Solid pharmaceutical composition with content of levothyroxine and/or liothyroninum salts
SUBSTANCE: invention relates to a chemico-pharmaceutical industry, and concerns the solid pharmaceutical composition containing water-soluble salts of levothyroxine and-or liothyroninum as an active substance where water activity is set equal to less than 0.4 at measurement at a room temperature. The composition with 0.4 water activity or less possesses high stability at storage.
EFFECT: development of a composition which possesses high stability at storage.
18 cl, 4 ex
The technical field to which the invention relates.
The invention relates to solid pharmaceutical compositions containing as active substance, a water-soluble salt of levothyroxine and/or liotironina.
The level of technology
Thyroid hormones the above-mentioned type are produced for sale in a different form. For the production of traditional tablet of thyroid hormones requires a number of measures ensuring uniform distribution of the active substances on all tablets of one party and keeping it the same content for a certain period of time. Such problems in relation to the provision of the so-called “same content” (content uniformity) also include issues related to the stability of the active substance. For example, it is known that the sodium salt of levothyroxine or liotironina in case of their presence in the form of potassium salts are insoluble in water and more effective for the body. In addition, it was found that depending on humidity, temperature and light they are unstable, particularly during storage. In this regard, many attempts have been made to improve stability of tablets with thyroid hormones, and so far has been the attempt to improve the resistance to what esteem additives of the positive impact of excipients. In the US 5225204 for this purpose it is proposed to apply along with the corresponding sodium salts are water-soluble polyvinylpyrrolidon and adsorption of the mixture to cellulose media for production in subsequent tablets, powders or capsules.
In the US 5635209 described the application along with the sodium salt sodium levothyroxine well as sodium iodide, means for breaking the tablets and sizing.
In the US 5958979 proposed sodium thiosulfate as a stabilizing component.
From US 6399101 it follows that the use of siliconized microcrystalline cellulose provides certain advantages.
All these known attempts though and contributed to increased resistance, however, still sufficient resistance at the required storage time was not reached, when this was not provided and trudnoobogatimye uniformity at relatively low dosage of thyroid hormones.
Levothyroxine sodium is usually kind of stable at room temperature pentahydrate. This pentahydrate detects at room temperature for a certain water activity, comprising about 0.4 to 0.6. Under the water activity is an equilibrium moisture content and 50% relative humidity at a certain temperature correspond to a water activity of 0.5.
Disclosure of inventions
The purpose of ISO is retene is to provide, largely irrespective of additives, excipients and, in particular, without the use of specific additives, allegedly improving the resistance of auxiliary substances, enhanced stability of the pharmaceutical composition, its quick and easy preparation, improved uniformity of distribution of the active substance and its rapid dissolution (biological availability). To achieve this goal, the solid pharmaceutical composition according to the invention lead mainly in the state in which the water activity of this composition is set equal to the index of less than 0.4, mostly 0.1 to 0.3 at room temperature. Unexpectedly, it was found that in the case when the active substance is present, usually in the form of the pentahydrate, is removed, at least one mole of water, the resistance increases substantially, it is necessary only to ensure that later, when the choice may become necessary for the use of auxiliary chemicals were not applied hygroscopic excipients in order to prevent re-water saturation. This unexpected effect is due to the fact that one mole of water normally present in the pentahydrate is in contrast to the rest of 4 moles of water is not a classic hydrate, and cluster. This part of the water way is t excess water, able to easily move into the gas phase and also easy to get back in the form of cluster crystals of levothyroxine. Thus, this present in the form of cluster mol of water is relatively easily movable and loosely coupled with the crystal, and this is reflected in increased activity of water at room temperature. If the active substance itself is quite stable, despite the presence of this fifth, relatively easy rolling mole of water, volatile and easily movable, is not associated with the crystal water leads together with the usual, necessary for the manufacture of tablets excipients to the fact that this cluster mol of water causes the interaction, in particular the dissolution of auxiliary substances, and dissolved excipients in combination with free water in the form of a cluster in an invalid extent degrade the stability of levothyroxine sodium. Liotironin sodium also contains up to 4% water and has the same resistance with levothyroxine sodium. It has been unexpectedly found that in the case when this relatively movable water is removed due to the decrease of water activity at room temperature to less than 0.4 and, in particular, to a value of from 0.1 to 0.3, then reached a corresponding resistance during long-term storage without the use of the special stabilizing additives auxiliary substances. When uncontrolled drying and reduction of water activity below 0.1 levothyroxine sodium passes into the amorphous state, and this makes it even more unstable. This also deteriorates the solubility. The specified optimal water activity can be achieved either as a result of corresponding dry processing in the manufacture of tablets, applying dry source of substances with controlled water activity, and the active substance may also in appropriate dry form (water activity) and then directly tabletroute, either by drying, tableting the mixture to the desired water activity, either by target additional drying of the finished tablets. Manufacturing of tablets with such a low water activity in practice is not straightforward, as it requires you to carefully follow the uniform application of the active substance on the carrier with a large surface area. In the Supplement of the relevant quantities of substances for destruction tablets can provide accurate adaptation to low water activity in the range of 0.1. If such a pill, for example, with a water activity of 0.1-0.3 then firmly Packed, it can be ensured durability and safety. Along with the possibility of applying for the NGOs dense packing can also provide optimal water activity due to the fact, used mostly or exclusively non-hygroscopic excipients, known for its low water activity at room temperature, as, for example, mannitol, and others, in the manufacture of tablets and then tablets are packaged in a conventional transparent materials.
