Agent for treatment of joint diseases
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
The invention relates to medicine, namely preparations for the treatment of diseases of the joints.
Disease affects about 70% of the population older than 45 years. They are manifested as pain in the joint, aggravated by motion, sensation of tightness. Inflammatory processes are accompanied by swelling, change in shape of the joints.
In addition, when astrologicheskih diseases of the joints gradually destroys the cartilage covering the articular surfaces, as well as bone tissue and the inner surface of the articular capsule.
Currently widespread in the world of medical practice for the treatment of diseases of the joints (arthritis, arthrosis, osteochondrosis, etc.) received drugs on the basis of saccharides (salts of glucosamine, chondroitin sulfate), mainly in the form of tablets, capsules and injections. Treatment with these drugs not only reduce inflammation and pain in the joints, but also produces the restoration of damaged cartilage tissue [Nasonov EL Clinical guidelines and algorithms for clinicians, Rheumatology, M., 2004; K.Pavelka, Archives Internal Medicine, №10, 2002, №7, 2003].
Known injectable preparation containing as active ingredient the polysaccharide is chondroitin sulfate with a molecular weight of 8000÷16000 daltons (8÷12 wt.%), preservative - gasoline alcohol (0,8÷1.2 wt.%) and water (OS is real) [RF patent №2021812]. Its disadvantages are that when used as a chondroprotective component of the polysaccharide is chondroitin sulphate with polydisperse high molecular weight (8000÷16000 daltons), limited diffusion of the active ingredient in the joint area, which significantly reduces the pharmacokinetics of the proceeds of the drug in the bloodstream and the cartilage of the joint when it is intramuscular, and, as a consequence, low bioavailability and effects of inhibition of the process of destruction of cartilage and its regeneration (product qualification Long).
Closest to the claimed means the composition is injectable preparation containing as an active ingredient saccharide-glucosamine hydrochloride (acidic saccharide with a pH of an aqueous solution of 1.2÷2,5), the neutralizing agent is Ethylenediamine, local anesthetic agent - trimekain and excipients [RF patent №2118156].
Low molecular weight glucosamine hydrochloride (215,0 daltons) and high pharmacological activity [Eszteca, Scientific-practical rheumatology, No. 2, 2003] in the treatment of diseases of the joints ensure the creation of effective chondroprotective drug.
The disadvantages of this drug are as follows:
the preparation contains as the active ingredient monomer salt of glucosamine short lane is one half of the body (T 1/2about two hours), which makes the drug only for the qualifications Rapid;
the drug consists of two vials: vials with a solution of glucosamine hydrochloride and capsules with a solution of Ethylenediamine. The preparation for the introduction of patient consists in mixing the contents of two vials in the syringe immediately before injection of;
neutralizing agent is Ethylenediamine - liquid with a boiling point 116°and, therefore, cannot be used for the preparation of monophasic preparation (HA + neutralizing agent) in the form of a lyophilisate;
- the use of Ethylenediamine in the product in relatively high concentrations (>3 wt.% in relation to glucosamine) requires a supplemental part of the preparation of local anesthetic products - trimekainom that, in turn, causes a number of undesirable side effects.
The problem solved by the invention is the development of monophasic injection of a drug for treatment of diseases of the joints in the form of a lyophilisate, combining chondroprotective effect of monomer - glucosamine and polymer - chondroitin sulphate with high pharmacokinetic parameters and bioavailability with the exception of the disadvantages of the prototype.
The technical result from the use of the invention is to create drug qualificat and Mikst, the increase of the specific concentration of active ingredient in the drug and, consequently, increase the speed and efficiency of diffusion of the active substance in the joint area.
For the achievement of the proposed remedy for the treatment of diseases of the joints, representing a lyophilisate containing saccharide - glucosamine salt, polysaccharide is chondroitin sulfate, and the neutralizing agent is an aliphatic amine - trometamol in the following ratio, wt.%:
Simultaneous inclusion of the drug mixture of monosaccharide - salt of glucosamine and polysaccharide chondroitin sulphate achieve a synergistic effect in the treatment of astrologicheskih diseases because of exogenous glucosamine additionally produces synthesis by chondrocytes endogenous chondroitin sulfates and proteoglycans, as their universal predecessor [international Medical journal, No. 3, 2000].
Variation in the composition of the drug in a wide range of the ratio of monosaccharide/polysaccharide provides freedom of choice in creating specific dosage forms kVA is of Rapid changes, Mikst, Long with different concentrations of active ingredients and, as a consequence, given pharmacological activity, pharmacokinetic and pharmacodynamic characteristics.
As salts of glucosamine can be used a known pharmaceutical substance (registered in the Russian Federation or imported, the relevant requirements of United States Pharmacopeia 27 editions): glucosamine hydrochloride, sodium or potassium salts of glucosamine sulfate. Preferred is the use of disodium salt of glucosamine sulfate and glucosamine hydrochloride.
