Method of treating chronic anal fissure

FIELD: medicine.

SUBSTANCE: invention refers to medicine, particularly coloproctology, and may be used for treating chronic anal fissure. The method involves an anal fissurectomy with a graduated sphincterotomy and a drug-induced therapy. A patient's preoperative psychoemotional status is assessed by questionnaire survey according to the Hospital Anxiety and Depression Scale (HADS). If the disorders have been shown by the questionnaire survey, namely 8-10 points "subclinical anxiety/depression" or 11 points and more "clinical anxiety/depression", a psychopharmaceutical therapy with Grandaxin or Tianeptine. The preparations are administered in common doses for 4 weeks.

EFFECT: method provides the effective treatment of the disease with comorbid psychoemotional disorders, exposure on the additional mechanisms of the anal fissure pathogenesis in this case.

3 ex

 

The invention relates to medicine, namely to surgery, and can be used in Coloproctology for the treatment of chronic anal fissure.

Anal fissure (fissures) - fairly common proctologic disease (from 8.5 to 16%). While women suffer in 1,5-2 times more often than men (Hierome, 2001). According to the use frequency of occurrence of anal fissure is 20-23 cases per 1000 of the adult population, more than one-third of patients - mostly in the younger and middle age, i.e. the age Hierome, 2001). Thus, in addition to health, this issue has great social significance.

Anal fissure is caused by damage to the mucosa of the anus, more than 90% of patients with anal fissure has a background of disease, leading to the defeat of the mucous membrane of the rectum and anoderm, such as proctosigmoiditis, gastritis, pancreatitis, hemorrhoids and other (Sveri, 2011). The reason for the formation of anal fissures can be neurogenic disorders with prolonged spasm of the internal and especially external anal sphincter (US). Thus, an anal fissure is polietiologic disease that need to be considered in the process of treatment (Grateful L.A., 2002).

Primary acute fissure can heal the ü conservative, however, without warranty of relapse. Radical treatment of chronic anal fissure (HAT) is possible only by surgical treatment (usually excision within healthy tissue in combination with metered sphincterotomies in the case of hypertonic sphincter of the rectum). Conservative treatment and surgical intervention was carried out based on functional state of the locking apparatus of the rectum can provide recovery 98-100% of patients.

However, after the surgical treatment of relapses occur in 0.6%-11,1% of cases (Wlivjin, Ausbrechen, Snin, 2001). High recurrence rate after surgery for about anal fissures sometimes negates qualified the actions of the surgeon (Grosselin B.C., 2010).

A high percentage of recurrence surgical treatment necessitates the search for new effective ways of treating this group of patients.

The prevalence of this disease and the urgency of the problem has led to the emergence of a large number of different treatment methods.

A study of patent and scientific and medical literature revealed the following methods of treatment of chronic anal fissure.

There is a method of treatment of chronic anal fissure (RF Patent No. 2216283, 20.11.2003), including its excision, characterized in that the prior is about conduct clinical and instrumental examination of the patient to determine the increased risk of anal incontinence and the presence of at least one of the following symptoms: reduced depth of the anal funnel, the stress incontinence, anterior rectocele any degree, a history of long labor or childbirth large 4000 g fruit, rupture or dissection of the perineum during childbirth, more than one birth, age older than 55 years, when defecography - prolapse of the pelvic floor at natureway more than 4 cm, anorectal manometry is an increase in the amplitude of the relaxation of the internal sphincter more than 26 mm Hg, increase relaxation of the internal sphincter more than 15 s, the reduction of pressure in the anal canal at the level of the external sphincter is less than 18 mm Hg, a decrease in the amplitude of contraction of the external sphincter less than 4.8 mm Hg if sphincterotomy - reducing power of volitional contractions in men less than 570 grams at 3 and 9 and less than 510 g at 6 and 12 hours, for women less than 520 grams at 3 and 9 hours and less than 385 g at 6 and 12 hours, the increase in time of the excitation on both nerve more than 2.4 MS, surgical intervention limit excision of anal fissure and applied to the perianal skin around the opening of the anus 0,3% nitroglycerine ointment, apply the ointment repeated after 12 h within 2-8 weeks.

