Agent for preventing and treating chronic venous insufficiency
SUBSTANCE: invention concerns preparing systemic and topical solid and soft dosage forms for external application in the form of a 1.5% hydrophilic gel and rectal capsules containing a 7.5% hydrophilic gel 1.9 g (in terms of the amount of the active substance of 0.14 g/capsule), for preventing and treating chronic venous insufficiency possessing anticoagulant, antithrombotic, anti-inflammatory, antiexudative and antitranssudative, capillary protective activities and improving haemorheology. An active pharmacologically active substance is presented by a substance of a potassium salt of sulphated arabinogalactan; a hydrophilic base is Aerosil, glycerol and pure water; the ingredients of the agent are taken in certain proportions, wt %.
EFFECT: invention provides the effective prevention and treatment of chronic venous insufficiency, has a broad spectrum of therapeutic action, improves haemorheology, tones the vessels and can be used in particular for treating varicose veins, thrombosis and posttraumatic oedema.
5 cl, 7 ex, 8 dwg
The invention relates to chemical-pharmaceutical industry, medicine, pharmacology, and related to hard and soft dosage forms for external use of systemic and topical action in the form of a hydrophilic gel and rectal capsules containing hydrophilic gel for the prevention and treatment of chronic venous insufficiency with anticoagulant, antithrombotic, anti-inflammatory, and antiexudative antitransglutaminase, cardio activities.
As an active pharmacologically active substances used formerly known semisynthetic heparinoid - sulfated arabinogalactan in the form of potassium salt (Acular®), which has hypolipidemic and anticoagulant activity (RU 2319707 and the Certificate of trademark registration "Acular®"No. 398618).
Treatment of chronic diseases of the venous system of the lower extremities, especially decompensated forms with distinct trophic disorders and recurrent ulcers, is a very complex task, as it requires either a large number of drugs of different pharmacological groups, or medicines with polyvalent mechanism of action, which range in the Arsenal of clinicians is very modest.
In phlebological practice of the group of drugs with polyvalent mechanism of pharmacological action of widely used drugs on the basis of heparin. Their range is very diverse and presents examples of both imported and domestic production.
The modern pharmaceutical market of Russia drugs topical action on the basis of heparin represented by such imported medicines, such as: "Wanabes®(Bozalek AO, Bosnia and Herzegovina: gel), "Venitan®Forte" (Lek D. D., Slovenia: gel), "Gearoid Zentiva" (Zentiva and.S., Czech. Republic: ointment 200 IU/g), "Gepatrombin®and Gepatrombin®(Hemofarm A. D., Serbia: gels and ointment), "Dolobene" (Merkle GmbH, Germany: gel), "Lioton®1000" (A. Menarini, Italy: gel). Of domestic drugs in this group include: "Heparin ointment" (CJSC Altayvitaminy, Biysk, OAO Nizhpharm, Nizhny Novgorod, CJSC "Green grove" , Sergiev-Posad, JSC "Biosynthesis" , Penza), "Troubles®"(OAO Nizhpharm, Nizhny Novgorod) and Fenolip®"(JSC "Akrikhin" , Staraya Kupavna).
Of dosage forms with systemic action on the basis of heparin for the prevention and treatment of chronic venous insufficiency of use: "Epsolon" (LLC "Antfarm" , Moscow: rectal suppositories), "Gepatrombin®G" (Hemofarm A. D., Serbia: ointment rectal and rectal suppositories), "Nighean®"(OAO Nizhpharm, Nizhny Novgorod: suppositories of rectal the (e) (State register of medicines. The website of the Ministry of health of the Russian Federation [electronic resource]. - Mode of access: http://www.gris.rosminzdrav.ru).
In these dosage forms heparin is presented in the form of sodium salts individually or in combination with other substances, such as local anesthetics (lidocaine, benzocaine, lauromacrogol 600), corticosteroids (prednisolone acetate and mometazon), capillarisation (β-escin, essential phospholipids, troxerutin), dermolipectomy (D-panthenol) and penetrators (benzylsuccinic, allantoin and dimethylsulfoxide).
Medicines on the basis of heparin, especially systemic action, have serious side effects such as allergic reactions associated with the feature of the receipt of the active substance from animal products, composed of traces of protein and histamine-like substances.
Therefore, the aim of this invention was to develop a highly effective pharmaceutical compositions in the form of hard and soft dosage forms for external use of systemic and topical actions for the prevention and treatment of chronic venous insufficiency with anticoagulant, antithrombotic, anti-inflammatory, and antiexudative antitransglutaminase, cardio activities with low toxicity and minimal side effects. Our first is e identified anti-inflammatory, antiexudative, antitransglutaminase and cardio activity of sulfated arabinogalactan in the form of potassium salt (Acular®and his ability to influence the hemorheological properties of blood.
