A method for the treatment of relapsing forms of urogenital candidiasis women
(57) Abstract:The invention relates to medicine, namely to dermatology, and for the treatment of chronic forms of urogenital candidiasis in women. To do this, hold the course of immunomodulatory therapy with the antiviral drug cycloferon 250 mg for 2 days, then every other day intravenous 15-20 injections to restore the phagocytic activity of neutrophils against fungi of the genus Candida. Then assign diflucan 150 mg 1 time per week for 2-3 weeks. The method allows to reduce the treatment time, reduce complications of treatment and recurrence of the disease. table 2. The invention relates to medicine, namely to dermatology.Over the last decade, the frequency of urogenital candidiasis has almost doubled. There is a trend of prevalence of relapsing forms of the disease (Serov C. N., 1997, Echenbach D., 1994).Fungi of the genus Candida - conditionally pathogenic flora. So yeast-like fungi in 10% of cases stand out from the mucous membrane of healthy people (A. N. Rebrov, 1979). With long-term chronic forms of Candida infection formed a certain kind of "symbiosis" between the microorganism and conditionally-patogennaya, usually develops only in terms of reducing the resistant forces of the body (E. N. Pakhomov, // Journal of Microbiology, epidemiology and immunology, No. 6, 1990, pp. 7-10).The basis of pathogenesis of Candida infection is a violation of T-cell immunity, it phagocytic link. The main type of cells that contribute to the elimination of yeast-like fungi from the body, are neutrophils, macrophages and monocytes. Having pronounced faguoqitirute properties, neutrophils are included in the fight against infection before specific remedies, and thus determine the further development of the infectious process (A., Katsitadze //Bulletin of dermatology, No. 12, 1990, pp. 20-24). Cells phagocytic link is able to destroy both blastospore and pseudomycelial elements fungi Candida.However, the immunity in Candida infection has several features that distinguish it from bacterial, viral and yeast infections. The peculiarity of immunity in Candida infection is the ability of fungi of the genus Candida to resist the destruction faguoqitirute cells: mycelium yeast-like fungi allocates a specific substance, inhibiting the chemotaxis of leukocytes; being favoritemovie, A. J. Tiernex Investigation of a cluster of sistemic Candida albicans infection in a neonatal care unit //J. Infec. Dis. - 1988. - Vol. 158, N6. - P. 1375-1379).Thus, the dynamics of phagocytosis when Candida infection to a certain extent, depend not only on the functional ability of leukocytes, but also from the pathogenic properties of these mushrooms. Therefore, standard methods of monitoring indicators of immunity used in viral, bacterial and other fungal infections, are not always clear criteria for evaluating the effectiveness of treatment for Candida infection.Based on the characteristics of complex pathogenetic mechanism candidiasis, where the leading role in the development of the disease given the state of the protective functions of the organism, the administration of specific drugs, even high-performance, does not guarantee complete recovery.Known methods of treatment of candidal infection, based on the idea that the basis of chronic recurrent candidiasis is the failure of local cellular immunity, it phagocytic link. There is a large Arsenal of immunomodulating drugs, however, in the absence of the methods is quite effective immune to appoint receiving long-term (under one year) od Med 1997). The disadvantages of this method are the long term treatment of the disease, and large exchange rate antimycotic drugs, if this does not resolve the main pathogenetic link of the origin and development of Candida infection.The closest way is the treatment of chronic forms of urogenital candidiasis fungistatic antifungal systemic drug action Diflucan (fluconazole) company Pfizer. In chronic relapsing forms of urogenital candidiasis dosage are selected individually controlled elimination yeast-like fungi from the body. Diflucan is prescribed in a dose of 150 mg 1 time per week for 4 weeks (N.M. Gerasimova, N. M. Tereshkina // guidelines for the diagnosis, treatment and prevention of vulvovaginal candidiasis: Information sheet No. 1 Ural State medical Academy. Department of skin and venereal diseases. Protocol No. 1 dated 24.01.1997).The disadvantages of this method are the high-dose antifungal drug, as well as a high percentage of recurrence (up to 60%).In this regard, it is advisable, along with the use of antimycotic drugs using methods of pathogenetic therapy, increasing rectitude immune status of the organism, enhance its protective properties, increasing the phagocytic activity of neutrophils, is the inducer of interferon, an antiviral drug, cycloferon, recommended by "Polysan", St. Petersburg (1996). Research in recent years shows and pathogenetically proved the high efficacy of interferon and its inducers