A method of treating schizophrenia in women
(57) Abstract:The invention relates to medicine, namely to psychiatry. For 40-90 days orally administered methyltestosterone dose of 0.0005 g twice a day with an interval of 25-30 minutes Then for 40-90 days to introduce methyltestosterone dose of 0, 0005 g and after 25-30 minutes haloperidol 0,00015, While during the entire course of treatment for 2 h before the first and after the last medication exclude food intake, tobacco Smoking and applying lipstick. The method allows to reduce the treatment time and increase the duration of remission. table 2. The invention relates to medicine, in particular to the field of psychiatry, and can be used to increase the effectiveness of treatment of continuous and protopopescu-having a progressive forms of schizophrenia in women.There is a pathogenetic concept that schizophrenia is regarded as one of the forms of biological inconsistencies sexual phenotype genotype . Based on this concept developed methods for diagnosing schizophrenia in men and women . Applied method for the treatment of male patients with schizophrenia, using small doses of hormonal drugs [4, 5]. There is a method of treatment of women, the ill and mealtimes, when derpession States continuously current schizophrenia sex hormones administered in two cycles within 2-4 months, in the first cycle for 30-60 minutes before a meal, during the second cycle through 30-60 minutes after a meal for 2-4 months .The above method is the closest to the claimed method of treatment. The disadvantage of this method is the limited application of the framework of depression and low duration of remission, reaching 1-1,5 years.The aim of the invention is the extension of remission and reduction of treatment time.Present goal is achieved by the fact that after the diagnosis of schizophrenia in women  treatment of schizophrenia in women through the introduction of sex hormones is that the patient is prescribed methyltestosterone 2 times a day with an interval of 25-30 minutes for 40-90 days, followed by determination of the change of transcapillary exchange for the introduction of methyltestosterone, and when this indicator is normal, the patient is administered methyltestosterone followed after 25-30 minutes with a single receiving haloperidol for 40-90 days.In the method of treatment used hormonal drug androgenic number - methyltestos is the quiet administered orally, daily, free from eating, Smoking tobacco, chewing gum, and applying lipstick before the first and after the second medication at least two hours.The time interval 25-30 minutes creates optimal conditions under which registered the beginning of a change of transcapillary exchange after the drug load .A wide range (40-90 days) holding fragments of treatment due to the fact that the time of occurrence of the normalization of transcapillary exchange in the process of therapy is strictly individual, and not exactly predictable.Two hormonal drugs in small doses provides no side effects and is sufficient for normalization violations of transcapillary exchange.Method for the treatment of schizophrenia in women is as follows.When violations of transcapillary exchange (THAT) when serial reception loads, expressed in acceleration after the introduction of drug-androgenic drug type methyltestosterone and in slowing down after adrenolytic drug type haloperidol compared with the previous PA (Methyltestosteroni) in a dose of 0.0005 g, which is administered orally for 40-90 Nam daily consistently 2 times with an interval between doses in 25-30 min and a two-hour period free from eating, chewing gum, Smoking and applying lipstick before and after the second dose of medication. After clinical examination and radiological studies of transcapillary exchange, pointing to its normalization, coming in response to drug oral load of methyltestosterone in a dose of 0.0005 g, the patient carried out the second stage of treatment with the drug androgenic number - methyltestosterone dose of 0.0005 g followed through 25-30 minutes adrenolytic drug - haloperidol (Haloperidoli) at a dose of 0.15 mg and a two-hour period free from food intake, tobacco Smoking and applying lipstick before the first and after the second medication with the subsequent clinical examination and radiological control changes transcapillary exchange before the normalization changes in transcapillary exchange for receiving haloperidol.Schizophrenia treatment by the above method was performed in 70 patients women with continuous and protopopescu-progredient course of terapia hormonal method was not. The characteristics of therapeutic effects come in 2-3 days; the establishment of clinical remission at 20-25 day. After stabilization of remission and normalization of character changes on hormone and drug load, coming to the end of the 1.5-3 months of treatment, hormonal drugs are canceled and the patients are in remission without any maintenance therapy, which is valuable in this method of treatment in comparison with the known. The duration of remission up to 4 years. Improvement in varying degrees was observed in all 70 patients.Examples of the method of treatment of women with schizophrenia:
