Liquid compositions containing valsartan

FIELD: medicine, pharmaceutics.

SUBSTANCE: group of inventions refers to a liquid oral solution for treating angiotensin II mediated disorders and conditions, and to a method for preparing it. The liquid oral solution contains valsartan in the concentration of 5 mg/ml or less, a wetting agent, a preserving agent, a flavouring agent, a buffer system and water with pH of the solution making 4.5-5.9. The wetting agent is poloxamer 188 described by the structure HO(CH2CH2O)a(CH(CH3)CH2OH)b(CH2CH2O)cH, wherein a is equal to 75, b is equal to 30, and c is equal to 75, with average molecular weight 8350. The buffer system contains alkali citrates and citric acid, alkali acetates and acetic acid, alkali succinates and succinic acid, or any mixtures thereof. The method for preparing the above solution involves mixing the ingredients added then with valsartan when heated.

EFFECT: group of inventions provides preparing the liquid solution of valsartan with an extended storage period.

8 cl, 12 tbl, 1 ex

 

The present invention relates to pharmaceutical compositions for treating disorders and conditions mediated by angiotensin II, including valsartan or its pharmaceutically acceptable salt, suitable for oral administration, as well as to methods for treating disorders and conditions mediated by angiotensin II, by oral administration of these pharmaceutical compositions valsartan.

All patents, applications for patents and other publications mentioned in this context included in full in the present description as a reference. In the event of any conflict between this description and the document incorporated by reference shall be governed by the present description.

The present invention features a composition for the treatment of disorders and conditions mediated by angiotensin II, including the solution of valsartan. Valsartan or ((S)-N-valeryl-N-{[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl}valine), suitable for use in the present invention is a commercial product, or it is produced by known methods. For example, receiving valsartan described in U.S. patent No. 5399578, the content of which in full is included in the present description by reference. According to the present invention valsartan can be used in free form and in the form of any suitable Sol is.

In the scope of the present invention also includes salts, esters, amides, prodrugs, active metabolites, analogs, etc. valsartan, primarily calcium salt of valsartan. A detailed description of the calcium salt and its preparation described in published U.S. application No. 2003/0207930, the contents of which are fully integrated into the present description by reference.

In the present invention are also methods of treating disorders or conditions mediated by angiotensin II, which is that introducing an effective amount of the compositions of the present invention, i.e. liquid oral dosage forms, including valsartan.

In U.S. patent No. 5399578 indicated that a class of compounds that includes valsartan, can be used to treat hypertension, congestive heart failure, angina, myocardial infarction, arteriosclerosis, diabetic nephropathy, diabetic cardiomyopathy, renal failure, peripheral vascular disease, stroke, left ventricle hypertrophy, disorders of cognitive abilities, headache and chronic heart failure when introducing a therapeutically effective amount of the pharmaceutical compositions of the present invention to a subject in need of specific treatment.

Some actors, etc who continued to be just, children and the elderly, have difficulty swallowing solid oral dosage forms. In addition, when treating children and the elderly often need to change the dosage in mg/kg In this regard, to ensure the above conditions in subjects who have difficulty swallowing solid oral dosage forms, requires a stable liquid oral dosage forms, including valsartan, with a long shelf life.

Unexpectedly, it was found that it is possible to obtain a liquid oral dosage form, including valsartan characterized by a long shelf life. Drug substance valsartan relatively poorly soluble in water and decomposes in water, and therefore the possibility of obtaining shape with a long shelf life is unexpected. Liquid oral dosage forms, including valsartan, preferably represent solutions of valsartan. The concentration of valsartan is from about 1 mg/ml to about 5 mg/ml, preferably about 3 mg/ml Formulations of the present invention also contain a wetting agent, for example, Polysorbate 80, poloxamer, including poloxamer 188, polyethoxysiloxane castor oil and gidrirovannoe polyethoxysiloxane castor m the words, and polyoxyl(40)stearate. Poloxamer 188 is characterized by the structure(CH2CH2O)and(CH(CH3)CH2OH)b(CH2CH2O)cH, where a is equal to 75, b is equal to 30, and 75, with an average molecular weight of approximately 8350. The wetting agent is typically present in amount from about 0.1% to about 5%, or from about 0.2% to about 1%, or approximately 0.5%

