A method for the treatment of dyscirculatory encephalopathy
The invention relates to medicine, namely to neurology, and can be used for the treatment of dyscirculatory encephalopathy. The method includes comprehensive medical therapy, which uses the introduction to the patient of Vinpocetine, Riboxin, vitamin B6, and ceruloplasmin, and ceruloplasmin injected daily for 8-10 days intravenous infusion at a rate of 30-35 drops per minute at a dose of 100-200 mg in the form of a solution containing 100 mg of ceruloplasmin 200 ml isotonic sodium chloride. The method allows to increase the effectiveness of treatment in reducing polipragmazie. 1 C.p. f-crystals, 2 PL.
The present invention relates to medicine, namely to neurology, and can be used for the treatment of dyscirculatory encephalopathy (hereinafter - DE).
Dyscirculatory encephalopathy (DE) - a widespread disease, slowly progressive disorders of brain blood flow, leading to diffuse structural changes with the disorder of brain function. The main role in the etiology of TE is given to atherosclerosis and arterial hypertension or their combination. Ve is ECCA.
A traditional method of treatment TE is a complex drug therapy (see, for example, Diseases of the nervous system./Ed. by N. N. Yakhno, D. R. of Stulman, T. 1, M.: Medicine, 2001, S. 283 and 284). According to this method, the treatment should include the effects aimed at the underlying disease, against which develops DAE (atherosclerosis, hypertension, vasculitis, and others), elimination of neurological and psychopathological syndromes, improve cerebral circulation and metabolic processes. To improve cerebral blood flow and metabolism using drugs of different groups - pentoxifylline, nootropic agents, calcium antagonists, and other Additional vasoactive drugs use drugs ergot (nicergoline 15-30 mg/day), periwinkle (Vinpocetine, Cavinton - 15-30 mg/day), Ginkgo biloba (tanakan 1-2 tablets 3 times a day), drugs of other groups - Cinnarizine or stugeron 75-150 mg/day, instenon (1 drop 2-3 times a day), pentoxifylline (agapurin, trental is 300-400 mg/day), nimodipine (nimotop - 90 mg/day), nicotinic acid drugs (nicotinate ksantinola is 300-400 mg/day). Among the antagonists of calcium ions preference has nimodipine, which operates predominantly in the cerebral ve metabolic means using Cerebrolysin (10-20 ml intravenous infusion of isotonic sodium chloride, only 20-30 injections per course), piracetam or nootropil (1.6 to 4 g/day), pyritinol (engjefabol 200-400 mg/day), gliatilin (0.4 g 2-3 times a day), Semax (500-5000 mg/day), eminole (1.5 to 3 g/day), recognis E (100-250 mg intravenously 1 time per day). Because in the pathogenesis of TE specific role of oxidative stress, pathogenetically justified seems to be holding antioxidant therapy Ginkgo biloba, vitamin E and other
In addition to the traditional comprehensive medical treatment, according to testimony, use of methods of physiotherapy (electro-stimulation, magnetic field, balneotherapy).
Also known is a method of treatment of patients with vascular diseases of the brain with the use of hyperbaric oxygen therapy (HBOT), which is the introduction of oxygen under a pressure of 1.25-1.5 ATM through the respiratory system. This allows you to reduce oxygen deficiency and reduce the appearance of disturbed brain function in patients with DE (N. Kazantseva.In., Gusev, E. I., Yellow N. N., Resurrection O. N. The influence of different modes of hyperbaric oxygenation on the aggregate state of the blood and the processes of free-radical oxidation in patients with early signs of failure krovosnabgenie the following contraindications: 1. Hypertensive heart disease. 2. Drain bilateral pneumonia. 3. Pneumothorax. 4. Impaired patency of the auditory tubes. 5. Acute respiratory disease. 6. Claustrophobia. 7. Increased sensitivity to oxygen.
Subjective reactions in connection with HBOT (tachycardia, tachypnea, hypertension, discomfort) described in 11% of all observations (5000 cases). Department of HBO apply to objects of great technical complexity and increased risk.
Also known is a method of treatment of TE, including the use of ozone therapy (RU # 2163124 C2, IPC a 61 K 33/00, a 61 P 25/00). However, despite the relatively high efficiency of ozone therapy even as monotherapy, wide application of the method is limited by the need for sophisticated equipment and specially trained personnel.
A prototype of the invention is selected known method of treatment of TE, including traditional comprehensive drug therapy using at least vasoactive, kardiologicheskij and vitamin preparations (Diseases of the nervous system./Ed. by N. N. Yakhno, D. R. of Stulman, T. 1, M.: Medicine, 2001, S. 283 and 284).