The technical result of the present invention is the creation of an original pharmaceutical compositions, hard and soft dosage forms for external use of systemic and topical action in the form of 1.5% hydrophilic gel and rectal capsules containing 1.9 grams of 7.5% hydrophilic gel (in terms of quantity of active substance 0.14 g/capsule) for the prevention and treatment of chronic venous insufficiency.
This technical result is achieved in that the means for prevention and treatment of chronic venous insufficiency, containing as an active pharmacologically active substances sulfated arabinogalactan in the form of potassium salt (Acular®) additionally comprises a hydrophilic base colloidal silicon dioxide (Aerosil), glycerin, methyl ester of para-oksibenzoynoy acid (methylparaben, nipagin) and purified water in the following ratio of components, wt.%:
|in the form of potassium salt (Acular®)||1,0-8,0|
|Purified water||To 100.0|
All the components of the hydrophilic base is allowed for medical use.
The technical result is achieved by using in contrast to the closest analogs of drugs "Wanabes®", "Venitan®Forte, Fenolip®", "Epsolon", "Gearoid Zentiva", "Gepatrombin®", "Gepatrombin®S", "Gepatrombin®G", "Dolobene", "Lioton®1000", "Heparin ointment", "Nighean®and Trembles®", in which the active pharmacologically active substances used heparin, semi-synthetic heparinoid - sulfated arabinogalactan in the form of potassium salt (Acular®).
Because the substance of Acular®is hydrophilic, soluble in water, for the manufacture of dosage forms for topical use on the basis of the most efficient and optimal from a technological point of view, and taking into account physico-Henichesk the x properties of the active substance, are hydrogels. In view of the strong electrolytic properties of this substance is of great difficulty obtaining stable hydrogels. In this regard, as the gel is used widely used in the pharmaceutical technology of medicinal forms thickener presented. Gels based on it provide a prolonged therapeutic effect of the active substances due to good adsorption, allowing medicine to linger on the skin, as well as the ability of Aerosil to maintain a uniform distribution of active ingredients in the dosage form that provides them with good bioavailability in tissues. In addition, when applied externally, Aerosil does not violate the metabolic processes in the skin and does not cause her irritation.
The use of glycerol as a component of a gel base provides not only stable and has good technological properties of the dosage form, but also increases its pharmacological effect (and antiexudative antitransglutaminase activity) through the creation of osmotically active system, and also contributes to the hydration of the skin.
Joint application of glycerin and Aerosil reduces microbial contamination of the dosage form, therefore, the introduction in its composition more preservatives may be minimal.
On ri is .1 presents the dependence of the shear stress τ (PA) shear rate D ( -1samples 1 - Acular®gel 1.5% and 2 Acular®the gel of 7.5% and their compliance with the rheological optimum extrusion hydrophilic gels - ABCDEFGH - border technological optimum consistency.
Figure 2 presents a pronounced neutrophil infiltration in the field of linear wounds on Pancino in the control group of animals (1 day, painting the hematoxylin-eosin).
Figure 3 presents a moderately severe neutrophilic infiltration in the field of linear wounds on Pancino in the group of animals treated with the drug, "Acular®the gel of 1.5% (1 day, painting the hematoxylin-eosin).
Figure 4 presents a pronounced swelling of the muscles in the area of linear wounds on Pancino in the control group of animals (1 day, painting the hematoxylin-eosin).
Figure 5 shows a poorly defined swelling of the muscles in the area of linear wounds on Pancino in the group of animals treated with the drug, "Acular®the gel of 1.5% (1 day, painting the hematoxylin-eosin).
Figure 6 presents the effect vasoprotective drugs on the development and involution of edema caused by acute venous congestion in the tail of the rats.
Figure 7 presents the effect of study drug on vascular permeability.
Figure 8 presents a table showing the effect of study drug on hemorheological parameters of blood.
The following PR the measures illustrate the invention.
1.5 g of the substance of Acular®and 0.1 g of nipagin was dissolved with stirring in 6 ml of purified water was then added 80,0 g glycerol. The resulting solution tagusari making 12.4 g of Aerosil with constant stirring to obtain a gel-like consistency. Received a 1.5% gel was filtered. Homogenization of the product was carried out until a homogeneous consistency, transparent gel light yellow color.
7.5 g of the substance of Acular®and 0.05 g nipagina was dissolved with stirring in 30 ml of purified water was then added 55,0 g glycerol. The resulting solution tagusari making was 7.45 g of Aerosil with constant stirring to obtain a gel-like consistency. Received a 7.5% gel was filtered. Homogenization of the product was carried out until a homogeneous consistency, transparent gel light yellow color. The obtained gel was dosed out by 1.9 grams in solid hollow gelatin rectal capsules, the hole was sealed.
On the effectiveness of the pharmacological action of soft medicinal forms are strongly influenced by its rheological properties characterizing technological and functional properties of the medicinal product, such as facemost and extrusion of tubes, convenience and ease of application to the skin, the duration of therapeutic impact and bioavailability of the active substance.