The pH of the composition is in the range from about 4.5 to 7.0, preferably from about 5.5 to about 6.5, and more preferably from about 5.5 to about 6.0, or from about 5.7 to about 6.2, most preferably to approximately 5.9. Suitable buffering agents include, for example, the buffer system on the basis of alkali metal citrates, such as alkali metal citrates and citric acid buffer systems on the basis of the acetates of alkali metals such as sodium acetate and acetic acid, and a buffer system based succinato alkali metals such as sodium succinate and succinic acid, and mixtures of these compounds. Preferred buffer systems include citric acid and sodium citrate.

The compositions usually contain protivovspenivayushchie agent, for example, simethicone, which is usually added in the form of an emulsion, for example, 0% of the emulsion. Found 30% of the emulsion is added at a concentration of from about 0.1% to about 0.25% in the calculation of the final composition. You can use sweeteners such as mannitol, Sucralose, saccharin, sodium saccharinate, aspartame, Sucralose, Acesulfame potassium, glucose, fructose, lactic, Malta, maltose, sorbitol, sucrose and xylitol. To improve the patients ' consent to treatment you can also add flavorings.

Suitable preservatives for oral solutions known to experts in the art and include, for example benzoic acid, sorbic acid (and its salts), parabens (butyl-, ethyl-, methyl-, propyl paraben, sodium benzoate and sodium propionate. A preservative, such as the aforementioned preservative or mixture of preservatives present in amounts from about 0.01% to about 0.5%, or from about 0.02% to 0,25%, or from about 0.1% to about 0.2%. In one embodiment, the composition comprises about 0.02% propyl paraben and about 0.18% methylparaben. Other options include compositions containing 0.03% propyl paraben and 0.12% of methylparaben, 0,148% of methylparaben and 0,016% propyl paraben, and compositions containing 0.16% of methylparaben and 0.2% potassium sorbate.

The solutions of the present invention receive standard equipment for liquid dosage forms. In one the embodiment of the solution according to the present invention is produced by way which is that the mixed water, the medicinal substance, then add the mixture components of the buffer system, sweeteners and flavorings. In another embodiment, preservatives, sweetener, flavor and components of the buffer system is dissolved in water. Separately when heated, dissolved in propylene glycol methylparaben and drug substance valsartan with obtaining a solution. This solution of propylene glycol is then mixed with water part and get the ultimate solution. The components of the buffer system used to produce the desired pH in the solution. The solution with the most stable drug substance were obtained when the pH is from about 4.5 to 7.0.

The following examples are provided to illustrate the present invention and do not limit the amount described in this context. In the examples offered the only way of implementing the present invention in practice.

Examples

Example 1

Composition

Table 1
The composition is an oral solution of diovan
Componentsmg/mlQuantity in 1000 lFunctionNOPAS No. no code HuningueReference standard
VAL489 DS1,01.0 kgDrug connection133730Monograph of the firm Novartis
Potassium sorbate2,02,0PreservativePh. Eur.,NF
Poloxamer 188, NF5,005,0Wetting agent10869528018Ph. Eur., NF
Methylparaben, NF1,621,62Preservative10835328014Ph. Eur.,NF
Peach flavoring1,01,0FlavorMonograph of the firm Novartis
Sucrose300,0300,0SweetenerPh. Eur., USP
Citric acid, anhydrous, USP1,021,02The buffer substance11544228017Ph. Eur., USP
Sodium citrate, dihydrate, USP13,1213,12The buffer substance11561020003Ph. Eur., USP
Purified water,to 1.0to 1116 kgMedia11576120442Ph. Eur., USP
USPml