in the treatment of viral and bacterial infections. In immunodeficiency States of various etiologies, including fungal, chronic forms of infection cycloferon is recommended as follows: 250 mg/in or/m 2 days in a row, then a day - from 10 to 15 injections (M, Romantsev, F. I. Ershov, I. etc. // Immunodeficiency States: correction cycloferon. NTFP "Polysan", St. Petersburg, 1998). However, urogenital candidiasis, this scheme is not efficient enough.The objective of the invention is improving the treatment of chronic flowing forms of urogenital candidiasis in women, reducing the number of relapses.This object is achieved in that pre-teach the course immunomodulatory therapy with the antiviral drug cycloferon 250 mg for 2 days, then every other day intravenous 15-20 injections to restore the 1 time per week for 2-3 weeks.The novelty of the method:
Consistent use of immunomodulating medication cycloferon under the control of the phagocytic activity of neutrophils against yeast-like fungi by the method of the coast, Stanko followed etiotropic therapy antifungal drug diflucan provides:
1. recovery of specific resistant forces of the microorganism and subsequent elimination yeast-like fungi from the body;
2. differential selection of doses, dose reduction antifungal drug diflucan and frequency of recurrence of the disease due to the normalization of phagocytic activity of neutrophils against yeast-like fungi and address the underlying pathogenetic background of the development of Candida infection.The essence of the method:
When the diagnosis of chronic urogenital candidiasis patients initially held a course immunomodulatory drug therapy cycloferon: 250 mg 2 days in a row, then every other day/under the control of the evaluation of the immunological status: indicators of T-cell immunity - CD3CD4CD8CD16functional activity of neutrophils - nst-test, cation-lysosomal proteins, as well as spacetree ability of neutrophils to culture fungi of the genus Candida).To restore the phagocytic activity of neutrophils against fungi of the genus Candida took from 15 to 20 injections of cycloferon.The ultimate effect upon the appointment of immunomodulating drugs in patients with candidiasis is to restore the phagocytic activity of neutrophils in relation to the fungal culture of the patient. Normalization only General indicators of immunity and phagocytic ability of neutrophils determined by standard methods of research, cannot serve as a clear criterion for the effectiveness of immunostimulatory therapy for this type of infection.When we conducted the treatment found that 15 injection of cycloferon are not always sufficient to restore the specific resistance of the organism, so in some cases (13,1%) patients were applied to 20 injections of the drug, whereas for the recovery of common indicators of T-cell immunity and phagocytic activity of neutrophils with Staphylococcus took from 10 to 15 injections of cycloferon.Speaker normalization factors of nonspecific immunity and phagocytosis with their own culture of the fungus is given in table. 1.After normalis is -80% (experimentally confirmed) - is etiotropic therapy antifungal drug diflucan 150 mg 1 time per week for 2-3 weeks under the supervision of elimination yeast-like fungi from the body.Given that the state of the phagocytosis of yeast fungi of neutrophils with Candida infection determines the clinical picture of the disease (severity, occurrence of relapses), the recovery of specific resistance resolve the main pathogenetic background of the development of vulvovaginal process. Use 15-20 injections of cycloferon leads to normalization of indicators of phagocytosis with their own culture of fungi, and the subsequent use of the drug diflucan is to eliminate the yeast-like fungi from the body. This combination of drugs and the sequence of their application to reduce the dose of an antifungal drug in the subsequent pathogenetic therapy, and to reduce the frequency of recurrences of the disease.We studied 34 patients with relapsing forms of urogenital candidiasis. Of these violations indicator of nonspecific immunity in CD3CD4CD8CD16observed in 34 women. Violation of phagocytic activity Nate the indicator of phagocytic activity of neutrophils with fungi of the genus Candida (native culture of the patient) were detected in all 34 women, that is, in 100% of cases.To restore the phagocytic activity of neutrophils with their own culture fungi (according to the technique coast, Stanko) it took 15 to 20 injections of the drug. After 15 injections of the drug normalization of parameters of phagocytic activity of neutrophils with their own culture fungi occurred in 30 patients after 20 injections - in 4 patients.Dynamics of the clinical picture - reduce itching and quantity of vaginal discharge is correlated in time with the normalization of indicators of phagocytic activity of neutrophils with their own culture yeast-like fungi.Thus, when immunostimulating therapy inducer of interferon - drug cycloferon in patients with chronic forms of urogenital candidiasis determination of phagocytic activity of neutrophils with their own culture of fungi according to the technique coast, Stanko is more effective for control of stimulation of immunity in comparison with control T-cell immunity CD3CD4CD8CD16as well as the standard methods of determining the functional activity of neutrophils and phagocytic ability with the culture of staphyloccocal features of immunity in this form of the disease - from 15 to 20 injections.The results of treatment are presented in table. 