However, according to some authors, the healing HUT within 1-2 months see approximately 45-60% of patients (Nov, Chronic anal fissure, No. 1, page 11, 2008). Every second of them in terms of the number is x months to 1 year, there is a relapse of the disease. Not all patients can adapt to treatment and are forced to abort due to the occurrence of such side effects as headache, tachycardia, orthostatic hypotension, dizziness (20-60% of patients), which significantly reduce the quality of their lives. Discontinue treatment with nitrates around 20% of patients

A known method of surgical treatment of chronic anal fissure (RF Patent No. 2293529, 20.02.2007), including excision of anal fissure, characterized in that before the operation executes sphincterotomy, when the basal pressure in the anal canal in the projection of the internal sphincter 60 cm column of water up to 120 cm column of water cut through the sphincter longitudinally to the upper edge of the anorectal ring on milfinternal furrow in persons dolichoderinae body type in the area from 3 to 5 h conditional dial, persons meso - and brachymorphic body types - the area from 4 to 6 h, and at the basal pressure in the anal canal in the projection of the internal sphincter above 120 cm column of water - in people of all body types, additionally cut the sphincter longitudinally to the upper edge of the anorectal ring on milfinternal the furrow with the contralateral side in the area from 9 to 7.5 h conditional dial.

The disadvantages of this method include limited its application at the location of hronicheskoi anal fissure atypical, the presence of 2 or more cracks, and when combined chronic anal fissure with other proctological diseases (hemorrhoids, paraproctitis, etc.).

There is a method of determining the tactics of treatment of anal fissure (RF Patent No. 2310371, 20.11.2007), characterized in that the estimate duration of disease, previous treatment, the basal level of pressure in the anal canal in the projection of the internal sphincter, the average pressure in the anal canal during volitional contraction, the presence of chronic hemorrhoids, then calculate the score index, the duration of the disease up to 1.5 months assigns 1 point, from 1.5 to 3 months - 2 points, from 3 months to 1 year - 3 points, more than 1 year - 4 points; evaluating the pre-treatment, assign 1 point if the treatment is not carried out, 2 points - if temporary, unstable effect from conservative therapy, 3 credits in the absence of effect from conservative therapy, 4 points - at relapse after surgical treatment; assessing the level of basal pressure in the anal canal in the projection of the internal sphincter, assign 1 point if the pressure is within normal limits, namely 49-67 mm Hg; 2 points - pressure increases by 15-30% with respect to the norm; 3 points - an increase of 31-50% with respect to the norm; 4 points - increasing more than 50%; estimating the average pressure in the anal canal when the strong-willed with the treatment assign 1 point if the pressure is within normal limits, namely 58.8 to 94,4 mm Hg; 2 points - pressure increases by 15-30% with respect to the norm; 3 points - an increase of 31-50% with respect to the norm; 4 points - increasing more than 50%; assessing the presence of chronic hemorrhoids, assign 1 point if no hemorrhoids or chronic hemorrhoids 1 stage, 2 points for chronic hemorrhoids 2 stage, 3 points for chronic hemorrhoids 3 phase, 4 points for chronic hemorrhoids (stage 4), and then summed scores, and when point index from 8 to 11 points shown excision cracks without sphincterotomy, and at point index of more than 11 points shown excision cracks in combination with metered sphincterotomies.

The disadvantage of this method of determining the tactics of treatment of anal fissure is a technical difficulty in determining the point of index patients, as well as limited use of this method associated with the presence of diagnostic equipment to determine the basal pressure in the anal canal.

The prototype of the claimed invention, we selected the method of treatment of chronic anal fissure (RF Patent No. 2216283, 20.11.2003).

The prototype disadvantages are eliminated in the invention.

The objective of the invention is to devise effective treatment for chronic anal fissure patients with naru is enemy psychoemotional sphere (i.e. anxiety and depression).