Poloxamer 188, preservatives, sweetener, flavor and components of the buffer system was dissolved in water, then added the drug connection, valsartan, when heated to 90°C. to obtain a solution. The following compositions were obtained as described above using the following components.

tr>
Table 2
The composition is an oral solution of diovan
Componentsmg/mlQuantity in 1000 lFunctionNOPAS No.no code HuningueReference standard
VAL489 DS1,01.0 kgDrug connection133730 830720830720Monograph of the firm Novartis
Potassium sorbate2,02,0Preservative9700861320047Ph. Eur.,NF
Poloxamer 188, NF5,005,0Wetting agent118209 big face 28018Ph. Eur., NF
Methylparaben, NF1,621,62Preservative10020328014Ph. Eur.,NF
Blueberry flavoring1,01,0Flavor9702541320076Monograph of the firm Novartis
Sucrose300,0300,0Sweetener97025025143Ph. Eur., USP
Citric acid, anhydrous, USP0,671,02The buffer substance11544228017Ph. Eur., USP
Sodium citrate, dihydrate, USP15,8413,12The buffer substance11561020003Ph. Eur., USP
Purified water, USPto 1.0 mlto 1116 kgMedia11576120442Ph. Eur., USP
pH of 5.9

Table 3
The composition is an oral solution of diovan
Componentsmg/mlQuantity in 1000 lFunctionNOPAS No.no code HuningueReference standard
VAL489 DS1,01.0 kgDrug connection133730Monograph of the firm
Novartis
Propylparaben0,180,18PreservativePh Eur., NF
Propylene glycol25,025,0Wetting agent10869528018Ph. Eur., NF
Methylparaben, NF1,621,62Preservative10835328014Ph. Eur., NF
Grape flavor3,03,0FlavorMonograph of the firm Novartis
Sucrose300,0300,0SweetenerPh. Eur., USP
Citric acid,1,021,02The buffer substance11544228017Ph. Eur., USP
anhydrous, USP
Sodium citrate, dihydrate, USP13,1213,12The buffer substance11561020003Ph. Eur., USP
Purified water, USPto 1.0 mlto 1116 kgMedia11576120442Ph. Eur., USP

Table 4
The composition is an oral solution of diovan
Componentsmg/mlQuantity in 1000 lFunction NOPAS No.no code HuningueReference standard
VAL489 DS1,01.0 kgDrug connection133730Monograph of the firm Novartis
Propylparaben0,180,18PreservativePh. Eur., NF
The polyethylene glycol 40025,025,0Wetting agent10869528018Ph. Eur., NF
Methylparaben, NF1,621,62Preservative10835328014Ph. Eur., NF
Grape flavor3,03,0Flavor Monograph of the firm Novartis
Sucrose300,0300,0SweetenerPh. Eur., USP
Citric acid, anhydrous, USP1,021,02The buffer substance11544228017Ph. Eur., USP
Sodium citrate, dihydrate, USP13,1213,12The buffer substance11561020003Ph. Eur., USP
Purified water,to 1.0to 1116 kgMedia11576120442Ph. Eur., USP
USPml
pH 6

Table 5
The composition is an oral solution of diovan
Componentsmg/mlQuantity in 1000 lFunctionNOPAS No.no code HuningueReference standard
VAL489 DS5,05,0 kgDrug connection133730Monograph of the firm Novartis
Potassium sorbate2,02,0PreservativePh. Eur., NF
Poloxamer 188, NP5,00 5,0Wetting agent10869528018Ph. Eur., NF
Methylparaben, NF1,621,62Preservative10835328014Ph Eur., NF
Peach flavoring1,01,0FlavorMonograph of the firm Novartis
Sucrose300,0300,0SweetenerPh. Eur., USP
Citric acid, anhydrous, USP1,021,02The buffer substance11544228017Ph. Eur., USP
Sodium citrate, dihydrate, USP13,1213,12The buffer substance 11561020003Ph. Eur., USP
Purified water, USPto 1.0 mlto 1116 kgMedia11576120442Ph. Eur., USP
pH 6