The problem with the lack of constant rapid solubility of the active substance in the known compositions and, therefore, with rapid and complete bioavailability, especially easily solved due to the fact that the active substance is evenly applied onto the water-soluble carrier. Such water-soluble carrier has subsequently after taking the pills, the effect that the active substance dissolves quickly and reliably, without the need to use damaging substances as insoluble in water, the active substance is applied onto a water-soluble carrier, a finely on it are distributed and with it quickly goes into solution. With optimal use mannitol as a water-soluble media.
It is advisable to prevent the problem of reduced activity due to the formation of water-insoluble salts to consider the content of calcium when using substances-carriers, excipients and solvents. The best option run is the tsya such when the carrier is treated with EDTA-sodium, the amount of which corresponds mainly to the content of CA++in the media, if necessary with the addition of citric acid to prevent the harmful effects of ions of CA++which is inevitably present, particularly in water-soluble media. The processing is carried out with an aqueous solution, and it is necessary to constantly monitor the removal of water to maintain a given water activity. In General, the required homogeneity, solubility and, in particular, the solubility with the formation of a clear solution, the ability to quickly manufacture and due to waterless technology enhanced resistance can be guaranteed due to the fact that composition was prepared in the form of tablets and its preparation are not used hygroscopic excipients and/or packaging is applicable with little or no permeability to water vapor.
The method is simple and fast preparation of the pharmaceutical compositions of the above type differs in the fact that the media of mannitol is filled or deposited methanol or alcohol solution of the active substance, after which the alcohol solvent is evaporated to obtain a water factor less than 0.4, in particular less than 0.3, and tabletirujut when necessary is Timoti with the addition of magnesium stearate as lubricant. In the use of alcoholic solvents, particularly methanol or ethanol solutions of sodium salts is achieved corresponding to a uniform distribution of the active substance on the carrier. Thus resolves the problems associated with a uniform distribution of active ingredients in the tablets (content uniformity). After evaporation of the solvent provided the corresponding uniform distribution of soluble salts in the media, and monitoring compliance with the required water factor can be obtained directly lasting product. Evaporation of the residual moisture with a drying process for evaporating solvent, such as methanol and/or ethanol, conducted for the water-soluble salts levothyroxine sodium or liotironin sodium provides immediate compliance required water factor, and using methanol or ethanol solutions can be observed during evaporation of some semblance effect of grip when drainage of excess water, resulting in rapid drying.
If during the tabletting process it is necessary to abandon other auxiliary substances, such as, for example, hygroscopic means the destruction of the tablets, as the carrier can be used directly tableting mannitol, the company shall and, pearlite. In any case, when choosing the necessary excipients for tableting, you must renounce the use of hygroscopic substances to avoid re-hydration. To do this optimally apply tabletiruemye excipients, in particular, oil, hydrophobic excipients such as magnesium stearate.
To avoid formation of water-insoluble salts of hormones, as mentioned above, the callee may be contained in the substance-carriers ions of CA++before applying or spraying of a solution of the active substance to the media mix EDTA-sodium, if necessary, with addition of citric acid, in a quantity sufficient to bind divalent ions of the carrier. After intermediate drying, including elevated temperature, put alcohol solution of the active substance. Immediately after that, add a further quantity of aqueous complexing solution, as described above, to link present additional ions, originating from the solvent or production equipment. The amount of EDTA-sodium, designed to bind ions of CA++in any case, should not be excessive, so as EDTA-PA/citric acid by themselves do not increase the resistance of the sodium salts of l is of vothyroxine and liotironina.
