FIELD: organic chemistry, pharmacy.
SUBSTANCE: invention relates to a pharmaceutical composition that comprises N-(chloro-4-morpholin-4-yl)-phenyl-N'-hydroxyimidoformamide and β-cyclodextrin sulfobutyl ester or its salt. Invention provides stability of a drug in storage, heating and light effect and shows practice in using also.
EFFECT: improved and valuable properties of pharmaceutical composition.
3 cl, 3 tbl, 7 ex
The scope of the invention
The present invention relates to pharmaceutical compositions, which may contain a highly concentrated solution of N-(3-chloro-4-morpholine-4-yl)phenyl-N'-gidroksiaminopirimidinov with improved stability of the medicinal product uniformity and quality.
The level of technology
N-(3-chloro-4-morpholine-4-yl)phenyl-N'-hydroxymaleimide is a compound which is disclosed in WO 01/32164, and in respect of which it was discovered that it has the ability to selectively inhibit 20-NET, producing the enzyme to monitor renal diseases, cardiovascular diseases and cerebrovascular diseases (in particular, cerebral infarction).
Known methods for improving the solubility of poorly soluble in water drug to obtain solutions for injection and so on., such as to redefine them in the form of salts, micelles, the use of auxiliary solvents and drugs in the form of fat emulsions and methods for incorporating β-cyclodextrin. In relation to solubilize poorly water medicines in WO 85/02767 disclosed solubilization of poorly soluble in water drug using hydroxypropyl β-cyclodextrin, and in U.S. patent 5134127 disclosed solubilization of poorly soluble in water medicines with Sul is outillage ether β -cyclodextrin.
However, there is no appropriate way solubilization, which can be easily achieved due to the differences of form or characteristics medicines. In addition, even if the drug can be solubilisation can receive thevarious problems in terms of stability over time and in relation to security.
Although N-(3-chloro-4-morpholine-4-yl)phenyl-N'-hydroxydopamine preferably be administered intravenously, by the way, it is poorly soluble in water, is not suitable for solubilization by the transferred in the form of acid salts due to the instability properties in acidic solutions and also instability in a state of solution when exposed to light. So needed some special tools to obtain pharmaceutical compositions, such as injection. In addition, as prolonged intravenous infusion should be considered for prevention or treatment of cerebral infarction, it is necessary to take into account the safety of the living organism in the production of pharmaceutical preparations.
Disclosure of invention
The object of the present invention is to provide a pharmaceutical composition, which may contain N-(3-chloro-4-morpholine-4-yl)phenyl-N'-hydroxymaleimide dissolved in high concentrations. F the pharmaceutical composition has not only excellent stability during storage, when heated or when exposed to light, but also safe for the living body.
As a result of multiple studiesto obtain the above object, the inventors have found that by adding sulfobutyl ether β-cyclodextrin or its salt to N-(3-chloro-4-morpholine-4-yl)phenyl-N'-hydroxymaleimide can be obtained the drug, which may contain a medicinal substance dissolved in a high concentration, stable when heated and exposed to light and safe,not causing damage to a living organism when introduced. The present invention was created based on these data. That is, the present invention is directed to a pharmaceutical composition that includes a pharmaceutically effective amount of N-(3-chloro-4-morpholine-4-yl)phenyl-N'-gidroksiaminopirimidinov and sulfobutyl ether β-cyclodextrin or its salts. In the pharmaceutical compositions of the present invention is its improved stability over time can be ensured by moving it in the dried product.
The preferred embodiment of the invention
The present invention can be further elaborated as follows.
The present invention relates to a pharmaceutical composition, which comprises N-(3-chloro-4-morpholine-4-yl)phenyl-N'-hydroximino Ramadin and sulfobutyl ether β -cyclodextrin or its salt.
In the present invention N-(3-chloro-4-morpholine-4-yl)phenyl-N'-hydroxymaleimide can be synthesized, for example, according to the method described in WO 01/32164 (revealed as the connection 302), and its dose is different depending on the disorders and forms of introduction, but it usually ranges from 0.1 to 3000 mg per day, and preferably from 1 to 300 mg per day.
