Therapeutical composition for local treatment of inflammatory lesions of joints and muscles
FIELD: pharmaceutical industry.
SUBSTANCE: invention relates to creating drugs for treatment and prevention of inflammatory lesions of support-motor apparatus (myosites, arthrites, tendovaginites, etc.). Therapeutical composition according to invention contains, wt %: essential oil of silver fir 1.0-2.0, camphor 4.0-5.0, oil extract of red capsicum 0.06-0.08, biologically active component isolated from medicinal leech or its parts 0.01-6.5, Ibuprofen 60.0-65.0, ethoxydiglycol 3.0-5.0, Emulgin B2 0.4-0.6, Carbomer 0.5-0.8, triethanolamine 0.6-0.8, methylparben 0.2-0.3, propylparben 0.02-0.03, butyloxyanisol 0.08-0.1, Bronopol 0.04-0.05, and water the rest. Composition activates metabolic processes in skin and subcutaneous fat layer, normalizes blood supply, eliminates stagnant phenomena, accelerates getting active therapeutical substances into membranes of biological cells, which results in rapid achievement of stable therapeutical effect in what concerns elimination of inflammatory process in joints and muscles.
EFFECT: increased therapeutical efficiency.
The invention relates to medicine and can be used for the treatment and prevention of inflammatory diseases of the musculoskeletal system (myositis, arthritis, tendovaginitis and so on).
Known medicinal composition for the local treatment of inflammatory diseases of the joints and muscles "Efkamon (Mashkovsky PPM Drugs: a Handbook for physicians. - M.: Medicine, 1993. - C - S.401), which includes ingredients: camphor, menthol, mustard, eucalyptus, clove essential oil, methyl salicylate, tincture of capsicum, cinnamic alcohol, thymol, chloral hydrate, spermaceti, vaseline, paraffin.
A disadvantage of known composition is a short-acting anesthesia, sharp odor, scarce and expensive spermaceti, allergic reactions.
Known medicinal composition for the local treatment of inflammatory diseases of the joints and muscles (chosen as a prototype) in the form of ointment called "Karagai" (Ed. St. USSR №1794454, IPC5A 61 K 35/78, 1993, bull. No. 6), which includes, wt.%
|oil extract of red capsicum||10-12|
|alcoholic extract of the resin of the Tien Shan spruce||6-7|
|COP the l||12-15|
A disadvantage of known composition of the prototype is the lack of anti-inflammatory activity. The reason for this is the lack of known composition in a strong anti-inflammatory properties. Known composition also does not provide deep penetration of active agents in the biological cell membrane. Its action is limited irritating, distracting and weak antiseptic effect.
The basis of the invention is the task in medicinal composition for the local treatment of inflammatory diseases of joints and muscles by introducing its new ingredients and change their quantitative ratio to ensure the activation of metabolic processes in the skin and subcutaneous fat layer, normalize blood circulation, eliminate stagnation in the areas of inflammation, accelerate the penetration of active therapeutic substances in the membrane of biological cells, which contributes to the rapid achievement of a stable treatment effect in the elimination of the inflammatory process in the joints and muscles. The effectiveness of treatment in comparison with the prototype will increase from 43% to 81%.
The problem is solved in that the known is th medicinal composition for the local treatment of inflammatory diseases of the joints and muscles, which contains the product of coniferous trees, camphor, oil extract of red pepper, as a product of coniferous trees introduced essential oil fir, and additionally introduced biologically active component isolated from the medicinal leech or its parts (TANK of leeches), ibuprofen, etokxidiglicol, emulgin B2, carbomer, triethanolamine, methylparaben, propylparaben, butylacetamide, bronopol and water in a ratio of components, wt.%:
|essential oil fir||1,0-2,0|
|oil extract of red capsicum||0,06-0,08|
|TANK of leeches||of 0.01 to 6.5|
Between the set of features of the invention and achievable technical R is a result of there is a causal relationship.
Known medicinal composition-the prototype for the local treatment of inflammatory diseases of the joints and muscles includes oil extract of red pepper, which is irritating and distracting action, camphor and menthol - irritating and weak antiseptic, alcoholic extract of the resin of the Tien Shan spruce prolong irritating pepper camphor and menthol, petrolatum, lanolin, paraffin - as ointment bases (Mashkovsky PPM Drugs: a Handbook for physicians. - M.: Medicine, 1993. - C - 731 S., C - 685 C.). Such a composition is known of the composition of the prototype can not ensure the elimination of serious inflammatory process in the joints and muscle pain, edema, and hyperemia. Therefore, a disadvantage of known composition is a low therapeutic efficacy.