Alternatively, the carrier consisting of mannitol, after mixing, if necessary, with starch, guar or other auxiliary granulating agents can be filled with methanol or alcohol solution of the active substance and immediately thereafter subjected to wet granulation using water solution with the content if necessary EDTA-sodium and/or citric acid. The water is evaporated before reaching the corresponding water activity, optionally with further addition of destroying pill substances. After mixing sizing pills get low water activity. Used preferred packaging should be impervious to water vapor. Manufactured in this way and stored at 25°C tablets exceptional durability.
Below the invention is explained more by using examples of its implementation and comparative experiments.
The water-soluble salts of the active substances are dissolved in an organic anhydrous solvent such as, for example, methanol and ethanol. A small amount of hygroscopic substance carrier in the form of mannitol (Pearlitol 400 DC) moistened with a solution of the active substance coating liquid layer or coating. Then the solvent is removed by drying in a fluidized bed or vacuumed who eat in the drying process the water factor set equal to 0.3. When pelletizing completely abandoned the use of substances for the destruction of the tablets. As lubricant when pelletizing was used stearate.
In this example implementation used the following structure:
|Pearlitol 400 DC||2749 g|
|magnesium stearate||32 g|
Thus prepared mixture were easy to direct pelletizing, and worked tablets with a flawless appearance, hardness, friability and other pharmaceutical properties. Decomposition of the tablets occurred within one minute, thus formed solution, which is transparent except for floating on the water surface of the stearate. It should be borne in mind that optimum bioavailability of active substances, as with the exception of small amounts of insoluble stearate solution does not contain any other insoluble substances.
At room temperature the re 25°With a water factor of tablets was 0.2. Water absorption was tested in the course of experience on storage at 25°C, 60% relative humidity and duration of 24 hours and compared with traditional tablets formulation (for example, media content for the destruction of tablets and other pharmaceutical auxiliary substances, which are also pre-dried before reaching the water factor of 0.2. In the embodiment of the invention was as follows: water absorption only of 0.11% and a water factor of 0.3, while the tablet formulation had a water absorption of 0.75% (almost 7 times more) and water factor of 0.5.
In example 2, before applying the solution of methanol and levothyroxine sodium, as described in example 1, the same amount pearlitol, 2749 g, moisturize first 60 g of methanol and then pretreated with a solution consisting of 40 g of water, 0.12 g of anhydrous citric acid and 4.0 g of EDTA-disodium. The resulting mixture is dried to achieve a water factor of 0.2-0.25 and then tabletirujut, at the same time was a good tabletirovanie, the disintegration of the tablets was within about 1 minute. The results of example 1 was confirmed in this case. The active substance as in example 1 was uniformly applied on the carrier, there was no risk of delamination (content uniformity). Additional protection against divalent ions generated by the application of complexing solution is, protected active substance from the corresponding loss of activity.
In example 3, the drying was carried out in two stages, with the first drying occurred after treatment pearlitol described above EDTA and methanol, after which the active substance is applied using the above methanol solution and at the same time additional partial amount of EDTA-disodium, after which drying is repeated.
This example suggests that in the manufacture of conventional methods of water granulation using traditional tabletiruemyh excipients, such as carriers (mannitol), granulating means (guar), means for breaking the tablets (natrocarbonatite starch), oiling agents (magnesium stearate, talc), and conventional complexing funds (EDTA-sodium, citric acid), you can get a tablet with an unusual resistance of the active substance, provided that the water activity will correspond to the specified values (0,3) and is hermetically sealed packaging.
In this example implementation used the following structure:
|levothyroxine sodium||0,00816 kg|
|citric acid||0,0024 kg|
|natrocarbonatite starch||1.2 kg|
|magnesium stearate||0.16 kg|
Mixed with guar carrier filled with a solution of the active substance, then stirred into an aqueous solution of EDTA-sodium and citric acid and damp granulation, and then dried to a water activity of less than 0.3. Tablets are manufactured with a water activity of 0.45, Packed in PVC at 25°C and 60% relative humidity and stored over 12 months, the content of the active substance was more than 88,6% of the stated rate (100% output), therefore, the tablets were to apply not suitable. Similar tablets, which are dried to achieve a water activity of 0.3, Packed in PVC and impermeable to water vapor bags, stored in similar conditions within 12 m of the months, have, taking into account normal fluctuations composition, the initial content (99,6%), that is, these pills have extraordinary durability.