Example 1. Patient GMV. The history N 401. Born in 1964.Diagnosis. Schizophrenia, indolent. Paranoid syndrome.From the anamnesis: Heredity - the mother of the mentally ill. There is about schizophrenia paranoid form. Father is healthy.Previously, the development of our patient without deviation from the norm. The character was active, lively, stubborn, volatile, loud. He studied at the school on their own, without assistance. The study did easily. At 11-12 years of age was a period of vague headaches, blurred in my head, feeling something neoplasticism healthy person. Graduated from high school, culinary College. Worked as a pastry chef. During this period of time has changed somewhat in character. Appeared unusual for earlier patient mistrust and anxiety. In March 1983 on the background of practical health appeared "near-unconscious state, fears. Was afraid to die. Began to call an ambulance. Despite the fact that this condition has been treated, since the constant concerns for the heart, because it will stop. Appeared General fatigue, the state of a breath that occur periodically. After 2 weeks again there was a sudden fear of death and fear of going crazy. Against the background of fear and anxiety was hospitalized in a psychiatric hospital. After 3-month treatment was transferred to the II group disability mental illness. The house was afraid to remain one. Felt the tension in my head, fear of going crazy. Began to complain that she had changed its face. It travels throughout the body. Sees the inner "eye" her face in his chest and stomach. Almost completely stopped reading. In my mind emptiness, periodically feels unnatural inversion of the feet", which at this time acquire a sense of otherness. Despite ongoing therapy is almost not changed.In the study of the nature of the changes on drug and hormonal load revealed the following violations: original level by the right hand is equal to 12 minutes. After administration of haloperidol in a dose of 0.15 mg, THEN accelerated to 8 minutes. After 25 minutes after administration of the hormone androgen load - methyltestosterone dose of 0.0005 g - slowed to 14 minutes. The presence of a specific sequence of changes of the load in terms of the violation on the receiving haloperidol in the form of acceleration and subsequent deceleration of the load methyltestosterone, is characteristic of the schizophrenic process.At the first stage of treatment the patient was assigned to oral methyltestosterone dose of 0.0005 g, consistently twice a day with an interval between taking the medicine in 25-30 minutes and a two-hour period free from food intake, tobacco Smoking applying lipstick before the first and after the second medication at least two hours. From the outset of therapy appeared sleepy. Sleeps up to 14 hours a day. Upon awakening Vala, apathetic, indifferent to the world around them. Actively their painful experiences are not expressed. Marked indifference to matters concerning her own painful on the awn pseudohallucinations visual impairment. Appeared the possibility of concentration. Became a bit of fiction, but gets tired quickly. After the second portion being significantly retarded, somnolence. 48 day therapy appeared disorders as early awakening. After receiving the second portion of the medication 30 minutes later the patient came to life, began to joke, to laugh. Accelerated the flow of thoughts. This state lasted about 1.5 hours and independently disappeared. Therapy was discontinued. 4 days after discontinuation of treatment performed radiological examination. The initial level THAT is 8 minutes. After the drug load-methyltestosterone oral dose of 0.0005 g fixed slow until 26 minutes, which corresponds to the normal response of the body female on this load.The second phase of treatment consisted in taking methyltestosterone dose of 0.0005 g, followed, after 25-30 minutes taking haloperidol at a dose of 0.15 mg and a two-hour period free from food intake, tobacco Smoking and applying lipstick before the first and after the second dose of medication. After the second portion of the medicine comes a sharp drowsiness, lethargy, muscle relaxation. Active productive padrote, tidal forces, increasing the overall tone occurred after the second portion of the drug. Therapy was canceled. After 4 Nam after discontinuation of treatment during radiological examination of its initial level equal to 6 minutes After exercise haloperidol at a dose of 0.15 mg is fixed corresponding to the rate of deceleration before 14 minutes.The patient calm, quite active. Painful experiences are not expressed. Rapid mental fatigue, which disappears after a short rest. About their painful experiences in the past, trying once again not to speak, because it's hard to remember. Currently active productive psychopathological symptoms cannot be diagnosed.Remission for 7 years. Works, no complaints. Indicators THAT 7 years after the end of therapy: initial level THAT is 8 minutes. After loading haloperidol at a dose of 0.15 mg, THEN slowed down to 16 minutes. 