The inventive tool shows high anti-inflammatory effect due to the chosen qualitative composition. Optionally, the inventive composition has analgesic, immunomodulatory, anti-stress and normalizing metabolism properties. One of the major therapeutically active components of the proposed drug is ibuprofen is a nonsteroidal anti-inflammatory, analgesic, antipyretic (Mashkovsky PPM Drugs: a Handbook for physicians. - M.: Medicine, 1993. - C. - C.214). Ibuprofen exerts a stimulating effect on the synthesis of endogenous interferon and its ability to perform immunomodulatory effects and to improve the nonspecific resistance of the organism (Andreikin M.A., Smyslova AV, Rudchik A.S. // Klin. medicine in 1991. No. 4. - P.77-81).
As research has shown, because of the low therapeutic efficacy of known drug composition of the prototype for the local treatment of joints and muscles is delayed the ability of the existing framework in the composition of the known means to penetrate biological tissues and cell membranes. Included in the compositions stated, TANK leeches enhances the effect of other ingredients. The mechanism of action of this component on the cell membrane has not yet been studied thoroughly. But the study authors showed that the TANK leeches increases the permeability of the skin, promotes deeper penetration into the skin structure of all components.
Essential oil fir manifests distracting irritant effect, increases the permeability of the skin due to its ability to dissolve in lipids in the subcutaneous layer. It is also known that the essential oil of fir improves blood circulation and lymph circulation, balances the processes occurring in the tissues of the body, increasing its resistance (Smells health / edited Whitaker nkova. - M., 1998. - P.17). In addition, the essential oil of fir less scarce and more cheap compared to alcoholic extract of the resin of the Tien Shan spruce. The paprika extract exhibits by local application of warming and distracting effect. Camphor is annoying and weak antiseptic (Mashkovsky PPM Drugs: a Handbook for physicians. - M.: Medicine, 1993. - Part 1. - S, 404).
Unlike the prototype of the proposed composition has not ointment base, or gel. therapeutic effect of the ointment is limited by the penetration of active therapeutic substances only in the fat part of the subcutaneous layer. But the main fluid of the human body is water - inorganic substance in which fats do not dissolve. In the gel are as fat-soluble active substances (oil extract of red pepper, essential oils of fir, camphor), and soluble (ibuprofen). They actively penetrate into the lipid and the water portion of the subcutaneous cells and therefore therapeutically act faster than when using known compositions.
The claimed composition was significantly more effective prototype. Probably, the reason for this well-chosen qualitative composition. The qualitative composition of the inventive pharmaceutical composition is chosen empirically. In it components, enhancing the action is s each other, show complex therapeutic effects: pain, inflammation and swelling, local europenizarii, improving blood circulation, increasing the resistance of the tissues and the whole organism. In addition, to accelerate the "transportation" of the active substances to the damaged biological tissue in the inventive composition is administered TANK leeches. The absence of any ingredient in the composition is not possible to obtain the necessary technical result (gain efficiency by 38%)as active ingredients in the composition are mutually potentiate the action of each other.
An important feature of the invention is the proportion of the ingredients in the claimed composition. Specified in the compounding ratio of the components is optimal. Any deviation from it will not have the desired therapeutic effect.
As preservatives in the composition of the gel composition introduced technological additives: methylparaben, propylparaben and bronopol. With the introduction of these components in amounts less than specified in the recipe, the bottom border is not provided microbiological stability of the gel, while exceeding the upper boundary of the quantities of these components are created redundant effect.
Absorption the basis of the proposed gel pharmaceutical composition for the local treatment of vos is Alitalia diseases of joints and muscles create water, etokxidiglicol, emulgin B2, carbomer, triethanolamine. Research has proved that the introduction of these components in optimal quantities according to the recipe provides the necessary consistency of the gel and its dissolving ability.
As an antioxidant in the formulation of the gel entered butylacetamide. It prevents oxidation of the components of the oxygen in the air.
TANK leeches secrete as follows.