The resistance of the preparations described in examples 1-3, increased as follows, and this increase was installed at various concentrations of the active substance: 100 mcg levothyroxine sodium, a relative humidity of 40-50% (water factor of 0.4-0.5). Within three months, the content of levothyroxine sodium had dropped to 87 wt.%, moreover, in order to faster results storage was carried out at 40°C and 75% relative humidity. Accordingly, the preparations containing 100 mcg levothyroxine sodium with a water factor of 0.3 three months had still the activity of 92.9%. For preparations containing 160 μg of levothyroxine sodium under the same storage conditions and measurements obtained with a water factor of 0.4-0.5 three months residual activity 90.7 percent, while when the water factor of 0.3 activity has accounted for 95.2 wt.% from the original number. In respect of the combined preparations containing levothyroxine sodium and liotironin sodium, observed comparable performance improvements, and drug content of pure liotironina sodium in the amount of 25 μg in a month with a water factor of 0.4-0.5 of its contents fell to 87.2%, at the same time when the water factor of 0.25 after one month according to stuudy analysis showed active content of 97.7 wt.% the used amount.
In General, it was found that the direct tableting in dry conditions is particularly quick and simple method of making homogeneous and persistent long time stand composition.
1. Solid pharmaceutical composition comprising as active substance a water-soluble salt of levothyroxine and/or liotironina, wherein the water activity of the pharmaceutical composition is less than 0.4 when measured at room temperature.
2. The pharmaceutical composition according to claim 1, characterized in that the water activity of the pharmaceutical composition is set to 0.1 to 0.3 when measured at room temperature.
3. The pharmaceutical composition according to claim 1, characterized in that the active substance contained in the methanol/ethanol solution, evenly applied to the carrier, mixed if necessary with starch, guar or granulating auxiliaries.
4. The pharmaceutical composition according to claim 2, characterized in that the active substance contained in the methanol/ethanol solution, evenly applied to the carrier, mixed if necessary with starch, guar or granulating auxiliaries.
5. The pharmaceutical composition according to claim 1, characterized in that the active substance is applied in water-soluble media.
6. farmacevticheskaja composition according to claim 2, characterized in that the active substance is applied in water-soluble media.
7. The pharmaceutical composition according to claim 5, characterized in that as the water-soluble carrier is mannitol.
8. The pharmaceutical composition according to claim 6, characterized in that as the water-soluble carrier is mannitol.
9. The pharmaceutical composition according to any one of claims 1 to 8, characterized in that the carrier is processed EDTA-Na and optionally citric acid, the amount of which basically corresponds to the content of CA++in the carrier.
10. The pharmaceutical composition according to any one of claims 1 to 8, characterized in that the composition has the form of tablets and made using non-hygroscopic excipients and/or Packed in the material, which is slightly or completely impermeable to water vapor.
11. A method of obtaining a pharmaceutical composition according to any one of claims 1 to 10, characterized in that the carrier of mannitol is applied or sprayed alcohol solution of the active substance, after which the alcohol solvent is evaporated to obtain a water factor less than 0.4, in particular less than 0.3, and then tabletirujut.
12. The method according to claim 11, characterized in that before evaporation of the solvent causing the water or aqueous solution with a content of EDTA-Na and/or citric acid.
13. Pic is b according to item 11, characterized in that as the carrier is applied directly tableting mannitol, in particular pearlitol.
14. The method according to claim 11, characterized in that as tabletiruemyh AIDS are used, in particular, oil, hydrophobic excipients, such as, for example, magnesium stearate.
15. The method according to claim 11, characterized in that before applying or spraying of a solution of the active substance on the carrier, supplementing it with EDTA-Na and optionally citric acid in a quantity sufficient to bind divalent ions from media and other sources, such as a solvent.
16. The method according to item 15, wherein before the adulteration of EDTA-Na and optionally citric acid carrier moistened with methanol.
17. The method according to any of § § 11 to 16, characterized in that the composition does not contain hygroscopic excipients.
18. The method according to any of § § 11 to 16, characterized in that the composition contains hygroscopic excipients, but Packed in impermeable to water vapor material.