20 minutes after load methyltestosterone dose of 0.0005 g, came acceleration with 16 minutes to 10 minutes.Dynamics of change: slow acceleration (normal).Example 2. Patient P. T. A. 1959 birth. The history N 1581. Diagnosis: schizophrenia, L - my father had chronic alcoholism. Mother nature suspicious, anxious, short-tempered and jealous.Our patient in early development from his peers did not lag behind. Was raised by his grandmother. Grew meek, was fair, honest and up to grade 6 student. The school was selectively sociable, characterized by shyness and lack of confidence in the choice of a particular line of conduct in a particular situaciiu. With 13 years has shown character traits such as stubbornness, temper, combined with emerging hysterical traits of behavior in conflict situations. Sometimes was dejected, gloomy. In this period of time no one spoke. However, these conditions did not last long and was treated independently. Began to keep a diary, which is constantly something down. With 14 years has become more lonely. Stopped playing sports, deepened in their own experiences. With 16 years appeared indifferent to, laziness. Cooled to study. With great difficulty passed the exams in school. After high school, despite the lethargy and apathy, tried to go to medical school, but did not pass a single exam. After the failure of submitted papers in College and was accepted to study in cooperative technitron and anxiety for the future. He started to realize that in these times people in her appearance, understand that it is not such as all. Became suspicious, anxiety did not leave the patient. Stopped to sleep. Thoughts went against the will, it has become difficult to cope with the work. In 1983, has been hospitalized in a psychiatric hospital. The mental condition of the patient was determined depersonalization and derealization disorders. The mood is sad, quiet voice. She is forced to constantly engage in soul-searching and introspection itself, because it did not feel "I". It is dissolved in it and disappeared compare yourself with others. Everything around me is grey, dull, through "thick glass in the fog". Herself sick as a machine, robot". There is no individuality. In the Department of surrounding understand that it is not in his mind. In my head thoughts are unusual - with breaks, stops, flows.Under the influence of therapy with amitriptyline, phrenolon, Melilla, haloperidol, fenazepam mental condition of the patient improved after 2 months the patient was discharged on the work. After 8 months of relatively good health readmitted with the same mental state.In the study of nature izmenenie 25 min THEN increased from 12 to 8 minutes After 25 min after administration of methyltestosterone in a dose of 0.0005 g THEN slowed down with 8 minutes to 18 minutes.The dynamics of change after loads: acceleration - deceleration. This dynamic is typical of schizophrenic process in women.At the first stage of treatment the patient was assigned methyltestosterone 0.0005 g two consecutive time intervals between taking the medicine in 25-30 min and a two-hour period free from eating, Smoking, applying lipstick before the first and after the second dose of medication at least two hours. On the 22nd day of medication was desactualizado depersonalization and derealization disorders. Improved mood, decreased anxiety fears disappeared pedophobia the idea of a relationship. On the 43rd day of therapy, after receiving the second portion of the medication after 30 minutes the patient felt instead of feelings of lethargy and complacency surge of strength and energy. Has elements of speech govorlivosti, joy, a sense of increasing efficiency. This state lasted for about 2 hours and independently disappeared. Therapy was cancelled. After 5 days radiological study. Its original level 10 minutes After exercise methyltestosterone in a dose of 0.0005 followed by a reception, after 25-30 minutes of haloperidol in a dose of 0.15 mg on a background of two-hour period free from food intake, tobacco Smoking and applying lipstick before the first and after the second medication. After the second portions of the medications the patient is asleep. In General, the behavior of the patient ordered, no complaints. 