Medical leeches, or part thereof (term starvation used leeches is 4-6 months) weight 1.5 g placed in a flat plastic bag up to 2 cm, and quickly frozen in a domestic freezer at a temperature of -20 to -25°C. Not less than 5 days frozen leeches are removed from the cooling chamber and lyophilizer (dried in a vacuum). The dal prepare a water extract of the dried raw material. For this lyophilized leeches pounded into powder, the powder is placed in a test tube, add the same volume of distilled water, the mixture shaken and placed in a laboratory centrifuge. Centrifuged the mixture for 20 minutes at a rotation speed of 2000 rpm./minutes Gathered above the precipitate, the solution is drained from the tube and filtered through filter paper. Received the TANK leeches used for preparation of the inventive pharmaceutical composition for the local treatment is Oia inflammatory diseases of joints and muscles.
There were the laboratory, experimental and clinical trials obtained gel pharmaceutical composition.
Laboratory research was to study odorimetric, physico-chemical and sanitary-hygienic properties of the resulting gel.
Laboratory tests showed that the gel has good organoleptic characteristics: appearance opal gel-like mass that is convenient for application to the skin texture, pleasant pine scent.
Experimental studies of the funds held in three groups (10 animals each) of adult Guinea pigs. In the first and second group of Guinea pigs in experiments established that the application of the funds were applied for 30 days did not irritating and allergenic effects on the skin of Guinea pigs.
In the third group of Guinea pigs did not show any effects of subacute toxic effects of the tool on the condition of the animals. Morphological and histological studies of the skin and liver of experimental animals showed the absence of any toxic changes.
In table. 1 shows the 12 examples of the composition of pharmaceutical compositions for the local treatment of inflammatory diseases of the joints and muscles: I-III examples of known composition tools-prototype n the ointment base, IV-VI examples of the quantitative composition of the inventive gel pharmaceutical composition, VII-IX examples of experimental composition No. 1, the quantitative proportions of which is beyond the scope of the claimed formulation, and X-XII examples of experimental composition No. 2. In each of the examples, prototype No. 2 is missing one of the active ingredients: the first is the essential oil of fir, the second TANK of leeches, in the third - ibuprofen. The amount of the other ingredients of all variants prototype No. 2 corresponds to example V of the claimed composition. In this same table shows the results of clinical studies of the above-mentioned compositions.
Table 2 shows examples XIII and V for evidence of a synergistic effect. Each of the 13 variants of the composition was tested in 7 patients. Only the study involved 91 volunteer. This is sick (miners) aged 20 to 57 years, with prescription of inflammatory diseases of the joints and muscles from 1 month to 5 years. Inflammatory changes in the joints collagenase Genesis had 52 experimental patients (rheumatoid arthritis in 26 people, gouty arthritis - 13, spondylitis - 13), 39 people had inflammatory changes of the muscular-ligamentous apparatus (nagnagnag character: rheumatic myositis in 13 persons, rheumatic myalgia - 13, sprain injury in 13). Each of hap included 7 subjects patients of these, 2 patients with rheumatoid arthritis, 1 with gouty arthritis, 1 with spondylitis, 1 - with rheumatic myositis, 1 - with rheumatic myalgia and 1 - with sprains. Test substance was applied exactly on the affected area 2-3 times a day. Studied local anesthetic, anti-inflammatory, antipyretic therapeutic effect on the joints and muscles, ligaments, and also the rate of recovery of function. The treatment was performed until complete disappearance of external signs (redness, swelling) and symptoms (pain, feeling of heat) disease.
Improved the status of only 9 patients out of 21 (43%), which was treated by known means according to the prototype (see table 1 examples I-III): 2 patients with rheumatic myositis, 1 - with rheumatic myalgia, 3 - with sprains and 3 patients with gouty arthritis decreased pain and swelling of tissue around the sore spot. Moreover, the clinical improvement of the patients in the treatment of known composition were observed at 12-14 days.
When using the claimed compositions clinical improvement was noted after 4-8 days. After 20 days of treatment claimed by the tool in 17 of 21 (81%) patients (see table 1 examples IV-VI), there was significant improvement in the health of joints and muscular-ligamentous apparatus: 4 patients with rheumatoid arthritis have decreased significantly over the first syndrome. Another 13 patients in this group pain disappeared: 3 patients with gouty arthritis, 2 with spondylitis, 2 with rheumatic myositis, 3 with myalgia and 3 sprains. All patients in this group had disappeared sensation of heat, redness and swelling of the tissues around the joints and muscles. 4 (of 21) patients of this group pain syndrome preserved: 2 with rheumatoid arthritis, 1 with spondylitis and 1 with myositis.