Study of the rheological properties of the original pharmaceutical compositions in the form hydrophilic gels based on sulfated arabinogalactan in the form of potassium salt (Acular®) was carried out by dynamic rheology on modified rebeccasommer Rheotest 2.1 (Germany) with the measuring module "cylinder-cylinder" (the ratio between the radii 1.02) using controlled shear rate. Shear rate D was changed in the range of 0.1-300-1. The method error was 3%. The results presented in figure 1.
As can be seen from figure 1, the rheological parameters of the investigated compositions (1 - Acular®gel 1.5% and 2 Acular®the gel of 7.5%) are in good accordance with the requirements of the optimum consistency for hydrophilic gels, enabling easy dosing when possible technological operations (filling capsules and tubes at packing, vydavlivaete of the tubes, and so on), as well as amazement soft dosage forms to the skin.
Thus, the developed formulations and technologies hydrophilic gels based on sulfated arabinogalactan in the form of potassium salt (Acular®) are optimal for obtaining the original pharmaceutical compositions, the usefulness of which as a means for the prevention and treatment of chronic wansn the th failure proven by the results of pharmacological studies.
Anti-inflammatory and antiexudative action
The study of anti-inflammatory and antiexudative activity of the pharmaceutical compositions of topical action "Acular®the gel of 1.5% conducted on the model of aseptic linear cutaneous wounds (Fencin K. M. wound Healing. - Kiev: Health, 1979. - 167 C.).
For this purpose under ketamine-droperidol-atropinum anesthesia at the Wistar rats weighing 220-250 g at the back on the paravertebral line inflicted wound to own fascia length 4 see equidistant imposed three knotted suture unites the edges of the wounds.
The experiments were performed in accordance with the standards of humane treatment of animals, which are regulated by the "Rules of work with the use of experimental animals" (Annex to order of the Ministry of health of the USSR from 12.08.1977, No. 755).
Animals of the experimental group immediately after surgery and then throughout the experiment applied the gel with a test compound, the rats of the control group - gel-based, does not contain investigated the connection.
The removal of animals from the experiment was carried out in terms: 1, 3, 7, 14, 21 and 28 days.
For histological evaluation of the pharmacological activity of fragments of linear wound and formed in its place connective tissue was fixed FineFix (Milestone, Italy). The resulting material was embedded in paraffin, cooked slices, which were stained with hematoxylin-eosin (Merkulov, A. Course patrologicheskoe technology. - L.: Medicine, 1969. - 422 C.).
Representative pictures of histological preparations presented in figures 2-5.
As shown by the results of the experiment, the control group of animals the healing process of the linear wound morphologically consistent with the canons of the development of the inflammatory response, in which the peak intensity of neutrophil infiltration in the damage zone was observed at 1 day (figure 2).
The use of the investigational pharmaceutical composition reduced the severity of neutrophilic infiltration in the wound compared with the control (figure 3), indicating that the anti-inflammatory effect of the drug, "Acular®the gel of 1.5%".
Edema is an important feature of the inflammatory process. The peak of its intensity, as in the control group and the experimental groups of animals had 1 day after modeling the linear wound.
Thus investigated soft dosage form for external use topical action in the form of pharmaceutical compositions Acular®the gel of 1.5% has antiexudative action, manifested in the reduction of severity of stromal edema and the reduction of cell swelling comparedwith the control (figures 4 and 5).
Thus, the pharmaceutical composition is a topical action "Acular®the gel of 1.5% has anti-inflammatory and antiexudative action.
Assessment antitransglutaminase activity of the pharmaceutical compositions of topical action "Acular®the gel of 1.5% conducted on a model of acute venous congestion in the tail of the rat (non-inflammatory swelling of Genesis) (Nordmann N., Gulati O. R. Hemodynamic studies in acute venous stasis edema in rats // Experientia. - 1984. - Vol.40, No. 4. - P. 346-348).
This was recorded dynamic growth of the tail of the experimental animals (Wistar rats weighing 220-250 g) in a certain period of time after applying ligatures (0-4 hours), as well as on the dynamics of involution swelling after removal of the ligatures (5-8 hours).
Experimental animals inflicted investigated gels before applying ligatures for 1 hour, after applying ligatures and immediately after removal of the ligatures, and the rats - gel-based, does not contain the substance of Acular®in similar time intervals.
As Comparators used officinal preparations "Lioton 1000®gel and Troksevazina®gel 2%" antitransglutaminase (genoprotective) effect.
So, on the model of acute venous congestion in the tail of the experimental animals caused by the imposition of the ligature, it was shown that the pharmaceutical composition is a topical action "Acular®the gel of 1.5% provides comparable with officinal drugs "Lioton 1000®gel and Troksevazina®gel 2%" antitransglutaminase effect. The averaged curves of the dynamics of extravasation is presented in figure 6.