Table 6
The composition is an oral solution of diovan
Componentsmg/mlQuantity in 1000 lFunctionNOPAS No.no code HuningueReference standard
VAL489 DS1,01.0 kgDrug connection133730Monograph of the firm Novartis
Potassium sorbate2,02,0Preservative Ph. Eur., NF
Poloxamer 188, NF5,005,0Wetting agent10869528018Ph. Eur., NF
Methylparaben, NF1,621,62Preservative10835328014Ph.Eur., NF
Peach flavoring1,01,0FlavorMonograph of the firm Novartis
Sucrose300,0300,0SweetenerPh. Eur., USP
Citric acid, anhydrous, USP1,831,83The buffer substance11544228017Ph. Eur., USP
Sodium citrate, dihydrate, USP11,8911,89The buffer substance11561020003Ph. Eur., USP
Purified water, USPto 1.0 mlto 1116 kgMedia11576120442Ph. Eur., USP
pH 5.5

Table 7
The composition is an oral solution of diovan
Componentsmg/mlQuantity in 1000 lFunctionNOPAS No.no code HuningueReference standard
VAL489 DS3,03.0 kgDrug connection 133730Monograph of the firm Novartis
Potassium sorbate2,02,0PreservativePh. Eur.,NF
Poloxamer 188, NF5,005,0Wetting agent10869528018Ph. Eur.,NF
Methylparaben, NF1,621,62Preservative10835328014Ph. Eur., NF
Peach flavoring1,01,0FlavorMonograph of the firm Novartis
Sucrose300,0300,0SweetenerPh. Eur., USP
Citric acid, anhydrous, USP3,23,2The buffer substance11544228017Ph. Eur., USP
Sodium citrate, dihydrate, USP11,1711,17The buffer substance11561020003Ph. Eur., USP
Purified water, USPto 1.0 mlto 1116 kgMedia11576120442Ph. Eur., USP
pH 5.0

td align="center" namest="c0" nameend="c1"> pH of 5.7
Table 8
The composition is an oral solution of diovan
Componentsmg/mlQuantity in 1000 l FunctionNOPAS No.no code HuningueReference standard
VAL489 DS3,03.0 kgDrug connection133730Monograph of the firm Novartis
Potassium sorbate2,02,0PreservativePh. Eur., NF
Propylene glycol25,025.0Wetting agent10869528018Ph. Eur.,NF
Methylparaben, NF1,621,62Preservative10835328014Ph. Eur.,NF
Blueberry flavoringthat 0 1,0FlavorMonograph of the firm Novartis
Sucrose300,0300,0SweetenerPh. Eur., USP
Citric acid, anhydrous, USP1,021.02The buffer substance11544228017Ph. Eur., USP
Sodium citrate, dihydrate, USP13,213,2The buffer substance11561020003Ph. Eur., USP
Purified water, USPto 1.0 mlto 1116 kgMedia11576120442Ph. Eur., USP

Table 9
The composition is an oral solution of diovan
Componentsmg/mlQuantity in 1000 lFunctionNOPAS No.no code HuningueReference standard
VAL489 DS1,01.0 kgDrug connection133730Monograph of the firm Novartis
Potassium sorbate2,02,0PreservativePh. Eur.. NF
Poloxamer 1885,05,0Wetting agent 10869528018Ph. Eur., NF
Methylparaben, NF1,621,62Preservative10835328014Ph. Eur., NF
Blueberry flavoring1,01,0FlavorMonograph of the firm Novartis
Sucrose300,0300,0SweetenerPh. Eur., USP
Citric acid,1,021,02The buffer substance11544228017Ph. Eur., USP
anhydrous, USP
Citrate intothree is, the dihydrate, USP13,1213,12The buffer substance11561020003Ph. Eur., USP
Purified water, USPto 1.0 mlto 1116 kgMedia11576120442Ph. Eur., USP
pH of 5.7