2.Clinical case N 1.Patient I., aged 32, with a diagnosis of chronic urogenital candidiasis, multiple recurrences, was admitted with complaints of intense burning sensation in the vagina, copious cheesy character. From the anamnesis: a disease duration of 6 years, the recurrence of urogenital candidiasis up to 8 times per year. When viewed in the mirrors vaginal mucosa is hyperemic, vagina abundance of cheesy mass. In the study of immune status showed a decrease in T-cell immunity (CD3- 45%, CD16- 7%, phagocytic background with Staphylococcus 64%, with a culture of Candida 32%).Treatment: cycloferon 250 mg/b - 17 injection under the control of the immunological status. In the course of treatment was observed following sequence normalization of immunity: after 10 injections of cycloferon normalization of indices of nonspecific immunity T-cell immunity (CD3- 69%, CD16- 12%) and phagocytic activity of neutrophils with Staphylococcus according to the standard method of determining - 82%, phagocytic background of neutrophils with private cheibub was observed after 17 injection of cycloferon (56%). Positive dynamics of clinical correlated with normalization of phagocytosis indices methodology coast, Stanko: itching and amount of discharge in the vagina decreased after 15-16 injection of cycloferon.After 17 injection the patient was taking diflucan dose 150 mg 1 time per week for 2 weeks. When mycological study, after 2 weeks of yeast-like fungi were not found. In this regard, repeated doses of the drug was not prescribed.When monitoring a patient within 6 months of acute urogenital candidiasis was not. When mycological research (bacterioscopic and bacteriological) with a frequency of 1 time per month fungi of the genus Candida was not found.Clinical case N 2.Patient P. , aged 32. Diagnosis: chronic urogenital candidiasis, constantly relapsing course. Was admitted with complaints of intense itching in the vagina and perianal region, rich cheesy vaginal discharge. From the anamnesis: disease duration 9 years, recurrent vulvovaginal process occur almost every menstrual cycle. Previously the patient on the urogenital candidiasis were treated diflucanno vagina detected fungi of the genus Candida. Examination: vaginal mucosa is hyperemic, with a large number of caseous masses. In the study of immune status showed a decrease in T-cell immunity (CD3- 34%, CD4- 25%, CD8- 12%, CD16- 5%), decreased phagocytic ability of neutrophils with Staphylococcus up to 64%, with their own culture fungus to 28%.Treatment: Cycloferon 250 mg/20 injection under the control of the immunological status after. In the treatment condition improved significantly: itching of the vagina and perianal region have stopped for 34 day (after 17 injection), decreased the number of allocations for 36 day (after 18 injection). After 10 injections normalization of indicators of cellular immunity (CD3- 69%, CD4- 34%, CD8- 36%, CD16- 16%), after a 15 - normalization phagocytic background culture of Staphylococcus 85%, after 20 injections of cold - phagocytic activity with their own culture fungus - 64%. After 20 injections the patient took diflucan dose 150 mg 1 time per week for 2 weeks. When mycological study, after 2 weeks of yeast-like fungi were not found. In this regard, repeated doses of the drug was not prescribed.When observing the deposits (bacterioscopic and bacteriological) with a frequency of 1 time per month fungi of the genus Candida was not found.The positive effect of the proposed method:
1. this method allows you to define a differentiated approach to the appointment of a certain dose of the drug in each case, effectively improve immunoresistance the body of the patient by activating the indicators of T-cell component of the immune system, specific indicators of phagocytosis of yeast fungi of neutrophils (above 50%), which eliminates one of the main pathogenesis of Candida infection;
2. to reduce the frequency of relapses in 2 times;
3. to reduce the dose of the antifungal drug in 1.5 times. A method for the treatment of relapsing forms of urogenital candidiasis in women, based on the use of antimikoticeski drugs and immunomodulatory therapy, wherein the pre undergo immunomodulatory drug therapy cycloferon 250 mg for two days, then every other day intravenously 15 to 20 injections to restore the phagocytic activity of neutrophils against fungi of the genus Candida, then prescribe diflucan 150 mg 1 time per week for 2 to 3 weeks.