The effectiveness of options for an experienced composition No. 1, where the quantitative composition is outside the claimed formulation of the gel composition does not exceed a better option ointment composition prototype - 57% (see table 1 examples VII-IX).
The qualitative composition of the claimed composition is chosen empirically. The absence of one of the active ingredients (for example, essential oils of fir, a TANK of leeches, ibuprofen) in its structure does not allow to obtain the necessary technical result, because the active ingredients in the composition are mutually potentiate the action of each other. For comparison: the improvement observed in 29-57% of patients who were treated with application of experimental composition No. 2 (table 1, "Experienced No. 2, examples X-XII) and 71-85,7% of patients who were treated with the use of the claimed composition (table 1, "Declare", examples IV-VI).
As you know, among Akti the different ingredients of the inventive compositions TANK leech has antithrombotic and thrombolytic effect (Hirudotherapy and hirudotherapy. Edited by Nikonov G.I. - M., 1996. - P.30). Essential oil fir improves circulation of blood and lymph, paprika extract exhibits by local application of warming and distracting action, camphor has irritant and a weak antiseptic. And only ibuprofen has analgesic properties (Mashkovsky PPM Drugs: a Handbook for physicians. - M.: Medicine, 1993. - C - S, 214, 404). Therefore, an experienced composition No. 3 for assurance synergistic (analgesic) effect ingredients of the claimed composition (table 2, example XIII) prepared with the presence of ibuprofen and the absence of other active ingredients: essential oils of fir, camphor, pepper extract, a TANK of leeches. For comparison of analgesic effect of the claimed composition in table 2 introduced the example of V. Quantitative content present in the composition of example XIII ingredients are the same as in example V. the Analgesic effect of both compounds was examined through a survey and examination of patients who were not informed about the composition of the used devices. As depicted in table 2 the results of the research, the claimed composition consisting of known ingredients, provides a synergistic effect, the possibility of achieving which clearly does not follow from the prior art: indicator percentage of patients with reduced is by giving pain syndrome (85.7 percent (6 of 7), example V) after treatment with the inventive tool higher than the percentage of patients with reduction of pain (43% (3 of 7), example XIII) after the treatment means based on one of ibuprofen. In addition, the timing of the clinical manifestations of pain 4-8 days in the treatment of the inventive composition (example V) is shorter than the composition of example XIII is 12-14 days (example XIII).
Ensuring synergy (analgesic) effect ingredients of the inventive composition
|Track||Qualitative composition||The quantitative content of ingredients, wt.%. Examples XIII, V (n=7)||The duration of treatment, days (n)||Decrease in pain. Examples XIII, V (n=7)|
|The % of patients||the timing of the clinical manifestations, days|
|Experienced №3||essential oil fir||0||1,5||20 (21)||43 (3)||85,7 (6)||12-14||4-8|
|TANK of leeches||0||3,0|
The results of studies on the effectiveness of different quantitative compositions of the claimed compositions are given in table. 1, show that the most effective is the ratio, wt.%:
|essential oil fir||1,0-2,0|
|oil extract of red capsicum||0,06-0,08|
|TANK of leeches||of 0.01 to 6.5|
We offer gel pharmaceutical composition for the local treatment of inflammatory diseases of the joints and muscles, improves microcirculation in the affected joints and muscles, reduces pain, sensation of heat, flushing, swelling of the tissues around the joints and muscles through stimulation of the immune system increases the efficiency of the results of rehabilitation after operations and injuries of musculoskeletal system.
The inventive gel pharmaceutical composition for the local treatment of inflammatory diseases of the joints and muscles prepared as follows. In the melting pot, placed in a steam bath, a load etokxidiglicol and heated to 70°C. Then, thereto was added soluble ingredients: methylparaben, propylparaben, butylacetamide and stirred until completely homogeneous mass with the help of a mixer. In the digester pour n is necessary in the recipe amount of demineralized water, download carbomer and leave it for 20-30 minutes for the swelling. Include low-speed mixer and add the triethanolamine. In the resulting gel weight enter emulgin B2. Stirred until complete dissolution of the components and pour in a solution of the melting pot. Upon reaching the homogeneity of the gel include high-speed stirrer (disperser) for 5-10 minutes. At the end of the process enter the TANK from leeches and bronopol and continuing the stirring, to achieve a homogeneous distribution. Then the gel is pumped into the intermediate vessel for curing for 2 days, then Packed in individual containers.
