TREATMENT METHOD FOR SARCOIDOSIS |
| RU (11) 2227034 (13) C2 (51) 7 A61K31/573, A61K38/13, A61M1/36 (12) DESCRIPTION OF THE INVENTION TO THE PATENT OF THE RUSSIAN FEDERATION Status: as of July 26, 2007 - terminated ------ -------------------------------------------------- ------------------------ (14) Publication date: 2004.04.20 (21) Application registration number: 2001106169/14 (22) Application filing date: 2001.03.07 (24) Start date of the patent term: 2001.03.07 (43) Date of publication of the application: 2003.01.20 (45) Published: 2004.04.20 (56) Analogs of the invention: (56) RU 2135183 C1, 08.27.1999 . RU 2082397 C1, 06/27/1997. Vaneeva T.V. and others. The use of lymphocytes extracorporeally immunomodified with cyclosporine in patients with sarcoidosis. Modern problems of phthisiology and pulmonology. International scientific and practical conference dedicated to the 100th anniversary of the birth of Professor S.I. Goldberg. Collection of scientific works in 2 parts. Grodno, 1999, part 2, pp. 177-182. Romanov V.V. The effectiveness of corticosteroid therapy in patients with sarcoidosis. Author's abstract. diss. Ph.D., M., 1988, pp. 20-24. Shmelev E.I. and others. Plasmapheresis in the treatment of patients with sarcoidosis of the respiratory system. Pulmonology, 1991, No. 3, pp. 39-42. (72) Name of inventor: Romanov V.V.; Shmelev E.I.; Shmeleva N.M.; Stepanyan I.E.; Kosmiadi G.A. (73) Name of the patent holder: Central Research Institute of Tuberculosis of the Russian Academy of Medical Sciences (98) Address for correspondence: 107564, Moscow, Yauzskaya Alleya, 2, Central Research Institute of Tuberculosis of the Russian Academy of Medical Sciences (54) METHOD FOR TREATING SARCOIDOSIS The invention relates to medicine, phthisiology, and can be used to treat sarcoidosis. Plasmapheresis is performed, while blood lymphocytes are treated with prednisolone at a dose of 300 μg/ml or cyclosporine at a dose of 10 μg/ml of centrifugate and the resulting concentrate is reinfused into the patient’s bloodstream. This invention promotes the rapid onset of a therapeutic effect, allows you to reduce the dose of systemic corticosteroids or completely eliminate them from therapy. DESCRIPTION OF THE INVENTION The invention relates to the field of medicine and can be used in pulmonological and TB practice for the treatment of patients with sarcoidosis. The goal is to increase the effectiveness of the treatment method and reduce the complications of corticosteroid therapy. To do this, extracorporeal treatment of 1-2 billion lymphocytes is carried out with prednisolone or cyclosporine A, followed by reinfusion of the lymphocyte concentrate into the bloodstream of a patient with sarcoidosis. The procedure is carried out twice with an interval of 7-10 days. Treatment of patients with the proposed method ensures a rapid onset of effect, allows you to reduce the dose of systemic corticosteroids, and in some patients completely eliminate them during treatment, which significantly reduces the possibility of developing complications from their use. The invention relates to the field of medicine and can be used in pulmonological and TB practice for the treatment of patients with sarcoidosis. There are known methods for treating patients with sarcoidosis with high doses of corticosteroid drugs (30-40 mg of prednisolone daily), as well as methods using plasmapheresis, which are based on the pathogenetic mechanism of action on the granulomatous process. Despite the high effectiveness of the use of corticosteroids in the treatment of patients with sarcoidosis, a significant percentage (50%) of complications from their use is observed. The use of plasmapheresis courses in the treatment of sarcoidosis, although it makes it possible to reduce the dose of steroids, but this reduction is insignificant, and most importantly, this method does not have an effect on the main link in the immunopathogenesis of sarcoidosis - the T-lymphocyte. In addition, when performing plasmapheresis, it is necessary to remove a fairly large volume of plasma from the patient’s bloodstream (800-1200 ml), which can lead, albeit short-term, to protein imbalance, with resulting undesirable consequences (impaired blood pressure, decreased body defenses) . It is generally accepted that in the area affected by sarcoidosis there is a significant accumulation of T-lymphocytes, and most importantly, a significant increase in their functional activity, expressed in an increase in the production of pro-inflammatory interleukins. The method was carried out as follows: from the patient's cubital vein, blood is taken sequentially, in parts of 300-500 ml, into standard plastic containers, such as "Gemakon", which is centrifuged in a medical centrifuge at 2700 rpm for 15 minutes. It has been proven that in this case, a film is formed at the boundary between plasma and erythrocyte mass, mainly consisting of leukocytes with an increased content of lymphocytes. Using this, we remove this centrifugate layer from 3-4 portions, bringing the total number of lymphocytes collected for further processing to 1-2109. Next, 300 µg/ml prednisolone or 10 µg/ml cyclosporine is added to this lymphocyte concentrate. The dosage of the drugs was worked out during bench tests based on their greatest functional inhibition (according to the in vitro response to the complex mitogen PHA) and the least cell death during the incubation