FIELD: organic chemistry, medicine, chemical-pharmaceutical industry, pharmacology, pharmacy.
SUBSTANCE: invention relates to a medicinal agent used for prophylaxis and treatment of diseases and disorders associated with dysfunction of benzodiazepine receptors. This medicinal agent comprises compound of the formula (I)
. Compound of the formula (I) elicits high cardioprotective, neurotrophic, renoprotective activity and enhanced bioavailability.
EFFECT: valuable medicinal properties of compounds.
5 cl, 1 tbl, 1 ex
FIELD: organic chemistry, medicine, pharmacy.
SUBSTANCE: invention relates to compounds of the formula (I):
wherein X means group of the formula (X-1) wherein R15 means halogen atom, (lower)-alkyl and perfluoro-(lower)-alkyl; R16 means hydrogen, halogen atom and (lower)-alkyl; or X means group of the formula (X-2) wherein Het means 5- or 6-membered heteroaromatic ring comprising 1 or 2 heteroatoms as nitrogen (N) atom; R15 and R16 have values indicated above for (X-1); R30 means hydrogen atom or (lower)-alkyl; p means a whole number from 0 to 1; or X means group of the formula (X-3) wherein R18 means aryl; R19 means unsubstituted arylalkyl or heteroarylalkyl representing 6-membered heteroaromatic ring comprising nitrogen (N) atom as a heteroatom; R20 means unsubstituted (lower)-alkanoyl; Y means group of the formula (Y-1) wherein R22 and R23 mean independently from one another hydrogen atom, (lower)-alkyl, halogen atom or perfluoro-(lower)-alkyl and at least one of radicals R22 and R23 doesn't mean hydrogen atom; R24 means hydrogen atom; or Y means group of the (Y-3) wherein R25 means group of the formula: R26-(CH2)e- wherein R26 means (lower)-alkoxy-group, (lower)-alkylthio-group, (lower)-alkylsulfonyl; or R26 means group of the formula: -NR28R29 wherein R28 means hydrogen atom; R29 means (lower)-alkanoyl or (lower)-alkylaminocarbonyl; Q means -(CH2)f- wherein e means a whole number from 0 to 4; f means a whole number from 1 to 3; a bond denoted as a dotted line can be hydrogenated optionally; and to its pharmaceutically acceptable salts and esters. Also, invention proposes a pharmaceutical composition designated for treatment or prophylaxis of rheumatic arthritis, cerebrospinal sclerosis, intestine inflammatory disease and asthma and containing compound of the formula (I) or its pharmaceutically acceptable salt or ester in combination with a compatible pharmaceutical carrier. Invention proposes derivatives of thioamide inhibiting interaction between α4-comprising integrins and VCAM-1.
EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.
20 cl, 1 tbl, 86 ex
FIELD: medicine, operative gynecology.
SUBSTANCE: at final stage of laparoscopic operation for 5-7 min one should introduce 16 U lidase in 1 ml 2%-lidocaine solution into uterine mesentery from both sides, and then, by not removing a needle - a half of single dose of antimicrobial preparation in 1 ml 2%-lidocaine solution, then in postoperational period - an antimicrobial preparation applied during laparoscopy lymphotropically under mucosa of lateral vaginal arch from both sides for 5-7 d once daily and one antimicrobial preparation - intravenously for 5-7 d, moreover, as antimicrobial preparations one should apply gentamicin, metrogyl and other preparations permitted for intravenous application. The present innovation stimulates lymphatic drainage in area of inflammation and activates interstitial humoral transport of antimicrobial preparations that, in its turn, favors complete sanitation of inflammation foci and prophylaxis of disease relapses.