The maximum degree of swelling caused by acute venous congestion, developed by 4 o'clock after compression (applying ligatures). In the control group of animals this index reached the highest value (63% from baseline) and did not disappear even after 4 hours after removal of the ligatures (25% from baseline). In experimental groups investigational drugs suppressed transudate in the acute phase of venostasis 4 hours after applying ligatures (25-33%) and increased resorption specimens after its removal (4-8% against 25% in the control group).
Thus, the drug, "Acular®the gel of 1.5% has vasoprotective (antitransglutaminase) action.
Probably, this is due to the decrease of the permeability of the veins and improve the tone of their walls. That was confirmed in the study of pharmacological activity of solid dosage forms for external use systemic action in the form of rectal capsules containing 7.5% of the hydrophilic gel sulfated arabinogalactan as to what leeway salt "Acular®rectal capsules 0.14 g".
Evaluation of systemic effects (cardio activity) pharmaceutical compositions Acular®rectal capsules 0.14 g" was carried out according to the method of determining the permeability of capillaries (Mankin Century Dynamics inflammation. - M: Medgiz, 1948. - 230 S.).
The experiments were performed on Wistar rats weighing 220-250 g in accordance with the standards of humane treatment of animals, which are regulated by the "Rules of work with the use of experimental animals" (Annex to order of the Ministry of health of the USSR from 12.08.1977, No. 755).
As the comparison drug used officinal drug "Nighean®". Experimental animals within 14 days of rectal introduced investigational medicinal forms, and the rats - gel-based, does not contain the substance of Acular®.
Then under ketamine-droperidol-atropinum anesthesia in rats dailymobile the abdomen and right thigh, analyzed the femoral vein, into which was introduced a 0.5% aqueous solution Trifanova blue (Trypan blue, Sigma) at a rate of 0.5 ml per 250 g weight of the animal. On nepilirovanny surface of the stomach was applied 0.1 ml of toluene (or xylene) and recorded the time development of the blue color of this region. The results of the EC is periment presented in figure 7.
Thus, in the control group of animals the appearance of blue color were recorded in the range of 1.38±0.05 minutes, in the group of the reference preparation "Nighean®this indicator amounted to 2.13±0.08 minutes, and in the group "Acular®rectal capsules 0.14 g" - 5,09±0.12 minutes, respectively.
Therefore, dosage form systemic action "Acular®rectal capsules 0.14 g" provides comparable with the comparison drug effects on vascular permeability, which consists in increasing the stability of the walls of blood vessels.
Impact on hemorheological properties of blood
Assessing the impact of pharmaceutical compositions Acular®rectal capsules 0.14 g" on hemorheological properties of blood was performed according to the time change of the blood plasma coagulation in the coagulation test APTT (activated partial thromboplastin time) (Barkagan the legislative Assembly, Momot A. P. fundamentals of diagnosis of disorders of hemostasis. - M.: Novamed JSC, 1999. - 224 C.) and change the dynamic (absolute) viscosity of whole blood (Fedorov, H. W., Kotovshikov M. A., Bessmeltsev S. S. a rapid method of determining the viscosity of red blood cells // lab. case. - 1988. No. 2. - S. 29-32).
The obtained data are presented in the table in Fig.8.
As can be seen from the presented data, the compared drugs have a positive effect on hemorheological properties of blood and, improve its rheology, reducing the viscosity and coagulability. Therefore, the pharmaceutical composition Acular®rectal capsules 0.14 g" can be used as drugs based heparin (Niepan®"and so on), to reduce the risk of ischemic damage and the effects of venous congestion.
Thus, in the study of the pharmacological activity of the pharmaceutical compositions on the basis of the substance of Acular®in models of vascular pathology was shown to be expressed vasoprotective action mechanism which plays a leading role anticoagulant, antithrombotic and anti-inflammatory activity, reducing vascular permeability and increase the tone of their walls, as well as the improvement of the rheological parameters of blood. This makes the inventive tool in the form of hard and soft dosage forms for external use of systemic and topical action in the form of 1.5% hydrophilic gel and rectal capsules containing 1.9 grams of 7.5% hydrophilic gel (in terms of quantity of active substance 0.14 g/capsule), promising for use in phlebology for the prevention and treatment of chronic venous insufficiency.
1. The tool is based on sulfotyrosine of arabinogalactan in the form of potassium salt with vasoprotective action, the mechanism of which a leading rol who plays an anticoagulant,
antithrombotic and anti-inflammatory activity, reducing vascular permeability (antiexudative and antitransglutaminase activity) and increase the tone of their walls (cardio activity), as well as the improvement of the rheological parameters of blood containing hydrophilic gel, which as the hydrophilic base used inorganic polymer - colloidal silicon dioxide (Aerosil), glycerin and purified water, as well as preservative - methyl ester of para-oksibenzoynoy acid (methylparaben, nipagin) in the following ratio, wt.%:
|in the form of potassium salt||1,0-8,0|
|Purified water||To 100.0|
2. The use of funds under item 1 for the prevention and treatment of chronic venous insufficiency in need of the subject.
3. Means under item 1, characterized in that it is made in a form acceptable to the outer por the use of systemic and topical actions.
