The method of treatment of autoimmune arthritis |
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IPC classes for russian patent The method of treatment of autoimmune arthritis (RU 2169560):
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The invention relates to novel di - and trivalent small selectin inhibitors of formula II, where X is selected from the group comprising-CN, -(CH2)nCO2H, -(CH2)nCONHOH, -O(CH2)m-CO2H, -(CH2)nCOZ, -(CH2)nZ, -CH(CO2H), (CH2)mCO2H,
-OH; Y = -(CH2)f; R1, R2independently selected from the group including hydrogen, lower alkyl, halogen, -OZ, -NO2, -NH2; R3selected from the group including hydrogen, lower alkyl, hydroxy-lower alkyl, amino-lower alkyl, lower alkyl-carboxylic acid; f = 1 - 6; n = 0 to 2; b = 0 - 2; m = 1 to 3; Z represents lower alkyl, phenyl, or their pharmaceutically acceptable salts, esters, Amida  The use of terpene compounds reduced the release of arachidonic acid and inflammatory mediators / 2161482
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The invention relates to medicine, namely to addiction, and can be used for treatment of alcoholism
Gel for the treatment of skin diseases and skin disinfection / 2142273
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(57) Abstract: The invention relates to medicine, and is intended for the treatment of autoimmune arthritis in mammals. The method comprises the daily oral administration of the drug "Wobenzym", along with him daily orally administered drug, "don", and intra-articular drug sodium Oxybutyrate". "Don" imposed at the rate of daily dose to 21.4 mg/kg weight, which before use are dissolved in 300 ml of water and injected 2 times a day for 4 weeks. "Wobenzym" imposed at the rate of daily dose 42,85 mg/kg 2 times a day for 4 weeks. 20% solution of the drug sodium Oxybutyrate" imposed at the rate of a daily dose of 5.7 mg/kg of body weight, mixed with 2 ml of isotonic solution of sodium chloride and administered 1 time per day for 4 weeks. The method leads to the prolongation of the remission of the disease by optimizing reparative regeneration of joint tissues. 3 C.p. f-crystals. The invention relates to medicine and biology and is intended for conservative treatment of autoimmune arthritis in mammals. There is a method of treatment of rheumatoid arthritis by application of medicinal mixtures containing 33.3% of Dimethylsulfoxide as a conductor, and 9.5% Oxybutyrate The 8216 A 61 K 9/08). Preparation of sodium Oxybutyrate - sodium salt of gamma-hydroxybutyric acid increases the body's resistance to the effects of different types of oxygen deficiency, including its local form. It antihypoxic effect is due to the activation of mitochondrial oxidation due to the increase of electron transport in the respiratory chain and accelerate the release of energy. Produced sodium Oxybutyrate" 20% ampoule of solution for intravenous injection, as well as 66,7% solution and 5% syrup for oral administration (Medicines: a Guide for clinicians / edited by M. D. Mashkovsky. - M.: Medicine, 1996. - 438 S.)This method allows, on the one hand, to reduce the activity of the inflammatory process due to the presence of drug compound hydrocortisone, and on the other to strengthen the system of mitochondrial oxidation, thereby blocking the damaging effects of hypoxia due to the presence of sodium oxybutyrate. The combination of the two mechanisms of action in different stages of the pathological process creates a braking effect of the destruction of joint tissues in terms of local tissue hypoxia. The disadvantage of this method is that the military preparations to articular tissues, and, secondly, excludes the impact of these drugs on metabolic changes in the connective tissue of the organism as a whole. It is known that rheumatoid arthritis is a chronic systemic autoimmune inflammatory disease of connective tissue with a primary lesion of the peripheral joints-type symmetric progressive erosive and destructive polyarthritis (Rheumatoid diseases: Guide for physicians / edited by C. A. Nasonova, N. In. Horsetail. - M.: Medicine, 1997. - 520 C.). Because of drastically disturbed metabolism of the connective tissue occurs destruction of the bones (osteoporosis, pseudocyst, thinning and destruction of the subchondral bone plate), which is accompanied by pathological regeneration. The result is the formation of fibrous cartilage lesions osteosclerosis and osteophytosis with the possibility of the formation of bone ankylosis (kopyova I.e. and Vanickova M. C. Clinical morphology of arthritis rheumatic diseases. - M.: Medicine, 1992. - 219 S.). In connection with the above treatment should be comprehensive and aimed at both local and General symptoms of the