EFFECT: higher efficiency of therapy.
1 cl, 1 ex
FIELD: organic chemistry, medicine.
SUBSTANCE: invention relates to applying compounds of the formula (I) for preparing an antibacterial composition and veterinary composition eliciting with the enhanced activity.
EFFECT: valuable properties of agents.
4 cl, 3 tbl, 78 ex
FIELD: medicine, neurology.
SUBSTANCE: method involves intravenous administration of autolymphocytes treated with an immunomodulating agent by extracorporal method using cycloferon (250 mg) as an immunomodulating agent. Simultaneously, the following medicinal mixture comprising lidocaine, 100 mg; lidazum, 32 U; dexamethasone, 4 mg; leukinferon, 10 000 U; 40% glucose solution, 4 ml is administrated into interspinal ligaments of spinal column at levels corresponding to thoracal and lumbar enlargements of the spinal cord. The procedure is repeated three times with interval for 48-72 h. Method provides enhancing the effectiveness of lymphostimulation and immunomodulation in cerebrospinal sclerosis. Invention can be used for lymphostimulation and immunomodulation in cerebrospinal sclerosis.
EFFECT: improved method for treatment.
1 tbl, 1 ex
FIELD: organic synthesis.
SUBSTANCE: invention provides novel biologically active N-(4-chlorobenzoyl)-5-bromoanthranyl acid amid depicted by formula I:
EFFECT: increased choice of inflammatory drugs and analgetics.
FIELD: organic synthesis.
SUBSTANCE: invention provides novel biologically active N-(4-chlorobenzoyl)-5-bromoanthranyl acid amid depicted by formula I:
EFFECT: increased choice of inflammatory drugs and analgetics.
FIELD: medicine, pharmaceutics.
SUBSTANCE: the suggested pharmaceutical composition includes formoterol and its pharmaceutically acceptable salt and flucticason propionate at their weight ratio being, correspondingly, 1 : 5 to 1 : 50. Combined application of flucticason propionate and formoterol fumarate provides synergistic therapeutic action that enables to decrease the dosage of flucticason propionate for achieving concrete antiphlogistic action that leads to possible unfavorable side effects.
EFFECT: higher efficiency of application.
10 cl, 216 ex
FIELD: pharmaceutical chemistry.
SUBSTANCE: invention relates to treatment of patients suffering from diseases associated with pathologic activity of matrix proteases. Treatment involves administration of compounds depicted by general formula (I).
EFFECT: increased treatment efficiency.
136 cl, 448 ex
FIELD: biochemistry, medicine.
SUBSTANCE: invention relates to phenylalanine derivatives of formula I , wherein X1 and X2 are halogen; Q is CH2 or -(CH2)-; Y is C1-C6-alkyl; CO2R is carboxylic group which may be transetherified; or pharmaceutically acceptable salts thereof. Pharmaceutical composition is disclosed having inhibition activity against α4-integrine mediated cell adhesion. Said composition includes therapeutically effective amount of claimed derivative or pharmaceutically acceptable salt thereof in mixture with pharmaceutically acceptable carrier or diluent. Derivatives of present invention or pharmaceutically acceptable salt thereof are useful as active therapeutic agent inhibiting α4-integrine mediated cell adhesion. Also disclosed are application of phenylalanine derivatives of formula I or pharmaceutically acceptable salts thereof to produce drug for treatment of diseases associated with α4-integrine mediated cell adhesion. Method for treatment or prophylaxis diseases associated with α4-integrine mediated cell adhesion includes administrating to patient effective amount of phenylalanine derivatives of formula I or pharmaceutically acceptable salt thereof. Further methods (variants) for production of target derivatives are disclosed.
EFFECT: α4-integrine inhibiting phenylalanine derivatives.
20 cl, 42 ex