4. Means on p. 3, characterized in that it is made in solid dosage form in the form of rectal capsules containing 1.9 grams of 7.5% hydrophilic gel (in terms of quantity of active substance 0.14 g/capsule), applied 2-3 times a day.
5. Means on p. 3, characterized in that it is made in soft dosage form in the form of 1.5% hydrophilic gel, applied 2-3 times a day to the maximum of the applied dose.
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to medicine, particularly to pharmaceutical industry, and describes a dosage form of Clopidogrel presented in the form of a solid gelatine capsule. The dosage form contains Clopidogrel hydrogen sulphate, lactose anhydride, microcrystalline cellulose, sodium croscarmellose, colloidal silicon dioxide and magnesium stearate.
EFFECT: according to the invention, the dosage form of Clopidogrel contains a high amount of the active ingredient; it is prepared without the use of a wet granulation technique, and provides the more accurate dosage of the ingredients and the stability of the substances used.
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention relates to field of immunology and biotechnology. Claimed is monoclonal antibody or its functional fragment, where said antibody and fragment bind with activated protein C and inhibit anticoagulant activity, but do not bind and do not inhibit activation of inactivated protein C, where said antibody is obtained by immunisation of mammal by APC and screening of binding ability of said antibody with APC, but not with protein C. Also described is pharmaceutical composition for treating diseases associated with anticoagulation activity of APC, including said antibody in effective amount and pharmaceutically acceptable carrier. Claimed are: method of inhibiting anticoagulation activity of activated protein C in subject, method of inhibiting amidolytic activity of activated protein C in subject, method of treating subject, requiring blood coagulation; method of treating subject with haemophilia; method of modulating haemostasis in subject; as well as method of modulating thrombogenesis in subject, which include introduction of effective quality of said antibody to subject. In addition, described is method of treating subject with sepsis, including introduction of effective quality of said antibody and activated protein C.
EFFECT: invention makes it possible to obtain monoclonal antibody or its functional fragment, where said antibody and fragment bind with activated protein C and inhibit anticoagulation activity, but do not bind and do not inhibit activation of inactivated protein C.
17 cl, 11 dwg, 6 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: group of inventions refers to medicine. What is described is a system of the transdermal delivery of a drug containing an effective dose of an antithrombotic agent, such as tirofiban, or its pharmaceutically acceptable salt. A dose of the delivered drug is proportional to an applied plaster size and reaches 60-85% of thrombocyte inhibition. The system enables providing the individualised treatment of patients. There are presented methods of treating various disorders, when the thrombocyte inhibition is required.
EFFECT: transdermal delivery system can deliver the drug to the patient for the prolonged period of time.
25 cl, 12 ex
SUBSTANCE: invention refers to medicine, namely to surgery, and can be used for treating trophic ulcers and purulonecrotic involvements of lower extremities in diabetic patients. That requires a baseline therapy and a regional fibrinolytic therapy. Conducting the regional fibrinolytic therapy following applying a rubber bandage on the lower one-third of the shin is accompanied by administering Urokinase medac in a dose of 100 thousand units into the heel bone once a day within 5 days.
EFFECT: in the setting of reducing the total dosage of the preparation, the invention enables providing the high concentration of Urokinase medac in a pathological centre, improving microcirculation and metabolic processes in the involved tissues, accelerating the wound healing and reducing the length of hospital admission of the patients suffering from diabetic foot syndrome.
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to a pharmaceutical composition containing a thrombosis inhibitor. Active substances of the above inhibitor are Triflusal and clopidogrel bisulphate with Triflusal:clopidogrel bisulphate ratio of (100-650):(30-150), preferentially (1-20):1, more preferentially (3-6):1, and most preferentially 3:1 or 6:1. The composition is applied in treating cardiovascular and cerebrovasacular disorders.
EFFECT: inhibiting thrombosis and thrombocyte aggregation using the combination has been more effective, than using Triflusal and clopidogrel bisulphate individually; six-month monitoring has shown that the stability of the combined drug preparation of Triflusal and clopidogrel bisulphate is higher than that of the combined drug preparation of Triflusal or clopidogrel bisulphate.
20 cl, 2 dwg, 4 tbl
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to new compounds of formula IV, VIII-A and X, and to their pharmaceutical acceptable salts possessing the inhibitory activity on PI3-kinase (phosphoinositide-3-kinase). In compounds of formula IV and IX and Wd is specified in a group consisting of, , , and each of which can be substituted. In formula VIII-A, the group Wd represents the group or , wherein Ra is hydrogen, R11 is amino; in compound IV, Wa 2 represents CR5; Wa 3 represents CR6; Wa 4 represents N or CR7; in compound IX, Wa 1 and Wa 2 independently represent CR5, N or NR4, and Wa 4 independently represents CR7 or S, wherein no more than two neighbouring atoms in a ring represent atom or sulphur; Wb 5 represents N; B represents a grouping of formula II, as well as in case of compound IV, B means C1-C10alkyl, C3-C10cycloalkyl, C3-C10heterocycloalkyl having one to six ring heteroatoms specified in N, O and S; in case of compound IX, B also means C1-C10alkyl, C3-C10cycloalkyl or 6-merous heterocycloalkyl having nitrogen atom; Wc represents C6-C10aryl or 5-18-merous heteroaryl having one or more ring heteroatoms specified in N, O and S, or phenyl or 6-merous heteroaryl respectively is equal to an integer of 0, 1, 2, 3 or 4; X is absent or represents -(CH(R9))z-, respectively; z is equal to 1; Y is absent. The other radical values are specified in the patent claim.