Sulfobutyl ether β-cyclodextrin or its salt is available as a commercial product (e.g., Captisol®produced by CyDex, Inc.) or can be synthesized by the introduction sulfobutyl group (s) in the HE group(s) β-cyclodextrin according to the method described in U.S. patent 5134127. The number sulfobutyl groups substituted by an Oh group(s)in one molecule β-cyclodextrinreferred to as "degree of substitution". The average degree of substitution forall molecules β-cyclodextrinreferred to as a "medium " degree of substitution". The average degree of substitution is preferably from about 5 to about 8, more preferably from about 6 to about 7, most preferably about 7. The preferred salt sulfobutyl ether β-cyclodextrin is a pharmaceutically acceptable salt such as a salt of an alkali metal. Especially preferred is nutrie the AI Sol.
Sulfobutyl ether β-cyclodextrin or its salt is usually contained in an amount of from 1.18 to 35,45 mol, preferably from 5,91 to 17.7 mol, per mole of N-(3-chloro-4-morpholine-4-yl)phenyl-N'-gidroksiaminopirimidinov.
For example, Captisol® usually contained in an amount of from 10 to 300 moschata on the basis of one Mascali N-(3-chloro-4-morpholine-4-yl)phenyl-N'-gidroksiaminopirimidinov.
In addition, if necessary, can be included pharmaceutically acceptable carriers or other additives, such as isotonic agents (e.g. glycerol or glucose) and pH modulators.
The pharmaceutical composition of the present invention may be formulated into various pharmaceutical forms, such as solutions for injection, lyophilized preparations for injections, tablets, granules, powders, capsules, solutions for indoor use or dry syrups. Particularly preferred solutions for injection and lyophilized preparations for injection. Data solutions for injection and lyophilized preparations for injection can be entered with a single introduction ofor intravenous infusion.
The pharmaceutical composition of the present invention can be prepared using conventional methods, for example, a conventional method for the production of drugs for injection, which comprises mixing N-(3-chloro-4-orfelin-4-yl)phenyl-N'-gidroksiaminopirimidinov, sulfobutyl ether β-cyclodextrin or its salt and water for injection with stirring and dissolving the mixture. In particular, there is a method that involves adding water for injection to the powders of N-(3-chloro-4-morpholine-4-yl)phenyl-N'-gidroksiaminopirimidinov and sulfobutyl ether β-cyclodextrin or its salt, and dissolving the mixture, or a method which comprises dissolving sulfobutyl ether β-cyclodextrin or its salts in water for injection pre, adding N-(3-chloro-4-morpholine-4-yl)phenyl-N'-gidroksiaminopirimidinov to the obtained solution and the dissolution of the mixture.
Mixing is usually carried out by conventional agitators, however, for specific purposes, such as reducing the time of dissolution, can be applied emulsifier or a homogenizer, using shear force or crushing force.
Conventional steam sterilization under high pressure and sterilization by filtrationconsidered as a stage sterilization to obtain a solution for injection, but in the case of the pharmaceutical compositions of the present invention steam sterilization under high pressure leads to a decrease inthe content of the medicinal product, therefore, the preferred filtration sterilization. Usually filtration sterilization can be carried out using f is ltr with a pore size of about 0.2 μm. The filter material is not specifically limited, unless there is anyproblems, such as adsorption.
For the production of lyophilized preparations may be used a conventional freeze dryer. In addition, in order to prevent decomposition of the medicinal product, the free space of the vials or ampoules above product is preferably filled with nitrogen regardless of whether the composition is in a state of solution or in a lyophilized state.