The inventive method of treatment of chronic anal fissure takes into account the individual characteristics of patients with chronic anal fissures, to avoid tactical mistakes when forming the indications for surgery and sphincterotomy. The problem is solved by the fact that carry out the surgical treatment (excision of anal fissure dosed sphincterotomies) in combination with medication, previously, in the preoperative period, the patient will explore the history and identify the impact of psychogenic stress factor, establish its relationship with disease (sharp crack of the stress) and determine the psycho-emotional status using the questionnaire on the hospital scale of anxiety and depression HADS. Those patients who have been diagnosed with disorders on the results of the questionnaire 8-10 points - "subclinical expressed anxiety/depression" or 11 points and above is "clinically severe anxiety/depression", I appoint psychopharmakotherapie (drugs grandaxin and tianeptine). This group of patients in the preoperative period additionally perform sphincterotomy to determine the objective status of the external and internal sphincters of the rectum. The study revealed an increased tonus of the sphincter of the rectum, and then carry out surgical treatment - excision of anal Tres who were dosed with sphincterotomies. During the postoperative period continue psychopharmakotherapie assigned in the preoperative period.

The technical result from the use of a new method of treatment of chronic anal fissure: improving the results of surgical treatment of chronic anal fissure, reduce the frequency of relapse after surgery, as well as the reduction of postoperative complications.

According to some researchers in 3.8% of patients with HAT has chronic colitis, 2.3% - proctitis and proktoshigmoidit and 3.3% of patients identified neuropsychiatric disorders (etiology and treatment of anal fissures // Kurbanov I.N., The Faizullaev AH 2002). Thus, confirms the importance of psycho-emotional status in the development of the HUT.

Although the influence of emotional factors on the condition of the anal sphincter should not be considered as the main cause of the disease, it was found that some patients with fissures have some changes of the nervous system. Of course, one cannot deny the influence of neurasthenia and neurosis on the development process of the disease or the aggravation of existing background (like "vicious circle"), thus, changes of the nervous system and psyche only weaken the body and create conditions for the development of adverse factors contributing to the occurrence of C is the disease and its recurrence (Grateful L.A., Flights N.N., Zharkov E.E., 2007).

We have developed a method for the treatment of chronic anal fissure is pathogenetically justified (directed on elimination of a spasm of the sphincter of the rectum). During our studies have established the need to identify and correct violations of psychoemotional sphere of patients with chronic anal fissures depending on different degrees of severity of anxiety and depression. Explore the history and conduct surveys of patients with chronic anal fissures on the hospital scale of anxiety and depression HADS. The scale developed by Zigmond A.S. and R.P. Snaith in 1983 to identify and assess the severity of depression and anxiety in conditions of General medical practice. The advantage of the scale is the ease of application and processing (filling scale does not require a long time and does not cause difficulties for the patient).

We consider the problem from the point that stress leads to the formation of anal fissure, this is confirmed by our clinical observations. If the stressful situation continues for more than 1 month and there are psycho-emotional disorders in patients fissure becomes chronic. If stress is spontaneously takes place in the period up to 1 month, the crack heals on the background of conservative events.

We have determined the correlation between the ima is beneficial to emotional disorders and an increased tonus of the sphincter of the rectum. In the preoperative period was additionally performed sphincterotomy, and identified hypertonic sphincter of the rectum poduridae the need to perform a sphincterotomy. This allowed to choose the adequate treatment and to improve the results of surgical treatment of patients with chronic anal fissures by conducting pharmacotherapy pre-and postoperative stages (reduced tone of the sphincter of the rectum and reduce the healing time of surgical wounds, which reduces the frequency of relapse after surgery).

Individually grounded algorithm postoperative rehabilitation treatment and rehabilitation allows at the outpatient stage to improve functional results of patients operated on for anal fissures. This allows to increase the share of remote positive treatment results in average up to 93.3%.