According to the authors of the present invention, the positive aptenia characterized by insufficient severity. Thus, the reduction in headaches occur from 6.3±0.4 to about 3.1±0.5 points (visual analogue scale); sample Schulte (reflects particular attention, speed switch) is characterized by the following dynamics - reducing time to 61.8±2,2 sec to 55.3±2,6 sec. Positive changes of EEG and REG, but the degree of these changes is also insufficient, namely, the increase of the amplitude of the alpha rhythm (EEG) and indicators improve venous outflow (REG) were insignificant.
The task of the invention is supposed to increase the effectiveness of treatment dyscirculatory encephalopathy due to: increase the number of patients with improvement; achieving greater severity reduce headaches and improve performance in a sample Schulte; more pronounced positive dynamics of EEG and REG.
The task in the treatment of TE, including traditional comprehensive drug therapy using at least vasoactive, kardiologicheskij and vitamin preparations, is achieved by the fact that more complex treatment includes ceruloplasmin, which is administered daily for 8-10 days intravenous infusion at a rate of 30-35 drops at a dose of 100-200 mg in the In the present invention for the first time are encouraged to apply ceruloplasmin for the treatment of TE. Conducted by the authors of this proposal studies first showed that the inclusion in the comprehensive treatment of DE ceruloplasmin increases the number of patients with improvement (with 80 to 89.9 percent), gives almost twice the intensity reduction of headaches and a significant growth improvement in the sample Schulte (see tab.1 and 2). In addition, the use of ceruloplasmin in conjunction with traditional medical treatment gives a more pronounced positive dynamics of EEG and REG, namely a significant reduction in the total disruption of bioelectric activity, the increase in the amplitude of alpha activity in the EEG, the settlement of vascular tone by improving blood circulation on the REG.
Comparison of treatment effect of TE on the prototype method and the proposed method are given in table.1 and 2. The tables indicate that additional positive effect of ceruloplasmin is expressed antioxidant properties (this was previously known to the authors of this application) that allows you to exclude from the complex treatment known antioxidant supplements (such as vitamin E, Semax, Mexidol, tanakan) and thus reduce the total drug burden and cost of treatment.BS, burns, inflammatory diseases and cancer, and is known as the carrier of copper, a stimulator of hematopoiesis and antioxidant (see, for example, the instructions for use of the drug ceruloplasmin produced Nizhny Novgorod state enterprise for production of bactericidal drugs firm “Ambio”, 2002).
Ceruloplasmin by the proposed method is entering a period of 8-10 days intravenous infusion at a rate of 30-35 drops per minute at a dose of 100-200 mg in the form of a solution containing 100 mg of ceruloplasmin 200 ml isotonic sodium chloride.
The course lasts 8-10 days due to the fact that shorter is not effective enough, and more than 8-10 days to be impractical due to the lack of further increase of the effect.
The introduction of the drug intravenously and slowly (at a rate of 30-35 drops per minute) due to the protein nature of the drug, in virtue of which it is necessary to introduce the drug to prevent possible allergic reactions.
Single dose of 100-200 mg was chosen on the principle of the smallest possible effective dose, so that an excessive increase did not lead to additional drug load on the body is FDI. It should be noted that the observed and described in the application above, a positive effect was observed in virtually all patients after a single dose of 100 mg of ceruloplasmin on the background of a comprehensive drug therapy with a minimum number of components (Vinpocetine, Riboxin, vitamin B6), i.e. the reduction of polipragmazie.
The use of ceruloplasmin in the form of a solution in isotonic sodium chloride at the rate of 100 mg per 200 ml solution is a common technique developed by the manufacturers of the drug.
The proposed method is as follows.
Treatment ceruloplasmin conducted against the backdrop of traditional comprehensive drug therapy (if necessary combined with physiotherapy, physiotherapy). As mentioned in the description of the method of the prototype, the selection of complex carry out individually. The authors of this application treatment ceruloplasmin was held while following traditional complex therapy: the ingestion of Vinpocetine of 0.005 to 3 times a day, vitamin B6 in the form of intramuscular injection, 5% 2 ml №20 and Riboxin of 0.2 to 3 times a day, and therapeutic exercises. Ceruloplasmin is entering a period of 8-10 days intravenous drip rate of the target sodium chloride.
Examples of specific performance of the method is given in the form of extracts from the history.