SUBSTANCE: invention relates to pediatrics and endocrinology and can be used for taking preventive measures aimed at treatment of thyroid gland diseases in children of early age born from mothers with opportunistic infections. Molecular-biological investigation of biological material is carried out by PCR method in order to indicate CMV and herpes infection. Immunoferment child's blood test is carried out with determination of IgM and IgG level. Also ultrasound examination of mother's and child's thyroid gland is performed, by results of diagnostics drug therapy is carried out in two stages. At first stage starting with twentieth week of pregnancy pregnant women are administered preventive therapy with iodine preparations: "iodomarin - 200" 200 mkg/day, "potassium iodide - 200" 200 mkg/day and vitamin-mineral complexes (VMC): "materna", "elevit", "folic acid". At second stage combined therapy is carried out in children with anti-viral medications famvir 0.25 in dose 10 mg/kg a day during 7-10 days, acyclovir 0.2 in dose 10 mg/kg a day during 10-14 days and viferon-1 in dose 150000 units 2 times a day during one month. Mothers in lactation period are administered therapy similar to preventive therapy.
EFFECT: ensuring increase of efficiency of thyroid gland treatment in children of early age.
SUBSTANCE: method concerns medicine, namely to endocrinology, and concerns treatments of a diffusive euthyroid struma. For this purpose the complex therapy including Iodidum of potassium is carried out - in a dose of 200 mkg/day, sodium selenate - in a dose - 150 mkg/day and Rekicene RD in a dose 10 g 3 times a day.
EFFECT: such complex of medicamental therapy provides effective pathogenetic treatment at the expense of a restore of deficiency of necessary trace substances in a combination to a selective sorption of salts of serious metals, arsenic and other potential goitrogens.
4 tbl, 1 ex
FIELD: medicine; endocrinology.
SUBSTANCE: lowered caloric content diet #5 is prescribed, in combination with fasting days 2 times a week with caloricity of 1000-1200 kilocalorie per day. Therapeutic physical training with individual exercise dosage is carried out daily in the first half the day for 30-40 minutes, within 21-24 days. The general manual massage is alternated by days with Charcot's douche, during the course of 8-10 procedures. A Charcot's douche effects the back thigh surface , buttocks, frontal abdominal wall - clockwise at pressure of 1.5-2 atmospheres, water temperature of 36°C, 0.5-1 minute per zone, total effect time is 4 minutes. The procedure is caried out in the second half of the day, in the course of 10-12 procedures. Electrosleep is carried out by oculo-cervical method at frequency of 10-20 Hz, current intensity up to 1-2 mA, exposure time is 30 minutes. Besides the procedure is carried out in the middle of the day, daily, in the course of 10-15 procedures. Group and individual appointments with the psychologist are carried out on the daily basis, during 45-60 minutes, within 21-24 days. Patients with combination of obesity and struma in addition are provided with iodide-bromine baths with iodine concentration of 10 mg/l, Bromum of 25 mg/l, water temperature is 37°C, procedure duration is 8-10 minutes, alternating by days with Charcot's douche, in the course of 8-10 procedures. The general massage is carried out at the same day with iodide-bromine baths, iodbalance intake is 100-200 mkg/per day, daily, after meal. In case of psychocorection additional activities are done for formation of motivation, loss of weight and long-term iodine drugs intake, reduction of anxiety, aggression and increase of self-appraisal.
EFFECT: body weight reduction, normalisation of arterial pressure, increase of exercise tolerance, correction of metabolic, hormonal and vegetative status parameters.
7 tbl, 2 ex
FIELD: chemistry, pharmacology.
SUBSTANCE: compound of formula [I]: is described, where the ring A represents halogen substituted benzene ring; the ring B represents benzene ring substituted with two lower, 1 to 4 carbon atoms, alcoxy-groups; the ring C represents benzene ring or five-member aromatic heterocyclic ring, that may be optionally substituted with substitute as follows: carboxyl group, C1-4-alkyl group, C2-7-alkanoiloxy-C1-6-alkyl group, phenyl-C1-4-alkyl group, phenyl group, optionally substituted with carboxyl group, or oxo-group; R1 represents C1-6-alkyl group, optionally substituted with hydroxyl group, that optionally substituted with C2-20-alkanoil or C1-7-alkyl group; X1a represents bound or C1-6-alkylen, optionally substituted with hydroxyl or oxo-group; X1b represents bound or C1-6-alkylen, optionally substituted with hydroxyl or oxo-group; X2 represents bound, -O- or -S- ; X3 represents bound or group, formed by one hydrogen atom elimination from either straight or branched chain C1-7-alkyl, or C2-6-alkenyl group, that optionally substituted with hydroxyl or oxo-group; and Y represents optionally etherified carboxyl group; or its salt. Benzoxazepin derivatives production method, medicine based on them, and their application are also described.