Table 10
The composition is an oral solution of diovan
Componentsmg/mlQuantity in 1000 lFunctionNOPAS No.no code HuningueReference standard
VAL489 DS1,01.0 kgDrug connection 133730Monograph of the firm Novartis
Potassium sorbate2,02,0PreservativePh. Eur., NF
Poloxamer 1885,05,0Wetting agent10869528018Ph. Eur., NF
Methylparaben, NF1,621,62Preservative10835328014Ph. Eur., NF
Blueberry flavoring1,01,0FlavorMonograph of the firm Novartis
Saccharin sodium0,50,5SweetenerPh. Eur., USP
Citric acid,3,23,2The buffer substance11544228017Ph. Eur., USP
anhydrous, USP
Sodium citrate, dihydrate, USP11,1711,17The buffer substance11561020003Ph. Eur., USP
Purified water, USPto 1.0 mlto 1116 kgMedia11576120442Ph. Eur., USP
pH of 4.7

Table 11
The composition is an oral solution of diovan
Componentsmg/mlFunctionNOPAS No.no code HuningueReference standard
VAL489 DS3,03.0 kgDrug connection133730Monograph of the firm Novartis
Potassium sorbate2,02,0PreservativePh. Eur., NF
Poloxamer 1885,05,0Wetting agent10869528018Ph. Eur.,NF
Methylparaben, NF1,621,62Preservative10835328014Ph. Eur., NF
Blueberry flavoring1,01,0Flavor Monograph of the firm Novartis
Sucrose300,0300,0SweetenerPh. Eur., USP
Citric acid, anhydrous, USP1,021,02The buffer substance11544228017Ph. Eur., USP
Sodium citrate, dihydrate, USP13,1213,12The buffer substance11561020003Ph. Eur., USP
Purified water, USPto 1.0 mlto 1116 kgMedia11576120442Ph. Eur., USP
pH of 5.7

Table 12The composition is an oral solution of diovanComponentsmg/mlQuantity in 1000 lFunctionNOPAS No.no code HuningueReference standardVAL489 DS1,01.0 kgDrug connection133730Monograph of the firm NovartisPotassium sorbate2,02,0PreservativePh. Eur., NFPoloxamer 1885,05,0Wetting agent10869528018Ph. Eur., NFMethylparaben, NF1,621,62Preservative28014Ph. Eur., NFBlueberry flavoring1,01,0FlavorMonograph of the firm NovartisSucrose300,0300,0SweetenerPh. Eur., USPCitric acid, anhydrous, USP1,021,02The buffer substance11544228017Ph. Eur., USPSodium citrate, dihydrate, USP13,1213,12The buffer substance11561020003Ph. Eur., USPPurified water, USPto 1.0 mlto 1116 kgMedia115761.20442 Ph. Eur., USPpH 6.5

It should be understood that although the present invention shown in combination with detailed description, the above description is intended to illustrate the present invention and does not limit its scope, which is defined in the following claims. Other objects, advantages, and modifications are included within the scope of the claims.

1. Liquid oral solution for the treatment of disorders and conditions
mediated by angiotensin II, including
water,
valsartan at a concentration of less than or equal to 5 mg/ml,
a buffer system,
wetting agent, which is poloxamer 188,
characterized by the structure
BUT(CH2CH2O)and(CH(CH3)CH2OH)b(CH2CH2O)withN, where a is equal to 75, b is equal to 30,
and 75, with an average molecular weight of 8350,
preservative,
flavor
moreover, the specified pH of the solution is between 4.5 to 5.9,
in which the specified buffer system contains a component selected from the group comprising alkali metal citrates and citric acid, acetates of alkali metals and acetic acid is, succinate alkali metals and succinic acid, and mixtures thereof.