For the preparation of the claimed pharmaceutical compositions preparations were used: "Ibuprofen" production company "Hubey Zenith Pharmaceutical. Ltd", "essential Oil fir" - JSC "Priluki aromatic plant", "Extract of Cayenne pepper thick" - JSC "Luniform", "Camphor DAB8, powder synthetic" company "Hinton", etokxidiglicol in the form of the drug "Ethyldiglycol" company "Combi Cmb Lager und Lodistik", emulgin B2 in the form of "Drug OS-20 m And" produced by Ivano-Frankivsk firm "Farbe", carbomer in the form of "Carbopol Ultrez 10" firm "BF Goodrich", chemical triethanolamine production of JSC "Synthez"methylparaben in the form of the drug "Methylparaben" - "Bio-Pharm-Chemie GmbH", propylparaben as reagent "Alcelaphine p-hydroxybenzoic acid" company "Sharon Laboratores Ltd", butylacetamide as reagent "Butylacetamide - antioxidant for medical purposes, clean - Shostka chemical plant, bronopol production company "Sharon Laboratories Ltd.". Water used distilled.
Three specific example of a composition which is claimed, and ten experimental variants are shown in tables 1 and 2.
Medicinal composition for the local treatment of inflammatory diseases of the joints and muscles, containing the product of coniferous trees, camphor, oil extract of red pepper, characterized in that as a product of coniferous trees in its composition the essential oil of fir, and additionally, it contains biologically active component isolated from the medicinal leech or its parts, ibuprofen, etokxidiglicol, emulgin B2, carbomer, triethanolamine, methylparaben, propylparaben, butylacetamide, bronopol and water in a ratio of components, wt.%:
|Essential oil fir||1,0-2,0|
|Oil extract red|
|Biologically active component|
|isolated from the medicinal leech|
|or its parts||of 0.01 to 6.5|
SUBSTANCE: method involves administering suspension containing up to 500 thousand of fibroblasts introduced on 50 to 400 mcm large microspheres as injections into connective tissue.
EFFECT: enhanced effectiveness in treating for periodontitis, age-specific skin defects, fistulas, wounds and ureteral reflux.
FIELD: veterinary science.
SUBSTANCE: one should carry out daily laser impact upon affected area and additionally once /2 d apply a compress of medicinal preparation containing the suspension of 25%-hydrocortisone, phenylbutazone, "Arnica" liniment and dimethylsulfoxide solution at the following ratio of components, weight%: 25%-hydrocortisone suspension 1.0; phenylbutazone suspension 0.65; "Arnica" liniment suspension 50.0, dimethylsulfoxide solution - the rest. Moreover, expenses of medicinal remedy should be fulfilled at 100 ml/200 sq. cm, as for laser impact, it should be carried out with low-intensity infrared laser radiation at impulses frequency being 512 Hz, power of 16 W and exposure time being 6 min. The innovation suggested enables to remove post-traumatic edema and inflammation, stimulates regenerative processes in inflammatory focus at the shortest terms.
EFFECT: higher efficiency of therapy.
FIELD: organic chemistry, medicine, pharmacy.
SUBSTANCE: invention describes derivatives of N-heterocyclic compounds of the formula: , wherein n and m mean independently a whole number from 1 to 4; A means -C(O)OR1 or -C(O)N(R1)R2; W means -CH; R1 means hydrogen atom or (C1-C8)-alkyl; R means hydrogen atom, (C1-C8)-alkyl, heterocyclyl-(C1-C4)-alkyl chosen from the group comprising benzodioxolyl-, benzodioxanyl- or dihydrobenzofuranylalkyl or phenyl-(C1-C4)-alkyl substituted possibly with alkoxy-group; R4 means cyano-group or heterocyclyl chosen from the group comprising pyridinyl, morpholinyl, benzodioxolyl or benzodioxanyl-radical if m = 1; if m means from 2 to 4 then R4 can mean additionally hydroxy-group, -NR1R2 wherein R1 and R2 mean independently hydrogen atom, (C1-C8)-alkyl or benzyl-radical, -N(R1)-C(O)-R1, -N(R1)-C(O)-OR1, -N(R1)-S(O)t-R1 wherein R1 means hydrogen atom or (C1-C8)-alkyl, -N(R1)-C(O)-N(R1)2 wherein R1 means hydrogen atom; R5 means (C1-C8)-alkyl; t = 2, and their stereoisomers and pharmaceutically acceptable salts, pharmaceutical composition based on thereof and a method for treatment of diseases, in particular, rheumatic arthritis.