As shown in the test example described below, the pharmaceutical composition of the present invention may contain N-(3-chloro-4-morpholine-4-yl)phenyl-N'-hydroxymaleimide dissolved in very high concentrations. That is, in the case of 10 wt.%/about. an aqueous solution of salt sulfobutyl ether β-cyclodextrin, the solubility of N-(3-chloro-4-morpholine-4-yl)phenyl-N'-gidroksiaminopirimidinov in aqueous solution sulfobutyl ether β-cyclodextrin or its salt is of 3.57 mg/ml at 25°and in the case of 20 wt.%/about. aqueous solubility of drugs is to 7.67 mg/ml at 25°C. on the Contrary, the solubility of the above drugs in 5% tween - 80, 10% polyethylene glycol, soybean oil and olive oil, which are used to move theit micelles, the alcohol and the drug is x fat emulsion is not more than 0.5 mg/ml at 25° C. Thus, it is proved that the pharmaceutical composition of the present invention contains the above-mentioned drug, dissolved in significantly higher concentrations compared with conventional drugs.
Moreover, in the solution sulfobutyl ether β-cyclodextrin N-(3-chloro-4-morpholine-4-yl)phenyl-N'-hydroxymaleimide also verystable when heated and exposed to light and, thus, it is convenient for practical application.
The present invention is illustrated in more detail using the following examples and test examples, which do not limit the scope of the invention. Based on a detailed description of the various changes and modifications will be obvious to experts in this field, and such changes and modifications arein the scope of the invention.
N-(3-chloro-4-morpholine-4-yl)phenyl-N'-hydroxymaleimide (1 g) and sodium salt sulfobutyl ether β-cyclodextrin (Captisol®; average degree of substitution of about 7) (110 g) is weighed and added distilled water (1 l) for injection; after dispersion stirrer, the mixture is dissolved using a homogenizer. Then the solution is sterilized by filtration using a filter (pore size: 0.22 μm). A solution (10 ml) fill the 20 ml vial a dark stack is and. The free space above the product each vial fillnitrogen; and the vial sealed and pressurized to obtain a solution for injection containing 1 mg/ml of the drug.
N-(3-chloro-4-morpholine-4-yl)phenyl-N'-hydroxymaleimide (1 g) and sodium salt sulfobutyl ether β-cyclodextrin (Captisol®; average degree of substitution of about 7) (110 g) is weighed and added distilled water (1 l) for injection; after dispersion stirrer, the mixture is dissolved using a homogenizer. Then the solution is sterilized by filtration using a filter (pore size: 0.22 μm). A solution (10 ml) is filled with 20-ml bottle of dark glass and subjected to freeze-drying, in which the set point temperature at -10°C. the Free space above the product each vial is filled with nitrogen, and the vials sealed and pressurized to obtain a lyophilized preparation for injection containing 10 mg/ml of drug in the vial.
Comparative example 1
A saturated aqueous solution of N-(3-chloro-4-morpholine-4-yl)phenyl-N'-gidroksiaminopirimidinov receive the same manner as in example 1, except that sodium salt sulfobutyl ether β-cyclodextrin is not used.
Comparative example 2
Liofilizarea the hydrated drug for the injection of N-(3-chloro-4-morpholine-4-yl)phenyl-N'-gidroksiaminopirimidinov get the same way as in example 2, except that 100 g of hydroxypropyl β-cyclodextrin and 30 g of d-mannitol was used as an isotonic agent instead of 110 g of sodium salt sulfobutyl ether β-cyclodextrin.
Test example 1 [Test to solubilize]
Excess amount of N-(3-chloro-4-morpholine-4-yl)phenyl-N'-gidroksiaminopirimidinov add 10 wt.%/about. and 20 wt.%/about. aqueous solutions of sodium salt sulfobutyl ether β-cyclodextrin (Captisol®; average degree of substitution of about 7) and purified water as a control, respectively. After shaking in a water bath set at 25°, 1 day measure the solubility of the drug.
As a result, the solubility of N-(3-chloro-4-morpholine-4-yl)phenyl-N'-gidroksiaminopirimidinov in purified water, ascontrol was 0.08 mg/ml, and it was found that it increases when you add sodium salt sulfobutyl ether β-cyclodextrin to the solutions, as shown in table 1.