B-I P., 56, East. disease No. 0223878. Date 01.10.2002, extracts 21.10.2002, Diagnosis: TE II senior with severe emotional disability and mild ataxic syndrome on the background of atherosclerosis of the coronary and cerebral vessels. Sick since 1995
Along with the traditional treatment, including the ingestion of Vinpocetine from 0.005 to 3 times a day, Riboxin 0.2 to 3 times a day, intramuscular injection, 2 ml of 5% solution of vitamin B6 No. 15 and therapeutic exercises conducted drip intravenous ceruloplasmin 100 mg isotonic sodium chloride 200 ml daily, just No. 10. Obtained a significant improvement of health, attention, sleep, mood, decrease headaches from 5 points to 1 point, eliminated the effects of cerebellar ataxia. REG in the dynamics of the increase of pulse flow all basins, improving venous outflow. EEG positive trend in the reduction of the total disorganization of the bioelectric activity, increasing the amplitude of the alpha rhythm. Changes of biochemical parameters before and after treatment: cholesterol total of 7.2-6.4 mmol/l, malonic dialdehyde receipt 30.08.2002,, statement 18.09.2002, Diagnosis: TE I Art. with moderate emotional-volitional disorders, cochleo-vestibular syndrome on the background of atherosclerosis of cerebral vessels and cervical degenerative disc disease. Sick since 1999
On the background of traditional treatment, including ingestion of Vinpocetine of 0.005 to 3 times a day, Riboxin, intramuscular injection, 2 ml of 5% solution of vitamin B6 No. 15, massage of neck and collar area and physiotherapy, a course of intravenous drip treatment ceruloplasmin in a dose of 100 mg in 200 ml of isotonic sodium chloride solution, just No. 10. The good effect of the treatment: headache, dizziness't bother, decreased noise in the ears. REG - improve blood circulation in the system of the vertebral-basilar arteries. EEG - reducing dysfunction of the median non-specific brain structures. Biochemical studies in the dynamics: cholesterol total of 6.8-6.4 mmol/l of malonic dialdehyde 0,212-0,096%, superoxide dismutase 213,27-398,15 units
The proposed method treated the main group of patients TE of 30 patients, the control group consisted of 25 patients, matched for age, gender, comorbidity. Positive effect from the proposed method of treatment in 27 patients (89.9 percent), tx2">1. A method for the treatment of dyscirculatory encephalopathy by complex drug therapy, characterized in that, as specified therapy using the introduction of the patient Vinpocetine, Riboxin, vitamin B6, and ceruloplasmin, and ceruloplasmin injected daily for 8-10 days intravenous infusion at a rate of 30-35 drops per minute at a dose of 100-200 mg in the form of a solution containing 100 mg of ceruloplasmin 200 ml isotonic sodium chloride.
2. The method according to p. 1, characterized in that the individual readings in the complex treatment include massage, physiotherapy, remedial gymnastics.
R1means alkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C-atoms; CandH2A-phenyl, where a = 0, which is unsubstituted or substituted by 1-3 substituents selected from the group consisting of F, Cl, Br, J, CF3, metoxygroup; CdH2d(C3-7-cycloalkyl, where d = 0; R2and R3independently from each other denote hydrogen, F, Cl, J, C=N; COR6where R6denotes hydrogen, alkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C-atoms, OR30where R30- alkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C-atoms; OR7where R7denotes hydrogen, alkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C-atoms; phenyl; or R2and R3, independently of one another, denote CqH2q-phenyl, where q=0; or R2and R3independently from each other mean-SOnR22where n stands for zero, R22- alkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C-atoms; R4and R5independently of one another denote hydrogen, alkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C-atoms, F, Cl, Br, J, CF3and their physiologically acceptable salts; and to medicines, inhibiting Na+dependent Cl-/HCO-3- exchange rate is
where: A means-OR1-C(O)N(R1R2or-N(R1R21; each X, Y and Z independently represents N or C(R19); each U represents N or C(R5), provided that U is N only when X represents N, and Z and Y denote CR19; each W represents N or CH; V denotes: (1) N(R4); (2) C(R4)H; or (3) the groupdirectly related to the group -(C(R14R20)n-A,denotes a 5-6-membered N-heterocyclyl, optionally containing 6-membered ring additional heteroatom selected from oxygen, sulfur and NR6where R6denotes hydrogen, optionally substituted phenyl, 6-membered heterocyclyl containing 1-2 nitrogen atom, optionally substituted 5-membered heterocyclyl containing 1-2 nitrogen atom, aminosulfonyl, monoalkylammonium, dialkylaminoalkyl,1-6alkoxycarbonyl, acetyl, etc
or their pharmaceutically acceptable salts, where Y and Z each for each case independently represents a D - or L-natural or unnatural-amino acid; n in each case independently is 0 or 4, (I) provided that both n cannot simultaneously be 0; and 0 or 4 (II)
moreover, these amino acids (I) are chain: X1-X2-X3-X4where X1represents Tyr or Trp, which may be protected by a BOC group; X2represents D-Trp; X3represents Lys, which may be protected by a BOC group; X4is a Nal, Tyr or Thr; m is 0; a represents N or R1b means HE or OR1; (II) X1is a natural or non-natural D - or L-isomer of Phe, Trp or Tyr, where in the case when X1is Tyr, an aromatic ring in its side chain optionally substituted by R6; X2is a D - or L-isomer of Trp; X3represents Lys; X4represents Opticheskie ring, disposed in its side chain may be optionally substituted by R6or in the case when X4is either Ser or Thr, the oxygen atom located in its side chain, optionally may be substituted by one or more R1