EFFECT: compounds can be used for treating such diseases, as cancer, bone disorders, an inflammatory or immune disease, diseases of the nervous system, metabolic disorders, respiratory diseases, thrombosis or cardiac diseases mediated by PI3-kinase.
68 cl, 11 dwg, 7 tbl, 55 ex
SUBSTANCE: group of inventions refers to medicine, and concerns using tetrapeptide Pro-Gly-Pro-Val as an agent for preventing or treating lipid storage disease; a method for preventing or treating lipid storage disease involving the intranasal administration of a therapeutic agent containing tetrapeptide Pro-Gly-Pro-Val in an effective amount; to a pharmaceutical composition for preventing or treating lipid storage disease, containing peptide Pro-Gly-Pro-Val with the anticholesteremic and triglyceridemic action as an active substance, and an auxiliary substance as a preserving agent.
EFFECT: group of inventions provides the more effective prevention and treatment of lipid storage disease as compared to natural tripeptide Pro-Gly-Pro.
6 cl, 4 ex, 5 tbl
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to phenol derivatives of formula (1), wherein R1 represents C1-C6 alkyl group, C1-C6 alkynyl group, C1-C6 halogen alkyl group, C1-C6 alkyl sulphanyl group or a halogen atom, R2 represents a cyano group or a halogen atom, R3 represents a hydrogen atom, and X represents -S(=O)2. Besides, the invention refers to a drug preparation containing a compound of formula (I) as an active ingredient.
EFFECT: phenol derivatives of formula (1) characterised by the high urine concentration of the permanent compound, and possess the uricosuric action.
11 cl, 1 dwg, 2 tbl, 42 ex
SUBSTANCE: invention describes antisense compounds capable of reduction of level of factor 11 and methods for treatment or prevention of thromboembolic disorders with an individual who requires it. Examples of pathogenic compounds that can be subject to treatment by introduction of antisense compounds aimed at factor 11 are thrombosis, embolism and thrombembolia, such as deep venous thrombosis, pulmonary embolism, myocardial infraction and cerebral crisis. Antisense compounds aimed at factor 11 can be also used as prophylactic agents for elimination of a risk of development of thrombosis and embolism with individuals.
EFFECT: improving compound application efficiency.
57 cl, 169 tbl, 47 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention relates to novel compounds of general formula  or their pharmaceutically acceptable salts, which possess properties of an inhibitor of the JAK2 thyrokinase activity. In general formula radicals are selected from group (I) or (II). In group (I) X represents CH or N; R1 represents a halogen atom and R2 represents H, a halogen atom, CN, or is selected from the groups of formulas
or a group -ORP or 5-6-membered heteroaryl, containing 1-4 nitrogen atoms and optionally additionally containing an oxygen or sulphur atom or containing an oxygen atom as a heteroatom, optionally substituted; or (II) X represents -CRA; and RA represents a group of formula , RB represents (a) amino, optionally substituted with one or two groups, selected from the group, consisting of C1-6alkyl, C3-6cycloalkyl, (C3-6cycloalkyl)C1-6alkyl and C1-3alcoxyC1-3alkyl, (b) C1-3alcoxy, (c) hydroxy or (d) a 5-6-membered saturated cyclic amino group, which additionally can contain a heteroatom, selected from an oxygen atom; R1 represents a halogen atom and R2 represents H; R3 -R5 have values given above. Other values of the radicals are given in the invention formula.
EFFECT: compounds can be applied for the prevention or treatment of cancer, for instance hematologic cancer disease or a solid form of cancer, inflammatory disorder, for instance, rheumatoid arthritis, inflammatory intestinal disease, osteoporosis or multiple sclerosis and angiopathy, for instance, pulmonary hypertension, arteriosclerosis, aneurism or varicose veins.