pathological process. There is also known a method lecci course, conducted every other day for two weeks (Belov S. C. Peroxidation-antioxidant imbalance in the conditions of rheumatoid inflammation and the possibility of medical correction - author. dis. Kida. Biol. Sciences. - Saratov, 1999. - 23 S.). However, the use of non-cellular enzymatic antioxidant ceruloplasmin allows you to adjust only one of many pathogenic mechanisms of autoimmune arthritis - of non-cellular level of the antioxidant system, therefore, can be effective only in combination with other drugs (Karyakin E. C. Endogenous intoxication and violation of connective tissue metabolism in patients with rheumatoid arthritis (pathogenetic mechanisms, diagnosis, treatment). - Abstract. dis. Dr. med. Sciences. - Moscow, 1998. - 46 S.). In addition, when the intravenous use of this drug, on the one hand, is short, since the period of his activity in the blood line is very small, and on the other hand, has its effect on the General manifestations of the pathological process, and not pronounced monoenoic, which is the main manifestation of autoimmune arthritis. Also known is a method of treatment of diseases of immune complexes, which include auto is m which is the human pepsin. In this way, the daily dose of this drug varies from 1 to 1000 mg, and may vary depending on the method of introduction (EP N 0100366, M CL A 61 K 37/54, publ. 15.02.84, bull. 84/7). However, one of the proteolytic enzymes, such as human pepsin, not able to significantly affect the process of elimination of existing metabolic changes of the joints. Closest to the claimed is a method of treatment of autoimmune arthritis by oral administration of the drug "Wobenzym" in the amount of from 5 to 10 pills at the reception three times a day. The course of treatment - from 4 weeks to 4 months (Kovalenko, C. N., Tertov A. I., holovatsky, I. C., ... Read O. L. Wobenzym: Strategy and tactics in the treatment of rheumatic diseases of the joints // Systemic enzyme therapy: proceedings of the II International conference. - St. Petersburg, 1996. S. 43-46. The drug used in the way, "Wobenzym" - is a combination of highly active enzymes of animal and vegetable origin. Releasing it in tablets or tablets, each of which contains Pancreatin 100 mg, papain 60 mg, bromelain 45 mg, 24 mg trypsin, chymotrypsin 1 mg amylase 10 mg lipase 10 mg rutin 50 mg This mod is integral influence on the individual components of immunopathological processes through effects on humoral (antibodies, immune complexes, complement) and cellular (T-lymphocytes, cytokines) immunity and phagocytic system (macro - and macrophages). "Wobenzym" has a pronounced anti-inflammatory effect, improves the rheological parameters (Denisov, L. N. Non-pharmacological therapies in rheumatology practice // Russian J. rheumatology. - 1998. - N 3. - S. 36-43). The disadvantage of this method is that its use eliminates the impact on the disturbed metabolism of the main structural components of bone tissue proteoglycans and collagen, as well as direct protection from the damaging effects of regional tissue hypoxia, which can lead to pathological regeneration of bone tissue with the formation of bone ankylosis. The objective of the invention is the lengthening remission of the disease by optimizing reparative regeneration of joint tissues. The problem is solved in that in the method of treatment of autoimmune arthritis, including daily oral administration of the drug "Wobenzym", along with him daily orally administered drug, "don", and intra-articular drug sodium Oxybutyrate". In addition, in the present method supply the drug is dissolved in 300 ml of water and administered orally 2 times a day for 4 weeks. The proposed optimal dose of the drug "Wobenzym" from calculation of a daily dose of 42,85 mg/kg of body weight, administered orally 2 times a day for 4 weeks. Patented mode of administration and dose of the drug sodium Oxybutyrate", 20% liquid solution which is based 5,7 mg/kg of body weight mixed with 2 ml of isotonic solution of sodium chloride and injected intra-articular 1 time per day for 4 weeks. The drug Dona - drug, the active ingredient of which is glucosamine sulfate, related to aminosaccharides with a molecular mass of 456,42. In norm it is present in the human body and is used for the biosynthesis of hyaluronic acid synovial fluid. Damage to these pathways of biosynthesis is the main pathogenetic link with osteoarthritis, dysmetabolic degenerative processes, the target of which is the articular cartilage. Glucosamine sulfate can stimulate the biosynthesis of proteoglycans and suppress the formation of superoxide radicals and enzymes that destroy collagen. Drug use "don" for the treatment of degenerative joint diseases. Release preparation "don" in the form of a crystalline powder, packaged in bags, SN times a day for 6-8 weeks (drugs in Russia: on the main page. - M.: Astroparticles, 1998. - 1600 C.). Combinations in the proposed method of oral administration of two drugs: enzymatic preparation Wobenzym", the vast immunopathological processes, and drug Dona stimulating the biosynthesis of proteoglycans and collagen, as well as intraarticular injection drug sodium Oxybutyrate" blocking the damaging effects of tissue hypoxia, creates the effect of optimization of process of reparative regeneration of bone and cartilage that prevents their pathological increase in conditions of autoimmune inflammation. The method is as follows. The powder of the drug, "don", containing 1500 mg of the active ingredient is glucosamine sulfate, dissolved in 300 ml of water or provide flooding. The resulting solution of the drug administered orally in two doses, with its daily dose is 21.4 mg/kg of body weight. The drug Vobenzim" take 10 drops 2 times a day, daily dose equal 42,85 mg/kg of body weight. It is possible to separate and co-administration of the two drugs. Immediately before injection, "sodium Oxybutyrate" 2 ml of a 20% ampoule solution is mixed with 2 ml ampoule isotonic dissolve Injections carried out once a week for 4 weeks. Daily dose equal to 5.7 mg/kg of body weight. EXAMPLE 1. Rabbit N 15/0. Animal formed with autoimmune arthritis of the right knee joint. Duration of disease since the introduction of the complete adjuvant's adjuvant - 14 days. Physical examination revealed clinical signs of disease in the form of weakness, limitation of motion in the affected knee joint, pain on palpation. Coat dull and wet places. The volume of the affected joint is increased compared with the control, the local temperature is increased, the skin is hyperemic. The animal moves in the cage on three legs, sparing the patient. The weight of the rabbit 2,0 kg General analysis of blood: erythrocyte sedimentation rate of 9 mm/h, leukocytes 8,9109/l, stab 8, segments 60. Rabbit completed the treatment according to the specified method comprising the daily oral administration of an aqueous mixture of drugs "Wobenzym" and "the don", as well as intra-articular introduction of 20% of the ampoule solution "sodium Oxybutyrate", mixed with isotonic sodium chloride solution. After treatment, marked improvement in clinical symptoms: the animal is active, moves on four legs, the coat smooth and blest Local temperature dropped to normal. The weight of the rabbit increased to 2.6 kg There was a positive dynamics laboratory parameters: the level of ESR decreased to 6 mm/h, WBC count decreased to 7,9109/l At macroscopic examination of the affected knee joint lesions were found. Misaki of the two bones forming the joint, had a normal shape, bone growths and nodules were absent. The cortical surface of the bone in the periarticular departments smooth. When histomorphometrical study of the femoral condyles and tibial bones experienced knee joints installed that hyaline cartilage saved all over, there were only small areas of razvlechenija its surface layer. The microstructure of periarticular and subchondral departments of both condyles changed little. The periosteum cortical plate near the joint, "calm", its proliferation of fibroblasts was not detected. Bone marrow pannus is missing. The integrity of the subchondral bone plate is retained throughout. We detected only a slight thinning in places corresponding to usuali cartilage-pannus, which did not penetrate the entire depth of the articular cartilage, leaving intdel pathologically not changed. Thus, the use rate of the proposed method of treatment resulted in significant improvement of clinical and laboratory parameters and to optimize the process of reparative regeneration of cartilage and bone tissue, preventing the formation of abnormal bone growths in the early stages of the development of autoimmune inflammation. EXAMPLE 2. Shown for comparison is the treatment method that includes only drug "Wobenzym". Rabbit N 8/0. Autoimmune arthritis is formed by introducing a comprehensive adjuvant-blockers in the periarticular tissue of the right knee joint. Disease duration is 14 days. On examination, the animal is dull, dull coat, sometimes ruffled. Moving on three legs, sparing affected. Visually and in the measurement of significant swelling in the affected area of the knee joint, palpation painful, the local temperature is raised. The weight of the rabbit 2,4 kg General analysis of blood: ESR 8 mm/h, leukocytes 9,1109/l stab 8, segmented 60. Rabbit held medical treatment only drug "Wobenzym". After