Detailed description of the method and examples of its clinical implementation

The method is as follows. Explore the history and identify the impact of psychogenic stress factor, establish its relationship with disease (sharp crack of the stress) and conduct surveys of patients with chronic anal fissures on the hospital scale of anxiety and depression HADS. On the basis of objective physical and the social and instrumental (synchromedia) studies reveal the absence or presence of comorbidity. Produce scoring of the results obtained on a scale HADS. When interpreting the results take into account the total for each podskali (anxiety and depression). Take into account the changes above 7 points: 8-10 points - "subclinical expressed anxiety/depression" and 11 points and above is "clinically severe anxiety/depression". In the preoperative period in consultation with the psychiatrist prescribe psychopharmakotherapie according to the results of the survey on a scale HADS (correction of identified psycho-emotional disorders). Apply the following medications: anxiolytic action Grandaxin 50-100 mg per day for 1-3 admission within 4 weeks, anxiolytic and antidepressant Tianeptine 12.5 mg 1 t × 3 times a day for 4 weeks, with a gradual reduction of the dose for 7-10 days (according to the instructions to the drug use only small doses):

1) subclinical expressed anxiety (8-10 points on podskali alarm) - Grandaxin 50 mg per day for 1-3 receive 4 weeks;

2) subclinical depression measured (8-10 points on podskali depression) - Grandaxin 50 mg per day for 1-3 receive 4 weeks;

3) subclinical expressed anxiety and depression (8-10 points on podskali anxiety, 8-10 points on podskali depression) - Grandaxin 100 mg per day for 1-3 receive 4 weeks;

4) clinically the Ki expressed anxiety (11 points or higher on podskali alarm) - Grandaxin 100 mg per day for 1-3 admission within 4 weeks;

5) clinically relevant depression (more than 11 points on podskali depression) - Tianeptine 12.5 mg 3 times a day for 4 weeks, with a gradual reduction of the dose for 7-10 days;

6) clinically relevant anxiety and depression (more than 11 points on podskali anxiety, more than 11 points on podskali depression) - Tianeptine 12.5 mg 3 times a day for 4 weeks, with a gradual reduction of the dose for 7-10 days;

7) clinically evident anxiety, subclinical depression (more than 11 points on podskali anxiety, 8-10 points on podskali depression) - Grandaxin 100 mg per day for 1-3 receive 4 weeks;

8) subclinical anxiety clinically relevant depression (8-10 points on podskali anxiety, more than 11 points on podskali depression) - Tianeptine 12.5 mg 3 times a day for 4 weeks, with a gradual reduction of the dose for 7-10 days.

Psychopharmakotherapie continue further in the postoperative period, an individual approach to each patient.

In the preoperative period in order to objectively assess the state of the external and internal sphincter of the rectum perform sphincterotomy. Use synchrometer S4401 (Germany). After the objective physical, instrumental (synchromedia), and also completed a questionnaire on the hospital scale of anxiety and depression HADS and appointed with the purpose is the correction of violations pharmacotherapy produce surgical treatment of patients in the volume of excision of chronic anal fissure with metered sphincterotomies. Hypertonic sphincter of the rectum confirms the need to perform a sphincterotomy. Criteria for the effectiveness of integrated treatment is the assessment by the patient (the scale of overall clinical experience), assessment of pain intensity after surgical treatment, the assessment of the postoperative period, the presence of postoperative complications, assessment of duration of hospital stay and the time of rehabilitation, conducting sphincterotomy 1 month after surgery and 6 months after surgery (a decrease of tonus of the sphincter of the rectum compared with the original data).

The performance of the proposed method is confirmed by the following clinical examples.