As chondroitin sulphate can be used a known pharmaceutical substance chondroitin sulphate, for example registered in the Russian Federation or imported substances that meet the requirements USP27 - United States Pharmacopeia 2004 edition.
The neutralizing agent is trisamin (trade name) is registered as a pharmaceutical substance in Russia №78/702/1. International name - trometamol. The chemical name is 2-Amino-2-(hydroxymethyl)-1,3-propandiol
The number added to the mixture of active ingredients trisamina is determined by the acidity of the commercial sample used salt and installed in each experiment specifically to obtain before filling the original solution with physiologists the definition pH value of 5.0 to 8.0.
It was established experimentally that the introduction of the injectable antacid systemic action - trisamina with buffer properties and local anesthetic action, which significantly accelerates the transport of the active substance into the bloodstream of a living organism. Trisamin, penetrating through the cell membrane, increases the transport, bioavailability and specific content of the saccharide in the joint area. These increases bioavailability of the active ingredient and increased anti-inflammatory properties of the drug is also associated with the ability of the proposed supramolecular structure to change the state of the environment in the microenvironment of the saccharide.
Pharmacological group - 8.8. Concealer metabolism of bone and cartilage (Register of medicines of Russia, 2005 edition).
The preparation is carried out by known methods lies in the dissolution of the active ingredients in water, sterile filtered, followed by filling into ampoules and freeze-drying the solution.
Control the quantitative content of the active ingredients (glucosamine, chondroitin sulfate, trisamin) in the preparations is carried out by known methods adopted for similar legform registered in the Russian Federation and contains the active ingredients (spectrophotometric, nephelometric the second titration).
Example 1. 95,0 g of glucosamine sulfate ×2NaCI and 5.0 g of chondroitin sulfate is dissolved at a temperature not exceeding 40°With 400 ml of distilled water, add with stirring for about 0.5 g trisamina (up to pH 6.0÷7,5). The solution is sterile filtered through a sterile 0.22 μm filters and pour into sterile ampoules of 2 ml Mode lyophilic drying of the drug includes its freezing at -80°and drying in vacuum at room temperature for 10 hours. In the final preparation of 1 ampoule contains 380 mg of glucosamine sulfate ×2NaCI, 20 mg of chondroitin sulfate and 2.0 mg (0.5 wt.%) trisamina.
Example 2. 5 g of glucosamine sulfate ×2l and 95 g of chondroitin sulfate is dissolved at a temperature not exceeding 70°With 400 ml of distilled water, add with stirring to about 0.1 g trisamina (up to pH 6.0÷7,5). The solution is sterile filtered through a sterile 0.22 μm filters and pour into sterile ampoules of 2 ml Mode lyophilization of example 1. In the final preparation of 1 ampoule contains 20 mg of glucosamine sulfate ×2l, 380 mg of chondroitin sulfate and 2.0 mg trisamina (0.1 wt.%).
Example 3. 50 g of glucosamine hydrochloride and 50 g of chondroitin sulfate is dissolved at a temperature not exceeding 40°With 400 ml of distilled water, add with stirring to about 2 g trisamina (up to pH 6.0÷7,5). The solution is sterile filtered through sterilized the e 0.22 μm filters and pour into sterile ampoules of 2 ml Mode lyophilization of example 1. In the final preparation of 1 ampoule contains 200 mg of glucosamine hydrochloride, 200 mg of chondroitin sulfate and 8.0 mg trisamina (2.0 wt.%).
The drug efficacy was studied in models of post-traumatic osteoarthritis, the collapse of the ears of rabbits and aseptic inflammation of the limbs of rats.
When the subchondral defects of the femoral head in rats caused by surgical injury of the articular cartilage, the proposed drug significantly reduces the size of the defect compared to * control animals.
When intravenous papain in rabbits there is a collapse of the ears - sagging their peripheral end. The use of the proposed drug allows you to restore turgor ears, which indicates the inhibition of the destruction of the cartilage of the ears.
Comparative evaluation of chondroprotective action of drugs Glucit-1, Glucat-2, Pusat-3 (obtained respectively in examples 1-3 describe) and Glyset-4 (obtained according to example 1 of the description to the patent of Russian Federation №2118156) was studied in experiments on rabbits rentgenograficheski to change the size of the joint space according to the established procedure (table 1).
|Medication||Pokazatel the (n=20)||Reducing the size of the joint space|
|Very good and good effect||Moderate effect||The lack of effect|
As can be seen from table 1, the introduction is part of the preparation of chondroitin sulfate and new neutralizing agent trisamine significantly increases chondroprotective activity of the drug is according to the accepted objective measure of changing the size of the joint space".