Accordingly, it is shown that sulfobutyl ether β-cyclodextrin useful for dissolving N-(3-chloro-4-morpholine-4-yl)phenyl-N'-gidroksiaminopirimidinov.
|of 3.57 mg/ml|
to 7.67 mg/ml
Test example 2 [Test photostability]
The solution of example 1 and the solution of comparative example 1, each, placed in colorless and transparent closed glass test tube and incubated under fluorescent lamp when the light 3000 Lux and measure the remaining amount of N-(3-chloro-4-morpholine-4-yl)phenyl-N'-gidroksiaminopirimidinov. As a result, N-(3-chloro-4-morpholine-4-yl)phenyl-N'-hydroxymetabolites in the solution of example 1 is much more stable than in the solution of comparative example 1, as shown in table 2. Accordingly, it is shown that sulfobutyl ether β-cyclodextrin useful for the stabilization of N-(3-chloro-4-morpholine-4-yl)phenyl-N'-gidroksiaminopirimidinov.
|Example 1||Comparative example 1|
the remaining share(%)
Test example 3 [Test on the stability of lyophilized for injection]
After keeping the lyophilized preparation for injectionp is the iMER 2 and lyophilized for injection of comparative example 2 at 60° C for 7 days to measure the remaining share of drugs.
As a result, N-(3-chloro-4-morpholine-4-yl)phenyl-N'-hydroxymetabolites in dried preparation for injection of example 2 was more stable than that of the lyophilized preparation for injection of comparative example 2, as shown in table 3. Accordingly, it was shown that sulfobutyl ether β-cyclodextrin very useful for the stabilization of N-(3-chloro-4-morpholine-4-yl)phenyl-N'-gidroksiaminopirimidinov. In conclusion, therefore, it was proved thatfreeze-dried preparation for injection, the pharmaceutical compositions of the present invention has theexcellentthe heat resistance ofandconvenient for practical storage and use.
|Example 2||Comparative example 2|
the remaining share(%)
Since the pharmaceutical composition of the present invention may contain N-(3-chloro-4-morpholine-4-yl)phenyl-N'-hydroxymaleimide, Rast is Genny in high concentrations, and ensures the stability of the medicinal product during storage, when heated and exposed to light, it is convenient for practical use.
1. Pharmaceutical composition, which comprises N-(3-chloro-4-morpholine-4-yl)phenyl-N'-hydroxymaleimide and sulfobutyl ether β-cyclodextrin or its salt.
2. The pharmaceutical composition according to claim 1, which is freeze-dried.
3. The pharmaceutical composition according to claim 1 or 2, which is a solution for injection.
FIELD: organic chemistry, medicine.
SUBSTANCE: invention relates to group of compound of the formula (I): wherein a wave-like bond means a racemate, (R)-enantiomer or (S)-enantiomer; A represents a linear bond or -(C=O); B represents a linear bond, oxygen or nitrogen atom; m has value 0 or 1; n has value 1, 2 or 3; each among R1 and R2 means independently hydrogen atom or (C1-C)-alkyl, and if R1 represents hydrogen atom then R2 can represents also -P(O)OR5OR6; each among R3 and R4 means independently hydrogen atom or (C1-C4)-alkyl; each among R5 and R6 means independently hydrogen atom, or its nontoxic pharmaceutically acceptable salt or solvate. Also, invention relates to a method for treatment of diseases showing sensitivity to opening calcium-activated potassium channels. Invention provides synthesis of novel biologically active compounds and a method for treatment of diseases showing sensitivity to opening calcium-activated potassium channels of large conductivity in mammals.
EFFECT: improved method of treatment, valuable medicinal properties of compounds.
9 cl, 1 tbl, 25 ex
FIELD: organic chemistry, medicine, pharmacy.