EFFECT: novel compounds have high lipids-decreasing effect and are helpful as hyperlipidemia prevention and treatment medicine.
20 cl, 168 ex
SUBSTANCE: invention concerns medicine, endocrinology. Perform insertion of an extract of dry roots of dropwort on 5 ml 3 times a day for 20 mines before meals. Course of treatment takes 20 days. Perform from 1 to 4 courses.
EFFECT: decrease of frequency and volume of operative measures.
2 cl, 5 ex
SUBSTANCE: method involves carrying out balneotherapy, foing physiotherapy exercises and intaking iodomarine and/or L-tiroksin. In first half of the day, physiotherapy exercises are performed, general artificial radon baths being performed in the second half of the day. Manual massages of a collar zone are perform in days free from baths. From November till March phonophoresis of Traumel S ointment on a thyroid gland projection is also performed with an intensity of 0.05 W/cm2, continuous regimen, duration of influence of 3-5 minutes on the right and at the left, general time of influence of 6-10 minutes, in a day with a magnetotherapy on a projection of palatine tonsils, size of a magnetic induction being 6-9 mT, for 5-6 minutes from each party, general time of 10-12 minutes, in a course of 8-10 procedures. At treatment during the period from April till October, patients are additionally prescribed a group galotherapy in the second half of the day, in a course of 10-15 procedures, and phototherapy of red range at a wavelength of 660-675 nanometers, densities of power of radiation of 1 mW/cm2 and an infra-red range at a wavelength of 840-950 nanometers, densities of power of radiation of 2.7 mW/cm2 to biologically active points: VC-20, VC-22, E-36 symmetrically on the right and the left, Gi-4 symmetrically on the right and the left. Time of influence for one point is 1.5-2 minutes, general time of influence being 9-12 minutes, daily, in 10-12 procedures, with duration of treatment making up 21-24 days.
EFFECT: decrease of exacerbations of chronic centres infection frequency; normalising action on the immunologic status during the most adverse periods of a year and maintenance of a condition of euthyroidism within all year.
3 tbl, 2 ex
SUBSTANCE: invention can be used for medical treatment of secondary hypothyroid state accompanied by low synthesis of thyrotrophic hormone by hypophysis and of iodine hormone by thyroid gland. Substance of invention implies application of peptide Lys-Glu-Asp-Gly as a medicine stimulating synthesis of thyrotrophic hormone by hypophysis and of thyroid hormone by thyroid gland.
EFFECT: high specific activity of introduced peptide and decrease of side effect risk.
4 tbl, 1 ex
FIELD: medicine, endocrinology, chemical-pharmaceutical industry, pharmacy.
SUBSTANCE: invention relates to design of agent used in treatment of iodine-deficient diseases, in particular, hypothyroidism. Agent for treatment of hypothyroidism comprises the following medicinal plants: walnut green fruits, wormwood herb, warty birch buds, licorice roots and clove flower buds taken in the ratio = 30:2:10:2:2, respectively. Agent is prepared as tincture in 35% ethyl alcohol. Method for treatment of hypothyroidism involves prescription of abovementioned agent to a patient orally in the dose 7-30 drops, 3 times per a day, 15 min before eating with 50 ml of water for 5-35 days. In all cases treatment of patients with the proposed agent resulted to the stable therapeutic effect without adverse effects.
EFFECT: valuable medicinal properties of agent.
2 cl, 2 ex
FIELD: medicine, endocrinology.
SUBSTANCE: one should inject cycloferon per 2.0 ml during the first 10 d daily and during the next 20 d - every 2 d. The course should be repeated in 6 mo. Moreover, in case of subclinical flow of hypothyroidism cycloferon should be injected as monotherapy. In case of light, average and severe degrees of hypothyroidism cycloferon should be injected at the background of L-thyroxine maintaining dosages.
EFFECT: higher efficiency of therapy.
1 ex, 1 tbl
FIELD: medicinal industry.