process. The concentrate processed in this way is placed in a thermostat for 2 hours at a temperature of 37C (time and temperature conditions were also determined experimentally). After this, the resulting lymphocyte concentrate is reinfused into the patient’s antecubital vein. The absence, in this case, of a systemic effect of cyclosporine was confirmed by determining the drug in the patient’s blood, both immediately after the procedure and 24 hours after it. At the same time, only trace concentrations of cyclosporine were detected - 1.6-26.6 ng/ml. A dose of 60 mg of prednisolone, or 2 tablets in tablet form, or 2-3 mg of cyclosporine A used in this technique cannot be considered therapeutic and could not directly influence the sarcoid process. Extracorporeal modification with prednisolone and cyclosporine was performed in 69 patients with sarcoidosis (37 patients with prednisolone and 32 with cyclosporine), with 8 patients as monotherapy, and the rest with simultaneous prescription of 15-20 mg of prednisolone every other day, which is supportive in everyday medical practice , and not a therapeutic dose and does not cause complications from its use. Under the influence of extracorporeal prednisolone hemotherapy, in 95% of cases, positive radiographic dynamics of the process were achieved, and in 41% of cases - significant. The X-ray dynamics of the process under the influence of extracorporeal modification of lymphocytes with cyclosporine was as follows: a significant reverse development of changes in the lung tissue and a decrease in intrathoracic lymph nodes was noted in 45% of patients, moderate - in 35%, insignificant - in 15% and the absence of positive X-ray dynamics was recorded in 5% examined patients. Positive radiological dynamics were also noted in 75% of patients who underwent extracorporeal modification of lymphocytes without simultaneous administration of systemic corticosteroids. No disease progression was detected in any patient in this group, which indicates the safety of this procedure in patients with sarcoidosis. Example 1. Patient S., 53 years old, has been observed for 3 years at the Central Research Institute of the Russian Academy of Medical Sciences for sarcoidosis of the lungs and intrathoracic lymph nodes. The diagnosis was verified by transbronchial intrapulmonary biopsy, which revealed epithelioid cell granulomas without caseous necrosis. The course of the disease is relapsing. Six-month courses of corticosteroid therapy were carried out twice with daily prednisolone at a dose of 30 mg (6 tablets), with a partial clinical and radiological effect. Regarding another exacerbation of sarcoidosis, on March 23, 1998, he was admitted to the 2nd hospital. TsNIIT RAMS. Upon admission, she was bothered by severe shortness of breath and a dry cough. X-rays of the lungs reveal significantly pronounced bilateral dissemination and enlargement of the VLN. When studying the function of external respiration, vital capacity was 72%, MSV 25-24%. The patient was prescribed corticosteroid therapy with prednisolone 20 mg every other day and underwent two extracorporeal modifications of blood lymphocytes with prednisolone. As a result of the therapy, the patient's condition improved significantly: shortness of breath and cough decreased, significant resorption of changes in the lung tissue and a decrease in VLLU were achieved. Within 2 years after completion of the course of therapy, no relapse of the disease was noted. Example 2. Patient Sh., 51 years old. Before admission to the Central Research Institute of the Russian Academy of Medical Sciences, she was observed for a year and treated at the place of residence with delagil and vitamin E without effect. Upon admission to the Central Research Institute of the Russian Academy of Medical Sciences on February 7, 2000, the condition was satisfactory; slight shortness of breath during physical exertion was a concern. FVD is within normal limits. Chest x-rays reveal significant enlargement of the intrathoracic lymph nodes. A bronchological examination revealed “vascular ectasia” and tuberculate rashes on the bronchial mucosa. Epithelioid cell granulomas were found in direct biopsy material of the bronchial mucosa. Diagnosis: Sarcoidosis of the upper lymph nodes, active phase. The clinic began treatment with flixatide 3 times 2 times a day and carried out two extracorporeal modifications of blood lymphocytes with cyclosporine. As a result of the therapy, there was a significant decrease in the intrathoracic lymph nodes. No exacerbation of sarcoidosis was noted within six months after the end of treatment. Technical, economic or other efficiency. The proposed method of treatment significantly increases the effectiveness of treatment of patients with sarcoidosis, reduces the length of stay of patients in the hospital, and also makes it possible to reduce the dose of systemic corticosteroids, and sometimes completely abandon them, which in general significantly reduces the costs of treating patients with sarcoidosis. Sources of information 1. Khomenko A.G. et al. Central Research Institute of Tuberculosis of the Russian Academy of Medical Sciences. Sarcoidosis as systemic granulomatosis. - M.: Medicine - 1999. 2. Shmelev E.I., Matskeplishvili M.Sh., Stepanyan I.E., Romanov V.V. Plasmapheresis in the treatment of patients with respiratory sarcoidosis. Pulmonology, 1991, No. 3, pp. 39-42. CLAIM |