treatment there was a slight improvement in the General condition of the animal and the local temperature of the affected knee joint. However, when moving the animal continued to spare right hind limb, and the volume of the affected knee and local temperature were higher than those of the control joint. Body weight remained unchanged 2,4 kg We detected only a slight positive trend of the General analysis of blood: erythrocyte sedimentation rate of 7 mm/h, leukocytes 8,8109/l, stab 7, segmented 60. Rabbits are derived from experience immediately after the end of treatment (4 weeks). Macroscopically articular cartilage of the femoral condyles and tibial bone was preserved throughout, but its surface was swapped dull, rough. The edges of the condyles of the tibia detected a slight expansion with bone density. Microscopic examination revealed the presence of areas of articular cartilage with loss of the surface layer, arthropathia its surface and core zones, and the presence of pathological signs of regeneration with the formation of clones of chondrocytes located in malacitana matrix. In bone tissue were the areas of thinning and the integrity of the subchondral bone plate and beams without the presence of bone-m is ptx2"> The results of this study indicate a lack of effect of treatment only drug "Wobenzym", which is not able to slow down the pathological regeneration of bone and cartilage tissue in conditions of autoimmune inflammation. In the laboratory of pathomorphology, Sarnico was serial experimental validation of the proposed method on 20 adult rabbits reproduced with autoimmune arthritis of the right knee joint (Sigidin J. A., Guseva N. G. , Ivanov, M. M. Diffuse connective tissue disease. - M.: Medicine, 1994. - 541 S.) Rabbits were divided into 2 series (10 pieces each). Animals of the 1st series was treated only "Wobenzyme". Animals of the 2nd series of the proposed method. Treatment was started 14 days after the introduction of the complete adjuvant's adjuvant. Rabbits out of the experience immediately after the end of treatment after 4 weeks the introduction of air into the ear vein. Produced histomorphometrical study standard sections of articular cartilage and bone of the affected knee joints. This, along with morphological signs of lesions of the articular tissues were considered parameters characterizing the processes of loss and bone tissue of the experimental animals had damaged articular cartilage typical of autoimmune arthritis. This damage was characterized by focal userarea of the outer layers of the surface zone, orthochromatic surface and partially the main areas, a decrease in the number of chondrocytes, degeneration of part of the existing chondrocytes. The amount of points the signs of destruction of articular cartilage in rabbits 1 series was significantly higher (8,561,20 points) than in animals of the 2nd series (4,260,50 points; P<0,05). While cloning of chondrocytes, which are characteristic pathological regeneration was absent in the 2nd series of experiments, but was detected in 60% of cases 1-series. These rabbits revealed a zone of sclerosis of the subchondral bone plate and surrounding trabeculae, as well as the growth of bone tissue at the edges of the condyles in the form of osteophytes. Animals 2-series signs of pathological bone regeneration was absent, and from the signs of its destruction were only thinning of the subchondral bone plate in 50% of cases. Thus, experimental research has shown that using the proposed method for the treatment of autoimmune arthritis prevents the development of pathological regeneration of bone and hyaline cartilage of the affected joints. the osteogenesis and prevention of bone ankylosis in conditions of autoimmune inflammation. 1. The method of treatment of autoimmune arthritis, including daily oral administration of the drug "Wobenzym", characterized in that along with him daily orally administered drug, "don", and intra-articular injected the drug sodium Oxybutyrate". 2. The method according to p. 1, characterized in that the drug is "don" from calculation of a daily dose to 21.4 mg/kg of body weight before use, dissolve in 300 ml of water, and ingested by 2 times daily for 4 weeks. 3. The method according to p. 1, characterized in that the drug "Wobenzym" from calculation of a daily dose 42,85 kg/kg administered orally 2 times a day for 4 weeks. 4. The method according to p. 1, characterized in that 20% ampoule solution "sodium Oxybutyrate" from calculation of a daily dose of 5.7 mg/kg combined with 2 ml of isotonic solution of sodium chloride, and the introduction of intra-articular spend 1 day a week for 4 weeks.
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