SUBSTANCE: invention relates to a method for isolating biologically active substance from mammalian pancreas and preparing a medicinal formulation for parenteral administration that can be used in medicine as agent normalizing functions of pancreas. Agent is made as a medicinal formulation for parenteral administration and represents peptide complex with the content of low-molecular fraction from 70% to 890%, molecular mass of its peptide components in the range 74-222 Da and the concentration of polypeptides 2.5-2.9 mg/ml. Agent is prepared from calf pancreas (age is 12 months, not above) or pigs by tissue extraction with acetic acid in the presence of zinc chloride. Method for preparing agent from calf pancreas (age is 12 months, not above) or pigs involves freezing at temperature -40°C (not less), keeping at temperature -20-22°C for two months (not less) and adding 3% acetic acid solution in the volume ratio = 1:5 at temperature 20 ± 5°C. Extraction is carried out at constant stirring and 1% zinc chloride solution is added to the prepared homogenous suspension in the volume ratio = 50:1 followed by cooling at constant stirring to temperature 7-16°C and the following stirring for 1 h in each 4 h in settling for 48 h. Extract is separated from inert substances by separating and acetone is added to extract in the volume ratio = 1:5 and kept at temperature 3-5°C for 4 h. Formed homogenized deposit is precipitated with acetone repeatedly twice (not less) and deposit containing active substance is washed out on Nutch filter with two-fold volume of acetone cooled to temperature 7-16° up to preparing light-gray deposit. Deposit is rubbed through metallic sieve, dried, dissolved in distilled water at room temperature at constant stirring up to the concentration of polypeptides 2.5-2.9 mg/ml. Solution is centrifuged, filtered and subjected for ultrafiltration treatment in device under anti-pressure 1.0 kgf/cm2 (not above) through materials with retaining capacity 15000 Da. Glycocol is added to ultrafiltrate to its final concentration 10-20 mg/ml at pH = 5.6-6.6, solution is subjected for sterilizing filtration under pressure 2.0 kgf/cm2 (not above), poured into ampoules in volume 2 ml and subjected for autoclaving at temperature 120°C for 8 min and under atmosphere pressure 1.1 kgf/cm2. Invention provides optimal technology in isolating peptide complex from calf pancreas (age is 12 months, not above) or pigs with the content of low-molecular fraction from 70% to 90%, molecular mass of its peptide components in the range 74-228 Da, and preparing aqueous solution of extract with the concentration of polypeptides 2.5-2.9 mg/ml. Invention provides both purifying the prepared product from impurities and to enhance its yield. The isolated substance differs from the known substances early prepared from mammalian raw by molecular mass of its peptide components, absence of toxicity and apyretic properties based on the complete removing impurities.
EFFECT: improved preparing method, valuable properties of agent.
3 cl, 2 tbl, 1 dwg, 4 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: present invention concerns area of medical products, in particular to a tablet for preventive maintenance or treatment of bacteriemic diseases at the animals, containing from 20 to 45 wt % of enrofloxacin, from 18 to 35 wt % of lactose, from 5 to 10 wt % of microcrystallic cellulose and from 5 to 20 wt % of meat aromatisers. Besides the invention concerns a way of reception of the specified tablet.
EFFECT: maintenance of optimum mechanical properties of tablets.
2 cl, 1 tbl, 1 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention concerns area of a chemicopharmaceutical industry and concerns the solid medicinal form possessing antianginal and hypotensive activity, containing amlodipine besylate and target additives in quality of active substance at a following parity of ingredients, wt %: amlodipine besylate - 6-10, lactose - 65-90, starch potato - 0.3-0.6, sodium croscarmellose - 1.5-3, stearin acid and-or its salts - 0.5-1, pre-gelled starch - the rest.
EFFECT: reception of tablets with the lowered total weight.
8 cl, 1 ex, 2 tbl
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention concerns medical products and concerns the method of obtaining of a Solifenacin composition or its salts for use in a solid preparation which includes at least one stage chosen of the group consisting of (i) stage of wet granulation with use of a dissolvent for Solifenacin or its salts, thereat quantity of Solifenacin or its salts which should be dissolved in 1 ml of a dissolvent makes less than 0.1 mg, (ii) stage of dicrease of quantity or rate of addition of a dissolvent if the dissolvent moves Solifenacin or its salt in an amorphous condition, and quantity of Solifenacin or its salts which should be dissolved in 1 ml of a dissolvent 10 mg or more and (iii) stage of activisation of process of crystallisation of a composition of the wet granulation received by means of a usual way. Also the pharmaceutical composition for use in the solid preparation, showing selective opposing action against muscarinic M3 receptors is revealed.
EFFECT: rising of stability of the compositions containing Solifenacin or its salt.
12 cl, 3 tbl, 10 ex
SUBSTANCE: invention refers to pharmaceutics and concerns a solid pharmaceutical composition applicable for oral introduction and containing: (a) S1P receptor agonist; and (b) sugar alcohol.
EFFECT: invention provides homogeneous distribution of an active component in the solid composition with its high stability.