Example 1

Patient M-Eva, 45 years, history No. 4327/147, was admitted to our Department with complaints on a periodic intensive nagging pain in the back passage, increasing during defecation and after him. From the anamnesis it is known that he was about 4 months, the disease was preceded by a stressful situation: divorce from her husband to the doctor about this disease is not treated, the treatment was not carried out. Objective examination of the anal area without scratching and MAZERATI, 6 hours conditional of the dial on the back in the anal canal is determined by the average crack size is 1.2*0,4*0.5 cm with elastic edges, a rectal examination is moderately painful, the tone of the sphincter subjectively increased, other colorectal pathologies it is not revealed. Indicators vnutrennego pressure according to sphincterotomy the following: the average pressure resting 63 mm RT. century, the average value during volitional contraction - 128 mm RT. Art. According to the results of a survey on the hospital scale of anxiety and depression HADS received 10 points for podskali alarm (subclinical expressed alarm") and 6 points on podskali depression (within normal limits). The patient in the preoperative period assigned to the following psychopharmacotherapy: Grandaxin 50 mg per day for 1-2 doses for 4 weeks. 17.04.09 operative treatment in the amount of excision of chronic anal fissure with dosed lateral sphincterotomy. The postoperative period was uneventful with moderate to severe pain when the finger examination of the rectum before discharge the patient from hospital marked subjective lowering the tone of the sphincter of the rectum compared with the original data. Assigned psychopharmacotherapy continued throughout the postoperative period. The patient was discharged on the 9th day from the hospital, the wound with signs of epithelialization, defecation moderately painful. At the control examination after 1 month the C after the operation of hypertonic sphincter of the rectum was not detected (data sphincterotomy: average pressure rest 55 mm RT. century, the average value during volitional contraction 115 mm RT. Art.), data for recurrence of the disease is not identified, other anorectal pathology is not detected, the patient is able-bodied. The patient rated their health on a scale of overall clinical experience as "a great improvement". 6 months after discharge at the control examination of the data for the recurrence of the disease was not detected.

Example 2

Sick And s, 30 years old, medical history, No. 5546/183, was admitted to our Department with complaints of pain in the anus during defecation and after him, poor allocation of red blood after each defecation. From the anamnesis it is known that he was about 6 months, the disease was preceded by a stressful situation: dismissal from work previously undertaken outpatient treatment is without effect. An objective examination of the anal area without scratching and MAZERATI, 6 hours conditional dial in the position of the patient on his back in the anal canal is defined by the rear crack size 1,5*1,0*0,5 cm, with dense edges, rectal examination sharply painful, the tone of the sphincter subjectively increased, other colorectal pathologies it is not revealed. Indicators vnutrennego pressure, according to sphincterotomy the following: the average pressure of peace - 68 mm RT. century, the average value during volitional contraction - 138 mm RT. Art. According to the results of the ANC is the pit on the hospital scale of anxiety and depression HADS received 12 points on podskali alarm ("clinically expressed alarm) and 9 points on podskali depression ("subclinical depression measured"). The patient in the preoperative period assigned to the following psychopharmacotherapy: Grandaxin 100 mg per day for 1-3 divided doses for 4 weeks. 14.12.2009, operative treatment in the amount of excision of chronic anal fissure with dosed lateral sphincterotomy. The postoperative period was uneventful, without complications, with a moderately severe pain. When the finger examination of the rectum before discharge of the patient from the hospital marked subjective significant reduction in tone of the sphincter of the rectum compared with the original data. Psychopharmacotherapy continued throughout the postoperative period, which greatly improved psycho-emotional state of the patient. Discharged from the hospital on the 8th day after surgery, postoperative wound with signs of epithelialization, defecation moderately painful, bleeding from the rectum is missing. At the control examination after 1 month after the operation of hypertonic sphincter of the rectum was not detected(data sphincterotomy: the average pressure from rest to 60 mm RT. century, the average value during volitional contraction - 120 mm RT. Art.), data for recurrence of the disease is not identified, other anorectal pathology is not found, the ability to work restored. The patient rated their health on a scale of overall clinical experience as "very is alsoe improvement". 6 months after discharge at the control examination of the data for the recurrence of the disease was not detected.