Conducted biological research harmlessness of the drug showed that acute administration of the drug in doses of 100÷200 times the minimum therapeutic for a person, it is practically non-toxic. The preparation is stable for at least 2 years of follow-up. Preliminary clinical tests have confirmed its high chondroprotective activity and good tolerability in the treatment of arthritis and degenerative disc disease.
1. For the treatment of diseases of the joints, representing a lyophilisate containing glucosamine salt, otlichayushiesya, it additionally contains chondroitin sulfate and trometamol in the following ratio, wt.%:
2. The tool according to claim 1, characterized in that salts of glucosamine uses glucosamine hydrochloride or sodium or potassium salts of glucosamine sulfate.
FIELD: medicine, surgery.
SUBSTANCE: invention relates to a method for treatment of relapse hemorrhages into the joint cavity in chronic synovitis in a patient with hemophilia. Method involves administration of 40% officinal glucose solution into the joint cavity in the dose 10 ml into knee joint and in the dose 5 ml into other joints. Administration is carried out 2 times per a week, 7 injections per a course into each joint. Method provides the effective treatment based on dehydration and the following sclerogenic process of synovia and with absence of adverse effects.
EFFECT: improved method of treatment.
FIELD: medicine, pharmacy.
SUBSTANCE: invention relates, in particular, to a solid pharmaceutical composition used in treatment and prophylaxis of osteoporosis. The composition comprises derivative of bis-phosphonic acid that involves carbohydrate alcohol-base nuclei, preferably, mannitol and uniformly distributed in a homogenous mixture of active component and filling agents. Also, invention discloses a process for preparing the composition described above. Invention eliminates the chemical instability problem of derivatives of bis-phosphonic acid that are ready for using in solid medicinal formulations and during the process for their preparing, good physical properties (strength) of the solid medicinal formulation.
EFFECT: improved and valuable medicinal and pharmaceutical properties of composition.
12 cl, 2 tbl, 1 ex
FIELD: organic chemistry, amino acids.
SUBSTANCE: invention proposes the novel derivatives of phenylalanine of the formula (I) and (II) possessing with antagonistic activity with respect to α4-integrin. Derivatives of phenylalanine are used as therapeutic agents in different diseases associated with α4-integrin.
EFFECT: valuable medicinal properties of compounds.
37 cl, 30 tbl, 215 ex
FIELD: chemico-pharmaceutical industry.
SUBSTANCE: the present innovation deals with developing a preparation out of plant raw material for treating motor system diseases. The compositions suggested are in the form of species and as the mixture of tinctures. Compositions manifest pain-relieving, diuretic, antiphlogistic, bacterio- and virusostatic action and, also, regulate corticosteroid and mineral exchange.
EFFECT: higher efficiency.
4 cl, 6 ex
SUBSTANCE: method involves carrying out physio-balneo-procedure in closed chamber in two stages. The first dry air stage lasts 15-20 min at 60°C and relative humidity of 20%. The second air aerosol stage lasts 15-20 min and involves spraying 50-150 ml of aerosol containing water extract of young maral horns or pantocrine with particle size of 15-50 mcm at 38-42°C and relative humidity of 45-50%. The total treatment course is 12-15 sessions long. The sessions are given every other day.
EFFECT: increased transepidermal barrier permeability; enhanced effectiveness of treatment; reduced extract and pantocrine consumption.
FIELD: medicine, in particular pharmaceutical composition useful in treatment of cartilage lesions, inflammation, arthritis, etc.
SUBSTANCE: claimed composition contains carrier, diluent or filler, valdecoxib and alpha-2-delta-ligand, selected from babapentin, pregabapentin, 3-(1-aminomethylcyclohexylmethyl)-4H-[1,2,4]oxadiazole-5-one hydrochloride, and (3S,4S)-(1-aminimethyl-3,4-dimethylcyclopentyl)acetic acid. Also disclosed are uses of combination, containing valdecoxib and abovementioned alpha-2-delta-ligand for production of drug and treatment of abovementioned diseases.
EFFECT: agent for more effective treatment.
9 cl, 12 ex
FIELD: organic chemistry of heterocyclic compounds, medicine, pharmacy.