58 day of treatment, after the second portion of the drug occurred temper and lifting mood, which lasted about 2 hours and passed independently. Therapy was canceled. After 6 Nam study. The initial level THAT is equal to 6 minutes After exercise haloperidol recorded corresponding to the rate of deceleration until 16 minutesThe patient ordered in behavior. Adequate in conversation, responds to questions. Thinking violations not detected. Estensione. Productive psychopathological symptoms no.Remission of 9.5 years. No complains. Works. Indicators after 9.5 years of remission. The initial level THAT is equal to 6 minutes After exercise haloperidol at a dose of 0.15 mg slow to 12 min 25 min after administration of methyltestosterone in a dose of 0.0005 came acceleration from 12 to 8 minutes Dynamics of change: slow acceleration (normal).Data reduction time Leche the table. 1, patients in remission "-S" after pharmacotherapy at carrying out the new method of treatment went into remission A and B. Patients who were in remission C and D, after a new method of treatment have passed in a group of patients with remission B and B-C. it is noteworthy that the new method of treatment in contrast to the prototype generates A remission, which is not observed in the prototype.Consider the effectiveness of the new method of treatment in terms of remission period (PL. 2).The results indicate significant differences of the proposed method of treatment from other methods according to the time of remission (p < 0,001). Another difference is that when pharmacotherapy short periods of remission lead to the need for permanent supportive drug therapy, needs a new way of treatment.The claimed method of treatment of women with schizophrenia provides long-lasting improvement, lengthen remission to 9 years, no side effects, and in remission does not need maintenance therapy.The sources of information.1. Smirnov, C. K. Schizophrenia as one of the forms of biological inconsistencies sexual phenotype to genotype. In the book: Tr. M is the changes in the clinic of certain mental illnesses. Method. REC. Decl. RSFSR Ministry of health, 1983.3. Smirnov, C. K., Ovsyannikov, S. A. treatment depressivnyj States. Copyright certificate for invention N 751400. Appl. 05.78/260 7704/28-13. Publ. 30.07.80. Bull. 28.4. Smirnov, C. K., etc. a Method of treating schizophrenia in men. Chipboard. Application "4044543/28-14 (031736) Floor. solution from 23.09.86.5. Smirnov, C. K., and Some other data for use in the outpatient setting gonadal hormones in patients with schizophrenia in acute psychotic state. In the book: New methods of treatment and rehabilitation of mentally ill in community-acquired conditions. M., 1979, S. 155-157.6. Smirnov, C. K., Ovsyannikov, S. A. method for the diagnosis of schizophrenia in women. Copyright certificate for invention N 1292738. Bull. 8 28.02.87. A method of treating schizophrenia in women through the introduction of hormonal preparations, characterized in that the patient is in the over 40 - 90 days orally administered methyltestosterone dose of 0.0005 g twice a day with an interval of 25 to 30 minutes, then after normalization of transcapillary exchange (SOMETHING) in the form of a slowdown after a single dose of Metallostroy in a dose of 0.0005 g for 40 - 90 days orally administered methyltestosterone dose of 0.0005 g and 25 - 30 min haloperidol at a dose of 0.00015 grams before and after the second dose, free from eating, Smoking tobacco, chewing gum and applying lipstick, is not less than 2 h, and between the first and second medication dose of at least 25 - 30 minutes
FIELD: organic chemistry, biochemistry, medicine, pharmacy.
SUBSTANCE: invention relates to new sulfur-containing compounds of the formula (I):
their pharmaceutically acceptable salts or solvates, or salt solvates wherein R1 represents (C1-C6)-alkyl, cycloalkyl, aryl, aliphatic or aromatic heterocyclyl substituted with one more basic group, such as amino-, amidino- and/or guanidine-group; R2 represents hydrogen atom (H), alkyl, alkylthio-, alkoxy- or cycloalkyl group; R3 represents COOR5, SO(OR5), SOR5 and others; R4 represents hydrogen atom (H) or (C1-C6)-alkyl; R6 represents hydrogen atom (H); X represents C(Z)2 or NR6CO; Y represents C(Z)2; Z represents hydrogen atom (H), (C1-C6)-alkyl, aryl or cycloalkyl. Indicated compounds inhibit activity of carboxypeptidase U and can be used for prophylaxis and treatment of diseases associated with carboxypeptidase U.
EFFECT: improved preparing method, valuable biochemical and medicinal properties of compounds.
14 cl, 36 ex