SUBSTANCE: invention relates to novel compounds of the formula (I) and their pharmaceutically acceptable salts. Proposed compounds possess properties of agonists of receptors activated by peroxisome proliferators (PPAR agonists) and can be used in treatment of such diseases as diabetes mellitus, hypertension, atherosclerotic diseases and others. In the general formula (I) R1 means lower alkyl, monocyclic (C3-C6)-cycloalkyl; R2 means hydrogen atom, halogen atom, lower alkyl, lower alkoxy-group wherein at least one of three radicals R3, R4, R5 or R6 is not hydrogen atom; or R3 and R4 are bound together to form a ring with carbon atoms to which they are bound, and R3 and R4 mean in common -CH=CH-S-, -S-CH=CH-, -CH=CH-CH=CH-, and R5 and R6 are given above; R7 means lower alkyl, lower alkenyl; R8 means hydrogen atom or lower alkyl; n = 1, 2 or 3. Also, invention relates to a pharmaceutical composition based on the invention compounds and to using compounds of the invention in preparing medicinal agents used in treatment and/or prophylaxis of diseases mediated by agonists PPARα and/or PPARγ.
EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.
20 cl, 1 tbl, 13 sch, 71 ex
FIELD: biopharmacology, medicine.
SUBSTANCE: claimed drug contains human granulocyte colony-stimulating factor (hG-CSF) as active ingredient. Disclosed are methods for treatment ob obstructive atheriosclerosis, ishemic diseases and other conditions by administering of abovementioned drug.
EFFECT: therapeutic agent of increased effectiveness.
16 cl, 5 ex, 1 dwg
FIELD: organic chemistry, medicine, pharmacy.
SUBSTANCE: invention describes compounds of the general formula (I) wherein radical values are given in the invention claim that are novel histamine receptors antagonist. Preferable compound is 3-[2-[4-(11,12-dihydro-6H-benzimidazo]2,1-b]benazepin-6-yl)-2-(phenylmethyl)-1-piperidinyl]ethyl]-2,10-dimethylpyrimido[1,2-α]benzimidazole-4(10H)-one or its salts, isomers and N-oxides. Proposed compounds are useful in prophylaxis and treatment of increased intracranial pressure and/or secondary ischemia caused by craniocerebral trauma.
EFFECT: valuable medicinal properties of compounds, improved method of synthesis.
13 cl, 13 tbl, 5 dwg, 14 ex
FIELD: medicine, therapy, reflexotherapy.
SUBSTANCE: the innovation in question deals with carrying out combined intravenous and external laserotherapy in combination with complex medicinal impact upon the body. Additionally, it is important to fulfill monitor intestinal emptying, daily, about 6-8 procedures/course. External laserotherapy should be carried out onto corporal and auricular points. Medicinal therapy deals with introducing T-activin immunomodulators intramuscularly at the dosage of 100 mcg/d and Halavit at the dosage of 100 mg/d, about 10-20 procedures/course. It is important to apply Aciclovir at the dosage of 1 g/d, therapy course corresponds to 14. The intake of Eiconol in capsules at the dosage of 6-9/d, copper derivatives of chlorophyll at the dosage of 0.1g/d and food additive sodium alginate at the dosage of 4 g/d should be carried out during the whole therapy course. Intravenous and external laserotherapy should be fulfilled at about 8-10 procedures/course. The innovation normalizes cellular and humoral immunity, prolongs the aftereffects of therapy conducted and decreases the number of its complications.
EFFECT: higher efficiency of therapy.
3 cl, 4 dwg, 6 ex, 1 tbl
FIELD: medicine, pharmacy.
SUBSTANCE: invention proposes an agent comprising the following components, mg: 2-ethyl-6-methyl-oxypyridine succinate, 25-1500; nicotinamide adenine dinucleotide, 0.5-100, and inositol, 100-1200. Agent can comprise additionally L-carnitine in the amount 10-100 mg. Also, agent can comprise additionally choline alphoscerate in the amount 50-1000 mg. Agent can be prepared in injection or tabletted medicinal formulation or as suppository. Agent provides effective delaying apoptosis and arresting transformation of apoptotic alterations to necrotic alterations in pathological processes of different etiology.