EFFECT: valuable medicinal properties of compounds and composition.
SUBSTANCE: method involves introducing oxygen gas is introduced into knee joint cavity on the background of traditional complex therapy at a dose of 40-150 ml in progressive mode with 3-4 days long pauses in a course of 5-6 procedures.
EFFECT: enhanced effectiveness in rapid cicatrix tissue involution; increased movement amplitude.
FIELD: pharmaceutical industry, in particular agent for treatment of joint diseases in form of injections.
SUBSTANCE: claimed agent contains glucoseamine salt, preservative, non-ionic surfactant, in particular oleic acid and polyoxyethylated sorbitan monoether, and water.
EFFECT: agent for treatment of joint diseases of improved effectiveness combining chondroprotevtive action with high pharmacokinetic properties and biological availability.
3 cl, 3 tbl, 4 ex
SUBSTANCE: remedy has saccharides like chondroitin sulfate (0.5-20.0% by mass) and salt of glycosamine (1.0-25.0% by mass), preservative (0.1-2.0% by mass), nonionogenic substance like monoester of oleic acid and polyoxyethylized sorbitan (1.0-5.0% by mass), and water (the rest).
EFFECT: increased active substances bioavailability and diffusion rate into articulation zone.
3 cl, 3 tbl
SUBSTANCE: method involves carrying out Indomethacin and Chondroxid ointments phonophoresis with enzymatic agent of Caripazyme. Indomethacin and Chondroxid are mixed in 1:1 proportion and Caripazyme is added in the amount of 50 mg dissolved in 5 ml of physiologic saline.
EFFECT: improved synergetic interaction of drug and physical factor.
4 dwg, 1 tbl
SUBSTANCE: method involves introducing solutions into articulation to inhibit cartilage destruction. The solutions contain: (a) therapeutically effective amount of anabolic chondroprotective agent selected from a group composed of interleukine antagonists stimulating anabolic processes in cartilage, members of superfamily transforming growth β-factor including TGF-β agonists and agonists of morphogenous bone proteins stimulating anabolic processes in cartilage, insulin-like fibroblast growth factors stimulating anabolic processes in cartilage; (b) therapeutically effective amount of a cartilage catabolism inhibitor selected from a group composed of antagonists of interleukine-1-receptors, antagonists of TGF-α-receptors, specific cyclo-oxygenase-2 inhibitors, nitrogen oxide synthase inhibitors, nuclear kB factor inhibitors, matrix metalloproteinase inhibitors, cell adhesion molecules including integrin agonists and integrin antagonists, anti-chemotaxis agents, intracellular signal transmission inhibitors including protein kinase C inhibitors and tyrosine protein kinase inhibitors, intracellular (protein-tyrosine)-phosphatases and SH2-domain inhibitors inhibiting cartilage catabolism. The solution is locally supplied.
EFFECT: stimulated integration and modulation of anti-inflammatory synoviocyte and chondrocyte responses.
54 cl, 9 dwg, 30 tbl
FIELD: medicine, pharmacy.
SUBSTANCE: invention relates to preparations for external using in treatment of joint diseases. The proposed agent comprises a saccharide - glucosamine salt and dimethylsulfoxide incorporated into an acceptable ointment base. Invention provides enhancing effectiveness of agent due to using low-molecular saccharides that results to the elevating diffusion delivery rate of active substance to the join zone.
EFFECT: improved and valuable properties of agent.
2 cl, 5 ex
FIELD: organic chemistry, medicine, pharmacy.