Example 3

Patient L-ova, 33 years old, medical history, No. 4604/158 was admitted to our Department with complaints of pain in the anus during defecation and after him, burning after defecation. From the anamnesis it is known that he was about 9 months, the disease was preceded by a stressful situation in the form of divorce, the previously held conservative outpatient treatment - unstable short-term effect. Objective examination of the anal area without scratching and MAZERATI, 6 hours conditional dial in the position of the patient on his back in the anal canal is defined by the rear crack sizes of 2.5*0,3*0,3 cm, with dense edges, painful rectal examination, when the finger rectal sphincter tone is subjective raised. Other colorectal pathology is not found. Indicators vnutrennego pressure according to sphincterotomy the following: the average pressure from rest to 62 mm RT. century, the average pressure during volitional contraction - 126 mm RT. Art. According to the results of a survey on the hospital scale of anxiety and depression HADS received 6 points on podskali alarm(within normal limits) and 5 points on podskali depression (within normal limits). Violations emotional status was not revealed who at the time of inspection, however., the patient notes that within about 6 months after traumatic situations, which coincided with the beginning of the disease, she had signs of depressive disorders, which were stopped on their own over time without medical treatment. 24.01.2009, operative treatment in the amount of excision of chronic anal fissure with dosed lateral sphincterotomy. The postoperative period was uneventful, bleeding from the rectum is not marked and the pain is moderate. When the finger examination of the rectum before discharge of the patient from the hospital marked subjective lowering the tone of the sphincter of the rectum compared with the original data. Discharged from the hospital 8 days after surgery, the wound with signs of epithelialization, defecation moderately painful, bleeding from the rectum is not. At the control examination after 1 month after the operation of hypertonic sphincter of the rectum was not detected (data sphincterotomy: the average pressure of peace - 54 mm RT. century, the average pressure during volitional contraction - 118 mm RT. Art.), data for recurrence of the disease is not identified, other anorectal pathology is not found, the ability to work restored. The patient rated their health on a scale of overall clinical experience as a "great improvement". Through 6 months after discharge at the control examination of the data for the recurrence of the disease was not detected.

The method was tested in 50 patients in the Department of Coloproctology Department of surgical diseases №2 Rostov state medical University. Results: reducing the frequency of relapse after surgery (study group relapse is not revealed), reducing healing time of surgical wounds (average for a few days) in comparison with the control group patients. Thus, detection of violations of the emotional sphere in patients with chronic anal fissures and their correction can improve the results of surgical treatment of such patients and to reduce the time of healing of postoperative wounds.

Analysis of the results showed that the application of the method of treatment of anal fissure objectivesare indications for surgical treatment of anal fissures, it is possible to quantitatively evaluate the feasibility sphincterotomy, improves the results of surgical treatment of such patients, allows to take into account the individual characteristics of the patient and his psycho-emotional status.

The method standardized indications for the choice of method of treatment of anal fissure, which allowed to improve the results and increase the effectiveness of the treatment, reducing the number of complications and relapses.

The advantages of the proposed method: the application of the proposed method contributes to improving the efficiency of treatment of patients with chronic anal fissures, improving the results of surgical treatment of chronic anal fissures, reducing the incidence of recurrence after surgery, and to reduce postoperative complications, taking into account individual peculiarities of the patient and by carrying out the correction of identified psycho-emotional disorders, which together contributes to improving the quality of life of such patients.

A method for the treatment of chronic anal fissure, including surgical treatment in conjunction with medication, characterized in that exercise excision of anal fissure dosed sphincterotomies previously in the preoperative period, the patient determine the psycho-emotional status by polling on the hospital scale of anxiety and depression HADS and patients who have been diagnosed with disorders on the results of the questionnaire 8-10 points - "subclinical expressed anxiety/depression" or 11 points and above is "clinically severe anxiety/depression", immediately after receiving the results of the questionnaire administered psychopharmakotherapie drugs grandaxin or tianeptine, which is injected in the usual doses for 4 weeks.



 

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4 cl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds presented by formula (IV) or to their pharmaceutically acceptable salts: , wherein: R140 specified in a group consisting of: H and halo; xa and xb mean the numbers each of which is independently specified in 0, 1 and 2; R150 and R160 are independently specified in a group consisting of H, halo, -CN, -CF3, -OCF3, -C1-C6alkyl, -C1-C6alkoxyl, -O-C2-C6alkyl-O-R53, -OR53, -C0-C6alkyl-S(O)0-2-R53, -C0-C6alkyl-C(O)NR50R51, -C0-C6alkyl-heterocyclyl wherein heterocyclyl is monocyclic and contains 6 atoms, and one or two atoms are independently specified in O and N; R50 and R51 and R53 are independently specified in a group consisting of -C1-C6alkyl.