EFFECT: valuable properties and enhanced effectiveness of agent.
4 cl, 2 dwg, 2 tbl, 9 ex
FIELD: organic chemistry, medicine, pharmacy.
SUBSTANCE: invention describes novel nitrogen-containing aromatic derivatives of the general formula (I): wherein X1 means nitrogen atom (N) or group -CR10= wherein R10 means hydrogen atom (H), halogen atom or -CN; X2 means N or group -CR11= but X1 and X2 can't mean N simultaneously; Y means oxygen atom (O) or group -NRY- wherein RY means hydrogen atom or (C1-C6)-alkyl group; R1 means phenoxy-group, group -NR12aR12b, group , group and other values; each radical among R3, R4, R5, R6 and R11 means hydrogen atom; R7 means hydrogen atom or (C1-C6)-alkyl group; R8 means hydrogen atom or (C1-C6)-alkyl group; R10 means hydrogen atom, halogen atom or cyano-group; R9 means group -NR16aR16b or group of the formula: wherein T2 means pyrrolidine, piperazine ring possibly substituted with (C1-C6)-alkyl group, or morpholine ring; R12a and R12b mean independently hydrogen atom, (C1-C6)-alkyl, (C1-C6)-alkoxy-group; R2 means hydrogen atom or (C1-C6)-alkyl; R16a means hydrogen atom or (C1-C6)-alkyl, and R16b means (C1-C6)-alkyl possibly substituted with phenyl, (C1-C6)-alkoxy-group, (C1-C6)-alkylthio-group or di-(C1-C6)-alkylamino-group, (C3-C6)-alkynyl, (C3-C8)-cycloalkyl, phenyl possibly substituted with halogen atom, thiazolyl or piperidinyl possibly substituted with (C1-C6)-alkyl, and their salts or hydrates. Also, invention describes a pharmaceutical composition, method for treatment or prophylaxis of tumor diseases and using the novel compounds for preparing an agent useful in treatment abovementioned diseases.
EFFECT: valuable medicinal properties of compounds and pharmaceutical composition, improved method for treatment.
26 cl, 17 tbl, 221 ex
FIELD: medicine, pharmacy.
SUBSTANCE: invention describes a pharmaceutical system for oral delivery of antioxidants, vitamin C and vitamin E. The delivery system comprises vitamin C in the amount providing delivery of the daily dose corresponding to 60 mg - 2 g of vitamin C, and comprises vitamin E in the amount providing delivery of the daily dose corresponding to 50 mg - 500 mg of α-tocopherol. Also, this delivery system provides the ratio of concentrations vitamin C and vitamin E in blood plasma in the range from 1:1 to 3:1, and wherein the solubility of vitamin E provides dissolving 90% of vitamin E for less in 30 min. The dissolving index is measured by heating at 37°C in 15 ml of water in the prescribed time intervals followed by decantation of the dissolving medium, washing out with 25 ml of 25% ethanol, combining the dissolving medium and decanted ethanol and measurement of the content of vitamin E in combined media for dissolving in ethanol, and wherein the solubility of vitamin C is so under conditions of the Test A that its dissolving after 1 h is less then 40% of vitamin C and wherein this test for solubility satisfies the order for the European Pharmacopoeia 711, and wherein administration of the indicated delivery system enhances the concentration of blood plasma vitamin E up to at least 20 mcmole/l, and the concentration of vitamin C to at least 40 mcmole/l. Also, invention represents methods for treatment including administration the claimed pharmaceutical system to a patient. The concentration and the ratio of these antioxidants corresponding to the stationary state of these antioxidants as was found are to be essential for prophylaxis and treatment of disorders associated with oxidative loading, such as arteriosclerosis, diabetes mellitus and damages of the nervous dystrophy type as Alzheimer disease.
EFFECT: improved and enhanced properties of pharmaceutical delivery system.