SUBSTANCE: invention relates to derivatives of pyrimidine of the general formula (I) and their pharmaceutically acceptable acid-additive salts possessing properties of neurokinin-1 (NK) receptors antagonists. In the general formula (I): R1 means lower alkyl, lower alkoxyl, pyridinyl, pyrimidinyl, phenyl, -S-lower alkyl, -S(O2)-lower alkyl, -N(R)-(CH2)n-N(R)2, -O-(CH)n-N(R)2, -N(R)2 or cyclic tertiary amine as a group of the formula: R1 means lower alkyl, lower alkoxyl, pyridinyl, pyrimidinyl, phenyl, -S-lower alkyl, -S(O2)-lower alkyl, -N(R)-(CH2)n-N(R)2, -O-(CH)-N(R)2, -N(R)2 or cyclic tertiary amine of the formula: that can comprise additional heteroatom chosen from atoms N, O or S, and wherein this group can be bound with pyrimidine ring by bridge -O-(CH2)n-; R2 means hydrogen atom, lower alkyl, lower alkoxyl, halogen atom or trifluoromethyl group; R3/R3' mean independently of one another hydrogen atom or lower alkyl; R4 means independently of one another halogen atom, trifluoromethyl group or lower alkoxyl; R means hydrogen atom or lower alkyl; R means independently of one another hydrogen atom or lower alkyl; X means -C(OH)N(R)- or -N(R)C(O)-; Y means -O-; n = 1, 2, 3 or 4; m means 0, 1 or 2. Also, invention relates to a pharmaceutical composition comprising one or some compounds by any claim among claims 1-19 and pharmaceutically acceptable excipients. Proposed compounds can be used in treatment, for example, inflammatory diseases, rheumatic arthritis, asthma, benign prostate hyperplasia, Alzheimer's diseases and others.
EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.
21 cl, 1 tbl, 76 ex
SUBSTANCE: preparation is intramuscularly introduced for achieving spasm relief.
EFFECT: avoided surgical intervention or harmful substances consumption.
12 cl, 2 tbl
FIELD: organic chemistry, biochemistry, medicine, pharmacy.
SUBSTANCE: invention relates to piperidine- and piperazine-substituted N-hydroxyformamides of the general formula (I) or their pharmaceutically acceptable salts wherein B represents phenyl group monosubstituted at 3- or 4-position with halogen atom or trifluoromethyl group or bisubstituted at 3- and 4-position with halogen atom (that can be similar or distinct); or B represents 2-pyridyl or 2-pyridyloxy-group monosubstituted at 4-, 5- or 6-position with halogen atom, trifluoromethyl group, cyano-group or (C1-C4)-alkyl; or B represents 4-pyrimidinyl group possibly substituted with halogen atom or (C1-C4)-alkyl at 6-position; X represents carbon or nitrogen atom; R1 represents trimethyl-1-hydantoin-(C2-C4)-alkyl or trimethyl-3-hydantoin-(C2-C4)-alkyl group; or R1 represents phenyl or (C2-C4)-alkylphenyl monosubstituted at 3- or 4-position with halogen atom, trifluoromethyl group, thio-group, (C1-C3)-alkyl or (C1-C3)-alkoxy-group; or R1 represents phenyl-SO2NH-(C2-C4)-alkyl; or R1 represents 2-pyridyl or 2-pyridyl-(C2-C4)-alkyl; or R1 represents 3-pyridyl or 3-pyridyl-(C2-C4)-alkyl; or R1 represents 2-pyrimidine-SCH2CH2; or R1 represents 2- or 4-pyrimidinyl-(C2-C4)-alkyl possibly monosubstituted with one of the following substitutes: halogen atom, trifluoromethyl, (C1-C3)-alkyl, (C1-C3)-alkoxy-group, 2-pyrazinyl possibly substituted with halogen atom, or 2-pyrazinyl-(C2-C4)-alkyl possibly substituted with halogen atom. Also, invention describes a method for synthesis (variants) of compounds of the formula (I) and a pharmaceutical composition. Compounds can be used as inhibitors of metalloproteinases and useful in such morbidity states as inflammatory and allergic ones.
EFFECT: valuable medicinal and biochemical properties of compounds and pharmaceutical compositions.
12 cl, 1 tbl, 10 ex
FIELD: medicine, traumatology.
SUBSTANCE: therapy complex that includes puncture and washing an articular cavity with a sterile medicinal preparation followed by introducing oxygenated perfluoran at the dosage of about 25-30 ml in combination with passive articular movements should be additionally supplemented with introducing oxygenated perfluoran into metaepiphyseal articular area at the dosage of 30 ml, once daily. Intraosseous injection of perfluoran should be fulfilled thrice , not rarely, moreover, passive articular movements should be performed for 7 d, not less. Such implementation of the method enables to reconstruct trophic cartilaginous processes due to the fact that perfluoran being introduced intraosseously and entering the area of the fracture removes local hypoxia and provides articular cartilage with oxygen from the side of subchondral layer.
EFFECT: higher efficiency.
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, gynecology.
SUBSTANCE: one should carry out basic antibioticotherapy and immunocorrection, moreover, as an immunocorrector it is necessary to apply affinoleukin preparation as submucous injections into uterine cervix. A single dosage of affinoleukin corresponds to 1.0 U once during 2 d. Therapy course consists of 10 injections. The innovation provides regional activation of T-lymphocytes' transition from immature forms into mature ones associated with mucous membranes of urogenital tract and, thus, efficient chlamydial elimination.
EFFECT: higher efficiency of therapy.
2 ex, 2 tbl