SUBSTANCE: invention relates to derivative of triazaspiro[5.5]undecane of the formula (I): wherein R1 means compound of the formula (1): or (2): wherein G represents a bond, (C1-C4)-alkylene, (C2-C4)-alkenylene or -CO-; ring A represents: (1) C5-10-membered mono- or bicarbocyclic ring or (2) 5-10-membered mono- or bicyclic heterocycle comprising 1-2 nitrogen atoms and/or 1-2 oxygen atoms; substitute R6 means the following values: (1) (C1-C4)-alkyl, (2) halogen atom, (3) nitrile group, (4) trifluoromethyl group and others; R2 represents: (1) (C1-C4)-alkyl, (2) (C2-C4)alkynyl or (3) (C1-C4)-alkyl substituted with a substitute represented in claim 1 of the invention claim; each R3 and R4 represents independently: (1) hydrogen atom, (2) (C1-C4)-alkyl or (3) (C1-C4)-alkyl substituted with 1-2 substituted taken among: (a) Cyc 2 and (b) hydroxy-group (wherein Cyc 2 represents (1) C5-6-membered monocarbocyclic ring or (2) 5-6-membered monocyclic heterocycle comprising 1-2 nitrogen atoms and/or one oxygen atom), or R3 and R4 form in common group of the formula: wherein R26 represents (C1-C4)-alkyl or Cyc 2; R5 represents hydrogen atom or (C1-C4)-alkyl, its quaternary ammonium salt, its N-oxide or its nontoxic salt. Also, invention relates to pharmaceutical composition inhibiting HIV, regulator of chemokine/chemokine receptor and agent used in treatment and prophylaxis of some diseases, such as inflammatory diseases, asthma, atopic dermatitis, nettle rash, allergic diseases, nephritis, hepatitis, arthritis and other diseases that comprise as an active component above described compound of the formula (I) or its quaternary ammonium salt, its N-oxide or its nontoxic salt. Also, invention relates to (3R)-1-butyl-2,5-dioxo-3-((1R)-1-hydroxy-1-cyclohexylmethyl)-9-(4-(4-carboxyphenyloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane or its pharmaceutically acceptable salt and pharmaceutical composition based on thereof, and to (3R)-1-butyl-2,5-dioxo-3-((1R)-1-hydroxy-1-cyclohexylmethyl)-9-(4-(4-carboxyphenyloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane hydrochloride and pharmaceutical composition based on thereof.
EFFECT: valuable medicinal properties of derivative and composition.
16 cl, 32 ex
FIELD: organic chemistry, biochemistry, medicine, pharmacy.
SUBSTANCE: invention relates to new derivatives of pyridopyrimidines of the formula (I): or (II): wherein Z means nitrogen atom (N) or -CH; W means -NR2; X1 means oxygen atom (O), -NR4 (wherein R4 means hydrogen atom or alkyl), sulfur atom (S) or -CR5R6 (wherein R5 and R6 mean hydrogen atom); X2 means oxygen atom (O); Ar1 means unsubstituted or substituted phenyl; R2 means hydrogen atom, alkyl or acyl; R1 means hydrogen atom, alkyl, halide alkyl and others; R3 means alkyl; cycloalkyl and others; R8 and R9 mean hydrogen atom, alkylsulfonyl and others, and to their pharmaceutically acceptable salts, and to intermediate compounds that are used for preparing compounds of the formula (I) and (II). Indicated compounds show inhibitory activity with respect to activity of p38 kinase and can be used in preparing a medicine agent for treatment of p38-mediated disturbances.
EFFECT: improved preparing methods, valuable medicinal properties of compounds and composition.
38 cl, 3 tbl, 116 ex
FIELD: medicine, rheumatology.
SUBSTANCE: the present innovation deals with treating rheumatoid and autoimmune osteoporosis-complicated arthritis. For this purpose one should perform intra-articular introduction of salmon calcitonin preparation named "Myacalcik" at its single dosage of 200 IU once weekly at total course of 4 injections once annually. The present innovation provides optimization of dosage: increased single intra-articular dosage and decreased multiplicity of preparation introduction and total course duration.
EFFECT: higher efficiency of therapy.
1 cl, 1 ex, 1 tbl
FIELD: pharmaceutical industry and cosmetics.
SUBSTANCE: composition contains, wt %: biologically active component isolated from medicinal leech or its parts 0.01-6.0, menthol 0.15-0.25, aqueous-alcoholic extract of horse-chestnut fruitage 8-10, camphor 0.15-0.30, ethoxydiglycol 3-5, polyethyleneglycol 1500, 0.8-1.2, emulgin B2, 0.8-1,2, Carbomer 0.6-0.8, triethanolamine 0.6-0.8, methylparben 0.25-0.35, Bronopol 0.04-0.06, butyloxyanisol 0.06-0.08, and water to 100%. Composition is made in the form of gel and provides antithrombic and analeptic effects on skin and hypodermic tissues, enhances antiinflammatory action, favors deep penetration of active components through skin, strengthens venous vessel walls, improves microcirculation of blood, and accelerated restoration of vascular wall tone.