EFFECT: developing a pharmaceutical composition, a method for histone deacetylase inhibition and a method of treating a polyglutamate disease wherein the polyglutamate disease is Huntington's disease.

8 cl, 332 ex, 10 tbl, 91 dwg

FIELD: chemistry.

SUBSTANCE: described is a composition with inhibitory activity on BACE1, which contains a compound of general formula (I), where ring A is an optionally substituted carbocyclic group or an optionally substituted heterocyclic group; E denotes a lower alkylene; X is S, O or NR1; R1 denotes a hydrogen atom or lower alkyl; each R2a, R2b, R3a, R3b, R4a and R4b independently denotes a hydrogen atom, an optionally substituted alkyl or optionally substituted carbocyclic group; each n and m independently denotes an integer from 0 and 3; n+m equals an integer from 1 to 3; R5 denotes a hydrogen atom or an optionally substituted lower alkyl; a pharmaceutically acceptable salt or solvate thereof. Described also is a compound of formula (I) and a pharmaceutical composition.

EFFECT: highly effective treatment.

21 cl, 170 tbl, 4 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: there are offered: the use of (S)-N-[2-(1,6,7,8-tetrahydro-2H-indeno[5,4-b]furan-8-yl)ethyl]propionamide (Ramelteon) in combination with one or more drug substances chosen from fluoxetine, sertraline, paroxetine, mianserine, milnacyprane, cytalopram, escytalopram, fluvoxamine, minaprine, duloxetine, venlafaxine, imipramine, clomipramine, doxepine, trazodone, nephazodone, amitriptyline, carbamazepine, mirtazapine, diazepam, flutazolam, lorazepam, buspirone, tandospirone, ethyl loflazepat, flutoprazepam, mexazolam, clothiazepam, ethizolam, hydroxysine, alprazolam, fludiazepam, chlorodiazepoxide, cloxazolam, clorazepat and oxazolam for making a pharmaceutical composition for prevention or treatment of depression or anxiety disorder, for prevention or treatment of depression or anxiety disorder in the patients with underlying diabetes, hyperlipidemia, hypertension or metabolic syndrome, as well as appropriate methods of treating.

EFFECT: intensified effect of diazepam or paroxetine in joint administration with Ramelteon with no adverse reactions.

4 cl, 14 dwg, 1 tbl, 5 ex

FIELD: medicine.

SUBSTANCE: present invention refers to a delivery system for pharmaceutical compositions, partially based on ionic interaction to regulate and facilitate release of therapeutic agents, and concerns a bioadhesive pharmaceutical composition in the form of the gel, not containing an oil phase, with prolonged controlled release, containing an ionic therapeutic agent and ionic polymer wherein polymer is ionised enough to release a therapeutic agent in a controlled way throughout a long period of time, and a composition does not require an emulsion system to be introduced.

EFFECT: composition provides controlled release of a therapeutic agent.

10 cl, 6 tbl, 1 ex

FIELD: medicine.

SUBSTANCE: invention relates to medicine, in particular to gastroenterology and cardiology and concerns method of objectifying indications for choosing treatment of patients with ulcer disease (UD) in combination with artery hypertension (AH). For this purpose in accordance with WHO/ISAH classification of 1999, degree of AH and risk of development of cardio-vascular complications (RDCVC) is determined for patients. Patients with UD in combination with AH of I degree and RDCVC of 1-4 degree, as well as patients with UD with AH of II degree and RDCVC of 2 degree undergo traditional anti-ulcer and conventional hypertension therapy. Patients with UD and AH of II degree and RDCVC of 3-4 degree and patients with UD and AH of III degree and RDCVC of 4 degree are examined for presence of immune disorders, intestine disbacteriosis, depressive disorders, sympaticotonia, metabolic syndrome. If said disorders are found immunomodulators, antidepressants, vegetotropic medications are administered and metabolic syndrome therapy is performed, as hypotensive medications ACE inhibitors are introduced. Patients with UD with AH of III degree and RDCVC of 4 degree are administered combined therapy with ACE inhibitors and pulse slowing calcium antagonists, excluding preparations with make QT interval longer.

