products. The nutrient mineral substances are easily digestible due to their containment in the additive in ion form.

EFFECT: salt hydrate melt in the amorphously hardening form may easily be stored during a long time and is easily adaptable to the process of a specific food product production due to its viscosity.

18 cl, 6 ex, 1 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: medicinal composition for treating cerebral ischemia and senile dementia contains 1-10 weight parts of ginseng root, 1-10 weight parts of ginkgo leaves, 0.05-0.5 weight parts of saffron snouts and 5-10 weight parts of soya bean; said ginseng root, ginkgo leaves, saffron snouts and soya bean can be presented in the form of raw vegetable materials or extracts prepared by extraction of the raw vegetable material in the same amounts. At least double amount of 60-80 % ethanol is added to ginkgo leaves, and immersing extraction is carried out at 50-70°C at least once to produce liquid extracts; the liquid extracts are mixed and concentrated to enable relative density of the produce liquid concentrate to reach approximately 1.05; water is added to the liquid concentrate, and the prepared mixture is filtered to produce a filtrate; the filtrate is chromatographed on polar macroporous adsorption styrene resin in a protonation form; resin and drug substances are eluted with water and 60% ethanol; an aqueous eluent is discharged, while an ethanol containing eluent is collected and concentrated to eliminate alcohol odour and to produce a concentrated eluent; water is added to the concentrated eluent, and said mixture is filtered to prepare another filtrate; the filtrate is chromatographed on weakly polar macroporous adsorption styrene resin; resin and drug substances are eluted with water, 15% ethanol and 60% ethanol, respectively; the aqueous eluent and 15% ethanol eluent are discharged, while 60% ethanol eluent is collected. The inventions allow implementing specified object matters.

EFFECT: preparation of the composition for treating cerebral ischemia and senile dementia.

12 cl, 5 ex, 12 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: pharmaceutical compositions in the form of a mouth dissolving tablet are described. The composition contains an effective amount of a narcotic active material representing fentanyl, and arginine being a pharmaceutically acceptable amine. The molar ratio of arginine to said active material is at least approximately 5:1. In the preferential version of the invention, tablet disintegration time in vivo is 5 to 25 minutes.

EFFECT: invention provides enhanced fentanyl absorption in transbuccal administration of the tablets.

7 cl, 2 tbl, 3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine, particularly to therapy and pharmacology, particularly to pharmacogenetic analysis, and concerns detecting genetic polymorphisms being efficacy markers of aliskiren as an antihypertensive agent. Aliskiren is used for preparing a drug for treating hypertension, for reducing mean derived systolic pressure and for reducing diastolic pressure. And aliskiren therapy is applied in a group of patients specified by genetic polymorphisms in biomarker genes where the aliskiren efficacy is indicated by genetic polymorphisms - SNP_4769 as specified in SEQ ID NO:1 in an angiotesin-converting enzyme (ACE) gene, SNP1445 as specified in SEQ ID NO:2 in an angiotensin II receptor type 2 (AGTR2) gene, and SNP_4795 as specified in SEQ ID NO:3 in an AGTR2 gene .

EFFECT: invention provides a method for determining sensitivity of a hypertensive individual to the aliskiren therapy, and application of a gene product of a gene specified in a group including the angiotesin-converting enzyme (ACE) gene and angiotensin II receptor type 2 (AGTR2) gene as a drug target.

6 cl, 1 dwg, 7 tbl, 2 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to chemical-pharmaceutical industry, namely to creation of a white turpentine emulsion with a herbal extract showing bracing, tonic and rejuvenating action, containing gum turpentine, baby soap or an emulsifier, camphor spirit, salicylic acid, a water-propyleneglycol herbal extract taken in equal proportions and demineralised water.

EFFECT: various versions of the white turpentine emulsion can be used for prevention and treatment of the locomotor apparatus, cardiovascular system, metabolic disorders (weight reduction and cellulitis).

3 cl

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