EFFECT: expanded therapeutical possibilities.
2 cl, 2 tbl
FIELD: pharmaceutical chemistry.
SUBSTANCE: agent contains active components foridonum (3.00-6.00%) and isosorbide dinitrate (3.00-6.00%) with pharmaceutically acceptable gel base. The latter is composed of thickener, non-aqueous hydrophilic solvents, hydrophobic solvents, preservative, neutralization agent, emulsifier, and purified water.
EFFECT: increased bioavailability of active components and reduced or suppressed negative side effects such as locally irritating effects.
9 cl, 3 tbl, 14 ex
FIELD: medicine, pharmaceutical industry, pharmacy.
SUBSTANCE: invention relates to an anti-inflammatory ointment with hypolipidemic effect. Proposed ointment comprises ephthylline-base for ointment, a statin wherein lescol (fluvastatin) is used as statin, and ephthylline comprises 40% of ephthiderm. Invention provides enhancing the curative effect and hypolipidemic effect and effects on enzymatic systems of biological membranes that results to prolongation of curative effect of ointment.
EFFECT: valuable medicinal properties of ointment.
3 cl, 2 tbl
FIELD: cosmetology, esthetic surgery, applied biopharmacology.
SUBSTANCE: invention relates to medicative and cosmetic agents, and uses of biologically active substances based on natural biological complexes. Claimed method includes application of Mirralgin balm having analgesic, anti-inflammation and resolving action, Reventon balm, having vessel restorative action, for edema reducing and microcirculation improving. In process of blepharoplastic eye boundary bandage microemulsion having recovery and animative action on eaves skin is applied, and in process of facelifting cream mask having bactericide, vessel restorative and recovering action, and enhancing of local immunity is applied. Mirralgin balm and Reventon balm treatment is carried out sequentially or alternatively. In another embodiment after skin cleaning and treatment of damaged zone with anti-septic agent Bacteriophage gel, which disinfects skin surface, prevents biofilm forming, accelerates cicatrizing process is applied, then posttraumatic zone is treated with cleaning milk, toned up with tonic lotion and cream mask having bactericide, vessel restorative and recovering action, and enhancing of local immunity is applied.
EFFECT: method for skin structure recovering without skin trauma.
4 cl, 7 ex, 1 tbl
FIELD: veterinary science, medicine, pharmacy.
SUBSTANCE: invention relates to agents used in treatment of dermatomycosis in animals and humans. Ointment for treatment of dermatomycosis in animals and humans comprises acetylsalicylic acid, 5% iodine alcoholic solution and glycerol taken in the definite ratio of components. Invention enhances effectiveness of treatment, decreases time in treatment of dermatomycosis and prevents appearance of new foci of diseases and relapses.
EFFECT: enhanced effectiveness of treatment.
FIELD: medicine, contraception.
SUBSTANCE: invention proposes antibacterial and contraceptive compositions that comprise the following components: (1) matrix-forming substance; (2) bioadhesive substance; (3) buffer substance; (4) moistening substance, optionally; (5) preserving agent, optionally, and (6) water. Proposed compositions are suitable for their placement into vagina wherein compositions form semisolid matrix in contact with testicular fluid, cause thickening cervical mucus, form a bioadhesive layer on vagina surfaces, maintain the natural acid pH value in vagina about less 5 in the presence of testicular fluid ejected by a male and don't disturb essentially the natural microbiological balance in vagina. Compositions and methods decrease and/or prevent transfer of diseases transferring by sexual way and act as vaginal contraceptives with less adverse effect as compared with conventional vaginal contraceptives and can be used therefore for a long time. Compositions and methods are simple for using and don't require a physical device for their retention into vagina during using.
EFFECT: improved and valuable properties of compositions and methods.
36 cl, 17 tbl, 11 ex
FIELD: medicine, pharmacy.
SUBSTANCE: invention relates to an agent for topical using used in treatment of joint diseases. The proposed agent comprises glucosamine salt, chondroitin sulfate and dimethylsulfoxide incorporated into an acceptable ointment base. Invention provides enhancing effectiveness due to using low-molecular saccharides that results to elevating diffusion delivery rate of the substance to the joint zone and providing the achievement of synergistic effect in treatment of joint diseases.
EFFECT: enhanced effectiveness and valuable medicinal properties of agent.
2 cl, 3 ex