14 cl, 19 tbl, 234 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: present invention refers to the pharmaceutical industry, namely to a composition possessing the analgesic and anti-inflammatory action (versions). A topical composition possessing the analgesic and anti-inflammatory action and containing chondroitin sulphate, phenyl trimethicone, stabilene 30, cetyl alcohol, cetyl palmitate, Carbopol, a wetting agent, triethanolamine, glucosamine hydrochloride, liposomes, beta-cyclodextrin, bitter orange flower oil, Lavandula angustifoiia oil, escin, betulin, hyaluronidase, ginger extract, harpagophytum extract, euxyl k727, demineralised water in certain proportions. The topical composition possessing the analgesic and anti-inflammatory action and containing chondroitin sulphate, phenyl trimethicone, stabilene 30, cetyl alcohol, cetyl palmitate, Carbopol, a wetting agent, triethanolamine, glucosamine hydrochloride, liposomes, beta-cyclodextrin, bitter orange flower oil, Lavandula angustifoiia oil, escin, betulin, hyaluronidase, ginger extract, harpagophytum extract, euxyl k727, demineralised water in certain proportions.
EFFECT: compositions possess the pronounced analgesic and anti-inflammatory effect; they are stable.
2 cl, 1 tbl, 6 ex
SUBSTANCE: group of inventions refers to agents for preventing and treating arthropathies containing a mixture of peptides H-Ala-Glu-Asp-OH, Lys-Glu-Asp and H-Lys-Glu-OH and a mixture of chondroitin and/or its salts, and/or glucosamines and/or its salts; methods for using them. The group of inventions provides a positive variation of clinical-biochemical dynamics. What is also provided is normalising the morphological structure of joint tissues, including a cytoarchitectonic characteristic of cartilaginous tissue with decreasing apoptotic chondrocyte count, especially at the final stages.
EFFECT: provided favourable effect on the metabolic processes in chondrocytes, activated synthetic processes and normalised biopolymer composition of the cartilage matrix An evident analgesic effect is manifested.
20 cl, 5 ex, 5 tbl
SUBSTANCE: what is described is an osteoplastic composition containing a mixture of hyaluronic acid, chondroitin sulphate and heparin in sodium chloride and an osteoconductive material presented by non-demineralised osseine or demineralised osseine in the following ratio of the ingredients, wt %: hyaluronic acid 0.1-4.0, chondroitin sulphate 0.1-4.0, heparin 0.1-0.5, non-demineralised osseine or demineralised osseine 25-94.0, sodium chloride 0.8-0.85, distilled water - the rest. According to the other version, the osteoplastic composition uses an osseous mineral ingredient as an osteoconductive material.
EFFECT: osteoplastic composition is presented in the form of gel or chips, and possesses the protective viscoelastic properties prolonging the osteoconductive and osteoinductive properties of the ingredients of the composition filling and keeping the bone defect volume by the fact that they are considered as the natural mechanical support components of the bone tissue.
4 cl, 3 dwg, 5 ex
SUBSTANCE: invention refers to using ultradisperse silver-containing systems as anti-inflammatory, anti-exudative and wound-healing agents. The ultradisperse silver-containing systems represent zero-valent silver metal nanocomposites at particle size 10-25 nm stabilised with arabinogalactine and its sulphated derivative. The invention also refers to an agent for wound and burn healing having anti-inflammatory, anti-exudative, wound-healing and antimicrobial activity, comprising said silver nanocomposites as a pharmacologically active substance and additionally containing carbomer, triethanolamine, glycerol or 1,2-propylene glycol and water. The agent is presented in the form of topical hydrophilic gel. The invention also refers to using the above agent for wound and burn healing in an individual in need thereof.
EFFECT: declared invention provides creating the hydrophilic gels of silver nanocomposites that are applicable for wound and burn healing.
3 cl, 8 dwg, 7 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to a recovered imidised biologically compatible polymer functionalised by an imide group. The above polymer is selected from the group consisting of polyethylene oxide, partially or completely hydrolysed by polyvinyl alcohol, polyvinylpyrrolidone, polyethyloxazoline, polyoxypropylene oxide block copolymers (poloxamers and meroxapol), polyethylene oxide and poloxamine copolymer, carboxymethyl cellulose and hydroxyalkylated cellulose, polypeptides, polysaccharides, carbohydrates, polysaccharose, hyaluronic acid, dextran, heparin sulphate, keratan sulphate, chondroitin sulphate, heparin, alginate, gelatin, collagen, albumin, ovalbumin, complex polyphosphoesters, polylactides, polyglycolides, polycaprolactones, polyamides, polyurethanes, polyesteramides, polyorthoesters, polydioxanones, polyacetals, polyketals, polycarbonates, polyorthocarbonates, polyphosphazenes, polyhydroxybutyrates, polyhydroxyvalerates, polyalkylene oxalates, polyalkylene succinates, polymaleic acids, polyamino acids, polyvinyl alcohol, polyvinylpyrrolidone, polyhydroxy cellulose, chitin, chitosan, and copolymers, ternary copolymers, or combinations or mixtures of the aforementioned materials. Also, the invention refers to a composition for a tissue adhesive, a medical device and a pharmaceutical composition.
EFFECT: invention represents additionally modified or functionalised imidised polymers.