EFFECT: method ensures individualised treatment of said category of patients taking into account unfavourable development of ulcerous process depending on expression of systemic microcirculation disorders, determined by AH and RDCVC degree, which allows to influence different links of pathologic process fully and prevent development of complications.

8 tbl, 2 ex

FIELD: chemistry.

SUBSTANCE: present invention pertains to a compound with general formula where R' stands for phenyl, unsubstituted or substituted with one or more substitutes, chosen from a group comprising alkyl, alkoxy group, halogen, -(CH2)oOH, -C(O)H, CF3, CN, S-alkyl, -S(O)1,2-alkyl, -C(O)NR'R", -NR'R"; R2 and R3 independently stand for hydrogen, halogen, alkyl, alkoxy group, OCHF2, OCH2F, OCF3 or CF3 and R4 and R5 independently stand for hydrogen, -(CH2)2SCH3, -(CH2)2S(O)2CH3, -(CH2)2S(O)2NHCH3, -(CH2)2NH2, -(CH2)2NHS(O)2CH3 or -(CH2)2NHC(O)CH3, R' stands for hydrogen, alkyl, -(CH2)oOH, -S(O)2- alkyl, -S(O)-alkyl, -S-alkyl; R" stands for hydrogen or alkyl; o stands for 0, 1, 2 or 3. The invention also relates to use of formula I compounds in making medicinal preparations for treating schizophrenia, for treating positive and negative symptoms of schizophrenia and medicine for treating schizophrenia.

EFFECT: obtaining new compounds with useful biological properties.

55 cl, 421 ex, 1 tbl

FIELD: medicine; pharmacology.

SUBSTANCE: composition contains lidocaine concentrated approximately 5 to 12.5 wt % as medical product and bioadhesive carrier including swelling, but water-insoluble cross-linked polymer of polycarboxilic acid, providing prolonged release of the agent. Furthermore, the invention refers to method of reduction or simplification of uterus rhythm disturbance including introduction of declared composition to the patient requiring treatment.

EFFECT: reduction or simplification of uterus rhythm disturbance due to normalisation of abnormal or undesirable uterus contraction.

11 cl, 33 ex

FIELD: medicine.

SUBSTANCE: invention concerns optimisation of activity of thrombocytes at patients with metabolic syndrome (MS). For this purpose within 2 months carry out the complex therapy including individually chosen hypohigh-calorie diet, and also introduction of preparations - Lisinopril 5 mg of 1 time in the morning, Diltiazem 90 mg 2 time a day and Metforminum 500 mg 2 times a day.

EFFECT: effective correction of functions of thrombocytes at AH patients with MS at the expense of potentiation of therapeutic effect of separate components of complex therapy.

1 ex

FIELD: medicine; pharmacology.

SUBSTANCE: IBAT antioxidant application (transport of bilious acids in a iliococcygeus gut), chosen of 1,2,5-benzothiadiazines in treatment and-or prevention of coprostasia at warm-blooded animals, such as the person (versions), corresponding method of treatment and a pharmaceutical composition is described.

EFFECT: increase in quantity of excrements at the expense of strengthening of impellent function of intestines, increase in quantity of water in its bottom part content, softening of the content and decrease in a stretching of walls of intestine, reduction of feeling of pain.

16 cl, 3 tbl

FIELD: veterinary medicine.

SUBSTANCE: invention is intended for treatment of acute poisoning of animals with neonicotinoid insecticides. The method comprises intravenous administration of diazepam, Ringer's solution and unitiol.

EFFECT: method improves effectively the survival of animals, reduces the concentration of neonicotinoid insecticides in the body.

3 tbl, 2 ex

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