33 cl, 9 tbl, 3 dwg, 5 ex
FIELD: medicine, pharmacy.
SUBSTANCE: invention relates to medicinal agents, namely, to a novel medicinal agent possessing hypolipidemic effect and representing molecular complex of simvastatin with β-glycyrrhizic acid in the mole ratio simvastatin : β-glycyrrhizic acid= 1:(1-4). Proposed complex possess higher effectiveness in lower doses that results to reducing toxicity in treatment.
EFFECT: improved and valuable medicinal properties of agent.
3 dwg, 5 ex
FIELD: organic chemistry.
SUBSTANCE: invention relates to new pyperidine derivative of formula I , wherein R represents hydrogen atom; n is integer from 1 to 5. Said compounds are useful in medicine in treatment of inflammation diseases, diabetes, allergic, autoimmune, and other diseases.
EFFECT: new piperidine derivative with pharmaceutical activity.
10 cl, 10 dwg, 18 ex
FIELD: medicine, oncology, pharmacy.
SUBSTANCE: invention discloses the lentinane aseptic antitumor lyophilized powder for injection and a method for its preparing also. The lentinane aseptic antitumor powder for injection comprises principally 0.50-1.20 weight parts of lentinane and 50-140 weight parts of a lyophilized excipient chosen from mannitol, glucose, sucrose or lactose. The proposed drug shows clinical effectiveness, safety and high stability as it doesn't comprises dextran that can cause adverse allergic response reactions.
EFFECT: valuable medicinal properties of drug, improved preparing method.
10 cl, 1 dwg, 1 tbl, 21 ex
FIELD: medicine, pharmaceutical industry.
SUBSTANCE: claimed method includes vacuum sublimation from solid layer of frozen suspension of thermolabile biologically active preparation; initially at irradiator temperature, which is at least 20°C higher than maximum critical temperature (+36°C)-(+60°C) and doesn't induce thermal inactivation of thermolabile biologically active preparation, up to experientially determined preparation temperature (+25°C)-(+35°C), wherein thermolabile biologically active preparation is not inactivated during irradiator temperature decrease. Then material is dried again at (+36°C)-(+60°C).
EFFECT: accelerated method of increased productivity; dried preparation of improved quality.
FIELD: medicine, pharmacy.
SUBSTANCE: invention relates to novel compositions and using kahalalide F, to a set containing the kahalalide F composition and to a reduced solution prepared from the kahalalide F composition. Combination of non-ionic surface-active substance and organic acid is suitable for using with a filling agent for preparing lyophilized formulation of kahalalide F.
EFFECT: improved preparing method.
10 cl, 7 ex
SUBSTANCE: means is found to be lyophilisate containing glycosamine salt and tromethanol taken in known proportions.
EFFECT: high active ingredient concentration in the preparation; high speed and effectiveness of diffusion into articulation zone.
2 cl,1 tbl
SUBSTANCE: method involves preparing composition comprising epotilone analogs by dissolving said epotilone analog in aqueous butanol. The produced solution is dried in two stages to produce lyophilized product being lyophilized epotilone analog and pharmacological means for treating cancer diseases containing lyophilized epotilone analog.
EFFECT: high solubility of obtained product.
20 cl,1 tbl
FIELD: chemical-and-pharmaceutical industry, in particular production of drugs for joint disease treatment.
SUBSTANCE: claimed agent represents lyophilizate containing glucoseamine salt, chondroitin sulfate and trisaminum in specific component ratio.
EFFECT: agent with increased active ingredient content; diffusion of active substance into joint region with increased rate and effectiveness.
2 cl, 3 ex, 1 tbl
FIELD: medicine, pharmacy.