9 cl, 2 ex, 20 dwg
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to a composition possessing analgesic, anti-inflammatory and locomotor function improving action. The composition contains 1-20 wt % of glucosamine sulphate, 1-10 wt % of chondroitin sulphate, 0.0001-10 wt % of methylsulphonylmethane, 0.01-5 wt % of L-proline, ascorbic acid, magnesium. The declared composition additionally contains zinc gluconate, citric acid, a sweetening agent, a flavour, a preserving agent and water.
EFFECT: composition is presented in the liquid form and possesses improved bioavailability and extended pharmacological action.
FIELD: medicine, pharmaceutics.
SUBSTANCE: group of inventions refers to medicine. A method for preparing a silver nanocomposite of semi-synthetic heparinoid - sulphated arabinogalactan (AGSO3H) in the form of the silver-containing system (AGSO3H +Ag°) of zero-valent metallic silver nanoclusters of particle size 10-15 nm (X-ray diffraction analysis) stabilised by sulphated arabinogalactan (AGSO3H) by the reaction of sulphated arabinogalactan in an aqueous medium for 30-60 minutes at temperature 20°C and silver oxide (Ag2O) accompanied by the product recovery. The silver content evaluated by atomic absorption analysis makes 8%.
EFFECT: group of inventions provides maintaining the structural organisation of silver nanocomposite and sulphated arabinogalactan (nanostructuredness of the biopolymer macromolecule system - particle oversize sinter size makes 200-600 nm), as well as water-solubility, biocompatibility, receptor-mediated transmembrane and immunomodulatory properties in relation or a living cell, antithrombotic activity, prolonged biological action, non-toxicity, synergism of antibacterial activity of silver.
2 cl, 3 dwg, 3 ex
SUBSTANCE: method involves preparation of material for enzymatic hydrolysis. Alkaline hydrolysis is carried out with proteolytic enzyme preparations with neutralisation of the obtained solution to pH=7. A salt is added to the obtained enzymatic hydrolysate to a value of not less than 0.1 mol/l. Successive ultrafiltration is carried out, first on a membrane with maximum retention of 50 kD with separation of high-molecular weight impurities, and then on a membrane with maximum retention of 5 kD with separation of low-molecular weight substances. The chondroitin sulphate solution retained at the membrane is washed on the same membrane with distilled water until complete removal of salts. Final washing with distilled water is carried out on a membrane with maxim retention of 50 kD.
EFFECT: invention enables to obtain a chondroitin sulphate preparation with weight ratio of the basic substance.
SUBSTANCE: invention relates to medicine, namely to traumatology and orthopedics and can be applied in complex treatment of posttraumatic, dystrophic, neurological, degenerative and scar-adhesion processes in joint area, deforming osteoarthrosis of large joints and osteochondrosis. Method of treatment includes introduction of drug mixture by ultraphonoresis for 5 minutes on a field, daily. To obtain said mixture applied are ointment "Indomethacyne", "Chondroxyde", gel "Essaven" in proportion 1:1:1, in dose, expressed in form of 3-10 cm long stripe of each ointment. These components are mixed with 50 mg of medication Karipasim, dissolved in 5 ml of physiological solution and 5 ml 2% solution of Trental. Treatment course includes 15-20 procedures.
EFFECT: method ensures fast achievement of antihydrophic and analgetic effect, reduction of total terms of patients' rehabilitation, increase of disease remission periods.
3 ex, 1 tbl, 4 dwg
FIELD: medicine, pharmaceutics.
SUBSTANCE: declared formulation of the combined pharmaceutical chondroprotective drug presented in a solid dosage form contains as active substances sodium chondroitin sulphate and glucosamine sulphate sodium chloride, a binding agent, antifriction substances, an aerating agent, an excipient; the composition is film-coated. The ingredients are taken in proportions, wt %: sodium chondroitin sulphate - 10-35, glucosamine sulphate sodium chloride - 15-45, the binding agent (low-molecular povidone and potato starch) - 3.1-11, the antifriction substances (aerosil, calcium stearate and talc) - 2.7-5, the aerating agent (kollidon) - 1.7-10, the excipient (ludipress) - 10-44.2. The coating ingredients are taken in proportions, wt %: film-forming material (hypromellose) - 1-2, a plasticiser (macrogol and propylene glycol) - 1-1.8, a pigment (titanium dioxide) - 0.5-1.
EFFECT: auxiliary ingredients enables high release rate of a tabletted mass, complete drug absorption and shelf-life stability of all measures.
3 dwg, 3 ex
FIELD: medicine, pharmacy.
SUBSTANCE: invention relates to the solid medicinal formulation comprising chondroitin sulfate. The proposed medicinal formulation comprises 250 mg of chondroitin sulfate as an active component, filling agent, binding agent, antifriction substances and can comprise a solubilizing agent additionally. Pharmaceutical composition is made as a tablet. Invention provides development of the preparation for oral administration with the less amount of active substance and with indices satisfying requirements of the State Pharmacopoeia.
EFFECT: improved and valuable properties of formulation.
8 cl, 16 tbl, 39 ex