2. Liquid oral solution according to claim 1, with the specified pH of the solution is from 5.5 to 5.9.

3. Liquid oral solution according to claim 2, with the specified pH of the solution is 5.9.

4. Liquid oral solution according to claim 1, wherein said preservative is selected from the group comprising benzoic acid, sorbic acid, butylparaben, ethylparaben, methylparaben, propylparaben, sodium benzoate, sodium propionate, and mixtures thereof or their salts.

5. Liquid oral solution according to claim 1, in which the specified component of the buffer system is citric acid and sodium citrate.

6. The method of producing a liquid oral solution according to claim 1 of the
water,
valsartan,
buffer systems,
the wetting agent representing poloxamer,
preservative,
flavoring,
moreover, the specified pH of the solution is between 4.5 to 5.9,
in which the specified buffer system contains a component selected from the group comprising alkali metal citrates and citric acid, acetates of alkali metals and acetic acid, succinate alkali metals and succinic acid, and mixtures thereof,
includes mixing water, a component of the buffer system, wetting agent, preservative and flavoring, and
add when heated valsartan with obtaining a solution.

7. Ways who according to claim 6, in which the pH of the specified liquid oral solution is from 4.5 to 5.9.

8. The method according to claim 6, in which the specified component of the buffer system is citric acid and sodium citrate.



 

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3 ex, 2 tbl

FIELD: medicine.

SUBSTANCE: invention refers to medicine. What is described is a solution for preparing a chitosan material, methods for preparing the haemostatic material of the solution and a medical device with using chitosan fibres. The solution consists of the following ingredients in ratio of total amount of the solution, wt %: dry chitosan with a degree of deacetylation - not less than 80%: 4-8 at dry basis, an aqueous solution of a polymer or a mixture of polymers: 1-10 at dry basis, an aqueous solution of an organic acid or a mixture of organic acids in the concentration of 50 - 80% - the rest. The method for preparing the haemostatic material of the aqueous-acidic solution containing a polyelectrolyte complex of chitosan and a water-soluble polymer comprising the electrochemical treatment of the chitosan solution in an electric field with a conductive substrate. The electrospun fibres have the following characteristics: viscosity - 1.4-2.5 Pa·s, surface tension - 31-35 mN/m and electrical conductivity no more than 2.3 mSm/cm due to the use of a viscoelastic solution.

EFFECT: method enables the chitosan fibre of a thinner diameter.

45 cl, 20 dwg, 6 tbl, 16 ex

FIELD: medicine.

SUBSTANCE: invention relates to field of ophthalmology. Ophthalmological medication in form of eye drops, contains 0.2-0.5 wt % of disulfiram, dissolved in pharmaceutically acceptable water-based carrier, 0.5-2.0 wt % of hydroxypropyl cyclodextrin, 2.0-5.0 wt % of taurine; agent, which ensures required resin condition, containing sodium chloride, sodium monohydrophosphate and dihydrophosphate, and methylparaben (nipagin) as a preservative.

EFFECT: invention ensures effective treatment of pathological conditions of eyes, such as cataract, glaucoma, ophthalmological hypertension and traumatic injuries of cornea, extends arsenal of existing preparations in form of eye drops.

6 cl, 5 tbl, 2 dwg, 5 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to food and pharmaceutical industry, namely the production of biologically active additives used for prevention of the conditions caused by vitamin and mineral deficiency, i.e. a powder for solution. The vitamin-mineral product contains a prebiotic (either sorbitol, or isomalt, or lactulose, or inulin), citric acid, a flavour, vitamins and minerals - retinol palmitate, alpha-tocopherol acetate, ascorbic acid, colecalciferol, nicotinamide, zinc, iodine, iron, selenium. The product represents a powder of weight 2.0±0.3 g.

EFFECT: vitamin-mineral product according to the invention is characterised by dosage uniformity, storage stability, bioavailability and neutral taste.