SUBSTANCE: invention relates to lyophilized composition comprising epotilone in the effective amount and mannitol or cyclodextrin. The second variant of the lyophilized composition involves epotilone and hydroxypropyl-beta-cyclodextrin. The preferable content of epotilone in the lyophilized composition is from 0.1% to 1.5%, and cyclodextrin - from 90% to 99% as measured for the total mass of solid components. Epotilone-containing lyophilized compositions can be used fro preparing an anti-tumor medicinal agent useful for parenteral administration and the lyophilized composition can be reduced preferably before administration directly. Epotilone-containing lyophilized compositions show improved indices of epotilone solubility and can retain stability for 24-36 months at temperature from 2°C to 30°C being without change of the solubility index.
EFFECT: improved and valuable properties of composition.
10 cl, 4 tbl, 14 ex
FIELD: chemico-pharmaceutical industry.
SUBSTANCE: the present innovation deals with new stabilized pharmaceutical composition in its lyophilized form including the compound of formula I
as an active ingredient and lactose disaccharide as a stabilizing agent. The present pharmaceutical compositions are of high stability at storage. As for active ingredient it is not destroyed in the course of time.
EFFECT: higher efficiency.
10 cl, 15 ex, 6 tbl
SUBSTANCE: preparation comprises echinocandine substance of formula I or its pharmaceutically permissible salt, pharmaceutically permissible micelle-forming surface-active agent and non-toxic aqueous solvent and stabilizing agent.
EFFECT: improved stability and bioaccessibility properties.
48 cl, 4 tbl
FIELD: medicine, hematology, pharmacy.
SUBSTANCE: invention relates to the composition of factor VIII composed without addition of albumin and comprising the following excipients of composition in addition to factor VIII: from 4% to 10% of filling agent taken among group consisting of mannitol, glycine and alanine; from 1% to 4% of stabilizing agent taken among group consisting of sucrose, trehalose, raffinose, arginine; from 1 mM to 5 mM of calcium salt, from 100 mM to 300 mM of NaCl, and buffer agent for pH value maintenance about between 6 and 8. Alternatively, the composition can comprise from 2% to 6% of hydroxyethylstarch; from 1% to 4% of stabilizing agent taken among group consisting of sucrose, trehalose, raffinose, arginine; from 1 mM to 5 mM of calcium salt, from 100 mM to 300 mM of NaCl, and buffer agent for pH value maintenance between 6 and 8. In additional variant of realization of invention the composition can comprise: from 300 mM to 500 mM of NaCl, from 1% to 4% of stabilizing agent taken among group consisting of sucrose, trehalose, raffinose and arginine; from 1 mM to 5 mM of calcium salt, and buffer agent. The composition provides stability in the absence of albumin or other proteins.
EFFECT: valuable properties of compositions.
35 cl, 11 tbl, 7 ex
FIELD: medicine, pharmacy.
SUBSTANCE: invention relates to injection depot-preparations containing ziprasidon or its pharmaceutically acceptable salts that solubilized with cyclodextrin and containing a viscosity modifying agent and comprising a cellulose derivative, polyvinylpyrrolidone, alginates, chitosan, dextran, gelatin, polyethylene glycols, polyoxyethylene ethers, polyoxypropylene ethers, polyactides, polyglycolides, polycaprolactones, polyanhydrides, polyamines, polyurethanes, polyetheramides, poly-ortho-esters, polydioxanones, polyacetals, polycarbonates, poly-ortho-carbonates, polyphosphazenes, succinates, polycarbonates, poly-(maleic acid), poly-(amino acids), polyhydroxycellulose, chitin, copolymers or terpolymers of abovementioned substances, sucrose butyrate acetate, PLGA, stearic acid/NMP or their combinations. Also, the claimed invention relates to depot-preparations containing ziprasidon mesylate and solubilized SBECD. Also, the claimed invention relates to a method for treatment of psychotic disease, for example, schizophrenia that involves using the claimed preparations. The claimed preparations provides prolonged administration of ziprasidon and its content from 70 to about 280 mgA/ml that provides possibility for a single administration and providing the therapeutic effect for prolonged period.
EFFECT: improved and valuable medicinal and pharmaceutical properties of preparations.
16 cl, 2 tbl, 2 ex