18 cl, 2 tbl, 39 ex
SUBSTANCE: invention relates to pharmacon immediately dealing with preparation of a solid medication for treatment of diabetes and its sequela. The medication contains metformin or a salt thereof, pioglitazone or a salt thereof, homogenously dispersed, as well as target admixtures. The ratio of the average particle size of metformin or the salt thereof to the average particle size of pioglitazone or the salt thereof varies from 2.23:1 to 8.06:1.
EFFECT: provision for high homogeneity and dissolution degree of the active ingredient.
5 cl, 3 tbl, 14 ex
SUBSTANCE: invention refers to pharmaceutical industry and concerns method for making antiulcer and antacid tablets containing an active material made of hairgrass rhizome and buckthorn bark, as well as base bismuth nitrate, base magnesium carbonate, sodium hydrocarbonate and microcrystalline cellulose, all being mixed with humid granulation and pelletisation. Herewith the active material is polyextracted buckthorn bark and hairgrass rhizome resulted from multistage counter-current extraction of hairgrass rhizome and buckthorn bark in specific environment followed by graduation of the extract.
EFFECT: method allows for tablets made of standardised extractive complexes of natural raw materials with low microbial semination, high biological activity of components, improved biological availability and stability.
2 tbl, 18 ex
SUBSTANCE: invention refers to pharmacology and medicine and concerns a pharmaceutical composition for treatment or prevention of vascular pathological condition, diabetes, obesity or low-sterol plasma concentration in mammals containing sterol absorption inhibitor of formula (II), lactose monohydrate, microcrystalline cellulose, polyvinylpyrrolidone, croscarmellose sodium salt, sodium lauryl sulphate and magnesium stearate.
EFFECT: invention provides improved solubility of the composition.
21 cl, 4 tbl, 1 ex
SUBSTANCE: invention refers to chemical-pharmaceutical industry and medicine, namely to solid formulation betahistine dihydrochloride containing lactose, microcrystalline cellulose, copolymer vinylpyrrolidone and vinyl acetate, as well as stearic acid and/or its salts as additives in ratio as specified in the patent claim, and to production procedure of the present formulation.
EFFECT: solid formulation under the invention is characterised with good disintergration and high strength.
6 cl, 1 ex
SUBSTANCE: invention refers to medicine, particularly to pharmacy. There is disclosed new preparation. Controlled-release Proxodolol is prepared effectively and conveniently with applying one or more mixed swelling or gelling components, an active component and pharmaceutically acceptable filler. It is preferential to apply a tableted preparation containing Proxodolol dosed 120 mg, hypromellose and pharmaceutically acceptable fillers, e.g. microcrystalline cellulose, calcium stearate and aerosil. New pharmaceutical forms with a suitable Proxodolol release profile allow reducing number of daily dosages while concentration of active component is constant within a therapeutic dose.
EFFECT: stable kinetic indicators of active material delivery.
8 cl, 5 ex, 5 tbl
SUBSTANCE: claimed invention relates to chemical-pharmaceutical industry and concerns auxiliary binding substances for manufacturing drop-shaped tablets and to preparation of drop-shaped tablets. Auxiliary binding substances according to claimed invention are selected from group which consists of monosaccharide, oligosaccharide, polysaccharide, sugar ester, sugar of alcohol structure, alpha-hydroxy acid, higher fatty acid derivative, higher aliphatic alcohol, polyol, urea and poly(ethyleneoxide) derivative.
EFFECT: claimed invention reduces toxicity caused by polyethylene glycol, improves drop-shaped tablet quality and accelerates development of drop-shaped tablets.
20 cl, 68 ex, 2 tbl
SUBSTANCE: method of obtaining soluble molecular complexes, containing one or several acting substances, poorly soluble in water medium, included into one or several host molecules representing cyclodextrin, which is distinguished by the fact that it includes following stages: (a) bringing one or several acting substances in contact with one or several host-molecules; (b) carrying out stage of molecular diffusion by bringing liquid liquefied under pressure in contact in static conditions with mixture obtained at stage (a), in presence of one or several agents favouring diffusion; (c) isolation of thus obtained molecular complex. Carrying out stage of molecular diffusion also favours dissolution in water medium with increase of solubility approximately by 100 fold.
EFFECT: method, including stage of molecular diffusion in static conditions applying liquid liquefied under pressure, excluding stage of further washing with liquid with supercritical parameters, considerably increases part of including depending on amount of favouring diffusion agent, added to medium.
6 cl, 7 ex