4 cl, 8 tbl, 6 ex

FIELD: medicine.

SUBSTANCE: claimed is application of levodopa and carbidopa for preparation of medication, intended for treatment of Parkinson's disease; or for treatment of sleep malfunction in patients with Parkinson's disease, for treatment of motive activity malfunction in patients with Parkinson's disease (versions), where medication contains levodopa and carbidopa in pharmaceutically effective quantity for continuous introduction into intestine for time period, which constitutes 24 h per day or more than one day. Sleep rating scale of patients with Parkinson's disease increased by 130% on the second night after starting twenty-four-hour introduction and remained within two following years.

EFFECT: twenty-four-hour introduction of medication replaces frequent per oral intake of medications, makes it possible to reach claimed prescriptions, with preservation of stable response to on medication introduction, which is not accompanied by development of clinically significant tolerance or side effects.

17 cl, 2 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to veterinary, namely to veterinary mycology, bacteriology and parasitology. Complex medication for treating dogs and cats with cutaneous mycoses, bacterioses and acaroses includes as active and auxiliary components (wt %): chlorhexidine digluconate - 0.05-0.075; cypermethrin - 10.0-15.0; tetramethrin - 1.5-2.25; pyperonyl butoxide - 10.0-15.0; dimethyl sulfoxide - 15.0-22.5; polyethylene glycol M-200 or M 400 - 10.0-15.0; glycerol - 10.0-15.0, 1,2-propylene glycol - the remaining part.

EFFECT: medication has complex effect, without staining skin and its derivatives, is easily washed away with water, is efficient at temperature from minus 30 to plus 30°C and higher, has 2-year long storage term.

9 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutical industry, particularly to therapeutic preparations of mumiyo. The therapeutic preparation which contains purified mumiyo, grapefruit citrosept, edible glycerol, ethanol and water at specific proportions.

EFFECT: preparation has a prolonged shelf life.

8 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed are: application of silibinin component of general formula (I) for obtaining medication for parenteral introduction for trweatment of viral hepatitis, with medication optionally containing cyclodextrin and/or phospholipid, and set of similar purpose, which includes said silibinin component and other medication, representing one or several pharmaceutical agents from: arginine, glutamate, silymarin, citiolone, epodemiol, ornithine oxoglurate, tidiacic arginine, myoinosite, methionine and N-acetyl methionine, choline, ornithine aspartate, cyanidanol, thiopronin, betaine, cyanocobalamin, leucine, levolose, acyclovir, idoxuridine, vidarabine, ribavirin, ganciclovir, famciclovir, valaciclovir, cidofovir, penciclovir, valganciclovir, brivudin, interferon. Medication preferably does not contain silidianin, and/or silicristin, and/or isosilibinin.

EFFECT: reduction of viral strain and reactivation of patients after parenteral introduction of claimed silibinin component.

21 cl, 12 dwg, 5 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to pharmaceutical industry, namely to stable water calcium gluconate solution for injections. Said stable water calcium gluconate solution for injections contains 0.5-1 wt % of succinic acid as stabiliser, content of calcium gluconate constituting 10 wt %.

EFFECT: increased stability of calcium gluconate solution, increased term of its storage, increased resistance to low temperatures and mechanical impact.

4 tbl, 3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to compounds of formula (I) or pharmaceutically acceptable salts thereof wherein A, R1, R2, R3 and m are specified in the patent claim. The present invention also refers to the number of specific compounds, and to a pharmaceutical composition containing the above compounds effective for inhibition of kinases, such as glycogen synthase kinase 3 (GSK-3), Rho kinase (ROCK), Janus kinase (JAK), AKT, PAK4, PLK, CK2, KDR, MK2, JNK1, aurora, pim 1 and nek 2.

EFFECT: preparing the specific compounds and pharmaceutical composition containing the above compounds effective for kinase inhibition.

18 cl, 393 ex

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